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Biomedical subjects

S Jackson

Publications and source records attributed to S Jackson.

At least 91 records · Page 5Linked to original sources
PubMed2000

Decreased insulin responsiveness of glucose uptake in cultured human skeletal muscle cells from insulin-resistant nondiabetic relatives of type 2 diabetic families.

To investigate the contribution of inherited biochemical defects to the peripheral insulin resistance of type 2 diabetes, we studied cultured skeletal muscle from 10 insulin-resistant nondiabetic first-degree relatives of type 2 diabetic families and 6 control subjects. Insulin stimulation of glucose uptake and glycogen synthesis was maximal in myoblasts. Insulin-stimulated glucose uptake (fold-stimulation over basal uptake) was decreased in relative compared with control myoblasts at 0.001 micromol/l (0.93 +/- 0.05 [mean +/- SE] vs. 1.15 +/- 0.06, P < 0.05) and 0.1 micromol/l (1.38 +/- 0.10 vs. 1.69 +/- 0.08, P = 0.025) insulin. Insulin responsiveness was markedly impaired in 5 of the relative myoblast cultures, and in 4 of these, there was an associated increase in basal glucose uptake (76.7 +/- 7.0 vs. 47.4 +/- 5.5 pmol x min(-1) x mg(-1) protein, relative vs. control; P < 0.02). Expression of insulin receptor substrate 1, phosphatidylinositol 3-kinase, protein kinase B, and glycogen synthase was normal in the relative cultures with impaired insulin responsiveness. Glycogen synthesis was also normal in the relative cultures. We conclude that the persistence of impaired insulin responsiveness in some of the relative cultures supports the role of inherited factors in the insulin resistance of type 2 diabetes and that the association with increased basal glucose uptake suggests that the 2 abnormalities may be linked.

Adult↗
PubMed2000

Role of the leucine-rich domain of platelet GPIbalpha in correct post-translational processing--the Nancy I Bernard-Soulier mutation expressed on CHO cells.

The mechanisms governing the biosynthesis and surface expression of platelet adhesive receptors on parent megakaryocytes are as yet poorly understood. In particular, the assembly and processing of the multisubunit glycoprotein (GP) Ib-IX-V complex, a receptor for von Willebrand factor (vWf) is not fully understood. In the present work, these questions were addressed by reproducing a natural mutation of GPIbalpha found in a variant case of Bernard-Soulier syndrome (Nancy I), due to the deletion of leucine 179 in the seventh leucine-rich repeat of the polypeptide. Wild type and mutated GPIbalpha were transfected into CHO cells expressing GPlbbeta and GPIX. Flow cytometry showed surface expression of the three subunits of both GPIb-IX complexes, but GPlbalphadeltaLeu was present at lower levels (20-40%) and was recognized only by a sub class of monoclonal antibodies which epitopes were not modified by the mutation. These properties reproduce the defect found in the patient's platelets, demonstrating the causative nature of the mutation and validate the use of the CHO cells model. Biochemical studies were performed in an attempt to elucidate the mechanism of the conformational change of GPIbalphadeltaLeu. They unexpectedly revealed a major glycosylation deficiency of the mutated GPIbalpha leading to a 40% decrease in molecular weight. The other two subunits of the complex were however normal and present at the plasma membrane. The deletion led to complete functional deficiency with lack of vWf binding of CHOalphadeltaLeu transfected cells in the presence of botrocetin and defective adhesion to a vWf coated surface under static conditions. Finally, in contrast to normal CHOalphabetaIX cells, which displayed rolling and deceleration when perfused over a vWf surface, CHOalphadeltaLeubetaIX cells were unable to roll over or attach to a vWf substratum. These results show that the integrity of the leucine-rich region of GPIbalpha is essential for normal processing and function of the GPIb-IX complex. In addition, these results obtained in a cellular system supported the suspected role of the macroglycopeptide region of GPIbalpha in maintaining a suitable conformation of this multisubunit receptor to perform its adhesive function.

Adolescent↗
PubMed2000

Phytochrome regulation of phytochrome A mRNA levels in the model short-day-plant Pharbitis nil.

The exposure of dark-grown Pharbitis nil seedlings to continuous R induces a rapid decrease in PHYA mRNA abundance with a half-life of about 2 h. A 5 min R pulse also induces this decline, and the effect is partially reversible by subsequent FR irradiation, confirming that the regulation of expression is mediated via the Pfr form of a phytochrome. When de-etiolated seedlings are returned to darkness after a W photoperiod, PHYA mRNA slowly reaccumulates from 20% to 50% of the dark level within 24 h. The rate of reaccumulation is greatly accelerated by the removal of Pfr with a FR pulse, resulting in reaccumulation to 100% within approximately 11 h. Without FR irradiation PHYA mRNA expression remains fully repressed for at least 11 h after the end of the photoperiod, suggesting that the controlling Pfr is highly stable.

Amino Acid Sequence↗
PubMed2000

Dichlorodiphenyldichloroethene, polychlorinated biphenyls, and breast cancer among African-American and white women in North Carolina.

We examined plasma dichlorodiphenyldichloroethene (DDE) and total polychlorinated biphenyl (PCB) levels in relation to breast cancer in a population-based, case-control study of African-American women (292 cases and 270 controls) and white women (456 cases and 389 controls) in North Carolina. Adjusted odds ratios (ORs) for breast cancer comparing the highest to lowest third of DDE were 1.41 [95% confidence interval (CI), 0.87-2.29] in African-American women and 0.98 (95% CI, 0.67-1.43) in white women. ORs comparing the highest to lowest third of total PCBs were 1.74 (95% CI, 1.00-3.01) in African-American women and 1.03 (95% CI, 0.68-1.56) in white women. Among African-Americans, the OR for total PCBs was highest for obese women (body mass index 234.2; OR, 4.92; 95% CI, 1.63-14.83). In contrast, the OR for DDE was highest for the leanest African-American women (body mass index, <25; OR, 3.84; 95% CI, 0.98-15.08). ORs for DDE were not elevated among women who lived or worked on farms or elevated among farming women who reported exposure to pesticides. Our results suggest absence of a strong effect for DDE or total PCBs in breast cancer but lend support for associations among subgroups of women. In our study, factors such as income, parity, breastfeeding, race/ethnicity, and body mass index influenced the relationship of organochlorines and breast cancer. Differing distributions of such factors may explain some of the inconsistencies across previous studies.

Adult↗
PubMed1999

Induction of autophagy and inhibition of tumorigenesis by beclin 1.

The process of autophagy, or bulk degradation of cellular proteins through an autophagosomic-lysosomal pathway, is important in normal growth control and may be defective in tumour cells. However, little is known about the genetic mediators of autophagy in mammalian cells or their role in tumour development. The mammalian gene encoding Beclin 1, a novel Bcl-2-interacting, coiled-coil protein, has structural similarity to the yeast autophagy gene, apg6/vps30, and is mono-allelically deleted in 40-75% of sporadic human breast cancers and ovarian cancers. Here we show, using gene-transfer techniques, that beclin 1 promotes autophagy in autophagy-defective yeast with a targeted disruption of agp6/vps30, and in human MCF7 breast carcinoma cells. The autophagy-promoting activity of beclin 1 in MCF7 cells is associated with inhibition of MCF7 cellular proliferation, in vitro clonigenicity and tumorigenesis in nude mice. Furthermore, endogenous Beclin 1 protein expression is frequently low in human breast epithelial carcinoma cell lines and tissue, but is expressed ubiquitously at high levels in normal breast epithelia. Thus, beclin 1 is a mammalian autophagy gene that can inhibit tumorigenesis and is expressed at decreased levels in human breast carcinoma. These findings suggest that decreased expression of autophagy proteins may contribute to the development or progression of breast and other human malignancies.

Animals↗
PubMed1999

Fc gamma receptor-mediated activation of phospholipase D regulates macrophage phagocytosis of IgG-opsonized particles.

Receptors for the Fc portion of IgG (Fc gamma Rs) integrate the innate and acquired components of immunity by coupling the specific recognition of IgG Abs to the activation of phagocytic leukocytes. Knowledge of the molecular mechanisms that regulate phagocyte stimulation by Fc gamma Rs may permit therapeutic modulation to augment immunoprotective aspects and minimize damage to host tissues in diverse inflammatory diseases. Since phospholipase D (PLD) has been linked to the stimulation of cytotoxic leukocyte responses, we characterized Fc gamma R-dependent activation of PLD in human macrophages. IgG-coated SRBCs (EIgG) stimulated a 9.4-fold increase in PLD activity compared with SRBCs treated with control Ab (p < 0. 001), determined by formation of the PLD-specific product phosphatidylethanol in the presence of 0.5% ethanol. Levels of phosphatidic acid, the physiologic product of PLD-mediated catalysis, were significantly increased in the absence of ethanol (6.4-fold, p < 0.001). PLD activity was also stimulated by immune complex-coated latex beads or cross-linking of Abs specific for Fc gamma RI, Fc gamma RII, or Fc gamma RIII. Phagocytosis of EIgG was reduced by two inhibitors of PLD-mediated signaling, 2,3-diphosphoglycerate or 1-butanol. Addition of purified PLD restored control levels of phagocytosis in cells in which endogenous PLD was inhibited. The tyrosine kinase inhibitors genistein and herbimycin A caused concordant reductions in Fc gamma R-stimulated PLD activity and phagocytosis. These studies demonstrate that Fc gamma R-mediated phagocytosis is accompanied by tyrosine kinase-dependent activation of PLD and support the hypothesis that stimulation of PLD functions to regulate the ingestion of IgG-opsonized particles.

Adult↗
PubMed1999

Prevention of falls in the elderly trial (PROFET): a randomised controlled trial.

BACKGROUND: Falls in elderly people are a common presenting complaint to accident and emergency departments. Current practice commonly focuses on the injury, with little systematic assessment of the underlying cause, functional consequences, and possibilities for future prevention. We undertook a randomised controlled study to assess the benefit of a structured inderdisciplinary assessment of people who have fallen in terms of further falls. METHODS: Eligible patients were aged 65 years and older, lived in the community, and presented to an accident and emergency department with a fall. Patients assigned to the intervention group (n=184) underwent a detailed medical and occupational-therapy assessment with referral to relevant services if indicated; those assigned to the control group (n=213) received usual care only. The analyses were by intention to treat. Follow-up data were collected every 4 months for 1 year. FINDINGS: At 12-month follow-up, 77% of both groups remained in the study. The total reported number of falls during this period was 183 in the intervention group compared with 510 in the control group (p=0.0002). The risk of falling was significantly reduced in the intervention group (odds ratio 0.39 [95% CI 0.23-0.66]) as was the risk of recurrent falls (0.33 [0.16-0.68]). In addition, the odds of admission to hospital were lower in the intervention group (0.61 [0.35-1.05]) whereas the decline in Barthel score with time was greater in the control group (p<0.00001). INTERPRETATION: The study shows that an interdisciplinary approach to this high-risk population can significantly decrease the risk of further falls and limit functional impairment.

Accidental Falls↗
PubMed1999

Acute chest syndrome in the postoperative sickle cell patient.

BACKGROUND/PURPOSE: Acute chest syndrome (ACS), a phenomenon of pulmonary sequestration in sickle cell disease (SCD) patients, is frequently missed in the postoperative SCD child. The constellation of symptoms range from fever and respiratory distress to abdominal discomfort. In its most fulminate state, the syndrome has been reported in some series to carry almost a 25% to 50% mortality rate in the postoperative patient. The incidence in pediatric patients in the era of minimally invasive surgery is unknown. METHODS: Since December 1995, 63 episodes of ACS have been documented in the nearly 500 SCD children seen at our institution. Six of 63 episodes occurred within 2 weeks after a surgical procedure under general anesthesia. During this period, 59 operations were performed by the pediatric surgery service on SCD patients with an ACS incidence of 10.2%. Careful review of the preoperative, intraoperative, and postoperative management of these patients was performed. RESULTS: All six received preoperative oxygen saturation monitoring and intravenous fluid (IVF) hydration. One half of these patients required transfusion to achieve a hemoglobin level of greater than 10 mg/dL. Documentation of intraoperative temperature, hypoxia, volume status, and hypercarbia as well as any atypical perioperative events were monitored and reviewed. All patients received postoperative oxygen supplementation and IVF hydration. Onset of ACS ranged from 1 hour to 7 days postoperatively. Only one of six was thought to be of microbial etiology (elevated mycoplasma titers), and all patients received prophylactic antibiotic and aggressive pulmonary therapy. Overall length of hospitalization was increased with an average stay of 6.1 days. There were no postsurgical ACS deaths. CONCLUSIONS: Despite close attention and avoidance of known risk factors for development of postoperative SCD complications, ACS occurred with an incidence much higher than previously reported in the literature (0.4% v 10.2%). Interestingly, five of six cases were after laparoscopic procedures suggesting that the advantages of laparoscopy, such as reduced postoperative pain, do not extrapolate to decreased incidence of ACS.

Adolescent↗
PubMed1999

Treatment of late-onset asthma with fluconazole.

BACKGROUND: Although the etiology of intrinsic or late-onset asthma is generally not known, some cases are associated with overt dermatophyte infection and immediate hypersensitivity to proteins derived from fungi of the genus Trichophyton. OBJECTIVE: We sought to test the efficacy of oral antifungal treatment for Trichophyton-induced asthma by using fluconazole in a placebo-controlled trial. METHODS: Eleven patients with severe or moderately severe asthma were randomized to treatment with fluconazole 100 mg daily or placebo for 5 months (phase 1); during the following 5 months, all patients received active drug (phase 2). Subjects were evaluated by skin tests, bronchial provocation tests, and measurement of serum antibodies to Trichophyton species antigens. Clinical response was monitored by changes in peak flow values measured during a 2-week period at the end of each phase and by changes in bronchial sensitivity, symptoms, and steroid requirements. RESULTS: At the end of the first 5 months of active treatment, there was a highly significant decrease in bronchial sensitivity to Trichophyton (P =.012) and in oral steroid requirement (P =.01). At the end of phase 2, mean peak expiratory flow rates increased in 9 of 11 patients. An improvement in symptoms, peak flow, and steroid use was maintained up to 36 months after starting fluconazole in patients who continued to receive treatment. CONCLUSION: The results show that fluconazole can be useful in the treatment of patients with severe or moderately severe asthma who have dermatophytosis. These findings are consistent with the argument that proteins derived from fungi on the skin and nails can contribute to allergic disease.

Adult↗
PubMed1999

Predicting abuse-prone parental attitudes and discipline practices in a nationally representative sample.

OBJECTIVE: According to sociological and ecological models of abuse, typically nonabusive parents could behave abusively towards their children under certain circumstances. The purpose of this study was to examine factors that place parents at risk of abusing their children by predicting parents' use of discipline practices and attitudes that may bias parents towards abusive behaviors, which we refer to as abuse-proneness. METHOD: A telephone interview was administered by the Gallup Organization to a nationally representative sample of 1,000 parents. Using a set of theoretically relevant risk factors, multiple regression was used to predict variations in parental attitudes (i.e., attitudes towards physical discipline and attitudes that devalue children) and parental discipline practices (i.e., physical discipline, nonphysical discipline, and verbal abuse). RESULTS: The findings confirmed the importance of examining elements of parental attitudes, history, personality characteristics, as well as religion and ideology in predicting abuse proneness. Child age also was an important predictor in all analyses except predicting parental attitudes that devalue children. The findings suggest also, however, that it may be unduly simplified to regard parents as somewhere on a continuum of nonpunitive to punitive disciplinarians. Social isolation was not a significant predictor in any of the analyses. CONCLUSIONS: Although many important theoretical predictors of abuse proneness were confirmed, many questions arise regarding the diversity of discipline practices that parents use, and the relevance of child's age and social isolation in predicting abuse proneness. Implications for practitioners and future research are discussed.

Adolescent↗
PubMed1999

Current knowledge in the management of children and adolescents with sickle cell disease: Part 1, Physiological issues.

This article reviews the current state of the knowledge in the management of children and adolescents with sickle cell disease (SCD). A thorough review of the literature concerning physiological issues including the clinical manifestations of SCD as well as current treatment modalities is included. Therapeutic management of health and illness for a child with SCD is discussed in relation to primary, secondary, and tertiary prevention. Recommendations for nursing practice and research are made.

Adolescent↗
PubMed1999

What are psychiatric nurses needed for? Developing a theory of essential nursing practice.

Contemporary developments in health care have encouraged a review of the professional status of psychiatric nursing. However, little study has been made, to date, of the discrete 'need' for psychiatric nursing within a multidisciplinary service. Employing an adapted grounded theory methodology, substantive theory was developed concerning the expressed need for psychiatric nursing, by patients, their carers and mental health professionals, based on six sites from England, Eire and Northern Ireland. The study found some consensus across both recipients and providers of mental health care, that the essential feature of nursing (the core category) involved a complex of relationships: 'knowing you--knowing me'. Within that complex, nurses either elected, or were required, to move--or 'toggle'--between three discrete domains of relating: the Ordinary Me (OM); the Pseudo-ordinary or Engineered Me (POEM); and the Professional Me (PM). Four internal dimensions involving the nurses' depth of knowing, power, use of time and use of translation, distinguished these domains. The emergent theory is discussed within the context of the emergent growth in user (consumer) influence and health care technology.

Attitude of Health Personnel↗
PubMed1999

The need for psychiatric nursing: towards a multidimensional theory of caring.

Contemporary developments in health care have encouraged a review of the professional status of psychiatric nursing. Although research has documented psychiatric nursing activity, little study has been made of the 'need' for psychiatric nursing within a multidisciplinary service. Employing adapted grounded theory methodology, substantive theory was developed concerning the expressed need for psychiatric nursing, by patients, their carers and mental health professionals. The study was based on six sites from England, Eire and Northern Ireland. The study found some consensus across both recipients and providers of mental health care, that the essential feature of nursing (the core category) involved a complex of relationships: 'knowing you, knowing me'. Within that complex, nurses either elected, or were required, to move--or 'toggle'--between three discrete domains of relating: the Ordinary Me (OM); the Pseudo-ordinary or Engineered Me (POEM); and the Professional Me (PM). Four internal dimensions involving the nurses' depth of knowing, power, use of time and use of translation distinguished these domains. The emergent theory extends current awareness of the importance of interpersonal relations in nursing. To what extent current health care policy, which emphasizes the promotion of alternative roles for nurses, will challenge this essential focus remains unclear.

Attitude of Health Personnel↗
PubMed1999

Keratin 15 expression in stratified epithelia: downregulation in activated keratinocytes.

Keratin 15 (K15) is a type I keratin without a defined type II partner whose expression in epidermal diseases has not been investigated. In this study we have used LHK15, a monoclonal antibody raised against the last 17 amino acids of the K15 polypeptide, to show that K15 is expressed primarily in the basal keratinocytes of stratified tissues, including the fetal epidermis and fetal nail. Although K15 in normal hair follicles was virtually absent from hair bulbs, it was expressed by a subset of keratinocytes in the outer root sheath. By comparison, K14 expression was found throughout the outer root sheath of hair follicles; however, when both K14 alleles were naturally ablated, the expression of K15 was also observed throughout the outer root sheath of the follicles. Expression of K15 mRNA was assessed by in situ hybridization and corroborated the data from immunostaining. An increase in K15 mRNA and protein expression in hair follicles from the K14 ablated epidermis suggested an upregulation of the K15 gene in the absence of the K14 protein. In organotypical cultures where differentiating keratinocytes expressed markers of activated phenotype, i.e., K6 and K16, expression of K15 was undetectable. The expression of K15 mRNA and protein was also downregulated in two hyperproliferating situations, psoriasis and hypertrophic scars. Because keratinocytes in psoriasis and hypertrophic scars are activated, we conclude that K15 expression is not compatible with keratinocyte activation and the K15 gene is downregulated to maintain the activated phenotype.

Adult↗
PubMed1999

Microsurgical reconstruction of the through-and-through defect in head and neck cancer: is it worth it?

As health resources diminish, there are compelling reasons to utilize health dollars in a fiscally responsible manner. The reconstruction of complex oromandibular defects involving mucosa, bone, and skin coverage poses one of the greatest challenges in microsurgery of the head and neck. The cancer patient who requires a through-and-through resection and microsurgical reconstruction usually has a poor prognosis. In this study, the authors examine whether this type of surgery is worthwhile in terms of cost, functional outcome, and patient satisfaction. Of 16 cases of through-and-through oromandibular reconstruction performed, the survival outcome of ten (n = 10) advanced cases requiring immediate oromandibular reconstruction (7 radial forearm flaps; 3 scapular flaps) is presented. Six cases were considered cured and required delayed reconstruction. Seven of the 10 patients died within 39 months postoperatively, while three survived up to 68 months postoperatively. The combined experience of these ten patients was examined using the Kaplan-Meier (product-limit) estimator of the survival curve. Results show that of the seven patients who died of disease, five did so within the first postoperative year. More important, among those five patients who survived for more than one postoperative year, three were still alive up to 68 months, representing a combined total of over 15 postoperative years. The probability of long-term survival is good in through-and-through oromandibular cancer patients who can survive to 1 year postoperatively, and it is proposed that microsurgical reconstruction, albeit costly, remains a worthwhile procedure,

Aged↗
PubMed1999

Studies of human immunodeficiency virus type 1 mucosal viral shedding and transmission in Kenya.

If human immunodeficiency virus type 1 (HIV-1) vaccines are to be highly effective, it is essential to understand the virologic factors that contribute to HIV-1 transmission. It is likely that transmission is determined, in part, by the genotype or phenotype (or both) of infectious virus present in the index case, which in turn will influence the quantity of virus that may be exchanged during sexual contact. Transmission may also depend on the fitness of the virus for replication in the exposed individual, which may be influenced by whether a virus encounters a target cell that is susceptible to infection by that specific variant. Of interest, our data suggest that the complexity of the virus that is transmitted may be different in female and male sexual exposures.

Adult↗