PubMed Health⌕ Search

Biomedical subjects

K Hashimoto

Publications and source records attributed to K Hashimoto.

At least 271 records · Page 15Linked to original sources
PubMed2000

Genetic changes in sweat gland carcinomas.

The molecular pathogenesis of malignant appendageal tumors is poorly understood. Immunohistochemical staining, polymerase chain reaction (PCR)-based loss of heterozygosity (LOH) and sequencing analyses were performed in a mixed group of 21 sweat gland carcinomas. LOH was mostly confined to the chromosome arm 17p. None of the remaining 17 tumors showed LOH at any loci. Nuclear accumulation of p53 protein was observed in 3 tumors, all of which also showed LOH of 17p. One eccrine gland adenocarcinoma showed allelic loss of 17p and a Cys 176 Arg mutation in the p53 gene. The other three tumors that showed LOH of 17p, however, had wild-type p53 genes. A clear transition from benign eccrine poroma to porocarcinoma that was associated with p53 protein stabilization and allelic loss was observed in one tumor. One eccrine porocarcinoma/undifferentiated adnexal carcinoma showed prominent microsatellite instability, probably reflecting an underlying defect in DNA mismatch repair. Overexpression of erbB-2 was observed in three tumors. The low frequencies of LOH and p53 alterations in sweat gland carcinomas contrasted with the multiple genetic defects normally observed in cutaneous squamous cell carcinomas, and may be partly explained by the relative protection of cutaneous appendages from ultraviolet light and other environmental mutagens.

Adenocarcinoma↗
PubMed2000

Experimental study of the effects of deletion variant of hepatocyte growth factor on hepatic ischaemia-reperfusion injury.

BACKGROUND: Hepatic ischaemia-reperfusion (IR) injury is still a serious complication following liver surgery. The effect of the deletion variant of hepatocyte growth factor (dHGF) on hepatic IR injury was examined in rats. METHODS: Male Wistar rats were divided into two groups after 90 min of partial liver ischaemia: the dHGF group which was given dHGF 0.5 mg/kg intravenously immediately after reperfusion, followed by 0.5 mg/kg every 12 h, and the control group, which received vehicle buffer only. Serum chemistry, histopathological findings and liver weights were compared between the groups. RESULTS: In the dHGF group, the increase in serum alanine transaminase and hyaluronic acid levels was significantly reduced, and the serum albumin level increased after reperfusion. The extent of hepatic necrosis 24 h after reperfusion was decreased in the dHGF group. Moreover, the proportion of terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labelling-positive hepatocytes 6 h after reperfusion was reduced in the dHGF group. The non-ischaemic-, ischaemic- and whole-liver weight : body-weight ratio significantly increased in the dHGF group after reperfusion. The proportion of proliferating cell nuclear antigen-positive hepatocytes in the dHGF group markedly increased after 6 h after reperfusion in the non-ischaemic lobes, while in the ischaemic lobes it increased 24 h after reperfusion. CONCLUSION: These data suggest that dHGF not only improves recovery from IR injury, but also accelerates recovery from these injuries. dHGF may be an effective pharmacological agent for prevention and treatment of hepatic IR injury.

Animals↗
PubMed2000

Induction of microthrombotic thrombocytopenia in normal mice by transferring a platelet-reactive, monoclonal anti-gp70 autoantibody established from MRL/lpr mice: an autoimmune model of thrombotic thrombocytopenic purpura.

MRL/MpJ-lpr/lpr (MRL/lpr) mice spontaneously develop immune complex-mediated glomerulonephritis and thrombocytopenia. Although the presence of cross-reactive anti-phospholipid antibodies in sera of MRL/lpr mice has been demonstrated, possible relationships between detected autoantibodies and the development of thrombocytopenia have not been elucidated. Recent genetic analyses in a few different strains of lupus-prone mice have pointed out a close correlation between autoantibodies reactive with endogenous retroviral env gene product, gp70, and the development and severity of glomerulonephritis. In the process of establishing possibly nephritogenic anti-gp70 autoantibody-producing hybridoma cells from MRL/lpr mice, we identified an IgG2a-producing anti-gp70 hybridoma clone that induced microvascular intraluminal platelet aggregation, thrombocytopenia, and amenia upon transplantation into syngeneic non-autoimmune mice. This and two other anti-gp70 antibodies bound onto the surface of mouse platelets, and purified IgG2a of the anti-gp70 autoantibody induced glomerular lesions with characteristics of thrombotic thrombocytopenic purpura when injected into non-autoimmune mice. The pathogenic anti-gp70 autoantibody specifically precipitated a platelet protein with an approximate relative molecular mass of 40 000.

Animals↗
PubMed2000

Asymmetry in jaw-jerk reflex latency in craniomandibular dysfunction patients with unilateral masseter pain.

The purpose of the present study was to elucidate the effects of unilateral masseter muscle pain on the jaw-jerk reflex. The latency and peak-to-peak amplitude of bilateral electromyographic activity recorded at the masseter muscles during the jaw-jerk reflex were measured in 18 patients with craniomandibular dysfunction (CMD) with strictly unilateral masseter pain or tenderness and 10 control subjects using a computerized recording and analysis system. The reflex was elicited, at the mandibular rest position, by tapping the centre of the chin downwards with a reflex hammer incorporating a microswitch that triggered the sweep of the recording apparatus upon contact with the chin. In the CMD group, the jaw-jerk latency on the affected side (6.89 +/- 0.98 ms) was significantly shorter (P < 0.01) than that on the unaffected side (7.59 +/- 0.92 ms). In the control group, there was no difference between the jaw-jerk latencies on the right (7.06 +/- 0.64 ms) and the left (7.08 + 0.65 ms) sides. The range of side asymmetry for jaw-jerk latencies in the CMD group was greater than that in the control group. In six patients, the latency difference exceeded 1 ms. The asymmetry of latency of the jaw-jerk reflex was thought to be due to facilitation on the side with masseter pain or tenderness. This facilitation on the ipsilateral side might be produced by enhanced gamma drive induced by sustained nociceptive stimulation. Such effects may be related with clinically derived concepts regarding such muscle dysfunction as myospastic activity or trigger points.

Adolescent↗
PubMed2000

T-0162, a novel free radical scavenger, reduces myocardial infarct size in rabbits.

1. We investigated the effects of 1-(3-tert-butyl-2-hydroxy-5-methoxyphenyl)-3-(3-pyridylmethyl)urea hydrochloride (T-0162), a novel low-molecular weight free radical scavenger, on the generation of superoxide anions and hydroxyl radicals in vitro and in vivo and on myocardial infarct (MI) size in an in vivo model of MI in rabbits. 2. It was found that T-0162 scavenged both superoxide anions and hydroxyl radicals in a concentration-dependent manner in vitro. 3. In an in vivo rabbit model with 30 min coronary occlusion and 30min reperfusion, T-0162 scavenged hydroxyl radicals generated in the myocardium during reperfusion. 4. Anaesthetized open-chest Japanese white male rabbits were subjected to 30 min coronary occlusion and 48 h reperfusion. The control group (n = 10) was infused with 10% lecithin solution for 220 min from 10 min before occlusion to 180 min after reperfusion. The pretreatment group (n = 10) was infused with T-0162 dissolved in 10% lecithin solution for 220 min from 10 min before occlusion to 180 min after reperfusion at a rate of 400 microg/kg per min. The post-treatment group (n = 10) was injected with an i.v. bolus of 10 mg/kg T-0162 and was then infused with 400 microg/kg per min T-0162 for 190 min from 10 min before reperfusion to 180 min after reperfusion. After 48 h reperfusion, infarct size was measured histologically and expressed as a percentage of area at risk (AAR). 5. There was no significant difference in haemodynamic parameters among the three groups throughout the experimental period. The per cent infarct size of the AAR in the T-0162 groups (24.8+/-4.3 and 30.5+/-3.9% for pre- and posttreatment groups, respectively) was significantly reduced compared with control (44.7+/-4.1%; P<0.05). There was no significant difference in the AAR among the three groups. 6. In conclusion, T-0162 reduces MI size through the inhibition of reperfusion injury.

Animals↗
PubMed2000

Delayed and sustained activation of p42/p44 mitogen-activated protein kinase induced by proteasome inhibitors through p21(ras) in PC12 cells.

Proteolysis by the ubiquitin/proteasome pathway regulates the intracellular level of several proteins, some of which control cell proliferation and cell cycle progression. To determine what kinds of signaling cascades are activated or inhibited by proteasome inhibition, we treated PC12 cells with specific proteasome inhibitors and subsequently performed in-gel kinase assays. N-Acetyl-Leu-Leu-norleucinal and lactacystin, which inhibit the activity of the proteasome, induced the activation of p42/p44 mitogen-activated protein (MAP) kinases [extracellular signal-regulated kinases (ERKs) 1 and 2]. In contrast, N-acetyl-Leu-Leu-methional, which inhibits the activity of calpains, but not of the proteasome, failed to induce ERK activation. Uniquely, the kinetics of MAP kinase activation induced by proteasome inhibitors are very slow compared with those resulting from activation by nerve growth factor; ERK activation is detectable only after a 5-h treatment with the inhibitors, and its activity remained unchanged for at least until 27 h. Proteasome inhibitor-initiated ERK activation is inhibited by pretreatment with the ERK kinase inhibitor PD 98059, as well as by overexpression of a dominant-negative form of Ras. Thus, proteasome inhibitors induce sustained ERK activation in a Ras-dependent manner. Proteasome inhibitor-induced neurite outgrowth, however, is not inhibited by PD 98059, indicating that sustained activation of ERKs is not the factor responsible for proteasome inhibitor-induced morphological differentiation. Our data suggest the presence of a novel mechanism for activation of the MAP kinase cascade that involves proteasome activity.

Acetylcysteine↗
PubMed2000

Serum arylesterase/diazoxonase activity and genetic polymorphisms in patients with type 2 diabetes.

Human serum paraoxonase (PON1) is associated with high-density lipoprotein (HDL) and inhibits the oxidation of low-density lipoprotein (LDL) in vitro, suggesting that PON1 protects against atherosclerosis. We detected 3 polymorphisms of the PON1 gene and investigated PON1 enzyme activities as paraoxonase (PON), arylesterase (ARYL) and diazoxonase (DIAZ), and serum PON1 concentration in 106 patients with type 2 diabetes and 161 control subjects. All 3 enzyme activities and specific activities of PON1 in diabetic patients were significantly lower than those in controls, while there was no difference in serum PON1 concentration between the patient and control groups. The specific activities of PON, ARYL, and DIAZ in patients were 6.82 +/- 3.14 nmol x min(-1) x U(-1) (mean +/- SD, U; unit for serum PON1 concentration), 4.77 +/- 0.17 micromol x min(-1) x U(-1), and 193 +/- 92 nmol x min(-1) x U(-1), respectively, whereas those in controls were 9.33 +/- 3.92 nmol x min(-1) x U(-1), 5.36 +/- 0.14 micromol x min(-1) x U(-1), and 242 +/- 103 nmol x min(-1) x U(-1), respectively. There was no significant difference in the allelic frequencies of -108C/T, 55L/M, or 192Q/R between the patient and control groups. When each enzyme activity was compared between the patient and control groups in each genotype subgroup, all activities were lower in the patient group. The PON and ARYL activities were lower in patients with retinopathy or nephropathy than in those without such complications, and the ARYL activity was also lower in patients with neuropathy. In conclusion, all specific enzyme activities of PON1 were lower in patients with type 2 diabetes independent of the -108C/T, 55L/M, or 192Q/R polymorphism, and this impaired PON1 function may be involved in development of diabetic microangiopathy.

Aged↗
PubMed2000

Acral peeling skin syndrome.

Peeling skin syndrome is a rare autosomal recessive disease characterized by widespread painless peeling of the skin in superficial sheets. We describe a 34-year-old man with a lifelong history of spontaneous asymptomatic peeling skin limited to the acral surfaces. This patient probably represents a localized variant of peeling skin syndrome, which has previously been described as a generalized condition. Light and electron microscopic studies of biopsy specimens taken before and after immersion in water were performed. It was concluded that this patient has abnormal keratohyalin granules and inadequate aggregation of keratin filaments that caused the separation of the epidermis in the stratum corneum through the clear zone. Alternatively, unknown keratin species expressed in the clear zone may also cause the abnormality. (J Am Acad Dermatol 2000;43:1112-9.).

Adult↗
PubMed2000

Hypertrophic branchial myopathy with uniform predominance of type 1 fibres. Case report.

A 17-year-old Japanese girl presented with left masseteric hypertrophy. She had a habit of chewing only on the affected side. Histochemical study of the masseter muscle showed myopathic changes characterised by uniform type 1 fibres with gross hypertrophy, increases of internal nuclei and split fibres, and endomysial fibrous tissue. This condition could be compatible with hypertrophic branchial myopathy, because it was confined to the masseter muscle and so cannot be classified into any known type of systemic myopathy.

Adolescent↗
PubMed2000

Lamellar ichthyosis: response to etretinate with transglutaminase 1 recovery.

We studied a case of typical lamellar ichthyosis before and after etretinate treatment for the expression of transglutaminase 1 (TGK) and the presence or absence of the marginal band. Before the treatment, TGK was undetectable, although two other components of the marginal band, loricrin and involucrin, were detected by immunostaining in a normal pattern. The marginal band of the corneocytes was either thin and irregular or completely absent by electron microscopic study. After therapy with etretinate, 50 mg/day, the patient' s skin improved, and biopsies were taken at 4 and 8 months. Transglutaminase 1 became detectable by immunostaining. The marginal band was still absent in most corneocytes.

Adult↗
PubMed2000

Comparison of cardiovascular effects of a new calcium channel blocker AH-1058 with those of verapamil assessed in blood-perfused canine heart preparations.

The cardiovascular effects of AH-1058, a novel calcium channel blocker, were examined in comparison with those of verapamil using canine isolated, blood-perfused papillary muscle, atrioventricular node, and sinoatrial node preparations. Intravenous administration of AH-1058 (20, 50, and 100 microg/kg) or verapamil (20, 50, and 100 microg/kg) to the blood-donor dog induced negative inotropic, dromotropic, and chronotropic effects and a coronary vasodilator action in cross-circulated isolated heart preparations, simultaneously inducing the same cardiac effects in the blood-donor dog. The order of potency of the effects of AH-1058 was ventricular contraction > coronary blood flow >> atrioventricular conduction > sinoatrial automaticity, whereas that of verapamil was coronary blood flow >> atrioventricular conduction >> sinoatrial automaticity > ventricular contraction. The cardiosuppressive effects of AH-1058, especially on ventricular contraction, were slower in onset and longer lasting than those of verapamil. These results suggest that this unique cardiovascular profile of AH-1058 may become beneficial for the treatment of certain pathologic processes, in which selective inhibition of ventricular calcium channels would be essential for drug therapy.

Animals↗
PubMed2000

Regulation of type-2 corticotropin-releasing hormone receptor mRNA in rat heart by glucocorticoids and urocortin.

A novel subtype of corticotropin-releasing hormone (CRH) receptor, designated type-2 CRH receptor (CRHR-2), has been cloned by a number of laboratories, and its mRNA has been found to be distributed not only in the brain but in peripheral tissues such as heart and skeletal muscle. To date, however, the regulation of CRHR-2 mRNA is poorly understood. Therefore, we examined the effect of glucocorticoid treatment, adrenalectomy, and systemic administration of urocortin, a possible endogenous ligand for CRHR-2, on heart CRHR-2 mRNA levels in male Wistar rats, using in situ hybridization histochemistry. CRHR-2 mRNA in the heart was significantly decreased 9 h after systemic administration of urocortin (5 microg/kg b.w.). Systemic administration of corticosterone (CORT; 10 mg/rat/day for 12 days) or CORT pellet (200 mg) implant for 7 and 14 days also decreased CRHR-2 mRNA in the heart, whereas it was unchanged 7 days after adrenalectomy. Thus, similar regulation of CRHR-2 mRNA in the rat heart by its ligand and glucocorticoids was observed. The precise mechanism of the regulation of CRHR-2 mRNA in the heart and the physiologic significance of cardiac CRHR-2 remains to be elucidated.

Adrenalectomy↗
PubMed2000

QT-prolonging effects of sparfloxacin, a fluoroquinolone antibiotic, assessed in the in vivo canine model with monophasic action potential monitoring.

Sparfloxacin, a fluoroquinolone antibacterial agent, prolongs cardiac repolarization, which may predispose to torsades de pointes. This study was designed to assess simultaneously the hemodynamic and electrophysiologic effects of sparfloxacin using the halothane-anesthetized, closed-chest in vivo canine model (n = 6). Sparfloxacin was intravenously administered in the following two doses with a pause of 20 min, a clinically relevant dose of 3.0 mg/kg/10 min and a 10 times higher dose of 30 mg/kg/10 min. After the low dose of sparfloxacin, cardiac output increased, heart rate decreased, and ventricular repolarization and refractory periods were prolonged. After the high dose, cardiac output increased, whereas heart rate and mean blood pressure decreased, and ventricular repolarization and effective refractory periods were prolonged. The increment was greater in repolarization than in refractoriness, indicating an increase of electrical vulnerability. Because sparfloxacin prolonged repolarization in a reverse use-dependent manner, its negative chronotropic effect may have potentiated the QT prolongation. Left ventricle preload, left ventricular contraction, and AV nodal as well as intraventricular conduction were minimally affected. These results suggest that caution should be used when administering sparfloxacin to patients having risk factors for QT prolongation.

Action Potentials↗
PubMed2000

Palmoplantar keratoderma (Voerner) with composite keratohyalin granules: studies on keratinization parameters and ultrastructures.

A case of the Voerner type palmoplantar keratoderma was studied for abnormalities of keratinization parameters. An enzyme and materials used to build the marginal band or cellular envelope of the cornified cell were all abnormally expressed; i.e. transglutaminase I (TGK), loricrin, and involucrin were abnormally immunostained. In the normal controls, their expression was limited to the upper epidermis, mainly in the granular layer. In the lesional skin, they were detected from the suprabasal layer to the lower horny layer. Filaggrin, the protein of the keratohyalin granule, was also expressed more widely than in controls. Ultrastructural abnormalities included a significantly higher frequency of composite keratohyalin granules than controls, early formation of a marginal band in the midepidermis, and, most remarkably, the clumping of tonofilaments causing vacuolization of the cytoplasm of affected keratinocytes.

Adult↗
PubMed2000

Post-scabetic nodules: a lymphohistiocytic reaction rich in indeterminate cells.

We studied six infants and two adult cases of nodular scabies with immunostains and electron microscopy. All eight cases have had either direct (KOH) or family histories of scabies and were treated with lindane 1% cream or permethrin 5% cream. Family members responded very well, but our patients developed multiple papulo-nodular lesions which were initially very pruritic and, in some cases, persisted from several months to over one year. H & E stain of biopsied tissue sections revealed a heavy perivascular and periappendageal lymphohistiocytic cell infiltration. Immunophenotype of these cells was compatible with Langerhans cells, i.e. CD1A (+), S-100 (+) and HLA-DR (+). Electron microscopy showed that these histiocytic cells satisfied all the ultrastructural criteria of Langerhans cells except for the absence of Birbeck's granules. Lag, a monoclonal antibody for Birbeck's granules, was negative. "Persistent nodules in scabies" or "nodular scabies" seems to represent a prolonged response of indeterminate cells-lymphocytes to mite antigens.

Adult↗
PubMed2000

Late onset hyalinosis cutis et mucosae.

Two cases of non-familial, late onset (50 and 62-years-old) hyalinosis cutis et mucosae were studied and compared with classical early onset cases. Late onset cases showed essentially the same histological and ultrastructural features described for early onset cases. The late onset variety should be distinguished from other diseases; they resemble systemic amyloidosis and sometimes the adult form of colloid milium.

Age Factors↗