Biomedical subjects

K Hashimoto

Publications and source records attributed to K Hashimoto.

At least 19 recordsLinked to original sources

PubMed1992

Activation of phospholipases in platelets by polyclonal antibodies against a surface membrane protein.

In a previous paper we demonstrated using immunochemical techniques that propolypeptide of von Willebrand factor was present on the surface of resting platelets. In the present paper we show that polyclonal antibodies against propolypeptide of von Willebrand factor induce activation of phospholipase(s) in platelets and lead to platelet aggregation. The antibody-stimulation of platelets induced the synthesis of thromboxane A2 (TXA2). Furthermore, the aggregation was inhibited by aspirin and an antagonist of TXA2. Aspirin inhibited not only the aggregation but also the activation of arachidonic acid liberation from phospholipids, but the effect of aspirin on arachidonic acid liberation was cancelled by the combined effect of the antibodies and a TXA2 mimetic agonist, which itself did not activate arachidonic acid liberation. The antibody-induced activation of arachidonic acid liberation and the aggregation were blocked by cytochalasin B. All these results obtained with antibodies were quite similar to the results obtained with collagen.

Antibodies↗

PubMed1992

[Hyperresponsiveness of TSH and prolactin and impaired responsiveness of GH in Japanese patients with isolated ACTH deficiency].

Two hundred and forty-one cases of isolated ACTH deficiency have been reported in Japan since 1969. Pituitary hormone responsiveness to stimulation tests before and after hydrocortisone supplementation was investigated in these cases. Plasma ACTH level showed no or little change in response to lysine vasopressin, metyrapone, CRF or insulin-induced hypoglycemia in 97.3-100% of the cases. Serum GH level changed little or not at all in response to GRF, insulin-induced hypoglycemia, glucagon, 1-dopa and arginine in 26.9, 29.3, 40.0, 50.0 and 56.1%, respectively. Serum TSH and prolactin (PRL) levels showed hyperresponse to TRH in 34.7 and 35.6%, respectively. After hydrocortisone therapy, GH secretion was more responsive than before therapy in 78.9% of the cases. After supplementation, TSH level was less responsive to TRH stimulation than before therapy in 59.3% of the cases. After hydrocortisone supplementation, TSH response to TRH decreased in 75% of ACTH-deficient patients without primary hypothyroidism but did not decrease in more than half of those with primary hypothyroidism. TSH response to TRH decreased after supplementation in 76.5% of the patients with TSH hyperresponsiveness before therapy, and increased after therapy in 66.7% of those with normal TSH responses before therapy. After supplementation, PRL response to TRH was less than that before therapy in 43.5% of ACTH--deficient patients, and greater than that before therapy in 30.4%. PRL response to TRH decreased after therapy in 66.7% of the patients with PRL hyperresponsiveness before therapy, and increased in 63.6% of those with normal PRL response before therapy. Primary hypothyroidism and Hashimoto's thyroiditis were complicated in 21.6 and 11.6%, respectively, of the 241 patients with isolated ACTH deficiency. In patients who had TSH hyperresponsiveness and/or high basal TSH levels and PRL hyperresponsiveness and/or high basal PRL levels, primary hypothyroidism was complicated in 58.4 and 42.3%, respectively. Hashimoto's thyroiditis was complicated in 29.8 and 20.5%, respectively, of these patients. Pituitary cell antibody (PCA) was detected in 36.6% of ACTH-deficient patients who were examined. Pituitary cell surface antibody (PCSA) to AtT-20 cells and GH3 cells was detected in 50.0 and 28.0% of the examined cases, respectively. The prevalence of PCA and PCSA did not differ between TSH-hyperresponsive patients and those with normal TSH basal levels and response, whereas PCA and PCSA were significantly more prevalent in PRL-hyperresponsive patients than in those with normal PRL levels and response. An empty sella was found in 30.2% of the examined case.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticotropic Hormone↗

PubMed1992

Effects of benzylpiperazine derivatives on the neurotoxicity of 3,4-methylenedioxymethamphetamine in rat brain.

The neurotoxicity of 3,4-methylenedioxymethamphetamine (MDMA) in rat brain was attenuated significantly by coadministration of several benzylpiperazines (p-nitrobenzylpiperazine, p-chlorobenzylpiperazine and 1-piperonylpiperazine), which were weak inhibitors for [3H]6-nitroquipazine binding to the 5-hydroxytryptamine (5-HT) transporter in rat brain. These results suggest that these benzylpiperazines may inhibit the MDMA-induced neurotoxicity by a novel neuropharmacological effect other than 5-HT uptake inhibition.

3,4-Methylenedioxyamphetamine↗

PubMed1992

Antagonism of 3,4-methylenedioxymethamphetamine-induced neurotoxicity in rat brain by 1-piperonylpiperazine.

The effects of 1-piperonylpiperazine and N,alpha-dimethylpiperonylamine, which are weak inhibitors for [3H]5-hydroxytryptamine (5-HT) uptake, on 3,4-methylenedioxymethamphetamine (MDMA)-induced neurotoxicity were examined. The reductions of serotonergic parameters in the rat cerebral cortex produced by multiple administration of MDMA (10 mg/kg) were attenuated significantly by coadministration of 6-nitroquipazine (10 mg/kg), paroxetine (10 mg/kg) or 1-piperonylpiperazine (20 mg/kg), but not by N,alpha-dimethylpiperonylamine (20 mg/kg). The present data suggest that 1-piperonylpiperazine might inhibit the MDMA-induced neurotoxicity by effect(s) other than 5-HT uptake inhibition.

3,4-Methylenedioxyamphetamine↗

PubMed1992

The magnocellular arginine-vasopressin mRNA responds differently to food deprivation between the supraoptic and paraventricular nuclei of the hypothalamus in adrenalectomized rats with low corticosterone replacement.

We previously reported that food deprivation significantly decreased arginine-vasopressin (AVP) mRNA levels in the supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamus and also greatly stimulated the pituitary-adrenocortical system in rats. In this study, we deprived adrenalectomized rats with subcutaneously implanted low-dose corticosterone pellets (ADX + B) of food for 3 days to investigate the involvement of corticosteroid feedback regulation in the food deprivation-induced decrease in AVP mRNA in both the SON and the PVN. The plasma corticosterone levels in these animals were maintained at low levels constantly over 24 h. The ACTH concentration in the morning plasma was markedly increased in the food-deprived ADX + B rats as compared to the fed ADX + B rats. Food deprivation significantly decreased the corticotropin-releasing hormone (CRH) content in the median eminence and increased the CRH and AVP content in the neurointermediate lobe of the pituitary. Semiquantitative in situ hybridization histochemistry revealed that AVP mRNA levels were decreased in the SON but, inversely, increased in magnocellular as well as parvocellular subdivisions of the PVN following food deprivation. These results suggest that: (1) AVP mRNA responds differently to food deprivation between the SON and the PVN; (2) the glucocorticoid feedback can exert on AVP mRNA in the PVN but not in the SON in the food-deprived rats; and (3) food deprivation affects the neurohypophysial levels of CRH and AVP.

Adrenalectomy↗

PubMed1992

Induction of cytotoxicity by photoexcited TiO2 particles.

Photoexcited TiO2 particles can drive various chemical reactions due to their strong oxidizing and reducing ability. To investigate the possible use of this effect for cancer treatment, the antitumor activity of photoexcited TiO2 particles was studied in vitro and in vivo. HeLa cells cultured in vitro were completely killed in the presence of TiO2 (50 micrograms/ml) with 10-min UV irradiation by a 500-W-Hg lamp. In contrast, very little cell death was observed from TiO2 treatment without UV irradiation. Photoexcited TiO2 particles also significantly suppressed the growth of HeLa cells implanted in nude mice, compared with those receiving TiO2 alone or UV irradiation alone. The cell death caused by photoexcited TiO2 particles was significantly protected in the presence of L-tryptophan and catalase. These molecules are quenchers of hydroxyl radicals and scavengers of hydrogen peroxide, respectively, suggesting that the cells were killed by the OH. and H2O2 produced from photoexcited TiO2 particles.

Animals↗

PubMed1992

Changes in cerebral energy metabolism and calcium levels in relation to delayed neuronal death after ischemia.

Using a brief transient ischemic model, we examined changes in regional tissue calcium content and energy metabolism in the hippocampus. In the CA1 region, tissue calcium ions began to increase 24 h after reperfusion, accompanied by changes in tissue pH and ATP. In the CA3 region, energy metabolism remained unchanged for 72 h after reperfusion, and the calcium pool was first noted 24 h after reperfusion, while tissue calcium ions began to increase 48 h after reperfusion. These results suggest that the neurons in the CA3 region seem to survive because of the well-preserved metabolic function to cope with excessive calcium ions.

Adenosine Triphosphate↗

PubMed1992

Identification of a shark sequence resembling the major histocompatibility complex class I alpha 3 domain.

Elasmobranchs (sharks and rays) branched off from the vertebrate line leading to the mammals more than 400 million years ago. They do not exhibit acute allograft rejection, and so far no report has pointed to the presence of major histocompatibility complex (MHC) antigen-like molecules in elasmobranchs. Here we demonstrate the existence of a gene in the shark (Triakis scyllia) genome with a sequence that resembles the MHC class I alpha 3 domains of other vertebrates. Several amino acids considered to be important for the interaction of the T-cell coreceptor CD8 with the MHC class I alpha 3 domain are conserved in the shark sequence.

Amino Acid Sequence↗

PubMed1992

Epidermal cell differentiation inhibitor ADP-ribosylates small GTP-binding proteins and induces hyperplasia of epidermis.

Epidermal cell differentiation inhibitor (EDIN) is a recently discovered protein which inhibits terminal differentiation of cultured keratinocytes (Sugai, M., Enomoto, T., Hashimoto, K., Matsumoto, K., Matsuo, Y., Ohgai, H., Hong, Y.-M., Inoue, S., Yoshikawa, K., and Suginaka, H. (1990) Biochem. Biophys. Res. Commun. 173, 92-98). The amino acid sequenced deduced from the EDIN gene has revealed that EDIN shares high amino acid sequence homology with the exoenzyme C3 of Clostridium botulinum (Inoue, S., Sugai, M., Murooka, Y., Paik, S.-Y., Hong, Y.-M., Ohgai, H., and Suginaka, H. (1991) Biochem. Biophys. Res. Commun. 174, 459-464), which has been shown to ADP-ribosylate the rho/rac proteins (members of the small GTP-binding protein family). We show here that EDIN ADP-ribosylates rhoB p21 in time- and dose-dependent manners in a cell-free system. Kinetic studies of the ADP-ribosylation and peptide mapping of the reaction products of rhoB p21 by EDIN and C3 suggest that the mode of action of the ADP-ribosylation by EDIN is quite similar to that by C3 and that the ADP-ribosylation site of rhoB p21 by EDIN is presumably the same as that by C3. Proteins in epidermal membranes and keratinocyte homogenate with Mr values of about 22,000 are ADP-ribosylated by EDIN or C3. Treatment of cultured human keratinocytes by EDIN or C3 results in an inhibition of terminal differentiation and a stimulation of growth of the cells. Moreover, EDIN and C3 injected into adult mouse skin induce hyperplasia of epidermis. These results suggest that EDIN and C3 affect growth and differentiation of keratinocytes by ADP-ribosylation of protein(s) with a Mr of about 22,000, which may be the rho/rac proteins or related proteins.

Adenosine Diphosphate Ribose↗

PubMed1992

Pathogenesis of pancreatic perilobular necrosis in patients with liver disease.

We often see perilobular necrosis of the pancreas in patients with liver disease at autopsy. This study was undertaken to determine the frequency and the mechanism of development of pancreatic perilobular necrosis in patients with liver disease. Pancreatic perilobular necrosis was seen in 21 per cent of 261 autopsied patients: in 41 per cent of 73 autopsied patients with liver disease and in 13 per cent of 188 autopsied patients without liver disease. Moreover, splanchnic congestion was present in 90 per cent of 30 pancreatic perilobular necrosis patients with liver disease. These data indicate that patients with liver disease develop perilobular necrosis of the pancreas more often than patients without liver disease, and that the high frequency may be a sequela of splanchnic congestion; that is, congestion of the pancreas and endotoxaemia due to congestion of the gut.

Adolescent↗

PubMed1992

Immunohistochemical study of kuru plaques using antibodies against synthetic prion protein peptides.

Prion protein (PrP) is a protein closely associated with the transmission of scrapie and Creutzfeldt-Jakob disease (CJD). Kuru plaques are composed of this protein. PrP33-35 is converted to protease-resistant PrP27-30 by proteinase K digestion. It has not yet been determined which of these PrPs is present in kuru plaques in vivo. Accordingly we synthesized two peptides (peptide-N and peptide-M) that, respectively, corresponded to the protease-sensitive and protease-resistant portions of PrP33-35, based on the amino acid sequence deduced from human PrP cDNA. These two synthetic peptides were used to immunize rabbits and produce antisera (anti-N and anti-M). Both antisera stained kuru plaques in a patient with Gerstmann-Sträussler syndrome and one with CJD. Peptide-N has an amino acid sequence which does not exist in PrP27-30. Staining of kuru plaques by the antiserum against peptide-N indicated that the entire molecule, including the N-terminal portion of PrP33-35, was deposited in the kuru plaques.

Aged↗

PubMed1992

Polymorphism of coagulation factor XIII B subunit: further occurrence of FXIIIB*15 in Japanese and phenotyping in bloodstains.

The polymorphism of FXIIIB was investigated in 555 unrelated Japanese individuals using isoelectric focusing and immunoblotting. Five common phenotypes and a rare variant type FXIIIB 15-3 were observed. The allele frequencies were FXIIIB*1 = 0.3063, FXIIIB*2 = 0.0162, FXIIIB*3 = 0.6766 and FXIIIB*15 = 0.0009. Phenotyping was also possible from bloodstains stored at 37 degrees C for up to 4 months and from bloodstains stored at room temperature and at 4 degrees C for over 6 months. The FXIIIB system can provide a new powerful genetic marker for the medicolegal grouping of bloodstains.

Alleles↗

PubMed1992

Structure-toxicity relationship of ethylene glycol ethers.

The ultimate purpose of the present study was to evaluate correlations between acute in vivo and in vitro toxicity and log P (P is n-octanol-water partition coefficient). The in vitro toxicity to cloned cells (neuroblastoma N18TG-2 and glioma C6) in culture (ED50) and the in vivo toxicity to mice (LD50) of ethylene glycol ethers were studied in terms of the structure-activity relationship. The test ethers showed a wide range of ED50 values in both cells. LD50 was determined under two conditions: LD50-cont. was estimated in mice pretreated with olive oil and LD50-CCl4 in CCl4-pretreated mice. Multiple regression analyses revealed a significant correlation between log 1/LD50 and log P as follows: log (1/LD50-cont.) = -0.120 (log P)2+0.487log P-1.182, and log (1/LD50-CCl4) = -0.128 (log P)2+0.566log P-1.157. There was no significant correlation either between ED50 and LD50 or between ED50 for N18TG-2 and ED50 for C6. The results suggest that metabolic activation might not occur during acute toxicity from the ethers, and that hydrophobicity, expressed as log P, plays an important role in acute toxicity.

Animals↗

PubMed1992

The combined effect of lymphokine activated killer cell and radiation therapy on rat brain tumor in vitro.

The in vitro effect of a combined treatment with lymphokine activated killer (LAK) cell and radiation therapy on rat brain tumor was examined using 51Cr release assay. The tumor cell-line used in this experiment was 9L rat brain tumor derived from a Fischer 344 rat. LAK cells were obtained by culturing rat lymphocytes with recombinant human interleukin 2 for at least 3 days. The cytotoxic activity of the LAK cells was examined by 51Cr release assay. Irradiation was done by exposing the microtiter plate in which the 51Cr labeled 9L cells and LAK cells were cultured to a 137Cs gamma cell unit. Without irradiation, there was 18% cytotoxicity in the 1:100 tumor-to-LAK cell ratio specimen after 24 hrs cocultivation. However, if 5 Gy of irradiation was given, followed by 12 hrs incubation, the cytotoxicity was enhanced significantly at the same cell ratio (30%). This enhancement effect was the most prominent when the cell ratio was 1:100 and the irradiation dose was 5 Gy. To generate the enhancement effect, an incubation time of over 8 hrs both before and after irradiation was required. The supernatant of the LAK cells showed 19.8% and 11.4% cytotoxicity with and without irradiation, respectively. This result indicates the participation of a cytotoxic factor released from LAK cells.

Animals↗

PubMed1992

Protein-losing enteropathy and pancreatic involvement in a case of connective tissue disease.

A patient with connective tissue disease presenting with both protein-losing enteropathy and pancreatic involvement is reported. A 52-year-old female was admitted because of mild epigastralgia, anasarca and ascites. Serum albumin, transferrin and zinc, showed low levels. An Upper G.I. series and endoscopy showed thickened folds of the duodenum and the jejunum. Biopsy specimens revealed lymphangiectasia in edematous villi. 99mTc-labeled human serum albumin scintigram showed abnormal radioactivity in the small intestine 90 minutes after intravenous injection, indicating protein-losing enteropathy. Hypoalbuminemia was ameliorated by glucocorticoid therapy, but recurred twice when glucocorticoid treatment was tapered. Hypoalbuminemia has not occurred since intestinal lymphangiectasia was improved with glucocorticoid treatment. Levels of elastase 1 and lipase were high in serum and ascites on admission. Endoscopic retrograde pancreatogram showed no abnormalities. Serum pancreatic enzymes were also ameliorated by glucocorticoid therapy, but slightly high levels continued for about one year and a half. This case might have been diagnosed as systemic lupus erythematosus although mixed connective tissue disease was also suspected. There are few reports of protein-losing enteropathy and pancreatic involvement associated with connective tissue diseases. Protein-losing enteropathy and pancreatic involvement were ameliorated with glucocorticoid treatment, suggesting participation of immunological mechanisms.

Connective Tissue Diseases↗

PubMed1992

Effects of maternal caffeine intake during lactation on molar enamel surfaces in new-born rats.

Dams were fed normal laboratory chow until delivery. At birth, the litters were combined, and eight pups were randomly assigned to each dam. Dams with the recombined litters were divided into two groups. Dams of group 1 were fed a 20% protein diet as a control; dams of group 2 were fed a 20% protein diet supplemented with caffeine (2 mg/100 g of the dam's weight). On day 22, the dams of group 2 were anaesthetized with ether. They were injected with 2 iu of oxytocin in order to collect milk. Blood was collected from pups and dams to determine its caffeine concentration. The first and second molars were removed from each pup's mandible and maxilla. Radiographs were taken of 10 randomly selected first or second molars from each group. Four randomly selected molars from each litter were placed in a specially designed chamber and bathed with a constant flow of acid solution to determine the amount of mineral dissolved from the enamel surfaces. The remaining non-acid exposed molars were pulverized in freezer mills. A small portion of this powder was then analysed for the total amount of minerals. No differences were found in the radiographic density of enamel between the groups. The amount of dissolved calcium, phosphorus and magnesium from enamel surfaces in the caffeine group was consistently greater than that of the non-caffeine group in the first molars, whereas, in the second molars, there was no difference between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Physical examination of caffeine's effects on the enamel surface of first molar in new-born rats.

Samples of the first molars of offspring whose dams were fed a diet supplemented with caffeine were examined by scanning electron microscopy, X-ray diffractometry and electron microprobe analysis. Scanning microscopy of the enamel surface of the caffeine group revealed a consistently rougher surface than in the non-caffeine controls, both before and after acid exposure. X-ray diffraction analysis of the pulverized whole tooth in the caffeine group showed broader diffraction peaks for the lattice plane reflections (202) and (300), indicating smaller crystallites. Pure enamel samples of the caffeine group examined with a Gandolfi X-ray camera also revealed more diffuse diffraction lines than in the non-caffeine controls, further indicating smaller crystallites in the enamel. The calcium and phosphorus contents of the acid-exposed samples in both control and caffeine groups were lower than the non-acid exposed control and caffeine groups by electron microprobe analysis. After exposure to acid, the calcium and phosphorus contents of the outer surface of the enamel in the caffeine group were greatly reduced as compared to that of the non-caffeine controls. Thus various methods consistently indicate that caffeine ingestion during early growth affects the enamel surface of the first molars, resulting in impaired mineralization. Caffeine intake may therefore have a negative effect on amelogenesis and possibly increases susceptibility to dental caries.

Animals↗

PubMed1992

4-Bromo-6-nitroquipazine: a new ligand for studying 5-hydroxytryptamine uptake sites in vivo.

The present study was undertaken to evaluate 2 bromo-derivatives (4-bromo-6-nitroquipazine and 6-bromoquipazine) of quipazine as potential ligands for studying 5-hydroxytryptamine (5-HT; serotonin) uptake sites in the brain in vivo. The inhibition experiments of [3H]5-HT uptake into synaptosomes from rat brain and of the binding of [3H]6-nitroquipazine to membranes of rat brain showed that 4-bromo-6-nitroquipazine and 6-bromoquipazine were very potent and selective inhibitors of 5-HT uptake in vitro, very close to that of 6-nitroquipazine. Furthermore, 4-bromo-6-nitroquipazine was about a 2-fold more potent inhibitor of specific binding of [3H]6-nitroquipazine in vivo in the hypothalamus of mouse brain than 6-bromoquipazine. Thus, 4-bromo-6-nitroquipazine seems to be superior to 6-bromoquipazine, as a potential ligand for in vivo imaging of 5-HT uptake sites in the brain.

Animals↗