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Biomedical subjects

S Harada

Publications and source records attributed to S Harada.

At least 415 records · Page 23Linked to original sources
PubMed1991

A combined rectus abdominis musculocutaneous flap and vascularized iliac bone graft with double vascular pedicles.

Although a free vascularized iliac bone graft has been successfully used for the reconstruction of large bone defects, there is a serious problem of how to repair in one stage patients having a large bone defect with a very wide skin defect. A free combined rectus abdominis musculocutaneous flap and vascularized iliac bone graft with double vascular pedicles seems to be one of the most suitable methods for patients having large defects of both bone and skin. Based on our patient, the main advantage of this flap is the extreme width of the skin territory. The pedicle vessels are large and long, and the donor scar can be made in an unexposed area. This flap should be considered for use in one-stage reconstructions of large defects of both bone and skin in the leg region.

Humans↗
PubMed1991

Coexistence of fusion receptors for human T-cell leukemia virus type-I (HTLV-I) and human immunodeficiency virus type-1 (HIV-1) on MOLT-4 cells.

Human immunodeficiency virus type-1 (HIV-1) and human T-cell leukemia virus type-I (HTLV-I) have a similar tropism for target cell types, especially for CD4+ T cells. In this study, we provide evidence that receptors of these two viruses exist independently on the target cell. We established an HTLV-I-producing CD8+ T cell line (ILT-8M2) with a remarkable cell fusion capacity. When cocultured with MOLT-4 cells, ILT-8M2 cells induced giant syncytia more efficiently than any other tested HTLV-I-producer cell lines. In contrast to other HTLV-I-producers, ILT-8M2 cells were minimally susceptible to cytopathic effects of HIV-1 due to very low expression of CD4, although they were able to be persistently infected by HIV-1. The indicator MOLT-4 cells are known to respond well to HIV-1-induced cell fusion, but they lose this ability if they become persistently infected with HIV-1 because of the reduction of CD4 receptor expression. ILT-8M2 was, however, still capable of inducing syncytia with the MOLT-4 cells persistently infected by HIV-1 (MOLT-4/IIIB). This syncytium formation was dependent on the HTLV-I-envelope, as it was inhibited by HTLV-I-positive human sera or a monoclonal antibody to HTLV-I gp46 but not by monoclonal antibodies to HIV-1 gp120 or CD4. Moreover, ILT-8M2 cells persistently infected by HIV-1 (ILT-8M2/IIIB) induced both HTLV-I- and HIV-1-mediated syncytia with uninfected MOLT-4 cells. These results suggest that HTLV-I induces cell fusion utilizing receptors on the target cells independent of HIV-1-receptors.

CD8 Antigens↗
PubMed1991

Expression of processed core protein of hepatitis C virus in mammalian cells.

A structural protein of hepatitis C virus (HCV) was expressed in monkey COS cells under the control of an exogenous promoter, and a protein of 22 kDa was identified by immunoblot analysis. This protein (p22), which was produced by processing in COS cells, reacted specifically to sera of chronic hepatitis C patients, and its coding region was mapped at the most amino-terminal part of the HCV polyprotein. These results suggested that the p22 protein is the nucleocapsid (core) protein of HCV. Moreover, the assay detecting antibody to p22 was found to be useful for early diagnosis of HCV infection.

Animals↗
PubMed1991

Arterial baroreflex control of cardiac and renal sympathetic nerve activities is uniform in frequency domain.

To investigate wideband dynamic properties of arterial baroreflex control of cardiac and renal sympathetic nerve activities, we assessed the transfer function using a "white-noise technique." In pentobarbital sodium-anesthetized cats, we simultaneously recorded, as the output, cardiac sympathetic nerve activity (CSNA) and renal sympathetic nerve activity (RSNA), while aortic pressure (AP) was randomly perturbed to impose input pressure changes with broad frequencies. We calculated the transfer function from AP to CSNA or to RSNA over the frequency range of 0.01-5 Hz through the spectral analysis of the input and output. We found that the gain, phase shift, and coherence of those transfer functions were statistically indistinguishable. The gain was rather flat below 0.05 Hz, steadily increased above 0.05 Hz, and plateaued above 0.3 Hz. The phase shift was out of phase up to 0.05 Hz and led by approximately 4 degrees above 0.05 Hz. The coherence was high (above 0.7) below 0.3 Hz and became lower above 0.3 Hz. These results suggest that arterial baroreflex control is uniform and similar between the two activities in the frequency range of 0.01-0.7 Hz.

Animals↗
PubMed1991

Extracellular production of mouse interferon beta by the Bacillus subtilis alpha-amylase secretion vectors: antiviral activity and deduced NH2-terminal amino acid sequences of the secreted proteins.

Using two Bacillus subtilis alpha-amylase secretion vectors, mouse interferon-beta (IFN-beta) cDNA was expressed. Ten kinds of mature and hybrid forms of biologically active mouse IFN-beta proteins were synthesized in B. subtilis and were secreted into the culture medium. Similar amounts of proteins, which were determined by immunoblot analysis, were secreted from the B. subtilis transformants, while the antiviral activity in the medium was markedly different in each one of them. The highest antiviral activity was observed in a hybrid protein, in which eleven amino acids consisting of the prosequence of alpha-amylase (eight amino acids) and three amino acids encoding in the HindIII linker DNA were assumed to be extended in front of the Leu residue at position 6 of the mature form of mouse IFN-beta. Its activity was higher than that of the mature form of the mouse IFN-beta secreted from a B. subtilis transformant. These results indicate that the amino acid sequence around the NH2-terminal region of the mouse IFN-beta is closely related to the antiviral activity, but the NH2-terminal amino acid is not. The hybrid proteins of mouse IFN-beta show no interferon activity against a human cell line, HEL.

Amino Acid Sequence↗
PubMed1991

Pheochromocytoma with pyrexia and marked inflammatory signs: a paraneoplastic syndrome with possible relation to interleukin-6 production.

Pheochromocytoma can cause several paraneoplastic syndromes. We report a patient with pheochromocytoma who exhibited pyrexia and marked inflammatory signs along with an elevated serum interleukin-6 (IL-6) level. All of these abnormalities disappeared and serum IL-6 became undetectable by removal of the tumor. In addition, immunohistochemical analysis revealed the presence of IL-6 in the tumor cells. It is suggested that pyrexia and the elevation of acute phase proteins can be a paraneoplastic syndrome with pheochromocytoma, and that the elaboration of IL-6 from pheochromocytoma may play an important role in the development of the syndrome.

Adrenal Gland Neoplasms↗
PubMed1991

Synthesis and biological activity of (S)-2-amino-3-(2,5-dihydro-5-oxo-4-isoxazolyl)propanoic acid (TAN-950 A) derivatives.

(S)-2-Amino-3-(2,5-dihydro-5-oxo-4-isoxazolyl)propanoic acid (TAN-950 A (1)) is a novel amino acid antibiotic which shows a high affinity for glutamate receptors of the central nervous system. To improve the affinity for glutamate receptors, the structure-activity relationships of TAN-950 A derivatives 6a--o, 15a--o were investigated. Optically active TAN-950 A analogs 15a--h were synthesized starting with methyl (S)- and (R)-N-Boc-pyroglutamate (8) via acylation at the C-4 position followed by isoxazolone formation with hydroxylamine and subsequent deprotection reactions. The lactam 16, prepared from (RS)-aminoadipic acid, and dimethyl esters 19 of (R)- and (S)-aspartic acid were converted to (RS)-3-methyl-homo-TAN-950 A (15i) and optically active nor-TAN-950 A derivatives 15j--o, respectively, utilizing a similar sequence of reactions. Most of TAN-950 A derivatives 6a--o, 15a--o showed an affinity for glutamate receptors. The 3-alkyl derivatives 15b, d--g, especially, showed a high affinity for the quisqualate subtype-receptor and had a strong activating effect on the hippocampal neurons (glutamate agonistic activity). The (R)-enantiomer 15a of TAN-950 A had increased selectivity for the N-methyl-D-aspartate (NMDA) subtype-receptor. This selectivity was further enhanced by removal of the methylene group in the amino acid moiety of 15a. The most potent and selective NMDA agonistic activity was observed with (R)-3-methyl-nor-TAN-950 A (15m).

Animals↗
PubMed1991

[A case of lupus erythematosus preceded by right heart failure due to pulmonary hypertension].

A 40-year-old woman was admitted because of increasing exertional dyspnea. Right heart failure was suggested by the presence of hepatomegaly, pretibial edema and also echocardiographic findings. Physical examination and echocardiography showed no evidence of valvular disease or congenital heart disease except for right ventricular dilatation and tricuspid regurgitation. The ventricular septum deviated toward the left ventricle throughout the cardiac cycle, but left ventricular function was preserved. Severe pulmonary hypertension averaging 44 mmHg was revealed by cardiac catheterization. Digital subtraction angiography and pulmonary blood flow scintigraphy showed no evidence of pulmonary artery embolism, and no interstitial pulmonary lesions that might have caused pulmonary hypertension were recognized. Hypergammaglobulinemia suggested an autoimmune disorder, and signs of systemic lupus erythematosus (SLE), such as pleural effusion, proteinuria, lymphocytopenia, LE cell phenomenon and antinuclear antibodies were present. Several autoimmune diseases are known to be causative factors of pulmonary hypertension. However, only ten cases of SLE complicated by pulmonary hypertension have been reported the present one. These cases were characterized by a high incidence of Raynaud's phenomenon and positivity for anti-RNP antibody. In our present case, SLE activity was suppressed using prednisolone, but pulmonary hypertension persisted and the patient eventually died due to right cardiac failure. Judging from the clinical course of the ten reported cases of SLE-pulmonary hypertension, there seems to be no hope of improving the pulmonary hypertension once it has become established. Therefore it is important to detect and cure pulmonary hypertension as early as possible.

Angiography, Digital Subtraction↗
PubMed1991

Gangliosides administration causes sugar moiety-specific enzymatic changes in brain.

Exogenous gangliosides are known to affect the metabolism when administered to the body. To study the mechanism of this effect three types of gangliosides were administered intraperitoneally to mice and the changes in the enzyme activity of the cerebral tissues studied. The effect of GM2 from bovine brain was characterized by a decrease in the activity of various aminopeptidases, while GD3 from cow's milk caused an increase in the activity of sugar-related enzymes such as sialidase, glucosidase, and fucosidase. GM3 from horse erythrocytes showed intermediate effects between GM2 and GD3. Multivariate analysis showed that the effects of the three gangliosides are clearly separable statistically. These results which demonstrate the sugar moiety-specificity of gangliosides are discussed in relation to the A and B pathways of ganglioside synthesis.

Amino Acid Sequence↗
PubMed1991

[Localization of glutathione-S-transferase in transparent and cataractous human lenses].

The localization of glutathione-S-transferase (GST) activity was investigated in 15 cataractous lenses obtained by intracapsular extraction of senile cataract. Additionally, 8 clear lenses, obtained from donor eyes in cases of corneal transplantation or of traumatic lens luxation, were used as controls. The lenses were divided into the central and peripheral portions with a trephine. The activity of GST was quantitated in each portion according to the method described by Habig. GST activity in clear lenses was significantly higher in the peripheral portion than in the central portion and in the former it was significantly higher in clear lenses than in cataractous ones. The ratio of GST activity between central and peripheral portions (C/P) was significantly higher in cataractous lenses than in clear ones. These findings suggested that the scavenging system of the human clear lens is more active in the equatorial portion than in the central portion. Nevertheless the activity of GST in human cataractous lenses decreased more significantly in the peripheral portion than in the central portion. These findings indicated that the human cataract usually develop from equatorial portion of lens.

Adult↗
PubMed1990

Generation of neutralization-resistant HIV-1 in vitro due to amino acid interchanges of third hypervariable env region.

Antigenic mutants of HIV-1 were isolated from three plaque-cloned viruses by the resistance of the virus to neutralizing mAb 0.5 beta against V3 domain of viral gp120, when the viruses were passaged in the presence of the antibody. However, when chronically infected MOLT-4 cells were treated with 0.5 beta mAb, recovered viruses from the 0.5 beta-treated cells showed no antigenic changes. The extent of genomic variation among antigenically distinct isolates was examined by nucleotide sequencing, which revealed a few base substitutions in 0.5 beta-binding site of all mutants isolated. The predicted amino acid replacements within 0.5 beta reacting epitope (V3 domain) causing the altered antigenicity were also identified for each of three isolates. Particularly, in one of the mutants, the most conserved Gly-Pro-Gly-Arg region located at the center of the V3 domain was changed to Gly-Gln-Gly-Arg. The radioimmunoprecipitation and synthetic peptide analyses revealed that this Pro320----Gln substitution reduced the binding affinity with 0.5 beta, although other mutations observed in the other mutants did not affect the binding affinity in radioimmunoprecipitation. We also observed that nucleic acid substitutions in the V3 domain occurred frequently in the absence of 0.5 beta mAb during our in vitro acute infection system using MT-4 cells.

Amino Acid Sequence↗
PubMed1990

Deficiency of kallikrein-like enzyme activities in cerebral tissue of patients with Alzheimer's disease.

We examined the changes in the intracerebral activities, at the time of postmortem autopsy, in patients with Alzheimer's disease. When compared with the control group, the activity of kallikrein-like enzyme was significantly decreased, while prolyl endopeptidase activity increased, in the patients group. Aprotinin inhibited 50% of the activity of the former enzyme at 2 x 10(-7) M. Taken together with the results of a multivariate study, the above findings may indicate that intracerebral kallikrein deficiency plays an important role in the pathogenesis of Alzheimer's disease.

Aged↗