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T Ohmori

Publications and source records attributed to T Ohmori.

At least 73 records · Page 4Linked to original sources

[Isolation of type-A blood group active glycoproteins from salivas and their reaction with monoclonal antibodies].

We have previously examined several ABO blood grouping antibodies with whole saliva and observed that there were two types of antibodies. One group of antibodies reacted with both secretory and non-secretory saliva, and the other with only secretory saliva. In order to clarify the differences in reaction of the antibodies with saliva, we needed to analyze of antigens in secretory and non-secretory saliva. Therefore, we prepared blood group active glycoproteins from secretory and non-secretory saliva by affinity chromatography and gel filtration. The secretory saliva gave three active peaks, one large peak in the void volume and two small peaks in fractions of smaller molecular weights on Sepharose-CL6B after the affinity chromatography. From the non-secretory saliva, a single active peak in the void volume, which corresponded to the major peak in the secretory saliva, was found. Most blood group activities were found in those void volume fractions. Moreover, capillary electrophoresis showed that these blood group active glycoproteins were identical, and that there were immunological differences between secretory and non-secretory salivary blood group substances.

ABO Blood-Group System↗

[Improvement of absorption-elution test using commercially available anti-A, anti-B monoclonal antibodies--ABO blood typing from hair samples].

An improved procedure for ABO blood typing by the absorption-elution test using commercially available monoclonal antibodies was established. The optimized elution temperature for anti-A monoclonal antibodies to be liberated from bloodstains was 54 degrees C and the temperature to deactivate the liberated antibodies was over 56 degrees C. The test condition was established using a monoclonal antibody manufactured by Biotest. For the anti-A monoclonal antibody the most effective elution time was 5 min and the long incubation time decreased the activity of the liberated antibodies. On the other hand, the conditions formerly used for absorption-elution tests were suitable for anti-B monoclonal antibody. A Type-A test and a Type-B test have to be performed separately for ABO blood grouping from forensic samples. The conditions established in this report were applied to the absorption-elution test to achieve an improved result for ABO blood grouping from hair samples.

ABO Blood-Group System↗

Blockade of tumor cell transforming growth factor-betas enhances cell cycle progression and sensitizes human breast carcinoma cells to cytotoxic chemotherapy.

We have examined the effect of neutralizing TGF-beta antibodies on cisplatin-mediated cytotoxicity against MDA-231 human breast tumor cell spheroids. These tridimensional in vitro systems have been shown to recapitulate the drug sensitivity pattern of tumor cells in vivo. MDA-231 tumor cell spheroids exhibit higher protein levels of the cyclin-dependent kinase (Cdk) inhibitors p21 and p27 and >10-fold lower Cdk2 activity compared to adherent cell monolayers, as well as pRb hypophosphorylation, a predominant G1 population, and a cisplatin 1-h IC50 of approximately 100 microM. Treatment of MDA-231 cells in monolayer with cisplatin for 1 h, subsequently grown as spheroids, increased steady-state TGF-beta1 mRNA levels, secretion of active TGF-beta, cellular Cdk2 activity, pRb phosphorylation, and p21 protein levels, while downregulating p27. Accumulation of cells in G2M and progression into S were noted 48 h after treatment with 100 microM cisplatin. We tested whether drug-induced upregulation of TGF-beta1 and p21, perhaps by preventing cell cycle progression, were protective mechanisms against drug-mediated toxicity by using neutralizing anti-TGF-beta antibodies. Anti-TGF-beta antibodies diminished the induction of p21, enhanced the activation of Cdk2, and facilitated progression into S and G2M following cisplatin treatment. This resulted in a >twofold enhancement of drug-induced DNA fragmentation and a shift in the cisplatin 1-h IC50 from 100 to <10 microM. These data suggest that tumor cell TGF-beta1 may protect from DNA damage and that postchemotherapy administration of TGF-beta inhibitors may facilitate progression beyond G1/S, potentially increasing the efficacy of cytotoxic chemotherapy.

Antineoplastic Agents↗

Oscillations of membrane potential across a polypeptide membrane, induced by an electrical current.

Oscillation of membrane potential across a tri-block copolypeptide membrane composed of (Glu)x-(Leu)y-(Glu)x (x = 0.18 and y = 0.64) was observed under an electrical current, when the membrane was placed between equimolar aqueous salt solutions. The amplitude of the oscillation was influenced by the type of cation and anion in the external salt solution, and the amplitude was in the sequence: K+ > Na+ > Cs+ > Ca2+ and Cl- > Br-. The frequencies of the oscillations were in the range 0.1 to 5 Hz, and were also slightly influenced by the type of cation and anion.

Anions↗

Alcohol-related cancers and aldehyde dehydrogenase-2 in Japanese alcoholics.

Aldehyde dehydrogenase-2 (ALDH2) eliminates most of the acetaldehyde produced during alcohol metabolism. In some drinkers, a mutant ALDH2 allele contributes to diminished activity of the enzyme, dramatically increasing the risk for esophageal cancer. This study was designed to evaluate the ALDH2 gene polymorphism as a predictor of the development of cancers prevalent in Japanese alcoholics. We performed ALDH2 genotyping on lymphocyte DNA samples from Japanese alcoholic men (487 cancer-free; 237 with cancer, including 34 oropharyngolaryngeal, 87 esophageal, 58 stomach, 46 colon, 18 liver, 7 lung, 9 other sites, and 19 multiple primary cancers in two or three organs). The frequencies of the mutant ALDH2*2 allele were significantly higher in alcoholics with oropharyngolaryngeal (52.9%), esophageal (52.9%), stomach (22.4%), colon (21.7%) and esophageal cancer concomitant with oropharyngolaryngeal and/or stomach cancer (78.6%), than in cancer-free alcoholics (9.0%). After adjustment for age, daily alcohol consumption and amount of cigarette smoking, significantly increased risks (odds ratios) in the presence of the ALDH2 *2 allele were found for oropharyngolaryngeal (11.14), esophageal (12.50), stomach (3.49), colon (3.35), lung (8.20) and esophageal cancer concomitant with oropharyngolaryngeal and/or stomach cancer (54.20) but not for liver or other cancers. These results suggest a general role of acetaldehyde, a recognized animal carcinogen, in the development of human cancers.

Adult↗

Protective effect of administration of skim milk on exogenous and endogenous infection in mice.

In order to minimize the denaturation of proteins in milk, normal cow's milk was pasteurized at 61 C for 20 min. The protective effects of the thus prepared skim milk (low-heat skim milk) on exogenous and endogenous infection were examined as compared with conventional skim milk which was pasteurized at 121 C for 2 sec. The antibody titers to Listeria monocytogenes and Escherichia coli of low-heat skim milk were almost equal to that of raw milk, while no antibody was detected in the conventional skim milk. When mice were given low-heat skim milk or conventional skim milk, the incidence of the translocation of orally inoculated Listeria monocytogenes to the spleen was lower in the low-heat skim milk group than that in the conventional skim milk group. The life span of 7 Gy X-ray irradiated mice given low-heat skim milk was significantly prolonged in comparison to that of mice given conventional skim milk. However, there were no differences in the number of bacteria in the feces or IgA production by Peyer's patch cells between the two groups. These results suggest that antibodies in low-heat skim milk, which still have reactivity to exogenous or indigenous bacteria, may contribute to the protective effects against bacterial infection.

Animals↗

Protein kinase C epsilon translocation and phosphorylation by cis-diamminedichloroplatinum(II) (CDDP): potential role in CDDP-mediated cytotoxicity.

Phorbol ester-like protein kinase C (PKC) activators, such as 12-O-tetradecanoylphorbol-13-acetate, and perturbation of some growth factor receptors have been reported to alter the cytotoxicity of cis-diamminedichloroplatinum(II) (CDDP). To study the mechanism of this alteration, we have examined the effect of CDDP per se on PKC isozymes. The SKBR-3 human breast carcinoma cell line exhibits at least six different PKC isozymes (PKC alpha, betaI, betaII, delta, epsilon, and zeta). After exposure to 10-100 microM CDDP for 3 h, only PKC epsilon translocated from the plasma membrane to the nuclear membrane and to the cytosolic fraction. This translocation was observed in a time- and dose-dependent manner by Western blot and confocal microscopy. CDDP also decreased the mobility of PKC epsilon in the nuclear membrane fraction, an effect that was blocked by protein phosphatase 2A, suggesting drug-mediated isozyme phosphorylation. This translocation and phosphorylation were also induced by the cisplatin analogue carboplatin but not with the anticancer agents Adriamycin and Taxol. Antisense oligodeoxynucleotides against PKC epsilon down-regulated isozyme content, blocked drug-induced translocation, and reduced cisplatin-mediated cytotoxicity 3-fold compared to that of sense-treated cells. Antisense PKC epsilon also decreased SKBR-3 cell sensitivity to carboplatin but not to Adriamycin and Taxol. These data support a role for PKC epsilon translocation and phosphorylation on CDDP-mediated toxicity.

Antineoplastic Agents↗

Short-term follow-up after endoscopic mucosectomy of early esophageal cancer and aldehyde dehydrogenase-2 genotype in Japanese alcoholics.

The risk of the future development of primary esophageal cancer after endoscopic esophageal mucosal resection of esophageal cancer is not known; hence, there are no established guidelines for follow-up surveillance programs. Simultaneous occurrence of multiple cancers associated with esophageal cancer is common among heavy drinkers who have the inactive form of aldehyde dehydrogenase-2 (ALDH2) as a risk factor. Thirty-four Japanese male alcoholics with intraepithelial or mucosal squamous cell carcinoma in the esophagus were treated by endoscopic esophageal mucosal resection, followed by endoscopy and esophageal iodine staining, to find the additional development of primary esophageal cancer. Primary esophageal squamous cell carcinoma was detected in nine patients (26.5%) at 3-21 months after the first cancer diagnosis. Cancer occurred more frequently in patients with inactive ALDH2 than it did in those with active ALDH2 [42.1% (8 of 19) versus 6.7% (1 of 15), P = 0.047], and it occurred more frequently in those with multiple esophageal cancers than it did in those without them [60.0% (6 of 10) versus 12.5% (3 of 24), P = 0.009]. Kaplan-Meier estimates of the proportions of patients with additional primary esophageal cancers showed that patients with inactive ALDH2 (P = 0.024) or multiple esophageal cancers (P = 0.007) had a significantly increased likelihood of the development of additional cancer. Close follow-up examinations using endoscopy and iodine staining are needed for such high-risk patients.

Adult↗

Self-sustained pH oscillations in a compartmentalized enzyme reactor system.

This work represents our continued effort toward fulfilling the need to discover a model system for experimental investigations of temporal oscillations in an enzyme-membrane system. In this paper, the regions in the parameter space where self-sustained pH oscillations can be induced for a compartmentalized enzyme reactor system, which consists of a well-stirred reactor, a reservoir and a membrane containing no enzyme, were determined via numerical simulation with two proteolytic enzymes: papain (EC 3.4.22.2) and alpha-chymotrypsin (EC 3.4.21.1). The sizes of the regions were qualitatively compared with those associated with enzymic membrane system. As a result, we found that the possibility of experimentally observing self-sustained oscillations in the compartmentalized papain reactor system, as well as in the papain-membrane system, is high. However, self-sustained pH oscillations are less likely in the compartmentalized alpha-chymotrypsin reactor system than in the alpha-chymotrypsin-membrane system.

Journal Article↗

Tolerance to the neurotoxic effect of methamphetamine in rats behaviorally sensitized to methamphetamine or amphetamine.

A series of experiments was conducted to examine whether rats behaviorally sensitized to methamphetamine (MA) would show supersensitivity or tolerance to the MA-induced neurotoxic effects on dopaminergic and serotonergic nerve terminals in the striatum (ST), nucleus accumbens (NA) and medial frontal cortex (MFC). Moderate to high doses of MA (3, 4 and 5 mg HCl salt/kg, s.c., at 2 h intervals, four injections) dose-relatedly decreased the contents of dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in ST, and the content of 5-HIAA in NA and that of 5-HT in MFC. These neurotoxic effects in ST were significantly attenuated in rats behaviorally sensitized to MA (4 mg HCl salt/kg, s.c., for 10 days). To examine the possibility that the attenuation in the toxic effects in sensitized rats was due to an accelerated metabolism from MA to amphetamine (AMPH), a high dose of MA (5 mg HCl salt/kg, s.c., at 2 h intervals, four injections) was administered to rats behaviorally sensitized to AMPH (4 mg HCl salt/kg, s.c., for 10 days). It was revealed that the MA-induced decrease in the striatal contents of DOPAC, homovanillic acid (HVA), 5-HT and 5-HIAA were attenuated in rats behaviorally sensitized to AMPH. The MA-induced decrease in the striatal DA content tended to be attenuated in AMPH-sensitized rats. These data suggest that rats behaviorally sensitized to MA or AMPH develop tolerance to MA-induced striatal dopaminergic and serotonergic neurotoxicity. It is speculated that the mechanism of tolerance might be mediated by an altered central response rather than peripheral metabolism.

Amphetamine↗

Clonazepam prevents the development of sensitization to methamphetamine.

The GABA-benzodiazepine neurotransmission has been implicated in various forms of plasticity such as kindling and learning. The present study examined the effects of clonazepam (CZP), a GABA-benzodiazepine agonist, on the development of behavioral sensitization to methamphetamine (MA). Rats treated with MA (1 mg/kg, S.C.) for 10 days displayed significantly enhanced motor activity when tested with MA (1 mg/kg) after a 7-8-day withdrawal, indicating the development of behavioral sensitization. Pretreatment with CZP (0.5 and 2.0 mg/kg) prior to MA administration prevented the development of the phenomenon. Rats treated with CZP alone showed no difference in the motor activity compared to those treated with saline. These results suggest that stimulation of GABA-benzodiazepine receptors plays a role in the development of behavioral sensitization.

Animals↗

Effect of no synthesis inhibition on striatal dopamine release and stereotyped behavior induced by a single administration of methamphetamine.

1. The authors performed both microdialysis and behavioral measurement in each of rats, in order to examine effects of nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (LNAME;30 mg/kg,i.p.) on striatal dopamine (DA) release and stereotypy induced by a single administration of methamphetamine (MA)(4 mg/kg,s.c.), simultaneously. 2. LNAME administered prior to MA significantly decreased level of locomotion-stereotypy rating scores induced by MA. 3. In the same animals, LNAME had no effect on MA-induced striatal DA release. 4. The results suggest that NO synthesis inhibition attenuated MA-induced stereotypy by modulating neuronal process subsequent to activation of postsynaptic DA receptors.

Animals↗

A fatal case of fungal endocarditis of the tricuspid valve associated with long-term venous catheterization and treatment with antibiotics in a patient with a history of alcohol abuse.

We report a fatal case of fungal (candidal) endocarditis of the tricuspid valve with clinico-pathologically interesting findings following and associated with candidal pneumonia during long-term central venous catheterization (CVC) for intravenous therapy and long-term treatment with antibiotics for bacterial and fungal infection in a patient with a history of alcohol abuse. We review the literature on fungal cardiac infection related to long-term catheterization and alcohol abuse, and discuss the pathogenesis.

Aged↗

In vitro and in vivo anti-platelet effects of enzymatic hydrolysates of collagen and collagen-related peptides.

Collagen-related peptides, Gly-Pro-Arg and its analogues, were examined for their inhibitory effects on platelet aggregation induced by the addition of ADP. Human platelet aggregation was suppressed by more than 50% with each of Gly-Pro-Arg and such Gly-Pro-Arg-containing peptides as Gly-Pro-Arg-Gly, Gly-Pro-Arg-Gly-Pro, Gly-Pro-Arg-Pro-Pro, and Gly-Pro-Arg-Pro-Pro-Pro at a concentration of 0.3 mM. The inhibitory effects of these peptides were about 10 times higher in human PRP than in rat PRP. Other Gly-Pro-Arg analogues such as Sar-Pro-Arg, Gly-Pro-Lys, Gly-Ala-Arg, and Ala-Gly-Pro-Arg had no inhibitory effect at a concentration from 0.1 to 0.8 mM even in human PRP. Intravenous and oral administrations of Gly-Pro-Arg and enzymatic hydrolysates of collagen suppressed the decrease in platelet count for endotoxin-induced DIC in rats. Collagen itself has been regarded as a potent inducer of platelet aggregation, but these findings suggest that collagen-related peptides and enzymatic hydrolysates of collagen prevent platelet aggregation.

Animals↗

[Context-dependent sensitization: reconsideration and a hypothesis].

The repeated administration of amphetamine-like psychostimulants results in an augmentation of their behavioral responses, a phenomenon known as behavioral sensitization. One important factor associated with the process of behavioral sensitization is environmental influence. It has been reported that, when drug administration is paired with a particular environment, sensitization is observed only in that particular environment. This phenomenon has been known as context-dependent sensitization. However, considering recent reports and our own studies, the classical concept of context-dependent sensitization may not be satisfactory. We propose an alternative hypothesis. Psychostimulants are known to induce different behaviors in different environments. We believe that the repeated administration of a psychostimulant in different environments results in the augmentation of different behaviors. For instance, rats treated with a stimulant in a small cage did not locomote but were observed to sniff and rear. After repeated treatment, they showed sensitization not in locomotion but in stereotyped behaviors such as sniffing and rearing. This suggests that environment does not facilitate the development of sensitization, but rather modifies the pattern and character of a stimulant-induced behavior in the sensitized animals. In this paper, we briefly review various literature and present our hypothesis.

Animals↗

Reliability of a flushing questionnaire and the ethanol patch test in screening for inactive aldehyde dehydrogenase-2 and alcohol-related cancer risk.

Molecular epidemiology of esophageal and upper aerodigestive tract cancers revealed that alcohol is more carcinogenic in persons with inactive aldehyde dehydrogenase-2 (ALDH2) than in those with active ALDH2. A simple questionnaire has been developed to screen for the facial flushing that occurs in persons with inactive ALDH2 when they drink even a single glass of beer. In this study, 266 of 284 consecutive male Japanese clinic patients (age > or = 50 years) completed the flushing questionnaire, and 239 underwent the ethanol patch test (a cutaneous model for the flushing response). Blinded genotyping showed inactive ALDH2 for 94.4% (102 of 108) of subjects who reported always flushing (early in their drinking history or currently) and for 47.7% (21 of 44) of those who reported sometimes flushing, whereas 95.6% (109 of 114) of subjects reporting that they never exhibited facial flushing had active ALDH2. When all three categories of flushing (current always, former always, and sometimes) were collapsed into one, the questionnaire's sensitivity and specificity for identifying inactive ALDH2 were 96.1 and 79.0%, respectively, compared with 72.4 and 71.4% for the ethanol patch test. The results suggest the utility of this simple flushing questionnaire in daily practice, as well as large-scale studies to assess cancer risks associated with drinking and ALDH2 and for activities aimed at preventing alcohol-related cancer.

Aged↗