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P Scott

Publications and source records attributed to P Scott.

At least 37 records · Page 2Linked to original sources
PubMed2000

IL-4-independent inhibition of IL-12 responsiveness during Leishmania amazonensis infection.

Leishmania amazonensis induces a nonhealing infection in C3H mice, whereas infection with Leishmania major is self-healing. We found that C3H mice infected with L. amazonensis exhibited decreased IL-12 production, which could account for the susceptibility to this organism. However, exogenous IL-12 administration failed to induce a healing immune response. The failure of L. amazonensis-infected C3H mice to respond to IL-12 was associated with a specific defect in IL-12 receptor beta2 (IL-12Rbeta2) mRNA expression by CD4+ T cells. Furthermore, decreased IL-12Rbeta2 mRNA expression correlated with a decrease in the IL-12-signaling capacity of the lymph node (LN) cells. IL-4 did not contribute to susceptibility or down-regulation of the IL-12Rbeta2 subunit, because IL-4-/- mice remained susceptible to L. amazonensis infection, even after IL-12 administration, and CD4+ cells from infected IL-4-/- mice also had reduced expression of IL-12Rbeta2 mRNA. These results demonstrate that regulation of the IL-12 receptor, independent of IL-4, is a point of control for the immune response to leishmaniasis. In contrast to experimental L. major infections, where host genetics control susceptibility, these studies demonstrate that the lack of IL-12 responsiveness may be dictated by the pathogen, rather than the host.

Animals↗
PubMed2000

Maintenance of IL-12-responsive CD4+ T cells during a Th2 response in Leishmania major-infected mice.

BALB/c and anti-IL-12-treated C3H mice infected with Leishmania major develop a Th2 cell response. However, in contrast to BALB/c mice, C3H mice treated transiently with an anti-IL-12 monoclonal antibody switch from a Th2 to a Th1 response and resolve their lesions once treatment is terminated. We report here that the critical difference in the Th2 response between BALB/c and C3H mice is in their ability to respond to IL-12. Thus, C3H mice with a Th2 response maintain a CD4+ T cell population that expresses IL-12 receptor beta1 and beta2 mRNA and produces IFN-gamma after exposure to IL-12. These results indicate that Th2 cell populations from different genetic backgrounds differ in their stability, and that this difference can be related to differential regulation of the IL-12 receptor.

Animals↗
PubMed2000

Photosynthetic carbon metabolism in leaves of transgenic tobacco (Nicotiana tabacum L.) containing decreased amounts of fructose 2,6-bisphosphate.

The aim of this work was to examine the role of fructose 2,6-bisphosphate (Fru-2,6-P2) in photosynthetic carbon partitioning. The amount of Fru-2,6-P2 in leaves of tobacco (Nicotiana tabacum L. cv. Samsun) was reduced by introduction of a modified mammalian gene encoding a functional fructose-2,6-bisphosphatase (EC 3.1.3.46). Expression of this gene in transgenic plants reduced the Fru-2,6-P2 content of darkened leaves to between 54% and 80% of that in untransformed plants. During the first 30 min of photosynthesis sucrose accumulated more rapidly in the transgenic lines than in the untransformed plants, whereas starch production was slower in the transgenic plants. On illumination, the proportion of 14CO2 converted to sucrose was greater in leaf disks of transgenic lines possessing reduced amounts of Fru-2,6-P2 than in those of the control plants, and there was a corresponding decrease in the proportion of carbon assimilated to starch in the transgenic lines. Furthermore, plants with smaller amounts of Fru-2,6-P2 had lower rates of net CO2 assimilation. In illuminated leaves, decreasing the amount of Fru-2,6-P2 resulted in greater amounts of hexose phosphates, but smaller amounts of 3-phosphoglycerate and dihydroxyacetone phosphate. These differences are interpreted in terms of decreased inhibition of cytosolic fructose-1,6-bisphosphatase resulting from the lowered Fru-2,6-P2 content. The data provide direct evidence for the importance of Fru-2,6-P2 in co-ordinating chloroplastic and cytosolic carbohydrate metabolism in leaves in the light.

Base Sequence↗
PubMed2000

Evaluation of the calcium-sensing receptor gene in idiopathic hypercalciuria and calcium nephrolithiasis.

BACKGROUND: Calcium urolithiasis is in part genetically determined and associated with idiopathic hypercalciuria. METHODS: We have used a candidate gene approach to determine whether the calcium-sensing receptor (CaR) gene is linked to idiopathic hypercalciuria and calcium urolithiasis in a cohort of French Canadian sibships with multiple affected members (64 sibships from 55 pedigrees yielding 359 affected sibling pairs with > or =1 stone episode). RESULTS: Using nonparametric linkage analysis with various intragenic and flanking markers, we showed that the CaR gene could be excluded as a major gene for hypercalciuric stone formation. We excluded the CaR (lod score <-2) at lambdas values of 1.5, 1.68, and 2.6 for sib pairs concordant for at least one stone passage, at least two stone passages, and at least one stone passage and calciuria above the 75th percentile, respectively. Quantitative trait linkage analyses did not suggest that the CaR gene was linked to biochemical markers of idiopathic hypercalciuria. CONCLUSIONS: This study shows that genetic variants of the CaR gene are not associated with idiopathic hypercalciuria and calcium nephrolithiasis in this population of French Canadians.

Calcium↗
PubMed2000

Low caloric expenditure in cardiac rehabilitation.

BACKGROUND: Total physical activity energy expenditure is a determinant of weight loss and risk factor modification in adults. There has been very little study of physical activity energy expenditure in cardiac rehabilitation populations. METHODS: Exercise-related energy expenditure was calculated in 112 patients with coronary artery disease in an outpatient cardiac rehabilitation program. Gross energy expenditure was estimated with the heart rate/oxygen consumption relation as measured during metabolic exercise testing with expired gas analysis. RESULTS: The average exercise training energy expenditure (ETEE) per cardiac rehabilitation exercise session was quite low at 270 +/- 112 kcal. Baseline fitness level (peak oxygen consumption), body weight, total exercise duration per session, age, and body mass index were all significant determinants of ETEE (r = 0.56 to -0.37, all P <.01). Additionally, patients who had undergone coronary bypass surgery and patients with medical comorbidities expended significantly fewer calories during exercise. In women, there was a relation between ETEE and change in total and LDL cholesterol (r = -0.43 and -0.45, respectively), although no such relation was observed in men. CONCLUSION: Cardiac rehabilitation exercise training, as currently structured, burns surprisingly few calories and has little impact in the short term (3 months) on measures of obesity and lipid risk factors. Alternative training programs should be considered to maximize caloric expenditure and modify specific risk factors such as obesity and dyslipidemia.

Aged↗
PubMed2000

Photosynthetic carbohydrate metabolism in the resurrection plant Craterostigma plantagineum.

The resurrection plant Craterostigma plantagineum (Hochst) is able to survive almost complete tissue dehydration when water is withheld from it, and then can rehydrate rapidly on rewatering. This ability is believed to be the result of the accumulation of sucrose in aerial tissues as a result of metabolism of 2-octulose. In this work the metabolic activity of well-watered Craterostigma plantagineum plants has been investigated. It is shown that Craterostigma makes raffinose series oligosaccharides as a product of photosynthesis and translocates them in the phloem. Evidence is also provided that 2-octulose is a product of photosynthesis and accumulates in the leaves over the light period and is mobilized at night. Thus 2-octulose acts as a temporary storage carbohydrate in leaves during photosynthesis in a similar fashion to starch in most C3 plants. Other potential roles of 2-octulose are discussed. Other than these observations Craterostigma plants are very similar to other C3 plants under these conditions.

Carbohydrate Metabolism↗
PubMed2000

Activated T cells induce macrophages to produce NO and control Leishmania major in the absence of tumor necrosis factor receptor p55.

The ability to activate macrophages in vitro for nitric oxide production and killing of Leishmania major parasites is dependent on tumor necrosis factor, although L. major-infected mice lacking the TNF receptor p55 (TNFRp55(-/-) mice) or both the TNFRp55 and TNFRp75 (TNFRp55p75(-/-) mice) are able to produce NO in vivo and eliminate the parasites. Here we report that activated T cells cocultured with macrophages results in TNFR-independent activation sufficient to control parasites and that both CD40/CD40L and LFA-1 contribute to T-cell-mediated macrophage activation. Thus, anti-CD3-stimulated T cells activated TNFR-deficient macrophages, while T cells from CD40L(-/-) mice were partially defective in triggering NO production by TNFRp55p75(-/-) macrophages. Moreover, in the presence of gamma interferon, anti-CD40 monoclonal antibody (MAb) activated TNFR-deficient macrophages. Finally, MAb blockade of LFA-1 completely inhibited macrophage NO production. Our data indicate that T cells can activate macrophages in the absence of TNF, thus providing a mechanism for how TNFR-deficient mice can control intracellular pathogens.

Animals↗
PubMed2000

Beryllium, an adjuvant that promotes gamma interferon production.

Beryllium is associated with a human pulmonary granulomatosis characterized by an accumulation of CD4(+) T cells in the lungs and a heightened specific lymphocyte proliferative response to beryllium (Be) with gamma interferon (IFN-gamma) release (i.e., a T helper 1 [Th1] response). While an animal model of Be sensitization is not currently available, Be has exhibited adjuvant effects in animals. The effects of Be on BALB/c mice immunized with soluble leishmanial antigens (SLA) were investigated to determine if Be had adjuvant activity for IFN-gamma production, an indicator of the Th1 response. In this strain of Leishmania-susceptible BALB/c mice, a Th2 response is normally observed after in vivo SLA sensitization and in vitro restimulation with SLA. If interleukin-12 (IL-12) is given during in vivo sensitization with SLA, markedly increased IFN-gamma production and decreased IL-4 production are detected. We show here that when beryllium sulfate (BeSO(4)) was added during in vivo sensitization of BALB/c mice with SLA and IL-12, significantly increased IFN-gamma production and decreased IL-4 production from lymph node and spleen cells were detected upon in vitro SLA restimulation. No specific responses were observed to Be alone. Lymph node and spleen cells from all mice proliferated strongly and comparably upon in vitro restimulation with SLA and with SLA plus Be; no differences were noted among groups of mice that received different immunization regimens. In vivo, when Be was added to SLA and IL-12 for sensitization of BALB/c mice, more effective control of Leishmania infection was achieved. This finding has implications for understanding not only the development of granulomatous reactions but also the potential for developing Be as a vaccine adjuvant.

Adjuvants, Immunologic↗
PubMed2000

Intravenous tissue plasminogen activator for acute ischemic stroke in patients aged 80 years and older : the tPA stroke survey experience.

BACKGROUND AND PURPOSE: Intravenous tissue plasminogen activator (tPA) administered within 3 hours of symptom onset is the first available effective therapy for acute ischemic stroke (AIS). Few data exist, however, on its use in very elderly patients. We examined the characteristics, complications, and short-term outcome of AIS patients aged >/=80 years treated with tPA. METHODS: Patients aged >/=80 years (n=30) were compared with counterparts aged <80 years (n=159) included in the tPA Stroke Survey, a US retrospective survey of 189 consecutive AIS patients treated with intravenous tPA at 13 hospitals. RESULTS: Risk of intracerebral hemorrhage (fatal, symptomatic, and total) was 3%, 3%, and 7% in the elderly age group and 2%, 6%, and 9%, respectively, in their younger counterparts (P=NS for all comparisons). Likelihood of favorable outcome, defined as modified Rankin score 0 to 1, National Institutes of Health Stroke Scale score </=5, or marked improvement by hospital discharge, was comparable between groups (37%, 54%, and 43% versus 30%, 54%, and 43%, respectively; P=NS for all comparisons). Elderly patients were more likely to be treated by stroke specialists (87% versus 60%; P=0.005) and less likely to have an identified protocol deviation (13% versus 33%; P=0.03). Elderly patients were discharged more often to nursing care facilities (17% versus 5%; P=0.003). In logistic regression models there were no differences in odds ratio for favorable or poor outcome, other than tendency for higher in-hospital mortality in elderly patients (odds ratio, 2.8; 95% CI, 0.81 to 9.62; P=0.10). CONCLUSIONS: Among AIS patients treated with intravenous tPA, age-related differences in characteristics and disposition were identified. No evidence for withholding tPA treatment for AIS in appropriately selected patients aged >/=80 years was identified.

Acute Disease↗
PubMed2000

The treatment of tetanus with intrathecal baclofen.

The treatment of severe tetanus generally requires prolonged mechanical ventilation. We describe two cases managed with continuous intrathecal infusion of baclofen via a subcutaneous tunnelled spinal catheter and an abdominal injection port. Baclofen, by diminishing spasms and spasticity, allowed reduced sedation and paralysis requirements. This potentially decreases the time and resources required for intensive care management. Complications include sedation, hypotension and CSF infection. After appropriate dose adjustment, baclofen improves the management of severe tetanus.

Aged↗
PubMed2000

Cerebrospinal fluid in critical illness.

OBJECTIVE: To detail the physiology, pathophysiology and recent advances in diagnostic analysis of cerebrospinal fluid (CSF) in critical illness, and briefly review the pharmacokinetics and pharmaco-dynamics of drugs in the CSF when administered by the intravenous and intrathecal route. DATA SOURCES: A review of articles published in peer reviewed journals from 1966 to 1999 and identified through a MEDLINE search on the cerebrospinal fluid. SUMMARY OF REVIEW: The examination of the CSF has become an integral part of the assessment of the critically ill neurological or neurosurgical patient. Its greatest value lies in the evaluation of meningitis. Recent publications describe the availability of new laboratory tests on the CSF in addition to the conventional cell count, protein sugar and microbiology studies. Whilst these additional tests have improved our understanding of the pathophysiology of the critically ill neurological/neurosurgical patient, they have a limited role in providing diagnostic or prognostic information. The literature pertaining to the use of these tests is reviewed together with a description of the alterations in CSF in critical illness. The pharmacokinetics and pharmacodynamics of drugs in the CSF, when administered by the intravenous and the intrathecal route, are also reviewed. CONCLUSIONS: The diagnostic utility of CSF investigation in critical illness is currently limited to the diagnosis of an infectious process. Studies that have demonstrated some usefulness of CSF analysis in predicting outcome in critical illness have not been able to show their superiority to conventional clinical examination. With further advances in our understanding of neurological function and refinement in biochemical analysis there remains the possibility of useful cerebrospinal fluid diagnostic and prognostic markers in the future.

Journal Article↗
PubMed1999

TNF receptor p55 is required for elimination of inflammatory cells following control of intracellular pathogens.

The elimination of lymphocytes within inflammatory lesions is a critical component in the resolution of disease once pathogens have been cleared. We report here that signaling through the TNF receptor p55 (TNFRp55) is required to eliminate lymphocytes from lesions associated with intracellular pathogens. Thus, TNFRp55-/- mice, but not Fas-deficient mice, maintained inflammatory lesions associated with either Leishmania major or Rhodococcus equi infection, although they developed a Th1 response and controlled the pathogens. Inflammatory cells from either L. major- or R. equi-infected C57BL/6 mice were sensitive to TNF-induced apoptosis, and conversely the number of apoptotic cells in the lesions from TNFRp55-/- mice was dramatically reduced compared with wild-type mice. Furthermore, in vivo depletion of TNF in wild-type mice blocked lesion regression following R. equi infection. Taken together, our results suggest that signaling through the TNFRp55, but not Fas, is required to induce apoptosis of T cells within inflammatory lesions once pathogens are eliminated, and that in its absence lesions fail to regress.

Actinomycetales Infections↗
PubMed1999

Initial clinical experience with IV tissue plasminogen activator for acute ischemic stroke: a multicenter survey. The t-PA Stroke Survey Group.

We assessed initial clinical experience with IV tissue plasminogen activator (t-PA) treatment of acute ischemic stroke in a standardized retrospective survey of hospitals with experienced acute stroke treatment systems. The incidence of symptomatic intracerebral hemorrhage (ICH) was 6% (11 of 189 patients; 95% CI 3 to 11%), similar to that in the National Institute of Neurological Disorders and Stroke (NINDS) t-PA Stroke Study. Deviations from the NINDS protocol guidelines were identified in 30% of patients (56 of 189). The incidence of symptomatic ICH was 11% among patients with protocol deviations as compared with 4% in patients who were treated according to the NINDS protocol guidelines, suggesting that strict adherence to protocol guidelines is prudent.

Aged↗
PubMed1999

Expression and contribution of B7-1 (CD80) and B7-2 (CD86) in the early immune response to Leishmania major infection.

CD28 interactions promote T cell responses, and whether B7-1 or B7-2 is utilized may influence Th cell subset development. CD28 blockade by CTLA-4Ig treatment or by targeted gene disruption has yielded different conclusions regarding the role of CD28 in the development of Th1 and Th2 cells following Leishmania major infection. In this study, we demonstrate that B7-mediated costimulation is required for the development of the early immune response following infection of resistant or susceptible mice. In contrast, CD28-/- BALB/c mice infected with L. major produce cytokines comparable to those of infected wild-type mice. Treatment of CD28-/- mice with CTLA-4Ig did not diminish this response, suggesting that a B7-independent pathway(s) contributes to the early immune response in these mice. In conventional BALB/c or C3H mice, B7-2 functions as the dominant costimulatory molecule in the initiation of early T cell activation following L. major infection, leading to IL-4 or IFN-gamma production, respectively. The preferential interaction of B7-2 with its ligand(s) in the induction of these responses correlates with its constitutive expression relative to that of B7-1. However, B7-1 can equally mediate costimulation for the production of either IL-4 or IFN-gamma when expressed at high levels. Thus, in leishmaniasis, costimulation involving B7-1 or B7-2 can result in the production of either Th1 or Th2 cytokines, rather than a preferential induction of one type of response.

Abatacept↗
PubMed1999

Transmetatarsal amputation of the toe: an analytic study of ischemic complications.

Transmetatarsal amputations of the toes are very common procedures, particularly involving patients with diabetes mellitus and peripheral vascular disease. A complication of these operations is the onset of gangrene of an adjoining toe, which is usually ascribed to the underlying disease. It is suggested that another explanation may be responsible for this occurrence, namely, a combination of the variability of the bifurcation of the dorsal metatarsal arteries and the operative technique. The former is either not described or has different levels in different texts. The operation in nearly all texts is a classic racquet incision, without mention of the width of the racket. The combination of an incision widely diverging from the handle of the racket is in danger of severing the dorsal metatarsal artery, its bifurcation, or the digital branch to the adjacent toe. A patient with a good blood supply may be able to salvage the situation by way of the plantar vessels, but when the vascular status is parlous, which is the case in many amputations, the adjacent digit is at considerable risk. Clinical, radiological, and anatomic evidence is presented to support this contention. Based on the above, a safer operative technique is suggested to avoid possible complications.

Amputation, Surgical↗