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Biomedical subjects

A Iwamoto

Publications and source records attributed to A Iwamoto.

At least 37 records · Page 2Linked to original sources

Perinatal development of the rat kidney: proliferative activity and epidermal growth factor.

The immunolocalization of proliferating cell nuclear antigen (PCNA), epidermal growth factor (EGF) and its receptor (EGFR) was examined in the perinatal rat kidney. As the index of proliferative activity, PCNA-positive cell ratios in glomeruli and proximal tubules were determined. The PCNA-positive ratios in both glomeruli and proximal tubules decreased significantly during the perinatal period and tended to decrease as the glomerular developmental stage proceeded as well. PCNA-positive cells were seen predominantly in the nephrogenic zone of the kidney throughout the period examined. They were noted in the collecting ducts of the nephrogenic zone and were rarely seen in those of the central zone of the kidney. On the other hand, PCNA-positive cells were noted in the straight portion of the proximal tubules and were rarely seen in the convoluted one. EGF-positive cells were seen in the proximal tubules, distal tubules and collecting ducts, though EGF-positive cells in the proximal tubules decreased after birth. EGFR-positive cells were seen along the entire length of the proximal tubules and collecting ducts as well as in immature glomeruli, not in mature ones. These results indicate that marked cell proliferation occurs in the collecting ducts in the peripheral area and in the proximal tubules in the central area of the kidney, that the proliferative activity decreases with age during the perinatal days and that EGF plays an important role in the proliferation of glomerular cells, and in both proliferation and maturation of the cells in the proximal tubules and collecting ducts.

Animals↗

Surfactant protein D and KL-6 as serologic indicators of Pneumocystis carinii pneumonia in a child with acute lymphoblastic leukemia.

Pneumocystis carinii pneumonia (PCP) in immunocompromised patients is one of the important causes of morbidity and mortality. Serum levels of surfactant protein D (SP-D) and KL-6 are useful biomarkers for understanding some pulmonary inflammatory responses in patients with idiopathic pulmonary fibrosis (IPF). We present a child with PCP following bone marrow transplantation (BMT) for acute lymphoblastic leukemia (ALL), for whom both SP-D and KL-6 in sera were simultaneously measured through the clinical course of PCP. Both serum levels of SP-D and KL-6 were rapidly elevated reflecting some inflammatory processes in the lung that chest X-ray films and CT scans showed as ground-glass attenuations. He died due to respiratory failure 40 days after PCP developed. A combination of the assays for SP-D and KL-6 in sera may be helpful in predicting the treatment results for PCP.

Adolescent↗

Viral and cellular cytokines in AIDS-related malignant lymphomatous effusions.

Kaposi sarcoma-associated herpesvirus encodes viral IL-6 (vIL-6). To investigate the potential role of vIL-6 in the pathogenesis of human immunodeficiency virus (HIV)- related primary effusion lymphomas (PEL), a sensitive enzyme-linked immunosorbent assay was developed for vIL-6 and applied to the study of PEL. Whereas vIL-6 was detectable in 6 of 8 PEL effusions (range, 1390-66 630 pg/mL), it was not detectable in any of the control effusions. As expected, all PEL effusions contained human IL-6 (range, 957-37 494 pg/mL), and 7 of 8 contained detectable human IL-10 (range, 66-2,521,297 pg/mL). Human and vIL-6 have previously been shown to induce vascular endothelial growth factor, which in turn can increase vascular permeability. The results of the current study suggest that these cytokines play a central role in the pathogenesis and manifestations of PEL. (Blood. 2000;96:1599-1601)

Body Fluids↗

Interleukin 18 and interleukin 1beta production is decreased in HIV type 1-seropositive hemophiliacs but not in HIV type 1-seropositive nonhemophiliacs.

In Japan, the proportion of hemophiliacs infected with human immunodeficiency virus type 1 (HIV-1) is 40%, whereas more than 90% are infected with hepatitis C virus (HCV). To evaluate the immunological status of hemophiliacs infected with HIV-1, we investigated the pattern of cytokine production in peripheral blood mononuclear cells (PBMCs) of HIV-1-seropositive and -seronegative hemophiliacs, HIV-1-seropositive non-hemophiliacs, and healthy individuals. The production of IL-18 and IL-1beta from PBMCs stimulated with Staphylococcus aureus Cowan strain 1 (SAC) in the HIV-1-seropositive hemophiliacs was significantly decreased in comparison with the other groups. On the other hand, IL-12 production in both HIV-1-seropositive groups was significantly lower than in HIV-1-seronegative groups. TNF-alpha and IL-6 production was similar among the four groups. In contrast, plasma levels of TGF-beta1 were increased in HIV-1-seropositive hemophiliacs, HIV-1-seropositive nonhemophiliacs, and HIV-1-seronegative hemophiliacs, with the highest levels being in HIV-1-seropositive hemophiliacs, suggesting that coinfection with HIV-1 and HCV increases the level of plasma TGF-beta in HIV-1-seropositive hemophiliacs. Treatment of PBMCs from healthy individuals with TGF-beta1 inhibited IL-18 and IL-1beta production without affecting IL-6, IL-10, or TNF-alpha production. Suppression of the expression of caspase 1 mRNA, which is known to be an IL-1beta-converting enzyme and which also cleaves the precursor of IL-18, was observed in the SAC-stimulated PBMCs from healthy individuals after treatment with TGF-beta1 and in the SAC-stimulated PBMCs from HIV-1-seropositive hemophiliacs, suggesting that the decreased production of IL-18 and IL-1beta in HIV-1-seropositive hemophiliacs may be related to the downregulation of caspase 1 mRNA induced by high levels of TGF-beta1 in plasma.

Adolescent↗

Antibodies to molluscum contagiosum virus in the general population and susceptible patients.

BACKGROUND: Since many attempts to cultivate molluscum contagiosum virus (MCV) in vitro have been unsuccessful, it is difficult to prepare a large quantity of antigens. To assess the seroprevalence of antibodies against MCV in 508 subjects with or without clinical MCV infection, a truncated recombinant protein from open-reading frame MC133L was synthesized using Sendai virus expression system and applied to enzyme-linked immunosorbent assay as an antigen. OBSERVATIONS: Antibodies to MCV were present in 7 (58%) of 12 patients with molluscum contagiosum, 7 (6%) of 108 healthy controls, 7 (9%) of 76 with atopic dermatitis, and 7 (18%) of 39 patients with systemic lupus erythematosus, although no clinical MCV infection was observed in the latter 3 groups. Of 7 human immunodeficiency virus (HIV)-positive patients with molluscum contagiosum, 1 (14%) was antibody positive, compared with 5 (2%) of 266 HIV-positive patients without molluscum contagiosum. Serum samples from patients with atopic dermatitis and systemic lupus erythematosus showed a higher reactivity (P<.001) than those from healthy controls, while serum samples from HIV-positive subjects showed a lower reactivity (P<. 001). CONCLUSION: The humoral immune response to MCV is usually confined to patients with molluscum contagiosum and may be affected by the immunological condition of the host.

Adolescent↗

Comparison of proviral accessory genes between long-term nonprogressors and progressors of human immunodeficiency virus type 1 infection.

We compared proviral accessory gene sequences (nef, vpu, vpr, vif, rev, tat) of human immunodeficiency virus type 1 (HIV-1) in the peripheral blood mononuclear cells (PBMC) between seven long-term non-progressors (LTNP) and seven progressors. LTNP frequently harbored proviruses with mutated accessory genes, while almost all accessory genes were intact in progressors. Presence of quasispecies in attenuated viruses suggests that they were not just a fossil record of nonreplication proviruses. These attenuated viruses in LTNP may be the source of their strong immune response against HIV-1. Our result might have relevance to a design of potent therapeutic vaccines.

AIDS Vaccines↗

Human herpesvirus 8-associated solid lymphomas that occur in AIDS patients take anaplastic large cell morphology.

Human herpesvirus type 8 (HHV-8; Kaposi's sarcoma-associated herpesvirus) is a recently isolated human herpesvirus frequently identified in Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. Here we report three cases of HHV-8-bearing solid lymphomas that occurred in AIDS patients (Cases 1-3). All three patients were homosexual men presenting extranodal masses in the lungs (Case 1) or skin (Cases 2 and 3), together with the presence of Kaposi's sarcoma (Case 1), primary effusion lymphoma (Case 2), or multicentric Castleman's disease (Case 3). These solid lymphomas exhibited anaplastic large cell morphology and expressed CD30, corresponding to the recent diagnostic criteria of anaplastic large cell lymphoma (ALCL). The chromosomal translocation t(2;5)-associated chimeric protein p80NPM/ALK was not observed in any of these cases. HHV-8 was detected in all of these cases by polymerase chain reaction, immunohistochemistry of HHV-8-encoded ORF73 protein, and in situ hybridization of T1.1. Epstein-Barr virus was detected only in Cases 2 and 3 by in situ hybridization. It is interesting that inoculation of a cell line obtained from a primary effusion lymphoma cell in Case 2 to severe combined immunodeficiency mice produced HHV-8-positive and Epstein-Barr virus-negative tumors in inoculated sites. These tumor cells exhibited phenotypes of ALCL that were identical to the subcutaneous tumor cells of this particular patient. These findings clearly show that HHV-8 can associate with solid lymphomas and that it can take anaplastic large cell morphology. Those lymphomas should be distinguished from the classical ALCL as were defined by the revised European-American classification of lymphoid neoplasms even though morphology and a part of immunophenotype mimic that of classical ALCL.

Adult↗

A new polymorphism in the promoter region of the human interleukin-16 (IL-16) gene.

Interleukin 16 (IL-16) is a chemotactic cytokine which binds to CD4 and affects T cell activation. Here we report a novel single nucleotide polymorphism, T to C, in the promoter region of the IL-16 gene in two distinct Asian populations, Japanese and Thai. This mutation occurs at an allele frequency of approximately 22% and 18%, respectively. Although IL-16 potently suppresses replication of human immunodeficiency virus type 1 (HIV-1), we observed no significant difference in the allele frequency of this polymorphism between HIV-1-infected and non-HIV-1-infected individuals in both Asian populations. Since differential IL-16 levels have been reported to be associated with inflammatory diseases such as systemic lupus erythematosus, atopic dermatitis and allergic asthma, it would be of interest to analyze the allele frequency of this mutation in patients with these autoimmune and allergic diseases.

Gene Frequency↗

The IgM antibody level against ganglioside GM2 correlates to the disease status of HIV-1-infected patients.

HIV-1 infection induces the expression of high level of GM2 ganglioside on infected cells and IgM antibody (Ab) against GM2 can cause complement (C)-mediated cytolysis of HIV-1-infected cells. Since GM2 is immunogenic in human, we proposed that an anti-GM2 IgM Ab may be produced by some HIV-1-infected patients and the titer of this Ab might provide some insight into the progress of the disease. On this premise, the amount of IgM Ab against GM2 was determined in 124 HIV-1-infected patients and 111 seronegative donors. As expected, the anti-GM2 IgM Ab titers of the patients was significantly higher than that of the seronegative donors while the total IgM levels remained unchanged. In addition, we determined the CD4+ cell count and the HIV-RNA load in the HIV-1-infected patients. The results showed a positive correlation between the anti-GM2 IgM Ab titer and CD4+ cell count but a negative correlation between the anti-GM2 IgM Ab titer and HIV-RNA load. These suggest that anti-GM2 IgM Ab induced and/or enhanced by HIV-1 infection causes C-mediated cytolysis of HIV-1-infected cells in vivo to a certain extent, and may help lower the plateau level of the HIV-RNA load. Therefore, the amount of IgM Ab against GM2 may be related to the prognosis of HIV-1 infected patients.

CD4 Lymphocyte Count↗

Genotyping of Pneumocystis carinii f. sp. hominis isolates in Japan based on nucleotide sequence variations in internal transcribed spacer regions of rRNA genes.

Genotyping of Pneumocystis carinii (Pc) isolated from 24 bronchoalveolar lavage (BAL) fluid specimens in Japan was examined based on nucleotide sequence variations in internal transcribed spacer regions 1 and 2 (ITS1 and ITS2, respectively) of rRNA genes. We found 11 ITS1 genotypes including 2 novel ones and 11 ITS2 genotypes including 3 new ones. Combining the ITS1 and ITS2 genotypes resulted in 30 ITS genotypes, of which 10 are newly described in this report. Two or more genotypes in ITS regions in a specimen were observed in 16 of 24 patients. Our results will be of help for the epidemiological investigation of Pc infection.

Adult↗

Seroprevalence of antibodies to Chlamydia spp. in human immunodeficiency virus-infected subjects in Japan.

To evaluate the seropositivity of Chlamydia spp. in human immunodeficiency virus (HIV)-infected subjects in Japan, Chlamydia-specific antibodies in sera collected from 106 HIV-infected subjects were measured by the microimmunofluorescence test. The prevalence of C. pneumoniae-specific IgA, C. trachomatis-specific IgG and IgA and mean titers were significantly higher in the homosexual and heterosexual HIV-infected subjects than in the hemophilic patients and HIV-negative controls. These data indicate that the higher C. pneumoniae and C. trachomatis seroprevalence among HIV-infected subjects is probably due to an HIV risk factor, such as promiscuous sexual behavior, rather than to HIV infection itself.

Adolescent↗

Relationship between mutations in dihydropteroate synthase of Pneumocystis carinii f. sp. hominis isolates in Japan and resistance to sulfonamide therapy.

We examined mutations in the dihydropteroate synthase (DHPS) genes of Pneumocystis carinii f. sp. hominis (P. carinii) strains isolated from 24 patients with P. carinii pneumonia (PCP) in Japan. DHPS mutations were identified at amino acid positions 55 and/or 57 in isolates from 6 (25.0%) of 24 patients. The underlying diseases for these six patients were human immunodeficiency virus type 1 infection (n = 4) or malignant lymphoma (n = 2). This frequency was almost the same as those reported in Denmark and the United States. None of the six patients whose isolates had DHPS mutations were recently exposed to sulfa drugs before they developed the current episode of PCP, suggesting that DHPS mutations not only are selected by the pressure of sulfa agents but may be incidentally acquired. Co-trimoxazole treatment failed more frequently in patients whose isolates had DHPS mutations than in those whose isolates had wild-type DHPS (n = 4 [100%] versus n = 2 [11.1%]; P = 0.002). Our results thus suggest that DHPS mutations may contribute to failures of co-trimoxazole treatment for PCP.

AIDS-Related Opportunistic Infections↗

Polymorphism in the interleukin-4 promoter affects acquisition of human immunodeficiency virus type 1 syncytium-inducing phenotype.

The emergence of syncytium-inducing (SI) variants of human immunodeficiency virus type 1 (HIV-1) in infected individuals is an indicator of poor prognosis and is often correlated with faster CD4(+) cell depletion and rapid disease progression. Interleukin-4 (IL-4) is a pleiotropic cytokine with various immune-modulating functions including induction of immunoglobulin E (IgE) production in B cells, down-regulation of CCR5 (a coreceptor for HIV-1 non-SI [NSI] strains), and up-regulation of CXCR4 (a coreceptor for HIV-1 SI variants). Here we show that homozygosity of a polymorphism in the IL-4 promoter region, IL-4 -589T, is correlated with increased rates of SI variant acquisition in HIV-1-infected individuals in Japan. This mutation was also shown to be associated with elevated serum IgE levels in HIV-1-infected individuals, especially in those at advanced stages of disease. In contrast, neither a triallele polymorphism in IL-10, another Th2 cytokine, nor a biallele polymorphism in the RANTES promoter affected acquisition of the SI phenotype. This finding suggested that IL-4-589T increases IL-4 production in the human body and thus accelerates the phenotypic switch of HIV-1 from NSI to SI and possibly disease progression of AIDS.

Alleles↗

Identification of antigenic proteins encoded by human herpesvirus 8 and seroprevalence in the general population and among patients with and without Kaposi's sarcoma.

To establish a sensitive and specific antibody assay, potent antigenic proteins encoded by human herpesvirus 8 (HHV8) were studied. Fifteen recombinant HHV8-encoded proteins were produced as glutathione S-transferase fusion proteins. The sera from AIDS-associated Kaposi's sarcoma (KS) patients reacted with four proteins encoded by open reading frames (ORFs) K8.1, 59, 65, and 73 in a Western blot assay. An enzyme-linked immunosorbent assay (ELISA) using these four proteins as antigens (mixed-antigen ELISA) revealed that all 26 sera derived from KS patients (24 with and 2 without human immunodeficiency virus infection) became positive for anti-HHV8 antibodies. The presence of HHV8 was demonstrated in 14 (1. 4%) of 1,004 sera from the Japanese general population and 10 (1.9%) of 527 sera from patients without HHV8-associated diseases. The presence of immunoglobulin G (IgG) and IgM antibodies against HHV8 examined further by the mixed-antigen ELISA and Western blotting revealed IgG antibody in all ELISA-positive sera, while IgM antibody against ORF K8.1 was absent. These data suggest that the ORF 73 and 65 proteins are potent antigens for a sensitive serological assay.

AIDS-Related Opportunistic Infections↗