Biomedical subjects
Publications and source records attributed to S Goldstein.
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We reported previously the age-dependent appearance of extrachromosomal circular DNA bands hybridizing to a human DNA fragment ('inter-Alu'), isolated from a genomic cluster of AluI repeats. Such bands appeared or increased at late passage in four out of six human fibroblast strains (six out of nine cell expansions); moreover, all DNAs (9/9) obtained from peripheral lymphocytes of aged donors, but none (0/8) from young donors, revealed a non-genomic inter-Alu band at congruent to 4.8 kilobases (kb). Subsequent data extended these numbers to 16/24 aged donors compared with 0/18 young donors. These results were interpreted as evidence of age-dependent DNA rearrangement in normal human cells. We now report that the 'extra' bands were of microbial origin, although clearly occurring in an age-dependent manner.
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Pirmenol hydrochloride (CI-845), a new antiarrhythmic agent available for both oral and intravenous administration, was given to seven patients with chronic ventricular dysrhythmia in an open-label fashion. After intravenous infusion of 150 mg over 30 min, the mean (+/- SD) peak plasma concentration achieved was 2.14 +/- 0.75 microgram/ml. The terminal elimination half-life, the volume of the central compartment, and the total body clearance averaged 6.5 h, 0.70 +/- 0.36 L/kg, and 3.0 +/- 2.6 ml/min/kg, respectively. After a single 150-mg oral dose, the peak plasma concentration of 1.3 +/- 0.55 microgram/ml was achieved 1 to 3 h after dosing. The mean apparent elimination half-life was 7.6 h. An estimated absorption lag time ranging from 14 to 37 min was observed in all but one patient. The mean absolute bioavailability for the oral dose was 87%. Dysrhythmia data were available in six patients. Complete (100%) suppression of ventricular ectopic beats occurred in four patients for 1/2 to 15 h after intravenous infusion, and in three patients for 7 to 25 h after oral dose. This suppression occurred with a plasma pirmenol level as low as 0.4 microgram/ml. No significant side effects were observed.
Homologous SIVsm stocks were generated by passage of a macaque isolate of SIVsm (SIVsm/E660) in human CEM x 174 cells or macaque peripheral blood mononuclear cells. Macaques were immunized with whole inactivated SIV vaccine consisting of virus generated by transfection of CEM x 174 cells with the SIVsmH4 clone and were challenged with either cell-free stock. Only vaccinees challenged with virus generated in human cells were protected from infection. This confirms the species-specificity of whole inactivated vaccine-mediated protection.
The CD95 receptor, also known as Fas/Apo-1, is a member of the Tumor Necrosis Factor receptor (TNF-R) family of death receptors. Apoptosis mediated by CD95 plays a central role in maintaining homeostasis of the immune system. Dysregulation of the CD95 apoptotic pathway has been proposed as a mechanism of oncogenesis by providing a survival advantage to potentially malignant cells. This extended lifespan could allow the accumulation of further mutations leading to malignant transformation. Several mechanisms of resistance to CD95 mediated apoptosis have been identified, including reduced surface expression of the receptor, overexpression of anti-apoptotic molecules, and loss of function mutations. This review will focus on the potential role of the CD95-CD95 ligand system in the pathogenesis of hematological malignancies, with particular emphasis on recent work from our laboratory examining the expression of CD95 in B cell lymphomas. We demonstrate that CD95 mutations occur at low frequency in NHL tumors, however, surface expression of the CD95 protein varies with the subtype of lymphoma. Loss of surface CD95 is more likely to occur in lymphomas of aggressive histology, and is unrelated to the detection of CD95 mutations.
A hydrogel strip relaxes when it is stretched. The decay in tensile stress can be ascribed primarily to strain-induced swelling of the polymer network--a result that follows from a continuum model of the gel-solvent system. An equation of motion and a linear constitutive law of the polymer network, Darcy's law, and the conservation of mass of the network and interstitial fluid are solved with boundary and initial conditions appropriate for a stress-relaxation experiment. This model predicts that the time constant of decay depends inversely upon the square of the thickness of the sample. This result is confirmed by experiments. In addition, the network shear modulus, mu, bulk modulus, k, and hydraulic permeability, 1/f, which are estimated by non-linear regression, all agree with measurements obtained using other methods.
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"This analysis is designed to provide insights into the relation between migration and fertility in China. Survey data collected from Anhui Province in 1989 are used to evaluate whether fertility is higher or lower among the temporary migrants to urban places in comparison to permanent residents in those locations.... Our analysis will...assess the extent to which socioeconomic characteristics, family planning, and migration help to explain observed differences in the fertility of temporary migrants and permanent residents. In doing so, the basic question to be answered is whether temporary migrants have used their movement as a way to avoid official policies controlling fertility and, in so doing, have they contributed to a higher than average fertility in China?"
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The comparative conformational analysis of four Substance P antagonists (NK1-) having different chemical structures allowed to formulate an hypothesis for a peptidic NK1 pharmacophore. The salient features of this pharmacophore (three aromatic groups and two carbonyl functions) belong to a beta-turn conformation. Thus, this kind of conformation might be the basis for the design of newer pseudo-peptidic and non-peptidic NK1 antagonists.
The binding cavity of histamine and histamine antagonists is explored using site directed mutagenesis of the human histamine H1 receptor and the amino acids involved in ligand binding are identified. Whereas Asp107 and Phe199 are important for both agonists and antagonists, two additional amino acids (Asn198 and Trp103) are required for efficient histamine binding. The binding site of antagonists is best defined as resulting from a strong ionic bond to Asp107, an orthogonal interaction between one of the aromatic rings with Phe199, and probably a hydrophobic interaction between the second aromatic ring and the lipophilic amino acids of the upper part of TMIV and TMV. This is consistent with structure-activity data of most described antagonists.
From information on mortality of Jews obtained from individual death certificates and population data from surveys of the Jewish population undertaken in 1963 and 1987, age specific death rates and life expectancy of the Jewish population of Rhode Island are compared with those of the total white population for 1963 and 1987 to assess changing differentials. The Jewish mortality experience continues to differ from that of the larger population even while both groups have experienced noticeable improvements. For males, the age standardized rates have widened in favor of Jews as have the life expectancies at birth and the percentage surviving to old age. By contrast, for females, the standardized death rate has widened considerably in favor of whites, while life expectancy has improved almost identically for both groups and therefore remained about equal, as it was in 1963. Reasons for these patterns are explored through attention to differences between Jews and the general white population in death rates at particular stages of the life cycle. Jews tend to be more advantaged at all but the most advanced ages, age groups in which proportionally more of the Jewish population and Jewish deaths are concentrated.