Effects of facial identity, facial expression, and subject's sex on laterality in monkeys.
Previously we showed that rhesus monkeys processed discriminations of monkey faces significantly better with the right hemisphere of the brain than with the left. The overall effects of the type of discrimination, i.e. facial identity or expression, and the sex of the subject on laterality are examined here for seven phases of this series of experiments. Both types of discrimination produced a right hemispheric advantage, with slightly greater laterality for expression, but generally the laterality did not differ significantly for the two types. Female monkeys demonstrated more consistent and significant right hemispheric laterality than did males. Furthermore, female monkeys tended to be more lateralised for discriminations of expression, whereas males were about equally lateralised for both types. Thus, in these experiments the overall right hemispheric advantage for facial discriminations in monkeys reflects the contribution of the female subjects, especially when discriminating expression, more than that of the males.


Enhanced de novo ceramide generation through activation of serine palmitoyltransferase by the P-glycoprotein antagonist SDZ PSC 833 in breast cancer cells.
SDZ PSC 833 (PSC 833), a P-glycoprotein-targeted multidrug resistance modulator, sensitizes cancer cells to chemotherapy. Here we show that PSC 833 also potentiates the formation of ceramide. Because ceramide is a second messenger in chemotherapy-induced apoptosis, knowledge of the lipid pathways influenced by PSC 833 is of relevance. In intact MDA-MB 468 breast cancer cells, ceramide generation increased 3-fold 1 h after PSC 833 addition (5.0 microM). Cyclosporine A, a structural analogue, failed to impact ceramide metabolism. Sphinganine, the upstream precursor of ceramide, also increased in response to PSC 833, and this could be blocked by adding L-cycloserine, a serine palmitoyltransferase (SPT) inhibitor. Exposure of cultured cells to PSC 833 (30 min to 4 h; 1-10 microM), followed by isolation of microsomes for in vitro assay, increased SPT activity 60%, whereas palmitoyl CoA synthetase and ceramide synthase activities were not altered. SPT activity was also heightened by pretreating cells with either paclitaxel, N-(4-hydroxyphenyl)retinamide, etoposide, or daunorubicin; however, activation was half that attained by PSC 833. PSC 833 stimulated ceramide generation in other breast cancer cell lines as well, including BT-20, MDA-MB 231, Hs 578T, T-47D, and MCF-7. In summary, several types of anticancer agents and the P-glycoprotein modulator PSC 833 share the ability to increase cellular ceramide levels by activation of SPT, the rate-limiting enzyme in the de novo pathway of ceramide synthesis. These data provide novel insight in the area of lipid-mediated cell death.


Dietary supplementation with inulin-propionate ester or inulin improves insulin sensitivity in adults with overweight and obesity with distinct effects on the gut microbiota, plasma metabolome and systemic inflammatory responses: a randomised cross-over trial.
To investigate the underlying mechanisms behind changes in glucose homeostasis with delivery of propionate to the human colon by comprehensive and coordinated analysis of gut bacterial composition, plasma metabolome and immune responses. Twelve non-diabetic adults with overweight and obesity received 20 g/day of inulin-propionate ester (IPE), designed to selectively deliver propionate to the colon, a high-fermentable fibre control (inulin) and a low-fermentable fibre control (cellulose) in a randomised, double-blind, placebo-controlled, cross-over design. Outcome measurements of metabolic responses, inflammatory markers and gut bacterial composition were analysed at the end of each 42-day supplementation period. Both IPE and inulin supplementation improved insulin resistance compared with cellulose supplementation, measured by homeostatic model assessment 2 (mean±SEM 1.23±0.17 IPE vs 1.59±0.17 cellulose, p=0.001; 1.17±0.15 inulin vs 1.59±0.17 cellulose, p=0.009), with no differences between IPE and inulin (p=0.272). Fasting insulin was only associated positively with plasma tyrosine and negatively with plasma glycine following inulin supplementation. IPE supplementation decreased proinflammatory interleukin-8 levels compared with cellulose, while inulin had no impact on the systemic inflammatory markers studied. Inulin promoted changes in gut bacterial populations at the class level (increased Actinobacteria and decreased Clostridia) and order level (decreased Clostridiales) compared with cellulose, with small differences at the species level observed between IPE and cellulose. These data demonstrate a distinctive physiological impact of raising colonic propionate delivery in humans, as improvements in insulin sensitivity promoted by IPE and inulin were accompanied with different effects on the plasma metabolome, gut bacterial populations and markers of systemic inflammation.


Lesions of nucleus accumbens affect morphine-induced release of ascorbic acid and GABA but not of glutamate in rats.
Our previous studies have shown that local perfusion of morphine causes an increase of extracellular ascorbic acid (AA) levels in nucleus accumbens (NAc) of freely moving rats. Lines of evidence showed that glutamatergic and GABAergic were associated with morphine-induced effects on the neurotransmission of the brain, especially on the release of AA. In the present study, the effects of morphine on the release of extracellular AA, γ-aminobutyric acid (GABA) and glutamate (Glu) in the NAc following bilateral NAc lesions induced by kainic acid (KA) were studied by using the microdialysis technique, coupled to high performance liquid chromatography with electrochemical detection (HPLC-ECD) and fluorescent detection (HPLC-FD). The results showed that local perfusion of morphine (100 µM, 1 mM) in NAc dose-dependently increased AA and GABA release, while attenuated Glu release in the NAc. Naloxone (0.4 mM) pretreated by local perfusion to the NAc, significantly blocked the effects of morphine. After NAc lesion by KA (1 µg), morphine-induced increase in AA and GABA were markedly eliminated, while decrease in Glu was not affected. The loss effect of morphine on AA and GABA release after KA lesion could be recovered by GABA agonist, musimol. These results indicate that morphine-induced AA release may be mediated at least by µ-opioid receptor. Moreover, this effect of morphine possibly depend less on the glutamatergic afferents, but more on the GABAergic circuits within this nucleus. Finally, AA release induced by local perfusion of morphine may be GABA-receptor mediated and synaptically localized in the NAc.


Early Mortality in Patients who Received Extensive Surgical Management for Acute Type A Aortic Dissection - Analysis of 452 Consecutive Cases from a Single-center Experience.
To detect the potential risk factors associated with early mortality in patients who received extensive surgical management, in the form of total arch replacement plus frozen elephant trunk and arch debranching (hybrid repair technique), for acute type A aortic dissection. The clinical and surgical data of 452 surgically treated patients with acute type A aortic dissection at our center, between March 2010 and December 2016, have been retrieved. Uni and multivariate logistic regression analyses were carried out to detect the effect of various preoperative demographics and different perioperative variables on early mortality. Overall 30-day mortality occurred in 70 out of 452 patients (15.4%). The principal causes of death were multiple organ failure (n=38), cardiac failure (n=18), and severe pulmonary infection (n=10). Risk factors for early mortality were identified with multivariate analysis. Preoperatively, overweight (P<0.025), alcohol drinking (P<0.002), coronary artery disease (P<0.014), hemodynamic shock (P<0.006), and elevated white blood cells count (P<0.002) were associated with higher mortality rate. Postoperatively, prolonged operation time (P<0.008), stroke (P<0.0001), and acute renal dysfunction (P<0.0001) were highly associated with death. Considering the advantages of extensive surgical management for acute type A aortic dissection over the other less aggressive surgical approaches, it should be advised whenever indicated, provided that being carried out by experts in the field of adult aortic surgery in high-volume centers. The surgeon should be aware of the patient's preoperative comorbidities and other risk factors for early mortality, in particular, prolonged operation time.


Atypical Rocky Mountain spotted fever with polyarticular arthritis.
Rocky Mountain spotted fever (RMSF) is an acute, serious tick borne illness caused by Rickettsia rickettsi. Frequently, RMSF is manifested by headache, a typical rash and fever but atypical disease is common, making diagnosis difficult. Inflammatory arthritis as a manifestation is rare. The purpose of this study is to describe a patient with serologically proven RMSF who presented in an atypical manner with inflammatory arthritis of the small joints of the hands and to review the previously reported patients with rickettsial infection and inflammatory arthritis. An 18-year-old woman presented with a rash that began on the distal extremities and spread centrally, along with hand pain and swelling. She had tenderness and swelling of the metacarpophlangeal joints on examination in addition to an erythematosus macular rash and occasional fever. Acute and convalescent serology demonstrated R rickettsi infection. She was successfully treated with doxycycline. Inflammatory arthritis is a rare manifestation of RMSF or other rickettsial infection with 8 previously reported patients, only 1 of whom had RMSF. Physician must have a high index of suspicion for RMSF because of atypical presentations.


[Development and application of the software for analysis of arterial blood gases in treatment suggestions and training].
Suggestions and training in developing a computer software for analysis of arterial blood gases in treatment to be used in clinic and teaching. The software was edited by means of Delphi 7.0 and closely combined with Windows operating system. The knowledge base was built with Microsoft Access and HTML format files. The treatment suggestions and knowledge base of the software were built according to the correlated diagnosis and treatment guidelines of Chinese Medical Association, Practical Medicine (edition 12) edited by CHEN Hao-zhu, Medicine (edition 6) edited by YE Ren-gao, Modern Clinical Blood Gases Analysis edited by QIAN Gui-sheng, Concise Clinical Blood Gas Analysis edited by LUO Yan-jie, and the experience of the experts of our hospital. (1)The model of treatment suggestions consisted of the treatment objective and the treatment suggestions,and its contents included simple acid-base disturbance, mixed acid-base disturbance, respiratory failure,metabolic disturbances of sodium potassium and chloride. The calculation formulae included calculation formulae for the correction of acid-base disturbance and electrolyte disturbance. (2)Arterial blood gas analysis training software contained knowledge database of arterial blood gas analysis, clinical opinions of arterial blood gas analysis, exam database of arterial blood gas analysis, knowledge of arterial blood gas analysis graph, calculation formulas, correlated books and websites,assistance and so on. The software could be used as a reference by clinical doctors in clinic, it could also be used for teaching and training. It is scientific, state-of-the art, and valuable in clinical practice.


Spontaneous apoptosis in mouse F4N-S erythroleukemia cells induces a nonrandom fragmentation of DNA.
This study characterizes the fragmented DNA of mouse erythroleukemia (MEL) cells spontaneously entering apoptosis. Fragmented DNA was isolated by introducing a novel procedure that ensured a complete extraction of the characteristic oligonucleosomal ladder. As the results show, less than 10% of DNA of apoptotic cells is fragmented in this form. The main conclusion from experiments to characterize the nature of fragmented DNA is that spontaneous apoptosis induces a nonrandom cleavage of genomic DNA. The Southern analysis performed with total apoptotic DNA revealed that it is strongly enriched in interspersed repetitive sequences. In situ hybridizations with such DNA showed further than in interphase nuclei these sequences flock together and form clusters spread throughout the whole nuclear area whereas in mitotic chromosomes they are located predominantly at their pericentromeric/peritelomeric ends. Partial cloning and sequencing reinforces the notion that the apoptotic DNA is representative for a heterochromatinic portion of the mouse genome. Support for such an unexpected conclusion is coming also from experiments indicating that this DNA is heavily methylated and poorly transcribed.


Longitudinal association between low self-esteem and depression in early adolescents: The role of rejection sensitivity and loneliness.
Although the relation between low self-esteem and depression has been well established, little is known about the possible psychological mechanisms that account for the relation between them. Based on Beck's cognitive theory of depression, the main aim of this study was to explore the notion that rejection sensitivity and loneliness serve as mediators of the relation between low self-esteem and depression among early adolescents. Using a longitudinal design, we evaluated the hypothesized model with a sample of 866 Chinese early adolescents (51% females) between 11 and 15 years old who completed questionnaires on three occasions at 1-year intervals. Structural equation modelling showed that: (1) low self-esteem at Time 1 positively predicted depression at Time 3; (2) rejection sensitivity at Time 2 partially mediated the relation between low self-esteem at Time 1 and depression at Time 3; (3) low self-esteem at Time 1 demonstrated partial indirect effects on depression at Time 3 successively via rejection sensitivity and loneliness at Time 2; and (4) rejection sensitivity predicted an increase in loneliness but not vice versa, and depression accounted for later loneliness, but not for rejection sensitivity. The associations between low self-esteem and depression among early adolescents may be explained by rejection sensitivity and loneliness. These results suggest implications for effective interventions for depression in early adolescents. Low self-esteem is a risk factor for depression in early adolescents, and rejection sensitivity and loneliness help explain the vulnerability model. Implementing empirically based intervention plans to overcome low self-esteem may be helpful in efforts to reduce depression in early adolescents. Effective interventions should likely include efforts to decrease rejection sensitivity and loneliness and their effects, such as training to interpret verbal and behavioural cues in social interactions more accurately and to develop more effective social skills to enhance social confidence.


Real-World Clinical Outcomes of Bamlanivimab and Casirivimab-Imdevimab Among High-Risk Patients With Mild to Moderate Coronavirus Disease 2019.
Bamlanivimab and casirivimab-imdevimab are authorized for treatment of mild to moderate coronavirus disease 2019 (COVID-19) in high-risk patients. We compared the outcomes of patients who received these therapies to identify factors associated with hospitalization and other clinical outcomes. Adult patients who received monoclonal antibody from 19 November 2020 to 11 February 2021 were selected and divided into those who received bamlanivimab (n = 2747) and casirivimab-imdevimab (n = 849). The 28-day all-cause and COVID-19-related hospitalizations were compared between the groups. The population included 3596 patients; the median age was 62 years, and 50% were female. All had ≥1 medical comorbidity; 55% had multiple comorbidities. All-cause and COVID-19-related hospitalization rates at 28 days were 3.98% and 2.56%, respectively. After adjusting for medical comorbidities, there was no significant difference in all-cause and COVID-19-related hospitalization rates between bamlanivimab and casirivimab-imdevimab (adjusted hazard ratios [95% confidence interval], 1.4 [.9-2.2] and 1.6 [.8-2.7], respectively). Chronic kidney, respiratory and cardiovascular diseases, and immunocompromised status were associated with higher likelihood of hospitalization. This observational study on the use of bamlanivimab and casirivimab-imdevimab in high-risk patients showed similarly low rates of hospitalization. The number and type of medical comorbidities are associated with hospitalizations after monoclonal antibody treatment.


[MR tomography in cardiology. II: Flow phenomena].
Flow phenomena modify the information of MR tomograms and can cause artefacts which degrade the image quality. When ECG triggering and suitable modes of excitation are used, flow effects can give diagnostically relevant information concerning global and regional cardiac function and blood flow in vessels. The signal intensity of blood excited by an SE-mode is usually low. The spin echo increases due to the TR-effect. However, the TE-effect reduces the signal of flowing blood with increasing flow velocity. Phase shifts caused by flow generate line-shaped artefacts in the reconstructed tomograms and decrease the signal intensity of all odd spin echoes. The second order phase errors are compensated by phase recombination occurring in all even echoes. Therefore, in double echo acquisition the second spin echo of flowing blood can be higher than the first echo, especially when the flow velocity is physiologically or pathologically reduced. In multi-slice acquisition, time-of-flight effects can be observed, by which a resonance signal induced in one particular slice is shifted to and recorded in another slice.


Crystallisation under microgravity of mistletoe lectin I from Viscum album with adenine monophosphate and the crystal structure at 1.9 A resolution.
The crystal structure of the ribosome-inactivating protein (RIP) mistletoe lectin I (ML-I) from Viscum album in complex with adenine has been refined to 1.9 A resolution. High quality crystals of the ML-I complex were obtained by the method of vapour diffusion using the high density protein crystal growth system (HDPCG) on the international space station, mission ISS 6A. Hexagonal crystals were grown during three months under microgravity conditions. Diffraction data to 1.9A were collected applying synchrotron radiation and cryo- techniques. The structure was refined subsequently to analyse the structure of ML-I and particularly the active site conformation, complexed by adenine that mimics the RNA substrate binding.


Results of a 3-year, nutrition and physical activity intervention for children in rural, low-socioeconomic status elementary schools.
Improving children's nutrition and physical activity have become priorities in the United States. This quasi-experimental study evaluated the longitudinal effects of a 3-year, school-based, health promotion intervention (i.e. nutrition and physical education, classroom physical activity, professional development and health promotion for teachers and families, and strengthening wellness policies and family/community partnerships) on children's health behaviors in four, rural, low-socioeconomic status elementary schools. A total of 999 kindergarten to third-grade children participated in data collection consisting of 4-day pedometer tracking and previous-day fruits and vegetables consumption recall from baseline in January, 2011 through 12 follow-up assessments ending May, 2013. The mixed-effects regression models showed that children's nutrition and physical activity behaviors significantly improved over the 3-year intervention. The percentages of children who met the nutrition recommendation increased from 11 to 23% for girls and 12 to 23% for boys, while the percent who met the physical activity recommendation increased from 1 to 16% for girls and 3 to 7% for boys. Further, children's age and their school impacted certain intervention effects. This school-based intervention could be disseminated to promote healthy behaviors among rural disadvantaged children. Engaging parents and community partnerships is recommended to expand the traditional, children-focused education interventions.


Prevalence of familial hypercholesterolemia among young north Karelian patients with coronary heart disease: a study based on diagnosis by polymerase chain reaction.
Two deletions of the low density lipoprotein (LDL) receptor gene account for about 90% of the mutations that cause familial hypercholesterolemia (FH) in eastern Finland. The FH-Helsinki mutation deletes exons 16, 17 and a portion of exon 18, while the FH-North Karelia allele is characterized by a deletion of seven nucleotides from exon 6 of the LDL receptor gene. We developed a DNA assay based on the use of polymerase chain reaction (PCR) which simultaneously detects both of these mutations. We have screened 90 young (< 45 years) eastern Finns with symptomatic coronary heart disease (CHD) for the presence of these FH genes. One or the other of the mutations was present in 4 out of 55 survivors of acute myocardial infarction (AMI) and 4 out of 35 patients with angina pectoris (AP), but in none of 50 healthy controls of similar age. These data show a relatively high prevalence of confirmed FH in young CHD patients (AMI and MI combined: 8/90, or 9%), and also demonstrate the feasibility of PCR techniques in diagnosis of FH among populations with enrichment of specific types of LDL receptor gene mutations.


Influence of peri-arterial hepatic denervation on the glycemic response to exercise in rats.
Exercise is known to increase hepatic glucose production. Previous studies have suggested that the sympathetic nerves only marginally contribute to this process. This study examined whether increased catecholamine response or increased adrenoceptor sensitivity might have affected previous results showing no effect of hepatic denervation on the increased hepatic glucose production during exercise. Hepatic sympathetic denervated rats, sham-operated rats and control rats were forced to swim against a counter current for 15 minutes. Denervations and sham operations were performed 9 days prior to swimming. The results show that denervation did not affect the changes in levels of blood glucose, plasma FFA, and catecholamines before, during and after swimming. Furthermore, hepatic adrenoceptor sensitivity was not altered in denervated rats, since intravenous infusions of epinephrine (20 ng/min) and norepinephrine (50 ng/min) similarly changed blood glucose and plasma FFA levels in liver-denervated, sham-operated and control rats. Thus, the increase in blood glucose levels during intravenous infusion of epinephrine and norepinephrine in the respective groups was 1.2 +/- 0.3 and 1.0 +/- 0.3 mmol/l (liver-denervated rats), 1.6 +/- 0.4 and 0.7 +/- 0.3 mmol/l (sham-operated rats) and 1.3 +/- 0.3 and 0.8 +/- 0.3 mmol/l (control rats), respectively. After adrenodemedullation, however, the rise of glucose levels during swimming in liver-denervated and control rats was completely abolished. Thus, the glucose response to swimming with and without adrenodemullation was 0.1 +/- 0.4 and 1.7 +/- 0.4 mmol/l in liver-denervated rats (P < 0.01) and -0.2 +/- 0.4 and 2.2 +/- 0.2 mmol/l in control rats (P < 0.001), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Voriconazole versus itraconazole for antifungal prophylaxis following allogeneic haematopoietic stem-cell transplantation.
Antifungal prophylaxis for allogeneic haematopoietic stem-cell transplant (alloHCT) recipients should prevent invasive mould and yeast infections (IFIs) and be well tolerated. This prospective, randomized, open-label, multicentre study compared the efficacy and safety of voriconazole (234 patients) versus itraconazole (255 patients) in alloHCT recipients. The primary composite endpoint, success of prophylaxis, incorporated ability to tolerate study drug for ≥ 100 d (with ≤ 14 d interruption) with survival to day 180 without proven/probable IFI. Success of prophylaxis was significantly higher with voriconazole than itraconazole (48·7% vs. 33·2%, P < 0·01); more voriconazole patients tolerated prophylaxis for 100 d (53·6% vs. 39·0%, P < 0·01; median total duration 96 vs. 68 d). The most common (>10%) treatment-related adverse events were vomiting (16·6%), nausea (15·8%) and diarrhoea (10·4%) for itraconazole, and hepatotoxicity/liver function abnormality (12·9%) for voriconazole. More itraconazole patients received other systemic antifungals (41·9% vs. 29·9%, P < 0·01). There was no difference in incidence of proven/probable IFI (1·3% vs. 2·1%) or survival to day 180 (81·9% vs. 80·9%) for voriconazole and itraconazole respectively. Voriconazole was superior to itraconazole as antifungal prophylaxis after alloHCT, based on differences in the primary composite endpoint. Voriconazole could be given for significantly longer durations, with less need for other systemic antifungals.


[Fatal outcome of poisoning with the benzodiazepines flunitrazepam and diazepam].
On a wintry day a 29-year-old woman was found dead beside her car showing head injuries and signs of hypothermia. Several empty packets of sedative and hypnotic drugs were lying inside the car. Toxicological analysis revealed the presence of flunitrazepam (heart blood of the left and right chamber 0.033 mg/L each), norflunitrazepam (left heart blood 0.029 mg/L, right heart blood 0.027 mg/L), 7-amino-flunitrazepam (left heart blood 0.090 mg/L, right heart blood 0.104 mg/L), diazepam (left heart blood 0.395 mg/L, right heart blood 0.386 mg/L), nordazepam (left heart blood 0.112 mg/L, right heart blood 0.115 mg/L) and temazepam (left heart blood 0.034 mg/L, right heart blood 0.033 mg/L). Neither alcohol nor other drugs were found. It was concluded that benzodiazepine intake led to a disturbance of consciousness. Whether the woman died in this situation due to the icy temperature as a result of hypothermia or whether she died or would have died solely due to benzodiazepine overdosage could not be clarified.


Studies on a Factor in Sweet Potato Root Which Agglutinates Spores of Ceratocystis fimbriata, Black Rot Fungus.
A factor which agglutinated the spores of Ceratocystis fimbriata in the presence of Ca(2+) was purified from sweet potato (Ipomea batatas Lam cv. Norin[1]) root. Element composition of the purified factor was as follows; analysis found: C (29.8%), H (3.97%), O (65.34%), N (0.81%): calculated for C(43)H(69)O(70)N(1): C (30.02%), H (4.01%), O (65.15%), N (0.81%). The factor was mainly composed of galacturonic acid (53% of dry weight) and contained arabinose, fucose, and unidentified component as minor components. The factor also agglutinated A-, B-, AB-, and O types of human erythrocytes to almost the same degree in the presence of Ca(2+). The differential spore-agglutinating activity of the factor depended on the pH of the assay medium; it agglutinated similarly the germinated spores of sweet potato and coffee strains at pH 7.5 and 5.5, whereas it displayed a distinct differential agglutinating activity at pH 6.5. The factor was assayed for spore-agglutinating activity at pH 6.5, using the germinated and ungerminated spores of seven strains of C. fimbriata; sweet potato, coffee, prune, cacao, oak, taro, and almond strains. The factor agglutinated ungerminated spores of all seven strains similarly, although small differences were observed among strains. On the other hand, a clear differential agglutination was observed among the germinated spores of various strains; sweet potato and almond strains were highly insensitive in comparison with other strains. The growth of the agglutinated spores of C. fimbriata was inhibited. These results are discussed in relation to host-parasite specificity.


Total gastrectomy for complications of the duodenal switch, with reversal.
Duodenal switch (DS) is one of the most effective techniques for the treatment of morbid obesity and its related co-morbidities, with mortality rates of <1%, but with 9.4% morbidity rates (6.5% due to leaks). We present our experience with 9 patients operated with a DS, who later underwent total gastrectomy (TG) for complications of the sleeve gastrectomy. From 1994 to March 2006, 846 patients underwent the DS. 9 patients (1%) underwent TG; 5 were due to gastric leak at the angle of His, 2 were related to leakage at the doudeno-ileal anastomosis (DIA), 1 was for stenosis of the gastric sleeve, and 1 for a gastroparesis. In 3 cases, the DS was the second bariatric operation. Full restoration of bowel anatomy was attempted in all patients. TG has been the final solution for gastric complications of the DS in 9 (1%) of our 846 patients. In all cases, bowel anatomy has been restored, and there was no mortality. Postoperative courses have been difficult and hospital stays have been long in all patients (mean 4.5 months; range 1-10 months), with several episodes of re-do surgery after the TG. The actual BMI and %EBMIL are acceptable. TG successfully treated all 9 cases with life-threatening complications and difficult reinterventions after DS, without mortality. Restoration of bowel anatomy was done in all cases, with good final results.


The sources of chemical substances in allergic nasal fluid.
The sources of different chemical substances in the NF of allergic patient, such as albumin, secretory IgA, histamine, leukotriene, kinin and substance P were investigated. To accomplish this, we challenged the inferior turbinate on one side, but separately collected NF from both sides in patients with nasal allergy to house-dust. Provocation was done with paper disc containing dried allergen extract. Collection was done by suction for the first five minutes immediately after the onset of a positive response to nasal provocation. The total amount of the chemical substances on each side was analyzed separately and compared. Significant differences were seen between both sides only for histamine and leukotriene. In consideration with the previous reports, it is suggested that in nasal allergen challenge the major sources are glandular secretion for secretory IgA, and albumin, and secretion for migrating cells for histamine and leukotriene. The major sources responsible for kinin and substance P, however, are not defined.


[Effectiveness of psychotherapy in the treatment of denture intolerance. Evaluation of 25 cases].
25 "problem-patients" of the Clinic of Prosthetic Dentistry participated in this study (21 female, 4 male, aged between 32-81 yr.; mean age: 56.92+/-12.09). All included therapies were provided by dentists specialised in psychotherapy, and the efficacy of our model to treat denture intolerance patients was analysed based on the time need, and other parameters. Psychiatric diagnostic (ICD-10) categories were: F20-29: 12%; F30-39: 40%, F40-48: 36%; F60-69: 12%. The efficacy of the provided psychotherapy was: recovery in 44% (patient accepted the denture); improvement in 32% (patient compromised to accept the denture); no effect in 24% (the patient did not accept the denture). Number of psychotherapeutic sittings ranged: 1-10 in 24%; 10-20 in 28%, 20-30 in 16%, 30-40 in 8%; 40-50 in 8%; 50-60 in 12%; and 80-90 in 4% of the cases. Our results indicate that, the efficacy of dentists specialised in psychotherapy is appropriate to treat denture intolerance patients. However, treatments are rather time consuming, and 24% of the cases are unsuccessful. Because of this, the prevention and early diagnosis of this problems are crucial.


Satisfaction with sexual life among persons with traumatic spinal cord injury and meningomyelocele.
To study satisfaction with sexual life and self-assessed sufficiency of sexual counselling in persons with traumatic spinal cord injury (SCI) and meningomyelocele (MMC). A postal questionnaire on aspects of health and functioning was answered by 190 persons with traumatic SCI who had been treated in the Spinal Injuries Unit in Sahlgrenska University Hospital, Göteborg, Sweden and 41 persons with MMC who were admitted to the Young Adult Teams in Göteborg, Borås and Skövde, Sweden. On a numerical scale from 0 (dissatisfied) to 10 (satisfied) the median of satisfaction with sexual life was 3 for the men and 4 for the women among the persons with traumatic SCI. In the MMC group the median of satisfaction with sexual life was 5 for the men and 8 for the women. Sexual dissatisfaction increased with increasing age in both groups. Inconvenience caused by urinary and faecal incontinence, as well as neuropathic pain increased sexual dissatisfaction in the men with traumatic SCI. A total of 69% of the men with traumatic SCI and 56-59% of the participants in other subgroups reported that the sexual counselling they had received was sufficient. The results corroborate findings from earlier studies that satisfaction with sexual life is rather low among persons with SCI. Especially ageing men with traumatic SCI who have sustained injury at an older age are a challenge for rehabilitation. The high satisfaction with sexual life in the women in comparison with the men with MMC is a finding not reported earlier. Our results suggest that adequate treatment of incontinence and pain might improve even sexual satisfaction. Sexual counselling should be given to all individuals with SCI and to their partners. Sexual counselling for young adults with MMC is an important part of the rehabilitation process.


Domestication and Divergence of Saccharomyces cerevisiae Beer Yeasts.
Whereas domestication of livestock, pets, and crops is well documented, it is still unclear to what extent microbes associated with the production of food have also undergone human selection and where the plethora of industrial strains originates from. Here, we present the genomes and phenomes of 157 industrial Saccharomyces cerevisiae yeasts. Our analyses reveal that today's industrial yeasts can be divided into five sublineages that are genetically and phenotypically separated from wild strains and originate from only a few ancestors through complex patterns of domestication and local divergence. Large-scale phenotyping and genome analysis further show strong industry-specific selection for stress tolerance, sugar utilization, and flavor production, while the sexual cycle and other phenotypes related to survival in nature show decay, particularly in beer yeasts. Together, these results shed light on the origins, evolutionary history, and phenotypic diversity of industrial yeasts and provide a resource for further selection of superior strains. PAPERCLIP.


G protein-coupled receptor 30 down-regulates cofactor expression and interferes with the transcriptional activity of glucocorticoid.
G protein-coupled receptor 30 (GPR30) has previously been described to be important in steroid-mediated growth and to inhibit cell proliferation. Here we investigated whether the effect of GPR30 on cell growth is dependent on steroid hormone receptors. We stably introduced GPR30 in immortalized normal mammary epithelial (HME) cells using retroviruses for gene delivery. GPR30 inhibited the growth and proliferation of the cells. They expressed glucocorticoid receptor, but not estrogen or progesterone receptor. GPR30 down-regulated the expression of cofactor transcription intermediary factor 2 (TIF2) analyzed using quantitative RT-PCR analysis, and also diminished the expression of TIF2 at protein level analyzed by Western blotting using nuclear extracts from mammary epithelial cells. When HME cells were transiently transfected with the glucocorticoid response element MMTV-luc reporter plasmid, stable expression of GPR30 resulted in the abolition of ligand-induced transactivation of the promoter. In COS cells, transient transfection of GPR30 with glucocorticoid receptor alpha resulted in an abrogation of the MMTV-luc and GRE-luc reporter activities induced by dexamethasone. The results suggest a novel mechanism by which membrane-initiated signaling interferes with steroid signaling.


Herpes Zoster and Postherpetic Neuralgia: a review of the effects of vaccination.
Herpes zoster (HZ) results from reactivation of varicella zoster virus which has been persistent but clinically latent in dorsal root and cranial nerve ganglia since primary infection, usually as a child, with varicella (chicken pox). HZ affects 20-30% of individuals during their lifetime and up to 50% of those > or =80 years old. Although serious life- or sight-threatening complications occur rarely, postherpetic neuralgia (PHN) is the most common complication. Both HZ and PHN are most common in the elderly. Declining cell-mediated immunity resulting from immune senescence appears to be the cause. Incidence of HZ is also high in individuals who are immunocompromised as a result of disease or its treatment. HZ also occurs in younger and fit individuals but is usually mild and complications are rare. Current management of HZ with antiviral drugs and analgesics attains quite good control of acute pain and skin rash but offers only partial protection against PHN. Other strategies studied to prevent PHN such as nerve blocks are relatively ineffective and clinically impractical. Although several drug classes are used to manage PHN, numbers needed to treat to obtain 50% pain reduction range from approx. 2.5-5 and adverse effects are common. The elderly population is growing and thus the number of HZ and PHN susceptible individuals is increasing. HZ and PHN are expensive in terms of suffering, loss of independence and healthcare costs. Significant numbers of the elderly with HZ require hospitalization. Short-term illness in the elderly can lead to long-term loss of independence. A live attenuated herpes zoster vaccine has been studied in a large number of subjects and shown to reduce incidence of HZ as well as incidence and severity of PHN. The safety profile of the vaccine is good, local soreness at the injection site being the only common adverse event. Health economics studies suggest that vaccination of adults about 60 years of age would be cost effective. Duration of protection following vaccination is the subject of ongoing surveillance, as is the potential benefit of vaccinating younger and sicker members of the population.


An fMRI study of functional abnormalities in the verbal working memory system and the relationship to clinical symptoms in chronic schizophrenia.
There has been evidence for functional abnormalities of the verbal working memory system in schizophrenia. Verbal working memory crucially involves the interplay between the anterior and posterior language systems, and previous studies have shown converging evidence for abnormalities in the posterior language system in schizophrenia. In this functional magnetic resonance imaging study, we measured cortical activity in chronic schizophrenic patients and matched healthy controls during auditory and visual verbal working memory tasks. We employed 1) regional analyses specifically targeting the posterior language system and 2) analyses of functional connectivity between anterior and posterior language regions. We performed these analyses separately for each memory stage and modality. In the regional analyses, the left sylvian-parietal-temporal (Spt) area consistently showed reduced activation during encoding and retrieval stages in schizophrenia. Magnitudes of activation in the left posterior superior temporal sulcus were correlated with the severity of delusions at every memory stage. Functional connectivity analyses revealed reduced connectivity between the left Spt and the anterior insula during the encoding of auditory words. In addition, the connectivity strength was correlated with the severity of auditory hallucinations. These findings identify abnormal components in the verbal working memory system and illustrate their possible overlap with the mechanisms of core schizophrenic symptoms.


Approaches to analyse dynamic microbial communities such as those seen in cystic fibrosis lung.
Microbial communities play vital roles in many aspects of our lives, although our understanding of microbial biogeography and community profiles remains unclear. The number of microbes or the diversity of the microbes, even in small environmental niches, is staggering. Current microbiological methods used to analyse these communities are limited, in that many microorganisms cannot be cultured. Even for the isolates that can be cultured, the expense of identifying them definitively is much too high to be practical. Many recent molecular technologies, combined with bioinformatic tools, are raising the bar by improving the sensitivity and reliability of microbial community analysis. These tools and techniques range from those that attempt to understand a microbial community from their length heterogeneity profiles to those that help to identify the strains and species of a random sampling of the microbes in a given sample. These technologies are reviewed here, using the microbial communities present in the lungs of cystic fibrosis patients as a paradigm.


Differential impact of executive function on visual memory tasks.
Despite their common use in neuropsychological evaluation, little is known about the differential contribution of executive functioning to visual memory tests. In this study, hierarchical regression was used to determine the role of executive functioning on the Visual Reproduction subtest of the Wechsler Memory Scale--Third Edition, and the Rey-Osterrieth Complex Figure (ROCF) in a mixed neurological sample of 193 patients. Executive functioning was predictive of Visual Reproduction but not ROCF recall variables after accounting for demographic variables and global cognitive functioning. Only executive tests with a visuospatial component, the Trail-Making Test Part B and Wisconsin Card Sorting Test perseverative responses, were predictive of recall of Visual Reproduction stimuli. Organization of the ROCF was predictive of both Visual Reproduction and ROCF recall. These findings increase our understanding of the executive contribution to two common visual memory tests and may aid in the clinical interpretation of seemingly discrepant visual memory performance.


Robotic lateral transabdominal adrenalectomy.
Laparoscopic transabdominal adrenalectomy is considered to be the standard of care for adrnalectomy. Widespread adoption of robotic technology has positioned robotic adrenalectomy as an option in some medical centers. Many studies have compared laparoscopic versus robotic approaches to perform adrenalectomy and evaluated potential advantages to balance higher costs. This review summarizes current available data regarding the use of the robotic system to perform adrenalectomy (RA) and its comparison with laparoscopic adrenalectomy (LA).


Arabidopsis Acetohydroxyacid Synthase Expressed in Escherichia coli Is Insensitive to the Feedback Inhibitors.
Acetohydroxyacid synthase (AHAS), the first enzyme unique to the biosynthesis of isoleucine, leucine, and valine, is the target enzyme for several classes of herbicides. The AHAS gene from Arabidopsis thaliana, including the chloroplast transit peptide, was cloned into the bacterial expression plasmid pKK233-2. The resulting plasmid was used to transform an AHAS-deficient Escherichia coli strain MF2000. The growth of the MF2000 strain of E. coli was complemented by the functional expression of the Arabidopsis AHAS. The AHAS protein was processed to a molecular mass of 65 kilodaltons that was similar to the mature protein isolated from Arabidopsis seedlings. The AHAS activity extracted from the transformed E. coli cells was inhibited by imidazolinone and sulfonylurea herbicides. AHAS activity extracted from Arabidopsis is inhibited by valine and leucine; however, this activity was insensitive to these feedback inhibitors when extracted from the transformed E. coli.


Negative inotropic effects of propofol as evaluated by the regional preload recruitable stroke work relationship in chronically instrumented dogs.
Propofol anesthesia often is associated with marked decreases in arterial blood pressure. Previous investigations in vivo have provided conflicting reasons for this clinical finding, including propofol-induced decreases in preload or afterload and/or direct myocardial depressant effects. Interpretation of the results of these studies is complicated by use of indices of myocardial contractility that may only indirectly indicate changes in inotropic state or are significantly dependent on ventricular loading conditions. Eight experiments were performed using dogs chronically instrumented for measurement of aortic and left ventricular pressure, the peak rate of increase of left ventricular pressure (dP/dtmax), subendocardial segment length, intrathoracic pressure, and cardiac output. Myocardial contractility was evaluated in conscious and anesthetized dogs using the preload recruitable stroke work (PRSW) relationship, a sensitive, easily quantified, and relatively load-independent index of contractile function in normal canine myocardium in vivo. The relationship was derived from ventricular pressure-segment length loops generated by abrupt vena caval constriction. Respiratory variation in ventricular pressure was reduced by calculation of transmural pressure via instantaneous subtraction of intrathoracic pressure from corresponding left ventricular pressure. Systemic hemodynamics and myocardial contractility were recorded and evaluated in the conscious state and after a bolus of 5 mg/kg and a propofol infusion for 15 min at 15, 30, 60, and 120 mg.kg-1.h-1. A significant (P < .05) and dose-dependent decrease in PRSW slope (106 +/- 7 during control to 54 +/- 3 mmHg at the 120 mg.kg-1.h-1 infusion) was observed, demonstrating a direct depression of contractility. Concomitant decreases in left ventricular dP/dtmax and percent segment shortening also were observed. In addition, a significant decrease in systemic vascular resistance occurred at the two largest infusions. The results indicate that the significant decrease in systemic arterial blood pressure observed during continuous propofol anesthesia in dogs is a result of direct negative inotropic actions of propofol along with its direct effects upon arterial and venous vascular tone.


Susceptibility variants for rheumatoid arthritis in the TRAF1-C5 and 6q23 loci: a meta-analysis.
Genome-wide association studies have proposed susceptibility variants for rheumatoid arthritis in the TRAF1-C5 locus and 6q23 region. Furthermore, additional independent studies have investigated the same or highly linked polymorphisms in the same regions. To carry out a meta-analysis of the available evidence for the association of polymorphisms in the TRAF1-C5 locus and 6q23 region with rheumatoid arthritis. Data were synthesised for four polymorphisms: rs3761847 (n=13 datasets) and rs2900180 (n=9 datasets) in the TRAF1-C5 locus, and rs10499194 (n=5 datasets) and rs6920220 (n=7 datasets) in the 6q23 region. Meta-analyses for subgroups defined by anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF) status were also performed. The polymorphism rs6920220 reached genome-wide statistical significance with p=7.9 x 10(-17) and an allelic odds ratio of 1.24 (95% CI 1.18 to 1.30) and no between-study heterogeneity (I(2)=0%). The risk was significantly stronger in patients with anti-CCP antibodies and in patients with RF. The other three variants showed large between-study heterogeneity across datasets (I(2) range 74-82%); rs10499194 was nominally statistically significant after exclusion of the discovery data. Two variants had genome-wide statistical significance in subgroups defined by the presence of RF (rs3761847 and rs6920220) or anti-CCP (rs6920220). Genetic markers in the 6q23 region and TRAF1-C5 are associated with rheumatoid arthritis, in particular with positive anti-CCP and RF profile. With the exception of rs6920220, which shows highly consistent results, other proposed markers have high between-study heterogeneity that may reflect unrecognised phenotypic or genetic variability (eg, gene environment interactions) within rheumatoid arthritis. Furthermore, these markers may not be the true causative loci but rather be in linkage disequilibrium with the true ones.


Selection of initial and maintenance dosages for lacidipine, a new once-daily calcium antagonist for the treatment of hypertension.
Selection of the appropriate dose of a new drug for initiation of treatment and then for maintenance is a complicated task. It requires the careful assessment and weighing of benefit vs. risk. A series of studies was carried out with lacidipine to determine the optimal initial dose in a general hypertensive population as well as in special populations in whom the pharmacokinetics may be different. The conclusions of these studies are that (a) in a general adult population, the initial dose should be 4 mg once daily; (b) in the elderly and in those with impaired liver function, the starting dose should be 2 mg once daily; and (c) renal dysfunction does not alter the usual starting dose of 4 mg once daily.


Primary malignant lymphoma of the uterine cervix. A clinicopathological evaluation of 3 cases.
Three cases of primary malignant lymphoma of the uterine cervix are presented; 1 in pre- and 2 in postmenopausal women. Two presented clinically with bleeding, one with pelvic discomfort. Histologically all were B cell lymphomas, two high, one low malignancy. Radiotherapy to the whole pelvis followed hysterectomy in 2 patients and in one wasthe primory modality. One of the patients was also treated with chemotherapy for dissemination within the abdomen and CNS. Two patients died, one is well at 38 months.


Primary cutaneous B-cell lymphoma arising from an inguinal hernioplasty scar.
The primary cutaneous B-cell lymphoma (PCBCL) is a rare neoplasm. It is believed that antigenic stimulation and chronic inflammation can be the basis of pathogenesis. Here, we report a case that to our knowledge is the first patient with a presentation of a PCBCL arising from a surgical scar, in particular, an inguinal hernioplasty. The case reminds us of the importance of raising clinical suspicion for malignant neoplasms in surgical scars, in particular, after mesh placement. MeSH terms: 'lymphoma, large b-cell, diffuse', 'skin' and 'cicatrix'.


Chronic renal failure, dialysis, and renal transplantation in Anderson-Fabry disease.
Anderson-Fabry disease (AFd) is a rare, inherited, x-linked disease characterized by the deficiency of the lysosomal enzymatic alpha-galactosidase A activity (alpha-Gal-A). The enzyme defect leads to progressive accumulation of glycosphingolipids (GL) in all kinds of cells, tissues, organs, and body fluids. The clinical manifestations are very protean, the residual activity of alpha-Gal-A and/or different gene mutations might explain different phenotypes, but as yet these concepts have not been proven. Usually, patients with AFd show 3 clinical phases, more evident in men than in heterozygous women. The first phase (childhood and adolescence) is characterized by myalgia, arthralgia, acroparesthesia, fever, cutaneous angiokeratomas, and corneal opacities. The second phase is characterized mainly by renal involvement. In the third phase, severe renal impairment and involvement of cerebrovascular and cardiovascular systems are present. The progression to end-stage renal disease (ESRD) is common in hemizygous males (3rd-5th decade of life); usually, death occurs because of cerebral and/or cardiovascular complications in patients undergoing chronic dialysis therapies. The survival of patients with AFd in dialysis is better than in diabetic patients, but it clearly is decreased compared with uremic patients with other nephropathies, despite a lower mean age of uremia (50 versus 60 y). The outcome of kidney transplantation is similar to that found in other patients with ESRD, despite controversial issues published in the past. The use of a kidney donor with normal alpha-Gal-A activity in the control of the metabolic systemic disease is unproven. The recurrence of GL deposits in the kidney graft has been documented rarely. The definitive treatment for AFd is enzyme replacement therapy with purified alpha-Gal-A produced by a genetically engineered human cell line or Chinese hamster oocytes: relatively short-term studies have shown a significant treatment effect on clinical outcome measures.


Polymer-assisted solution-phase chemical library synthesis.
Polymer-assisted solution-phase (PASP) synthesis has become a prevalent method for the parallel synthesis of chemical libraries. PASP methodology enables the chemist to prepare libraries of compounds more quickly and efficiently than previously. PASP technology encompasses a number of purification techniques for intermediate and final product purification. This methodology continues to progress, providing the practitioner with a broad range of ingenious purification methods, enabling multi-step syntheses of complex compounds. This review covers significant new advances in the use of tagged-reagents/substrates, resin capture-release techniques and PASP multi-step synthesis, some of which incorporate microwave heating and automation.


Hepatocarcinogenicity in the male B6C3F1 mouse following a lifetime exposure to dichloroacetic acid in the drinking water: dose-response determination and modes of action.
Male B6C3F, mice were exposed to dichloroacetic acid (DCA) in the drinking water in order to establish a dose response for the induction of hepatocellular cancer and to examine several modes of action for the carcinogenic process. Groups of animals were exposed to control, 0.05, 0.5, 1, 2, or 3.5 g/L DCA in the drinking water for 90-100 wk. Mean daily doses (MDD) of 8, 84, 168, 315, and 429 mg/kg/d of DCA were calculated. The prevalence (percent of animals) with hepatocellular carcinoma (HC) was significantly increased in the 1-g/L (71%), 2-g/L (95%), and 3.5-g/L (100%) treatment groups when compared to the control (26%). HC multiplicity (tumors/animal) was significantly increased by all DCA treatments-0.05 g/L (0.58), 0.5 g/L (0.68), 1 g/L (1.29), 2 g/L (2.47), and 3.5 g/L (2.90)-compared to the control group (0.28). Based upon HC multiplicity, a no-observed-effect level (NOEL) for hepatocarcinogenicity could not be determined. Hepatic peroxisome proliferation was significantly increased only for 3.5 g/L DCA treatment at 26 wk. and did not correlate with the liver tumor response. The severity of hepatotoxicity increased with DCA concentration. Below 1 g/L, hepatotoxicity was mild and transient as demonstrated by the severity indices and serum lactate dehydrogenase activity. An analysis of generalized hepatocyte proliferation reflected the mild hepatotoxicity and demonstrated no significant treatment effects on the labeling index of hepatocytes outside proliferative lesions. Consequently, the induction of liver cancer by DCA does not appear to be conditional upon peroxisome induction or chemically sustained cell proliferation. Hepatotoxicity, especially at the higher doses, may exert an important influence on the carcinogenic process.


Transmyocardial laser revascularization.
In transmyocardial laser revascularization a series of channels are created between the left ventricular cavity and the myocardium. The operation is usually performed in isolation via a left thoracotomy without cardiopulmonary bypass, but has been done in combination with coronary artery bypass grafting. Angina pectoris with coronary artery anatomy unsuitable for either angioplasty or bypass grafting is currently the most common indication for this procedure.


[Prevalence and Control of Parasitic Zoonoses].
At present, parasitic zoonoses in China are characterized by the reappearance of traditional parasitic zoonoses and constant emergence of new ones, which makes the prevention and control more difficult. In this review, we introduce the classification, epidemiological features, the endemic factors of the infection, as well as the principles and strategies for control, in the aim to provide hints on the control of such diseases in the future.


A Comparison of Face to Face and Video-Based Self Care Education on Quality of Life of Hemodialysis Patients.
End stage renal disease negatively affects the patients' quality of life. There are different educational methods to help these patients. This study was performed to compare the effectiveness of self-care education in two methods, face to face and video educational, on the quality of life in patients under treatment by hemodialysis in education-medical centers in Urmia. In this quasi-experimental study, 120 hemodialysis patients were selected randomly; they were then randomly allocated to three groups: the control, face to face education and video education. For face to face group, education was given individually in two sessions of 35 to 45 minutes. For video educational group, CD was shown. Kidney Disease Quality Of Life- Short Form (KDQOL-SF) questionnaire was filled out before and two months after the intervention. Data analysis was performed in SPSS software by using one-way ANOVA. ANOVA test showed a statistically significant difference in the quality of life scores among the three groups after the intervention (P=0.024). After the intervention, Tukey's post-hoc test showed a statistically significant difference between the two groups of video and face to face education regarding the quality of life (P>0.05). Implementation of the face to face and video education methods improves the quality of life in hemodialysis patients. So, it is suggested that video educational should be used along with face to face education.


Evidence of a conformational change in the human cytomegalovirus protease upon binding of peptidyl-activated carbonyl inhibitors.
A series of N-tert-butylacetyl-l-tert-butylglycyl-l-Ngamma, Ngamma-dimethylasparagyl-l-alanyl-derived inhibitors (trifluoromethyl ketone 1, pentafluoroethyl ketone, 2, methyl ketone 3, and alpha-ketoamide 4, with respective KI values of 1.1, 0.1, 2100, and 0.2 microM) of the human cytomegalovirus protease were used to study the effect of binding of peptidyl inhibitors on the intrinsic fluorescence and CD properties of the enzyme. In the presence of saturating concentrations of compounds 1, 2, and 4, an identical blue shift in the fluorescence maximum of the enzyme upon specific tryptophan excitation was observed relative to that of the free protease. In the case of the methyl ketone 3, whose inhibition of the enzyme does not involve formation of a covalent adduct as evidenced by 13C NMR studies of carbonyl-labeled inhibitors, the blue shift in the emission was also observed. For both compounds 1 and 2 which exhibit slow-binding kinetics, the observed rate constants for the slow onset of inhibition of substrate hydrolysis correlate well with the kobs values of the time-dependent change in the emission spectra. Studies employing a double mutant of HCMV protease Ala143Gln/Trp42Phe identified Trp-42 as the principal fluorescence reporter. Taken together with information provided by our recent elucidation of the crystallographic structure of the enzyme [Tong, L., Qian, C., Massariol, M.-J., Bonneau, P. R., Cordingley, M. G., & Lagacé, L. (1996) Nature 383, 272], these observations are consistent with the inhibition of HCMV protease by peptidyl ketones involving a conformational change of the protease. A mechanism involving a kon limited by dehydration of the hydrated species, followed by rapid ligand binding and a conformational change prior to covalent adduct formation, is proposed for activated inhibitors such as 1 and 2.


Investigation of blood transfusion recipients with West Nile virus infections.
An investigation conducted by CDC, the Food and Drug Administration (FDA), the American Red Cross, and state health departments in Georgia and Florida has confirmed transmission of West Nile virus (WNV) from a single organ donor to four organ recipients. During treatment for injuries that eventually proved fatal, the organ donor received numerous transfusions of blood products. However, the source of the organ donor's infection remains unknown.


Autofluorescence Imaging of 3D Tumor-Macrophage Microscale Cultures Resolves Spatial and Temporal Dynamics of Macrophage Metabolism.
Macrophages within the tumor microenvironment (TME) exhibit a spectrum of protumor and antitumor functions, yet it is unclear how the TME regulates this macrophage heterogeneity. Standard methods to measure macrophage heterogeneity require destructive processing, limiting spatiotemporal studies of function within the live, intact 3D TME. Here, we demonstrate two-photon autofluorescence imaging of NAD(P)H and FAD to nondestructively resolve spatiotemporal metabolic heterogeneity of individual macrophages within 3D microscale TME models. Fluorescence lifetimes and intensities of NAD(P)H and FAD were acquired at 24, 48, and 72 hours poststimulation for mouse macrophages (RAW264.7) stimulated with IFNγ or IL4 plus IL13 in 2D culture, confirming that autofluorescence measurements capture known metabolic phenotypes. To quantify metabolic dynamics of macrophages within the TME, mouse macrophages or human monocytes (RAW264.7 or THP-1) were cultured alone or with breast cancer cells (mouse polyoma-middle T virus or primary human IDC) in 3D microfluidic platforms. Human monocytes and mouse macrophages in tumor cocultures exhibited significantly different FAD mean lifetimes and greater migration than monocultures at 24, 48, and 72 hours postseeding. In cocultures with primary human cancer cells, actively migrating monocyte-derived macrophages had greater redox ratios [NAD(P)H/FAD intensity] compared with passively migrating monocytes at 24 and 48 hours postseeding, reflecting metabolic heterogeneity in this subpopulation of monocytes. Genetic analyses further confirmed this metabolic heterogeneity. These results establish label-free autofluorescence imaging to quantify dynamic metabolism, polarization, and migration of macrophages at single-cell resolution within 3D microscale models. This combined culture and imaging system provides unique insights into spatiotemporal tumor-immune cross-talk within the 3D TME. SIGNIFICANCE: Label-free metabolic imaging and microscale culture technologies enable monitoring of single-cell macrophage metabolism, migration, and function in the 3D tumor microenvironment.


Lymphocyte propionyl-CoA carboxylase and its activation by biotin are sensitive indicators of marginal biotin deficiency in humans.
Marginal biotin deficiency may be a human teratogen. A biotin status indicator that is not dependent on renal function may be useful in studies of biotin status during pregnancy. A previous study of experimental biotin deficiency suggested that propionyl-coenzyme A carboxylase (PCC) activity in peripheral blood lymphocytes (PBLs) is a sensitive indicator of biotin status. We examined the utility of measuring PCC activity and the activation of PCC by biotin in detecting marginal biotin deficiency. Marginal biotin deficiency was induced in 7 adults (3 women) by egg-white feeding for 28 d. Blood and urine were obtained on days 0, 14, and 28 (depletion phase) and 44 and 65 (repletion phase). PBLs were incubated with (activated) or without (control) biotin before PCC assay. The activation coefficient of PCC is the ratio of PCC activity in activated PBLs to that in control PBLs. The significance of differences for all measurements was tested by repeated-measures analysis of variance with Fisher's post hoc test and Bonferroni correction. Changes in the urinary excretion of biotin and of 3-hydroxyisovaleric acid confirmed that marginal biotin deficiency was successfully induced. By day 14, PCC activity had decreased (P < 0.0001) to below the lower limit of normal in all subjects. By day 28, the activation coefficient of PCC had increased significantly (P = 0.003) and was above the upper limit of normal in 6 of 7 subjects. PCC activity is the most sensitive indicator of biotin status tested to date. In future pregnancy studies, the use of lymphocyte PCC activity data should prove valuable in the assessment of biotin status.


Y2K compliance readiness and contingency planning.
As the millennium approaches, discussion of "Y2K compliance" will shift to discussion of "Y2K readiness." While "compliance" focuses on the technological functioning of one's own computers, "readiness" focuses on the operational planning required in a world of interdependence, in which the functionality of one's own computers is only part of the story. "Readiness" includes the ability to cope with potential Y2K failures of vendors, suppliers, staff, banks, utility companies, and others. Administrators must apply their traditional skills of analysis, inquiry and diligence to the manifold imaginable challenges which Y2K will thrust upon their facilities. The SPICE template can be used as a systematic tool to guide planning for this historic event.


[Relationship between dynamic contrast-enhanced and perfusion magnetic resonance imaging and T-staging of nasopharyngeal carcinoma].
To perform the dynamic contrast-enhanced and perfusion magnetic resonance imaging (MRI) of nasopharyngeal carcinoma (NPC) and analyze the correlation with T-staging. A total of 46 naïve NPC patients underwent MRI. The parameters of dynamic contrast-enhanced and perfusion MRI included time to peak (TTP), Slopemax and area under the curve (AUC). The increasing period of signal intensity-time curve of all cases was steep. And the perfusion image of AUC could reflect the blood perfusion of tumor tissue. Parameters (TTP/Slopemax/AUC) in different T-staging were T1-staging (60.45/10.59/20 619.56), T2-staging (58.12/12.47/23 037.23), T3-staging (70.61/15.06/26 507.23) and T4-staging (41.72/19.87/30 092.27). Their statistical results were r = -0.247, P > 0.05 and r = 0.859, P < 0.050 and r = 0.963, P < 0.05 respectively. And statistical significance existed in Slopemax, AUC with T-staging. Dynamic contrast-enhanced and perfusion MRI can reflect angiogenesis of NPC. And there is a positive correlation between the parameters of dynamic contrast-enhanced and perfusion MRI (Slopemax, AUC) and T-staging.


Wound infection after ileostomy closure: a prospective randomized study comparing primary vs. delayed primary closure techniques.
Closure of ileostomy is considered a contaminated operation. The infection rate of the stoma wound is > or = 30%. Several ileostomy-closure techniques intended to reduce the high rate of infection have been described in the literature. Among them, delayed primary closure of the stoma wound is a commonly used method that was reported to reduce the infection rate according to several retrospective studies. We therefore conducted the first prospective randomized trial comparing primary with delayed primary closure of a stoma wound. During 2003, 40 patients were admitted to our ward for closure of ileostomy. The ileostomies were taken down by the same team using the same surgical technique except for the technique of wound closure. We randomly divided the patients into two groups. In Group 1 (n = 20), the wound was left open for delayed primary closure and not closed until postoperative day 4. In Group 2, the wound was primarily closed at the end of the procedure. The total wound infection rate was relatively low (15%). Infection occurred more frequently (4 cases, 20%) in Group 1 than in Group 2 (2 cases, 10%). The length of hospital stay was similar for both groups. In this first prospective comparison of two techniques during ileostomy take down, primary closure unexpectedly produced less wound infection than delayed primary closure.


Functional dissection of COP-I subunits in the biogenesis of multivesicular endosomes.
In the present paper, we show that transport from early to late endosomes is inhibited at the restrictive temperature in a mutant CHO cell line (ldlF) with a ts-defect in epsilon coatomer protein (epsilonCOP), although internalization and recycling continue. Early endosomes then appear like clusters of thin tubules devoid of the typical multivesicular regions, which are normally destined to become vesicular intermediates during transport to late endosomes. We also find that the in vitro formation of these vesicles from BHK donor endosomes is inhibited in cytosol prepared from ldlF cells incubated at the restrictive temperature. Although epsilonCOP is rapidly degraded in ldlF cells at the restrictive temperature, cellular amounts of the other COP-I subunits are not affected. Despite the absence of epsilonCOP, we find that a subcomplex of beta, beta', and zetaCOP is still recruited onto BHK endosomes in vitro, and this binding exhibits the characteristic properties of endosomal COPs with respect to stimulation by GTPgammaS and sensitivity to the endosomal pH. Previous studies showed that gamma and deltaCOP are not found on endosomes. However, alphaCOP, which is normally present on endosomes, is no longer recruited when epsilonCOP is missing. In contrast, all COP subunits, except obviously epsilonCOP itself, still bind BHK biosynthetic membranes in a pH-independent manner in vitro. Our observations thus indicate that the biogenesis of multivesicular endosomes is coupled to early endosome organization and depends on COP-I proteins. Our data also show that membrane association and function of endosomal COPs can be dissected: whereas beta, beta', and zetaCOP retain the capacity to bind endosomal membranes, COP function in transport appears to depend on the presence of alpha and/or epsilonCOP.


The Role of Endothelial Progenitor Cells in Atherosclerosis and Impact of Anti-Lipemic Treatments on Endothelial Repair.
Cardiovascular complications are associated with advanced atherosclerosis. Although atherosclerosis is still regarded as an incurable disease, at least in its more advanced stages, the discovery of endothelial progenitor cells (EPCs), with their ability to replace old and injured cells and differentiate into healthy and functional mature endothelial cells, has shifted our view of atherosclerosis as an incurable disease, and merged traditional theories of atherosclerosis pathogenesis with evolving concepts of vascular biology. EPC alterations are involved in the pathogenesis of vascular abnormalities in atherosclerosis, but many questions remain unanswered. Many currently available drugs that impact cardiovascular morbidity and mortality have shown a positive effect on EPC biology. This review examines the role of endothelial progenitor cells in atherosclerosis development, and the impact standard antilipemic drugs, including statins, fibrates, and ezetimibe, as well as more novel treatments such as proprotein convertase subtilisin/kexin type 9 (PCSK9) modulating agents and angiopoietin-like proteins (Angtpl3) inhibitors have on EPC biology.


Alpha 2-adrenoceptor mediated inhibition of forskolin-stimulated cyclic AMP accumulation in isolated porcine palmar lateral veins.
The aim of this study was to use a 3H-adenine pre-labelling technique to characterise the effect of alpha 2-adrenoceptor activation on forskolin-stimulated cyclic AMP accumulation in the isolated porcine palmar lateral vein. Forskolin (10(-7)-10(-4) M) stimulated 3H-cyclic AMP accumulation in the isolated porcine palmar lateral vein in a biphasic and concentration-dependent manner. In the absence of the cyclic AMP-selective phosphodiesterase inhibitor rolipram, forskolin stimulated 3H-cyclic AMP accumulation approximately 7-8 fold. The response reached a peak after 5 min. In the presence of rolipram (10(-5) M), basal 3H-cyclic AMP levels were approximately 70% higher than in its absence (basal: 1823 +/- 57 dpm; rolipram: 3088 +/- 229, n = 3) and forskolin (3 x 10(-5) M) stimulated 3H-cyclic AMP accumulation approximately 8 fold. The latter response reached a plateau 10 min after the addition of forskolin. In all subsequent studies, the tissues were incubated with forskolin (3 x 10(-5) M) for 5 min in the absence of rolipram. Noradrenaline (NA; 10(-9)-10(-4) M) and UK14304 (10(-9)-10(-4) M) inhibited forskolin-stimulated 3H-cyclic AMP accumulation in a concentration-dependent manner with mean pIC50 values of 7.61 +/- 0.37 (n = 4) and 7.76 +/- 0.23 (n = 5), respectively. With either NA or UK14304, the maximal inhibition of the forskolin response obtained was approximately 75%. Neither NA (10(-4) M) nor UK14304 (10(-4) M) altered basal 3H-cyclic AMP levels.(ABSTRACT TRUNCATED AT 250 WORDS)


Cyanidin-3-O-Glucoside Supplement Improves Sperm Quality and Spermatogenesis in a Mice Model of Ulcerative Colitis.
Impaired fertility and low sperm quality are the global health problem with high attention. It has been noted that inflammation may impact fertility by affecting testicular spermatogenesis. Cyanidin-3-O-glucoside is a natural functional pigment with various health benefits. Nevertheless, studies on the mechanism by which C3G protects male reproduction in mice with ulcerative colitis remain scarce. The purpose of this study is to illustrate the potential mechanism of C3G for improving impaired fertility caused by colitis. A DSS-induced colitis model was applied to assess the effects of sperm quality with colitis and the health benefit role of C3G. Results indicated that C3G-treated mice exhibited higher body weight, longer colon length, less crypt damage and focal inflammation infiltration. Being consistent with that, low sperm count, low testis weight, high inflammation levels and abnormal thickness of seminiferous epithelium also observed in the DSS group were significantly recovered upon C3G treatment. These findings suggested that colitis has a close link to impaired fertility. Further analysis found that C3G could significantly suppress the inflammatory mediators in serum. Results conjointly indicated that C3G might improve the impaired fertility of mice with colitis by inhibiting inflammatory cytokines through the blood-testis barrier. C3G could be a promising daily supplement for ameliorating impaired fertility caused by colitis.


Prenatal maternal dried blood screening with alpha-fetoprotein and free beta-human chorionic gonadotropin for open neural tube defect and Down syndrome.
Our purpose was to evaluate second-trimester prenatal screening for open neural tube defects and Down syndrome by use of dried blood specimen collection and transport. A prospective study of 7497 dried blood specimens from patients <35 years old was performed. Specimens were assayed for maternal blood alpha-fetoprotein and free beta-human chorionic gonadotropin. Patient-specific risks for both disorders were calculated and used to determine whether further evaluation was indicated. The study included an evaluation of the median and SD of analyte multiple of the median levels. The initial positive rate for open neural tube defect was 4.4% adjusted to 2.7% after ultrasonographic revision and collection of a second sample. The initial positive rate for Down syndrome was 3.6% adjusted to 2.8% after ultrasonographic revision. All seven cases of open neural tube defect were detected within the increased risk group. Six of 8 (75%) cases of Down syndrome were detected. The median alpha-fetoprotein multiple of the median was 3.5 in open neural tube defect cases and 0.6 in Down syndrome cases. The median free beta-human chorionic gonadotropin multiple of the median was 2.4 in Down syndrome cases. The SD (log e) of alpha- fetoprotein and free beta-human chorionic gonadotropin in 5868 unaffected white patients was 0.4022 and 0.5635, respectively. Second-trimester dried blood screening for open neural tube defects and Down syndrome can achieve screening efficiency comparable to serum-based protocols with distinct advantages over the conventional method of blood collection.


Microbiological indication of municipal solid waste landfill non-stabilization.
Accidental collapse resulted from unstable factors is an important technological problem to be solved in sanitary landfill. Microbiological degradation of organic matters in landfilled solid waste are an important unstable factor. A landfill reactor was thus manufactured and installed to examine quantitative and population dynamics of microorganisms during degradation of landfilled solid waste. It was showed that unstable landfill can be reflected and indicated by microbiological features such as rapidly decreased growth amount of microorganisms, no detection of fungi and actinomyces, and changing the dominant population into methanogenic bacteria and Acinotobacter.


Two genetic determinants acquired late in Mus evolution regulate the inclusion of exon 5, which alters mouse APOBEC3 translation efficiency.
Mouse apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like editing complex 3 (mA3), an intracellular antiviral factor, has 2 allelic variations that are linked with different susceptibilities to beta- and gammaretrovirus infections among various mouse strains. In virus-resistant C57BL/6 (B6) mice, mA3 transcripts are more abundant than those in susceptible BALB/c mice both in the spleen and bone marrow. These strains of mice also express mA3 transcripts with different splicing patterns: B6 mice preferentially express exon 5-deficient (Δ5) mA3 mRNA, while BALB/c mice produce exon 5-containing full-length mA3 mRNA as the major transcript. Although the protein product of the Δ5 mRNA exerts stronger antiretroviral activities than the full-length protein, how exon 5 affects mA3 antiviral activity, as well as the genetic mechanisms regulating exon 5 inclusion into the mA3 transcripts, remains largely uncharacterized. Here we show that mA3 exon 5 is indeed a functional element that influences protein synthesis at a post-transcriptional level. We further employed in vitro splicing assays using genomic DNA clones to identify two critical polymorphisms affecting the inclusion of exon 5 into mA3 transcripts: the number of TCCT repeats upstream of exon 5 and the single nucleotide polymorphism within exon 5 located 12 bases upstream of the exon 5/intron 5 boundary. Distribution of the above polymorphisms among different Mus species indicates that the inclusion of exon 5 into mA3 mRNA is a relatively recent event in the evolution of mice. The widespread geographic distribution of this exon 5-including genetic variant suggests that in some Mus populations the cost of maintaining an effective but mutagenic enzyme may outweigh its antiviral function.


Determination of ellagic acid by capillary electrophoresis in Argentinian wines.
Rising interest in ellagic acid (EA) present in functional foods is supported by its antimutagenic, anticarcinogenic, antiviral, antibacterial and antioxidative effects. The present approach presents for the first time the determination of ellagic acid and other phenolics in wines by miniaturized solid phase extraction prior to capillary zone electrophoresis (CZE) with UV. The extraction was performed using a home-made miniaturized pipette tip column. The procedure allowed a significant reduction in conditioning/sample/washing/elution volumes. The effects of important factors affecting the extraction efficiency as well as electrophoretic performance were investigated to acquire optimum conditions. The analytes were separated within 10 min with a BGE containing 30 mmol/L sodium tetraborate 10% v/v MeOH pH 9.10. The optimized method was applied to the determination of ellagic acid in commercial and pilot-scale wines. Indeed, the content of EA was correlated with viticultural parameters such as grape varietal, production area, and aging conditions (oak wood guard and glass bottle ward). In order to validate the results, a comparison between the CZE and HPLC data was made.


Population pharmacokinetics of enrofloxacin in purple sea stars (Pisaster ochraceus) following an intracoelomic injection or extended immersion.
OBJECTIVE To determine population pharmacokinetics of enrofloxacin in purple sea stars (Pisaster ochraceus) administered an intracoelomic injection of enrofloxacin (5 mg/kg) or immersed in an enrofloxacin solution (5 mg/L) for 6 hours. ANIMALS 28 sea stars of undetermined age and sex. PROCEDURES The study had 2 phases. Twelve sea stars received an intracoelomic injection of enrofloxacin (5 mg/kg) or were immersed in an enrofloxacin solution (5 mg/L) for 6 hours during the injection and immersion phases, respectively. Two untreated sea stars were housed with the treated animals following enrofloxacin administration during both phases. Water vascular system fluid samples were collected from 4 sea stars and all controls at predetermined times during and after enrofloxacin administration. The enrofloxacin concentration in those samples was determined by high-performance liquid chromatography. For each phase, noncompartmental analysis of naïve averaged pooled samples was used to obtain initial parameter estimates; then, population pharmacokinetic analysis was performed that accounted for the sparse sampling technique used. RESULTS Injection phase data were best fit with a 2-compartment model; elimination half-life, peak concentration, area under the curve, and volume of distribution were 42.8 hours, 18.9 μg/mL, 353.8 μg•h/mL, and 0.25 L/kg, respectively. Immersion phase data were best fit with a 1-compartment model; elimination half-life, peak concentration, and area under the curve were 56 hours, 36.3 μg•h/mL, and 0.39 μg/mL, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that the described enrofloxacin administration resulted in water vascular system fluid drug concentrations expected to exceed the minimum inhibitory concentration for many bacterial pathogens.


Construction of redox-active multilayer film for electrochemically controlled release.
An electrochemically controlled drug release from a redox-active multilayer film is reported. The multilayer film is fabricated by alternate assembly of the electrochemical redox-active micelles and DNA. The buildup of multilayer films is monitored by spectroscopic ellipsometry, UV-vis spectroscopy, and fluorescence spectroscopy. A ferrocene-modified poly (ethyleneimine) (PEI-Fc) is used to form a hydrophobic ferrocene core and hydrophilic PEI shell micelle, showing the electrochemical redox-active properties. Hydrophobic pyrene (Py) molecules are then incorporated into the micelles. The PEI-Fc@Py micelles are assembled into the (PEI-Fc@Py/DNA) multilayer film by layer-by-layer assembly. Thanks to ferrocene groups with the properties of the hydrophilic-to-hydrophobic switch based on the electrical potential trigger, pyrene molecules can be control released from the multilayer film. The electrochemically controlled release of pyrene is investigated and confirmed by electrochemical quartz crystal microbalance and electrochemistry workstation. The (PEI-Fc@drug/DNA) multilayer film may have potential applications in the field of biomedical and nanoscale devices.


Bacterial Load in Daily Urine Samples of Patients Infected with Mycoplasma genitalium, Mutation Analysis, and Response to Treatment.
Objective. Increasing macrolide resistant strains of Mycoplasma genitalium is a challenge, and to differentiate between treatment failure and reinfection a timely test of cure (TOC) is warranted. The aim of this study was to evaluate the best time for TOC after five days' treatment of Mycoplasma genitalium infection with azithromycin. Methods. Nineteen patients with positive PCR for Mycoplasma genitalium in urine provided urine samples daily for 2 weeks and on days 21, 28, and 35. Samples were tested by a commercial qPCR and by sequencing of the 23S rRNA gene. Results. Eight patients with a wild type of Mycoplasma genitalium responded successfully within four days after treatment initiation. Eleven patients had a mutation in the 23S rRNA gene. These samples exhibited high variations in bacterial load, and some patients tested negative at several time points during the observation period. Conclusions. Day-to-day fluctuations in the mutation samples allow for false negative TOC during the first 5 weeks after start of treatment. Due to increasing macrolide resistance of Mycoplasma genitalium, pretreatment mutation analysis is recommended. When a wild type is verified, TOC performed one week after initiation of treatment is suggested.


Basic fibroblast growth factor gene transfection in repair of internal carotid artery aneurysm wall.
Surgery or interventional therapy has some risks in the treatment of cerebral aneurysm. We established an internal carotid artery aneurysm model by dripping elastase in the crotch of the right internal and external carotid arteries of New Zealand rabbits. Following model induction, lentivirus carrying basic fibroblast growth factor was injected through the ear vein. We found that the longer the action time of the lentivirus, the smaller the aneurysm volume. Moreover, platelet-derived growth factor expression in the aneurysm increased, but smooth muscle 22 alpha and hypertension-related gene 1 mRNA expression decreased. At 1, 2, 3, and 4 weeks following model establishment, following 1 week of injection of lentivirus carrying basic fibroblast growth factor, the later the intervention time, the more severe the blood vessel damage, and the bigger the aneurysm volume, the lower the smooth muscle 22 alpha and hypertension-related gene 1 mRNA expression. Simultaneously, platelet-derived growth factor expression decreased. These data suggest that recombinant lentivirus carrying basic fibroblast growth factor can repair damaged cells in the aneurysmal wall and inhibit aneurysm dynamic growth, and that the effect is dependent on therapeutic duration.


Hydrophobic attachment of Trypanosoma cruzi to the rectal cuticle of Triatoma infestans and its influence on metacyclogenesis - a review.
Trypanosoma cruzi colonizes mainly the rectum of the vector, especially the rectal glands. We investigated the basic architecture of the rectal cuticle of Triatoma infestans and the mode of attachment of T. cruzi in the small intestine and the rectum. In addition, we determined the capacity of culture-derived epimastigotes to attach to artificial substrates and the influence of attachment on metacyclogenesis. After incubation of the rectum with wheat germ lectin (WGA) coupled to gold particles, the procuticle contained chitin, but the two layers of the epicuticle and the superficial layer bordering the rectal lumen did not. The specific fluorochrom Nile Red stained the entire rectal cuticle green, indicating the waxy composition of the superficial layer. In electron microscopic analysis the parasites were attached to the hydrophobic superficial wax layer but not to the epithelium of the midgut. In vitro culture-derived epimastigotes attached with a high affinity to all hydrophobic substrates tested, whereas hydrophilic substrates did not permit attachment. Emulsified hexadecane localized the attachment molecules to the terminal part of the flagellum. Inhibition of attachment by coating the culture tubes with hydrophilic agarose and constant agitation decreased the rate of epimastigote to trypomastigote transformation, whereas wax coating enhanced metacyclogenesis.


Biosynthesis of the Snowdrop (Galanthus nivalis) Lectin in Ripening Ovaries.
The biosynthesis and processing of the Galanthus nivalis agglutinin were studied in vivo in ripening snowdrop ovaries. Using labeling and pulse chase labeling experiments it could be demonstrated that the snowdrop lectin is synthesized as a precursor of relative molecular weight (M(r)) 15,000 which is posttranslationally converted into the authentic lectin polypeptide of M(r) 13,000 with a half-life of about 6 hours. Gel filtration of an extract of [(3)H]leucine labeled ovaries on Sepharose 4B showed that a significant portion of the newly synthesized lectin is associated with the particulate fraction. When the organellar fraction was fractionated on isopycnic sucrose gradients this lectin banded in the same density region as the endoplasmic reticulum (ER) marker enzyme NADH cytochrome c reductase. Both radioactivity in lectin and in enzyme activity shifted towards a higher density in the presence of 2 millimolar Mg-acetate indicating that the labeled lectin was associated with the rough ER. Labeled lectin could be chased from the ER with a half-life of 4 hours and then accumulated in the soluble fraction. Whereas the ER-associated lectin contains exclusively polypeptides of M(r) 15,000 the soluble fraction contains both precursor molecules and mature lectin polypeptides. The snowdrop lectin in the ER is fully capable of binding immobilized mannose. It is associated into tetramers with an appropriate molecular weight of 60,000. These results indicate that newly synthesized snowdrop lectin is transiently associated with the ER before transport and processing.


The effects of bone cement powder on human adherent monocytes/macrophages in vitro.
This study reports the effects of Simplex bone cement powder (BC) on the proliferation and production of bone resorbing factors in vitro by human adherent monocytes/macrophages. Adherent peripheral blood cells were isolated from seven healthy individuals and exposed to a dispersion of BC powder (1 mg/mL), phytohemagglutinin (PHA, 40 micrograms/mL), or medium alone at different periods of cell incubation (days 0-2, 0-7, 5-7, or 10-12). Cell proliferation was quantified by incorporation of 3H-thymidine uptake. Culture supernatants were evaluated for levels of interleukin 1-like activity (IL-1) by murine thymocyte proliferation assay, prostaglandin E2 (PGE2) by radioimmunoassay, lysosomal enzyme activity (N-acetyl-beta-D-glucosaminidase and beta-glucuronidase using fluorometry, and collagen and casein degrading activity using radioactive substrates. Human adherent peripheral blood cells showed a proliferative response to PHA that coincided with cell maturation; BC did not inhibit PHA-induced cell proliferation of either adherent or nonadherent blood cells, indicating the non-toxic nature of these particles at the concentrations tested. BC stimulated increased release of the lysosomal enzyme N-acetyl-beta-D-glucosaminidase; the levels of PGE2, IL-1, collagenase, and caseinase were unchanged.


Serum macrophage migration inhibitory factor reflects adrenal function in the hypothalamo-pituitary-adrenal axis of septic patients: an observational study.
The hypothalamo-pituitary-adrenal (HPA) axis modulates the inflammatory response during sepsis. Macrophage migration inhibitory factor (MIF), which counteracts the anti-inflammatory activity of glucocorticoid (GC), is one of the mediators of the development of inflammation. An inflammatory imbalance involving GC and MIF might be the cause or result of adrenal insufficiency. Our objective was to clarify the relationship between serum MIF and adrenal function in the HPA axis of sepsis patients using the adrenocorticotropic hormone (ACTH) stimulation test. An observational study was performed in a university intensive care unit over a two-year period. Of 64 consecutive sepsis patients, 41 were enrolled. The enrolled patients underwent an ACTH stimulation test within 24 h of the diagnosis of severe sepsis or septic shock. Clinical and laboratory parameters, including serum MIF and cortisol, were measured. Based on their responses to the ACTH stimulation test, the patients were divided into a normal adrenal response (NAR) group (n = 22) and an adrenal insufficiency (AI) group (n = 19). The AI group had significantly more septic shock patients and higher prothrombin time ratios, serum MIF, and baseline cortisol than did the NAR group (P < 0.05). Serum MIF correlated significantly with the SOFA (Sequential Organ Failure Assessment) score, prothrombin time ratio, and delta max cortisol, which is maximum increment of serum cortisol concentration after ACTH stimulation test (rs = 0.414, 0.355, and -0.49, respectively, P < 0.05). Serum MIF also correlated significantly with the delta max cortisol/albumin ratio (rs = -0.501, P = 0.001). Receiver operating characteristic curve analysis identified the threshold serum MIF concentration (19.5 ng/mL, P = 0.01) that segregated patients into the NAR and AI groups. The inverse correlation between serum MIF and delta max cortisol or the delta max cortisol/albumin ratio suggests that high serum MIF reflects an insufficient adrenal response in the HPA axis. Serum MIF could be a valuable clinical marker of adrenal insufficiency in sepsis patients.


[Prognostic predictors for non-small cell lung cancer patients with brain metastasis after radiotherapy.].
Brain metastasis (BM) is often found in the patients with lung cancer. Radiotherapy is regular and effective means of therapy and it aims at palliating symptoms and prolonging survival time. However, now there are different viewpoints on protocols of radiotherapy and prognostic factors. A retrospective analysis is used to evaluate the results of treatment for 82 cases with brain metastasis from non-small cell lung cancer (NSCLC) and explore the prognostic factors to establish a prognostic index (PI) model. From Feb.1995 to Oct. 2006, 82 patients irradiated for BM from NSCLC, with both complete medical charts and follow-up data available, were eligible for this retrospective analysis. A number of potential factors which might affect prognosis after irradiation were evaluated. The significance of prognostic variables in the survival resulted from both univariate analysis by Kaplan-Meier combining with log-rank test and multivariate Cox regression model. The prognostic index (PI) was established based on Cox regression analysis and subgrouping values. The follow-up time was 1-120 months. For the entire cohort, the median survival from the start of radiation for BM was 10.5 months, and the actuarial overall survival rate was 50.8%, 23.7% and 5.1% at 0.5, 1 and 2 years respectively. Univariate analysis showed KPS, control of primary tumor, interval from the beginning of diagnostic to BM, extracranial systemic metastasis, counts of lymphocyte and solitary BM were predictors of prognosis. However, in the Cox multivariate analysis, only KPS, control of primary tumor, interval from the beginning of diagnostic to BM and solitary BM were significant prognostic factors. The prognostic index was established based on Cox regression analysis and 82 patients were stratified good, intermediate and poor prognostic sub-groups. The difference of survival rate among 3 subgroups is significant (P <0.001). Radiotherapy is proved to be effective for NSCLC patients with BM. KPS, control of primary tumor, interval from the beginning of diagnostic to BM and solitary BM are independent prognostic factors. PI model can well predict the prognostic of patients with BM from NSCLC.


Radiation efficiency of a distribution of baffled pistons with arbitrary phases.
The radiation resistance and efficiency of a collection of circular pistons, randomly placed on a plane and vibrating with arbitrary phases, are expressed as a combination of the self- and mutual-radiation components. We use the first product or bridge theorem to construct the directivity pattern of this type of arrangement and the radiation properties are calculated according to Bouwkamp's impedance theorem. To illustrate the versatility of our approach, we refer to special cases for symmetric arrangements, for example, to compare with the modal radiation efficiency in structures having "regular" modal patterns.


Relationship between the 137Cs whole-body counting results and soil and food contamination in farms near Chernobyl.
We measured the radioactivity in the soil and child food samples from farms near Mogilev (56-270 GBq km(-2) 137Cs), Gomel (36-810 GBq km(-2) 137Cs), and Klincy (59-270 GBq km(-2) 137Cs), who had whole-body 137Cs counting results measured as part of a health examination in the Chernobyl Sasakawa Health and Medical Cooperation Project. Soil contamination on the family farm seems to be the main source of human contamination because most of the people in the area live on small farms and they and their domestic animals eat crops from the farms. A clear correlation was found between the children's whole-body 137Cs counting results and the radioactivity in their food (correlation coefficient: 0.76; confidence level of correlation: 3.2 x 10(-9)). There were also significant correlations between the whole-body 137Cs counting results and both the radioactivity of the soil samples (correlation coefficient: 0.22; confidence level of correlation: 0.0107) and the average contamination level of their current residence (correlation coefficient: 0.20; confidence level of correlation: 0.0174).


The effect of chronic obstructive pulmonary disease on quality of life.
Lazarus and Folkman's (1984) theory of stress, coping, and adaptation served as the framework for a path model of quality of life in chronic obstructive pulmonary disease (COPD). It was hypothesized that psychosocial variables (depression, anxiety, self-esteem, optimism, and social support) would mediate the effects of demographic (age, socioeconomic status) and disease (dyspnea, disease severity, and functional status) variables on life quality in COPD. Interview, pulmonary function, and 6-minute walk test data obtained from 126 subjects with COPD resulted in support for the majority of the hypothesized relationships. Variables having direct effects on life quality were self-esteem, depression, social support, and age. Anxiety and optimism did not have their hypothesized effects on quality of life, suggesting the need to reconsider their importance in influencing life quality in COPD.


Late-stage inhibition of autophagy enhances calreticulin surface exposure.
Calreticulin (CRT) exposure on the cell surface is essential for inducing immunogenic cell death by chemotherapy. Recent studies have shown conflicting effects of chemotherapy-induced autophagy on CRT exposure in cancer cells. Our data revealed that surface-exposed CRT (Ecto-CRT) emission was attenuated by inhibition of autophagy at early stages; however, inhibition of autophagy at late stages resulted in increased Ecto-CRT. Furthermore, neither autophagy activation nor endoplasmic reticulum (ER) stress induction alone was sufficient for CRT surface exposure. Moreover, chemotherapeutic agents that only activated autophagy without inducing ER stress could not increase Ecto-CRT; therefore, combined use of an autophagy activator and ER stress inducer could effectively promote CRT translocation to the plasma membrane. Together, our results highlight the potential of the combined use of ER stress inducers and autophagy late-stage inhibitors to reestablish and strengthen both the CRT exposure and immunogenicity of chemotherapeutic agents induced death cells.