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Biomedical subjects

S Winokur

Publications and source records attributed to S Winokur.

15 recordsLinked to original sources
PubMed2001

Methylation of the FSHD syndrome-linked subtelomeric repeat in normal and FSHD cell cultures and tissues.

Facioscapulohumeral muscular dystrophy (FSHD) has an unusual molecular etiology. In a putatively heterochromatic subtelomeric region of each chromosome 4 homologue (4q35), unaffected individuals have 11 to about 95 tandem copies of a complex 3.3-kb repeat (D4Z4). Most FSHD patients have less than 10 copies at one allelic 4q35. This has been proposed to lead to the loss of heterochromatinization and, thereby, inappropriate gene expression by position effects, explaining the dominant nature of FSHD and the role of a decreased number of copies of D4Z4 at 4q35 but not at 10q26. Consistent with the proposed heterochromatinization of this repeat, by Southern blot analysis, we found that SmaI, MluI, SacII, and EagI sites in D4Z4 are highly methylated in normal and FSHD cell lines and somatic tissues, including skeletal muscle. Like repeated DNA sequences in the juxtacentromeric heterochromatin of chromosomes 1, 9, and 16, D4Z4 was hypomethylated at numerous CpGs in sperm and in cell lines from patients with an unrelated DNA methyltransferase deficiency syndrome (ICF; immunodeficiency, centromeric region instability, facial anomalies) in contrast to its hypermethylation in non-ICF postnatal somatic tissues. Our data on FSHD samples suggest that the disease-associated 4q35 D4Z4 repeats, which constitute a small percentage of the total D4Z4 repeats, are not generally hypomethylated relative to the other repeats of this sequence. However, in individuals not affected with FSHD, the hypermethylation of tandem, high-copy-number D4Z4 repeats might help stabilize heterochromatinization at allelic 4q35 regions just as hypermethylation elsewhere in the genome has been linked to chromatin compaction.

Bacterial Proteins↗
PubMed2000

Characterization of the murine homolog of C1qR(P): identical cellular expression pattern, chromosomal location and functional activity of the human and murine C1qR(P).

Human C1qR(P) is a highly glycosylated transmembrane protein that is the human C1q receptor/receptor component that in vitro mediates enhancement of Fc- and C3b-mediated phagocytosis. A human genomic clone and a murine genomic clone that is 73% identical in sequence with the coding region for human C1qR(P) cDNA have been isolated. Chromosomal localization of the human and murine gene demonstrates that these genes are syntenic. Murine cell lines of diverse myeloid origins are shown to respond to interaction of C1q with the enhancement of phagocytosis similar to that seen previously in human peripheral blood monocytes. Northern blot, RT-PCR, Western blot and FACS analyses demonstrated that mC1qR(P) is expressed in these murine myeloid cell lines, but not in a mouse epithelial cell line, similar to the cell type expression of the human gene product. A polyclonal antibody to a peptide sequence common to the deduced sequence from the both murine and human C1qR(P) inhibited the enhancement of phagocytosis response to C1q when cells were permeabilized to permit access of the antibody to the intracellular milieu. These data support the postulate that the identified murine and human genes are homologs, confirm the previously predicted intracellular location of the C-terminus of the molecule, and indicates the necessary role of this intracellular domain in transducing the signal that leads to enhancement of phagocytic function.

Amino Acid Sequence↗
PubMed1993

Mapping the facioscapulohumeral muscular dystrophy gene is complicated by chromsome 4q35 recombination events.

A gene responsible for facioscapulohumeral muscular dystrophy (FSHD) has been linked to polymorphisms on chromosome 4q35. Multipoint linkage analyses have placed this gene distal to all reported genetic markers on the chromosome. By using as a probe a clone isolated from a cosmid containing sequences related to a homeobox domain, de novo DNA rearrangements were reported in sporadic and familial cases of FSHD. Linkage analysis of an EcoRI polymorphism detected by this clone in twenty-four multigenerational FSHD families revealed recombinants between this marker and the disease with a recombination fraction of 0.05. Two families with apparent germline mosaicism were also identified.

Blotting, Southern↗
PubMed1987

Pulmonary veno-occlusive disease following therapy for malignant neoplasms.

We report three cases of pulmonary veno-occlusive disease which developed following treatment for malignant neoplasms. Two patients received single agent BCNU chemotherapy for malignant gliomas. The third patient underwent combination radiation and chemotherapy for Hodgkin's disease. Isolated case reports of pulmonary veno-occlusive disease following therapy for malignant disease are reviewed and clinical features summarized. Pulmonary veno-occlusive disease in this setting is thought to be rare. However, the diagnosis is rarely suspected clinically and is difficult to diagnose pathologically. Therefore, the true incidence of this complication is unknown and may be higher than believed. It is important that both clinician and pathologist be aware of this entity; otherwise, elastic tissue stains may not be performed and the diagnosis missed.

Adolescent↗
PubMed1980

A phase II study of chlorozotocin in metastatic malignant melanoma.

Thirty-five patients with metastatic malignant melanoma underwent treatment with chlorozotocin administered as a single dose of 120 mg/m2 by means of rapid intravenous infusion every six weeks. There were 1 complete and 4 partial remissions with an overall response rate of 14%. The median duration of response was 18 weeks; the patient in complete remission continues disease-free in excess of 42 weeks. The sites of response included: lung, 2; subcutaneous, 2; and lymph node, 1. There was minimal myelotoxicity: for the first cycle, the median white blood cell count nadir was 5400/mm3, and the platelet nadir was 210,000/mm3. No evidence of cumulative platelet toxicity was observed. Chlorozotocin is active against metastatic melanoma to the same degree as other chloroethylnitrosoureas in clinical use, but without causing bone marrow toxicity. These data suggest that chlorozotocin should be evaluated in combination with other agents active against melanoma.

Adult↗
PubMed1978

A procedure for studying echoic control in verbal behavior.

Male and female college students answered standard questions about the women's liberation movement on three occasions. A set of target words was embedded in the questions, with one set used in Sessions 1 and 3, and a synonymous, but different set used in Session 2. The relative frequencies of usage of a given target word were directly related to whether the questions for that session contained the word. The results supported the hypothesis of echoics as proposed in Skinner's theory of verbal behavior.

Journal Article↗
PubMed1976

The antiarrhythmic and cardiovascular properties of 1-dimethyl isopropylamino-3-(2-phenylphenoxy)-propan-2-ol chloride, UM-424.

The quarternary ammonium compound, UM-424 [1-dimethyl isopropylamino-3-(2-phenylphenoxy)-propan-2-ol chloride], was evaluated for its antiarrhythmic and hemodynamic effects. UM-424 converted ouabain-induced ventricular tachycardia in the anesthetized dog when administered in an average dose of 4.6 mg/kg i.v. Pretreatment of anesthetized dogs with UM-424, 10 mg/kg, provided complete protection against the development of premature beats and ventricular fibrillation when the left anterior descending coronary artery was occluded for 20 minutes and then released. UM-424 was effective in reversing ventricular arrhythmias in conscious animals which had been subjected to a two-stage ligation of the anterior descending coronary artery. The mean ectopic rate in a group of five dogs was 143 +/- 4.0 (S.E.M.) beats/min 24 hours after coronary ligation. Normal sinus rhythm was restored with a mean dose of 9.5 mg/kg of UM-424 and was maintained for a period in excess of 60 minutes. The ventricular fibrillation threshold was increased from a control value of 4.0 +/- 0.4 to 26.2 +/- 8.6 mA (P less than .05) 30 minutes after pretreatment with UM-424, 10 mg/kg. Inotropic and chronotropic dose-response studies to isoproterenol in the anesthetized dog demonstrated that the quarternary compound lacked beta adrenergic receptor blocking properties. UM-424, 10 mg/kg, did not produce any persistent changes in spontaneous heart rate, cardiac contractile force, left ventricular dP/ct, mean arterial blood pressure, cardiac output and mean pulmonary arterial pressure.

Adrenergic beta-Antagonists↗
PubMed1973

Controls for and constraints on auto-shaping.

Auto-shaping the pigeon's key-peck response was examined as a respondent conditioning procedure with the use of Rescorla's truly-random control procedure. In the first experiment, pigeons received presentations of brief light on the response key and brief presentations of food where the light and the food were independently presented. All birds failed to key peck after many light and food presentations, but explicit pairing of the light and food rapidly conditioned pecking to the light. Experiment 2 showed that even when an independent light/food presentation schedule was reduced to variable-time 30 sec, additional naive birds would not key peck and only one bird pecked when the schedules were variable-time 15 sec. A third experiment examined an explicit-unpairing control procedure, where the light and food were not only presented on independent schedules but were also separated by a minimum time, and found that auto-shaping did not occur. A fourth experiment investigated a number of control procedures and found them ineffective. A fifth experiment investigated the effects of a physical separation of the locus of the response key and the food dispenser, and a sixth experiment investigated using a tone in place of the light. It was concluded that pecking is generated by auto-shaping procedures only when an intermittently presented keylight is regularly paired with food.

Journal Article↗
PubMedDate not supplied

The positive inotropic effect of glucagon in the chronically failed right ventricle as demonstrated in the isolated cat heart.

Previous in vitro studies had provided evidence to show that papillary muscles obtained from cats with chronic right ventricular failure had lost their ability to develop a positive inotropic response to glucagon. Since it is difficult to extrapolate from the isolated papillary muscle to the intact heart, studies were done to assess the effects of glucagon in the perfused isovolumically beating heart obtained from cats four months after surgical banding of the pulmonary artery for the experimental production of chronic right ventricular failure (CRVF). At the peak of the dose-response curve, glucagon increased right ventricular isovolumic pressure 25% (39.00 +/- 4.37 to 49.67 +/- 5.15 mm Hg; p less than 0.001) and right ventricular dP/dt 63% (522.2 +/- 93.9 to 852.6 +/- 159.9 mm Hg/sec; p less than 0.001) in 6 normal hearts. Similar dose related increases in right ventricular isovolumic pressure and dP/dt were obtained in 6 hearts taken from cats with chronic right ventricular failure. The respective increases in right ventricular isovolumic pressure and dP/dt were 43% (30.33 +/- 4.01 to 43.67 +/- 6.25 mm Hg; p less than 0.025) and 73% (317.50 +/- 30.29 to 550.83 +/- 89.04 mm Hg/sec; p less than 0.025). These results provide evidence that glucagon possesses the capacity to augment myocardial contractility in the heart with experimentally induced chronic right ventricular failure.

Animals↗