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Biomedical subjects

S Inoue

Publications and source records attributed to S Inoue.

At least 1,171 records · Page 65Linked to original sources

The effect of verapamil on halothane-epinephrine or digitalis-induced ventricular dysrhythmias in dogs.

The effect of verapamil on ventricular dysrhythmias was evaluated using two canine models. In one model, ventricular dysrhythmias were induced by 1% halothane-epinephrine (1.5 approximately 30 micro g/kg/min.) in 20 dogs (Group I). In the other model, ventricular dysrhythmias were induced by digoxin (0.1 approximately 0.2 mg/kg) in 27 dogs (Group II). Verapamil (0.2 approximately 0.5 mg/kg) was given to treat these ventricular dysrhythmias. When verapamil was ineffective, lidocaine (1 approximately 2 mg/kg) was given following the administration of verapamil. In 7 dogs of group II, lidocaine alone was given. Verapamil was effective in 16 animals of group I, and in 10 animals of group II. Lidocaine was ineffective in the remaining 4 of group I, whereas effective in the remaining 17, including those given lidocaine alone of group II. From these findings, it was inferred that Ca(2+) dependent abnormal automaticity and/or re-entry may be more closely related to the genesis of halothane-epinephrine-induced ventricular dysrhythmias refractory to lidocaine, whereas triggered activity may be more closely related to that of digitalis-induced ventricular dysrhythmias. In conclusion, verapamil was more effective against halothane-epinephrine-induced ventricular dysrhythmias than against digitalis-induced ventricular dysrhythmias.

Journal Article↗

Biphasic effects of 12-O-tetradecanoylphorbol-13-acetate on the cell morphology of low calcium-grown human epidermal carcinoma cells: involvement of translocation and down regulation of protein kinase C.

The present study was performed to investigate involvement of protein kinase C in the biphasic effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) on cell morphology in low calcium (0.07 mM)-grown cells of a human epidermal squamous cell carcinoma cell line. The low calcium-grown cells formed no desmosomal cell-cell contact and showed roughly circular arrangements of keratin intermediate filaments around the nucleus. Treatment with 10 ng/ml of TPA induced a rapid formation (within 15 min) of cell-cell contact and reorganization of keratin intermediate filaments from a circular organization to a radial arrangement in these low calcium-grown cells. These structural phenomena were associated with a transient increase in membrane-bound protein kinase C activity. However, the prolonged treatment longer than 24 h led to a prominent decrease in the number of cell-cell contacts, that had been once formed, and caused fibroblastic changes of cell morphology in association with a decrease in the membrane-bound protein kinase C activity. Addition of 20 microM 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride, a potential inhibitor of protein kinase C, to the medium with TPA blocked the formation of cell-cell contact. Addition of 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride alone to normal calcium-grown cell cultures exhibiting cell-cell contact resulted in a decrease in the number of cell-cell contacts and in the fibroblastic morphological changes after 24-h incubation. These results suggest that the effects of TPA are biphasic as follows: the initial stage, inducing cell-cell contact formation associated with the translocation of protein kinase C activity from the cytosol to the membrane; and the late stage, exhibiting a fibroblastic morphological change with a decrease in the number of cell-cell contacts associated with the down regulation of this enzyme activity by TPA.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Seasonal clustering of transient erythroblastopenia of childhood.

In a prospective study over two years, a clustering of transient erythroblastopenia of childhood (TEC) and aplastic crises in patients with hereditary hemolytic anemia was noted during the fall and winter months. Despite this clustering, evidence for human parvovirus infection was found only in aplastic crises in patients with hemolytic anemia but not in children with TEC. The seasonal clustering noted in the small group of patients in the prospective study was corroborated by a retrospective review of 39 consecutive patients with TEC seen in our institution over a five-year period.

Anemia, Aplastic↗

Visualization of the large heparan sulfate proteoglycan from basement membrane.

Kleinschmidt spreading, negative staining, and rotary shadowing were used to examine the large form of (basement membrane) heparan sulfate proteoglycan in the electron microscope. Heparan sulfate proteoglycan was visualized as consisting of two parts: the core protein and, emerging from one end of the core protein, the glycosaminoglycan side chains. The core protein usually appeared as an S-shaped rod with about six globules along its length. Similar characteristics were observed in preparations of core protein in which the side chains had been removed by heparitinase treatment ("400-kDa core") as well as in a 200-kDa trypsin fragment ("P200") derived from one end of the core protein. The core protein was sensitive to lyophilization and apparently also to the method of examination, being condensed following Kleinschmidt spreading (length means = 52 nm) and extended following negative staining (length means = 83 nm) or rotary shadowing (length means = 87 nm; 400-kDa core length means = 80 nm; P200 length means = 44 nm). Two or three glycosaminoglycan side chains (length means = 146 +/- 53 nm) were attached to one end of the core protein. The side chains often appeared tangled or to merge together as one. Thus, the large heparan sulfate proteoglycan from basement membrane is an asymmetrical molecule with a core protein containing globular domains and terminally attached side chains. This structure is in keeping with that previously predicted by enzymatic digestions and with the proposed orientation in basement membranes, i.e., the core protein bound in the lamina densa and the heparan sulfate side chains in the lamina lucida arranged along the surface of the basement membranes.

Animals↗

Three-dimensional network of cords: the main component of basement membranes.

Basement membranes were divided into two types: 1) thin basement membranes, such as those of the epidermis, trachea, jejunum, seminiferous tubule, and vas deferens of the rat, the ciliary process of the mouse, and the seminiferous tubule of the monkey, and 2) thick basement membranes, such as the lens capsule of the mouse and Reichert's membrane of the rat. High-magnification electron microscopy was used to examine both types after fixation either in glutaraldehyde followed by postosmication or in potassium permanganate. The basic structure of thin and thick basement membranes was found to be a three-dimensional network of irregular, fuzzy strands referred to as "cords"; the diameter of these cords was variable, but averaged 4 nm in all cases examined. The spaces separating the cords differed, however. In the lamina densa of thin basement membranes, the diameter of these spaces averaged about 14 nm in every case, whereas in the lamina lucida it ranged up to more than 40 nm. Intermediate values were recorded in thick basement membranes. Finally, the third, inconstant layer of thin basement membranes, pars fibroreticularis, was composed of discontinuous elements bound to the lamina densa: i.e., anchoring fibrils, microfibrils, or collagen fibrils. In particular, collagen fibrils were often surrounded by processes continuous with the lamina densa and likewise composed of a typical cord network. Finally, two features were encountered in every basement membrane: 1) a few cords were in continuity with a 1.4- to 3.2-nm thick filament or showed such a filament within them; the filaments became numerous after treatment of the seminiferous tubule basement membrane with the proteolytic enzyme, plasmin, since cords decreased in thickness and could be reduced to a filament, and 2) at the cord surface, it was occasionally possible to see 4.5-nm-wide sets of two parallel lines, referred to as "double tracks." On the basis of evidence that the filaments are type IV collagen molecules and the double tracks are polymerized heparan sulfate proteoglycan, it is proposed that cords are composed of an axial filament of type IV collagen to which are associated glycoprotein components (laminin, entactin, fibronectin) and the double tracks of the proteoglycan.

Alouatta↗

A proteinase associated with cortices of rainbow trout eggs and involved in fertilization-induced depolymerization of polysialoglycoproteins.

A novel proteinase that acts on polysialoglycoprotein (PSGP) was found in the cortex fraction of the unfertilized eggs of rainbow trout. This enzyme (designated PSGPase) is responsible for specific depolymerization of cortical vesicular 200- to 9-kDa PSGP in vivo upon fertilization. We have succeeded in measuring the enzyme activity in an in vitro system by using 3H-labeled PSGP as the substrate. In the in vitro system PSGPase is active only at concentrations of NaCl below 40 mM and at low temperature (optimum temperature, about 16 degrees C), which are the conditions most suitable for egg activation.

Animals↗

Candida albicans translocation across the gut mucosa following burn injury.

Normal guinea pigs were challenged intragastrically with Candida albicans 1 hr prior to a 30 or 50% flame burn to determine if burn injury increased translocation of the yeasts across gut mucosa. Tissues were harvested between 3 and 24 hr postburn and cultured on Sabouraud dextrose agar. Control animals (no yeast challenge) showed no yeast in intestinal homogenates or in the mesenteric lymph nodes (MLN). At a dose of 1 X 10(9) yeasts, they did not escape from the gut lumen, with either a 30 or 50% burn. At a dose of 2 to 4 X 10(10) organisms, they translocated to the MLN in 92% of the 50%-burned animals (P less than 0.001), 75% of the 30%-burned animals (P less than 0.05), and 12.5% of unburned animals. The ileal mucosa appeared to be the most susceptible site for yeast invasion. To observe the penetration through the gut mucosa and/or translocation to other tissues, yeasts were labeled with biotin before administration, and tissues were stained with avidin-peroxidase diaminobenzidine sequence. With biotinylated yeasts, phagocytized organisms were observed in large numbers in the lamina propria and mesenteric lymph nodes but they were not viable upon culture. Toluidine blue staining of semithin sections revealed that translocated yeasts were located selectively in the lymphoid follicles of the MLN, entrapped by macrophages.

Animals↗

Electrical stimulation of the suprachiasmatic nucleus of the hypothalamus causes hyperglycemia.

We have presented evidence suggesting that the suprachiasmatic nucleus (SCN) is involved in central regulation of glucose homeostasis. To elucidate this role of the SCN, we examined the effects of its electrical stimulation on glucose metabolism in male Wistar rats. During and shortly after this stimulation, we observed hyperglycemia associated with enhanced hyperglucagonemia but no immediate hyperinsulinemia. In addition, we detected significant increase in liver glycogen phosphorylase alpha activity and significant decrease in the liver glycogen content. These findings suggest that the SCN is important in control of glucose homeostasis through effects on glucagon and insulin secretions and liver glycogen metabolism.

Animals↗

Mechanism underlying relaxations caused by prostaglandins and thromboxane A2 analog in isolated dog arteries.

In helical strips of dog cerebral, coronary, mesenteric, and renal arteries treated with ONO3708, an inhibitor of vasoconstricting prostaglandin (PG) receptors, and previously contracted with serotonin, PGF2 alpha, PGD2 and epithio-methano thromboxane A2 (sTxA2), a TxA2 analog, caused a relaxation. The cerebral arterial relaxation was suppressed by treatment with indomethacin and abolished by diphloretin phosphate (DPP), a PG antagonist. On the other hand, the relaxation of mesenteric arteries was not influenced by indomethacin but was markedly attenuated by DPP. Removal of endothelium did not alter the relaxation. Relaxations of coronary and renal arteries by PGF2 alpha were suppressed by indomethacin and DPP, whereas the PGD2-induced relaxation was not affected by indomethacin but was abolished by DPP. Concentration--relaxation curves for PGI2 were shifted to the right by treatment with DPP. It is concluded that after ablation of the constrictor response, dog cerebral arteries relax in response to PGs and TxA2, probably due mainly to the release of PGI2-like substance from the arterial wall and to the action of PGI2 receptive sites, whereas the mesenteric arterial relaxation appears to be associated with their action on PGI2 receptors in smooth muscle cells. PGF2 alpha-induced relaxations in coronary and renal arteries may result from the release of PGI2, and relaxations by PGD2 from the action on PGI2 receptors.

Animals↗

Clinical, electrophysiological, and histopathological observations in supraventricular tachycardia.

Fifty patients with supraventricular tachycardia (SVT) underwent clinical electrophysiological studies (EPS), endomyocardial biopsies and cardiac catheterizations. EPS revealed AV nodal reentrant tachycardia (AVNRT) in seven patients, AV reentrant tachycardia utilizing concealed AV bypass tracts (AVR-CBT) in nine patients, AV reentrant tachycardia utilizing AV bypass tracts with ventricular preexcitation (manifest WPW) in 13 patients, sinus nodal or intra-atrial reentrant tachycardia (SNRT or IART) in three patients, atrial flutter (AF) in nine patients, automatic atrial tachycardia (AAT) in five patients, and multifocal atrial tachycardia (MAT) in four patients. According to the clinical observations, three patients with AVNRT (43%), six with AVR-CBT (67%), six with manifest WPW (46%), two with SNRT or IART (67%), eight with AF (89%), two with AAT (40%), and two with MAT (50%) showed other accompanying clinical abnormalities. In all patients who were studied histologically, changes in the myocardium were seen; myocarditic changes, postmyocarditic changes and nonspecific abnormalities were present in six (12%), 15 (30%), and nine (18%) respectively. Myocardial changes were observed in four out of seven cases with AVNRT (57%), in six out of nine with AVR-CBT (67%), in five out of 13 with manifest WPW (38%), in two out of three with SNRT or IART (67%), in six out of nine with AF (67%), in all five cases of AAT (100%), and in two out of four with MAT (50%). Nineteen out of 32 without clinical abnormalities except for arrhythmias (59%) had myocardial changes (six had myocarditic changes, ten had postmyocarditic changes, and three had nonspecific abnormalities). On the other hand, nine out of 21 with myocarditic or postmyocarditic changes were accompanied with various arrhythmias other than SVT (two had SSS, five had AV block or rBBB, and two had VT). Elevated LVEDP was present in 36% of the group with normal myocardium and in 53% of the group with myocardial changes. However, the low EF was shown in no patients with normal myocardium but in 21% of the group with myocardial changes. The low CI was also shown in only 9% of the group with normal myocardium but in 28% of the group with myocardial changes. These results suggest that patients with SVT may exhibit several histopathological changes in the myocardium, even in the absence of any clinical organic heart disease.

Adult↗

Human renin gene assigned to chromosome band 1q42 by in situ hybridization.

A gene coding for renin was assigned to human chromosome region 1q42 by in situ hybridization. Many genes in this region belong to multigene families whose members may be located on the same or different chromosomes. Genes located on the long arm of chromosome 1 appear to have been involved in several instances of gene duplication.

Chromosome Mapping↗

Glucose stimulation of protooncogene expression and deoxyribonucleic acid synthesis in rat islet cell line.

The rat islet cell line, RIN, established from a transplantable, radiation-induced islet cell tumor represents a unique model to study mechanisms in the control of insulin secretion and biosynthesis. In this study, we have examined the effects of glucose on the protooncogene expressioN and cell growth using a clonal strain of RIN cell, RINr, under serum-free and glucose-free conditions. After 24 h pretreatment, cells were treated with different concentrations of glucose for up to 24 h and then subjected to RNA analysis. Agarose gel electrophoresis of total RNA extracts of RINr cells, followed by hybridization with v-myc DNA yielded a 2.4 kilobase c-myc messenger RNA (mRNA) transcripts. After 24 h pretreatment with serum-free and glucose-free medium, RINr cells expressed a low level of c-myc mRNA transcripts. An increase in c-myc transcripts was detectable within 30 min of D-glucose (200 mg/dl) addition, reaching a maximum of 10-fold within 2 h. Glucose stimulated the steady state of c-myc mRNA transcripts in a dose-responsive manner without any change of gamma-actin mRNA levels after 2 h of treatment. The level of c-myc transcripts then declined as the cells proceeded through G1 to the cycle. [3H]Thymidine uptake into DNA was dramatically increased after 24 h of glucose addition, suggesting that glucose itself stimulates DNA synthesis in RINr cells. These results indicate that glucose-induced proliferation of RINr cells is associated with the stimulation of c-myc gene expression.

Animals↗