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Biomedical subjects

K Shimada

Publications and source records attributed to K Shimada.

At least 919 records · Page 51Linked to original sources

Are secondary bile acids in choledochal cysts important as a risk factor in biliary tract carcinoma?

Since secondary bile acids have mutagenic potency and choledochal cyst patients with or without cyst-enterostomy have a high risk of developing bile duct carcinoma, we examined the hypothesis that secondary bile acids are elevated in the choledochal cyst and possibly cause biliary tract carcinoma. Eleven choledochal cyst patients with or without previous cyst-enterostomy or biliary tract carcinoma, seven patients with biliary tract carcinoma not associated with choledochal cyst and five patients with cholecystolithiasis were examined. Samples were directly needle aspirated from the cyst or by cannulating a tube into the common bile duct through the cystic duct. The concentrations of each bile acid in these samples were quantified by gas-liquid chromatography and compared. Neither the relative composition nor the absolute concentration of secondary bile acids (deoxycholic acid, lithocholic acid) elevated in patients with choledochal cyst compared with the values in the non-choledochal cyst patients with or without biliary tract carcinoma. The presence of biliary tract carcinoma or previous cyst-enterostomy did not affect the concentrations of secondary bile acids. The results suggest that the factor other than secondary bile acids can be primarily responsible for the high risk of bile duct carcinoma in patients with choledochal cyst.

Adult↗

[Prevalence of HIV infection among stable female partners of seropositive men].

Prevalence of HIV transmission to female sexual partners of seropositive men is not known yet. In order to know the condition in Japan, 11 HIV-seropositive men (25-42 years old; mean +/- SD, 32.5 +/- 6.0) and their stable female partners (24-42 years old; mean +/- SD, 31.3 +/- 6.0) were analyzed. Seropositive men consisted of seven hemophiliacs including a hemophiliac with intravenous drug abuse, three men who acquired HIV infection through heterosexual contact, and a man with intravenous drug abuse. Six of them were asymptomatic carriers, two had AIDS-related complex, and three had AIDS. All of the female partners had no risk factors other than sexual contact with their stable, seropositive male partners, except one who used to inject intravenous drug. Four of 11 female partners (36%) were found to be infected with HIV. All of the male partners of infected females had AIDS or AIDS-related complex, and had CD4 counts fewer than 100 cells/microliters. Asymptomatic carriers and men with CD4 counts more than 200 cells/microliters did not transmit HIV to their partners: rate of transmission of HIV by symptomatic men was significantly higher than that by asymptomatic men (p < 0.01), and the rate by men with CD4 counts fewer than 100 cells/microliters was also significantly higher than that by men with larger CD4 counts (p < 0.01). HIV-p24 antigen was measured in 10 of 11 seropositive men. The antigen was positive in four men, and negative in six.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

Carnitine status and safety after administration of S-1108, a new oral cephem, to patients.

The metabolism and clinical safety of the pivalic acid-containing antibiotic S-1108, an orally active pro-drug cephalosporin, were investigated to assess the clinical effects, with special emphasis on the influence of carnitine consumption in 15 patients with various infectious diseases receiving S-1108 three times a day at a 300- or 600-mg total daily dose for 3 to 7 days. The free carnitine concentrations in plasma were greatly reduced to approximately 65% of pretreatment levels, and the plasma pivaloylcarnitine (the main metabolite of pivaloyloxymethyl ester) concentrations were increased during the 200-mg (three times a day) regimens but returned to the pretreatment levels within 3 to 5 days after the cessation of treatment. In three elderly patients with declining renal function (creatinine clearance rate, 31 to 50 ml/min), the acylcarnitine/free carnitine ratio increased from 0.1 to 0.4 up to 0.7 to 1.5 at day 5 during the 7-day treatment, showed a tendency to decrease, and then returned to the pretreatment ratio 4 days after discontinuation of the drug. The degree of free carnitine reduction and increase of the acylcarnitine/free carnitine ratio depended mostly on the dose and the duration of S-1108 treatment. The increased acylcarnitine/free carnitine ratio in elderly patients was due to reduction of the free carnitine concentration in plasma and mainly to the retardation of nontoxic pivaloylcarnitine excretion. This study indicated that there was a decrease in free carnitine levels in plasma, but there were no clinical symptoms or adverse effects associated with carnitine reduction in patients during the 7-day multiple administration of S-1108.

Administration, Oral↗

Increased expression of interleukin 6 mRNA in cardiac myxomas.

In three patients with cardiac myxoma increased expression of interleukin 6 (IL-6) mRNA was found in the myxoma tissue by polymerase chain reaction (PCR) and in situ hybridisation. These cases suggest that IL-6 is overproduced in the myxoma tissue and secreted into the systemic circulatory system. This might contribute to the systemic inflammatory or autoimmune manifestations seen in cardiac myxoma. This study also showed the usefulness of PCR and in situ hybridisation for the evaluation of mRNA expression in small samples of tissue.

Aged↗

Regulation of Na-K-ATPase gene expression by aldosterone in vascular smooth muscle cells.

Na-K-adenosinetriphosphatase (ATPase) activity profoundly influences vascular cell excitability, contractility, and volume regulation. The recent finding of mineralocorticoid hormone receptors in vascular tissue suggests the possibility that Na-K-ATPase gene expression in vascular tissue is regulated by the mineralocorticoid aldosterone. In this study, we investigated Na-K-ATPase gene expression by aldosterone in cultured rat vascular smooth muscle cells (VSMC). Na-K-ATPase alpha 1- and beta 1-isoform mRNAs, but not alpha 2- and alpha 3-isoform mRNAs, were expressed in cultured rat VSMC. Aldosterone caused a 2.3-fold increase in the alpha 1 mRNA and a 4.7-fold increase in the beta 1 mRNA accumulation with peak elevations at 24 and 6 h, respectively. Aldosterone induced the alpha 1 mRNA expression at physiological concentrations (half-maximum effective concentration = 2-3 nM), consistent with the binding of aldosterone to mineralocorticoid hormone receptors. The augmented alpha 1 mRNA expression by aldosterone was associated with a twofold increase in the alpha 1-subunit protein accumulation. Pretreatment of VSMC with cycloheximide caused a 10-fold increase in the alpha 1 mRNA expression, and the aldosterone-mediated alpha 1 mRNA accumulation was not observed in the presence of cycloheximide. Transfection experiments with the luciferase reporter gene revealed that aldosterone response sequences are located within the 5'-flanking regions of the alpha 1-isoform gene. These data demonstrate that the mineralocorticoid aldosterone directly stimulates Na-K-ATPase gene expression and protein accumulation in VSMC.

Aldosterone↗

Thyroid hormone stimulates Na(+)-K(+)-ATPase gene expression in cultured rat mesangial cells.

Thyroid hormone 3,3',5-triiodothyronine (T3) is an important regulator of Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) activity in a variety of mammalian target tissues. In the present study, we examined the expression of Na(+)-K(+)-ATPase alpha- and beta-subunit mRNAs by T3 in cultured rat mesangial cells. Northern blot analysis of total RNA isolated from cultured rat mesangial cells revealed the expression of mRNAs encoding Na(+)-K(+)-ATPase alpha 1- and beta 1-subunits; mRNAs encoding alpha 2- and alpha 3-subunits were undetectable. Exposure of mesangial cells to T3 (10(-8) M) caused a threefold increase in the alpha 1-mRNA expression, which was first detected at 6 h and sustained for at least 48 h. The beta 1-mRNA expression was gradually increased by T3, with a maximum fourfold elevation at 48 h. The 50% effective concentration (EC50) for the alpha 1- and beta 1-mRNA induction by T3 was approximately 10(-10) M. The half-life of alpha 1-mRNA analyzed by actinomycin D chase was approximately 3 h and was not affected by T3. The augmented alpha 1-mRNA expression by T3 was associated with a 2.4-fold increase in the alpha 1-subunit protein accumulation and a 1.6-fold increase in Na(+)-K(+)-ATPase activity. These data suggest that thyroid hormone stimulates Na(+)-K(+)-ATPase gene expression, protein accumulation, and enzyme activity in rat mesangial cells.

Animals↗

Homocysteine, a thrombogenic agent, suppresses anticoagulant heparan sulfate expression in cultured porcine aortic endothelial cells.

Previous studies showed that homocysteine, a thrombo-atherogenic and atherogenic agent, inhibits an endothelial thrombomodulin-protein C anticoagulant pathway. We examined whether homocysteine might affect another endothelial anticoagulant mechanism; i.e., heparin-like glycosaminoglycan-antithrombin III interactions. Incubations of porcine aortic endothelial cell cultures with homocysteine reduced the amount of antithrombin III bound to the cell surface in a dose- and time-dependent fashion. The inhibitory effect was observed at a homocysteine concentration as low as 0.1 mM, and the maximal suppression occurred at 1 mM of homocysteine after 24 h. In contrast with a marked reduction in the maximal antithrombin III binding capacity (approximately 30% of control), the radioactivity of [35S]sulfate incorporated into heparan sulfate on the cell surface was minimally (< 15%) reduced. The cells remained viable after homocysteine treatment. Although neither net negative charge nor proportion in total glycosaminoglycans of cell surface heparan sulfate was altered by homocysteine treatment, a substantial reduction in antithrombin III binding capacity of heparan sulfate isolated from homocysteine-treated endothelial cells was found using both affinity chromatography and dot blot assay techniques. The antithrombin III binding activity of endothelial cells decreased after preincubation with 1 mM homocysteine, cysteine, or 2-mercaptoethanol; no reduction in binding activity was observed after preincubation with the same concentration of methionine, alanine, or valine. This sulfhydryl effect may be caused by generation of hydrogen peroxide, as incubation of catalase, but not superoxide dismutase, with homocysteine-treated endothelial cells prevented this reduction, whereas copper augmented the inhibitory effects of the metabolite. Thus, our data suggest that the inhibited expression of anticoagulant heparan sulfate may contribute to the thrombogenic property resulting from the homocysteine-induced endothelial cell perturbation, mediated by generation of hydrogen peroxide through alteration of the redox potential.

Animals↗

Alterations of binding characteristics of alpha 1-,beta 1-adrenoceptors and Ca2+ binding sites in the myocardium of spontaneously hypertensive rats (SHR) by chronically administered bunazosin, atenolol, ketanserin and verapamil.

The effects of chronic treatment with bunazosin, atenolol, ketanserin and verapamil on the myocardium of the spontaneously hypertensive rat (SHR) were examined by the radioligand binding assay method using [3H]prazosin, [125I]iodocyanopindolol and [3H]nitrendipine binding to alpha 1- and beta 1-adrenergic receptors and Ca2+ binding sites. The norepinephrine concentration in the rat myocardium was also determined. (1) All of these drugs lowered the elevated blood pressure of the SHR. (2) Only ketanserin administration increased the Kd value of the alpha 1-adrenoceptor in the SHR. (3) Administration of atenolol and ketanserin to the SHR decreased the Bmax value of the beta 1-adrenoceptor. (4) Verapamil, bunazosin and atenolol also lowered the Bmax values of the Ca2+ binding sites of SHRs. (5) All drugs except for atenolol lowered the norepinephrine concentration in the myocardium of the SHR. These findings suggest that the SHR has an abnormality of the alpha 1- and beta 1-adrenoceptors and Ca2+ binding site of the myocardium, that the drugs had a beneficial effect on these receptors, that the drugs could also lower the high norepinephrine content in the myocardium of the SHR and that some of these drugs also affected the binding characteristics of other types of membrane receptors.

Adrenergic alpha-Antagonists↗

Cardiomyopathic hamster hearts: long-term effects of drugs on catecholamine contents and binding characteristics of alpha 1- and beta 1-adrenergic receptors.

Changes were examined in myocardial catecholamine content and alpha 1- and beta 1-adrenoceptors during the development of cardiomyopathy in Syrian hamsters (Bio 14.6) and age-matched healthy controls. In addition, the effects of bunazosin, atenolol, xamoterol, ketanserin, and verapamil on the catecholamine content and [3H]prazosin, [3H]CGP12177 bindings to alpha 1- and beta 1-adrenergic receptors of myocardium were compared with those of the controls. (1) Lower norepinephrine and dopamine levels were observed in 35-week-old cardiomyopathic hamster hearts than in the controls. There was, however, a tendency for a slight decrease of alpha 1- and beta 1-adrenoceptors in cardiomyopathic hamsters. (2) Administration of bunazosin induced lower dopamine values in 18-week-old cardiomyopathic hamsters. (3) Xamoterol induced a higher Kd value for beta 1-adrenoceptors and lower dopamine content than for those with cardiomyopathy. Ketanserin also induced a higher Bmax value than for cardiomyopathy. Thus, drug treatments clearly change catecholamine content and binding characteristics of the adrenoceptors which play an important role in the development of cardiac hypertrophy and heart failure.

Adrenergic alpha-Antagonists↗

Nucleotide sequence of the Clostridium stercorarium xynA gene encoding xylanase A: identification of catalytic and cellulose binding domains.

The nucleotides of the xynA gene of Clostridium stercorarium were sequenced. The structural gene consists of an open reading frame of 1533 bp encoding 511 amino acids with an M(r) of 56,519. The signal peptide cleavage site was identified by comparison with the N-terminal amino acid sequence of the enzyme produced by a recombinant Escherichia coli. Xylanase A consists of a catalytic domain belonging to family G at the N-terminus and two direct repeats of about 90 amino acids with a short spacing at the C-terminus. Deletion analysis showed that the repeated sequences were responsible for binding the enzyme to Avicel and were not essential for catalytic activity. The catalytic domain of this enzyme is highly homologous to xylanase A of Clostridium acetobutylicum (identity: 69%) and xylanase B of Bacillus pumilus (identity: 64%).

Amino Acid Sequence↗

Pneumocystis carinii pneumonia monitored by P. carinii shedding in sputum by the polymerase chain reaction.

This study investigated the efficacy of applying the polymerase chain reaction (PCR) technique to the monitoring of therapy to P. carinii pneumonia (PCP). The PCR method was sensitive enough to determine P. carinii shedding in sputum samples which was not detectable by Diff-Quik (International Reagent Corp., Kobe, Japan) stain. By PCR, P. carinii disappeared in sputa on days 8 to 15 after treatment. Clinical improvements correlated with the loss of detectable P. carinii. This study represents a potential usefulness of PCR to monitor P. carinii shedding in sputum during treatment.

Adult↗

Becker muscular dystrophy with early manifestation of left heart failure.

We encountered a case of dystrophin-verified Becker muscular dystrophy which exhibited left heart failure as an initial symptom but no subjective muscle weakness. Severe cardiac involvement has been thought to rarely occur in the early stage of this disease, however accurate diagnosis was limited until the dystrophin diagnosis became available. This case suggests that some cases of dilated cardiomyopathy might be Becker muscular dystrophy, and that dystrophin tests should be added to the conventional investigation of patients with dilated cardiomyopathy.

Adolescent↗

Pasteurella ureae endocarditis.

Pasteurella ureae is found in the normal human respiratory flora. We encountered a case of endocarditis caused by Pasteurella ureae. The patient was a 59-year-old man with a history of Staphylococcus aureus endocarditis. After treatment with antibiotics, blood cultures became negative, and the patient recovered completely. The incidence of endocarditis due to this organism is very rare; this case is the second clinically diagnosed case report.

Anti-Bacterial Agents↗

Patterns of jaw reflexes induced by incisal and molar pressure stimulation in relation to background levels of jaw-clenching force in humans.

Patterns of jaw reflexes induced by periodontal stimulation were examined in ten adults. Surface electromyograms (EMGs) from the masseter and anterior temporal muscles were recorded when pressure stimulation was applied to either an incisor or a molar. Reflex responses to periodontal pressure stimulation varied, depending on the background levels of jaw-clenching force that preceded stimulation (background clenching force, BCF). At low BCF, excitatory reflexes were elicited from the jaw-closing muscles and jaw-clenching force. However, the magnitude of excitatory reflexes varied with the location of the stimulated tooth along the dentition. While excitatory reflexes were induced equally in the masseter and temporal muscles during incisal stimulation, stronger excitatory reflexes were induced in the temporal muscle than in the masseter muscle during molar stimulation. At high BCF, inhibitory reflexes in the jaw-closing muscles and jaw-clenching force were elicited in eight subjects (group A) during periodontal stimulation. However, excitatory reflexes in the muscles and force were elicited in the remaining two subjects (group B). In the subjects of group A, stronger inhibitory reflexes were elicited in the temporal muscle than in the masseter muscle, and jaw-clenching force also decreased during both incisal and molar stimulation. In the subjects of group B, the magnitude of excitatory reflexes decreased with increases in BCF.

Adult↗

Fine structure and elemental analysis of the enamel in the cryptobranchid salamander Megalobatrachus japonicus.

Teeth from Megalobatrachus japonicus were prepared for scanning electron microscopy (SEM) and electron microprobe analyzer (EMPA) to assay the elements of the enamel layer. The enamel layer of each of tooth is thin and the arrangement of the enamel crystals is regular in the Megalobatrachus japonicus. Based on calcium, phosphate and magnesium levels of distribution, the calcification level of the enamel layer differs between the labial and lingual surfaces. Concentrations of iron and fluoride are located in both portions of the enamel layer as well. The presence of trace elements and distribution of calcified levels are related to the mineral formation in the enamel layer and function of the teeth during feeding.

Animals↗

Morphological study of the teeth of Ambystoma maculatum, Salamandra salamandra and Aneides lugubris: fine structure and chemistry of enamel.

The functional teeth of adult salamander (Caudata): Ambystoma maculatum, Salamandra salamandra and Aneides lugubris were prepared for transmission electron microscopy and electron microprobe analysis of the elements and trace elements of the enamel layer. The arrangement of enamel crystals in these species is variable. The outer part of the enamel layer in which hydroxyapatite elements (Ca, P) and trace elements (e.g., F, Fe, Mg) are concentrated, is most mineralized. The concentration of trace elements are arrangement of crystals in the enamel layer differed in these species, may be related to the pattern of mineralization of enamel.

Ambystoma↗