Theiler's murine encephalomyelitis virus (TMEV): the role of a small out-of-frame protein in viral persistence and demyelination

Theiler's murine encephalomyelitis virus (TMEV) belongs to the genus Cardiovirus of the family Picornaviridae and is divided into two subgroups on the basis of different biological activities. GDVII subgroup strains produce acute and fatal polioencephalomyelitis in mice with no virus persistence. In contrast, DA or TO subgroup strains cause an early nonfatal polioencephalomyelitis. TMEV is thought to be an excellent animal model for the human demyelinating disease, multiple sclerosis. Data suggest that macrophages are a major reservoir harboring the virus. A small out-of-frame protein designated L* is synthesized in DA subgroup strains from an alternative, out-of-frame, initiation site. Studies of a DA mutant virus, having an ACG rather than an AUG and therefore does not synthesize L* protein, demonstrate that this protein is important for virus growth in particular cell types and is critical for DA-induced demyelinating disease and virus persistence. In addition, TMEV can be used as a vector for delivering foreign sequences into the central nervous system.     

Co-expression of CD4 and CD8 associated with elevated interleukin-4 in a cord T cell line derived by cocultivating normal cord leukocytes and an HTLV-II-producing simian leukocyte cell line (Si-IIA)

A new interleukin-2(IL-2)-dependent T cell line, designated CS-IIA, was established by cocultivating normal human cord leukocytes and a lethally X-irradiated HTLV-II-producing simian leukocyte cell line (Si-IIA). CS-IIA showed CD4 dominance during the early culture. However, after addition of IL-2, CS-IIA predominantly co-expressed CD4 and CD8 (69.5%) and also expressed the surface markers CD1^–, CD3⁺, CD19^–, CD25⁺ and HLA-DR⁺. A significantly elevated level of IL-4 (1697 pg/ml) was observed in the culture supernatant from CS-IIA. In addition, the conversion of phenotype from some CD4⁺CD8⁺ cells to CD4⁺CD8^– was demonstrated by the neutralization assay using anti-IL-4 antibody. CS-IIA had a normal human karyotype and was free from Epstein-Barr virus nuclear antigen and immunoreactive with sera of HTLV-I- or HTLV-II-infected patients and anti-HTLV-1, p19 or p24 mAb. The provirus genome of HTLV-II was detected in this cell line by the polymerase chain reaction combined with a digoxigenin-enzyme-linked immunosorbent assay. However, electron microscopy of CS-IIA cells revealed no C-type virus particles in the extracellular space. These results indicate that HTLV-II can be transmitted from an HTLV-II-infected simian leukocyte cell line to human cord T lymphocytes and suggest that co-expression of CD4 and CD8 on T cells may be induced by the high level of IL-4, which can mediate CD8 induction on CD4⁺ T cell clones.     

Clinical significance of biliary sludge

Although biliary sludge has been considered to be a benign condition associated with factors promoting bile stasis, its clinical significance and whether it contributes to biliary tract symptoms are uncertain. We conducted a retrospective review of patients with ultrasonographic diagnosis of biliary tract sludge during the 6-year period from 1979 to 1985. Of the 87 patients with gallbladder sludge alone, 11 (13%) had definite clinical findings and evolving laboratory abnormalities consistent with acute biliary tract disease. Four of these 11 patients proved to have gallstones at the time of surgery, while three had sludge alone as the apparent cause of their biliary tract symptoms. The clinical illness in four remaining patients resolved with medical therapy. We conclude that gallbladder sludge, as defined by ultrasound, may be associated with acute biliary tract disease.     

Functional differentiation in steroidogenesis of two types of luteal cells isolated from mature human corpora lutea of menstrual cycle

Enriched small and large cell fractions were prepared from mature corpora lutea from 15 women in the midluteal phase by enzymatic dissociation, followed by Percoll gradient centrifugation. The steroidogenic function of each cell type was assessed by measuring the gonadal steroids released into the incubation medium. The large cell fraction was estimated to be 97% pure, with minimal contamination by small cells, whereas the small cell fraction was approximately 68% pure, being contaminated with 10% large cells and 22% nonsteroidogenic cells. In the unstimulated state, large cells were approximately 2-fold more potent in progesterone formation and aromatase activity, but only half as potent in androstenedione and testosterone formation as an equal number of small cells. When stimulated with hCG, the small cells responded with significant increases in progesterone, androstenedione, and testosterone release, but the large cells did not. Both cell types secreted estrone and 17 beta-estradiol in the presence of androgen substrate, but the addition of FSH significantly stimulated aromatization only in large cells. Thus, small and large human luteal cells have steroidogenic properties similar to those exhibited by follicular thecal and granulosa cells, respectively.     

Expression profile of mRNAs from human pancreatic islet tumors

In order to understand the tIssue specificity of the endocrine pancreas, it is important to clarify the expression profile of mRNAs in various states of the tIssue. A total of approximately 9000 non-redundant expressed genes from human pancreatic islets and insulinoma have so far been determined as expressed sequence tags (ESTs) and deposited in public databases. In the present study towards the identification of a complete set of genes expressed in human pancreatic islets, we have determined 3'-ESTs of 21267 clones randomly selected from a cDNA library of human pancreatic islet tumors. Clustering analysis generated 6157 non-redundant sequences comprising 2323 groups and 3834 singletons. Nucleotide and peptide database searches show that 3103 of them represent known human sequences or homologs of genes identified in other species and 58 are new members of structurally related families. The sequences were classified on the basis of the putative protein functions encoded, and were assigned to the respective chromosome by database analysis. The sequences were also compared with the EST databases (dbEST and EPConDB) including ESTs from normal pancreatic islet, insulinoma, and fetal pancreas. Since 3384 genes were newly found to be expressed in human pancreatic islets and 587 of them were unique to the islets, this study has considerably expanded the catalog of genes expressed in the endocrine pancreas. The larger collection of pancreatic islet-related ESTs should provide a better genome source for molecular studies of differentiation, tIssue-specific functions, and tumorigenesis of the endocrine pancreas as well as for genetic studies of diabetes mellitus.     

Management of oral complications of disease-modifying drugs in rheumatoid arthritis

Stomatitis is a troublesome adverse effect of disease-modifying anti- rheumatic drug (DMARD) therapy in rheumatoid arthritis (RA) patients. This review presents data to examine the incidence, clinical features and consequences of DMARD-related stomatitis, and suggests an algorithm for its clinical management. The specific objectives of the two studies presented here were to determine the incidence of DMARD-related stomatitis and its effect on DMARD continuation, and secondly to identify the clinical and laboratory risk factors. We investigated two cohorts of patients: (i) a retrospective survey of data collected from drug monitoring clinics run for patients on DMARDs from 1987 to 1994 involving 1539 patients and 2394 drug exposures; (ii) a prospective study of 25 consecutive RA patients presenting with DMARD-related stomatitis compared to 29 RA controls with no history of DMARD stomatitis. The retrospective survey showed that 2% of DMARD patients stopped therapy because of stomatitis, but 55% of these were able to resume the same therapy. In the case control study. 24% of patients discontinued temporarily and 8% permanently. Cases of DMARD-related stomatitis differed from controls in that they had a higher incidence of previous mouth ulcers (40% vs 14%), they smoked less (8% vs 31%) and Schirmer's test was more often abnormal (44% vs 21%). There were no differences in RA severity, disease activity or oral hygiene. Haematinic deficiencies were equally common in cases and controls: 30% for iron, 8% for vitamin B12 and 24% for folic acid. Herpes simplex virus was involved in a minority (8%) of cases. In conclusion, the occurrence of stomatitis in RA patients on DMARD should not lead to cessation of drug therapy, but to a careful evaluation so that patients may be maintained on effective treatment.      

Salivary epidermal growth factor in patients with peptic ulcer]

Recent animal studies suggest salivary epidermal growth factor (EGF) has a cytoprotective effect in the upper GI tract and is one of the important factors to promote the healing of experimental ulcer. The present study was undertaken to clarify the role of salivary EGF in peptic ulcer patients. Saliva samples were collected from 129 endoscopically normal subjects and 232 peptic ulcer patients. Salivary EGF concentration was measured by RIA. Salivary EGF output in normal subjects was 5.26 +/- 0.26 (ng/5 min) (mean +/- SE). Those in patients with gastric ulcer (GU), duodenal ulcer (DU) and gastroduodenal ulcer (GDU) were 10.74 +/- 0.15, 8.13 +/- 0.83 and 9.79 +/- 0.91. EGF output in GU and GDU patients were higher than that in normal subjects respectively. Tractable GU patients (healed within 3 months with regular regimen) had higher EGF output than intractable GU patients. Among tractable GU patients, those who had healing within 8 weeks had higher output. EGF output in patients with recurrent GU was lower than that in non-recurrent GU patients. In 10 GU patients, EGF output became higher in healing stage than in active stage. Salivary EGF may promote the healing and prevent the recurrence of human gastric ulcer.     

Can pain beliefs change in middle school students? A study of the effectiveness of pain neuroscience education

Pain neuroscience education (PNE) is an educational strategy aimed at teaching people more about pain from a neurobiological and neurophysiological perspective. Current best-evidence provides strong support for PNE to positively influence pain ratings, dysfunctions, fear-avoidance and pain catastrophization, limitations in movement, pain knowledge, and healthcare utilization. To date, all PNE studies have been conducted on adult populations. This study set out to explore if an abbreviated PNE lecture to middle school children would result in a positive shift in pain knowledge as well as healthier beliefs regarding pain. One-hundred-and-thirty-three middle school students spanning 5th to 8th grade attended a 30-minute PNE lecture. The primary outcome measures of pain knowledge (neurophysiology of pain questionnaire [NPQ]) and beliefs regarding pain (numeric rating scale) were measured before and immediately after the PNE lecture. Significant improvement in knowledge was found with mean score on NPQ test scores improving from 3.83 (29.5%) pre-PNE to 7.90 (60.8%) post-PNE (p < 0.001), with a large effect size (r = .711). Significant shifts in beliefs were also found in all but one of the pain beliefs questions, with a medium effect size for “you can control how much pain you feel” (p < 0.001; r = 0.354) and large effect size for “your brain decides if you feel pain, not your tissues” (p < 0.001; r = 0.545). This study shows that a 30-minute PNE lecture to middle school children resulted in a significant increase in their knowledge of pain as well various beliefs regarding pain.