Nitroreduction of nitrated and C-9 oxidized fluorenes in vitro

Intracerebroventricular administration of neuropeptide Y to normal rats induces a syndrome characterised by obesity, hyperinsulinaemia, insulin resistance and over expression of the adipose tissue ob gene. Little is known about the effect of circulating neuropeptide Y on glucose metabolism, insulin secretion and leptin. We therefore aimed to evaluate the effect of an intravenous infusion of neuropeptide Y on glucose disposal, endogenous glucose production, whole body glycolytic flux, and glucose storage as assessed during euglycaemic hyperinsulinaemic clamp. In addition, the insulin-stimulated glucose utilisation index in individual tissues was measured by the 2-deoxy-[1-3H]-glucose technique. The effect of neuropeptide Y on insulin secretion was evaluated by hyperglycaemic clamp. Infusion did not induce any change in endogenous glucose production during basal conditions or at the end of the clamp. Glucose disposal was significantly increased in the rats given neuropeptide Y compared with controls (27.8 +/- 1.3 vs 24.3 +/- 1.6 mg x min(-1) x kg(-1); p < 0.05) as was the glycolytic flux (18.9 +/- 1.6 vs 14.4 +/- 0.8 mg x min(-1) x kg(-1); p < 0.05), while glucose storage was comparable in the two groups. In skeletal muscle, the glucose utilisation index was increased significantly in rats given neuropeptide Y. The glucose utilisation index in subcutaneous and epididimal adipose tissue was not significantly different between the two groups. Plasma leptin was significantly increased by hyperinsulinaemia, but was not affected by neuropeptide Y infusion. Both the early and late phase of the insulin response to hyperglycaemia were significantly reduced by neuropeptide Y. In conclusion neuropeptide Y infusion may increase insulin-induced glucose disposal in normal rats, accelerating its utilisation through the glycolytic pathway. Neuropeptide Y reduces both phases of the insulin response to hyperglycaemia.     

APOE in non-Alzheimer amyloidoses: transmissible spongiform encephalopathies

We have identified a member of the VEGF family by computer-based homology searching and have designated it VEGF-D. VEGF-D is most closely related to VEGF-C by virtue of the presence of N- and C-terminal extensions that are not found in other VEGF family members. In adult human tissues, VEGF-D mRNA is most abundant in heart, lung, skeletal muscle, colon, and small intestine. Analyses of VEGF-D receptor specificity revealed that VEGF-D is a ligand for both VEGF receptors (VEGFRs) VEGFR-2 (Flk1) and VEGFR-3 (Flt4) and can activate these receptors. However. VEGF-D does not bind to VEGFR-1. Expression of a truncated derivative of VEGF-D demonstrated that the receptor-binding capacities reside in the portion of the molecule that is most closely related in primary structure to other VEGF family members and that corresponds to the mature form of VEGF-C. In addition, VEGF-D is a mitogen for endothelial cells. The structural and functional similarities between VEGF-D and VEGF-C define a subfamily of the VEGFs.     

Abdominal and thoracoabdominal aortic aneurysm

Most abdominal aortic aneurysms (AAA) and thoracoabdominal aortic aneurysms (TAAA) are asymptomatic and are found on physical exam or incidentally during radiological studies for other indications. These aneurysms are repaired primarily because their risk of rupture increases geometrically as the size exceeds 5 cm. The potential morbidity of intraoperative visceral and spinal ischemia involved with TAAA repair may be reduced with various adjunctive maneuvers.     

v-raf suppresses apoptosis and promotes growth of interleukin-3-dependent myeloid cells

Interleukin-3 (IL-3) is required for the proliferation, survival and differentiation of myeloid progenitors. In the absence of IL-3, murine myeloid 32D.3 cells accumulate in the G1 phase of the cell cycle and subsequently undergo programmed cell death, or apoptosis. Here we demonstrate that enforced expression of the v-raf oncogene suppresses apoptosis of myeloid 32D.3 cells following the withdrawal of IL-3. Surprisingly, steady state levels of Bcl-2, an oncogene known to suppress apoptosis, were not dependent upon IL-3 in 32D.3 cells and its levels were not augmented in v-raf clones. This suggests that ability of v-raf to suppress apoptosis in the absence of ligand is either Bcl-2 independent or that v-raf kinase promotes Bcl-2 function. v-raf also promoted growth of these cells in the presence of IL-3. v-raf clones proliferated at an increased rate due to a shortened G1 phase and had decreased requirements for IL-3 for growth. Therefore, transformation of myeloid cells by v-raf involves signaling pathways which promote both cell cycle progression and cell survival.     

Inactivity of N229A thymidylate synthase due to water-mediated effects: isolating a late stage in methyl transfer

Mutation of thymidylate synthase N229(177) to alanine results in an essentially inactive enzyme, yet it leads to formation of a stable ternary complex. The kinetics of N229(177)A show that kcat for Escherichia coli is reduced by 200-fold while the Km for dUMP is increased 200-fold and the Km for folate increased by tenfold versus the wild-type enzyme. The crystal structures of N229(177)A in complex with dUMP and CB3717, and in complex with dUMP alone are determined at 2.4 A, and 2.5 A resolution. These structures identify the covalently bound ternary complex and show how N229(177)A traps an intermediate, and so becomes inactive in a later step of the reaction. Since the smaller alanine side-chain at N229(177)A does not directly sterically impair binding of ligands, the structures implicate, and place quantitative limits on the involvement of the structured water network in the active site of thymidylate synthase in both catalysis and in determining the binding affinity for dUMP (in contrast, the N229(177)V mutation in Lactobacillus casei has minimal effect on activity).     

Varix of the vortex vein ampulla simulating choroidal melanoma: report of four cases

Increasing evidence demonstrates that ultraviolet A radiation (UVA) contributes to photoaging, which results in the accumulation of massive amounts of abnormal elastic material in the dermis of photoaged skin. To study UVA-induced photoaging in an in vivo system, we utilized a line of transgenic mice containing the human elastin promoter linked to a chloramphenicol acetyl transferase reporter gene. Our prior work demonstrates promoter activation in response to ultraviolet B radiation (UVB), UVA, and psoralen plus ultraviolet A radiation in the skin of these mice. The addition of psoralen (8-MOP) prior to administration of UVA results in substantial increases in promoter activation, as compared with UVA alone. To demonstrate the utility of these mice as a model of UVA-induced photodamage, we administered four lotions to the skin of our transgenic mice that included: a sunscreen containing octyl methoxycinnamate and benzophenone-3 with a sun protection factor (SPF) of 15, the UVA filter butyl methoxydibenzoylmethane, the SPF 15 sunscreen and the UVA filter together, and the lotion vehicle alone. Following sunscreen administration, mice received a single psoralen plus ultraviolet A radiation treatment. All sunscreens decreased chloramphenicol acetyl transferase activity with the SPF 15 sunscreen, the UVA filter, and the combination SPF 15 sunscreen and UVA filter, resulting in increasing degrees of protection against psoralen plus ultraviolet A radiation. These results demonstrate that this model functions as a rapid and sensitive model of UVA photodamage for the identification and comparison of compounds that protect against UVA-induced photoaging.     

The Numbing Scale: psychometric properties, a preliminary report

Twenty-one antimicrobial agents were incorporated individually into Frey's agar to evaluate their inhibitory activities against 86 isolates of avian mycoplasmas recently detected in Taiwan. Among them, 45 and 37 isolates were found positive with Mycoplasma gallisepticum and Mycoplasma synoviae fluorescent antibody conjugate, respectively. Twenty-one other isolates were unable to be identified by the above 2 conjugates. All of the field isolates were highly sensitive (with MIC50 < 1 microgram/ml) to enrofloxacin, gentamicin, myplabin, tiamutin and tylosin. However, those field isolates were highly resistant (with MIC50 > 32 micrograms/ml) to apramycin, chlortetracycline (CTC), erythromycin (ER), flumequine (FI), nalidixic acid (NA), oxolinic acid (OA), oxytetracycline (OTC) and spiramycin (SP). The inhibitory activities of the antibiotics which possessed an MIC90 of 50 micrograms/ml or less against local isolates were, in decreasing order, enrofloxacin (< 0.004 microgram/ml), gentamicin (1.53 micrograms/ml), tiamutin (1.81 micrograms/ml), tylosin (3.2 micrograms/ml), streptomycin (SM; 12.0 micrograms/ml), colistin (13.1 micrograms/ml), chloramphenicol (14.0 micrograms/ml), spectinomycin (15.0 micrograms/ml), myplabin (16.0 micrograms/ml), spiramycin (30.0 micrograms/ml), minocycline (32.0 micrograms/ml). The MIC90 of OA, CTC, SM, FI, SP, OTC, ER or NA was greater than 50 micrograms/ml; which work poorly in the control of mycoplasmoses. Since the antibiotic control policy is quite loose in Taiwan, many antimicrobial agents are often freely used in clinics, with a resulting gradual decrease in the inhibitory activity to the avian mycoplasmas.     

Do resources bolster coping and does coping buffer stress? An organizational study with longitudinal aspect and control for negative affectivity

Psychiatric workers facing redeployment completed questionnaire measures of stressors, resources (locus of control and perceived social support), coping, well-being, and negative affectivity, at baseline (N = 109) and 1 year later (loss of 7 participants). Regression analyses of the baseline data suggested that as stressors increased, so did avoidance coping, but less so for those high in internality or perceived social support. Problem-focused coping was bolstered by internality and emotion-focused coping by perceived social support. Other regression analyses, with a longitudinal aspect, suggested that stressors had a deleterious effect on well-being. Problem- and emotion-focused coping had beneficial effects, whereas avoidance coping had a (delayed) deleterious effect. These effects of coping were predominantly main and not buffering effects.