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Biomedical subjects

M Ohta

Publications and source records attributed to M Ohta.

At least 325 records · Page 18Linked to original sources
PubMed1997

Prevalence of the speA2 and speA3 alleles in Streptococcus pyogenes isolated from TSLS patients in Japan.

More than 100 cases have been identified as streptococcal toxic shock-like syndrome (TSLS) in Japan, since the first case was reported in 1993. Of 26 S. pyogenes isolates associated with TSLS, 69% were M-types 1 and 3. This study focused on speA alleles which were carried by all M-type 1 and 3 isolates and isolates of some other M-types, irrespective of sources. We sequenced the nucleotides of the relevant region of the speA allele in all of these isolates. Consistent with other reports, these M-type 1 and 3 isolates carried the speA2 and speA3 alleles, respectively. Our results indicate that these two speA alleles, which were prevalent world-wide have been disseminating in Japan.

Alleles↗
PubMed1997

Positions of chromosome 3p14.2 fragile sites (FRA3B) within the FHIT gene.

The FHIT gene spans approximately 1 Mb of DNA at chromosome band 3p14.2, which includes the familial renal cell carcinoma chromosome translocation breakpoint (between FHIT exons 3 and 4), the most frequently expressed human constitutive chromosomal fragile site (FRA3B, telomeric to the t(3;8) translocation), and numerous homozygous deletions in various human cancers, frequently involving FHIT exon 5. The FRA3B has previously been shown to represent more than one specific site, and some specific representatives of FRA3B breaks have been shown to fall in two regions, which we know to be in FHIT introns 4 and intron 5. Because breakage and integration of exogenous DNA in this chromosome region is frequent in aphidicolin-treated somatic cell hybrids, cancer cells, and, presumably, aphidicolin-treated normal lymphocytes that exhibit gaps or breaks, we determined by one- and two color fluorescence in situ hybridization, using cosmids covering specific regions of the FHIT gene, that most of the aphidicolin-induced gaps at FRA3B fall within the FHIT gene, with the highest frequency of gaps falling in intron 5 of the FHIT gene, less than 30 kb telomeric to FHIT exon 5. Gaps also occur in intron 4, where a human papillomavirus 16 integration site has been localized, and in intron 3, where the t(3;8) break point is located. These results suggest that the cancer-specific deletions, which frequently involve introns 4 and 5, originated through breaks in fragile sites.

Acid Anhydride Hydrolases↗
PubMed1997

Structure and expression of the human FHIT gene in normal and tumor cells.

The FHIT gene, encoded by 10 exons in a 1.1-kb transcript, encompasses approximately 1 Mb of genomic DNA, which includes the hereditary RCC t(3;8) translocation break at 3p14.2, the FRA3B common fragile region, and homozygous deletions in various cancer-derived cell lines. Because some of these genetic landmarks (e.g., the t(3;8) break between untranslated FHIT exons 3 and 4, a major fragile region that includes a viral integration site between exons 4 and 5, and cancer cell homozygous deletions in intron 5) do not necessarily affect coding exons and yet apparently affect expression of the gene product, we examined the FHIT locus and its expression in detail in more than 10 tumor-derived cell lines to clarify mechanisms underlying aberrant expression. We observed some cell lines with apparently continuous large homozygous deletions, which included one or more coding exons; cell lines with discontinuous deletions, some of which included or excluded coding exons; and cell lines that exhibited heterozygous and/or homozygous deletions, by Southern blot analysis for the presence of specific exons. Most of the cell lines that exhibited genomic alterations showed alteration of FHIT transcripts and absence or diminution of Fhit protein.

Acid Anhydride Hydrolases↗
PubMed1997

(3R)-N-(1-(tert-butylcarbonylmethyl)-2,3-dihydro-2-oxo-5-(2-pyridyl)-1H-1,4-benzodiazepin-3-yl)-N'-(3-(methylamino)phenyl)urea (YF476): a potent and orally active gastrin/CCK-B antagonist.

A number of new 1,4-benzodiazepin-2-one-based gastrin/CCK-B receptor antagonists related to the archetypal analogue L-365,260, and more closely to the recently reported compound YM022, have been synthesized and evaluated for biological activity. The compounds were screened for their ability to inhibit the binding of [125I]CCK-8 to gastrin/CCK-B receptors prepared from rat brains and that of [3H]L-364,718 to CCK-A receptors from rat pancreas, and were shown to be potent and selective ligands for the gastrin/CCK-B receptor. Functional studies in vivo demonstrated the compounds to be antagonists of the receptor as evidenced by their ability to inhibit pentagastrin-induced gastric acid secretion in anesthetized rats. More extensive evaluation in vivo included determination of ED50 values in the rat acid secretion model for selected compounds and an examination of the effect of these compounds on pentagastrin-induced gastric acid secretion in Heidenhain pouch dogs following oral and intravenous administration. Two compounds, i.e. (3R)-N-[1-[(tert-butylcarbonyl)methyl]-2,3-dihydro-2-oxo-5-(2-pyri dyl) -1H-1,4-benzodiazepin-3-yl]-N'-[3-(methylamino)phenyl]urea, 15c (YF476), and (3R)-N-[1-[(tert-Butylcarbonyl)methyl]-2,3-dihydro-2-oxo-5- (2-pyridyl)-1H-1,4-benzodiazepin-3-yl]-N'-[3-(dimethylamino)phenyl ]urea hydrochloride, 15d, showed potent dose-dependent effects in both models with the former showing excellent oral bioavailability and an ED50 of 21nmol/kg po in dogs. 15c is currently under clinical investigation for the treatment of gastro-oesophagal reflux disease (GORD).

Administration, Oral↗
PubMed1997

Antibodies to glutamic acid decarboxylase in Japanese diabetic patients with secondary failure of oral hypoglycaemic therapy.

Some patients with non-insulin-dependent (Type 2) diabetes mellitus (NIDDM) are positive for antibodies to glutamic acid decarboxylase (anti-GAD), which have been shown to be a useful marker for the diagnosis and prediction of insulin-dependent (Type 1) diabetes mellitus (IDDM). Anti-GAD positive NIDDM patients tend to develop insulin deficiency. We investigated the prevalence of anti-GAD in 200 NIDDM with secondary failure of oral hypoglycaemic therapy (SF) and 200 NIDDM well controlled by diet and/or sulphonylurea agents (NSF). Twenty-two of 200 (11%, p < 0.05) SF patients and 6 of 200 (3%) NSF patients were anti-GAD positive. The positive. The positive rate for anti-GAD was as high as 23.8% in the non-obese and insulin deficient SF patients. The SF patients with anti-GAD tended to be non-obese and to have an impaired release of endogenous insulin. The internal before development of secondary failure was not associated with the presence of anti-GAD in this study. In conclusion we found that anti-GAD was positive in as many as 11% of the SF patients, suggesting that autoimmune mechanisms may play an important role in the pathogenesis of secondary failure or sulphonylurea therapy.

Analysis of Variance↗
PubMed1997

Coagulation and vascular abnormalities in Crow-Fukase syndrome.

Coagulation and vascular abnormalities were studied in 4 patients with Crow-Fukase syndrome (CFS or POEMS) to understand the pathophysiology. Fibrinogen, fibrinopeptide A, and thrombin-antithrombin complexes (TAT) increased in sera during active phase of CFS. In nerves of 2 untreated cases, the endothelium of small vessels was immunohistochemically stained with antithrombin III antibody, which indicates the existence of TAT. HLA-DR+ inflammatory cell infiltrate surrounded these vessels. Blood-nerve barrier opening was suggested by strong immunoglobulin staining in the endoneurium. More than 50% of endoneurial blood vessels had narrowed or closed lumina with thick basement membranes. Endothelial cell abnormality and chronic intravascular coagulation may play an important role in the pathogenesis of CFS, in addition to a still unknown demyelinating factor. Refractory cases responded to combined treatment of prednisolone, human leukocyte interferon, and antithrombin drug.

Antifibrinolytic Agents↗
PubMed1997

Diagnostic significance of antibodies to glutamic acid decarboxylase in Japanese diabetic patients with secondary oral hypoglycemic agents failure.

Some non-insulin-dependent diabetes mellitus (NIDDM) patients are positive for antibodies to glutamic acid decarboxylase (anti-GAD), and they tend to develop insulin deficiency. The aim of this study was to evaluate the prevalence of anti-GAD in NIDDM with secondary failure of sulfonylurea agents (NIDDM-SF) and to investigate the diagnostic significance of seropositivity for anti-GAD in NIDDM-SF patients by evaluating human leukocyte antigen (HLA)-DRB1 alleles concurrently. The prevalence of anti-GAD in NIDDM-SF, NIDDM, and new-onset (within 1 year after onset) insulin-dependent diabetes mellitus (IDDM) was 9.3% (39/420), 3.1% (12/392), and 65.0% (13/20), respectively. Pancreatic beta cell function deteriorated in NIDDM-SF patients positive for anti-GAD. HLA-DRB1 allele typing revealed that NIDDM-SF patients positive for anti-GAD were significantly associated with DRB1*0901 (RR = 2.81, P < 0.01), which is one of the susceptible alleles to IDDM. Shorter interval before development of secondary failure and insulin deficiency were significantly associated with the presence of DRB1*0901 (P < 0.05) in NIDDM-SF patients positive for anti-GAD. In conclusion, nearly 10% of NIDDM-SF patients are positive for anti-GAD, suggesting that an autoimmune mechanism might play an important role in the pathogenesis of NIDDM-SF patients. In addition, a combination of serological marker (anti-GAD) and genetic marker (HLA-DRB1) is useful for predicting clinical course of NIDDM patients with secondary failure of sulfonylurea agents.

Adolescent↗
PubMed1997

Acute gastric outlet obstruction following the administration of prostaglandin: an additional case.

We present a case of neonatal acute gastric outlet obstruction related to prostaglandin-induced gastric foveolar hyperplasia, which developed following infusion of prostaglandin E1 (PGE1) for treatment of hypoplastic left heart syndrome. Abdominal distension occurred after administration of PGE1 in a cumulative dose of 2914 microg/kg. Ultrasonography performed after a cumulative dose of 5074 microg/kg had been administered disclosed a lobulated thickening of the gastric mucosa with a brush-like appearance composed of alternately echogenic and hypoechoic, vertically oriented lines. These ultrasonographic findings corresponded to the histological abnormalities of gastric foveolar hyperplasia with impacted interfoveolar mucin products and dilated mucosal glands. The development of gastric outlet obstruction in our patient, a relatively rare manifestation of prostaglandin-induced foveolar hyperplasia, might have been related to the unusually high cumulative dose of PGE1.

Acute Disease↗
PubMed1997

High-dose chemotherapy with autologous hematopoietic stem-cell transplantation in breast cancer.

Since 1981 we have conducted four studies of the treatment of metastatic and postoperative high-risk breast cancer with high-dose chemotherapy supported by autologous hematopoietic stem-cell transplantation (AHSCT). Study I, involving 56 metastatic cancer patients, proved that induction chemotherapy produces a lasting complete response (CR) in only a few cases despite the achievement of a CR rate higher than that expected from standard chemotherapy. Study II was designed to examine consolidation chemotherapy in metastatic cancer patients responding to induction chemotherapy. At a median follow-up of 26 months (range 2-66), consolidation therapy produced a 5-year progression-free survival rate of 27.1% in 30 patients showing a CR or a partial response to induction therapy and 58.6% in 13 patients showing a CR to consolidation therapy. No treatment-related death occurred during study II. The same regimen used in study I was employed for 58 postoperative high-risk patients in study III. The 10-year disease-free survival rate recorded for patients with > or = 10 positive axillary lymph nodes was significantly higher (P < 0.05) in the AHSCT-supported chemotherapy group than in the conventional chemotherapy group. A double high-dose regimen was adopted for 21 postoperative high-risk patients in study IV. The 3-year disease-free survival rate recorded for 9 patients with > or = 10 positive axillary lymph nodes was 71.4% at a median follow-up of 25 (range 8-45) months. No treatment-related death occurred during study IV. Peripheral blood stem-cell transplantation shortened the duration of bone marrow suppression more effectively than did bone marrow transplantation, thereby optimizing high-dose chemotherapy.

Adult↗
PubMed1997

Expression of a 70-kDa heat-shock-related protein during transformation from free-living infective larvae to the parasitic stage in Strongyloides venezuelensis.

The in vitro transformation system of Strongyloides venezuelensis has been established which induces free-living infective larvae to transform into the parasitic stage by a temperature shift from 25 to 37 degrees C. Comparison of the profiles of proteins labeled with [35S]-methionine in infective larvae at 25 and 37 degrees C with marked morphological transformation revealed an increase in the 70-kDa protein, thus showing these proteins to be related to the family of heat-shock proteins. In addition, the new appearance of two complexes between 16-kDa and 22-kDa proteins was observed. The 70-kDa protein cross-reacted with monoclonal antibody against human heat-shock protein 70, which was constitutively expressed. These proteins, synthesized during the transformation of S. venezuelensis from the infective larval stage to the parasitic stage, might be crucial for biochemical events that regulate the infectivity of the parasite for the host.

Animals↗
PubMed1997

Field evaluation of chicken egg yolk immunoglobulins specific for bovine rotavirus in neonatal calves.

The oral efficacy of chicken egg yolk immunoglobulins (yIg) specific for bovine rotavirus (BRV) serotypes G6 and G10 in protecting neonatal calves was examined in a herd of cattle under field conditions. In one of the three trials, yIg-treated calves tested under high relative humidity (RH) showed a significantly increased mean body weight (P < 0.05) and a decrease in number of calves shedding high titer of BRV (G6) in stool compared to control calves (P < 0.01), suggesting that our yIg product was effective in a field condition with an epidemic outbreak of BRV diarrhea.

Animals↗
PubMed1997

Genotype analysis of prepro-vasopressin signal peptide in vasopressin-producing and -non-producing lung tumors.

A polymorphism in the nucleic acid sequence encoding the signal peptide of the human prepro-vasopressin (AVP) has been reported in an AVP producing small cell lung carcinoma (SCLC) cell line. The difference predicts expression in tumor cells of a variant signal peptide with Pro for Leu 11. To clarify whether this difference is required for AVP secretion from SCLC cells and/or reflects increased mutagenesis in malignant tumors, the exon encoding the signal peptide of prepro-AVP in two AVP producing SCLC and 9 non-producing lung tumors was amplified using polymerase chain reaction. The variant sequence was neither found by direct sequencing nor by restriction enzyme analysis. These results suggest that similar to the hypothalamus the normal signal peptide is functional in tumor cells and that the variant signal peptide is not a prerequisite for AVP secretion from SCLC cells.

Animals↗
PubMed1997

Overexpression of endothelin-1 mRNA and protein in portal hypertensive gastric mucosa of rats: a key to increased susceptibility to damage?

BACKGROUND: Portal hypertension predisposes gastric mucosa to increased injury by various noxious factors. Because endothelin-1 (ET-1) is a potent vasoconstrictor that enhances gastric mucosal injury, we examined ET-1 expression in the portal hypertensive (PHT) gastric mucosa and its possible role in increased mucosal susceptibility to damage. METHODS: In gastric specimens of PHT or sham-operated rats, ET-1 mRNA expression was studied by S1-nuclease protection assay and ET-1 protein by enzyme immunoassay and immunostaining. We also determined the extent of ethanol-induced gastric mucosal necrosis in PHT and sham-operated rats after administering either a placebo or FR 139317, a selective ETA receptor antagonist. RESULTS: In PHT stomachs ET-1 mRNA expression and protein concentration were significantly increased compared with sham-operated controls: mRNA expression (ET-1/glyceraldehyde-3-phosphate-dehydrogenase ratio), 0.54 +/- 0.18 versus 0.30 +/- 0.08; protein concentration, 7.36 +/- 2.21 pg/mg versus 3.93 +/- 0.40 pg/mg, respectively; both p < 0.01. Immunofluorescence signal of ET-1 protein was predominantly localized to endothelia of gastric mucosal and submucosal vessels. In PHT stomachs FR 139317 significantly reduced mucosal necrosis (percentage of necrotic area, from 24.9 +/- 5.9% to 10.8 +/- 4.0%; p < 0.01), although it had no effect on sham-operated controls. CONCLUSIONS: Portal hypertension activates the ET-1 gene with overexpression of ET-1 protein in the gastric mucosa. Protection of PHT gastric mucosa by ETA receptor antagonist against damage indicates that overexpression of ET-1 plays an important role in increased susceptibility of PHT gastric mucosa to injury.

Animals↗
PubMed1997

Transient expression of FGF-5 mRNA in the rat cerebellar cortex during post-natal development.

Previously, we showed that fibroblast growth factor (FGF) receptor-4 mRNA was transiently expressed in proliferative granule cells of the external granule layer of the rat cerebellar cortex during early post-natal development (A. Miyake et al., Mol. Brain Res., 31 (1995) 95-100). In this study, we examined the expression of FGF-5 mRNA in the rat brain during post-natal development by in situ hybridization. FGF-5 mRNA was transiently expressed in granule cells of the internal granule layer of the cerebellar cortex during early post-natal development. The temporal sequence of FGF-5 mRNA expression was similar to that of FGFR-4 mRNA expression. As the proliferation of granule cells in the external granule layer and their migration through the molecular layer into the internal granule layer actively occur during these periods, the present findings suggest that FGF-5 as well as FGFR-4 might play important roles in the proliferation and/or migration of granule cells during the post-natal development of the cerebellar cortex.

Animals↗
PubMed1997

Prevention of infection in dental procedures.

The efficacy of a newly-developed anti-cross-contamination device in dentistry, the Air Flushing Clean System (AFCS), was tested under experimental and clinical conditions. In the experimental situation, a dental air turbine handpiece with or without AFCS was contaminated with two bacterial strains, Staphylococcus aureus FDA209P and Streptococcus mutants ATCC25175. After contamination with these bacteria, the handpieces were subjected to two disinfecting methods. Residual bacteria inside the handpiece or an air/water line were cultured and counted, and compared with controls. In this experiment, with AFCS but no dental vacuum suction, wiping of the handpiece with 70% ethanol gauze reduced the count of S. aureus by 99%. No bacterial contamination in the air/water line was detected after exchanging with an autoclaved handpiece. With AFCS and dental vacuum suction, bacterial contamination in the air/water line, as well as in the interior of the handpiece, was not detected. These results indicate that AFCS could reduce bacterial contamination within the air turbine handpiece more effectively than the conventional handpiece regardless of whether or not the dental vacuum suction was used.

Adult↗
PubMed1997

Passive protection of neonatal calves against bovine coronavirus-induced diarrhea by administration of egg yolk or colostrum antibody powder.

The protective effect of egg yolk and colostrum powders prepared from hens and cows vaccinated with inactivated bovine coronavirus (BCV) antigen was evaluated in a challenge model with a virulent BCV strain. Twenty three calves from BCV-free herds were randomly divided into control and several treatment groups. All calves were orally challenged with 1 x 10(9) TCID50 of the virulent Kakegawa strain of BCV at 24 to 36 h after birth. Calves in treatment groups received either egg yolk powder or cow colostrum containing BCV specific antibodies. Daily treatment with these antibody preparations started 6 h until 7 days post-challenge. Control calves which received no antibody had severe diarrhea and all died within 6 days after infection. In contrast, calves fed milk containing egg yolk or colostrum with neutralization titers of 1:2560 or 1:10,240 respectively all survived and had positive weight gain unlike the other treatment groups. These results indicate that the orally administered egg yolk and colostrum powders protected against BCV-induced diarrhea in neonatal calves and that the egg yolk used provided a higher degree of protection compared to colostrum powder on a titer basis. Treatment with whole egg yolk from immunized hens therefore provides a more efficacious alternative to the existing methods of specific passive protection against BCV.

Animals↗