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Biomedical subjects

D Scott

Publications and source records attributed to D Scott.

At least 289 records · Page 16Linked to original sources

Fibrinopeptide A during normal pregnancy.

Fibrinopeptide A (FPA) is the first peptide released from fibrinogen upon thrombin action. Plasma FPA is cleared rapidly with a first order kinetics and therefore its level reflects the rate of thrombin cleavage of fibrinogen. A prospective study was undertaken to establish normal values of FPA during pregnancy. The mean FPA for the pregnant group (n = 136) was 2.8 ng/ml (SD = 3.3) while it was 1.24 ng/ml (SD = 0.4) for a nonpregnant control group of healthy women (n = 30). The median FPA for the pregnant group was 2.2 ng/ml and 1.4 ng/ml for the nonpregnant group (Wilcoxon test P less than 0.0001). Plasma FPA levels increased with gestational age. The median value was 1.5 ng/ml in the first trimester (n = 18), 1.8 ng/ml in the second trimester (n = 40), and 2.5 ng/ml in the third trimester (n = 78). Plasma FPA concentrations in the third trimester were significantly higher than in the first and second trimester. These findings suggest increased thrombin activity and fibrin generation during the course of normal pregnancy.

Cross-Sectional Studies↗

Beta-thromboglobulin during normal pregnancy, labor, and puerperium.

Platelet activation has been implicated in the pathogenesis of several obstetrical conditions such as preeclampsia and intrauterine growth retardation. Plasma beta-thromboglobulin (BTG) concentration is an index of in vivo platelet activation. The purpose of this study was to establish normal values of plasma BTG during pregnancy, labor and puerperium. Plasma BTG concentrations were determined from 121 uncomplicated pregnant women, 20 women in labor, 20 puerperal women, and a control group of 28 healthy non-pregnant volunteers. There was no significant difference in plasma BTG concentrations between non-pregnant and pregnant women. Gestational age, labor, and puerperium did not affect plasma BTG concentrations.

Female↗

A genetic analysis of male-predominant pheromones in Drosophila melanogaster.

Chemical signals from males play an important role in stimulating Drosophila melanogaster females to mate, and male-predominant pheromones may influence a female's choice of mates. Male-predominant pheromones also inhibit courtship, thereby functioning as antiaphrodisiacs. Interstrain variation in the ratio of two male-predominant pheromones (7-tricosene and 7-pentacosene) has been reported, but the genetic basis for this potentially important variation has not been examined. In a series of crosses between strains that differ radically in the amounts of 7-tricosene and 7-pentacosene, we have identified both X-linked and autosomal contributions to interstrain variation in the amounts of these compounds. The X-linked loci act as enhancers for production of the compound predominant in the strain from which the X chromosome originated. Autosomal factors for each of the two compounds appear to segregate as high vs. low, with incomplete dominance of high 7-tricosene over low, and low 7-pentacosene over high. A significant negative correlation between the quantities of 7-pentacosene and 7-tricosene in the F2 and backcross progeny, but not in the F1s or parentals, indicates linkage between autosomal loci regulating the expression of each compound. However, the phenotypic distributions of the backcross progeny indicate that additional unlinked loci are also directly involved in the production of these two hydrocarbons.

Animals↗

Cytomegalovirus infection complicating renal transplantation and its relationship to acute transplant glomerulopathy.

The incidence of cytomegalovirus (CMV) infection was established, using laboratory criteria, in 298 patients receiving 362 renal allografts (164/298 = 55%). The incidence of CMV infection did not differ between azathioprine/prednisolone-treated and cyclosporine-treated patients (55% vs. 57% NS). The use of antithymocyte globulin (ATG) increased the incidence of CMV infection (78% vs. 51%: P less than 0.01). Donor and recipient CMV status, known for 116 allografts, did not correlate with the incidence of CMV infection (recipient CMV-positive = 50%; recipient CMV-negative = 54%: NS). CMV infection was responsible for 8 patients' deaths (2.7% mortality). Thirty-three patients with acute transplant glomerulopathy were identified (11%). There was no correlation between acute transplant glomerulopathy and CMV infection. Glomerulopathy was associated with poor graft survival (22/33 patients with a graft survival of less than 6 months). Thus CMV infection, although a common complication of renal transplantation with significant morbidity and mortality, is not closely associated with acute transplant glomerulopathy. Further, the lack of correlation of donor-recipient CMV serologic status with graft outcome limits the usefulness of pretransplantation donor screening.

Acute Disease↗

The effects of feeding pelleted diets made from either coarsely or finely ground hay on phosphorus balance and on the partition of phosphorus excretion between urine and faeces in the sheep.

Mature sheep fitted with rumen and duodenal cannulae were fed pelleted diets made from hay that had been either coarsely or finely ground. The diets were supplemented with phosphorus and the effects on salivary phosphorus secretion, net intestinal phosphorus absorption and the route of excretion were examined. Changing the particle size of the diet had no effect on overall phosphorus balance but did affect the route of excretion with urine levels being higher and faecal levels lower in periods when the more finely ground diet was fed. This increase in urine excretion was not due to differences in phosphorus intake nor could it be attributed to increased net phosphorus absorption from the intestine. Salivary phosphorus secretion was, however, lower when the more finely ground diet was fed and it would appear that this change in the balance between that absorbed relative to its secretion back into the gut was the major factor contributing to the increased phosphorus excretion in the urine. The significance of these findings in relation to the high levels of phosphorus normally found in the urine of sheep fed concentrate diets compared to those fed roughage diets is discussed.

Animal Feed↗

The thigh flap: an osteomyocutaneous free-flap model in the rat.

A new experimental model for free-flap transfer has been developed in the rat. This "thigh flap" is an osteomyocutaneous free flap of bone (femur), muscle (thigh), and skin (groin) based on the femoral vessels. The flap is harvested from the left groin and thigh of an inbred female rat and is transferred to a subcutaneous pocket in the left groin of a male rat of the same inbred strain. The femoral vessels supplying the flap are anastomosed end-to-end with the femoral vessels of the recipient. Thirty flaps have been transferred, with 5 technical failures. Three of the remaining 25 flaps developed necrosis within 24 hours. The other 22 flaps remained viable until the rat was sacrificed at 7 days. The survival rate of the thigh flap was thus 88 percent. The model is suitable for use in metabolic, vascular, and immunologic studies of composite free flaps.

Animals↗

Long-term repair in vivo of colony-forming ability and chromosomal injury in X-irradiated mouse hepatocytes.

The radiosensitivity of mouse hepatocytes in vivo was measured in terms of clonogenicity or chromosome damage (micronucleus production). Within 24 h of irradiation there was a dose-dependent increase in clonogenicity (dose-modifying factor, DMF = 1.37 +/- 0.09) followed by long-term repair which resulted in a DMF of 3.49 +/- 0.23 at 11 months. Such repair also took place, but to a lesser extent, after the end of fractionated irradiation. Cell proliferation, measured by tritiated thymidine autoradiography, was insufficient to explain the long-term reduction in radiosensitivity in terms of a dose-dependent replacement of damaged cells. Although there was a reduction in the frequency of cells with micronuclei, postirradiation, the magnitude of this decrease was relatively small; the DMF for micronucleus-free cells at 11 months was only 1.49 +/- 0.25. Thus the long-term increase in clonogenicity can only partially be explained in terms of repair of chromosome injury, assessed by the production of micronuclei.

Animals↗

Impairment of pancreatic acinar function by reserpine in vivo and in vitro.

Chronic reserpine treatment of animals, an experimental model for cystic fibrosis (CF), results in generalized exocrinopathy, impaired pancreatic secretion, and decreased pancreatic content of amylase. The mechanisms of altered acinar function and decreased amylase content in both CF and the reserpine-treated rat are unknown. To examine this alteration, the rate of [3H]phenylalanine (phe) incorporation into cellular protein was determined in pancreatic acinar cells after reserpine treatment of rats in vivo (7 d) and of cells in vitro (1 to 24 h). Acinar cells isolated from control, chronic reserpine-treated, and pair-fed rats were incubated in vitro with 0, 30, 50, or 100 microM reserpine. Reserpine treatment in vitro for 24 h of acinar cells from control rats significantly decreased amylase activity (20 to 70%), an effect similar to that of reserpine treatment in vivo. In vivo, reserpine treatment decreased [3H]phe incorporation (disintegrations per minute per milligram protein) 56% in freshly isolated cells, but did not alter intracellular specific activity (disintegrations per minute per nanomole phe, SA) of [3H]phe. Reserpine treatment (30 and 50 microM) in vitro for 1 h also decreased [3H]phe incorporation by freshly isolated cells from control (53 to 85%) and pair-fed (40 to 68%) rats. Reserpine treatment for 24 h in vitro significantly decreased [3H]phe incorporation by cells from control (82 and 98%), pair-fed (80 and 95%), and chronic reserpine-treated (90 and 97%) rats as compared with cells from respective in vivo treatments cultured with no reserpine. In vitro reserpine treatment also decreased the intracellular SA of [3H]phe in freshly isolated cells from control (14 and 36%) and pair-fed (35 and 39%) rats and in cultured cells from control (11 and 86%), pair-fed (60 and 88%), and chronic reserpine-treated (49 and 76%) rats. However, these alterations of SA by reserpine did not account for the decreased incorporation of [3H]phe into acinar protein, which remained significantly lower (70 to 88%) when expressed as total phe incorporation. These results suggest that reserpine acts directly on acinar cells to alter function and that the ability of the pancreas to synthesize digestive enzymes may be impaired in this model of cystic fibrosis.

Amylases↗

Extrapolation from in vitro tests to human risk: experience with sodium fluoride clastogenicity.

Genotoxic effects observed in vitro, only at high doses or high levels of cytotoxicity, will be false positives if such conditions are not achieved or cannot be tolerated in vivo. However, for such effects to be disregarded there must be a threshold dose or level of cytotoxicity below which genotoxicity is absent. Sodium fluoride (NaF) has previously been shown to be clastogenic in vitro in Syrian hamster cells and human fibroblasts. We have extended these studies in human fibroblasts and included a positive control (mitomycin C, MMC) which is clastogenic in vivo and carcinogenic, and a chemically related control (NaCl). Cytotoxicity was measured as mitotic inhibition and cell death (loss of clonogenicity). The results are used to illustrate the problems associated with quantitative extrapolation from in vitro tests to human risk, as follows. (1) There appears to be a threshold response (clastogenicity vs. dose) with NaF at around 10 micrograms/ml (48 h exposure) but a more definitive conclusion must await elucidation of the mechanisms of clastogenicity. (2) NaCl is weakly clastogenic at 1000 times the threshold dose for NaF. The mechanisms are unlikely to be similar. (3) No clastogenicity was detected with NaF below about 30% mitotic inhibition but the relationship between clastogenicity and mitotic inhibition was similar for NaF and MMC. (4) There was no obvious threshold in the relationship between clastogenicity and cell killing with NaF. MMC was less clastogenic than NaF at equitotoxic doses. Observations 3 and 4 preclude the possibility of regarding the clastogenicity of NaF as a false positive by virtue of associated cytotoxicity.

Cell Line↗

The effects of feeding either hay or grass diets on salivary phosphorus secretion, net intestinal phosphorus absorption and on the partition of phosphorus excretion between urine and faeces in the sheep.

Mature sheep fitted with ruminal and duodenal cannulas were fed either a pelleted hay or a pelleted grass diet with or without supplementary phosphorus. Salivary phosphorus secretion, net intestinal phosphorus absorption and the route of phosphorus excretion were determined. The route of excretion was markedly affected by diet with urinary excretion being much higher and faecal excretion lower when the grass diet was fed. These effects were not due to differences in phosphorus intake or to differences in net intestinal phosphorus absorption. Salivary phosphorus secretion was, however, lower when the grass diet was fed. The significance of these changes in relation to the control of phosphorus balance in ruminants is discussed.

Animal Feed↗

Hepatitis B and renal transplantation.

Renal transplantation in HBsAg+ chronic carriers has a relative low risk of progressive liver disease, with mortality associated with liver disease at 7%. In contrast, HBsAg+ recipients who acquired their disease in the early posttransplant period had a mortality of 60%. HBeAg-positive patients who remain persistently positive are a subgroup with a poor prognosis and should not be offered a renal transplant.

Adult↗

Demonstration of an indomethacin-sensitive mechanism regulating immune reactivity in American cutaneous leishmaniasis patients.

We investigated some aspects of the regulation of the immune response that were sensitive to the effect of indomethacin (INDO), an inhibitor of prostaglandin synthesis, in 84 patients with American cutaneous leishmaniasis (ACL), and in normal controls. The patients were classified on the basis of clinical and histopathological criteria as suffering localized (LCL), mucocutaneous (MCL) or diffuse (DCL) forms of the disease. The responses in vitro to mitogens (PHA and Con A) and leishmanial antigens were evaluated in the presence or absence of INDO. It was found that the drug significantly increased in vitro the mitogenic stimulation by PHA of peripheral blood mononuclear cells from LCL, MCL and DCL patients, but the effect was less evident in the controls. Considering specific responses to leishmanial antigens, we showed that in the presence of INDO, these were significantly increased in LCL patients, but not in MCL or DCL. Also, only in LCL was an inverse correlation found between the initial response to leishmanial antigen and the increase caused by INDO. Significant correlations were found between the INDO-induced enhancement of PHA and Con A responses in the patient groups, but not in the controls. In LCL patients there was a significant correlation between the increases caused by INDO of the mitogen and antigen responses. It can be suggested that an indomethacin-sensitive (prostaglandin dependent) suppressor mechanism operates in LCL patients, that is possibly responsible for the modulation of the immune response against the parasite. In MCL, where this suppressive mechanism is apparently not functional, the response to the parasite is intense, and a possible consequence of this could be tissue damage. Our results indicate, however, that the anergy observed in DCL patients is not due to an involvement of prostaglandins in the suppression of the specific immune response.

Adolescent↗