Biomedical subjects
Publications and source records attributed to H Katoh.
A new set of rat RI strains consisting of 11 independent strains and 13 of their substrains was established by inbreeding F2 rats between F344/DuCrj and LE/Stm. The strain distribution pattern was examined for 66 microsatellite loci, 8 biochemical genetic markers, 2 histocompatibility loci, and 2 coat color genes. A rat salivary protein gene Spe1 was newly mapped on Chr 1.
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cotA of Synechocystis sp. strain PCC6803 is a gene involved in light-induced proton extrusion (A. Katoh, M. Sonoda, H. Katoh, and T. Ogawa, J. Bacteriol. 178:5452-5455, 1996). There are two possible initiation codons in cotA, and either long (L-) or short (S-) cotA encoding a protein of 440 or 247 amino acids could be postulated. To determine the gene size, we inserted L-cotA and S-cotA into the genome of a cotA-less mutant (M29) to construct M29(L-cotA) and M29(S-cotA), respectively. M29(L-cotA) showed essentially the same net proton movement profile as the wild type, whereas no light-induced proton extrusion was observed with M29(S-cotA). Two kinds of antibodies were raised against partial gene products of the N- and C-terminal regions of L-cotA, respectively, fused to glutathione S-transferase expressed in Escherichia coli. Both antibodies cross-reacted with a band at 52 kDa in both cytoplasmic and thylakoid membrane fractions of the wild-type cells. The same cross-reacting band was present in the membranes of M29(L-cotA) but not in M29 or M29(S-cotA). These antibodies cross-reacted more strongly with the cytoplasmic membrane fraction than with the thylakoid membrane fraction. The antibody against NrtA, a nitrate transporter protein present only in the cytoplasmic membrane, also cross-reacted with the thylakoid membrane fraction strongly. Based on these results we concluded that CotA of 440 amino acids (51 kDa) is located in the cytoplasmic membrane. Whether CotA is absent in the thylakoid membrane remains to be solved.
Cytosolic Ca2+ and protein kinase C (PKC) may regulate the myogenic contraction of arterial myocytes. The role of these second messengers is examined in skeletal muscle small arteries, which have strong myogenic activity, and mesenteric small arteries, which have weak myogenic activity. The vessels were isolated and cannulated. The inner diameter was measured with a video-digitizing system. Cytosolic Ca2+ concentration was assessed by fura 2. Skeletal muscle small arteries dilated from 122 +/- 6 to 153 +/- 6 microm immediately after the transmural pressure change from 40 to 100 mmHg and constricted to 121 +/- 5 microm (myogenic contraction) with an increase in the 340/380 fluorescence ratio (by approximately 33%) in control vessels. Nifedipine abolished myogenic contraction and the increase in the fluorescence ratio. PKC inhibitors (H7 and staurosporine) abolished myogenic contraction but did not depress the increase in the fluorescence ratio. In mesenteric small arteries, myogenic contraction was insignificant in control vessels. A relatively low dose of PKC activator (4.4 +/- 1.4 nmol/l) elicited myogenic contraction, but a higher dose (21 +/- 6 nmol/l) depressed it. Thus the cytosolic Ca2+ increase and PKC activity may cooperatively act on the myogenic contraction of skeletal muscle small arteries. The activity of PKC should play an important role in myogenic contraction of rat small arteries.
We report 7 patients with severe acute asthma unresponsive to standard medication, including sympathomimetic agents, aminophylline and corticosteroids, who responded to inhaled frusemide. All were hypercapneic with a mean PaCO2 of 7.7 kPa (57.7 mm Hg) [range 6.2-8.8 kPa (46.2-66.3 mm Hg)]. Following nebulization of 20 mg frusemide, clinical response was rapid, and the mean PaCO2 fell significantly to 5.4 kPa (40.6 mm Hg) [range 5.0-6.2 kPa (37.5-46.5 mm Hg)] within 20-60 min. No adverse effect was recognized. Inhaled frusemide should be considered for treatment of acute asthma refractory to conventional therapy.
A 72-year-old man was admitted with palpitations caused by sustained ventricular tachycardia. He had been followed for 27 years, with admissions on 7 occasions, on account of ventricular tachycardias, atrial fibrillation, and congestive heart failure. Electrophysiologic examination detected 2 points of origin of ventricular tachycardia in the right and left ventricles. During the examination a myocardial infarction led to death. At autopsy, most areas of the right ventricle and the left ventricular apex were found to have been replaced by fatty tissue, pointing to severe fatty infiltration into the myocardium. Thus, this patient represented a unique cause of arrhythmogenic right ventricular dysplasia (ARVD) with severe fatty degeneration causing progression of ARVD. It is important that a diagnosis of ARVD is made carefully and rigorously in elderly subjects.
The kinetics of global use-dependent conduction slowing produced by sodium channel blockers in the human heart, estimated as a change in the QRS width, are known to be similar to those of use-dependent block of the maximum rate of depolarization in in vitro studies. However, the kinetics of the regional use-dependent decrease in conductivity have not been investigated. We examined whether the rise time of the monophasic action potential would be clinically useful as a marker of the local use-dependent decrease in conductivity by sodium channel blockers. In 12 patients without organic heart disease, monophasic action potentials (MAPs) were recorded at the right ventricular endocardium using a contact electrode before and after the administration of disopyramide (n = 6, 2 mg/kg, i.v.) or pilsicainide (class Ic agents, n = 4, 1 mg/kg, i.v., and n = 2, 150 mg, po) while the stimulus frequency was abruptly increased from 100/min to 150/min. The rise time, defined as the interval from the pacing pulse to the first peak deflection of the monophasic action potential, and the ORS width were measured simultaneously. In the absence of the sodium channel blockers, the abrupt increase in heart rate did not alter the QRS width or the rise time. In the presence of the agents, both variables were lengthened exponentially. The rate constants of onset changes in the QRS width and the rise time were 2.1 +/- 0.5 beats and 2.1 +/- 0.4 beats after the administration of disopyramide, and 7.5 +/- 3.0 beats and 8.2 +/- 4.0 beats after pilsicainide, respectively. The rate constant of the rise time was closely correlated with that of the QRS width. The present results are very closely comparable with the onset rate constants of use-dependent block of the maximum rate of depolarization in in vitro studies. These results suggest that (1) the rise time is a good indicator of local use-dependent decrease in conductivity by sodium channel blockers in human hearts and (2) the local use-dependent decrease in conductivity has kinetics similar to those of use-dependent sodium channel blocks.
Human tumour xenografts (HTXs) are a useful tool for animal experiments especially for evaluation of new antitumour drugs. We have been establishing HTXs, and have developed tumour chemosensitivity panels for new drug evaluation using them. With regard to quality control (problems in changes into mouse-type tumours and/or artificial cross-contamination among tumour lines), we studied genetic profiling, and effects of long-term passaging on tumour properties such as growth and chemosensitivities, and we discuss the use of cryopreservation stock of HTXs and periodic replacement in order to maintain reproducibility of the experimental results. We examined isozyme markers and DNA fingerprinting to identify species and individuality of the tumours, respectively. Growth curves and sensitivities to antitumour drugs were examined using HTXs with different passaging in nude mice. Among the tumours we maintained, five human tumours were found to have changed to mouse origin from their isozyme markers and were excluded. We identified the individuality of tumours which we used for the chemosensitivity panels by DNA fingerprinting, and their properties were stable for long-term passaging in nude mice. However, growth speed and chemosensitivities to drugs were altered with long-term passaging, although DNA fingerprint analysis did not show any obvious changes with passaging. Genetic profiling, such as isozyme markers and DNA fingerprinting, is useful to identify individuality of experimental HTXs, and tumours should be renewed periodically even when there are no signs of artificial contamination when they are used in experiments which require continuous reproducibility of experimental results.
Chemoradiotherapy combined with hyperthermia was administered to 35 patients with advanced esophageal carcinoma who either required preoperative treatment or had nonresectable disease. As a rule, each patient received a total dose of 30 Gy in 15 daily fractions of 2 Gy, 5 d/wk. Bleomycin or cisplatin, in combination with fluorouracil, was employed as chemotherapy. Hyperthermia was applied by intraluminal heating twice a week for a total of six sessions using an apparatus (IH-500T; Japan Crescent Co Ltd; Tokyo, Japan) (radiofrequency, 13.56 MHz) with an intraesophageal applicator and two extracorporeal applicators placed on the chest and back. This treatment method obtained a response rate of 80%, consisting of a complete response rate of 22.9% and partial response of 57.1%. In 15 cases, the tumor became resectable (resectability rate, 42.9%) following treatment. The histologic study of the resected specimens revealed absence of viable tumor cells in five patients (33.3% of the resected cases) (markedly effective), and in six patients (40.0%), the combined therapy was considered to be moderately effective. No complications considered due to hyperthermia itself were recognized. The overall 5-year survival rate was 11.8%. In conclusion, chemoradiotherapy combined with hyperthermia was locally effective, yielding an overall response of 80.0%. However, the prognosis of the patients remains unfavorable. Advanced esophageal carcinoma requires treatment taking into account lymphatic and hematogenic metastasis at the beginning of treatment.
Eleven children, 4 males and 7 females, with biliary atresia receiving living related liver graft were studied. The mean age was 1.8 years and the mean body weight was 10.3 kg. The donors were 4 fathers and 7 mothers. The graft was the lateral segment or left lobe. ABO blood group matching was compatible in 9 and incompatible in 2. All patients except one were crossmatch negative. Immunosuppression at induction was triple therapy (cyclosporine, azathioprine and steroid) or FK506 plus steroid. Acute rejection episodes were treated with pulse steroids. When the signs of rejection persisted despite steroid pulse therapy, 15-deoxyspergualin (DSG) was added. The survival rate of the patients was 73%. Three patients died of portal vein thrombosis, hepatic artery thrombosis and sepsis respectively. Other major complications included hyperbilirubinemia, bile duct stenosis, bile leakage and portal vein anastomosis narrowing. Complications of the donor were sepsis in one, and liver dysfunction in two. Although there are some complications related to graft size mismatch and operative procedure, living related partial liver transplantation is an effective therapy in countries where donor source is restricted.
BUF/Mna (B) rat is a mutated strain, having much larger thymus than WKY/ NCrj (W), ACI/NMs (A), and F344 (F) rats throughout their life-span. Rats of the latter 3 strains have normal sized thymuses, being less than 5.3 in the thymus to body weight ratio (mg/g), when they were killed at 6 weeks of age. Genetic segregation of large thymus size in the B strain at 6 weeks of age was studied by crossing B rats with W, A or F rats. All of 3 types of the F1 hybrid rats between the B strain and the other strains showed intermediate thymus ratios between those of both parental strains. In F2 rats between the B and W strains, the distribution of thymus ratios showed about 5 different peaks. These findings might indicate that two polymeric autosomal loci, thymus enlargement-1 (Ten-1) and thymus enlargement-2 (Ten-2), can enlarge the thymus size in B rats. Histometrically, whole thymus and cortex areas of the B rats were 2-5 times larger than the W rats during 6-12 weeks of age, but medulla areas were slightly different between the strains, showing that larger thymuses in B rats were mainly due to the enlarged cortex areas.
We investigated the expression of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) on alveolar macrophages and on lung tissue in the early stage of radiation-induced lung injury. Cells in the bronchoalveolar lavage and lung tissue were obtained from rats at various times between 1 and 8 weeks after 20 Gy of 60Co gamma irradiation of a hemithorax. These specimens were stained immunohistochemically with anti-ICAM-1 and anti-LFA-1alpha monoclonal antibodies. The expression of these factors was compared with that of a control group. The total number of alveolar macrophages in the bronchoalveolar lavage was significantly reduced from 1 to 3 weeks, and the number of neutrophils was significantly increased 2 and 3 weeks after irradiation. ICAM-1 and LFA-1 expression on alveolar macrophages was significantly increased starting 1 week after irradiation. The expression of ICAM-1 and LFA-1 on lung tissue was not elevated up to 8 weeks after irradiation. In conclusion, the increased expression of ICAM-1 and LFA-1 on alveolar macrophages as early as 1 week after irradiation suggests that adhesion molecules play a role in the development of radiation-induced lung injury.
We report here a unique case of acute-onset dementia caused by a posterior fossa dural arteriovenous fistula (AVF), which was successfully treated by surgical resection of the isolated transverse-sigmoid sinus combined with endovascular procedures. A 70-year-old female was admitted to our hospital with acute-onset dementia and pulsatile tinnitus on the left side. CT scan revealed a low-density area in the parieto-temporal region. Cerebral angiography revealed a dural AVF of the transverse-sigmoid sinus with retrograde drainage into cerebral cortical veins. After transarterial endovascular embolization of the dural AVF, a xenon-CT scan revealed increased cerebral blood flow. Four months postoperatively, however, she was admitted to our hospital again with seizure and aphasia due to recanalizaion of the dural AVF. After trans-arterial embolization, transvenous embolization was attempted, but was unsuccessful due to inaccessibility of the isolated sinus segment. Since this patient could not be cured by endovascular embolization, an open surgical resection of the isolated sinus segment was performed. Following this, CT scans revealed that the low density area present on the first admission had disappeared. The patient's dementia resolved postoperatively. We discuss the pathophysiological mechanism by which venous ischemia due to dural AVF can cause reversible dementia.
Dahl-Iwai salt-sensitive (S) and salt-resistant (R) rat strains were established as inbred strains at Brookhaven National Laboratory, NY, and were introduced into Eisai Co., Ltd., Japan, and designated DIS/Eis and DIR/Eis. To examine whether there are different allele distributions among the substrains of inbred Dahl S and R rats, we determined biochemical and immunological alleles of DIS/Eis and DIR/Eis, and SS/Sea and SR/Sea, which were derived from SS/Jr and SR/Jr, which were developed by Rapp and Dene. Several differences of allele distribution were observed, indicating that the substrains have different genetic backgrounds. The phenotypic differences between the substrains, such as the severity of the hypertension induced, could be ascribed to the different genetic backgrounds.
We sought to determine whether nuclear magnetic resonance relaxation times of water in tissue would be useful to detect molecular damage in lung tissue within 2 weeks after irradiation. Tissue samples were obtained from the lungs of rats at various times between 1 and 14 days after exposure of a hemithorax to 20 Gy 60Co gamma irradiation. The spin-lattice relaxation time, T1, was measured by the inversion recovery method, and the spin-spin relaxation time, T2, was measured by both the Hahn spin-echo (Hahn T2) and the Carr-Purcell-Meiboom-Gill (CPMG T2) methods. The T2 of lung tissue could be divided into two components, T2 fast (T2f) and T2 slow (T2s), which reflected changes in the intracellular and extracellular water, respectively. The CPMG T2f increased significantly 3 days after irradiation (66.3 +/- 2.3 ms compared to 60.8 +/- 2.6 ms), and the CPMG T2s increased significantly 1 day after irradiation (155 +/- 11 ms compared to 138 +/- 7 ms), prior to the observation of abnormalities upon examination of the lung by light microscopy. The CPMG T2 values increased further up to 14 days after irradiation when significant increases were observed in values for T1, Hahn T2 and water content. Our results indicate that the molecular derangement in irradiated lung tissue was detected by the CPMG T2 measurement in the very early stage, and that MRI may be superior to conventional radiographs for detecting the early damage to lung tissue after irradiation.
Sixteen cases of primary lung cancer in patients younger than 40 years old had been operated on at the department. There were 8 males and 8 females and the male-to-female ratio was 1:1 that was closer than the ratio in elder patients over 40 years. Histologic types were adenocarcinoma in 7 cases, squamous carcinoma in 5 cases, carcinoid in 2 cases, and small cell carcinoma in 2 cases. In younger patients, adenocarcinomas, small cell carcinomas, and carcinoids were more commonly found than squamous cell carcinomas. Patients in stage I, II, and IIIA and those undergoing a curative resection were predominant in cases without any symptoms preoperatively. The 5-year survival rate of the 16 patients younger than 40 years was 42.9%, that was not significantly different from that of elder patients over 40 years old. This relatively better prognosis might be owing to a fact that operated patients were dominantly composed of asymptomatic patients. In younger patients who have good physical status and respiratory function compared with elder patients, aggressive surgical diagnosis followed by resection, if the definitive diagnosis of malignancy is established may contribute to the improvement of prognosis for patients who was suspected of having malignancy.
Prostaglandin E receptor EP3 subtype is widely distributed in the nervous system and is specifically localized to neurons, suggesting that the EP3 receptor plays important roles in the nervous system. We established a PC12 cell line that stably expresses the EP3B receptor isoform isolated from bovine adrenal chromaffin cells and examined the effect of agonist stimulation on the neuronal morphology of the PC12 cells. In the differentiated cells, M&B28767, an EP3 agonist, caused neurite retraction in a pertussis toxin-insensitive manner. 12-O-Tetradecanoylphorbol-13-acetate (TPA) also induced neurite retraction. However, when protein kinase C was down-regulated by long term exposure to TPA, TPA failed to induce neurite retraction, while the EP3B receptor-mediated retraction occurred normally. Clostridium botulinum C3 exoenzyme completely inhibited both EP3 agonist- and TPA-induced neurite retraction when microinjected into the cells, indicating that the morphological effect of the EP3B receptor is dependent on Rho activity. Thus, the activation of the EP3B receptor induced neurite retraction through a protein kinase C-independent Rho-activation pathway.
Hyperbaric oxygen (HBO; 100% oxygen at 2 atmospheres absolute) was administered for 1 h to male Mongolian gerbils either for a single session or every other day for five sessions. Two days after HBO pretreatment, the gerbils were subjected to 5 min of forebrain ischemia by occlusion of both common carotid arteries under anesthesia. Seven days after recirculation, neuronal density per 1-mm length of the CA1 sector in the hippocampus was significantly better preserved in the five-session HBO pretreatment group (n = 10: 175.7 (47.8/mm, 54.9% of normal) than in the ischemic control group (n = 10: 26.2 (11.6/mm, 8.0% of normal) and in the single-session HBO pretreatment group (n = 7: 37.3 (21.7/mm, 11.4% of normal). Immunohistochemical staining for the 72-kDa heat-shock protein (HSP-72) in the CA1 sector performed 2 days following pretreatment revealed that the five-session HBO pretreatment increased the amount of HSP-72 present compared with that in the ischemic control group and in the single HBO pretreatment group. These results suggest that tolerance against ischemic neuronal damage was induced by repeated HBO pretreatment, which is thought to occur through the induction of HSP-72 synthesis.