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Biomedical subjects

B Bennett

Publications and source records attributed to B Bennett.

At least 19 recordsLinked to original sources
PubMed1992

A comparison of commercially available adjuvants for use in research.

We evaluated an adjuvant, TiterMax, as an alternative to complete Freund's adjuvant (CFA) for producing antisera in animals. TiterMax, consists of a microparticulate stabilized water-in-oil emulsion of a metabolizable oil, squalene, with the adjuvant block copolymer CRL89-41. This paper reports two evaluations of TiterMax versus CFA and other commercially available adjuvants. In the first study, mice were immunized with a hapten, trinitrophenol, conjugated to hen egg albumin (TNP-HEA) in one of several adjuvants: TiterMax, CFA, Adjuvax, Ribi adjuvant system (RAS), Alhydrogel or Lipovant. TiterMax induced higher longer lasting titers with fewer injections than any of the other adjuvants. The magnitude of the response to TNP varied with species and route of immunization. In the second study, CFA, TiterMax, Adjuvax and RAS were compared in rabbits, mice and goats. Animals were immunized with luteinizing hormone-releasing hormone (LHRH) conjugated to BSA in each adjuvant using comparable protocols. TiterMax induced titers against the peptide equivalent to CFA in all three species. The inflammatory responses induced by TiterMax were mild and transient compared with those induced by CFA. These data suggest that TiterMax is an effective alternative to CFA in many situations.

Adjuvants, Immunologic↗
PubMed1992

Significance of accessory ductal structures in hernia sacs.

The finding of ductal structures resembling a vas deferens during pathological examination of a hernia sac specimen has significant medical and legal implications. A method of distinguishing these accessory structures from an inadvertently transected vas has been lacking and is needed. Between July 1989 and January 1990 we examined 147 hernia sacs from 105 consecutive prepubertal and adolescent boys to determine the incidence and salient histological features distinguishing these ductal structures from a true vas deferens. Luminal diameters of the ductal structures were compared with published normal age-related established vas deferens diameters and with those measured during hernia repair in 10 of our youngest patients. Among the 147 specimens 6 hernia sacs (4.1%) contained ductal structures. We found that the mean ductal diameter (0.263 mm.) was significantly smaller than that of a normal vas deferens (0.69 to 1.5 mm.). Furthermore, the surrounding mantle of tissue of these ductal structures lacked muscle tissue when studied with Masson trichrome stain. We conclude that duct diameter and trichrome staining are simple ways of differentiating these structures from a true vas deferens.

Adolescent↗
PubMed1992

Management of ventricular arrhythmias: then and now.

OBJECTIVE: To review the changing environment of antiarrhythmic therapy. DATA SOURCES: The majority of articles chosen were written by experts in the field of arrhythmia management. The references include a pilot study, abstracts, original articles and results of study groups. An equal number of sources used in this article were obtained from fellow healthcare professionals and MEDLINE searches. STUDY SELECTION: Large, controlled clinical trials in which patient populations had structural heart disease, prior myocardial infarction and/or frequent ventricular premature beats. All were treated with either antiarrhythmic therapy or devices. DATA SYNTHESIS: Past research in the field of arrhythmia management has indicated that ventricular premature beat suppression is the key to increasing patient survival. After reviewing the results of such pivotal trials as the Cardiac Arrhythmia Suppression Trial, however, the question of whether to initiate therapy remains. CONCLUSIONS: Several trials investigating the efficacy of antiarrhythmic drugs in decreasing sudden death have yielded disappointing results. These trials have been beneficial, however, in classifying arrhythmias and assessing patient risk. The outcomes of these trials, combined with advances in the treatment of heart disease, provide us with a framework for antiarrhythmic therapy. Additional controlled clinical trials are necessary if we are to learn the best means of increasing survival in ventricular arrhythmia patients.

Action Potentials↗
PubMed1991

Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes.

In the present study we demonstrate that human monocytes activated by lipopolysaccharides (LPS) were able to produce high levels of interleukin 10 (IL-10), previously designated cytokine synthesis inhibitory factor (CSIF), in a dose dependent fashion. IL-10 was detectable 7 h after activation of the monocytes and maximal levels of IL-10 production were observed after 24-48 h. These kinetics indicated that the production of IL-10 by human monocytes was relatively late as compared to the production of IL-1 alpha, IL-1 beta, IL-6, IL-8, tumor necrosis factor alpha (TNF alpha), and granulocyte colony-stimulating factor (G-CSF), which were all secreted at high levels 4-8 h after activation. The production of IL-10 by LPS activated monocytes was, similar to that of IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF alpha, granulocyte-macrophage colony-stimulating factor (GM-CSF), and G-CSF, inhibited by IL-4. Furthermore we demonstrate here that IL-10, added to monocytes, activated by interferon gamma (IFN-gamma), LPS, or combinations of LPS and IFN-gamma at the onset of the cultures, strongly inhibited the production of IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF alpha, GM-CSF, and G-CSF at the transcriptional level. Viral-IL-10, which has similar biological activities on human cells, also inhibited the production of TNF alpha and GM-CSF by monocytes following LPS activation. Activation of monocytes by LPS in the presence of neutralizing anti-IL-10 monoclonal antibodies resulted in the production of higher amounts of cytokines relative to LPS treatment alone, indicating that endogenously produced IL-10 inhibited the production of IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF alpha, GM-CSF, and G-CSF. In addition, IL-10 had autoregulatory effects since it strongly inhibited IL-10 mRNA synthesis in LPS activated monocytes. Furthermore, endogenously produced IL-10 was found to be responsible for the reduction in class II major histocompatibility complex (MHC) expression following activation of monocytes with LPS. Taken together our results indicate that IL-10 has important regulatory effects on immunological and inflammatory responses because of its capacity to downregulate class II MHC expression and to inhibit the production of proinflammatory cytokines by monocytes.

Base Sequence↗
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↗
PubMed1979

Graves' disease, follicular thyroid carcinoma and functioning pulmonary metastases.

We present a case with the unusual association of Graves' disease and functioning pulmonary metastases of follicular thyroid carcinoma. Unlike other reports of thyroid cancer and thyrotoxicosis, this patient's hyperthyroidism was related to a hyperfunctioning primary thyroid neoplasm and not merely to large amounts of functioning metastatic tumor. Thyroidectomy cured her hyperthyroidism. A lung biopsy confirmed the impression of metastatic thyroid cancer. Following therapeutic radioactive I131 pulmonary metastases completely disappeared.

Adenocarcinoma↗
PubMed1978

Familial thrombosis: inherited deficiency of antithrombin III.

Several members of a family living on the west coast of Scotland and on one of the islands off the coast had serious thrombotic disease. The plasma antithrombin III (ATIII) concentrations were measured by both functional and immunological assay in all available members of the family. Concentrations were 25% to 66% of normal in 12 people, including all seven with thrombotic disease. The inheritance pattern was characteristic of an autosomal dominant disorder. Thrombotic disease generally affected the leg, mesenteric, and axillary veins, although one man who had died before the study began had had severe arterial atheroma. In women the first thrombotic symptoms usually occurred during pregnancy. None of these patients have developed thrombotic symptoms until they were at least 18, so four younger members of the family who have ATIII deficiency but no thrombotic disease may eventually develop symptoms.

Adolescent↗
PubMed1978

Carcinoma of prostate presenting as retroperitoneal mass.

The pattern of dissemination of prostatic carcinoma varies, but skeletal metastasis is the single most common symptomatic mode of presentation. The clinical course and treatment of the 2 cases presenting with symptomatic metastases to the retroperitoneum are described in detail and pertinent literature is reviewed.

Adenocarcinoma↗