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Biomedical subjects

T Kanno

Publications and source records attributed to T Kanno.

At least 361 records · Page 20Linked to original sources

Carbamazepine-induced systemic lupus erythematosus-like disease.

A 14-year-old female developed systemic lupus erythematosus (SLE)-like symptoms, rash, fever, leukopenia and positive anti-nuclear antibody (ANA) two weeks after administration of carbamazepine (CBZ; Tegretol) used against benign Rolandic epilepsy. Clinical symptoms and leukopenia normalized after discontinuation of CBZ and administration of prednisolone at 40 mg. The cases of CBZ-induced SLE reported in the literature were reviewed.

Adolescent↗

Lactate dehydrogenase (LDH)-linked immunoglobulin in a patient with Graves' disease treated with methimazole.

A 26-year-old woman who received methimazole treatment for Graves' disease is discussed. Two months following treatment, her serum GOT level rose to 45 K.U, her GPT to 60 K.U, and her lactate dehydrogenase (LDH) to 645 W.U; a hepatic disorder was then suspected. Later, the serum GOT and GPT concentrations decreased to a normal range, but her serum LDH continued to maintain a high level. An LDH isoenzyme analysis showed an abnormally broad LDH. The IgG that was linked to the LDH is suspected to have been the result of her underlying autoimmunity, the methimazole treatment, and the development of her hepatic disorder. Thus, this IgG was thought to be the autoantibody to LDH.

Adult↗

Pulmonary C-fibers do not play a role in ammonia-induced brief tachypnea in the rabbit.

To determine the role of pulmonary C-fibers in evoking a brief tachypnea induced by ammonia vapor, we examined the responses of diaphragm electromyogram (DIAP EMG) to ammonia inhalation before and after procaine treatment to the contralateral vagus nerve in urethane-anesthetized, spontaneously breathing rabbits with unilateral vagotomy. Procaine treatment that blocked the conduction of vagal afferent C wave did not significantly alter the response of brief tachypnea to ammonia. Furthermore, the stimulation of pulmonary C-fibers by ammonia inhalation did not coincide with the induction of brief tachypnea. In addition, we also examined the responses of rapidly adapting receptors (RARs) and slowly adapting receptors (SARs) to ammonia inhalation in rabbits, particularly in which inhalation of this chemical gas produced a brief tachypnea. The burst activity of RARs evoked by ammonia inhalation coincided with the phase of rapid shallow breathing for a few breaths. The discharge rates of SARs during both inspiration and expiration increased when ammonia inhalation caused a brief tachypnea. From these results, it can be suggested that the ammonia-induced brief tachypnea is probably mediated by transient stimulation of both SAR and RAR activities but does not occur as a result of the pulmonary C-fiber stimulation.

Adaptation, Physiological↗

Effects of hexamethonium on bradycardiac responses to brain ischemia in the rabbit.

The present study investigated the bradycardiac responses to brain ischemia for approximately 30s before and after intravenous administration of hexamethonium (C6, 15 mg/kg) in urethane-anesthetized spontaneously breathing rabbits. The brain ischemia was performed by clamping both common carotid arteries in rabbits whose vertebral arteries were previously occluded. The brain ischemia caused bradycardia, pressor response and apnea. Administration of C6 blocked the bradycardia evoked by brain ischemia and reduced pressor response at the initial period after the onset of brain ischemia. The brain ischemia-induced apnea was not significantly altered by C6-treatment. In a separate series of experiments, we examined the effects of C6 on the response of heart rate (HR) to vagal stimulation in rabbits following unilateral vagotomy. Electrical stimulation of the peripheral end of the cut left vagus nerve that selectively activated myelinated fibers caused the bradycardia and this effect was entirely blocked by administration of C6. When the intensity of stimulus to activate both myelinated and non-myelinated fibers was increased, part of the bradycardia was retained following C6 administration. These results suggest that the brain ischemia-induced bradycardia is totally mediated through the activation of myelinated efferent fibers in the vagus nerve.

Animals↗

New three-dimensional moving field radiation therapy for brain tumors.

A new modified rotation radiation method called "three-dimensional moving field radiation therapy" is described. The new method uses rotation in many planes while maintaining the the same isocenter to achieve a good spatial dose distribution. This delivers a high dose to tumors and spares the surrounding normal structures. This easy method can be carried out using the equipment for conventional rotation radiation therapy. The new method was superior to the one plane rotation radiation therapy using a physical phantom with film, a chemical phantom using the iodine-starch reaction, and a new biological model using tumor cells. Treatment of six brain tumors irradiated with total air doses of 50-60 Gy caused no hair loss or radiation necrosis.

Animals↗

[Prognostic significance of echogenic lesion within small hepatocellular carcinoma].

To evaluate prognostic significance of echogenic lesion within small hepatocellular carcinoma (SHCC, less than or equal to 2 cm in diameter), clinical and pathological findings of 32 cases with SHCC containing echogenic lesion (echogenic SHCC) were compared with those of 55 cases with non-echogenic SHCC. Compared with the non-echogenic SHCC group, the frequency of clinical stage I was significantly higher, and there were significantly more cases with solitary tumor relative to cases with multiple tumors in the echogenic SHCC group. Histologically, the incidence of the HCC composed of well-differentiated tumor cells corresponding to Edmondson's grade I was significantly higher in the echogenic SHCC group than in the non-echogenic SHCC group. Although HCCs tended to become progressively less differentiated with increasing tumor sizes in the both groups, the process of cellular change appeared to proceed more slowly in the echogenic SHCC group. Survival rate after tumor detection was 73% at three years, 56% at five years and 48% at seven years and nine years in the echogenic SHCC group, while it was 46% at three years, 42% at five years and 0% at seven years in the non-echogenic SHCC group. The present results showed that the presence of echogenic lesion within SHCC could be useful prognostic indicator.

Aged↗

Molecular analysis of genetic mutation in electrophoretic variant of human lactate dehydrogenase-A(M) subunit.

An electrophoretic variant of lactate dehydrogenase-A (M) subunit was discovered in a patient with multiple myeloma. DNA analysis of the variant allele revealed a nucleotide substitution (transition) of C to T at codon 314 (CGT-TGT), and this mutation resulted in the replacement of an arginine by a cysteine (R314C). This amino acid replacement affects the net charge of the subunit and makes the LDH-A variant have a faster electrophoretic mobility. The responsible missense mutation created a new restriction site, AGGCCT, which can be simply detected by endonuclease AatI digestion. In addition, four synonymous substitutions with no amino-acid replacements were found at codons 51, 119, 163 and 175 in the LDH-A gene from the patient.

Aged↗

[Prolongation of circulation time during brain ischemia-induced hypertension in the rabbit].

Circulation time (CT) is markedly prolonged when arterial pressure is extremely elevated by global brain ischemia which elicits also bradycardia, decrease in cardiac output and apnea in anesthetized rabbits. To study the cause of the prolongation of CT, we measured separately CT in the large veins, cardiopulmonary circulation system (CPS) and large arteries by a dye-densitometer before and during the brain ischemia, and also examined effects of apnea and bradycardia on CT in the large veins and CPS. CT during the brain ischemia was prolonged in each portion as compared to that before the brain ischemia. The prolongation was shortest in the large veins and longest in the CPS. During the brain ischemia with apnea, there was a significant linear relationship between heart rate and the inverses of CT in the large veins, but not in the CPS. When artificial ventilation was performed during brain ischemia-induced apnea, the linear relationship became significant also in the CPS. We conclude as follows; During global brain ischemia the prolongation of CT occurs primarily in the large arteries due to constriction of the small arteries and it progresses towards the CPS and large veins. The bradycardia prolongs CT in the large veins and CPS, and the apnea may produce hypoxic pulmonary vasoconstriction which may also contribute to the prolongation of CT in the CPS.

Animals↗

[The clinical usefulness of the molar ratio of branched-chain amino acids to tyrosine (BTR) in discriminating stage of chronic liver diseases].

We determined the molar ratio of branched-chain amino acids to tyrosine (BTR) in plasma and in serum by enzymatic method and compared it with Fischer ratio (the molar ratio of branched-chain amino acids to tyrosine and phenylalanine) in plasma obtained by conventional HPLC method. BTR in plasma and in serum was well correlated with plasma Fischer ratio. The normal range (mean +/- 2SD) of BTR was determined to be 4.41-10.05 in 210 normal subjects. In addition, we investigated the distribution of BTR values in patients with various liver diseases. BTR value decreased according to the severity of liver disease. We evaluated the clinical usefulness of BTR in patients with chronic liver diseases by cumulative distribution analysis (CDA) graph and receiver operating characteristic curve (ROC) analysis. The area under the curve for BTR analyzed by ROC for CH versus LC.HCC group was the highest (86.3%) of any for various concurrently-measured liver function tests, and was significantly higher than AST/ALT, ALT, AST, gamma-GT (each, p less than 0.001) and ALB (p less than 0.05). These diagnostic results showed that BTR is a superior indicator in discriminating between liver cirrhosis and chronic hepatitis.

Adult↗

Analysis of genetic mutations in human lactate dehydrogenase-A(M) deficiency using DNA conformation polymorphism in combination with polyacrylamide gradient gel and silver staining.

Human lactate dehydrogenase (LDH)-A mutant gene was analyzed by polymerase chain reaction - DNA conformation polymorphism (DCP). We used polyacrylamide gradient gel and silver staining procedures for DCP analysis and observed abnormal migration patterns in individuals heterozygous for LDH-A deficiency. Further sequence determination of the mutant alleles consistently resulted in detection of base substitutions, a G to T transversion at codon 328 (GAG----TAG), and synonymous substitutions at codon 115, 160 and 172. Such mutations were easily detectable using the DCP technique. The DCP technique using the polyacrylamide gradient gel and silver staining method seems likely to be useful for the rapid screening of mutations and for further genotype detection.

Amino Acid Sequence↗

Respiratory tract gene transfer. Transplantation of genetically modified T-lymphocytes directly to the respiratory epithelial surface.

To evaluate the strategy for potentially treating respiratory disorders with genetically modified T-lymphocytes, the interleukin-2 (IL-2)-dependent murine T-cell line, CTLL2, was genetically altered with the Escherichia coli beta-galactosidase (beta-gal) gene (lacZ) in vitro with a retroviral vector and the modified T-cells were transplanted directly to the respiratory epithelial surface of syngeneic C57Bl/6 mice. Southern and Northern analyses confirmed that the neomycin-selected modified T-cells contained and expressed the lacZ gene. The fate of the modified T-cells (CTLL2/lacZ) was followed by flow cytometry with T-cell surface marker Thy1.2 and fluorescent beta-gal analysis. One day after transplantation (7.5 x 10(5) CTLL2/lacZ T-cells/g of body weight), 95 +/- 3% of the Thy1.2+ T-cells recovered from respiratory epithelial lining fluid (ELF) were beta-gal+. Importantly, the modified T-cells remained in the lung for some time; at 3 days, Thy1.2+ beta-gal+ T-cells represented 63 +/- 12% of ELF Thy1.2+ T-cells and 59 +/- 6% of Thy1.2+ T-cells recovered from the whole lung. At 7 days, 33 +/- 8% of the Thy 1.2+ cells in ELF and 75 +/- 6% of the Thy1.2+ cells in whole lung were Thy1.2+ beta-gal+. In contrast, the proportion of the Thy1.2+ beta-gal+ T-cells in the spleen, the major extrapulmonary lymphatic organ, never rose above 3 +/- 1% of the total Thy1.2+ cells. The number of Thy1.2+ beta-gal+ T-cells in the lung could be modified by the systemic administration of IL-2, with whole lung Thy1.2+ beta-gal+ T-cells increasing 4.6-fold 3 days after transplantation, compared with non-IL-2-treated animals. These studies suggest that direct transplantation of genetically modified T-cells into the lung is feasible and represents a viable strategy for lung-specific gene transfer.

Animals↗

Genotypic analysis of families with lactate dehydrogenase A (M) deficiency by selective DNA amplification.

Genomic DNA prepared from LDH-A-deficient whole blood was amplified by the polymerase chain reaction technique using two primers specific for the active human LDH-A gene. The amplified fragment was examined by direct agarose gel electrophoresis, and a deletion of 20 base pairs (bp) in exon 6 of the LDH-A gene was found. The results permitted a clear distinction between the homozygous mutant, the heterozygous mutant, and wild-type genotypes. Moreover, HinfI digestion and direct sequencing of the amplified product confirmed the results from direct agarose gel electrophoresis. Four families, including 18 individuals, were shown to contain the same mutation, that is a 20-bp deletion in exon 6. All genotypes were consistent with their biochemical phenotypes as evaluated by the ratio of LDH-B to LDH-A subunits in erythrocytes. Thus, all four known affected families in Japan have been shown to carry the same mutant gene, which may have been derived from a single mutational event.

Amino Acid Sequence↗

Elevation of resting fluid secretion precedes trophic responses in the rat pancreas following a single oral administration of Camostat.

A single dose of the synthetic proteinase inhibitor, Camostat (FOY-305; 100 mg/kg), was administered orally to rats. Pancreata were isolated and then perfused to examine the change in the level of resting fluid secretion. As early as 6 h after administration of the single dose of Camostat, the resting fluid secretion was significantly elevated. Twelve hours after administration, resting fluid secretion was maximally elevated, whereas contents of trypsinogen, chymotrypsinogen, and amylase per DNA in the pancreas were significantly decreased. After 12 h, the level of resting fluid secretion gradually decreased to the control resting level in contrast to significant increases in contents of the pancreatic enzyme and zymogens, and wet weight in acinar cells. We further examined the mechanism mediating the elevated resting fluid secretion. Our results are compatible with the view that the elevation of resting fluid secretion may be maintained by spontaneous activation of ion transporters: an ouabain-sensitive Na-K ATPase, an amiloride-sensitive Na-H antiporter, and a unique Cl transporter that is insensitive to furosemide, bumetanide, SITS, and DNDS.

Administration, Oral↗

BHV-1 adsorption is mediated by the interaction of glycoprotein gIII with heparinlike moiety on the cell surface.

The gIII glycoprotein of bovid herpesvirus 1 (BHV-1) has been shown to mediate the adsorption of the virions to cells (K. Okazaki, E. Honda, T. Minetoma, and T. Kumagai, 1987, Arch. Virol. 97, 297-307). In this study, the cellular receptor for BHV-1 was investigated. Addition of heparin to the virus inoculum and treatment of the cells with heparinase prevented the virus from adsorbing to and infecting the cells. Of the major glycoproteins of BHV-1 only gIII was found to bind specifically to heparin. The binding of gIII was inhibited by a monoclonal antibody against antigenic site Ia, which interferes with the adsorption of the virus. These findings indicate that the virus adsorption to cells is mediated by interaction of the gIII antigenic site Ia with a heparinlike moiety on the cell surface, which serves as a receptor for BHV-1.

Adsorption↗

Dose-dependency in spatial dynamics of [Ca2+]c in adrenal chromaffin cells.

The spatial dynamics of cytosolic Ca2+ concentration, [Ca2+]c, in guinea pig adrenal chromaffin cells was monitored by a digital image analysing technique using Fura-2. When a freshly isolated cluster of cells was stimulated with lower concentrations of carbachol (CCh; 0.3-1 microM), the [Ca2+]c began to increase in the region beneath the plasma membrane facing the extracellular environment. The [Ca2+]c increase depended on the presence of extracellular Ca2+ ([Ca2+]o). CCh at a higher concentration (100 microM), however, caused [Ca2+]c increase even in the absence of [Ca2+]o. These results are compatible with the view that the receptor activation with a physiological concentration of secretagogue accelerates Ca2+ entry, and that stimulation with a higher concentration of the secretagogue induces small transient Ca2+ release from intracellular stores and predominant continuous Ca2+ entry.

Animals↗