Search PubMed⌕ Search

Biomedical subjects

H Hara

Publications and source records attributed to H Hara.

At least 559 records · Page 31Linked to original sources
PubMed1991

The possible involvement of tetrodotoxin-sensitive ion channels in ischemic neuronal damage in the rat hippocampus.

To determine the role of tetrodotoxin-sensitive ion channels in post-ischemic selective neuronal death, the effect of tetrodotoxin on ischemia-induced brain cell injury was studied in rats. The animals were subjected to 20 min of cerebral ischemia in a four vessels occlusion model. Thirty min before ischemia, tetrodotoxin at a dose of 10(-7) or 10(-6) M was topically applied into the hippocampal CA1 subfield. Morphological changes in the CA1 subfield were evaluated 7 days after ischemia and compared with those of a vehicle-injected group. The average cell density of CA1 pyramidal neurons ipsilateral to the injection (cells/mm, mean +/- S.E.M.) was 27 +/- 7 (n = 6) in the vehicle-treated group, and 56 +/- 13 (n = 6) and 83 +/- 17 (n = 6) in the group treated with tetrodotoxin at doses of 10(-7) and 10(-6) M, respectively. Tetrodotoxin mitigated the ischemic hippocampal neuronal damage in a limited but dose-dependent manner. This suggests that activation of tetrodotoxin-sensitive ion channels might contribute to the process of the ischemic neuronal damage.

Animals↗
PubMed1991

Pharmacokinetics of SUN 1165, a new antiarrhythmic agent, in renal dysfunction.

The pharmacokinetics of a new Class I antiarrhythmic agent, SUN 1165, has been studied in 32 patients with varying degrees of renal impairment following a single oral dose of 50 mg. The apparent volume of distribution at steady state was 1.48 l.kg-1, the absorption rate constant was 2.2 h-1, and plasma protein binding was 26.8% in subjects with normal renal function. These variables were not altered with renal impairment. More than 60% of SUN 1165 given orally was excreted unchanged via the kidney, both by tubular secretion and glomerular filtration. The elimination rate constant, the apparent total body clearance and the apparent renal clearance were linearly correlated with the endogenous creatinine clearance. The half-time of elimination was 3.4 h in normal subjects and it was prolonged to 23.7 h in severe renal failure (creatinine clearance below 20 ml.min-1.1.48 m-2). Dosage adjustment of SUN 1165 is necessary in renal failure.

Acute Kidney Injury↗
PubMed1991

Two monoclonal antibodies against small-cell lung cancer show existence of synergism in binding.

Murine IgG1 monoclonal antibodies (mAbs), ITK-2 and ITK-3, were generated against a small-cell lung cancer (SCLC) cell line. Enzyme-linked immunosorbent assay using a variety of established cell lines as substrates, immunoperoxidase staining of freshly frozen tissue sections, and fluorescence-activated cell sorter analysis of peripheral blood leukocytes showed that these mAbs recognize a part of the SCLC-associated cluster 1 antigen. In immunoprecipitation studies, both ITK-2 and ITK-3 bound to a 145-kDa glycoprotein of SCLC cell membrane extracts, as did MOC-1 and NKH-1, which both recognize the cluster 1 antigen. However, because the binding of 125I-labeled ITK-2 to SCLC cells was not inhibited by MOC-1 or NKH-1, the binding site of ITK-2 on SCLC cells appeared to be different from that of either MOC-1 or NKH-1. Unexpectedly, binding of 125I-labeled ITK-2 to SCLC cells increased in the presence of ITK-3. This ITK-3-induced increase in ITK-2 binding was due partly to an increase in the number of binding sites for ITK-2 on SCLC cells. Addition of ITK-3 may, therefore, improve the effectiveness of ITK-2-based tumor detection or therapy.

Antibodies, Monoclonal↗
PubMed1991

Pharmacological properties of YM461, a new orally active platelet-activating factor antagonist.

The antagonistic effect of YM461 [1-(3-phenylpropyl)-4-[2- (3-pyridyl)thiazolidin-4-ylcarbonyl]piperazine fumarate] against platelet-activating factor (PAF) was examined in several in vitro and in vivo systems. We found that YM461 inhibited [3H]PAF binding to rabbit platelet membranes with a pKi value of 8.90. YM461 inhibited PAF induced rabbit and human platelet aggregation with pA2 values of 7.52 and 7.29, respectively; the slopes of the Schild plots were 1.07 and 1.01, respectively. However, YM461 at 10(-4)M did not affect rabbit and human platelet aggregation induced by ADP, collagen, arachidonic acid or epinephrine. YM461 inhibited PAF induced death in mice with an ED50 (50% effective dose) value of 0.35 mg/kg p.o. YM461 at doses above 0.3 mg/kg i.v. inhibited PAF induced hypotension in rats. YM461 showed a dose-dependent inhibition of PAF induced hemoconcentration in rats with ED50 values of 0.15 and 0.21 mg/kg p.o., respectively, at 0.5 and 1 hr after oral administration. The anti-PAF effect of YM461 persisted more than 6 hr after 3 mg/kg p.o. in rats. YM461 inhibited the bronchoconstriction induced by PAF with an ED50 value of 1.2 mg/kg p.o. in anesthetized guinea pigs. Furthermore, the compound at doses above 3 mg/kg p.o. significantly inhibited antigen-induced anaphylactic asthma in conscious guinea pigs pretreated with mepyramine and propranolol. These results indicate that YM461 is a selective, potent and orally active PAF antagonist.

Administration, Oral↗
PubMed1991

Immunoelectron microscopic identification of asialo GM1-positive cells in adult rat liver.

For the electron microscopic identification of asialo GM1-positive cells, fresh-frozen sections fixed with cold acetone and PLP-fixed vibratome sections of adult rat livers were prepared immunocytochemically using the avidin-biotin-peroxidase complex method. Asialo GM1-positive cells were located mainly in the sinusoids, and rarely in Glisson's sheath and portal veins. In the sinusoids, most pit cells, showing the ultrastructural characteristics of large granular lymphocytes (LGL), were positive for asialo GM1 but a few pit cells were asialo GM1-negative. There were several, morphological differences between asialo GM1-positive and -negative pit cells. The asialo GM1-negative pit cells were smaller and had less-developed cell organelles and fewer dense granules, suggesting a more immature stage of development. Almost all the monocytes, segmented neutrophils and eosinophils, and small or large lymphocytes in the sinusoids also showed positive reaction for asialo GM1. In Glisson's sheath, in addition to pit cells and lymphocytes, mast cells were also positive for asialo GM1. In contrast, fixed cells such as liver parenchymal cells, endothelial cells, Kupffer cells and Ito cells within the liver lobules, as well as biliary epithelial cells, smooth muscle cells, fibroblasts, endothelial cells and pericytes in Glisson's sheath were all negative for asialo GM1. Thus, cell surface asialo GM1 expression is not specific for pit cells (LGL) in the rat liver.

Animals↗
PubMed1991

Involvement of lipid peroxidation and inhibitory mechanisms on ischemic neuronal damage in gerbil hippocampus: quantitative autoradiographic studies on second messenger and neurotransmitter systems.

We investigated, to examine the involvement of lipid peroxidation and inhibitory mechanisms, a novel lipid peroxidation inhibitor (KB-5666) and a GABAA receptor-effector (pentobarbital) on ischemic neuronal damage and the alterations in the second messenger and neurotransmitter systems in Mongolian gerbils by means of morphology and in vitro receptor autoradiography. Quantitative receptor autoradiography visualized binding sites for [3H]inositol 1,4,5-trisphosphate, [3H]forskolin, [3H]phorbol 12,13-dibutyrate, [3H]isradipine (PN200-110), [3H]N6-cyclohexyl-adenosine, and [3H]quinuclidinyl benzilate indicating binding sites for inositol 1,4,5-trisphosphate, forskolin, protein kinase C, L-type calcium channels (or dihydropyridine binding sites), adenosine A1, and muscarinic cholinergic receptors, respectively. In the morphological study, KB-5666, 10 and 50 mg/kg, i.v., 5 min before ischemia, protected against ischemic neuronal damage to the hippocampal CA1 subfield following 5 min of bilateral carotid artery occlusion in a dose-dependent manner. Pentobarbital, 30 mg/kg, i.v., 5 min before ischemia, also had a protective effect. In receptor autoradiographic studies, all receptor bindings decreased significantly in the CA1 subfield seven days after ischemia. In particular, [3H]inositol 1,4,5-trisphosphate binding in the CA1 subfield was completely lost after ischemia. [3H]Inositol 1,4,5-trisphosphate and [3H]forskolin binding decreased as early as 6 h after ischemia. In the CA3 subfield, [3H]inositol 1,4,5-trisphosphate, [3H]PN200-110, and [3H]N6-cyclohexyladenosine bindings decreased seven days after ischemia. In the dentate gyrus, [3H]inositol 1,4,5-trisphosphate binding decreased seven days after ischemia. KB-5666 and pentobarbital prevented reductions in these receptor bindings in the CA1 subfield at 6 h and seven days after ischemia. These results indicate that KB-5666 and pentobarbital protect the brain from both structural and functional damage after ischemia, and that lipid peroxidation and inhibitory mechanisms may play a pivotal role in the neuronal damage of the hippocampal CA1 subfield after ischemia.

Adenosine↗
PubMed1991

Autoradiographic analysis of second-messenger systems in the gerbil hippocampus following repeated brief ischemic insults.

Using [3H]inositol 1,4,5-triphosphate (IP3), [3H]phorbol 12,13-dibutyrate (PDBu) and [3H]forskolin, we performed quantitative autoradiography to determine sequential alterations in second-messenger systems in the gerbil hippocampus following repeated brief ischemic insults. Changes following three 2-min ischemic insults were compared with those following single 2- or 6-min ischemia. [3H]IP3 binding was extremely sensitive to ischemic insult, and more than 80% of the binding sites were lost after destruction of CA1 pyramidal cells following 6-min ischemia and three 2-min ischemic insults. Furthermore, a 30% reduction was observed after 2-min ischemia which leads to no neuronal loss. [3H]PDBu binding in the CA1 subfield decreased by 1 day after three 2-min ischemic insults and by 4 days after 6-min ischemia, and 40-50% reductions were observed at 1 month. In contrast, [3H]forskolin binding was relatively preserved. [3H]PDBu and [3H]forskolin binding transiently increased early in the reperfusion period. We also observed a difference in the pattern and severity of alterations between repeated ischemic insults and single ischemia.

Animals↗
PubMed1991

Absorptive behavior of oligo-L-methionine and dietary proteins in a casein or soybean protein diet: porto-venous differences in amino acid concentrations in unrestrained rats.

In a low casein methionine-deficient diet, supplementation with oligo-L-methionine (OM) has a similar improvement on rat growth to supplementation of free L-methionine. Rat growth is little improved, however, when OM is added to a low soybean protein isolate (SPI) diet. To evaluate the mechanisms of the different effects of OM supplementation, we observed intestinal absorption of OM added to either an 8 g/100 g casein diet or an 8 g/100 g SPI diet. Using portal and venous cannulated rats under unrestrained conditions, we evaluated OM absorption by subtracting methionine porto-venous differences after feeding the diets without OM from the values after feeding the diets with 3% added OM. OM absorption was faster after feeding the casein-based diet than after the SPI-based diet during the initial stages of the experiment only, but throughout the experiment there were greater increments of methionine concentrations in both portal and venous blood after the casein-based diet than after the SPI-based diet. We also discovered that amino acids from the dietary casein were absorbed faster than those from SPI, using the porto-venous difference of isoleucine as an indication. The larger increment of methionine concentrations in the blood after feeding of OM with a casein diet and the rapid absorption of amino acids from casein may result in much growth improvement in rats.

Amino Acids↗
PubMed1991

Giant aneurysms of the horizontal segment of the anterior cerebral artery: report of two cases.

Two cases of giant aneurysm of the horizontal segment of the anterior cerebral artery (A1) are presented. The rare occurrence of a giant aneurysm in this location necessitates evaluation of the cross-flow through the anterior communicating artery when planning surgical strategy. On the basis of angiographic findings, trapping of the A1 on both sides of the aneurysm neck was performed in Case 1, and aneurysmorrhaphy utilizing an angioplastic multiple-clipping method of A1 endarterectomy was accomplished in Case 2. The postoperative courses of both patients were satisfactory.

Aged↗
PubMed1991

Characterization and purification of an immunosuppressive factor produced by a small cell lung cancer cell line.

The present study was undertaken to determine whether small cell lung cancer (SCLC) cell lines produce immunosuppressive factors and, if they do, to characterize the factors. The supernatants of SCLC cell lines, H69 and N857, inhibited not only the blastogenic response of human peripheral blood lymphocytes (PBL) to phytohemagglutinin or concanavalin A, but also the cytotoxic activity of lymphokine-activated killer cells. Neither was inhibited by supernatants from non-SCLC cell lines PC9, QG56, and A549. The immunosuppressive activity of H69 supernatant was stable upon heating to 56 degrees C for 60 min, but labile when heated to 70 degrees C for 10 min. The activity was abolished after dialysis at pH 2.0 or pH 11.0, but not at pH 4.5 or pH 9.0. Digestion with trypsin or proteinase eliminated the immunosuppressive activity, whereas treatment with neuraminidase, mixed glycosidase, DNase or RNase had no effect, suggesting that the immunosuppressive activity in H69 supernatant is due to a protein factor. This H69-derived immunosuppressive factor was isolated by ion exchange chromatography using a gradient of 0.04 to 0.08 M NaCl solution. Gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed the factor to have molecular weights of 98 kD and 102 kD, respectively. These results suggest that SCLC cells produce a potent immunosuppressive factor which may account for the immune deficiency in SCLC patients.

Carcinoma, Small Cell↗
PubMed1991

A case of pheochromocytoma associated with meningioma.

We have recently observed a rare case of pheochromocytoma associated with meningioma. To determine the mechanism of such a coexistence in this particular case, we compared the constitutional and pheochromocytoma genotypes of the patient using polymorphic four DNA markers, and we found a loss of heterozygosity at the D1S7 locus. A loss of heterozygosity at this locus has previously been reported by Mathew et al. in pheochromocytoma patients, and our results were in agreement with that study. Therefore the allelic deletion at the D1S7 locus may be an important step in the tumorigenesis of pheochromocytoma in this case.

Adrenal Gland Neoplasms↗
PubMed1991

Distribution of protein kinase C in the hippocampus of the gerbil and rat: autoradiographic analysis by [3H]phorbol 12,13-dibutyrate.

In-vitro quantitative receptor autoradiography with [3H]phorbol 12,13-dibutyrate (PDBu) was used to determine the affinity constant (Kd) and the maximum number of receptor sites (Bmax) for protein kinase C (PKC) in subregions of the gerbil hippocampus, and to compare the distribution of [3H]PDBu binding sites in the gerbil hippocampus with that in the rat hippocampus. The Kd and Bmax values in the subregions of the gerbil hippocampus were estimated at 2.6-3.8 nM and 2.38-2.54 pmol (mg tissue)-1, respectively. The distribution of hippocampus [3H]PDBu binding sites was uniform in the gerbil but not in the rat. The [3H]PDBu binding activities in the strata oriens of the CA1 and CA3 subfields and the molecular layer of the dentate gyrus in the rat hippocampus were significantly higher than in the gerbil hippocampus. However, binding activity in the stratum lacunosum-moleculare of the rat CA1 subfield was statistically lower. These data demonstrate a difference in the distribution of [3H]PDBu binding activity in the hippocampus between the gerbil and rat.

Animals↗
PubMed1991

Nuclease-sensitive binding of an Actinobacillus actinomycetemcomitans leukotoxin to the bacterial cell surface.

A leukotoxin of Actinobacillus actinomycetemcomitans 301-b was solubilized from cell-associated membrane vesicles by treatment with externally added DNase and RNase and was further purified by a procedure which included ammonium sulfate fractionation, gel filtration chromatography, and ion-exchange chromatography. The purified toxin had a molecular mass of 113,000 Da by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and a high isoelectric point (approximately 8.8). From these characteristics, it was to be expected that the membrane vesicle toxin was almost identical to the leukotoxin extracted with polymyxin B in an earlier study (C.-C. Tsai, B. J. Shenker, J. M. DiRienzo, D. Malamud, and N. S. Taichman, Infect, Immun. 43:700-705, 1984). The treatment with DNase and RNase was also highly effective for solubilizing the leukotoxin directly from whole cells, suggesting that the toxin is secreted extracellularly but retained in nucleic acids on the outermost surface of bacterial cells.

Aggregatibacter actinomycetemcomitans↗
PubMed1991

Cloning, mapping, and characterization of the Escherichia coli prc gene, which is involved in C-terminal processing of penicillin-binding protein 3.

The prc gene, which is involved in cleavage of the C-terminal peptide from the precursor form of penicillin-binding protein 3 (PBP 3) of Escherichia coli, was cloned and mapped at 40.4 min on the chromosome. The gene product was identified as a protein of about 80 kDa in maxicell and in vitro systems. Fractionation of the maxicells producing the product suggested that the product was associated with the periplasmic side of the cytoplasmic membrane. This was consistent with the notion that the C-terminal processing of PBP 3 probably occurs outside the cytoplasmic membrane: the processing was found to be dependent on the secY and secA functions, indicating that the prc product or PBP 3 or both share the translocation machinery with other extracytoplasmic proteins. DNA sequencing analysis of the prc gene region identified an open reading frame, with two possible translational starts 6 bp apart from each other, that could code for a product with a calculated molecular weight of 76,667 or 76,432. The prc mutant was sensitive to thermal and osmotic stresses. Southern analysis of the chromosomal DNA of the mutant unexpectedly revealed that the mutation was a deletion of the entire prc gene and thus that the prc gene is conditionally dispensable. The mutation resulted in greatly reduced heat shock response at low osmolarity and in leakage of periplasmic proteins.

Amino Acid Sequence↗
PubMed1991

Potential nootropic agents, 4-alkoxy-2-(1-piperazinyl)quinazoline derivatives.

A series of 4-alkoxy-2-(1-piperazinyl)quinazoline derivatives was synthesized and evaluated for its ability to reverse a scopolamine-induced learned impairment in a one-trial passive avoidance task (antiamnestic activity). 2-(4-Allyl-1-piperazinyl)-4-pentyloxyquinazoline (4) showed more potent antiamnestic activity than such reference compounds as aniracetam, idebenone and bifemelane at a wide dose range (1-30 mg/kg]. Compound 4 also exhibited potent anticonvulsive and antihypoxic activities, and was selected as the most promising nootropic candidate agent.

Animals↗
PubMed1991

A case of pituitary adenoma producing both growth hormone (GH) and adrenocorticotropic hormone (ACTH).

The authors report a very rare case of pituitary adenoma producing both GH and ACTH. A 29-year-old female was admitted with obesity, amenorrhea, acromegaly, hirsutism, excessive pigmentation, acne, and diabetes mellitus. Computed tomography revealed an intrasellar tumor 16 mm in height, with a destroyed sellar floor. The blood concentrations of GH, ACTH and cortisol were increased (GH: 92 ng/ml, ACTH: 94 pg/ml, cortisol: 18.3 micrograms/dl). No diurnal variation in the amount of cortisol was observed. The urinary 17-OHCS was suppressed by 8 mg but not by 2 mg of dexamethasone. A subtotal adenomectomy was then performed through the transsphenoidal approach, which led to a sufficient reduction of both blood GH and ACTH (cortisol). Histologically the tumor was an acidophilic pituitary adenoma. Immunoperoxidase staining showed diffuse GH and sporadic ACTH producing cells, but failed to show any cells producing both hormones. The electron micrograms of neoplastic cells showed the ultrastructural characteristics of respective GH and ACTH cells. Another increase in both GH and cortisol, which occurred 19 months after the operation, has been controlled by bromocriptine administration. This case may be the first reported case of a pituitary adenoma producing both GH and ACTH, not accompanied by prolactin (PRL) hypersecretion, which has been fully confirmed endocrinologically and histopathologically.

Adenoma↗
PubMed1991

Prevalence of chondrocalcinosis in patients with primary hyperparathyroidism in Japan.

One hundred and thirty-two consecutive patients with primary hyperparathyroidism were studied preoperatively for the presence of chondrocalcinosis, the roentgenographic marker of calcium pyrophosphate dihydrate (CPPD) crystal deposition disease, by obtaining radiographs of knees, wrists and pelvis. Chondrocalcinosis was found in 8 patients (6.1%), each of whom was over 50 years of age. In 72 of the patients over 50 years of age, the prevalence of chondrocalcinosis in the hyperparathyroid patients (11.1%) was greater than that found in 72 control patients (2.8%) with thyroid nodular disease who were exactly matched for age and sex, but the difference was not significant. The prevalence of chondrocalcinosis in the hyperparathyroid patients sharply increased with age. In the group in their 50's it was 4.4%, rising to 15.8% in patients in their 60's and reaching 37.5% for those over 70 years of age. Patients with chondrocalcinosis were significantly older than those without this finding (p < 0.005). Those with chondrocalcinosis also had significantly higher preoperative serum calcium levels than those without it (p < 0.05). While chondrocalcinosis was detected by taking joint radiographs in all patients with primary hyperparathyroidism, acute arthritis (pseudogout attack) occurred in only 2 of the 132 patients (1.5%) after parathyroidectomy, but this represents 25% (2 of 8) of those who had chondrocalcinosis. An attack of pseudogout may therefore be one of the most common postoperative complications of parathyroid surgery in the elderly. Considering the low incidence of pseudogout attack following parathyroidectomy, preoperative radiological studies of the knee joints are sufficient to screen for chondrocalcinosis and are recommended for patients over 60 years old in Japan.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗