Search PubMed⌕ Search

Biomedical subjects

B Bennett

Publications and source records attributed to B Bennett.

At least 91 records · Page 5Linked to original sources
PubMed1991

31P ENDOR studies of xanthine oxidase: coupling of phosphorus of the pterin cofactor to molybdenum (V).

31P ENDOR spectra are described for three different molybdenum(V) species in reduced xanthine oxidase samples. The spectra were not affected by removing the FAD from the enzyme, implying that this is located at some distance from molybdenum. Furthermore, in confirmation of the work of J. L. Johnson, R. E. London, and K. V. Rajagopalan [(1989) Proc. Natl. Acad. Sci. U.S.A. 86, 6493-6497], NMR and chemical analysis of the phosphate content of highly purified xanthine oxidase showed there are only three phosphate residues per subunit of the enzyme. It is concluded that the ENDOR features are due to hyperfine coupling of the phosphate group of the pterin cofactor to the molybdenum atom. Evaluation of the dipolar component of the coupling has permitted estimation of the molybdenum-phosphorus distances as 7-12 A. This implies that the cofactor is in an extended conformation in the enzyme molecule. Less detailed 31P ENDOR data on sulfite oxidase are consistent with a similar conformation for the cofactor in this enzyme.

Animals↗
PubMed1991

The receptor for tissue plasminogen activator (t-PA) in complex with its inhibitor, PAI-1, on human hepatocytes.

The binding of t-PA-PAI-1 to human hepatocytes at 4 degrees C reached a maximum at 2 h. Scatchard analysis indicated 74,000 +/- 11,000 high-affinity binding sites for complex per human hepatocyte, with a Kd of 0.87 +/- 0.09 nM. Almost identical results were achieved with the human hepatoma cell line Hep G2. Binding of [125I]t-PA-PAI-1 complex was unaffected by high concentrations of unlabelled t-PA, PAI-1, u-PA or u-PA-PAI-1 complex; only t-PA-PAI-1 complex competed for binding. Hepatocyte-bound t-PA-PAI-1 was internalized and degraded at 37 degrees C. Thus, hepatocytes have a specific t-PA-PAI-1 receptor that participates in clearance of this complex.

Binding, Competitive↗
PubMed1991

Distribution of plasminogen activator inhibitor (PAI-1) in tissues.

Extracts of human tissue were analysed for plasminogen activator inhibitor (PAI-1) antigen and activity. PAI-1 was localised in tissues by an immunochemical method, using monoclonal antibodies. PAI-1 occurred throughout the body; its concentration and activity differed considerably from organ to organ. Extracts of liver and spleen had the greatest abundance of PAI-1, but the activity of the inhibitor was much higher in liver than in spleen: the liver may be a source of plasma PAI-1. Immunochemical staining for PAI-1 was observed in endothelium, platelets and their precursor cells, the megakaryocytes, and locations central to the process of haemostasis. PAI-1 also occurred in neutrophil polymorphs and macrophages, cells important in inflammatory and immune processes, but not in lymphocytes. Other cell types, in particular, vascular smooth muscle cells and mesangial cells, also stained positively for PAI-1 and such cells seem to represent an important reservoir of PAI-1.

Autopsy↗
PubMed1991

Continuation and maintenance treatment of major depression with the monoamine oxidase inhibitor phenelzine: a double-blind placebo-controlled discontinuation study.

Long-term treatment with antidepressant drugs has received little attention until recently. A study is reported comparing the effectiveness of maintenance treatment with phenelzine in responding major depression patients. If they responded initially to nonblind phenelzine treatment and sustained remission for 16 weeks, patients were randomized to 2-year double-blind treatment with phenelzine 60 mg/day, phenelzine 45 mg/day, or placebo. Both doses of phenelzine were significantly better than placebo in preventing relapse of depression. Phenelzine 45 mg/day may be an optimal maintenance dose for many patients.

Adult↗
PubMed1991

Clearance of t-PA, PAI-1, and t-PA-PAI-1 complex in an isolated perfused rat liver system.

The role of physiologic inhibitors of tissue-type plasminogen activator (t-PA) in its clearance has not yet been defined. In this study, the clearance of t-PA, plasminogen activator inhibitor 1 (PAI-1), and t-PA-PAI-1 complex was determined in an isolated perfused rat liver system. The clearance of t-PA-PAI-1 complex was twice as fast as that of t-PA, whereas PAI-1 was cleared slowly. The half-lives for t-PA, determined by a two-compartmental pharmacokinetic model, were: alpha, 20.1 minutes, and beta, 120.0 minutes. The corresponding values for t-PA-PAI-1 complex were: alpha, 9.7 minutes, and beta, about 7 hours. The model microconstants were computed for t-PA and t-PA-PAI-1 complex and the marked difference between the "on" microconstants k12 for t-PA (0.026 +/- 0.001 min-1) and t-PA-PAI-1 complex (0.090 +/- 0.025 min-1) suggests that the effect on binding to liver cells is the most important factor in the faster clearance of t-PA-PAI-1 complex when compared with t-PA.

Animals↗
PubMed1991

The effect of double gloving on frequency of glove perforations.

OBJECTIVE: The purposes of this prospective investigation were to determine the frequency of glove perforation during obstetric and gynecologic procedures and to assess the value of double gloving in preventing damage to the inner glove. METHODS: During a 2-month period, surgeons in the Department of Obstetrics and Gynecology were asked to double glove during all operative procedures. At the conclusion of surgery, the gloves were collected and the surgeons noted the type of procedure and their role as primary surgeon or first assistant. They also indicated whether a perforation was recognized intraoperatively. The gloves were tested for damage by first filling them with air and immersing them in water and then by directly filling them with water. RESULTS: Four hundred forty-one sets of double gloves were evaluated. Of these, 61 sets (14%, 95% confidence interval 10.8-17.2%) had holes in at least one of the four gloves and six sets had more than one perforation, for a total of 67 holes. Fifty-two holes (78%) penetrated only the outer glove and nine (13%) were only in the inner glove. Penetration of both gloves at identical sites occurred in only six of the total glove sets (1.4%, 95% confidence interval 0.3-2.5%). The two most common sites of perforation were the thumb and index finger of the nondominant hand. Glove perforation occurred in 15% of cesarean deliveries and 11% of vaginal deliveries, a nonsignificant difference. In contrast, penetration occurred in 28% of major gynecologic procedures (P less than .05 compared with cesarean or vaginal delivery). Chief and third-year residents were significantly more likely to sustain perforation than were attending physicians or junior residents (P less than .01). Perforation to the gloves of chief residents typically occurred while they were serving as assistants for first- and second-year residents. Third-year residents usually sustained perforations while functioning as primary surgeons. CONCLUSIONS: Glove perforations occur with relatively high frequency during pelvic surgery, particularly abdominal procedures. Double gloving offers a measure of protection against damage to the inner glove and may prevent subsequent exposure of the surgeon to blood and other body fluids.

Gloves, Surgical↗
PubMed1990

Complexing of tissue plasminogen activator with PAI-1, alpha 2-macroglobulin, and C1-inhibitor: studies in patients with defibrination and a fibrinolytic state after electroshock or complicated labor.

Release of tissue plasminogen activator (t-PA) and its interaction with plasma protease inhibitors were studied in two patients with massive defibrination, one after electroshock and soft tissue injury and the other after complicated labor; both had very severe hemorrhage. Large quantities of free t-PA were present in the circulation for several hours. Complexes of t-PA with plasminogen activator inhibitor 1 (PAI-1), alpha 2-macroglobulin and C1-inhibitor were also observed. PAI-1 antigen rose dramatically in both patients, and complexes of t-PA with PAI-1 rose rapidly during the period of observation. In contrast, the complexes of t-PA with alpha 2-macroglobulin and C1-inhibitor, present initially, persisted for short periods only and disappeared when free t-PA disappeared from the circulation. Plasmin was generated initially, as indicated by the presence of plasmin-alpha 2-antiplasmin complexes. Plasma concentrations of alpha 2-macroglobulin, C1-inhibitor, antithrombin III, and alpha 2-antiplasmin were severely depleted initially, but rapidly returned to normal. The observations demonstrate that there is a major release of t-PA in such defibrinating patients, that there is a role for protease inhibitors other than PAI-1 in the regulation of endogenous t-PA, and indicate the great rapidity with which such free t-PA is complexed and cleared.

Adult↗
PubMed1990

The platelet and plasma pools of plasminogen activator inhibitor (PAI-1) vary independently in disease.

The relative importance and behaviour of plasma and platelet plasminogen activator inhibitor (PAI-1) in disease has not hitherto been examined. In this study the concentration of PAI-1 in the plasma and platelets of patients with a variety of disorders was examined using a specific ELISA and a functional assay. Mean plasma PAI-1 was elevated in groups of patients with diabetes mellitus, hypertension, alcoholic cirrhosis, angina and myocardial infarction. Plasma PAI-1 was raised in the post-operative phase and the PAI-1 released after surgery was not derived from platelets. In all groups PAI-1 in the platelet pool reflected the platelet count, except in type II diabetes mellitus and chronic renal failure, where a reduced quantity of PAI-1 antigen per platelet was found. In severe chronic renal failure, abnormal platelets and diminished platelet PAI-1 may contribute to the haemorrhagic tendency sometimes seen in this disorder. Plasma PAI-1 represents a larger proportion of total circulating PAI-1 in disease than it does in healthy individuals; PAI-1 per platelet is abnormal only in a minority of disorders. Plasma and platelet pools of PAI-1 vary independently in disease and both merit consideration in evaluating the importance, if any, of PAI-1 in thrombosis or haemorrhage.

Blood Platelets↗
PubMed1989

Differential regulation of calcitonin gene-related peptide and substance P in cultured neonatal rat vagal sensory neurons.

Nodose (inferior vagal sensory) ganglia were removed from neonatal rats, enzymatically dispersed using neutral protease, and maintained on previously dispersed rat atriacytes. After 7-10 days in culture, calcitonin gene-related peptide (CGRP) was present in 1-3 times the molar amount of substance P (SP). The content of SP was doubled by the addition of nerve growth factor (NGF) whereas CGRP was significantly less increased by 50% or less. The addition of forskolin increased SP and CGRP levels in cultures with or without NGF by 60-80 percent. Phorbol ester (PMA) did not alter SP content but significantly raised CGRP content by 40% in NGF supplemented cultures (P less than 0.001). Corticosterone, 0.01-0.1 microM, reduced SP content by 30% independently of NGF but had no effect on CGRP. These studies demonstrate that SP in vagal sensory neurons is more sensitive than CGRP to the effects of NGF or corticosterone. Both peptides are up-regulated by presumed increases in intracellular cyclic AMP, while CGRP (or CGRP neurons) may be independently regulated by protein kinase C.

Animals↗
PubMed1989

The utility of MMPI subtle, obvious scales for detecting fake good and fake bad response sets.

The MMPI was administered twice to 40 graduate students to determine the utility of the Weiner subtle and obvious scales (D, HY, PD, PA, MA) for estimating how fake good and fake bad response sets might influence full scale scores. The first time, the MMPI was administered under standard conditions. Subjects then were divided randomly into two groups: fake good (complete MMPI for job application) and fake bad (qualify for psychotherapy). There were significant multivariate test effects (standard vs. response set) for the raw scores of all five obvious, subtle, and full scales. However, when raw scores were converted to T scores to ascertain practical significance, the obvious scales appeared to provide the most useful information to enhance the interpretation of full scale scores in normal populations.

Adult↗
PubMed1989

An improved method for determining the microbial inhibitory activity of serum and its application to the study of patients with leukemia.

Numerous investigators have demonstrated that derangements in serum transferrin and iron can contribute to susceptibility to infection, but the complexity and imprecision of assays have impeded both research and development of clinical testing in this area. This article describes an automated assay for measuring the microbial inhibitory activity of transferrin in serum and its use in patients with acute myelogenous leukemia (AML) and in normal controls. The assay measured the ability of heat-inactivated serum to inhibit the growth of an antibiotic-resistant strain of Pseudomonas aeruginosa. The serum dilutions were prepared in a special low iron chemically defined broth. An inhibition index, the reciprocal of the serum dilution producing 50% inhibition of bacterial growth when compared with the growth in broth alone, was determined. The results showed the serum from the patients with leukemia had a significantly lower inhibition index than that of controls (16 +/- 11 vs. 35 +/- 13, P less than 0.01). In addition, they had higher serum iron levels (162 +/- 65 vs. 75 +/- 27, P less than 0.01), lower serum transferrin levels (231 +/- 65 vs. 309 +/- 71, P less than 0.01), and higher percentage saturation of transferrin with iron (59 +/- 21 vs. 20 +/- 8, P less than 0.01) than did controls. Because the assay uses equipment available in many clinical laboratories, it could be developed for routine use as an index of susceptibility to infection in selected patients.

Blood Bactericidal Activity↗
PubMed1989

The bleeding disorder in acute promyelocytic leukaemia: fibrinolysis due to u-PA rather than defibrination.

Three consecutive patients with acute promyelocytic leukaemia who presented with severe haemorrhagic syndromes were studied and the findings contrasted with those of two patients with classical defibrination after electroshock or complicated labour. The leukaemic patients showed no depletion of fibrinogen. There was no evidence of disordered thrombin generation by either intrinsic or extrinsic pathway sufficient to account for their haemorrhage. All, however, showed strikingly enhanced fibrinolytic activity, which could have accounted for bleeding. This fibrinolytic disorder was characterized by free u-PA in the plasma and differed from that seen after classical defibrination, where free t-PA was observed. U-PA was found also in malignant promyelocytes, which may be the source of u-PA activity in the patients' plasma. Bleeding in promyelocytic leukaemia may be primarily a fibrinolytic disorder.

Electrophoresis, Polyacrylamide Gel↗
PubMed1989

A critical care helicopter system in trauma.

Civilian helicopters and emergency medical services in the United States have been in existence for approximately 15 years. The rapid growth of this type of health care delivery coupled with an increasing number of accidents has prompted professional and lay scrutiny of these programs. Although they have a demonstrated history of benefit to patients, the type and severity of injuries to patients who are eligible for helicopter transportation need further definition. The composition of the medical crews and the benefits that particular crew members bring to the patients require ongoing evaluation. Significant questions regarding the number of pilots in a helicopter and in a program remain to be answered. This article reviews the role of emergency medical air transport services in providing care to trauma patients, staff training and evaluation, and safety criteria and offers recommendations to minimize risks to patients and crews.

Aircraft↗
PubMed1989

Experience with minimal complications in implanted catheters in children.

Eighty-two patients, ranging in age from 11 months to 24 years, underwent the percutaneous placement of an implanted catheter in order to have improved venous access. Thirty-five patients (43%) were beginning chemotherapy for cancer, four (5%) had a chronic hematologic disorder, and the remaining 43 (52%) were on chemotherapy for cancer. The mean duration of catheter function was 168 days (range of 7-1,030 days), with a cumulative experience of 18,812 days of catheter use. Complications were minimal. Only four catheters (5%) required removal secondary to infection, infiltration, or tissue breakdown. Substantially reduced complication rates were observed as compared to other studies using implanted central venous catheters. Implanted central venous catheters were proven to be safe in patients with hematologic disorders. These catheters enhance the ability to infuse chemotherapy, hyperalimentation, blood products, anesthesia, and imaging solutions and are safe to use in patients with a hemostatic or host defense deficiency.

Adolescent↗
PubMed1988

Dermal penetration of avermectin B1a in the rhesus monkey.

Forearms of rhesus monkeys were treated with [3H]avermectin B1a in three different vehicles and concentrations so that the penetration of avermectin B1a through skin could be determined. In order to simulate exposure of farm workers, such as mixer-loaders, applicators, and harvesters, to this pesticide, avermectin B1a was applied to the forearms of the monkeys as an emulsifiable concentrate (300 micrograms/monkey), a diluted emulsifiable concentrate (4.5 micrograms/monkey), and as a suspension in water (216 micrograms/monkey). After 1 or 10 hr of exposure, the treatment area was washed. The levels of radioactivity were determined in the urine, feces, plasma, and wash. On the basis of the amounts of radioactivity excreted in the urine and feces and the levels of radioactivity in the plasma after dermal application compared to those found after intravenous administration of the compound, less than 1% of the doses was absorbed. These data indicate that avermectin B1a would not readily penetrate the skin of farm workers exposed to it. Therefore, the hazard to farm workers exposed to this compound would be substantially mitigated.

Animals↗
PubMed1988

A plasminogen activator inhibitor (PAI-2) circulates in two molecular forms during pregnancy.

During normal pregnancy maternal haemostasis alters to protect against bleeding with a rise in plasma clotting factor levels and increased inhibition of fibrinolysis. The latter is due in part to increased levels of the 48 kDa plasminogen activator inhibitor (PAI-1) present in the plasma of non-pregnant individuals. A second plasminogen activator inhibitor (PAI-2) occurs in placenta and in a cultured histiocytic lymphoma cell line. We report here the identification by SDS-PAGE and zymography of PAI-2 in plasma during normal pregnancy. PAI-2 was present in two molecular forms of about 75 and 130 kDa, which were detectable at 12 weeks gestation and which persisted in the maternal circulation for up to 7 days after delivery. These forms of PAI-2 appear to be distinct from purified PAI-2, which has a molecular mass of 47-60 kDa and which is not normally detectable in this zymographic system, since it is sensitive to denaturants. The novel forms of PAI-2 may represent complexes or aggregates that retain activity after SDS-PAGE.

Female↗