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Biomedical subjects

Y Hinuma

Publications and source records attributed to Y Hinuma.

At least 55 records · Page 3Linked to original sources
PubMed1988

Effects and virulences of recombinant vaccinia viruses derived from attenuated strains that express the human T-cell leukemia virus type I envelope gene.

We constructed recombinant vaccinia viruses (RVVs) that expressed human T-cell leukemia virus type I (HTLV-I) envelope glycoproteins by using attenuated vaccinia viruses (VVs) which have much lower neurovirulence than the WR strain that is extensively used as a vector. The RVV produced from the LC16mO strain, one of the attenuated VVs, elicited a high titer of anti-HTLV-I antibody in rabbits and protected them against HTLV-I infection. The env gene was inserted into the VV hemagglutinin gene. The resultant inactivation of the hemagglutinin gene led to the attenuation of VVs, but the extent of their attenuation depended on the VV strain. The propagation of LC16mO and its RVV in rabbit brain was poorer than that of LO-1, a cloned derivative of Lister strain, and its RVV, although LC16mO replicated in other organs better than did LO-1. Taken together, these results suggest that LC16mO is a good candidate as a vector for vaccination of humans.

Animals↗
PubMed1988

Soluble interleukin 2 receptors in sera of Japanese patients with adult T cell leukemia mark activity of disease.

Serum concentrations of soluble interleukin 2 receptors (sIL 2R) were measured by an enzyme-linked immunosorbent assay (ELISA) in 30 patients with adult T cell leukemia (ATL), in 9 patients with other hematopoietic malignancies, and in 17 asymptomatic individuals seropositive for human T cell leukemia virus type I (HTLV-I). Sixty HTLV-I seronegative, age-matched controls showed a normal range of form 63.2 to 480.8 U/mL. All asymptomatic carriers of HTLV-I had sIL 2R in their sera within the normal range. sIL 2R in sera was not related to the anti-HTLV-I antibody titer. Eleven patients with acute ATL, a clinical phenotype with median survival rate of 4.4 months, had markedly elevated sIL 2R (11,100 to 99,000 U/mL), but eight patients with smoldering ATL had low sIL 2R values (less than 480.8 U/mL) comparable to controls. Eleven patients with chronic ATL had intermediate elevated levels of sIL 2R (480.8 to 37,300.0 U/mL). Serum levels of sIL 2R correlated with the number of ATL cells (r = 0.812) and CD25-positive cells (r = 0.725) circulating in the peripheral blood. Longitudinal studies performed in four patients with ATL showed significant correlation between serum concentration of sIL 2R and activity of the malignancy. These findings suggest that the level of sIL 2R in serum indicated tumor load and, possibly, prognosis.

Adult↗
PubMed1987

12-O-tetradecanoylphorbol-13-acetate induces the enhancer function of human T-cell leukemia virus type I.

Phorbol esters were employed in studies on the molecular mechanism of the induction of expression of human T-cell leukemia virus type I (HTLV-I) by a tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). Experiments using the chloramphenicol acetyltransferase (CAT) system showed that CAT expression directed by the long terminal repeat (LTR) of HTLV-I was induced by TPA, but not by 4 alpha-phorbol-12,13-didecanoate, which is not an activator of protein kinase C, and that like other known enhancers, irrespective of its position and orientation, a 230-bp fragment in the U3 region of the HTLV-I LTR confers susceptibility to induction by TPA.

Deltaretrovirus↗
PubMed1987

Monoclonal integration of HTLV-I proviral DNA in patients with strongyloidiasis.

The relationship between strongyloidiasis and HTLV-I was investigated in Okinawa, an area where both conditions are endemic. Thirty-six patients with strongyloidiasis were seropositive for HTLV-I and suffered from several related clinical complications. Fourteen of these patients (39%) were shown to have monoclonal integration of HTLV-I proviral DNA in their blood lymphocytes, a condition designated as "smouldering" adult T-cell leukaemia (ATL). Monoclonal integration of proviral DNA correlated with an increased CD4/CD8 ratio and the presence of abnormal lymphocytes in the peripheral blood, and with a trend for greater severity of the parasitic infection. Although the immunodeficiency caused by HTLV-I could predispose to hyperinfestation by Strongyloides, it is also possible that both the parasitic and the retroviral infestations are important co-factors leading to the development of ATL.

Adult↗
PubMed1987

Characterization of interleukin 2-stimulated phosphorylation of 67 and 63 kDa proteins in human T-cells.

We have investigated rapid and marked phosphorylation of cellular proteins induced by interleukin 2 (IL-2) in both phytohaemagglutinin-stimulated normal peripheral blood leucocytes, and IL-2-dependent or -independent human T-cell lines bearing human T-cell leukaemia (lymphotropic) virus type I. Two-dimensional electrophoretic analysis showed that the IL-2-induced phosphoprotein was of Mr 67,000 with a pI of 5.8 (pp67) and was distinct from the IL-2 receptor. IL-2 also stimulated phosphorylation of four other proteins, with an Mr of 63,000 and pI values 5.3-6.1 (pp63s). The stimulation of pp67 phosphorylation was observed within 5 min after addition of IL-2 and was maximal after 15 min. The maximal phosphorylation was more than 10-fold that observed initially. In IL-2-dependent cells, IL-2 dose responses of pp67 phosphorylation and cell proliferation were exactly correlated. Phosphoamino acid analysis showed that the phosphorylation site of pp67 and pp63s was a serine residue. Subcellular-fractionation studies indicated that pp67 was localized in cytosol, whereas pp63s phosphorylation was induced by IL-2 in nuclear and cytosol fractions. Similar phosphorylation of pp67 and pp63s was observed when the cells were treated with phorbol 12-myristate 13-acetate instead of IL-2. These results suggest that IL-2-IL-2-receptor interaction leads to activation of protein kinase(s), resulting in phosphorylation of certain cellular proteins such as pp67 and pp63s, and that this phosphorylation could be an early event in the transmission of intracellular growth signalling from the IL-2 receptors.

Cell Division↗
PubMed1987

Effect of the recombinant vaccinia viruses that express HTLV-I envelope gene on HTLV-I infection.

The human T-lymphotropic virus type I (HTLV-I) is etiologically linked to adult T-cell leukemia (ATL). To develop a vaccine against ATL, we constructed recombinant vaccinia viruses containing the envelope gene of HTLV-I in the vaccinia virus hemagglutinin (HA) gene, a new site where foreign genes can be inserted. A single inoculation of the recombinant virus induced antibodies to the env proteins of HTLV-I in rabbits and had a protective effect against HTLV-I infection.

Animals↗
PubMed1987

Identification of two distinct elements in the long terminal repeat of HTLV-I responsible for maximum gene expression.

Human T-cell leukemia virus type I has a unique sequence, pX, between env and the 3' long terminal repeat (LTR). One of its products, p40, activates gene expression directed by the LTR in a trans-acting manner. We have analysed the mechanism of this trans-activation mediated by p40 in human T cells co-transfected with a plasmid expressing p40 using the transient CAT gene expression. We identified two distinct elements in the LTR which are involved in maximum gene expression. The first was present in a 230-bp fragment upstream from TATA box in the U3 region and behaved as a classical enhancer. This region was also shown to be responsible for trans-activation by p40. This element alone together with functional p40 could direct the gene expression at only approximately 10% of the level achieved by the complete LTR and p40. The second element was present within a 300-bp fragment downstream from the RNA start site and profoundly enhanced the gene expression in a way independent from trans-activation mechanism. This enhancement was observed only when the element was located immediately downstream from the RNA start site without orientation preference. These two elements participate independently in the enhancement of gene expression.

Base Sequence↗
PubMed1987

High affinity interleukin 2 receptors in HTLV-1-infected T cells can mediate signals for gene expression.

The expression of transcripts of the c-myb and c-myc protooncogenes and the interleukin 2 receptor (IL-2R) gene in human T cells infected with human T-cell leukemia virus type 1 (HTLV-1) after exposure to interleukin 2 (IL-2) were examined. Infection with HTLV-1 is known to be associated with constitutive expression of IL-2R, although infected cells do not require IL-2 for growth. Northern blot analysis showed that expression of the mRNAs of the c-myb, c-myc, and IL-2R genes were markedly increased by addition of IL-2 into the cultures, indicating that IL-2R transduced signals for gene expression in these cells as in normal T cells. Studies on distinct HTLV-1-infected T cell clones that differed in numbers of high-affinity IL-2R, showed that the extents of increase in mRNA expression by IL-2 were correlated with the number of high-affinity IL-2R. This correlation was confirmed by demonstration that the levels of mRNA expression were proportional to the numbers of IL-2-bound high-affinity but not low-affinity receptors. Thus, the signals induced by IL-2 for gene expression may be through high-affinity IL-2R.

Blotting, Northern↗
PubMed1987

Clonal analysis of functional differences among strains of human immunodeficiency virus (HIV).

Different isolates (HTLV-IIIB, LAV1 and ARV2) of human immunodeficiency virus (HIV) were cloned by a plaque-forming assay using MT-4 cells. The reverse transcriptase (RT) activity and plaque-forming unit (PFU) titers of all viral preparations were assayed. PFU/RT values, which indicate the relative proportions of incomplete and infectious viruses, were used for determination of viral infectivity. High values were obtained mainly for clones of HTLV-IIIB and LAV1, and low values for ARV2-derived clones, suggesting that ARV2 and its clones were genetically less infectious. For studies on cytocidal effects of the viruses, four clones of HTLV-IIIB, LAV1 and ARV2 were selected that had similar PFU/RT (infectivity) values for proliferation in infected MT-4 cells. When compared at the same dose (MOI), one clone (HTLV-IIIB-C-2) was found to be more cytocidal than the others. Furthermore, plaques induced by HTLV-IIIB-C-2 were larger than those induced by other clones, suggesting that the release of progeny from HTLV-IIIB-C-2-infected cell and their proliferation were the most efficient. Among the cloned viruses tested, three were found to induce strong cytopathic changes (fusion and ballooning) selectively in MT-4 cells. Thus, the infectivity, proliferation and cytopathic fusion-effects were proposed to be encoded by the viral genome and be separable by the plaque-cloning method.

Cell Fusion↗
PubMed1987

Human T-lymphoblastoid cell lines with high and low abilities to produce interferon-gamma constitutively and their susceptibilities to interferon.

A human T-lymphoblastoid cell line, TCL-Fuj, produces large amounts of interferon (IFN)-gamma constitutively. A variant cell line, 2M, was derived from it. Both cell lines express similar surface antigen markers, but differ in surface morphology. Compared with the parent TCL-Fuj cell line, 2M produced less IFN-gamma constitutively but more in response to IFN inducers. The IFNs produced constitutively and on stimulation with inducers were analyzed by SDS-polyacrylamide gel electrophoresis. In TCL-Fuj cells, the constitutive and induced IFNs consisted of the same molecular species (22K and 39K). In 2M cells, smaller IFNs were produced constitutively (18K and 32K) and induction resulted in a marked increase of 22K molecules. These two cell lines also differed in sensitivity to the antiviral activity of IFN. Other T-lymphoblastoid cell lines, HPB-ALL and TCL-Fuj 4 cells, which did not produce IFN-gamma were permissive for vesicular stomatitis virus (VSV) replication; its growth was markedly suppressed by IFN-gamma and -alpha. TCL-Fuj cells were also permissive for VSV, but were not susceptible to the antiviral effect of the IFNs. In contrast, in 2M cells the multiplication of VSV was restricted; the viral yield was further reduced by the IFNs and increased by treatment with anti-human IFN-gamma serum. Several clonal cell lines derived from TCL-Fuj and 2M cells had characteristics similar to the respective parent cell lines. The growth of both cell lines was not affected by IFN-gamma or by -alpha. The separation of antiviral and anti-proliferative susceptibilities was peculiar to 2M cells unlike other cell lines.

Cell Line↗
PubMed1987

Transmission of adult T-cell leukemia retrovirus (HTLV-I) from mother to child: comparison of bottle- with breast-fed babies.

HTLV-I is commonly believed to be transmitted from HTLV-I seropositive mothers to infants via breast milk. In 11 of 24 breast-fed infants born to HTLV-I seropositive mothers, HTLV-I antigen-positive cells were detected in peripheral blood samples obtained 12 months after birth. In sharp contrast, they were detected in only one of 11 bottle-fed infants of HTLV-I seropositive mothers. Thus bottle-feeding appears to be an effective method to avoid HTLV-I transmission from HTLV-I seropositive mothers to infants.

Antigens, Viral↗
PubMed1987

Immune suppression in healthy carriers of adult T-cell leukemia retrovirus (HTLV-I): impairment of T-cell control of Epstein-Barr virus-infected B-cells.

We have examined the activities of Epstein-Barr virus (EBV)-specific memory T-cells of carriers of adult T-cell leukemia (ATL) associated retrovirus (HTLV-I) and non-carriers in an ATL-endemic area, all of whom were EBV-seropositive, by assay of EBV-induced B-cell focus regression. The result showed that immune suppression, as represented by lowering of the regression, was present in 18 (29%) out of 63 healthy HTLV-I carriers, in contrast to none of 63 matched control persons (healthy non-carriers). This finding suggests that a suppression of cell-mediated immunity is induced by a persistent infection with ATL retrovirus.

Adult↗
PubMed1987

[The effects of hyperoxemia on cerebral blood flow in subarachnoid hemorrhage patients].

The effects of oxygen inhalation at atmospheric pressure (1 ATA.O2) on CBF were studied in subarachnoid hemorrhage (SAH) patients due to ruptured intracranial aneurysms to prove the usefulness of the "O2 response" test for the evaluation of the cerebral vascular response. "O2 response" means the CBF (or ICP) decrease during hyperoxemia. CBF was measured by 10 m Ci 133Xe intravenous injection method using rCBF analyzer BI-1400 (Valmet). Two-compartmental analysis was used for the calculation of initial slope index (ISI). Studied cases were 53 postoperative SAH patients and 100 times examinations were done under the condition of Rest-1 ATA.O2. The incidence of global disturbance of the O2 response was 33% from day 0 to 3, 31% during day 4 to 7, 30% during day 8 to 14, and 23% at day 15 to 30. But, after day 31, there was no case which revealed an impaired O2 response. It was not possible to detect focal or hemispheric abnormalities of the O2 response because of the limitation of noninvasive two-dimensional CBF measurement method employed. The causes of O2 response abnormality, within a month after the onset, were increased ICP, hydrocephalus and diffuse brain damage. Multiple regression analysis proved that elevated PaO2 is the major factor in reducing CBF. CBF and ICP correlation study showed that the higher the Rest ICP, the fewer the CBF decreases during pure O2 inhalation. This may indicate that the increase in ICP in the acute stage changes the O2 response according to the level of increased ICP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

[Reproducibility of somatosensory evoked potentials and EEG in normal humans under hyperbaric oxygenation].

Hyperbaric oxygenation (HBO) was reported to have a favorable influence on ischemic brain dysfunction, and also appeared to be useful in improving brain edema. Somatosensory evoked potentials (SEP) and EEG would be available as indicators of brain function. The purpose of this paper is to study reproducibility of the N1-amplitude of SEP and EEG under HBO. Materials were 10 normal volunteers, from 21 to 31 (mean age: 26) years old. Two stimulating needle electrodes were inserted into the skin at the wrist and somatosensory stimulations were applied to the median nerve with 1 msec duration square pulses. Stimulation pulses were generated regularly every 1 sec., and stimulus intensity was adjusted just above the thumb twitch threshold. Monopolar EEGs were recorded from 16 silver-cup electrodes on the scalp, and SEPs were recorded by averaging 250 responses in those EEGs using computer technique. N1-amplitude was determined by the vertical distance between peaks of the P1 and N1 components. EEGs were analyzed by Fast Fourier Transform and the square root of the averaged power of each frequency band (delta, theta, alpha 1, alpha 2, beta) was obtained and evaluated as the equivalent potential. EEGs under the influence of sleeping or artifacts, such as electromyograms, eye lid movements and wandering of the base line, were excluded in evaluating the EEGs. SEPs and EEGs recorded consecutively. The first record was taken before HBO under air breathing at 1ATA, the second during HBO under pure oxygen breathing at 2ATA, and the third after HBO under air breathing at 1ATA once again.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗