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Biomedical subjects

Masami Murakami

Publications and source records attributed to Masami Murakami.

13 recordsLinked to original sources

Expression of type 2 iodothyronine deiodinase in corticotropin-secreting mouse pituitary tumor cells is stimulated by glucocorticoid and corticotropin-releasing hormone.

We identified the presence of iodothyronine deiodinase in AtT-20 mouse pituitary tumor cells that secrete corticotropin. Iodothyronine deiodinating activity in AtT-20 cells fulfills all the characteristics of type 2 iodothyronine deiodinase (D2), including the inhibition by thyroid hormones, the insensitivity to inhibition by 6-propyl-2-thiouracil, and the low Michaelis-Menten constant value for T4. Northern analysis using mouse D2 cRNA probe demonstrated the hybridization signal of approximately 7.0 kb in size in AtT-20 cells. D2 activity and D2 mRNA were stimulated by glucocorticoid in a dose-dependent manner but were not stimulated by testosterone or beta-estradiol. D2 expression was stimulated by (Bu)2cAMP, and CRH in a dose-dependent manner in the presence of dexamethasone. These results suggest the previously unrecognized role of local thyroid hormone activation by D2 in the regulation of pituitary corticotrophs.

Adrenocorticotropic Hormone↗

High-density lipoprotein stimulates endothelial cell migration and survival through sphingosine 1-phosphate and its receptors.

OBJECTIVE: Plasma high-density lipoprotein (HDL) level is inversely correlated with the risk of atherosclerosis. However, the cellular mechanism by which HDL exerts antiatherogenic actions is not well understood. In this study, we focus on the lipid components of HDL as mediators of the lipoprotein-induced antiatherogenic actions. METHODS AND RESULTS: HDL and sphingosine 1-phosphate (S1P) stimulated the migration and survival of human umbilical vein endothelial cells. These responses to HDL and S1P were almost completely inhibited by pertussis toxin and other specific inhibitors for intracellular signaling pathways, although the inhibition profiles of migration and survival were different. The HDL-stimulated migration and survival of the cells were markedly inhibited by antisense oligonucleotides against the S1P receptors EDG-1/S1P1 and EDG-3/S1P3. Cell migration was sensitive to both receptors, but cell survival was exclusively sensitive to S1P1. The S1P-rich fraction and chromatographically purified S1P from HDL stimulated cell migration, but the rest of the fraction did not, as was the case of the cell survival. CONCLUSIONS: HDL-induced endothelial cell migration and survival may be mediated by the lipoprotein component S1P and the lipid receptors S1P1 and S1P3.

Cell Adhesion↗

Relationship between gastric disease and deletion of cag pathogenicity island genes of Helicobacter pylori in gastric juice.

The cag pathogenicity island genes of Helicobacter pylori (ie, cag1, cag5, cagT, cagE, and cagA) were detected by PCR in DNA extracted from endoscopically collected gastric juice, and the relationship between these genes and gastric disease was studied in 25 patients with early gastric cancer, 9 patients with gastric ulcer, and 15 patients with chronic active gastritis. In three patients with early gastric cancer and one patient with gastric ulcer, cag pathogenicity island genes were amplified although H. pylori was not detected by conventional methods. Compared with conventional methods, the sensitivity of detection of cag genes was 92.3% (36/39) and the specificity was 60% (6/10). Among the patients with cagA amplification, only cagE was not amplified in one case each with early cancer and chronic active gastritis. In addition, none of cag1, cag5, cagT, and cagE were amplified in spite of cagA amplification in one patient with gastric ulcer. This method is a simple procedure, has a high sensitivity, and appears to be useful for accurate assessment of infection with cagA-positive strains. Because deletion of cag PAI genes was found in the patients with all three gastric diseases that we studied, it was suggested that the pathogenicity of H. pylori might not be determined by cag PAI genes in those cases.

Aged↗

Hormone replacement therapy causes a decrease in hepatocyte growth factor in hypertensive women.

OBJECTIVE: Serum hepatocyte growth factor (HGF) is associated with blood pressure. We investigated whether the serum HGF level differs between hypertensive and normotensive postmenopausal women (PMW) and whether hormone replacement therapy (HRT) alters the serum HGF level and blood pressure in hypertensive and normotensive PMW. DESIGN: Prospective observational study. METHODS: A total of 33 PMW with mild to moderate essential hypertension controlled by antihypertensive treatment (mean age, 57 +/- 6 years) and 23 normotensive PMW (mean age, 57 +/- 7 years) received continuous HRT (0.625 mg of conjugated equine estrogen combined with 2.5 mg of medroxyprogesterone acetate) once a day orally for 12 months, and we measured serum HGF levels and blood pressure before and 12 months after the start of HRT. RESULTS: The baseline serum HGF level was significantly higher in hypertensive PMW than in normotensive PMW. HRT significantly decreased the serum HGF level in hypertensive subjects, from 2.85 +/- 0.64 pmol/l to 2.49 +/- 0.65 pmol/l (P < 0.001), but not in normotensive subjects. HRT did not change blood pressure in either group. CONCLUSIONS: Serum HGF level before the start of HRT was higher in the hypertensive PMW than in the normotensive PMW. Furthermore, HRT decreases serum HGF without decreasing blood pressure in hypertensive PMW. The HRT-induced decrease in serum HGF was greater in hypertensive PMW than in normotensive PMW, and the decrease was independent of blood pressure changes.

Aged↗

Presence of Pseudomonas putida strains harboring plasmids bearing the metallo-beta-lactamase gene bla(IMP) in a hospital in Japan.

To determine the persistence and spread of antibiotic-resistant strains in Gunma University Hospital, 83 Pseudomonas putida strains (each from a different patient) were isolated from January 1997 through December 2001. Of the 83 strains isolated, 27 were resistant to carbapenems. All 27 produced metallo-beta-lactamase and were found to be PCR positive for the bla(IMP) gene. Most (22 strains) were primarily isolated from the wards (W7 [9 strains] and W4 [8 strains]). Another five bla(IMP)-positive P. putida strains from wards W7 and W4 were obtained by swabbing around the water pipes. A total of 32 bla(IMP)-positive P. putida strains were assessed by pulsed-field gel electrophoresis (PFGE) and testing of drug susceptibility to 10 chemotherapeutic agents. Both PFGE and MIC patterns revealed that there were long-term resident strains among inpatients and hospital environments. The bla(IMP) genes of 22 of 32 strains were all transferable to a recipient strain of Pseudomonas aeruginosa by conjugation or transformation and conferred resistance to carbapenems and cephems. The bla(IMP) plasmids were conjugally transmissible among P. aeruginosa strains and mediated resistance to amikacin as well as beta-lactams. Ten of the 22 plasmids mediated additional resistance to gentamicin and tobramycin. Plasmids with identical DNA and drug resistance patterns were found in P. putida strains with identical PFGE patterns and with different PFGE patterns. We presumed that P. putida was one of the resident species in inpatients and especially in hospital environments, spreading drug resistance genes via plasmids among P. putida strains and supplying them to more pathogenically important species, such as P. aeruginosa.

Conjugation, Genetic↗

Hormone replacement therapy decreases insulin resistance and lipid metabolism in Japanese postmenopausal women with impaired and normal glucose tolerance.

OBJECTS: To investigate the effect of combined estrogen and progesterone therapy on insulin resistance (IR) and carbohydrate and lipid metabolism in postmenopausal women (PMW) with impaired (IGT) and normal glucose tolerance (NGT). METHODS: Sixteen Japanese PMW with IGT and 33 with NGT received daily oral hormone replacement therapy (HRT; 0.625 mg of conjugated equine estrogen plus 2.5 mg of medroxyprogesterone acetate) for 12 months. As controls, 13 Japanese PMW with IGT and 31 with NGT were enrolled and not treated by HRT. Fasting plasma glucose (FPG), fasting immunoreactive insulin (IRI), and IR were measured in each subject at study initiation and 12 months later. We used homeostasis model assessment (HOMA) to determine IR. RESULTS: FPG and HOMA IR were decreased in both HRT groups, and fasting IRI was reduced in the HRT-NGT group. In controls, FPG, fasting IRI, and HOMA IR were unaltered. Total and low-density lipoprotein cholesterol were decreased and high-density lipoprotein cholesterol was increased in both HRT groups, but triglyceride was unchanged. In controls, lipid metabolism was unaltered. CONCLUSION: HRT decreased IR and improved carbohydrate and lipid metabolism in Japanese PMW with IGT and NGT. These beneficial effects argue for the use of HRT in PMW with IGT as well as NGT.

Asian People↗

Effects of angiotensin II receptor antagonists on insulin resistance syndrome and leptin in sucrose-fed spontaneously hypertensive rats.

In order to investigate the usefulness of angiotensin II type 1 receptor (AT1) antagonists (ARA) in the treatment of hypertension with insulin resistance syndrome, we studied the effects of a high dose sucrose diet and ARA on insulin sensitivity, plasma lipids, and leptin in spontaneous hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). SHR and WKY were divided into three groups and treated for 12 weeks: those fed a standard chow, those given a sucrose-rich chow or those given a sucrose-rich chow and ARA. While in SHR the weight of both subcutaneous and mesenteric adipose tissue was greater in the sucrose-rich chow fed animals than in the standard chow fed animals, ARA treatment significantly decreased the weights of both subcutaneous and mesenteric adipose tissue. ARA treatment decreased free fatty acid and triglyceride in SHR, and increased high density lipoprotein cholesterol in SHR and WKY. Homeostasis model assessment-insulin resistance (HOMA-IR) index, plasma levels of leptin, and leptin mRNA in mesenteric adipose tissue were significantly greater in the sucrose-rich chow fed animals than in the standard chow fed animals, and significantly lower in the ARA-treated sucrose-rich chow fed animals than in the sucrose-rich chow fed animals in both SHR and WKY. ARA improved insulin resistance, and reduced plasma leptin and leptin mRNA in adipose tissue. These results suggest that the improvement of insulin resistance by ARA may be attributed, at least in part, to the reduction of adipose tissue weight. It is concluded that ARA is useful in the treatment of patients with hypertension and concomitant insulin resistance syndrome.

Adipose Tissue↗

Effects of hormone replacement therapy on circulating docosahexaenoic acid and eicosapentaenoic acid levels in postmenopausal women.

Hormone replacement therapy (HRT) has antiatherosclerotic effects of which the mechanism remains unclear. The ingestion of fish oil or other sources of n-3 polyunsaturated fatty acids has been included in comprehensive strategies to prevent atherosclerosis. Many epidemiologic studies have shown that the dietary intake of docosahexaenoic acid and eicosapentaenoic acid has antiatherosclerotic effects. We investigated the effect of HRT on plasma docosahexaenoic acid and eicosapentaenoic acid concentrations in postmenopausal women. Fifty-nine postmenopausal women, who received conjugated estrogens (0.625 mg/day) and medroxyprogesterone (2.5 mg/day) for 12 months, and 45 control postmenopausal women, who did not receive HRT, volunteered to participate in this study. Plasma docosahexaenoic acid and eicosapentaenoic acid concentrations were measured at baseline and at 6 and 12 months after the start of HRT. HRT significantly increased the plasma docosahexaenoic acid and eicosapentaenoic acid concentrations from 134 +/- 5 microg/ml and 69 +/- 4 microg/ml at baseline to 156 +/- 7 microg/ml and 85 +/- 7 microg/ml after 12 months (both p<0.01). However, the control group showed no significant change in their plasma docosahexaenoic acid and eicosapentaenoic acid levels during the study. HRT increased plasma docosahexaenoic acid and eicosapentaenoic acid levels in postmenopausal women. We propose that the increase in docosahexaenoic acid and eicosapentaenoic acid may be partially responsible for the beneficial mechanisms by which HRT induces an antiatherosclerotic effect in postmenopausal women.

Adult↗

[Study on blood rheology measured by MC-FAN].

We investigated the effects of various factors on blood rheology, which was evaluated by the passage time of heparinized whole blood using MC-FAN (Micro Channel array Flow ANalyzer). The time for 100 microliters of whole blood to pass through a microchannel array (Bloody 6-7) was determined. Each passage time was corrected by the saline passage time determined just before the measurement of sample blood. Our results suggest that blood rheology measured by MC-FAN is related to aging, body weight, body mass index and serum lipid parameters (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglyceride). These results suggest that MC-FAN is useful to analyze blood rheology in pathophysiological conditions.

Adult↗

[Studies on electroencephalographic changes after liver transplantation].

EEG was performed before and after surgery in the patients who received living donor livers at our hospital between 1999 and 2001. There were ten patients (6 men and 4 women) and mean ages were 37.0 years. Their disorders were citrullinemia, biliary atresia, liver cirrhosis, and liver cell cancer. EEG was performed at 17 sites according to 10-20 international methods. Power spectra analysis using FFT was also performed. We classified the ten patients into Group A, one patient; Group B, three patients; and Group C; five patients based on EEG basal activity before the operation. Eight of ten patients showed improvement in EEG findings, and two patients showed no change after the operation. One patient of these two patients did not show improvement in liver function after the operation. The other developed cerebral infarction after the operation. EEG is useful for the evaluation of brain function after the liver transplantation.

Adult↗

Type 1 iodothyronine deiodinase in the house musk shrew (Suncus murinus, Insectivora: Soricidae): cloning and characterization of complementary DNA, unique tissue distribution and regulation by T(3).

The house musk shrew Suncus murinus (Insectivora: Soricidae) has been reported as having low thyroxine to 3,3'5-triiodothyronine (T(3)) converting activity in liver and kidney homogenates and was assumed to be type 1 iodothyronine deiodinase (D1)-deficient. To study whether this is due to structural abnormality of shrew D1, we cloned the cDNA and characterized the enzyme. The deduced amino acid sequence of shrew D1 was found to be highly homologous to other known D1s and the enzyme itself to have similar catalytic activity. However, unlike in other species, the D1 activity was detected only in liver. Moreover, the D1 activity in liver of the shrew was less than half of that in rat liver and its expression was not up-regulated by T(3). In contrast, a very high activity of D2 was demonstrated in brain and brown adipose tissue. The present study also revealed that the serum level of T(3) in the shrew was in the same range as these in other mammals. These results suggest that D2 contributes to the production and maintenance of T(3) levels in the house musk shrew.

Adipose Tissue, Brown↗

The antipsoriatic effect of thiamazole is not accompanied either by significant changes in blood lymphocyte subsets nor by serum concentration of TNF-alpha.

It has been reported that the antithyroid thiourethylenes, propylthiouracil and methimazole can bring about significant clinical improvement in patients with psoriasis vulgaris. In this paper, we reconfirmed the clinical usefulness of the antithyroid drug thiamazole, which is similar to methimazole, in Japanese patients with psoriasis vulgaris. We further asked whether the clinical improvement was linked to the changes in some immunological parameters or not. To answer this question, we analyzed peripheral blood lymphocyte subsets and measured serum concentrations of TNF-alpha and IL-1beta in 13 patients with psoriasis vulgaris before and during thiamazole administration. The mean percentage of CD4+ HLA-DR+ lymphocytes in the patients was constantly elevated before and 12 weeks after the administration. The patients treated with thiamazole showed a significant increase in the ratio of CD4+/CD8+ at the 4th week, though it declined at the 8th and 12th week. Other lymphocyte subsets showed no significant change during the treatment. The concentrations of serum TNF-alpha exhibited no significant change during thiamazole administration. Serum concentration of IL-1beta was under the detection level. These results indicate that thiamazole may improve the psoriatic lesion via other immune mechanisms, or the effects can not be reflected by the peripheral lymphocyte subsets and cytokine which we investigated.

Adult↗