Biomedical subjects

Bruce Shiramizu

Publications and source records attributed to Bruce Shiramizu.

At least 19 recordsLinked to original sources

PubMed2006

HIV DNA and dementia in treatment-naïve HIV-1-infected individuals in Bangkok, Thailand.

High HIV-1 DNA (HIV DNA) levels in peripheral blood mononuclear cells (PBMC) correlate with HIV-1-associated dementia (HAD) in patients on highly active antiretroviral therapy (HAART). If this relationship also exists among HAART-naïve patients, then HIV DNA may be implicated in the pathogenesis of HAD. In this study, we evaluated the relationship between HIV DNA and cognition in subjects naïve to HAART in a neuro AIDS cohort in Bangkok, Thailand. Subjects with and without HAD were recruited and matched for age, gender, education, and CD4 cell count. PBMC and cellular subsets were analyzed for HIV DNA using real-time PCR. The median log(10) HIV DNA copies per 10(6) PBMC for subjects with HAD (n=15) was 4.27, which was higher than that found in subjects without dementia (ND; n=15), 2.28, p<0.001. This finding was unchanged in a multivariate model adjusting for plasma HIV-1 RNA levels. From a small subset of individuals, in which adequate number of cells were available, more HIV DNA was in monocytes/macrophages from those with HAD compared to those with ND. These results are consistent with a previous report among HAART-experienced subjects, thus further implicating HIV DNA in the pathogenesis of HAD.

AIDS Dementia Complex↗

PubMed2006

Lowest ever CD4 lymphocyte count (CD4 nadir) as a predictor of current cognitive and neurological status in human immunodeficiency virus type 1 infection--The Hawaii Aging with HIV Cohort.

Low CD4 lymphocyte count was a marker for neurological disease in human immunodeficiency virus type 1 (HIV-1); but is now less common among patients with access to highly active antiretroviral therapy. In this study, the authors determine the reliability of self-reported CD4 nadir and its predictive value for neurological status. The authors identify a high degree of reliability (r = .90). After adjusting for age, current CD4 count, and duration of HIV-1, CD4 nadir relates to a current diagnosis of HIV-associated dimentia (HAD) (odds ratio [OR]: 1.395 (1.106-1.761), P = .005) and distal symmetric polyneuropathy (DSPN) (OR: 1.479 (1.221-1.769, P < .001).

Acquired Immunodeficiency Syndrome↗

PubMed2006

Feasibility assessment of cerebrospinal fluid from HIV-1-infected children for HIV proviral DNA and monocyte chemoattractant protein 1 alleles.

The objective of the study was to assess the feasibility of measuring human immunodeficiency virus 1 (HIV-1) proviral deoxyribonucleic acid (DNA) and associated single-nucleotide polymorphism (SNP) of monocyte chemoattractant protein 1 (MCP1) in pediatric cerebrospinal fluid (CSF). The importance of HIV DNA and MCP1 SNP has been suggested to be independently important in progression to acquired immune deficiency syndrome (AIDS) and neurocognitive impairment in adults. In children, measuring both factors in the CSF may help us understand the neuropathogenic process leading to HIV-1-associated encephalopathy (HAE). Repository specimens from 27 perinatally HIV-1-infected children with HAE were assessed for HIV DNA copy by real-time polymerase chain reaction and compared with MCP1 2578G SNP mutations measured by digesting amplified 361 bp fragments. When compared with MCP1 2578G SNP, a significant number with the mutation had high HIV DNA compared with those with wild type (p < .01), with no levels detected in HIV-1-seronegative control specimens. There were six CSF specimens with enough supernatant to measure MCP1 levels by enzyme-linked immunosorbent assay, which showed high levels in those with the MCP1 2578G mutation. This study demonstrates, for the first time, that CSF HIV DNA and MCP1 SNP can be measured and could be potential tools in future clinical studies to understand the pathogenesis of pediatric HAE.

AIDS Dementia Complex↗

PubMed2005

HIV-associated wasting in the era of highly active antiretroviral therapy: a syndrome of residual HIV infection in monocytes and macrophages?

Human immunodeficiency virus (HIV) infection in peripheral blood mononuclear cells (PBMCs) might be influencing the development of wasting in the era of potent antiretroviral therapy. In a retrospective study of 57 subjects, HIV proviral DNA levels in PBMCs were higher in subjects whose body weight decreased by >5% one year after initiation of highly active antiretroviral therapy, compared with subjects whose body weight was stable or increased (median HIV proviral DNA load, 8.9 vs. 0.9 copies/10(6) PBMCs; P = .006).

Adult↗

PubMed2005

Circulating proviral HIV DNA and HIV-associated dementia.

OBJECTIVE: Individuals continue to develop HIV-1-associated dementia (HAD) despite treatment with highly active antiretroviral therapy (HAART). Monocytes/macrophages (M/MPhi) can harbor proviral DNA that is not eradicated by HAART. To determine if HAD is associated with the level of HIV-1 infection within circulating leukocytes, we quantified HIV-1 DNA copy number in peripheral blood mononuclear cells (PBMC), and in PBMC subsets. DESIGN: Cross-sectional analysis within the Hawaii Aging with HIV Cohort comparing participants with HAD to those with normal cognition (NC). METHODS: Real-time PCR assays assessing HIV DNA copy number/1 x 10 cells were performed on PBMC and subsets. RESULTS: Individuals with HAD (n = 27) had a median (interquartile range) of 9.11 (37.20) HIV DNA per 1 x 10 PBMC compared to 0.49 (0.89) HIV DNA per 1 x 10 PBMC in individuals with NC (n = 22). Using a univariate analysis in the subset of individuals with undetectable viral load (HAD, n = 11; NC, n = 13), the odds of HAD attributable to HIV DNA copy number was 2.76 (1.28-5.94), P < 0.01. Preliminary analysis of a small subset of patients (n = 5) suggested that the primary source of HIV DNA may be the activated M/MPhi (CD14/CD16) subset. CONCLUSIONS: These findings suggest a potentially important association between circulating provirus and HAD.

AIDS Dementia Complex↗

PubMed2005

Viruses and cancer.

Explore the source record for details and available documents.

Epstein-Barr Virus Infections↗

PubMed2005

Mitochondrial DNA levels of peripheral blood mononuclear cells and subcutaneous adipose tissue from thigh, fat and abdomen of HIV-1 seropositive and negative individuals.

Mitochondrial dysfunction has been demonstrated in subcutaneous adipose tissue from lipoatrophic HIV-1-infected patients treated with nucleoside reverse transcriptase inhibitors (NRTIs). To further assess mitochondrial toxicity, mitochondrial DNA (mtDNA) copies/cell were measured in subcutaneous fat from various sites. Peripheral adipose tissues were obtained from the abdominal wall near the umbilicus, anterior lateral thigh, and dorsal cervical region of the neck of individuals from four cohorts: 1) seven lipoatrophic HIV-1-infected patients receiving a regimen with nucleoside reverse transcriptase inhibitors (NRTIs) as part of highly active antiretroviral therapy (HAART) for > 6 months; 2) seven non-lipoatrophic HIV-1-infected patients receiving NRTIs-containing HAART; 3) five HIV-1-infected patients on antiretroviral therapy < 2 weeks (naive); 4) and five HIV-1-negative participants. Along with the adipose tissue samples, peripheral blood mononuclear cells (PBMC) were also obtained from each patient for mtDNA depletion examination. Total DNA was isolated and mtDNA copies/cell quantitated by competitive and real-time PCR. MtDNA copies/cell in abdomen, thigh, and neck fat were depleted in lipoatrophic HIV-1 seropositive compared to the seropositive naive and seronegative cohorts. MtDNA copies/cell in thigh and neck fat were also decreased in non-lipoatrophic subjects exposed to NRTIs compared with NRTI-naive and HIV seronegative controls. PBMC values did not differ among the cohorts and there was no correlation with lipoatrophy state or HIV-1 serostatus. Additionally, differences in mtDNA copies/cell were observed in the fat depots from seronegative subjects. Thigh fat mtDNA levels were 45-55% lower than abdomen and neck. These studies help demonstrate that mtDNA levels can vary in different subcutaneous adipose depots suggesting possible metabolic differences.

Adipose Tissue↗

PubMed2004

Assessment of HIV-1 DNA copies per cell by real-time polymerase chain reaction.

Measurements of HIV-1 DNA and plasma RNA levels represent unique entities, thus clinically and molecularly, data obtained from each can be used independently in assessing therapy or experiments. Plasma HIV-1 RNA levels are used to make clinical decisions regarding treatment strategies, but viral DNA can still be detectable when plasma RNA levels are undetectable. At the molecular level, accurate assessment of HIV-1 DNA copies/cell could increase the ability to target specific tissues for further analysis such as identification of site-specific integration of HIV in cellular DNA. Using real-time polymerase chain reaction (PCR), HIV-1 copies/cell were determined in peripheral blood mononuclear cells (PBMC), bone marrow (BM), and tissue. Duplicate specimens were analyzed for plasma HIV-1 RNA levels and for viral DNA copies/cell from 24 HIV-1 infected individuals. DNA from an additional 58 PBMC and 34 other tissue specimens were also assayed with the results reported as a log of HIV-1 DNA copies/cell. The log viral DNA copies/cell of the 24 matched specimens ranged from -2.699 to 0.278 with no correlation to the plasma HIV-1 RNA levels (range 52 to 2 X 105 copies/mL). Similar range in log HIV-1 DNA copies/cell was found in the other specimens. Real-time PCR assay for viral DNA copies/cell provides a rapid assessment of HIV-1 copies/cell in specimens independent of plasma HIV-1 RNA levels. From selected cases with relatively high HIV-1 DNA copies/cell, inverse PCR successfully identified viral integration. This type of assay could facilitate further studies when relatively high viral copies/cell are needed for screening.

Computer Systems↗

PubMed2004

HIV-associated dementia, mitochondrial dysfunction, and oxidative stress.

Over the past several decades, researchers have made large advances in unraveling the pathogenesis of HIV-related neurological disease leading to substantial benefits for affected individuals. Concomitant advances in HIV-treatment have changed the landscape of HIV care, resulting in alterations in HIV neuroepidemiolgy and potentially the neuropathogenesis of cognitive disorders. Specifically, widespread ARV medications use has heightened our awareness of mitochondrial toxicity, oxidative stress, and metabolic abnormalities and stimulated more research into the related cognitive consequences. Specific sources of oxidative stress among HIV-1-infected individuals to be discussed in this article include the direct effects of HIV-1, chronic immune activation in response to HIV-1 and other pathogens, and co-morbid factors. Continued research in this area could provide novel therapeutic targets.

Journal Article↗

PubMed2004

HIV-associated mitochondrial toxicity in pregnancy.

Pregnancy is associated with a variety of physiologic and metabolic changes designed to support the fetoplacental unit. In the presence of maternal human immunodeficiency virus (HIV) infection, the use of combination antiretroviral therapy including the nucleoside analog reverse transcriptase inhibitor (NRTI) zidovudine to prevent perinatal HIV transmission, has resulted in a dramatic decrease in perinatally acquired HIV. Human and animal studies during pregnancy report a possible association between NRTI containing antiretroviral regimens and mitochondrial toxicity in the newborn and mother. However, the possible long-term consequences on the fetus and mother of these NRTI containing regimens during pregnancy are largely unknown. This review will examine the data available on NRTI-induced mitochondrial toxicity associated with combination antiretroviral regimens used to prevent perinatal HIV transmission.

Journal Article↗

PubMed2004

Pathogenesis of HIV-associated non-Hodgkin lymphoma.

In the current era of highly active antiretroviral therapy (HAART), the prevalence of HIV-associated non-Hodgkin lymphoma (H-NHL) is not as high as in the beginning of the acquired immunodeficiency syndrome (AIDS) epidemic, but still remains above that of non-HIV-infected individuals. Therefore, the epidemiology suggests that the pathogenesis of H-NHL may be multifactoral, involving the interaction of the immune system with HIV or other pathogens. Although HIV is a retrovirus, it is not characterized with the typical oncogenic potential associated with insertional mutagenesis. HIV integration occurs as a necessary step in the life cycle allowing for replication and transcription of the viral genome to take place. While HIV is thought to integrate randomly, more recent studies have suggested that integration occasionally occurs in a less random fashion. While the majority of H-NHL may be secondary to immune dysfunction, this non-random integration may be a factor leading to pathogenesis of a small subset of H-NHL since the pathways involved in malignancies usually require an accumulation of abnormalities leading to proliferation and transformation. A common element among lymphomas in this setting of immune dysfunction is the inability to control a pathogen that acts as an ongoing immune activator. Thus, an increased risk of H-NHL emerges from the combination of immunodeficiency, increased immune activation and possible HIV insertional mutagenesis. The focus of this review will be on the role viral pathogenesis plays in oncogenic transformation.

B-Lymphocytes↗

PubMed2004

Assessing immunoglobulin heavy chain rearrangements in pediatric CD20-positive and CD20-negative classic Hodgkin's disease.

Approximately 15% of all cases of childhood classical Hodgkin's disease (HD) express CD20, a B-cell marker associated with immunoglobulin heavy chain rearrangements. Immunoglobulin heavy chain rearrangements in Reed-Sternberg cells could be used to assess minimal residual disease (MRD), as was shown with immunoglobulin heavy chain patient-specific primers (PSPs) in non-Hodgkin's lymphoma. The aim of this study was to analyze pediatric HD for future design of immunoglobulin heavy chain PSP for MRD detection. DNA was extracted from paraffin-embedded tissue from unstained slides of 8 pediatric CD20+ nodular sclerosis HD cases and 10 CD20-nodular sclerosis HD cases. Immunoglobulin heavy chain polymerase chain reaction and sequencing were performed on 16 of 18 cases, which had adequate DNA for further analysis. Sequence analysis from 3 cases (19% of HD cases) demonstrated unique V(D)J regions, which could potentially be used to design PSP. Unique PSPs could be used to assess MRD in advanced-stage HD specimens. Future studies should focus on improved detection and analysis of more cases to identify appropriate specimens in assessing clinical implications of MRD detection.

Adolescent↗

PubMed2003

Correlation of single photon emission computed tomography parameters as a noninvasive alternative to liver biopsies in assessing liver involvement in the setting of HIV and hepatitis C virus coinfection: a multicenter trial of the Adult AIDS Clinical Trials Group.

Performing a liver biopsy in patients infected with HIV and hepatitis C virus (HCV) is considered the standard of practice to assess hepatic involvement but carries risks to patients. This pilot study was designed to identify single photon emission computed tomography (SPECT) parameters that correlate with liver disease stage. HIV-coinfected and HCV-coinfected individuals undergoing a liver biopsy had a SPECT scan performed. The results showed that a number of SPECT parameters were associated with histologic changes in architecture, fibrosis, and cirrhosis, of which two SPECT parameters, the minimum pixel count for spleen region of interest and maximum pixel count for right hepatic lobe, correctly classified 39 of 46 SPECT/biopsy pairs. In conclusion, this pilot trial identified SPECT parameters that correlated with liver histology changes. A larger study is needed to demonstrate whether SPECT parameters alone or with other markers can provide information on fibrosis with the clinical significance obtained through liver biopsy.

Adult↗

PubMed2003

Placenta and cord blood mitochondrial DNA toxicity in HIV-infected women receiving nucleoside reverse transcriptase inhibitors during pregnancy.

Recent studies of pregnant women and animal models have raised concerns regarding potentially serious mitochondrial toxicity-related side effects in infants born to mothers who received nucleoside reverse transcriptase inhibitors (NRTIs) during their pregnancy to prevent HIV-1 perinatal transmission. The aim of this study was to assess mitochondrial DNA (mtDNA) content of cord blood and placenta in HIV-infected pregnant women receiving NRTI compared with HIV-negative women, hypothesizing that placenta and cord blood mtDNA copies per cell would be decreased in women on NRTI therapy. Immediately following delivery, placenta and cord blood were obtained from eight HIV-infected pregnant women on NRTIs and five HIV-negative women. Assessment of mtDNA copies per cell was accomplished by quantitative real-time PCR. The mean mtDNA copies per cell from the placenta of the HIV-infected women compared with HIV-negative women was 152 +/- 119 and 880 +/- 136 ( =.0016), respectively. Similarly, the mean mtDNA copies per cell from the cord blood of the HIV-positive women compared with HIV-negative women was 144 +/- 101 and 865 +/- 331 ( =.0026), respectively. There was a statistically significant decrease in mtDNA copies per cell in placenta and cord blood between the HIV-infected women on NRTIs compared with HIV-negative women. Further studies are needed to better understand the morbidity to infants and mothers treated with NRTI to prevent vertical transmission of HIV.

Base Sequence↗

PubMed2003

Epigenetic changes in the DAP-kinase CpG island in pediatric lymphoma.

BACKGROUND: Hypermethylation of CpG islands in the promoter region of death-associated protein kinase (DAP-kinase) coupled with the loss of gamma-interferon-induced apoptosis have been reported in B-cell malignancies suggesting a role in pathogenesis or prognosis. Along with B-cell malignancies, pediatric lymphomas also include T-cell non-Hodgkin lymphoma (NHL), anaplastic large cell lymphoma, and Hodgkin disease, each with unique prognoses. The purpose of this study was to elucidate epigenetic changes in the DAP-kinase promoter region of pediatric cases to determine associations with aberrant hypermethylation. PROCEDURES: Thirty-nine cases of different lymphoid pathology [10 Burkitt lymphoma, 1 B-cell NHL; 7 T-cell lymphoblastic lymphoma; 4 anaplastic large cell lymphoma (LCL); 2 B-cell LCL; 14 nodular sclerosing Hodgkin disease (NSHD); and 1 B-cell acute lymphoblastic leukemia (ALL)] had methylation-specific polymerase chain reaction performed on bisulfite-treated DNA, which distinguishes the methylation status of the promoter region, and DAP-kinase mRNA expression assays performed on available specimens. RESULTS: In normal lymphocytes, the CpG islands in the promoter region were unmethylated, as were the T-cell lymphoblastic lymphoma and anaplastic LCL. In contrast, 100% of the Burkitt lymphoma (10/10) and B-cell ALL (1/1) were hypermethylated. Of the specimens with mRNA available, 7/8 Burkitt lymphoma had no DAP-kinase mRNA expression compared to normal expression in 3/3 and 4/4 T-cell lymphoblastic lymphoma and NSHD, respectively. CONCLUSIONS: In these pediatric lymphoid tumors, hypermethylation of the DAP-kinase promoter region with associated loss of DAP-kinase gene expression was associated with B-cell malignancies and thus may be important in the development and/or provide a prognostic tool in B- cell lymphomas.

Adolescent↗

PubMed2003

Assessment of minimal residual disease in childhood non-hodgkin lymphoma by polymerase chain reaction using patient-specific primers.

A feasibility study was undertaken to identify patient-specific primers (PSPs) from childhood non-Hodgkin lymphoma (NHL) specimens to detect minimal residual disease (MRD). Eleven tumor specimens were amplified using immunoglobulin heavy chain and T-cell receptor primers to identify PSPs, which were then used to evaluate staging/follow-up specimens. Disease was detected in 19 of 21 staging and 16 of 17 follow-up specimens. Among seven patients in remission by 1 month, PSPs identified MRD in follow-up specimens. This study demonstrated the feasibility of PSPs to identify disease in staging and follow-up specimens, which could be used to develop strategies for MRD analysis in a larger setting.

Adolescent↗

PubMed2002

TT virus: preferential distribution in CD19(+) peripheral blood mononuclear cells and lack of viral integration.

In order to determine whether peripheral blood mononuclear cells (PBMC) contain proviral DNA or double-stranded replicative forms of TT virus (TTV) and to define which cell subset harbors TTV, we analyzed 126 PBMC DNA samples by PCR, using the NG059/NG061/NG063 and the T801/T935 primer sets. TTV sequences were detected in nearly 20% (25/126) of PBMC DNA samples. Analysis of PBMC subsets revealed that TTV was preferentially distributed in CD19(+) cells. TTV DNA was also detected in CD3(+)/CD19(+) double-depleted cells but was undetectable in CD3(+) cells. After degradation of single-stranded DNA using mung bean nuclease (MBN), TTV could not be detected in previously TTV-positive PBMC DNA samples nor in DNA from CD19(+) cells, CD3(+)-depleted, and CD3(+)/CD19(+) double-depleted cells, indicating the lack of TTV DNA integration and the absence of viral double-stranded replicative intermediates in PBMC or PBMC subset cells. Our data indicate that PBMC and PBMC subsets are not the major sites of TTV replication.

Adult↗

PubMed2002

Investigation of TT virus in the etiology of pediatric acute lymphoblastic leukemia.

Infectious agents have been implicated in the pathogenesis of pediatric acute lymphoblastic leukemia (ALL). A novel human DNA virus, TT virus (TTV), has been identified in children possessing characteristics as an etiologic agent, making the virus a potential candidate. Analysis of specimens from children with ALL was performed to determine if an association exists. Archived specimens (79 peripheral blood mononuclear cells, PBMC/bone marrow cells, BMC, and 125 cerebrospinal fluid, CSF) obtained at diagnosis and during therapy from 28 pediatric patients were tested for TTV. All of the diagnostic BMC/PBMC were negative for TTV, but 7 patients had follow-up specimens that converted to TTV positivity. TTV was not detected in any CSF. The absence of TTV at diagnosis suggests TTV is unlikely to be causally associated with ALL in the cases analyzed. However, the data support TTV transmission through blood products and suggest that the CNS is not a sanctuary site for TTV.

Blood Cells↗