Induction of rainbow trout MH class I and accessory proteins by viral haemorrhagic septicaemia virus

Major histocompatibility (MH) class I receptors are glycoproteins which play a critical role during responses to intracellular pathogens by presenting endogenous peptides to cytotoxic T cell lymphocytes (CD8+). To date, little is known about MH class I regulation at the protein level during viral infections in fish. In this study, we characterised the MH class I pathway response to polyinosinic–polycytidylic acid (poly I:C) and upon infection with viral haemorrhagic septicemia virus (VHSV) genotype IVa using the rainbow trout monocyte/macrophage cell line RTS11. A 14-day challenge with VHSV IVa at 14 °C demonstrated enhanced expression of the class I heavy chain, β2 microglobulin (β2M) and tapasin, while the expression of other accessory molecules ERp57 and calreticulin remained unchanged. However, when infection occurred at 2 °C no change in expression levels of any of these molecules was observed. β2M accumulated in the media of RTS11 over time, however the β2M concentrations were 2 fold higher in cultures infected with VHSV 14 days post infection. Strikingly, when cells were maintained at 2 °C the secretion of β2M was significantly reduced in both infected and non-infected cultures. These results indicate that VHSV infection alters the kinetics of β2M release as well as the expression of MH class I and suggests that cellular immunity against VHSV can be compromised at low temperatures which may increase host susceptibility to this virus during the winter.     

美国教学医院教师专业发展的全国性调查

在当前医学教育持续变革的背景中,医学教师的专业发展成为广泛关注的焦点.为了解目前美国以提高教师的教学技能为目标的教师专业发展(faculty development,FD)活动的参与率、课程设计、教学方法和评估策略等情况,美国约翰·霍普金斯大学预防、流行病学和临床研究中心采取邮件调查的方式,对美国277家教学医院进行了调查.     

Mortality and long-term course in schizophrenia with a poor 2-year course: a study in a developing country

BACKGROUND: The short-term course of schizophrenia is reported to be better in some developing country settings. The long-term course in such settings, however, has rarely been studied. AIMS: To examine the long-term course and mortality of schizophrenia in patients with a poor 2-year course. METHOD: The report is based on two incidence cohorts of first-contact patients in urban and rural Chandigarh, India, originally recruited for the World Health Organization Determinants of Outcome of Severe Mental Disorders study. Patients were assessed using standardised instruments at 2- and 15-year follow-ups. RESULTS: Ninety-two per cent of the patients with a poor 2-year course had a poor long-term course and 47% died - a nine times higher mortality rate than among patients with other 2-year course types. CONCLUSIONS: In this developing country setting, a poor 2-year course was strongly predictive of poor prognosis and high mortality, raising questions about the adequacy of care for such patients.     

Cytogenetic and molecular genetic analysis of tumorigenic human bronchial epithelial cells induced by radon alpha particles

To establish a cell culture model for lung carcinogenesis, independent populations of the human papillomavirus 18-immortalized human bronchial epithelial cell line BEP2D were treated with high linear energy transfer radon-simulated alpha-particles, expanded and xenotransplanted into Nu/Nu mice. Six independent cell lines were established from tumors that developed from three separate radiation treatments as follows: treatment (Tx) 1 (30 cGy--two doses), H2BT, Tx 2 (30 cGy-- single dose), R30T1L, R30T2 and R30T3L, Tx 3 (30 cGy--single dose), H1ATN and H1ATBA1. Cytogenetic analysis revealed common changes in all tumor lines: loss of the Y chromosome (ch), one of three copies of ch8, one of three copies of ch14, and one of two copies of ch4p16-pter and ch11p15-pter. Analysis of polymerase chain reaction-amplified short tandem repeats of informative loci confirmed the loss of chY in all lines and loss of heterozygosity (LOH) at eight loci spanning the length of ch8 in all lines from Tx's 1 and 2. Our data support previous studies indicating the presence of tumor suppressor genes on ch8. LOH also was confirmed on ch14 at locus D14S306 in all cell lines from Tx 2 and in one of two lines from Tx 3. This region, 14q12-q13, may contain changes in one of the five known somatostatin receptor genes (SSTR1). No LOH was detected at any of the informative loci tested for on ch4 or ch11.      

Subtypes of codeine cough syrup abusers

This paper highlights the abuse potential of the codeine containing cough syrups, which may take two forms. One, experimental abuse in school or college students which later persists in a dependent pattern. Two, pre-existing opioid abusers, as a substitute which starts after the school or college years. The short term treatment outcome is better in the former group in that they are able to maintain abstinence for a relatively longer period.     

Nucleotide degrading enzymes in Neurospora crassa

Considerable amounts of GTP, GMP, adenosine, guanine, and adenine accumulated in Neurospora crassa when a culture grown on low phosphate (0.01%) medium was transferred to a high phosphate (1%) medium. The levels of alkaline phosphatase, nucleotidase, and nucleosidase decreased by 2.4, 5.4, and 3 folds, respectively, in cultures grown on high phosphate medium. Substrate kinetics of these enzymes revealed that: (1) alkaline phosphatase isolated from the organism grown on low phosphate medium demonstrates nonlinear reciprocal plots with two distinct apparent Km values for β-glycerophosphate compared to one apparent Km value (associated with 32% decrease in the apparent V_max value) obtained with that grown on high phosphate medium; (2) nucleotidases and nucleosidases isolated from organisms cultivated on low phosphate and high phosphate media showed the same apparent Km values, 0.25 mM for nucleotidase and 0.909 mM for nucleosidase. There was, however, >3 times decrease in the catalytic activity of the latter enzymes isolated from organisms grown on high phosphate medium as compared to those grown on low phosphate. Inclusion of inorganic phosphate in standard assay mixtures of the three enzymes resulted in a considerable inhibition in the catalytic activities of all of them. High levels of phosphate in the medium caused marked repression of three out of six of alkaline phosphatase, two out of three of nucleotidase, and one out of two of nucleosidase isozymic forms detected in the low phosphate grown culture.     

Femoral lengthening over an intramedullary nail using the external fixator: risk of infection and knee problems in 22 patients with a follow-up of 2 years or more

BACKGROUND: The time for femoral lengthening is shortened if external fixation is combined with intramedullary nailing. However, several complications have been reported with this procedure. PATIENTS AND METHODS: We retrospectively reviewed the outcome of femoral lengthening performed over an intramedullary nail using external fixation in 22 patients. These patients were followed for a mean of 3.2 (2-5.2) years. The mean age was 22 (13-35) years at the time of the index procedure. The mean lengthening was 5 (2.7-8.1) cm and the external fixator was removed after median 20 (8-30) weeks. The mean external fixation index was 24 (11-35) days/cm and the mean consolidation index was 43 (26-55) days/cm of lengthening. RESULTS: 3 patients who had a past history of infection or open trauma developed osteomyelitis which required removal of the nail. There were 4 knee joint complications when the lengthening was over 20%, including posterior knee subluxation and patella subluxation. In 1 patient, the lengthened segment collapsed with breakage of locking screws. INTERPRETATION: Although lengthening over a nail can reduce the duration of external fixation, caution is required to prevent major complications.     

Calciphylaxis in pediatric end-stage renal disease

Calciphylaxis is a rare, but life-threatening complication of end-stage renal disease (ESRD) that has been reported mostly in adult patients. The exact etiology is unknown, but the disease is commonly associated with a high calcium-phosphorus product and elevated levels of parathyroid hormone (PTH). We herein review the published reports on calciphylaxis in ESRD patients less than 18 years old and report the case of a patient with severe calciphylaxis who presented with lower extremity pain, muscle tenderness and difficulty in walking. The serum PTH was low, and the calcium-phosphorus product was normal. The diagnosis of calciphylaxis was confirmed by a muscle biopsy. Treatment with low calcium peritoneal dialysate and substitution of calcium-based phosphorus binders with sevelamer (Renagel) was unsuccessful. The patients clinical condition progressed to extensive soft tissue calcification and ulcerating skin lesions. Nine months after the onset of symptoms, the patient died of cardiopulmonary arrest.