Review: collected materials and records of HIV/AIDS prevalence and the contemporary social changes in Thailand.
Explore the source record for details and available documents.
AIDS Vaccines↗
Biomedical subjects
T Kurata
Publications and source records attributed to T Kurata.
Intensive chemotherapy with cisplatin, doxorubicin, cyclophosphamide, etoposide and granulocyte colony-stimulating factor for advanced thymoma or thymic cancer: preliminary results.
A study was conducted to evaluate the impact of cisplatin, doxorubicin, cyclophosphamide and etoposide (PACE) with granulocyte colony-stimulating factor (G-CSF) on advanced thymoma or thymic cancer. Between August 1989 and December 1994, 14 patients with invasive, metastatic or recurrent thymoma or thymic cancer were treated with cisplatin (80 mg/m2, on day 1), doxorubicin (45 mg/m2, on day 1), cyclophosphamide (800 mg/m2, on day 1) and etoposide (80 mg/m2, on day 1-3) with G-CSF (90 micrograms/m2, on day 5-18) at the National Cancer Center Hospital, Tokyo. Courses were repeated every 3 or 4 weeks for a maximum of 4 cycles. Twelve patients were treated with 2 or more courses of PACE. Two patients were treated with only one course, one refused and another required emergency thoracic radiotherapy after one course of PACE. Six patients had partial responses (3 thymomas and 3 thymic cancers) but there were no complete remissions (response rates, 42.9%; 95% confidence interval, 17.7% to 71.1%). Moderate hematological toxicities were observed: grade 3 or 4 leukopenia, neutropenia, anemia and thrombocytopenia in 10, 13, 8 and 6 patients, respectively. Six patients developed infections that required antibiotics. Surgical resection or thoracic radiotherapy after PACE treatment was performed in 2 and 7 patients, respectively. The overall median survival time was 14.7 months (range, 5.9 to 59.7 months). For 9 patients who had received no prior treatment before chemotherapy, the median survival time was 8.9 months, and one patient survived for 4 years and is still alive. In conclusion, PACE with G-CSF frequently produces objective remissions in patients with advanced thymoma or thymic cancer. A large-scale intergroup study is necessary to determine the impact of this regimen on advanced thymoma and thymic cancer.
Adult↗
Nonsense mutations in the vpr gene of HIV-1 during in vitro virus passage and in HIV-1 carrier-derived peripheral blood mononuclear cells.
Long-term, persistent infection by HIV-1 is a prerequisite for the development of AIDS. However, little is known of the determinants required for HIV-1 to cause persistence. We have reported previously that persistent infection of a T cell line by a cytopathogenic strain of HIV-1 became increasingly likely with in vitro serial passage of the virus. DNA sequencing of the persistent strains revealed a nonsense mutation in the vpr gene in all isolates tested. Here, we report the development and use of a semi-quantitative PCR method to detect the vpr nonsense mutation within populations of virus. Our results show that vpr mutants also arise in cells during acute infection and increase progressively with serial passage of the virus. In addition, HIV-1-seropositive individuals were examined and found to carry the same vpr nonsense mutation at high frequency in virus-infected PBMC. These data are consistent with a mechanism of HIV-1 persistence in vivo and in vitro in which virus cytopathogenic potential is lost by the build up of nonsense mutations in vpr.
AIDS-Related Complex↗
C3G, a guanine nucleotide-releasing protein expressed ubiquitously, binds to the Src homology 3 domains of CRK and GRB2/ASH proteins.
CRK protein, together with GRB2/ASH and Nck proteins, belongs to the adaptor-type Src homology (SH)2-containing molecules, which transduce signals from tyrosine kinases. Here another guanine nucleotide-releasing protein (GNRP), C3G, has been identified as a CRK SH3-binding protein. The nucleotide sequence of a 4.1-kb C3G cDNA contains a 3.2-kb open reading frame encoding a 121-kDa protein, and antibodies against C3G have been shown to detect a protein of 130-140 kDa. The carboxyl terminus of C3G has a peptide sequence homologous to GNRPs for Ras, and the expression of this carboxyl terminus region suppresses the loss of CDC25 function in the yeast Saccharomyces cerevisiae. The C3G protein expressed in Escherichia coli binds to CRK and GRB2/ASH proteins. Mutational analysis of C3G assigns the SH3 binding region to a 50-amino acid region containing a proline-rich sequence. The mRNAs of both the C3G and CRK proteins are expressed ubiquitously in human adult and fetal tissues. The results of these studies suggest that the complex of CRK and C3G, or GRB2/ASH and C3G, may transduce the signals from tyrosine kinases to Ras in a number of different tissues.
Adaptor Proteins, Signal Transducing↗
A comparative study of congenital and postnatally acquired human cytomegalovirus infection in infants: lack of expression of viral immediate early protein in congenital cases.
Postmortem tissues from infants with congenital and postnatally acquired human cytomegalovirus (HCMV) infection were examined by routine histology, immunohistochemistry (IHC) and in situ hybridization (ISH) to determine the dynamics of viral replication in vivo. Histologically, infants in both groups showed characteristic inclusion-bearing cells most commonly in lung, kidney, liver and pancreas. IHC for late proteins using a rabbit polyclonal antibody and ISH for viral genomes detected most of the infected cells as nuclear and/or cytoplasmic signals. However, immunostaining with a monoclonal antibody against viral immediate early (IE) proteins was variable depending on the stage of viral replication within an individual infected cell. In tissues of infants with postnatal HCMV infection, many cells harboured IE antigens, while in tissues from congenital cases most of the affected cells lacked IE antigens and only a few showed cytoplasmic staining. The difference was not caused by the antigenic diversity among viral strains as confirmed by in vitro study. Our findings suggested that congenital infections exhibited uniformly late stage proteins with inactive viral replication at death, while acquired ones remained active. The different viral activity may reflect the immune status of congenital and acquired HCMV infections.
Cytomegalovirus↗
Formulation of inactivated influenza vaccines for providing effective cross-protection by intranasal vaccination in mice.
Attempts were made to formulate an inactivated influenza vaccine to provide effective cross-protection by intranasal vaccination in mice. Mice were immunized with a nasal site-restricted volume of various HA vaccines (split-product virus vaccines), prepared from some of the H1N1 subtype viruses which circulated in humans from 1934 to 1986, together with cholera toxin B subunit (CTB) as an adjuvant. Four weeks later, they were challenged intranasally with a lethal dose of the earliest H1N1 virus strain, A/PR/8/34 (PR8) or the latest virus strain, A/Yamagata/120/86 (Yamagata/86). The adjuvant-combined vaccines, prepared from drift H1N1 viruses, A/Kumamoto/37/79 and A/Bangkok/10/83, provided a higher degree of cross-protection against a challenge with Yamagata/86 than with PR8. A booster with another drift virus vaccine given 4 weeks after the primary vaccination increased the protection against Yamagata/86; the effect was higher when mice were vaccinated with a later strain as the second antigen than when boosted with PR8. These results suggest that vaccination with a later virus strain followed by another later strain in a two-dose nasal vaccination regimen gives effective cross-protection against the current epidemic virus strains.
Administration, Intranasal↗
Effects of cholera toxin adjuvant on IgE antibody response to orally or nasally administered ovalbumin.
Effects of cholera toxin B subunits supplemented with 0.1% cholera toxin (CTB*) on systemic IgE antibody responses to ovalbumin (OVA) were examined in BDFI (H-2b/d), Balb/c (H-2d) and C3H (H-2k) mice given OVA intragastrically or intranasally. Two successive doses of OVA intragastrically administered to Balb/c and C3H mice induced little IgE response and resulted in almost complete unresponsiveness to subsequent intraperitoneal challenge with OVA in Al(OH)3, while the intragastric administration to BDF1 mice induced high IgE response and resulted in abrogation of the unresponsiveness to the subsequent challenge. The intranasal administration of OVA induced little IgE response and suppressed response to the subsequent challenge in any strain of mice. On the other hand, two successive doses of intragastric or intranasal OVA together with CTB* enhanced IgE response in all three strains and the subsequent challenge with OVA in Al(OH)3 induced higher IgE responses. These results suggest that CTB* augments IgE response to OVA and abrogates the unresponsiveness when administered orally or intranasally into mice together with OVA, regardless of the H-2 haplotype of the mice.
Adjuvants, Immunologic↗
The rash of measles is caused by a viral infection in the cells of the skin: a case report.
Measles skin rash was immunohistochemically examined in an effort to detect virus antigen in skin samples taken from a 15-year-old girl with measles. A sectioned specimen obtained by punch biopsy from a 2nd-day skin lesion showed localized parakeratosis and acanthosis with multinucleated giant cells in the epidermis, thickening and cellular edema of epithelia in the hair follicles, and vascular dilation in the papillary plexus. Measles virus antigen was detected by ABC immunoperoxidase in the epidermis, follicular epithelia, and lympho-histiocytic cell infiltrates in the upper of the dermis. This rash deemed to be caused in part by direct viral infection of the epidermal cells.
Adolescent↗
[Sexually transmitted disease infection in HIV carriers].
Heterosexual transmission of the human immunodeficiency virus (HIV) appears to occur readily all over the world. Recent reports have suggested an association between HIV and sexually transmitted disease (STD). We conducted a case study among foreign female prostitutes who were seropositive to HIV to determine the prevalence of STD. In this study, we checked the prevalence of STD infection in 19 HIV seropositive female prostitutes. Overall, 84 percent were seropositive for Chlamydia trachomatis, 37% for HBs, 32% for Treponema pallidum (Tp) and 6% for hepatitis C virus (HCV). The high frequency of a history of STD may be associated with an increased risk of HIV infection acquired through heterosexual contact. Prevention of heterosexually transmitted HIV infection will require an extensive educational program aimed specifically at the risk associated with the number and selection of sexual partners and at promoting safer sexual practices.
Adolescent↗
Major antigenic region on the integrase (IN) protein of human immunodeficiency virus type 1 determined by reactivity of human sera and a monoclonal antibody to IN protein.
The gene encoding the integrase (IN) protein of human immunodeficiency virus type 1 (HIV-1) was expressed in vaccinia virus and Escherichia coli, and sera from 55 HIV-1-infected individuals were examined for immunoreactivity to the recombinant IN proteins by Western immunoblot. Approximately 98% (54 of 55) of the HIV-1-infected individuals showed reactivity to both the full-length IN protein of 32 kDa (IN32 protein) and the carboxy-terminal portion of the IN protein (IN17 protein). Serum samples from only 6 of the 54 antibody-positive individuals and a monoclonal antibody against the IN protein, 6F4, reacted with the amino-terminal portion of the IN protein (IN15 protein). The eight AIDS patients tested were seronegative to IN15 protein. The magnitude of reactivity to the recombinant IN proteins decreased slightly in the progression of the course of HIV-1 infection. These results suggest that a B-cell immunodominant epitope(s) on the IN protein is located on the C-terminal IN17 portion and that a minor epitope(s) recognizable by 6F4 and by rare patients is on the N-terminal IN15 portion.
Amino Acid Sequence↗
Transgenic mice carrying the human poliovirus receptor: new animal models for study of poliovirus neurovirulence.
Recombinant viruses between the virulent Mahoney and attenuated Sabin 1 strains of poliovirus type 1 were subjected to neurovirulence tests using a transgenic (Tg) mouse line, ICR-PVRTg1, that carried the human poliovirus receptor gene. The Tg mice were inoculated intracerebrally with these recombinant viruses and observed for clinical signs, histopathological lesions, and viral antigens as parameters of neurovirulence of the viruses. These parameters observed in the Tg mice were different for different inoculated viruses. Dose-dependent incidences of paralysis and of death were observed in the Tg mice inoculated with any viruses used. This indicates that values of 50% lethal dose are useful to score a wide range of neurovirulence of poliovirus. The neurovirulence of individual viruses estimated by the Tg mouse model had a strong correlation with those estimated by monkey model. Consequently, the mouse tests identified the neurovirulence determinants on the genome of poliovirus that had been identified by monkey tests. In addition, the mouse tests revealed new neurovirulence determinants, that is, different nucleotides between the two strains at positions 189 and 21 and/or 935 in the 5'-proximal 1,122 nucleotides. The Tg mice used in this study may be suitable for replacing monkeys for investigating poliovirus neurovirulence.
Animals↗
CRK protein binds to two guanine nucleotide-releasing proteins for the Ras family and modulates nerve growth factor-induced activation of Ras in PC12 cells.
It has been reported that growth factors activate Ras through a complex of an adaptor type SH2-containing molecule, Grb2, and a Ras guanine nucleotide-releasing protein (GNRP), mSos. We report on the involvement of another adaptor molecule, CRK, in the activation of Ras. Overexpression of wild-type CRK proteins CRK-I and CRK-II enhanced the nerve growth factor (NGF)-induced activation of Ras in PC12 cells, although the basal level of GTP-bound active Ras was not altered. In contrast, mutants with a single amino acid substitution in either the SH2 or SH3 domain of the CRK-I protein inhibited the NGF-induced activation of Ras. Two GNRPs for the Ras family, mSos and C3G, were coimmunoprecipitated with the endogenous Crk proteins in PC12 cells. The association between C3G and the CRK mutants was dependent upon the presence of intact SH3. The SH2 domain of CRK bound to the SHC protein phosphorylated on tyrosine residues by NGF stimulation. The results demonstrate that, in addition to Grb2, CRK participates in signaling from the NGF receptor and that two GNRPs appear to transmit signals from these adaptor molecules to Ras.
Animals↗
Mechanisms of hearing disturbance in an autoimmune model mouse NZB/kl.
A subline of the NZB mouse, NZB/kl, was found to develop severe hearing disturbances at high frequency sound at the age of 4 to 6 months. Deposition of IgG was observed on the capillary wall of the stria vascularis of the mice, but the concentration of circulating immune complex did not seem to be correlated to the deposition. Electron microscopic examination revealed that the capillaries had a thick basement membrane, and in severe cases the membrane contained foamy structures of various size. In some cases the base membrane was so thick that the capillary lumen was narrowed, and the intermediate cells seemed to be damaged. No pathological findings were found in other inner ear tissues. These results suggest that the changes in the stria vascularis were possibly caused by an autoimmune mechanism which resulted in hearing disturbance.
Animals↗
[Pleuropulmonary aspergillosis with defective neutrophil functions--G-CSF effects on neutrophil functions].
A 66-year-old man was admitted to our hospital with productive cough and fever. Chest X-ray films showed pleural thickening of the right apex and calcification of the lung field. Antibiotic therapy was administered but no improvement was obtained. Chest CT scan revealed pleural thickening with effusion in the right apex. Needle aspiration biopsy was performed and Aspergillus fumigatus was isolated from pleural fluid. We began pleural drainage and intrapleural infusion of miconazole, with systemic administration of miconazole, amphotericin B and fluconazole. In spite of normal bone marrow findings, the neutrophil functions, NAP score and phagocytosis, of the patient were found to be subnormal. We commenced to treatment with granulocyte colony stimulating factor and his neutrophil functions improved (NAP score: 156-->309.5, phagocytosis: 64.9-->70.0%). However, his fever persisted and he died following cardiopulmonary arrest. Autopsy revealed Aspergillus mycelia invading the visceral pleura. No intrapulmonary lesions caused by Aspergillus were found.
Aged↗
The distribution of ascorbic acid and dehydroascorbic acid during tissue regeneration in wounded dorsal skin of guinea pigs.
The distribution of L-ascorbic acid AA and dehydroascorbic acid DHA in wounded and intact skin of guinea pig was investigated to elucidate the utilization of AA during tissue regeneration. Male guinea pigs fed an AA-free diet for 14 days were surgically injured on the dorsal skin, followed by intraperitoneal supplementation of AA (0.5, 5 and 50 mg/day/animal) for 4 days. The wounded skin, its surroundings and intact skin in each animal were removed for the determination of AA, DHA and collagen. The collagen content in wounded and intact skin increased in dose-dependent manner up to 5 mg AA/day, although neither the wounded nor the intact skin of the group supplemented with 50 mg AA had a higher content of collagen than those supplemented with 5 mg. In each group, the wounded skin had only about half the collagen of intact skin. AA content in the wounded skin of the groups supplemented with 5 and 50 mg AA were significantly lower than that in the other parts of their skin, whereas DHA content in wounded skin increased markedly. These results indicate that other factors besides collagen synthesis may enhance the oxidation of AA in the early stage of tissue regeneration.
Animals↗
Structural requirement of CRK SH2 region for binding to phosphotyrosine-containing proteins. Evidence from reactivity to monoclonal antibodies.
The SH2 region of signal-transducing proteins mediates binding to phosphotyrosine-containing proteins. We analyzed the structure-function relationship of the SH2 region of the human CRK protein by using a series of monoclonal antibodies (mAbs). Seventeen mAbs against the CRK SH2 region were classified into 5 groups according to the reactivity with mutant CRK proteins expressed in COS7 cells and in Escherichia coli and by epitope scanning with synthetic nonapeptides. Two groups of mAbs (groups A and B) were reactive only with intact SH2. Mutation(s) in either the amino-terminal B box or the carboxyl-terminal C box, which are the two subdomains of SH2, abolished the reactivity of the CRK mutants to the mAbs of groups A and B. Group A mAbs competed the binding of the CRK SH2 region to the phosphotyrosine-containing proteins. Moreover, the spectrum of the CRK mutants which were recognized by group A mAbs coincided with that of the CRK mutants which could bind phosphotyrosine-containing proteins, suggesting that group A mAbs were directed against the site of binding to phosphotyrosine-containing proteins. Group C mAbs, directed against the region between the B and C boxes, were reactive with both wild-type and mutant CRK proteins and did not affect the capacity of SH2 to bind phosphotyrosine-containing proteins. Contrary to group A and B mAbs, mAbs belonging to groups D and E, which were mapped onto the C box, did not bind well to the native CRK proteins, but bound to CRK mutants with mutation(s) in either the B or the C box. These results suggest that the B and C boxes, which are separated by a hinge region, coordinately form the functional SH2 domain that binds to the phosphotyrosine-containing proteins and to the group A mAbs.
Animals↗
The pathogenicity of a US3 protein kinase-deficient mutant of herpes simplex virus type 2 in mice.
We have investigated the pathogenicity of a US3 protein kinase-deficient mutant (L1 BR1) of herpes simplex virus type 2 (HSV-2) for 4-week-old ICR mice to define the role of the viral protein kinase in virus-host interaction. When mice were intraperitoneally infected with 10(5)PFU of L1 BR1, the virus disappeared from the peritoneal cavity by 2 days postinfection and failed to induce any significant histopathological changes in the liver and spleen although viral antigens were occasionally detected in the epithelial cells of small bile ducts and small vascular wall. The parental virus (HSV-2 186) and a revertant of the mutant (L1 B-11) both caused severe hepatitis, and viral antigens were clearly detected in the hepatocytes and Kupffer cells in the focal necrotic areas. Both of the virulent viruses, unlike L1 BR1, could produce infectious progeny and cytopathic effects in freshly harvested peritoneal macrophages. The growth of L1 BR1 in peritoneal macrophages was restricted at a stage of or prior to viral DNA synthesis but after the induction of viral DNA polymerase. In addition, the production and/or the spread of mutant in mouse embryo fibroblasts (MEF) was found to be much more effectively suppressed by cocultivation of peritoneal macrophages than that of 186. An almost complete inhibition of L1 BR1-plaque formation was observed at a macrophage-to-MEF ratio of 4:1. These results suggest that the attenuation of L1 BR1 following intraperitoneal infection is primarily due to its high sensitivity to intrinsic and extrinsic inhibition of peritoneal macrophages and that the US3 protein kinase may play a role in viral DNA replication in peritoneal macrophages.
Animals↗
The evidence of human herpesvirus 6 infection in the lymph nodes of Hodgkin's disease.
Human herpesvirus 6 (HHV-6), the causative agent of exanthem subitum, has been implicated in other diseases. Recently HHV-6-specific sequences have been detected by Southern blot analysis and polymerase chain reaction in the lymph nodes of three patients with Hodgkin's disease. The pathological localization of HHV-6, however, is still unknown. In order to study the pathological role of HHV-6 in Hodgkin's disease, we investigated, by immunohistochemical and molecular methods, two lymph node biopsies taken from a 7-year-old boy with Hodgkin's disease during the course of disease evolution. Although the histopathological findings of the first biopsy differed from those of the second, HHV-6 antigens and sequences could be detected in both lymph nodes by immunohistochemistry and in situ hybridization, respectively. HHV-6 was localized in macrophages, predominantly in lymphoid follicles, but not in Reed-Sternberg cells. Antibody titres to HHV-6 were consistent with reactivation of latency. Neither cytomegalovirus nor Epstein-Barr virus was present. Our data suggest a role for HHV-6 in the pathogenesis of Hodgkin's disease.
Antibodies, Viral↗