Angiosarcoma arising in a testicular teratoma.
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Biomedical subjects
Publications and source records attributed to M Weinstein.
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PURPOSE: We report the findings of a transperineal magnetic resonance image (MRI) guided biopsy of the prostate in a man with increasing prostate specific antigen who was not a candidate for a transrectal ultrasound guided biopsy. MATERIALS AND METHODS: Using an open configuration 0.5 Tesla MRI scanner and pelvic coil, a random sextant sample was obtained under real time MRI guidance from the peripheral zone of the prostate gland as well as a single core from each MRI defined lesion. The patient had previously undergone proctocolectomy for ulcerative colitis and, therefore, was not a candidate for transrectal ultrasound guided biopsy. Prior attempts to make the diagnosis of prostate cancer using a transurethral approach were unsuccessful. RESULTS: The random sextant samples contained benign prostatic hyperplasia, whereas Gleason grade 3 + 3 = 6 adenocarcinoma was confirmed in 15% and 25% of the 2 cores obtained from the MRI targeted specimens of 2 defined lesions. The procedure was well tolerated by the patient. CONCLUSIONS: Transperineal MRI guided biopsy is a new technique that may be useful in detecting prostate cancer in men with increasing prostate specific antigen who are not candidates for transrectal ultrasound guided biopsy.
Fibroblast growth factor (FGF) receptors constitute a family of four membrane-spanning tyrosine kinases (FGFR1-4) which serve as high-affinity receptors for 17 growth factors (FGF1-17). To study functions of FGF/ FGFR signals in development, mice that carry mutations in each receptor have been created by gene targeting. Analysis of these mutant mice revealed essential functions of FGF receptors in multiple biological processes, including mesoderm induction and patterning, cell growth and migration, organ formation and bone growth. In this review we discuss recent work with FGF receptors to illustrate mechanisms, through which the FGF/FGFR signals specify vertebrate limb initiation, outgrowth and patterning.
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Decalcification during orthodontic treatment is a serious problem. A glass ionomer agent is now available to bond orthodontic brackets as an alternative to composite resins. This prospective study was a clinical trial to determine if a glass ionomer bonding system (Fuji Ortho LC) decreases the incidence of decalcification without increasing the amount of bonding failures. A prospective clinical trial with 16 patients encompassing a total of 298 teeth was conducted. The 149 control teeth were bonded with a light-cured composite resin (Reliance Light Bond) whereas the 149 experimental teeth were bonded with the light-cured glass ionomer agent. Patients were followed for a period of 12 to 14 months. All teeth were evaluated for breakage (bonding failure rate), and all maxillary anterior teeth (96) were evaluated for decalcification on a graded scale. The glass ionomer failure rate was 24.8%, and was higher than the composite resin failure rate of 7.4% (P <.001). There were more glass ionomer bond failures in 12 of 16 patients (P <.001). Enamel decalcification was similar in the 2 bonding systems.
Decalcification and caries during orthodontic treatment still remains a problem. A method to protect the susceptible area beneath and adjacent to bonded attachments, independent of patient compliance, would be extremely beneficial. A clinical trial was performed using a dual-cured lightly filled BIS-GMA fluoride-releasing sealant. The barrier effect of this material on white spot formation, gingival irritation, and plaque accumulation during fixed orthodontic therapy was examined. Twenty patients with a total of 225 metal brackets placed on anterior teeth participated in this study. Brackets were placed in both arches in a conventional manner with a chemically cured, unfilled bonding resin; 112 teeth (every other tooth) received the barrier material after bracket placement, while the remaining 113 teeth served as controls. Intraoral photographic slides were taken before and after treatment and were evaluated blindly by 7 observers for white spot formation. Gingival and plaque indexes were recorded initially and consecutively every 6 months. Observation time ranged from 5 to 18 months. The results of this prospective clinical study indicated that there was no significant difference (P >.05) between the decalcification rates of the treatment or control groups. Likewise there was no added benefit with respect to plaque accumulation or gingival irritation.
The generation of animals lacking SMAD proteins, which transduce signals from transforming growth factor-beta (TGF-beta), has made it possible to explore the contribution of the SMAD proteins to TGF-beta activity in vivo. Here we report that, in contrast to predictions made on the basis of the ability of exogenous TGF-beta to improve wound healing, Smad3-null (Smad3ex8/ex8) mice paradoxically show accelerated cutaneous wound healing compared with wild-type mice, characterized by an increased rate of re-epithelialization and significantly reduced local infiltration of monocytes. Smad3ex8/ex8 keratinocytes show altered patterns of growth and migration, and Smad3ex8/ex8 monocytes exhibit a selectively blunted chemotactic response to TGF-beta. These data are, to our knowledge, the first to implicate Smad3 in specific pathways of tissue repair and in the modulation of keratinocyte and monocyte function in vivo.
OBJECTIVE: The intensity and continuity of services delivered to individual clients in a community-based psychosocial rehabilitation program were examined in relationship to functional changes in the clients that occurred during the first 12 months of the program. METHODS: Subjects were 41 clients with schizophrenia or schizoaffective disorder who were admitted to an intensive psychosocial rehabilitation program. Measures of clinical and psychosocial functioning were derived from client interviews administered at baseline and six and 12 months later. Measures of service intensity and continuity came from data gathered daily by staff over 12 months. RESULTS: The results supported the hypotheses that greater intensity and longitudinal continuity of services are related to more client improvement as indicated by reduced rates of hospitalization and improved psychosocial functioning after both six and 12 months. Although clients' symptom levels increased over time, a significant relationship was noted between service intensity and continuity and better symptom outcomes after 12 months. Multiple regression analyses indicated that an average of 22 percent, and as much as 28 percent, of the change in clinical and functional outcomes after 12 months of rehabilitation was explained by the intensity and longitudinal continuity of services. CONCLUSIONS: Clients who received more contact hours with staff and who had fewer gaps in service delivery achieved greater rehabilitative improvement in social, work, and independent-living domains and had fewer days of hospitalization. Based on these findings, clinicians, administrators, and researchers can assume that the intensity and longitudinal continuity of services are important to achieving rehabilitative outcomes in some community-based psychosocial rehabilitation models.
The transforming growth factor-beta (TGF-beta) signals are mediated by a family of at least nine SMAD proteins, of which SMAD5 is thought to relay signals of the bone morphogenetic protein (BMP) pathway. To investigate the role of SMAD5 during vertebrate development and tumorigenesis, we disrupted the Smad5 gene by homologous recombination. We showed that Smad5 was expressed predominantly in mesenchyme and somites during embryogenesis, and in many tissues of the adult. Mice homozygous for the mutation died between days 10.5 and 11.5 of gestation due to defects in angiogenesis. The mutant yolk sacs lacked normal vasculature and had irregularly distributed blood cells, although they contained hematopoietic precursors capable of erythroid differentiation. Smad5 mutant embryos had enlarged blood vessels surrounded by decreased numbers of vascular smooth muscle cells, suffered massive apoptosis of mesenchymal cells, and were unable to direct angiogenesis in vitro. These data suggest that SMAD5 may regulate endothelium-mesenchyme interactions during angiogenesis and that it is essential for mesenchymal survival.
The present study examined the relationship between two measures of sustained attention on the Continuous Performance Test (reaction time and omission errors) and several performance measures on neuropsychological tests. Analysis suggests that sustained attention as measured by processing speed predicts performance on neuropsychological measures of relatively greater complexity and that the Stroop test, which requires maintaining steady focus on a changing stimulus field, may be more sensitive to lapses in attention than other neuropsychological tests.
The present study compared means of 54 nonpatients on two Continuous Performance Test measures in five administration conditions. Both response measures differentiated performance among the conditions, certain of which may have an alerting function that facilitates deployment of attention. Appreciable attentional demand or effort, however, may limit this facilitative effect.
We surveyed the 71 doctoral programs in counseling psychology approved by the American Psychological Association to examine whether and how group counseling or therapy was taught. Responses from 31 programs listed at least one graduate course in group counseling; over half offered more than one. In most cases the introductory course was required. Analysis also indicated that introductory courses often included an in-class or an out-of-class experiential component, focused either primarily or exclusively on outpatient therapy and used Yalom's interpersonal approach. Discussion focused on the importance of courses in group interventions in doctoral programs in counseling psychology and the differences and similarities in academic training of group interventions in programs in counseling and clinical psychology.
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Germline mutations of the Brcal gene are responsible for most cases of familial breast and ovarian cancers, but somatic mutations are rarely detected in sporadic events. Moreover, mouse embryos deficient for Brca1 have been shown to die during early embryogenesis due to a proliferation defect. These findings seem incompatible with the tumor suppress function assigned to this gene and raise questions about the mechanism by which Brca1 mutations cause tumorigenesis. We now directly demonstrate that BRCA1 is responsible for the integrity of the genome. Murine embryos carrying a Brca1 null mutation are developmentally retarded and hypersensitive to gamma-irradiation, suggesting a failure in DNA damage repair. This notion is supported by spectral karyotyping (SKY) of metaphase chromosomes, which display numerical and structural aberrations. However, massive chromosomal abnormalities are only observed when a p53-/- background is introduced. Thus, a p53 dependent cell cycle checkpoint arrests the mutant embryos and prevents the accumulation of damaged DNA. Brca1-/- fibroblasts are not viable, nor are Brca1-/-:p53-/- fibroblasts. However, proliferative foci arise from Brca1-/-: p53-/- cells, probably due to additional mutations that are a consequence of the accumulating DNA damage. We believe that the increased incidence of such additional mutations accounts for the mechanism of tumorigenesis associated with Brca1 mutations in humans.
smad genes constitute a family of nine members whose products serve as intracellular mediators of transforming growth factor beta signals. SMAD2, which is a tumor suppressor involved in colorectal and lung cancer, has been shown to induce dorsal mesoderm in Xenopus laevis in response to transforming growth factor beta and activins. The smad2 gene is expressed ubiquitously during murine embryogenesis and in many adult mouse tissues. Animals that lacked smad2 died before 8.5 days of development (E8.5). E6.5 homozygous mutants were smaller than controls, lacked the extraembryonic portion of the egg cylinder, and appeared strikingly similar to E6.5 smad4 mutants. This similarity was no longer evident at E7.5, however, because the smad2 mutants contained embryonic ectoderm within their interiors. Molecular analysis showed that smad2 mutant embryos did not undergo gastrulation or make mesoderm. The results demonstrate that smad2 is required for egg cylinder elongation, gastrulation, and mesoderm induction.
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