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Biomedical subjects

B Goldman

Publications and source records attributed to B Goldman.

280 records · Page 16Linked to original sources

Hematopoietic progenitor cells as targets for non-invasive prenatal diagnosis: detection of fetal CD34+ cells and assessment of post-delivery persistence in the maternal circulation.

Culture expansion of fetal cells from the maternal circulation will provide an increased number of cells for non-invasive prenatal diagnosis. Hematopoietic CD34+ cells are potential candidates for this application. More information is needed regarding the frequency of these cells and the phenomenon of post-delivery persistence in the maternal circulation. In this study we assessed the number of fetal CD34+ cells in the maternal circulation, the effect of culture expansion on the number of fetal cells and the persistence of fetal CD34+ cells from previous pregnancies. Fetal cells were identified by the presence of Y-chromosome sequences detected by FISH and nested PCR. Fetal CD34+ cells were detected in all samples from women carrying a male fetus. A low number of residual fetal cells from previous pregnancies was detected (1-3 XY cells in 20 ml blood) in less than 1/3 of the samples from both non-pregnant women and those pregnant with a female fetus. Culturing of CD34+ cells resulted in a significant increase in fetal cell numbers. However, the number of fetal cells persisting from previous pregnancies also increased after culture. It is proposed that information derived from CD34+ cells could potentially support data derived from other cell types for more accurate non-invasive prenatal diagnosis.

Antigens, CD34↗

Germline mutational analysis of presenilin 1 and APP genes in Jewish-Israeli individuals with familial or early-onset Alzheimer disease using denaturing gradient gel electrophoresis (DGGE).

Germ line mutations in three genes have been detected in patients with familial Alzheimer's disease (FAD) and sporadic, early onset disease: amyloid precursor protein (APP), presenilin 1 (PS-1), and presenilin 2 (PS-2). The relative proportions in which mutations in these genes occur among AD patients in Israel has not been evaluated. To that end, we screened 52 Jewish-Israeli patients with AD: 22 with sporadic, early-onset disease (below 65 years), and 30 with FAD. Mutation screen employed denaturing gradient gel electrophoresis (DGGE) of exon-specific PCRs and restriction enzyme digest. Five patients from three different families displayed mutations within the PS-1 gene: three patients of one family showed a mis-sense mutation in codon 120 (Glu 120Lys), and two other unrelated patients showed an identical mis-sense mutation in codon 318 (Glu318Gly). No patient showed an abnormal migration on DGGE (for APP) or mutant restriction digest pattern (for PS-2) genes. These data may indicate the existence of another familial Alzheimer disease (FAD) gene locus in the Israeli Jewish population.

Adult↗

Lower frequency of Gaucher disease carriers among Tay-Sachs disease carriers.

The heterozygote frequency of Gaucher disease (GD) and Tay-Sachs disease (TSD) is distinctly high among Ashkenazi Jews (1:29 for TSD and 1:16 for GD). Two main theories have been suggested to explain this high occurrence: a founder effect with subsequent genetic drift, and a selective advantage of heterozygotes. We compared the frequency of the GD most common mutation (1226A-->G) among carriers of the common TSD mutation (+1277 TATC) with the frequency of this mutation in the general Ashkenazi population. The frequency of GD carriers among 308 TSD heterozygotes was 1:28 which is about half the expected (P = 0.03). These results indicate that carriers of both diseases do not possess additional evolutionary advantage over single mutation carriers. A reasonable interpretation of these findings is that one or both mutations have arisen relatively recently in different regions of Europe and have not yet reached genetic equilibrium.

DNA Mutational Analysis↗

Clinical results of endarterectomy of the right and left anterior descending coronary arteries.

In this study, we examined the clinical outcome of coronary endarterectomy. From 1990 to 1998, 4839 patients underwent surgical revascularization. Coronary artery bypass graft surgery (CABG) was performed alone on 4516 patients, was combined with right coronary artery endarterectomy (RCA-E) in 242 patients, and was combined with left anterior descending coronary artery endarterectomy (LAD-E) in 81 patients. An analysis of preoperative variables revealed a higher proportion of males (90.7% vs 80.2%, p < 0.001), of patients with low ejection fraction (< 35%; 4.6% vs 1.7%, p < 0.001), and of three-vessel disease (47.9% vs 36%, p < 0.001) in the RCA-E versus the CABG patients. There was a higher proportion of unstable angina (51.9% vs 40.3%, p = 0.04) in the LAD-E patients. The 30-day mortality rate for CABG was 2% versus 2.5% for RCA-E and 3.7% for LAD-E (p = NS). Perioperative myocardial infarction (MI) rate for CABG was 3.4% versus 7.0% for RCA-E (p < 0.001) and 4.9% for LAD-E patients (p = NS). Postoperative low cardiac output syndrome was recorded in 11.5% of CABG, 18.6% of RCA-E (p = 0.01), and 11.1% of LAD-E (p = NS) patients. Predictors of postoperative bad outcome (death, MI, low cardiac output, cerebrovascular accident) were preoperative intra-aortic balloon pump, repeat operation, ejection fraction of < 35%, renal insufficiency, female gender, RCA-E, and age over 70. Protective factors included the use of internal mammary artery, multiple arterial grafts, and warm cardioplegia. Actuarial analysis at 6, 12, and 24 months showed late mortality rates of 0.8%, 1.3%, and 2.1% for CABG; 1.2%, 3.7%, and 3.7% for RCA-E; and 2.9%, 2.9%, and 2.9% for LAD-E, respectively. Late MI occurrence was 0.4%, 0.4%, and 0.7% for CABG; 1.5%, 1.5%, and 2.7% for RCA-E; and 0% for LAD-E, respectively. Multivariate analysis found renal insufficiency, ejection fraction of < 35%, repeat operation, female gender, New York Heart Association functional class IV, and diabetes to be predictors for late adverse events (recurrence of angina, MI, and cardiac death), and RCA-E was found to be a predictor of late MI. We conclude that the use of coronary endarterectomy to achieve complete revascularization in patients with diffuse distal coronary artery disease is a reasonable option, associated with a minimal addition in complication rates.

Cause of Death↗

HTLV-associated diseases: human retroviral infection and cutaneous T-cell lymphomas.

An array of neurologic, oncologic, and autoimmune disorders are associated with infection with the human pathogenic retroviruses human T-cell leukemia virus types I and II (HTLV-I, II), as well as the human immunodeficiency viruses (HIV). The cutaneous T-cell lymphomas, mycosis fungoides (MF) and its hematogenous variant Sezary Syndrome (SS), share similar clinical and pathological features to HTLV-I-associated adult T-cell leukemia (ATL) and speculation of a retroviral link to MF and SS, especially in areas non-endemic for ATL, has lead to an intensified search for HTLV- and HIV-like agents in these diseases. To further explore a potential role for human retroviruses in MF and SS, skin biopsy-derived or peripheral blood mononuclear cell-derived DNA from 17 patients (MF, n = 7; erythrodermic MF (EMF), n = 5; SS, n = 5) from the North Eastern United States were screened using gene amplification by PCR and a liquid hybridization detection assay. Previously published primers and probes for HTLV-I (LTR, gag, pol, env, and pX), and our own primers and probes for HTLV-I (gag, pol, and env), HTLV-II (pol and env) and HIV-I (gag and pol) were employed. Serum antibodies to HTLV-I were negative in all but one EMF patient. The single HTLV-I seropositive patient carrying a diagnosis of EMF generated positive amplified signals for all of the eight HTLV-I regions tested. Ultimately, this individual evolved to exhibit clinical manifestations indistinguishable from ATL. The other 16 patients were negative for all 12 HTLV and HIV retroviral regions. Our findings suggest that none of the known prototypic human retroviruses are associated with seronegative MF and SS. The uniformly positive results for HTLV-I in the seropositive patient suggests that this patient initially presented with a smoldering form of ATL and illustrates the difficulty that sometimes may be encountered in the differential diagnosis of MF, SS, and ATL based solely on clinical and histopathological criteria.

Adult↗

Human embryo chromosomes: preliminary results of a study to karyotype multipronuclear human oocytes fertilized in vitro.

Using special techniques the authors have analyzed the chromosome constitution of human gametes participating in fertilization in vitro. Only oocytes with multiple pronuclei have been used in this study. Two conclusions are reached by the Authors: first, that the gametes involved in the production of oocytes with multiple pronuclei can be chromosomally abnormal, specifically aneuploid and that not all oocytes with three pronuclei will cleave to form triploid embryos. The Authors underline that even normal, normospermically fertilized oocytes could have a chromosomal abnormality. They conclude that embryos with chromosomal abnormalities may be produced by IVF and ET and that their existence is reflected by the inability of the vast majority of transferred embryos to survive to term delivery.

Cell Nucleus↗

Postpartum multivessel coronary dissection.

A 29-year-old woman had an acute myocardial infarction 5 days after giving birth. Serial coronary angiography showed multiple progressive coronary artery dissections, which eventually involved both the right and left coronary trees. Persistent cardiogenic shock necessitated emergent orthotopic heart transplantation. Examination of the cardiectomy specimen confirmed the presence of multiple myocardial infarctions, coronary artery dissection, and fibromuscular dysplasia of the coronary arteries. Fibromuscular dysplasia combined with changes in the arterial ground substance and hormonal milieu attributable to pregnancy or parturition are proposed as possible causes of coronary artery dissection in this case.

Adult↗