Biomedical subjects

H Hara

Publications and source records attributed to H Hara.

At least 19 recordsLinked to original sources

PubMed1992

Hepatocyte growth factor is linked by O-glycosylated oligosaccharide on the alpha chain.

The glycosylation site and the structure of O-glycosylated oligosaccharide of recombinant human HGF were investigated. N-acetylgalactosamine (GalNAc) in the alpha chain suggested the presence of O-glycosylated oligosaccharide. Sugar analysis and amino acid sequence analysis of peptide fragments produced by limited degradation revealed that O-glycosylated oligosaccharide linked to Thr445 of the alpha chain. The molecular weight of the oligosaccharide was determined with ion spray mass spectrometry. From these studies, the structure of the O-glycosylated oligosaccharide on the alpha chain of HGF was concluded as [formula: see text].

Amino Acid Sequence↗

PubMed1992

Midline malignant B-cell lymphoma with leukemic transformation.

This article presents a case of lethal midline granuloma on the palate of a 44-year-old woman, which had been identified histologically as B-cell lymphoma with leukemic transformation in the terminal stages. At the first visit, physical and laboratory examinations showed no remarkable findings except for a necrotizing ulcer of the palate, and the biopsy specimens only showed massive inflammatory cell infiltration and necrosis of the granulation tissue. There was a short-term resolution after treatment with cyclophosphamide and prednisolone, but the disease reactivated and the necrotic ulcerative lesion progressively advanced into the nasal cavity. Specimens from the third biopsy exhibited histologic features that were consistent with malignant lymphoma of the diffuse, mixed B-cell type. Chemotherapy with the regimen of cyclophosphamide, doxorubicin, vincristine, and prednisolone was adopted but was interrupted after a short time because of bone marrow suppression. Subsequently, large numbers of enlarged abnormal lymphocytes with a few vacuoles in the cytoplasm appeared in the circulating blood, indicating leukemic transformation of the midline lymphoma. The patient died on the seventh day after the initiation of chemotherapy. In the presentation of this case, the authors mention clinically important matters regarding midline lethal lymphoma and briefly discuss the pathophysiology and pathogenesis.

Adult↗

PubMed1992

Effects of baicalein and alpha-tocopherol on lipid peroxidation, free radical scavenging activity and 12-O-tetradecanoylphorbol acetate-induced ear edema.

The effects of baicalein, a flavonoid, and alpha-tocopherol (vitamin E) on lipid peroxidation in rat forebrain homogenates, on free radical scavenging action against diphenyl-p-picrylhydrazyl (DPPH), and on 12-O-tetradecanoylphorbol acetate (TPA)-induced ear edema in mice were studied. Baicalein inhibited lipid peroxidation in forebrain homogenates, DPPH-induced free radical and TPA-induced ear edema as potently as did quercetin and nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, and more potently than BW755C, a mixed cyclooxygenase and lipoxygenase inhibitor. Lipid peroxidation in forebrain homogenates, DPPH-induced free radical and TPA-induced ear edema were also inhibited by alpha-tocopherol. Flavone showed no reaction. These results suggest that lipid peroxidation may play an important role in the pathogenesis of TPA-induced ear edema in mice.

Animals↗

PubMed1992

[Change in serum G-CSF levels in patients with Graves' disease by treatment with methimazole].

We evaluated the determination of serum G-CSF in the diagnosis of granulocytopenia due to methimazole (MMI) in 54 patients with Graves' disease, while they were being treated with MMI, by way of measuring WBC counts and serum levels of G-CSF, thyroid hormones, IgE, and interleukin-2. Serum TSH was measured by immunoradiometric assay, serum G-CSF was done by enzyme immunoassay, thyroid hormones and IgE were done by radioimmunoassay, and serum Interleukin-2 was done by enzyme-linked immunosorbent assay. The population whose G-CSF levels were higher than the minimum detectable level (30pg/ml) was 6 (30%) in normal subjects, 4 (22%) in patients with untreated Graves' disease, 2 (12%) in patients with treated euthyroid Graves' disease, 3 (23%) in patients with Graves' disease who had gone through agranulocytosis, and 2 (33%) in patients with Graves' disease complicated with granulocytopenia. There was no significant change in WBC counts for 4 weeks, but there was a significant difference between WBC counts before treatment and those at 8 weeks after treatment. We observed no significant change of serum G-CSF levels in patients with Graves' disease under treatment. However, there were significantly high levels of serum G-CSF and significantly low counts of WBC in patients with Graves' disease complicated with granulocytopenia induced by MMI, compared with those in normal subjects, patients with untreated Graves' disease, patients with treated euthyroid Graves' disease, and patients with euthyroid Graves' disease who had gone through agranulocytosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Activation of hepatocyte growth factor by proteolytic conversion of a single chain form to a heterodimer.

Hepatocyte growth factor (HGF) is a heterodimeric protein consisting of a heavy chain and a light chain held by a disulfide bond. These chains are produced by endoproteolytic processing from a single chain precursor. In this study, we examined whether the processing is a prerequisite for the mitogenic activity of HGF on hepatocytes in primary culture. Single chain HGF was proteolytically converted to the heterodimeric form during incubation with hepatocytes and was as mitogenic as the heterodimeric form. When the conversion was inhibited by serine-protease inhibitors, the mitogenic activity of single chain HGF was markedly reduced. Furthermore, a mutant resistant to the proteolytic processing, which was prepared by in vitro mutagenesis, completely lost the mitogenic activity. From these results, we concluded that the single chain form of HGF is endoproteolytically processed by a serine-protease and that this processing is a prerequisite for the mitogenic activity of HGF.

Amino Acid Sequence↗

PubMed1992

Resistance of smooth muscle cells to assembly of high density lipoproteins with extracellular free apolipoproteins and to reduction of intracellularly accumulated cholesterol.

Removal of intracellularly accumulated cholesterol by lipid-free human apolipoproteins (apo) A-I and A-II was studied for aortic smooth muscle cells (SMC) of rat, monkey and rabbit, human skin fibroblasts (FB), and mouse peritoneal macrophages (MP). The reaction generated high density lipoprotein (HDL)-like lipoproteins as did those and other helical apolipoproteins with MP, causing efflux of cellular cholesterol. From FB and MP, the maximum efflux rates with apoA-I and A-II per 24 h were as much as 30% of the apparent maximum efflux rate of prelabeled cellular cholesterol to human HDL. From rat SMC these rates were 7.2 and 6.8%, respectively, being independent of cellular cholesterol content. Those from monkey and rabbit SMC were also very low. When standardized for the initial cellular unesterified cholesterol pool size, the maximum efflux rates/24 h were 5.4 and 5.0% for apoA-I and A-II from rat SMC and even less from monkey and rabbit SMC in contrast to 42.4 and 39.7% from FB, and 53.0 and 45.5% from MP, respectively. The standardized apparent maximum efflux to HDL was 76% from rat SMC, 45 and 31% from monkey and rabbit SMC, 139% from FB and 166% from MP. Accordingly, the reaction with free apolipoproteins caused significant net reduction of cellular cholesterol, predominantly in cholesteryl ester, in FB and MP, but not in SMC. While the efflux Km with apoA-I and A-II were 7.5 and 4.5 micrograms/ml for MP, those for SMC and FB were both 1 microgram/ml or lower, as low as 1/1500 and 1/500 of their plasma concentrations, respectively. The apparent efflux Km for HDL were, on the other hand, all in the range of 36 to 65 micrograms of protein/ml for SMC, FB, and MP, showing that the mode of cholesterol exchange of these cells with lipoprotein surface is not significantly different from each other. Thus, peripheral cells such as FB may provide a significant source of HDL by interacting with extracellular free apolipoproteins in interstitial fluid, reducing intracellularly accumulated cholesterol. However, SMC seem very resistant to this interaction, suggesting that atheromatous lesions predominantly consisting of SMC are resistant to regression.

Animals↗

PubMed1992

Effects of protein kinase inhibitors on the mitogenic activity of human hepatocyte growth factor on rat hepatocytes in primary culture.

To evaluate the role of protein phosphorylation reactions in signal transduction of human hepatocyte growth factor (hHGF), now known to be the same protein as the scatter factor and tumor cytotoxic factor, we examined the effects of various inhibitors of protein kinases on the mitogenic activity of hHGF on rat hepatocytes in primary culture. Genistein, a specific inhibitor of tyrosine kinase, dose-dependently inhibited the effect of hHGF in stimulating DNA synthesis of hepatocytes. By contrast, 1-(5-isoquinolinesulfonyl)-2- methylpiperazine (H7), a specific inhibitor of protein kinase C, potentiated the stimulatory effect of hHGF on DNA synthesis of hepatocytes. H7 was effective at over 2 micrograms/ml and potentiated the effect of hHGF over 2-fold at 20 micrograms/ml. On the other hand, an inhibitor of Ca++/calmodulin-dependent protein kinase inhibited both the basal and hHGF-stimulated DNA synthesis in the cells, whereas an inhibitor of cyclic nucleotide-dependent protein kinases had little effect on the action of hHGF. These results suggest that tyrosine phosphorylation is required for stimulation of hepatocyte DNA synthesis by hHGF and that the action of hHGF is negatively regulated by protein kinase C activation.

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

PubMed1992

Catecholamine histofluorescence depletion in the infarcted brain parenchyma but not in the adventitia of the occluded cerebral arteries in rats.

The effect of acute cerebral ischemia on the catecholamine-containing nerve fibers in the brain parenchyma and in the adventitia of the cerebral arteries was studied in the rat. Unilateral cerebral ischemia was produced with an intraluminal thread technique which does not damage the adventitia of cerebral arteries. One to three days after surgery the ischemic damage of the brain was consistently observed in the territory of the middle cerebral artery of the operated side. Depletion of catecholamine histofluorescence was observed in the infarcted brain parenchyma. However, in the adventitia of the middle cerebral arteries of the operated side, catecholamine histofluorescence remained intact. No detectable changes in fluorescence were observed in the brain parenchyma or adventitia of the cerebral arteries in the contralateral side. The results indicate that the perivascular catecholamine-containing nerve fibers are not impaired by the intraluminal occlusion of the cerebral artery in the early stage of ischemia.

Animals↗

PubMed1992

Regional variations in particulate cyclic AMP dependent-protein kinase binding activity in the gerbil hippocampus following transient forebrain ischemia by [3H]cyclic AMP binding.

Changes in the binding of [3H]cyclic AMP as an indicator of particulate cyclic AMP-dependent protein kinase (AMP-DPK) binding activity following transient forebrain ischemia were studied in the gerbil using in vitro autoradiography. [3H]Cyclic AMP binding in the strata pyramidale and lacunosum-moleculare of the hippocampal CA1, the stratum pyramidale of the CA3, and the dentate gyrus decreased transiently in the early postischemic phase but then recovered. However, [3H]cyclic AMP binding in the strata pyramidale and radiatum of the CA1, the granular layer of the dentate gyrus, and the upper layer of the cortex decreased again 7 days after ischemia. In the CA4 subfield and the lower layer of the cortex, the binding showed no significant alterations after ischemia. Administration of pentobarbital prior to the induction of ischemia prevented the decrease in [3H]cyclic AMP binding in the CA1 subfield 6 h and 7 days after ischemia, and showed protective effects against neuronal death of the CA1 pyramidal cells 7 days after ischemia. These results indicate that marked alteration of intracellular signal transduction precedes neuronal damage in the hippocampal CA1 subfield. Furthermore, postischemic reduction of [3H]cyclic AMP binding in the histologically intact cerebral cortex, CA3, and dentate gyrus may be the reflection of cellular dysfunction after energy failure.

Animals↗

PubMed1992

Role of apolipoproteins in cholesterol efflux from macrophages to lipid microemulsion: proposal of a putative model for the pre-beta high-density lipoprotein pathway.

Lipid microemulsion of phospholipid and triglyceride with the size of low-density lipoprotein was capable of removing cholesterol from cholesterol-loaded mouse peritoneal macrophages, resulting in reduction of intracellularly accumulated cholesteryl ester. Apolipoproteins (apo) A-I, A-II, C-III, and E bound to the surface of the microemulsion did not modulate the interaction of the microemulsion with the cells in terms of the cholesterol efflux. The cholesterol removal by the microemulsion was enhanced by some 30% only when apoA-I, -A-II, and -E were present in excess to provide their free forms in the medium, but apoC-III did not show such an effect even by its excess amount. The kinetics including the results with apoC-III were consistent with a model that the apparent enhancement was due to generation of pre-beta high-density lipoprotein (HDL)-like particles upon the interaction of free apolipoproteins with macrophages [Hara, H., & Yokoyama, S. (1991) J. Biol. Chem. 266, 3080-3086]. However, pre beta-HDL-like particle was not detected after 6- and 24-h incubation in the medium where cholesterol efflux to the emulsion was maximally enhanced by the apolipoproteins, and cholesterol and phospholipids removed from the cells were all found with the microemulsions. It was also shown separately that the lipids in pre beta-HDL-like particles generated by apoA-I and macrophages were rapidly, within the order of minutes, transferred to the apo-lipoprotein-covered microemulsions when they were incubated together. Thus, the data were consistent with a model that the free form of certain apolipoproteins, such as apoA-I, -A-II, and -E but not apoC-III, generates pre beta-HDL-like particles with cellular lipids in situ and these particles act as mediators for cholesterol transfer from the cells to other lipoproteins.

Apolipoproteins↗

PubMed1992

Continuing evolution in the operative management of primary hyperparathyroidism.

During the past several decades the operation for primary hyperparathyroidism at The University of Chicago, Ill, has changed from subtotal parathyroidectomy for all patients to removal of an adenoma with performance of biopsies of all other glands to bilateral neck exploration, resection of the adenoma, and performance of fewer biopsies of normal glands. During the 1980s, 308 operations were performed; 288 patients underwent first operations. Two hundred forty-five (85.1%) of these patients had an adenoma and forty-three (14.9%) had hyperplasia (multiglandular disease); none had a carcinoma. Resolution of hypercalcemia was achieved in 281 patients (97.5%); seven patients experienced failed explorations. The early cure was the same whether or not preoperative localization studies were performed. Nineteen patients underwent 20 reoperative parathyroidectomies during this period. Preoperative localization studies, done in 16 (80%) of 20 cases, were very helpful. Ninety percent of patients with abnormal parathyroid glands in their neck or mediastinum were cured with their initial reoperation.

Adenoma↗

PubMed1992

The effect of taurine on the age-related decline of the immune response in mice: the restorative effect on the T cell proliferative response to costimulation with ionomycin and phorbol myristate acetate.

1. Proliferative responses to the costimulation with phorbol-12-myristate-13-acetate (PMA) and suboptimal doses of ionomycin in the purified T and B cells from old mice were lower than those from young mice. 2. The degree of the age-related decline was more significant in T cells than in B cells. 3. Taurine, a sulfur containing amino acid, augmented the proliferative responses of T cells from both young and old mice. 4. The augmentation of the proliferative response by taurine was more marked in old T cells than in young T cells. 5. The concentration of intracellular free calcium ion ([Ca2+]i) was significantly lower in old T cells when stimulated with PMA and ionomycin than observed in young T cells. 6. In the presence of taurine, the concentration of [Ca2+]i in the old T cells significantly increased under stimulation by PMA and ionomycin. 7. The results indicate that taurine improved the proliferative response in old T cells by restoration of the increment of the concentration of [Ca2+]i under the stimulation by PMA and ionomycin.

Aging↗

PubMed1992

Extracellular matrix changes of the optic nerve lamina cribrosa in monkey eyes with experimentally chronic glaucoma.

Using light microscopic immunohistochemistry, we studied the immunolocalization and immunoreactivity of the extracellular matrix, including collagen types III, IV, VI, laminin, and alpha elastin in the lamina cribrosa of monkey eyes with normal and experimentally chronic glaucoma. Our results showed: (1) abnormal linearlike immunodeposits of both collagen type IV and laminin in the margin of the lamina cribrosa with significant density in the glaucomatous eyes; (2) the immunoreactivity of collagen type III resembled that of the normal eye, but was slightly stronger at the laminar surface; (3) findings with collagen type VI resembled those of type III with an enhanced linearlike staining surrounding the nerve-fiber bundles. Furthermore, staining of alpha elastin demonstrated dramatic changes in both reactivity and localization. The lamina cribrosa of glaucomatous eyes showed a markedly reduced immunoreactivity as well as an irregular, interrupted pattern. These observations suggest that the changes might be a secondary to the long-standing elevation of intraocular pressure. The alteration of these macromolecules may modify the course of glaucomatous optic damage.

Animals↗

PubMed1992

Beta-thalassemia major resulting from a compound heterozygosity for the beta-globin gene mutation: further evidence for multiple origin and migration of the thalassemia gene.

We describe in a Japanese family beta zero-thalassemia resulting from a compound heterozygosity for a beta-globin gene mutation. One mutation is a C-to-T transition at IVS-2 nucleotide position 654 on the background of Mediterranean haplotype IX. Another mutation is a G-to-A transition at IVS-2 nucleotide position 1, associated with a novel haplotype XI. The occurrence of these mutations on various chromosomal backgrounds provides strong evidence for an interplay of gene migration, interallelic gene conversion, and multiple origins of the same mutation.

Adult↗

PubMed1992

Secretory meningioma associated with numerous meningothelial rosettes.

A case of secretory meningioma with numerous meningothelial rosettes is reported. A 66-year-old man with moyamoya disease gradually developed skull deformity, and underwent surgery for the skull tumor overlying the hemisphere. Histological examination disclosed numerous meningothelial rosettes quite similar to those induced by subarachnoid injection of epinephrine and pseudopsammoma bodies described by Kepes. This may be the first case of meningioma associated with numerous rosette formations.

Aged↗

PubMed1992

Glycerol injection to the rat trigeminal nerve: histological and immunohistochemical studies.

The effect of topical glycerol injection into the rat trigeminal nerves was investigated histologically and immunohistochemically. Anhydrous glycerol was injected into the preganglionic portion of the trigeminal nerves via a ventral approach. Extensive myelin swelling and axonolysis were observed in the rats killed 1 and 2 weeks after glycerol injection. Numerous inflammatory cells were seen especially in the animals sacrificed 1 week after surgery. Myelin disintegration continued up to 4 weeks after glycerol injection. In normal and saline injected sham operated nerves, calcitonin gene-related peptide (CGRP)- and substance P(SP)-like immunoreactivities were densely localized in the nerve fibers. A marked decrease in both CGRP- and SP-like immunofluorescence was seen in the nerves after glycerol injection. The remaining nerve fibers often had blunt endings with increased fluorescence. Swollen and winding structures were also found. These immunohistochemical changes were observed in the rats killed 1 and 2 weeks following surgery. A similar change but of lesser degree was seen in the 4-week-animal. The present study suggests that topical glycerol injection into the trigeminal nerve induces degeneration of the nerves immunoreactive to CGRP and SP. These changes emphasize the putative functional implications of the peptides in relieving the pain of trigeminal neuralgia after topical glycerol injection.

Animals↗

PubMed1992

Alpha-helical requirements for free apolipoproteins to generate HDL and to induce cellular lipid efflux.

The structural requirement has been studied for apolipoproteins in their free form to interact with cells, to generate high density lipoprotein (HDL), and to cause cellular lipid efflux (J. Biol. Chem. 266, 3080-3086, 1991). It is shown that human apolipoprotein (apo) A-IV and apolipophorin III of Manduca sexta cause cholesterol efflux from cholesterol-loaded mouse peritoneal macrophages and reduce intracellularly accumulated cholesteryl ester as a result of forming HDL-like particles with cellular lipids, as do apoA-I, A-II and E. On the other hand, similar to apoC-III, reduced-and-carboxymethylated human apoA-II had no such effect. Thus, apolipoproteins seem to require at least four amphiphilic helical segments per molecule to express this function.

Animals↗

PubMed1992

Increased receptor binding of low-density lipoprotein from individuals consuming a high-carbohydrate, low-saturated-fat diet.

The substitution of saturated fat by complex carbohydrate, according to current dietary recommendations, results in a decrease of plasma and low-density lipoprotein (LDL) cholesterol levels. To determine whether this decrease might result from structural and thus functional changes in LDL particles, the binding internalization and degradation of 125I-LDL were measured using TR715-19 cells, a mutant CHO line into which has been transfected the human LDL receptor, and in which measurements of binding are highly reproducible. Eleven nondiabetic subjects (35 +/- 4 years, 27% +/- 3% body fat) were studied after they had 15% protein, and 560 mg cholesterol/d and the other containing 21% fat (6% saturated), 65% carbohydrate, 14% protein, and 524 mg cholesterol/d.LDL cholesterol levels decreased form 125 +/- 6 to 108 +/- 5 mg/dl (P < .01) on the high-carbohydrate diet. There was an increase in the binding affinity of LDL (Kd 6.6 +/- 2.6 v 7.3 +/- 2.7 micrograms/mL +/- SD; P < .02), and internalization (P < .10), and degradation (P < .05) were also higher. The data suggest that decreasing dietary saturated fat may cause alterations in LDL composition that result in increased receptor clearance; this may partially explain the LDL-decreasing effect of this dietary change.

Adult↗