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Biomedical subjects

T Hirota

Publications and source records attributed to T Hirota.

At least 217 records · Page 12Linked to original sources
PubMed1987

Malignant transformation of gastric hyperplastic polyps.

Four hundred and seventy-seven hyperplastic polyps, removed by endoscopic polypectomy, were reviewed with special reference to the appearance of dysplastic foci and their malignant transformation. Focal carcinomas were found in 10 hyperplastic polyps, which corresponded to 2.1% of the total of 477 hyperplastic polyps. The location of cancer was at the head or at the surface of the polyp, and was intramucosal. Dysplastic foci equivalent in the degree of histological atypia to adenoma were found adjacent to the cancerous foci in these 10 polyps. Dysplastic foci were also found in 19 hyperplastic polyps without cancerous foci, which corresponded to 4.0% of the total hyperplastic polyps. In connection with the histogenesis of malignant transformation of hyperplastic polyps, the results of clinicopathological examination and immunohistochemical stains strongly suggested that cancer cells arose from the dysplastic area in hyperplastic polyps, rather than directly from nondysplastic hyperplastic epithelium.

Adenocarcinoma↗
PubMed1986

Characterization of dehydropeptidase I in the rat lung.

The activity of dehydropeptidase I in rat tissues decreases in the order of lung greater than kidney greater than liver-spleen greater than other tissues, while aminopeptidase activity is high in the kidney, and lower in the lung than in other tissues. Dehydropeptidase I was solubilized from the membrane fraction of rat lung by treatment with papain and purified by DEAE-cellulose column chromatography, affinity chromatography on concanavalin-A-Sepharose and high-performance liquid chromatography gel filtration. The purified preparation was found to be homogeneous on sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The relative molecular mass was estimated to be 150,000 by gel filtration, comprising a homodimer of two 80,000-Mr subunits. The enzyme activity was inhibited by cilastatin, o-phenanthroline and ATP. This enzyme catalyzed the hydrolysis of S(substituent)-L-cysteinyl-glycine adducts such as L-cystinyl-bis(glycine) and N-ethylmaleimide-S-L-cysteinyl-glycine, as well as the conversion of leukotriene D4 to E4. Furthermore it catalyzed a hydrolytic splitting of L-Leu-L-Leu, but not S-benzyl-L-cysteine p-nitroanilide, which is a good substrate for aminopeptidase. Our enzyme preparation was immunologically identical to the rat renal dehydropeptidase I. The physiological significance of the pulmonary dehydropeptidase I on the metabolism of glutathione and its adducts is discussed.

Animals↗
PubMed1986

The intramucosal cysts of the stomach. VII: A pathway of gastric carcinogenesis?

Gastric specimens from 259 patients (69 Swedish and 190 Japanese) were examined for the presence of intramucosal cysts. The number of cysts for each centimeter of mucosa analyzed (cystic index) was calculated. The material included 153 patients with peptic gastric ulcer, 41 with elevated dysplasias, and 65 with early gastric cancer. The results demonstrated that in the Japanese material, the normal-looking gastric mucosa adjacent to a variety of gastric lesions such as gastric peptic ulcer, focal elevated dysplasias, or incipient adenocarcinomas, had a significantly higher cyst index than the gastric mucosa adjacent to similar lesions in Swedish patients. At this point, it should be stressed that the Japanese have a high incidence of gastric cancer (82/100,000 males) while the Swedish have a relatively low incidence (28/100,000 males). The results presented herein appear to suggest that cystic formation in the gastric mucosa may herald an early neoplastic growth at the luminal aspect in some of the cysts.

Adenocarcinoma↗
PubMed1986

Gonadotropin release and redistribution of calcium-activated, phospholipid-dependent protein kinase in phorbol-stimulated rat pituitary cells.

The effect of phorbol esters on calcium-activated, phospholipid-dependent kinase (protein kinase C) and luteinizing hormone (LH) secretion was examined in cultured rat anterior pituitary cells. The potent tumor promoter 12-O-tetra-decanoylphorbol-13-acetate (TPA) stimulated LH secretion and activated pituitary protein kinase C in the presence of calcium and phosphatidylserine. The enzyme activity present in cytosol and particulate fractions was eluted at about 0.05 M NaCl during DE52-cellulose chromatography. Preincubation of pituitary cells with TPA markedly decreased cytosolic protein kinase C activity and increased enzyme activity in the particulate fraction. The maximal TPA-induced change in enzyme activity, with a 76% decrease in cytosol and a 4.3-fold increase in the particulate fraction, occurred within 10 min. The dose-dependent changes in protein kinase C redistribution in TPA-treated cells were correlated with the stimulation of LH release by the phorbol ester. These results suggest that activation of protein kinase C by TPA is associated with intracellular redistribution of the enzyme and is related to the process of secretory granule release from gonadotrophs.

Animals↗
PubMed1986

A case of advanced gastric cancer with long-term survival as the results of combined radiation therapy and chemotherapy.

A case report on a long-term surviving patient with advanced gastric cancer with supraclavicular lymph node metastasis treated by radiation and chemotherapy is presented. The Borrman type 2 of advanced gastric cancer was found on the greater curvature of the antrum at the first radiological examination. Radiation was administered to the supraclavicular lymph node at 60 Gy and to the stomach at 64 Gy. The patient received mitomycin C (24 mg) and Tegafur (230 g). After completion of the combined therapy the endoscopy revealed an irregular mucosal change with erosion and hemorrhage. Radiological examination revealed atrophic and hyperplastic areas throughout the stomach. These findings lasted more than six years. The patient died of unknown cause in February 1983. She had survived nine years and seven months after her initial diagnosis. Radiotherapy may play a role as a means of radical treatment in certain cases of advanced gastric cancer.

Aged↗
PubMed1986

[Immunohistochemical study of oncogene-related products in human gastrointestinal malignancies--expression of ras p 21, fes p 85 and EGF receptor].

An immunohistochemical examination by the avidin-biotin-peroxidase complex method was carried out to assess the expression of oncogene-related products, i.e., ras p 21 protein, fes p 85 protein and epidermal-growth-factor (EGF) receptors, in human gastrointestinal malignancies. The presence of ras p 21, fes p 85 and EGF receptors was detected in 48%, 62%, and 62% of 29 colorectal carcinomas and in 65%, 65% and 40% of 20 gastric cancers, respectively. More than one oncogene protein was demonstrated in 18 of 29 colorectal carcinomas and in 10 of 20 gastric cancers. These results suggest that multiple oncogenes are important in the occurrence and progress of gastrointestinal malignancies.

Colonic Neoplasms↗
PubMed1986

[A case report of neoplastic aneurysm due to metastatic choriocarcinoma].

A twenty-year-old female, who had multi-agent chemotherapy for eighteen months after surgical resection of a choriocarcinoma originating from the left adnexa, was hospitalized because of a cerebrovascular accident. Her complaints were unconsciousness, generalized convulsion and left hemiparesis. Although both plain and contrast enhanced CT scans demonstrated only acute subdural hematoma in the right frontoparietal region associated with midline shift, no tumor shadow was recognized over the cortex or intraparenchymally. A carotid angiogram revealed a large and irregularly shaped aneurysm at a peripheral branching of the angular artery. Evacuation of the hematoma, resection of the aneurysm and revascularization for the defect of the parent artery by transplantation of a part of STA by means of microsurgical anastomosis were done at an emergency operation. Nevertheless the graft did not prove to be patent on the post-operative angiogram. Due to retrograde filling of the distal portion of the angular artery through collateral channels, the patient has been completely free of neurological deficit and her performance of daily activities has been excellent. No appearance of other intracranial metastasis of the tumor has been detected for six months thereafter. Histological examination of the resected aneurysm demonstrated that choriocarcinoma composed of cytotrophoblasts and syncitiotrophoblasts filled the lumen of the aneurysm. The van Gieson's staining clarified the invasion of the tumor into the vascular wall causing disruption of lamina elastica beneath the fairly intact adventitia. Microscopic findings of the specimens taken from adjacent brain tissue and overlying dura mater confirmed absence of metastatic lesion in them.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Physicochemical characterization of a new glucocorticoid receptor.

A new glucocorticoid-binding protein (Peak C) eluted with 0.14 M NaCl on DEAE-cellulose chromatography was identified previously in the rats subjected to stress or treated with glucocorticoid (100 micrograms/100 g body wt.), while the 'classic' glucocorticoid receptor (Peak B) eluted with 0.07 M NaCl was found predominantly in untreated rats. The new glucocorticoid-binding protein, Peak C, was characterized by Scatchard analysis and competition with other steroids as a glucocorticoid receptor. The saturation curve of Peak C for dexamethasone was sigmoidal, whereas that of Peak B was hyperbolic. The Hill coefficient was 1.0 for Peak B and 3.1 for Peak C. These results show that Peak C has multiple binding sites. Peak C bound specifically to only natural or synthetic glucocorticoids, whereas Peak B bound not only to glucocorticoids but also to progesterone and aldosterone. Peak C was far more labile than Peak B, its binding activity decreasing 80% when it was incubated for 30 min at 25 degrees C. The molecular sizes of these two peaks (B and C) were similar, being about 90 000-100 000 as determined by Sepharose 6B column chromatography at high ionic strength (0.34 M KCl). The hormone-receptor complex of Peak C bound to rat liver chromatin specifically, but did not bind to calf thymus DNA. The complex of Peak B bound to not only the chromatin but also calf thymus DNA. Peak B reacted well with antiserum to the 'classic' glucocorticoid receptor, but Peak C did not react with this antiserum. These results indicate that Peak C is a different glucocorticoid receptor protein from Peak B, or classic glucocorticoid receptor, and plays physiologically important roles as a glucocorticoid receptor mediating the action of the hormone at a high level.

Animals↗
PubMed1985

Precocious induction of tryptophan dioxygenase by glucocorticoid in suckling rats and correlation with change in glucocorticoid receptor.

When young rats (less than 14 days old) were treated once a day for 2 days with 100 micrograms/100 g body weight of dexamethasone, their liver cytosol showed a sharp new peak of glucocorticoid binding protein (peak C) eluted with 0.14 M NaCl on DEAE-cellulose chromatography. When the young rats were given a single injection of the hormone, the chromatogram showed a dominant peak of binding protein (peak B), eluted with 0.07 M NaCl, which was similar to that in untreated rats. The appearance of peak C on two treatments of young rats with hormone was confirmed by both in vivo and in vitro labeling and also studies on the nuclear fraction. Peaks B and C were specific hormone-binding proteins as shown with excess unlabeled hormone. The appearance of peak C was concomitant with the precocious induction of tryptophan dioxygenase in the liver of the young rats, and pretreatment with two injections of dexamethasone were necessary for maximal enzyme induction. On the other hand, in adult rats a single injection of dexamethasone (of 20 micrograms/100 g body weight or more) was enough to cause the appearance of peak C and induce tryptophan dioxygenase activity maximally; an additional injection of the hormone did not change the chromatographic pattern of the specific binding or the enzyme activity. For this effect in young rats, dexamethasone could not be replaced by other hormones such as glucagon, growth hormone, thyroid hormones, insulin, sex steroids or short-acting glucocorticoid.

Aging↗
PubMed1985

Hormone-induced redistribution of calcium-activated phospholipid-dependent protein kinase in pituitary gonadotrophs.

The distribution of calcium-activated, phospholipid-dependent protein kinase (protein kinase C) between cytosol and membrane fractions was analyzed in cultured pituitary gonadotrophs during treatment with gonadotropin-releasing hormone (GnRH). In pituitary cells purified by centrifugal elutriation, the extent of protein kinase C redistribution during GnRH stimulation was correlated with the enrichment of gonadotrophs. GnRH-stimulated release of luteinizing hormone (LH) from gonadotroph-enriched cells was accompanied by a rapid and dose-dependent decrease in cytosolic protein kinase C and by a corresponding increase in protein kinase C activity in the particulate fraction. Retinal directly inhibited the activity of cytosolic protein kinase C and also attenuated the release of LH from GnRH-stimulated gonadotrophs. These findings, and the ability of GnRH to cause rapid translocation of cytosolic protein kinase C to a membrane-associated form, suggest that hormonal activation of protein kinase C is an intermediate step in the stimulation of pituitary LH secretion by GnRH.

Animals↗
PubMed1985

A two-molecule mechanism of haem degradation.

Coupled oxidation of octaethylhaemin and phenylhydrazine hydrochloride with 16,16O2 and 18,18O2 produced octaethyl[16O]verdohaemochrome and octaethyl[18O]-verdohaemochrome respectively. Reactions of these products with 16,16O2 in the presence of phenylhydrazine hydrochloride yielded octaethyl[16O, 16O]biliverdin and octaethyl[18O, 16O]biliverdin. The same reactions with 18,18O2 yielded octaethyl[16O, 18O]biliverdin and octaethyl[18O, 18O]biliverdin. Accordingly, the two oxygen atoms of biliverdin are incorporated from different O2 molecules in separate reactions, namely the formation of verdohaemochrome and the conversion of verdohaemochrome into biliverdin. These reactions account for a "two-molecule mechanism' of biliverdin formation from haem with verdohaemochrome participating as an intermediate product.

Bile Pigments↗
PubMed1985

Atypical mitoses in elevated dysplasias of the stomach.

The number and topographic localization of spontaneously occurring mitotic figures were studied in 22 elevated dysplasias of the stomach. The lesions were divided into 3 equally thick zones. Mitoses occurred in 5 of 7 slight dysplasias, in 7 of 8 moderate dysplasias, and in all 7 severe dysplasias. When present, mitoses were localized to the superficial zone in slight, moderate and severe dysplasias, in the middle zone in some moderate dysplasias, and in almost all severe dysplasias. In the deeper zone, mitoses were seen in one of the moderate dysplasias and in as much as 5 of the severe dysplasias. The number of mitoses were significantly higher in moderate and severe dysplasia, when compared to slight dysplasia. The percentage of atypical mitoses increased gradually from 27% in slight dysplasia to 41% in moderate, and 52% in severe dysplasias. In the adjacent, non-dysplastic gastric mucosa, a 1.5% of atypical mitoses was found. Significantly higher amounts of atypical mitoses were recorded in severe dysplasias, as compared to slight and moderate dysplasias. The results suggest that the various types of elevated dysplasias (slight, moderate and severe) of the stomach may be distinguished, not only by the characteristics of the atypical cells in interphase--as is the case today--but also by the topographic distribution of mitoses and by the difference in percentage of atypical mitoses occurring in these lesions. The possible significance of the mitosis as a biohistological marker of the behaviour of elevated dysplasias of the stomach is discussed.

Biopsy↗
PubMed1985

Appearance of new hepatic glucocorticoid binding proteins under various stressful conditions: relation to endogenous glucocorticoid secretion.

When rats were subjected to the stress of burns, tumors, or partial hepatectomy, a notable new peak of glucocorticoid binding protein appeared on DEAE-cellulose chromatography. This peak accompanied the original peak, which was the only dominant peak in intact rats. The appearance of the new binding protein was concomitant with a high rise in serum corticosterone levels. The new peak was eluted with 0.12-0.14 M NaCl and another, small new peak with 0.02-0.03 M NaCl, while the original peak of intact rats was eluted with 0.05-0.08 M NaCl. In rats adrenalectomized prior to the stress, the new peaks did not appear. To mimic these stressful conditions which provoked a burst of endogenous glucocorticoid, rats were administered with an exogenous high dose of dexamethasone (100 micrograms/100 g B.W.) in vivo. The new peak eluted with 0.12-0.14 M NaCl was again observed and was more dominant in the hormone-treated rats than the stressed rats. These three peaks eluted with 0.02-0.03 M, 0.05-0.08 M, and 0.12-0.14 M NaCl are called here Peak A, B, and C, respectively. This is the first demonstration of the effect of physiological changes in serum levels of glucocorticoid hormone on the nature of glucocorticoid binding protein by DEAE-cellulose chromatography.

Adrenalectomy↗
PubMed1985

Conversion of estrogen receptor from a state with low affinity for estradiol into a state of higher affinity does not require 4S to 5S dimerization.

This study was undertaken to establish whether the heat-promoted conversion of receptor-estradiol complex (RE2) from a state with fast into a state with slow E2 dissociation requires 8S/4S to 5S transformation. The calf uterine estrogen receptor labeled with [3H]E2 at 0 C (state with low affinity for E2) was immobilized on hydroxylapatite (HAP) in the absence (8S oligomer) or presence (4S monomer) of 0.4 M KCl and heated at 28 C in the presence of unlabeled diethylstilbestrol. Under these conditions, the dissociation of [3H]E2 was biphasic and occurred at rates similar to those obtained with R[3H]E2 free in cytosol. In contrast to the latter, however, the heat-promoted conversion of HAP-immobilized R[3H]E2 into a state of higher affinity for E2 was not accompanied by receptor dimerization, since the HAP eluate (0.4 M phosphate buffer) contained only the 4S monomer; upon reheating or desalting of this eluate, 4S to 5S dimerization occurred. The heat-promoted formation of 4S RE2 monomers with higher affinity for E2 was not due to monomer-HAP interactions, since even after elution from HAP, the 4S RE2 remained in the state of higher affinity for E2. Addition of pyridoxal 5'-phosphate to slow dissociating, high affinity 5S R[3H]E2 dimers free in cytosol induced rapid [3H]E2 dissociation, although the receptor remained unaltered in the transformed dimerized state. The effect of PLP was readily reversed by the addition of lysine. It is proposed that the 4S receptor monomers exist in two conformational states; upon E2 binding to the low affinity state, conformational changes result in stronger interactions between the steroid and the amino acid residues of the estrogen-binding domain; thus, the rate of E2 dissociation decreases. The formation of this 4S RE2 state with higher affinity for E2 is independent from receptor dimerization. A model is presented in which 4S to 5S transformation may lead to stabilization of 4S monomers in the conformation with higher affinity for E2.

Animals↗