An alternate pathway for T cell development supported by the bone marrow microenvironment: recapitulation of thymic maturation

In the principal pathway of alpha/beta T cell maturation, T cell precursors from the bone marrow migrate to the thymus and proceed through several well-characterized developmental stages into mature CD4+ and CD8+ T cells. This study demonstrates an alternative pathway in which the bone marrow microenvironment also supports the differentiation of T cell precursors into CD4+ and CD8+ T cells. The marrow pathway recapitulates developmental stages of thymic maturation including a CD4+CD8+ intermediary cell and positive and negative selection, and is strongly inhibited by the presence of mature T cells. The contribution of the marrow pathway in vivo requires further study in mice with normal and deficient thymic or immune function.     

Oral glucocorticosteroid-sparing effect of budesonide administered by Turbuhaler: a double-blind, placebo-controlled study in adults with moderate-to-severe chronic asthma. Pulmicort Turbuhaler Study Group

The purpose of this study was to evaluate the correlation between alteration in telomere length and prognosis in patients with pathological stage I-II non-small cell lung cancer. We measured telomeric repeat length and telomerase activity by use of southern blot analysis of terminal restriction fragments and a non-radioactive ELISA-based assay, respectively. RESULTS: Alterations in TRF lengths were present in 17(29.8%) of 57 patients. Patients with altered TRF length had significantly shorter survival than did patients without (P = 0.0051). In multivariate analysis, only alteration in TRF length independently correlated with shortened survival (P = 0.0033).     

Collagen gene expression in the neomatrix of carcinoma of the breast

Excessive deposition of extracellular matrix or neomatrix is a characteristic of desmoplastic invasive breast carcinomas. Type I and III collagens are abundant neomatrix components. Archival breast tissue sections were studied using 35S-labeled cDNA probes for alpha 1(I) and alpha 1(III) procollagen and in situ hybridization. Among the 33 invasive breast cancers, hybridization was seen forming a gradient-like pattern in fibroblasts closest to tumor cells. In the 10 ductal carcinomas in situ studied, a ring-like pattern of hybridization was seen in proximity to the basement membrane zone. Adjacent normal and benign tissues did not demonstrate the patterns of hybridization described in malignant tissues. Gene expression for neomatrix interstitial collagens occurs before there is evidence of invasion in carcinoma of the breast.     

Pulse oximetry at fibre-optic bronchoscopy in local anaesthesia: indication for postbronchoscopy oxygen supplementation?

To investigate the clinical significance of p53 and p21WAF1/CIP1 in the advanced squamous cell carcinoma (SCC) of the pyriform sinus, we performed immunohistochemical staining of p53 and p21WAF1/CIP1 on the biopsy specimens from patients with stage III or stage IV SCC of the pyriform sinus. The results were compared with clinico-pathological features, including age, histological grade, TNM classification, number of neck lymph node metastases on histopathological examination (pLN) and prognosis. Specific staining for p53 and p21WAF1/CIP1 was detected in 36% and 32% of the specimens, respectively. Positive staining of p21WAF1/CIP1 was observed not only in the p53-negative specimens but also in the p53-positive specimens. Age (p < 0.05) and pLN (p < 0.001) were regarded as the significant prognostic factors. The 5-year survival rate of the p53-positive patients (55%) was significantly higher than that of the p53-negative patients (26.5%: p < 0.03). However, there is no significant difference between the p53 groups after controlling pLN. Although it was not statistically significant, the 5-year survival rate of the p21WAF1/CIP1-positive patients (58.8%) was higher than that of the p21WAF1/CIP1-negative patients (26.9%). These results suggest that expressions of p53 and p21WAF1/CIP1 are independent genetic alterations that may play different roles in the SCC of the pyriform sinus. Expression of p53 could not be regarded as an independent prognostic factor at this point. Further studies including the molecular biological analysis should be performed in order to determine the clinical role of p21WAF1/CIP1.     

Effects of hyperventilation and hypocapnic/normocapnic hypoxemia on renal function and lithium clearance in humans

BACKGROUND: Using the renal clearance of lithium as an index of proximal tubular outflow, this study tested the hypothesis that acute hypocapnic hypoxemia decreases proximal tubular reabsorption to the same extent as hypocapnic normoxemia (hyperventilation) and that this response is blunted during normocapnic hypoxemia. METHODS: Eight persons were studied on five occasions: (1) during inhalation of 10% oxygen (hypocapnic hypoxemia), (2) during hyperventilation of room air leading to carbon dioxide values similar to those with hypocapnic hypoxemia, (3) during inhalation of 10% oxygen with the addition of carbon dioxide to produce normocapnia, (4) during normal breathing of room air through the same tight-fitting face mask as used on the other study days, and (5) during breathing of room air without the face mask. RESULTS: Hypocapnic and normocapnic hypoxemia and hyperventilation increased cardiac output, respiratory minute volume, and effective renal plasma flow. Glomerular filtration rate remained unchanged on all study days. Calculated proximal tubular reabsorption decreased during hypocapnic hypoxemia and hyperventilation but remained unchanged with normocapnic hypoxemia. Sodium clearance increased slightly during hypocapnic and normocapnic hypoxemia, hyperventilation, and normocapnic normoxemia with but not without the face mask. CONCLUSIONS: The results indicate that (1) respiratory alkalosis with or without hypoxemia decreases proximal tubular reabsorption and that this effect, but not renal vasodilation or natriuresis, can be abolished by adding carbon dioxide to the hypoxic gas; (2) the increases in the effective renal plasma flow were caused by increased ventilation rather than by changes in arterial oxygen and carbon dioxide levels; and (3) the natriuresis may be secondary to increased renal perfusion, but application of a face mask also may increase sodium excretion.     

Production of inflammatory mediators by human macrophages obtained from ascites

Ascites is a readily available source of human macrophages (M phi), which can be used to study M phi functions in vitro. We characterized the mediators of inflammation produced by human peritoneal M phi (hp-M phi) obtained from patients with portal hypertension and ascites. The production of the cytokines interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) was found to be lipopolysaccharide (LPS) concentration dependent (0-10 micrograms/ml) with a maximal production at 10 micrograms/ml and also dependent on the time of exposure to the stimulus (0-36 h). IL-1 beta, IL-6 and TNF-alpha production after LPS administration reached a plateau at 24 h. In vitro stimulation for 24 h with LPS does not influence the eicosanoid production from endogenous arachidonate. 13 min of exposure of the cells to the calcium ionophore A23187 gives a significant increase in eicosanoid production from both exogenous and endogenous arachidonate. The main eicosanoids produced are the 5-lipoxgenase products LTB4 and 5-hydroxyeicosatetraenoic acid (HETE). The increase in production of the other eicosanoids is not significant. The eicosanoid production depends on the stimulus concentration. The optimal A23187 concentration is 1 microM. Oxygen radical production was measured in the M phi by a flowcytometric method. The fluorescence intensity of phorbol 12-myristate 13-acetate stimulated and dihydro-rhodamine 123 loaded hp-M phi increases significantly after 15 min. We conclude that LPS stimulation of hp-M phi from liver disease results in similar production of IL-1 beta, IL-6 and TNF-alpha, but that the profile of the eicosanoid production of these M phi stimulated with LPS and A23187 differs from M phi of other origin and species.