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Biomedical subjects

M Goto

Publications and source records attributed to M Goto.

At least 343 records · Page 19Linked to original sources
PubMed1997

Isolation of a novel cytokine from human fibroblasts that specifically inhibits osteoclastogenesis.

A factor which inhibits osteoclast-like cell formation was found in the conditioned medium of human embryonic lung fibroblasts, IMR-90. The factor, termed osteoclastogenesis inhibitory factor, OCIF, was purified to homogeneity. OCIF is a heparin-binding basic glycoprotein and has been isolated as a monomer with an apparent molecular weight (Mr) of 60,000 and a homodimer with a Mr of 120,000. The N-terminus of OCIF is blocked and the determination of internal amino acid sequences revealed that OCIF has no homology to known proteins. OCIF inhibited in a dose-dependent manner osteoclastogenesis elicited through three distinct signaling pathways stimulated by 1 alpha,25-dihydroxy vitamin D3, parathyroid hormone, and interleukin-11, respectively, in a dose range of 1 to 40 ng/ml (IC50 = 4 to 6 ng/ml). OCIF neither inhibits bone resorption by mature osteoclasts nor exerts any other biological activities. These data strongly suggest that OCIF is a novel cytokine which specifically inhibits osteoclastogenesis.

Acid Phosphatase↗
PubMed1997

Cloning and characterization of a novel gene, WS-3, in human chromosome 8p11-p12.

A novel human gene referred to as the WS-3 gene, in the short arm of human chromosome 8, was cloned by a combination of exon trapping, thermal asymmetric interlaced-PCR (TAIL-PCR) and the Marathon-Ready cDNA amplification method. The gene consists of 7 exons separated by 6 introns, and is at the telomere side of the STS marker, D8S1055. The full-length WS-3 gene contains 1052 nucleotides and codes for a protein of 190 amino acids with a calculated mol. wt. of 20,747. Southern blot experiments showed that the WS-3 gene exists as a single copy in the human genome. A protein encoded by the WS-3 gene has an R-G-D (Arg-Gly-Asp) motif in the N-terminal region, which seems to confer adhesive properties to macromolecular proteins like fibronectin. Although WS-3 is a small gene with unknown biological function, its ubiquitous expression in various tissues and organs suggests that the encoded protein is one of the essential components of all organs and tissues.

Amino Acid Sequence↗
PubMed1997

Sodium dodecyl sulfate-Tween 20 mixed micellar electrokinetic chromatography for separation of hydrophobic cations: application to adrenaline and its precursors.

Separation of hydrophobic cations in capillary electrophoresis under the mixed micellar system composed of SDS and Tween 20 was investigated from the viewpoints of thermodynamics and practical application. Hydrophobic cations interact strongly with the anionic SDS micelle, and this often lead to predominant dissolution of the analytes into the micellar phase, resulting in poor resolution. The ionic interaction was evaluated to be close in strength to the hydrophobic interaction between benzenes and the SDS micelle. Tween 20 as a component to the mixed micelle was found to weaken the attractive ionic interactions between the cationic solutes and SDS. In addition, the polyether chain of Tween 20 serves also as a hydrogen acceptor to cause the attractive hydrogen-bonding interactions with hydrogen-donating analytes. The two different functions of Tween 20 improve the separation of hydrophobic cations remarkably. Separation patterns are well controlled by varying the mixing ratio of the two surfactants. Adrenaline and its six precursors were successfully separated with this mixed micellar system. The improved separation efficiency was not affected by the presence of bovine serum matrix, realizing the direct MEKC analysis of serum sample without deproteination, in which proteins were comigrated with the micelle.

Animals↗
PubMed1997

Premature aging syndrome with osteosarcoma, cataracts, diabetes mellitus, osteoporosis, erythroid macrocytosis, severe growth and developmental deficiency.

We describe a premature aging disorder in a 15-year-old girl with severe growth and developmental deficiency. Her clinical findings included osteosarcoma, nuclear and subcapsular cataracts, insulin-resistant diabetes mellitus, osteoporosis, epilepsy, foot ulcers, erythroid macrocytosis, and unusual facial appearance. Hyaluronic acid levels in serum and urine were normal. Cultured skin fibroblasts had a normal potential for in vitro growth. This finding represents a new and unique premature aging syndrome.

Abnormalities, Multiple↗
PubMed1997

Infarct size limitation by a new Na(+)-H+ exchange inhibitor, Hoe 642: difference from preconditioning in the role of protein kinase C.

OBJECTIVES: This study examined the effect of a new specific Na(+)-H+ exchange inhibitor, Hoe 642, on infarct size and the protective role of protein kinase C (PKC) by this agent. In addition, we assessed the possible alteration of Hoe 642-induced cardioprotection by commonly used animal anesthetic drugs. BACKGROUND: Earlier studies on the contribution of Na(+)-H+ exchange to ischemic injury were complicated by nonspecific actions of the Na(+)-H+ exchange inhibitors, and the role of this exchanger in myocardial infarction in vivo remains unclear. The difference in anesthetic agents used in experiments could have resulted in discrepant findings regarding cardioprotection of some interventions, such as preconditioning and adenosine triphosphate-sensitive potassium channel openers. METHODS: Infarction was induced by 30 min of coronary occlusion and 3 h of reperfusion in the rabbit heart. In the first series of experiments, rabbits were anesthetized with pentobarbital or ketamine/xylazine. Hoe 642 was injected intravenously 10 min before ischemia or 5 min before reperfusion. In the second series of experiments, rabbits received 25 mg/kg body weight of polymyxin B (polyB), Hoe 642 plus polyB, preconditioning with 5 min of ischemia and 5 min of reperfusion plus polyB or preconditioning alone before 30 min of ischemia. RESULTS: In pentobarbital-anesthetized rabbits, 0.3 mg/kg and 0.6 mg/kg of Hoe 642 given before ischemia limited infarct size (as percent area at risk [%IS/AR]) to 42.7 +/- 4.4% (SEM) and 26.2 +/- 5.4%, respectively, from the control value of 55.1 +/- 3.5%. However, injection of Hoe 642 before reperfusion did not change infarct size (%IS/AR 49.6 +/- 4.9%, p = 0.387; power 0.81 for detecting 50% reduction). Infarct size limitation by the preischemic treatment with Hoe 642 was similarly observed in the rabbits anesthetized with ketamine/xylazine. In the polyB-treated rabbits, 0.6 mg/kg of Hoe 642 significantly limited infarct size (%IS/AR was 28.3 +/- 3.8% with Hoe 642 and 50.1 +/- 7.5% without Hoe 642), although preconditioning was blocked by the same dose of polyB (%IS/AR was 39.3 +/- 6.1% with polyB and 11.3 +/- 2.4% without polyB). CONCLUSIONS: Hoe 642 enhanced myocardial tolerance against infarction, and this enhanced tolerance was not influenced by anesthetic agents commonly used for infarct size studies. Infarct size limitation by Hoe 642 was not inhibited by polyB, suggesting that cardioprotection by Na(+)-H+ exchange inhibition is not PKC mediated and thus may be unrelated to preconditioning.

Animals↗
PubMed1997

[The effect of brain-derived neurotrophic factor on elongation of axons after transection with suture-morphometric evaluation].

Brain-derived neurotrophic factor (BDNF) is considered to play an important role in survival, maintenance, development and repair of the peripheral neuron. In this study, the effect of human recombinant BDNF on sprouting and elongation of axons, the early phase of regeneration of nerve fibers, was morphometrically evaluated 7 days following the sciatic nerve transection and juxtaposition of proximal and distal stumps with suture in Sprague-Dawley rats. In the experimental group (test), 20 mg/kg of BDNF was injected subcutaneously every day for seven days in eight rats, starting 30 minutes after the transection. In the control group (control), phosphate buffered-saline alone was injected in nine rats as in the experimental group. The various morphometric parameters were evaluated in the sciatic nerve of each rat of the control and test, 3 mm distal to the site of the transection on light and electron microscopy of Epon-embedded sections. On both light and electron microscopy only a few myelinated fibers with a very thin myelin sheath were found only in one nerve in each of the control and test. However, significant numbers of unmyelinated axons were found in each nerve of the control and test. There were no statistically significant differences in the total fascicular area per nerve, the numbers of myelinated and unmyelinated axons per mm2 of fascicular area and per nerve, their maximum and median diameters and their size distribution histograms between control and test. In addition, there were no statistically significant differences in the numbers of myelin ovoids per mm2 of the fascicular area and per nerve, their maximum and median diameters and their size distribution histograms between control and test. Therefore, we concluded that there was no definite evidence that BDNF promoted the sprouting and elongation of axons, the early phase of the regeneration of nerve fibers, at least under this experimental conditions.

Animals↗
PubMed1997

Cloning and characterization of Rep-8 (D8S2298E) in the human chromosome 8p11.2-p12.

A novel human gene referred to as the Rep-8 gene (D8S2298E) was cloned by a combination of exon trapping, thermal asymmetric interlaced-PCR, and screening of a cDNA library. It is located in human chromosome 8p11.2-p12. The gene consists of eight exons and spans about 20 kb between the glutathione S-reductase and the protein phosphatase 2A beta subunit genes. The full-length Rep-8 gene contains 1483 nucleotides and codes for a protein of 270 amino acids. Southern blot experiments showed that the Rep-8 gene exists as a single copy per haploid. With a zoo blot analysis, human Rep-8 DNA hybridized strongly with the monkey DNA, but only weakly with the DNAs of species other than Homo sapiens. Northern blot analysis showed that it is expressed abundantly in the testis and ovary, suggesting that the Rep-8 gene product may play a role in reproduction.

Amino Acid Sequence↗
PubMed1997

Persistent infiltration of CD45RC- CD4+ T cells, Th2-like effector cells, in prolonging hepatic allografts in rats pretreated with a donor-specific blood transfusion.

A single intravenous injection of freshly heparinized blood from a donor-specific blood transfusion (DST) seven days before transplantation significantly prolongs the subsequent survival of hepatic allografts from ACI(RT1a) to LEW(RT1(1)) rats. We used W3/25 (anti-CD4) and OX22 (anti-CD45RC: an isoform of leukocyte-common antigen [CD45R]) monoclonal antibodies to investigate the cellular identity of hepatic allograft infiltrates following transplantation. The number of CD4+ and CD45RC+ cells in untreated allografts increased equally over time by day seven. However, in DST-treated hepatic allografts, CD4+ and CD45RC+ cells also increased over time by day 14, but the increment in the number of CD4+ cells was significantly greater than that in CD45RC+ cells. While the number of CD4+ cells remained persistently elevated in the hepatic allografts of rats pretreated with DST, they did not initiate rejection. Fluorescence-activated cell sorter (FACS) analysis revealed that the accumulated CD4+ T cells could be divided into two subsets, CD45RC- CD4+ and CD45RC+ CD4+ T cells, and that the ratio of CD45RC- CD4+/CD45RC+ CD4+ T cells in the hepatic allografts of recipients pretreated with DST was significantly greater than that in untreated allografts. Reverse-transcriptase polymerase chain reaction (RT-PCR) analysis demonstrated that CD45RC- CD4+ T cells expressed interleukin (IL)-4 and IL-10 messenger RNA (mRNA), but not IL-2 and interferon gamma (IFN-gamma). The pattern of messenger RNA expression in hepatic allograft infiltrates from animals pretreated with DST provides compelling evidence for the selective in vivo preservation of T-helper (Th2)-specific cytokines in the rat system. Our studies show that CD45RC leukocyte-common antigen expression can define different populations of hepatic infiltrating CD4+ T cells. A persistent infiltration of CD45RC- CD4+ T cells, Th2-like effector cells, is characteristic of hepatic allografts with a prolonged survival in DST-pretreated rats.

Animals↗
PubMed1997

Oxygen radicals released during ischemic preconditioning contribute to cardioprotection in the rabbit myocardium.

Previous studies have proposed that oxygen radicals may play a role in the triggering of ischemic preconditioning. However, studies evaluating the effects of radical scavengers have yielded conflicting results, possibly because of differences in the number of preconditioning episodes used. The present study tested whether N-2-mercaptopropionylglycine (MPG) could block protection of both single and multiple episodes of preconditioning in in situ and in vitro rabbit hearts. All hearts were subjected to 30 min of regional ischemia followed by reperfusion for 2 (in vitro) or 3 (in situ) h. Infarct size was measured by tetrazolium. Infarction in control in situ hearts was 37.5+/-3.5% of the risk zone. A single cycle of preconditioning (PC1), with 5 min ischemia/10 min reperfusion, reduced infarct size to 12.3+/-2.0% (P<0.05). Four cycles of preconditioning (PC4) were equally protective. MPG (1 mg/kg/min i.v.) alone had no effect on infarction but abolished protection afforded by PC1 (35.4+/-3.9%). However, MPG failed to block protection in the PC4 group. In isolated control hearts, infarct size was 31.1+/-1.8% and was reduced to 10.2+/-2.2% (P<0.05) by preconditioning. MPG (300 microM) aborted protection. Infusion of hypoxanthine or xanthine oxidase separately in lieu of preconditioning had no effect on infarct size, but induced protection when combined (14.1+/-2.2%; P<0.05). Polymyxin B, an inhibitor of protein kinase C (PKC), abolished this protection (53.1+/-4.1%). In conclusion, oxygen radicals contribute to ischemic preconditioning in the rabbit and appear to do so via activation of PKC. The fact that MPG could not block protection by PC4 suggests that oxygen radicals act in concert with other triggers of preconditioning such as adenosine and bradykinin.

Analysis of Variance↗
PubMed1997

Hyperimmunoglobulinemia D in idiopathic retinal vasculitis.

BACKGROUND: We examined four patients who exhibited both idiopathic retinal vasculitis and elevated serum IgD levels. Uveitis caused by Behçet's disease is also associated with high levels of serum IgD. Therefore, the clinical features of these patients were investigated and the possible relationship between retinal vasculitis and elevated serum IgD was examined after undertaking a study of increased IgD levels in patients diagnosed with uveitis. METHODS: The study population was composed of 110 patients: 49 with Behçet's disease, 15 with sarcoidosis, 10 with Vogt-Koyanagi-Harada disease, and 36 with other forms of uveitis. IgD measurements were performed using modifications of the latex photometric immunoassay. Surface IgD (sIgD) expression in peripheral lymphocytes was determined by immunofluorescence, and the correlation between serum IgD levels and the percentage of sIgD-positive cells was examined. RESULTS: Twelve of the 110 patients had an elevated serum IgD. Eight of the 12 had Behçet's disease, and 4 were diagnosed with idiopathic retinal vasculitis. These 4 patients were HLA-A24+ females whose ages ranged from 8 to 25 years. A linear correlation between the serum IgD levels and the percentage of sIgD-positive cells was found. CONCLUSION: Hyperimmunoglobulinemia D state was found in Behçet's disease and idiopathic retinal vasculitis. These diseases may represent a new clinical entity characterized by signs of retinal vasculitis and hyperimmunoglobulinemia D that results from abnormal B cell activation and immune complex-mediated responses.

Adolescent↗
PubMed1997

Acinar-islet cell carcinoma presenting as insulinoma.

A case of acinar-islet cell carcinoma presenting as insulinoma is reported. The patient was a 28-year-old man who presented with two convulsive episodes. Fajans' index [immunoreactive insulin (IRI; microU/ml/ glucose mg/dl)] and Turner's [IRI (microU/ml) x 100/glucose (mg/dl) - 30] index were high (2.8 and 308, respectively), as were serum proinsulin levels (550 pg/ml). Abdominal computed tomography and angiography revealed a highly vascular tumor in the pancreatic tail and several similar tumors in the liver. Histologic features of a biopsy specimen from a hepatic tumor were those of a malignant pancreatic endocrine tumor. Insulin secretion by the liver metastases was confirmed by venous sampling after arterial stimulation with calcium. These findings led us to diagnose malignant insulinoma with liver metastases. Serum levels of alpha-fetoprotein and trypsin were markedly elevated, to 2234 ng/ml (normal < 10) and 22,000 ng/ml (normal < 460) respectively, and these levels continued to rise with further growth of the liver metastases. Immunohistochemically, the metastatic liver tumor specimen was positive for alpha-fetoprotein, alpha 1-antichymotrypsin, chromogranin A, and neuron-specific enolase. These findings of amphicrine features in the tumor were indicative of acinar-islet cell carcinoma that produced alpha-fetoprotein and trypsin in addition to insulin.

Adenoma, Islet Cell↗
PubMed1997

Analysis of helicase gene mutations in Japanese Werner's syndrome patients.

The profile of helicase gene mutations was studied in 89 Japanese Werner's syndrome (WRN) patients by examining the previously described mutations 1-4 as well as a new mutation found during this study, designated mutation 5. Of 178 chromosomes (89 patients), 89 chromosomes (50%) had mutation 4, 11 (6.2%) chromosomes had mutation 1, and two chromosomes (1.1%) contained mutation 5. Mutations 2 and 3 were not observed in this patient population. The remaining 76 (42.7%) chromosomes had none of these mutations. A significant fraction of all patients (22 total patients, 24.7%) appear to be compound heterozygotes, including those carrying mutations of both types 1 and 4. The genotypes analysis of the markers surrounding the. WRN helicase gene strongly suggests that most of the chromosomes carrying either mutation 1 or 4 were derived from two single founders.

DNA Helicases↗
PubMed1997

Mutation and haplotype analyses of the Werner's syndrome gene based on its genomic structure: genetic epidemiology in the Japanese population.

The correlation between mutations in the Werner's syndrome (WRN) gene and the haplotypes of surrounding markers was studied in Japanese patients. We have elucidated the genomic structure of WRN helicase, and found five additional mutations, designated mutations 6-10. Mutations 4 and 6 were found to be the two major mutations in this population; these mutations comprised 50.8% and 17.5%, respectively, of the total in a sample of 126 apparently unrelated chromosomes. Almost all the patients homozygous for mutation 4 shared a haplotype around the WRN gene, consistent with the view that they are derived from a single ancestor. This important advantage demonstrated in the identification of the WRN gene suggests that the Japanese present a unique population for the cloning of other disease genes. The conserved haplotype was observed across 19 loci, extending a distance estimated to be more than 1.4 Mbp around the WRN gene. This haplotype is rare among random Japanese individuals. Unexpectedly, all the nine patients homozygous for mutation 6 shared a haplotype that was identical to this haplotype at 18 of these 19 markers. These results suggest that mutations 4 and 6 arose independently in almost identical rare haplotypes. The remaining mutations (1, 5, 7, 8, 9, and 10) occurred rarely, and were each associated with different haplotypes.

DNA Helicases↗
PubMed1997

Factors affecting carbohydrate and free amino acid content in overwintering larvae of Enosima leucotaeniella.

Amounts of several metabolites were measured in overwintering larvae of Enosima leucotaeniella acclimated to temperatures between -5 and 15 degrees C for 30days. In the diapausing stage, cold hardiness, as shown by the survival rate, began rising below 15 degrees C. Glycogen content decreased as the temperature decreased from 10 to 0 degrees C. Trehalose content rose as the temperature decreased from 15 to 5 degrees C, but remained unchanged as the temperature decreased from 5 and 0 degrees C. Twenty-eight free amino acids were detected in the haemolymph; levels of proline, glutamine and glutamic acid increased at high temperatures, but alanine increased at low temperatures, especially as temperature decreased from 5 to 0 degrees C. Lipid content was unchanged by the different acclimation temperatures. The effects of temperature, diapause and aerobic conditions on the levels of carbohydrates and amino acids in overwintering larvae were analyzed. Alanine levels rose at low temperature only when the larvae were in the diapausing stage. The level of trehalose rose at low temperature in both the diapausing and post-diapausing stages, although it was higher at aerobic conditions in the post-diapausing stage. These results suggest that efficient trehalose synthesis occurs under the combination of low temperature and aerobic conditions of the post-diapausing stage, so that cold hardiness in overwintering E. leucotaeniella larvae may rise to a high level in winter.

Journal Article↗
PubMed1997

Analysis of heart rate variability demonstrates effects of development on vagal modulation of heart rate in healthy children.

OBJECTIVES: Analysis of heart rate variability (HRV) has been found to be a useful method of assessing cardiovascular autonomic control, but normal values for standard HRV measures in children have not been established. We analyzed HRV in 60 healthy children aged 3 to 15 years to determine normal values and to assess the effects of development on cardiac autonomic control with the use of ambulatory electrocardiographic monitoring. RESULTS: The high-frequency (HF) component, an index of cardiac autonomic tone, increased significantly with age from 3 to 6 years (p < 0.01) and decreased with age from 6 to 15 years (p < 0.01), and the magnitude of HF correlated significantly with the R-R intervals. Thus the changes in cardiac autonomic tone could be described as a simple equation using age and heart rate. CONCLUSIONS: We present normal values and changes in the cardiac autonomic system during childhood after HRV analysis, which could lead to a better understanding and treatment of cardiac disease in children.

Adolescent↗
PubMed1997

Hierarchical deterioration of body systems in Werner's syndrome: implications for normal ageing.

Normal human ageing is a complicated biological phenomenon. 'Werner's syndrome (WS)', caused by mutations of RecQ type DNA helicase, has been recognized as a top ranking 'segmental' progeroid syndrome. Patients with WS show a wide variety of clinical and biological manifestations in the four major self-assembly body systems (nervous, immune, connective tissue and endocrine-metabolic systems) similar to normal ageing at an early stage of their life, followed by death at an average age of 46. The sequential appearance of clinical and biological deterioration of the body systems observed in WS suggested that the disorder is more than a segmental progeroid syndrome, analysis of which may shed new light on the question 'Why and how we age?'

Aging↗
PubMed1997

Allergenic activity of heated and ovomucoid-depleted egg white.

BACKGROUND: No egg white products have been clearly proven to be hypoallergenic. The role of egg white proteins in allergic reactions to eggs is still debatable. OBJECTIVE: This study was designed to determine the importance of ovomucoid, an egg white protein, in the development of allergies to egg white. METHODS: We performed a double-blind, placebo-controlled food challenge in subjects with high levels of IgE antibodies for egg white to compare the allergenicities of heated and ovomucoid-depleted egg white, freeze-dried egg white, and heated egg white. Levels of IgE antibodies for egg white, ovomucoid, ovalbumin, ovotransferrin, and lysozyme were measured in serum by RAST. RESULTS: Twenty-one of 38 subjects with positive challenge responses to freeze-dried egg white had negative challenge responses to heated egg white, whereas 16 of 17 subjects (94.1%) with positive responses to heated egg white did not respond to the heated and ovomucoid-depleted egg white challenge. The subjects with positive challenge responses to freeze-dried egg white tended to have higher IgE antibody values to ovomucoid than those with negative responses. IgE antibody levels to ovomucoid were significantly higher in subjects with positive responses to a challenge with heated egg white than in those with no response. There were no significant differences in the levels of IgE antibodies to the other proteins, except ovomucoid, in the negative-response and positive-response groups in challenge tests with freeze-dried and heated egg white. CONCLUSION: The heated and ovomucoid-depleted egg white preparation was less allergenic than heated or freeze-dried preparations. Ovomucoid has a more important role in the pathogenesis of allergic reactions to egg white than other proteins in egg white.

Allergens↗