Increased histidine preference during specific alteration of rhythm of environmental temperature stress in rats.

It has been reported that specific alteration of rhythm of environmental temperature (SART) stress induces various physiological changes. In this study, changes in taste preference during SART stress were investigated in rats. Rats were given free access to six amino acid solutions, saline, and water in a choice paradigm. During SART stress, daily food intake increased significantly by 50% whereas the rate of body weight gain decreased significantly to one third that observed during the prestress baseline period. In addition, consumption of histidine solution increased significantly, whereas intakes of water, monosodium glutamate, saline, glycine, arginine, lysine, and threonine were unaffected. Results suggest that a specific preference for histidine emerges during SART stress, which may be related to the stress-induced changes in the histamine turnover in the brain and peripheral tissues. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Two mechanisms in the action of repressor deltaEF1: binding site competition with an activator and active repression

BACKGROUND: Counteraction between activators and repressors is crucial for the regulation of a number of cell-specific enhancers, where an activator and a repressor are mutually competitive in binding to the same site. DeltaEF1 is a repressor protein of delta1-crystallin minimal enhancer DC5 binding at the CACCT site, and inhibits activator deltaEF3 from binding to the overlapped site. It has two zinc finger clusters N-fin and C-fin, close to N- and C-termini, respectively, and a homeodomain in the middle. deltaEF1 also binds to the E2-box sequence CACCTG, and represses E2-box-dependent enhancers. RESULTS: The mechanism of the repressor action of deltaEF1 was investigated by examining various deletion mutants of deltaEF1 for their activity to repress delta1-crystallin enhancer fragment HN which contained DC5 sequence and an additional activator site. Both zinc finger clusters were found to be essential for DNA binding and repression, but the homeodomain was not. In addition, the NR domain close to the N-terminus was required for full repression. The NR domain showed active repression when fused to the Gal4 DNA binding domain. Active repression by deltaEF1, dependent on the NR domain, was also demonstrated in a situation where the binding sites of deltaEF1 and deltaEF3 were separated. N-fin and C-fin in their isolated forms bind the 5'-(T/C)ACCTG-3' and 5'-(t/C)ACCT-3' sequences, respectively, while the homeodomain showed no DNA binding activity. An analysis of DNA binding of the delta(Int)F form, having both N-fin and C-fin, indicated that a single DNA binding domain is assembled from two zinc finger clusters. CONCLUSION: Two mechanisms are involved in the repressor action of deltaEF1. First, a binding site competition with an activator which depends on the integrity of both zinc finger clusters, and second, an active repression to silence an enhancer which is attributed to the NR domain.     

Planning for PACS at Osaka University Hospital.

We have a plan to adopt PACS as a medical image information system in the new hospital. In order to construct PACS suitable for our hospital, a preliminary survey was carried out to determine how PACS should be introduced and what are the physicians requirements for a new medical image system. The most important requirement of the physicians was a good quality workstation. Our plan of a new medical image information system is as follows. A primary database will be constructed according to each of modalities in the Department of Radiology. In the Department of Medical Information Science, we will make a secondary database according to the patient. Although it may be difficult for us to obtain a sufficient budget digitalizing all medical images by our move to the new hospital, our goal is to establish total PACS throughout the new hospital in 1995.     

Influence of step-like portions on the surface of ZnO/glass SAWfilters on their frequency characteristics

The frequency amplitudes of surface acoustic wave (SAW) filters mass produced of zinc oxide (ZnO) films on glass were found to be different among the filters even when their center frequencies are the same. We attempted various experiments In order to reduce the deviation of amplitudes. We accidentally found that the frequency characteristics and the amplitude deviation could be improved by mirror-polishing the ZnO film surface. In a SAW filter with a ZnO/interdigital transducer (IDT)/glass substrate structure, periodic step-like portions due to the thickness of the finger electrode of IDT and fine roughness were present on the ZnO film surface. As a result of investigating the effect of surface structure on amplitude deviation, the step-like portions did not affect the electromechanical coupling factors but reduced the SAW phase velocities, experimentally and theoretically. In addition, it was clarified that the step-like portions due to the finger electrodes and fine roughness on the ZnO surface caused deviations in the SAW velocities and their reflections, causing the deviation in the amplitude characteristics     

Role of a signal transduction pathway which controls disassembly of microfilament bundles and suppression of high-molecular-weight tropomyosin expression in oncogenic transformation of NRK cells

Role of disassembly of microfilament bundles and suppression of high-molecular-weight tropomyosin (TM) expression in growth factor- and various oncogene-induced transformation was studied by using NRK cells and its transformation-deficient mutants. In NRK cells which show a transformed phenotype by treatment with EGF and TGF-beta, cellular stress fibers became dissociated by EGF or EGF and TGF-beta combination, whereas TGF-beta alone caused thicker appearance of stress fibers. Accompanying these changes, the expression of TM isoforms 1 and 2 was suppressed by treatment with EGF or EGF and TGF-beta, but elevated by TGF-beta with similar time courses. On the other hand, the transformation-deficient mutant cell lines, 39-1 and 39-3, did not show the transformed phenotypes by treatment with EGF and TGF-beta. Neither EGF nor EGF and TGF-beta combination affected cellular stress fibers and expression of TM isoforms 1 and 2 in both mutant lines. The relationship between the formation of stress fibers and the expression of TM isoforms was consistent in NRK cells, the mutant lines and their various oncogene-expressing sublines under various culture conditions. NRK cells overexpressing exogenous mouse TM isoform 2 showed markedly decreased susceptibility to EGF-induced dissociation of stress fibers and decreased anchorage-independent growth potential in the presence of EGF and TGF-beta. These results indicate that the transformation-deficient NRK mutant lines, 39-1 and 39-3 have defects in an EGF signal transduction pathway which induces suppression of high-molecular-weight TM expression and disassembly of microfilament bundles and suggested that the activation of the pathway is important for morphological transformation and oncogenic growth in growth factors- and various oncogene-induced transformation of NRK cells.     

Effects of FK506 on experimental membranous glomerulonephritis induced by cationized bovine serum albumin in rats

BACKGROUND: There have been no reports on the effect of FK5 06, a new immunosuppressive agent, on experimental membranous glomerulonephritis (MN) induced by an exogenous antigen. Therefore we investigated the effects of FK506 on MN induced by cationized bovine serum albumin (C-BSA) in rats. METHODS: Two weeks after the rats were immunized with 1 mg of C-BSA and Freund's complete adjuvant, they received intravenous injections of 3 mg/kg of C-BSA 3 times weekly for 4 weeks. Rats were divided into four groups: group A (n = 5) received intramuscular injections of 3 mg/kg of FK506 daily for 5 days beginning 2 days before the first immunization; group B (n =4) received 1 mg/kg of FK506 daily for 2 weeks beginning 2 weeks after the first immunization; and group C (n =4) received 1 mg/kg of FK506 daily for 2 weeks beginning 4 weeks after the first immunization. Group D (n = 5) received no FK506 and served as the control group. Rats were sacrificed 8 weeks after the first immunization. RESULTS: Administration of FK506 in the preimmunization stage almost completely suppressed the development of MN in group A. Histological findings in groups B and C were similar to those in group D, the control group. However, urinary protein excretion was significantly lower in group B (24+/-46 mg/day) and C (220+/-44 mg/day) than in group D (330+/-61 mg/day). Expression of intracellular adhesion molecule-1 in glomeruli and the number of leukocyte functioning-associated molecules-1 were significantly decreased in groups A, B, and C compared with the control group. Administration of FK506 was not associated with any significant side-effects or histological abnormalities. The whole-blood trough levels of FK506 in groups B and C were 9.1 ng/ml and 9.2 ng/ml respectively. CONCLUSIONS: The efficacy of FK506 was significantly increased when the drug was administered in the early phase of immunization in this model. The present study suggests that FK506 may be useful in patients with intractable nephrotic syndrome such as MN.     

Fluidity and Tableting Characteristics of a Powder Solid Dispersion of the Low Melting Drugs Ketoprofen and Ibuprofen with Crospovidone

ABSTRACT

A powder solid dispersion system (SD) of ketoprofen (KP) or ibuprofen (IP), which possess low melting points, plus crospovidone (CrosPVP), have good fluidity characteristics and can be used to formulate tablets. Tablets of KP or IP in the SD of adequate hardness within a narrow weight range can be prepared by direct compression. Addition of microcrystalline cellulose (MCC) resulted in greater hardness characteristics and less variation in tablet weight. Forces during the tableting process were measured with a tableting process analyzer (TabAll) equipped with a single-punch for determining capping and sticking properties during the tableting process. Pressure transmission ratio from the upper to the lower punch and die wall force were increased by adding 1% magnesium stearate (MS) to the SD. Ejection force decreased when MS was added to the SD. When tablets of the IP SD were prepared without excipient, scraper pressure (SP) was large, resulting in sticking. However, addition of 1% MS, lowered the SP value and eliminated sticking. Thus, an SD of compounds with a low melting point such as KP or IP is suitable for tablet manufacture by direct compression with the addition of 1% MS.     

Ultrastructural changes in colonic epithelial cells in a rat model of inflammatory bowel disease

Inflammatory bowel disease (IBD) is a global, chronic intractable disease. The functions of drugs and food components have been evaluated in models of IBD induced by 2,4,6‐trinitrobenzene sulfonic acid (TNBS). Here, we used transmission (TEM) and osmium‐maceration scanning (SEM) electron microscopy to evaluate the ultrastructure of colonic epithelial cells in rat models of IBD induced by TNBS. Histological evaluation revealed that the intestinal crypts in the most regions of the IBD‐model colons were deformed and we classified them as having high cell migration rates (HMIG). The remaining regions in the intestinal crypts retained a relatively normal structure and we classified them as having low cell migration rates (LMIG). Osmium‐maceration SEM revealed the mucosal fluid flowing in spaces without secretory granules in crypt goblet cells of both HMIG and LMIG regions, indicating the depletion of goblet cell mucin that is found in patients with IBD. The Golgi apparatus in absorptive cells was stacked and curled in both regions. Osmium‐maceration SEM showed membrane network structures resembling endoplasmic reticulum that were large and expanded in absorptive cells with HMIG rather than with LMIG regions in IBD‐model colons. These findings indicated that endoplasmic reticulum stress is associated with susceptibility to IBD and that the effects of various agents can be evaluated according to endoplasmic reticulum stress revealed by using electron microscopy in models of IBD induced by TNBS.