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S Durham

Publications and source records attributed to S Durham.

At least 55 records · Page 3Linked to original sources
PubMed1994

Acute cerebral blood flow response to dopamine-induced hypertension after subarachnoid hemorrhage.

The effects of dopamine-induced hypertension on local cerebral blood flow (CBF) were investigated in 13 patients suspected of suffering clinical vasospasm after aneurysmal subarachnoid hemorrhage (SAH). The CBF was measured in multiple vascular territories using xenon-enhanced computerized tomography (CT) with and without dopamine-induced hypertension. A territorial local CBF of 25 ml/100 gm/min or less was used to define ischemia and was identified in nine of the 13 patients. Raising mean arterial blood pressure from 90 +/- 11 mm Hg to 111 +/- 13 mm Hg (p < 0.05) via dopamine administration increased territorial local CBF above the ischemic range in more than 90% of the uninfarcted territories identified on CT while decreasing local CBF in one-third of the nonischemic territories. Overall, the change in local CBF after dopamine-induced hypertension was correlated with resting local CBF at normotension and was unrelated to the change in blood pressure. Of the 13 patients initially suspected of suffering clinical vasospasm, only 54% had identifiable reversible ischemia. The authors conclude that dopamine-induced hypertension is associated with an increase in flow in patients with ischemia after SAH. However, flow changes associated with dopamine-induced hypertension may not be entirely dependent on changes in systemic blood pressure. The direct cerebrovascular effects of dopamine may have important, yet unpredictable, effects on CBF under clinical pathological conditions. Because there is a potential risk of dopamine-induced ischemia, treatment may be best guided by local CBF measurements.

Adult↗
PubMed1994

Erythrocyte-depleted allogeneic human umbilical cord blood transplantation.

Cord blood is a recently recognized source of hematopoietic stem cells. It can be employed successfully to reconstitute hematopoiesis following allogeneic transplantation. One current drawback of cord blood as a treatment has been a risk of transfusion reactions attributable to ABO blood group mismatch. Removal of red cells from the cord blood has led to reduction of the stem cells by 30-50%. In this paper we report red cell depletion by a method that employs 3% gelatin to effectively sediment the erythrocytes and selectively deplete red cells but permits 94% recovery of nucleated cells and enrichment of colony-forming cells by granulocyte-macrophage colony-forming units, erythrocyte burst-forming units, and granulocyte-macrophage-megakaryocyte colony-forming units in the cord blood preparation. This technique has been employed in our study to remove red cells from the cord blood of a male infant delivered by cesarean section, which has permitted treatment of a female sibling suffering from leukemia. The recipient was 8 years old and weighted 36.7/kg. Complete HLA identity between the two siblings was established. A cord blood cell transplant of cryopreserved and later thawed cells (4 x 10(7) nucleated cells per kilogram) was administered to the patient after intensive myeloablative chemotherapy. The patient exhibited a prompt hematologic recovery (absolute neutrophil count > 500 by day 31, 100% male cells in bone marrow and peripheral blood by day 25) and has experienced a 13-month disease-free survival to date.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Prednisolone treatment in asthma is associated with modulation of bronchoalveolar lavage cell interleukin-4, interleukin-5, and interferon-gamma cytokine gene expression.

Although corticosteroids are effective in improving asthma symptoms and bronchial responsiveness, their mechanism of action is unknown. We examined whether changes in bronchial responsiveness with corticosteroid therapy of asthma are accompanied by a reduction in cytokine gene expression and eosinophil infiltration in the airways. Bronchoalveolar lavage (BAL) was performed in 18 patients with moderate asthma before and after 2 wk of treatment with prednisolone, 0.6 mg/kg/day, or matched placebo in a randomized double-blind parallel group study. Cells were counted in BAL cytocentrifuge preparations, and the numbers of cells expressing cytokine mRNA were assessed by in situ hybridization using 35S-labeled RNA probes. When the actively treated and placebo groups were compared, there was a decrease in airway methacholine responsiveness (p < 0.01) after prednisolone. This was accompanied by a decrease in bronchoalveolar lavage eosinophils (p < 0.05), a reduction in the numbers of BAL cells per 1,000 expressing mRNA for interleukin-4 (IL-4, p < 0.01) and interleukin-5 (IL-5, p < 0.005), and an increase in numbers of cells expressing mRNA for interferon-gamma (p < 0.005). These results are compatible with the hypothesis that the beneficial effects of corticosteroids in asthma may result from modulation of cytokine production, with consequent inhibition of local bronchial eosinophilia.

Adult↗
PubMed1993

Recurrent Pseudallescheria boydii sinusitis in acute leukemia.

Most episodes of fungal sinusitis in immunocompromised patients are caused by Aspergillus species. To treat such infections, surgical debridement and anti-fungal therapy have been recommended; it is also clear however that an adequate neutrophil count is important in controlling such infections. We report a case in which fungal sinusitis was shown to be due to P. boydii and in which the infection recurred over a period of 2 years during episodes of neutropenia in spite of vigorous surgical and medical therapy.

Adult↗
PubMed1991

Hepatic clearance and biliary secretory rate maximum of taurocholate in the recirculating and single pass isolated perfused rat liver. Effects of the cholestatic agent, estradiol-17 beta-(beta-D-glucuronide).

The ability of the cholestatic steroid glucuronide, estradiol-17 beta-(beta-D-glucuronide) (E(2)17G), to inhibit the hepatic clearance (ClH) and biliary secretory rate maximum (SRm) of taurocholate was investigated in the recirculating and single pass isolated perfused male rat liver. In the recirculating perfused liver, E(2)17G (0, 2, 4, or 6 mumol) was added as a bolus dose to the reservoir at zero time while taurocholate was infused into the portal vein in increasing amounts (15, 30, 45, or 60 mumol/mL; 1 mL/hr for 15 min each). E(2)17G (4 mumol) caused a significant (P less than 0.05) inhibition of bile flow and bile acid secretion at 10-15 min during infusion of 15 mumol/hr taurocholate but did not inhibit the SRm which occurred at 42 min, indicating that E(2)17G had not caused an irreversible inhibition of taurocholate transport. E(2)17G (6 mumol) caused a profound and irreversible inhibition of bile flow attributable to retention of E(2)17G in the liver. The noncholestatic estradiol-3-(beta-D-glucuronide) (E(2)3G; 6 mumol) had no significant effect on bile flow or the SRm. In the single pass perfused liver (10 mL/min flow rate), E(2)17G (0, 1, 2, 5, or 10 nmol/mL) or E(2)3G (2 nmol/mL) was added to the perfusate resulting in a stable infusion to the liver. [3H]Taurocholate was infused into the portal vein in increasing amounts to give inflow concentrations (Cin) of 25, 50, 75 or 100 nmol/mL. In the absence of E(2)17G, taurocholate ClH decreased from 0.92 to 0.70 mL/min/g liver with increasing taurocholate concentrations. Neither E(2)17G nor E(2)3G altered the ClH of 25 nmol/mL taurocholate. E(2)17G (10 nmol/mL) inhibited bile flow and bile acid secretion first at 20-25 min, followed by inhibition of ClH of 75 and 100 nmol/mL taurocholate (35-60 min). In contrast, E(2)3G stimulated bile acid secretion and increased the SRm by 80%. Thus, at doses that did not block its own elimination, E(2)17G did not cause an irreversible inhibition of taurocholate transport into bile. E(2)17G did not directly inhibit the uptake of taurocholate into the liver but first inhibited the biliary excretion of taurocholate, resulting in its intrahepatic accumulation and decreased clearance from the perfusate.

Animals↗
PubMed1990

Characterization of [3H]estradiol-17 beta-(beta-D-glucuronide) binding sites in basolateral and canalicular liver plasma membranes.

The specific binding of [3H]estradiol-17 beta-(beta-D-glucuronide) ([3H]E217G) was examined in isolated basolateral (bLPM) and canalicular (cLPM) liver plasma membranes. Two distinct binding sites were identified in each membrane fraction by competition and saturation experiments. Binding parameters obtained from competition studies were: Kd1 = 26 nM, Bmax1 = 0.26 pmol/mg protein; Kd2 = 2.6 microM, Bmax2 = 27 pmol/mg protein for bLPM; and Kd1 = 81 nM, Bmax1 = 0.61 pmol/mg protein; Kd2 = 6.7 microM, Bmax2 = 79 pmol/mg protein for cLPM. Binding parameters obtained from saturation experiments were not significantly different. There was no Na+ requirement for binding. Kinetic dissociation experiments showed that binding was reversible and revealed two components. The dissociation rate constants did not vary with the method of dilution of radioligand, i.e. by "infinite" volume, or excess unlabeled ligand, thus ruling out the possibility of cooperativity. The ability of a series of compounds to inhibit the binding of [3H]E217G was also examined. In bLPM, taurocholate (TC), estrone sulfate (E1SO4) and bromosulfophthalein (BSP) were able to compete with both binding sites, whereas estriol-17 beta-(beta-D-glucuronide) (E317G), estriol-16 alpha-(beta-D-glucuronide) (E316G), testosterone glucuronide (TG), estradiol-3-(beta-D-glucuronide) (E23G), estriol-3-(beta-D-glucuronide) (E(3)3G), cholate and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) were able to inhibit binding to only the low-affinity site. In cLPM, only the cholestatic steroid D-ring glucuronides (E(3)17G, E(3)16G and TG) and TC were able to compete with both sites, whereas the non-cholestatic steroid A-ring glucuronides (E(2)3G and E(3)3G), BSP and DIDS competed for only the low-affinity site. Based on the observed substrate specificities, the low-affinity sites in bLPM and cLPM are postulated to represent multispecific organic anion carriers. The high-affinity site in cLPM may play a role in mediating steroid D-ring glucuronide-induced cholestasis.

Animals↗
PubMed1990

Identification of activated T lymphocytes and eosinophils in bronchial biopsies in stable atopic asthma.

We have used immunohistochemistry and monoclonal antibodies to analyze the phenotypic composition and activation status of the cellular infiltrate of bronchial biopsies obtained by fiber optic bronchoscopy of 11 atopic asthmatic subjects (FEV1% predicted range 78 to 114), 9 atopic nonasthmatic control subjects, and 10 normal healthy subjects. Examination of mucosal biopsies obtained from both central (level I) and subsegmental (level II) bronchi showed that the highest number of CD45-, DC3-, DC4-, and CD8-positive cells were found in the group with asthma. There was a significant increase in the number of interleukin-2 receptor (CD25)-positive cells (a marker of lymphocyte activation) at airway level I in the asthmatic group compared with both nonasthmatic atopic (p less than 0.05) and normal control subjects (p less than 0.01). Eosinophil numbers were significantly increased in asthma at both airway levels and at airway level II in the nonasthmatic atopic group when compared with normal healthy control subjects (p less than 0.05). EG2-positive cells (an index of secretion of eosinophil cationic protein following activation) were found at both airway levels in the asthmatic group and at level I in the nonasthmatic atopic control group (p less than 0.05). When asthmatic subjects were compared with normal healthy subjects, there was a reduction in the number of neutrophil elastase-positive cells in the asthmatic subjects which, as a percentage of leukocytes, was significant (p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Etomidate infusions for the control of refractory status epilepticus.

Etomidate was used in eight patients to control status epilepticus which had been refractory to previous anticonvulsant therapy. Cortical activity was measured using a Cerebral Function Analysing Monitor and etomidate administered to achieve a 5 microV mean amplitude, avoiding burst suppression if possible with obliteration of any paroxysmal increase in amplitude. Neuromuscular blockade facilitated endotracheal intubation and mechanical ventilation, and corticosteroid replacement was provided. Rapid control of seizure activity, with cardiovascular stability, was obtained in all cases. Initially the mean infusion rate of etomidate required to achieve adequate suppression of cortical activity was 25 micrograms kg-1 min-1, but several patients exhibited tachyphylaxis. Weaning from the infusion presented difficulties in four patients due to recurring seizures. Adrenocortical function returned to normal within 96 hrs of stopping the infusion. At six month follow up, two patients had died, and two patients had significant reduction in cerebral function compared with their pre-morbid state.

Adult↗
PubMed1989

Structure-activity relationship of the cholestatic activity of dihydrotestosterone glucuronide, allo bile acids and lithocholate.

Dihydrotestosterone glucuronide (DHTG), a series of 5 alpha-bile acids, or allo-bile acids (3 alpha-hydroxy-5 alpha-cholanic acid, 3-keto-5 alpha-cholanic acid and 3 beta-hydroxy-5 alpha-cholanic acid) and their normal bile acid analogues (3 alpha-hydroxy-5 beta-cholanic acid or lithocholate, 3-keto-5 beta-cholanic acid and 3 beta-hydroxy-5 beta-cholanic acid) were administered intravenously to female rats in order to determine their effects on bile flow. All agents caused a rapid and profound inhibition of bile flow which was dose-dependent. The logarithm of the dose vs the cholestatic response curve for DHTG, the allo-bile acids and lithocholate were all parallel. DHTG was the most potent congener and was two times more potent than 3-keto-5 alpha-cholanic acid and 5 times more potent than lithocholate. These data indicate that the glucuronic acid moiety and the trans configuration of the A and B rings of the steroid nucleus confer the greatest cholestatic potency.

Animals↗
PubMed1989

Cryopreserved venous homografts as vascular conduits in canine carotid arteries.

In this study we evaluated the histologic condition, prostacyclin production, and compliance of morphologically intact cryopreserved venous homografts (CVH) and autografts 3, 6, and 9 months after arterial implantation. Eighteen external jugular veins were cryopreserved and implanted into the carotid arteries of mongrel dogs. All grafts were patent at the time of excision. Electron microscopy documented a disrupted endothelium in the homografts at 3 months that was intact at 9 months. The cellular infiltrate, suggestive of rejection, in the 3-month homografts resolved by 9 months. Prostacyclin production at 3 months was 8.7 +/- 3.2 pg/ml/cm2 compared with 24.1 +/- 9.6 pg/ml/cm2 (p less than 0.025) in the adjacent carotid artery. The prostacyclin production in the 6-month homografts was 21.7 +/- 12.4 pg/ml/cm2, not significantly different from the adjacent carotid artery. The return of prostacyclin paralleled the return of an intact endothelium. Compliance of fresh vein was diminished by cryopreservation, from 1.57 +/- 0.39% radial change/mm Hg (10(-2] to 0.79 +/- 0.21% radial change/mg Hg (10(-2] (p less than 0.02). The compliance of CVH at 3 months (1.7 +/- 1.0) and at 6 months (1.1 +/- 0.42) was not significantly different from cryopreserved veins. These data showed that CVH remained patent in dogs for 9 months, without loss of compliance for 6 months, and developed a morphologically intact and functional endothelium that paralleled the resolution of the inflammatory infiltrate.

Animals↗
PubMed1987

High and low affinity binding of [3H]cholate to rat liver plasma membranes.

The transport of bile acids across sinusoidal and canalicular membranes of hepatocytes is characterized as carrier mediated. Such a carrier should specifically bind bile acids at physiological concentrations. We examined the binding of [3H]cholate to rat liver plasma membranes using a microcentrifugation technique and detected high (KD = 1.23 +/- 0.44 microM, Bmax = 21.8 +/- 3.3 pmol/mg protein) and low (KD = 1.97 +/- 1.33 mM, Bmax = 41.5 +/- 25.3 nmol/mg protein) affinity binding sites. Maximal binding was achieved within 15-45 sec and was stable for 2 min at 37 degrees. Binding to the high affinity site was reversible, was not Na+ dependent or attributable to vesicular uptake, and exhibited a broad pH optimum. Binding to this site was negligible or not detected in liver mitochondrial and microsomal fractions, was saturable, and was inhibited by other bile acids. The IC50 values for bile acids as inhibitors of [3H]cholate binding at the high affinity site were: taurocholate, 1.9 nM; glycodeoxycholate, 3.1 nM; chenodeoxycholate, 5.6 nM; taurochenodeoxycholate, 7.3 nM; glycochenodeoxycholate, 11 nM; lithocholate, 13 nM; taurodeoxycholate, 20 nM; glycocholate, 3.6 microM; and deoxycholate, 5.6 microM. [3H]Cholate specific binding was inhibited by 10(-5) M bromosulfophthalein, bilirubin and indocyanin green. These data support the hypothesis that the high affinity binding site represents a carrier which is shared by bile acids and nonbile acid organic anions.

Animals↗
PubMed1987

Biological equilibration of allergen preparations: methodological aspects and reproducibility.

A method for biological equilibration (BE) of allergen reference preparations using the skin-prick test (SPT) method and histamine HCl 10 mg/ml as reference substance (reference method), was evaluated. The precision was low for weals less than 10 mm2. The slope (log weal area/log concentration) of allergen and histamine did not vary significantly between investigators and allergens. The median slopes were 0.39 (n = 384) and 0.34 (n = 397), for allergen and histamine, respectively (P less than 0.01). The concentration of allergen eliciting a weal of the same size as that of histamine HCl 1 mg/ml (Chl) in the median sensitive patient, 1000 Biological Units/ml (BU/ml), did not vary significantly between clinics/geographical regions (grasses, mites and moulds). As BE is repeatable between regions, BUs estimated by this method are generally valid. A high correlation (r = 0.91, P less than 0.001) was found between the median Chl as estimated with histamine 1 and 10 mg/ml as reference substance, respectively. Thus, this reference method for BE is valid. The precision of the SPT method with histamine HCl 1 mg/ml is not as good as with 10 mg/ml, which is therefore recommended as the reference concentration.

Adolescent↗
PubMed1987

Multiple carriers for uptake of [3H]estradiol-17 beta(beta-D-glucuronide) in isolated rat hepatocytes.

The transport of the cholestatic steroid glucuronide, 3H-estradiol-17 beta-(beta-D-glucuronide) (E2 17G), was examined in isolated female rat hepatocytes over a broad substrate concentration range (0.1-100 microM). Two different carrier systems were identified with the following kinetic parameters: Km1 = 4.54 microM; Vmax1 = 0.149 nmol/min/mg protein; Km2 = 149 microM; Vmax2 = 0.641 nmol/min/mg protein. Taurocholate and testosterone glucuronide selectively and competitively inhibited [3H]-E2 17G uptake at the high affinity site. Ki values calculated for taurocholate (43 microM) and testosterone glucuronide (28 microM) indicated that these two inhibitors were relatively weak competitors for this E2 17G transport site. Conversely, E2 17G inhibited [3H]taurocholate uptake into isolated hepatocytes (Ki = 43 microM). Bromosulfophthalein (10 microM) inhibited uptake of 0.5-50 microM [3H]-E2 17G by 55-85%, whereas morphine glucuronide (100 microM) had no significant effect on uptake of [3H]-E2 17G at these concentrations. The effects of taurocholate, testosterone glucuronide, bromosulfophthalein, and morphine glucuronide on [3H]-E2 17G uptake into isolated rat hepatocytes correlated with the ability of these agents to inhibit binding of [3H]-E2 17G to specific sites in rat liver plasma membranes. These data support the postulate that the two [3H]-E2 17G binding sites identified in female rat liver plasma membranes represent two distinct organic anion carriers and indicate that the high affinity site for [3H]-E2 17G represents a carrier that is shared by organic anions and bile acids.

Animals↗
PubMed1986

Taurocholate and steroid glucuronides: mutual protection against cholestasis in the isolated perfused rat liver.

Estradiol-17 beta-(beta-D-glucuronide) (E217G) was shown to be cholestatic in the isolated perfused female rat liver. Doses of 0.85, 1.3, 1.7 and 2.1 mumol decreased bile flow maximally at 15 to 30 min by 29, 37, 68 and 76% respectively. Approximately 95% of a dose of [3H]E217G was cleared from the perfusate in 30 min and was secreted in bile, with 93, 85, 71 and 55% of the dose appearing in bile within 120 min after doses of 0.85, 1.3, 1.7 and 2.1 mumol, respectively. Neither vehicle nor 1.7 mumol of estradiol-3-(beta-D-glucuronide) (E23G) significantly altered bile flow. Infusion of taurocholate at 40 and 60 mumol/hr, respectively, partially and completely protected against the cholestasis induced by 1.7 mumol of E217G. The log dose-response curve for E217G-induced cholestasis was much steeper and was shifted to the right in the presence of a 60 mumol/hr infusion of taurocholate. Infusion of taurocholate at 80 mumol/hr in the absence of E217G or E23G decreased bile flow by 79%. However, addition of 1.7 mumol of either E217G or E23G offered marked protection against taurocholate-induced cholestasis and increased bile acid secretion. Higher doses (3.4 mumol) of E217G or E23G further increased bile flow and bile acid secretion. A model system is presented to explain the mutual protection against cholestasis.

Animals↗
PubMed1984

Characterization of the interaction between estrogen metabolites and taurocholate for uptake into isolated hepatocytes. Lack of correlation between cholestasis and inhibition of taurocholate uptake.

The cholestasis induced by estrogen metabolites has been postulated to be due to an inhibition of bile acid transport. Therefore, the uptake of [3H]taurocholate (TC) into isolated hepatocytes was examined in the presence of known cholestatic steroid glucuronides. The cholestatic D-ring glucuronide conjugates of estradiol, estriol, ethynylestradiol and dihydrotestosterone did not inhibit the uptake of TC suggesting that these organic anions are transported by different carrier systems. Estrone sulfate inhibited TC uptake 65% but did not decrease bile flow following i.v. administration to the rat (22 mumol/kg), under conditions which the steroid glucuronide estradiol-17 beta-(beta-D-glucuronide) ( E217G ) decreased bile flow 100%. The hepatocytic uptake of [3H] E217G (100 microM) was inhibited by estriol-16 alpha-(beta-D-glucuronide) (200 microM, 40%) and estradiol-17 beta-3-(beta-D-glucuronide) (200 microM, 22%) as well as by the organic anions bromosulfophthalein (150 microM, 57%), dibromosulfophthalein (150 microM, 59%), indocyanine green (150 microM, 62%), rose bengal (150 microM, 56%) and bilirubin (50 microM, 40%). Thus, the bile acids and steroid glucuronides are transported into the hepatocyte by different carrier systems so that the cholestasis induced by the steroid D-ring glucuronides cannot be explained by an inhibition of bile acid uptake. Furthermore, the hepatocytic uptake of E217G occurs by a carrier system similar to that for the other steroid glucuronides and organic anions.

Animals↗
PubMed1982

Assignment of the human gene for muscle-type phosphofructokinase (PFKM) to chromosome 1 (region cen leads to q32) using somatic cell hybrids and monoclonal anti-M antibody.

Human phosphofructokinase (PFK; EC 2.7.1.11) is under the control of three structural loci which encode muscle-type (M), live-type (L), and platelet-type (P) subunits; human diploid fibroblasts and leukocytes express all three loci. In order to assign human PFKM locus to a specific chromosome we have analyzed human x Chinese hamster somatic cell hybrids for the expression of human M subunits, using an anti-human M subunit-specific mouse monoclonal antibody. In 18 of 19 hybrids studied, the expression of the PFKM locus segregated concordantly with the presence of chromosome 1 (discordance rate 0.05) as indicated by chromosome and isozyme marker analysis. The discordance rates for all the other chromosomes were 0.32 or greater, indicating that the PFKM locus is on chromosome 1. For the regional mapping of PFKM, eight hybrids were studied that contained one of five distinct regions of chromosome 1. These results further localize the human PFKM locus to region cen leads to q32 chromosome 1.

Antibodies, Monoclonal↗