Regional localization of the human epithelial membrane protein genes 1, 2, and 3 (EMP1, EMP2, EMP3) to 12p12.3, 16p13.2, and 19q13.3.
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Biomedical subjects
Publications and source records attributed to V Taylor.
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Recent studies have shown that, in addition to its role as an adhesion receptor, platelet endothelial cell adhesion molecule 1/CD31 becomes phosphorylated on tyrosine residues Y663 and Y686 and associates with protein tyrosine phosphatases SHP-1 and SHP-2. In this study, we screened for additional proteins which associate with phosphorylated platelet endothelial cell adhesion molecule 1, using surface plasmon resonance. We found that, besides SHP-1 and SHP-2, platelet endothelial cell adhesion molecule 1 binds the cytoplasmic signalling proteins SHIP and PLC-gamma1 via their Src homology 2 domains. Using two phosphopeptides, NSDVQpY663TEVQV and DTETVpY686SEVRK, we demonstrate differential binding of SHP-1, SHP-2, SHIP and PLC-gamma1. All four cytoplasmic signalling proteins directly associate with cellular platelet endothelial cell adhesion molecule 1, immunoprecipitated from pervanadate-stimulated THP-1 cells. These results suggest that overlapping immunoreceptor tyrosine-based inhibition motif/immunoreceptor tyrosine-based activation motif-like motifs within platelet endothelial cell adhesion molecule 1 mediate differential interactions between the Src homology 2 containing signalling proteins SHP-1, SHP-2, SHIP and PLC-gamma1.
Peripheral myelin protein 22 (PMP22) is an integral membrane protein that is essential for the normal formation and maintenance of peripheral myelin. Duplications, deletions, or mutations in the PMP22 gene account for a set of dominantly inherited peripheral neuropathies. The heterozygous Trembler-J (TrJ) genotype in mice is similar genetically to a Charcot-Marie-Tooth disease type 1A pedigree in humans, whereas the homozygous TrJ condition leads to the most severe form of PMP22-associated neuropathies. To characterize the consequences of the TrJ mutation, we labeled wild-type (wt-) and TrJ-PMP22 in the third loop of the protein with different epitope tags and expressed them separately or together in COS7 cells and primary Schwann cells. Here we show that the transport of the mutant TrJ-PMP22 is interrupted in the intermediate compartment, preventing its insertion into the plasma membrane and affecting the morphology of the endoplasmic reticulum. In addition, TrJ-PMP22 forms a heterodimer with the wt-PMP22. This interaction causes a fraction of the wt-PMP22 to be retained with TrJ-PMP22 in the intermediate compartment of COS7 and Schwann cells. The relative stability of a wt-mutant PMP22 heterodimer as compared with the wt-wt PMP22 homodimer may determine whether a particular mutation is semidominant or dominant. The neuropathy itself appears to result both from decreased trafficking of wt-PMP22 to the plasma membrane and from a toxic gain of function via the accumulation of wt- and TrJ-PMP22 in the intermediate compartment.
OBJECTIVE: The objective was to evaluate the effect of a clinic-based intervention program on mammography use by inner-city women. DESIGN: A randomized controlled trial employing firm system methodology was conducted. SETTING: The study setting was a general internal medicine clinic in the university-affiliated county hospital serving metropolitan Seattle. PARTICIPANTS: Women aged 50 to 74 years with at least one routine clinic appointment (when they were due for mammography) during the study period were enrolled in the trial (n = 314). INTERVENTIONS: The intervention program emphasized nursing involvement and included physician education, provider prompts, use of audiovisual and printed patient education materials, transportation assistance in the form of bus passes, preappointment telephone or postcard reminders, and rescheduling assistance. Control firm women received usual care. MEASUREMENTS AND MAIN RESULTS: Mammography completion within 8 weeks of clinic visits was significantly higher among intervention (49%) than control (22%) firm women (p < .001). These effects persisted after adjustment for potential confounding by age, race, medical insurance coverage, and previous mammography experience at the hospital (odds ratio 3.5; 95% confidence interval 1.9, 6.5). The intervention effect was modified by type of insurance coverage as well as prior mammography history. Process evaluation indicated that bus passes and rescheduling efforts did not contribute to the observed increases in screening participation. CONCLUSIONS: A clinic-based program incorporating physician education, provider prompts, patient education materials, and appointment reminders and emphasizing nursing involvement can facilitate adherence to breast cancer screening guidelines among inner-city women.
To assess predictors of reported performance of screening clinical breast examination (CBE) by internists, family physicians, and obstetrician/gynecologists, we surveyed members of these specialties in four counties of Washington State. We contacted all physicians in the counties and identified 334 providers who saw women ages 50-75 and provided primary care as their principal activity. Seventy-five percent (252 of 334) responded. Physicians were mailed a survey and contacted for telephone completion if they did not respond in writing. The survey inquired about their current performance of CBE and factors that might predispose, enable, or reinforce its use. Differences across specialties were assessed using the chi-square statistic. Factors associated with reported performance of screening CBE in > or =90% of women were evaluated using logistic regression. Fifty-one percent of physicians reported that they perform regular CBE on > or =90% of their patients, although the proportion varied across specialty type. Beliefs about the benefit of CBE were positive and similar across specialties. Twelve percent of male physicians, but no female physicians, reported that women's embarrassment affected their use of screening CBE. In a multivariate model, male gender, family practice specialty, and the perception of patient embarrassment were all associated with lower reported rates of performing regular CBE (p < 0.05). Work to increase the performance of CBE should consider the role of male physician embarrassment and family physician training. Ways to facilitate delivery of preventive care and factors influencing the women themselves may also be important to increased use of CBE.
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PECAM-1 (CD31) is a highly abundant cell surface glycoprotein expressed on haemopoietic and endothelial cells. As well as mediating homophilic (PECAM-1/PECAM-1) adhesion, PECAM-1 can also bind the integrin alphavbeta3. Both PECAM-1 and alphavbeta3 have been shown to have roles in regulating angiogenesis, endothelial tube formation and in the case of alphavbeta3, endothelial cell apoptosis. In this study we show that despite being expressed at equivalent levels, endothelial alphavbeta3 is not a ligand for PECAM-1. Rather, PECAM-1 supports homophilic binding on HUVEC with similar characteristics to those we have previously reported for leukocytes and becomes tyrosine phosphorylated after homophilic PECAM-1 and integrin/fibronectin engagement. Immunoprecipitation studies show that in addition to SHP-2, tyrosine phosphorylated PECAM-1 can interact with at least four other phosphoproteins in pervanadate stimulated HUVEC. While PECAM-1/PECAM-1 interactions support robust endothelial cell adhesion, they do not support cell spreading or migration. In addition PECAM-1 homophilic adhesion rescues HUVEC from serum deprivation-induced apoptosis. Taken together our results indicate that PECAM-1 homophilic interactions play an important role in interendothelial cell adhesion, survival and signalling.
OBJECTIVES: This study examined whether Asian American women with breast cancer have tumor characteristics associated with delayed detection of their disease. METHODS: Breast cancer size and stage were examined in relation to subjects' ethnic group and birthplace, on the basis of Surveillance, Epidemiology, and End Results program data. RESULTS: Asian-born Asian American women with breast cancer had a greater proportion of tumors larger than 1 cm at diagnosis (79%) than did US White women (70%) (P < .001). In contrast, the proportion of tumors larger than 1 cm among Asian American women born in the United States (67%) did not differ significantly from that among US White women. CONCLUSIONS: Lower utilization of breast cancer screening by Asian-born Asian American women is probably responsible for their greater proportion of tumors larger than 1 cm relative to US White women in the study population. Interventional measures should be taken to increase the use of mammographic screening by first-generation Asian American women.
We have identified and isolated a cDNA that codes for the novel protein NMP35 (neural membrane protein 35) using RNA arbitrarily primed PCR (RAP-PCR) for differential display in the developing rat sciatic nerve. NMP35 is predominantly found in the adult nervous system where both transcripts and protein are strongly upregulated during postnatal development. In situ hybridization studies show that NMP35 mRNA is widely distributed in the brain and spinal cord with a neuronal expression pattern. Database comparisons reveal that NMP35 shares significant homologies with the rat glutamate-binding protein (GBP), the Drosophila NMDARA1, and two orphan C. elegans genes. Comparative analysis of NMP35 and GBP expression indicates that they are similarly regulated during development and display regionally overlapping cellular patterns. We conclude that NMP35 and GBP are members of a gene family which is likely to play a role in the development and the maintenance of the nervous system.
BACKGROUND AND OBJECTIVES: Faculty development is an established method for increasing the number and effectiveness of faculty in family medicine. However, few published studies focus specifically on the use of faculty development to increase minority representation among faculty. Underrepresented minorities comprise 20% of the nation's population but only 3% of medical school faculty. In the entire nation, only 52 full-time teachers of family medicine are African-Americans. Morehouse School of Medicine has developed an effective model for training large numbers of underrepresented minority physicians to become academic family physicians. From 1993-1996, we trained 23 community-based physicians, three new faculty, six existing faculty, and three full-time fellows as teachers of family medicine. Of 35 participants, 33 were underrepresented minorities. Cultural issues in teaching and communication are an integral part of the curriculum. Seventy-three percent of graduates now teach medical students or residents either full-time or part-time. Further studies are needed to test the replicability of this model in non-minority institutions, as well as to achieve greater cost-effectiveness and improve academic outcomes such as publications and research. Significant faculty diversity is necessary and achievable, if institutions are willing to commit significant resources and network with minority health professionals and institutions.
EHK-1 is a neuronal ELK-related receptor tyrosine kinase which interacts with multiple, membrane-anchored ligands. Recent experiments have suggested a role for some of these ligands in the formation of neuronal pathways. Here, we report the isolation of human EHK-1 cDNAs and the localization of the human EHK-1 gene to chromosome 4q12. Six EHK-1 mRNA splice variants encoding cell-surface receptors with catalytic domains were identified in adult human brain where a 120-kDa EHK-1 protein predominates. Immunohistochemistry for EHK-1 reveals a dendritic staining pattern in cortical neurons and cerebellar Purkinje cells and a marked accumulation of EHK-1 in the somas of pyramidal neurons within the cortex and hippocampus. Interestingly, we have identified lineage aberrant expression of EHK-1 in a number of human gliomas. In addition to functions during development, EHK-1 may be involved in the maintenance of the adult nervous system and contribute to glioma development.
OBJECTIVES: In the face of escalating medical costs for injured workers, the Washington State Department of Labor and Industries (L&I), which pays for most workers' compensation costs in the state, established guidelines for elective lumbar fusion as part of its inpatient utilization review program. The guidelines were tied to reimbursement strictures. The authors attempt to assess the effects of these guidelines, which were introduced in November 1988, upon subsequent L&I fusion procedures. METHODS: Discharge data from the Comprehensive Hospital Abstract Reporting System and algorithms using International Classification of Diseases, Version 9, Clinical Modification diagnosis and procedure codes were used to identify lumbar surgical cases. Population estimates were from the 1990 US Census Bureau. RESULTS: During the period of years 1987 through 1992, the lumbar fusion rate for the state showed a 26% decline compared with a 3% decrease for all lumbar operations. After November 1988, when the guidelines went into effect, the state fusion rate declined 33%, whereas rates for nonfusion operations essentially were unchanged. The sharpest decline corresponded in time to implementation of the guidelines. Prior to the initiation of L&I guidelines, the proportion of fusions among L&I patients was higher than among non-L&I patients. The opposite was true by the end of 1992, and the L&I proportion decreased more rapidly than the non-L&I proportion. Time series analysis revealed that both the decline in Washington state lumbar fusion rates and the decline in the proportion of lumbar fusion among L&I patients were statistically significant. CONCLUSIONS: The data suggest that the L&I lumbar fusion surgery criteria and reimbursement standards implemented in 1988 contributed to a decline in rates of performing that procedure. The utilization review aspect of the guidelines as well as the process of involving surgeons in the preparation and dissemination of guidelines also may have been contributory.
OBJECTIVE: To investigate the protective efficacy of a pool of denatured membrane protein antigens of Mycoplasma hyopneumoniae (J strain) in the molecular size range 70 to 85 kDa (F3 antigen) in combination with adjuvants for pigs challenged with M hyopneumoniae. DESIGN: A vaccine efficacy experiment with assessment of serum and respiratory tract antibody responses. PROCEDURE: F3 antigens were emulsified with five different adjuvants. To groups of three pigs per vaccine, four vaccines were given by intramuscular injection, and two vaccines, including one of those given intramuscularly, were given by intraperitoneal injection. RESULTS: Compared to six unvaccinated pigs, animals vaccinated with F3 antigen displayed significantly reduced pneumonia (54% reduction in mean lung score) following experimental challenge. Analysis of post-vaccination, pre-challenge IgG and IgA ELISA antibody absorbances in serum and respiratory tract washings revealed no correlation with lung score. Six weeks after challenge, pigs previously vaccinated intramuscularly mostly demonstrated greater IgG and IgA responses in respiratory tract washings, and greater IgG serum antibody responses, than those vaccinated by intraperitoneal injection. CONCLUSION: Pigs vaccinated with M hyponeumoniae antigens in the molecular size range of 70 to 85 kDa showed a significant reduction in lung lesions compared with unvaccinated control animals after experimental challenge. IgG and IgA antibody concentrations in serum and respiratory tract washings after vaccination do not provide a useful prognostic indicator of protection from enzootic pneumonia.
Although overall use of mammography is steadily increasing, low-income and minority women consistently have relatively lower screening rates than white, middle-class women. To assess the mammography-seeking behavior of low-income women using an urban public hospital, this study sought to understand why women in this population decide whether or not to obtain a screening mammogram. Two qualitative techniques, elicitation interviews and focus groups, were used to develop an understanding of attitudes, concerns, and barriers of this group relative to mammography. Fear, embarrassment, susceptibility to breast cancer, inconvenience, cost, concerns about efficacy of mammography, fear of acquiring cancer, and scheduling difficulties were identified as important concerns. "People in the news" were the most influential social referents for mammography decision making, followed by physicians, family members, and friends. The insights gained from these women will assist in developing interventions that encourage mammography-seeking behavior by low-income women.
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Peripheral myelin protein 22 (PMP22) is expressed by Schwann cells in the peripheral nervous system (PNS), and mutations affecting the PMP22 gene are associated with hereditary motor and sensory neuropathies. We have previously defined the PMP22/EMP/MP20 gene family by characterizing the PMP22-related epithelial membrane protein-1 (EMP-1). We now report the identification of two additional members of the same family, epithelial membrane protein-2 and epithelial membrane protein-3 (EMP-2 and EMP-3). Both cDNA-predicted polypeptides share approx. 40% aa identity with PMP22. In human, EMP-2 and EMP-3 mRNA transcripts are found in most tissues with an expression pattern partially overlapping that of PMP22 and EMP-1. EMP-2 is most prominently expressed in the adult ovary, heart, lung and intestine and in fetal lung. The levels of EMP-3 transcripts are highest in peripheral blood leukocytes, ovary, intestine and various embryonic tissues. In contrast to PMP22 and EMP-1, EMP-2 and EMP-3 expression is detectable in the liver. In vitro transcription-translation generates EMP-2 and EMP-3 polypeptides of 18 kDa which is in agreement with their predicted sizes. Since PMP22 has been implicated in the regulation of cell proliferation and apoptosis, it appears likely that these novel members of the PMP22/EMP/MP20 protein family are also involved in similar regulatory processes in a variety of tissues.
The PMP22/EMP/MP20 gene family includes four closely related proteins, peripheral myelin protein-22 (PMP22), epithelial membrane protein-1 (EMP-1), epithelial membrane protein-2 (EMP-2), and epithelial membrane protein-3 (EMP-3), which share amino acid identities ranging from 33 to 43%. In addition, the lens-specific membrane protein MP20 represents a more distant relative. Functionally, this family of proteins is likely to play important roles in the control of cell proliferation, cell differentiation, and cell death. In particular, mutations affecting the PMP22 gene are responsible for various hereditary peripheral neuropathies in humans and mice. We report the isolation and characterization of a mouse EMP-1 cDNA and the corresponding emp-1 gene. Mouse EMP-1 displays 93% amino acid identity to rat EMP-1 and 39% identity to mouse PMP22. The cDNA-predicted EMP-1 protein contains four putative membrane-associated domains and can be N-linked glycosylated in vitro. EMP-1 is encoded by a single-copy gene with the positions of introns exactly conserved between emp-1 and PMP22, corroborating the hypothesis that both genes belong to the same family. Computer-predicted structural domains of EMP-1 are partially mirrored by the exon/intron structure of emp-1. Most interestingly, exon 4, which covers the potential second transmembrane domain, a small intracellular loop, and half of the third transmembrane domain, encodes the most highly conserved regions between the EMP-1 and PMP22 proteins and is also remarkably conserved in the MP20 gene, indicating some shared functional significance for this module in the PMP22/EMP/MP20 family.
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