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Biomedical subjects

T Kurata

Publications and source records attributed to T Kurata.

At least 163 records · Page 9Linked to original sources
PubMed1997

Dual phasic suppression of viral replication following de novo human immunodeficiency virus type 1 (HIV-1) infection in lymphocytes of asymptomatic HIV-1 carriers.

Replication of human immunodeficiency virus type 1 (HIV-1) is suppressed in asymptomatic HIV-1 carriers (ACs). By using an in vitro experimental system, the mechanism of this suppression was investigated. Following in vitro infection of a laboratory HIV-1 strain, the peripheral blood mononuclear cells (PBMC) of ACs transiently supported a low level of viral replication, then the virus production rapidly decreased. PCR analysis revealed that HIV-1 proviral DNA integrated in the PBMC of ACs following infection gradually decreased. Such tapering consequences of in vitro HIV-1 infection in the PBMC of ACs were abrogated by depletion of CD8+ T cells from the culture. Furthermore, the viruses subsequently produced by the PBMC of an AC were less able to replicate than the virus produced by CD8+ cell-depleted PBMC of the same donor. These observations suggested that the CD8+ T cell-mediated suppression of HIV-1 replication in ACs may involve both cytocidal and cytostatic mechanisms: the former kills the cells producing viruses, and the latter inhibits viral spread by reducing viral infectivity.

CD8-Positive T-Lymphocytes↗
PubMed1997

Infection of a human retinal pigment epithelial cell line with human herpesvirus 6 variant A.

A retinal pigment epithelial (RPE) cell line (K-1034) was examined for its susceptibility to human herpesvirus 6 variant A (HHV-6A). Exposure of K-1034 cells to HHV-6A induced the formation of multinucleated giant cells, which was suppressed by an inhibitor of viral DNA synthesis. In the giant cells, herpesvirus nucleocapsids were demonstrated by electron microscopy and the viral glycoprotein B was detected by immunofluorescence assay. These results indicate that K-1034 cells are susceptible to HHV-6A and suggest that HHV-6A has an ability to directly destroy epithelial cells.

Cells, Cultured↗
PubMed1997

[Mucosal immune responses against influenza virus].

The respiratory tract-mucosa is the site of either contact with influenza virus or defense against the virus. Such a defense is mediated by immune competent cells. The precursors of IgA-producing B cells and immune T cells are first induced in the mucosal inductive sites such as nasal-associated lymphoid tissues (NALT) or bronchus-associated lymphoid tissues (BALT). They are disseminated to mucosal effector sites for the development of immune responses, where IgA-producing cells in the lamina propria produce polymeric IgA, which are secreted through the epithelial cell into the external. The secretory IgA and serum IgG are mainly involved in protection against influenza in the upper respiratory tract and pneumonia in the lower respiratory tract, respectively. CD8+ cytotoxic T cells and Th1 cells are involved in recovery from influenza.

Animals↗
PubMed1997

[Ultrasonographic assessment of carotid atherosclerosis emphasizing the variety of intimal-medial thickness and the relationship with coronary risk factors].

Intimal-medial thickness (IMT) of the extracranial carotid arteries measured by B-mode ultrasonography has been used as a marker of systemic and coronary atherosclerosis. Previous studies have indicated that maximum and mean carotid IMT are significantly correlated with the extent and severity of coronary artery disease (CAD), but the clinical usefulness of these markers is limited because they are neither specific nor sensitive enough to identify patients with or without significant CAD. The correlation of a new IMT marker, variance of IMT, with coronary risk factors and coronary atherosclerosis was investigated in 200 patients who underwent carotid ultrasonography and coronary angiography. IMT was measured in 16 sites of the extracranial carotid arteries for the calculation of mean, maximum and variance of IMT. Univariate analysis showed that these three indexes were significantly correlated with age, serum lipoprotein (a) and hypertension. However, age was correlated weakly with variance of IMT. There were significant gender differences in the mean and maximum IMT but not in the variance. There were also significant correlations of mean IMT with smoking, and maximum and variance of IMT with high-density lipoprotein. Multiple logistic regression analysis in 100 age and sex matched patients indicated that the only significant predictor for CAD in this subgroup was variance of IMT (odds ratio = 1.6). These results indicated that each risk factor causes different morphologic manifestations in the carotid atherosclerotic lesion. Variance of IMT, which represents the irregularity of carotid IMT, was correlated well with CAD and appears to be useful for assessing systemic and coronary atherosclerosis.

Aged↗
PubMed1997

Specific binding of Burkholderia pseudomallei cells and their cell-surface acid phosphatase to gangliotetraosylceramide (asialo GM1) and gangliotriaosylceramide (asialo GM2).

Specific binding between bacterial cells and host tissue is an early step of the pathogenesis of infection. Burkholderia pseudomallei cells, the causative micro-organisms of melioidosis, were demonstrated to bind specifically to tissue glycolipids (asialo GM1 and asialo GM2) by solid phase binding assay on thin layer chromatograms. The detection limit was around 400 pmol of the glycolipids. Acid phosphatase purified from the culture filtrate of B. pseudomallei was tested for such binding properties, and the same results were obtained. According to our previous studies, the enzyme is a glycoprotein located on the cell surface, and hydrolysed tyrosine phosphate most actively among the substrates so far tested. The mode of binding between the enzyme and the glycolipids was analyzed by comparison of binding levels among three samples different in protein content, sugar content and specific phosphatase activities per protein and sugar residue. The results suggested the possibility of a receptor-ligand relationship between the bacterial enzyme and the host-cell glycolipids (asialo GM).

Acid Phosphatase↗
PubMed1997

Serum levels of pro-gastrin-releasing peptide for follow-up of patients with small cell lung cancer.

To assess the clinical usefulness of serum pro-gastrin-releasing peptide (Pro-GRP) as a tumor marker for small cell lung carcinoma (SCLC), we measured serum levels of Pro-GRP with a newly developed ELISA and measured serum levels of neuron-specific enolase (NSE) in 44 patients with untreated SCLC and 77 patients with untreated non-SCLC. We prospectively measured serum levels of Pro-GRP and NSE in SCLC patients after initial treatment until relapse. The sensitivity (70%) and specificity (91%) of Pro-GRP were similar to those of NSE (70 and 86%). Thirty-nine % of patients who had a partial response still had elevated serum levels of Pro-GRP at the time of restaging after initial treatment. In follow-up study, 94% of patients had elevated serum levels of Pro-GRP again at the time of relapse, whereas 37% of patients showed elevated levels of NSE. Levels of Pro-GRP increased a median of 35 (-95 to 151) days before clinical evidence of relapse was detected with successive physical examinations and imaging studies, whereas levels of NSE increased 20 (-85 to 124) days after relapse was detected (P < 0.05). Pro-GRP was helpful as a diagnostic aid and a marker for therapeutic effect and relapse in patients with SCLC, supplemented to serum NSE.

Adult↗
PubMed1996

Interaction between the amino-terminal SH3 domain of CRK and its natural target proteins.

CRK is a human homolog of chichen v-Crk, which is an adaptor protein. The SH2 domain of CRK binds to several tyrosine-phosphorylated proteins, including the epidermal growth factor receptor, p130(Cas), Shc, and paxillin. The SH3 domain, in turn, binds to cytosolic proteins of 135-145, 160, 180, and 220 kDa. We screened expression libraries by Far Western blotting, using CRK SH3 as a probe, and identified partial cDNA sequences of four distinct proteins, including C3G, DOCK180, EPS15, and clone ST12. The consensus sequence of the CRK SH3 binding sites as deduced from their amino acid sequences was Pro+3-Pro+2-X+1-Leu0-Pro-1-X-2-Lys-3. The interaction of the CRK SH3 domain with the DOCK180 peptide was examined with an optical biosensor, based on the principles of surface plasmon resonance. A low dissociation constant of the order of 10(-7) resulted from a high association rate constant (kassoc = 3 x 10(4)) and low dissociation rate constant (kdiss = 3 x 10(-3)). All CRK-binding proteins except clone ST12 also bound to another adaptor protein, Grb2. Mutational analysis revealed that glycine at position +1 of ST12 inhibited the binding to Grb2 while retaining the high affinity binding to CRK SH3. The result suggests that the amino acid at position +1 also contributes to the high affinity binding of the peptides to the SH3 domain of Grb2, but not to that of CRK.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Acceleration of influenza virus clearance by Th1 cells in the nasal site of mice immunized intranasally with adjuvant-combined recombinant nucleoprotein.

The protective roles of influenza viral nucleoprotein (NP), together with the cellular mechanism of the protection in the nasal site, were examined in BALB/c mice immunized intranasally with an adjuvant (cholera toxin B subunit containing 0.2% of the whole toxin)-combined A or B virus recombinant NP. The NP-immune mice, when challenged intranasally with a sublethal dose of the virus 3 wk after immunization, had accelerated virus clearance from the nasal site in both an influenza type-specific and a nonspecific manner, as shown by the protection from high morbidity from the second day after challenge. Both type-specific and nonspecific acceleration of recovery was confirmed by the increased survival rate after challenge with a lethal dose of virus in mice immunized and boosted with adjuvant-combined NP. The acceleration of nasal virus clearance was accompanied with acceleration of type-specific systemic delayed-type hypersensitivity (DTH) and with IFN-gamma production by nasal lymphocytes. The nasal lymphocytes from the immunized and challenged mice generated a significantly high level of DTH when transferred locally, but no class I MHC-restricted CTL response. Moreover, nasal CD4+ T cells, induced by NP immunization and increased in number by the subsequent challenge, were involved in the accelerated IFN-gamma production. These results suggest that nasal Th1 cells, capable of producing IFN-gamma and mediating DTH, are involved in the type-specific acceleration of recovery from influenza after challenge in mice immunized intranasally with adjuvant-combined NP, although the nonspecific mechanism of accelerated recovery remains to be solved.

Adjuvants, Immunologic↗
PubMed1996

Hepatitis C and B virus infections in hepatocellular carcinoma. Analysis of direct detection of viral genome in paraffin embedded tissues.

BACKGROUND: Although there have been many seroepidemiologic studies on hepatitis C virus (HCV) infection and hepatocellular carcinoma (HCC) occurrence, the actual role of HCV in hepatocarcinogenesis is unknown. METHODS: We have previously reported on a highly sensitive method of detecting and identifying sequences of RNA genome in formalin fixed, paraffin embedded (FFPE) tissue by polymerase chain reaction (PCR) assay. Using this method, we carried out a retrospective study to determine the prevalence of HCV and hepatitis B virus (HBV) genomes in FFPE specimens from 102 Japanese patients with HCC. RESULTS: HCV-RNA was detected by nested PCR reverse transcription (RT) in 64 of the 102 patients (62.7%), and 78.1% (50/64) of those HCV-RNA-positive patients had HCV genotype II. HCV-RNA was present in 54 of 70 (77.1%) anti-HCV-positive patients, and also in 5 of 20 (25%) anti-HCV-negative patients. HBV-DNA was detected by nested PCR in FFPE liver specimens from 21 of 102 (20.6%) patients. HBV-DNA positivity was consistent with seropositivity for serum HBV markers in 17 of these 21 patients (80.9%). HBV-DNA was present in FFPE samples from 2 patients who were seronegative for HBV markers, and in 1 patient who was seropositive for anti-HBs. Double infection of these two viruses was found in 6 patients (5.9%). Three patients (2.9%) were negative for both hepatic viral genomes and serum viral markers. CONCLUSIONS: The precise prevalence of HCV and/or HBV infection among HCC patients can be determined by studying routinely-processed FFPE HCC samples preserved for up to 11 years using the technique of nested PCR. HCV-RNA was detected in the majority of our HCC cases; type II was the most common genotype of HCV encountered. The incidence of HCV-associated HCC was three times greater than that of HBV. Thus, the hepatitis virus infection most frequently associated, and probably ectologically implicated, with HCC in Japanese people is HCV infection.

Adult↗
PubMed1996

Hair follicle involvement in herpes zoster: pathway of viral spread from ganglia to skin.

Herpes zoster is caused by reactivation of varicella-zoster virus (VZV) persisting in dorsal root or trigeminal ganglia. To clarify the pathway of viral spread from the ganglia to skin, 16 biopsy specimens of early skin lesions of herpes zoster obtained from the face and trunk of 13 patients were studied histologically and immunohistochemically using monoclonal antibodies to the structural proteins of VZV. VZV-infected cells were detected in the hair follicles in 10 of the 16 specimens and in the epidermis in 2 specimens. Infected cells were localized in the isthmus of every involved follicle (12/12), frequently in the stem (8/10) and infundibulum (6/10), and never in the bulb. The high frequency of follicular involvement in herpes zoster suggests that VZV spreads to the area of skin innervated by myelinated nerves, which end around the isthmus of hair follicles and sebaceous glands.

Antigens, Viral↗
PubMed1996

Antibody responses in volunteers induced by nasal influenza vaccine combined with Escherichia coli heat-labile enterotoxin B subunit containing a trace amount of the holotoxin.

Evaluation of the efficacy of nasal influenza vaccine combined with Escherichia coli heat-labile enterotoxin B subunit (LTB) containing a trace amount of the holotoxin (LT) in inducing antibody responses among volunteers, which was conducted during the winter season of 1993-1994, is reported. A trivalent inactivated vaccine, composed of A/Yamagata/32/89 (H1N1), A/Kitakyusyu/159/93 (H3N2) and B/Bangkok/163/90 influenza virus strains, was used alone or together with the adjuvant, recombinant LTB supplemented with 0.5% recombinant LT (LTB*). The volunteers were divided into two groups: 73 volunteers (mean age 35.0 +/- 12.0 years) inoculated intranasally (i.n.) with LTB*-combined vaccine and 49 volunteers (37.9 +/- 11.3) inoculated i.n. with the vaccine alone. Vaccination was done twice 4 weeks apart. Salivary secretory IgA and serum hemagglutination-inhibiting (HI) antibodies were measured before and 8 weeks after the primary vaccination. For the sake of convenience, more than a 1.4-fold rise in IgA antibody response (units of specific IgA antibody per microgram of total IgA) and a fourfold or greater rise in HI antibody titer after vaccination were regarded as a positive antibody response. Thirty-seven (50.3%) and 36 (49.3%) of the 73 vaccinees, respectively, given the nasal LTB*-combined vaccine showed positive IgA and HI antibody responses to one or more of the three vaccine strains. In comparison, positive antibody responses in the group given vaccine alone were 32.7% for IgA and 30.6% for HI antibody. There was a significant difference between these two groups. These results suggest that the nasal LTB*-combined vaccine could enhance the production of higher levels not only of serum HI antibody but IgA antibodies in the respiratory tract than do the nasal vaccine alone.

Adjuvants, Immunologic↗
PubMed1996

Emerging components of the Crk oncogene product: the first identified adaptor protein.

v-Crk, identified as an oncogene product of the CT10 retrovirus, became the first example of an adaptor protein. It consists mostly of the Src homology 2 (SH2) and Src homology 3 (SH3) domains. Two of the three major proteins bound to Crk SH2 have been identified as paxillin and p130Cas. Both paxillin and p130Cas are phosphorylated upon stimulation by integrin, suggesting that Crk transduces signals from integrin. The cloning of the complementary DNA of two major proteins bound to Crk SH3 was recently completed. Both cDNAs encoded novel proteins: C3G, a guanine nucleotide exchange protein for Rap1, and DOCK180, an SH3-containing protein of unknown function. The SH3 domain of Crk also binds to Sos, Abl, and Eps15. The variety of the proteins bound to Crk SH3 implies that Crk provides a set of effector proteins that are triggered together. Alternatively, other domains of the SH3-binding proteins enable Crk to specifically activate each of the SH3-binding proteins according to the particular form of stimulation.

Animals↗
PubMed1996

Retrospective analysis of the treatment of patients with small cell lung cancer showing poor performance status.

To assess the feasibility of treatments for patients with small cell lung cancer (SCLC) showing a poor performance status (PS, Eastern Cooperative Oncology Group; ECOG 3 or 4), we retrospectively reviewed the outcome for 13 SCLC patients showing poor PS treated at the National Cancer Center Hospital between January 1984 and May 1994. The main factors which contributed to poor prognosis were superior vena cava (SVC) syndrome, massive pleural effusion, tracheal stenosis due to lymph node swelling, pericardial effusion and pulmonary fibrosis (causing dyspnea in combination), brain metastasis resulting in neurological disturbance, cachexia, Eaton-Lambert syndrome causing muscle weakness, retroperitoneal lymph node metastasis causing abdominal pain, peritoneal effusion due to abdominal lymph node swelling, vertebral metastasis causing paraplegia, and dermatomyositis/polymyositis (DM/PM) causing muscle weakness. All of the patients received chemotherapy with or without radiotherapy. The PS of 8 patients improved with treatment, but no improvement was seen in 5. We analyzed these 13 patients and considered the treatments for those with poor PS. Chemo-radiotherapy was tolerable in SCLC patients showing PS 3, and improved their PS if severe conditions or combined disease did not arise concurrently. It was further suggested that PS 4 patients with severe conditions or combined disease should not be given the treatments.

Adult↗
PubMed1996

Human T lymphotropic virus type II (HTLV-II): epidemiology, molecular properties, and clinical features of infection.

Human T lymphotropic virus, type II (HTLV-II), infection has been shown to be endemic in a number of American Indian populations, and high rates of infection have also been documented in intravenous drug abusers in urban areas throughout the world. Although the role of HTLV-II in human disease has yet to be clearly defined, there is accumulating evidence that like HTLV-I, infection may also be associated with rare lymphoproliferative and neurological disorders. In this article we review and summarize the epidemiology, molecular properties and clinical features of HTLV-II infection.

Amino Acid Sequence↗
PubMed1996

A novel neutralization epitope on the 'thumb' subdomain of human immunodeficiency virus type 1 reverse transcriptase revealed by a monoclonal antibody.

We have prepared a MAb, 7C4, which inhibits the RNA-dependent DNA polymerase activity of human immunodeficiency virus type 1 (HIV- 1) reverse transcriptase (RT); this MAb has allowed identification of a previously unknown neutralizing epitope of RT. Analysis of the epitope and of the mechanism of polymerase inhibition revealed that 7C4 acts by interfering with the interaction between RT and the template-primer. 7C4 recognizes a discontinuous epitope on the two alpha-helices, alphaH and alpha(I), that make up the 'thumb' subdomain of RT. The existing crystallographic model of HIV-1 RT suggests that the 'thumb' subdomain, together with the 'fingers' and 'palm', form a nucleic-acid-binding cleft in the 66 kDa subunit of RT and that alphaH is in contact with the primer strand of the template-primer. The extent of inhibition of enzyme activity produced by 7C4 correlates with the reported primer-length-dependency of template-primer binding to RT. Inhibition by 7C4 was competitive with respect to the template-primer and mixed with respect to the substrate. Binding of 7C4 to RT was prevented by preincubation of the enzyme with high concentrations of template-primer but not with substrate. Thus, the 7C4 epitope apparently exists on part of the template-primer binding site of the alphaH and alpha(I) regions of the 'thumb' subdomain. This neutralization epitope is a logical target for the development of new types of HIV-1 RT inhibitors.

Animals↗