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Biomedical subjects

M Weinstein

Publications and source records attributed to M Weinstein.

At least 73 records · Page 4Linked to original sources
PubMed1998

FGFR-3 and FGFR-4 function cooperatively to direct alveogenesis in the murine lung.

Mammalian lungs begin as an outpocket of the foregut, and depend on multiple stages of branching morphogenesis and alveogenesis to reach their final form. An examination of fgf receptor gene expression indicated that all four receptors (fgfr-1 to fgfr-4) are expressed in postnatal lungs at varying levels. We show that mice homozygous for a targeted mutation of fgfr-4 exhibited no overt abnormalities in the lungs or any other organ. However, mice doubly homozygous for disruptions of the fgfr-3 and fgfr-4 genes display novel phenotypes not present in either single mutant, which include pronounced dwarfism and lung abnormalities. Lungs of fgfr-3(-/-)fgfr-4(-/- )animals, which are normal at birth, are completely blocked in alveogenesis and do not form secondary septae to delimit alveoli. Consequently, air spaces in the lung are expanded and no alveoli can be seen. The mutant lungs failed to downregulate postnatal elastin deposition despite their normal levels of surfactant expression and cell proliferation. These data revealed a cooperative function of FGFR-3 and FGFR-4 to promote the formation of alveoli during postnatal lung development.

Animals↗
PubMed1998

Fibroblast growth factor receptor 2 (FGFR2)-mediated reciprocal regulation loop between FGF8 and FGF10 is essential for limb induction.

FGFR2 is a membrane-spanning tyrosine kinase that serves as a high affinity receptor for several members of the fibroblast growth factor (FGF) family. To explore functions of FGF/FGFR2 signals in development, we have mutated FGFR2 by deleting the entire immunoglobin-like domain III of the receptor. We showed that murine FGFR2 is essential for chorioallantoic fusion and placenta trophoblast cell proliferation. Fgfr2(DeltaIgIII/DeltaIgIII) embryos displayed two distinct defects that resulted in failures in formation of a functional placenta. About one third of the mutants failed to form the chorioallantoic fusion junction and the remaining mutants did not have the labyrinthine portion of the placenta. Consequently, all mutants died at 10-11 days of gestation. Interestingly, Fgfr2(DeltaIgIII/DeltaIgIII) embryos do not form limb buds. Consistent with this defect, the expression of Fgf8, an apical ectodermal factor, is absent in the mutant presumptive limb ectoderm, and the expression of Fgf10, a mesenchymally expressed limb bud initiator, is down regulated in the underlying mesoderm. These findings provide direct genetic evidence that FGF/FGFR2 signals are absolutely required for vertebrate limb induction and that an FGFR2 signal is essential for the reciprocal regulation loop between FGF8 and FGF10 during limb induction.

Animals↗
PubMed1998

Academic training in group psychotherapy in clinical psychology doctoral programs.

We surveyed 185 clinical psychology doctoral programs accredited by the American Psychological Association to examine whether and how group psychotherapy was taught. While respondents of all Psy.D: programs to the survey offered a course in group psychotherapy, less than one-third of Ph.D. programs offered one. Among programs that offered a course in group psychotherapy, less than half required that students take it. Most instructors had an in-class experiential component, focused either primarily or exclusively on outpatient therapy and used Yalom's interpersonal approach. Discussion focused on the importance of making group psychotherapy a higher priority and the suggestion that courses include a variety of theoretical approaches and important specialty groups such as psychiatric inpatients.

Accreditation↗
PubMed1998

CG island methylation changes near the GSTP1 gene in prostatic intraepithelial neoplasia.

Prostate intraepithelial neoplasia (PIN) is a purported prostate cancer precursor lesion and a candidate biomarker for efficacy assessment in prostate cancer chemoprevention trials. Loss of expression of the pi-class glutathione S-transferase enzyme GSTP1, which is associated with the hypermethylation of deoxycytidine residues in the 5'-regulatory CG island region of the GSTP1 gene, is a near-universal finding in human prostate cancer. GSTP1 expression was assessed by immunohistochemistry in 60 high-grade PIN samples adjacent to and distant from prostate adenocarcinoma. Whereas abundant enzyme polypeptide expression was evident in all normal prostatic tissues, all samples of high-grade PIN and adenocarcinoma were completely devoid of GSTP1. DNA from 10 high-grade PIN lesions was analyzed for GSTP1 CG island methylation changes using a PCR technique targeting a polymorphic (ATAAA)n repeat sequence in the promoter region of the GSTP1 gene. Somatic GSTP1 CG island methylation changes were detected in DNA from 7 of the 10 PIN lesions. Allele discrimination was possible for 5 of the 10 DNA samples: 2 of the 5 samples exhibited DNA methylation changes at both alleles; whereas 3 samples displayed no DNA methylation changes at either allele. GSTP1 CG island methylation changes were present in each of the five homozygous samples. Hypermethylation of the 5'-regulatory region of the GSTP1 gene may serve as an important molecular genetic biomarker for both prostate cancer and PIN. The finding of frequent GSTP1 methylation changes in PIN and prostate cancer supports a role for PIN lesions as a prostate cancer precursor and may provide insight to the molecular pathogenesis of prostate cancer.

Adenocarcinoma↗
PubMed1997

Spx1, a novel X-linked homeobox gene expressed during spermatogenesis.

Spx1, a novel mouse homeobox gene, encodes a homeodomain characteristic of the paired-like class of homeobox genes and has been mapped to the distal end of the X chromosome. Northern blot hybridization of adult tissues detected high levels of a single Spx1 transcript in the testis. Further analysis by in situ hybridization revealed predominant Spx1 expression within the spermatogonia/preleptotene spermatocytes and round spermatids of spermatogenic stages IV-VII. These expression data suggest SPX1 may play a role in the regulation of spermatogenesis.

Amino Acid Sequence↗
PubMed1996

Intravenous ondansetron in established postoperative emesis in children. S3A-381 Study Group.

BACKGROUND: In pediatric postsurgical patients, postoperative vomiting is a common occurrence that can delay recovery and result in unplanned hospital admissions after outpatient surgery. This randomized, double-blind, placebo-controlled, multicenter study evaluated the efficacy and safety of ondansetron in the control of established postoperative emesis in outpatients aged 2-12 yr. METHODS: Screened for the study were 2,720 ASA physical status 1-3 children undergoing outpatient surgery during general anesthesia, which included nitrous oxide. Children experiencing two emetic episodes within 2 h of discontinuation of nitrous oxide were given intravenous ondansetron (n = 192; 0.1 mg/kg for children weighing < or = 40 kg; 4 mg for children weighing > 40 kg) or placebo (n = 183). RESULTS: The proportion of children with no emetic episodes and no use of rescue medication was significantly greater (P < 0.001) in the ondansetron group compared with placebo for both 2- and 24-h periods after study drug administration (78% of the ondansetron group and 34% of the placebo group for 2 h; 53% of the ondansetron group and 17% of the placebo group for 24 h). Among patients with at least one emetic episode or with rescue medication use, the median time to onset of emesis or rescue was 127 min in the ondansetron group compared with 58 min in the placebo group (P < 0.001). The median time from study drug administration until discharge was significantly shorter (P < 0.01) in the ondansetron group (153 min, range 44-593 min) compared with the placebo group (173 min, range 82-622 min). The incidence of potentially drug-related adverse events was similar in the ondansetron (3% of patients) and the placebo (4% of patients) groups. CONCLUSION: A single dose of ondansetron (0.1 mg/kg up to 4 mg) is effective and well tolerated in the prevention of further episodes of postoperative emesis in children after outpatient surgery. Administration of ondansetron also may result in a shorter time to discharge.

Antiemetics↗
PubMed1996

Temporal consistency and stability of three scales for measuring stress in adults.

We investigated the 30-min. temporal consistency and temporal stability of three focal scales for measuring stress: the Cognitive Anxiety Scale-State, the Focusing Inventory Scale-State, and the Somatic Symptom Scale-State. These scales are applicable for individually measured reduction in stress in research on outcome with older adolescents and adults. All possess excellent internal consistency. All manifested significant temporal consistency and good to excellent temporal stability over 30 min. in a nonclinical sample of 60 undergraduates. Small significant differences in means on the Cognitive Anxiety Scale-State and the Somatic Symptom Scale-State were noted. The phenomenological states associated with stress were stable and consistent over 30 min., the optimal time interval used in research on stress.

Adult↗
PubMed1995

Gsh-1: a novel murine homeobox gene expressed in the central nervous system.

We report the characterization of Gsh-1, a novel murine homeobox gene. Northern blot analysis revealed a transcript of approximately 2 kb in size present at embryonic days 10.5, 11.5, and 12.5 of development. The cDNA sequence encoded a proline rich motif, a polyalanine tract, and a homeodomain with strong homology to those encoded by the clustered Hox genes. The Gsh-1 expression pattern was determined for days E8.5 to E13.5 by whole mount and serial section in situ hybridizations. Gsh-1 transcription was restricted to the central nervous system. Expression is present in the neural tube and hindbrain as two continuous, bilaterally symmetrical stripes within neural epithelial tissue. In the mesencephalon, expression is seen as a band across the most anterior portion. There is also diencephalon expression in the anlagen of the thalamus and the hypothalamus as well as in the optic stalk, optic recess, and the ganglionic eminence. Moreover, through the use of fusion proteins containing the Gsh-1 homeodomain, we have determined the consensus DNA binding site of the Gsh-1 homeoprotein to be GCT/CA/CATTAG/A.

Amino Acid Sequence↗
PubMed1995

Gsh-2, a murine homeobox gene expressed in the developing brain.

A novel murine dispersed homeobox gene, designated Gsh-2, is described. Analysis of cDNA sequence, including the full open reading frame, reveals an encoded homeodomain that is surprisingly similar to those of the Antennapedia-type clustered Hox genes. In addition, the encoded protein includes polyhistidine and polyalanine tracts, as observed for several other genes of developmental significance. In situ hybridizations showed Gsh-2 expression in the developing central nervous system, including the ganglionic eminences of the forebrain, the diencephalon, which gives rise to the thalamus and hypothalamus, and in the hindbrain. Furthermore, a random oligonucleotide selection and PCR amplification procedure was used to define a target DNA binding sequence, CNAATTAG, as a first step towards the identification of downstream target genes.

Amino Acid Sequence↗
PubMed1995

Hoxa 11 structure, extensive antisense transcription, and function in male and female fertility.

Hoxa 11 is a murine Abdominal-B-type homeobox gene. The structure of this gene is presented, including genomic and cDNA sequence. The cDNA includes the complete open reading frame and based on primer extension results is near full length. Surprisingly, the antisense strand of Hoxa 11 was found to be transcribed. Moreover, these antisense transcripts were processed and polyadenylated. The developmental expression patterns for both sense and antisense transcripts were examined using serial section and whole-mount in situ hybridizations. Hoxa 11 transcription patterns were defined in the limbs, kidney and stromal cells surrounding the Mullerian and Wolffian ducts. Of particular interest, in the developing limbs, the sense and antisense transcripts showed complementary expression patterns, with antisense RNAs increasing in abundance in regions where sense RNAs were diminishing in abundance. Furthermore, targeted mutation of Hoxa 11 is shown to result in both male and female sterility. The female mutants produce normal ova, which develop properly post-fertilization when transferred to wild-type surrogate mothers. The Hoxa 11 homozygous mutants are shown to provide a defective uterine environment. The mutant males exhibited a malformation of the vas deferens that resembles a partial homeotic transformation to an epididymis. In addition, the mutant testes fail to descend properly into the scrotum and, likely as a result, spermatogenesis is perturbed.

Amino Acid Sequence↗
PubMed1994

Gsh-4 encodes a LIM-type homeodomain, is expressed in the developing central nervous system and is required for early postnatal survival.

We present an initial characterization of the murine Gsh-4 gene which is shown to encode a LIM-type homeodomain. Genes in this category are known to control late developmental cell-type specification events in simpler organisms. Whole mount and serial section in situ hybridizations show transient Gsh-4 expression in ventrolateral regions of the developing neural tube and hindbrain. Mice homozygous for a targeted mutation in Gsh-4 suffer early postnatal death resulting from immature lungs which do not inflate. Prenatal administration of progesterone and glucocorticoid, to extend gestational term and accelerate maturation, resulted in lung inflation at birth. Nevertheless, the hormonally treated mutants generally failed to survive beyond an hour after birth, due to ineffective breathing efforts. It is concluded that Gsh-4 plays a critical role in the development of respiratory control mechanisms and in the normal growth and maturation of the lung.

Amino Acid Sequence↗
PubMed1994

Estramustine sensitizes human glioblastoma cells to irradiation.

Estramustine is an estradiol-based antimicrotubule agent that accumulates in malignant glioma cells, resulting in a concentration-dependent inhibition of proliferation. This agent has been shown to synchronize human glioma cells at G2-M consistent with its known effects on the mitotic spindle and potentially could be used as a radiation enhancer. We determined the effects of estramustine on the cell cycle of glioblastoma cells by flow cytometry. These findings were compared with clonogenic survival in cells pretreated with varying concentrations of estramustine prior to irradiation. These experiments indicated that 24 h treatment with 1 microM estramustine had no effect on the percentage of G2-M cells and did not enhance the cytotoxic effects of radiation while 10 microM estramustine increased the G2-M fraction by 100% associated with a potentiation factor as high as 8.5 and a relative radiation sensitivity at 70% cytotoxicity of 5.2 compared with 15.4 for control cells. Estramustine can be administered p.o. on a daily schedule with minimal systemic toxicity. These data suggest that estramustine may be an effective radiation enhancer for glioblastoma.

Brain Neoplasms↗
PubMed1994

Behavioral and biological determinants of fecundability.

Our discussion has focused on a set of behavioral and physiological factors which influence fecundability. Some potentially important determinants are notable primarily because of their absence. Foremost among these determinants (as a group) are the male attributes. We have, by and large, ignored the links between male sexual behavior and hormonal profiles and the effects of hormones (or other factors) on sperm function. The fact that we have not reviewed them here does not imply that we believe that they are unimportant. Indeed, the effects of male factors may be particularly important because in some settings men are the predominant, if not the sole, decision-makers regarding reproductive behaviors including initiation of sexual intercourse and use of contraception. Also conspicuous by their absence are the effects of nutrition, consumption of alcohol, exercise, smoking, and behavioral and hormonal correlates of stress, all of which may affect fecundability. We have, though, reviewed a wide range of factors which contribute to fecundability and identified several points of potential interaction between the behavioral and biological determinants. We expect that our future understanding of these processes will be enhanced by empirical work and modeling efforts which also interact to draw upon the insights provided by each.

Behavior↗
PubMed1994

A multistate model of fecundability and sterility.

This paper develops a multistate hazards model for estimating fecundability and sterility from data on waiting times to conception. Important features of the model include separate sterile and nonsterile states, a distinction between preexisting sterility and sterility that begins after initiation of exposure, and log-normally distributed fecundability among nonsterile couples. Application of the model to data on first birth intervals from Taiwan, Sri Lanka, and the Amish shows that heterogeneity in fecundability is statistically significant at most ages, but that preexisting sterility and new sterility are unimportant before age 40. These results suggest that sterility may not be an important determinant of natural fertility until later reproductive ages.

Adolescent↗