Biomedical subjects

M Ohmori

Publications and source records attributed to M Ohmori.

At least 163 records · Page 9Linked to original sources

PubMed1992

Dynamic process between the clotting and the lytic activities on intracardiac thrombi--its relationship with systemic embolization.

To clarify the relationship between clotting and lytic activities of intracardiac thrombi, and to elucidate whether this could be used to evaluate the embolic risk the ratio of indium-111 radioactivity accumulated on thrombi to that in the blood pool using dual-tracer technique %IE as a parameter of the clotting activity, and D-dimer, which is a fibrin specific degradation product, as a parameter of lytic activity were measured in 37 patients with intracardiac thrombi. Fifteen of the 37 patients had past histories of arterial embolization. The values of D-dimer correlated significantly with those of %IE (r = 0.758, p less than 0.01), e.g., the higher the values of D-dimer the higher the values of %IE. 37 patients were divided into 2 groups using the regression line for the D-dimer and %IE domains. Eleven patients above the regression line had thrombosis in excess of fibrinolysis but the remaining 26 patients under the regression line had fibrinolysis in excess of thrombosis. The incidence of past embolic episodes was 82% (9/11) in patients with thrombosis in excess of fibrinolysis but 23% (6/26) in patients with fibrinolysis in excess of thrombosis. These results demonstrated that intracardiac thrombi were under the dynamic process between the clotting and the lytic activities and moreover patients with intracardiac thrombi and thrombosis in excess of fibrinolysis had a substantial risk of arterial embolization.

Aged↗

PubMed1992

Immunization with human thyrotrophin receptor peptide induces an increase in thyroid hormone in rabbits.

Eight rabbits were immunized with a synthetic peptide corresponding to the unique N-terminal region (termed N peptide; amino acid residues 29-57) in the extracellular domain of the human thyrotrophin (TSH) receptor. After 10 weeks, all of the eight rabbits produced anti-N peptide antibodies. Western blot analysis revealed that the antibodies recognized rabbit TSH receptor as an approximately 100 kDa protein. We compared the level of thyroid hormone in serum taken before immunization (preimmune sera) with that of serum taken after immunization (postimmune sera) in these immunized rabbits. Postimmune sera from the eight rabbits had higher mean (+/- S.D.) levels of tri-iodothyronine (T3) and thyroxine (T4) than did preimmune sera (T3, preimmune 0.82 +/- 0.26 micrograms/l vs postimmune 1.33 +/- 0.35, P < 0.01; T4, preimmune 33.7 +/- 10.0 micrograms/l vs postimmune 41.0 +/- 6.0, P < 0.05). T3 levels in four rabbits and T4 levels in four rabbits after immunization were over the normal range obtained from six age-matched control rabbits. Seven rabbits exhibited thyroid-stimulating antibody (TSAb) activity with various degrees (241-545%). The concentration of T3 and T4 did not increase over 10 weeks in either non-immunized rabbits (T3, preimmune 0.89 +/- 0.34 micrograms/l vs postimmune 0.82 +/- 0.22; T4, preimmune 31.1 +/- 7.3 micrograms/l vs postimmune 30.3 +/- 5.1) or other peptide-immunized rabbits (T3, preimmune 0.68 micrograms/l (n = 2) vs postimmune 0.69; T4, preimmune 33.1 micrograms/l vs postimmune 26.4). These results indicate that experimentally produced anti-TSH receptor antibody with TSAb activity induces an increase in thyroid hormone in rabbits.

Animals↗

PubMed1992

[Late potentials in dilated cardiomyopathy in relation to ventricular tachycardia and cardiac function: their significance].

We assessed the usefulness of ventricular late potentials (VLP) for detecting ventricular tachycardia (VT), and of the relationship between VLP and left ventricular dysfunction. The subjects consisted of 21 patients with dilated cardiomyopathy (DCM) not accompanied with ventricular conduction disturbances. Signal-averaged electrocardiograms were recorded by using VCM-3000. The signals of 200 or more beats were averaged through the 40-300 Hz band-pass filter until the noise level was reduced to less than one microvolt (microV). The duration (fQRSd) and the root mean square voltage (LP40) for the last 40 msec of the filtered QRS complex were calculated. The left ventricular diastolic dimension (LVDd), systolic dimension (LVDs) and the ejection fraction (EF) were obtained by echocardiography. Five of 21 patients had VT. fQRSd was significantly longer in patients with VT than in those without VT (158.8 +/- 8.6 vs 126.5 +/- 10.4 msec, p < 0.01). LP40 was significantly less in patients with VT than in those without VT (8.7 +/- 2.7 vs 24.1 +/- 12.3 microV, p < 0.01). If the presence of "fQRSd > or = 120 msec" or "LP40 < or = 20 microV" was defined as VLP positive, as in patients with old myocardial infarction, the criteria sensitivity was 100% and their specificity was 25% for detecting VT. If the presence of both "fQRSd > or = 135 msec" and "LP40 < or = 20 microV" was defined as VLP positive, the criteria sensitivity was 100%, and their specificity, 88%.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

PubMed1991

Rabbit antibodies toward extracellular loops of the membrane spanning region of human thyrotropin receptor possess thyroid stimulating activities.

We have synthesized three different peptides, E1 (amino acid residues 478-497), E2 (amino acid residues 561-580) and E3 (amino acid residues 649-652), corresponding to the first, the second and the third extracellular loops of the membrane spanning region of human thyrotropin receptor (TSH-R), respectively. We have produced rabbit antibodies toward these peptides and evaluated their thyroid stimulating antibody (TSAb) and TSH-binding inhibitor immunoglobulin (TBII) activities. Although only slight TSAb activity was observed in E1 antibodies, E2 and E3 antibodies possessed strong TSAb activities, the values of which were 1118% and 910%, respectively. None of these antibody had TBII activities. These results suggest that antibodies against the extracellular loops of the TSH-R can stimulate cAMP formation in thyroid cells and that these regions may be one of the candidates for the epitope against autoantibodies from patients with Graves' disease.

Amino Acid Sequence↗

PubMed1991

Thyrotropin receptor non-mediated thyroid stimulating immunoglobulin in Graves' disease.

There exists a consensus that hyperthyroid Graves' disease is caused by thyrotropin receptor (TSH-R) autoantibodies. To test the possibility that the TSH-R is the sole antigen for thyroid stimulating antibodies (TSAb), we compared bioactivities of Graves' IgGs between non-thyroid mammalian cells transfected with human TSH-R cDNA and the reference thyroid bioassay. A Graves' IgG with TSH-binding inhibitor immunoglobulin (TBII) activity (89%) markedly stimulated cAMP formation in both CHO-K1 cells transfected with TSH-R cDNA (340 microU/ml of TSH equivalent) and rat thyroid cells, FRTL-5, (410 microU/ml of TSH equivalent). In contrast, a TBII negative (-1.5%) IgG from another patient with Graves' disease showed a strong thyroid stimulating activity (87 microU/ml of TSH equivalent) when FRTL-5 cells were used for the assay. But no stimulating activity was observed in this IgG when CHO-K1 cells transfected with TSH-R cDNA were used, suggesting a possible existence of TSH-R non-mediated thyroid stimulating immunoglobulin in some cases of Graves' disease.

Animals↗

PubMed1991

Rabbit antibodies against two different extracellular domains of human thyrotropin receptor possess thyroid stimulating activities.

We have produced rabbit antibodies against synthetic peptides corresponding to the mid-region (amino acid residues 172-202, C peptide) and to the unique segment near the transmembrane region (amino acid residues 341-370, P peptide) in the extracellular component of the human thyrotropin (TSH) receptor and evaluated their biological activities. Both anti-C peptide antibodies raised in two rabbits showed strong thyroid stimulating activities (TSAb) (4127% and 2548%). Anti-P peptide antibodies raised in two rabbits were also strongly positive for TSAb activities (359% and 3468%). However, none of these antibodies had TSH-binding inhibitor immunoglobulin (TBII) activities. These results suggest that the domains responsible for TSAb are likely to span the entire extracellular component of the TSH receptor.

Amino Acid Sequence↗

PubMed1991

Role of N-terminal region of the thyrotropin (TSH) receptor in signal transduction for TSH or thyroid stimulating antibody.

To identify the site(s) on the thyrotropin (TSH) receptor that interacts with TSH or thyroid stimulating antibody (TSAb), we examined the effect of the synthetic TSH receptor peptide (termed N2 peptide, No. 35-50) on the cAMP accumulation induced by TSH or TSAb. Preincubation of bovine TSH with N2 peptide resulted in a significant and dose-dependent decrease in cAMP accumulation. This decrease was not observed when bovine TSH was preincubated with P1 peptide, which was used as a control (No. 398-417). In contrast, the N2 peptide did not affect TSAb activity in immunoglobulin fractions from three TSAb-positive patients with Graves' disease. P1 peptide also had no effect on TSAb activity. These results suggest that the N-terminal region of the TSH receptor is important for TSH action, and also that TSAb activity cannot be suppressed only by the application of the synthetic peptide corresponding to the N-terminal region.

Animals↗

PubMed1991

K-ras activation in gastric epithelial tumors in Japanese.

Point mutation in codons 12, 13 and 61 of the K-ras oncogene in gastric epithelial tumors were investigated by polymerase chain reaction from sections of formalin-fixed, paraffin-embedded tissue followed by dot-blot hybridization with mutation-specific oligonucleotide probes. Point mutations were found specifically in four of 20 tumors of intestinal histological subtype; GGT to GAT in three cases and to GTT in one case, all in codon 12 of K-ras. These mutations were also confirmed by direct sequencing. In contrast, none of 11 diffuse-type tumors showed K-ras point mutations. While K-ras point mutations may not be frequent events in gastric tumorigenesis, the similarity of the intestinal-type gastric tumors and colorectal tumors for K-ras point mutations as well as the association of mutations in K-ras with a particular gastric tumor histology implicates K-ras activation in the development of these tumors.

Adenoma↗

PubMed1991

Thyroid stimulating activity of rabbit antibodies toward the human thyrotropin receptor peptide.

We have produced antibodies against a peptide corresponding to the unique N-terminal segment (amino acid residues 29-57) in the extracellular domain of the human thyrotropin (TSH) receptor by immunizing it to rabbits, and evaluated for their thyroid stimulating antibody (TSAb), thyroid stimulation blocking antibody (TSBAb) and TSH-binding inhibitor immunoglobulin (TBII) activities. Antibody raised in rabbit B showed significant TSAb activity but not TSBAb activity. In contrast, antibody raised in rabbit A lacked TSAb activity but possessed TSBAb activity. None of these antibodies had TBII activity. These results indicate that TSH receptor antibody can successfully mimic the action of TSH and also suggest that the N-terminal region of TSH receptor is substantially associated with both TSAb and TSBAb activities, but not parallel to TBII activity.

Amino Acid Sequence↗

PubMed1991

Development of chicken antibodies toward the human thyrotropin receptor peptides and their bioactivities.

We have synthesized four peptides (P2, P4, E3 and P1) corresponding to different segments of human thyrotropin (TSH) receptor. We have obtained antibodies by immunizing them to chickens, and antibodies are evaluated for their thyroid stimulating antibody (TSAb), thyroid stimulation blocking antibody (TSBAb) and TSH-binding inhibitor immunoglobulin (TBII) activities. None of the antibodies had TSAb activity. Antibodies against human TSH receptor specific region such as P2 and P4 (P2: No. 372-397, P4: No. 341-358) had TSBAb and TBII activities. Anti-E3 antibody (E3: the third putative extracellular loop, No. 649-661) had only TSBAb activity. Anti-P1 antibody (P1: high homology with pig LH/CG receptor, No. 398-417), however, had none. These results suggest that anti-TSH receptor antibodies to different antigenic epitopes show heterogeneity in their biological activities.

Animals↗

PubMed1991

Ineffective hemopoiesis in the myelodysplastic syndromes (MDS) as studied by daily in situ observation of colony-cluster formation.

Daily in situ observation of individual proliferating cells was performed to examine ineffective hemopoiesis in vitro. Bone marrow mononuclear cells (BMMNC) from 24 myelodysplastic syndrome (MDS) patients and 12 controls were cultured for granulocyte-macrophage progenitor (CFU-gm) assays using methylcellulose. Individual proliferating cells were mapped at 3 days of culturing and their fates were followed by daily in situ cell counting contained within each cell aggregate until day 8. By retrospective analysis of the daily growth of the cells, a significantly greater proportion of noncolony-forming cells in MDS were found to proliferate initially, but failed to do so thereafter and degenerated in the culture. Cells showing these abnormal growth characteristics apparently contributed to ineffective granulopoiesis. The present method may be useful for clarifying ineffective granulopoiesis.

Adolescent↗

PubMed1991

Effectiveness of long-term beta-blocker therapy for dilated cardiomyopathy--echocardiographical follow-up.

To evaluate the effectiveness of long-term beta-blocker therapy for dilated cardiomyopathy (DCM), two groups (Group I: 18 patients, Group II: 17 patients) with DCM divided by the order at the entry were followed echocardiographically for 16.9 +/- 3.0 months in Group I and 21.4 +/- 3.9 months in Group II. Metoprolol (final dose: 60 mg/day) was administered in Group I, but not in Group II (the control), although the conventional treatment for heart failure was continued. The left ventricular end-systolic dimension and ejection fraction assessed by echocardiography improved significantly after 6 months in Group I, but not in Group II, even after 48 months, although there were no significant differences in baseline data between the two groups. The end-diastolic dimension decreased significantly after 12 months in Group I only. It was estimated, using the point count method on a left ventricular endomyocardial biopsy specimen taken at entry, that the improvement (delta EF) of the ejection fraction 12 months after metoprolol administration inversely correlated (r = -0.677, p less than 0.01) with percent fibrosis, indicating that the more myocardium remains, the more improvement is expected. These findings suggested a favorable effect of beta blockade in DCM, especially in cases with less fibrosis, showing that the endomyocardial biopsy could be of clinical use in selecting candidates for chronic beta-blocker therapy in DCM.

Adrenergic beta-Antagonists↗

PubMed1991

Detection of patients at risk for paroxysmal atrial fibrillation during sinus rhythm by P wave-triggered signal-averaged electrocardiogram.

To determine whether patients at risk for paroxysmal atrial fibrillation could be detected while in sinus rhythm, the signal-averaged electrocardiogram triggered by P waves was recorded in 42 patients with paroxysmal atrial fibrillation (Paf group) and in 50 control patients. The root mean square voltages (LP10, LP20, and LP30) for the last 10, 20, and 30 msec and the duration (Ad) of filtered (40-300 Hz) P wave of the spatial magnitude were measured. LP10 and LP20 were significantly lower in the Paf than in the control group (LP10, 1.92 +/- 0.58 versus 2.49 +/- 0.78 microV, p less than 0.001; LP20, 2.47 +/- 0.78 versus 3.46 +/- 1.20 microV, p less than 0.0001), although no significant difference in LP30 was found between groups. Ad was also significantly longer in the Paf than in the control group (137.0 +/- 14.3 versus 118.6 +/- 11.3 msec, p less than 0.001). These differences between the Paf and control groups remained significant even after dividing by the presence or absence of organic heart diseases. The criteria of "LP20 = 3.5 microV or less" and "Ad greater than 120 msec" as defining "atrial late potential" gave a sensitivity of 91% and a specificity of 76%. These findings suggest that patients at risk for paroxysmal atrial fibrillation could be detected while in sinus rhythm by using the P wave-triggered signal-averaged electrocardiogram.

Algorithms↗

PubMed1991

Thyrotropin stimulates glucose-regulated protein (GRP78) gene expression in rat functional thyroid epithelial cells, FRTL.

We cloned a 1.2-kilobase cDNA (C17-16) from a transformed FRTL thyroid cell library. Northern blot analysis revealed that the size of the corresponding mRNA was 2.0 kilobases. C17-16 mRNA was found in all tissues investigated, but interestingly, its expression was 5- to 10-fold higher in the thyroid glands than in other tissues. Addition of TSH to FRTL cells showed a time- and dose-dependent increase in the steady state level of C17-16 mRNA, and the effect was mimicked by (Bu)2cAMP. An in vitro nuclear run-off assay demonstrated that the stimulatory effect was due to an increase in the transcription rate of the C17-16 gene. TSH had no effect on the half-life of the C17-16 mRNA. Transcriptional induction of the C17-16 gene was inhibited when the cells were treated with cycloheximide. Nucleotide sequencing revealed that C17-16 was identical to the cDNA of rat glucose-regulated protein (GRP78), a member of the heat shock protein family. These results suggest that the expression of GRP78 in thyroid cells is regulated by TSH via cAMP, for which cycloheximide-sensitive protein synthesis might be required, and that more GRP78 might be needed to assist in the synthesis and transport of glycoprotein molecules in TSH-stimulated cells.

Animals↗

PubMed1991

[Estimating the year of eradication of tuberculosis in Japan].

The time of eradication of tuberculosis has been discussed for several countries, and based on those results, a new strategic plan and goals have been elaborated. Considering such developments, and in order to make a new tuberculosis control strategy, it is important to determine the point at which eradication of tuberculosis would be achieved in Japan. Styblo proposed the two conventional definitions of eradication of tuberculosis, namely that the incidence of smear-positive tuberculosis has fallen below 1 per million population or that the prevalence of tuberculosis infection in the general population has fallen below 1% and continues to decrease. The bacteriological results of new cases have been reported since 1975 in Japan. However, those results are still of doubtful validity and reliability. Therefore, the author estimated the year of eradication of tuberculosis, according to the criterion that tuberculosis is eradicated when the proportion of the population infected with tubercle bacilli is less than 1%. If the risk of infection is changing at a regular rate, it is possible to estimate the risk of infection at any time in the past and in the future. Once the risk of infection is determined, it is also possible to calculate the age-specific prevalence of infection and the proportion of the population infected with tubercle bacilli at various times in the past and in the future. In Japan, the risk of infection before World War II was assumed to be around 4% and not to vary with calendar year. And based on the data from the prevalence surveys in Okinawa in 1968 and 1973, the risk of infection was estimated 0.3% in 1968 and has declined on average, by 10 to 11% annually. At that time, Okinawa was the only area free from BCG vaccination in Japan. The incidence rate in Japan also has declined, on average, by 10% annually. However, since late 1970s, the annual speed of decline of the incidence rate has been slowed down. Therefore, I assumed that the recent trend of the infection risk is the same as the trend of the recent incidence rate among the 0-29 year age-group. The size of the effect of age on the risk of infection has been discussed. The author also considered age-effects in the model. The weight applied to the risk of infection by age was determined by examining the age-specific positive rate in the 1930s before the era when BCG vaccination was widely used.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMed1991

[Essential thrombocythemia transformed to myelofibrosis with myeloid metaplasia after seven years].

A 29-year-old male was diagnosed as having essential thrombocythemia (ET) in 1975. From that time, his platelet count gradually increased to more than 2 X 10(6)/microliter until 1979. However, his platelet count gradually decreased to less than 6 X 10(5)/microliter in 1985. Also, in 1982, erythroblasts and immature myeloid cells began to appear in the peripheral blood, and the liver and spleen became palpable in 1985. Bone marrow then revealed osteomyelosclerosis. These findings suggested that ET had transformed to myelofibrosis with myeloid metaplasia. Increased hepatosplenomegaly was accompanied by the appearance of ascites in June, 1988, and an esophageal varix ruptured in December of the same year. The varix was resected and the spleen was removed. After the operation, ascites did not recur and his condition became stable. Portal hypertension in this patient was considered to be due mainly to increased blood flow from the enlarged spleen.

Humans↗

PubMed1990

Hepatotoxicity of geniposide in rats.

The hepatotoxic effects of geniposide were investigated in rats. Increases in serum alanine aminotransferase and aspartate aminotransferase activities as a result of oral administration of 320 mg geniposide/kg body weight were suppressed when geniposide was administered ip or when the rats were pretreated with chloramphenicol. The non-protein sulphydryl content of the liver 4 hr after oral administration of geniposide decrease in a dose-dependent manner. Genipin, the aglycone of geniposide, had a marked reactivity with sulphydryl groups of glutathione and cysteine in vitro. The hepatotoxic effects of ip administration of genipin at a dose of 80 mg/kg body weight were comparable with those of oral administration of geniposide at a dose of 320 mg/kg. Buthionine sulphoximine pretreatment enhanced the toxicity of geniposide, while cysteine pretreatment completely suppressed it. These results suggest that the conversion of geniposide to genipin is causally related to the hepatotoxicity of geniposide and that hepatic non-protein sulphydryls are important in modulating the toxicity.

Administration, Oral↗

PubMed1990

Increased intracardiovascular clotting in patients with chronic atrial fibrillation.

To clarify whether the formation of thrombi could be induced by atrial fibrillation itself or by factors predisposing to atrial fibrillation such as mitral stenosis, plasma D-dimer levels (cross-linked fibrin degradation products) were measured in 73 patients without atrial fibrillation (Group 2). In Group 1, 49 of the 73 patients had factors predisposing to atrial fibrillation such as valvular heart disease, and the remaining 24 had lone atrial fibrillation. In Group 2, 16 patients had organic heart disease and the remaining 5 had a chest pain syndrome. The plasma D-dimer level was significantly higher in Group 1 (150 +/- 19 ng/ml) than in Group 2 (61 +/- 3 ng/ml) (p less than 0.01, mean +/- standard error of the mean). In both groups, there were no significant differences in plasma D-dimer level between patients with and without organic heart disease (146 +/- 18 versus 156 +/- 46 ng/ml in Group 1; 61 +/- 4 versus 59 +/- 10 ng/ml in Group 2). These findings indicate that atrial fibrillation itself may be more important than factors predisposing to atrial fibrillation in the development of intracardiovascular clotting.

Atrial Fibrillation↗