Tuft-to-capsule adhesions and their precursors: differences between the vascular and tubular poles of the human glomerulus

The hypothalamo-pituitary-adrenal (HPA) axis is modulated by sex hormones. Few data exist on the relation between acute estrogen deficit and HPA axis response to corticotropin-releasing hormone (CRH). The effects of a sudden drop in estradiol levels on basal and CRH-stimulated levels of ACTH, cortisol, testosterone, androstenedione and 17-hydroxyprogesterone (17-OHP) were assessed in nine premenopausal women (44-48 years of age), before and after ovariectomy. The CRH test was performed before and 8 days after ovariectomy. A significant reduction in ACTH and adrenal steroids but not in cortisol response to CRH was observed after ovariectomy. The ratio of deltamax androstenedione/17-OHP after CRH stimulation was substantially the same before and after ovariectomy, whereas deltamax 17-OHP/cortisol was significantly lower in ovariectomized women showing increased 21- and 11beta-hydroxylase activity. The results show that the acute estrogen deficit induces changes in the HPA axis characterized by reduced stimulated secretion of ACTH and steroids but normal stimulated cortisol production.     

Usefulness and limitations of thyrotropin measurements as a first-line test for follow-up of Graves'' patients

Although the good appearance and biocompatibility of dental porcelains, failures are still of considerable concern because of the limited properties to all ceramic system. Physical properties that might be considered ideal include high strength, resistance to abrasion, and resistance to the hostile oral environment. Porcelain has been considered by many of its physical characteristic are similar to those of enamel. In 1983 a new modality of treatment, the etched porcelain restoration was introduced by Simonsen and Calamia. Numerous investigations have shown the strength of the etched porcelain bonded to composite resin and also the clinical success of this porcelain to be used as laminated veneers and etched inlays and onlays.     

NADP-Isocitrate dehydrogenase from Pseudomonas nautica: kinetic constant determination and carbon limitation effects on the pool of intracellular substrates

Variations of intracellular concentrations of isocitrate and NADP+ were measured throughout all growth phases of the marine bacterium Pseudomonas nautica. The intracellular isocitrate concentration tracked the intracellular protein concentration throughout all phases of growth. It rapidly increased in early exponential phase to a maximum and fell to nearly zero in parallel with pyruvate exhaustion in the culture medium. The intracellular NADP+ and protein concentrations increased in parallel during the exponential phase but were poorly correlated. Even after carbon exhaustion, the intracellular NADP+ concentration stayed high, as did protein levels. The results demonstrated that the intracellular isocitrate concentration, but not the intracellular NADP+ concentration, was affected by the carbon availability in the culture. They also suggest that, because of its variability, isocitrate, but not NADP+, plays the larger role in the control of the respiratory CO2 production rate (RCO2). From initial rate studies, bisubstrate Michaelis constants and the dissociation constant were determined for NADP+-specific isocitrate dehydrogenase (IDH) from P. nautica. These studies support the hypothesis that the mechanism of IDH's activity involves the ordered addition of the substrates, D-isocitrate and NADP+. Furthermore, the results support the use of a bisubstrate enzyme kinetic equation to model RCO2 in P. nautica.     

Management of thyroid carcinoma invading the aerodigestive tract

OBJECTIVES: To evaluate approaches to thyroid carcinoma invading the aerodigestive tract, with particular attention to well-differentiated carcinomas. STUDY DESIGN: Retrospective review of experience with thyroid carcinoma invading the aerodigestive tract over a 20-year period at a tertiary referral hospital. METHODS: The medical records of all patients with a diagnosis of thyroid cancer treated at Emory University Hospital, Atlanta, Georgia, from 1977 through 1997 were reviewed. Multiple clinical variables were analyzed including treatment, development of recurrence, and survival. Survival and time to local recurrence were determined by Kaplan-Meier analysis, and statistical comparisons were made using log-rank analysis. RESULTS: Five hundred thirty-six cases were identified; 28 patients (5.2%) were identified with invasive disease involving the aerodigestive tract. Histologic findings at the time of invasion included 15 well-differentiated (WD) carcinomas and 13 poorly differentiated (PD) carcinomas. Eight of the 28 patients (5 WD, 3 PD) underwent surgical resection of some portion of the aerodigestive tract with curative intent. Ten patients (8 WD, 2 PD) underwent incomplete resection with tumor left adjacent to aerodigestive tract structures. All patients undergoing incomplete resection developed local recurrence. Six required salvage resection, as opposed to no recurrences in WD carcinomas following complete resection (P = .01). Survival at 5 years for WD carcinomas undergoing complete resection versus initial incomplete resection was 100% versus 50%, respectively (P = .27). CONCLUSION: Review of our experience shows that complete resection of thyroid carcinoma invading the aerodigestive tract can offer prolonged palliation, improved local control, and the opportunity for cure in selected patients.     

Three-dimensional analysis of the 16 nm urothelial plaque particle: luminal surface exposure, preferential head-to-head interaction, and hinge formation

The luminal surface of mouse urothelium in contact with the urine is almost entirely covered with plaques consisting of uroplakin-containing particles that form p6 hexagonal crystals with a center-to-center distance of 16 nm. A combination of quick-freeze/deep-etch images and our previous negative staining data indicate that the head domain of the uroplakin particle, which is exposed without an extensive glycocalyx shield, interacts closely with the head domains of the neighboring particles, while the membrane-embedded tail domains are farther apart; and that urothelial particles and plaques are not rigid structures as they can change their configuration in response to mechanical perturbations. Based on these data, we have constructed three-dimensional models depicting the structural organization of urothelial particles and plaques. Our models suggest that the head-to-head interaction may play a key role in determining the shape and size of the urothelial plaques. These models can explain many properties of urothelial plaques including their unique shape, detergent-insolubility, and morphological changes during vesicle maturation.     

Camptothecin causes cell cycle perturbations within T-lymphoblastoid cells followed by dose dependent induction of apoptosis

We have investigated the effect of the anticancer compound, camptothecin on Jurkat T-cells, a lymphoblastoid leukemic cell-line. Exposure to low concentrations led to rapid cessation of DNA (more than 95%) and RNA (more than 75%) synthesis. Perturbations to the cell cycle were observed following exposure which caused a significant accumulation of cells within G1 (P = 0.03) with a concomitant decrease in G2/M (P = 0.025). Concentrations below 0.1 microM could inhibit DNA synthesis but not induce apoptosis. Induction of apoptosis was dose dependent and could be detected as early as 3 h post exposure. The apoptotic population appeared to be derived from G1 and S-phase cells but not G2/M, coinciding with the cell cycle compartments in which DNA and RNA polymerases function. However, direct inhibition of DNA polymerase alone was not shown to be associated the induction of apoptosis or with a decrease in susceptibility to camptothecin-induced cell death. The effects of camptothecin on Jurkat T-cells and the potential mechanisms involved are discussed in the context of observations made in other transformed cell lines.