'Red Flags': essential factors in recognizing serious spinal pathology.
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Diagnosis, Differential↗
Biomedical subjects
G Greene
Publications and source records attributed to G Greene.
Distribution analysis of the two chicken estrogen receptor-alpha isoforms and their transcripts in the hypothalamus and anterior pituitary gland.
Estrogen plays a key role in the control of reproductive behavior and in the regulation of the neuroendocrine system. To elucidate the mechanisms by which it controls these functions it is important to understand how estrogenic effects are mediated. We have investigated the distribution of the two isoforms of the chicken estrogen receptor alpha (cER-alpha) protein; the previously characterized cER-alpha 66 and a new N-terminal truncated isoform, cER-alpha 61. Immunolocalization demonstrated the presence of cER-alpha 66 protein in hypothalamic areas, principally the nucleus septalis lateralis, bed nucleus striae terminalis medialis, nucleus preopticus medialis, and nucleus infundibuli hypothalami, and in the anterior pituitary gland. When the distribution of ER-alpha immunoreactive cells was compared using the antibodies H 222 (directed against the hormone-binding domain) and ER 221 (directed against the 21-amino acid N-terminus), no apparent differences could be detected. Because this immunocytochemical approach was not able to distinguish whether full-length cER-alpha 66 is the only isoform observed in the ER-positive regions or whether both cER-alpha receptor isoforms are present, SI nuclease assays were performed to compare the relative abundance in these regions of the two distinct classes of cER-alpha mRNA variants (A1-D and A2), which encode the cER-alpha 66 and cER-alpha 61 protein isoforms, respectively. In cockerels and hens, both variants of cER-alpha mRNA are expressed in the anterior pituitary gland and basal hypothalamus with a dominance of the mRNA that encodes cER-alpha 66, whereas the mRNA that encodes cER-alpha 61 was not detectable in the anterior hypothalamus. Therefore, because both receptor isoforms differ in their ability to modulate estrogen target gene expression in a promoter and cell type-specific manner, these differences may mediate the pleiotropic actions of estrogen in reproductive behavior and neuroendocrine functions.
Animals↗
A novel mitogen-activated protein kinase is responsive to Raf and mediates growth factor specificity.
The proto-oncogene Raf is a major regulator of growth and differentiation. Previous studies from a number of laboratories indicate that Raf activates a signaling pathway that is independent of the classic MEK1,2-ERK1,2 cascade. However, no other signaling cascade downstream of Raf has been identified. We describe a new member of the mitogen-activated protein kinase family, p97, an ERK5-related kinase that is activated and Raf associated when cells are stimulated by Raf. Furthermore, p97 is selectively responsive to different growth factors, providing a mechanism for specificity in cellular signaling. Thus, p97 is activated by the neurogenic factor fibroblast growth factor (FGF) but not the mitogenic factor epidermal growth factor (EGF) in neuronal cells. Conversely, the related kinase ERK5 is activated by EGF but not FGF. p97 phosphorylates transcription factors such as Elk-1 and Ets-2 but not MEF2C at transactivating sites, whereas ERK5 phosphorylates MEF2C but not Elk-1 or Ets-2. Finally, p97 is expressed in a number of cell types including primary neural and NIH 3T3 cells. Taken together, these results identify a new signaling pathway that is distinct from the classic Raf-MEK1,2-ERK1,2 kinase cascade and can be selectively stimulated by growth factors that produce discrete biological outcomes.
Animals↗
Low-bandwidth, Internet-based videoconferencing for physical rehabilitation consultations.
Low-bandwidth, Internet-based videoconferencing was used to provide physical rehabilitation consultation services for eight community hospitals. Videoconferencing and file transmission used a PC and modem. A separate telephone line was used for voice. Over 21 months, 47 physical rehabilitation consultations were completed for communication disorders, foot care, gait problems, orthotics, prosthetics, arm weakness and wheelchair prescription. Consultations were approximately 40 min long. Clinician questionnaires were completed by 47 individuals. While more than 80% of the questionnaire responses supported the telemedicine approach, remote clinicians rated their satisfaction higher than did the specialists. Client questionnaires were completed by 24 individuals (a response rate of 51%). All clients were comfortable with and had confidence in the teleconsultations.
Attitude of Health Personnel↗
The role of teaching the doctor-patient relationship in medical education.
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Clinical Clerkship↗
Oestrogen receptor function at classical and alternative response elements.
The oestrogen receptor (ER), bound to classical response elements (EREs) in the promoter of target genes, activates transcription by recruiting coactivator proteins. We will describe structural studies that show that oestrogens allow the formation of a hydrophobic cleft on the surface of the ER that serves as a docking site for coactivators. Anti-oestrogens displace part of the receptor, which then occludes the site, blocking coactivator access. In addition to activating at classical EREs, the ER activates transcription at alternative elements such as AP-1 sites. These bind the Jun/Fos proteins but not ER. Interestingly both oestrogen and tamoxifen activate transcription at AP-1 sites. We propose a mechanism whereby oestrogen and anti-oestrogen allow ER to activate transcription from alternative response elements. ER binds to the coactivators, CBP and GRIP1, that have been recruited by Jun/Fos and through this contact 'triggers' these coactivators into full activity. In this circumstance the ER is part of the coactivator complex for Jun/Fos.
Animals↗
A biopsychosocial approach to finding common ground in the clinical encounter.
PURPOSE: Little is known about how clinicians find common ground in conflicts with their patients or how educators can teach physicians-in-training to do so. The authors set out to create a conceptual model for the process of finding common ground. METHOD: Students in a third-year family practice clerkship wrote up cases they had encountered in which conflicts arose in the patient-doctor relationship. The authors analyzed these cases, first independently and then collectively. After several iterations, they arrived at a model grounded in the case material. RESULTS: The authors suggest that a modification of the biopsychosocial model first proposed by Engel and later updated by McWhinney is an appropriate and practical schema for classifying sources of conflict. This hierarchical system consists of five levels: (1) individual patient, (2) relationship between patient and physician, (3) patient's family, (4) ethnic belief systems of patient and family, and (5) political economy. CONCLUSION: This hierarchical, multilevel biopsychosocial approach allows the clinician to identify the level in the system at which a conflict has arisen. This clarifies the strategies for resolution, making it easier for patient and doctor to find common ground. This may also be a useful heuristic model for teaching such skills to physicians-in-training.
Aged↗
Technical evaluation of a low-bandwidth, Internet-based system for teleconsultations.
A low-bandwidth telemedicine system was evaluated in eight community hospitals connected to a central hospital via the Internet. PCs were used with videoconferencing software and modem connections to the telephone network. The average data connection rates, still-image transfer times and live-video transmission rates were determined. The time to send 640 x 480, 320 x 240 and 160 x 120 pixel, 24-bit still images ranged from 29 s to 411 s. The average file transfer times for a 10 s MPEG video-clip was 8.6 min. The average live video frame rate was 1 frame/s (at the best image quality), with an average latency of 3 s. The results suggest that Internet-based videoconferencing is acceptable for certain telemedicine applications.
Canada↗
A man with inflamed ears.
A 23-year-old man presented with fever, dyspnea, nonproductive cough, left eye redness, reduced vision, and bilateral ear pain and tenderness. The symptoms had begun two days earlier, eight days after he was discharged from the hospital with a presumptive diagnosis of Still's disease. He was first seen a month before the current admission for complaints of fever (as high as 39.4 degrees C), nonproductive cough, and asymmetric arthritis. The workup at that time included arthrocentesis of the right knee. Analysis of the joint fluid showed 7,500 white blood cells/mm3 and no crystals. A gram stain and culture of the fluid were negative. HIV and hepatitis tests, bone marrow biopsy and culture, transesophageal echocardiography, abdominal computed tomography, radionuclide bone scanning, and rheumatologic tests failed to identify the problem. The development of an evanescent macular pink rash on day 15 suggested the possibility of Still's disease. Treatment with prednisone (40 mg po qd) was initiated, and the patient was discharged on day 19.
Adult↗
Suppression of angiogenesis, tumorigenicity, and metastasis by human prostate cancer cells engineered to produce interferon-beta.
We determined whether the IFN-beta gene can be used to suppress angiogenesis, tumor growth, and metastasis of human prostate cancer cells growing in the prostate of nude mice. Highly metastatic PC-3M human prostate cancer cells were engineered to constitutively produce murine IFN-beta subsequent to infection with a retroviral vector containing murine IFN-beta cDNA. Parental (PC-3M-P), control vector-transduced (PC-3M-Neo), and IFN-beta-transduced (PC-3M-IFN-beta) cells were injected into the prostate (orthotopic) or subcutis (ectopic) of nude mice. PC-3M-P and PC-3M-Neo cells produced rapidly growing tumors and regional lymph node metastases, whereas PC-3M-IFN-beta cells did not. PC-3M-IFN-beta cells also suppressed the tumorigenicity of bystander nontransduced prostate cancer cells. PC-3M-IFN-beta cells produced small tumors (3-5 mm in diameter) in nude mice treated with anti-asialo GM1 antibodies and in severe combined immunodeficient/Beige mice. Immunohistochemical staining revealed that PC-3M-IFN-beta tumors were homogeneously infiltrated by macrophages, whereas control tumors contained fewer macrophages at their periphery. Most tumor cells in the control tumors were stained positive by an antibody to proliferative cell nuclear antigen; very few were positively stained by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling. In sharp contrast, PC-3M-IFN-beta tumors contained fewer proliferative cell nuclear antigen-positive cells and many terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling-positive cells. Staining with antibody against CD31 showed that control tumors contained more blood vessels than PC-3M-IFN-beta tumors. PC-3M-IFN-beta cells were more sensitive to lysis mediated by natural killer cells in vitro or to cytostasis mediated by macrophages than control transduced cells. Conditioned medium from PC-3M-IFN-beta cells augmented splenic cell-mediated cytolysis to control tumor cells, which could be neutralized by antibody against IFN-beta. Collectively, the data suggest that the suppression of tumorigenicity and metastasis of PC-3M-IFN-beta cells is due to inhibition of angiogenesis and activation of host effector cells.
Animals↗
Rural health professionals' satisfaction with a rehabilitation mobile outreach program.
OBJECTIVE: To assess the extent to which rural physicians and allied health professionals are satisfied with consultation services provided by an interdisciplinary rehabilitation outreach team. DESIGN: Descriptive survey. SETTING: A rehabilitation outreach team that travels to 14 rural communities in eastern and northern Ontario, Canada. SUBJECTS: Thirty-six rural physicians (response rate, 53.7%) and 62 allied health professionals (response rate, 92.5%) involved in the care of patients referred to the program. MAIN OUTCOME MEASURE: Consumer satisfaction questionnaire. RESULTS: Most respondents (94.7%) indicated that they were satisfied with the interdisciplinary consultation, with comparable rates of satisfaction reported by physicians and allied health professionals. The highest satisfaction ratings were given to items addressing the clarity of recommendations provided by team members and the quality of the team's interaction with patients. The lowest ratings were associated with the waiting time between visits. Of all the individual disciplines on the team, physiatry was rated as most important for rural consultations. However, in open-ended comments, respondents indicated that the interdisciplinary aspect of the service was its most valued characteristic, whereas infrequent visits were the greatest drawback. CONCLUSION: The interdisciplinary outreach approach to rehabilitation consultation receives high satisfaction ratings from rural health professionals who refer patients to the outreach team, which supports this model as a way to enhance rehabilitation services in rural communities.
Aged↗
Body weight, body composition, and energy intake changes in breastfeeding mothers.
Body weight, body composition, and energy intake changes are described for 13 breastfeeding mothers followed for 18-24 months after delivery. Body weight was assessed at 1-6, 9, 12, 18, 24 months postpartum and 1 month after infant weaning, and energy intake was assessed at 2-6, 9, 12, 18, 24 months postpartum and 1 month after infant weaning. Compared to prepregnancy weight, participants were an average of 4.0 +/- 6.6 kg heavier 18 months postpartum (p < 0.05). The mean rate of weight loss from 1 month postpartum until termination of lactation was 0.32 +/- 0.27 kg/month. Eight of the 12 women gained weight after weaning their infant. Percent body fat assessed by underwater weighing declined from 34.6 +/- 2.8% at 1 month postpartum to 31.4 +/- 4.8% at 1 month after infant weaning (p < 0.05). Further research is needed to study the factors which affect weight loss postpartum, and how weight gain after weaning can be prevented.
Adult↗
A dazed and disoriented man found by the roadside.
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Adult↗
Apoptosis resistance increases with metastatic potential in cells of the human LNCaP prostate carcinoma line.
The aim of this study was to determine whether stable differences in apoptosis sensitivity were selected for in nonmetastatic and metastatic variants of the LNCaP human prostate carcinoma line that had been isolated from tumors grown orthotopically in the prostate glands and regional lymph nodes of nude mice. The nonmetastatic LNCaP-Pro5 cells were significantly more sensitive to thapsigargin-induced apoptosis than were the metastatic LNCaP-LN3 cells, as measured by viability, DNA fragmentation, and interleukin 1beta-converting enzyme family-mediated cleavage of the DNA repair enzyme, poly(ADP-ribose) polymerase. Apoptosis resistance in the metastatic cells was associated with higher levels of expression of the cell death suppressor BCL-2 and lower levels of the death promoters BAX and BAK than were detected in the nonmetastatic LNCaP-Pro5 cells, whereas levels of two other BCL-2 family members (BCL-X(L) and BAD) were indistinguishable. Our data support the hypothesis that apoptosis resistance contributes to prostate cancer metastasis and that elevated expression of BCL-2 is involved.
Animals↗
Cellular and subcellular studies of the radiation effects of Auger electron-emitting estrogens.
We studied the effect of 123I-labeled estrogen (123I-E) in estrogen receptor (ER)-rich cells in culture and in cell free model systems in vitro to elucidate the nature of the radiotoxicity for ER + cells of estrogens containing nuclides which emit Auger electrons. In cells the 123I-E caused a dose-dependent, unlabeled estrogen-inhibitable induction of chromosome aberrations. A dose of about 1000 decays per cell, which is approximately the mean lethal dose for these cells, resulted in an average of 1 chromosome break per cell. This supports the hypothesis that the lethal lesion induced by 123I-E is a chromosome break. Incubation of 123I-E/ER complex, but not 123I-E alone, with 27-mer duplex estrogen response element (ERE) DNA produced a dose-dependent cleavage of the ERE. However, we were unable to detect any fragmentation of either the 66 kDa full length ER in cell extracts or a purified 31 kDa hormone binding domain when incubated with excess 123I-E. Thus it appears that 123I-E effects its radiotoxicity by binding to ER, associating with ERE DNA and, by directing high LET radiation to DNA, inducing lethal chromosome breaks.
Animals↗
Selection of highly metastatic variants of different human prostatic carcinomas using orthotopic implantation in nude mice.
The purpose of this study was to determine whether the implantation of human prostate cancer cells into the prostates of nude mice and their subsequent growth there can be used to select variants with increasing metastatic potential. PC-3M and LNCaP cells were injected into the prostates of athymic mice. Tumors from the prostate or lymph nodes were harvested, and cells were reinjected into the prostate. This cycle was repeated three to five times to yield cell lines PC-3M-Pro4, PC-3M-LN4, LNCaP-Pro3-5, and LNCaP-LN3-4. Parental and variant cells were injected into the prostates of nude mice. PC-3M-LN4 cells produced enhanced regional lymph node and distant organ metastasis as compared to PC-3M-Pro4 or PC-3M cells. After i.v. or intracardiac inoculation, PC-3M-LN4 cells produced a higher incidence of lung metastasis and bone metastasis, respectively, than PC-3M or PC-3M-Pro4 cells. Subsequent to implantation into the prostate, LNCaP-LN3 cells produced a higher incidence of regional lymph node metastases than LNCaP-Pro5 or LNCaP cells. After intrasplenic implantation, LNCaP-LN3 cells also yielded experimental liver metastases. The metastatic LNCaP-LN3 cells exhibited clonal karyotypic abnormalities, were less sensitive to androgen (in vitro and in vivo), and produced high levels of prostate-specific antigen. Collectively, the data show that the orthotopic implantation of human prostate cancer cell lines in nude mice is a relevant model with which to study the biology of prostate cancer metastasis and to select variant cell lines with enhanced metastatic potential.
Animals↗
Consumer satisfaction with a rehabilitation mobile outreach program.
Accessibility to rehabilitation services is often difficult for people with disabilities who live in rural areas. This study examined consumer satisfaction with a rehabilitation outreach approach that utilizes a mobile clinic to provide consultation services. The descriptive survey took place in fifteen rural communities in eastern and northeastern Ontario, Canada. Valid postconsultation mail surveys were completed by 143 consecutive patients with mixed diagnoses (or proxy family members) who had been seen during mobile clinic visits to their home communities (85.1% of patients approached). There were 59 men and 84 women, with an average age of 58.7 years. The main outcome measure was a consumer satisfaction scale. A high level of global satisfaction was reported, with 97.2% of respondents reporting a preference for community outreach over the alternative of traveling to an urban rehabilitation center. Enhanced accessibility was considered to be the major advantage of the outreach program, but concerns about the continuity of care were also expressed. Providing interdisciplinary rehabilitation consultation services on an outreach basis is associated with a high level of consumer satisfaction. From a consumer perspective, the outreach approach seems to be a viable way of addressing some of the rehabilitation needs of rural people with disabilities.
Persons with Disabilities↗
Isolation of the human peroxisome proliferator activated receptor gamma cDNA: expression in hematopoietic cells and chromosomal mapping.
The nuclear receptor superfamily of transcription factors, which includes the retinoic acid receptors and v-erb A, play important roles in the molecular control of hematopoiesis. To identify nuclear receptors expressed in hematopoietic cells, we screened a human bone marrow cDNA library using a degenerate oligonucleotide and isolated a 1.85-kb full-length cDNA encoding a new human member of this superfamily, the peroxisome proliferator activated receptor gamma (hPPAR gamma). Two different hPPAR gamma transcripts were expressed in hematopoietic cells: a 1.85-kb transcript, which corresponds to the full-length mRNA (PPAR gamma 1), and a 0.65-kb transcript (PPAR gamma 2), which cannot encode all of the nuclear receptor functional domains. Normal neutrophils and peripheral blood lymphocytes, as well as circulating leukemic cells from patients with AML, ALL, and CML, express only PPAR gamma 2 on Northern blot analysis. In contrast, only the PPAR gamma 1 transcript was detected in a variety of human leukemia cell lines and in cultured normal primary bone marrow stromal cells. Both transcripts were detected in various fetal and adult nonhematopoietic tissues. We mapped the location of the hPPAR gamma gene to human chromosome 3p25 by somatic cell hybridization and linkage analysis. PPARs have been shown to be activated by peroxisome proliferating agents, long-chain fatty acids and arachidonic acid. Human PPAR gamma, although homologous to the PPAR gamma s of other species, has unique sequence and amino acid differences. Identification of hPPAR gamma will allow further understanding of its role in human cellular leukotriene, prostaglandin, and peroxide degradative or synthetic pathways, as well as its role in lipid metabolism and regulation of adipocyte differentiation.
Adult↗