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Biomedical subjects

M Ohmori

Publications and source records attributed to M Ohmori.

At least 109 records · Page 6Linked to original sources

[Future prediction of tuberculosis incidence rates by prefecture].

We tried to predict the tuberculosis incidence rates by the year 2000 and 2005, based on the trends of incidence rates from the year 1981 to 1995 reported by the Ministry of Health and Welfare (MOHW). According to the studies conducted, the tuberculosis incidence rate in 2000 was predicted as 29.8 (95% CI: 28.7-30.8) per 100,000 population and that in 2005 was predicted as 25.2 (95% CI: 24.2-26.3 per 100,000 population in Japan. The incidence rates by prefecture in 2000 and 2005 were also predicted. The MOHW introduced some new tuberculosis control plans and has set on interim goal by the year 2000 to achieve a tuberculosis incidence at below 20 per 100,000 population. Whereas the possibility of achieving the stated incidence rate goal even by the year 2005 is very low in Japan, among prefectures, several prefectures were predicted to reach this level by the year 2000. Over several years the incidence rate in Japan has been high in the west and low in the east. However this is expected to greatly change in the future. The speed of decline in tuberculosis incidence rates has been stagnated since around 1980 with average annual declination rate from the year 1981 to 1995 was 3.3%. Among 17 prefectures, Tokyo Metropolitan had the lowest declination rate with an average annual declination rate of 1.1%. The prefecture surrounding Tokyo also showed low declination speed. This may indicate that in the future, the problems of tuberculosis will be concentrated in and around the big cities.

Forecasting↗

Environmental magnetic fields change complementary DNA synthesis in cell-free systems.

A number of studies have shown that exposures to environmental magnetic fields (MFs) increase cellular transcription and enhance DNA synthesis. However, little is known about the basic mechanisms underlying specific biological responses to MFs. We looked directly at the effect of MFs by using a cell-free rabbit globin cDNA synthesis system. cDNA synthesis reaction mixtures were placed in each of four exposure conditions and were tested simultaneously. Condition one was the control, with no exposure during either single-strand or double-strand synthesis (M-M-). The second condition was MF exposure only during single-strand synthesis (M+M-). The third condition was exposure only during double-strand synthesis (M-M+). The fourth condition was exposure during both single-strand and double-strand synthesis (M+M+). Results showed that cDNA synthesis was affected by 5-100 microT, 60 Hz MFs. Double-strand cDNA synthesis increased with MF exposure only during double-strand synthesis reactions (M-M+), and the greatest increase of double-strand cDNA synthesis was detected when MF exposure was at 10 microT, only during double-strand synthesis. Double-strand cDNA synthesis decreased when only single-strand synthesis reactions were exposed (M+M-; 100 microT). An increase of cDNA synthesis caused increased synthesis of rabbit globin cDNA and large-sized molecules. These results suggest that exposure to MF induced structural changes of synthesized cDNA, therefore altering the amount of cDNA. Our results show that environmental MFs can significantly alter cDNA synthesis in a cell-free system.

Animals↗

No evidence of a direct venodilatory effect of furosemide in healthy human subjects.

The present study was undertaken to examine whether furosemide, a loop diuretic, has a direct venodilatory effect in healthy male subjects. Furosemide, or amrinone, an inotropic agent with a vasodilatory action, was infused into a dorsal hand vein that had been preconstricted by phenylephrine. The diameter of the vein was measured by a linear variable differential transformer. Venodilation was observed during the infusion of amrinone, but such a response was not detected with furosemide. These findings do not support the hypothesis that furosemide has a direct venodilatory effect in healthy human subjects.

Adult↗

Molecular characterization of an adenylate cyclase gene of the cyanobacterium Spirulina platensis.

A cyaA gene, encoding an adenylate cyclase, was isolated from a filamentous cyanobacterium, Spirulina platensis, by functional complementation of a cya mutant of Escherichia coli, defective in adenylate cyclase activity. The predicted gene product of cyaA contains a signal peptide-like domain, a putative sensor domain similar to the gene product of vsrA of Pseudomonas solanacearum, a putative membrane-spanning domain and an adenylate cyclase-like catalytic domain. Two other positive clones that complemented the E. coli mutant were isolated from the same cyanobacterium, suggesting that several cya genes are functioning in S. platensis.

Adenylate Cyclase Toxin↗

Comparison of the antagonistic activity of tamsulosin and doxazosin at vascular alpha 1-adrenoceptors in humans.

alpha 1-Adrenoceptor blockers such as prazosin and doxazosin are used to treat hypertension as well as benign prostatic hyperplasia (BPH), whereas the new alpha 1-adrenoceptor blocker tamsulosin is used only for BPH and does not reduce blood pressure at the doses used to relax prostatic smooth muscle. In contrast to prazosin, tamsulosin has a higher affinity for prostatic than vascular alpha 1-adrenoceptors in vitro. The functional correlate of this observation in humans is the subject of this study. The alpha 1-adrenoceptor blockade by oral tamsulosin (0.2 mg), doxazosin (1 mg) or placebo on finger tip vascular and dorsal hand venous alpha 1-adrenoceptors stimulated by cold treatment (immersion in ice water) and the alpha 1-adrenoceptor agonist phenylephrine, was thus studied in a 3-way crossover study in eight, healthy, male adults. Finger tip vasoconstriction after cold stimulation was assessed by laser Doppler flowmetry. A linear variable differential transformer was used to assess the drug effect on phenylephrine-induced venoconstriction. All study parameters were assessed at around 2 and 3.5 h after oral intake of doxazosin and tamsulosin respectively. The drug plasma levels were not significantly different. No significant differences were found for blood pressure or heart rate in the three treatments in supine and erect position. The reduction in finger tip blood flow after cold stimulation was significantly smaller after doxazosin treatment (P < 0.01) than after tamsulosin or placebo, whereas there was no significant difference between tamsulosin and placebo treatments. The infusion rate of phenylephrine producing a half-maximum venoconstriction was significantly larger after doxazosin than after tamsulosin (P < 0.05) or placebo (P < 0.01), whereas there was again no significant difference between tamsulosin and placebo treatments. The data suggest that, at doses producing equal plasma levels after single oral doses in human subjects, the blocking activity at vascular alpha 1-adrenoceptors is lower for tamsulosin than for doxazosin.

Administration, Oral↗

Influence of age on venodilator effect of isoproterenol and amrinone.

OBJECTIVE: To investigate the influence of age on the venodilator effect of isoproterenol, a beta-adrenoceptor agonist, and amrinone, a selective phosphodiesterase (PDE) III inhibitor, in human subjects. METHODS: In eight young and eight elderly male subjects, the drugs were infused into a dorsal hand vein preconstricted with phenylephrine and its diameter was measured using a linear variable differential transformer. RESULTS: The maximum venodilation (Emax) induced by isoproterenol was significantly smaller and the infusion rate of isoproterenol required to induce 50% of maximum venodilation (ED50) was significantly larger in the elderly than in the young subjects [Emax: 29.8 vs 95.1%, ED50: 97.3 vs 51.6 ng.min-1]. A significant age-related change in Emax or ED50 was not observed for amrinone (Emax: 95.8 vs 100.8%, ED50: 40.1 vs 31.6 micrograms.min-1). CONCLUSION: The data show that the venodilator effect of amrinone is not influenced by age. As amrinone increases cyclic AMP by inhibition of PDE III, it is suggested that the action of cyclic AMP is not altered by age. The decreased effect of isoproterenol might be caused by reduced production of cyclic AMP in elderly subjects.

Adrenergic beta-Agonists↗

Effect of ranitidine on renal clearance of lomefloxacin.

OBJECTIVE: To examine the effect of ranitidine on the renal clearance of lomefloxacin. SETTING: Department of Clinical Pharmacology, Jichi Medical School. METHODS: Lomefloxacin 200 mg and ranitidine 300 mg or its placebo were given orally in a randomised, double-blind, crossover design. Blood and urine samples were obtained during a 24-h period after dosing. RESULTS: The area under the plasma concentration-time curve and the elimination half-life of lomefloxacin were significantly increased following coadministration with ranitidine. These effects were caused by significant decreases in total (7.8%) and renal (22%) clearance of lomefloxacin. In contrast, creatinine clearance and urinary excretion of electrolytes were not influenced by ranitidine. CONCLUSION: As lomefloxacin and ranitidine are excreted in urine by renal tubular secretion, the present results suggest that the renal tubular secretion of lomefloxacin is diminished by ranitidine. As the reduction in lomefloxacin clearance is only marginal, it is probable that the drug interaction observed in this study is not of clinical significance.

Adult↗

Malignant neoplasms in the Japanese community of Hisayama: mortality and changing pattern during a 30-year observation period based on a consecutive autopsy series.

To obtain a relatively true mortality from malignant neoplasms, we studied the frequency of cancers in the different sites and the changing patterns of the frequency and sites over time among residents of the community of Hisayama, where an autopsy-based population survey (autopsy rate, 80%) has been conducted since 191. During the 30-year period from 1962 to 1991, we found 438 malignant neoplasms in 407 cases among 1,250 consecutive autopsies. Stomach cancer was not frequent in type of cancer, with 123 cases (9.8%), followed by lung cancer in 62 (5.0%), colorectal cancer in 42 (3.4%), liver cancer in 37 (3.0%), and pancreatic cancer in 30 (2.4%). We compared the mortality from cancers for both autopsy and nonautopsy cases (the proportional mortality) among three 10-year periods. The proportional mortality from all cancers, as well as for lung, colorectal, and liver cancers, showed an increase in recent years, while stomach and pancreatic cancer showed a decrease. These figures were nearly similar to the mortality statistics for the Japanese population as a whole except for the observed decreasing trend in mortality from pancreatic cancer.

Adolescent↗

A Y-box protein is a suppressor factor that decreases thyrotropin receptor gene expression.

The decanucleotides in a tandem repeat, -162 to -140 bp, are suppressor elements that decrease TSH receptor (TSHR) gene expression by different mechanisms. A factor(s) interacting with the 3'-decanucleotide compete for proteins that bind the cAMP response element, -139 to -132 bp, a constitutive enhancer necessary for efficient TSHR expression. The 5'-decanucleotide is in a CT-rich, S1 nuclease-sensitive region of the promoter; its suppressor activity has been related to its ability to bind a nonthyroid-specific protein to its coding strand. In this report we clone a complementary DNA encoding a single strand DNA-binding protein that forms a specific protein-DNA complex with the coding strand of the 5'- but not the 3'-decanucleotide and not with the 5'-decanucleotide noncoding or double strand. We show, by cotransfection with TSHR promoter-chloramphenicol acetyltransferase chimeras, that the protein is a suppressor that regulates the function of the 5'- but not the 3'-decanucleotide. The protein is a Y-box protein that was previously cloned as an enhancer factor from the rat liver; it is, however, 95% identical to human YB-1, which suppresses major histocompatibility class II gene expression, and to human nuclease-sensitive element protein-1, a Y-box protein identified by its ability to bind single strand, CT-rich, nuclease-sensitive elements of genes that, like the TSHR, have GC-rich promoters. Unexpectedly, the Y-box protein binds two other sites in the minimal TSHR promoter in a single strand-specific fashion and acts a suppressor at each of these sites. One is associated with the insulin response element of the minimal TSHR promoter and is not in an overtly CT-rich region. The other is located 3' to the cAMP response element in a region termed the S-box, -120 to -113 bp, because of its homology to the S-box of the major histocompatibility class II promoter; this site is in a CT-rich area and, as in the class II promoter, is linked to cAMP-induced gene suppression. A conserved CCTC sequence in each site is important for the binding and suppressor function of the Y-box protein.

Amino Acid Sequence↗

Cloning of the single strand DNA-binding protein important for maximal expression and thyrotropin (TSH)-induced negative regulation of the TSH receptor.

Contiguous with the 5'-end of the thyroid transcription factor-1 (TTF-1) element upstream of the minimal TSH receptor (TSHR) promoter and within it, there is an element on the noncoding strand with single strand- binding activity. Mutation analyses indicate that it is functionally distinct from the TTF-1 element and is important for the constitutive expression and TSH/cAMP-induced negative autoregulation of the TSHR in thyroid cells but only constitutive expression in nonthyroid cells. In this report we identify a cDNA encoding a single strand-binding protein (SSBP) that forms a specific complex with the noncoding strand of the TSHR, contiguous with the 5'-end of both TTF-1 elements; we term it SSBP-1. SSBP-1 increases promoter activity when contransfected with heterologous SV40 promoter-chloramphenicol acetyltransferase (CAT) chimeras containing the upstream SSBP-binding element from the TSHR promoter or with TSHR promoter-CAT chimeras containing both or only the downstream SSBP element. Mutational analyses reveal that a GXXXXG motif is important for the binding and enhancer function of SSBP-1. TSH/cAMP decreases SSBP-1 RNA levels, as well as SSBP-1/TSHR DNA complex formation, in functioning rat FRTL-5 thyroid cells but not nonfunctioning FRT thyroid or Buffalo rat liver cells that have no TTF-1. SSBP-1 RNA is present ubiquitously; however, its levels are higher in FRTL-5 cells and are increased by overexpression of TTF-1 in cells treated with TSH. This reverses TSH-induced negative regulation of the TSHR. SSBP-1 is, therefore, a positive regulator of TSHR gene expression that contributes to TSHR maximal expression by binding to the SSBP elements. It is a ubiquitous, single-strand transcription factor whose expression in FRTL-5 thyroid cells is, however, regulated by a thyroid-specific gene, TTF-1. TSH/cAMP induces negative autoregulation of the TSHR, in part, by decreasing maximal expression resultant from SSBP-1 binding to the SSBP elements. Like Y-box proteins, which are involved in negative regulation of the TSHR, SSBP-1 also interacts with the major histocompatibility class II promoter S-box; the interaction is single strand-specific. This supports the hypothesis that common transcription factors regulate TSHR and major histocompatibility gene expression. Of additional interest and again like Y-box proteins, SSBP-1 is a member of a family of SSBPs that interact with RNA and are important in RNA processing, can interact with the promoter of retroviruses, and can interact with a gene linked to growth and DNA replication, c-myc.

Amino Acid Sequence↗

Screening for bacteria producing sucrose phosphorylase and characterization of the enzymes.

Two microbial strains, No. 165 and No. 168, were isolated from soil as sucrose phosphorylase producers and identified as Leuconostoc mesenteroides subsp. mesenteroides and subsp. dextranicum, respectively. The sucrose phosphorylases were purified, characterized, and compared with the enzymes of L. mesenteroides AKU1102 and ATCC12291. As for the catalytic properties, these enzymes were close to each other, while as for the enzyme molecules, the No. 165 enzyme (Mr: 58,000) was slightly different from the other (Mr: 54,000), though their N-terminal amino acid sequences were almost the same.

Amino Acid Sequence↗

Cloning and expression in Escherichia coli of sucrose phosphorylase gene from Leuconostoc mesenteroides No. 165.

The sucrose phosphorylase gene of an isolate, Leuconostoc mesenteroides No. 165, was amplified by PCR, cloned on pUC118, and expressed in E. coli. The nucleotide sequence of the gene showed 96.3% similarity to that of L. mesenteroides ATCC12291 and 67% to that of Streptococcus mutans, but low similarity to the Agrobacterium vitis gene. The cloned gene, which fusing with lacZalpha, was expressed inducibly with IPTG in E. coli to produce an active enzyme in large quantities that accounted for about 50% of the total cell protein.

Amino Acid Sequence↗

[Familial cancer and oncogenic factors].

The recent remarkable progress in molecular biology has revealed that various kinds of genetic alteration occur in cancers. Recently, many genes that cause hereditary cancer have been identified. For example, hMSH2 and hMLH1, which are known as DNA mismatch repair genes have been found to cause HNPCC (hereditary non-poliposis colorectal cancer). Mutation of RET oncogene has been recognized in the families of MEN (multiple endocrine neoplasia) type II. Mutations of the tumor suppressor genes are the most common changes in the genes of familial cancer. BRCA1 and BRCA2 are tumor suppressor genes that have recently been identified as familial breast and ovarian cancer, familial breast cancer genes. This paper reviewed the hereditary cancer families in which genetic alterations have been revealed and the recent progress in mapping and cloning of familial breast cancer candidate genes which have not been identified.

Breast Neoplasms↗

Presence of poorly stained myocytes in acute myocarditis predicts improvement in cardiac function.

Histological findings in the acute phase of myocarditis were evaluated as a prediction of hemodynamic state in the chronic phase in 20 patients with clinical and pathological diagnoses of myocarditis who were followed up with echocardiography for at least 1 year. Endomyocardial biopsy samples were obtained from the left ventricle within 1 year of the onset of symptoms. Azan-Mallory staining was performed on the myocytes, which were categorized as either well stained or poorly stained. The point counting method was used to determine the fraction of each type. The improvement in ejection fraction within 1 year correlated significantly with the fraction of poorly stained myocytes (r = 0.46, p < 0.05). The ejection fraction at biopsy was negatively correlated with the volume fraction of well stained myocytes (r = -0.64, p < 0.01). The staining condition of myocytes may be useful in predicting the hemodynamic recovery of patients with myocarditis.

Acute Disease↗

Lesser sac herniation through the greater omentum and gastro-pancreatic ligament: report of a case.

We report herein the case of a woman who developed a lesser sac hernia which was especially unusual in that the small bowel prolapsed through a defect in the greater omentum and was thereafter strangulated by a hole in the gastro-pancreatic ligament. The gastro-pancreatic ligament has never before been documented as causing an internal hernia. In our patient, a plain abdominal X-ray demonstrated as soft-tissue mass displacing the stomach to the left while abdominal computed tomography and ultrasonography showed a sac-like encapsulation of the small bowel loops between the liver and stomach. Careful evaluation of these radiographic findings allowed for the preoperative diagnosis of a lesser sac hernia to be made.

Adult↗

Flow cytometric analysis of the DNA content in colorectal adenomas with focal cancers.

BACKGROUND & AIMS: Variable results have been reported on the nuclear DNA content of colorectal polyps. The significance of DNA aneuploidy in the malignant transformation of colorectal polyps was evaluated. METHODS: We analyzed by flow cytometry the nuclear DNA content of freshly frozen samples of 50 colorectal adenomas with or without focal cancers, analyzing separately the adenomatous and cancerous regions of the polyps. RESULTS: In the adenomatous regions of the 50 polyps, the DNA was diploid in 43 and aneuploid in 7; the adenomas with DNA aneuploidy in the adenomatous regions were more frequently accompanied by focal cancers than were the DNA-diploid adenomas (P < 0.01). In 60% of the polyps with DNA aneuploidy in the cancerous regions, the DNA was also aneuploid in the adenomatous region and had similar DNA indices; this result suggests that the DNA aneuploidy had already occurred during the adenomatous stage, which lends support to the concept of the adenoma-carcinoma sequence. DNA aneuploidy in the adenomatous region was significantly correlated with the size of colorectal polyps (P < 0.05). CONCLUSIONS: DNA aneuploidy may be an important indicator for the early diagnosis of malignant transformation of colorectal polyps.

Adenoma↗

The thyrotropin receptor.

This chapter has outlined the complex process required for thyroid growth and function. Both events are regulated by TSHR via a multiplicity of signals, with the aid of and requirement for a multiplicity of hormones that regulate the TSHR via receptor cross-talk: insulin, IGF-I, adrenergic receptors, and purinergic receptors. Cross-talk appears to regulate G-protein interactions or activities induced by TSH as well as TSHR gene expression. The TSHR structure and its mechanism of signal transduction is being rapidly unraveled in several laboratories, since the recent cloning of the receptor. In addition, the epitopes for autoantibodies against the receptor that can subvert the normal regulated synthesis and secretion of thyroid hormones, causing hyper- or hypofunction, have been defined. Studies of regulation of the TSHR minimal promotor have uncovered a better understanding of the mechanisms by which TSH regulates both growth and function of the thyroid cell. A key novel component of this phenomenon involves TSH AMP positive and negative regulation of the TSHR. Negative transcriptional regulation is a common feature of MHC class I genes in the thyroid. Subversion of negative regulation or too little negative regulation is suggested to result in autoimmune disease. Methimazole and iodide at autoregulatory levels may be important in reversing this process and returning thyroid function to normal. Their action appears to involve factors that react with the IREs on both the TSHR and the TG promoter. Too much negative regulation, as in the case of ras transformation, results in abnormal growth without function. TTF-1 is implicated as a critical autoregulatory component in both positive and negative regulation of the TSHR and appears to be the link between TSH, the TSHR, TSHR-mediated signals, TG and TPO biosynthesis, and thyroid hormone formation. Differentially regulated expression of the TSHR and TG by cAMP and insulin depend on differences in the specificity of the TTF-1 site, that is, the lack of Pax-8 interactions with the TSHR, and the IRE sites. Single-strand binding proteins will become important in determining how TSHR transcription is controlled mechanistically.

Amino Acid Sequence↗

Molecular cloning of the cyanobacterial adenylate cyclase gene from the filamentous cyanobacterium Anabaena cylindrica.

Molecular cloning of the structural gene for adenylate cyclase (cya) of the cyanobacterium Anabaena cylindrica was carried out by complementation of an Escherichia coli strain defective in the cya gene. The cya-defective strain produced significant amounts of cyclic AMP when it was transformed with the cya gene isolated from A. cylindrica. This gene encodes a polypeptide consisting of 502 amino acid residues (molecular weight, 55,300). The deduced primary protein structure showed that the carboxyl-terminal region of the adenylate cyclase of A. cylindrica shows strong structural similarity to the conserved regions of the adenylate cyclases of various eukaryotes. No similarity was found between the amino acid sequences of the cya gene of A. cylindrica and that of E. coli. A hydropathy plot suggests that this protein has two hydrophobic regions, a transmembrane span and a signal peptide. An antiserum specific to this adenylate cyclase was prepared by immunizing a rabbit with a glutathione S-transferase-adenylate cyclase fusion protein expressed in E. coli. This antiserum recognized a 55-kDa protein in Anabaena cell lysates. Subcellular fractionation analysis showed that A. cylindrica adenylate cyclase localized in the thylakoid membrane.

Adenylyl Cyclases↗