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Biomedical subjects

M Ohta

Publications and source records attributed to M Ohta.

At least 253 records · Page 14Linked to original sources
PubMed1998

Mathematical modeling to predict the bactericidal effect of processed vinegar on Escherichia coli O157:H7.

The combined effects of acetic acid, temperature and sodium chloride on Escherichia coli O157:H7 inactivation were examined in processed vinegar. To express their effects, quadratic polynomial models were applied. The logarithm transformation of sodium chloride concentration provided a better fit of the data than the use of a non-transformation value. On the basis of this finding, the polynomial models should be distinguished into two types, i.e. the non-sodium chloride model and the sodium chloride model, both of which had high R2 values (0.988 and 0.978, respectively).

Acetic Acid↗
PubMed1998

The murine Fhit locus: isolation, characterization, and expression in normal and tumor cells.

The murine Fhit locus maps near the centromere nu proximal Ptprg locus on mouse chromosome 14. The cDNA sequence and structure are similar to those of the human gene, with exons 5-9 encoding the protein. The predominant mRNA in the tissues and cell lines tested was an alternatively spliced form missing exon 3. Most murine cell lines tested, including lines established from normal mouse embryos and tumors, expressed very low or undetectable levels of Fhit mRNA. Most normal mouse tissues expressed wild-type Fhit mRNA, whereas approximately 40% of murine lung carcinomas expressed wild-type and aberrant Fhit RT-PCR products that lacked various exons. Several tumorigenic mouse cell lines exhibited homozygous deletions of Fhit exons. We conclude that the murine Fhit gene, like its human counterpart, is a target of alterations involved in murine carcinogenesis.

Acid Anhydride Hydrolases↗
PubMed1998

Absence or reduction of Fhit expression in most clear cell renal carcinomas.

The FHIT gene at human chromosome region 3p14.2 straddles the common fragile site, FRA3B, and numerous homozygous deletions in cancer cell lines and primary tumors. Also, the 3p14.2 chromosome breakpoint of the familial clear cell kidney carcinoma-associated translocation, t(3;8)(p14.2;q24), disrupts one FHIT allele between exons 3 and 4, fulfilling one criterion for a familial tumor suppressor gene: that one allele is constitutionally inactivated. Because the FHIT gene sustains biallelic intragenic deletions rather than mutations, there has not been evidence that the FHIT gene frequently plays a role in kidney cancer, although replacement of Fhit expression in a Fhit-negative renal carcinoma cell line suppressed tumor growth in nude mice. We have now assessed 41 clear cell renal carcinomas for expression of Fhit by immunohistochemistry. Normal renal tubule epithelial cells express Fhit uniformly and strongly, whereas 51% of the tumors are completely negative, 34% of tumors show a mixture of positive and negative cells, and 14% are uniformly positive, although usually less strongly positive than the normal epithelial cells. Most interestingly, there was a correlation between complete absence of Fhit and the G1 morphological grade and early clinical stage. Morphological grades G2 and G3 exhibited a mixture of positive and negative cells with a tendency for a higher fraction of negative cells in G3. Fhit inactivation is likely to be an early event in G1 tumors and may be associated with progression in G2 and G3 tumors.

Acid Anhydride Hydrolases↗
PubMed1998

Autoregulation of thyroid-specific gene transcription by thyroglobulin.

Thyroglobulin (TG), the primary synthetic product of the thyroid, is the macromolecular precursor of thyroid hormones. TG synthesis, iodination, storage in follicles, and degradation control thyroid hormone formation and secretion into the circulation. Thyrotropin (TSH), via its receptor (TSHR), increases thyroid hormone levels by up-regulating expression of the sodium iodide symporter (NIS), thyroid peroxidase (TPO), and TG genes. TSH does this by modulating the expression and activity of several thyroid-specific transcription factors, thyroid transcription factor (TTF)-1, TTF-2, and Pax-8, which coordinately regulate NIS, TPO, TG, and the TSHR. Major histocompatibility complex class I gene expression, which also is regulated by TTF-1 and Pax-8 in the thyroid, is decreased simultaneously. This helps maintain self-tolerance in the face of TSH-increased gene products necessary for thyroid hormone formation. In this report we show that follicular TG counter-regulates TSH-increased, thyroid-specific gene transcription by suppressing expression of the TTF-1, TTF-2, and Pax-8 genes. This decreases expression of the TG, TPO, NIS, and TSHR genes, but increases class I expression. TG acts transcriptionally, targeting, for example, a sequence within 1.15 kb of the 5' flanking region of TTF-1. TG does not affect ubiquitous transcription factors regulating TG, TPO, NIS, and/or TSHR gene expression. The inhibitory effect of TG on gene expression is not duplicated by thyroid hormones or iodide and may be mediated by a TG-binding protein on the apical membrane. We hypothesize that TG-initiated, transcriptional regulation of thyroid-restricted genes is a normal, feedback, compensatory mechanism that limits follicular function and contributes to follicular heterogeneity.

Animals↗
PubMed1998

Dose-Intensified Chemotherapy for Breast Cancer: Present and Future Prospects.

With the trend to maximize chemotherapy in breast cancer, the use of peripheral blood stem cells in addition to hematopoietic growth factors to alleviate myelosuppression caused by dose-intensified chemotherapy has been shown to be beneficial. In treatment of metastatic breast cancer, response rates and complete response rates as high as 100%and nearly 80%, respectively, have been reported. Such treatments have shown even greater promise in an adjuvant setting for high-risk breast cancer. High-dose chemotherapy studies, however, involve highly-selected patient populations who are generally compared with unselected patients, and controversy still surrounds the question of whether it is substantially superior to conventional-dose chemotherapy. There are now more than sufficient data to justify ongoing randomized trials, and the most important overall recommedation is to encourage patients to participate in these clinical trials.

Journal Article↗
PubMed1998

Suppression of hematopoietic activity in tenascin-C-deficient mice.

Tenascin-C (TN-C), a member of the extracellular matrix (ECM) glycoprotein family, is expressed on the surface of stromal cells in the hematopoietic system or lymphoid organs. Recently, TN-C-deficient mutant mice produced by TN-C gene targeting through homologous recombination were shown to develop normally, although TNs have been reported to play important roles in organogenesis and carcinogenesis. In the present study, we found that colony-forming capacity of bone marrow (BM) cells was considerably lower in TN-C-deficient mice (a decrease of approximately 35% from control), although their mononuclear cell count and BM architecture showed no significant difference from those of normal mice. Furthermore, in long-term BM culture in vitro, hematopoietic cell production (a decrease of approximately 40% in Dexter's condition and of approximately 65% in Whitlock-Witte's condition from control), colony-forming capacity of the produced cells (a decrease of approximately 60% from control), and longevity of the cultures were markedly lower in the TN-C-deficient mice than in control mice, whereas hematopoiesis in the TN-C-deficient mutant mice was sustained. The addition of TN-C glycoprotein to long-term BM cultures of TN-C-deficient mice clearly induced the recovery of hematopoietic cell production and colony-forming capacity of hematopoietic progenitor cells. Thus, these results provide direct evidence that an ECM glycoprotein component, TN-C, plays a relevant role in hematopoiesis through interactions between stromal cells and hematopoietic progenitor cells.

Animals↗
PubMed1998

Conformation-function relationship of vitamin D: conformational analysis predicts potential side-chain structure.

In previous studies, we have grouped regions in space occupied by the vitamin D side chain into four: A, G, EA, and EG. We showed that the receptor (VDR) affinity of 1alpha,25-dihydroxyvitamin D3 derivatives increases, in terms of side-chain region, in the order EG, G, A, and EA. We called this the active space group concept. In the present study, we used this active space group concept to analyze the conformation-activity relationship of about 40 representative potent 1alpha,25-dihydroxyvitamin D3 analogues. We initially listed structural modifications in the side chain of potent vitamin D analogues and estimated their potency factor. Possible side-chain conformations of representative analogues were calculated by the molecular mechanics method and plotted on a dot map compared with the regions A, G, EA, and EG. The cell-differentiating potency of the analogues was correlated with our active space group concept with few exceptions. Among potent analogues with a natural configuration at C(20), the side chains of those with a 22-oxa, 22-ene, 16-ene, or a 18-nor modification were located in front of region EA (termed F). The side chains of the most potent 20-epi-22-oxa-24-homovitamin D analogues were concentrated at the left side of the EA region (L-EA). Thus, the side chains of almost all potent analogues were distributed around the EA region, and potency increased in the order A, F, EA, and L-EA.

Calcitriol↗
PubMed1998

Differential contribution of Na+-K+ pump and K+ conductance to the post-tetanic hyperpolarization of the subtypes of tetrodotoxin-resistant C-fibers in the isolated bullfrog sciatic nerve.

The post-tetanic hyperpolarizations (PTHPs) of the fast and slow tetrodotoxin-resistant (TTX-R) C-fibers were recorded from isolated bullfrog sciatic nerves using a modified vaseline gap method. Under control solutions, the monophasic fast and slow TTX-R C-fibers compound action potentials (C-CAPs) increased in amplitude up to 133.9+/-17.9% (mean+/-SD; n = 9) and 167.0+/-41.5% (n = 7), respectively, shortly after tetanic stimulation. The recovery time constants of the fast and slow ones were 66.5 and 101.2 s, respectively. Significant differences between the rates of amplitude augmentation of the fast and slow TTX-R C-CAPs were found for the most pairs of measured points (P < 0.05 or P < 0.01). After application of ouabain solutions, the augmentation of the fast TTX-R C-CAP was inhibited to an insignificant level, while that of the slow TTX-R C-CAP remained significant with the recovery time constant being 90.9 s. After additional application of TEA, the post-tetanic augmentation of the slow TTX-R C-CAP was blocked. These results suggest that Na+-K+ pump contributes to the PTHPs of the fast and slow TTX-R C-fibers and that K+ conductance contributes only to the PTHP of the slow TTX-R C-fibers, indicating differential modulation of the firing rate of each TTX-R C-fibers group.

Action Potentials↗
PubMed1998

Genetic contribution of the tumor necrosis factor region in Guillain-Barré syndrome.

We studied genetic polymorphisms in the tumor necrosis factor (TNF) region in 81 Japanese patients with Guillain-Barré syndrome (GBS) and 85 controls. A significantly higher frequency of the 100-base pair (bp) (TNFa2) allele of the TNFa microsatellite marker, which is associated with high TNF alpha production, existed in Campylobacter jejuni-positive (Cj+) GBS patients than in controls, suggesting the involvement of a genetic predisposition to high TNF alpha secretion in the development of C. jejuni-related GBS.

Alleles↗
PubMed1998

Tumor necrosis factor alpha regulates nitric oxide synthase expression in portal hypertensive gastric mucosa of rats.

Anti-tumor necrosis factor alpha (TNF-alpha) treatment decreases nitric oxide (NO) synthesis and ameliorates the hyperdynamic circulation in portal hypertensive rats. We have recently demonstrated that nitric oxide synthase isoform 3 (NOS3) is overexpressed in portal hypertensive gastric mucosa and that resultant NO overproduction probably is responsible for the increased susceptibility of the mucosa to damage. In the present study, we examined whether TNF-alpha is overexpressed in portal hypertensive gastric mucosa and whether anti-TNF-alpha treatment affects gastric NOS3 messenger RNA (mRNA) and protein expression. We examined plasma concentrations of TNF-alpha and its protein expression in gastric specimens from portal hypertensive and sham-operated rats using Western blotting and immunohistochemistry. We also measured gastric mucosal blood flow, gastric expression of NOS3 mRNA and protein, and NOS3 enzyme activity in rats with and without TNF-alpha-neutralizing antibody treatment. The TNF-alpha protein levels in portal hypertensive stomachs were significantly increased by 57% compared with levels in sham-operated controls. TNF-alpha antibody treatment normalized gastric mucosal blood flow in portal hypertensive stomachs and significantly reversed overexpression of gastric NOS3 mRNA, protein, and its enzyme activity in portal hypertensive rats by 48%, 45%, and 33%, respectively. These results suggest that TNF-alpha may regulate NOS3 expression in the portal hypertensive stomach and that anti-TNF-alpha treatment may ameliorate the pathophysiological abnormalities of portal hypertensive gastric mucosa.

Animals↗
PubMed1998

Therapeutic effects of aldose reductase inhibitor on experimental diabetic neuropathy through synthesis/secretion of nerve growth factor.

We investigated alterations in nerve growth factor (NGF) and ciliary neurotrophic factor (CNTF) contents during treatment with epalrestat, an aldose reductase inhibitor (ARI), on streptozotocin (STZ)-induced diabetic neuropathy in rats. Diabetic rats showed a statistically significant reduction in H-wave-related sensory nerve conduction velocity (HSNCV) and in NGF content in sciatic nerves during the experiment of 8 weeks. No reduction in the CNTF content in sciatic nerves was seen in the diabetic rats. The epalrestat treatment, which started 4 weeks after STZ injection, resulted in a significantly greater NGF content and faster HSNCV than those in untreated diabetic rats. But no statistically significant alterations of motor nerve conduction velocity (MNCV) or CNTF content were seen during the treatment. ARI showed the stimulating effect for NGF synthesis/secretion in rat Schwann cell culture in vitro. These findings suggest that decreased levels of NGF in diabetic sciatic nerves may be involved in the pathogenesis of diabetic neuropathy in these rats and further show that epalrestat treatment can be useful for the treatment of diabetic neuropathy through NGF-induction in Schwann cells and/or inhibition of the polyol pathway.

Aldehyde Reductase↗
PubMed1998

Serum 1,5-anhydro-D-glucitol levels in liver cirrhosis.

We studied the serum 1,5-anhydro-D-glucitol (AG) levels, a marker of glycemic control, in liver cirrhotic patients who had no evidence of glycosuria in 24-h urine samples in order to clarify the effects of impaired liver function on serum AG metabolism. We showed first that serum AG concentrations were significantly lower in cirrhotic patients than in age- and sex-matched healthy controls (17.6+/-1.6 vs 26.3+/-1.7 microg/ml, P<0.05). Moreover, serum AG levels were found to be positively correlated with both serum cholinesterase and albumin levels. The observations indicate that serum AG levels were decreased in liver cirrhosis, especially in cases of severely reduced hepatic functions, suggesting the possibility of altered AG synthesis in liver cirrhosis.

Cholinesterases↗
PubMed1998

Induction of mitogen-activated protein kinase signal transduction pathway during gastric ulcer healing in rats.

BACKGROUND & AIMS: Previous studies have shown that gastric ulceration stimulates epithelial cell proliferation and overexpression of epidermal growth factor (EGF) and EGF receptor (EGF-R) in the mucosa bordering necrosis. The aim of this study was to investigate whether extracellular signal-regulated kinase (ERK) cascade is involved in the healing of experimental gastric ulcers. METHODS: We studied EGF-R levels, EGF-R phosphorylation levels, and ERK1 and ERK2 activity in normal and ulcerated rat gastric mucosa. We also examined the effect of Tyrphostin A46 (potent inhibitor of EGF-R and EGF-R kinase-dependent proliferation) on the above parameters. RESULTS: During the initial stages of healing (3 and 7 days), ulcerated mucosa showed significant increase (vs. controls) in protein tyrosine kinase activity, EGF-R levels (510% and 550%), EGF-R phosphorylation levels, ERK1 activity (430% and 880%), and ERK2 activity (550% and 990%). Tyrphostin A46 treatment significantly inhibited ulcer healing and reduced EGF-R levels, EGF-R phosphorylation, and ERK1 and ERK2 activity. CONCLUSIONS: These findings indicate that experimental gastric ulcer healing involves activation of EGF-R-ERK signal transduction pathway.

Animals↗
PubMed1998

A novel splicing mutation in the ceruloplasmin gene responsible for hereditary ceruloplasmin deficiency with hemosiderosis.

Hereditary ceruloplasmin deficiency with hemosiderosis (aceruloplasminemia) is a newly recognized autosomal recessive disorder of copper-iron metabolism due to mutations in the ceruloplasmin (Cp) gene. We report here a novel mutation in the Cp gene in a 54-year-old Japanese woman with this disease. She showed clinical triad; diabetes mellitus, retinal degeneration and neurological disorder in her middle age. Laboratory findings were characteristic for no detectable serum ceruloplasmin and increased serum ferritin. Liver biopsy revealed excessive storage of iron in hepatocytes and magnetic resonance imaging of the brain was indicative of increased iron content in the basal ganglia, thalamus and dentate nucleus. The a-->g substitution at the splice acceptor site of the intron 6 (1209-2) caused a 8-bp deletion in Cp mRNA by defective splicing, resulting in a premature termination codon at the amino acid position 388. Truncation of Cp, even if effectively translated, may cause loss of its normal function because of drastic change in its triangular structure.

Alternative Splicing↗
PubMed1998

Discrepant intracellular pH changes following intracellular Ca2+ increases induced by glutamate and Ca2+ ionophores in rat hippocampal neurons.

We investigated changes in intracellular pH (pHi) in relation to intracellular Ca2+ concentration ([Ca2+]i) in primary cultured hippocampal neurons treated with glutamate. [Ca2+]i and pHi were imaged with fluorescent dyes and confocal microscopy. Exposure to 1 mM glutamate for 10 min increased [Ca2+]i and evoked acidosis. These changes persisted for at least 60 min, even after removal of glutamate. The increase in [Ca2+]i and the acidosis were not observed in Ca2+-free solution and were attenuated in the presence of MK-801, an NMDA receptor antagonist. We also found that the increase in [Ca2+]i and acidosis could be induced by addition of Ca2+ to the extracellular solution in the cells pretreated with glutamate in Ca2+-free solution, even if glutamate did not exist in the extracellular solution. On the other hand, ionomycin and Br-A23187, calcium ionophores, increased [Ca2+]i to almost the same level as glutamate and increased pHi. Extracellular Ca2+ was also indispensable for the increase in [Ca2+]i and the alkalosis. These results suggest the followings: 1) intracellular acidosis by glutamate is dependent on the presence of extracellular Ca2+; 2) the acidosis does not result from only the increase in [Ca2+]i; and 3) glutamate induces the irreversible disorder of regulatory mechanisms of [Ca2+]i not only by Ca2+-dependent process, but also by Ca2+-independent process.

Animals↗
PubMed1998

Role of brain vasopressin in regulation of blood pressure.

Using recent advances in brain physiological, neurohistochemical, and molecular biological techniques, it could be demonstrated that the central action of vasopressin (VP) is important in cardiovascular regulation and in the pathogenesis of hypertension. VP is now known to be located in the area of the brain involved in cardiovascular regulation. Furthermore, in various pathophysiological states, brain VP secretion is regulated separately from the peripheral VP secretion system. The role of brain VP in the regulation of the circadian rhythm of blood pressure is becoming a topic of major interest.

Animals↗