Receptor editing in self-reactive bone marrow B cells

A central paradigm of immunology is clonal selection: lymphocytes displaying clonally distributed antigen receptors are generated and subsequently selected by antigen for growth or elimination. Here we show that in mice transgenic for anti-H-2Kk,b antibody genes, in which a homogeneous clone of developing B cells can be analyzed for the outcome of autoantigen encounter, surface immunoglobulin M+/idiotype+ immature B cells binding to self-antigens in the bone marrow are induced to alter the specificity of their antigen receptors. Transgenic bone marrow B cells encountering membrane-bound Kb or Kk proteins modify their receptors by expressing the V(D)J recombinase activator genes and assembling endogenously encoded immunoglobulin light chain variable genes. This (auto)antigen-directed change in the specificity of newly generated lymphocytes is termed receptor editing.     

Evaluation of the antireflux mechanism following laparoscopic fundoplication

BACKGROUND: Laparoscopic Nissen fundoplication is an effective procedure for the treatment of gastro-oesophageal reflux disease (GORD), but the underlying motility mechanisms that explain the success of this operation remain unclear. METHODS: Twenty patients with a history of GORD underwent stationary oesophageal manometry and prolonged ambulatory pH monitoring, both before and 3 months after fundoplication. RESULTS: Eighteen patients were completely cured of reflux symptoms and stopped all antireflux medication after operation. After fundoplication there was a significant increase (P < 0.01) in median resting lower oesophageal sphincter (LOS) pressure and length. Median residual LOS pressure during swallow-induced LOS relaxation also increased significantly after operation (P < 0.01). The number of reflux episodes decreased from a median of 48 to 3 after fundoplication (P < 0.01). The time at pH less than 4 decreased from 5.7 to 0 per cent in the supine position (P < 0.01), and from 9.8 to 0.2 per cent while upright (P < 0.001). CONCLUSION: Early subjective results at 3 months following laparoscopic antireflux surgery show improved symptoms. One of the mechanisms underlying the antireflux action of fundoplication is an increase in median residual LOS pressure at the gastro-oesophageal junction. This may be a purely mechanical effect of the fundic wrap extrinsic to the LOS.     

Submitochondrial distribution of three key steroidogenic proteins (steroidogenic acute regulatory protein and cytochrome p450scc and 3beta-hydroxysteroid dehydrogenase isomerase enzymes) upon stimulation by intracellular calcium in adrenal glomerulosa cells

In adrenal glomerulosa cells, angiotensin II (Ang II) and potassium stimulate aldosterone synthesis through activation of the calcium messenger system. The rate-limiting step in steroidogenesis is the transfer of cholesterol to the inner mitochondrial membrane. This transfer is believed to depend upon the presence of the steroidogenic acute regulatory (StAR) protein. The aim of this study was 1) to examine the effect of changes in cytosolic free calcium concentration and of Ang II on intramitochondrial cholesterol and 2) to study the distribution of StAR protein in submitochondrial fractions during activation by Ca2+ and Ang II. To this end, freshly prepared bovine zona glomerulosa cells were submitted to a high cytosolic Ca2+ clamp (600 nM) or stimulated with Ang II (10 nM) for 2 h. Mitochondria were isolated and subfractionated into outer membranes, inner membranes (IM), and contact sites (CS). Stimulation of intact cells with Ca2+ or Ang II led to a marked, cycloheximide-sensitive increase in cholesterol in CS (to 143 +/- 3. 2 and 151.1 +/- 18.1% of controls, respectively) and in IM (to 119 +/- 5.1 and 124.5 +/- 6.5% of controls, respectively). Western blot analysis revealed a cycloheximide-sensitive increase in StAR protein in mitochondrial extracts of Ca2+-clamped glomerulosa cells (to 159 +/- 23% of controls). In submitochondrial fractions, there was a selective accumulation of StAR protein in IM following stimulation with Ca2+ (228 +/- 50%). Similarly, Ang II increased StAR protein in IM, and this effect was prevented by cycloheximide. In contrast, neither Ca2+ nor Ang II had any effect on the submitochondrial distribution of cytochrome P450scc and 3beta-hydroxysteroid dehydrogenase isomerase. The intramitochondrial presence of the latter enzyme was further confirmed by immunogold staining in rat adrenal fasciculata cells and by immunoblot analysis in MA-10 mouse testicular Leydig cells. These findings demonstrate that under acute stimulation with Ca2+-mobilizing agents, newly synthesized StAR protein accumulates in IM after transiting through CS. Moreover, our results suggest that the import of StAR protein into IM may be associated with cholesterol transfer, thus promoting precursor supply to the two first enzymes of the steroidogenic cascade within the mitochondria and thereby activating mineralocorticoid synthesis.     

Cervical esophageal web associated with a patch of heterotopic gastric mucosa

Cervical esophageal webs are a relatively common finding on esophograms. We report a web resulting from the squamocolumnar junction produced by heterotopic gastric mucosa. The clinical significance of this lesion is discussed and the importance of differentiating it from Barrett's esophagus is stressed.     

In search of tuberculosis virulence genes

The identity of the virulence genes that enable tuberculosis organisms to survive in macrophages and to induce the features of tuberculosis remains largely unknown. Numerous putative virulence genes have been identified, but so far there is only conclusive evidence for the role of two genes, KatG and rpoV, in virulence.     

Qualitative approach: a contribution to nursing

This paper focus on some characteristics of the qualitative methodology. Some of these methods are explored such as: participatory research, phenomenology, grounded theory and ethnography critical theory Perspectives of their utilization in nursing research are examined.     

Serum amyloid P component scintigraphy and turnover studies for diagnosis and quantitative monitoring of AA amyloidosis in juvenile rheumatoid arthritis

OBJECTIVE: To evaluate aspects of the natural history of AA amyloidosis complicating juvenile rheumatoid arthritis (JRA), and its response to therapy with chlorambucil. METHODS: Scintigraphy and 7-day turnover studies were performed in JRA patients with histologically proven (n = 35) or clinically suspected (n = 30) AA amyloidosis, following intravenous injection of 123I and 125I-labeled serum amyloid P component (SAP). Prospective monitoring studies were performed over 2-3 years in 20 patients with amyloidosis. All but 2 amyloidosis patients were treated with chlorambucil. RESULTS: Positive scanning results were obtained in all patients in whom imaging was performed within 12 years of positive biopsy findings of amyloid and in 5 patients with clinically suspected amyloidosis. Negative scanning results with normal SAP metabolism, indicating regression of amyloid, were obtained in 4 patients whose amyloidosis had been in full clinical remission for more than 12 years. Prospective monitoring studies in patients whose JRA-associated inflammatory activity was in remission demonstrated regression of amyloid in 8 patients and no substantial changes in 8 others; however, in 4 further patients with active inflammation, there was accumulation of amyloid. There was a very poor correlation between the amount of amyloid present at a particular site and the resultant organ dysfunction. CONCLUSION: Radiolabeled SAP scintigraphy and turnover studies are useful complementary tools in the diagnosis, screening, and quantitative monitoring of type AA amyloidosis in JRA. The amyloid deposits may progress and/or regress at different rates in different anatomic sites over short periods.     

Underrecognition of cervical Neisseria gonorrhoeae and Chlamydia trachomatis infections in the emergency department

OBJECTIVES: 1) To quantify the frequency of underrecognized Neisseria gonorrhoeae and Chlamydia trachomatis cervical infections in women tested in the ED, 2) to describe and compare the characteristics of those treated and not treated during the initial visit, and 3) to quantify the delay interval until treatment was provided. METHODS: A 2-year, retrospective consecutive case series was performed from June 1, 1992, to May 31, 1994. There were 148 women with > or = 1 discrete occurrence of culture-proven cervical N. gonorrhoeae or C. trachomatis infection studied. All the patients were evaluated in a university-affiliated, tertiary care hospital-based ED with a large rural referral area. The main outcome measures were the proportions of patients with positive cultures both treated and not treated in the ED, the clinical characteristics of each group, and the proportion remaining untreated or experiencing treatment delays of > 2 weeks after attempted phone, mail, and public health follow-up. RESULTS: Of 157 occurrences of positive cultures for N. gonorrhoeae or C. trachomatis, 86 (53%) were treated with a regimen suggested by the CDC prior to ED release. The proportion of women with isolated C. trachomatis infections that were underrecognized and untreated initially was larger than the proportions with isolated N. gonorrhoeae or combined infections (79% vs 27% and 53%, respectively, p < 0.0001). Women with findings suggestive of advanced disease (history of fever or chills, or examination evidence of temperature > 38 degrees C, purulent vaginal discharge, or any uterine/salpinx/ovarian tenderness) were more often recognized and treated with appropriate antibiotics initially (p = 0.02 to < 0.00001 for all). After phone, mail, and public health follow-up, treatment could not be documented for 25% of the occurrences, in all cases due to an inability to locate the patient. An additional 20% of the women did not receive treatment for 14-60 days. CONCLUSIONS: In this population, both N. gonorrhoeae and C. trachomatis cervical infections are frequently underrecognized in the ED, with isolated C. trachomatis infections associated with significantly higher proportions of underrecognition. Many affected women remain untreated for extended intervals, creating public and individual health risks. Improved point of contact detection, follow-up, and treatment policies are needed to limit these risks.