Insulin activates the hepatitis B virus X gene through the activating protein-1 binding site in HepG2 cells

OBJECTIVES: To study the turnaround time (TAT) for rendering diagnoses on routine biopsy specimens, to examine pathology practice variables that influence TAT, and to assess the level of surgeons' satisfaction with biopsy TAT. DESIGN: Over a 3-month period, voluntary participants in the College of American Pathologists Q-Probes laboratory quality improvement program prospectively collected TAT data on up to 20 biopsy specimens performed on elective surgical cases, completed questionnaires profiling their institution's practice characteristics, and had surgeons complete questionnaires indicating their satisfaction with biopsy report TAT. SETTING AND PARTICIPANTS: One hundred fifty-seven private and public small hospitals located in 43 American states (n = 153), Canada (n = 1), and Australia (n = 3). MAIN OUTCOME MEASURES: The routine surgical biopsy report TATs for 2 testing intervals, each commencing when surgeons acquired the biopsy specimens. One interval concluded when pathologists signed off the biopsy diagnoses, and the other concluded when surgeons received the hard-copy reports. RESULTS: Pathologists signed off 85.9% of 5384 biopsy diagnoses by the second working day, and surgeons received 88.3% of the hard-copy reports by the fourth working day. In 90% of hospitals participating in this study, pathologists signed off half their biopsy diagnoses between the second and third postcollection days, and 90% of surgeons received half their final hard-copy reports by the fourth postcollection day. Institutional practice variables associated with fewer sign-off and/or hard-copy receipt TATs exceeding the institutional 90th percentile performance benchmarks included yearly surgical caseloads greater than 2000 cases per full-time equivalent pathologist, provision of pathology support services on site, and accreditation of the hospital by the Joint Commission on Accreditation of Healthcare Organizations and of the laboratory by the College of American Pathologists. Most (96.4%) surgeons indicated that they were satisfied with hard-copy TATs and that they believed most (98.1%) of the hard-copy TATs had no effect on the lengths of their patients' hospital stays. CONCLUSIONS: Pathologists are capable of signing off most routine biopsy diagnoses within 2 working days and delivering the final hard-copy reports to surgeons within 4 working days (both intervals measured from the time that surgeons collect biopsy specimens). Most surgeons report they are satisfied with this level of performance.     

A concise synthesis and in vitro cytotoxicity of new labdane diterpenes

A new series of labdane-related diterpenes have been synthesized from (-)-sclareol and assayed in vitro cytotoxicity against mouse and human cancer cells. A key intermediate, homodrimane and furanolabdane derivatives show good in vitro cytotoxicity comparable to those of mitomycin C and adriamycin.     

Revisional lumbar microdiscectomy: an analysis of operative findings and clinical outcome

Forty-one consecutive patients who underwent a revision microlumbar exploration for recurrent or persistent sciatica were reviewed retrospectively to analyse the operative findings and assess the clinical outcome following surgery. Thirty-three (80%) patients were found to have a recurrent intervertebral disc protrusion at the previous site, two patients had a disc herniation at a new site, one had severe perineural scarring, two had lateral recess stenosis, one patient had undergone previous exploration at an incorrect site and in two patients no cause for ongoing symptoms was found. Nineteen of the 33 patients with a re-prolapse presented with persistent or recurrent sciatica within 1 year of their first operation. The other 14 patients presented with a late re-prolapse (after 1 year) and their clinical outcome was better than for those patients with an early re-prolapse (12/14 vs 11/19 satisfactory result, respectively). The result of operating on patients with a late re-prolapse was comparable to the 80-95% satisfactory outcomes following primary lumbar microdiscectomy reported by other authors.     

Activation of bovine lymphocyte subpopulations by staphylococcal enterotoxin C

Staphylococcus aureus is a major mastitis-causing pathogen in cattle. The chronic nature of bovine staphylococcal mastitis suggests that some products or components of S. aureus may interfere with the development of protective immunity. One class of molecules that could be involved are superantigens (SAgs). Although a significant number of mastitis isolates produce SAgs, the effect of these molecules on the bovine immune system is unresolved. To determine if immunosuppression caused by SAgs could play a role in pathogenesis, we monitored bovine lymphocytes exposed to staphylococcal enterotoxin C1 (SEC1). Activation of bovine lymphocytes by either SEC1 or concanavalin A (ConA) was influenced by the gammadelta/alphabeta T-cell ratio in the culture. Compared to ConA-induced stimulation, cultures stimulated with SEC1 generated small numbers of CD4+ alphabeta T cells expressing high levels of interleukin-2 receptor alpha chain (IL-2R alpha) and major histocompatibility complex class II (MHCII), suggesting that SAg exposure does not lead to full activation of these cells. This state of partial activation was most pronounced in cultures with a high gammadelta/alphabeta ratio. In contrast, significant numbers of CD8+ alphabeta T cells expressed high levels of IL-2R alpha and MHCII, regardless of the gammadelta/alphabeta ratio and the stimulant used. CD8+ blasts in cultures stimulated with SEC1 also expressed another activation marker, ACT3, previously detected predominantly on thymocytes and CD4+ T cells. Although gammadelta CD2- and CD2+ T cells expressed MHCII and IL-2R alpha following stimulation with SEC1, only a few cells increased to blast size, suggesting that they were only partially activated. The results suggest ways in which SAgs might facilitate immunosuppression that promotes the persistence of bacteria in cattle and contributes to chronic intramammary infection.     

The Chemical Differentiation between Sinapis arvensis and Brassica napus Seeds by Surface Wax Analysis

The hydrocarbons were extracted and isolated from the surface of both Sinapis arvensis and Brassica napus seeds. The major hydrocarbon of the weed seed was found to be hentriacontane (C₃₁H₆₄) whereas nonacosane (C₂₉H₆₀) was the predominant hydrocarbon in rapeseed. This can be used as a criterion upon which differentiation can be made. Total “wax” extracts of the two seed types were analysed by gas chromatography. The waxy material extracted from the weed seed was found to have a major peak at 3320 Kovats retention indices which was absent in all rapeseed varieties. By studying a series of known composites of rapeseed and wild mustard, the level of wild mustard contamination could be accurately determined down to a level of 1 % using a ratio of two peaks at 2900 and 3320 Kovats retention indices.     

The Veterans Affairs Implantable Insulin Pump Study: effect on cardiovascular risk factors

OBJECTIVE: To determine whether implantable insulin pump (IIP) and multiple-dose insulin (MDI) therapy have different effects on cardiovascular risk factors in insulin-requiring patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A randomized clinical trial was conducted at seven Veterans Affairs medical centers in 121 male patients with type 2 diabetes between the ages of 40 and 69 years receiving at least one injection of insulin per day and with HbA1c, levels of > or =8% at baseline. Weights, blood pressures, insulin use, and glucose monitoring data were obtained at each visit. Lipid levels were obtained at 0, 4, 8, and 12 months, and free and total insulin levels were obtained at 0, 6, and 12 months. All medications being taken were recorded at each visit. RESULTS: No difference in absolute blood pressure, neither systolic nor diastolic, was seen between patients receiving MDI or IIP therapy, but significantly more MDI patients required anti-hypertensive medications. When blood pressure was modeled against weight and time, IIP therapy was significantly better than MDI therapy for systolic blood pressure in patients with BMI <33 and for diastolic blood pressure in patients with BMI >34 kg/m2. Total cholesterol levels decreased in the overall sample, but IIP patients exhibited significantly higher levels than MDI patients. Triglyceride levels increased over time for both groups, with IIP patients having significantly higher levels than patients in the MDI group. BMI was a significant predictor of, and inversely proportional to, HDL cholesterol level. No difference in lipid-lowering drug therapy was seen between the two groups. Free insulin and insulin antibodies tended to decrease in the IIP group as compared with the MDI group. C-peptide levels decreased in both groups. CONCLUSIONS: IIP therapy in insulin-requiring patients with type 2 diabetes has advantages over MDI therapy in decreasing the requirement for antihypertensive therapy and for decreasing total and free insulin and insulin antibodies. Both therapies reduce total cholesterol and C-peptide levels.     

Expression of peptide YY in all four islet cell types in the developing mouse pancreas suggests a common peptide YY-producing progenitor

The islets of Langerhans contain four distinct endocrine cell types producing the hormones glucagon, insulin, somatostatin and pancreatic polypeptide. These cell lineages are thought to arise from a common, multipotential progenitor cell whose identity has not been well established. The pancreatic and intestinal hormone, peptide YY, has been previously identified in glucagon-producing cells in islets; however, transgenic mice expressing Simian Virus 40 large T antigen under the control of the peptide YY gene expressed the oncoprotein in beta, delta and pancreatic polypeptide cells, and occasionally developed insulinomas, suggesting relationships between peptide YY-producing cells and several islet cell lineages. The four established pancreatic islet cell types were examined for coexpression of peptide YY in islets of normal and transgenic mice throughout development. Peptide YY immunoreactivity was identified in the earliest endocrine cells in the fetal pancreas and was coexpressed in each islet cell type during development. Peptide YY showed a high degree of co-localization with glucagon- and insulin-producing cells in early pancreatic development, but by adulthood, peptide YY was expressed in less than half of the alpha cells and was no longer expressed in beta cells. Peptide YY was also coexpressed with somatostatin and pancreatic polypeptide when these cell types first appeared, but most delta and pancreatic polypeptide cells continued to express peptide YY throughout development. The use of conditions that distinguish peptide YY from the related peptides, pancreatic polypeptide and neuropeptide Y, as well as the ability of the peptide YY gene to direct expression of a reporter gene in islets of transgenic mice, establishes expression of peptide YY in the earliest pancreatic endocrine cells.(ABSTRACT TRUNCATED AT 250 WORDS)