Nicotine and gastrointestinal disease.
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Biomedical subjects
Publications and source records attributed to J Green.
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Bovine and ovine pregnancy-associated glycoproteins-1 (PAG-1) are products of binucleate trophoblast cells and belong to the aspartic proteinase gene family. Estimates of their relative molecular masses have varied considerably, from 47 to 90 kDa, even though the mature polypeptide has been inferred to be no more than 330 amino acids in length and that the glycosylated recombinant form synthesized in Chinese hamster ovary (CHO) or COS-1 cells had an apparent mass of 46 kDa. To establish the relationships among the various molecular forms, metabolic labeling, immunoprecipitation, and electrophoretic analysis were used to follow the biosynthesis of ovine PAG-1 (ovPAG-1) in placental explants. In time-course studies, ovPAG-1 could first be detected within 10 min as a 70-kDa form within the tissue. With time, forms of intermediate (53-61 kDa) and low (47 kDa) molecular mass began to accumulate. The latter predominated in medium after 6 h labeling. Pulse chase studies established that the 70-kDa forms were the precursors of the smaller species. Inhibition of glycosylation with tunicamycin or treatment with N-glycosidase F confirmed that ovPAG-1 contained N-linked oligosaccharide chains, but that this carbohydrate accounted for only a relatively small fraction (8-10 kDa) of the apparent mass. Consecutive treatment with neuraminidase and O-glycanase also reduced the apparent molecular mass of the precursor by approximately 11 kDa. OvPAG-1 incorporated 32P from [32P]orthophosphate into phosphoserine and phosphothreonine, but there was no incorporation of 35S from [35S]sulfate. The basis of the differences in molecular mass between the precursor and the final products remains to be elucidated, but the differences seem likely to be due to some unusual form of posttranslational modification introduced in the binucleate cell. The results of the study appear to explain the disparate size values that have been reported for these placenta-derived proteins.
The ndh gene that encodes the non-proton-translocating NADH dehydrogenase II of Escherichia coli is anaerobically repressed by FNR. However, in the absence of FNR, ndh expression is enhanced by anaerobic growth in media containing amino acids. Two potential regulatory proteins that may be associated with this activation have previously been detected, Arr (amino acid response regulator) and Nbp (ndh-binding protein). Studies with the heat-stable Nbp have now shown that it is present in E. coli grown both aerobically and anaerobically in rich and minimal media, indicating that it is not specifically associated with the anaerobic enhancement of ndh expression. The Nbp activity of aerobic cultures was maximal during exponential growth phase (when ndh promoter activity is minimal) but fell rapidly as cultures entered stationary phase and ndh expression increased. Protein purification and mutant studies have further shown that Nbp is identical to the Fis protein (factor for inversion stimulation). Three major and two minor Nbp (Fis)-binding sites have been identified in the ndh promoter by gel retardation and DNase I footprinting. The major sites are centred at -123, -72 and +51, in decreasing order of binding affinity. At low concentrations, Nbp (Fis) increased transcription from the ndh promoter by up to 25%, whereas at higher concentrations it prevented RNA polymerase (RNAP) binding and open complex formation. Consequently, Nbp (Fis) can both activate and repress transcription from the ndh promoter. The results suggest that Nbp (Fis) serves to ensure that the energetically efficient proton-translocating NADH dehydrogenase I is used in preference to the non-proton translocating NADH dehydrogenase II during periods of rapid growth, by repressing expression of the ndh gene.
1. We investigated the nature of the adrenoceptors in the dog saphenous vein (DSV) and dog mesenteric vein (DMV) to determine the nature of the unexpected interactions of phenylephrine and methoxamine with rauwolscine in the DSV, i.e. the ability of the putative alpha 2-adrenoceptor antagonist to inhibit competitively contractions to these alpha 1-agonists. Radioligand binding studies were performed in parallel with contractility studies. 2. Functionally, in the DSV, phenylephrine and methoxamine-induced, contractions were antagonized by rauwolscine with Schild slopes of -0.52 and -0.46, respectively and apparent pA2 values of 8.5 and 9.2, respectively. Such antagonism was not observed in the DMV. In the DSV, prazosin competes for [3H]-rauwolscine binding sites with a high and a low affinity binding site (Ki of 1.49 +/- 0.65 and 94.7 +/- 51 microM, n = 6, respectively). 3. Pretreatment with 100 microM chloroethylclonidine (CEC) for 15 min abolished [3H]-prazosin binding in microsomes from both veins and reduced binding (Bmax) of [3H]-rauwolscine in microsomes by 55.1 +/- 0.8% (n = 3) in the DSV but did not affect the Bmax in the DMV. CEC pretreatment in the venular rings denuded of endothelium caused persistent contraction in the DSV but not in the DMV. In the DSV, CEC appeared to interact with a single [3H]-rauwolscine binding site. In both the DSV and the DMV, CEC (100 microM) caused a significant shift in the EC50 values for phenylephrine and methoxamine. Maximum responses in the DMV were significantly attenuated while those in the DSV were unaffected when total tension was considered. 4. Studies of the functional interactions of the DSV and the DMV with WB 4101 or 5-methylurapidil (5-MU) suggested the presence of alpha 1D-adrenoceptors in the DSV and alpha 1A-adrenoceptors in the DMV. The receptors inactivated by CEC in the DMV and DSV may represent some or all of the receptors with properties of alpha 1D and alpha 1A-receptors present in the two veins. Studies of radioligand binding interactions of these two antagonists with [3H]-prazosin, were consistent with the presence of some alpha 1D-receptors in DSV and alpha 1A-receptors in DMV. These findings raise questions about the selectivity of CEC in differentiating alpha 1-adrenoceptor subtypes. 5. B-HT 920 caused contractions in the DSV smaller than those to the alpha 1-agonists but the maximum was not affected by CEC pretreatment. The EC50 values were shifted to the left after CEC. In radioligand binding studies, B-HT 920 competition for [3H]-rauwolscine binding was not significantly affected by CEC pretreatment. 6. These results suggest the presence of unusual alpha-adrenoceptors in the DSV. In addition to alpha 2-adrenoceptors, receptors recognizing rauwolscine as well as prazosin, WB 4101, phenylephrine and methoxamine and susceptible to inactivation by CEC are present. They appear to be, in part, unusual alpha 1D-adrenoceptors.
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During the last two decades, health promotion has concentrated on lifestyle factors. However, recent research in genetics has shown that inherited susceptibility may be important in many common conditions. This raises questions about how these two different messages are integrated into people's beliefs about their own susceptibility. We report a study based on interviews with 58 young people, who had all recently completed the National Curriculum science course including basic human genetics, and 54 of their parents. We aimed to examine the extent to which people take account of family history when considering their susceptibility to health risks, with comparisons being made between generations, gender, and between different diseases. Family health histories were compared between generations and the relationship between reported family history and perceived vulnerability was examined. Family health history was seen as more relevant for a perceived vulnerability to heart disease and diabetes than cancer, while actions and behaviour were seen as important in determining the chance of developing heart disease and cancer but less so for diabetes. Chance was seen as an important factor in the risk of cancer and diabetes, but was barely mentioned in connection with heart disease. Nearly half of those who reported affected family members with heart disease or cancer did not perceive this to have any effect on their own susceptibility. Notably, women were much more likely than men to see the presence or absence of affected relatives as being relevant to the chances of developing cancer. Differences were found between generations in the reporting of the family tree and in knowledge of health of family members. Although words such as genes, chromosomes, and DNA were used by both generations there was no evidence of any understanding of the process of inheritance in scientific terms.
The physical creation of a gamma unit facility requires the development of a broad-perspective multidisciplinary plan. The primary goal is radiosurgical treatment of intracranial lesions in a functional environment. The practical realization of a facility optimally designed for patient treatment is dependent on factors which include the facility setting, architectural goals, radiation safety requirements, and patient and medical team needs. This necessitates combined intellectual resources from neurosurgery, radiation oncology and physics, anesthesia, radiology, nursing, administration, and architectural and engineering teams. We undertook the development of a gamma unit facility which optimized the ergonomics and efficiency of patient evaluation, care and treatment, given the instrument requirements. This general plan based on our experience can be used for the development of other gamma unit facilities.
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Osteocalcin (OC) is a bone-specific vitamin D- responsive protein that is developmentally expressed during osteoblast differentiation. In transient transfection assays, as little as approximately 0.1 kilobase (kb) of the OC proximal promoter is sufficient for basal expression. Because eukaryotic genes are packaged as nucleosomes that contribute to both chromatin organization and transcriptional control, we functionally examined the activity of OC promoter constructs within a chromatin context. ROS 17/2.8 osteosarcoma cells were stably transfected with a series of rat OC promoter-reporter constructs, containing progressive 5'-deletions. The results demonstrate that in contrast to transient transfection assays, the proximal 0.11-kb promoter is no longer active when integrated in the genome. Progressive gain of basal expression with 0.35-, 0.53-, and 0.72-kb promoters suggests that upstream sequences facilitate the formation of an appropriate higher order nuclear structure, thereby potentiating the activity of the chromosomally integrated proximal promoter elements. This is consistent with location of both deoxyribonuclease I (DNase I)-hypersensitive sites and nuclear matrix protein-DNA interaction sites in the osteocalcin promoter. Vitamin D responsiveness in the stably transfected cells is obtained with the inclusion of 0.53 kb or additional upstream promoter sequences. Therefore, these sequences satisfy the requirements for binding of basal and enhancer transcription factors as well as interactions between them within a chromatin context. Both maximal basal expression and maximal vitamin D responsiveness are obtained with cells carrying either the 0.72-kb or the 1.1-kb promoter fragment. Cells carrying the 1.1-kb promoter show DNase I hypersensitivity at both the basal promoter and the vitamin D response element-containing domains, locations that also exhibit DNase I hypersensitivity in the endogenous OC promoter. In addition, we have documented changes in the basal activity and vitamin D responsiveness of the stably integrated 1.1 kb promoter as a function of cell density-mediated growth inhibition, which is accompanied by up-regulation of bone phenotypic genes. Thus, important aspects of OC gene transcriptional regulation that cannot be investigated in transient transfection assays can be addressed using ROS 17/2.8 cells stably transfected with OC promoter-reporter constructs.
PTH-related protein activates a G protein-coupled PTH/PTHrP receptor in many cell types and produces diverse biological actions. To study the signal transduction events associated with biological activity of the PTH/PTHrP receptor in vascular smooth muscle, a principal PTHrP-responsive tissue, rat aortic smooth muscle cells (A10) were stably transfected with a plasmid encoding a PTH/PTHrP receptor and tested for ligand binding, PTHrP-(1-34)-induced cAMP levels, inositol phosphate production, and cytosolic calcium transients. Of nineteen G418-resistant lines recovered, all exhibited high affinity binding [approximately dissociation constant (Kd) > 10(-10)) of iodinated [Tyr36]hPTHrP(1-36)NH2 and ligand-induced cAMP accumulation (2- to 100-fold), which was directly proportional to PTH/PTHrP receptor number (range 4 x 10(3) to 7 x 10(7) sites/cell]. PTHrP had no effect on intracellular calcium or inositol phosphate formation in any cell line regardless of receptor number despite the presence of detectable G alpha q). Transient overexpression of individual G alpha q proteins (G alpha q, G alpha 11 or G alpha 14) into PTH/PTHrP receptor-expressing A10 cells conferred the ability of PTHrP to increase intracellular calcium and inositol phosphate formation. Ligand activation of the recombinant PTH/PTHrP receptor elicited appropriate downstream biological effects in A10 cells including inhibition of DNA synthesis and osteopontin messenger RNA (mRNA) expression. Thus, a single PTH/PTHrP receptor, though capable of coupling to different G proteins, signals exclusively through a cAMP-dependent pathway in vascular smooth muscle.
This study sought to identify the prevalence of unstable housing situations, and for whom they occurred, and to examine differences in health care utilization by housing status. Housing status and inpatient and outpatient health care utilization of 1,851 HIV-infected individuals was ascertained through interviews. Nine percent of respondents were in unstable housing situations. Unstable housing was associated with significantly lower functional status. The unstably housed were more likely to visit an emergency room (p < 0.05) and had fewer ambulatory visits than persons with stable housing (p < 0.03). They incurred nearly five more hospital days and their average hospitalization was approximately 1.5 days longer than the stably housed, although these differences were not significant. Utilization of ambulatory care is lower among unstably housed persons with HIV disease, which may have led to their increased reliance upon emergency rooms and hospitals. Helping HIV-infected individuals maintain adequate housing could reverse this pattern.
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That love promotes health surprises few people, yet the scientific study of love and physical health is in its infancy. Because love has many facets and is manifested in many ways, as described here, it was banned from Western science, which insisted on observable and simple independent variables. This article presents data indicating the salutary effects of love on physical health. These data are from several areas-psychology, sociology, medicine, epidemiology, and healing-and together form a foundation for understanding and enhancing love and its effects. Three processes are formulated to explain the health-promoting effects of love: psychophysiologic, psychophysical, and psychosocial/behavioral. Love is described as an energy by virtue of its capacity to produce effects.
BACKGROUND: The growing number of specialist services being provided within primary care has lead to the argument that this will reduce the clinical threshold for referrals to these clinics. AIM: The possibility that increasing the accessibility of primary care psychology services will reduce the threshold for referral was examined by comparing levels of psychological disturbance among patients seen by practice-based clinical psychologists with those attending outpatient clinics. METHOD: Psychological symptoms, distress, disruption in daily life and satisfaction with life were assessed using a questionnaire-based methodology. A consecutive series of 177 patients, assessed in a local general practice or an outpatient department across a wide range of urban locations, was studied over a fixed period. RESULTS: The study revealed equivalent levels of psychopathology within both specialist and primary care clinics. Of the overall sample, 79% were likely to merit a formal psychiatric diagnosis, relating primarily to mood disorder. Levels of subjective distress and life satisfaction were also equivalent at both service locations. CONCLUSION: The lack of evidence for a reduction in clinical threshold for referral within the primary care sample suggests that general practitioners' referral rates are similar regardless of whether practice-based clinical psychology services are available. This has implications for primary-care-led commissioning of mental health services.
Schwannomas (neurilemmomas) are neurogenic tumors that arise from the Schwann cells of the neural sheath. They are most often benign and solitary. Extracranial schwannomas are rare, and can be mistaken for metastatic disease or other non-neurogenic tumors. Ancient schwannoma is a rare variant of schwannoma with a course typical of a slow-growing benign tumor. Histologically, it can be confused with a malignant mesenchymal tumor. An unusual case of an ancient schwannoma of the submandibular gland is reported. The clinical, histological and surgical aspects of this tumor are discussed, and the literature regarding this rare entity is reviewed.
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Charting is an essential part of midwifery care. Charts are the backbones of our practice. As midwives, we talk and interact with many clients all the time. One way we can keep track of what we say and do with our women is by recording this information in the chart. The chart is considered a permanent record for the future; it ensures quality and continuity of care. Most importantly, it is a legal record.