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Biomedical subjects

R A Good

Publications and source records attributed to R A Good.

At least 91 records · Page 5Linked to original sources
PubMed1996

Diagnosis of pediatric human immunodeficiency virus infection by means of a commercially available polymerase chain reaction gene amplification.

OBJECTIVE: To assess the sensitivity and specificity of polymerase chain reaction (PCR) in infants and children at risk for human immunodeficiency virus (HIV) infection. DESIGN: A prospective, blinded study of 286 HIV-seropositive infants and children. Infection was diagnosed by antibody detection after 18 months of age, two positive direct tests (p24 antigen and HIV culture), or the presence of an illness that defines the acquired immunodeficiency syndrome. SETTING: University of South Florida and All Children's Hospital, St Petersburg, inpatient and outpatient centers. PARTICIPANTS: Two hundred eighty-six infants and children seropositive for HIV who were examined between July 1988 and September 1992. MAIN OUTCOME MEASURES: Sensitivity, specificity, and predictive values of a commercially available PCR test. RESULTS: Five hundred sixty-seven PCR tests were performed on samples from 286 seropositive subjects followed up for a minimum of 16 months. Of the subjects, 105 were confirmed to be infected and 181 uninfected. Overall, 96 of 105 initial PCRs in infected subjects were positive (sensitivity, 91.4%; positive predictive value, 99%). If samples obtained during the first week of life are excluded, 95 to 100 samples were positive (sensitivity, 95%). Of 181 initial PCR tests from seropositive subjects who seroreverted, 180 were negative (specificity, 99.4%,; negative predictive value, 95.2%). The predictive value of a positive test was 90.9% and that of a negative test was 93.1% in the first month of life. All 145 initial samples obtained between 5 weeks and 12 months of age correctly predicted infection status (positive predictive value, 100%). CONCLUSIONS: Gene amplification by means of a commercially available PCR is useful in the diagnosis of HIV infection for infants born to seropositive mothers. Between day 7 through 1 year of age, HIV infection is accurately diagnosed by the PCR assay.

Age Factors↗
PubMed1996

A promiscuous T cell hybridoma restricted to various I-A molecules.

In a previous study, we identified T cell receptor and major histocompatibility complex (MHC) contact sites on the pigeon cytochrome c p43-58 peptide. Positions 46 and 54 of p43-58 were shown to be the MHC-binding sites. Specific amino acids were identified on the MHC-binding sites which bound to the relevant I-A molecule. In the present study, using NOD (I-Ag7) mice, we established a T cell hybridoma specific for a p43-58 analog 46R50E54A with arginine (R) and alanine (A) at positions 46 and 54, respectively. Interestingly, NOE 33-1-2 recognized 46R50E54A in the presence of not only I-Ag7, but also I-Ad, s, u and v. In contrast to previous reports that promiscuous T cells were able to recognize peptide antigens with various HLA-DR or I-E molecules consist of monomorphic alpha and polymorphic beta chains, the promiscuous T cell clone NOE33-1-2 recognized peptides with various I-A molecules lacking the monomorphic chain.

Amino Acid Sequence↗
PubMed1996

Allergen-specific IgE levels and mite allergen exposure in children with acute asthma first seen in an emergency department and in nonasthmatic control subjects.

BACKGROUND: Sensitization to allergens has been shown to be a risk factor for adults with acute asthma first seen in the emergency department. OBJECTIVE: The purpose of this study was to evaluate the prevalence of specific IgE to common aeroallergens in children with asthma first seen in the emergency department and in control subjects. METHODS: Fifty-four children, aged 3 to 16 years (mean age, 8.34 years) who visited the emergency department for treatment of acute bronchospasm or other illness, were evaluated. Specific IgE to seven common aeroallergens and four common storage mites was determined. Group I consisted of 29 patients who had acute bronchospasm and histories of recurrent asthma. Group II consisted of 25 control subjects who had no clinical history of atopic disease. Group I and II were compared for differences in the prevalence of positive RAST responses to the 11 allergens tested. Dust samples were collected from 17 homes of subjects in group I and from 13 homes of subjects in group II and were analyzed for levels of Der p 1 and Der f 1. RESULTS: Statistically significant differences in the prevalence of positive RAST results between groups I and II were found in response to: Dermatophagoides pteronyssinus, 89.6% versus 36% (p = 0.0001); Blattella germanica, 45.8% versus 9.5% (p = 0.018); Alternaria tenuis, 44.8% versus 4% (p = 0.001); and the storage mites Aleuroglyphus ovatus, 39.2% versus 4% (p = 0.002); Blomia tropicalis, 42.8% versus 0% (p = 0.0002); Chortoglyphus arcuatus, 46.4% versus 0% (p = 0.0001); and Lepidoglyphus destructor, 32.1% versus 0% (p = 0.0019). Mean specific IgE levels, expressed as percent of the total counts bound, were significantly higher in group I compared with group II only in response to D. pteronyssinus, 21.9% versus 2.1% (mean percent of total counts bound) (p = 0.0001). Analysis of dust samples revealed no significant differences between the two groups, except for a higher concentration of Der f 1 in the sofas of subjects in group II. CONCLUSION: Sensitization to D. pteronyssinus, storage mites, and, to a lesser extent, to A. tenuis and B. germanica is associated with acute childhood asthma that requires emergency treatment in Florida.

Acute Disease↗
PubMed1996

Serum total and specific IgE levels in children infected with human immunodeficiency virus.

BACKGROUND: Human immunodeficiency virus (HIV) infection is associated with polyclonal B-cell activation, and elevated IgE levels are found in infected adults. Chronic nasal symptoms, sinusitis, and otitis media are particularly common in children infected with HIV. The possible allergic cause of nasal symptoms in children infected with HIV has not been explored. OBJECTIVE: The study was designed to evaluate the relationship between HIV infection and IgE levels in a group of children infected with HIV. METHODS: Total serum IgE was measured by enzyme immunoassay and compared with values for age-matched normal subjects. Specific IgE was determined by RAST test to Dermatophagoides pteronyssinus, American cockroach, Bahia grass, short ragweed, cat, and oak. Lymphocyte subpopulations were determined by standard flow cytometry. RESULTS: Fifty-seven total IgE and 342 specific IgE levels were determined from 29 infected children (19 girls and 10 boys; ages, 7 to 150 months; mean age, 49 months). Initial IgE levels of 29 subjects ranged from 1.4 to 787.6 IU/ml (mean = 123.4 +/- 34.4 IU/ml). Nine of 29 (31%) subjects had initial IgE levels greater than two standard deviations higher than age-matched normal subjects. No patients had detectable specific IgE to any of the six aeroallergens. There was no correlation, as determined by linear regression analysis, between IgE levels and absolute CD4 number or CD4:CD8. CONCLUSION: Elevated total but not specific IgE is common in children infected with HIV and does not correlated with absolute CD4 lymphocyte count, suggesting that the elevated IgE level reflects a somewhat independent polyclonal activation of B-lymphocytes.

Adolescent↗
PubMed1996

Fgr expression restricted to subpopulation of monocyte/macrophage lineage in resting conditions is induced in various hematopoietic cells after activation or transformation.

The c-fgr gene product (Fgr) is a member of the src-family of protein tyrosine kinases. We have established a monoclonal antibody (2H2) which recognizes the unique N-terminal domain of the murine Fgr. In the present study, using immunohistochemical analysis and immune complex kinase assay with the 2H2, we investigated expression of Fgr in various cell populations and tissues in a murine system. In resting conditions, Fgr expression was confined to subsets of a monocyte/macrophage lineage. Thus, Fgr+ cells were detected in paracortical areas and medullas of lymph nodes, but seen only in marginal zones of the spleen and the medulla of the thymus. No Fgr+ macrophage was detected in other tissues, Peyer's patches, brain, heart, lung, liver, pancreas, kidney and peritoneal cavity. However, immune complex kinase assay revealed that, upon stimulation, T and B cells as well as peritoneal macrophages expressed significant levels of Fgr molecules. Transformed cell lines of lymphoid origin, EL-4 and LK35.2, which are T and B lineage lymphomas, respectively, also expressed Fgr molecules. Thus, various cells of hematopoietic origin appeared to possess a potentiality to express Fgr following activation or transformation. The present findings may help elucidate the functional significance of Fgr in immunologically committed cells in either activated or non-activated conditions.

Animals↗
PubMed1996

Normalization of cellular zinc levels in patients with Downs syndrome does not always correct low thymulin levels.

Retrospective analysis of five Down's syndrome (DS) patients who presented with recurrent infection revealed that all had initial low thymulin levels. Three patients had low cellular zinc levels that normalized after zinc replacement. Contrary to previous studies, thymulin levels were persistently low in four of five DS patients despite maintaining or achieving normal cellular zinc levels. A primary thymic epithelial defect may be responsible for the persistent thymulin deficiency in DS patients.

Adult↗
PubMed1996

Selective gamma-chain T-cell receptor gene rearrangements in a patient with Omenn's syndrome: absence of V-II subgroup (V gamma 9) transcripts.

Only gamma-chain T-cell receptor transcripts utilizing V-1 subgroup gene segments were found in peripheral blood lymphocytes from a patient with Omenn's syndrome. gamma-Chain T-cell receptor transcripts utilizing the V gamma 9 (V-II subgroup) gene segment were absent in peripheral blood lymphocytes from this patient. V gamma 9 J gamma 1.2 C gamma 1 rearrangements are those primarily found in peripheral blood lymphocytes (70 to 85%) from normal donors.

Eosinophilia↗
PubMed1996

Relationship between tumor necrosis factor alpha and feline immunodeficiency virus expressions.

The presence of feline immunodeficiency virus (FIV) proviral DNA, expression of FIV p26 core protein, and production of tumor necrosis factor alpha (TNF-alpha) were assessed in sequential biopsies of spleen and lymph node sections, of mononuclear cells of the peripheral blood, and of the serum of specific-pathogen-free cats during the acute phase of FIV infection. A temporal relationship between TNF-alpha production and FIV p26 expression was noted. Two months following FIV infection, and preceding the detection of FIV viremia, levels of TNF-alpha in serum increased significantly (P = 0.04), and they remained elevated during FIV viremia in the third month postinfection. Immunoprecipitates representing expression of TNF-alpha and of FIV p26 were localized in common foci of lymph nodes of FIV-infected cats during this period of active viremia. With the advent of anti-FIV antibodies, circulating levels of TNF-alpha and p26 antigen and expression of TNF-alpha and p26 in the lymph nodes decreased during the fifth month postinfection, and p26 production became undetectable. With clearance of viremia, burden of proviral DNA in peripheral blood mononuclear cells became reduced (P = 0.041), with provirus remaining integrated principally within lymph nodes (P = 0.046). During aviremia, p26 expression was undetectable in any tissue but remained inducible in vitro. During acute FIV infection, TNF-alpha production and p26 expression are intimately linked.

Animals↗
PubMed1996

Ataxia-telangiectasia: mutations in ATM cDNA detected by protein-truncation screening.

We have examined the distal half of the ataxia-telangiectasia (A-T) gene transcript for truncation mutations in 48 A-T affecteds. We found 21 mutations; 4 of the mutations were seen in more than one individual. Genotyping of the individuals sharing mutations, by using nearby microsatellite markers, established that three of the four groups shared common haplotypes, indicating that these were probably founder effects, not public mutations. The one public mutation was found in two American families, one of Ashkenazi Jewish background and the other not. Most truncations deleted the PI3-kinase domain, although some exceptions to this were found in patients with typical A-T phenotypes. All patients not previously known to be consanguineous were found to be compound heterozygotes when mutations could be identified--that is, normal and abnormal protein segments were seen on SDS-PAGE gels. All 48 patients gave RT-PCR products, indicating the presence of relatively stable mRNAs despite their mutations. These results suggest that few public mutations or hot spots can be expected in the A-T gene and that epidemiological studies of A-T carrier status and associated health risks will have to be designed around populations with frequent founder-effect mutations, despite the obvious limitations of this approach.

Ataxia Telangiectasia↗
PubMed1996

HLA-identical sibling bone marrow transplants vs chemotherapy for acute myelogenous leukemia in first remission.

There is controversy whether adults with acute myelogenous leukemia (AML) in first remission are best treated with chemotherapy or an HLA-identical sibling bone marrow transplant. We studied 1097 adults, 16-50 years old, with AML in first remission. Results of transplants from HLA-identical siblings reported to the International Bone Marrow Transplant Registry (IBMTR; n = 901) were compared with results of chemotherapy in comparable persons treated by the German AML Cooperative Group (GAMLCG; n = 196). Preliminary analyses identified subject- and disease-related variables differing between the cohorts and associated with treatment outcome within each cohort. We adjusted for these variables and differences in time-to-treatment in subsequent comparisons of treatment-related mortality, relapse, survival and leukemia-free survival (LFS). Five-year probability of treatment-related mortality was greater for transplants than chemotherapy (43% (95% confidence interval, 37-49%) vs 7% (3-11%); P< 0.0001). Five-year relapse probability was less for transplants than chemotherapy (24% (20-28%) vs 63% (55-71%); P< 0.0001). Five-year probability of survival was similar with transplants and chemotherapy (48% (43-53%) vs 42% (33-51%); P = 0.24). Five-year LFS probability was higher for transplants than chemotherapy (46% (42-50%) vs 35% (28-41%); P= 0.01). These data indicate that bone marrow transplants from HLA-identical siblings result in comparable survival but greater LFS than chemotherapy in adults with AML in first remission.

Adolescent↗
PubMed1995

Bone marrow transplantation for Fanconi anemia.

Fanconi anemia is a genetic disorder associated with diverse congenital abnormalities, progressive bone marrow failure, and increased risk of leukemia and other cancers. Affected persons often die before 30 years of age. Bone marrow transplantation is an effective treatment, but there are few data regarding factors associated with transplant outcome. We analyzed outcomes of HLA-identical sibling (N = 151) or alternative related or unrelated donor (N = 48) bone marrow transplants for Fanconi anemia performed between 1978 and 1994 and reported to the International Bone Marrow Transplant Registry. Fanconi anemia was documented by cytogenetic studies in all cases. Patient, disease, and treatment factors associated with survival were determined using Cox proportional hazards regression. Two-year probabilities (95% confidence interval) of survival were 66% (58% to 73%) after HLA-identical siblings transplants and 29% (18% to 43%) after alternative donor transplants. Younger patient age (P .0001), higher pretransplant platelet counts (P = .04), use of antithymocyte globulin (P = .005), and use of low-dose (15 to 25 mg/kg) cyclophosphamide plus limited field irradiation (P = .009) for pretransplant conditioning and cyclosporine for graft-versus-host disease prophylaxis (P = .002) were associated with increased survival. Bone marrow transplants are effective therapy for Fanconi anemia. The adverse impact of increasing age and lower pretransplant platelet count on transplant outcome favors earlier intervention, especially when there is an HLA-identical sibling donor.

Adolescent↗
PubMed1995

Dietary lipids and calorie restriction affect mammary tumor incidence and gene expression in mouse mammary tumor virus/v-Ha-ras transgenic mice.

We have studied the effects of food restriction (FR) and substitution of fish oil (FO; omega 3) for corn oil (CO; omega 6) on breast tumor incidence and survival in mouse mammary tumor virus/v-Ha-ras transgenic (Onco) mice. The diets were as follows: group 1, 5% (wt/wt) CO fed ad libitum (AL); group 2, 5% CO, restricted calories (40% fewer calories than AL; FR); group 3, 20% CO fed AL; and group 4, 20% FO fed AL. After 3 years, 40% of FR Onco (group 2) mice were alive, whereas there were no survivors in the other three groups. Similarly, tumor incidence was reduced to 27% (5 out of 18) in FR animals (group 2), whereas it was 83% (11 out of 13) in group 1 mice, 89% (16 out of 18) in group 3 mice, and 71% (10 out of 14) in group 4 mice. These protective effects of FR on survival and tumor incidence were paralleled by higher expression of the tumor suppressor gene p53 (wild type) and free-radical scavenging enzymes (catalase and superoxide dismutase) in breast tumors. Immunoblotting showed less ras gene product, p21, and increased p53 levels in the tumors of FR mice. In addition, FR decreased RNA levels of c-erbB-2, interleukin 6, and the transgene v-Ha-ras in tumors. In contrast, analysis of hepatic mRNA from tumor-bearing FR mice revealed higher expression of catalase, glutathione peroxidase, and superoxide dismutase. Survival and tumor incidence were not influenced significantly by dietary supplementation with FO in place of CO. Taken together, our studies suggest that moderate restriction of energy intake significantly inhibited the development of mammary tumors and altered expression of cytokines, oncogenes, and free-radical scavenging enzymes.

Animals↗
PubMed1995

Gamma delta T cells play an important role in hsp65 expression and in acquiring protective immune responses against infection with Toxoplasma gondii.

Previously, we reported that the expression of hsp65 within and on host macrophages correlates closely with protection against infection with Toxoplasma gondii in mice. Herein, we propose that gamma delta T cells play a crucial role in the induction of hsp65 and also in the protective immune response to T. gondii. Intraperitoneal inoculation with this protozoan resulted in hsp65 being expressed on and in host peritoneal macrophages and resulted in an increase of T cells bearing the gamma delta receptor with Thy-1+ and Thy-1- phenotypes in the peritoneal cavity and spleen. When mice were depleted of gamma delta T cells by the administration of a mAb, hsp65 expression was markedly decreased. In contrast, the expression of this protein was rather enhanced and gamma delta T cells were prominently expanded in mice depleted of alpha beta T cells. The protection in mice treated with the mAb paralleled the magnitude of hsp65 expression. Mice depleted of gamma delta T cells died most frequently in the early stages of infection, whereas most of those depleted of alpha beta T cells survived the early stages of lethal infection with T. gondii. However, the latter group of mice did not definitely control the T. gondii infection in its late stages. IFN-gamma was not essential for either the expression of hsp65 or the resistance induced by gamma delta T cells, as demonstrated in mice treated with mAb to murine IFN-gamma. These findings indicated that gamma delta T cells having both the Thy-1+ and Thy-1- phenotypes contribute to hsp65 expression within and on macrophages in an IFN-gamma-independent manner. This, in turn, plays a role in the development of protective immunity during the early stage of this parasitic infection.

Animals↗
PubMed1995

Long-term repopulation of hematolymphoid cells with only a few hemopoietic stem cells in mice.

A PCR-based assay has been devised for the detection and semiquantitation of cells originating from a few donor hematopoietic stem cells (HSCs) in a background of recipient cells. Upon sequencing a segment of murine Y chromosome contained in the plasmid pY2, oligonucleotide primers were designed for specific amplification of the Y chromosome-restricted segment. The HSCs were isolated from the bone marrow of mice on day 4 following a single i.v. injection of 5-fluorouracil and were readily distinguished from other bone marrow elements by the characteristics of low density, absence of lineage-specific surface markers, lack of expression of transferrin receptor, and a high expression of major histocompatibility complex class I antigen. Injection of as few as four such HSCs was shown to produce donor-derived cells (including lymphoid cells) for at least 8 months after transplantation into syngeneic female recipients. Retransplantation, employing 10(6) bone marrow cells from the initial recipients, also yielded clear evidence of repopulation with detectable levels of male donor cells. On statistical grounds, it is clear that long-term repopulation in vivo may result from even a single HSC having the characteristics defined herein.

Animals↗
PubMed1995

Induction of intracellular cAMP by a synthetic retroviral envelope peptide: a possible mechanism of immunopathogenesis in retroviral infections.

A synthetic heptadecapeptide, CKS-17, represents the highly conserved amino acid sequences occurring within the transmembrane envelope protein of many animal and human retroviruses. CKS-17 has been demonstrated to exhibit suppressive properties for numerous immune functions. We have recently shown that CKS-17 acts as an immunomodulatory epitope causing an imbalance of human type 1 and type 2 cytokine production and suppression of cell-mediated immunities. cAMP, an intracellular second messenger, plays an important role in regulation of cytokine biosynthesis--i.e., elevation of intracellular cAMP levels selectively inhibits type 1 cytokine production but has no effect or enhances type 2 cytokine production. Here, we demonstrate that CKS-17 induces dramatic rises in the intracellular cAMP levels of a human monocyte cell line and of human peripheral blood mononuclear cells in a time- and dose-dependent manner. A peptide corresponding to the reverse sequence of CKS-17, used as control, has no effect on intracellular cAMP levels. The cAMP-inducing ability of CKS-17 is significantly blocked by SQ-22536, an inhibitor of adenylate cyclase. These results indicate that CKS-17, a highly conserved component of the transmembrane proteins of immunosuppressive retroviruses, induces increased intracellular levels of cAMP via activation of adenylate cyclase and suggest that this retroviral envelope peptide may differentially modulate type 1 and type 2 cytokine production through elevation of intracellular cAMP levels.

Adenylyl Cyclases↗