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D Cox

Publications and source records attributed to D Cox.

At least 19 recordsLinked to original sources
PubMed1992

Pentamidine: a non-peptide GPIIb/IIIa antagonist--in vitro studies on platelets from humans and other species.

In this paper we show that the non-peptide anti-parasite agent pentamidine is a broad spectrum anti-platelet agent with an IC50 of 1.1 microM in ADP-induced platelet aggregation in human platelet rich plasma (PRP). It had similar activity when collagen, arachidonic acid, platelet activating factor, thrombin and epinephrine were used. It had no effect on platelet intracellular cAMP levels. It inhibited 125I-fibrinogen, 125I-fibronectin and 125I-von Willebrand factor binding to ADP-activated fixed platelets with IC50 values of 160, 160 and 60 nM respectively. Pentamidine showed a high degree of species selectivity with slightly less activity in monkey and dog PRP and little activity in guinea pig, rabbit, rat and mouse PRP compared with human. This was similar to the other RGD analogues tested. This species specificity was shown to be dependent on the species of platelets and independent of the species of fibrinogen. Thus, pentamidine is a potent non-peptide inhibitor of fibrinogen binding to GPIIb/IIIa.

Amino Acid Sequence↗
PubMed1992

Quality of life measures in health care. I: Applications and issues in assessment.

Many clinicians remain unsure of the relevance of measuring quality of life to their clinical practice. In health economics quality of life measures have become the standard means of assessing the results of health care interventions and, more controversially, the means of prioritising funding; but they have many other applications. This article--the first of three on measuring quality of life--reviews the instruments available and their application in screening programmes, audit, health care research, and clinical trials. Using the appropriate instrument is essential if outcome measures are to be valid and clinically meaningful.

Clinical Protocols↗
PubMed1992

Transforming growth factors type-beta and dexamethasone attenuate group II phospholipase A2 gene expression by interleukin-1 and forskolin in rat mesangial cells.

Treatment of rat mesangial cells with interleukin-1 beta (IL-1 beta) and forskolin induced, in a synergistic fashion, the expression of group II phospholipase A2 (PLA2) mRNA, with subsequent increased synthesis and secretion of PLA2. In contrast, interleukin-6 did not increase PLA2 mRNA levels of PLA2 activity. Transforming growth factor (TGF) beta 1, TGF beta 2 and TGF beta 3 equipotently attenuated the IL-1 beta- and forskolin-induced elevation of PLA2 mRNA, as well as PLA2 synthesis and secretion. The glucocorticoid dexamethasone only partially suppressed the IL-1 beta- and forskolin-induced elevation of PLA2 mRNA, but totally inhibited PLA2 synthesis and secretion.

Animals↗
PubMed1992

Differential effect of transforming growth factor beta on the synthesis of Th1- and Th2-like lymphokines by human T lymphocytes.

(TGF)-beta is a pluripotent cytokine exerting differential effects on distinct components of the immune response. The present report, based on lymphokine determination in culture supernatants and Northern blot analysis of lymphokine mRNA, demonstrates that TGF-beta 2 markedly inhibits interleukin (IL)-4 and IL-5 synthesis by polyclonally activated human T cells in the absence of any significant effect on (IFN)-gamma, lymphotoxin or IL-2, suggesting a modulatory effect of TGF-beta 2 on the interferon Th1/Th2) balance of immune responses. The inhibitory effect of TGF-beta on IFN-gamma production by unfractionated peripheral blood mononuclear cells is likely to reflect the blunting of natural killer cell activation by TGF-beta.

Humans↗
PubMed1992

Modulation of human IgE synthesis by transforming growth factor-beta.

Exogenous transforming growth factor-beta 2 (TGF-beta 2) markedly inhibits the interleukin 4 (IL4)-stimulated synthesis of human IgE in three models where the B cell co-stimulation signals are contact dependent. This concerns T cell-dependent IgE production by (i) unfractionated peripheral blood mononuclear cells (PMBC) cultured with IL4 and (ii) highly purified B cells cocultured with irradiated EL4 thymoma cells in the presence of IL4 and phorbol myristate acetate, as well as monocyte-dependent IgE production by rigorously T cell-depleted PBMC cultured with IL4 and hydrocortisone. The suppression is not isotype specific. TGF-beta exerts its effect by inhibiting the proliferation of B cells and perhaps also the differentiation of proliferating B cells. However, at a later stage of differentiation, IgE B cells are refractory to the inhibitory effect of TGF-beta, as shown by the slight but significant increase of the spontaneous secretion of IgE by PBMC of atopic patients. This enhancement is due to the suppression of endogenous interferon-gamma production. Most interestingly the synthesis of IgE by highly purified B cells costimulated with IL4 and Epstein-Barr virus is unaffected by TGF-beta. It is concluded that TGF-beta mainly acts by inhibiting IL4-supported B cell proliferation; however, its effects depend upon the B cell costimulation signals that are required together with IL4 for the induction of IgE synthesis.

Antibody-Producing Cells↗
PubMed1992

Modest reduction of serum albumin in continuous ambulatory peritoneal dialysis patients is common and of no apparent clinical consequence.

It is commonly assumed that a reduction in serum albumin is a reliable sign of nutritional inadequacy affecting prognosis in continuous ambulatory peritoneal dialysis (CAPD) patients. We studied prospectively 19 patients starting CAPD and monitored them for a minimum of 15 months. Serum albumin, changes in dry weight, morbid events, and, where possible, protein catabolic rates (PCR) and urea nitrogen appearance (UNA) were determined. A modest reduction in serum albumin (25 to 33 g/L [2.5 to 3.3 g/dL]) was found in the majority of patients 3 months after starting CAPD, which persisted for 12 months. Most of these patients gained weight and were not hospitalized in that period. PCR and UNA values showed adequate nutrition. Two patients developed serious medical problems leading to clinical malnutrition and serum albumin rapidly falling below 20 g/L. A modest reduction in serum albumin (25 to 33 g/L) is common in healthy CAPD patients and, if stable, does not indicate a poor prognosis or nutritional inadequacy.

Female↗
PubMed1992

Fear of hypoglycemia: relationship to physical and psychological symptoms in patients with insulin-dependent diabetes mellitus.

Among diabetic patients, experience with hypoglycemia ranges from the unpleasant to the life threatening. The aversiveness of these episodes often results in fear. To examine the impact of hypoglycemia on fear, 69 patients with insulin-dependent diabetes mellitus completed the Behavior and Worry subscales of the Hypoglycemia Fear Survey along with measures of psychological symptoms, perceived stress, risk of future hypoglycemic episodes, and glycosylated hemoglobin. Behavior and Worry scores were positively related to psychological symptoms, perceived stress, and previous experiences with hypoglycemia. Fear was unrelated to glycosylated hemoglobin but was significantly higher for patients who had greater variability and lower mean daily blood glucose.

Adult↗
PubMed1992

Development of common cold symptoms following experimental rhinovirus infection is related to prior stressful life events.

Previous studies of rhinovirus infection indicate that about one third of the persons with confirmed viral infection do not show evidence of cold symptoms. Factors that determine which infected individuals will develop colds are not known. Using a rhinovirus inoculation protocol, the authors explored the possible role of recent life events, current mood, and perceived stress in the development of symptoms in individuals known to be infected. As part of a larger study, 17 subjects were exposed to a rhinovirus and were individually isolated for 5 consecutive days; cold symptoms, mucus weights, and tissue use were monitored on a daily basis during this period. Although all 17 subjects had confirmed rhinovirus infection, only 12 subjects developed clinical colds, as indicated by self-reported symptoms and by objective symptom indices. The average number of reported major life events for the previous year was significantly higher for those who developed colds than for those who did not (p < .05). Measures of affect and perceived stress before the inoculation were not different for those who did and did not develop colds. Complementing recent research demonstrating psychosocial influences on experimental infection rates, these results provide evidence that the development of cold symptomatology in experimentally infected individuals is related to prior life events.

Adolescent↗
PubMed1992

Targeted disruption of the ABP-120 gene leads to cells with altered motility.

The actin-binding protein ABP-120 has been proposed to play a role in cross-linking F-actin filaments during pseudopod formation in motile Dictyostelium amebas. We have tested this hypothesis by analyzing the phenotype of mutant cell lines which do not produce ABP-120. Two different transformation vectors capable of targeted disruption of the ABP-120 gene locus have been constructed using a portion of an ABP-120 cDNA clone. Three independent cell lines with different disruption events have been obtained after transformation of amebas with these vectors. The disruption of the ABP-120 gene by vector sequences results in either the production of a small amount of truncated ABP-120 or no detectable protein at all. The phenotypes of two different clones lacking ABP-120, generated in strains AX3 and AX4, have been characterized and show identical results. ABP-120- cells tend to remain rounder before and after cAMP stimulation, and do not reextend pseudopods normally after rapid addition of cAMP. In addition, ABP-120- cells translocating in buffer exhibit defects in both the rate and extent of pseudopod formation. The amount of F-actin cross-linked into the cytoskeleton after cAMP stimulation of ABP-120- cells is reduced at times when ABP-120 has been shown to be incorporated into the cytoskeleton, and this correlates temporally with the absence of reextension of pseudopods after cAMP stimulation. The instantaneous velocity is significantly reduced both before and after cAMP stimulation in the ABP-120- cells, and the cells show decreased chemotactic efficiency compared to ABP-120+ controls. This phenotype is consistent with a role for ABP-120 in pseudopod extension by cross-linking actin filaments as proposed by the "cortical expansion model" (Condeelis, J., A. Bresnick, M. Demma, C. Dharmawardhane, R. Eddy, A. L. Hall, R. Sauterer, and V. Warren. 1990. Dev. Genet. 11:333-340).

Actins↗
PubMed1992

The replicative restriction of lymphocytotropic isolates of HIV-1 in macrophages is overcome by TGF-beta.

In vitro exposure of human blood monocyte-derived macrophages to T-cell tropic human immunodeficiency virus (HIV) isolates fails to establish a productive viral infection. Several studies have shown that such preferential HIV-1 replication in T cells or in mononuclear phagocytes (HIV tropism) may be determined by distinct viral characteristics. In the present study it was demonstrated that transforming growth factor-beta (TGF-beta), a factor known to be produced by platelets, macrophages, and other cells present at a wound site, can act as a mediator in overcoming the lymphocytotropic restriction of several well-characterized viral isolates of HIV-1 (i.e., LAV, Z84, pLAI, NY5). Macrophages infected with these isolates show cytopathic changes comparable to those seen upon infection with the monocytotropic isolate ADA. To achieve this effect with TGF-beta, the factor must be present after the infection period. The emerging virus retains its original cellular tropism. Based on these observations the authors propose a role for TGF-beta in the establishment and progression of HIV infection and disease.

Cells, Cultured↗
PubMed1992

Dementia and the nursing home: association with care needs.

OBJECTIVE: To determine whether RUG reimbursement categories accurately predict requirements for care in nursing homes. DESIGN: Prospective descriptive study of residents in lower reimbursement categories according to RUG. SETTING: Three nursing homes in New York City. PARTICIPANTS: Convenience sample of 173 residents who agreed to participate, not significantly different from 201 who did not agree to participate. MAIN MEASURES: Chart review; assessment of residents' cognitive and functional abilities; nursing assistants' ratings of residents' functional abilities, behavioral problems, the amount of effort required in care; and time-motion studies of staff-resident interactions. RESULTS: Both the residents' RUG classification (P less than 0.01) and the level of ADL independence (P less than 0.001) had significant impacts on the staff effort required in their care, with more dependent residents requiring greater effort. The residents' level of cognitive impairment also had a significant impact on the staff effort, with the severely impaired requiring greater effort (P less than 0.05). The time-motion analysis indicated that residents within the same RUG category differed in the number of staff-resident interactions based on their level of cognitive impairment. CONCLUSIONS: Cognitive impairment is a significant morbidity (or co-morbidity) in determining the quantity of staff effort required by the resident, and behavioral interventions are an important care component. There is marked heterogeneity within lower (RUG) reimbursement categories which translates into strikingly different care requirements.

Activities of Daily Living↗
PubMed1992

Muscle and nerve dysfunction in rats with experimental galactosaemia.

The effects of up to 4 months dietary supplementation with 40% galactose on muscle and nerve function were examined in rats. Galactitol, a polyol pathway metabolite, accumulated to high levels in both tissues. This led to changes similar to those found in experimental diabetes, which were largely prevented by treatment with an inhibitor of the first enzyme in the pathway, aldose reductase. For fast twitch extensor digitorum longus muscle there was weight loss, fibre damage, slowing of twitch time to peak, increased twitch tension, and reduced tetanic tension. There were no relaxation deficits. For slow twitch soleus there were no changes in tension production. However, contraction and relaxation for both twitch and tetanus were prolonged. Fatigue resistance was reduced after 1 week. Damage in soleus led to a reduction in mean fibre area after 2 months, which largely recovered by 4 months. There was a selective loss of fast oxidative glycolytic fibres. Histochemical staining for succinic dehydrogenase was normal in galactosaemic soleus, in contrast to the marked reduction seen in diabetes. Sciatic nerve conduction velocity was reduced after 2 months, particularly in normally fast conducting motor and sensory fibres. Resistance to hypoxic conduction block was increased in galactosaemic nerves to diabetic levels. It was concluded that polyol pathway hyperactivity is likely to contribute to the aetiology of diabetic myopathy and neuropathy, and that experimental galactosaemia provides a good model in which to study pathway effects without the complicated hormonal changes found in diabetes.

Adenosine Triphosphatases↗
PubMed1991

In vitro effect of transforming growth factor-beta on progression of HIV-1 infection in primary mononuclear phagocytes.

In vitro-differentiated monocytes can be infected with the monocytotropic isolate of HIV-1/ADA. The infection is characterized by formation of giant cells and production of virus that can be found in cell supernatants or cell-associated. In this study, we demonstrate that the above described parameters of infection can be enhanced by a factor present in acidified M phi supernatants, suggesting that it might be transforming growth factor beta-1 (TGF-beta 1). When recombinant or purified TGF-beta were examined, similar activities were detected. This effect apparently is not because of changes in the cellular phenotype that could favor infection. The effect of TGF-beta is exerted on cells once infection is established or on cells with active virus production. The activity can be also demonstrated using U-937 cells.

Cells, Cultured↗
PubMed1991

The intra-operative use of trasylol (aprotinin) in liver transplantation.

Aprotinin has been reported to reduce blood loss in difficult cases requiring cardiopulmonary bypass surgery and more recently in liver transplantation. Over a 9-month period we compared the effects of an intra-operative infusion of aprotinin on transfusion requirements and coagulation profiles in 12 patients undergoing liver transplantation for end-stage cirrhosis with an equal number of consecutive transplants in patients with similar pathology who did not receive aprotinin. Transfusion of blood and blood products was reduced to one-third in the aprotinin-treated group. Operative time was also significantly reduced, as was ICU stay post-operatively. Aprotinin profoundly inhibits fibrinolysis and this is likely to be the major effect by which blood loss is reduced. Thromboelastography revealed severe fibrinolytic changes in the anhepatic stage in 4 of 6 controlled patients; this accelerated in 3 following reperfusion of the new graft. By contrast, only 1 patient of 12 in the aprotinin-treated group showed fibrinolytic activity in the anhepatic period, and none showed evidence of fibrinolysis following reperfusion of the new graft.

Aprotinin↗