Hemodynamics of pancreatic ischemia in cardiogenic shock in pigs

BACKGROUND & AIMS: Previous studies have shown that the renin-angiotensin axis plays a pivotal role in vasoconstriction of the gastric, intestinal, and hepatic circulations during cardiogenic shock. The aim of this study was to evaluate the fundamental hemodynamic mechanism of pancreatic ischemia during cardiogenic shock induced by pericardial tamponade. METHODS: Cardiogenic shock was induced by pericardial tamponade. Cardiac output (and total peripheral vascular resistance) was determined by thermodilution. Pancreatic blood flow (and vascular resistance) was determined with radiolabeled microspheres. RESULTS: Graded increases in pericardial pressure produced corresponding decreases in cardiac output to 42% +/- 1% and arterial pressure to 67% +/- 3% of baseline and increases in total peripheral vascular resistance to 146% +/- 5% of baseline. Pancreatic blood flow decreased disproportionately to 30% +/- 3% of baseline, because of a disproportionate increase in pancreatic vascular resistance to 220% +/- 19% of baseline. Previously confirmed blockade of the renin-angiotensin axis ablated this response, whereas confirmed blockade of the alpha-adrenergic system or vasopressin system had no significant effect. Without shock, central intravenous infusions of angiotensin II closely mimicked this selective vasoconstriction. CONCLUSIONS: Angiotensin-mediated selective pancreatic vasoconstriction results in significant pancreatic ischemia during cardiogenic shock.     

Opposite effects of tumour necrosis factor-alpha on type I and III collagen gene expression by human dermal fibroblasts in monolayer and three-dimensional cultures

An HIV-1 infected immunosuppressed patient (CD4+ cell counts: 382 cells/microL; viral load 94,000 copies/mL) with recurrent perianal herpes simplex virus type 2 (HSV-2) infections is described, showing an unusual exophytic tumour resembling a squamous cell carcinoma in the lateral part of the tongue. He also had persistent facial herpes infection, oral candidosis, oral hairy leukoplakia and lymphadenopathy. The presence of HSV-2 was detected by polymerase chain reaction both in smears and in a tissue biopsy taken from the involved tongue area. Treatment with brivudin, a new oral virustatic drug, led to rapid regression of the tumour.     

Primary biliary cirrhosis sera recognize not only gp210 but also proteins of the p62 complex bearing N-acetylglucosamine residues from rat liver nuclear envelope. Anti-p62 complex antibody in PBC

We have recently observed reactivity of primary biliary cirrhosis (PBC) sera with several proteins bearing N-acetylglucosamine residues from rat liver nuclear envelopes. The aim of this study was to characterize the reactive antigens. Sera from 31 patients with PBC, 30 with rheumatoid arthritis (RA) and 30 with Sj?gren's syndrome (SS) were examined. Rim-like immunofluorescence staining was observed in 15 of 31 (48%) sera from patients with PBC, in 1 of 30 with RA and in 1 of 30 with SS. Upon immunoblotting using preparations of whole rat liver nuclear envelopes and their Triton X 100-KCl extract as antigen sources, a 200 kDa protein band was observed in 9 of sera with PBC. Furthermore, upon immunoblotting using the wheat germ aggulutinin-bound fraction of rat liver envelope as antigen, 62, 60 and 54 kDa protein bands corresponding to components of the p62 complex in the nuclear pore complex (Kita et al. Biochem. 113, 377-382) were observed in 7, 5 and 6 samples respectively, of the 31 PBC sera. Our data suggest that PBC sera recognize not only the 210 kDa protein but also the p62 complex proteins.     

Optimization of alignment in semiconductor lithography equipment

Recent enhanced integration of semiconductors permits less and less overlay error at exposure. Accordingly, higher-order alignment adjustment, which considers not only linear but also nonlinear error components, has been recently carried out. However, conventional higher-order alignment adjustment methods are based on least squares, and thus are only approximation approaches toward the goal of maximizing die yields. In particular, outliers taking place at exposure or alignment measurement strongly affect alignment adjustment and decrease die yields. From such a background, this paper models a problem finding optimal higher-order alignment adjustment under the purpose of maximizing die yields as an integer programming problem. Furthermore, we evaluate the proposed method based on integer programming and conventional least-squares approaches using numerical simulation. The experimental results demonstrate that the proposed method produces a solution that is excellent compared to the conventional approaches, irrespective of existence of outliers.     

Structural Biology-Based Exploration of Subtype-Selective Agonists for Peroxisome Proliferator-Activated Receptors

Progress in understanding peroxisome proliferator-activated receptor (PPAR) subtypes as nuclear receptors that have pleiotropic effects on biological responses has enabled the exploration of new subtype-selective PPAR ligands. Such ligands are useful chemical biology/pharmacological tools to investigate the functions of PPARs and are also candidate drugs for the treatment of PPAR-mediated diseases, such as metabolic syndrome, inflammation and cancer. This review summarizes our medicinal chemistry research of more than 20 years on the design, synthesis, and pharmacological evaluation of subtype-selective PPAR agonists, which has been based on two working hypotheses, the ligand superfamily concept and the helix 12 (H12) holding induction concept. X-ray crystallographic analyses of our agonists complexed with each PPAR subtype validate our working hypotheses.     

Primary cutaneous histoplasmosis in papuloerythroderma (Ofuji)

We report the first Japanese patient with primary cutaneous histoplasmosis who was infected inside Japan. He was not an immunocompromised host but his cutaneous lesions developed on preexisting papuloerythroderma (Ofuji). The long-term topical corticosteroid treatment for papuloerythroderma, which could have suppressed the local immunological defence system of the skin, might have been responsible for the histoplasma infection in the present case.     

Effects of GABA antagonists on spectral responses of horizontal cells in the carp retina

Previous experiments have shown that, in the carp retina, a GABA-mediated feedback from horizontal cells to cones is involved in neural mechanisms of color opponency. In this article, we investigated effects of GABA antagonists, picrotoxin and bicuculline, on spectral responses of horizontal cells. These chemicals caused selective suppression of responses to long wavelength, probably because the feedback was blocked. In particular, a biphasic spectral response curve in the H2 cell turned into almost monophasic. The presence of feedback in the carp retina was further supported by the fact that depolarizing synaptic potentials were detected in cones at the center, when horizontal cells were hyperpolarized by a peripheral annulus illumination.