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Biomedical subjects

T Mitsuhashi

Publications and source records attributed to T Mitsuhashi.

At least 109 records · Page 6Linked to original sources
PubMed1991

[Alteration of leukotriene C4 levels in experimental spinal cord injury].

Leukotriene C4 (LTC4) production in the guinea pig spinal cord following compression injury was determined by radioimmunoassay, in the same way thromboxane B2 (TXB2), a stable metabolite of thromboxane A2 (TXA2), was also measured. When the spinal cords were compressed under a 20 gram weight for 10 minutes, LTC4 levels reached peak values (2.2 +/- 0.4 pmol/g cord) 10 minutes after release, then gradually decreased until being undetectable 60 minutes later. TXB2 levels reached peak values (146.8 +/- 6.2 pmol/g cord) 5 minutes after the release from compression, the TXB2 level then gradually decreased, but remained at about 1/2 of the peak level even 60 minutes after the release. When the spinal cords were compressed with various weights, TXB2 production depended on the degree of compression, while LTC4 production was not affected by the compression injury. The LTC4 production confirmed in the injured spinal cords is suggestive of its relation to secondary disorders after spinal cord injury, spinal edema, in particular.

Animals↗
PubMed1991

Agonistic activities of histamine-albumin conjugates at histamine H2 receptors on human HL-60 promyelocytic leukemia cells.

We previously identified functional histamine H2 receptors on human HL-60 promyelocytic leukemia cells [J. Biol. Chem. 264: 18356-18362 (1989)]. In the present study, we have compared the action of histamine-albumin conjugates on H2 receptor activation with that of histamine alone. Both histamine and conjugates increased intracellular levels of Ca2+ in an H2 receptor-specific manner. However, binding of fluoresceinated histamine-albumin conjugates to HL-60 cells was not dissociated by 10(-4) M unlabeled histamine, although this concentration of histamine significantly desensitized conjugate responses. These data suggest that histamine-albumin conjugates not only activate H2 receptors but also bind to HL-60 cells nonspecifically or in an H2 receptor-unrelated manner. Moreover, histamine-induced Ca2+ mobilization was transient, whereas conjugate-induced Ca2+ mobilization was sustained for more than 10 min, as a result of the influx of extracellular Ca2+. Therefore, the functional difference between histamine and conjugates may provide a good model for the further understanding of the activation mechanisms of receptor-operated Ca2+ influx.

Albumins↗
PubMed1991

[A case report of aortic stenosis complicated with complete atrioventricular block].

A case of aortic stenosis complicated with complete atrioventricular block preoperatively was reported. The patient was a 73-year-old woman who had been suffering from dyspnea and fatigability. Preoperative echocardiography revealed severe left ventricular hypertrophy, marked left ventricular-aortic pressure gradient (144 mmHg), and the impairment of left ventricular distensibility. Therefore, DDD pacemaker was implanted in addition to aortic valve replacement. Postoperative cardiac catheterization revealed that cardiac output was increased about 25% by DDD pacing compared with VVI pacing. It is more reasonable to employ DDD pacemaker to the case of which distensibility is impaired.

Aged↗
PubMed1990

Identification of a thyroid hormone response element in the malic enzyme gene.

We have studied the rat malic enzyme gene as a model for thyroid hormone (triiodothyronine (T3)) regulation of transcription. Our previous studies showed that transcription of this gene is controlled by T3 in vivo. In this study, we used COS-7 cells in culture to determine the location of a T3 response element (TRE) within this gene. Cotransfection of the rat T3 alpha-receptor cDNA with a reporter gene linked to 5'-deletion mutants of the malic enzyme gene 5'-flanking region revealed the presence of a TRE between positions -315 and -248. Using T3 receptors synthesized in vitro from their cDNAs, we have identified, through the use of gel shift assays and footprinting, a single DNA-binding site (positions -281 to -261) for the receptor within the rat malic enzyme gene TRE. The site was capable of binding either the rat alpha- or human beta-receptor with similar affinities. Competition binding studies indicated that the apparent affinity of receptor binding to the malic enzyme gene was similar to that of the rat alpha-myosin heavy chain gene TRE (positions -151 to -122) and was significantly greater than that of the rat growth hormone TRE (positions -192 to -163). These results indicate that both the alpha- and beta-forms of the nuclear T3 receptor are capable of binding directly to the malic enzyme gene 5'-flanking region at a site which functions as a hormone-inducible cis-regulatory element. In conjunction with our previous finding that T3 induces or activates essential transcription factors which bind to the promoter, it appears that the regulation of transcription of the malic enzyme gene by thyroid hormone involves at least two regulatory pathways.

Animals↗
PubMed1990

[A physiological study of the effect of vibration on reflexive control of cats' larynx: the changes in respiratory phase and the role of internal branch of superior laryngeal nerve].

It is generally considered that the vocal cord is finely and reflexively controlled during phonation. In order to investigate the effect of vibratory stimulation of the subglottis on laryngeal reflex, experiments have been performed using cats' larynx under urethane-chloralose general anesthesia. The effect of vibration was estimated by the latency and the area of integrated EMG of the reflex. The glottic closure reflex was induced by electrical stimulation of the internal branch of the superior laryngeal nerve (ISLN) and electromyogram was recorded from contralateral Thyroarytenoid muscle (TA). When ISLN was stimulated, short latency response (early response) and long latency response (late response) in TA was observed. Maximum responses were obtained during the transitional phase, namely, from inspiration to expiration, especially before the denervation of ISLN from the larynx. This phase was tentatively designated as "phase I", being followed by "phase II", the phase prior to "phase I", as "phase III". Vibratory stimulation (100 or 200Hz, 40 microns), applied to the contralateral subglottic portion as a conditioning stimulation, had no effect on early response but enhanced late response, particularly in phase I. After denervation of ISLN, the vibratory effect on late response became phase independent. Furthermore, when the vibratory frequency was elevated from 100Hz to 350Hz at 50Hz interval in phase I, vibration effect was observed in all frequencies investigated. Maximum effect was obtained at 300Hz. However, after denervation of ISLN, this effect was minimized, and no peak observed. The vibratory effects disappeared soon after local anesthesia of the subglottic mucosa. These results suggest that the activity of the mechanoreceptors to vibration in the subglottic mucosa enhances reflexive contraction of the contralateral TA primarily via the recurrent laryngeal nerve and partially via ISLN, both of which are indispensable for reflexive laryngeal control. It is conceivable that early response is one of the primitive reflexes for the protection of the lower airway, and late response is a sort of more evolved reflexes involved in vibration and respiration during phonation.

Animals↗
PubMed1990

Esophageal cancer complicated by acute myelofibrosis--report of an autopsy case.

An autopsy case of esophageal cancer complicated by myelofibrosis was studied. A 62-year-old Japanese patient with esophageal cancer, received surgical treatment and then splenectomy. The resected spleen was normal in appearance. Five months later he received radiation therapy for the cancer. After the therapy, his blood profile revealed thrombocytopenia and leukoerythroblastosis, and the bone marrow punctures were dry tap. He died of disseminated fungal infections at eleven months after the first operation. An autopsy of the patient revealed a striking increase in the megakaryocytes and a moderate increase in the reticulin fibers in the bone marrow. Myeloid metaplasia was noted in the lymph nodes, kidneys, and other organs and tissues, although the lymph nodes were not grossly swollen. These findings suggest esophageal cancer complicated by acute myelofibrosis. This it the first case report on esophageal cancer complicated by acute myelofibrosis.

Acute Disease↗
PubMed1990

[An early cancer of the descending colon, histologically showing a poorly differentiated adenocarcinoma].

Reported is the case of a 71 year-old male with a poorly differentiated adenocarcinoma of the colon that had invaded the submucosal layer. A barium enema had revealed a polyp, 1.5 cm in diameter, in the descending colon, and an endoscopic polypectomy was performed. The resected specimen mainly consisted of an adenoma and a partial, poorly differentiated adenocarcinoma that had massively infiltrated into the submucosal layer. A left hemicolectomy was carried out, and no carcinoma was identified in the resected colon and/or the regional lymph nodes.

Adenocarcinoma↗
PubMed1990

IgA myeloma complicated by fractures of the bones and hyperviscosity syndrome--report of an autopsied case.

A case of IgA (kappa type) myeloma complicated by fractures of the bones and hyperviscosity syndrome is presented. A 56-year-old woman who had been followed as an outpatient with diabetes mellitus for about 16 years, developed multiple myeloma. She also showed symptoms and signs of hyperviscosity syndrome; hemorrhagic diathesis, blurred vision and episodes of transient ischemic attacks of the brain, and fractures of the bones by small powers of trauma. At autopsy, almost all bones showed infiltration of multiple myeloma of IgA-kappa type and severe osteoporosis accompanied with proliferation of osteoclasts. The association of IgA myeloma with hyperviscosity syndrome and/or bone destruction was discussed. The "serum hyperviscosity syndrome" has been described clinically as the triad of bleeding, visual signs and symptoms, and neurologic manifestations. And this syndrome has been associated frequently with macroglobulinemia of Waldenström, occasionally with immunoglobulin (Ig) G myeloma, rarely with IgA myeloma, and with other dysproteinemia. Myeloma is also characterized by extensive bone destruction and is accompanied by susceptibility to fracture, although Waldenström's macroglobulinemia, acute leukemia or chronic leukemia are rarely associated with bone resorption. The present report describes a patient with IgA myeloma complicated by hyperviscosity syndrome and multiple bone fractures.

Blood Viscosity↗
PubMed1989

Multiple signaling pathways of histamine H2 receptors. Identification of an H2 receptor-dependent Ca2+ mobilization pathway in human HL-60 promyelocytic leukemia cells.

In order to analyze the complex activities of histamine H2 receptor activation on neutrophils, human HL-60 promyelocytic leukemia cells were differentiated into neutrophils by incubation with dimethyl sufoxide, loaded with the Ca2+-sensitive indicator dyes, indo-1 or fura-2, and the levels of intracellular Ca2+ ([Ca2+]i) measured in a fluorescent-activated cell sorter and fluorimeter, respectively. Histamine increased [Ca2+]i in a dose-dependent manner with a half-maximal concentration (EC50) of approximately 10(-6) to 10(-5) M, which exhibited H2 receptor specificity. Prostaglandin E2 and isoproterenol also induced [Ca2+]i mobilization in HL-60 cells, whereas the cell permeable form of cAMP and forskolin failed to increase [Ca2+]i. Since H2-receptor mediated [Ca2+]i mobilization was not inhibited by reducing the concentration of extracellular Ca2+ nor by the addition of Ca2+ channel antagonists, LaCl3 and nifedipine, [Ca2+]i mobilization is due to the release of Ca2+ from intracellular stores. Furthermore, both 10(-4) M histamine and 10(-6) M fMet-Leu-Phe increased the levels of 1,4,5-inositol trisphosphate. However, histamine-induced mobilization of [Ca2+]i was inhibited by cholera toxin but not by pertussis toxin, whereas the action of fMet-Leu-Phe was inhibited by pertussis toxin but not by cholera toxin. These data suggest that H2 receptors on HL-60 cells are coupled to two different cholera toxin-sensitive G-proteins and activate adenylate cyclase and phospholipase C simultaneously.

Calcium↗
PubMed1989

Thyroid hormone regulation of transcription factors involved in malic enzyme gene expression.

The mechanisms by which triiodothyronine (T3) regulates gene transcription are inadequately understood. In order to examine the effect of T3 on transcriptional mechanisms, we utilized several techniques to characterize trans-acting factors which interact with cis-regulatory elements of the promoter for the T3-responsive rat malic enzyme gene. Transcription of deletion mutants of the promoter by HeLa extracts revealed the existence of three cis-regulatory elements at -144 to -123, -70 to -50, and -30 to +5 (relative to the cap site at +1). DNase I footprinting disclosed the presence of proteins which bound to each of these regions. Gel mobility shift assays showed that specific binding of liver nuclear proteins to two of these regions (-144/-114 and -76/-47) was diminished in hypothyroid and elevated in hyperthyroid rats. Similar but less marked effects of T3 on the binding of kidney (a T3-responsive tissue) nuclear proteins to the -76/-47 and cap site regions were observed while binding of testis (a T3-nonresponsive tissue) nuclear proteins was unaffected by T3 treatment. Changes in the magnitude and time course of binding of liver proteins to this promoter correlated closely with previously documented T3-induced increases in the hepatic malic enzyme gene transcription rate. These results are consistent with a model in which the regulation of malic enzyme gene transcription by T3 in responsive tissues is mediated in part by hormone-induced increases in the binding of trans-acting factors to cis-regulatory elements.

Animals↗
PubMed1989

Regulation of expression of the alternative mRNAs of the rat alpha-thyroid hormone receptor gene.

The rat alpha-thyroid hormone receptor gene encodes through alternative splicing at least three protein isoforms with different functions, and three mRNA species (2.6, 5.4, 6.8 kilobase (kb) in size) are detected using alpha gene-specific probes (Mitsuhashi, T., Tennyson, G. E., Nikodem, V. M. (1988) Proc. Natl. Acad. Sci. U. S. A. 85, 5804-5808). In the present study, the identities of these mRNAs were analyzed by Northern analysis, and it was demonstrated that in rat brain the receptor protein is encoded by the minor 5.4- and 6.8-kb mRNAs and the variant proteins are encoded by the major 2.6-kb mRNA. Relative quantities of these mRNAs were determined by RNase protection assay, and the ratio of the receptor mRNAs to the variant mRNAs was estimated to be 1:6 in adult brain. The ratio between the mRNAs was regulated in both a tissue-specific and developmental stage-specific manner. The receptor mRNA levels were also regulated by the thyroid state of the animal showing an increased level in hypothyroid rat liver while those in brain were not affected. Analysis of the alpha-thyroid hormone receptor gene suggested that the choice between two poly-adenylation sites and subsequent RNA processing appear to generate the 3' heterogeneity of these alternative mRNAs.

Animals↗
PubMed1989

Structural characterization of the rat malic enzyme gene.

We have identified and characterized lambda bacteriophage clones containing genomic DNA encoding rat malic enzyme [(S)-malate:NADP+ oxidoreductase (oxaloacetate-decarboxylating); EC 1.1.1.40]. The malic enzyme gene is unexpectedly large, spanning at least 95 kilobases. It is divided into 14 exons that range in size from 76 to 1513 base pairs. The sizes and boundaries of the exons were determined by Southern blotting and DNA sequencing. The sequences at the 5' and 3' ends of each intron conformed to the consensus sequence for mammalian introns. S1 nuclease and primer-extension assays showed that transcription of the malic enzyme gene initiates at multiple sites, the strongest one at position -31 relative to the ATG. "TATA and CCAAT box" homologies are not present in the proximal promoter region. Analysis of the 3' end of the gene showed that the utilization of alternate polyadenylylation signals in exon 14 results in two mRNAs with 3' untranslated regions of 345 and 1345 nucleotides, respectively.

Amino Acid Sequence↗
PubMed1989

Endothelin-induced increases in vascular smooth muscle Ca2+ do not depend on dihydropyridine-sensitive Ca2+ channels.

Endothelin is a potent mammalian vasoconstrictive peptide with structural homology to cation channel-binding insect toxins. We tested the proposal that this peptide directly activates dihydropyridine-sensitive Ca2+ channels in cultured vascular smooth muscle (VSM) cells. First, we found that cell Ca2+ can be altered in VSM by activation of voltage-operated Ca2+ channels. KCl-induced depolarization and the dihydropyridine Ca2+ channel agonist (-) Bay K 8644 (10 microM) both raised cell Ca2+ more than twofold; the effect of KCl was blocked by the inhibitory enantiomer, (+) Bay K 8644 (40 microM). Similar responses were observed in Chinese hamster ovary (CHO) cells. Synthetic endothelin (4 x 10(-8) M) raised Ca2+ in VSM but not CHO cells from 100 +/- 17 to 561 +/- 34 nM within 12 s. Ca2+ subsequently fell to basal levels after 30 min. Half maximal Ca2+ response was at 4 x 10(-9) M endothelin. Unlike endothelin, thrombin raised Ca2+ in both VSM and CHO cells. The Ca2+ responses to endothelin and thrombin were not affected by nicardipine (1 microM), (+) Bay K 8644, or Ca2+-free solutions. Lastly, both hormones caused release of inositol phosphates in VSM cells. However, the response to thrombin was more than 10-fold larger and was more rapid than the response to endothelin; the thrombin response was sensitive to pertussis toxin, while the response to endothelin was not. Thus endothelin, like thrombin, raises cell Ca2+ in VSM by mobilization of intracellular stores and not by activation of dihydropyridine-sensitive Ca2+ channels. However, their receptors are distinct and they exhibit important differences in signal transduction.

Animals↗
PubMed1989

Carrageenan-induced pulmonary emphysema of rabbit.

A transbronchial injection of 0.75% carrageenan in physiologic saline induced pneumonia followed by emphysema in the insulted lobe. In the stages of pneumonia, scattered infiltration of polymorphonuclear leukocytes was seen throughout the affected lobe within a few days of treatment; later this was replaced by the accumulation of carrageenan-laden macrophages, which lasted for one to two months. Enlargement of alveoli and alveolar ducts appeared 2 weeks to 2 months after the treatment, and pulmonary emphysema was observed at 4 months. The lobes that were not treated with carrageenan were normal in appearance during both the pneumonia and the emphysema. Morphometric analysis of the lung at 4 months showed decrease of the alveoli and/or alveolar ducts and enlargement of their luminal spaces, also suggesting the development of emphysema. In contrast to various kinds of elastases that are known to produce emphysematous changes in animals, the elastolytic activity of carrageenan solution did not show any such effects, although in the homogenate of the lobes given carrageenan, a moderate but significant increase in the proteinase activities of alveolar macrophages are said to occur (Bowers et al. 1985). It was suggested that carrageenan-induced emphysema is a chronic disorder associated with both carrageenan toxicity and accumulated carrageenan-laden macrophages in the insulted lobes.

Animals↗
PubMed1989

Immunohistochemical localization of two types of carbonic anhydrase isozymes in oncocytoma and oncocytic epithelial cells.

An immunohistochemical study was performed on the localization of carbonic anhydrase isozymes I and II (CA I and CA II, respectively) in oncocytoma and oncocytic epithelial cells. Tumors examined were those deserved to be called oncocytomas such as Warthin's tumor, Hürthle cell tumor of the thyroid gland and renal oncocytoma. In addition, the same immunostaining was done on several pathologic lesions, accompanying moderate number of cells similar in tinctorial character to oncocytes, such as some type of adenoma of the thyroid gland, endometrial hyperplasia, endometriosis and so on. Specific antibodies against CA I and CA II prepared from human erythrocytes were converted into Fab' fragment and labeled with horseradish peroxidase. In each tissue sample, the majority of oncocytes or oncocytic epithelial cells showed a tendency to exhibit an immunostaining reaction for CA I and II intenser than that of adjacent original normal epithelium from which they might derive. To the authors' knowledge, no reports have been appeared on biological relevance of an increased activities of carbonic anhydrase in conjunction with a large number of mitochondria appearing in such oncocytic cells. In the present study, it is revealed that the immunoreactivities of CA isozymes increased in oncocytes as the number of mitochondria increased, suggesting that oncocytes have a high level of carbonic anhydrase for catalyzing the hydration of an increased amount of carbon dioxide generated chiefly via oxidative metabolism by mitochondria, the number of which is notably increased compensatorily for their deficient coupling of oxidative phosphorylation or other metabolic anomaly.

Adenoma↗
PubMed1989

[Mass screening of cardiovascular disorders by two-dimensional echocardiography].

We used two-dimensional echocardiography (2-D echo) for the mass screening of 2,673 subjects for cardiovascular disorders (1,032 men, 1,641 women, aged 23-95 years with a mean age of 59), who lived in 12 rural areas in Japan. In 1,665 of the 2,673 subjects (62.3%), cardiac abnormalities were recognized. Three major abnormalities included sclerotic aortic (33.0%) and mitral valves (21.8%), and left ventricular (LV) hypertrophy (15.9%). Apparent pericardial effusion (54 cases), mitral valve prolapse (44 cases), and dilated cardiomyopathy (4 cases) were incidentally found in this study. Prevalence of the abnormalities insidiously increased with age (below 49 years: 39%, and above 80 years: 97%), and this was apparently higher in men than in women. The abnormal findings which were significantly higher in men were the sclerotic aortic valves, LV hypertrophy and dysfunction, the prevalence of which was particularly high in ages 40-79, but it became nearly equal beyond 80 years of age. These results may indicate a sexual difference in the influence of age on the cardiovascular system. It was concluded that 2-D echo is helpful for primary screening and prevention of cardiovascular disorders.

Adult↗
PubMed1989

Concentration of interleukin-1 beta in serum and synovial fluid in patients with rheumatoid arthritis and those with osteoarthritis.

The concentration of interleukin-1 beta (IL-1 beta) in serum and synovial fluid of the knee of patients with rheumatoid arthritis (RA) and those with osteoarthritis (OA) was examined using a recently developed radioimmunoassay method. The serum concentration of IL-1 beta was below the detection limit of 0.25 ng/ml in all RA and OA patients. The IL-1 beta concentration in the synovial fluid was higher in RA patients than in OA patients. In RA patients, a significant correlation was demonstrated between the synovial fluid IL-1 beta concentration and the erythrocyte sedimentation rate, C-reactive protein level, synovial fluid white blood cell count and Lansbury index. The synovial fluid IL-1 beta concentration decreased with the reduction of the rheumatoid activity by the medication, but tended to increase or remain high when inflammatory activity of RA could not be adequately controlled. The IL-1 beta concentration, easily determined, shows promise as a new quantitative indicator of rheumatoid activity.

Aged↗