Increased CSF HVA with craving in long-term abstinent cocaine abusers.
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Biomedical subjects
Publications and source records attributed to S Stewart.
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A second immediate early (IE) regulatory gene of the baculovirus Orgyia pseudotsugata multicapsid nuclear polyhedrosis virus (OpMNPV) has been identified. The IE-2 gene which is homologous to the IE-N gene of Autographa californica MNPV was mapped to the HindIII A fragment of OpMNPV between 0.41 to 1.37 map units. The IE-2 gene codes for a predicted protein of 45,640 Da and analysis of the amino acid sequence shows that the protein has a highly basic amino terminal domain and a cysteine-rich domain that is similar to a zinc finger motif that is also found in the baculovirus proteins GC30 and PE-38. The IE-2 gene is expressed as a 1.3-kb transcript that was detectable by 0.5 hr postinfection (hr p.i.), reached maximum steady state levels by 6 hr p.i., and declined slightly by 48 hr p.i. Cis-acting 5' regulatory sequences were analyzed by deletion analysis of the IE-2 promoter linked to the reporter gene chloramphenicol acetyl transferase. Maximum expression was obtained when the IE-2 promoter contained sequence 275 bp upstream from the transcriptional start site. trans-Activation analysis revealed that IE-2 trans-activated the IE-1 promoter and in addition appeared to be autoregulatory.
An enhancer element was identified in the virus Orgyia pseudotsugata multicapsid nuclear polyhedrosis virus (OpMNPV) that is located adjacent to the 3' end of the IE-2 gene and 5' to an open reading frame that codes for a predicted protein that has 37% homology to the AcMNPV PE-38 gene. The OpMNPV enhancer (OpE) consists of a 66-bp element that is tandemly repeated partially or completely 12 times. The OpE sequences were shown to increase gene expression from the Autographa californica MNPV delayed early p39 promoter independently of position or orientation, and were also shown to increase expression from the promoter of the OpMNPV immediate early gene, IE-2. Sequences homologous to the OpE sequences were mapped by Southern blot hybridization to four additional locations around the OpMNPV genome. This indicates that OpMNPV is similar to other baculoviruses such as AcMNPV, Lymantria dispar MNPV, and Choristoneura fumiferana MNPV that have homologous regions in several locations in the genome.
Standard microscopic suture vasovasostomy represents a challenge to many urologists. It is technically demanding, and requires two to five hours of operative time. In an attempt to decrease the technical demand and the time requirement, we report the use of a microvascular anastomotic clip and compare this microclip to a standard eight-suture nonstented technique and a six-suture stented technique using a hollow, absorbable 0.5-mm polyglycolic acid stent. The control group with suture required an average of 38.5 minutes per anastomosis for the nonstented group and twenty-two minutes for the stented group. The clip group required 7.6 minutes for the unstented vasovasostomy and 6.5 minutes for the stented vasovasostomy. We obtained a 91 percent patency rate for the stented clip group and 100 percent patency for the unstented clip group. In a rat vasovasostomy, the operative time as well as the inherent technical demand were significantly reduced.
Acute myocardial infarction (AMI) was previously treated with conservative strategies that allowed the process of ischaemia to proceed uninterrupted. The resultant myocardial necrosis and reduced ventricular function were accepted outcomes. The emergence of thrombolytic agents such as streptokinase and tissue plasminogen activator (tPA) revolutionised the management of coronary artery occlusion, yet the spectre of further myocardial necrosis and ventricular dysfunction remains. The concept of 'reperfusion injury', an acute process described as occurring after thrombolysis of a coronary artery occlusion and referring to an unexpected loss of ventricular function, has been extensively researched. Current research papers describing the mechanisms involved appear either to emphasise those processes that occur within the actual myocytes, or those events within the coronary vasculature. In most papers however, oxygen free radicals (OFRs) are accepted as mediators of cellular injury; despite the debate surrounding their primary source. Efforts to minimise the effects of primary ischaemia and subsequent 'reperfusion injury', appear to be focused upon restoring cardioprotection against the increased levels of these damaging molecules. Scavenging agents such as N-acetylcysteine (NAC) which can also assist in dilating coronary vessels as well as preventing further platelet aggregation, when combined with glyceryl trinitrate (GTN), are being closely scrutinised. Despite the advances made, the processes within the myocardium remain somewhat a mystery and the search continues for more effective strategies to ensure myocardial viability and long-term function. Critical care nurses need not only to be aware of the aim of these new strategies, but should also be conscious of their effect on the patients receiving them.
Intraoperative color Doppler transesophageal echocardiography (TEE) was performed in 26 patients undergoing corrective or palliative surgery for congenital heart disease. Age ranged from 1 day to 15 years, and body weight ranged from 2.9 to 42 kg. Objectives of the study were to determine the smallest infant in whom the pediatric probe could be used safely, additional diagnostic value, and it role in the intraoperative assessment of the surgical repair. The insertion of the pediatric probe was possible in all 26 patients. The smallest infant in this series was a newborn weighing 2.9 kg. Excellent correlation was obtained with preoperative transthoracic echocardiographic findings and operative findings. Assessment of the surgical repair was obtained in the immediate postcardiopulmonary bypass period. No short-term complications occurred in this series. Intraoperative color Doppler TEE provided a detailed and accurate assessment of the morphology, the function of the heart, and altered the management of at least two patients.
We report two patients with silent oesophageal perforation. In neither patient was the diagnosis made preoperatively by the referring physicians and a history of swallowing difficulty was elicited in only one patient. The appearances on computed tomography were very similar in both patients: there was a soft tissue mass in the upper retro-oesophageal region with destruction of the underlying vertebral body.
Bird fancier's lung, the most common form of extrinsic allergic alveolitis in Britain, can be a difficult diagnostic problem. The symptoms are non-specific, often insidious in onset and frequently misdiagnosed as influenza or a viral or bacterial pneumonia. Frequently there is a delay in eliciting the history of exposure to the antigen. The chest radiograph is often less impressive than the clinical presentation and may be normal despite severe symptoms, impaired respiratory function and florid pathological changes. We present three cases demonstrating these diagnostic problem. In two cases, high resolution computed tomography demonstrated the typical 'ground glass' opacification seen in active alveolitis. This allowed targeting of transbronchial biopsies which revealed an inflammatory infiltrate of the interstitium with granuloma formation and inflammatory cells in some alveoli. The problems in diagnosis and the potential role of high resolution computed tomography are discussed.
OBJECTIVE: To evaluate the efficacy and toxicity of vincristine and bleomycin when used in combination to treat patients with progressive Kaposi's sarcoma. DESIGN: A retrospective case notes review. SETTING: The departments of Immunology and Genito-Urinary Medicine, St Mary's Hospital, London, UK. PATIENTS: All patients presenting with progressive Kaposi's sarcoma and requiring chemotherapy between January 1987 and January 1990, who had received no previous systemic chemotherapy. INTERVENTIONS: Treatment with vincristine (2 mg) and bleomycin (30 mg, 18 h infusion), or vinblastine (2.5-5.0 mg) if peripheral neuropathy developed. Treatment with zidovudine and prophylaxis of opportunistic infections where indicated. OUTCOME MEASURES: Response, toxicity and survival. RESULTS: Overall, patients had a poor prognosis: 33 out of 46 (72%) had had a previous opportunistic infection, had a mean CD4 count of 144 x 10(6) (20 out of 46 tested) and a mean Karnofsky index of 75.4. They received a median of five cycles of therapy: a partial response was achieved in twenty-six patients (57%), disease progression was halted in a further 16 (35%), while disease progression continued in four (9%) despite therapy; there were no complete responders. Mean duration of response was 2 months (s.d., 1.26 months), survival was 8 months (s.d., 6.7 months) from start of therapy and 17 months (s.d., 8.9. months) from first AIDS diagnosis. On multivariate analysis the best predictor of mortality was the presence of previous opportunistic infection (P = 0.00653). Side-effects were minimal in comparison with other studies. The most common side-effect, in 13 cases (28%), was peripheral neuropathy, which may in part represent the prevalence of HIV neuropathy or remain as background. Haematological toxicity was uncommon. CONCLUSIONS: Treatment for HIV-related Kaposi's sarcoma in advanced HIV disease is becoming more necessary as disease profiles change. Conventional chemotherapy regimens for malignancy are not well tolerated in these patients and may not be indicated. This regimen is effective and has low toxicity in AIDS patients. Non-responders should be considered for more intensive regimens.
The human tumour cell lines RPMI 8226 and Daudi are potent inducers of V gamma 9-expressing T cells. The inducing element of RPMI 8226 has not been defined but evidence suggests that a member of the GroEL heat shock protein (HSP) family (HSP 58) may have a role in the induction by Daudi cells. The present study examined the reactivity patterns of gamma delta T-cell clones generated in response to RPMI 8226 and addressed the possible role of HSP 58 in this process. RPMI 8226 induced a population of V gamma 9 TCR+ cells which were heterogeneous in terms of their cell surface markers, patterns of proliferation and cytotoxic responses. All clones expressed CD3, CD2, CD18 and CD29. They demonstrated variability in expression of CD56, CD8 and HLA-DR. RPMI 8226 stimulated proliferation in purified bulk gamma delta cultures and clones. Daudi was also capable of inducing these cells to proliferate while mycobacterial products were not effective. The clones demonstrated a limited non-MHC-restricted cytotoxicity pattern with some evidence of clonal heterogeneity. Although both Daudi and RPMI 8226 were sensitive to lysis by the clones, cold inhibition experiments indicated differential activity towards these targets. Anti-HSP 58 was inhibitory to gamma delta T-cell induction by RPMI 8226, Daudi and mycobacterial products. However, the anti-HSP 58 antibody appears to bind to the surface of at least six different tumour cell lines with no correlation to their ability to induce gamma delta T cells and the anti-HSP 58 inhibited non-gamma delta responses.
Purified populations and clones of human gamma delta T cells were examined for their ability to interact with extracellular matrix (ECM) components. The stimulation of these cells with phorbol ester induced cellular adhesion for ECM. The adhesion structures for fibronectin and collagen were shown to be members of the CD29 integrin family. The expression patterns of beta 1, beta 2 and beta 3 integrins by these cells were examined. The receptor expression and utilization patterns suggest that alpha beta, gamma delta T cells and B cells have similar repertoires of adhesion structure.
The internal mammary artery is currently the arterial replacement of choice for coronary artery bypass grafts. The authors studied the permeability of the vessel wall of the internal mammary artery and the ascending aorta in 12 patients undergoing coronary artery bypass grafts by comparing the 125I-albumin binding profiles. Their results suggest that albumin crosses the internal mammary artery more easily than in the aorta.
A new system for tissue approximation consisting of a nonpenetrating arcuate-legged clip applied to everted tissue edges to form an elastomeric flanged joint is described. The flanged joint has unusual physical and morphologic properties. Novel systems for tissue eversion, clip application and clip removal have been tested at the micro scale in blood vessels and the rat vas deferens (vasovasostomy). Human applications have been successful (cerebrovascular reconstruction, free-flap transfer, skin grafting, A-V access). The system is biologically and technically equivalent to or superior to the needle-and-suture technique. Avoidance of intimal or mucosal penetration or intraluminal foreign body is associated with prompt wound healing and the reconstitution of tubular integrity. The system is readily adaptable for endoscopic surgical reconstructions, providing the surgeon with enhanced reconstructive abilities.
The pathology of lung transplantation has many features in common with other solid organ grafts. Acute pulmonary rejection is characterized by perivascular, peribronchiolar, and interstitial mononuclear infiltrates. Chronic rejection causes obliterative bronchiolitis and vascular sclerosis. The transplanted lung is uniquely susceptible to infections, both usual and opportunistic, and these can be difficult to differentiate from rejection. Infection in the foreign graft can produce unusual histological appearances. Posttransplant lymphoproliferative disease can affect the lung allograft primarily. Transbronchial lung biopsy and bronchoalveolar lavage are considered essential to the postoperative management of lung transplants and to the understanding of the pathological processes limiting graft survival.
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Both DNA and RNA were found to co-purify with Clostridium difficile toxin B but not toxin A. DNAase treatment greatly reduced the cytotoxicity of toxin B but not of toxin A. RNAase had no effect on either toxin. The effects on toxin B were shown to be due to a contaminating protease and could be inhibited by the serine protease inhibitor phenylmethylsulphonyl fluoride.
Members of the beta 1 (CD29) integrin family are involved in cellular adhesion to extracellular matrix. However, there have been several reports of CD29 integrin participation in intercellular adhesion. For example, the treatment of the human T cell line Jurkat with antibodies to alpha 4 (CD49d) causes homotypic aggregation. The present report describes the induction of aggregation of Jurkat cells by antibodies to alpha 5 (CD49e) and to a lesser extent by antibodies to the common beta 1/CD29 chain of these integrins. The metabolic requirements for these aggregations are compared with that of the CD49d-induced process. The possible involvement of fibronectin in the cytoadhesion appears to be unlikely as (1) the aggregates form in the absence of plasma fibronectin; (2) antibodies to fibronectin do not inhibit the cell adhesion; and (3) exogenous fibronectin does not influence the process. One of the cognate partners involved in the CD49e-induced aggregation appears to be present on non-antibody-treated Jurkat cells as the cells are coincorporated into aggregates of anti-CD49e-stimulated cells. The adhesion does not appear to involve members of the CD2, CD3, CD4, or CD18 receptor groups. These results indicate that interaction with alpha 4, alpha 5 chain or the beta 1 chain of the CD29 integrins leads to the induction of intercellular adhesion. The possible biological significance of this process is discussed.
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