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Biomedical subjects

K Kusumi

Publications and source records attributed to K Kusumi.

33 records · Page 2Linked to original sources
PubMed1992

Human immunodeficiency virus type 1 envelope gene structure and diversity in vivo and after cocultivation in vitro.

Nested-primer polymerase chain reaction (PCR) has been applied to the molecular cloning of 4.6-kb half-genome fragments of human immunodeficiency virus type 1 (HIV-1) taken directly from the peripheral blood mononuclear cells (PBMC) of an individual with neurological symptoms of HIV-1 infection. In a similar manner, gp120-coding portions of the envelope gene were cloned after PBMC from the same blood sample were cocultivated with uninfected PBMC for 28 days. The complete 1.6-kb nucleotide sequence of the gp120 gene was determined from each of 35 clones examined. Two of 13 (15%) PBMC-derived gp120 genes and 3 of 22 (14%) coculture-derived gp120 genes were defective as a result of frameshifts and an in-frame stop codon(s). Mean diversity between individual gp120-coding sequences in PBMC was fivefold greater (3.24%) than after coculture (0.65%). A predominant sequence of "strain" was found after coculture that was distinct from the diverse viral genotypes detected in vivo and therefore was selectively amplified during in vitro propagation. Multiple distinct third variable (V3) regions encoding the principal neutralizing domain of the envelope protein were detected in PBMC-derived genes, suggesting the presence of immunologic diversity of HIV env genes in vivo not reflected in the cocultured virus sample. The large size of the HIV fragments generated in this study will permit analysis of the diversity of immunologic reactivity, gene function, and pathogenicity of HIV genomes present within infected individuals, including the functional significance of the loss of diversity that occurs upon coculture.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Genetic mapping of a gene causing hypertension in the stroke-prone spontaneously hypertensive rat.

The stroke-prone spontaneously hypertensive rat (SHRSP) is a well-characterized model for primary hypertension in humans. High blood pressure in SHRSP shows polygenic inheritance, but none of the loci responsible have previously been identified. To locate genes controlling this quantitative trait, we mapped a large collection of DNA polymorphisms in a cross between SHRSP and the normotensive WKY strain. Here we report strong genetic evidence that a gene, Bp1, having a major effect on blood pressure maps to rat chromosome 10 with a LOD score of 5.10 and is closely linked to the rat gene encoding angiotensin-converting enzyme (ACE), an enzyme that plays a major role in blood pressure homeostasis and is an important target of anti-hypertensive drugs. We also find significant, albeit weaker, linkage to a locus, Bp2, on chromosome 18. We discuss the implications of genetic dissection of quantitative disease-related phenotypes in mammals.

Animals↗
PubMed1991

Immunization of chimpanzees confers protection against challenge with human immunodeficiency virus.

Sustained high titers of neutralizing antibodies were elicited in three chimpanzees after sequential injections of different human immunodeficiency virus 1 (HIV-1) antigen preparations derived from the HIV-1 BRU strain that included whole inactivated virus or purified recombinant proteins and then synthetic peptides identical to the major HIV-1 neutralizing epitope V3. The animals were challenged i.v. with 40 chimpanzee infectious doses (equivalent to 100 tissue culture 50% infectious doses) of a stock of HIV-1 IIIB isolate. After 6 mo of follow-up, all three animals appeared uninfected by serologic and virologic criteria, including polymerase chain reaction analysis and failure to isolate virus from peripheral blood lymphocytes, bone marrow, and lymph node tissue. Of two chimpanzees monitored for 1 yr, virus was isolated initially from one animal at 32 weeks, but the second chimpanzee was virus negative by all assays through 12 mo; the third animal has remained virus negative through 9 mo of follow-up. These results indicate that it is possible to elicit protection against, or significantly delay infection of, HIV-1 by immunization, thus laying the foundation for development of an HIV-1 vaccine.

Amino Acid Sequence↗
PubMed1990

Cardiotoxicity in magnesium-deficient rats fed cadmium.

We studied the cardiotoxicity in magnesium (Mg)-deficient male rats fed 50 micrograms/g Cd for 45 consecutive days. Cd at a low concentration (0.28 ppm) in the heart induced cardiotoxic effects manifested by a decrease of the heart rate and weight and histopathological changes in the presence of Mg deficiency through Cd supplementation to a normal diet did not induce any cardiotoxic effect. Cardiac output (CO) did not increase in response to the decrease in the total peripheral resistance (TPR) in the Mg-deficient rats fed Cd, suggesting that supplementation of Cd to the Mg-deficient diet may lead to a decrease in the myocardial contractile function. However, supplementation of Cd to Mg-deficient diet also alleviated myocardial necrosis and Ca overload observed in the heart of Mg-deficient rats. The present data suggest that Cd ameliorates Ca overload in the heart of Mg-deficient rats but also may inhibit the release of Ca2+, which is a major determinant of the level of contractile force.

Animals↗
PubMed1983

Plasma lipid concentrations and enzyme activities in Nagase analbuminemia rats (NAR).

Plasma lipid concentrations in NAR (Nagase Analbuminemia Rats) of 4 to 52 weeks old were examined. Plasma enzymes of NAR were also measured in relation to liver function. The concentrations of total lipid, total cholesterol, phospholipid and triglyceride tended to be increased in NAR, while that of non-esterified fatty acid (NEFA) was decreased. The lipid levels (except NEFA) were especially high in female adult NAR, and they were increased with aging. The effect of 17 beta-estradiol or testosterone administration on serum lipid concentrations was studied in gonadectomized NAR. Administration of 17 beta-estradiol to gonadectomized NAR increased lipid concentrations, while testosterone administration did not affect lipid levels. The effect of albumin injection on lipid concentrations in female NAR was also investigated. Albumin treatment to female NAR lowered serum lipid concentrations. Plasma glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, lactate dehydrogenase and leucine aminopeptidase activities were higher in NAR than in normal rats. Plasma alkaline phosphatase and cholinesterase activities of NAR were similar to those of normal rats.

Age Factors↗
PubMed1981

Qualitative and quantitative abnormalities of argininosuccinate synthetase in citrullinemia.

Enzymological and immunochemical analyses of the liver were preformed in seven Japanese patients with citrullinemia. Among the urea cycle enzymes in the liver, only the activity of argininosuccinate synthetase was specifically decreased to 2 to 50% of normal controls. Liver argininosuccinate synthetase of patients was indistinguishable from that of controls when tested immunochemically by Ouchterlony's double immunodiffusion technique with anti-rat argininosuccinate synthetase antiserum. Immunochemical analysis by means of the single radial immunodiffusion revealed that the decrease in the activity of liver argininosuccinate synthetase was explainable by a decrease in the amount of the enzyme protein in five patients, while the decrease in the activity in the other two patients was not accompanied by a decrease of enzyme protein. The Km values for the substrates of liver argininosuccinate synthetase of the former five were similar to those of the control, while the kinetic properties of the latter two were quite different in terms of higher Km values and negative cooperativity. From these results, we consider that citrullinemia may consist of more than one type including qualitative or quantitative abnormalities of argininosuccinate synthetase caused by some defects in certain genes or in the epigenetic processes in the liver.

Adolescent↗
PubMedDate not supplied

Establishment of a liver metastatic model of human ovarian cancer.

We have established an in vivo experimental model in which human ovarian cancer grows in the ovary of nude mice and metastasizes to parenchymatous organs. An ovarian cancer cell line was orthotopically injected into the nude mouse ovary together with Matrigel by microsurgical techniques. The cells grew locally in the ovary and metastasized to the peritoneum, colon, omentum, liver, and spleen. When the cells were injected into the intraperitoneal cavity with Matrigel, they formed carcinomatous peritonitis but neither ovarian tumor formation nor the metastasis to parenchymatous organs was detected. Taken together, these findings indicate that the microenvironment of the ovary seems to be essential for metastasis of implanted human ovarian cancer cells. This in vivo experimental model allows us to investigate the mechanism of the metastasis of ovarian cancer, it will be also useful for the establishing a new therapeutic approach to preventing metastasis of human ovarian cancer to parenchymatous organs.

Animals↗