Outbreak of Japanese spotted fever in the southeastern part of Awaji Island.
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Disease Outbreaks↗
Biomedical subjects
T Noguchi
Publications and source records attributed to T Noguchi.
Multiple gastric carcinomas 21 years after gastrojejunostomy without gastrectomy. Report of a case.
We report a case of gastric carcinoma after gastrojejunostomy (GJ-stomy) without gastrectomy. Multiple gastric carcinomas were discovered 21 years after GJ-stomy without gastrectomy which had been performed for treatment of pyloric stenosis due to severe gastric ulcer. Multiple gastric carcinomas were found in the stomach, or the esophagocardiac junction, and in the corpus and anastomotic lesion of the GJ-stomy. Under the light microscope, intestinal metaplasia was detected in the antral mucosa and the area around the anastomosis. In immunohistochemical analysis, p53-specific antibodies gave a positive reaction in every gastric carcinoma and in the noncancerous gastric glands around the carcinoma at the anastomosis and in the corpus. Cells positive for immunostaining with Ki-67-specific antibodies were more numerous in all gastric carcinomas and in the area around the anastomotic lesion than in the normal gastric mucosa. Hsp70-specific antibodies reacted with cells in the noncancerous glands around the carcinoma in the anastomotic area. Mucosal injury and the potential for carcinogenesis due to exposure to gastroduodenal reflux are discussed. The results of this study suggest that similar cases with gastroduodenal reflux should be followed carefully.
Adenocarcinoma↗
Intravascular free tissue factor pathway inhibitor is inversely correlated with HDL cholesterol and postheparin lipoprotein lipase but proportional to apolipoprotein A-II.
To elucidate the distribution and clinical implications of tissue factor pathway inhibitor (TFPI) concentrations, we measured TFPI levels consisting of preheparin free, lipoprotein-bound (Lp-bound), and endothelial cell-anchor pools in 156 patients with coronary artery disease (average age, 61.2+/-9.1 years; range, 32 to 78 years) by heparin infusion (50 IU/kg) and compared them with the preheparin TFPI levels of 229 healthy subjects (average age, 59. 6+/-9.4 years; range, 41 to 80 years). The patients had lower preheparin free TFPI and lower HDL cholesterol (HDL-C) levels than the healthy subjects with equivalent Lp-bound forms (free TFPI, 15. 9+/-6.5 versus 19.2+/-8.1 ng/mL). In a partial correlation analysis, the preheparin free TFPI levels were shown to be inversely correlated with the HDL-C concentrations in both the patients (r=-0. 454, P<0.001) and the healthy subjects (r=-0.136, P<0.05). As determined by comparison of preheparin and postheparin plasma, the patients generally showed preheparin free TFPI <10%, Lp-bound TFPI at 30%, and endothelial cell-anchor TFPI at 60%. When the patients were divided into 4 categories by their LDL cholesterol (LDL-C, 130 mg/dL) and HDL-C (40 mg/dL) levels to specify their coronary risks, the low-HDL-C groups had significantly increased preheparin and postheparin free TFPI levels and decreased postheparin LPL levels, whereas the high-LDL-C groups showed increased levels of Lp-bound TFPI. In a partial correlation analysis, we found a proportional relation between postheparin free TFPI and apolipoprotein A-II (r=0. 5327) and between HDL-C and LPL (r=0.4906), whereas postheparin free TFPI was inversely correlated with HDL-C (r=-0.4280) and postheparin LPL (r=-0.4791). The inverse relationship between TFPI and LPL suggests that increased free TFPI concentrations as a compensatory response of the endothelium to prevent atherothrombotic processes compete with and displace LPL on endothelial surface, resulting in reduced LPL and low HDL-C.
Adult↗
Unwashed shed blood infusion causes deterioration in right ventricular function after coronary artery surgery.
We investigated right ventricular function after infusion of unwashed shed blood collected from mediastinal and chest tube drainage. Changes in thromboxane B2 (TXB2) and 6-keto-PGF1 alpha, which are stable metabolites of thromboxane A2 (TXA2) and prostacyclin respectively, were also investigated. The amount of infused shed blood was 484 +/- 76 ml (mean +/- SD). Right ventricular ejection fraction decreased rapidly after the infusion and did not return to its original level until 120 minutes later (P < 0.05). Mean pulmonary artery pressure rose after infusion of the shed blood (P < 0.05). The TXB2 level in the unwashed shed blood was about 20,000 times higher than the preoperative plasma level. The plasma TXB2 level at 30 minutes after the infusion was significantly elevated (P < 0.05), and at 120 minutes it had returned to the original level. Unwashed shed blood may contain vasoactive substances that induce the release of TXA2 and increase right ventricular afterload.
6-Ketoprostaglandin F1 alpha↗
Antitumor effects of a novel lipophilic platinum complex (SM-11355) against a slowly-growing rat hepatic tumor after intra-hepatic arterial administration.
The antitumor effects of cis[((1R,2R)-1,2-cyclohexanediamine-N,N')bis(myristato)] platinum(II) (SM-11355) were evaluated in a rat hepatic tumor model, and were compared with those of cisplatin (CDDP). A novel slowly-growing rat hepatic tumor model was established by the successive transplantation of rat AH109A tumor into the liver. The drugs, which were suspended in Lipiodol, were administered into the proper hepatic artery of tumor-bearing rats. Tumor growth was suppressed in the group that received SM-11355 suspended in Lipiodol (SM-11355/Lipiodol). Mean tumor growth rates in the groups administered 20 microl of Lipiodol containing 0, 0.02, 0.04, 0.1, 0.2, or 0.4 mg of SM-11355 were 244, 86, 110, 81, 51, and 40%, respectively, 1 week after treatment. Those in the groups administered 20 microl of Lipiodol containing 0.1, 0.2, or 0.4 mg of CDDP were 240, 110, and 45%, respectively. In the groups administered 0.2 and 0.4 mg of SM-11355 or 0.4 mg of CDDP, massive necrosis was observed in the tumor tissue 1 week after drug administration, and the tumors disappeared 4 weeks after drug administration. Serum glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) levels were measured as markers of liver damage one day after the drug was administered into the hepatic artery of rats. The minimum toxic dose, which raised serum GOT and GPT levels significantly compared with Lipiodol alone, was 0.2 mg for SM-11355/Lipiodol and 0.1 mg for CDDP/Lipiodol, respectively. The results demonstrated that SM-11355/Lipiodol exerted antitumor activity at a dose that showed no hepatic toxicity in the rat model, but CDDP/Lipiodol did not.
Alanine Transaminase↗
In vitro cytotoxicity of cis[((1R,2R)-1,2-cyclohexanediamine-N,N')bis(myristato)] platinum(II) suspended in lipiodol in rat hepatoma AH-109A cells and human tumor cell lines.
SM-11355, cis[((1R,2R)-1,2-cyclohexanediamine-N,N ')bis(myristato)] platinum(II), is a lipophilic platinum complex. SM-11355 suspended in Lipiodol (SM-11355/Lipiodol) was shown to have antitumor activity against hepatic tumors after intra-hepatic arterial administration in animal models. In this study, the in vitro growth inhibitory activities of SM-11355 and cisplatin (CDDP) following 7-d drug exposure were examined using rat ascite hepatoma AH-109A cells and various human tumor cell lines. In monolayer or suspension cell cultures, SM-11355 did not inhibit the cell growth, whereas SM-11355/Lipiodol had dose-dependent growth inhibitory activities, as did CDDP suspended in Lipiodol (CDDP/Lipiodol). This was also the case in the colony formation assay in agarose gel. CDDP/Lipiodol released platinum compound into the culture medium rapidly, whereas SM-11355/Lipiodol released it slowly but constantly for 7 d. Furthermore, a significant amount of platinum was detected in the cells treated with CDDP/Lipiodol and SM-11355/Lipiodol. These results suggest that Lipiodol plays an important role in the in vitro cytotoxicity of SM-11355, and certain platinum compounds released from SM-11355/Lipiodol have growth inhibitory effects on these cells.
Animals↗
In vitro release of SM-11355, cis[((1R,2R)-1,2-cyclohexanediamine-N,N')bis(myristato)] platinum(II) suspended in lipiodol.
SM-11355, cis[((1R,2R)-1,2-cyclohexanediamine-N,N')bis(myristato)] platinum(II) is a lipophilic platinum complex. SM-11355 suspended in Lipiodol (SM-11355/Lipiodol) was previously shown to have antitumor effects against rat hepatic tumors after intra-arterial administration. In the present study, the in vitro release of platinum compounds from SM-11355/Lipiodol was examined. A test tube containing 10 ml of saline and 1 ml of SM-11355/Lipiodol was rotated at 5 rpm in a vertical orientation. The platinum concentration in saline gradually increased for 28 d. From HPLC analysis, cyclohexane-1,2-diamineplatinum(II) dichloride (DPC) and cyclohexane-1,2-diamineplatinum(II) chloroiodide (DPCI) were detected in the saline, and the sum of these two compounds was equivalent to the total platinum amount in the saline determined by atomic absorption spectrophotometry at days 21 and 28. DPC showed significant growth inhibitory activities, with IC50 values of 0.1-0.7 nmol/ml in rat hepatoma AH-109A cells and 5 human tumor cell lines, as effective as cisplatin. These findings suggest that SM-11355/Lipiodol exerts antitumor effects by releasing active platinum compounds, and that DPC is one of the candidates of the active compounds.
Animals↗
Refractory coronary spasm relieved by intracoronary administration of nicorandil.
Two patients in whom coronary spasm was refractory to intracoronary injection of nitroglycerin were relieved by intracoronary administration of nicorandil (a nitrate and potassium channel opener) during catheterization. These findings suggest that nicorandil may prove useful as an additional therapeutic agent.
Adult↗
Molecular cloning and expression of the nucleoside deoxyribosyltransferase-II gene from Lactobacillus helveticus.
Nucleoside deoxyribosyltransferase-II, which catalyzes transfer of glycosyl residues from a donor deoxynucleoside to an acceptor base, was purified from Lactobacillus helveticus and its gene was cloned. Analysis of the nucleotide sequence showed the presence of a 474-nucleotide open reading frame encoding a protein of 158 amino acids with a molecular weight of 18,317. The active enzyme can be produced in large quantities in E. coli cells using the cloned gene.
Amino Acid Sequence↗
An efficient method for production of uridine 5'-diphospho-N-acetylglucosamine.
Uridine 5'-diphospho-N-acetylglucosamine (UDP-GlcNAc) has been synthesized by a yeast-based method from 5'-UMP and glucosamine, in which yeast cells catalyze the conversion of 5'-UMP to 5'-UTP and provide enzymes involved in UDP-GlcNAc synthesis using 5'-UTP and glucosamine as substrates. However, this conventional method is not suitable for practical production of UDP-GlcNAc because of the low yield of the product. We found that the yqgR gene product of Bacillus subtilis, which has been identified as a glucokinase, can catalyze the phosphorylation of N-acetylglucosamine (GlcNAc) to give GlcNAc-6-phosphate, an intermediate of UDP-GlcNAc biosynthesis. The addition of the yqgR gene product to the yeast-based reaction system enabled us to synthesize UDP-GlcNAc using GlcNAc in place of glucosamine. The addition of two enzymes, GlcNAc-phosphate mutase and UDP-GlcNAc pyrophosphorylase, increased the yield of UDP-GlcNAc. Using this novel method, UDP-GlcNAc was produced at an amount of 78 mM from 100 mM 5'-UMP and 100 mM GlcNAc.
Amino Acid Sequence↗
Assessment of in vivo oxidative stress in hypertensive rats and hypertensive subjects in Tanzania, Africa.
Oxidative stress has been reported to be involved in not only cardiovascular diseases but in hypertension, which is a major risk for cardiovascular diseases. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) has been recognized as a sensitive biomarker of oxidative DNA damage and also of oxidative stress. In the present study, we assessed the oxidative stress in human subjects with hypertension and in hypertensive rats. In stroke-prone spontaneously hypertensive rats at the age of 14 weeks, the excretion of urinary 8-OHdG was significantly (p < 0.05) increased compared with that in age-matched normotensive Wistar-Kyoto rats. Next, we investigated the relationship between oxidative DNA damage and cardiovascular risk factors among Tanzanians aged 46-58 years in a population study carried out in 1998 in at Dar es Salaam, Tanzania, according to the WHO-CARDIAC Study Protocol. Sixty subjects (male/female, 28/32) were selected by SPSS Base 8.0 from those who completed a 24-h urine collection. The 24-h urinary 8-OHdG of the hypertensive subjects (SBP > or =140 mmHg and/or DBP > or =90 mmHg) was significantly (p < 0.05) higher than that of the normotensive subjects (SBP <140 mmHg and DBP <90 mmHg) after adjusting for age and gender (Hypertensives: 17.31 +/- 2.0 ng/mg creatinine, n=38; Normotensives: 10.10 +/- 2.64 ng/mg creatinine, n=22). Oxidative stress was thought to be involved in hypertensive subjects and in hypertensive rats.
8-Hydroxy-2'-Deoxyguanosine↗
Evolution of urate-degrading enzymes in animal peroxisomes.
The end product of purine metabolism varies from species to species. The degradation of purines to urate is common to all animal species, but the degradation of urate is much less complete in higher animals. The comparison of subcellular distribution, intraperoxisomal localization forms, molecular structures, and some other properties of urate-degrading enzymes (urate oxidase, allantoinase, and allantoicase) among animals is described. Liver urate oxidase (uricase) is located in the peroxisomes in all animals with urate oxidase. On the basis of the comparison of intraperoxisomal localization forms, mol wt, and solubility of liver urate oxidase among animals, it is suggested that amphibian urate oxidase is a transition form in the evolution of aquatic animals to land animals. Allantoinase and allantoicase are different proteins in fish liver, but the two enzymes form a complex in amphibian liver. The subcellular localization of allantoinase and allantoicase varies among fishes. Hepatic allantoinase is located both in the peroxisomes and in the cytosol in saltwater fishes, and only in the cytosol in freshwater fishes. Hepatic allantoicase is located on the outer surface of the peroxisomal membrane in the mackerel group and in the peroxisomal matrix in the sardine group. Amphibian hepatic allantoinase-allantoicase complex is probably located in the mitochondria. On the basis of previous data, changes of allantoinase and allantoicase in molecular structure and intracellular localization during animal evolution may be as follows: Fish liver allantoinase is a single peptide with a mol wt of 54,000, and is located both in the peroxisomes and in the cytosol, or only in the cytosol. Fish liver allantoicase consists of two identical subunits with a mol wt of 48,000, and is located in the peroxisomal matrix or on the outer surface of the peroxisomal membrane. The evolution of fishes to amphibia resulted in the dissociation of allantoicase into subunits, and in the association of allantoinase with the subunit of allantoicase. This amphibian enzyme was lost by further evolution.
Amidohydrolases↗
Amino acid regulation of gene transcription of rat insulin-like growth factor-binding protein-1.
To investigate the molecular mechanisms of increased transcription of the insulin-like growth factor-binding protein-1 (IGFBP-1) gene in dietary protein-deprived animals, the cis-acting sequence that is involved in this regulation was analyzed. We first showed that IGFBP-1 gene transcription was up-regulated by amino acid deprivation in cultured liver cell lines: H4IIE and HuH-7. Since HuH-7 cells showed a greater increase in IGFBP-1 mRNA in response to amino acid deprivation, this cell line was used in further experiments. Using a promoter function assay, we found that up-regulation of promoter activity responding to amino acid deprivation was abolished by deleting the region between -112 and -81 bp from the cap site from the gene construct. This cis-acting region includes the insulin-responsive element (IRE) and glucocorticoid responsive element (GRE) of IGFBP-1. In summary, the present observation suggests that the 32-bp (-112 to -81) in the IGFBP-1 gene 5' promoter region is involved in the induction of the IGFBP-1 gene in response to amino acid deprivation.
Amino Acids↗
Gene expression of the three members of hepatocyte nuclear factor-3 is differentially regulated by nutritional and hormonal factors.
Hepatocyte nuclear factor-3 (HNF-3) belongs to a large family of forkhead transcription factors and is made up of three members (HNF-3alpha, -3beta and -3gamma). It has been shown that HNF-3 regulates a number of metabolically important genes. However, the mechanisms underlying this regulation of HNF-3 activity by hormones and nutrition have not yet been well elucidated. In attempting to explore the regulation of gene expression of HNF-3 members by physiological status, we analyzed the effects of insulin, dexamethasone and protein malnutrition on the hepatic mRNA level of each member. Male Wistar rats were fed on a 12% casein diet, 12% gluten diet (deficient in lysine and threonine) or a protein-free diet for 1 week. The protein-free diet and gluten diet caused a 3. 7-fold increase in HNF-3g mRNA in the liver and did not affect the mRNA level of either HNF-3alpha or HNF-3beta. Daily administration of dexamethasone caused the mRNA levels of HNF-3alpha and HNF-3beta to increase (2.3- and 1.4-fold, respectively), but had no effect on the HNF-3gamma mRNA level. In diabetic rats that had been injected with streptozotocin, an elevation of the hepatic mRNA levels of HNF-3beta and HNF-3gamma was observed (1.6-and 1.9-fold, respectively). Insulin replacement in the diabetic rats decreased both mRNA levels in a dose-dependent manner. HNF-3alpha mRNA was not affected by insulin status. These results show that the genes of the three members of the HNF-3 family respond differently to hormonal and nutritional factors suggesting that the activities of HNF-3 members are regulated, at least in part, by the levels of their gene expression.
Animals↗
Chronic inhalation toxicity and carcinogenicity studies of 3-chloro-2-methylpropene in BDF1 mice.
Chronic toxicity and carcinogenicity studies of 3-chloro-2-methylpropene (CMP), which has been widely used as an insecticide and chemical intermediate, were carried out in BDF1 mice. CMP was administered to mice in groups of 50 male and 50 female mice by the inhalation route 5 days per week for 104 weeks at doses of 0, 50, 100 or 200 ppm. Male and female mice in the CMP-exposed groups had decreased body weight but no noticeable clinical signs when compared with the control group. Dose-related increases in the incidences of gastric mucosal hyperplasia and squamous cell papilloma were observed in both sexes, and squamous cell carcinoma was observed in only one male mouse in the 100 ppm group. An increased incidence of Harderian gland adenoma in female mice was also recognized. In the nasal cavity, eosinophilic exudate associated with atrophy of olfactory epithelia, respiratory metaplasia of olfactory epithelia and olfactory gland, and eosinophilic changes in respiratory and olfactory epithelia were increased in both sexes.
Allyl Compounds↗
New multifunctional percutaneous transluminal coronary angioplasty catheter device capable of balloon inflation, local drug delivery and coronary perfusion.
A new percutaneous transluminal coronary angioplasty catheter with multiple functions of balloon inflation, local drug delivery and coronary perfusion has been devised. The device consists of an inflatable lumen, a drug delivery lumen, and a perfusion (or guide wire) lumen. A drug can be infused from the port located distal to the inflated balloon during continuous blood perfusion via the perfusion lumen. Fluorescence-labeled heparin and peroxidase administered using the device permeated into denuded vessel tissues during ongoing perfusion and remained there for over 24 hr. This prototype device indicates the potential therapeutic implications of the concepts of the device.
Angioplasty, Balloon, Coronary↗
Inorganic polyphosphate and polyphosphate kinase: their novel biological functions and applications.
In this review, we discuss the following two subjects: 1) the physiological function of polyphosphate (poly(P)) as a regulatory factor for gene expression in Escherichia coli, and 2) novel functions of E. coli polyphosphate kinase (PPK) and their applications. With regard to the first subject, it has been shown that E. coli cells in which yeast exopolyphosphatase (poly(P)ase), PPX1, was overproduced reduced resistance to H2O2 and heat shock as did a mutant whose polyphosphate kinase gene is disrupted. Sensitivity to H2O2 and heat shock evinced by cells that overproduce PPX1 is attributed to depressed levels of rpoS expression. Since rpoS is a central element in a regulatory network that governs the expression of stationary-phase-induced genes, poly(P) affects the expression of many genes through controlling rpoS expression. Furthermore, poly(P) is also involved in expression of other stress-inducible genes that are not directly regulated by rpoS. The second subject includes the application of novel functions of PPK for nucleoside triphosphate (NTP) regeneration. Recently E. coli PPK has been found to catalyze the kination of not only ADP but also other nucleoside diphosphates using poly(P) as a phospho-donor, yielding NTPs. This nucleoside diphosphate kinase-like activity of PPK was confirmed to be available for NTP regeneration essential for enzymatic oligosaccharide synthesis using the sugar nucleotide cycling method. PPK has also been found to express a poly(P):AMP phosphotransferase activity by coupling with adenylate kinase (ADK) in E. coli. The ATP-regeneration system consisting of ADK, PPK, and poly(P) was shown to be promising for practical utilization of poly(P) as ATP substitute.
Adenosine Triphosphate↗
Protective effects of imidapril on He-Ne laser-induced thrombosis in cerebral blood vessels of stroke-prone spontaneously hypertensive rats.
Inhibitors of angiotensin converting enzyme (ACE) have been developed recently for therapeutic purposes in hypertension and ischemic cardiovascular diseases. Ogiku et al. reported that one such inhibitor, imidapril, significantly prolonged survival in stroke-prone spontaneously hypertensive rats (SHRSP). The present study was designed to investigate the effect of imidapril on cerebral blood vessels in SHRSP to clarify role of the ACE inhibitor in mechanisms of cerebral thrombosis and stroke. Imidapril was administered orally at 1.0 and 5.0 mg/kg/day for 3 weeks from the age of 7 weeks, and was shown to prevent the usual increase in blood pressure seen in these animals. It also delayed He-Ne laser-induced cerebral thrombosis and increased significantly the plasma concentration of nitric oxide metabolites (NO2/NO3). To confirm the association between nitric oxide (NO) and these effects of imidapril, an inhibitor of nitric oxide synthase, N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME) was dissolved in drinking water and administered to the animals for 3 weeks. Four of six rats died from stroke when L-NAME was given alone. When imidapril (5.0 mg/kg/day) was administered with L-NAME, however, the animals showed no signs or symptoms of stroke. In these instances, therefore, the concurrent administration of L-NAME with imidapril reversed significantly the effects of imidapril. Intravenous injection of imidaprilat (100 microg/kg), an active metabolite of imidapril, also decreased blood pressure significantly and increased the plasma levels of NO2/NO3 after 5 min. Moreover, imidaprilat enlarged arteriolar diameters and caused an increase in red cell velocity and mean blood flow in pial arterioles after 15 min. The results strongly suggested that imidapril protects cerebral vessels in SHRSP by elevating the release of NO, thereby improving the cerebral circulation and reducing the tendency to thrombosis and stroke.
Angiotensin-Converting Enzyme Inhibitors↗