Evidence for a catabolic role of glucagon during an amino acid load

Despite the strong association between protein catabolic conditions and hyperglucagonemia, and enhanced glucagon secretion by amino acids (AA), glucagon's effects on protein metabolism remain less clear than on glucose metabolism. To clearly define glucagon's catabolic effect on protein metabolism during AA load, we studied the effects of glucagon on circulating AA and protein dynamics in six healthy subjects. Five protocols were performed in each subject using somatostatin to inhibit the secretion of insulin, glucagon, and growth hormone (GH) and selectively replacing these hormones in different protocols. Total AA concentration was the highest when glucagon, insulin, and GH were low. Selective increase of glucagon levels prevented this increment in AA. Addition of high levels of insulin and GH to high glucagon had no effect on total AA levels, although branched chain AA levels declined. Glucagon mostly decreased glucogenic AA and enhanced glucose production. Endogenous leucine flux, reflecting proteolysis, decreased while leucine oxidation increased in protocols where AA were infused and these changes were unaffected by the hormones. Nonoxidative leucine flux reflecting protein synthesis was stimulated by AA, but high glucagon attenuated this effect. Addition of GH and insulin partially reversed the inhibitory effect of glucagon on protein synthesis. We conclude that glucagon is the pivotal hormone in amino acid disposal during an AA load and, by reducing the availability of AA, glucagon inhibits protein synthesis stimulated by AA. These data provide further support for a catabolic role of glucagon at physiological concentrations.     

Zoonotic Brugian lymphadenitis. An unusual case with florid monocytoid B-cell proliferation

Human infection with a zoonotic Brugia species in the United States is uncommon. Positive identification of the filarial nematode is required for histopathologic diagnosis. Many cases may go unrecognized because of the nonspecific clinical manifestations and the nondiagnostic histologic changes occurring in involved lymph nodes. A case of zoonotic Brugia lymphadenitis is described in a patient from Rhode Island, in which a small nongravid female worm was identified in a lymph node biopsy specimen. The lymph node also showed a spectrum of reaction changes including the presence of florid monocytoid B-cell proliferation, which has not been described in association with zoonotic Brugian filariasis.     

Interferon-gamma upregulates the stromelysin-1 gene expression by human skin fibroblasts in culture

Beliefs about human nature, adult education, adult learners, and moral commitment are at the heart of the educator-learner agreement. In continuing nursing education, it is the point where professional values, morals, and ethical principles meet. Using Husteds' bioethical decision-making model, the values, beliefs, and actions within the educator-learning agreement are identified and organized by the bioethical standards. By relating the bioethical standards to practice, continuing nurse educators can find their own basis for practice and work toward attaining a consistent professional ethical orientation.     

RANTES-induced T cell activation correlates with CD3 expression

The chemokine RANTES induces a unique biphasic cytoplasmic Ca2+ signal in T cells. The first phase of this signal, similar to that of other chemokines, is G-protein mediated and chemotaxis associated. The second phase of this signal, unique to RANTES and evident at concentrations greater than 100 nM, is tyrosine kinase linked and results in a spectrum of responses similar to those seen with antigenic stimulation of T cells. We show here that certain jurkat T cells responded to RANTES solely through this latter pathway. A direct correlation between the RANTES-induced second phase response and CD3 expression was demonstrated in these cells. Sorting the Jurkat cells into CD3(high) and CD3(low) populations revealed that only the CD3(high) cells were responsive to RANTES. Furthermore, stimulation of these Jurkat cells with anti-CD3 mAb significantly depresses their subsequent response to RANTES. While a RANTES-specific chemokine receptor is expressed at a low level on these Jurkat cells, the RANTES-induced activation is dependent on the presence of the TCR. Thus, stimulation through TCR may partially account for RANTES' unique pattern of signaling in T cells.     

Temperature-regulated expression of the tac/lacl system for overproduction of a fungal xylanase in Escherichia coli

Temperature-regulated expression of recombinant proteins in the tac promoter (Ptac) system was investigated. Expression levels of fungal xylanase and cellulase from N. patriciarum in E. coli strains containing the natural lacI gene under the control of the Ptac markedly increased with increasing cultivation temperature in the absence of a chemical inducer. The specific activities (units per milligram protein of crude enzyme) of the fungal xylanase and cellulase produced from recombinant E. coli strain pop2136 grown at 42 degrees C were about 4.5 times higher than those of the cells grown at 23 degrees C and were even slightly higher when compared with cells grown in the presence of the inducer isopropyl beta-D-thiogalactopyranoside. The xylanase expression level in the temperature-regulated Ptac system was about 35% of total cellular protein. However, this system can not be applied to E. coli strains containing lacIq, which confers over production of the lac repressor, for high-level expression of recombinant proteins. In comparison with the lambda PL system, the Ptac-based xylanase plasmid in E. coli pop2136 gave a considerably higher specific activity of the xylanase than did the best lambda PL-based construct using the same thermal induction procedure. The high-level expression of the xylanase using the temperature-regulated Ptac system was also obtained in 10-litre fermentation studies using a fed-batch process. These results unambiguously demonstrated that the temperature-modulated Ptac system can be used for overproduction of some non-toxic recombinant proteins.     

Cardiac dysrrhthmia in systemic disease

This is an ECG of a 6-year-old girl. She presented to us for management of epilepsy. Magnetic resonance imaging (MRI) of the brain showed multiple lesions consistent with cortical and subcortical tubers. There were also achromic spots on her skin and echocardiography demonstrated a rhabdomyoma near the right ventricular outflow tract. A diagnosis of tuberous sclerosis, an autosomal-dominantly inherited condition, was made. What is abnormal about the ECG?     

Characterization of arylamine N-acetyltransferase in Enterobacter aerogenes

N-acetyltransferase (NAT) activity was determined by incubation of purified Enterobacter aerogenes enzyme with 2-aminofluorene (2-AF) as the substrate, followed by high pressure liquid chromatography assays. The NAT activity from E. aerogenes was 0.58 +/- 0.08 nmol/min/mg protein for 2-AF. The values of apparent K(m) and Vmax were 0.72 +/- 0.14 mM and 2.45 +/- 0.29 nmol/min/mg protein, respectively, for 2-AF. The optimal pH value for the enzyme activity was 7.5 for the 2-AF tested. The optimal temperature for enzyme activity was 37 degrees C for the 2-AF substrate. The molecular weight of NAT from E. aerogenes was 44.9 kD. Among a series of divalent cations and salts, Zn2+, Ca2+, and Fe2+ were demonstrated to be the most potent protease inhibitors, and only ethylenediaminetetraacetic acid significantly protected the NAT. Iodoacetamide, in contrast to other agents, markedly inhibited NAT.     

Risk of benzene-induced leukemia: a sensitivity analysis of the pliofilm cohort with additional follow-up and new exposure estimates

This report updates the risk assessment by Crump and Allen (1984) for benzene-induced leukemia that was used by OSHA (1987) to support its reduction of the permissible exposure limit (PEL) to 1 ppm and that also was the basis for EPA's (1985) interim "unit risk" for benzene. The present study derives new risk estimates using data from follow-up through 1987 (whereas the earlier assessment only had follow-up available through 1978), and using new exposure estimates for this cohort developed by Paustenbach et al. (1992) that account for a number of factors that were unknown or not fully evaluated in earlier exposure assessments. There was a significant excess of acute myelocytic or acute monocytic leukemia (AMML, the only forms of acute nonlymphatic leukemia observed) in this cohort, and this end point also exhibited a strong dose-response trend. AMML was the only hematopoietic or lymphatic cancer that was clearly linked to benzene exposure. However, quantitative estimates of risk based on modeling either AMML or all leukemia differed by only 20%. Differences between the two Pliofilm plant locations in the occurrence of AMML were not statistically significant (.12 < or = p < or = .21) after differences in levels of benzene exposure were taken into account. The Paustenbach et al. exposures predicted a quadratic dose response, based on a measure of exposure that weighted intensity of exposure more heavily than duration of exposure. The best-fitting quadratic models predicted an additional lifetime risk of a benzene-related death from 45 yr of exposure to 1 ppm of between 0.020 and 0.036 per thousand. Statistical confidence intervals (90%) on these estimates were barely wide enough to include risk estimates based on linear dose response models. These linear models predicted risks of between 1.6 and 3.1 per thousand.     

Interaction of transport resistances with biochemical reaction in packed-bed solid-state fermentors: effect of temperature gradients

Subdermal superficial liposuction, first presented by the authors at the ISAPS Congress at Zurich in 1989, is performed with thin three-hole Mercedes cannulas (diameter ranges from 1.8 to 2 mm) to treat small and secondary adiposities and to allow better skin retraction. Suction of the subdermal layer of fat reduces the thickness and consistency of the superficial fat and enhances the possibility of skin retraction. In cases where there is a large adiposity of the abdomen, arms, or inner thighs, there is a conspicuous volume of fat whose weight tends to overstretch and to carry the overlying skin downward. In these cases we need to reduce the large fat volume to permit effective skin retraction. Therefore, we apply the principles of traditional liposuction with those of subdermal superficial liposuction to aspirate large amounts of fat from all the adipose layers. We call this technique Massive All Layer Liposuction (MALL). The amount of skin shrinkage after this "defatting" procedure is remarkable and the clinical results are very good. The MALL technique can be applied to other areas as well. In our experience this new liposuction technique has dramatically reduced the indications of abdominoplasties and dermolipectomies of inner thighs and arms.     

Epidemiology and ethics: the perspective of the Third World

The relation of epidemiology and ethics is discussed from a Third World perspective, including the following issues: the structure and dynamics of a Third World Society; the nature of the relationship between the First World "islanders" in the Third World and their counterparts in the First World, and between the "islanders" and their fellow citizens; the inner dynamics of Third World researchers; the different knowledge systems; and the role of institutions in the Third World and the First World.