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Biomedical subjects

A Kawaguchi

Publications and source records attributed to A Kawaguchi.

At least 73 records · Page 4Linked to original sources
PubMed1999

Effects of thyrotropin on the proliferation and differentiation of cultured rat preadipocytes.

Thyrotropin receptor (TSHR) is expressed during the differentiation of rat preadipocytes and is highly abundant in mature fat adipocytes, but its physiological role is unknown. In this article, long-term effects of thyrotropin (TSH) on the proliferation and the differentiation were investigated using cultured rat preadipocytes. When TSH was added at the beginning of differentiation, TSH increased the number of preadipocytes and 3H-thymidine uptake. Apoptosis of the cells was not influenced by TSH. Preadipocytes incubated in the presence of TSH had fewer fat droplets, decreased level of mRNA for lipoprotein lipase (LPL), a marker of adipocyte differentiation. Histochemical study showed that the cells that increased their number and expressed lower level of LPL in response to TSH were preadipocytes, and not contaminating fibroblasts. In conclusion, TSH causes the proliferation and inhibits the differentiation of rat preadipocytes. Results suggest that TSH may be a potent regulator of preadipocyte proliferation and differentiation in vivo.

Adipocytes↗
PubMed1999

Relapsing polychondritis diagnosed by Tc-99m MDP bone scintigraphy.

PURPOSE: Relapsing polychondritis is a generalized recurring disease of cartilage that involves joints, trachea, bronchi, laryngeal cartilages, costal cartilages, and cartilages of the ear and nose. It is associated with autoimmune diseases, including Hashimoto disease in some cases. METHODS: The authors evaluated a 29-year-old man with relapsing polychondritis who had symptoms and signs of a common cold for 2 months and anterior chest pain near the sternum for 1 month. RESULTS: After the diagnosis, the authors found that the patient had a history of thyroid therapy for hyperthyroidism 15 years before. Tc-99m MDP bone scintigraphy performed to evaluate anterior chest pain showed diffusely increased accumulation of radioactivity in all costocartilages and sternoclavicular joints. Based on that information, relapsing polychondritis was diagnosed. Ga-67 citrate scintigraphy was preformed to determine the optimum biopsy site of the cartilage. The diagnosis was histologically supported by the results of the open biopsy. CONCLUSIONS: In this case, Tc-99m MDP bone scintigraphy was useful for diagnosing relapsing polychondritis, and Ga-67 citrate scintigraphy was helpful in determining the biopsy site.

Adult↗
PubMed1999

Fasting insulin and leptin serum levels are associated with systolic blood pressure independent of percentage body fat and body mass index.

OBJECTIVE: To examine the relationship between leptin and insulin serum levels and systolic and diastolic blood pressure in young men. SETTING: Kobe University of Mercantile Marine, Kobe, Japan. PARTICIPANTS: One hundred and ninety-eight male students aged 18-20 years (comprising 100% of those eligible). DESIGN AND MEASUREMENTS: A cross-sectional survey of a sample of male college students was performed, with measurements to include anthropometry, blood pressure and blood tests after overnight fasting. RESULTS: Compared with 90 men with an optimal blood pressure, 56 men with high-normal and high blood pressure had an increase in body mass index (23.7 +/- 5.2 versus 20.4 +/- 2.2 kg/m2), percentage body fat (21.7 +/- 8.0 versus 16.3 +/- 4.2%) and serum leptin (3.7 +/- 4.7 versus 1.5 +/- 0.8 ng/ml). In addition, they had greater serum insulin (59 +/- 31 versus 43 +/- 12 pmol/l) despite there being no differences in plasma glucose, resulting in a reduction of the ratio of glucose to insulin (x 10(6)) (107 +/- 43 versus 126 +/-, which is an estimate of insulin sensitivity in a nondiabetic population. Furthermore, the 56 men had higher serum triglyceride levels, although there was no difference in low density lipoprotein-cholesterol and high density lipoprotein-cholesterol between men with optimal and high-normal plus high blood pressure. Similar differences were found between men in a top versus low tertile of systolic and diastolic blood pressure. In multiple regression analysis, both log leptin and log insulin emerged as determinants for systolic blood pressure independent of body mass index and percentage body fat, but an association with diastolic blood pressure was only shown for log leptin. CONCLUSION: Hyperleptinemia and hyperinsulinemia may be regulators of arterial pressure, independent of body mass index or percentage body fat.

Adipose Tissue↗
PubMed1999

[Histologic occurrence of Barrett's carcinoma].

It is generally agreed that the diagnosis of Barrett's esophagus is justified when the columnar epithelium 3 cm or more from the E-C junction is involved. Microscopically, the epithelium has three distinct appearances: (1) gastric fundic type; (2) junctional type: and (3) specialized columnar type. In mucin histochemistry in 6 cases of Barrett's carcinoma, 5 cases of Barrett's esophagus were positive for HID-AB. Four cases of Barrett's carcinoma were also positive. These results suggest that Barrett's carcinoma developed from the specialized columnar type of Barrett's esophagus.

Barrett Esophagus↗
PubMed1998

Increased expression of the sodium/iodide symporter in papillary thyroid carcinomas.

Iodide is concentrated to a much lesser extent by papillary thyroid carcinoma as compared with the normal gland. The Na+/I- symporter (NIS) is primarily responsible for the uptake of iodide into thyroid cells. Our objective was to compare NIS mRNA and protein expression in papillary carcinomas with those in specimens with normal thyroid. Northern blot analysis revealed a 2.8-fold increase in the level of NIS mRNA in specimens with papillary carcinoma versus specimens with normal thyroid. Immunoblot analysis using anti-human NIS antibody that was produced with a glutathione S-transferase fusion protein containing NIS protein (amino acids 466-522) showed the NIS protein at 77 kD. The NIS protein level was elevated in 7 of 17 cases of papillary carcinoma but was not elevated in the normal thyroid. Immunohistochemical staining revealed abundant NIS in 8 of 12 carcinomas, whereas NIS protein was barely detected in specimens with normal thyroid. Although considerable patient-to-patient variation was observed, our results indicate that NIS mRNA is elevated, and its protein tends to be more abundant, in a subset of papillary thyroid carcinomas than in normal thyroid tissue.

Carcinoma, Papillary↗
PubMed1998

Ligand-inducible retinoid X receptor-mediated protein: DNA interactions in the retinoic acid receptor beta2 gene promoter in vivo.

Retinoid X receptors (RXRs) are recently characterized transcription factors that are members of the nuclear hormone receptor superfamily. However, it is not known whether the endogenous RXR complex requires its ligand for access to its hormone response element (HRE) of a target gene in vivo. Hence, dimethyl sulfate-based genomic footprinting was carried out to examine occupancy of HREs in the retinoic acid (RA) receptor beta2 (RARbeta2) gene promoter in the murine melanoma cell line S91 cultured in the absence or presence of T3, all-trans-RA (atRA), or CD2624, an RXR-selective retinoid. No footprint was observed at the RA-response element (betaRARE) in the absence of ligands. However, a footprint was detected at the betaRARE and other cis-acting elements after a 6 h incubation with CD2624 and atRA. Interestingly, only the betaRARE was footprinted after 60 min incubation with CD2624. These results suggest that the endogenous RXR complex can interact with an HRE of a target gene in the presence of ligand, and subsequently may initiate additional interactions between DNA and other transcription factors.

Animals↗
PubMed1998

Accumulation of chylomicron remnants in homozygous subjects with familial hypercholesterolaemia.

BACKGROUND: Post-prandial lipoprotein kinetics were investigated in subjects who lack functioning low-density lipoprotein (LDL) receptors [homozygous familial hypercholesterolaemia (FH)]. METHODS: An oral fat load was given, and chylomicron plasma kinetics was determined by monitoring the clearance of triglyceride, retinyl palmitate and apolipoprotein B48, calculated as the area under the curve, for 7.5 h. In addition, the binding and uptake of chylomicron remnants by fibroblasts of FH and control subjects were assessed in vitro. RESULTS: Based on the plasma kinetics of chylomicron triglyceride, retinyl palmitate and apolipoprotein B48 after a lipid meal, chylomicron clearance was found to be substantially delayed compared with normolipidaemic control subjects. Consistent with involvement of the LDL receptor in chylomicron clearance, binding and uptake of chylomicron remnants by fibroblasts of FH subjects was found to be substantially less than in cells from control subjects. CONCLUSION: This study shows that, in addition to LDL, chylomicron metabolism is severely impaired in FH and that the LDL receptor is significantly involved in the clearance of post-prandial lipoproteins. Moreover, this study raises the possibility that in FH, and in other disorders in which LDL receptor expression is reduced, atherogenesis might be a post-prandial disease.

Adolescent↗
PubMed1997

Attenuated inhibition of adrenergic contraction by nitric oxide in injured guinea pig femoral artery.

The present study aimed to examine the altered modulation of adrenergic contraction by nitric oxide and sensory neuropeptides in balloon-injured muscular artery. A guinea pig femoral artery (GPFA) was injured by a newly developed silastic microballoon catheter. The contralateral GPFA served as the control. The studied GPFAs consisted of six groups; control (C) and injured (I) GPFA, isolated at 0 days, and 2 and 8 weeks after injury (C0, I0, C2, I2, C8, and I8). Isometric tension was measured in the presence of indomethacin (10(-5) M), to exclude effects of cyclooxygenase-generated eicosanoids. Endothelial removal with the catheter was confirmed by histological examination. In each group, except for 10, NG-nitro-I-arginine methyl ester (L-NAME, 10(-6) M) induced significant augmentation of perivascular nerve stimulation (PNS)-evoked adrenergic contraction, which was blocked by L-arginine (3 x 10(-4) M). The degree of L-NAME augmentation in I8 was significantly smaller than that in C8 and I2. Capsaicin (10(-6) M) did not significantly affect PNS-contraction in any group, indicating that there was no sensory neuropeptide involvement in this contraction. In I8, acetylcholine (10(-6) M)-induced relaxation after noradrenaline (10(-5) M)-precontraction was significantly smaller than that seen in the other groups, except for I0, which was lacking in acetylcholine-induced relaxation. Histologically, injured GPFAs showed progressive intimal thickening. The present findings thus showed attenuated nitric oxide-mediated inhibition of adrenergic contraction, accompanying intimal thickening, in balloon-injured muscular artery, 8 weeks after injury.

Acetylcholine↗
PubMed1997

Serum HDL cholesterol values are associated with apoB-containing lipoprotein metabolism and triglyceride-body fat interrelation in young Japanese men.

Serum levels of total cholesterol, high density lipoprotein (HDL) cholesterol, triglyceride, apolipoprotein (apo) AI, ApoB, ApoE and body fat were measured in 226 fasting male Japanese college students aged 18 to 20 years. They were normolipidemic (total cholesterol: 169 +/- 31 mg/dl, triglyceride: 56 +/- 25 mg/dl) and their HDL cholesterol concentrations were high (61 +/- 13 mg/dl). An HDL cholesterol value < 35 mg/dl was observed in only one student (0.4%). In contrast, 112 men (49.6%) had an HDL cholesterol level > or = 60 mg/dl. Even in this normolipidemic group, as compared with students in a top HDL cholesterol tertile (HDL cholesterol; 75 +/- 9 mg/dl), students in a lower HDL cholesterol tertile (HDL cholesterol; 48 +/- 5 mg/dl) had significantly increased serum levels of LDL cholesterol (103 +/- 30 vs. 91 +/- 26 mg/dl), triglyceride (68 +/- 30 vs. 45 +/- 16 mg/dl) and apoB (83 +/- 20 vs 73 +/- 17 mg/dl). In addition, they had greater body mass index (23.2 +/- 3.6 vs. 20.6 +/- 2.5 kg/m2) and greater percent body fat (20.2 +/- 6.2 vs. 16.2 +/- 4.2%) determined using a bioelectrical impedance analyzer. HDL cholesterol levels were much more strongly related to triglyceride (r = -0.37) than was apoAI (r = -0.13). In stepwise multiple regression analysis in 184 nonsmokers, apoE, apoB and fat mass explained 21% of apoAI variability. Triglyceride in addition to these three parameters explained 41% of HDL cholesterol variability. These results suggest that serum levels of HDL cholesterol are associated with metabolism of apoB-containing lipoproteins as well as triglyceride-body fat interrelationship.

Adipose Tissue↗
PubMed1997

Inhibitory effects of various spasmolytics on the vagal afferent gastric excitatory response in cats.

The inhibitory effects of atropine, cimetropium, pirenzepine and N-butylscopolamine on the vagal afferent gastric excitatory response in cats under anesthesia with pentobarbital sodium and infusion of gallamine were examined. Electrical stimulation of vagal trunk in left side (10 Hz in frequency, 3 msec in duration, 15 V in intensity and for 10 sec) caused an initial gastric excitatory response during the period of stimulation followed by a late excitatory gastric response after stimulation in normal cats. The initial response was inhibited by atropine (100 microg/kg, i.v.) and hexamethonium (10 mg/kg, i.v.), while the late response was inhibited by atropine but not by hexamethonium (10 mg/kg, i.v.). In chronic supranodose vagotomized cats 11-15 days after the operation, stimulation of the vagal trunk caused a late gastric excitatory response after the stimulation period, which was inhibited by atropine (100 microg/kg, i.v.) but not by hexamethonium (10 mg/kg, i.v.). The two types of gastric responses in normal cats have been defined as follows: the initial gastric excitatory response (atropine- and hexamethonium- sensitive) is due to activation of vagal efferent fibers and the late gastric excitatory response (atropine-sensitive and hexamethonium-resistant) is due to activation of vagal afferent fibers. ED50 values of atropine, cimetropium, pirenzepine and N-butylscopolamine in inhibiting the vagal afferent gastric response were 7.2 microg/kg (n=4), 2.4 microg/kg (n=6), 82.6 microg/kg (n=3) and 93.0 microg/kg (n=4), respectively. The inhibitory effects of atropine and cimetropium on the vagal afferent gastric excitatory response (hexamethonium-resistant) were more potent than those of pirenzepine and N-butylscopolamine. These results suggested that the potent inhibitory effects of cimetropium and atropine on the vagal afferent gastric response may involve a potent spasmolytic effect.

Animals↗
PubMed1997

Phagocytic degradation of chylomicron remnants by fibroblasts from subjects with homozygous familial hypercholesterolaemia.

1. Familial hypercholesterolaemia is a common genetic abnormality in man characterized by premature atherogenesis as a consequence of disturbed lipoprotein metabolism. Chylomicrons, which represent intestinally derived lipoproteins, are cleared poorly in familial hypercholesterolaemia which may explain the increased retention of chylomicron remnants in arterial fatty lesions. However, cellular uptake of chylomicron remnants in familial hypercholesterolaemia remains unclear. This study determined the quantitative significance of non-low-density lipoprotein receptor-mediated uptake in fibroblasts from subjects with homozygous familial hypercholesterolaemia. 2. The metabolism of chylomicron remnants was assessed in fibroblasts from subjects with homozygous familial hypercholesterolaemia who lack low-density lipoprotein receptors. Compared with fibroblasts from normolipidaemic subjects, binding and degradation of chylomicron remnants was reduced by about two-thirds. Nevertheless, degradation of chylomicron remnants in cells from subjects with familial hypercholesterolaemia persisted in the absence of functioning low-density lipoprotein receptors. 3. Binding of chylomicron remnants to fibroblasts from subjects with familial hypercholesterolaemia was saturable. Unlabelled chylomicron remnants competed efficiently for binding but unlabelled low-density lipoprotein or a monoclonal antibody specific to the human low-density lipoprotein receptor had little effect on binding or degradation. 4. Polyinosinic acid did not alter binding and degradation of chylomicron remnants by fibroblasts from subjects with familial hypercholesterolaemia, ruling out involvement of the scavenger receptor. Lactoferrin was found to inhibit binding and degradation of chylomicron remnants by fibroblasts from subjects with familial hypercholesterolaemia by approximately 50%, implicating involvement of the alpha 2-macroglobulin receptor. 5. Cytochalasin D blocked degradation of chylomicron remnants at 37 degrees C in fibroblasts from subjects with familial hypercholesterolaemia by more than 80% but had no effect on binding at 4 degrees C, consistent with a phagocytic uptake pathway. Collectively, the data suggest that chylomicron remnants bind to a cell-surface protein which initiates phagocytosis and that lactoferrin interferes with binding to this putative cell-surface protein. Phagocytic uptake of chylomicron remnants provides an additional mechanism whereby cells from subjects with familial hypercholesterolaemia can accumulate lipid.

Adult↗
PubMed1997

Transforming growth factor-beta1 suppresses thyrotropin-induced Na+/I- symporter messenger RNA and protein levels in FRTL-5 rat thyroid cells.

Iodide transport into the thyroid catalyzed by the Na+/I- symporter (NIS), is the first and main rate-limiting step in thyroid hormone synthesis. Recently, we have demonstrated that thyrotropin (TSH) increases NIS messenger RNA (mRNA) and protein levels, as well as iodide uptake activity. Although transforming growth factor-beta1 (TGFbeta1) is known to affect thyroid cell function, it is still unclear how TGFbeta1 regulates TSH-stimulated iodide accumulation. Therefore, the effects of TGFbeta1 on TSH-stimulated NIS mRNA and protein levels were examined in FRTL-5 rat thyroid cells by Northern and Western blot analyses, and iodide uptake was assessed. Northern blot analysis revealed that TGFbeta1 suppressed TSH-stimulated NIS mRNA levels in a dose- and time-dependent manner. Western blot analysis demonstrated that TGFbeta1 suppressed TSH-stimulated NIS protein levels. TGFbeta1 also suppressed (Bu)2 cyclic adenosine monophosphate (cAMP)- and forskolin-stimulated NIS mRNA and protein levels, indicating a role for TGFbeta1 downstream of cAMP production. As predicted, TGFbeta1 inhibited TSH-stimulated iodide uptake activity. These results suggest that the inhibitory effect of TGFbeta1 on TSH-stimulated iodide uptake is at least in part due to a suppression of NIS specific transcription. Therefore, TGFbeta1 may act as an autocrine or paracrine local modulator of thyroid hormone synthesis by influencing NIS mRNA levels in the thyroid.

Animals↗
PubMed1997

Fatty acid synthesis of an eicosapentaenoic acid-producing bacterium: de novo synthesis, chain elongation, and desaturation systems.

The fatty acid synthesis systems of a Shewanella sp., strain SCRC-2738, that produces a large amount of eicosapentaenoic acid were investigated. Two kinds of fatty acid synthesis system, de novo synthesis and chain elongation ones, were detected in the cytosol. The de novo synthesis system required an acyl carrier protein, and produced palmitoyl- and palmitoleoyl-acyl carrier proteins as final products. The chain elongation system also required an acyl carrier protein, and produced an acyl-acyl carrier protein as a product, using palmitoyl-, palmitoleoyl-, stearoyl-, and oleoyl-CoAs as primers but not eicosanoyl- or eicosenoyl-CoA. There were an anaerobic pathway and an aerobic desaturation one for the production of unsaturated fatty acids. Eicosapentaenoic acid seemed to be produced through the aerobic desaturation pathway and not through the anaerobic one, since the latter pathway produced n-7 type monoenoic fatty acids, which are different from eicosapentaenoic acid in the position of the double bond. The desaturase utilized an acyl-acyl carrier protein as a substrate, and this activity increased in the presence of ferredoxin and ferredoxin NADP+ reductase. Thus, Shewanella sp., strain SCRC-2738, has novel characteristics as to both fatty acid chain elongation and desaturation systems.

Acetyl Coenzyme A↗
PubMed1997

Cloning of a gene for chloroplast omega6 desaturase of a green alga, Chlamydomonas reinhardtii.

A gene for chloroplast omega6 desaturase, which catalyzes the desaturation of monoenoic to dienoic acids in chloroplasts, was isolated from Chlamydomonas reinhardtii. We first performed reverse transcriptase-polymerase chain reaction with oligonucleotide primers corresponding to regions conserved among plastid omega6 desaturases of higher plants and delta12 desaturases of cyanobacteria, using C. reinhardtii poly(A)+ RNA. An amplified DNA fragment of 0.5 kb, containing a frame for a protein homologous to these desaturases, was used as a probe for screening cDNA and genomic DNA libraries of C. reinhardtii. The cDNA clone of 2.2 kb obtained contained an open reading frame encoding a protein of 424 amino acids with a putative molecular mass of 48.4 kDa, the amino acid sequence of which showed 46-51% homology to those of higher plant plastid omega6 and cyanobacterial delta12 desaturases. Introduction of the cloned genomic counterpart of this cDNA, designated as des6, into a Chlamydomonas mutant with defects in chloroplast omega6 desaturation and in the activities of photosystems I and II (PSI and PSII) complemented the desaturation mutation, indicating that the des6 gene codes for chloroplast omega6 desaturase. The complemented strains did not recover from the photosynthetic lesions, but showed lower PSII activity at 45 degrees C than the desaturation mutant, proving that the photosynthetic lesions in hf-9 are not caused by the desaturation mutation, and that the lowered unsaturation level of chloroplast lipids in the mutant is responsible for the expression at this high temperature of PSII activity, one of the thylakoid membrane functions.

Animals↗
PubMed1997

Three-dimensional helical computed tomography with intravenous cholangiography for sclerosing cholangitis manifested as postcholecystectomy symptom.

A 46-year-old woman who had upper abdominal pain 10 years after cholecystectomy, and who had incidental sclerosing cholangitis (SC), was investigated by three-dimensional helical computed tomographic (3-DHCT) cholangiography with contrast medium, because endoscopic retrograde cholangiography (ERC) was unsuccessful and a second ERC was not permitted by the patient. The cholangiogram demonstrated annular strictures of the bilateral hepatic duct at the confluence of the common hepatic duct, and dilatation of the left intrahepatic biliary duct. Although we could not clarify the cause of the biliary tract deformity at the time of the 3-DHCT, the tentative diagnosis of postcholecystectomy deformity of the biliary tree led to successful treatment by right liver lobectomy and hepaticojejunostomy. Histologic findings were compatible with SC. From this experience and the literature, we suggest that 3-DHCT cholangiography with contrast medium can contribute to the preoperative diagnosis of morphological changes in the biliary tree in patients with postcholecystectomy symptoms.

Cholangiography↗
PubMed1997

Apheresis technology for prevention and regression of atherosclerosis: an overview.

Low density lipoprotein (LDL) apheresis is at present one method of treatment in homozygous cases of familial hypercholesterolemia (FH). It is also effective in the prevention of the development of coronary atherosclerosis in patients with heterozygous FH and other types of mild hypercholesterolemia, leading to the regression of the stenosing lesions. In this paper, an overview is presented on the development of the devices for LDL apheresis and its short- and long-term effects on FH mainly based upon experience with the Liposorber system. LDL apheresis has served to protect the lives of patients from life threatening diseases like myocardial infarction although observations for more than 10 years in some laboratories have shown that the progression of atherosclerosis has taken place in many patients, and more importantly, the involvement of the aortic valve with calcification has developed, especially in patients who had homozygous FH, making this the most obstinate complication of FH. Therefore, more aggressive treatment or the combination of LDL apheresis with other therapies is required in the future. LDL apheresis has also been approved for the treatment of glomerulosclerosis and arteriosclerosis obliterans.

Arteriosclerosis↗