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2.
J Appl Microbiol ; 103(2): 365-71, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17650196

ABSTRACT

AIMS: To characterize the cause for the lack of conjugated linoleic acid (CLA) reductase (CLA-R) activity in the Butyrivibrio fibrisolvens MDT-5 strain that rapidly isomerizes linoleic acid (LA) to CLA without hydrogenation, the CLA-R was purified and its gene (cla-r) sequence was determined. METHODS AND RESULTS: CLA-R was purified to near homogeneity as a 53-kDa monomeric protein from the high CLA-R activity-expressing strain MDT-10. The purified CLA-R recognized conjugated double bonds. Unsaturated fatty acids containing 18 carbons markedly increased the CLA-R expression at the transcriptional level. Complete sequencing of the cla-r gene revealed that the CLA-R is a novel protein. Sequence analysis of the cla-r gene from the MDT-5 strain revealed that the MDT-5 CLA-R protein sequence differed from that of the MDT-10 at four consecutive amino acids. Northern and Western blotting analyses confirmed that the cla-r mRNA and protein are expressed normally in MDT-5. CONCLUSIONS: Strain MDT-5 expresses the CLA-R protein that lacks enzyme activity because of mutation, which explains why MDT-5 exclusively produces CLA from LA. SIGNIFICANCE AND IMPACT OF THE STUDY: The cla-r gene was sequenced for the first time. Exogenous fatty acids affected the cla-r transcription. These results will provide additional knowledge on biohydrogenation, and may also augment the CLA production in the gastrointestinal tract.


Subject(s)
Butyrivibrio/genetics , Linoleic Acids, Conjugated/genetics , Oxidoreductases Acting on CH-CH Group Donors/genetics , Amino Acid Sequence/genetics , Bacterial Proteins/genetics , Base Sequence , Blotting, Northern/methods , Blotting, Western/methods , Butyrivibrio/enzymology , Cloning, Molecular/methods , Culture Media , Fatty Acids, Unsaturated/genetics , Gene Expression Regulation, Bacterial/genetics , Genes, Bacterial/genetics , Oxidoreductases Acting on CH-CH Group Donors/isolation & purification , RNA, Bacterial/genetics , RNA, Messenger/genetics , Substrate Specificity/genetics , Transcription, Genetic/genetics
3.
J Dairy Sci ; 89(3): 1043-51, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16507700

ABSTRACT

To increase ruminal outflow of trans-vaccenic acid (t-VA), a new strain of Butyrivibrio fibrisolvens (MDT-10) was isolated that has a great ability to hydrogenate linoleic acid (LA) to t-VA. When strain MDT-10 was added to the batch cultures of mixed ruminal microbes (1% of the total number of viable ruminal bacteria), LA conversion to t-VA increased greatly; after 3 h, t-VA levels were > 4-fold higher than the control. By 10 h, all of the t-VA was hydrogenated to stearic acid. However, when a new strain of Bifidobacterium adolescentis (HF-11), which has a high capacity for incorporation of t-VA, was added in conjunction with MDT-10 (1% of the total number of ruminal bacteria), t-VA levels after 10 h were 6 times higher than with MDT-10 alone. These results suggest that t-VA produced by MDT-10 was incorporated into HF-11 cells, resulting in protection of t-VA from t-VA-hydrogenating microbes. Similar results were obtained in a continuous culture of mixed ruminal microbes in which addition of HF-11 simultaneously with MDT-10 increased the amount of t-VA in the effluent 2.5-fold. Both MDT-10 and HF-11 appeared to grow readily in the presence of mixed ruminal microbes. Sixty-two percent of t-VA incorporated by HF-11 was present in the free form, whereas 19, 15, and 3%, respectively, were incorporated into monoacylglycerol, glycerophospholipid, and diacylglycerol fractions. Because these lipids can be digested in the small intestine, it is likely that most t-VA in HF-11 cells is absorbed. Thus, introduction of MDT-10 and HF-11 simultaneously to the rumen might increase the amount of t-VA absorbed and might consequently increase the conversion of t-VA to conjugated linoleic acid in tissue.


Subject(s)
Oleic Acids/biosynthesis , Oleic Acids/metabolism , Rumen/microbiology , Animals , Bifidobacterium/metabolism , Butyrivibrio/isolation & purification , Butyrivibrio/metabolism , Carboxylic Acids/analysis , Escherichia coli/metabolism , Fatty Acids/analysis , Feces/microbiology , Goats , Humans , Hydrogenation , Lactobacillus/metabolism , Linoleic Acid/metabolism , Stearic Acids/metabolism
4.
J Appl Microbiol ; 100(4): 787-94, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16553734

ABSTRACT

AIM: Isolation of a new strain of Butyrivibrio fibrisolvens possessing great capacity to produce conjugated linoleic acid (CLA) in order to utilize as a probiotic for animals. METHODS AND RESULTS: A novel strain (MDT-5) was isolated from the goat rumen, which exclusively converted linoleic acid (LA) to CLA, because of its high LA isomerase activity with virtually no CLA reductase activity. MDT-5 also converted linolenic acid to conjugated linolenic acid that may be more bioactive than CLA. The oral administration of MDT-5 every other day to mice for 2 weeks resulted in increased amounts of CLA in the contents of the large intestine (2.5-fold), as well as in adipose tissue (threefold). Feeding a high-LA diet, as well as prolonging the period of MDT-5 administration, further increased the CLA content in body fat. CONCLUSIONS: MDT-5 has by far greater ability to produce CLA than any other known bacteria. Administration of MDT-5 to mice increases CLA production in the large intestine, which results in increased CLA absorption. SIGNIFICANCE AND IMPACT OF THE STUDY: MDT-5 may be useful in pet animals as a probiotic to provide CLA continuously.


Subject(s)
Butyrivibrio/isolation & purification , Linoleic Acids/metabolism , Probiotics/administration & dosage , Adipose Tissue/metabolism , Administration, Oral , Animals , Diet , Goats , Intestine, Large/metabolism , Isomerism , Linoleic Acid/administration & dosage , Linoleic Acid/metabolism , Linoleic Acids, Conjugated/analysis , Linoleic Acids, Conjugated/metabolism , Male , Mice , Mice, Inbred ICR , Rumen/microbiology
5.
Endocrinology ; 142(8): 3332-9, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11459775

ABSTRACT

The antiinflammatory action of glucocorticoids is mediated partly by the inhibition of the expression of several cytokines and adhesion molecules. Some activators for nuclear receptors other than the GR have also been shown to inhibit the expression of these inflammatory molecules, although their molecular mechanisms remain unidentified. We therefore examined the effects of the PPARalpha activator fenofibrate and the GR activator dexamethasone on TNFalpha-stimulated expression of IL-6 and vascular cell adhesion molecule-1 in vascular endothelial cells. Both fenofibrate and dexamethasone reduced TNFalpha-induced IL-6 production in human vascular endothelial cells, but only fenofibrate reduced TNFalpha-stimulated vascular cell adhesion molecule-1 expression in these cells. Transient transfection of bovine aortic endothelial cells with an IL-6 promoter construct or a vascular cell adhesion molecule-1 promoter construct revealed that fenofibrate inhibited TNFalpha-induced IL-6 promoter as well as vascular cell adhesion molecule-1 promoter activities, whereas dexamethasone inhibited only the former. EMSA demonstrated that both fenofibrate and dexamethasone reduced nuclear factor-kappaB binding to its recognition site on the IL-6 promoter, but only fenofibrate reduced such binding to the vascular cell adhesion molecule-1 promoter. Thus, down-regulation of nuclear factor-kappaB activity by PPARalpha occurs in both the IL-6 and vascular cell adhesion molecule-1 genes, whereas that by GR occurs only in the IL-6 gene in vascular endothelial cells. These results strongly suggest the existence of a target gene-specific mechanism for the nuclear receptor-mediated down-regulation of nuclear factor-kappaB activity.


Subject(s)
Down-Regulation/physiology , Endothelium, Vascular/physiology , Gene Expression/physiology , NF-kappa B/physiology , Receptors, Cytoplasmic and Nuclear/physiology , Receptors, Glucocorticoid/physiology , Transcription Factors/physiology , Biological Transport/drug effects , Cell Nucleus/metabolism , Cells, Cultured , Dexamethasone/pharmacology , Endothelium, Vascular/cytology , Fenofibrate/pharmacology , Glucocorticoids/pharmacology , Humans , Hypolipidemic Agents/pharmacology , Interleukin-6/biosynthesis , Interleukin-6/genetics , Promoter Regions, Genetic/drug effects , Promoter Regions, Genetic/physiology , Tumor Necrosis Factor-alpha/pharmacology , Vascular Cell Adhesion Molecule-1/genetics , Vascular Cell Adhesion Molecule-1/metabolism
6.
Appl Environ Microbiol ; 66(9): 3773-7, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10966389

ABSTRACT

The enzyme system of pyruvate formate-lyase (PFL) in Streptococcus bovis was investigated by isolating PFL and PFL-activating enzyme (PFL-AE) from S. bovis, flavodoxin from Escherichia coli, and chloroplasts from spinach. In this study, the PFL and PFL-AE in S. bovis were found to be similar to those in E. coli, suggesting that the activating mechanisms are similar. The optimal pH of S. bovis PFL was 7.5, which is in contrast to the optimal pH of S. bovis lactate dehydrogenase, which is 5.5. The apparent K(m) of S. bovis PFL was 2 mM. The intermediates of glycolysis, dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde-3-phosphate (GAP), were shown to inhibit PFL activity. The concentrations of intracellular DHAP and GAP in S. bovis ranged from 1.9 mM to less than 0.1 mM and from 0.6 mM to less than 0.05 mM, respectively, depending on the energy supply. The wide variations in DHAP and GAP levels indicated that PFL activity is allosterically regulated by these triose phosphates in vivo. The amount of PFL protein, as determined by Western blot analysis with polyclonal antibody, changed in parallel with the level of pfl-mRNA, responding to the culture conditions. These observations confirm that PFL synthesis is regulated at the transcriptional level and support the hypothesis that S. bovis shifts the fermentation pathway from acetate, formate, and ethanol production to lactate production when the pH is low and when excess energy is supplied.


Subject(s)
Acetyltransferases/metabolism , Gene Expression Regulation, Enzymologic , Streptococcus bovis/enzymology , Acetyltransferases/chemistry , Acetyltransferases/genetics , Chloroplasts , Culture Media , Dihydroxyacetone Phosphate/metabolism , Dihydroxyacetone Phosphate/pharmacology , Enzymes/metabolism , Escherichia coli/enzymology , Flavodoxin/metabolism , Formates/metabolism , Glyceraldehyde 3-Phosphate/metabolism , Glyceraldehyde 3-Phosphate/pharmacology , Hydrogen-Ion Concentration , Kinetics , Streptococcus bovis/growth & development
7.
J Dairy Sci ; 82(4): 780-7, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10212465

ABSTRACT

The effect of fumarate used as a feed additive on the reduction of methanogenesis in the rumen was evaluated by in vitro experiments. The addition of fumarate to the culture of mixed ruminal microorganisms that were fermenting hay powder and concentrate reduced methane production. Most fumarate was metabolized to propionate, and a slight increase was noted in other volatile fatty acids. Fumarate was utilized by mixed bacteria but not by mixed protozoa. Fibrobacter succinogenes, Selenomonas ruminantium ssp. ruminantium, Selenomonas ruminantium ssp. lactilytica, Veillonella parvula, and Wollinella succinogenes oxidized H2 by using fumarate as a final electron acceptor, suggesting that these bacteria compete with methanogens for H2, which is the main substrate for methanogenesis in the rumen. However, the affinity of these bacteria to H2 was lower than their affinity to methanogens. These fumarate-utilizing bacteria metabolized malate to products that were similar to those from fumarate, suggesting the possession of fumarate dehydratase. Fibrobacter succinogenes, V. parvula, and W. succinogenes utilized formate, another substrate for methanogenesis, as an electron donor for fumarate reduction. The affinity of these bacteria to formate was higher than the affinity methanogenes have for formate. When methanogens were cocultured with an equal cellular amount of each of the fumarate-utilizing bacteria, methane production was markedly decreased, not only from formate, but also from H2. These results suggest that the addition of fumarate to ruminant feed reduces methanogenesis and enhances propionate production in the rumen.


Subject(s)
Bacteria/metabolism , Fumarates/administration & dosage , Goats/microbiology , Methane/metabolism , Rumen/microbiology , Adenosine Triphosphate/metabolism , Animals , Deuterium/metabolism , Eukaryota/metabolism , Euryarchaeota/metabolism , Fumarates/metabolism , Hydrogen-Ion Concentration , Oxidation-Reduction
8.
Nihon Kokyuki Gakkai Zasshi ; 36(10): 896-901, 1998 Oct.
Article in Japanese | MEDLINE | ID: mdl-9893434

ABSTRACT

A 52-year-old man was admitted because of increasing dyspnea on exersion and presence of pulmonary infiltrates. The patient had pulmonary tuberculosis at the age of 31, which resulted in volume loss and calcified foci in the upper lobe of his left lung. As a construction worker for more than 20 years, he had been exposed to inorganic dusts. Chest radiographs showed a symmetrical consolidation of infiltrates in both lungs with the exception of the left upper lobe, where no apparent infiltrates were shown. A computed tomographic scan of the chest revealed widely panlobular consolidation with the exception of the left upper lobe. A diagnosis of pulmonary alveolar proteinosis (PAP) was established by analysis of bronchoalveolar lavage fluid. Although the patient underwent segmental bronchoalveolar lavage four times under general anesthesia, he suffered frequent pulmonary infection and died two years after the onset his symptoms. Interestingly, the patient had a markedly narrowed orifice in the left upper lobe, as demonstrated by fiberoptic bronchoscopy. Chest radiographs of this lung field revealed no infiltrative shadows. These results suggest that some inhalative agent was involved in the pathogenesis of PAP in this case. In addition, significantly increased levels of KL-6 detected in both serum and bronchoalveolar lavage fluid were attributable to overproduction of KL-6 by Type II pneumocytes that had been stimulated or damaged by PAP.


Subject(s)
Dust/adverse effects , Occupational Diseases/etiology , Occupational Exposure/adverse effects , Pulmonary Alveolar Proteinosis/etiology , Construction Materials , Fatal Outcome , Humans , Male , Middle Aged , Occupational Diseases/diagnostic imaging , Pulmonary Alveolar Proteinosis/diagnostic imaging , Tomography, X-Ray Computed
9.
Trends Pharmacol Sci ; 19(12): 496-9, 1998 Dec.
Article in English | MEDLINE | ID: mdl-9871411

ABSTRACT

For normal glucose homeostasis, insulin release by the pancreatic beta cell is vital. Until recently, it was thought that glucose-induced ionic events, such as closure of the ATP-sensitive K+ (KATP) channels, membrane depolarization, activation of the L-type voltage-dependent Ca2+ channels, Ca2+ influx and elevation of cytosolic free Ca2+, constitute the main signalling pathway in beta-cell stimulus-secretion coupling. However, since the discovery of 'non-ionic' glucose actions in the beta cell by the Aizawa and Henquin laboratories in 1991, data have accumulated that strongly indicate the physiological relevance of this signalling pathway. In this review, Toru Aizawa and colleagues discuss how the KATP channel-Ca2+ hypothesis was formulated, what was overlooked in the hypothesis, and then provide a comprehensive view of stimulus-secretion coupling in the beta cell, with an emphasis on non-ionic glucose actions.


Subject(s)
Glucose/physiology , Insulin/metabolism , Islets of Langerhans/physiology , Adenosine Triphosphate/metabolism , Animals , Calcium/metabolism , Glucagon/pharmacology , Glucagon-Like Peptide 1 , Insulin Secretion , Peptide Fragments/pharmacology , Potassium Channels/physiology , Protein Precursors/pharmacology , Rats
11.
Arch Intern Med ; 157(6): 693-6, 1997 Mar 24.
Article in English | MEDLINE | ID: mdl-9080924

ABSTRACT

We describe 4 patients with Graves disease who had abnormal increases of serum creatine kinase (CK) concentrations during treatment with antithyroid medications. Three of the patients experienced myalgia and muscle cramps. All of the patients manifested an increase in serum CK levels 1 to 3 months after the administration of antithyroid drugs. Thyrotropin concentrations and cardiac systolic time indexes during the elevation of serum CK concentrations were not consistent with hypothyroidism. The mechanisms are not obvious, but it is likely that the rapid decrease of thyroid hormones in tissues may temporarily cause hypothyroid states, resulting in alterations in CK concentrations. It is suggested that hasty correction of thyrotoxicosis should be avoided in susceptible patients, unless the thyrotoxic conditions are critical.


Subject(s)
Antithyroid Agents/adverse effects , Creatine Kinase/blood , Creatine Kinase/drug effects , Graves Disease/blood , Graves Disease/complications , Hyperthyroidism/blood , Hyperthyroidism/drug therapy , Methimazole/adverse effects , Adult , Antithyroid Agents/therapeutic use , Female , Humans , Hyperthyroidism/etiology , Male , Methimazole/therapeutic use , Thyroid Hormones/blood
12.
Endocrinology ; 138(3): 1106-10, 1997 Mar.
Article in English | MEDLINE | ID: mdl-9048616

ABSTRACT

This study was designed to delineate the nature of beta-cell dysfunction in a model of genetically determined nonobese diabetes, the Goto-Kakizaki (GK) rat. Pancreatic beta-cell function was analyzed immediately after weaning and 5 weeks thereafter, comparing animals with or without insulin treatment during the interval. In 3.5-week-old GK rats, fasting plasma glucose was mildly elevated with normoinsulinemia, and the islet insulin content was reduced by 33%. When incubated with 3-30 mM glucose in vitro, the GK rat islets showed reduced glucose sensitivity, i.e. the EC50 values were 19.5 and 15.9 mM, and the Hill constants for the positive cooperativity 2.1 and 4.2 in the islets of GK and the control rats, respectively. On the other hand, the maximum response to glucose was not attenuated when reduced islet insulin content was considered. In 8.5-week-old GK rats hyperglycemia worsened and glucose-stimulated insulin release by the islets more severely impaired. A daily insulin injection from the 3.5-8.5 weeks of age significantly lowered plasma glucose in the GK rat, accompanied by a marked suppression of both basal (with 3 mM glucose) and glucose (6-30 mM)-stimulated insulin release by the islets. In the GK rat, beta-cell dysfunction develops by the age of 3.5 weeks, and insulin treatment during the subsequent 5 weeks accelerates its progression.


Subject(s)
Diabetes Mellitus, Type 2/physiopathology , Insulin/pharmacology , Islets of Langerhans/drug effects , Islets of Langerhans/physiopathology , Rats, Mutant Strains/physiology , Animals , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/metabolism , Disease Progression , Insulin/metabolism , Insulin Secretion , Islets of Langerhans/metabolism , Phenotype , Rats , Rats, Mutant Strains/genetics , Rats, Wistar , Time Factors
13.
J Clin Invest ; 99(5): 861-6, 1997 Mar 01.
Article in English | MEDLINE | ID: mdl-9062343

ABSTRACT

Non-insulin-dependent diabetes mellitus (NIDDM) is considered a polygenic disorder in which insulin resistance and insulin secretory defect are the major etiologic factors. Homozygous mice with insulin receptor substrate-1 (IRS-1) gene knockout showed normal glucose tolerance associated with insulin resistance and compensatory hyperinsulinemia. Heterozygous mice with beta cell glucokinase (GK) gene knockout showed impaired glucose tolerance due to decreased insulin secretion to glucose. To elucidate the interplay between insulin resistance and insulin secretory defect for the development of NIDDM, we generated double knockout mice with disruption of IRS-1 and beta cell GK genes by crossing the mice with each of the single gene knockout. The double knockout mice developed overt diabetes. Blood glucose levels 120 min after intraperitoneal glucose load (1.5 mg/g body wt) were 108 +/- 24 (wild type), 95 +/- 26 (IRS-1 knockout), 159 +/- 68 (GK knockout), and 210 +/- 38 (double knockout) mg/dl (mean +/- SD) (double versus wild type, IRS-1, or GK; P < 0.01). The double knockout mice showed fasting hyperinsulinemia and selective hyperplasia of the beta cells as the IRS-1 knockout mice (fasting insulin levels: 0.38 +/- 0.30 [double knockout], 0.35 +/- 0.27 [IRS-1 knockout] versus 0.25 +/- 0.12 [wild type] ng/ml) (proportion of areas of insulin-positive cells to the pancreas: 1.18 +/- 0.68%; P < 0.01 [double knockout], 1.20 +/- 0.93%; P < 0.05 [IRS-1 knockout] versus 0.54 +/- 0.26% [wild type]), but impaired insulin secretion to glucose (the ratio of increment of insulin to that of glucose during the first 30 min after load: 31 [double knockout] versus 163 [wild type] or 183 [IRS-1 knockout] ng insulin/mg glucose x 10(3)). In conclusion, the genetic abnormalities, each of which is nondiabetogenic by itself, cause overt diabetes if they coexist. This report provides the first genetic reconstitution of NIDDM as a polygenic disorder in mice.


Subject(s)
Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/metabolism , Glucokinase/genetics , Insulin Resistance/genetics , Insulin/metabolism , Islets of Langerhans/enzymology , Phosphoproteins/genetics , Animals , Gene Expression Regulation , Glucose/administration & dosage , Glucose/metabolism , Glucose/pharmacology , Glucose Tolerance Test , Hyperinsulinism/genetics , Immunohistochemistry , Insulin/immunology , Insulin Receptor Substrate Proteins , Insulin Secretion , Islets of Langerhans/growth & development , Islets of Langerhans/metabolism , Mice , Mice, Knockout , Pancreas/metabolism , Pancreas/pathology
14.
Endocrinology ; 138(2): 751-5, 1997 Feb.
Article in English | MEDLINE | ID: mdl-9003011

ABSTRACT

In the rat pancreatic beta cell, low concentrations of glucose potentiate D-glyceraldehyde (GA)-induced insulin release without any potentiation of the triose-induced elevation of cytosolic free Ca2+ concentration. Namely, 2-3 mM glucose strongly potentiates 5 mM GA-induced insulin release, and the combination of stimulatory concentration of glucose (10 mM) and 5 mM GA elicits far more than additive insulin release: this glucose action is independent of ATP-sensitive K+ channel closure because it can be seen in the presence of diazoxide, an opener of the K+ channel. The triose-induced elevation of cytosolic free Ca2+ concentration was not potentiated by the presence of 3 mM glucose, and oxidation of labeled GA by the islet cells was not enhanced by the presence of glucose. The glucose action can be mimicked by mannose, but not by galactose, and was suppressed by inhibition of glucose phosphorylation with mannoheptulose or 2-deoxyglucose. Glucose also potentiates 2-ketoisocaproate-induced insulin release. In contrast, a combination of GA and 2-ketoisocaproate elicits only additive insulin release. Strikingly, 3 mM glucose does not potentiate insulin release in response to a depolarizing concentration of K+. Therefore, at least two signal pathways, one from upper glycolytic flux and one from mitochondrial metabolism, must converge to provide the potentiation of insulin release. We conclude that the upper glycolytic flux, acting at a site unrelated to the elevation of cytosolic free Ca2+, potentiates insulin release triggered by triose and mitochondrial fuels.


Subject(s)
Glycolysis , Insulin/metabolism , Islets of Langerhans/metabolism , Mitochondria/metabolism , Signal Transduction , Animals , Calcium/metabolism , Cytosol/metabolism , Diazoxide/pharmacology , Dihydroxyacetone/pharmacology , Drug Synergism , Glucose/pharmacology , Glyceraldehyde/pharmacology , Insulin Secretion , Islets of Langerhans/drug effects , Islets of Langerhans/ultrastructure , Keto Acids/pharmacology , Male , Mannose/pharmacology , Rats , Rats, Wistar
15.
Am J Med Sci ; 313(1): 67-9, 1997 Jan.
Article in English | MEDLINE | ID: mdl-9001169

ABSTRACT

In a 32-year-old woman, alopecia universalis went into unequivocal remission during pregnancy and prednisolone therapy. A skin biopsy specimen showed intense infiltration of the lymphocyte around the hair follicle without immunoglobulin and complement deposition. Autoantibody test results were negative except for the antithyroid and anti-nuclear antibodies. Human leukocyte antigen haplotypes common in Japanese patients with insulin-dependent diabetes were found in this patient. However, thyroid function and glucose tolerance were normal, and other clinical evidence of collagen vascular disorders was not found. In this patient, alopecia was considered to have been caused by autoimmune abnormalities. This is the first documentation of remission of autoimmune alopecia universalis during pregnancy.


Subject(s)
Alopecia/immunology , Autoimmune Diseases , Prednisolone/therapeutic use , Pregnancy/immunology , Adult , Alopecia/drug therapy , Antibodies, Antinuclear/blood , Biopsy , Female , Hair/pathology , Histocompatibility Testing , Humans , Immunoglobulins, Thyroid-Stimulating/blood , Lymphocytes/pathology , Remission, Spontaneous , Skin/immunology , Skin/pathology
16.
Biochem Biophys Res Commun ; 229(2): 460-5, 1996 Dec 13.
Article in English | MEDLINE | ID: mdl-8954920

ABSTRACT

This is the first systematic study on the pancreatic beta cell function in the heterozygous mouse with targeted disruption of the beta cell glucokinase gene. The heterozygotes' beta cell displayed the following characteristics: (1) impaired glucose sensitivity with normal glucose responsiveness, (2) poor discrimination of alpha and beta glucose anomers, and (3) normal response to glucose in the presence of 25 mM K+ and 150 microM diazoxide. Both the first and the second phases of glucose-stimulated insulin release were depressed. Although the heterozygotes were mildly hyperglycemic, insulin treatment further suppressed beta cell function, implying the beta cell glucose toxicity is not the cause of impaired glucose sensitivity. The data are compatible with the glucokinase glucose sensor concept inasmuch as glucose sensitivity is reduced in the heterozygotes' beta cell. The anomeric malaise and preservation of the ATP-sensitive K+ channel-independent glucose action were considered due to chronic hyperglycemia.


Subject(s)
Glucokinase/genetics , Islets of Langerhans/enzymology , Animals , Glucose Tolerance Test , Heterozygote , Insulin/metabolism , Insulin Secretion , Islets of Langerhans/metabolism , Male , Mice
17.
Chem Senses ; 20(2): 231-7, 1995 Apr.
Article in English | MEDLINE | ID: mdl-7583016

ABSTRACT

Guanylyl cyclase activity was cytochemically demonstrated in rabbit foliate taste buds. The enzymatic activity was localized in the apical portion (microvilli and neck) of taste bud cells. Especially strong activity was observed on the microvillous membrane of type I (dark) cells and often on a blunt process of type III cells. The microvilli of type II (light) cells showed weak enzymatic activity. Considering that the apical portion of taste cells is a likely site of interaction between taste stimuli and the cells, the results support the idea that cyclic GMP is involved in taste transduction.


Subject(s)
Guanylate Cyclase/metabolism , Taste Buds/enzymology , Animals , Cadmium/pharmacology , Cadmium Chloride , Chlorides/pharmacology , Cyclic GMP/physiology , Guanylate Cyclase/antagonists & inhibitors , Histocytochemistry , Male , Mercuric Chloride/pharmacology , Rabbits , Signal Transduction/physiology , Taste/physiology , Taste Buds/cytology , Zinc Compounds/pharmacology
18.
Life Sci ; 57(14): 1375-81, 1995.
Article in English | MEDLINE | ID: mdl-7564885

ABSTRACT

This is the first report as to the effects of thapsigargin (Tg), an inhibitor of intracellular Ca2+ pumps, on insulin release by pancreatic B-cells. Tg does not alter basal insulin release by the isolated islets, with 3 mM glucose. However, it potentiates high glucose-induced insulin release: potentiation of the first phase response is dose-related in a concentration range of 1.3-40 microM. In isolated B-cells, Tg causes a minimal rise in basal cytosolic free calcium concentration ([Ca2+]i) and eliminates high glucose-induced initial lowering of [Ca2+]i. Tg does not alter glucose oxidation by the islets and the islet insulin content. An elimination of glucose-induced sequestration of Ca2+ into Tg-sensitive intracellular pool(s) is considered to be the cause of Tg potentiation of glucose effect on insulin release.


Subject(s)
Calcium-Transporting ATPases/antagonists & inhibitors , Insulin/metabolism , Islets of Langerhans/drug effects , Islets of Langerhans/metabolism , Terpenes/pharmacology , Animals , Calcium/metabolism , Glucose/metabolism , In Vitro Techniques , Insulin Secretion , Male , Rats , Rats, Wistar , Thapsigargin
19.
Histochem J ; 25(5): 348-56, 1993 May.
Article in English | MEDLINE | ID: mdl-8391521

ABSTRACT

Cyclic 3',5'-nucleotide phosphodiesterase activity was demonstrated cytochemically in the rat olfactory mucosa using cyclic AMP as substrate. Strong activity was observed on the plasma membrane of the cilia, dendritic knob and axon of olfactory cells; weak activity was apparent on the membrane of the dendritic shaft and cell body. This suggests that the cyclic AMP produced by odorant-sensitive adenylate cyclase in the dendritic terminal acts mainly in its original site and to a lesser extent in the dendritic shaft and cell body. The enzyme also hydrolysed cyclic GMP but the hydrolysis was not as great as in the case of cyclic AMP. Besides its presence in olfactory cells, enzymatic activity was also observed on the plasma membrane of basal cells and certain supporting cells with an astrocyte-like morphology.


Subject(s)
3',5'-Cyclic-AMP Phosphodiesterases/metabolism , Olfactory Mucosa/enzymology , Animals , Axons/enzymology , Axons/ultrastructure , Cell Membrane/enzymology , Cell Membrane/ultrastructure , Cyclic AMP/metabolism , Cyclic GMP/metabolism , Dendrites/enzymology , Dendrites/ultrastructure , Histocytochemistry , Hydrolysis , Male , Microscopy, Electron , Olfactory Mucosa/ultrastructure , Rats , Rats, Wistar
20.
Histochem J ; 23(2): 83-90, 1991 Feb.
Article in English | MEDLINE | ID: mdl-1655680

ABSTRACT

Adenylate cyclase activity was demonstrated in the cilia, dendritic knob and axon of rat olfactory cells by using a strontium-based cytochemical method. The activity in the cilia and the dendritic knob was enhanced by non-hydrolyzable GTP (guanosine triphosphate) analogues and forskolin, and inhibited by Ca2+, all in agreement with biochemical reports of the odorant-sensitive adenylate cyclase. The results support the hypothesis of cyclic AMP working as a second messenger in olfactory transduction and imply that the transduction sites exist not only in the olfactory cilia but also in the dendritic knob. Enzymatic activity was also observed in the olfactory dendritic shaft by treating the tissue with 0.0002% Triton X-100, although the properties and role of the enzyme in this region are uncertain. The detergent inhibited the enzymatic activity in the cilia and the dendritic knob.


Subject(s)
Adenylyl Cyclases/analysis , Cyclic AMP/metabolism , Olfactory Mucosa/enzymology , Olfactory Mucosa/ultrastructure , Signal Transduction , Animals , Calcium/pharmacology , Cilia/chemistry , Cilia/ultrastructure , Colforsin/pharmacology , Dendrites/chemistry , Dendrites/ultrastructure , Guanosine Triphosphate/analogs & derivatives , Histocytochemistry , Microscopy, Electron , Rats , Rats, Inbred Strains , Strontium
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