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Biomedical subjects

M Higa

Publications and source records attributed to M Higa.

At least 37 records · Page 2Linked to original sources

Hyponatremia with increased plasma antidiuretic hormone in a case of hypothyroidism.

We report a 70-year-old woman with hypothyroidism and severe hyponatremia. Her plasma antidiuretic hormone (ADH) level was inappropriately high for her low plasma osmolality. Her low serum sodium level was gradually corrected by water restriction and sodium supplementation prior to the initiation of thyroid hormone replacement. After a diagnosis of Hashimoto's thyroiditis had been made, the patient was treated with levothyroxine. Following this treatment, the patient's serum sodium level increased drastically. It is suggested that the elevated plasma ADH level played an important role in the development of hyponatremia in this case.

Adrenal Glands↗

Preventive procedures against GBS infection by means of antibody measurement.

OBJECTIVE: Screening group B Streptococcus (GBS) in the vagina of pregnant women and measuring serum level of its type-specific antibody would be useful for cost-benefit of the prevention against GBS infection. STUDY DESIGN: The subjects included a total of 1,150 pregnant women who consented to the study. Serotypes of GBS detected were classified with antiserum. Serum type-specific antibody titers were measured by a bacterial agglutination method. RESULTS: Of a total of 1,150 pregnant women, 250 cases (21.7%) had GBS in the vagina. The turn of GBS serotype occurrence was types VI (NT6) (27. 2%), VIII (JM9) (25.2%), III (11.2%), Ia (8.8%), and Ib (8.0%). None or low type-specific antibody titer was 41.0% of Ia, 20.0% of Ib, 22. 0% of II, 15.0% of III, 65.0% of VI, and 69.0% of VIII incarriers. Noneonatal GBS infection occurred under the empirically treatment. CONCLUSION: The measurement of serum type-specific antibody against GBS would be informative for the cost-benefit treatment of the vaginal GBS in pregnant women.

Antibodies, Bacterial↗

[A case of non-small-cell lung cancer successfully treated using combination chemotherapy with CDDP and vinorelbine].

A 67-year-old woman presented to our hospital with a chief complaint of bloody sputum. A plain chest X-ray a CT scan revealed a tumor shadow 3 cm in size in the middle lobe of the right lung, multiple nodular shadows in the bilateral lung fields and enlarged hilar and mediastinal lymph nodes. A tumor biopsy done under bronchoscopy revealed poorly differentiated adenocarcinoma of the lungs (cT2N3M1). She was given two courses of combination therapy consisting of cisplatin (80 mg/m2) and vinorelbine (20 mg/m2). The primary tumor in the middle lobe of the right lung and the lung metastases were markedly reduced in size, and a complete response was obtained. The only adverse events were grade 4 neutropenia and grade 2 nausea and vomiting.

Aged↗

[A case of Klebsiella pneumoniae infection causing a buccal abscess complicated with multiple lung abscesses].

A 51 year-old man fitted with a dental prosthesis was hospitalized with buccal swelling, fever and chest pain. Laboratory data showed marked inflammatory changes, and chest radiography and CT scanning revealed small nodular shadows within the lung. A diagnosis of multiple lung abscesses secondary to a buccal abscess possibly caused by the prosthesis was made from needle aspiration biopsies of the lung nodules and of a buccal lesion. Klebsiella pneumoniae was isolated from these lesions and from a blood culture. The patient was successfully treated with antibiotics and by surgical drainage of the buccal abscess. It is important to note that the patient was immunodeficient at the time as a result of diabetes and alcohol intoxication.

Abscess↗

Troglitazone prevents mitochondrial alterations, beta cell destruction, and diabetes in obese prediabetic rats.

To determine whether the antidiabetic action of troglitazone (TGZ), heretofore attributed to insulin sensitization, also involves protection of beta cells from lipoapoptosis, we treated prediabetic Zucker Diabetic Fatty rats with 200 mg/kg per day of TGZ. Their plasma-free fatty acids and triacylglycerol fell to 1.3 mM and 111 mg/dl, respectively, compared with 2.0 mM and 560 mg/dl in untreated controls. Their islet triacylglycerol content was 34% below controls. In islets of control rats, beta cells were reduced by 82% and the islet architecture was disrupted; beta-cell glucose transporter-2 was absent, 85% of their mitochondria were altered, and they were unresponsive to glucose. In treated rats, the loss of beta cells was prevented, as were the loss of beta cell glucose transporter-2, the mitochondrial alterations, and the impairment of glucose-stimulated insulin secretion. We conclude that the antidiabetic effect of TGZ in prediabetic Zucker Diabetic Fatty rats involves prevention of lipotoxicity and lipoapoptosis of beta cells, as well as improvement in insulin sensitivity.

Animals↗

Comparing the hypothalamic and extrahypothalamic actions of endogenous hyperleptinemia.

To determine whether the depletion of body fat caused by adenovirus-induced hyperleptinemia is mediated via the hypothalamus, we used as a "bioassay" for hypothalamic leptin activity the hypothalamic expression of a leptin-regulated peptide, cocaine- and amphetamine-regulated transcript (CART). The validation of this strategy was supported by the demonstration that CART mRNA was profoundly reduced in obese rats with impaired leptin action, whether because of ablation of the ventromedial hypothalamus (VMH) or a loss-of-function mutation in the leptin receptor, as in Zucker diabetic fatty rats. We compared leptin activity in normal rats made hyperleptinemic by adenovirus-leptin treatment (43 +/- 9 ng/ml, cerebrospinal fluid leptin 100 pg/ml) with normal rats made hyperleptinemic by a 60% fat intake (19 +/- 4 ng/ml, cerebrospinal fluid leptin 69 +/- 22 pg/ml). CART was increased 5-fold in the former and 2-fold in the latter, yet in adenovirus-induced hyperleptinemia, body fat had disappeared, whereas in high-fat-fed rats, body fat was abundant. Treatment of the high-fat-fed rats with adenovirus-leptin further increased their hyperleptinemia to 56 +/- 6 ng/ml without changing CART mRNA or food intake, indicating that leptin action on hypothalamus had not been increased. Nevertheless, their body fat declined 36%, suggesting that an extrahypothalamic mechanism was responsible. We conclude that in diet-induced obesity body-fat depletion by leptin requires supraphysiologic plasma concentrations that exceed the leptin-transport capacity across the blood-brain barrier.

Adipose Tissue↗

Hyperleptinemia depletes fat from denervated fat tissue.

Adenovirus-mediated transfer of the leptin gene causes severe hyperleptinemia with rapid disappearance of visible body fat. To determine if this dramatic lipopenic action is mediated by neurotransmitted signals from the central nervous system, we transplanted the right epididymal fat pad of normal rats to the anterior abdominal wall. Four weeks later, rats were infused with either adenovirus-leptin cDNA (AdCMV-leptin) or adenovirus-beta-galactosidase (AdCMV-beta-gal). Eight days later, plasma leptin averaged 23 +/- 12 ng/ml in the former and 1.2 +/- 0.4 ng/ml in the latter. The fat transplant was intact in all 4 AdCMV-beta-gal-infused rats but had disappeared in all 4 hyperleptinemic rats. Tyrosine hydroxylase staining of the fat pad remnant was negative, excluding regrowth of sympathetic nerves. Thus, the lipopenic action of severe hyperleptinemia on adipocytes is not mediated by neurotransmitters, but must have resulted either from direct action of leptin and/or from leptin-mediated neurohormones.

Adenoviridae↗

Reversing adipocyte differentiation: implications for treatment of obesity.

Conventional treatment of obesity reduces fat in mature adipocytes but leaves them with lipogenic enzymes capable of rapid resynthesis of fat, a likely factor in treatment failure. Adenovirus-induced hyperleptinemia in normal rats results in rapid nonketotic fat loss that persists after hyperleptinemia disappears, whereas pair-fed controls regain their weight in 2 weeks. We report here that the hyperleptinemia depletes adipocyte fat while profoundly down-regulating lipogenic enzymes and their transcription factor, peroxisome proliferator-activated receptor (PPAR)gamma in epididymal fat; enzymes of fatty acid oxidation and their transcription factor, PPARalpha, normally low in adipocytes, are up-regulated, as are uncoupling proteins 1 and 2. This transformation of adipocytes from cells that store triglycerides to fatty acid-oxidizing cells is accompanied by loss of the adipocyte markers, adipocyte fatty acid-binding protein 2, tumor necrosis factor alpha, and leptin, and by the appearance of the preadipocyte marker Pref-1. These findings suggest a strategy for the treatment of obesity by alteration of the adipocyte phenotype.

Adenoviridae↗

[Evaluation of inoculum density prepared by prompt inoculation system and antimicrobial susceptibility test results by the automated MicroScan WalkAway system].

The Prompt Inoculation System adapted to the susceptibility testing by the automated microbiology system, MicroScan WalkAway (Dade MicroScan Inc., West Sacramento, CA, U.S.A.) was evaluated by determining colony forming units (cfu) per ml of the inocula and by the susceptibility test results obtained through repeated testing of the American Type Culture Collection (ATCC) reference strains described by the National Committee for Clinical Laboratory Standards (NCCLS). The colony forming units per ml of the inocula prepared by the Prompt ranged 2x10++(5) to 2x10(6)++ cfu/ml for the ATCC reference strains, the results indicating that the Prompt gave a higher inoculum density and was more reproducible when compared to the standard turbidity, McFarland adjustment. Also, most inocula prepared from the clinical isolates, comprising the strains of Enterobacteriaceae,no-entericbacilli,staphylococci,enterococci, and streptococci,contained 1x10(6) to 3x10(6) cfu/ml. Although the inocula prepared by the Prompt contained more viable bacterial cells, the outcome results for susceptibility testing by the MicroScan WalkAway were highly acceptable. Four ATCC reference strains were repeatedly tested. Of 540 MIC determinations, 489 (90. 6%) were within the acceptable MIC ranges described by the NCCLS M100-S9, whereas the inocula prepared by the photometric adjustment gave 87.4%. In conclusion, the Prompt inocula were found to give more precise susceptibility test results mostly equivalent to those obtained from inocula prepared by the conventional photometric procedures.

Bacteriological Techniques↗

Lipoapoptosis in beta-cells of obese prediabetic fa/fa rats. Role of serine palmitoyltransferase overexpression.

We reported that the lipoapoptosis of beta-cells observed in fat-laden islets of obese fa/fa Zucker Diabetic Fatty (ZDF) rats results from overproduction of ceramide, an initiator of the apoptotic cascade and is induced by long-chain fatty acids (FA). Whereas the ceramide of cytokine-induced apoptosis may be derived from sphingomyelin hydrolysis, FA-induced ceramide overproduction seems to be derived from FA. We therefore semiquantified mRNA of serine palmitoyltransferase (SPT), which catalyzes the first step in ceramide synthesis. It was 2-3-fold higher in fa/fa islets than in +/+ controls. [3H]Ceramide formation from [3H]serine was 2.2-4. 5-fold higher in fa/fa islets. Triacsin-C, which blocks palmitoyl-CoA synthesis, and L-cycloserine, which blocks SPT activity, completely blocked [3H]ceramide formation from [3H]serine. Islets of fa/fa rats are unresponsive to the lipopenic action of leptin, which normally depletes fat and prevents FA up-regulation of SPT. To determine the role of leptin unresponsiveness in the SPT overexpression, we transferred wild type OB-Rb cDNA to their islets; now leptin completely blocked the exaggerated FA-induced increase of SPT mRNA while reducing the fat content. Beta-cell lipoapoptosis was partially prevented in vivo by treating prediabetic ZDF rats with L-cycloserine for 2 weeks. Ceramide content and DNA fragmentation both declined 40-50%. We conclude that lipoapoptosis of ZDF rats is mediated by enhanced ceramide synthesis from FA and that blockade by SPT inhibitors prevents lipoapoptosis.

Acyltransferases↗

[Evaluation of Fluo-Card Milleri to Identify the Isolates of Streptococcus milleri Group: Comparative Identication with Referral Fluorogenic Phenotypic Dierentiation]

Clinical isolates which belong to the "Streptococcus milleri" group were identied by the referral uorogenic phenotypic tests described by Whiley et al. [J. Clin. Microbiol., 28: 1497-1501 (1990)] and a rapid, commercially available test kits; Fluo-Card Milleri (KEY Scientific Products, Round Rock, Tex., U.S.A.) to the species level. Of 218 clinical isolates included, 196 (89.9%) were correctly identied by the Fluo-Card Milleri when compared with the reference identications. Ten isolates (4.6%) of S. constellatus resulted in the "unidentied" due to the negative interpretations for all the three enzymatic reactions. A total of twelve isolates (5.5%); five of S. anginosus, five of S. constellatus, and two of S. intermedius, were misidentied. The levels of agreement were 95.7% for S. anginosus, 91.3% for S. intermedius, and 92.6% for S. constellatus when the unidentied results were excluded.

Journal Article↗

Role of peroxisome proliferator-activated receptor alpha in disease of pancreatic beta cells.

Expression of peroxisome proliferator-activated receptor alpha (PPARalpha) and enzymes of fatty acid (FA) oxidation is markedly reduced in the fat-laden, dysfunctional islets of obese, prediabetic Zucker diabetic fatty (fa/fa) rats with mutated leptin receptors (OB-R). Leptin, PPARalpha/retinoid x receptor ligands, and FA all up-regulate PPARalpha and enzymes of FA oxidation and stimulate [3H]-palmitate oxidation in normal islets but not in islets from fa/fa rats. Overexpression of normal OB-R in islets of fa/fa rats corrects all of the foregoing abnormalities and reverses the diabetic phenotype. PPARalpha is a OB-R-dependent factor required for normal fat homeostasis in islet cells.

Animals↗

Enhanced de novo lipogenesis in the leptin-unresponsive pancreatic islets of prediabetic Zucker diabetic fatty rats: role in the pathogenesis of lipotoxic diabetes.

Overaccumulation of fat in pancreatic islets of obese ZDF fa/fa rats is believed to cause beta-cell failure and diabetes. Previously, we demonstrated that ZDF islets have an increased capacity to esterify fatty acids imported via the circulation. Here we examine the capacity of ZDF islets to synthesize fatty acids de novo. Compared with age-matched wild-type (+/+) control islets, acetyl CoA carboxylase (ACC) mRNA was fivefold and sixfold higher and fatty acid synthetase (FAS) was fourfold and sevenfold higher in prediabetic and diabetic ZDF islets, respectively. Incorporation of label from [14C]glucose into lipids was 84% higher in ZDF islets and was not suppressed normally by fatty acids. Chronic hyperleptinemia, induced by adenoviral transfer of leptin cDNA, reduced ACC and FAS mRNA in +/+ islets by 93 and 80%, respectively, but did not decrease the high ACC and FAS expression in islets of fa/fa rats. Recombinant leptin cultured with islets isolated from +/+ rats lowered ACC and FAS expression by 66 and 47%, respectively, but had no effect in fa/fa islets. We conclude that de novo lipogenesis in islets is controlled by leptin and remains low in leptin-responsive islets. It is increased in leptin-insensitive fa/fa islets, contributing to the fat overload that leads to beta-cell dysfunction and diabetes.

Acetyl-CoA Carboxylase↗

Distinct promoter sequences of two precursor genes for salmon gonadotropin-releasing hormone in masu salmon.

Two types of genes encode salmon gonadotropin-releasing hormone (sGnRH), which is thought to act on both sexual maturation and reproductive behavior, in salmonids. We characterized the two sGnRH genes (sGnRH-I and -II) and their upstream regions in masu salmon, Oncorhynchus masou, since such information is a prerequisite for molecular approaches to salmon reproduction. The two genes have similar exon-intron structures composed of four exons and three introns. Sequence analyses of the two genes showed that coding regions are highly conserved, but upstream regions are distinctively divergent. In the upstream regions, only the sGnRH-II gene has a large palindromic sequence, which has been proposed to be involved in control of transcription via estrogen receptors. In contrast, the sGnRH-I gene is missing the large palindromic sequence, but has three distinct palindromes in the upstream region. These results may suggest divergent transcription regulatory mechanisms between the two sGnRH genes in masu salmon. The differences in the upstream regions of sGnRH genes in Atlantic salmon (Salmo salar), sockeye salmon (Oncorhynchus nerka) and masu salmon are discussed with respect to the evolution of sGnRH genes in salmonid fish.

Animals↗

[Intranasal midazolam for sedation before anesthesia in pediatric patients].

To evaluate the efficacy of nasally administered midazolam for sedation before anesthesia in pediatric patients, the authors studied 45 ASA PS 1 or 2 patients (aged 9 months-6 years) scheduled for elective surgery. The sedative effect of intranasal midazolam (0.2 mg.kg-1 or 0.3 mg.kg-1) was compared with that of our standard premedication by score. Significant sedative effect was obtained 4 min (in the 0.2 mg.kg-1 group) and 3 min (in the 0.3 mg.kg-1 group) after nasal administration. Most patients (93%) in the midazolam group became either free from anxiety or calm allowing easy separation from the parents and a smooth induction of anesthesia 10 min after nasal administration. There was no respiratory depression or anesthetic complication during induction of anesthesia, and no delayed recovery was observed. These results indicate that intranasal midazolam 0.2 mg.kg-1 is an effective and useful method for rapid sedation of children just prior to the induction of anesthesia.

Administration, Intranasal↗

Molecular cloning and characterization of two genes encoding gp138, a cell surface glycoprotein involved in the sexual cell fusion of Dictyostelium discoideum.

The sexual development of cellular slime molds is initiated by acquisition of sexual fusion competence of myxamoeboid cells. During the acquisition of fusion competence in NC4 and HM1 strain cells of Dictyostelium discoideum, opposite in mating types, a glycoprotein gp138, relevant to sexual cell fusion, is expressed on the cell surfaces of both the strains. To investigate the mechanisms controlling cell fusion, gp138 was purified and its N-terminal amino acid sequence was determined. An oligonucleotide with sequence predicted from the amino acid sequence was synthesized to isolate the gene encoding gp138. Two genes, referred to as GP138A and GP138B, were then cloned. They contain the region which encodes the N-terminal amino acid sequence of the gp138 protein and their structure is very similar on the whole. The C-terminal portion of the predictive polypeptides produced by the genes is highly hydrophobic and proline rich. It has homology with a portion of gp80, a glycoprotein for cell-cell adhesion, and PsA, a glycoprotein specific for prespore cells, reported previously in D. discoideum. The expression of GP138A is greater than that of GP138B. The mRNA of GP138A is expressed at the time of acquisition of fusion competence of cells during cultivation but the mRNA of GP138B is not.

Amino Acid Sequence↗

Antisense RNA inactivation of gp138 gene expression results in repression of sexual cell fusion in Dictyostelium discoideum.

A glycoprotein, gp138, is implicated in the sexual cell fusion of Dictyostelium discoideum. We previously cloned and sequenced the two genes encoding the gp138 protein, GP138A and GP138B (Fang et al. (1993) Dev. Biol. 156, 201-208). Here, we have constructed a vector producing antisense RNA for the gp138 genes and have transformed the vector into Dictyostelium cells. The transformed cells showed a reduction in the amounts of gp138 mRNA and protein and their sexual cell fusion activity was considerably repressed.

Animals↗