Pathogenesis of renal calculi in distal renal tubular acidosis. Possible role of parathyroid hormone

Elevated circulating levels of immunoreactive parathyroid hormone (PTH), hypercalciuria and renal calculi were found in 3 patients with distal renal tubular acidosis (RTA). Treatment with alkali resulted in a fall of PTH toward normal and a reduction in urinary calcium, but the frequency of urolithiasis was unchanged. In one patient in whom prolonged follow-up was possible, a subtotal parathyroidectomy was performed. This was followed by virtual cessation of stone formation despite persistence of the acidification defect. This study suggests that RTA may be associated with secondary hyperparathyroidism and that the consequent elevation in PTH may play a contributory role in the pathogenesis of renal calculi.     

Chronic obstructive pulmonary disease: role of bronchiolar mast cells and macrophages

Chronic obstructive pulmonary disease (COPD) is considered to be caused in part by smoking-induced inflammation, but it is unknown which inflammatory cells within the small airways are associated with the obstruction. We investigated the inflammatory infiltrate in the small airways of 16 current or ex-smokers with COPD (FEV1 < or = 75% predicted) and 15 without COPD (FEV1 > or = 85% predicted) in pneumectomy specimens that were removed for lung cancer. Mast cells, macrophages, neutrophils, eosinophils, T cells, and B cells were identified using immunohistochemistry on formalin-fixed, paraffin-embedded specimens. These cells were quantified in the epithelium and the remainder of the airway wall. The number of mast cells and macrophages in the epithelium, but not in the remainder of the airway wall, was significantly increased in patients with COPD. Neutrophil and T cell numbers did not differ between the groups. Only few B cells and eosinophils were present in both groups. Smoking history, perioperative steroid usage, tumor localization, or reversibility in the FEV1 to salbutamol could not account for the observed differences. We conclude that the number of epithelial mast cells and macrophages is increased in the bronchioli in smokers with airflow limitation, suggesting a role in development of COPD.     

Expression of the retinoblastoma (RB) tumor suppressor gene inhibits tumor cell invasion in vitro

To determine if replacement of the retinoblastoma (RB) tumor suppressor gene could inhibit invasion of RB-defective tumor cells, the capacity of tumor cells to migrate or invade was quantitated by the Boyden chamber assay. The studies were done in a diverse group of stable RB-reconstituted human tumor cell lines, including those derived from the osteosarcoma and carcinomas of the lung, breast and bladder. The expression of the exogenous wild-type RB protein in these tumor cell lines was driven by either a constitutively active promoter or an inducible promoter. It was found that significantly more tumor cells from the parental RB-defective cell lines and the RB revertants than from the RB-reconstituted RB+ cell lines penetrated through the Matrigel (P<0.001, two-tailed t-test), although both RB+ and RB- cells migrated at approximately the same rate on uncoated polycarbonate filters in the Boyden chambers. Of note, the inhibition of invasiveness of various RB-defective tumor cells by RB replacement was apparently well correlated with suppression of their tumorigenicity in vivo. In contrast, although either functional RB or p53 re-expression effectively suppressed tumor formation in nude mice of the RB-/p53null osteosarcoma cell line, Saos-2, replacement of the wild-type p53 gene had much less impact on their invasiveness as compared to the RB gene. These studies provided an insight into the broader biological basis of the RB-mediated tumor suppression in RB-defective tumor cells.     

Practice trends of American urologists in the treatment of impotence, incontinence and infertility

PURPOSE: Trends of urologist practice patterns in evaluating and treating impotence, incontinence and infertility in the United States were assessed. MATERIALS AND METHODS: In July 1995 the executive interviewing branch of the Gallup Organization selected randomly and interviewed by telephone 533 practicing urologists in the United States who had provided urological patient care for more than 20 hours per week, practiced in 1994 and completed a urological residency program. RESULTS: Treatment of male sexual dysfunction and female urinary incontinence comprises a significant portion of the professional activity of United States urologists. However, evaluation and management of male infertility occupy a small portion of the average urological work load. While more than half of United States urologist office clinical laboratories were inspected in 1994, only 2% failed evaluation due to major deficiencies. CONCLUSIONS: Male sexual dysfunction and female urinary incontinence are major areas of urological practice in the United States but male infertility is not. Few United States urologist clinical laboratories failed inspection because of major deficiencies.     

Cell-cell signaling during Dictyostelium development

Specific proteins and peptides, as well as cAMP, are used as intercellular signals in Dictyostelium. Our understanding of the signal transduction pathways activated by these signals has been expanded by inclusion of newly characterized proteins. cAMP-dependent protein kinase (PKA) and its associated phosphodiesterase, RegA, play multiple roles in these pathways.     

Alveolar permeability enhancement by oleic acid and related fatty acids: evidence for a calcium-dependent mechanism

Pulmonary exposure to oleic acid (OA) is associated with permeability alterations and cellular damage; however, the exact relationship between these two effects has not been clearly established. Using cultured alveolar epithelial monolayers, we demonstrated that OA and some other fatty acids (< or = 50 microM) can induce permeability changes without detectable cellular damage. At higher concentrations, however, OA caused severe membrane damage and leakage to solute flux. The permeability enhancing effect of OA was observed with both the paracellular marker 3H-mannitol and the lipophilic transcellular indicator 14C-progesterone. While the effect of OA on transcellular permeability may be attributed to its known effect on membrane fluidity, the paracellular promoting effect of OA and its mechanism are not well established. We postulated that OA may increase paracellular permeability through a Ca(2+)-dependent tight junction mechanism. Using dual-excitation fluorescence microscopy, we demonstrated that OA can increase intracellular calcium, [Ca2+]i, in a dose-dependent manner. This effect was transient at low OA concentrations (< or = 50 microM) but became more pronounced and sustained at higher concentrations. Free hydroxyl and unsaturated groups were required for this activation since esterified OA (oleic methyl ester) and stearic acid (a saturated fatty acid with equal chain length) had much reduced effects on both the [Ca2+]i and the permeability alterations. Degree of unsaturation was unimportant since linolenic acid (18:3), linoleic acid (18:2), and OA (18:1) had similar and comparable effects on the two parameters.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diagnostic scalene node biopsy in the preoperative evaluation of the surgical cancer patient: Five-year experience with 108 cases and literature review

Records were reviewed of 108 consecutive patients with a variety of surgically approachable malignancies undergoing scalene node biopsy as part of a preoperative staging evaluation. Metastases to the scalene nodes were detected in 12 patients (11.1%). In six patients the scalene nodes were clinically suspicious before biopsy, but in six with nonpalpable nodes the scalene metastases were occult clinically. Four of the patients with clinically benign, but pathologically positive, scalene biopsies were found among the group of 62 patients with epidermoid carcinoma of the cervix. It was concluded that routine scalene biopsies are justified in the properative evaluation of cancer patients only if the nodes are clinically suspicious, except for in patients with advanced pelvic cancers, in whom the incidence of completely occult scalene metastases is 6% or more.     

Kinetic analysis of biochemical differentiation in Dictyostelium discoideum

The metabolic network leading to accumulation of cellulose, trehalose, and mucopolysaccharide during development of Dictyostelium discoideum was simulated on a computer. The program consists of a metabolic map, the measured specific activity of the enzymes involved at each stage in development, and the substrate and inhibitor affinities. The Km values of four enzymes, amylase, UDP-galactose polysaccharide transferase, UDP-galactose epimerase, and cellulose synthetase, were determined for this study. At each iteration (1 min) during the period simulated (1500 min), the in vivo activity was calculated for each enzyme using Michaelis-Menten equations and new values for metabolites and end products were generated. The computed values for the concentration of both metabolites and polysaccharides were in close agreement with the measured values at all stages of development. We conclude that the in vitro measured values correlate well with the measured in vivo rates when treated in this manner. The program was modified to simulate the alterations in carbohydrate metabolism which might be expected in mutant strains with reduced activity of various enzymes. Trehalose was found to overaccumulate when either the peak value of the developmentally controlled increase in the specific activity of UDPGlc pyrophosphorylase was reduced. Trehalose accumulation was decreased in simulations of mutants lacking glycogen phosphorylase or glycogen synthetase. The interaction of these metabolic pathways is discussed.