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Biomedical subjects

T Hara

Publications and source records attributed to T Hara.

At least 595 records · Page 33Linked to original sources
PubMed1995

Neurotropin prevents neurophysiological abnormalities and ADP-induced hyperaggregability in rats with streptozotocin-induced diabetes.

Neurotropin, a non-proteinaceous extract from the inflamed dermis of rabbits inoculated with vaccinia virus, was administered for 8 weeks to rats with streptozotocin-induced diabetes. The physiological and biochemical changes of the nerves were studied as well as ADP-induced platelet aggregation. Neurotropin improved the caudal motor nerve conduction velocity, R-R variability, sciatic nerve blood flow, and platelet hyperaggregability in diabetic rats, despite having no effect on sorbitol and fructose accumulation or myoinositol depletion in the sciatic nerve. The correlation between nerve conduction velocity, R-R variability, nerve blood flow, and platelet aggregation were significant between each two parameters (p < 0.0001). Thus, the mechanism of action of neurotropin differed from that of aldose reductase inhibitors. These findings suggest that vascular factors may play an important role in the development of diabetic neuropathy, and that neurotropin may be useful for the treatment of this condition.

Adenosine Diphosphate↗
PubMed1995

Prevention of abnormalities in motor nerve conduction and nerve blood-flow by a prostacyclin analog, beraprost sodium, in streptozotocin-induced diabetic rats.

The effects of the prostacyclin analog beraprost sodium on motor nerve function and nerve blood-flow were examined in streptozotocin-induced diabetic rats. Oral administration of beraprost sodium 0.1 mg/kg/day for 8 wks significantly (P < 0.001) improved caudal motor nerve conduction velocity and sciatic nerve blood-flow, both of which are impaired in diabetic rats. Beraprost sodium did not affect glucose, sorbitol, or fructose levels in the sciatic nerve. However, a decreased content of cyclic AMP in the sciatic nerve and higher level of thromboxane B2 in the thoracic aorta of diabetic rats, as compared with those in normal rats, were reversed by the treatment with beraprost sodium (P < 0.01). Results suggest that beraprost sodium may have value in treating diabetic neuropathy, mainly by improving endoneurial blood-flow.

Animals↗
PubMed1995

Covalently-bound human C4b dimers consisting of C4B isotype show higher hemolytic activity than those of C4A in the C3-bypass complement pathway.

The ability to form a covalent dimer of human C4b was investigated with purified isotypes C4A and C4B, and antibody-sensitized liposomes supplemented with C1. In this system, no C4A or C4B formed a complex with the antibody or C1. Whereas both C4A and C4B isotypes formed dimers to a similar extent, C4B formed an ester-linked dimer and C4A an amide-linked dimer. Both of these dimers served as a subunit for the C3-bypass pathway C5 convertase, since liposomes bearing Ab, C1 and a dimer of C4A or C4B, allowed the formation of C5 convertase by the addition of C2. The degree of complement-mediated liposome lysis however, was observed to be 2-3 times higher in the C4B-bearing particles than in those bearing C4A. These results indicate that the second C4b-binding site on the first C4b is different between C4A and C4B, and that in the C3-bypass pathway, C4B has a higher degree of hemolytic activity than C4A, as in the conventional classical complement pathway.

Biopolymers↗
PubMed1995

Human lymphocytes are more susceptible to measles virus than granulocytes, which is attributable to the phenotypic differences of their membrane cofactor protein (CD46).

Membrane cofactor protein (MCP, CD46) of the complement system is a measles virus (MV) receptor. Human lymphocytes express a heavily glycosylated (H) and a lightly glycosylated (L) form of MCP, which confers a two-band profile on SDS-PAGE the ratio of which is controlled genetically and organ-specifically. In contrast, granulocytes express a single heavily glycosylated form regardless of lymphocyte MCP phenotype. We investigated susceptibility to MV of granulocytes and lymphocytes from individuals with different lymphocyte MCP phenotypes. In any individual, granulocytes were > 10-fold less susceptible to MV than lymphocytes, and the lymphocytes with predominant H form were generally less susceptible to those with an increasing amount of L form. Thus, lymphocytes always exhibit high susceptibility to MV compared to granulocytes in all individuals. This finding may explain the lymphopenia and immunosuppression observed secondary to MV infection.

Animals↗
PubMed1995

Functional role of coronary collaterals with exercise in infarct-related myocardium.

We evaluated the regional myocardial blood flow in collateral dependent infarct-related areas to examine the functional role of coronary collaterals. Regional myocardial blood flow was measured by positron emission tomography with 13N-ammonia at rest and during low-grade exercise (bicycle ergometer fixed at 25 W for 6.5 min). The study was performed in 24 subjects, consisting of 19 patients with prior myocardial infarction, and five normal individuals. Regional myocardial blood flow was calculated using the radioactivity in myocardial tissue measured by positron emission tomography and the radioactivity in arterial blood. Concerning the infarct related area, the exercise caused myocardial blood flow to decrease by 18.4% (P < 0.01) in the collateral-dependent areas (n = 8) of angiographically positive collaterals, and to increase by 14.4% (P = not significant) in the areas (n = 10) of negative collaterals. Four patients in whom the myocardial blood flow in all walls, including the normal areas, decreased with exercise were excluded from this evaluation. Myocardial blood flow in collateral-dependent infarct-related areas appeared to decrease transiently by low-grade exercise. Our results suggest that collaterals increase the incidence of exercise-induced ischemia, but may protect the infarct related but viable myocardium from necrosis.

Adult↗
PubMed1995

Effect of a potent new aldose reductase inhibitor, (5-(3-thienyltetrazol-1-yl)acetic acid (TAT), on diabetic neuropathy in rats.

(5-(3-Thienyl)tetrazol-1-yl)acetic acid (TAT), a novel potent aldose reductase inhibitor, was administered for 4 weeks to rats with streptozotocin-induced diabetes. Physiological and biochemical studies were subsequently conducted on rat nerve tissue and erythrocyte sorbitol content was estimated. Sciatic nerve blood flow (SNBF) was markedly lower (about 43.4%) in untreated diabetic (DC) rats than in non-diabetic controls (NC). A significant delay in caudal motor nerve conduction velocity (MNCV) and significantly higher glucose, sorbitol and fructose values were observed in the sciatic nerve, accompanied by a markedly higher sorbitol concentration in erythrocytes. In contrast, TAT-treated diabetic groups (DT-10, DT-40 and DT-200) had significantly higher SNBF, MNCV and sciatic nerve myo-inositol values and lower sciatic nerve sorbitol and fructose levels and erythrocyte sorbitol concentration than the DC group. There were good correlations between SNBF and MNCV (r = 0.672, P < 0.001) and between SNBF and erythrocyte sorbitol (r = 0.455, P < 0.003). These findings suggest that both vascular and metabolic factors play an important role in diabetic neuropathy and the effect of aldose reductase inhibitors on diabetic neuropathy may be mediated by at least these two factors.

Aldehyde Reductase↗
PubMed1995

Purification and characterization of rat adrenodoxin.

Adrenodoxin was purified from the rat adrenal gland. The A414/A280 value of the purified rat adrenodoxin was 0.90 and the oxidized spectrum showed absorption maxima at 320, 414 and 455 nm, similar to those of bovine adrenodoxin. On SDS-PAGE, the rat adrenodoxin showed a single band with a molecular mass of 11.2 kDa, while the apparent molecular mass by gel filtration through Sephadex G-75 equilibrated with 10 mM K-phosphate (pH 7.5) was 27 kDa. In the reconstituted system, Vmax of NADPH-cytochrome c reduction activity and the Km for the rat adrenodoxin were much the same as those for recombinant bovine adrenodoxin. In the case of cholesterol side-chain cleavage activity, however, these values of the rat adrenodoxin were about half of those of the bovine adrenodoxin. The CD spectrum of the rat adrenodoxin was similar to that of the bovine adrenodoxin but showed a significantly lower ellipticity value in the 195-205 nm region than that of the bovine adrenodoxin. The structural differences may possibly explain differences in the enzymic properties between rat and bovine adrenodoxins.

Adrenal Glands↗
PubMed1995

Corneal endothelial cell loss caused by detached opacified anterior lens capsule in the anterior chamber.

From 1984 to 1986, we performed cataract surgery through a 1.5 mm anterior capsule hole in 77 eyes. The hole was enlarged to 6.0 mm by a slit incision, and an intraocular lens was implanted into an almost completely intact capsular bag. Twelve (16%) eyes developed severe postoperative anterior capsule opacification. The opacified central anterior capsule, approximately 5 mm in diameter, was detached by can-opener anterior capsulotomy using a neodymium:YAG laser and fell into the inferior anterior chamber. Inferior corneal endothelial cell loss occurred in nine of the 12 eyes within 20 months after detachment; in six of the nine, inferior corneal endothelial cell density decreased 50% more than central cornea cell density. This method will be unsuitable for treating the extensive anterior capsule opacification that will occur when endocapsular cataract surgery that retains most of the lens capsule is widely performed in the future.

Aged↗
PubMed1995

Purification and functional properties of soluble forms of membrane cofactor protein (CD46) of complement: identification of forms increased in cancer patients' sera.

Normal human sera contained 10-60 ng/ml of soluble membrane cofactor protein (MCP, CD46) whereas sera of > 50% of the cancer patients contained > 60 ng/ml. MCP purified by immunoaffinity chromatography from both normal and cancer patients' sera consisted of three bands of 56, 47 and 29 kDa on SDS-PAGE/immunoblotting. The upper two components were increased in cancer patient sera. The 56 and 47 kDa soluble forms served as a cofactor for factor I-mediated cleavage of C3b. MCP expressed on Chinese hamster ovary (CHO) cells protects host cells from human C3 deposition and complement-mediated cytolysis, especially by activation of the alternative pathway. In this same assay system, exogenously added soluble MCP also protected untransfected CHO cells; however, its potency was much less than that of the endogenous membrane form. For example, 8 micrograms/ml of soluble MCP was equal to 10(4) copies/cell of the expressed MCP. Recombinant soluble forms possessed similar activity to the naturally occurring soluble forms and high doses (> 150 micrograms) blocked Arthus-like reaction induced in guinea-pigs by anti-Forssman antibody. These data establish that soluble forms of MCP are present in human sera that possess cofactor activity and their concentrations, especially the 56 and 47 kDa forms, are increased in sera of cancer patients. High doses of the recombinant soluble forms may be therapeutically useful for suppressing inflammatory responses.

Animals↗
PubMed1995

Site-directed mutagenesis of glutathione synthetase from Escherichia coli B: mapping of the gamma-L-glutamyl-L-cysteine-binding site.

Lys18, Arg86, Asn283, Ser286, Thr288 and Glu292 of glutathione synthetase from Escherichia coli B are presumed to be highly concerned with the substrate, gamma-L-glutamyl-L-cysteine (gamma-Glu-Cys), binding by X-ray crystallography and affinity labeling studies. Using site-directed mutagenesis, we investigated functional roles of those residues for gamma-Glu-Cys binding. The mutant enzymes of Arg86 and Asn283 altered their kinetic parameters, especially the Michaelis constants of gamma-Glu-Cys. In the case of Asn283, the residue is not likely to have an essential role in gamma-Glu-Cys binding but its side chain would extend to make a van der Waals contact with bound gamma-Glu-Cys. Chemical modification of a cysteine residue with 5,5'-dithiobis(2-nitrobenzoate) (DTNB) showed Arg86 would not only be much responsible for gamma-Glu-Cys binding but would also have a role in maintaining the structural integrity of the enzyme. The other mutant enzymes showed little defect in their kinetic parameters of gamma-Glu-Cys.

Base Sequence↗
PubMed1995

An aldose reductase inhibitor, TAT, prevents electroretinographic abnormalities and ADP-induced hyperaggregability in streptozotocin-induced diabetic rats.

Rats with streptozotocin-induced diabetes were oral given TAT, a potent aldose reductase inhibitor, at a dose of 10 mg kg-1 day-1 or 40 mg kg-1 day-1 for 30 days. Prolongation of the peak latency of oscillatory potentials in the b-wave of the electroretinogram (ERG), which is associated with retinal Müller cell dysfunction, was significantly improved by treatment with TAT as compared with untreated diabetic rats [sigma(O1 + O2 + O3) was 106.8 +/- 1.8 ms in normal controls (NC), 118.2 +/- 1.1 ms in diabetic controls (DC) (P < 0.001 vs. NC), 110.8 +/- 1.5 ms with 10 mg kg-1 TAT (P < 0.001 vs. DC) and 111.4 +/- 1.6 ms with 40 mg kg-1 TAT (P < 0.01 vs. DC)]. The improvement in ERG abnormalities in diabetic rats was accompanied by partial reduction of elevated sorbitol levels in the retina and erythrocytes, and by correction of platelet hyperaggregability. The authors' findings suggest that a better understanding of the mechanism by which TAT acts may provide new insights into the pathogenesis of hyperglycaemic retinal dysfunction and contribute to establishing effective therapy for diabetic retinopathy.

Adenosine Diphosphate↗
PubMed1995

High expression of membrane cofactor protein of complement (CD46) in human leukaemia cell lines: implication of an alternatively spliced form containing the STA domain in CD46 up-regulation.

Human membrane cofactor protein (MCP, CD46) is a receptor for the measles virus and serves as a complement regulator which protects host cells from autologous complement attack. MCP is highly polymorphic due to a variety of mRNA splice products. The levels of MCP expression on T and myeloid cell lines are usually two-eightfold higher than those on their normal counterparts, whereas Burkitt's lymphoma B cell lines express less MCP than B cell lineages carrying no EB virus. The molecule has a Ser/Thr-rich (ST) domain adjacent to the functional domain, namely short consensus repeats (SCR). The ST domain and a cytoplasmic tail (CYT) contribute to the MCP polymorphism. The ST domain is encoded by three exons (A, B and C) and major ST isoforms are STABC, STBC and STC. The authors investigated the relationship between the expression levels and isoform usage of MCP by flow cytometry using specific antibodies against STA and STC, by reverse transcriptase-polymerase chain reaction (RT-PCR) with size markers for each splice variant, and by RT-PCR/Southern blotting using a specific probe for STA. The results were (1) the profiles of mean shifts of myeloid and T cell lines were STC < STA on flow cytometry while those of B cell lines and normal blood cells were STA < STC; (2) all cell lines tested by RT-PCR expressed the messages for the isoforms STBC/CYT1, STC/CYT1, STBC/CYT2, and STC/CYT2. The band for STABC/CYT2 overlapped that for STC/CYT1, and the band for STABC/CYT1 was marginal in all cell lines examined; (3) semi-quantitative analysis of the STABC isoforms by Southern blotting indicated the presence of high levels of the STABC messages in myeloid and T-cell lines in comparison with B lymphoid cells and normal leucocytes. Thus, the quantity of MCP expressed parallels the STABC message level, which is up-regulated in T and myeloid leukaemia cell lines.

Alternative Splicing↗
PubMed1995

Suppressive effects of benidipine on the development of hypertension and renal lesions in salt-loaded stroke-prone spontaneously hypertensive rats.

1. The effects of benidipine hydrochloride (benidipine), a long-acting dihydropyridine calcium antagonist, on the development of hypertension and renal lesions were examined in stroke-prone spontaneously hypertensive rats (SHRSP). 2. SHRSP were fed with 8% NaCl diet for 3 weeks from 13 weeks of age, and benidipine (1 or 3 mg/kg per day) was orally administered during the same period. 3. The high salt diet accelerated an increase in urinary excretions of total protein and albumin, and caused marked arteriole, glomerular and tubular lesions in the kidney. 4. Benidipine significantly inhibited these changes, and also suppressed the elevation of blood pressure in salt-loaded SHRSP. 5. These results reveal that benidipine has protective effects against the development of hypertension and the progression of renal lesions induced by the high salt diet in SHRSP.

Animals↗
PubMed1995

Detection of immunodeficiencies and persistent infections by urinary neopterin measurement.

We evaluated the clinical significance of measurement of urinary neopterin levels in primary immunodeficiencies and persistent infections exclusively at afebrile or asymptomatic periods. Despite the examinations at afebrile or asymptomatic periods, urinary neopterin levels were elevated in some patients with primary immunodeficiencies and in patients with persistent infections of human immunodeficiency virus (HIV) or Epstein-Barr virus (EBV). Therefore, urinary neopterin measurement at afebrile periods will be useful as one of the screening tests in the detection of such disorders among children with occasional episodes of infections.

Adolescent↗
PubMed1995

When do brain abnormalities in cerebral palsy occur? An MRI study.

The authors used MRI to analyse retrospectively the brain images of patients with cerebral palsy (CP) to evaluate its the role in the assessment of brain abnormalities and injury, and the relationship of pre-, peri- and postnatal events to CP. 70 patients with CP aged two to 16 years who underwent MRI were divided into four groups: group 1 (26 patients) comprised subjects whose CP was considered to have been caused by neuronal migration disorders in the embryonal stage; group 2 (30 patients) contained subjects whose cause was vascular disorders; in group 3 patients (five) the cause was intra-uterine infection; and CP clearly attributable to birth asphyxia (group 4) was noted in only nine patients. The results indicate that CP of term infants is often the result of prenatal factors, and their MRI findings indicated migration and cerebral infarction. Brain MRI is an essential examination in identifying the factors causing brain damage in CP.

Adolescent↗
PubMed1995

Sequential mutations in the interleukin-3 (IL3)/granulocyte-macrophage colony-stimulating factor/IL5 receptor beta-subunit genes are necessary for the complete conversion to growth autonomy mediated by a truncated beta C subunit.

An amino-terminally truncated beta C receptor (beta C-R) subunit of the interleukin-3 (IL3)/granulocyte-macrophage colony-stimulating factor/IL5 receptor complex mediates factor-independent and tumorigenic growth in two spontaneous mutants of a promyelocytic cell line. The constitutive activation of the JAK2 protein kinase in these mutants confirms that signaling occurs through the truncated receptor protein. Noteworthily, in addition to a 10-kb deletion in the beta C-R subunit gene encoding the truncated receptor, several secondary and independent mutations that result in the deletion or functional inactivation of the allelic beta C-R subunit and the closely related beta IL3-R subunit genes were observed in both mutants, suggesting that such mutations are necessary for the full oncogenic penetrance of the truncated beta C-R subunit. Reversion of these mutations by the expression of the wild-type beta C-R in the two mutants resulted in a fivefold decrease in cloning efficiency of the mutants in the absence of IL3, confirming a functional interaction between the wild-type and truncated proteins. Furthermore, expression of the truncated beta C-R subunit in factor-dependent myeloid cells did not immediately render the cells autonomous but increased the spontaneous frequency to factor-independent growth by 4 orders of magnitude. Implications for both leukemogenic progression and receptor-subunit interaction and signaling are discussed.

Amino Acid Sequence↗
PubMed1995

Identification of macrophage colony-stimulating factor in human milk and mammary gland epithelial cells.

Human milk contains cellular and soluble host-protective components. Macrophages in human milk constitute a major cellular component in contrast to those in the peripheral blood. We have investigated a mechanism of local expansion of macrophages in human milk. First, biologically active macrophage colony-stimulating factor (M-CSF) was identified in human milk. The maximal concentrations of M-CSF in human milk were 10- to 100-fold higher than those in the serum. The concentrations of M-CSF in the milk had no correlation with those in the serum. M-CSF was immunohistochemically detected in the epithelial cells of the ducts and alveoli of the mammary gland. In situ hybridization study confirmed the local synthesis of M-CSF in the mammary gland epithelial cells. A possible role of female sex steroids was discussed in the regulation of M-CSF production by mammary gland epithelial cells.

Adult↗