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Biomedical subjects

H Goldstein

Publications and source records attributed to H Goldstein.

At least 55 records · Page 3Linked to original sources
PubMed1996

Culturally appropriate measures for monitoring child development at family and community level: a WHO collaborative study.

Culturally appropriate techniques for monitoring child psychosocial development were prepared and tested in China, India and Thailand on a total of 28,139 children. This is the largest study of its kind ever undertaken. Representative groups aged between birth and 6 years were examined and the results were used to produce national development standards-separately for rural and urban children in China and India, and for all children combined in Thailand-which are considered to be more satisfactory than foreign-based standards. In each country, between 13 and 19 key milestones of psychosocial development were selected for a simplified developmental screening operation and these have been incorporated on a home-based record of a child's growth and development. Between 35 and 67 tests have been devised in each country to test the children at first-referral level.

Child↗
PubMed1996

Epilepsy in Down syndrome--prevalence in three age groups.

A prevalence study of epilepsy in patients with Down syndrome (n = 85) in three age-groups (14-16 years, 23-29 years, 50-60 years) was conducted in the county of Aarhus, Denmark. Seventy-two patients (85%) participated. An interview and a neurological examination were performed. An EEG was recorded in 50 patients. Twelve patients (17%) had epilepsy. ILAE-1981-classification: two with partial seizures, seven with primary generalized and three with unclassifiable generalized seizures. Two patients with epilepsy had a normal EEG and 13 patients without epilepsy had an abnormal EEG.

Adolescent↗
PubMed1995

Divergent effects of chronic HIV-1 infection on human thymocyte maturation in SCID-hu mice.

We have recently developed a modified SCID-hu mouse model in which the implanted human thymus and liver (hu-thy/liv) and human peripheral T cells become infected with HIV-1 after i.p. inoculation. By using this model, we evaluated the effect of HIV-1 infection on thymic maturation and observed that different HIV-1 strains had divergent effects of thymic maturation. Although minimal effects on continued thymopoiesis in the hu-thy/liv implant were observed after chronic infection with two primary patient isolates, HIV-1(28) and HIV-1(59), and with HIV-1ADA, HIV-1Ba-L, HIV-1JR-CSF, HIV-1JR-FL, and HIV-1SF162, significant thymocyte depletion was detected after infection with HIV-1IIIB and HIV-1RF. Thus, the effect of HIV-1 infection on thymocyte maturation may depend upon the strain of HIV-1 infecting the thymus. Despite the minimal effects on thymopoiesis observed in the hu-thy/liv implanted in SCID-hu mice 6 mo after infection with HIV-1(28), significant changes were seen in the human T cell population circulating in the peripheral blood of these mice. These changes ranged from an inversion of the CD4/CD8 ratio of peripheral human T cells in some SCID-hu mice to the almost complete depletion of peripheral human T cells observed in other SCID-hu mice. Because these effects were associated with the detection of HIV-1 infection of the peripheral human T cells, these modified SCID-hu mice should prove to be a valuable model for investigating the effects of chronic HIV-1 infection on the peripheral human T cell population.

Animals↗
PubMed1995

Human immunodeficiency virus-1 principal neutralizing domain peptide-toxin A conjugate vaccine.

To enhance the potential efficacy of peptide-based vaccines for human immunodeficiency virus-1 (HIV-1), a principal neutralizing domain (PND) peptide (KRIHIGPGRAFYT) (HIV-1MN) was covalently coupled to Pseudomonas aeruginosa toxin A (TA). Immunization of guinea-pigs with this conjugate vaccine, in the absence of an adjuvant, engendered a high-affinity antibody response to the homologous HIV-1MN PND peptide and to analogous peptides from variant strains of HIV-1. A substantial proportion of such antibodies was directed to the conserved GPGRAF motif. Anti-PND peptide antibodies were capable of neutralizing the homologous strain, HIV-1MN, in addition to two heterologous (RF, IIIB) variants, as determined either by inhibition of syncytia formation or by suppression of p24 antigen production in cultured cells. Therefore, the method of conjugation used preserved critical neutralizing epitopes expressed by the PND peptide. Monovalent or polyvalent PND-TA conjugates, which meet all safety criteria for human use, are a promising approach towards the development of an acquired immunodeficiency syndrome (AIDS) vaccine.

ADP Ribose Transferases↗
PubMed1995

Dysmenorrhea is related to the number of implants in endometriosis patients.

OBJECTIVE: To determine whether the symptoms of endometriosis were related to the number and/or location of endometrial implants and the number and/or location of adhesions. DESIGN: Prospective, double-blind study. PATIENTS: Seventy consecutive female surgical patients undergoing diagnostic and operative laparoscopy for pain, infertility, or both. INTERVENTIONS: Patients completed a self-administered questionnaire one day before laparoscopy. MAIN OUTCOME MEASURES: The number, type, and location of endometrial implants and the number, type, and location of adhesions were evaluated during laparoscopy. These were compared with the type and severity of endometriosis symptoms as reported by patients. RESULTS: The total number of ectopic endometrial implants was associated directly with the intensity of dysmenorrhea experienced by patients in the 60 days before operative laparoscopy (n = 47). Patients with low pain scores had significantly fewer implants than patients with high pain scores. CONCLUSIONS: The intensity of menstrual pain is related to the number of endometrial implants in patients with endometriosis.

Adult↗
PubMed1995

Safety and immunogenicity of a V3 loop synthetic peptide conjugated to purified protein derivative in HIV-seronegative volunteers.

OBJECTIVES: To develop a peptide-based model for a preventive vaccine for HIV-1 infection. DESIGN: Phase I trial in HIV-1-seronegative volunteers. PARTICIPANTS: Adult healthy subjects HIV-1-antibody-seronegative in an enzyme-linked immunosorbent assay, screened for tuberculin [purified protein derivative (PPD)] reactivity with 2 tuberculin units PPD-administered intradermally. INTERVENTIONS: Submicrogram doses of a PPD conjugate with a peptide of the primary neutralizing domain (PND) of HIV-1MN (PPD-MN-PND) were administered intradermally to tuberculin skin-test-positive and -negative volunteers. RESULTS: Antibodies to the MN-PND were measured after two immunizations in 10 out of 11 PPD skin-test-positive volunteers. After the fourth immunization high-affinity antibodies were detected, which persisted for over 1 year. High titers of MN-PND-specific immunoglobulin (Ig) G and IgA were detected in the serum and saliva of all volunteers tested. Serum antibodies were cross-reactive with PND peptide from some other HIV-1 strains but neutralized only the HIV-1MN prototype. Human leukocyte antigen (HLA)-B7-restricted MN-PND-specific cytotoxic T lymphocytes (CTL) were also detected. CONCLUSIONS: The PPD-MN-PND vaccine at submicrogram doses is safe and immunogenic in PPD skin-test-positive healthy adult volunteers. Long lasting humoral immune responses in the serum and saliva were possibly accompanied by HLA-B7-restricted CTL responses. This is a vaccine prototype that can be rapidly and inexpensively modified to include other peptide epitopes. It is especially suitable for use in a worldwide multibillion Bacillus Calmette-Guérin (BCG)-primed or tuberculosis-exposed population at risk for HIV-1 infection.

AIDS Vaccines↗
PubMed1994

Multilevel time series models with applications to repeated measures data.

The analysis of repeated measures data can be conducted efficiently using a two-level random coefficients model. A standard assumption is that the within-individual (level 1) residuals are uncorrelated. In some cases, especially where measurements are made close together in time, this may not be reasonable and this additional correlation structure should also be modelled. A time series model for such data is proposed which consists of a standard multilevel model for repeated measures data augmented by an autocorrelation model for the level 1 residuals. First- and second-order autoregressive models are considered in detail, together with a seasonal component. Both discrete and continuous time are considered and it is shown how the autocorrelation parameters can themselves be structured in terms of further explanatory variables. The models are fitted to a data set consisting of repeated height measurements on children.

Adolescent↗
PubMed1994

Reconstitution of SCID mice with human lymphoid and myeloid cells after transplantation with human fetal bone marrow without the requirement for exogenous human cytokines.

Investigation of human hematopoietic maturation has been hampered by the lack of in vivo models. Although engraftment of irradiated C.B-17 scid/scid (SCID) mice with human progenitor cells occurred after infusion with human pediatric bone marrow cells, significant engraftment of the mouse bone marrow with human cells was dependent upon continuous treatment with exogenous human cytokines. Furthermore, despite cytokine treatment, only minimal peripheral engraftment of these mice with human cells was observed. In the present study, after infusion of irradiated SCID mice with pre-cultured human fetal bone marrow cells (BM-SCID-hu mice), their bone marrow became significantly engrafted with human precursor cells and their peripheral lymphoid compartment became populated with human B cells and monocytes independently of the administration of extraneous human cytokines. Examination of the bone marrow of the BM-SCID-hu mice for human cytokine mRNA gene expression demonstrated human leukemia inhibitory factor mRNA and interleukin 7 mRNA in nine of nine BM-SCID-hu mice and macrophage-colony-stimulating factor mRNA in seven of eight BM-SCID-hu mice. This was an intriguing observation because these cytokines regulate different stages of human hematopoiesis. Since engraftment occurs in the absence of exogenous cytokine treatment, the BM-SCID-hu mouse model described should provide a useful in vivo system for studying factors important in the maturation of human myeloid and lymphoid cells in the bone marrow and the behavior of the mature human cells after dissemination into the peripheral lymphoid tissue.

Animals↗
PubMed1994

Disseminated human immunodeficiency virus 1 (HIV-1) infection in SCID-hu mice after peripheral inoculation with HIV-1.

A small animal model that could be infected with human immunodeficiency virus 1 (HIV-1) after peripheral inoculation would greatly facilitate the study of the pathophysiology of acute HIV-1 infection. The utility of SCID mice implanted with human fetal thymus and liver (SCID-hu mice) for studying peripheral HIV-1 infection in vivo has been hampered by the requirement for direct intraimplant injection of HIV-1 and the continued restriction of the resultant HIV-1 infection to the human thymus and liver (hu-thy/liv) implant. This may have been due to the very low numbers of human T cells present in the SCID-hu mouse peripheral lymphoid compartment. Since the degree of the peripheral reconstitution of SCID-hu mice with human T cells may be a function of the hu-thy/liv implant size, we increased the quantity of hu-thy/liv tissue implanted under the renal capsule and implanted hu-thy/liv tissue under the capsules of both kidneys. This resulted in SCID-hu mice in which significant numbers of human T cells were detected in the peripheral blood, spleens, and lymph nodes. After intraimplant injection of HIV-1 into these modified SCID-hu mice, significant HIV-1 infection was detected by quantitative coculture not only in the hu-thy/liv implant, but also in the spleen and peripheral blood. This indicated that HIV-1 infection can spread from the thymus to the peripheral lymphoid compartment. More importantly, a similar degree of infection of the hu-thy/liv implant and peripheral lymphoid compartment occurred after peripheral intraperitoneal inoculation with HIV-1. Active viral replication was indicated by the detection of HIV-1 gag DNA, HIV-1 gag RNA, and spliced tat/rev RNA in the hu-thy/liv implants, peripheral blood mononuclear cells (PBMC), spleens, and lymph nodes of these HIV-1-infected SCID-hu mice. As a first step in using our modified SCID-hu mouse model to investigate the pathophysiological consequences of HIV-1 infection, the effect of HIV-1 infection on the expression of human cytokines shown to enhance HIV-1 replication was examined. Significantly more of the HIV-1-infected SCID-hu mice expressed mRNA for human tumor necrosis factors alpha and beta, and interleukin 2 in their spleens, lymph nodes, and PBMC than did uninfected SCID-hu mice. This suggested that HIV-1 infection in vivo can stimulate the expression of cytokine mRNA by human T cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Enhancement of HIV type 1 infectivity in vitro by capsular polysaccharide of Cryptococcus neoformans and Haemophilus influenzae.

High concentrations of the cryptococcal capsular polysaccharide (CCP) are present in the serum, cerebrospinal fluid or both in the majority of AIDS patients infected with Cryptococcus neoformans. Because the prognosis of AIDS patients infected with cryptococcus is poor, we investigated whether the presence of CCP enhanced HIV-1 infection. The presence of CCP markedly increased the infectivity of HIV-1-infected H9 cells and subsequent production of infectious HIV-1 and formation of syncytia. In addition to enhancing the infectivity of H9 cells infected with laboratory isolates of HIV-1, the presence of CCP also increased the infectivity of peripheral blood mononuclear cells (PBMCs) infected with primary field strains of HIV-1. The in vitro infectivity of PBMCs from 20 of 44 HIV-1-infected individuals was significantly increased when cultured with CCP. Furthermore, HIV-1 was isolated from the PBMCs of three of these individuals only when cultured in the presence of CCP. CCP increased the binding of HIV-1 and recombinant gp120 to H9 cells and recombinant CD4, respectively. Thus, it is possible that the enhancement of HIV-1 infectivity by CCP is due to its capacity to increase the adherence of HIV-1 to target cells. Whereas the capsular polysaccharide of Haemophilus influenzae also markedly enhanced the infectivity of HIV-1, the capsular polysaccharides of C. freundii or S. flexneri had minimal effects on the infectivity of HIV-1. This indicated that the capacity to enhance HIV-1 infectivity was a property of polysaccharides from some pathogens and not others.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗
PubMed1993

Immunoglobulin secretion and phosphorylation of common proteins are induced by IL-2, IL-4, and IL-6 in the factor responsive human B cell line, SKW6.4.

After the binding of IL-2, IL-4, or IL-6 to their respective receptors on activated human B cells, a multistep cascade of intracellular events is initiated that results in the secretion of Ig. However, it is not known whether these different cytokine receptors use common or divergent signal transduction pathways to stimulate Ig secretion. Therefore, we examined the signaling mechanisms used by a human lymphoblastoid cell line arrested at a late stage of differentiation, SKW6.4, that secretes IgM following stimulation with IL-2, IL-4, or IL-6 alone. Our study demonstrated that IL-2, IL-4, and IL-6-stimulation of IgM secretion by SKW6.4 cells was inhibited by either the serine/threonine kinase inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperizine dihydrochloride (H7) or the tyrosine kinase inhibitor, genistein. To investigate the early phosphorylation events initiated by these cytokines, a membrane-enriched preparation from SKW6.4 cells was isolated in a manner that minimized the disruption of membrane protein complexes and then incubated with IL-2, IL-4, or IL-6 in the presence of [gamma-32P]ATP. IL-2, IL-4, and IL-6 stimulated the rapid serine/threonine phosphorylation of 47-, 49-, and 91-kDa proteins. However, in contrast to the 47- and 49-kDa proteins that remained phosphorylated for up to 30 min poststimulation, the 91-kDa protein was rapidly dephosphorylated within 15 min of stimulation. The observation that serine/threonine phosphorylation of the same proteins was stimulated by IL-2, IL-4, and IL-6 suggested that the cytokines activated either different protein kinases with the same substrate specificity or the same protein kinase. In addition, stimulation of intact SKW6.4 cells with either IL-2, IL-4, or IL-6 induced the phosphorylation of two proteins with molecular masses of 45- to 50-kDa and 85 to 90-kDa. Taken together, our data demonstrate that activation of both a serine/threonine kinase and a tyrosine kinase is involved in the IL-2, IL-4, and IL-6-stimulation of IgM secretion by SKW6.4 cells and activation of the same or a similar serine/threonine protein kinase is an early step in the signal transduction pathway used by these cytokines.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1993

Modelling lactation using an inverse polynomial in a multilevel statistical model.

A method is outlined for modelling the relationship between breast-milk production and time from delivery, suitable for data collected longitudinally. The relationship is described using inverse polynomials. In a two-level model the coefficients are specified as random variables across subjects, allowing within- and between-subject variation to be separately estimated. In a three-level model, day-to-day variation can also be separately estimated. The model is illustrated using data from the Chiang Mai Lactation Project. It allows the use of covariates that vary over time, and provides a method of analysis that is compatible with the practical constraints on the timing of data collection that are inherent in longitudinal studies.

Age Factors↗
PubMed1993

The concurrent maturation of mouse and human thymocytes in human fetal thymus implanted in NIH-beige-nude-xid mice is associated with the reconstitution of the murine immune system.

To determine whether the human thymus provides an environment for the maturation of murine T cells, human fetal thymus and liver (hu-thy/liv) were implanted into congenitally athymic NIH-beige-nude-xid (BNX) mice or C.B-17 scid/scid (SCID) mice. 3 mo after implantation, in contrast to the hu-thy/liv implant in SCID mice, which was populated only with human CD4/CD8 single- and double-positive thymocytes, the hu-thy/liv implant in BNX mice contained a chimeric population of human and mouse CD4/CD8 single- and double-positive thymocytes. Immunohistochemical staining of the hu-thy/liv implant in BNX mice indicated that the population of double-positive mouse thymocytes was localized to discrete areas of the human fetal thymus. Quantitative improvements in mouse T cell and immunoglobulin (Ig) G parameters were observed after grafting of the human fetal thymus and liver tissue into BNX mice. In addition, in contrast to the nonimplanted BNX mice, the implanted BNX mice were capable of mounting a keyhole limpet hemocyanin-specific IgG response and their peripheral T cells were responsive to stimulation with mitogens and antibodies directed to the T cell receptor. Furthermore, after in vivo priming, T cells present in lymph nodes of the implanted BNX mice were capable of mounting an antigen-induced in vitro T cell-dependent proliferative response. Thus, concurrent with the continued maturation of human T cells, murine T cells differentiated within the human fetal thymus implanted in the BNX mice and mediated the phenotypic and functional reconstitution of the murine immune system. Mice with a reconstituted immune system that contain a human thymic implant that is infectible with human immunodeficiency virus (HIV) should prove useful in the investigation of T cell maturation in the thymus and in the evaluation of potential HIV vaccines.

Animals↗
PubMed1993

A rapid test for the detection of human immunodeficiency virus antibodies in cord blood.

A commercially available rapid test (HIVCHEK) was compared with an enzyme-linked immunosorbent assay (ELISA) for identifying human immunodeficiency virus type 1 in the serum of newborn infants. Of 1309 cord blood samples tested, the HIVCHEK test detected all the true-positive samples detected by ELISA. Of the 35 samples with positive ELISA results, six had negative results on Western blot; only 1 of the 30 samples with positive HIVCHEK results had negative results on Western blot. Thus the HIVCHEK test can be used to facilitate the rapid identification of HIV-1 in the serum of newborn infants.

Colorimetry↗