Biomedical subjects

M Hirota

Publications and source records attributed to M Hirota.

At least 73 records · Page 4Linked to original sources

PubMed1999

Fas ligand is frequently expressed in human pancreatic duct cell carcinoma.

Fas ligand (Fas-L) is a key molecule in normal immune development, homeostasis, modulation, and function. Recent reports suggested that tumor cells can evade immune attack by killing lymphocytes through expressing Fas-L on the tumor cell surface. The expression of Fas-L has been demonstrated in pancreatic cancer cell lines and in tissues. The messenger RNA (mRNA) and protein expression of Fas-L was investigated in four pancreatic cancer cell lines and 19 human pancreatic duct cell carcinomas (PDCs) by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry, respectively. In addition, coculture assay of Fas-L and Fas-expressing PANC-1 cells and Fas-sensitive Jurkat cells was performed. Fas-L mRNA expression was observed in all four cell lines as well as in 10 PDC tissues, and the protein expression was frequently detected in the PDC tissues (16 of 19 cases). The coculture experiments showed that PANC-1 cells induced apoptosis of Jurkat cells, whereas the PANC-1 cells themselves and Jurkat cells cultured without the presence of PANC-1 showed few apoptotic changes. These findings suggest that Fas-L may play an important role in the ability of PDCs to escape from immune surveillance through the induction of apoptosis in tumor-attacking lymphocytes. The frequent expression of Fas-L in PDCs may partly explain the notorious biologic behavior of PDCs.

Apoptosis↗

PubMed1999

Inhibitory effects of the antihistamines epinastine, terfenadine, and ebastine on potassium currents in rat ventricular myocytes.

We examined and compared the inhibitory effects of three non-sedating antihistamines, terfenadine, ebastine, and epinastine, on delayed rectifier potassium current (IK) and transient outward potassium current (Ito) of rat isolated ventricular myocytes, using a patch clamp technique. Terfenadine, ebastine and epinastine were found to inhibit IK with IC50 values of 5.96, 15.3 and 145 microM, respectively. Ito was suppressed by epinastine with an IC50 value of 69.5 microM. The order of arrhythmogenicity, assessed by the inhibition of IK, was ranked as terfenadine > ebastine > epinastine, consistent with that of the potencies of each drug for QT prolongation reported in rats.

Animals↗

PubMed1999

A simple purification method and morphology and component analyses for carotovoricin Er, a phage-tail-like bacteriocin from the plant pathogen Erwinia carotovora Er.

Carotovoricin Er has been isolated as a phage-tail-like bacteriocin from the plant pathogen Erwinia carotovora Er [Kamimiya, S. et al., (1977), Agric. Biol. Chem. 41, 911-912]. However, the fine morphology and structural composition of carotovoricin Er remained to be studied because a large amount of contracted carotovoricin Er were present in the bacteriocin preparations so far obtained. To obtain intact carotovoricin Er and its major parts, we developed simple and efficient purification methods including the use of sucrose density gradient centrifugation in the presence of 10-20% (v/v) ethanol. Electron microscopy for the purified carotovoricin Er showed the presence of a novel antenna-like structure at the proximal end of the phage-tail-like particle, which consisted of a sheath-and-core part, a baseplate, and tail fibers. Contracted sheath and inner core were purified as hollow cylindrical structures with longitudinal lengths of 69 and 174 nm, respectively, and tail fibers were purified as a fibrous structure with length of 63 nm. SDS-polyacrylamide gel electrophoresis showed the presence of single major proteins of 50, 20, and 68 kDa in the isolated sheath, core, and tail fiber, respectively. Three other minor proteins of 46, 44, and 35 kDa were also identified as the structural proteins of carotovoricin Er, which may be the candidate proteins for the antenna-like and the base plate structures. Thus carotovoricin Er consists of at least 6 protein components.

Amino Acid Sequence↗

PubMed1999

3-Geranyl-4-hydroxy-5-(3'-methyl-2'-butenyl)benzoic acid as an anti-inflammatory compound from Myrsine seguinii.

Bioassay-guided isolation of anti-inflammatory compounds from the methanol extract of Myrsine seguinii yielded an anti-inflammatory compound (1). The structure of compound 1 was elucidated to be 3-geranyl-4-hydroxy-5-(3'-methyl-2'-butenyl)benzoic acid on the basis of its spectroscopic data. Compound 1 strongly suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation on mouse ears at a dose of 500 micrograms (inhibitory effect (IE): 65%). The acetate and the methyl ether of 1 showed moderate activity at a 500-microgram application, with IE 38% and 27%, respectively. However, the methyl ester and the dimethyl derivative of 1 did not show activity at the same dose. The related compounds of 1, o-, m- and p-hydroxybenzoic acids also did not exhibit notable activity. These results indicate that the carboxylic acid and lipophilic terpene moieties of 1 were significant structural features for anti-inflammatory activity.

Animals↗

PubMed1999

Clinicopathological studies of odontoma in 47 patients.

A 14-year retrospective study was performed on 47 odontomas from the files of the 1st Department of Oral and Maxillofacial Surgery at Nihon University School of Dentistry. Fifty-seven percent of the patients were male and 42.6% were female. The age distribution was 8 to 48 years with a mean age of 22 +/- 9.0 years. There were no particular symptoms associated with the odontomas, and 63.8% of our patients had no symptoms. However, 12 patients complained of swelling and 9 of pain. The tumor was found in the maxilla in 42.6% and in the mandible in 57.4%. According to the WHO histological type classification, 53.2% of the tumors were classified as compound odontoma and 46.8% as complex odontoma. The size of the tumor ranged from 5 mm to 42 mm in diameter. The average complex odontoma was much bigger than the average compound odontoma. Ghost cells were found 11 cases in our series. In addition, odontogenic epithelium was found in 16 cases. Twenty seven patients had impacted teeth in association with odontoma and 24 of the 27 teeth were removed at the time of surgical enucleation of the tumor, while 3 cases were treated by orthodontically assisted eruption. There was no recurrence in any of the studied cases.

Adolescent↗

PubMed1999

FUT-175 inhibits the production of IL-6 and IL-8 in human monocytes.

We investigated the effect of FUT-175, a serine protease inhibitor, on the production of pro-inflammatory cytokines, interleukin-6 (IL-6) and interleukin-8 (IL-8), by monocytes stimulated with lipopolysaccharide (LPS). Monocytes isolated from healthy volunteers were incubated with LPS and various concentrations of FUT-175 for 12 hours. The productions of both IL-6 and IL-8, measured by enzyme-linked immunosorbent assay, were significantly inhibited by FUT at the concentration of 1 to 100 microg/ml in a dose-dependent manner. Furthermore, the expressions of IL-6 and IL-8 mRNAs were also inhibited by FUT-175. These data suggest that FUT-175 may reduce the pathological inflammatory conditions associated with enhanced production of proinflammatory cytokines including IL-6 and IL-8.

Benzamidines↗

PubMed1999

[A long-term surviving case of multiple metastatic liver tumors from rectal cancer treated with microwave coagulation therapy (MCT)].

We experienced a long-term surviving case from excellent control of a multiple metastatic liver tumor from rectal cancer. The patient was a 38-year-old male, and his chief complaint was pain at defecation. The primary lesion was diagnosed as rectal cancer (Rb), and it was histologically found to be well-differentiated adenocarcinoma. The preoperative enhanced CT demonstrated 8 metastatic lesions in bilateral lobes of the liver. Low anterior resection for rectum and open microwave coagulation therapy (MCT) for liver metastasis were synchronously performed. The coagulated areas after MCT revealed no enhancement. The serum CEA levels returned to normal for 9 months. Nine months after the first operation, we detected 6 recurrent lesions in the other sites of the remnant liver. We used second open MCT because the hepatic arterial chemotherapy was ineffective. We performed percutaneous MCT for the next new lesions. The patient was diagnosed with lung metastasis 2 years after the first operation, and died of cancer growth 2 years and 9 months after the first operation. This long-term surviving case of nine metastatic liver tumors achieved adequate quality of life by a combination therapy mainly consisting of MCT.

Adenocarcinoma↗

PubMed1999

[Shock and its mediators].

Shock is a biological response associated with hypotension and signs of altered tissue perfusion. Shock can be induced by many different mechanisms. Shock itself induces cytokine production as a result of disturbed microcirculation or ischemia-reperfusion injury. Alternatively, severe inflammatory conditions, such as sepsis and severe acute pancreatitis, are usually associated with prominent mediator production, which often leads to shock. TNF-alpha and IL-1 beta increase the vascular permeability, and nitric oxide reduces systemic vascular resistance. In the management of patients who have experienced clinical insult, we must consider the symptoms of systemic inflammatory response syndrome provoked by inflammatory mediators as a warning sign of the development of shock and organ dysfunction. Early withdrawal from SIRS and avoidance of infectious complications (second attack) should be attempted.

Acute Disease↗

PubMed1999

[Clinical evaluation of PCR method for detection of cytomegalovirus DNA].

Polymerase chain reaction (PCR) to detect Cytomegalovirus (CMV)-DNA from the clinical specimens is useful to diagnose CMV infection. Eighty-one specimens of 31 patients including peripheral blood, bronchioalveolar lavage fluid, biopsy tissues, feces, urine, sputum and etc. and normal peripheral blood from 59 volunteers were used in this study. After DNA extraction each samples was amplified by the seminested PCR using primers recognizing sequences in the Immediate-early gene of CMV. This PCR method specifically detected more than 10 virus copies even in the presence of the genomic DNA. CMV-DNA was detected in only one of 59 normal peripheral bloods (1.7%). Six of 31 patients were clinically diagnosed as CMV infection by anti-CMV therapy. These 6 patients were positive in the peripheral blood by PCR for CMV, and 5 of them were positive in other samples. However, 3, 5 and 1 of 25 patients, who were clinically diagnosed as not having CMV infection, were also positive in peripheral blood, in the other samples and in both, respectively. The PCR method was able to examine any clinical samples. To examine both the peripheral blood and the samples from infected organs is helpful for the diagnosis of CMV infection.

Adolescent↗

PubMed1998

Localization and characterization of curved DNA in the human erythropoietin receptor gene by experimental and theoretical approaches.

We report here the locations of curved DNA in the human erythropoietin receptor gene. A total of 13 DNA bend sites were mapped by circular permutation assays, appearing at an average interval of 651.2+/-214.6 (S.D.) in the 8-kb region. The bend centers in these 13 bend sites were confirmed by oligonucleotide-based assays where most of these centers had bend angles higher than that shown by (AAACCGGGCC) x (A)20 and lower than that shown by (AAACCGGGCC)2 x (A)10. DNA curvature mapping by TRIF software, which is based on the distribution of dinucleotides, primarily AA and TT, provided a highly accurate prediction for the locations of the bend sites. They showed approximately 20 degrees to 40 degrees of bend angles demonstrated by the oligonucleotide assays and by computer analysis.

DNA↗

PubMed1998

Conservation and continuity of periodic bent DNA in genomic rearrangements between the c-myc and immunoglobulin heavy chain mu loci.

Periodic bent DNA was mapped in the human c- myc and immunoglobulin heavy chain mu (Ig mu) loci. A total of 12 DNA bend sites in the c- myc gene and 11 sites in the Ig mu locus were aligned at average intervals of 694.2 +/- 281.4 and 654.5 +/- 222.7 bp respectively. Although some of the bend sites retained the distance of 700 bp, their periodicity was disturbed at several locations, including the exons of the c- myc gene and the enhancer element present in the Ig mu locus. Analysis of rearrangements that resulted in tumorigenesis of lymphocytes showed that the continuity of DNA bend sites was conserved in three lymphoma cell lines, Manca, BL22 and Ramos, suggesting that the genomic rearrangements gain stability by retaining their periodicity. This adds further evidence that the periodic bent DNA plays a crucial role in genomic structure.

Base Sequence↗

PubMed1998

Complications and management of microwave coagulation therapy for primary and metastatic liver tumors.

Microwave coagulation therapy (MCT) has been widely used, both percutaneously and directly, as effective minimal invasive therapy for liver tumors. To facilitate the use of MCT, we describe the complications we have encountered, and their possible management and prophylaxis. MCT was performed for 42 patients with hepatocellular carcinoma (HCC) and for 29 with metastatic liver tumors, following which complications developed in 14.2% and 20.6% of the HCC and metastatic groups, respectively. The complications included abscess, biloma, bleeding, hepatic failure, and dissemination of cancer cells. In the HCC group, the mean value of tumor size and the clinical stage of patients with complications were significantly larger (P = 0.006) and higher (P = 0.032), respectively, than those of patients without complications. The incidence of complications increased significantly when the tumor size was more than 4cm (P = 0.008). Abscesses and bleeding were successfully treated using percutaneous drainage and interventional angiography, respectively, but as the other serious complications were not able to be treated effectively once induced, prophylaxis is important to facilitate MCT. Transcatheter cooling of the intrahepatic bile duct during MCT and the administration of an anticancer agent into the abdominal cavity are recommended to prevent biloma and dissemination, respectively. MCT is indicated for tumors less than 4 cm in diameter to reduce the risk of complications. The prophylaxis and treatment of these complications enhance the safety of MCT.

Aged↗

PubMed1998

Effects of hypokalaemia on arrhythmogenic risk of quinidine in rats.

Plasma potassium concentration plays an important role in the induction of arrhythmia and is closely related to the arrhythmogenicity of various drugs. We quantitatively analyzed the influence of plasma potassium concentration on QT intervals before drug administration and on drug-induced QT prolongation, to estimate the risk of drug-induced arrhythmia under hypokalaemic conditions. The hypokalaemic models were produced by intraperitoneal administration of furosemide and hydrochlorothiazide in male Sprague-Dawley rats. The relationship between the changes in QT intervals and time profiles of plasma quinidine (QND) concentration were analyzed during constant intravenous infusion of QND (10 or 30 mg/kg/h) and post infusion in normal and hypokalaemic rats. The plasma QND concentration reached the therapeutic range (3-7 microg/ml) at the high infusion rate (30 mg/kg/h). No pharmacokinetic differences between normal and hypokalaemic rats were observed. QND induced QT prolongation in parallel with the plasma concentration without hysteresis. Although the potency of QND for QT prolongation was not affected by hypokalaemia, the QT intervals before drug administration were significantly prolonged in hypokalaemic rats (65.90 +/- 1.40 vs 56.60 +/- 0.748 msec, mean +/- SEM, p < 0.0001). Thus, the prolongation of QT intervals before drug administration may act as a risk factor of arrhythmia under hypokalaemic conditions.

Animals↗

PubMed1998

Determinant analysis of IgE and IgG4 antibodies and T cells specific for bovine alpha(s)1-casein from the same patients allergic to cow's milk: existence of alpha(s)1-casein-specific B cells and T cells characteristic in cow's-milk allergy.

In an effort to clarify the etiology of milk allergy from the standpoint of allergen-specific immune reactions, we investigated the determinants of IgE, IgG4, and T cells specific for bovine alpha(s)1-casein from the same individual patients by using its synthetic peptides and cyanogen bromide-digested fragments. Alpha(s)1-casein is a major allergen in cow's milk, and its unique conformation enabled us to investigate the determinants of antibodies without consideration about missing the reactivities because of conformational changes. Nine patients were selected as subjects from among 129 milk-sensitive infants screened by ELISA to assess the anti-alpha(s)1-casein IgE levels in their sera. By using ELISA for epitope mapping, a C-terminal region of alpha(s)1-casein was identified as a common binding site for IgE from all of these patients, whereas those for anti-alpha(s)1-casein IgG4 were located in multiple regions of alpha(s)1-casein. We determined the specificities of seven alpha(s)1-casein-specific T-cell lines established from peripheral blood mononuclear cells of two of the patients. These T cells have been shown to secrete IL-4. All of the T-cell lines had different specificities to alpha(s)1-casein. However, a common amino acid residue use was found among the determinants of various T-cell lines from each patient. The results suggest that patients allergic to cow's milk have characteristic B cells recognizing a limited region of alpha(s)1-casein and secreting alpha(s)1-casein-specific IgE. These B cells may interact particularly with T cells recognizing determinants with a common structure.

Amino Acid Sequence↗

PubMed1998

Expression of transforming growth factor beta1 (TGFbeta1) and its receptors in pancreatic duct cell carcinoma and in chronic pancreatitis.

Transforming growth factor beta1 (TGF beta1) is a multifunctional factor that regulates many aspects of cellular functions such as epithelial cell growth and synthesis of extracellular matrices. TGFbeta transduces signaling through a heterodimeric complex of type I and type II TGFbeta receptors (TbetaRI and TbetaRII). Recently, it has been shown that enhanced expression of TGFbeta1 is associated with the progress of pancreatic duct cell carcinoma (PDC) and chronic pancreatitis (CP). In this study, the expression of TGFbeta1 and its receptors, TbetaRI and TbetaRII, is examined in 21 cases of PDC by immunohistochemistry using specific antibodies, and the results are compared with those for 13 cases of CP. In the epithelial cells of PDC and CP, there are no significant differences in the expression of TGFbeta1, TbetaRI, and TbetaRII. In contrast, stromal expression of this cytokine and its receptors tends to be stronger in PDC than in CP; especially, the expression of TbetaRII is significantly stronger in PDC (p < 0.05). These findings suggest that there are some pathological differences in the properties of stromal reactions between PDC and CP, although the morphologies of their stroma resemble each other.

Aged↗

PubMed1998

Effect of cholinergic blockade on inhibited GH secretion by feeding and intraruminal SCFA infusion in sheep.

The effect of cholinergic blockade on suppressed growth hormone (GH) secretion caused by feeding or the intraruminal infusion of an acetate, propionate, and butyrate mixture (107 and 214 mumol.kg-1.min-1 over 6 h) was examined in ovariectomized ewes. Intraruminal infusion at the rate of 107 mumol.kg-1.min-1 increased peripheral plasma short-chain fatty acid (SCFA) concentrations to approximately the physiological levels noted after feeding. Plasma GH was markedly suppressed by feeding and at both the 107 and 214 mumol.kg-1.min-1 SCFA infusion rates; however, cholinergic blocking agents completely blocked the suppressed GH secretion after feeding and only at the 107 mumol.kg-1.min-1 infusion rate. Plasma glucose increased at both infusion rates, and the plasma free fatty acids decreased after feeding and at both infusion rates. However, both metabolites were unchanged relative to the saline control after the injection of the cholinergic antagonists. It is suggested that the decrease in plasma GH observed after feeding and a near-physiological ruminal SCFA increment is mediated via the parasympathetic nerve and not by pharmacological ruminal SCFA increments attributed to other pathways.

Animals↗

PubMed1998

A new experimental device for the measurement of moisture emission and heat release from respiratory organs and body surface.

A new experimental device was developed to investigate respiratory diseases. The moisture and heat released from respiratory organs and the body surface of a rat were determined by means of this device as well as the rectal temperature. The high recovery of results was statistically confirmed, and the measured values at various environmental temperatures were significantly different from each other. Some standard drugs, such as ephedrine, aminophylline and chlorpromazine, were examined. Their stimulant or depressant actions were clearly observed. The results of some traditional medicines for the treatment of rhinitis and bronchial asthma from this measuring system were consistent with their clinical applications. These results suggest that this new experimental system is not only effective in the experimental understanding of cold-hot syndrome, but also contributes to the evaluation of the effects of traditional medicines.

Animals↗

PubMed1998

[Measurement of fibrinogen binding to platelets by flow cytometry: evaluation method for reflecting platelet activation].

Platelet aggregation, induced by agonist-mediated activation of membrane glycoprotein (GP) IIb/IIIa, and binding of fibrinogen to GPIIb/IIIa, is commonly analyzed using an aggregometer in the clinical laboratories. However, this method has a limitation to get precise results on the samples with small number of platelet (less than 100,000/1) or hyperlipidemia. Recently, flow cytometry has been used to evaluate platelet function due to the detection of fibrinogen binding to activated platelets using fluorescence labeled fibrinogen or anti-fibrinogen antibody. However, the appropriate rule for evaluation of the results has not been established yet. We converted a ratio of fibrinogen binding platelets to a velocity per unit concentration of ADP as follows: a difference of two ratios of fibrinogen binding platelets on neighboring two ADP concentrations was divided by a difference of ADP concentrations. It was considered to be a mean velocity between the two ADP concentrations. We adopted the range of ADP concentration, which gave the maximum velocity, as an index of platelet activation. If the peak of maximum velocity move toward lower or higher ADP concentration, it means hyper- or hypoactivation of the platelets, respectively. The objectivity of this method may make it a useful technique for clinical examination of platelet function.

Adenosine Diphosphate↗