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Biomedical subjects

S Stewart

Publications and source records attributed to S Stewart.

At least 181 records · Page 10Linked to original sources

Increased serum levels of anti-elastin antibodies in patients with Peyronie's disease.

The cause of Peyronie's disease is unknown. Immunological mechanisms in the pathogenesis have been previously suggested. Antibodies to elastin are present in all individuals. However, abnormal serum levels of anti-tropoelastin (reflecting elastin synthesis) and anti-alpha-elastin (reflecting elastin destruction) are seen in a variety of autoimmune diseases. We show that patients with Peyronie's disease have higher levels of antibodies to tropoelastin (p < 0.047) and alpha-elastin (p < 0.012) than age-matched controls, suggesting an increase in elastin synthesis and breakdown, respectively. These findings suggest the presence of autoimmune mechanisms in the pathogenesis of Peyronie's disease, which may have future diagnostic and therapeutic implications.

Antibodies↗

Public health medicine advice to local authorities: does it happen?

The views of public health physicians on the extent and quality of their specialty's collaboration with local government in Scotland was ascertained by postal questionnaire. Responses were received from 84 out of 97 (85%) Consultants in Public Health Medicine (CPHMs) working in Scottish health boards. Those working in health boards were more likely than colleagues in university departments to consider their service department to be sufficiently aware of and involved in issues having a bearing on health but not directly related to provision of health services (48/70 vs 4/12, RR 2.1, 95% CI 1.1-3.8). Seventy CPHMs gave advice to local authorities. They were in contact with a median of two local authority departments (range 0-6); most commonly Social Work (38 CPHMs), Environmental Health (36), and Education (26). CPHMs participated in a median of one multi-disciplinary group (range 0-3); most commonly Health Promotion (16 CPHMs), Child Welfare (9), Emergency Planning (9). The majority, 42 of 67 (63%), valued this contact highly, only three considering it of doubtful utility. Difficulties with bringing an item to the attention of a local authority department were identified by six out of 56 (11%) CPHMs and 32/69 (46%) recorded problems in ensuring Public Health Medicine input to local authority committees. In most health boards (12/14) there were formal meetings between CPHMs and heads of local authority departments; in each these were supplemented by informal meetings. One Director of Public Health and eight other CPHMs reported neither formal nor informal contact with local authorities. Spontaneous comments from respondents indicated a desire to strengthen the links with local authority departments.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Risk factors for survival following combined heart-lung transplantation. The first 100 patients.

As the numbers of heart and lung transplant recipients have increased it has become possible to identify major risk factors for early (within 3 months) and later (after 3 months) death after this procedure. For 100 patients receiving organs between April 1984 and February 1991, and followed up until February 1992, patient characteristics, operative details, and early morbidity were assessed for their effects on early and later deaths. Recipient age, sex, and preoperative diagnosis did not have a significant effect on early (within 3 months) or later death. Positive cytomegalovirus antibody status of donor or recipient conferred greater risk of death within 90 days (odds ratio [OR] = 3.24, P = 0.06). Greater than 2 L blood in the first 24 hr after operation (OR = 6.00, P = 0.05), and ventilation for greater than 24 hr (OR = 4.87, P = 0.006) were significant prognostic indicators of early death. After the first 3 months, the main risk factor for death was rejection in the first 3 months (OR = 1.38 per episode, P = 0.008). Early infection in general and CMV infection in particular were associated with a small increase in risk. This study confirms the importance of matching donor and recipient for CMV and shows that difficulties during operation, reflected in postoperative bleeding and ventilation times increased the chance of early death. Later death was associated with early acute rejection. A detrimental effect of infection, including CMV infection, either does not exist, or is too small to be detected in a study of this size.

Actuarial Analysis↗

Adhesion of peripheral blood lymphocytes of children with arthritis to human umbilical vein endothelial cells.

To determine whether adhesion of peripheral blood lymphocytes (PBL) of patients with juvenile rheumatoid arthritis (JRA) may be enhanced, adhesion of PBL of children with JRA, children with seronegative spondyloarthropathies (SSA), age-appropriate and adult controls, to human umbilical vein endothelial cells (HUVEC) was assessed in vitro. B and CD4 T lymphocytes in initial, adherent, and non-adherent cell fraction were identified by flow cytometry. B lymphocytes of all the younger subjects combined had a higher adherence to activated HUVEC compared with B lymphocytes of the adult donors. Except for greater adherence of HLA-DR+ CD4 T cells, lymphocytes of children with JRA showed no enhanced adhesion to either unactivated or activated HUVEC. The percentage of B cells adherent to activated HUVEC in each of the subject groups was 1.5-3.6-fold higher than adherent CD4 T lymphocytes. Surface analyses indicated higher percentages of CD49d (alpha 4)+ and CD29 (beta 1)+ CD4 T lymphocytes in adherent cells, but less of a differential in CD49 (alpha 4)+ and no difference in CD29 (beta 1)+ B lymphocytes. There were fewer Leu-8 (L-selectin)+ B and Leu-8+ CD4 T cells among adherent cells. The data suggest a greater adhesive capacity of B lymphocytes compared with CD4 T lymphocytes which is unrelated to disease, and the possibility that B lymphocytes may utilize adhesion molecules distinct from those of CD4 T lymphocytes. Only a small subset of T cells of patients with JRA may have an enhanced capacity for adhesion to endothelium.

Adolescent↗

CD40 expression in Hodgkin's disease.

CD40 is a transmembrane protein that belongs to a superfamily of proteins related to nerve growth factor receptor. CD40 is expressed on B cells and some B cell malignancies. It appears to be involved in B cell proliferation and the prevention of apoptosis in germinal center cells, which is accompanied by expression of bcl-2. Its expression is up-regulated by the EBV protein latent membrane protein-1 and cytokines interleukin-4 and interferon-gamma. The expression of CD40 in 37 cases of Hodgkin's disease and 23 cases of non-Hodgkin's lymphoma (11 T cell lymphomas and 12 B cell lymphomas) was examined by paraffin section immunohistochemistry using the BB-20 monoclonal antibody. In 26 of 37 cases of Hodgkin's disease the Reed-Sternberg cells showed strong membrane or cytoplasmic expression of CD40. Only 3 of 23 non-Hodgkin's lymphomas showed any expression of CD40 and then only weakly. There was no correlation between expression of bcl-2 or latent membrane protein-1 with CD40 expression. These results show that there is probable hyperexpression of CD40 in Hodgkin's disease and suggest that dysregulation of CD40 expression may play a role in the pathogenesis of Hodgkin's disease.

Antigens, CD↗

Transthoracic and transesophageal echocardiographic sizing of the aortic annulus to determine prosthesis size.

To assess the accuracy of 2-dimensional echocardiography versus transesophageal echocardiography (TEE) in predicting aortic annulus diameter, and to determine which part of the cardiac cycle should be used for measuring the size of the aortic valve prosthesis in patients undergoing aortic valve replacement, the aortic annulus was measured retrospectively in a blinded fashion in a group of 94 patients who had undergone aortic valve replacement: 66 had preoperative transthoracic echocardiography (TTE), 69 had intraoperative TEE, and 41 had both. Accuracy of measurements was calculated by the mean biases (differences between annular size by echo and actual valve size chosen by intraoperative mechanical sizing of the aortic annulus). TTE was compared with TEE and end-diastolic (ED) measurements with end-systolic (ES) measurements. The mean biases +/- SD were -1.7 +/- 3.4 mm by TTE-ES versus -0.9 +/- 3.5 mm by TEE-ES measurements (p = NS), and +0.03 +/- 3 mm by TTE-ED versus +0.5 +/- 2.8 mm by TEE-ED (p = NS). Examination of the magnitudes of the biases gave the same result. ED measurements were found to have a smaller amount of bias than ES measurements, both by TTE and by TEE: -1.7 +/- 3.4 mm by TTE-ES versus +0.03 +/- 3 mm by TTE-ED (p = 0.0001) and -0.9 +/- 3.5 mm by TEE-ES versus +0.5 +/- 2.8 mm by TEE-ED (p = 0.0001). Examination of the magnitudes of the biases also gave the same result.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Body composition analysis in liver cirrhosis. The measurement of body fat by dual energy X-ray absorptiometry in comparison to skinfold anthropometry, bioelectrical impedance and total body potassium.

In this cross-sectional study of methods to determine total body fat in patients with abnormal body composition secondary to chronic liver disease, we have demonstrated that TBFDXA by four-site skinfold anthropometry was highly correlated to TBFDXA, with small SEE and no bias in patients with ascites, but a small and significant bias in patients without ascites. TBFBIA showed no bias but a weaker correlation with a large SEE. In the presence of fluid retention the correlation coefficient decreased. TBFTBK showed a highly significant bias, and the correlation was not as good as SFA, and decreased in the presence of fluid retention.

Absorptiometry, Photon↗

Nodular transformation of the liver associated with portal and pulmonary arterial hypertension.

A case of multiple focal nodular hyperplasia (FNH) of the liver associated with noncirrhotic portal hypertension and later complicated by pulmonary arterial hypertension leading to death from right heart failure is reported. In retrospect, the portal hypertension diagnosed in early life was most likely due to a congenital hypoplasia of portal vein branches and multiple FNH, a hyperplastic response of the liver parenchyma in association with anomalies of hepatic arterial branches as found within the lesions. This case may represent a form of multiple FNH syndrome restricted to the liver, because neither extrahepatic vascular malformation nor brain tumor was identified at autopsy. The FNH lesions had considerably expanded over the years, and the severe sinusoidal congestion due to chronic right-sided heart failure with subsequent prolonged parenchymal exposure to blood-borne hepatotrophic factors is a likely explanation for both the massive enlargement of FNH lesions and the nodular regenerative hyperplasia observed in the intervening parenchyma.

Adolescent↗

Characterization of an early gene coding for a highly basic 8.9K protein from the Orgyia pseudotsugata multicapsid nuclear polyhedrosis virus.

A new gene of the baculovirus Orgyia pseudotsugata multicapsid nuclear polyhedrosis virus (OpMNPV) has been identified that encodes a highly basic 8.9K protein. The gene called p8.9 is expressed as a 0.5 kb transcript by 1 h post-infection and initiates at an early gene motif. The promoter of the 0.5 kb transcript has two upstream elements, repeats I and II, which are similar to motifs previously characterized in the OpMNPV IE-2 gene and the Autographa californica nuclear polyhedrosis virus IE-N and PE38 genes. A second p8.9 transcript expressed from 8 to 72 h post-infection was shown to initiate 634 bp upstream from the early gene motif in a region that has no similarity to any previously described baculovirus promoter or initiation site. Transient assays utilizing a reporter gene have shown that the p8.9 early promoter is active in a Lymantria dispar (LD652Y) and Spodoptera frugipeda (Sf9) cell lines in the absence of other viral factors. In addition, it was also demonstrated that the p8.9 promoter is trans-activated by the OpMNPV IE-2 and p34 genes, but not by IE-1.

Amino Acid Sequence↗

Analysis of the Orgyia pseudotsugata multicapsid nuclear polyhedrosis virus trans-activators IE-1 and IE-2 using monoclonal antibodies.

We have produced monoclonal antibodies against two Orgyia pseudotsugata multicapsid nuclear polyhedrosis virus (OpMNPV) transcriptional trans-activators, IE-1 and IE-2. Temporal analysis of IE-1 and IE-2 proteins have shown that IE-1 continues to increase in steady-state levels from 0 to 120 h post-infection, whereas IE-2 declines by 36 h post-infection. At least five different electrophoretic forms of IE-1 are present in OpMNPV-infected LD652Y cells of which three appear to be from the non-spliced IE-1 gene. Cotransfection experiments also showed that IE-1 causes a reduction in the levels of IE-2 protein but concurrently IE-2 increases IE-1 expression. Western blot analysis indicated that a form of IE-1 copurified with budded virions but did not copurify with the polyhedron-derived virus.

Animals↗

Alternative transcriptional initiation as a novel mechanism for regulating expression of a baculovirus trans activator.

In this report, we show that the Orgyia pseudotsugata nuclear polyhedrosis virus p34 gene, which is homologous to the Autographa californica nuclear polyhedrosis virus PE-38 gene, is a trans activator. The predicted p34 protein contains a number of motifs that are similar to those found in other eukaryotic transcriptional trans activators, including a putative zinc finger DNA-binding domain, a glutamine-rich domain, and a leucine zipper. Northern (RNA) blot analysis showed that the p34 gene is expressed as a 1.1-kb mRNA from 1 to 48 h postinfection and as a 0.7-kb mRNA from 18 to 120 h postinfection. Mapping of these transcripts showed that they were 3' coterminal but initiated at different 5' start sites. The 1.1-kb transcript initiates at a baculovirus early gene motif (CACAGT) and encodes the entire p34 open reading frame (ORF). The 0.7-kb transcript initiates at a baculovirus late gene start site (GTAAG) internal to the p34 ORF. Western blot (immunoblot) analysis using p34 antisera showed that the 0.7-kb transcript is translated as an amino-terminally truncated 20-kDa form of the full length 34-kDa protein. Functional analysis indicated that the 34-kDa protein transcriptionally trans activates the IE-2 promoter whereas the 20-kDa protein does not. Therefore, p34 produces two functionally different proteins from the same ORF, using the novel mechanism of alternative transcriptional initiation.

Alternative Splicing↗

Multiple recurrent intrapulmonary and endobronchial mesenchymomas (hamartomas).

A patient is described with multiple, benign, chondromatous intrapulmonary and endobronchial mesenchymomas of the lung, which recurred after resection on two occasions over a period of 30 years. In such a patient presenting at a young age or with a history of previous recurrence, a wedge excision may be necessary to prevent further recurrence.

Adult↗

Bronchoalveolar lavage and transbronchial lung biopsy during acute rejection and infection in heart-lung transplant patients. Studies of cell counts, lymphocyte phenotypes, and expression of HLA-DR and interleukin-2 receptor.

The total and differential cell counts of 135 bronchoalveolar lavages (BAL) in 48 heart-lung transplant (HLT) patients were compared with the histologic findings in concurrent transbronchial lung biopsies (TBBs). Counts of CD3+, CD4+, and CD8+ lymphocytes were recorded, and a semiquantitative assessment of HLA-DR and interleukin-2 receptor (IL-2R) expression was made on 29 occasions. There were five diagnostic categories: normal (n = 8), acute rejection (ALR) (n = 57), treated rejection (TR) (n = 19), infection (INF) (n = 24), and chronic rejection (CR) (n = 24). Total cell counts in INF were significantly higher than counts in all the other diagnostic groups. The highest BAL lymphocyte counts, significantly higher than in INF, were found in ALR because of increased CD8+ cells, exceeding 15% in 13 of 57 BALs. TBBs in ALR by contrast showed significantly increased numbers of both CD8+ and CD4+ cells. High dose corticosteroid treatment of ALR caused a fall in cellularity of BAL and TBB specimens but not always to values seen when patients were well. During INF and CR, significantly increased numbers of PMNs were seen in the BAL. HLA-DR and IL-2R expression was enhanced in cells of BAL and TBB in all complications. BAL can only supplement at present histologic examination of TBB in the diagnosis of complications after HLT.

Acute Disease↗