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Biomedical subjects

A Iwamoto

Publications and source records attributed to A Iwamoto.

At least 19 recordsLinked to original sources
PubMed2001

Simultaneous determination of the HIV protease inhibitors indinavir, amprenavir, saquinavir, ritonavir and nelfinavir in human plasma by high-performance liquid chromatography.

A reversed-phase high-performance liquid chromatographic method for the simultaneous quantitative determination of five HIV protease inhibitors (i.e. indinavir, amprenavir, saquinavir, ritonavir and nelfinavir) in human plasma is described. An aliquot of 500 microl plasma was extracted with 0.5 ml of 0.1 M NH4OH and 5 ml of methyl tert.-butyl ether. After evaporating, the residue was dissolved in eluent mixture of acetonitrile and 50 mM KH2PO4 adjusted to pH 5.6 with 50 mM Na2HPO4 (43:57, v/v). Subsequently, the eluent was washed with hexane. Chromatography was performed using a C18 reversed-phase column. Ultraviolet detection at 215 nm was used. Linearity of the method was obtained in the concentration range of 0.05-20 microg ml(-1) for all five protease inhibitors. Our method is now in use to analyse plasma samples from patients treated with co-administration of HIV protease inhibitors.

Adult↗
PubMed2001

Elevated plasma stromal cell-derived factor 1 protein level in the progression of HIV type 1 infection/AIDS.

Stromal cell-derived factor 1 (SDF-1) is a unique chemokine involved in multiple organogenesis as well as in the regulation of HIV infection. Here we determined the plasma SDF-1 concentrations of 193 HIV-1-infected individuals and 154 normal Japanese volunteers by developing a highly sensitive measurement system based on time-resolved fluoroimmunoassay (SDF-1 TR-FIA). This system is also valid for the mouse model to quantitate circulating SDF-1 concentration in vivo and thereby its correlation with CXCR4 expression level on CD4(+) T cells. Interestingly, plasma SDF-1 concentrations in HIV-1-infected individuals were three times higher than those in a normal control group and plasma SDF-1 protein levels showed an inverse correlation with CD4(+) T cell count and a positive correlation with plasma HIV-1 RNA load. Notably, individuals with later stage HIV-1 infection, who maintained fewer than 200 CD4(+) T cells per cubic milliliter and more than 10,000 copies of HIV-1 RNA per milliliter, showed the highest plasma SDF-1 level among individuals at any stage of HIV-1 infection. These results suggest that endogenous SDF-1 is upregulated by HIV-1 infection, particularly in late-stage HIV-1 infection/AIDS.

Adolescent↗
PubMed2001

Human alveolar macrophages and granulocyte-macrophage colony-stimulating factor-induced monocyte-derived macrophages are resistant to H2O2 via their high basal and inducible levels of catalase activity.

Human alveolar macrophages (A-MPhi) and macrophages (MPhi) generated from human monocytes under the influence of granulocyte-macrophage colony-stimulating factors (GM-MPhi) express high levels of catalase activity and are highly resistant to H(2)O(2). In contrast, MPhi generated from monocytes by macrophage colony-stimulating factors (M-MPhi) express low catalase activity and are about 50-fold more sensitive to H(2)O(2) than GM-MPhi or A-MPhi. Both A-MPhi and GM-MPhi but not M-MPhi can induce catalase expression in both protein and mRNA levels when stimulated with H(2)O(2) or zymosan. M-MPhi but not GM-MPhi produce a large amount of H(2)O(2) in response to zymosan or heat-killed Staphylococcus aureus. These findings indicate that GM-MPhi and A-MPhi but not M-MPhi are strong scavengers of H(2)O(2) via the high basal level of catalase activity and a marked ability of catalase induction and that catalase activity of MPhi is regulated by colony-stimulating factors during differentiation.

Catalase↗
PubMed2001

Quantitative and qualitative abnormalities in HIV-1-specific T cells.

OBJECTIVE: To assess the characteristics of CD4 and CD8 T cells specific for HIV-1 and cytomegalovirus (CMV) antigens in untreated and treated HIV-1-infected patients. METHODS: Antigen-specific T cell frequencies were determined by flow cytometric detection of antigen-induced intracellular cytokines. RESULTS: In untreated patients, HIV-1-specific CD4 T cell counts in peripheral blood were less than one tenth of CMV-specific CD4 T cell counts, while the number of specific CD8 T cells was approximately the same for both HIV-1 and CMV. In patients treated with highly active antiretroviral therapy (HAART) for less than 1.5 years, HIV-1-specific CD4 and CD8T cell counts were significantly lower than those in untreated patients. Perforin expression in HIV-1-specific CD8 T cells was significantly lower than that in CMV-specific CD8 T cells. CONCLUSION: These data indicate that HIV-1-specific T cells in HIV-1-infected patients have quantitative and qualitative abnormalities.

Adult↗
PubMed2001

Nuclear fission modes and fragment mass asymmetries in a five-dimensional deformation space.

Nuclei undergoing fission can be described by a multi-dimensional potential-energy surface that guides the nuclear shape evolution--from the ground state, through intermediate saddle points and finally to the configurations of separated fission fragments. Until now, calculations have lacked adequate exploration of the shape parameterization of sufficient dimensionality to yield features in the potential-energy surface (such as multiple minima, valleys, saddle points and ridges) that correspond to characteristic observables of the fission process. Here we calculate and analyse five-dimensional potential-energy landscapes based on a grid of 2,610,885 deformation points. We find that observed fission features--such as the distributions of fission fragment mass and kinetic energy, and the different energy thresholds for symmetric and asymmetric fission--are very closely related to topological features in the calculated five-dimensional energy landscapes.

Journal Article↗
PubMed2001

Predominance of genotype A HBV in an HBV-HIV-1 dually positive population compared with an HIV-1-negative counterpart in Japan.

Hepatitis B virus (HBV) has seven genotypes, A to G. Previous studies have shown that genotype C is the most prevalent strain in chronic HBV carriers in East Asia. This study was undertaken to investigate the epidemiology of HBV genotypes among Japanese patients who are coinfected with human immunodeficiency virus type 1 (HIV-1). The sequences of the complete hepatitis B surface antifen (HBsAg) genes were obtained from 18 coinfected Japanese patients. Among the 18 patients, 12 of 13 men who had sex with men (MSM) had genotype A (92%), whereas only one of five heterosexual or hemophiliac patients had genotype A. The predominance of genotype A HBV in MSM showed a striking contrast to the current genotype prevalence in the Japanese population. Owing to the recent decrease in the rate of vertical transmission in Japan, the role of sexual behavior in the transmission of HBV cannot be overestimated. Thus, the relative proportion of genotype A may gradually increase in Japan.

Adult↗
PubMed2001

Acute parvovirus B19 infection during anti-retroviral therapy.

Human parvovirus B19 (B19) has been described as a causative agent of chronic anemia in human immunodeficiency virus type-1 (HIV-1)-infected patients. We report an HIV-1 infected patient who had been receiving anti-retroviral therapy who showed sudden pancytopenia. Primary B19 infection was confirmed by the detection of plasma viremia and seroconversion. Although clearance required a prolonged period of time, the patient eventually cleared the B19 viral DNA from the plasma. More than likely, highly active anti-retroviral therapy (HAART), including a protease inhibitor, played a role in clearing the virus.

AIDS-Related Opportunistic Infections↗
PubMed2001

Mycobacterium haemophilum infection in a Japanese patient with AIDS.

Mycobacterium haemophilum has been described as a pathogen that causes cutaneous lesions in immunocompromised patients. A specimen from a skin ulcer on the leg of a Japanese patient with acquired immunodeficiency syndrome yielded acid-fast bacilli on blood agar plates after 4 weeks of incubation at 30 degrees C, but the organism was not found on Ogawa egg slants. The organism was identified as M. haemophilum, on the basis of 16S rRNA gene sequence analysis. Prolonged culture in an optimal environment that includes an iron supplement, and growth temperatures at 28 degrees to 33 degrees C are necessary to grow M. haemophilum. Genotypic characterization of 16S rRNA is useful for a rapid diagnosis of this slowly growing mycobacterium.

AIDS-Related Opportunistic Infections↗
PubMed2001

Novel polymorphisms in human macrophage inflammatory protein-1 alpha (MIP-1alpha) gene.

Human macrophage inflammatory protein-1 alpha (MIP-1alpha) is a chemotactic cytokine, which binds to macrophages, T cells, and B cells affecting their activation. We found novel polymorphisms at four sites within MIP-1alpha gene in Japanese population: C to T in exon 2; A to G in intron 2; C to G and A to G in exon 3. They occurred on the same allele. Although MIP-1alpha effectively suppresses the replication of HIV-1 in vitro, we observed no statistically significant difference in the allele frequency of this polymorphism between HIV-1-infected and uninfected individuals in Japanese population. Since an increased transcription level of MIP-1alpha has been reported to be associated with inflammatory diseases such as atopic dermatitis, we also investigated the frequency of these polymorphisms among patients with atopic dermatitis, HIV-1-infected individuals (with a normal IgE level), and healthy donors. A small increase in ratio of homozygotes to other genotypes was observed in patients with atopic dermatitis (P = 0.04).

Alleles↗
PubMed2001

Naturally occurring deletional mutation in the C-terminal cytoplasmic tail of CCR5 affects surface trafficking of CCR5.

CCR5 is an essential coreceptor for the cellular entry of R5 strains of human immunodeficiency virus type 1 (HIV-1). CCR5-893(-) is a single-nucleotide deletion mutation which is observed exclusively in Asians (M. A. Ansari-Lari, et al., Nat. Genet. 16:221-222, 1997). This mutant gene produces a CCR5 which lacks the entire C-terminal cytoplasmic tail. To assess the effect of CCR5-893(-) on HIV-1 infection, we generated a recombinant Sendai virus expressing the mutant CCR5 and compared its HIV-1 coreceptor activity with that of wild-type CCR5. Although the mutant CCR5 has intact extracellular domains, its coreceptor activity was much less than that of wild-type CCR5. Flow cytometric analyses and confocal microscopic observation of cells expressing the mutant CCR5 revealed that surface CCR5 levels were greatly reduced in these cells, while cytoplasmic CCR5 levels of the mutant CCR5 were comparable to that of the wild type. Peripheral blood CD4(+) T cells obtained from individuals heterozygous for this allele expressed very low levels of CCR5. These data suggest that the CCR5-893(-) mutation affects intracellular transport of CCR5 and raise the possibility that this mutation also affects HIV-1 transmission and disease progression.

Amino Acid Sequence↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗