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Biomedical subjects

J Powell

Publications and source records attributed to J Powell.

At least 217 records · Page 12Linked to original sources
PubMed1989

Interferon-gamma-treated K562 target cells distinguish functional NK cells from lymphokine-activated killer (LAK) cells.

In vitro incubation of the erythroleukemic cell line K562 with interferon-gamma (IFN-gamma) renders these cells relatively resistant to natural killer (NK) cell lysis. However, such treatment does not alter their sensitivity to LAK cell lysis. Thus, the lytic susceptibility of interferon-gamma-treated K562 (I-K562) cells to LAK cells as opposed to its relative resistance to NK cell lysis provides a functional assay to help distinguish these two types of effector cells. The relative resistance of I-K562 for NK cell-mediated lysis was not secondary to the release of soluble factors or the frequency of Leu-19+, CD3+ T cells, residual IFN-gamma, or expression of MHC Class I molecules. Coincubation of I-K562 cells with NK or LAK cells overnight did not appreciably change the pattern of lytic responses against K562 and I-K562 target cells. However, incubation of PBMC in vitro with I-K562 but not native K562 in the presence of r-IL-2 leads to a marked decrease in the generation of LAK cells. The inhibition of LAK cell generation was not secondary to differences in the consumption of bioactive levels of IL-2. Differences in the lytic capability of NK and LAK effector cells suggest heterogeneity among cells that mediate such non-MHC-restricted lysis. Use was made of cells from a patient with a large granular lymphocyte lymphoproliferative disease (greater than 85% Leu-19+) to determine if such cells could be used to distinguish clonal population of cells which would represent NK or LAK cell function. Of interest was the finding that such cells, even after incubation in vitro with IL-2, showed lytic function representative of NK cells but not LAK cells. Data concerning the inhibition of LAK cell generation by I-K562 cells have important implications for future therapeutic trials of IFN-gamma and IL-2 in the treatment of human malignancies.

Antigens, Differentiation↗
PubMed1989

Use of a synthetic peptide adjuvant for the immunization of baboons with denatured and deglycosylated pig zona pellucida glycoproteins.

Baboons were immunized using a synthetic peptide adjuvant with two purified pig zona pellucida glycoproteins. The major zona pellucida glycoprotein (ZPI) was purified by preparative isoelectric focusing, and the 80 K deglycosylated zona pellucida protein (ZPIII) was purified by preparative sodium dodecyl sulfate polyacrylamide gel electrophoresis. The immunogenicity as well as the antigenicity of these proteins were evaluated by characterizing antibodies using the enzyme-linked immunoassay and by immunoblotting of zona pellucida proteins separated by high-resolution two-dimensional polyacrylamide gel electrophoresis. Both groups of animals developed antibodies that recognize the major zona pellucida glycoprotein, (ZPI) and immunoblotting procedures provide evidence that two of the major porcine zona pellucida glycoprotein families (ZPI and ZPIII) contain shared antigenic determinants. The animals immunized with ZPI showed decreased levels of estrogen throughout their menstrual cycles, and two of the animals ceased ovulation. All animals in the group immunized with ZPIII had a significant reduction in the numbers of antral follicles as compared with control animals. Although ovarian cyclicity was not altered significantly within a few months after immunization, two of the five animals in this group became amenorrheic by 8 months. Histologic analysis of ovarian tissue shows that follicles were absent or frequently abnormal in animals of both groups following long-term immunization. These studies demonstrate that the synthetic adjuvant is effective in inducing antibodies (to purified zona pellucida glycoproteins) that recognize antigenic determinants to either denatured or deglycosylated zona pellucida glycoproteins, and that some of these antibodies may interfere with normal ovarian function.

Adjuvants, Immunologic↗
PubMed1989

Lipids and apolipoprotein profiles in men with aneurysmal and stenosing aorto-iliac atherosclerosis.

The plasma lipids, lipoproteins and apolipoproteins have been compared in two groups of men with aorto-iliac atherosclerosis: Aneurysmal disease (n = 42) and stenosing disease (n = 86). The mean age of the men aneurysmal disease was 67.5 +/- 5.8 years and the mean age of the men with stenosing disease was 65.0 +/- 6.1 years: There was no significant different in body mass indices or smoking habits between the groups. The patients with aneurysmal disease had lower levels of plasma cholesterol than patients with stenosing disease (5.53 +/- 1.17 versus 6.11 +/- 1.20 mmol/L, P less than 0.05), but carried more cholesterol in VLDL compared to patients with stenosing disease (1.00 +/- 0.90 versus 0.60 +/- 65 mmol/L, P less than 0.05). Significantly lower concentration of apolipoprotein AI and HDL-cholesterol in patients with aneurysmal disease (ApoAI 1.01 +/- 0.31 versus 1.18 +/- 0.31 mmol/L, P less than 0.02, HDL 0.93 +/- 0.53 versus 1.13 +/- 0.34, P less than 0.05) was another characteristic difference between these two groups of patients with peripheral arterial disease. Otherwise, there were no obvious differences in the levels of plasma triglyceride, VLDL-triglyceride, LDL-cholesterol, and apolipoproteins B, C-III and E between the two groups. Although lipid and apolipoprotein profiles may not discriminate between aneurysmal and stenosing disease, different types of lipoprotein particles may contribute to the atherosclerotic process characterising both diseases.

Aged↗
PubMed1989

Cellular, enzymatic, and genetic factors in the pathogenesis of abdominal aortic aneurysms.

Aneurysms of the abdominal aorta occur with atherosclerosis or connective tissue disorders. Changes of three components of aortic media, smooth muscle cells, elastin, and collagen, which could contribute to medial weakening, are discussed. Smooth muscle cells cultured from the aging abdominal aorta (normal, atherosclerotic, or aneurysmal) have limited replicative potential at five to six cell doublings, whereas cells from aneurysmal thoracic aorta undergo more than 20 cell doublings in culture. The elastin content is much reduced in aneurysms and this is associated with an increase in elastase activity of medial homogenates to 17.8 U/ng of deoxyribonucleic acid (DNA) compared with 8.3 and 4.4 U/ng of DNA in atherosclerotic and normal aorta, respectively. An elastinolytic enzyme has been purified from aneurysmal aorta and appears to have different properties from human leukocyte elastase. Ruptured aneurysms are associated with an increased total collagenase activity but the increase could be stimulated by, or result from, an influx of inflammatory cells and does not necessarily have a causal significance. In patients with a family history of aneurysm there appears to be a decreased content of type III collagen in aortic media: 24% +/- 4% compared with 32% +/- 5% in most aneurysms. Familial aneurysms are most common in women, and preliminary results suggest that a polymorphic variant of the type III collagen gene, defined by restriction enzyme digest, may be associated with aneurysmal disease in women. The genetic approach may define causal mechanisms predisposing patients to aneurysmal dilatation.

Aged↗
PubMed1989

Comprehensive health care for high-risk adolescents: an evaluation study.

This study was designed to evaluate the effectiveness of a large scale program to improve health care for high-risk adolescents. Seven clinics, funded to provide comprehensive primary care to adolescents, were compared to three non-funded clinics. The majority of the 2,788 adolescent patients sampled in these clinics were female (78 percent) and Black (71 percent). Each patient was initially interviewed at the time of a clinic visit and reinterviewed 12 months later; their medical records were systematically reviewed. As expected, the funded clinics detected and treated a wider range of medical and behavioral problems than the comparison clinics, a finding that was based on the self-reports of patients and confirmed by documentation in the medical records. However, improvements in life-style and in specific medical outcomes were not observed. To build on the limited success of this program, efforts are needed to encourage more males to receive care and to develop more specific interventions for patients in this age group.

Adolescent↗
PubMed1989

Two methods of scoring sleep with the Oxford Medilog 9000: comparison to conventional paper scoring.

This study evaluated two methods of scoring taped polysomnographic data directly on the Medilog 9000 scanner: (a) screen-by-screen scoring, and (b) rapid screen scoring. Sixteen overnight polysomnograms recorded on Medilog 9000 recorders were scored using the above two methods and were also printed on paper for conventional paper scoring. Interscorer agreement was 87.8% for paper scoring, 85.5% for screen-by-screen scoring, and 84.2% for rapid screen scoring. Comparison of screen-by-screen scoring with paper scoring revealed small absolute deviations and correlations of r greater than 0.90 for all sleep parameters, with the exception of brief (less than 2 min) awakenings (r = 0.69). Rapid screen scoring resulted in slightly lower correlations and greater deviations from paper scoring on several sleep parameters, but appeared acceptable for most clinical purposes and greatly reduced the required scoring time. Although some statistically significant differences between scoring methods were observed, the size of effect was small and of doubtful clinical importance. These findings suggest that polysomnographic data recorded on Medilog 9000 recorders can be reliably and accurately scored on the Medilog scanner, obviating the laborious task of printing the taped data on paper.

Adolescent↗
PubMed1989

The surgical margin in soft-tissue sarcoma.

In a retrospective review of 231 patients who were referred to Princess Margaret Hospital because of a soft-tissue sarcoma in an extremity, 100 patients were identified who had no metastases when they were first seen and who had been treated by local resection and adjuvant radiation therapy. Complete data were collected for each patient for the following variables: age; sex; location of the tumor and its size, grade, depth, and compartmental status; chemotherapy; and dose of radiation. The surgical margins were characterized as positive or negative for histological evidence of disease on the basis of an independent review of the pathological and operative reports by a surgeon and a radiation oncologist who were experienced in the management of sarcoma. Cox multivariate analysis was used to determine which of these variables contributed to local recurrence and evidence of systemic disease. Adequacy of the margin of resection was the only variable that was associated with local relapse (p = 0.0004). The size of the tumor (p = 0.0008) was the major determinant of the risk of systemic disease.

Adolescent↗
PubMed1988

Phase I clinical trial of a World Health Organisation birth control vaccine.

A birth control vaccine incorporating a synthetic peptide antigen representing the aminoacid sequence 109-145 of the C-terminal region of the beta subunit of human chorionic gonadotropin (hCG-beta) was submitted to a phase 1 clinical trial. Thirty surgically sterilised female volunteers, divided into five equal groups for different vaccine doses, received two intramuscular injections six weeks apart. Over a six-month follow-up there were no important adverse reactions, and potentially contraceptive levels of antibodies to hCG developed in all subjects. In the highest vaccine dose group, the results gave promise of a contraceptive effect of six months' duration.

Adult↗
PubMed1988

Pilot study of a screening test for peripheral arterial disease in middle aged men: fibrinogen as a possible risk factor.

A simple one minute exercise test was used as a screening test for asymptomatic peripheral arterial disease in a sample of 100 men in their sixth decade with no previous referrals for cardiovascular disease. Other investigations included resting ECG, non-invasive carotid artery assessment, and plasma biochemical analysis. Of these 100 men (mean age 56), 10 had evidence of peripheral disease on exercise testing, four had ischaemic changes on resting ECG, and one showed evidence of carotid artery stenosis. A total therefore of 15 out of 100 (15%) had asymptomatic arterial disease. These 15 men had increased concentrations of plasma fibrinogen (4.3(0.7) g.litre-1) compared with men with no evidence of arterial disease (3.5(0.7) g.litre-1; p less than 0.01). The one minute exercise test is a useful screening test for peripheral arterial disease, and this pilot study suggests that raised plasma fibrinogen concentrations may be an important risk factor.

Arterial Occlusive Diseases↗
PubMed1988

Ultrastructural changes in scleral proteoglycans precede destruction of the collagen fibril matrix in necrotizing scleritis.

Proteoglycans were localized using cuprolinic blue and visualized by electron microscopy in sclera from the eye of a 58-year-old woman with necrotizing scleritis. Samples of sclera taken from clinically normal anterior and posterior sclera and from sites involved in anterior necrotizing scleritis with ulceration and posterior scleritis showed markedly different patterns of proteoglycan distribution. Proteoglycans appeared as stain-positive filaments associated regularly with the 'd/e' bands of the collagen fibrils in normal anterior sclera, but were absent from intact collagen fibrils in the zone of anterior ulcerative scleritis. In posterior sclera including a site of posterior scleritis, proteoglycans were reduced in number with more heterogeneous associations with collagen fibrils. Depletion of scleral proteoglycans therefore precedes the degradation of scleral collagen in necrotizing scleritis, which may also involve the synthesis of atypical proteoglycan types in pathological sclera.

Adult↗
PubMed1988

Prevention of unexpected infant death. A review of risk-related intervention in six centers.

Over seventy percent of unexpected infant deaths are registered as SIDS. Over 85,000 infants have been screened at birth and one month of age for risk of unexpected death using the Sheffield Score system. Scores range from below 400 to over 800 points. Infants with scores over 800 are at more than 16 times greater risk than infants with scores below 400. Family doctors and health visitors were alerted to high-risk infants, who were examined at home and weighed naked at home five times in the first six months. Mortality in the high-risk group was reduced by more than 50% (p less than 0.02 in one area and p less than 0.05 in another). It is concluded that with few extra resources unexpected infant mortality can be reduced by 25% by this approach.

Child Health Services↗
PubMed1988

Platelet enhancement of O2-. responses in stimulated human neutrophils. Identification of platelet factor as adenine nucleotide.

Human neutrophils stimulated with immune complexes in the presence of platelets show enhanced superoxide anion (O2-.) responses that are proportional to the amount of agonist present and the number of platelets added. Platelet related enhancement of O2-. responses also occurs with the neutrophil agonists phorbol ester, formyl chemotactic peptide and zymosan particles. Pretreatment of platelets with cycloheximide does not alter their ability to enhance O2-. responses of neutrophils. In parallel with platelet-related enhancement of O2-. responses of immune complex-stimulated neutrophils, secretory release of myeloperoxidase is also increased. The platelet effects on O2-. responses can be reproduced with platelet lysates or with supernatant fluids which have been obtained from thrombin or immune complex-stimulated platelets and are rich in ATP and ADP content. Solutions containing ATP and ADP in amounts similar to those found in supernatant fluids of activated platelets reproduce the enhancement of O2-. responses in N-formyl methionyl leucyl phenylalanine (FMLP) or immune complex-activated neutrophils. The platelet factor responsible for the effects of neutrophils is heat-stable, elutes in gel sieving chromatography near the position of phenol red and does not, in the absence of a neutrophil agonist, trigger an O2-. response. With formyl peptide-stimulated neutrophils, ATP and ADP enhance O2-. responses while the responses are depressed by addition of AMP or adenosine. In immune complex-stimulated neutrophils, adenosine and all adenine nucleotides enhance the O2-. responses. Taking advantage of this information, treatment of ATP or of supernatant fluids from thrombin-stimulated platelets with alkaline phosphatase (resulting in formation of adenosine) converts the O2-. enhancing activity for formyl peptide-activated neutrophils into an inhibitory activity. In contrast, using immune complex-activated neutrophils, similar manipulations of ATP or supernatant fluids from stimulated platelets result only in enhanced O2-. responses. These data support the conclusion that the platelet-derived factor responsible for enhanced O2-. responses in neutrophils is ATP/ADP. In FMLP stimulated neutrophils, the presence of ATP or ADP leads to enhanced increases in intracellular levels of Ca++ as determined by the fura-2 probe, while the presence of AMP or adenosine results in inhibition of the increases in FMLP induced elevations in cytosolic Ca++. These data demonstrate a direct relationship between effects of adenine compounds on FMLP induced changes in cytosolic Ca++ and the associated O2-. responses.

Adenine Nucleotides↗