Biomedical subjects
S Kane
Publications and source records attributed to S Kane.
Infantile hemangioendothelioma of the liver.
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Patient compliance and outcomes.
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EGF activates ErbB-2 and stimulates phosphatidylinositol 3-kinase in human airway smooth muscle cells.
The epidermal growth factor (EGF)-receptor (EGFR) family includes four homologous transmembrane receptor protein tyrosine kinases, EGFR, ErbB-2, ErbB-3, and ErbB-4. This receptor family plays a pivotal role in regulating cell proliferation, differentiation, and transformation. Ligand-induced activation of these receptors results in formation of homo- and heterodimers, which undergo transphosphorylation and transactivation. The aim of this study was to characterize the role of EGFR family members in signaling EGF-induced human airway smooth muscle (HASM) cell proliferation. Here, we show that EGF stimulates activation of EGFR and transactivation of ErbB-2 in quiescent HASM cells. Phosphatidylinositol (PI) 3-kinase, a critical signaling enzyme that modulates HASM cell growth, is preferentially associated with ErbB-2, and EGF-stimulated transactivation of ErbB-2 induces PI 3-kinase activation. ErbB-3 and ErbB-4 are present in HASM cells; however, EGF has no effect on their activation. Betacellulin, a ligand for EGFR, ErbB-3, and ErbB-4, induced DNA synthesis of HASM cells and stimulated signaling through the activation of EGFR and ErbB-2 but not of ErbB-3 and ErbB-4. Heregulin, a specific ligand for ErbB-3 and ErbB-4, did not effect DNA synthesis and did not activate its specific receptors. These data suggest that EGF imparts signals that involve activation of ErbB-2 and are associated with ErbB-2 PI 3-kinase activation. Despite the mRNA and protein expression of all members of the EGFR family, ligand-stimulated signaling induced activation of EGFR and ErbB-2 but not of ErbB-3 and ErbB-4.
The relationship of school breakfast to psychosocial and academic functioning: cross-sectional and longitudinal observations in an inner-city school sample.
OBJECTIVE: To determine if a relationship exists between participation in a school breakfast program and measures of psychosocial and academic functioning in school-aged children. METHODS: Information on participation in a school breakfast program, school record data, and in-depth interviews with parents and children were collected in 1 public school in Philadelphia, Pa, and 2 public schools in Baltimore, Md, prior to the implementation of a universally free (UF) breakfast program and again after the program had been in place for 4 months. One hundred thirty-three low-income students had complete data before and after the UF breakfast program on school breakfast participation and school-recorded measures, and 85 of these students had complete psychosocial interview data before and after the UF breakfast program. Teacher ratings of behavior before and after the UF breakfast program were available for 76 of these students. RESULTS: Schoolwide data showed that prior to the UF breakfast program, 240 (15%) of the 1627 students in the 3 schools were eating a school-supplied breakfast each day. Of the 133 students in the interview sample, 24 (18%) of the students ate a school-supplied breakfast often, 26 (20%) ate a school-supplied breakfast sometimes, and 83 (62%) ate a school-supplied breakfast rarely or never. Prior to the UF breakfast program, students who ate a school-supplied breakfast often or sometimes had significantly higher math scores and significantly lower scores on child-, parent-, and teacher-reported symptom questionnaires than children who ate a school-supplied breakfast rarely or never. At the end of the school term 4 months after the implementation of the UF breakfast program, school-supplied breakfast participation had nearly doubled and 429 (27%) of the 1612 children in the 3 schools were participating in the school breakfast program each day. In the interview sample, almost half of the children had increased their participation. Students who increased their participation in the school breakfast program had significantly greater increases in their math grades and significantly greater decreases in the rates of school absence and tardiness than children whose participation remained the same or decreased. Child and teacher ratings of psychosocial problems also decreased to a significantly greater degree for children with increased participation in the school breakfast program. CONCLUSION: Both cross-sectional and longitudinal data from this study provide strong evidence that higher rates of participation in school breakfast programs are associated in the short-term with improved student functioning on a broad range of psychosocial and academic measures.
The future of pediatric psychopharmacology.
The future of pediatric psychopharmacology will be a collaborative effort among the public, the federal government, the pharmaceutical industry, and clinical scientists. Clinical scientists and the NIH have initiated the process. The federal regulatory guidelines are in place but may need to be amended further to truly facilitate needed research. The pharmaceutical industry is making efforts to study medications in childhood psychiatric disorders. More new drugs are being tested in humans. Many of the new agents offer the promise of more clinical benefit with milder side effects. The future is indeed promising.
Motorbike toe: a toddler's sporting injury.
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Functional studies of human GLUT5: effect of pH on substrate selection and an analysis of substrate interactions.
The adsorption of D-fructose within the lumen of the human small intestine is thought to be mediated by the GLUT5 isoform of the human facilitative sugar transporter family. This isoform has been expressed in oocytes and shown to be capable of D-fructose transport. Some debate remains regarding the absolute substrate specificity of this isoform. To that end, we have undertaken an analysis of the functional properties of this protein when expressed in Xenopus oocytes. We have examined the pH dependence of transport activity, the ability to transport D-fructose versus deoxyglucose, and employed a range of sugar analogues to probe the nature of the exofacial substrate binding site. Our data show that the human GLUT5 isoform functions exclusively as a D-fructose transporter between pH 4.5 and 8. The Km for D-fructose was found to be 15 +/- 4 mM at pH 7. 5, and was relatively unaltered even at pH 4.5. Analysis of the effects of a range of compounds on GLUT5 function suggests that this isoform transports D-fructose preferentially in the furanose ring form.
Structure-function studies of the brain-type glucose transporter, GLUT3: alanine-scanning mutagenesis of putative transmembrane helix VIII and an investigation of the role of proline residues in transport catalysis.
The brain-type glucose transporter (GLUT3) is a high-affinity transporter for D-glucose and D-galactose and is a member of a family of mammalian sugar transporters, each of which are proposed to adopt a secondary structure containing 12 transmembrane helices. In an effort to understand structure-function relationships within such transporters, we have employed alanine-scanning mutagenesis to examine the functional importance of each residue within putative transmembrane helix VIII of the human GLUT3 isoform. Each residue in this helix was replaced individually with alanine, and the functional properties of the mutants were examined by microinjection of in vitro transcribed mRNA into Xenopus oocytes. We show that substitution of residues 305, 306, 308-314, and 316-325 with alanine had minimal effect on the functional activity of the transporter, as determined by measurement of the Km for deoxyglucose transport and the Ki for maltose. In contrast, Asn-315 > Ala-315 exhibited a significant increase in the Km for deoxyglucose independently of any effect on the Ki for maltose. This data suggests that, despite the strong sequence conservation in this helix among the GLUT family, no individual residue is absolutely required for transport catalysis by this isoform. We have also examined the role of proline residues in transport catalysis mediated by GLUT3. Substitution of Pro-203 (helix VI), Pro-206, Pro-209 (cytoplasmic loop between helices VI and VII), Pro-381, Pro-383 and Pro-385 (helix X), Pro-399 (intracellular loop between helices X and XI), or Pro-451 (in the carboxy terminus, close to the end of helix XII) with alanine did not change the Km for deoxyglucose transport for any mutant. However, both Pro-381 and Pro-385 when mutated to alanine exhibited a reduction in the Ki for cytochalasin B. In addition, the Ki for maltose inhibition of deoxyglucose transport was increased for mutants Pro206Ala, Pro381Ala, Pro383Ala, and Pro451Ala. These results will be discussed in terms of proposed structural models for the transporters.
Structure-function studies of the brain-type glucose transporter, GLUT3: alanine-scanning mutagenesis of putative transmembrane helix 8.
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Structure-function analysis of liver-type (GLUT2) and brain-type (GLUT3) glucose transporters: expression of chimeric transporters in Xenopus oocytes suggests an important role for putative transmembrane helix 7 in determining substrate selectivity.
The liver-type (GLUT2) and brain-type (GLUT3) human facilitative glucose transporters exhibit distinct kinetics (K(m) values for deoxyglucose transport of 11.2 +/- 1.1 and 1.4 +/- 0.06 mM, respectively) and patterns of substrate transport (GLUT2 is capable of D-fructose transport, GLUT3 is not) [Gould, G. W., Thomas, H. M., Jess, T. J., & Bell, G. I. (1991) Biochemistry 30, 5139-5145]. We have generated a range of chimeric glucose transporters composed of regions of GLUT2 and GLUT3 with a view to identifying the regions of the transporter which are involved in substrate recognition and binding. The functional characteristics of these chimeras were determined by expression in Xenopus oocytes after microinjection of cRNA. Replacement of the region from the start of putative transmembrane helix 7 to the C-terminus of GLUT3 with the corresponding region from GLUT2 results in a chimera with the ability to transport fructose and exhibits a K(m) for 2-deoxyglucose transport of close to that observed for wild-type GLUT2 (8.3 +/- 0.3 mM compared to 11.2 +/- 1.1 mM). Replacement of the region in GLUT3 from the end of helix 7 to the C-terminus with the corresponding region from GLUT2 resulted in a species which was unable to transport fructose and whose K(m) for 2-deoxyglucose was indistinguishable from wild-type GLUT3. We have determined the affinity for 2-deoxyglucose, D-fructose, and D-galactose of these and other chimeras. In addition, the Ki for maltose, a competitive inhibitor of 2-deoxyglucose transport, which binds to the exofacial sugar binding site was determined for these chimeras. The results obtained support a model in which the seventh putative transmembrane-spanning helix is intimately involved in the selection of transported substrate and in which this region plays an important role in determining the K(m) for 2-deoxyglucose. Additional data is presented which suggests that a region between the end of putative transmembrane helix 7 and the end of helix 10, together with sequences in the N-terminal half of the protein may also participate in substrate recognition and transport catalysis.
Hormonal regulation of the insulin-responsive glucose transporter, GLUT4: some recent advances.
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Clinical case presentation: orbital reconstruction after traumatic optic neuropathy.
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Mammalian glucose transporters: intracellular signalling and transporter translocation.
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Transport by capillary waves: Fluctuating Stokes drift.
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Cystic neoplasms of the pancreas: a heterogeneous disorder.
Cystic neoplasms of the pancreas are rare tumors with a relatively better prognosis as compared to other pancreatic cancers. They may be mistaken for pseudocysts. Seventeen patients who underwent surgical resection were analyzed. Seventy percent of the patients were females and 76.7% of the tumors were located in the tail of the pancreas. Preoperative diagnosis was made on the basis of ultrasonography and/or computed tomography findings in 60% of patients. Retrospective review of the imaging modalities revealed one or more findings suggestive of cystic neoplasms in 90% of the patients. These included multiloculated cysts, thickened cyst wall, intracystic mass or calcifications, and presence of liver metastasis. All the tumors were completely or partly excised. The final histopathological diagnosis was microcystic adenoma in 2, mucinous cyst adenoma in 1, papillary cystic neoplasm in 3, cystic neuroendocrine tumor in 5, and cystadenocarcinoma in 6. Of the 17 patients, 10 had malignant tumors. Seven patients with benign tumors and 3 patients with malignant tumors are disease free 12-30 months after resection. Cystic neoplasm must always be considered as a possibility when dealing with cystic lesions of the pancreas and a careful evaluation of ultrasonography and computed tomographic scan may give a clue to the diagnosis.
Use of patient care extenders in critical care nursing.
This article explores the implementation and use of patient care extenders in two critical care units. Experimentation and diversity in changing the care-delivery system were the forces motivating the management team to redesign the existing nursing care-delivery system. The impetuses for the change process were the use of the role of the registered nurse and cost containment. Two case studies will illustrate from a practical perspective how the change occurred. Although the same nurse manager was responsible administratively for the two units, the patient care extender models were implemented differently. This was based on the conviction that each unit is unique with regard to patients and staff needs. The first case study occurred in an 18-bed cardiac telemetry unit in which the patient extender care model was integrated with direct patient care activities of the unit. In the second case study, which occurred in a ten-bed cardiac care unit, the patient care extender was integrated with indirect patient care activities. The approach to this article is practical, and it is intended for units that may be dealing with these issues in these changing times in health care.
HIV, heroin and heterosexual relations.
This ethnographic study describes part of the social context in which heterosexual transmission of the human immunodeficiency virus (HIV) may be taking place. Based on interviews with sex partners of intravenous (IV) drug users in an urban, African American community of the United States, the study documents the personal experience of 35 men and women to show how living with one's own and/or one's partner's heroin habit may structure one's response to public health information and one's possibility of becoming infected with HIV. As described by sex partners of intravenous drug users, people who use heroin habitually are drawn into social networks that are loosely organized according to their preferred route of drug administration, i.e. 'shooters' (intravenous) and 'tooters' (intranasal), both of which tend to exclude 'squares' (non-use). Social divisions such as these may slow rates of HIV transmission to those outside the drug life. But nevertheless, as sex partners explain, there are many types of social and sexual exchanges taking place among shooters, tooters and squares, including but not limited to the exchange of bodily fluids. Ethnography analyzes discursive representations of such exchanges, filling in and questioning the empty categories of epidemiological prediction. How does risky behavior actually figure in the lives of individuals who happen to fall in the category of 'sex partner'? How is sexual behavior shaped by drug use behavior? Being sexually involved with an IV drug user for some years alters a person's relative position betwixt and between the drug subculture, on the one hand, and mainstream pursuits of family, work and church, on the other. Differences in personal need and group identity create conflicts. Couples in long-term relationships develop rules to manage these. But in which terms will they interpret and negotiate the new threat of AIDS? If the strategic aspect of discursive representations of experience is taken into account, and if discursive representations are interpreted within appropriate social and historical contexts, they can provide a rich source of material for understanding the social impact of the AIDS epidemic. Without this discursive dimension, analytic power to interpret seroprevalence data cross-culturally would be lacking. In addition, and independently of the problem of interpreting seroprevalence data, ethnographic analysis links local, culturally-specific meanings through which AIDS is interpreted to our understanding of AIDS as a global phenomena.