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Biomedical subjects

T Ohmori

Publications and source records attributed to T Ohmori.

At least 91 records · Page 5Linked to original sources
PubMed1997

[Relationship between the morphological changes of Japanese cedar (Cryptomeria japonica) pollen grains and the release of major allergens from the pollen].

Release of major allergens (Cry j 1, Cry j 2) from Japanese cedar (C. japonica) pollen grains treated with high pressure was investigated. C. japonica pollen grains crushed by high pressure treatment using FRENCH Pressure Cell Press released greater amounts of major allergens, particularly Cry j 2, compared to those without crush. This suggests that the cytoplasm of C. japonica pollen grains contains more Cry j 2 than previously reported. The effect of nasal fluid on the release of major allergens from C. japonica pollen grains was analyzed in vitro. Nasal fluid from patients with nasal allergy remarkably increased the release of major allergens from pollen grains, compared to controls, and the amount of Cry j 1 was greater than Cry j 2. Further studies revealed that nasal fluid affects the outer wall of pollen grains, where Cry j 1 is located, to a greater extent than its effect on the cytoplasm, where Cry j 2 is located.

Allergens↗
PubMed1996

In vitro hypoxia of cortical and hippocampal CA1 neurons: glutamate, nitric oxide, and platelet activating factor participate in the mechanism of selective neural death in CA1 neurons.

We prepared neuron-rich cultures from cortical and hippocampal CA1 regions of postnatal day 1 (P1) rats. Using these cultures, we investigated the sensitivity of neurons to hypoxic insults. The effects of MK-801, cycloheximide, NG-nitro-L-arginine (L-NNA), and anti-platelet-activating factor (anti-PAF) IgG on neuronal injury under hypoxic conditions also were examined. The percentage of astroglial cells was higher in CA1 than cortical cultures despite use of the same culture procedure. Despite this finding, the percentage of lactate dehydrogenase (LDH) released into the medium was greater in CA1 than cortical cultures under the conditions of 24-h hypoxia and 24-h incubation (P < 0.05). We then added MK-801 (500 nM), cycloheximide (3 microM), L-NNA (100 microM) and anti-PAF IgG (50 micrograms/ml) prior to inducing the hypoxia and measured LDH in the medium after 24-h hypoxia and 48-h incubation. Under the hypoxic condition, MK-801, L-NNA, and anti-PAF IgG significantly protected the CA1 neurons from hypoxic injury compared with cortical neurons, while cycloheximide protected both cultures equally. These results suggest that CA1 neurons are more sensitive to hypoxia than cerebral cortical neurons, and glutamate, nitric oxide, and PAF may participate in the mechanism of selective neural death in neurons of the CA1 region due to hypoxia.

Animals↗
PubMed1996

Cancer screening of upper aerodigestive tract in Japanese alcoholics with reference to drinking and smoking habits and aldehyde dehydrogenase-2 genotype.

In this study, 1,000 Japanese male alcoholics were consecutively screened by upper gastrointestinal endoscopy with esophageal iodine staining. Associations among cancer-detection rates, drinking and smoking habits, and aldehyde dehydrogenase-2 (ALDH2) genotypes were evaluated. A total of 53 patients (5.3%) had histologically confirmed cancer. Esophageal cancer was diagnosed in 36, gastric cancer in 17, and oropharyngolaryngeal cancer in 9 patients: 8 of the esophageal-cancer patients were multiple-cancer patients, with additional cancer(s) in the stomach and/or oropharyngolaryngeal region. Multiple logistic regression revealed that use of stronger alcoholic beverages (whisky or shochu) in contrast with lighter beverages (sake or beer) and smoking of 50 pack-years or more increased the risks for esophageal (odds ratio 3.2 and 2.8 respectively), oropharyngolaryngeal (4.8 and 5.1 respectively) and multiple cancer (10.5 and 11.8 respectively). The inactive form of ALDH2, encoded by the gene ALDH2*1/2*2 prevalent in Orientals, exposes them to higher blood levels of acetaldehyde, a recognized animal carcinogen, after drinking. This inactive ALDH2 was detected in 19/36 (52.8%) patients with esophageal cancer, in 5/9 (55.6%) patients with oropharyngolaryngeal cancer, and in 7/8 (87.5%) patients with multiple cancer. All of these gene frequencies far exceeded that in a large alcoholic cohort (80/655, 12.2%). The triple combination of the risk factors of the inactive ALDH2, stronger alcoholic beverages and heavy smoking was more commonly associated with multiple-cancer patients than with patients with esophageal cancer alone (62.5% vs. 7.1%). These results show that the 3 risk factors are important for the development of upper-aerodigestive-tract cancer in Japanese alcoholics. For these high-risk drinkers, regimented screening appears to be indicated.

Adult↗
PubMed1996

Effect of citalopram, a selective serotonin reuptake inhibitor, on the acquisition of conditioned freezing.

The present study examined the effects of the selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitor citalopram on the acquisition of conditioned freezing, an index of anxiety. Acute treatment with citalopram (1-10 mg/kg) dose dependently prevented the acquisition of conditioned freezing, while acute treatment with noradrenaline or dopamine reuptake inhibitors failed. The acute effect of citalopram was not antagonized by the 5-HT1A receptor antagonist NAN190, 1-(2-methoxyphenyl)-4-[4-(2-phthalimmido)butyl]piperazine or the 5-HT2A/2C receptor antagonist ICI169,369, 2-(2-dimethylaminoethylthio)-3-phenylquinoline hydrochloride. These results indicate that selective 5-HT reuptake inhibitors reduce not only the expression of conditioned freezing as reported previously, but also the acquisition of conditioned freezing. Both these effects of selective 5-HT reuptake inhibitors may be related to their clinical efficacy in the treatment of anxiety disorders.

Adrenergic Uptake Inhibitors↗
PubMed1996

Multiple primary esophageal and concurrent upper aerodigestive tract cancer and the aldehyde dehydrogenase-2 genotype of Japanese alcoholics.

BACKGROUND: Multiple intraesophageal primary cancer and upper aerodigestive tract (UADT) cancer associated with esophageal cancer are common diseases, especially in heavy drinkers. They are often explained by the concept of field cancerization, which suggests a similar etiology. However, little is known about the nature of the hypothesized etiology. METHODS: Among 901 Japanese male alcoholics systematically screened by upper gastrointestinal endoscopy (with esophageal iodine staining), 33 had squamous cell carcinoma of the esophagus. The multiplicity of their esophageal carcinoma and their concurrent UADT cancer was compared with their genotype for aldehyde dehydrogenase-2 (ALDH2), the major determinant of blood acetaldehyde concentration after drinking. RESULTS: Of 17 patients with inactive ALDH2, 13 (76.5%) had multiple primary carcinoma of the esophagus, whereas 5 of 16 (31.3%) with active ALDH2 had multiple carcinomas (P < 0.01). The prevalence of concurrent UADT cancer was 29.4% in those patients with inactive ALDH2, compared with 6.3% in those patients with active ALDH2. CONCLUSIONS: Inactive ALDH2 is a risk factor for multiple carcinoma of the esophagus in alcoholics. Acetaldehyde, a recognized animal carcinogen, appears to play a critical role in field cancerization.

Alcoholism↗
PubMed1996

Effect of the selective CCKB receptor antagonist LY288513 on conditioned fear stress in rats.

In order to investigate the involvement of cholecystokinin (CCK) in the regulation of anxiety, the effect of the selective non-peptide CCKB receptor antagonist LY288513 ((4S, 5R)-N-(4-bromophenyl)-3-oxo-4,5-diphenyl-1-1-pyrazolidinecarboxamide+ ++) on freezing behavior induced by conditioned fear stress was examined using a time-sampling procedure. Rats were individually subjected to 5 min of inescapable electric footshock in a shock chamber. Twenty-four hours after the footshock, the rats were again placed in the shock chamber and observed for 5 min without shocks: this procedure is termed conditioned fear stress. Subcutaneous administration of LY288513 30 min before footshock (0.3 mg/kg) and 30 min before conditioned fear stress (0.03 mg/kg) reduced conditioned freezing. This indicates that LY288513 blocked both the acquisition and expression of conditioned fear. The relatively selective non-peptide CCKA receptor antagonist, lorglumide (D, L-4-(3,4-dichlorobenzoylamino)-5-(diphentylamino)-5-oxo-pent anoic acid), blocked the expression of conditioned fear, though only at a high dose (1.0 mg/kg). The peripheral non-peptide CCKA/B receptor antagonist, loxiglumide (D, L-4-(3,4-dichlorobenzoylamino)-5- (N-3-methoxypropyl-pentylamino)-5-oxo-pentanoic acid), failed to do so. These results suggest that brain CCKB receptors are involved in the regulation of anxiety.

Animals↗
PubMed1996

Self-sustained pH oscillations in immobilized proteolytic enzyme systems.

This work represents our first step toward fulfilling the need to discover a model system for experimental investigations of temporal oscillations, pattern formations, and other non-linearity related dynamic behavior in immobilized-enzyme-membrane systems. In this paper, the regions in the parameter space where self-sustained pH oscillations can be induced were determined via extensive numerical simulation for five enzyme-membrane systems involving four proteolytic enzymes: alpha-chymotrypsin, trypsin, bromelain, and ficin. From this study, we concluded that, even with current enzyme-immobilization techniques, the possibility of experimentally observing self-sustained pH oscillations in a flat membrane immobilized with alpha-chymotrypsin and using N-acetyl-L-tryptophan ethyl ester as a substrate is high. Under suitable conditions and with extra efforts, self-sustained oscillations may also occur in membrane systems immobilized with ficin, trypsin and bromelain.

Arginine↗
PubMed1996

Effects of nitric oxide synthesis inhibition on methamphetamine-induced dopaminergic and serotonergic neurotoxicity in the rat brain.

We examined effects of nitric oxide (NO.) synthesis inhibition on methamphetamine (MA)-induced dopaminergic and serotonergic neurotoxicity. The toxic dose of MA (5 mg/kg, sc, x4) significantly decreased contents of dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum (ST), and significantly decreased contents of serotonin (5-HT) in the ST, nucleus accumbens (NA) and medial frontal contex (MFC). Coadministration with a NO. synthase inhibitor, N omega-nitro-L-arginine methyl ester (LNAME) (30 mg/kg, i.p., x2), reduced the MA-induced decreases in contents of DA, DOPAC and HVA in the ST, but not reduced the MA-induced decreases in contents of 5-HT in the ST, NA and MFC. These findings suggest that the MA-induced dopaminergic, but not serotonergic neurotoxicity, may be related to the neural process such as NO. formation caused by the activation of postsynaptic DA receptor.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1996

The role of glutamate in behavioral and neurotoxic effects of methamphetamine.

Studies on the mechanisms of behavioral and neurochemical effects of amphetamine or methamphetamine (MA) have focused on the dopaminergic system. However, recent reports suggest that the glutamatergic system may be involved in the MA effects. Our laboratory has been conducting a series of experiments to further examine the role of glutamate in both behavioral and neurotoxic effects of MA. These studies include (1) behavioral studies on the effect of N-methyl-D-aspartate (NMDA) antagonists on the development of MA-induced behavioral sensitization, (2) neurochemical studies on the effects of NMDA antagonists on MA-induced neurotoxicity, and (3) in vivo microdialysis studies on the effects of MA on glutamate release. In the present paper, the authors comment on an important role of glutamatergic systems in the behavioral and toxic effects of MA.

Animals↗
PubMed1996

Defective organification of iodide causing congenital goitrous hypothyroidism.

A 26-yr-old Japanese woman with congenital goitrous hypo-thyroidism and sensorineural deafness underwent a thyroidectomy. Examination of the thyroid gland revealed characteristic features of multinodular goiter. The T3 and T4 content in thyroglobulin (Tg) were 0.03 and 0.02 mol/mol Tg, respectively. Iodide incorporation into Tg, using slices of the thyroid tissue, revealed that iodide organification of thyroid tissue from our patient was markedly lower than that of normal controls. Then, guaiacol and iodide oxidation activities of thyroid peroxidase (TPO) in our patient's thyroid tissue were lower than those of normal controls (guaiacol assay: 1.92 vs. 30.0 +/- 5.7 mGU/mg protein; iodide assay: 1.1 vs. 6.6 +/- 2.8 mIU/mg protein). Lineweaver-Burk plot analysis of the oxidation rates of guaiacol and iodide indicated that this patient's TPO had a defect in the binding of guaiacol and iodide, but the coupling activity of the patient's TPO was not decreased compared with those of two normal thyroids. In this case and in control subjects, Nothern gel analysis of TPO messenger RNA from unstimulated and TSH-stimulated thyroid cells revealed a 3.2 kilobase species in the former and four distinct messenger RNA species of 4.0, 3.2, 2.1, and 1.7 kilobases in the latter. Western blot analysis of TPOs obtained from this patient and from control subjects identified the same 107 kDa protein, using antimicrosomal antibody-positive serum. We analyzed the coding sequence in the patient's TPO gene by using polymerase chain reaction technique. A single point mutation of G-->C at 1265 base pair was detected only in the TPO gene, but this point mutation does not alter the amino acid residue. It is possible that posttranslational modification such as abnormal glycosylation may occur in the TPO molecules. Furthermore, it is possible that there are differences in the tertiary structures of the TPO molecules between our patient and normal subjects. The above abnormalities of TPO molecules may play an important role in our patient's dyshormonogenesis.

Adult↗
PubMed1996

Prolylendopeptidase inhibitory activity of a glial fibrillary acidic protein fragment and other proline-rich peptides.

The brain prolylendopeptidase (PEP) inhibitory activity of synthetic peptides related to the bovine brain-derived PEP inhibitor, GFAP-(38-55) (MPPPLPARVDFSLAGALN), was investigated. Homologous peptides such as MPPPLPTRVDFSLAGALN (human type) and MTPPLPARVDFSLAGALN (mouse type) also inhibited PEP. Among various synthetic fragments of GFAP-(38-55), only MPPPLP had a Ki essentially the same as that of GFAP-(38-55). Similar synthetic proline-rich peptides such as synapsin fragments and SH3 domain-binding peptides had more or less inhibitory activity.

Amino Acid Sequence↗
PubMed1996

Immunoreactivity to neurohormonal polypeptide in colorectal carcinomas and tumor-neighboring mucosa, and its significance.

OBJECTIVE: To clarify whether advanced colorectal carcinomas possess an amphocrine nature and produce both pancreatic and gut neurohormonal polypeptide and epithelial mucin in comparison with surrounding colorectal mucosa. DESIGN: Retrospective analysis of paraffin-embedded specimens from 100 cases of colorectal carcinoma (39 colonic and 61 rectal) and surrounding mucosa, with histochemical and immunohistochemical studies. RESULTS: The immunoreactivity of the carcinomas and surrounding mucosa by the labeled streptavidin-biotin complex method for polyclonal rabbit antibody against human vasoactive intestinal polypeptide, pancreatic polypeptide, and somatostatin was 61%, 59%, and 82% respectively; that of mucosa neighboring immunoreactive tumors was 87%, 85%, and 90%; and that of mucosa neighboring nonimmunoreactive tumors was 67%, 63% and 61%. Double staining for different types of neurohormonal polypeptide revealed that most carcinoma cells had a multiendocrine nature, and a number of neurohormonal polypeptide--positive and epithelial mucin-positive carcinoma cells (amphocrine cells) were found in almost every histological type of carcinoma by double staining for immunoreactivity and periodic acid-Schiff reaction or mucicarmin. CONCLUSION: Colorectal carcinomas exhibit not only multiendocrine characteristics, producing various types of neurohormonal polypeptide, but also amphocrine characteristics of different grades, and most tumor-neighboring crypt cells possess those characteristics, too. We concluded that these characteristics of colorectal carcinomas may be related to their origin as multipotential endodermal stem cells.

Adenocarcinoma↗
PubMed1996

[Survey and treatment strategy of antidepressant-resistant depression].

The present study investigated the phenomenology and treatment of antidepressant-resistant depressions (ARD). To be classified a nonresponder, a patient had to have been treated adequately with two tricyclic (or tetracyclic) antidepressants (i.e., a minimum of the equivalent of 150 mg of imipramine for 4 weeks). The 34 depressed patients (25 unipolar patients and 9 bipolar patients) failed to respond to these antidepressant trials. Seventy-two % of the unipolar patients were in their first depression episodes, but 89% of the bipolar patients had 2 or more previous affective episodes. The mean duration of the current episode of depressions was 3.8 years. In 5 unipolar patients, the duration of the current depression episode was 10 years or more. The addition of lithium, bromocriptine or levothyroxine treatment to tricyclic or tetracyclic antidepressants were effective in the treatment of ARD. Levothyroxine were more effective in the treatment of the bipolar patients than the unipolar patients. Safrazine, a monoamine oxidase inhibitor, and electroconvulsive therapy were also effective in the treatment of ARD, but had the drawbacks of the high incidence of moderate or severe adverse reactions and high relapse rates, respectively. We propose a step-wise approach to the treatment of ARD, which mainly includes the pharmacotherapy and can be used in Japan.

Antidepressive Agents↗
PubMed1996

Esophageal cancer and aldehyde dehydrogenase-2 genotypes in Japanese males.

Although drinking alcohol is an established esophageal cancer risk factor, the mechanisms by which alcohol induces this high-mortality rate cancer are not clear. To help elucidate this problem and develop an implementable preventive strategy, this genetic epidemiological study focused on aldehyde dehydrogenase 2 (ALDH2), the key enzyme for elimination of acetaldehyde generated by alcohol consumption. This enzyme is polymorphic; its mutant allele, ALDH2*2, which leads to the enzyme inactivity, is prevalent in Orientals. This Japanese case-control study of ALDH2-related risk for esophageal squamous cell carcinoma included alcoholics (40 cases and 55 controls) and nonalcoholic drinkers (29 cases and 28 controls). The analysis of the results of genotyping these subjects showed that the increased risk for esophageal cancer in those with one ALDH2*2 allele was substantially higher in both alcoholics (odds ratio = 7.6; 95% confidence interval = 2.8-20.7) and nonalcoholic drinkers (odds ratio = 12.1; 95% confidence interval = 3.4-42.8). The results strongly suggest that because persons who have this mutant ALDH2*2 allele have a high concentration of blood acetaldehyde after drinking alcohol, acetaldehyde (a recognized animal carcinogen) plays a pivotal role in the pathogenesis of alcohol-related esophageal cancer in humans. These results suggest that to help lower their risk for esophageal cancer, persons with the ALDH2*2 allele should be encouraged to reduce their consumption of alcoholic beverages.

Acetaldehyde↗
PubMed1996

Molecular characterization of heterochromatic regions around the Tm-2 locus in chromosome 9 of tomato.

The gene Tm-2 (tomato mosaic virus (ToMV) resistant), which is tightly linked to a morphological marker gene nv (netted virescent), resides in a heterochromatic region near the centromere of chromosome 9 in tomato. Tm-2 and Tm-2a are known to be allelic, and exhibit similar phenotypes to each other, but can be differentiated by their response to different ToMV strains. An inoculation experiment demonstrated that Tm-2 helped a mutant strain of ToMV to infect a heterozygous tomato (Tm-2/Tm-2a). Aiming at investigating the structures of DNA around these active genes and their influence on gene activities, we attempted to identify and characterize random amplified polymorphic DNA (RAPD) markers linked to these genes using nearly isogenic lines (NILs) of tomato. Genetic analysis using 13 RAPD markers linked to the Tm-2 locus and cytological analysis by fluorescence in situ hybridization (FISH) demonstrated that the lines resistant to ToMV had a large block derived from a chromosome of Lycopersicon peruvianum. Among these markers, we estimated that two, OPE16(900) and OPN31(1000), are nearest to the Tm-2 locus. Out of the 13 markers six, distributed within about 0.7 centi-Morgan (cM), were cloned and sequenced to be converted to sequence characterized amplified region (SCAR) markers. Of these, four were successfully converted to SCAR markers. The six clones were also used as probes for Southern hybridization of genomic DNA from NILs to characterize structures around the Tm-2 locus. One clone was estimated to be derived from a sequence that was present in one copy. The other five clones appeared to be derived from different kinds of moderately or highly repetitive sequences.

Gene Expression↗
PubMed1995

Successful screening for early esophageal cancer in alcoholics using endoscopy and mucosa iodine staining.

BACKGROUND: Epidemiologic studies have provided evidence that alcohol abuse is an important risk factor for esophageal carcinoma. However, no systematic screening program has been established yet in the early detection of esophageal cancer in high risk populations of heavy drinkers. METHODS: A cohort of 629 male alcoholics (54 +/- 8 years old) were consecutively and systematically screened by endoscopy combined with iodine staining and targeted biopsy at the National Institute on Alcoholism (Kanagawa, Japan). For mucosal carcinomas, endoscopic esophageal mucosal resection (EEMR) was used to serve confirmatory diagnostic and therapeutic purposes. RESULTS: Iodine-unstained lesions, distinctly demarcated, white, and 5 mm or larger in greatest dimension, were observed on the esophageal wall in 162 patients (25.8%). Thirty-six such unstained lesions in 21 of 629 patients, with an unexpectedly high rate of 3.3%, turned out to be squamous cell carcinomas of the superficial type. According to some established criteria, EEMR was performed in 17 of these patients, 3 of whom were given additional irradiation. Esophagectomy was performed in two patients, chemotherapy combined with irradiation in one, whereas still another was followed endoscopically. The cancer invasion was confined within the epithelium in eight patients, to the proper mucosal layer in nine, and to the submucosa in four. Multiple logistic regression revealed that the risks for distinct iodine-unstained lesions and superficial esophageal carcinoma increased independently for users of stronger alcoholic beverages, i.e., whiskey or shochu (odds ratio [OR] = 1.47 and 2.94, respectively) compared with lighter beverages, i.e., sake or beer and 30+ cigarettes/day (OR = 1.68 and 3.85, respectively). CONCLUSION: Routine application of this program for these high risk individuals yielded an unusually high rate of detection of esophageal carcinoma.

Adult↗
PubMed1995

Effects of nitric oxide (NO) synthesis inhibition on the development of supersensitivity to stereotypy and locomotion stimulating effects of methamphetamine.

The present study examined the effects of nitric oxide (NO) synthase inhibitor, N omega-nitro-L-arginine methyl ester (LNAME; 30 and 60 mg/kg, i.p.) on the development of supersensitivity to stereotypy as well as locomotion stimulating effects of methamphetamine (MA) (3.22 and 0.805 mg free base/kg, s.c., respectively). Rats treated with MA for 10 days showed enhancement in MA-induced stereotypy and locomotor activity. Rats pretreated with LNAME prior to MA also showed enhancement in the two types of behavior, also they showed significantly reduced stereotypy scores compared to those treated with MA alone. The results suggest that NO synthesis is not critically involved in the development of behavioral supersensitivity to stereotypy stimulating as well as locomotion stimulating effect of MA. However, No synthesis may have a modulatory role in behavioral sensitization in stereotypy.

Amino Acid Oxidoreductases↗