Biomedical subjects

T Ohmori

Publications and source records attributed to T Ohmori.

At least 163 records · Page 9Linked to original sources

PubMed1992

Phospholipase C-mediated hydrolysis of phosphatidylcholine is activated by cis-diamminedichloroplatinum(II).

We have investigated the effect of cis-diamminedichloroplatinum(II) (CDDP) on signal transduction pathways. CDDP treatment did not cause any change in the binding of [3H]-phorbol dibutyrate to PC-9 (human lung adenocarcinoma cell line) cells, a measure of protein kinase C activation. However, 2-h CDDP treatment (20 micrograms/ml) caused approximately 200% increase in 1,2-sn-diacylglycerol (DAG) production and approximately 50% decrease in inositol 1,4,5-triphosphate production. To explore the different source of DAG, we analyzed phospholipids labeled with [14C]choline by TLC and revealed that [14C]choline-labeled phosphatidylcholine (PC) was decreased to 50% by CDDP treatment. This suggested that PC turnover was increased by CDDP-treatment. PC-specific phospholipase C (PC-PLC) activity was increased to 2.5-fold (2.58 +/- 0.28 nmol/mg protein per min) by 2 h CDDP (20 micrograms/ml) treatment compared with control (1.05 +/- 0.24 nmol/mg protein per min). Treatment of CDDP also stimulated PC-PLC in the crude membrane extract from PC-9 cells. CDDP had no effect on the activities of phospholipase A2 and D. Trans-DDP, which has far less cytotoxicity than its stereoisomer, CDDP, did not cause any change in PC-PLC activity. A significant inhibition of DNA synthesis (less than 80%) occurred 4 h after 2 h CDDP (20 micrograms/ml) treatment. These results demonstrated that CDDP-induced PC-PLC activation was an early event in CDDP-induced cytotoxicity and suggested that the effects of CDDP on signal transduction pathways had an important role in CDDP-induced cytotoxicity.

Cisplatin↗

PubMed1992

Anatomical study of the accessory mental foramen and the distribution of its nerve.

We examined the range of the accessory mental foramen [AMF] and its accessory mental nerve in three Japanese cadavers. The diameters of the AMF were relatively small: 0.74 mm, 0.80 mm and 0.89 mm. The distances between the mental foramen and AMF were: 0.67 mm, 2.1 mm and 5.74 mm. The distribution of the accessory mental nerve was different in the three cases. These nerves communicated with the branches of the facial and buccal nerves.

Aged↗

PubMed1992

Vimentin metaplasia in renal cortical tubules of preneoplastic, neoplastic, aging, and regenerative lesions of rats and humans.

Vimentin expression was studied immunohistochemically in renal cortical tubules of untreated male rats of various ages, rats exposed to toxins (barbital sodium, folic acid) and carcinogens (streptozotocin, N-bis(2-hydroxypropyl)nitrosamine, barbital sodium, and in humans of various ages with or without renal epithelial tumors. Fetal, neonatal, and young adult rats did not express vimentin in renal cortical tubules. Regenerative renal tubular lesions from rats with aging nephropathy and from rats with toxic nephropathy both expressed vimentin. Mitogenic lesions induced by folic acid at 24 hours, however, were not immunoreactive for vimentin. Carcinogen-induced preneoplastic renal cortical tubular lesions in rats were most often focally immunoreactive whereas strong vimentin expression was found in almost all induced renal tumors. In kidneys of three children (younger than 2 years of age), vimentin was not found in renal cortical tubular cells except in rare individual cells in one case. Vimentin was abundant in basophilic regenerative tubules in kidneys of aged individuals, however. Most (7/10) human renal carcinomas and latent preneoplastic or neoplastic renal tubular lesions found incidentally at autopsy (2/4) showed vimentin expression. The authors suggest that the switching to vimentin expression in phenotypically normal renal cortical tubular cells in rats and humans, which do not usually express the intermediate filament protein vimentin, should be considered vimentin metaplasia. Vimentin expression is dissociated from increased cell proliferation in hyperplastic and neoplastic lesions, however. Instead the degree of dedifferentiation of the tubule cells and changes in phenotype were associated with vimentin expression.

Age Factors↗

PubMed1991

[Enzymatic iodination of thyroglobulins obtained from patients with thyroid disease].

Iodination of the isolated thyroglobulin (Tg) by peroxidase was compared with various Tg preparations obtained from patients with thyroid diseases. For the purpose, the iodination process was observed in the incubation medium containing Tg, iodide, H2O2-generating system, and thyroid peroxidase (TPO) or lactoperoxidase (LPO). During the incubation, iodination of Tg preparations increased gradually and reached a plateau after 90 min., and 5 min. incubation with 3mIU or 14mIU of TPO, respectively. The degree of iodination level at the plateau region was different in each Tg preparation, depending on the iodine content of the original starting (native) preparation before incubation. The iodination level of cancer Tg with a very low iodine content (less than 0.1%) was low compared with the normal Tg level (obtained from normal thyroid tissue which contained about 0.4% iodine). The above findings suggest the possible existence of some structural differences of Tg in terms of the susceptibility to the iodination between the preparations of normal and diseased Tgs. As far as the immunological aspect concerned, there was no significant difference in the affinity (avidity) of Tg with polyclonal anti-Tg antibody between the native Tg and the enzymatically iodinated one. These results suggest that the changes of iodine and thyroid hormone contents of Tg by in vitro iodination, has no significant effect on the immunological property of Tg molecule.

Antigen-Antibody Reactions↗

PubMed1991

Molecular cloning and characterization of a ras p21-like GTP-binding protein (24KG) from rat liver.

We have isolated cDNA clones from a rat liver cDNA library that encode a ras p21-like small GTP-binding protein (24KG) which was purified from the microsomes-Golgi complex fraction of the rat liver. The cloning was accomplished using polymerase chain reaction amplified with a set of oligonucleotide primers which were designed from the partial amino acid sequences for 24KG. The cDNA contained an open reading frame encoding a 216 amino acid protein with a calculated Mr weight of 24,397. This Mr weight was similar to that of the purified 24KG estimated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The sequence analysis of 24KG revealed that a 24KG cDNA is the rat counterpart of a rab11 cDNA cloned from a Madin-Darby canine kidney cell cDNA library. The 1.0-kilobase 24KG mRNA corresponding to the isolated cDNA was also detected in various rat tissues, such as brain, testis, spleen, and heart.

Amino Acid Sequence↗

PubMed1991

Metallothionein content correlates with the sensitivity of human small cell lung cancer cell lines to cisplatin.

We have established cis-diamminedichloroplatinum(II) (cisplatin) resistant human small cell lung cancer cell lines, H69/CDDP0.2 and H69/CDDP, to investigate the mechanism of acquired resistance to cisplatin. H69/CDDP0.2 and H69/CDDP were 6- and 11-fold resistant to cisplatin compared with the H69 parental cell line. H69/CDDP was also resistant to cadmium chloride (2-fold), cis-diammine(glycolato)platinum (4-fold), 4-hydroperoxycyclophosphamide (3-fold) and 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosour ea (4-fold) if the drug concentrations that inhibit cell growth by 50% from growth inhibition assay were compared. There was no significant difference in the cisplatin accumulation among these cell lines. Although DNA interstrand cross-link formations, determined by filter elution assay in H69/CDDP0.2 and H69/CDDP, was decreased to 20 to 30% of that in H69 parental cells, the repair capacity of DNA interstrand cross-links was equivalent in all three cell lines. Intracellular glutathione content was equal in all cell lines. H69/CDDP had the highest glutathione S-transferase activity (H69, 11 nmol/min/mg protein, H69/CDDP0.2, 12 nmol/min/mg protein; H69/CDDP, 74 nmol/min/mg protein, respectively) and an overexpression of glutathione S-transferase pi mRNA. The drug concentrations that inhibit cell growth by 50% for cisplatin in all cell lines were decreased by treatment with ethacrynic acid, an inhibitor of glutathione S-transferase pi, but this did not alter the relative degree of resistance. Intracellular metallothionein content (H69, 14 pmol/mg protein, H69/CDDP0.2, 22 pmol/mg protein; H69/CDDP, 33 pmol/mg protein, respectively) and expression of metallothionein mRNA were correlated with the drug concentrations that inhibit cell growth by 50% of the three cell lines for cisplatin and cadmium chloride. The present study suggested the importance of metallothionein in the mechanisms of cisplatin resistance.

Antineoplastic Agents↗

PubMed1991

Purification and characterization from rat liver cytosol of a GDP dissociation inhibitor (GDI) for liver 24K G, a ras p21-like GTP-binding protein, with properties similar to those of smg p25A GDI.

A regulatory protein for a liver GTP-binding protein (G protein) with a molecular weight value of 24,000 (24K G), which we have recently purified, was purified to near-homogeneity from rat liver cytosol and characterized. This regulatory protein, designated here as GDP dissociation inhibitor for 24K G (24K G GDI), inhibited the dissociation of GDP from and the subsequent binding of GTP to 24K G. 24K G GDI was inactive for other ras p21/ras p21-like small G proteins including c-Ha-ras p21, rhoB p20, smg p21B, and smg p25A. 24K G was, however, recognized by bovine brain smg p25A GDI which regulated the GDP/GTP exchange reaction of smg p25A. By analyses of sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE), immunoblotting with anti-smg p25A GDI antibody, two-dimensional PAGE, and C4 column chromatography, 24K G GDI showed physical properties very similar to those of smg p25A GDI. The peptide map and the partial amino acid sequences of 24K G GDI were not identical with those of smg p25A GDI. Among the 83 residues, 2 amino acids were different between rat liver 24K G GDI and bovine brain smg p25A GDI. These results indicate that there is a specific regulatory protein for 24K G, 24K G GDI, in rat liver cytosol and that 24K G GDI has close similarity to smg p25A GDI.

Amino Acid Sequence↗

PubMed1991

Prediction of the antitumor activity of new platinum analogs based on their ex vivo pharmacodynamics as determined by bioassay.

We report the predictive model for the clinical response of new platinum analogs against lung cancer by a bioassay using human lung-cancer cell lines including small-cell (SCLC) and non-small-cell lung cancer (NSCLC). Exponentially growing cells of six different SCLC and six NSCLC lines were exposed to different concentrations of the three platinum compounds, cisplatin, carboplatin, and 254-S in a double-agar colony-forming cell assay. The concentrations inhibiting 50% of colony formation (IC50 value) for cisplatin, carboplatin and 254-S in SCLC cell lines were significantly lower than those in NSCLC cell lines. A total of 15 patients entered the pharmacological study. In all, 80 mg/m2 cisplatin, 450 mg/m2 carboplatin, and 100 mg/m2 254-S were each given to five patients by intravenous drip infusion. Bioassay as well as chemical assay was achieved by clonogenic techniques using NCI-H-69 (SCLC cell line) and PC-9 (NSCLC cell line) as target cells. Biological comparison of antitumor activity was performed on the basis of the antitumor activity of patients' plasma using the antitumor index (ATI), which was defined as the area under the percentage of colony suppression versus time curve obtained by bioassay and calculated by the trapezoidal rule. When NCI-H-69 and PC-9 were used as target cells for bioassay, colony-inhibitory activity was revealed by the ATIs. The ATIs obtained by bioassay showed better correlation than the AUCs obtained by chemical assay with the clinical response for cisplatin and carboplatin against SCLC and NSCLC, according to the following equation: [Reported Response (%)] = 11.5668 + 0.0014 x [ATI] (r = 0.97). The response rates for 254-S against SCLC and NSCLC were predicted by this formula to be 40%-65% and 14%-16%, respectively. 254-S is prospectively suspected of having the same, if not more, activity then carboplatin against SCLC and of having almost the same activity as cisplatin against NSCLC.

Antineoplastic Agents↗

PubMed1991

Ultrastructure of oesophageal melanocytosis.

Four examples of an endoscopically detected oesophageal melanotic lesion were examined by light microscopy, light microscope histochemistry and transmission electron microscopy, and were compared with 13 control samples of normal oesophageal epithelium. By light microscopy, pigmented melanocytes lacking atypia and mitoses were observed amongst the keratinocytes in the basal layer of the oesophageal mucosa. Junctional activity was absent. The mechanism of pigmentation was studied and found to consist of: an increase in the number of melanocytes in the basal layer of the mucosa, an increase in the quantity of melanin in these melanocytes, transfer of melanin from melanocytes to keratinocytes and to macrophages and fibroblasts in the tunica propria. Since all the lesions demonstrated increased numbers of both melanocytes and melanosomes, the term oesophageal melanocytosis rather than melanosis is suggested, to emphasise the essential character of the lesion as a cellular proliferation. The value of sampling these pigmented lesions during endoscopy is emphasised as a means of obtaining well-preserved material for the evaluation of a lesion which some authorities have viewed as a possible precursor for oesophageal malignant melanoma.

Aged↗

PubMed1991

Measurement of endogenous dopamine and norepinephrine release from superfused slices of rat prefrontal cortex in vitro: modulation by D2 and alpha-2 presynaptic receptors.

Endogenous dopamine (DA) and norepinephrine (NE) in the superfusate from slices of rat medial prefrontal cortex were measured by high-performance liquid chromatography coupled to electrochemical detection (HPLC-ECD). Stimulation with high K+ or methamphetamine (MAP) evoked a dose-dependent elevation in the release of DA and NE, although spontaneous release of DA or NE was barely detectable. The K(+)-evoked release was Ca++ dependent, whereas the MAP-evoked release was not. The K(+)-evoked DA release was inhibited by the DA agonist apomorphine (1 microM or 10 microM) and enhanced by the D2 antagonist (-)-sulpiride (1 microM). The K(+)-evoked NE release was inhibited by the alpha-2 agonist clonidine (0.1 microM or 1 microM) and enhanced by the alpha-2 antagonist idazoxan (1 microM). These results confirm the existence of release modulatory D2 and alpha-2 receptors in the medial prefrontal cortex. The present study is the first description of a method which allows evaluation of the release of endogenous DA or NE in the cortex slices and is competent to examine the properties of the two catecholamines release and their regulation by presynaptic receptors.

Animals↗

PubMed1991

Effects of high hydrostatic pressure on characteristics of pork slurries and inactivation of microorganisms associated with meat and meat products.

Pork slurries inoculated with various test microorganisms were prepared and subjected to high hydrostatic pressure at 1000 to 6000 atm for 10 min at 25 degrees C to examine for the pressure effects on characteristics of the slurries and the inactivation of the microorganisms associated with meat and meat products. Pressure treatment at higher than 3000 atm caused coagulation and discoloration of the pork slurries. Harder and more white coagulants were obtained by increasing the pressure. Pressure treatment at 3000 to 6000 atm killed all the microorganisms tested by more than 6-log colony-forming units (cfu)/g except Bacillus cereus spores. Gram-negative microorganisms were more labile to pressure than Gram-positive ones. Campylobacter jejuni, Pseudomonas aeruginosa, Salmonella typhimurium and Yersinia enterocolitica were inactivated at pressures higher than 3000 atm; Escherichia coli, Saccharomyces cerevisiae and Candida utilis at pressures higher than 4000 atm; Micrococcus luteus, Staphylococcus aureus and Streptococcus faecalis at 6000 atm. Only less than one-log cfu/g of B. cereus spores were inactivated at 6000 atm. Ultraviolet absorption spectra and acridine orange staining suggested that E. coli became permeable and leaked cytoplasmic RNA at lower pressure than S. aureus. From the present findings, the authors propose high hydrostatic pressure treatment as a promising means of preparing wholesome meat and meat products.

Animals↗

PubMed1991

The analysis of the defense mechanism against indigenous bacterial translocation in X-irradiated mice.

The defense mechanism against indigenous bacterial translocation was studied using a model of endogenous infection in X-irradiated mice. All mice irradiated with 9 Gy died from day 8 to day 15 after irradiation. The death of mice was observed in parallel with the appearance of bacteria from day 7 in various organs, and the causative agent was identified to be Escherichia coli, an indigenous bacterium translocating from the intestine. Decrease in the number of blood leukocytes, peritoneal cells and lymphocytes in Peyer's patches or mesenteric lymph nodes was observed as early as 1 day after irradiation with 6 or 9 Gy. The mitogenic response of lymphocytes from various lymphoid tissues was severely affected as well. The impairment of these parameters for host defense reached the peak 3 days after irradiation and there was no recovery. However, in vivo bactericidal activity of Kupffer cells in mice irradiated with 9 Gy was maintained in a normal level for a longer period. It was suggested that Kupffer cells play an important role in the defense against indigenous bacteria translocating from the intestine in mice.

Animals↗

PubMed1991

Reversal of cisplatin resistance with amphotericin B in a non-small cell lung cancer cell line.

The potentiation of anticancer agents by non-anticancer drugs is one of the possible strategies for overcoming cellular resistance to chemotherapy. In order to overcome cis-diamminedichloroplatinum(II) (CDDP) resistance, we evaluated the sensitizing effect on CDDP-induced cytotoxicity of various non-anticancer agents which might alter membrane transport, by means of a colorimetric [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay. Drugs which have previously been demonstrated to modify multidrug resistance did not show a sensitizing effect to cisplatin. Only amphotericin B (AmB) selectively conquered CDDP resistance in the CDDP-resistant cell line. A drug accumulation study done by the atomic absorption method demonstrated that the accumulation of CDDP in the resistant cell line recovered to the level of the parental cell line after treatment with AmB. Thus, AmB might overcome CDDP resistance by increasing the accumulation of CDDP.

Amphotericin B↗

PubMed1991

Morphological studies of the foramen caecum linguae of the human and guinea pig tongue.

A three-dimensional study of the development of the thyroid gland in human and guinea pig embryos was made together with a histological investigation of the foramen caecum of the human adult tongue. In the human embryo, an epithelial depression was not seen between the first and second branchial arches except a shallow sulcus. Ciliated cells were observed on the dorsal surface of the tongue in all embryos which exceeded 18 mm in crown-rump length. The presence of a foramen caecum was observed in 18 (51%) cadavers from 35 human adults. Several circumvallate papillae were found in a 10-mm-deep foramen caecum on the side adjacent to the anterior two thirds of the tongue. In all specimens serous glands open into the foramen caecum.

Animals↗

PubMed1991

Application of improved coupling assay method for peroxidase of diseased thyroids: report of three cases.

Recently we have developed an assay method for peroxidase-catalyzed coupling of iodotyronine residues of thyroglobulin, which is applicable to human diseased thyroid tissues. In the present study, the assay method as well as usual peroxidase assay methods were applied to thyroids of three patients (No. 1: familial goiter with impaired thyroglobulin synthesis, No. 2: mild chronic thyroiditis, No. 3: dyshormonogenetic goiter) who showed organification of iodine with high TSH levels and low thyroid hormone levels in sera. In general, these patients showed relatively high activities measured by guaiacol oxidation assay, iodide oxidation and coupling assay compared with those of control thyroids. Iodothyronine content in thyroglobulin was very low except thyroxine in No. 2. These results indicate that factors other than peroxidase may be responsible for the cause of the hypothyroid state. The coupling assay method used here is therefore useful for the detection of the 'coupling defect' in patients in a hypothyroid state.

Adolescent↗

PubMed1991

Methemoglobin formation by potassium ferrocyanide in the hemolysate of acatalasemic mice.

Increased methemoglobin (metHb) formation is harmful to the normal oxygen transport. There are some mechanisms to reduce metHb formation in the erythrocyte. In the present study, effect of catalase (EC 1.11.1.6) on metHb formation by potassium ferrocyanide was examined spectrophotometrically in the hemolysates of acatalasemic, homozygous hypocatalasemic and normal mice. MetHb formation in the hemolysate of acatalasemic mice was significantly higher than that of normal mice. The addition of catalase reduced the metHb level, while superoxide dismutase (SOD) had little effect on it. A negative intimate correlation was observed between the logarithm of catalase activity (PU/gHb) and the metHb level (%) in the hemolysate. 3-Amino-1,2,4-triazole (AT), a specific catalase inhibitor, significantly increased the formation of metHb. These results indicate that hydrogen peroxide is generated in the process of metHb formation by potassium ferrocyanide and that catalase inhibits the metHb formation by destroying the H2O2 produced.

Acatalasia↗

PubMed1991

The role of catalase in protecting erythrocytes against methemoglobin formation.

Some mechanisms to reduce methemoglobin (metHb) formation for the maintenance of normal oxygen transport have been proposed. To study the role of catalase (EC 1.11.1.6), metHb formation in the hemolysate of normal and Japanese acatalasemic human subjects were examined spectrophotometrically. Significantly increased level of metHb was induced by potassium ferrocyanide in the hemolysate of acatalasemic subject. The addition of catalase reduced the metHb formation, while 3-amino-1,2,4-triazole (AT), a specific inhibitor of catalase-H2O2 compound I, increased it. These results obtained from human subjects were well consistent with those from mice and suggested that catalase plays a role in protecting erythrocytes against metHb formation.

Amitrole↗

PubMed1991

Warthin's tumor as a hamartomatous dysplastic lesion: a histochemical and immunohistochemical study.

The etiology of Warthin's tumor was sought by histochemical and immunohistochemical methods using 7 surgically extirpated samples and normal salivary glands as a control for the epithelial component. All the samples exhibited a variety of amyloid deposition in the interfollicular area of the lymphoid component. The interfollicular lymphoid cells were both T-cells and cells of B-cell lineage with an almost 1 to 2 population ratio. Most antigen-positive B-cells were plasma cells that exhibited polyclonality of immunoglobulin. B-cells were also present in the lymphoid mantles and a few were found in the germinal centres. The epithelial component exhibited mucinous and proteinaceous fluid in the lumen and varied immunohistological reactions; being particularly positive to carcinoembryonic antigen, S-100 protein, and B-cell antigen; quite similar to that of normal salivary duct cells. The results suggest that Warthin's tumor may not be a hamartomatous neoplasm at all but a hamartomatous dysplastic lesion.

Adenolymphoma↗