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K Ariyoshi

Publications and source records attributed to K Ariyoshi.

At least 73 records · Page 4Linked to original sources
PubMed1993

HIV-specific cytotoxic T-cell activity in an HIV-exposed but uninfected infant.

The factors necessary for protective immunity against HIV-1 are unknown. Important information about these factors should come from study of people at high risk of HIV infection who have not apparently become infected. Among these are the estimated 60-85% of children who may be exposed in utero or perinatally to HIV-1 but do not become infected. We observed the transient appearance of HIV-specific cytotoxic T-lymphocyte (CTL) activity in a baby born to HIV-1-infected parents, in whom all standard markers of infection remained negative. These findings suggest that HIV-specific CTLs may be a marker for recently exposed, but uninfected, individuals.

CD4-CD8 Ratio↗
PubMed1993

Mycoplasma fermentans in individuals seropositive and seronegative for HIV-1.

Mycoplasmas have been suggested as a co-factor to explain various puzzling features of infection by human immunodeficiency virus 1 (HIV-1). We sought Mycoplasma fermentans by means of a semi-nested polymerase chain reaction (PCR) in samples of peripheral-blood mononuclear cells (PBMC), throat swabs, and urine samples from 117 HIV-seropositive patients (of whom 114 were homosexual men). M fermentans was detected in 12 (10%) PBMC samples, 15 (23%) of 65 throat samples, and 4 (8%) of 55 urine samples from the seropositive subjects. The organism was detected in similar proportions among 73 HIV-seronegative patients recruited from a sexually transmitted diseases clinic (9%, 20%, and 6%, respectively); again, most of the men (40 of 50) in this group were homosexual. We found no association between infection by the mycoplasma and stage of disease, CD4 count, or HIV-1 load. These findings do not, however, eliminate the possibility that the mycoplasmal infection could affect the speed of disease progression.

Blotting, Southern↗
PubMed1993

Variable relationship between proviral DNA load and infectious virus titre in the peripheral blood mononuclear cells of HIV-1-infected individuals.

OBJECTIVES: To determine the relationship between infectious virus titre and proviral copy number in peripheral blood mononuclear cells (PBMC) of infected subjects and to ascertain which, if either, is most closely related to CD4+ cell loss and disease progression. DESIGN AND METHODS: Cellular HIV-1 viraemia was quantified in 45 infected subjects who had not received antiretroviral therapy using limiting dilution tissue culture infective dose (PBMC TCID) and quantitative polymerase chain reaction (PCR) techniques. RESULTS: Proviral DNA was detected in 44 (98%) and infectious virus in 38 (82%) of the 45 subjects. Viraemia as measured by both culture and PCR was inversely correlated with patient CD4+ cell count and associated with disease status. Measurement using both techniques correlated with each other (Spearman's rank correlation rho = 0.52; P = 0.0006). The ratio of proviral copies to PBMC TCID ranged from 1:1 1000:1. to > 1000:1. CONCLUSIONS: The ratio of provirus:PBMC TCID was highest when the PBMC TCID was low, and approached unity when PBMC TCID was high. This ratio could be influenced by a variety of factors but did not correlate significantly with patient disease status or CD4+ cell count.

Base Sequence↗
PubMed1993

An approach for assaying benzodiazepine receptor binding with radioiodinated ligand: 125I-labeled diazepam derivative.

[125I]2'-Iododiazepam (IDZ) was prepared and its application in a benzodiazepine receptor binding assay was studied. [125I]2'-IDZ binds to the rat cortical membrane with a high affinity (Kd, 0.66 nM). Various benzodiazepines showed competition with [125I]2'-IDZ for the binding sites in the rat cortical membrane, and the specificity of its binding correlated well with that of [3H]diazepam (r = 0.992, p < 0.001). These findings suggested that [125I]2'-IDZ binds to the same sites as [3H]diazepam and indicated that [125I]2'-IDZ can be used in a benzodiazepine receptor assay.

Animals↗
PubMed1993

Radioiodinated 2'-iododiazepam: a potential imaging agent for SPECT investigations of benzodiazepine receptors.

2'-Iododiazepam (2'-IDZ) is the diazepam analogue iodinated at the 2'-position of C-5 phenyl ring which was synthesized and evaluated as a potential radiopharmaceutical for investigating brain benzodiazepine receptors by SPECT. The 125I-2'-iododiazepam was synthesized by halogen exchange reaction and purified by HPLC. In vitro competitive binding studies with 3H-diazepam, using rat cortical synaptosomal membranes, showed that the affinity of 2'-IDZ for benzodiazepam receptors was higher than that in diazepam and flumazenil (RO15-1788). Biodistribution studies in mice showed that the brain uptake of 2'-iododiazepam was rapid and profound, and in the brain higher accumulation was found in the cortex than in other regions. Furthermore, the cortical uptake was displaced by benzodiazepinergic compounds. In vivo uptake was assessed by autoradiographic studies. Thus, 2'-iododiazepam bound to benzodiazepine receptors in vivo and therefore holds great potential for in vivo benzodiazepine receptor studies.

Animals↗
PubMed1992

Is clearance of HIV-1 viraemia at seroconversion mediated by neutralising antibodies?

The mechanism of clearance of human immunodeficiency virus-1 (HIV-1) viraemia is not fully understood. In two patients with acute HIV-1 infection, initial high titres of free infectious virus in plasma declined rapidly to undetectable levels within 4-8 weeks, an event that was coincident with seroconversion. Neutralising antibodies directed against the first autologous isolates taken during the viraemic periods could not be detected in either patient around the time of disappearance of plasma virus. In the absence of functional neutralising antibody, it is unlikely that humoral factors are responsible for the suppression of primary viraemia in early HIV infection.

Adult↗
PubMed1992

Effector cell analysis of human multidrug-resistant cell killing by mouse-human chimeric antibody against P-glycoprotein.

A mouse-human chimeric monoclonal antibody (mAb), MH162, against P-glycoprotein was previously found to be more effective than an all-mouse mAb (MRK16) in lysis of multidrug-resistant (MDR) tumor cells by blood mononuclear cells. The present study was performed to identify the effector cells responsible for the chimeric mAb-dependent cell-mediated cytotoxicity (ADCC) against MDR cells. The ADCC reaction was assessed by a 6-h 51Cr release assay. Highly purified lymphocytes (greater than 99%), monocytes (greater than 99%) and neutrophils (greater than 96%) were obtained from peripheral blood of the same healthy donors. A comparison of these three effector cell populations showed no difference between MH162 and its all-murine counterpart MRK16 in MDR cell lysis by monocytes or neutrophils. But MH162 was more effective than MRK16 in lymphocyte-mediated lysis of the MDR cells. The lymphocytes responsible for this ADCC had CD16+ Fc receptors. Pretreatment of monocytes with colony-stimulating factors (IL-3, GM-CSF and M-CSF) caused significant increase in their MH162-mediated lysis of MDR cells. Another anti-P-glycoprotein chimeric mAb (MH171) was also more effective than its murine counterpart MRK17 in lymphocyte-mediated lysis of MDR cells. These findings suggest that mouse-human chimeric mAbs may be useful therapeutically for in vivo destruction of MDR cancer cells by the ADCC reaction.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Mouse-human chimeric antibody MH171 against the multidrug transporter P-glycoprotein.

We have developed a mouse-human chimeric antibody MH171, in which the antigen-recognizing variable regions of the mouse monoclonal antibody MRK17 are joined with the constant regions of human IgG1 antibodies. The MRK17 recognizes specifically the multidrug transporter P-glycoprotein and inhibits the growth of human multidrug resistant (MDR) tumor cells in vitro and in the xenograft nude mouse model system. The established chimeric MH171 antibody forms an apparently intact IgG composed of heavy and light chains covalently assembled via disulfide bonds in sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis and is specific to MDR cell lines with a similar affinity to the original mouse MRK17. MH171 also displays strong antibody-dependent cell-mediated cytotoxicity to the target cells in vitro, when human mononuclear cells are used as effector cells. The chimeric antibody against P-glycoprotein, MH171, should be a useful agent in the treatment of human drug-resistant tumors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

Pathological study on beagles after long-term oral administration of cadmium.

Histopathological, histochemical, and electron microscopic examinations were performed on beagles after a long-term oral cadmium (Cd) administration of greater than 8 years. Although renal atrophy was remarkable in groups receiving doses of 50 and 100 mg/kg body weight/day, bone lesions could not be demonstrated by roentgenological and histopathologic examination. It was noticed that concomitant regeneration or recovery and cell death of the epithelium occurred in the proximal convoluted tubules. The cell death was consistent with apoptosis, a special feature of cell death, which was shown to play a major part in the tubular damage of cadmium by electron microscopic examination. Fatty degeneration of the pars recta tubules was seen to show dose-dependence. The intrarenal cadmium was localized predominantly in the cytoplasm of the proximal tubular epithelium by histochemical and ultracentrifugal cell fractionation examinations. Although no remarkable changes were found in the other organs, aggregates of siderophages in the liver and focal hemorrhage in the spleen, known as spontaneous lesions, might be related to Cd intoxication. In conclusion, the present study revealed that no bone lesions occur with Cd administration in adult beagles in spite of long-term administration. An excessive cell death to regeneration or recovery in the proximal tubules might result in the renal cortical atrophy. No remarkable changes were seen in the glomeruli and distal nephrons, which were in good agreement with Cd distribution.

Administration, Oral↗
PubMed1991

[A report of the state of health in Zimbabwe].

The health state in Zimbabwe is reported in terms of currently significant diseases, health statistics and hygiene and health care system in conjunction with the author's experiences as a visiting doctor in the country between June and September in 1989. Since independence in 1980 the government has transformed the colonial and racial health system and attempted to redistribute health care resources to the rural population. Similar to many countries in Central and East Africa, the accumulative number of AIDS cases in Zimbabwe is increasing rapidly despite the vigorous governmental campaigns launched in the early stage. The incidence of tuberculosis has also been rising since 1986 apparently in association with HIV spread in the country. On the other hand Zimbabwe is unique among the countries in Africa because rural clinics and preventive medicine such as immunization, basic sanitation and health education have been well-established throughout the country. As a result various communicable diseases common to the tropics and subtropics have been successfully controlled. The country now needs to improve quality and quantity of hospital medicine. While hospital facilities are available, the number of doctors, particularly in the district, is far below demand. Zimbabwe is one of the few countries in Africa where doctors trained in Japan could work efficiently and therefore it is suggested that it be considered as a country amenable to international medical cooperation.

Delivery of Health Care↗
PubMed1990

Mouse-human chimeric antibody against the multidrug transporter P-glycoprotein.

In an effort to devise an effective treatment for human drug-resistant cancers, we have generated a monoclonal antibody, MRK16, reactive to the multidrug transporter P-glycoprotein. The monoclonal antibody inhibited the growth of human drug-resistant tumor cells in a xenograft model, suggesting its potential usefulness in the immunotherapy of drug-resistant cancers. In this study, we have developed a recombinant chimeric antibody in which the antigen-recognizing variable regions of MRK16 are joined with the constant regions of human antibodies. When human effector cells were used, the chimeric antibody, MH162, was more effective in killing drug-resistant tumor cells than the all-mouse monoclonal MRK16. The chimeric antibody against the multidrug transporter P-glycoprotein will be a useful agent in immunotherapy of human drug-resistant cancers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

Quantitative correlation between cardiovascular and plasma epinephrine response to mental stress.

To investigate the quantitative correlations between cardiovascular and endogenous catecholamine response to mental stress, we gave a mental arithmetic test to 20 young healthy men. A direct and non-invasive haemodynamic measurement was performed by serial M-mode echocardiography. Heart rate, blood pressure, cardiac output, stroke volume, ejection fraction, left ventricular end-systolic pressure-volume ratio and plasma epinephrine increased over the baseline period during the test. The peripheral resistance and left ventricular end-systolic volume decreased, whereas left ventricular end-diastolic volume and plasma norepinephrine were unaltered. Furthermore, the degree of change in each haemodynamic parameter showing significant reaction, was well correlated with that of the increase in plasma epinephrine. The data suggest that acute mental stress induces endogenous epinephrine secretion resulting in a beta-adrenergic activated state in the cardiovascular system, namely, positive chronotropism, positive inotropism and vasodilatation.

Adult↗
PubMed1975

Four new pyruvate kinase (PK) variants and a classical PK deficiency.

Four new red-cell pyruvate kinase (PK) variants are presented along with one case of so-called classical type PK deficiency. PK 'Tokyo II' had a low activity, Km (PEP) and Vmax, but a normal urea stability and only slight deviation from normal in neutralization tests by antiserum. It had a normal nucleotide specificity, abnormal electrophoretic mobility (fast moving) and the variant was associated with a mild hemolytic anaemia. PK 'Maebashi' had a low activity, high Km (PEP), low Vmax, urea instability, decreased reactivity to antiserum, normal electrophoretic mobility, normal nucleotide specificity and was associated with a moderate haemolytic anaemia. PK 'Tsukiji' had low activity, high Km (PEP), markedly high Vmax, urea instability, decreased reactivity to antiserum, abnormal electrophoretic mobility (fast moving) and grossly abnormal nucleotide specificity especially abnormal behaviour to ADP. The haemolytic process in this case was moderate to severe. PK 'Ube' was electrophoretically abnormal (fast moving) but otherwise had normal characteristics and the propositus was healthy and not anaemic. PK 'Ube' was found by electrophoretic screening for genetic PK polymorphism. In the classical type PK deficiency, the usual red-cell PK (PK-R1 and PK-R2) was not demonstrable by electrophoresis but instead M2-type PK was present, presumably by compensatory process. Kinetic studies confirmed that the patient's red-cell PK consisted of M2-type PK. This patient had a severe haemolytic anaemia.

Adult↗