Effects of benfluorex metabolites on membrane fluidity and insulin-related processes

Hepatocyte growth factor (HGF) is a potent mitogen for the maturation of hepatocytes in vitro which plays a role in liver regeneration in vivo. In addition, transforming growth factor-beta 1 (TGF-beta 1) is also a potent regulator of liver regeneration. In attempting to clarify the mechanisms related to liver regeneration after partial hepatectomy, we investigated the expression of HGF and TGF-beta 1 in rats with liver cirrhosis (LC). A rat model of LC was prepared using carbon tetrachloride (CCl4). The expression of HGF mRNA in both the LC and control groups showed a similar time-course with the highest expression seen at 18h after a 70% hepatectomy. The expression of TGF-beta 1 mRNA peaked at 18h after partial hepatectomy in the LC group and at 48h in the control group. The 5-bromo-2'-deoxyuridine (BrdU) labeling index for the LC group at 24, 48, and 72 h after partial hepatectomy was 9.2%, 5.9%, and 1.8%, while for the control group it was 7.0%, 11.7%, and 6.8%, respectively. The BrdU labeling index in the LC group was thus suppressed earlier than that in the control group. We therefore postulate that regeneration of the remnant liver in the presence of LC accelerates immediately after partial hepatectomy, but the extent of regeneration is insufficient because of an early cessation due to an early expression of TGF-beta 1.     

Respiratory infections in patients with HIV

Pneumocystis carinii pneumonia has long been considered the predominant pulmonary disease in patients with HIV, but several factors are changing this perception. The population infected with HIV is increasingly composed of injection drug users, and racial and ethnic minorities, which represent groups that have a high incidence of bacterial pneumonia and tuberculosis. The increased longevity attributed to antiretroviral therapy and P. carinii pneumonia prophylaxis is accompanied by more profound immunosuppression, rendering patients susceptible to Pseudomonas, Aspergillus, and other opportunistic pneumonias. Trimetrexate and atovaquone are now available for the treatment of P. carinii pneumonia. Both are less effective than standard regimens of trimethoprim-sulfamethoxazole, but have fewer adverse effects. The diagnosis of respiratory infections complicating HIV usually depends on isolation of the pathogen. The routine use of transbronchial biopsy during bronchoscopy is controversial because the prevalence of P. carinii pneumonia is high in most centers caring for patients with AIDS, and bronchoalveolar lavage is usually diagnostic in this disease. However, biopsy enhances the yield of bronchoscopy, especially in the diagnosis of noninfectious pulmonary disorders and infections other than P. carinii pneumonia.     

Anti-inflammatory action of dapsone: inhibition of neutrophil adherence is associated with inhibition of chemoattractant-induced signal transduction

Dapsone has clinical utility as an anti-inflammatory agent but the mechanism of this action remains unknown. We have previously reported that dapsone inhibits beta2 integrin (CD11b/CD18)-mediated adherence of human neutrophils in vitro and now describe studies designed to discover how dapsone-mediated inhibition of this neutrophil function occurs. Results indicate that dapsone interferes with the activation or function of the G-protein (Gi type) that initiates the signal transduction cascade common to chemotactic stimuli. They also show that dapsone-mediated suppression of this pathway inhibits the generation of second messengers essential to the activation of beta2 integrin molecules, as well as respiratory and secretory functions of neutrophils exposed to chemoattractants. We propose that the inhibition of chemoattractant-induced signal transduction by dapsone suppresses neutrophil recruitment and local production of toxic respiratory and secretory products in the affected skin of dermatitis herpetiformis and other neutrophilic dermatoses.     

Electrophysiologic and electrocardiographic aspects of the transplanted heart

The authors suggest that academic institutions build business-oriented policies and practices into the development of any nurse-run clinic to set the stage for financial independence when special or development funding ends. One university-affiliated program that provides 4,000 to 5,000 annual visits drastically changed its strategies when threatened with closure after free rent and other subsidies were withdrawn. The growing emphasis on ambulatory care roles for nurses at all levels makes such clinics critical to the success of the broad-based curricula of nursing education programs, as well as the clinic's value to communities they serve. Funding difficulties frequently threaten the existence of such nurse-run clinics once the initial grant funding is no longer available. This has caused a new emphasis on running such clinics in a business-wise manner. Among the strategies initiated were: direct full-pay at the time of service; a realistic business management plan; aggressive planned marketing; contracts and agreements with other agencies; obtaining provider status with selected HMOs.     

Co-localization of serotonin and FMRFamide-like immunoreactivities in the central nervous system of the earthworm, Eisenia fetida

In addition to receptor-type pinealocytes, the mammalian pineal organ contains small and large neurons and ependymal/glial cells as well. Axons of pinealocytes form synaptic ribbon-containing axo-dendritic synapses on large secondary pineal neurons and/or terminate as neurohormonal endings on the basal lamina of the vascular surface of the organ. The small pineal neurons were found to be gamma-aminobutyric acid (GABA)-immunoreactive, while large secondary neurons and pinealocytes contained immunoreactive amino acids (glutamate and aspartate). Glutamate accumulated presynaptically in pinealocytic axon terminals on large secondary neurons and in the axons of these neurons. Glutamate immunoreactive axons of pineal neurons were traced via the pineal tract to the habenular nucleus. Axons containing granular vesicles and coming from extrapineal perikarya are glutamate immunoreactive as well. Aspartate and GABA are also present in some of the myelinated axons, supposedly pinealopetal in the pineal tract.     

Long-term follow-up of immunosuppressive treatment for obstructive airways disease after allogeneic bone marrow transplantation

BACKGROUND: Locally advanced thyroid cancer invading the tracheal cartilage represents a difficult treatment dilemma during thyroidectomy. METHODS: A retrospective chart review was performed to determine the results of laryngotracheal resection or tracheal cartilage shave with adjuvant radiotherapy in patients with locally advanced thyroid cancer invading the upper airway. RESULTS: Of 597 patients undergoing thyroidectomy for thyroid cancer, 40 were found to have laryngotracheal invasion. Thirty-five patients with superficial invasion underwent cartilage shave procedures with adjuvant radiotherapy; five with full-thickness invasion underwent radical resection, including tracheal sleeve resection (n = 3) or total laryngectomy (n = 2). Histologic subtypes included papillary (n = 32), follicular (n = 2), Hurthle cell (n = 1), medullary (n = 3), and anaplastic (n = 2). Of the cartilage shave group, 25 are currently alive with no evidence of disease at a mean follow-up of 81 months (range 1-290). Six developed isolated local/regional recurrence and were managed with total laryngectomy (n = 1), tracheal resection (n = 1), cervical lymphadenectomy (n = 1), or repeat radiotherapy (n = 3). All six patients remain free of disease at a mean follow-up of 5 years. Of those who underwent initial laryngotracheal resection, four remain free of disease at a mean follow-up of 5 years. The rates of 10-year disease-free survival and overall survival for all patients were 47.9% (95% confidence interval [CI] 24.8, 71.0) and 83.9% (95% CI 70.3, 97.5), respectively. CONCLUSIONS: These data suggest that adequate management of thyroid cancer with laryngotracheal invasion can be achieved with a more conservative surgical approach and adjuvant radiotherapy, reserving more radical resections for extensive primary lesions or locally recurrent disease.     

NMR structure and mutagenesis of the FADD (Mort1) death-effector domain

When activated, membrane-bound receptors for Fas and tumour-necrosis factor initiate programmed cell death by recruiting the death domain of the adaptor protein FADD to the membrane. FADD then activates caspase 8 (also known as FLICE or MACH) through an interaction between the death-effector domains of FADD and caspase 8. This ultimately leads to the apoptotic response. Death-effector domains and homologous protein modules known as caspase-recruitment domains have been found in several proteins and are important regulators of caspase (FLICE) activity and of apoptosis. Here we describe the solution structure of a soluble, biologically active mutant of the FADD death-effector domain. The structure consists of six antiparallel, amphipathic alpha-helices and resembles the overall fold of the death domains of Fas and p75. Despite this structural similarity, mutations that inhibit protein-protein interactions involving the Fas death domain have no effect when introduced into the FADD death-effector domain. Instead, a hydrophobic region of the FADD death-effector domain that is not present in the death domains is vital for binding to FLICE and for apoptotic activity.     

Minimal inhibition concentrations of selected antibiotics for strains of Staphylococcus aureus

Minimal inhibition concentrations (MIC) of gentamycin (Ge), neomycin (Neo), rifampicin (Rif), ampicillin (Amp), lincomycin (Lin), erythromycin (Ery), and streptomycin (STM) were determined by the agar dilution technique using 46, 130, 131, 125, 140, 139 and 142 strains of Staphylococcus aureus, respectively. The strains, selected from the collection of the authors' laboratory, were isolated from mammary gland secretions of cows affected with clinical or subclinical mastitis. The following ranges of MIC (micrograms/ml) were assessed for the antibiotics under study: Ge 0.125-0.50, Neo 0.06-0.50, Rif 0.0039-0.030, Amp 0.015-1.00, Lin 0.25-1.00, Ery 0.06-0.25, STM 0.50-64.0. Modal MIC (micrograms/ml) were as follows; Ery 0.125 (86%), Lin 0.5 (71.4%), Rif 0.007 (68.7%), Ge 0.25 (56.5%), STM 1.00 (54.2%), Neo 0.25 (53.8%), Amp 0.06 (41.6%). The order of efficiency expressed in MIC 90 (micrograms/ml) was as follows: Rif (0.015), Ery (0.125), Ge (0.25), Neo (0.25), Amp (0.5), STM (4.0).