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Biomedical subjects

H Terada

Publications and source records attributed to H Terada.

At least 109 records · Page 6Linked to original sources

[Male sexual insufficiency].

There are patients who complaint the loss of sexual desire, loss of erection, absence of emission, absence of orgasm, and premature ejaculation. When the primary disturbance is in the producing or releasing process of testosterone in the testis, it increases the gonadotropic stimulation and results in the hypergonadotropic hypogonadism. Hypogonadotropic hypogonadism, in contrast, suggests that the disturbance in the hypophysis or hypothalamus. Patients who have the primary disturbance in the hypothalamus sometimes do not respond to LHRH, but repeated pulsatile LHRH stimulation induces the response. LH-testosterone is known to be the main axis of sexual function. However, growth hormone (GH) also has an important role. GH is necessary for adults, not only for children. Its deficiency arises easy fatiguability, loss of sexual desire, loss of erection, and oligo- or azoospermia. Erectile dysfunction is frequently caused by vascular, neurological and psychosomatic disorders. A variety of drugs are known to cause male sexual insufficiency. Many environmental factors and stress may affect the release of LH and GH, and therefore disturb the male sexual function.

Adult↗

Alteration of enzyme function of the type II hexokinase C-terminal half on replacements of restricted regions by corresponding regions of glucokinase.

To know the structural properties responsible for the enzymic activity of the 50-kDa C-terminal half of type II hexokinase (HKII-C) derived from rat hepatoma cell line AH130, we constructed cDNAs of HKII-C and its recombinants in which restricted regions containing highly conserved sequences, referred to as regions 2 and 3, were replaced by the corresponding regions of glucokinase. The binding domains of ATP and glucose were proposed to exist in these regions, respectively. Then, the HKII-C and chimera HKII-Cs were overexpressed in Escherichia coli BL21(DE3)pLysS. They all exhibited hexokinase activity, and their activities were inhibited by glucose-6-phosphate (Glc-6-P) competitively for ATP and uncompetitively for glucose. The replacement of region 2 of HKII-C by the corresponding region of glucokinase increased the affinity for glucose and decreased the affinity for Glc-6-P, but it did not significantly affect the affinity for ATP. In contrast, the replacement of region 3 did not cause an appreciable change in hexokinase activity. These findings suggest that region 2 is associated with the binding of ATP and Glc-6-P, and that the latter binding site is located close to the ATP binding site. In addition, region 2 was suggested to be directly related with the binding of glucose and other hexoses.

Amino Acid Sequence↗

Distribution of nitric oxide synthase-immunoreactive neurons in fetal rat brains at embryonic day 15 and day 19.

Although nitric oxide (NO) is hypothesized to play a role in the modelling of neuronal connections in the developing brain, no precise histological information has been reported on nitric oxide synthase immunoreactive (NOS-IR) structures in the embryonic brain. Thus, we examined the distribution of NOS-IR structures in the rat brain at embryonic day 15 (E15) and day 19 (E19), as a stage of early embryonic neurogenesis and active synaptogenesis, respectively. In the brain at E15, a few NOS-IR cell bodies were observed in the diencephalon near the 3rd ventricle and in the pons. By E19, the number of NOS-IR cells was greatly increased. Many NOS-IR cells were distributed throughout the forebrain and the medulla oblongata. NOS-IR cells of the neostriatum were located in its ventrolateral two-thirds. NOS-IR cells in the hypothalamus were distributed densely in the medial part while sparsely in the latero-ventral part, suggesting medio-lateroventral directions of NOS development. In the lower brainstem, on the other hand, NOS-IR cells were distributed in a similar pattern to that reported in adult rat, indicating earlier development of synaptic refinement in this area. The number of NOS-IR cells in the cerebral cortex and the cerebellum was very few.

Animals↗

Prevention of reoxygenation-induced arrhythmias in guinea pig papillary muscles.

Effects of various agents on reoxygenation-induced arrhythmias, action potentials, and tension of guinea pig papillary muscles were recorded to investigate the site of action. Triggered activities due to delayed afterdepolarizations (DADs) and aftercontractions were elicited on reoxygenation after 60-min substrate-free hypoxia. Low extracellular Ca2+ (0.1 mM) abolished arrhythmias, and high Ca2+ (4.9 mM) increased the amplitudes of DADs and aftercontractions. D-600 at the high concentration (20 microM) decreased the incidence of arrhythmias (p < 0.05 vs. no drug) and decreased the recovery of developed tension after reoxygenation (p < 0.001). Ryanodine (1 microM) abolished aftercontractions and arrhythmias but did not affect the recovery of developed tension. Tetrodotoxin (TTX 3 microM) and nicorandil (100 microM) decreased the incidence of arrhythmias (p < 0.05), but did not affect the recovery of developed tension or the amplitudes of aftercontractions. TTX caused only a slight decrease in Ca2+ transients in a fluo-3-loaded guinea pig ventricular myocyte. The Ca2+ entry through the Ca2+ channels apparently synchronized Ca2+ release from the sarcoplasmic reticulum, and D-600 at the high concentration apparently decreased the incidence of arrhythmias. TTX and nicorandil decreased arrhythmias, probably by decreasing the Na+ current or by increasing the ATP-sensitive K+ current, respectively.

Action Potentials↗

Effects of Mg2+ on Ca2+ waves and Ca2+ transients of rat ventricular myocytes.

It has been shown that the occurrence of the transient inward current, which is responsible for triggered activity, was often associated with propagating regions of increased intracellular Ca2+ concentration ([Ca2+]i), i.e., the "Ca2+ wave." To investigate the mechanism of antiarrhythmic action of Mg2+, we have studied effects of high concentrations of Mg2+ on Ca2+ waves in isolated rat ventricular myocytes. [Ca2+]i was estimated using the Ca(2+)-indicating probe indo 1. Ca2+ waves in myocytes, stimulated at 0.2 Hz, were induced by perfusion of isoproterenol (10(-7) M). High Mg2+ concentration suppressed Ca2+ waves in a concentration-dependent manner (36% at 4 mM, 70% at 8 mM, and 82% at 12 mM). The Ca2+ channel blocker verapamil also suppressed Ca2+ waves in a similar way. In contrast with marked depression of Ca2+ transients by verapamil, Ca2+ transients were not affected by high Mg2+ concentration (8 mM). High Mg2+ concentration also reduced frequencies of Ca2+ waves in the absence of electrical stimulation, whereas verapamil failed to reduce frequencies of Ca2+ waves. Reduction in frequency of Ca2+ waves by high Mg2+ concentration was associated with slowing of propagation velocity of Ca2+ waves. To examine whether suppressive effects of high Mg2+ concentration on Ca2+ waves were related to an increase in intracellular Mg2+ concentration ([Mg2+]i), the effect of high-Mg2+ solution on [Mg2+]i was examined in myocytes loaded with mag-fura 2. An increase in extracellular Mg2+ concentration from 1 to 12 mM increased [Mg2+]i from 1.06 +/- 0.16 to 1.87 +/- 0.22 mM (P < 0.01) in 30 min. To examine the effect of high Mg2+ concentration on amount of releasable Ca2+ in the sarcoplasmic reticulum, the effect of high Mg2+ concentration on the Ca2+ transient induced by a rapid application of caffeine was examined. High-Mg2+ solution increased the peak of the caffeine-induced Ca2+ transient. These results suggest that the inhibitory effect of Mg2+ on Ca2+ waves was not due to inhibition of the sarcolemmal Ca2+ channel but could be due to a decreased propensity for the sarcoplasmic reticulum to divest itself of excess Ca2+.

Animals↗

Polarity of cultured newborn rat skin basal cell layer.

Basal cells were prepared from the newborn rat skin epidermis and cultured on a type I collagen-coated filter. This cultured basal cell layer showed an amiloride-sensitive polarity, and the apical surface of the cell layer was more acidic than the basal surface. When the basal cells were cultured with ascorbic acid, a polarity reverse of the cultured cell layer was observed. In this case, synthesized and accumulated type IV collagen was detected on the whole apical surface of the cultured cell layer. An inhibitor of collagen synthesis, cis-hydroxyproline (cis-OH-Pro), suppressed the ascorbic acid-induced polarity reversal. Furthermore, when basal cells were cultured on a type IV collagen-coated filter, the amiloride-sensitive polarity of the cultured cell layer resembled the cultivation on a type I collagen-coated filter. In this case, the polarity was reversed by the addition of ascorbic acid, and cis-OH-Pro suppressed this reversal. Based on these results, we concluded that cultured skin basal cell layer showed an amiloride-sensitive polarity. Moreover, newly synthesized and accumulated type IV collagen was deduced to affect the polarity reversal in the cultured basal cell layer.

Amiloride↗

Intracellular pH regulation of newborn rat skin basal cells.

The regulation of intracellular pH (pHi) was examined in newborn rat skin basal cells. When basal cells were acid-loaded by externally applied weak acid or by pretreatment with NH4+, the pHi recovered toward its resting value. This recovery was accompanied by Na+ influx and H+ efflux. The recovery of pHi and concomitant Na+/H+ fluxes were reversibly inhibited by amiloride. Other ionic flux inhibitors 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and furosemide slightly inhibited the pHi recovery from an acid load. The recovery rate from an acid load depended on the concentration of the external Na+.Li+ could substitute for Na+ in the pHi recovery, but K+ had no effect on the recovery. The keratin synthesis of basal cells was decreased by amiloride, and this decrement was deduced to be due to the acidification of the intracellular space. Although ascorbic acid had no effect on the pHi recovery of basal cells, it enhanced the keratin synthesis of the cells. Moreover, an inhibitor of the collagen synthesis, cis-hydroxyproline, suppressed the keratin synthesis but had no effect on the pHi recovery. We therefore believe that the keratin synthesis of the cells was also regulated by the environment, which was formed by the synthesized collagen. Thus, the pHi in the skin basal cells was regulated by the amiloride-sensitive exchange system, and this system seems to be involved in the keratin synthesis.

Animals↗

Effects of biscoclaurine alkaloid cepharanthine on newborn rat skin epidermal and dermal cells.

Effects of biscoclaurine alkaloid cepharanthine on proliferation of skin cells were examined in vitro. The alkaloid was found to enhance attachment and cell layer formation of newborn rat skin epidermal cells in culture on type I collagen-coated Millipore filter, and to potentiate production of keratins in these cells. Spreading and growth of skin dermal fibroblasts were inhibited by cepharanthine in a dose-dependent manner, but the alkaloid-treated cells still retained the ability to synthesize type IV collagen. In culture of skin cells containing both epidermal and dermal cells, no growth of epidermal cells or over-growth of dermal fibroblasts was observed in medium without cepharanthine. In contrast, the presence of the alkaloid suppressed the growth of fibroblasts and promoted the formation of epidermal cell layers accompanied by production of keratins. Thus, in comparison with the cells untreated with the alkaloid, cepharanthine-treated skin epidermal and dermal cells in vitro expressed in vivo-like characters.

Alkaloids↗

Effect of culture matrix on newborn rat skin basal cells; modification of cell response to extracellular calcium.

Basal cells from newborn rat skin epidermis were cultured on various culture matrixes, and the response of the cells to extracellular calcium was examined. When the cells were cultured on a type I collagen-coated Millipore filter to maintain clearance under the cultured cells as intact skin, the cells responded to a fluctuation in extracellular calcium and were detached from the collagen layer in a high calcium environment. In this case, protein synthesis of the cells increased calcium-dependently. In contrast, calcium-dependent protein synthesis of the cells was not detected in culture, neither on the plastic plate nor the type I collagen-coated plate. Moreover, in culture on a type I collagen-coated filter, the size of basal cells was unchanged for 2 d. This should be consistent with the fact that morphological changes in cells are very gradual in vivo. On the other hand, when basal cells were cultured either on a plastic plate or collagen-coated plate, the cells lost their normality; they were markedly enlarged for 2d of culture. Thus, the responses of skin basal cells to extracellular calcium fluctuated according to the types of culture matrixes. In this case, keratin synthesis and a morphological change of the cells seems to be concerned with the clearance, which was established in the basal side of the cultured basal cells as intact skin.

Animals↗

Electrical heterogeneity and conduction block in reoxygenated guinea pig papillary muscles.

To investigate the changes in electrical activity after reoxygenation, guinea pig papillary muscles were reoxygenated with 5 mM glucose solution after various durations (30-120 min) of substrate-free hypoxia. Action potential duration recovered to the control level on reoxygenation following 30-120 min hypoxia. The recovery of developed tension or resting tension was incomplete after reoxygenation following longer periods of hypoxia. There was a high incidence of arrhythmias on reoxygenation after 60 min hypoxia, which have been shown to be triggered activities due to delayed afterdepolarizations. In some muscles reoxygenated after prolonged hypoxia (90-120 min), there was electrical heterogeneity which was shown by variable action potential durations and configurations. There was also conduction block around the microelectrode site in muscle. It was suggested that the electrical heterogeneity and conduction block could predispose to reentry, and that triggered activities and reentry could be involved in the genesis of arrhythmias on reperfusion.

Action Potentials↗

[Evaluation of subrenal capsule assay (SRC) for clinical cancers].

For clinical cancers of esophagus (10 cases), stomach (7), colon and rectum (11) and breast (5), subrenal capsule assays (SRC) were performed using normal or AF nude mice. The sensitivity of anticancer drugs (UFT, CDDP) was evaluated by both the change in graft size under the renal capsule and the histological findings of these grafts. SRC was found to be a very reliable testing method for cancer of esophagus, colon and rectum because these grafts possessed remarkable viability. Evaluability of these two cancers was very high (approximately 80%). Sensitivity of UFT was 29% (2/7) for esophageal cancer, 50% (5/10) against colon and rectal cancer, and that of CDDP was 40% (2/5) and 17% (1/6), respectively. Evaluability of gastric and breast cancers was very low because of the poor growth of the grafts irrespective of the immunity of host animals. It was discussed why the evaluation rate depended on the type of cancer. These results suggest that indications for SRC are restricted, but that for colon and rectal or esophageal cancer SRC is a reliable testing method for anticancer drugs in clinical use.

Adult↗

Evolution of high-intensity basal ganglia lesions on T1-weighted MR in neurofibromatosis type 1.

PURPOSE: To characterize the temporal evolution of the foci of T1 shortening in basal ganglia lesions in patients with neurofibromatosis type 1 (NF-1). METHODS: A retrospective review of MR images of 37 patients with NF-1 revealed 8 patients in whom regions of T1 shortening were noted in the basal ganglia. We reviewed sequential images obtained in these selected patients with special attention to chronological changes in the foci of T1 shortening and their relationship to changes on T2-weighted images. RESULTS: Regions of short T1 in the globus pallidus were observed in 8 patients. In 2 of 3 patients in whom foci of T1 shortening were not identified on the initial imaging study, T1 shortening developed and T2 prolongation diminished after an initial increase. In the third patient, T1 and T2 prolongation appeared simultaneously. Sequential scans in the other 5 patients, in whom areas of increased signal intensity in the globus pallidus were present on both T1-weighted and T2-weighted images on the initial MR examination, showed a diminution in the size of the region of T2 prolongation in 2 patients, an increase in the size of the region of T2 prolongation in 1 patient, a mixed pattern of change in the size of the region of T2 prolongation in 1 patient, and no change in the region of T2 prolongation in 1 patient. During the periods of these T2 changes, the areas of T1 shortening showed no significant interval change. CONCLUSION: The foci of prolonged T2 relaxation in the basal ganglia appear to evolve in a manner similar to the foci of T2 prolongation in the white matter of the posterior fossa. However, the corresponding foci of short T1 in the basal ganglia may evolve with a different time course. In some patients, the foci of short T1 develop at a later time than the T2 prolongation and progress; these foci of short T1 do not appear to regress over periods as long as 90 months. Possible causes of the T1 shortening are remyelination and calcification.

Adolescent↗

[Hereditary high red cell membrane phosphatidylcholine hemolytic anemia (HPCHA)].

HPCA is a rare disease among hemolytic anemias. A dominantly transmitted chronic anemia characterized by an increase of erythrocyte membrane phosphatidylcholine (PC) and cholesterol with decrease of phosphatidylethanolamine (PE). On peripheral blood smears stomatocytes and target cells are evident. The MCV may be increased, but the life span of red cells is decreased. The osmotic fragility is normal or increased, but splenectomy is not effective. These two points are different from other hereditary hemolytic anemias. As in other hemolytic anemias, gallstone and biliary tract disease more frequently occur than in the general population. An imbalance in membrane phospholipid content is attributed to a defect in the enzyme required for the transfer of membrane fatty acid from PC to PE. As a result, Cation flux glycolysis and membrane cation pump activity are increased. These abnormality is probably for hemolysis.

Anemia, Hemolytic, Congenital↗

Translocation of loops regulates transport activity of mitochondrial ADP/ATP carrier deduced from formation of a specific intermolecular disulfide bridge catalyzed by copper-o-phenanthroline.

The cross-linking reagent copper-o-phenanthroline complex (Cu(OP)2) specifically caused a decrease in the amount of the 30-kDa ADP/ATP carrier in bovine submitochondrial particles associated predominantly with formation of a 60-kDa protein consisting of a cross-linked dimer of the carrier. However, Cu(OP)2 had no effect on mitochondria. The transport of ADP via the carrier through submitochondrial particle membranes was found to be inhibited in parallel with the progress of intermolecular cross-linking. Analysis of the cross-linked site showed that a disulfide bridge was formed only between two Cys56 residues in a pair of the first loops facing the matrix space. The transport inhibitor bongkrekic acid, which locks the m-state conformation of the carrier, had no effect on disulfide bridge formation catalyzed by Cu(OP)2, but carboxyatractyloside, which locks the c-state conformation by acting from the cytosolic side, completely inhibited the cross-linking. These results show that the ADP/ATP carrier functions as a dimer form, and a pair of the first loops protrudes into the matrix space in the m-state, but possibly intrudes into the membrane in the c-state. Thus, it is suggested that a pair of the first loops acts as a gate and that its opening and closing are regulated by their translocation.

Animals↗

High expression of a novel carnitine palmitoyltransferase I like protein in rat brown adipose tissue and heart: isolation and characterization of its cDNA clone.

To characterize energy metabolism in rat brown adipose tissue (BAT), we carried out differential screening of a cDNA library of BAT with a cDNA probe of white adipose tissue (WAT) and isolated one cDNA clone. It contained a single open reading frame of 2,316 bases which encodes a protein of 88.2 kDa. The predicted amino acid sequence showed the highest homology (62.6%) with that of rat carnitine palmitoyltransferase I (CPTI). The transcript corresponding to this cDNA was found to be abundantly expressed in BAT and heart. Therefore, the isolated clone is concluded to encode a CPTI like protein expressed in BAT and heart.

Adipose Tissue, Brown↗

Stabilities of the fluorescent SH-reagent eosin-5-maleimide and its adducts with sulfhydryl compounds.

The stabilities of the SH-reagent eosin-5-maleimide (EMA) and its adducts with the SH-compounds L-cysteine, N-acetyl-L-cysteine and glutathione (reduced form) were studied under various conditions in comparison with those of the adducts of N-ethylmaleimide (NEM). Studies by reversed-phase high performance liquid chromatography and mass spectrometry showed that EMA was less stable than NEM at neutral and moderately alkaline pH values. EMA formed a succinimide-type adduct with SH-compounds, and then underwent further modification by nucleophilic attack of OH- or an amino group. The succinimide-type adducts with acetylcysteine and glutathione were converted to open-type adducts, in which the succinimide ring was cleaved, whereas the adduct with cysteine was modified to a thiazine-type adduct. Kinetic analyses showed that these open-type and thiazine-type adducts were readily formed and were stable at moderately alkaline pH values such as pH 8.0 or 9.0.

Acetylcysteine↗

Inhibitory effect of Mg2+ on the protonophoric activity of palmitic acid.

To discriminate whether fatty acids are uncouplers that cause acceleration of State-4 respiration, associated with a decrease in the protonmotive force, or decouplers that increase respiration without associated decrease in the protonmotive force, we examined the effect of palmitate on functions of rat-liver mitochondria under various conditions. We found that palmitate itself increases State-4 respiration, releases oligomycin-inhibited State-3 respiration, inhibits ATP synthesis and ATP<->Pi exchange reaction, and increases H+ permeability in mitochondrial and model bilayer phospholipid membranes. Thus, palmitate is a classical uncoupler of oxidative phosphorylation. However, these effects were inhibited by Mg2+, due to rapid formation of a stable complex between palmitate and Mg2+.

Animals↗