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Biomedical subjects

T Horikoshi

Publications and source records attributed to T Horikoshi.

At least 127 records · Page 7Linked to original sources
PubMed1987

The cytochrome P-450-dependent hydroxylation of T-2 toxin in various animal species.

Gas-liquid chromatography was used to investigate the hepatic and intestinal metabolism of T-2 toxin, a cytotoxic and immunodepressive trichothecene produced by species of Fusarium. The hepatic S-9 and microsomal fractions of various species hydroxylated T-2 toxin to form 3'-hydroxy-T-2. HT-2 toxin, a deacetylated metabolite of T-2 toxin formed by reactions involving microsomal esterases, was also hydroxylated, to 3'-hydroxy HT-2 toxin. Experiments with inhibitors and inducers of the cytochrome P-450-dependent system revealed that these two hydroxylation reactions were catalysed by the cytochrome P-450-dependent monooxygenase system. Species comparisons using rats, mice, guinea-pigs, rabbits, pigs, cows and chickens showed that the rate of the hydroxylation reaction was highest in the hepatic microsomes of guinea-pigs, followed by mice. Chickens possessed a low activity both in the hydrolysis and hydroxylation reactions. No hydroxylated metabolites were produced by the intestinal microsomes of rabbits. These two hydroxylated metabolites were far less cytotoxic to Reuber hepatoma cells than the parent compound, T-2 toxin.

Animals↗
PubMed1987

Dysplastic melanocytic nevus. Electron-microscopic observation as a diagnostic tool.

Dysplastic melanocytic nevi (DMN) are distinctive cutaneous nevomelanocytic lesions that possess unique clinical and histopathological features. In our previous study, we showed that the fine structure of melanosomes in epidermal melanocytes of DMN are abnormal and reveal deranged melanogenesis. This study is an extension of our previous study and clarifies the fine structure of melanosomes in both epidermal melanocytes and keratinocytes with observations in an additional 10 cases of DMN with and without a marked mesenchymal response. We found that a poor mesenchymal response does not exclude fine structural abnormality of melanosomes in DMN; that abnormal melanosomes are manifested by a spherical shape with either fine granules or incompletely developed lamellae and/or both; that melanization occurs unevenly on the spherical granular and/or incompletely on the lamellar matrices; and that these abnormal melanosomes are transferred to keratinocytes before being completely melanized, and they reveal marked degradation. We suggest that the fine structural characterization of abnormal melanosomes is a new adjunct for histopathological diagnosis of DMN.

Dysplastic Nevus Syndrome↗
PubMed1987

Fluorescent dye monitoring of mitochondrial changes associated with malignant cell transformation.

The fluorescent dyes, rhodamine 6G and 123, which specifically stain mitochondria, were used to examine changes in mitochondria that follow malignant transformation. The spatial distribution and shapes of mitochondria differ in untransformed and malignant-transformed cells. In untransformed C3H/10T1/2 clone 8 cells, the mitochondria were distributed radially around the nucleus, and each had a fibrous shape. In chemically transformed MCA clone 16 cells, the mitochondria were distributed randomly in the cytoplasm, and each was shaped like a short rod. Another important mitochondrial change after malignant transformation was the change in the time course of fluorescence emission from the rhodamine present in the mitochondria. A slow increase in fluorescence, which was instantaneous at the time of excitation irradiation occurred in untransformed but not in transformed cells. This slow fluorescence emission, peculiar to untransformed cells was affected by proton ionophore but not by calcium ionophore treatment. The difference in the time courses of fluorescence emission for untransformed and transformed cells may reflect differences in the quenching of the dye fluorescence. The data reported provide evidence that mitochondria are affected by malignant cell transformation.

Animals↗
PubMed1987

Once-daily administration of famotidine for reflux esophagitis.

An open-labeled study of once-daily administration of 40 mg famotidine was conducted in 24 patients with endoscopically confirmed reflux esophagitis. The mean age of the patients was 62.8 years. Most had stage I or stage II esophagitis of 1 years' duration or less. After 4, 8, 12, and 16 weeks of treatment, endoscopically documented healing was reported in 50%, 75%, 82%, and 83% of patients, respectively. Among specific endoscopic findings documented at the start of the study there was clearing of white exudate in 83% of patients, and redness cleared in 50% of patients after 16 weeks of treatment. Symptomatic improvement was observed in 73% of patients after 2 weeks, and this increased to 81% and 85% after 4 and 8 weeks of treatment, respectively. Painful symptoms cleared within 2 weeks in 68% of patients, and this increased to 77% after 8 weeks of once-daily therapy. Famotidine was well tolerated. Historically, reflux esophagitis has not responded satisfactorily to drug treatment. The reported symptomatic response and the response documented by endoscopy after therapy with 40 mg famotidine once daily at bedtime are encouraging. Further studies should be conducted to define the role of famotidine in the treatment of reflux esophagitis.

Adolescent↗
PubMed1986

Induction of taurine responsiveness in Xenopus oocytes by messenger RNA from mouse brain.

A taurine response was induced in the surface membrane of the oocytes of Xenopus laevis by injection of the mRNA from the neonatal mouse brain, and the response was studied electrophysiologically. The permeability of mRNA-injected oocytes to chloride ions was increased by the application of taurine in a dose-dependent manner. The same oocyte also responded to GABA, but bicuculline suppressed only the GABA response. These results suggest a possibility that taurine could be a neurotransmitter of certain neurons as yet unknown in the central nervous system.

Animals↗
PubMed1986

A sensitive assay of GTP cyclohydrolase I activity in rat and human tissues using radioimmunoassay of neopterin.

A highly sensitive and simple assay for the activity of GTP cyclohydrolase I (EC 3.5.4.16) was established using a newly developed radioimmunoassay. D-erythro-7,8-Dihydroneopterin triphosphate formed from GTP by GTP cyclohydrolase I was oxidized by iodine and dephosphorylated by alkaline phosphatase to D-erythro-neopterin, and quantified by a radioimmunoassay for D-erythro-neopterin. This method was highly sensitive and required only 0.2 mg of rat liver tissues for the measurement of the activity. It was reproducible and can be applied for the simultaneous assay of many samples. The activity of GTP cyclohydrolase I was measured in several rat tissues. For example, the enzyme activity in rat striatum (n = 5) was 13.7 +/- 1.5 pmol/mg protein per hour (mean +/- SE), and agreed well with those obtained by high-performance liquid chromatography with fluorescence detection. The activity in the autopsy human brains (caudate nucleus) was measured by this new method for the first time. The activity in the caudate nucleus from parkinsonian patients (n = 6) was 0.82 +/- 0.56 pmol/mg protein per hour which was significantly lower than the control value, 4.22 +/- 0.43 pmol/mg protein per hour (n = 10).

Aminohydrolases↗
PubMed1986

Effect of oxygen on the growth of human epidermal keratinocytes.

We studied the growth of secondary cultures of neonatal human keratinocytes at oxygen concentrations between 1 and 89%. Keratinocytes were grown in MCDB medium with 5% fetal bovine serum, 10 ng/ml epidermal growth factor, 5 micrograms/ml insulin, 0.5 microgram/ml hydrocortisone, and 0.1 mM ethanolamine and phosphorylethanolamine. Medium in the flasks was equilibrated with gas mixtures containing 5% CO2, various percentages of oxygen from 0-95% and nitrogen to balance. Cells were seeded at 10(4) cells/cm2 in sealed flasks (25 cm2). These were incubated at 37 degrees C in incubators maintained at the experimental oxygen tensions. Cells grew best at PO2 (partial pressure of oxygen) 133 mm Hg (18% O2), with a mean population doubling time of 2.8 days. Growth was retarded by 60% at PO2 38 mm Hg (5% O2) and by 98% at PO2 7 mm Hg (1% O2). However, the oxygen tension that resulted in the best plating efficiency was at PO2 12 mm Hg (2% O2). When oxygen tensions were shifted to 78-133 mm Hg, cells seeded under low oxygen tensions began to proliferate. These data suggest that a better harvest of keratinocytes is obtained when cells are seeded under low oxygen tension and then shifted to ambient oxygen tensions. At high oxygen tensions, above 20%, growth was inhibited by 75% at PO2 241 mm Hg (34% O2) and 98% at PO2 374 mm Hg (52% O2). At PO2 637 mm Hg (89% O2) no cell growth occurred. These findings showed that high oxygen tensions, above 20%, have no beneficial effect on the growth of keratinocytes.

Cell Adhesion↗
PubMed1986

Plasminogen activator secreted by cultured human melanocytes.

A plasminogen activator (PA), Mr 72,000, was detected in conditioned medium from human melanocyte cultures by fibrin autography. The electrophoretic mobility was identical to that of tissue PA produced by Bowes melanoma cells. PA activity in human melanocyte culture medium was inhibited by anti-tissue PA IgG, but not by anti-urokinase IgG. Our results are the first to show that normal human melanocytes in culture secrete tissue plasminogen activator.

Cells, Cultured↗
PubMed1986

[Effects of cisapride on lower esophageal sphincter pressure and gastroduodenal motor activity in man].

Manometric study was performed to investigate the effects of cisapride, a new non-antidopaminergic gastrointestinal prokinetic compound, on interdigestive lower esophageal sphincter pressure (LESP) and gastroduodenal motility using infused catheter technique. The subjects consisted of 9 healthy volunteers and 29 patients with progressive systemic sclerosis (19), reflux esophagitis (8) and others (2). 4 mg of cisapride was given by bolus injection, continuous infusion or oral administration. The following results were obtained: Intravenous and oral cisapride increased LESP compared with basal pressure. Especially, bolus injection of cisapride caused a significant elevation of LESP during 30 minutes after administration. After administration of cisapride, gastroduodenal motility was accelerated gradually, then inducing IMC-like contractions. By bolus injection, IMC-like contractions were induced in healthy subjects more frequently than in patients group. On the other hand, motility index of stomach and duodenum showed persistent increase in patients group compared with healthy subjects. Cisapride-induced IMC-like contractions initiated from LES and upper part of stomach and mediated to duodenum, though aborad migration was not confirmed in the present study.

Adolescent↗
PubMed1985

Fine structural characterization of melanosomes in dysplastic nevi.

This study characterized the fine structure of melanosomes in melanocytes of the dysplastic nevi in six cases with lentiginous melanocytic dysplasia and one case with epithelioid-cell melanocytic dysplasia, and compared that structure with those of common melanocytic nevi and malignant melanoma. It was found that: fine structural features of melanosomes in dysplastic melanocytes were similar in these two histologic variants, and they were markedly aberrant and quite different from those of common melanocytic nevi; the aberrant melanosomes could be grouped into four subtypes, type 1 melanosomes corresponding to ellipsoidal-lamellar melanosomes, type 2 to spherical-incompletely lamellar melanosomes, type 3 to spherical-granular melanosomes, and type 4 to spherical-vacuolated melanosomes; type 2, 3, and 4 melanosomes were seen in all seven cases although their substructures and numbers varied in individual cases; and these type 2, 3, and 4 melanosomes were not seen in epidermal melanocytes of common melanocytic nevi, but were characteristically seen in superficial spreading melanoma and nodular melanoma. The findings indicated that the fine structural changes in synthesis and melanization of melanosomes are unique to the dysplastic nevi and that they may be helpful in diagnosis of the nevi and may fill the gap of abnormal melanogenesis that exists between common melanocytic nevi and malignant melanoma.

Adult↗
PubMed1985

Purification and in vitro growth of human epidermal basal keratinocytes using a monoclonal antibody.

We have made a new monoclonal antibody, EL-2, and used it with an immunorosetting procedure combined with Ficoll-Hypaque gradient centrifugation to purify and culture basal keratinocytes. Immunofluorescence of cell suspensions and immunoperoxidase staining of tissue sections demonstrate that EL-2 reacts with malignant cell lines, activated lymphocytes and monocytes, and basal keratinocytes. Sequential immunoprecipitation studies demonstrate that monoclonal antibodies EL-2 and 4F2 detect the same membrane protein. However, we have extended previous studies by making the new observation that both EL-2 and 4F2 react with cultured melanocytes. Basal keratinocytes were purified from single-cell epidermal suspensions by incubation with EL-2 followed by rosetting with rabbit antimouse IgG antibodies covalently linked to bovine red blood cells. Rosetting (basal) keratinocytes were separated from EL-2 negative cells by Ficoll gradient centrifugation. We obtained basal keratinocyte populations of greater than 90% purity as assessed by reactivity with EL-2 and another basal keratinocyte-specific monoclonal antibody, HCl. Langerhans cell, fibroblast, and melanocyte contamination was negligible. Cultures of basal keratinocytes were enriched in EL-2-reactive cells throughout the entire 19 days of culture studied. EL-2 is being used to characterize disorders of keratinocyte proliferation; EL-2 reacted with both squamous and basal cell carcinomas. EL-2 stained only the basal layer of lesional skin from patients with psoriasis, pityriasis rubra pilaris, and Darier's disease. Purification of basal keratinocytes will be important in biochemical and functional studies of normal skin and in establishing long-term keratinocyte lines from normal cells.

Antibodies, Monoclonal↗