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Biomedical subjects

A Kobayashi

Publications and source records attributed to A Kobayashi.

At least 361 records · Page 20Linked to original sources
PubMed1993

Verapamil induced reduction of the myocardial beta-adrenoceptor density in BIO 14.6 cardiomyopathic Syrian hamsters.

In general, it is recognized that prolonged exposure to catecholamine leads to a reduction in the beta-adrenoceptor density (downregulation). However, it has been previously reported that the myocardial beta-adrenoceptor densities and norepinephrine levels significantly increase in the hearts of BIO 14.6 cardiomyopathic hamsters in the early stage. The mechanism of the increased beta-adrenoceptor density is not clearly elucidated, and it can not be excluded that this phenomenon may be a secondary effect. The purpose of this study was to assess the effect of verapamil on the density of beta-adrenoceptors in the heart of BIO 14.6 cardiomyopathic hamsters. The total number of beta-adrenoceptors in untreated BIO 14.6 hamsters was significantly higher at 90 days of age (30.4 +/- 2.2 v.s. 25.9 +/- 1.4 fmol/mg protein, p < 0.05). BIO 14.6 hamsters received daily intraperitoneal injections of 5 mg/kg verapamil for 70 days, from an age of 20 days. Verapamil protected against progressive myocardial damage (total damage; 8.2 +/- 0.7 v.s. 0.4 +/- 0.2%/area, p < 0.05) and the myocardial beta-adrenoceptor density returned to that of the normal control group (26.9 +/- 3.0 fmol/mg protein). Conversely, verapamil did not have an effect on the number of myocardial beta-adrenoceptors in normal golden hamsters. This study showed that verapamil protected against progressive myocardial damage and myocardial beta-adrenoceptor density returned to those of normal hamsters. These results suggest that an increased number of beta-adrenoceptors in the early stage of BIO 14.6 cardiomyopathic hamsters may be involved in the secondary pathogenesis of cardiomyopathy.

Animals↗
PubMed1993

31P-NMR magnetization transfer study of reperfused rat heart.

The relationships between pressure rate product (PRP) and flux (PCr-->ATP) or flux(Pi-->ATP) were studied in isolated perfused rat hearts by the method of saturation transfer using 31P-NMR during the preischemic and reperfusion periods. The hearts were made ischemic for 15 min, followed by 60 min of reperfusion. PRP was almost completely depressed, and recovered to 60% of the control level (preischemic period) after reperfusion. The ATP level during reperfusion was significantly decreased, whereas there was no significant change in PCr level. Pi level of reperfused hearts was significantly higher than that in the control. Both flux(PCr-->ATP) and flux(Pi-->ATP) were significantly decreased during the reperfusion period (both p < 0.05). However, the flux(PCr-->ATP)/PRP ratio during reperfusion did not differ from that of the control. This result indicates that the decrease in flux(PCr-->ATP) was matched by a similar decrease in cardiac performance. In contrast, the flux(Pi-->ATP)/PRP ratio during reperfusion was significantly decreased compared to that of control. These results suggest that the stunned heart needs less ATP turnover in proportion to its depressed contractile activity, and flux(Pi-->ATP) may lmit the recovery of postischemic performance.

Adenosine Triphosphate↗
PubMed1993

Triiodothyronine increases desipramine with changing the concentrations of monoamines, in the brain of rat given imipramine.

After treatment with triiodothyronine (T3) for 5 days, rats received a single i.p. injection of imipramine. The concentrations of imipramine and desipramine decreased and increased, respectively, in the brains of T3-treated rats, and the elimination half-time of desipramine was increased. In rats that had received imipramine for 7 days, cotreatment with T3 also resulted in reduced imipramine and elevated desipramine concentrations in the brain. Coadministration of T3 with imipramine appeared to accelerate the desipramine-induced changes in norepinephrine and 3-methoxy-4-hydroxyphenylglycol concentrations in brain. Since T3 treatment elevated the 5-hydroxyindole acetic acid concentration in the brain, the concentration in rats receiving both drugs was equivalent to that of vehicle-treated rats.

Animals↗
PubMed1993

Consequences of reduced cerebral blood flow in brain development. I. Gross morphology, histology, and callosal connectivity.

Reduced blood flow produced by bilateral carotid artery occlusion (BCAO) caused multiple histopathological alterations in the cerebral cortex of developing cats. BCAO was performed in the second postnatal week. At 1 and 2 months, global structural observations were made using magnetic resonance imaging (MRI). At 3 months, neuron and glial density, extent of myelination, blood vessel distribution, and the distribution of visual callosal projecting neurons (as visualized with the retrogradely transported tracer horseradish peroxidase) were assessed by light microscopy. MRI showed lateral ventricular dilatation at 1 month in five of eight subjects, with wide-ranging severity, although at 2 months only two animals still had enlarged ventricles. Histological observations at 3 months showed that neuron density in the motor cortex, but not the occipital cortex, of BACO animals was significantly lower than that in controls. BCAO animals had more dilated small vessels, again more evident in the motor cortex than in the occipital cortex. From frontal to occipital cortex, the corpus callosum was thinned and the subcortical white matter was reduced. Even with the reduction of white matter, the number of neurons in visual areas 17 and 18 contributing a callosal projection was much higher than normal. BCAO thus altered cerebral vascularization, caused neuronal death, and reduced myelinization over an area much greater than the direct area of carotid perfusion. The excess callosal projection in these animals suggests that neonatal ischemia interferes with the normal process of axon retraction during development.

Aging↗
PubMed1993

Intracranial calcifications associated with nephrogenic diabetes insipidus.

A 6-year-old boy with nephrogenic diabetes insipidus (NDI) and intracranial calcification is reported. The calcifications were symmetrical and located in the basal ganglia and in the subcortical regions of the frontal, temporal, parietal and occipital lobes. Episodes of hyperosmolality during infancy are considered to be one of the causes of intracranial calcification in NDI. However, other unknown factors may be involved, because up to now there have been no reports of intracranial calcification in patients with central diabetes insipidus.

Brain Diseases↗
PubMed1993

Design of hepatocyte-specific extracellular matrices for hybrid artificial liver.

For the development of an artificial liver which can assist multiple metabolic functions of liver, the effective cultivation of hepatocytes on substrate as extracellular matrix analogs was examined. Adult rat hepatocytes attached on an asialoglycoprotein model polymer, poly-N-p-vinylbenzyl-D-lactonamide (PLVA), formed anchored multilayer aggregates which had a stable three-dimensional structure when epidermal growth factor (EGF) and insulin were added to the culture medium. The formation of multilayer aggregates was also dependent on the specific cellular attachment mediated by asialoglycoprotein receptor of hepatocyte surface. Cells in the aggregates expressed higher level of albumin secretion and lower proliferative ability than those in monolayer cultures on collagen. It seemed likely that the cells in multilayer aggregates experienced stable differentiated states resembling in vivo status through the forming multilayer aggregates. The culture system described here has useful potentiality for the development of hepatic module systems for a hybrid artificial liver.

Animals↗
PubMed1993

Evidence that cyclosporine causes both intracellular migration and inappropriate urinary excretion of magnesium in rats.

We determined the effects of cyclosporine on calcium, magnesium, and potassium metabolism in rats. Thirty Sprague-Dawley rats were randomized into three groups of ten animals each--control rats given olive oil, rats given cyclosporine at a dosage of 5 mg/kg daily, and rats given 15 mg/kg daily for four weeks. Urinary excretion of calcium, magnesium, and potassium was determined before and after 2 and 4 weeks of cyclosporine therapy. All rats were sacrificed after 4 weeks of therapy, and calcium, magnesium, and potassium concentrations in serum and tissues were determined. Serum magnesium levels were significantly lower in the cyclosporine-treated groups than in the control group, but there was no significant difference between the control and either of the cyclosporine-treated groups with regard to total urinary excretion of magnesium after four weeks of treatment. Magnesium content in the kidney, muscle, and liver was significantly higher in the 15 mg/kg group than in the control group. Calcium content in the kidney and liver was significantly higher as well. Potassium content in any type of tissue was similar in the three groups. We conclude that the intracellular migration of magnesium plays an important role--as does impaired renal conservation of magnesium--in the pathogenesis of cyclosporine-induced hypomagnesemia and that there is a discrepancy between magnesium and potassium metabolism in cyclosporine-treated rats.

Animals↗
PubMed1993

Functional expression and characterization of the Epstein-Barr virus DNA polymerase catalytic subunit.

A recombinant baculovirus containing the complete sequence for the Epstein-Barr virus (EBV) DNA polymerase catalytic subunit, BALF5 gene product, under the control of the baculovirus polyhedrin promoter was constructed. Insect cells infected with the recombinant virus produced a protein of 110 kDa, recognized by anti-BALF5 protein-specific polyclonal antibody. The expressed EBV DNA polymerase catalytic polypeptide was purified from the cytosolic fraction of the recombinant virus-infected insect cells. The purified protein exhibited both DNA polymerase and 3'-to-5' exonuclease activities, which were neutralized by the anti-BALF5 protein-specific antibody. These results indicate that the 3'-to-5' exonuclease activity associated with the EBV DNA polymerase (T. Tsurumi, Virology 182:376-381, 1991) is an inherent feature of the polymerase catalytic polypeptide. The DNA polymerase and the exonuclease activities of the EBV DNA polymerase catalytic subunit were sensitive to ammonium sulfate in contrast to those of the polymerase complex purified from EBV-producing lymphoblastoid cells, which were stimulated by salt. Furthermore, the template-primer preference for the polymerase catalytic subunit was different from that for the polymerase complex. These observations strongly suggest that the presence of EBV DNA polymerase accessory protein, BMRF1 gene product, does influence the enzymatic properties of EBV DNA polymerase catalytic subunit.

Ammonium Sulfate↗
PubMed1993

Purification and characterization of a 59-kilodalton protein that specifically binds to NF-kappa B-binding motifs of the defense protein genes of Sarcophaga peregrina (the flesh fly).

Various Sarcophaga peregrina (flesh fly) defense protein genes were shown to be activated when NIH-Sape-4 cells were cultured with bacterial lipopolysaccharides or beta-1,3-glucan. The 5' upstream regions of the defense protein genes were found to have common motifs showing similarity to the mammalian NF-kappa B-binding consensus sequence. A protein with affinity to the NF-kappa B-binding motif of the Sarcophaga lectin promoter was identified and purified to near homogeneity. This 59-kDa protein also bound to the NF-kappa B-binding motifs of other defense protein genes, e.g., sarcotoxin I and sarcotoxin II genes. This protein was found in both the cytoplasmic and the nuclear fractions of the cells, and it appeared to migrate from the cytoplasm to the nucleus on treatment of the cells with lipopolysaccharides. This 59-kDa protein is probably a transcriptional regulator of the genes for defense proteins of S. peregrina.

Animals↗
PubMed1993

Effects of hydrogen peroxide on stimulatory guanine nucleotide-binding protein in rat heart.

This study was undertaken to examine the effects of hydrogen peroxide on stimulatory guanine nucleotide-binding protein (Gs), and coupling in the beta-adrenergic receptor-Gs-adenylate cyclase system in rat heart, in vitro. Cardiac membranes were preincubated with various concentrations (0.1, 1, and 10 mM) of hydrogen peroxide at 30 degrees C for 5, 10, 30 and 60 min. Although the assay of beta-adrenergic receptors involving [3H]-dihydroalprenolol ([3H]-DHA) binding revealed that the maximal number of binding sites (Bmax) was not altered, the dissociation constant (Kd) for [3H]-DHA was increased in the presence of 1 mM and 10 mM hydrogen peroxide (control 0.68 +/- 0.16 nM, vs 1 mM H2O2 1.13 +/- 0.16, 10 mM H2O2 1.01 +/- 0.12). Conversely, no significant changes in Gs activities were observed in hydrogen peroxide-treated groups. Adenylate cyclase activity (stimulated by forskolin) was significantly reduced by 10 mM hydrogen peroxide after a 5 min preincubation period (control 277.1 +/- 19.2 pmol cAMP/mg protein/min, H2O2 230.3 +/- 14.9). The amounts of cyclic AMP produced by the stimulation of membranes with GTP, GTP+(l)-isoproterenol, guanylimidodiphosphate (Gpp(NH)p) or Gpp(NH)p+(l)-isoproterenol were significantly lower in 10 mM hydrogen peroxide-treated groups than those in controls (GTP: control 57.6 +/- 5.6 pmol cAMP/mg protein/min vs H2O2 46.4 +/- 6.9, GTP+(l)-isoproterenol: control 83.9 +/- 10.2 vs H2O2 67.7 +/- 10.3, Gpp(NH)p: control 77.5 +/- 8.8 vs H2O2 61.0 +/- 8.6, Gpp(NH)p+(l)-isoproterenol: control 105.0 +/- 13.1 vs H2O2 83.9 +/- 12.2, forskolin: control 223.2 +/- 13.8 vs H2O2 182.8 +/- 18.4).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclase Inhibitors↗
PubMed1993

Dual-tracer autoradiography with thallium-201 and iodine-125 MIBG in BIO 14.6 cardiomyopathic Syrian hamsters.

Dual-tracer imaging of the heart with 125I-metaiodobenzylguanicline (MIBG) and 201Tl can simultaneously demonstrate the distribution of sympathetic nerve endings and the underlying myocardial perfusion. A quantitative dual-tracer autoradiographic study with 201Tl and 125I-MIBG was performed to investigate changes in the distribution of cardiac sympathetic innervation with the progression of cardiomyopathy in BIO 14.6 hamsters. The distribution of 201Tl was uniform in control hamsters and BIO 14.6 hamsters at all stages of cardiomyopathy. In contrast, a reduction in MIBG accumulation occurred in the endocardial region of the left ventricular free wall and the left ventricular aspect of the interventricular septum in BIO 14.6 hamsters at 3 and 8 months of age. Thus, there was an uncoupling of the left ventricular distribution of 201Tl and 125I-MIBG in BIO 14.6 hamsters. In addition, interstitial fibrosis was increased in the interventricular septum, the subendocardial region of the left ventricular free wall, and the right ventricular wall, which were the sites of reduced MIBG accumulation. This study shows that dual myocardial imaging with MIBG and 201Tl may be useful for investigating patients with cardiomyopathy.

3-Iodobenzylguanidine↗
PubMed1993

Effects of phospholipase C on action potentials and intracellular Ca2+ concentration in guinea pig heart.

To clarify the role of phospholipase C (PLC) in arrythmias and cell injury during myocardial ischemia/reperfusion, we studied its effects on electrophysiology and [Ca2+]i in guinea pig hearts. After exposure to PLC (1 and 2 U/ml), the action potential durations of right ventricular papillary muscles were decreased. Delayed afterdepolarizations were observed in all of the preparations, and some developed into triggered activities. Developed tension decreased after an initial increase for the first 5 min, while resting tension increased consistently. The effects of PLC (0.02, 0.1, and 0.2 U/ml) on [Ca2+]i of ventricular myocytes were measured using fura-2 fluorescence. The ratio of rod-shaped cells to all cells decreased in a time- and a concentration-dependent manner. Perfusion with 0.1 U/ml PLC elevated [Ca2+]i from 56 +/- 5 nM to 245 +/- 47 nM before cell rounding, and to 1167 +/- 172 nM after cell rounding, suggesting that PLC causes Ca2+ overload. In conclusion, activation of PLC may play a role in arrhythmias and cell injury during ischemia/reperfusion. The increase in [Ca2+]i during ischemia/reperfusion may activate phospholipase, which would further increase [Ca2+]i to form a vicious cycle.

Action Potentials↗