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Biomedical subjects

M Skinner

Publications and source records attributed to M Skinner.

At least 127 records · Page 7Linked to original sources
PubMed1989

Hierarchy of cytotoxic T cell clones. II. Intraclonal triggering of lysis by hapten-specific CTL.

Cells from clones of anti-hapten murine cytotoxic T lymphocytes (CTL) can act as both target and effector cells, but will not lyse members of the same clone. The effect of haptenation on the cytolytic activity of anti-fluorescein (FL) and anti-trinitrophenol (TNP) CTL clones was examined. Treatment of anti-FL clones with fluorescein isothiocyanate or anti-TNP clones with trinitrobenzene sulphonic acid induces these clones to kill in an antigen-independent fashion. Targets killed by the haptenated CTL included syngeneic and allogeneic B lymphocyte blast cells, P815, YAC-1 and in one case human GM 4072 tumor cells. The importance of CD8 and T cell receptor (TCR) occupancy is demonstrated by the ability to block autotriggering by antibody directed against Ly 2 and the TCR. The results demonstrate that effects other than antigen recognition of the target play a role in the final outcome of effector-target cell interactions and provide a mechanism which could lead to autodestruction and immunosuppression particularly in some types of viral infection.

Animals↗
PubMed1989

The effect of prostaglandins and indomethacin on cytotoxic T-lymphocytes and their precursors.

The effect of prostaglandins of the E and F series on the generation of cytotoxic T-lymphocytes (CTL) was investigated. High concentrations (10(-6)-10(-7) M) of prostaglandin E2(PGE2) inhibited the generation of both antigen-specific CTL and "activated" killers from precursor cells. Virtually no effect on the growth and cytotoxic activity of antigen-specific CTL clones was detectable. As with prostaglandins of the F series, lower concentrations of the E series (10(-8)-10(-9) M) enhanced the generation of antigen-specific CTL but inhibited the generation of lymphokine and spontaneously-activated CTL. When endogenous PG production was blocked with indomethacin, the generation of antigen-specific CTL was enhanced in bulk culture. Indomethacin also increased the frequency of allo-reactive CTL precursors and in anti-fluorescein responses it created conditions in which suppression was overridden. These results indicate that prostaglandins can exert both negative and positive regulatory effects on an antigen-specific cytotoxic response and can influence the apparent specificity of the cytotoxic cells that are generated.

Animals↗
PubMed1989

Growth of fetal thymocytes in organ culture: effect of recombinant lymphokines on thymocyte maturation.

Interleukin 2 (IL2) has a dose-dependent inhibitory effect on the growth and phenotypic maturation of thymocyte populations grown in fetal thymus organ culture. Addition of IL2 (100 U/ml) to 14-day fetal thymus organ cultures induces the appearance of a population of lymphokine-activated killer (LAK) cells which lyse allogeneic, syngeneic, and syngeneic tumor cell targets. The addition of the monoclonal antibody, PC-61, blocks the IL2-dependent growth and activation of LAK cells but does not influence the maturation of CD4+ CD8+ fetal thymocytes. These data imply that IL2 is not a major regulator of normal fetal thymocyte maturation. The effects of a range of recombinant lymphokines (IL1 alpha, IL1 beta, IL3, IL4, GM-CSF, G-CSF, M-CSF) on the proliferation and phenotypic maturation of fetal 14-day thymocytes in organ culture has been analysed. Two significant changes were seen. First, IL1 alpha and IL1 beta inhibited growth and the expression of the CD4 and CD8 antigens in organ culture, and second, GM-CSF increased the expression of Mac-1+ cells. IL4, which has known T cell growth-promoting activity, IL3, G-CSF, and M-CSF did not alter either normal growth or surface antigen expression in fetal thymocytes. While some of these lymphokines may function as accessory molecules in fetal thymocyte development, our experiments suggest that they do not have a significant influence on thymocyte maturation when used alone.

Animals↗
PubMed1989

Peripheral neuropathy as an early marker of AL amyloidosis.

Fifty-one of 146 patients with primary amyloid deposits of light-chain origin (AL) examined between 1972 and 1986 were found to have peripheral neuropathy as part of their systemic amyloidosis. Peripheral neuropathy was the presenting symptom in 11 patients, and it was a later symptom or an incidental physical examination finding at the time of amyloid workup in 40 additional patients. The median duration of time from first symptom to the diagnosis of primary amyloidosis was longer in those whose first symptom was neuropathy (48 months vs 12 months). In addition, survival time after diagnosis for these patients was significantly longer (at least 35 months vs 16 months). Peripheral neuropathy is not an uncommon symptom of primary amyloidosis and may mark the onset of the disease process years before infiltration of vital structures of the heart, kidneys or gastrointestinal tract leads to failure and a subsequent downhill course. Appreciating amyloid disease at this early stage may widen the potential therapeutic window.

Amyloidosis↗
PubMed1989

Teaching of breast self examination. Is it practical?

In this study 348 patients attending outpatient clinics at Royal Hobart Hospital were interviewed, assessed in their breast self examination (BSE) technique, and taught BSE by the authors. A standard method of assessing BSE competence was devised applying the criteria outlined in a Tasmanian Cancer Committee brochure (Further reading) using a silicone breast examination teaching model. The measurable benefits of this form of teaching BSE were shown to persist for seven to 10 months in 11 women who re-attended clinics and were tested a second time after receiving instruction by the authors in the initial part of the study.

Breast↗
PubMed1988

High-performance liquid chromatographic analysis of josamycin in serum and urine.

A high-performance liquid chromatographic assay for the analysis of josamycin in human serum and urine is presented. The assay involves a simple solid-phase extraction procedure coupled with a phase separation step, separation on a reversed-phase C18 column with UV detection by a multi-wavelength programmable detector. The mobile phase was acetonitrile-0.015 M phosphate buffer, pH 6.0 (5:2) at a flow-rate of 1.2 ml/min. The column temperature was maintained at 35 degrees C. Linear calibration curves over the concentration ranges 0.1-2.0 mg/l (serum) and 0.5-5 mg/l (urine) were obtained with correlation coefficients of 0.9983 and 1.0000, respectively. The relative standard deviations of five replicate samples at the upper and lower limits of each calibration curve were below 7%. The recoveries at the upper and lower ends of the calibration range for serum were 77% and 70%, respectively, and those for urine were 76% and 80%, respectively.

Chemical Phenomena↗
PubMed1988

Phenotypic variation in the response to the human immunodeficiency virus among derivatives of the CEM T and WIL-2 B cell lines.

Derivatives of the CEM T and WIL-2 B cell lines showed striking diversity in their responses to the HTLV-IIIB strain of the human immunodeficiency virus (HIV). Several stable phenotypic patterns could be defined, based on whether cells were permissive (P+, P-) for virus production, were sensitive or insensitive to cytopathic effects after infection by free virus (C+, C-), and whether they underwent fusion on contact with virus-infected cells (F+, F-). Although expression of CD4 was essential for infection by HTLV-IIIB, very low levels were sufficient for productive infection of WIL-2 derivatives. Conversely, some CEM T cell lines that expressed ample CD4, and which were able to bind virus gp120 and undergo fusion, did not support productive infection by free virus. One nonpermissive, CD4+ derivative of CEM could bind gp120 but failed to undergo fusion, suggesting an alteration in some membrane protein other than CD4 that is essential for virus entry and HIV-induced cell fusion. The AA2 derivative of the WIL-2 cell line is also described, which is remarkably permissive for HIV replication and exquisitely sensitive to virus cytopathic effect. The panel of related cell lines with different host-virus phenotypes could be useful for more precisely defining steps in the infectious cycle of HIV, and for identifying host cell genes and gene products that determine the outcome of HIV infection.

Antigens, Surface↗
PubMed1988

The carbohydrate composition of human serum amyloid P component.

The carbohydrate moiety of human serum amyloid P component was analyzed and found to consist of equal amounts of galactose and mannose (total 4.0%), of glucosamine and galactosamine in a ratio of 7:1 (total 2.7%) and sialic acid (3.9%). It should be noted that this is the first report on the separate quantification of the neutral hexoses and the demonstration of the presence of galactosamine. The contents of glucosamine and galactosamine suggest that this protein possesses both an N- and an O-glycan.

Carbohydrates↗
PubMed1988

Effect of interleukin 2 on fetal thymocytes in organ cultures: generation of lymphokine-activated killer cells.

Cells with cytolytic activity can be detected in mouse fetal thymic lobes cultured in the presence of interleukin 2 for 6 days. The lymphokine-activated killer cells from 14-day fetal thymic lobes are relatively resistant to treatment with anti-Ly-2 antibody and complement (CD8-) but sensitive to anti-Thy-1 and complement treatment (Thy-1+). They display major histocompatibility complex-unrestricted killing, lysing both syngeneic and allogeneic tumor cells, but will not lyse human xenogenic target cells. Low levels of cytotoxic activity can be detected in thymic lobes from Day 12-13 embryos and this activity increases with embryonic age. While the events which lead to the inhibition of normal maturation of fetal thymocytes by inclusion of IL-2 in fetal thymus organ cultures are unknown, the appearance of cytotoxic cells raises the question of whether they are involved in the normal intrathymic cell death process.

Animals↗
PubMed1988

Amyloid P component.

Explore the source record for details and available documents.

Chromatography, DEAE-Cellulose↗
PubMed1988

Isolation and sequence analysis of amyloid protein AA from a patient with cystic fibrosis.

This study represents the first sequence analysis of an amyloid fibril protein from a patient with cystic fibrosis. Although chronic infections are a hallmark of cystic fibrosis, secondary amyloidosis is a rare complication, and during the past 20 years, only 16 cases of amyloidosis in patients with cystic fibrosis have been reported. We examined amyloid fibrils isolated from the spleen of a 25-year-old man who had a history of a chronic cough since infancy and a diagnosis of cystic fibrosis at age 6 years. After solubilization in 6 mol/L guanidine and purification by gel filtration, the major component of the amyloid fibrils was a homogeneous 8000 dalton protein that reacted positively with antiserum to human amyloid A (AA) protein. Complete protein sequence analysis was carried out by using the whole protein and fragments obtained by treatment of the protein with cyanogen bromide, lysyl endopeptidase, and carboxypeptidase. The protein contained 76 residues and showed minor heterogeneity when compared with other AA protein sequences. The cystic fibrosis AA protein represents a product of the SAA-specific cDNA clone now known to be the alpha-allelic form of SAA1 in which valine is present at position 52 and alanine is at position 57.

Adult↗
PubMed1987

Lymphokines induce specificity degradation in virus-induced cytolytic T-cell clones.

The target cell specificity of antiviral cytolytic T-lymphocyte (CTL) clones is influenced by in vitro tissue culture conditions. We have demonstrated that high concentrations of lymphokines such as recombinant interleukin-2 (rIL-2) induce killer T cells to lose virus specificity. Our experiments do not indicate that the cells become like natural killer (NK) cells. The loss of specificity is more general and can be reversed upon culture in more physiological concentrations of lymphokines. The implications of these observations for the pathogenesis of viral infection is discussed.

Animals↗
PubMed1987

Development of fetal thymocytes in organ cultures. Effect of interleukin 2.

Most fetal thymocytes from 14-d mouse embryos are Thy-1+, L3T4-, Ly-2-, and express the receptor for interleukin 2 (IL-2). The development of thymocytes has been followed in fetal thymus organ cultures. When fetal thymus from 14-d embryos were cultured for a 6-d period, thymocytes increased in number 20-40-fold, and 95% became Thy-1+, L3T4+, Ly-2+. The addition of IL-2 to organ cultures of 14-d fetal thymus inhibited, in a dose-dependent manner, cell proliferation and the appearance of Thy-1+, L3T4+, Ly-2+ thymocytes. The addition of IL-2 also resulted in the appearance of a population of cells that were cytotoxic for syngeneic and allogeneic fetal thymocytes and syngeneic tumour targets. While the events that lead to the expression of the IL-2 receptor on 14-d fetal thymocytes are unknown, IL-2 in fetal thymus organ cultures inhibits the normal maturation of fetal thymocytes and raises the question of whether the cytotoxic cells that appear reflect selection through an alternative pathway of development.

Animals↗
PubMed1987

Sensitivity and specificity of the echocardiographic features of cardiac amyloidosis.

Thirty-one patients with documented cardiac amyloidosis were compared to 39 control subjects with left ventricular hypertrophy to determine specific 2-dimensional echocardiographic features of amyloid. In 16 patients, increased myocardial echogenicity was present when a single short-axis view was examined, and had a sensitivity of 63% and a specificity of 74% for the diagnosis of amyloidosis. When complete echocardiograms were reviewed (15 patients), an improved sensitivity of 87% and specificity of 81% based on increased echogenicity was seen. Increased atrial septal thickness was present in 60% of amyloid patients and no controls. The combination of increased myocardial echogenicity and increased atrial thickness was 60% sensitive and 100% specific for the diagnosis of amyloidosis. The ratio of electrocardiographic voltage (S in V1 + R in V5 or V6) to left ventricular cross-sectional area also was examined. A ratio of less than 1.5 was 82% sensitive and 83% specific for amyloid (excluding the 2 patients with left bundle branch block), but added little to the diagnosis as determined from the 2-dimensional echocardiogram.

Amyloidosis↗
PubMed1987

Survival of patients with primary (AL) amyloidosis. Colchicine-treated cases from 1976 to 1983 compared with cases seen in previous years (1961 to 1973).

Primary amyloidosis has a variable course, but is generally associated with a short life expectancy. To date, no specific therapy has been available. Fifty-three patients with AL amyloidosis seen between 1976 and 1983 were treated with colchicine, and their clinical course and survival were compared with that in 29 other patients seen between 1961 and 1973. Of the variables measured, the treatment, the patient's sex, and the time interval from diagnosis to referral of treatment were significantly associated with length of survival. Median survival for the colchicine-treated patients was 17 months, compared with six months for the non-colchicine-treated patients. A surprising finding was the longer life span in female patients (median eight months versus four and a half months in the non-colchicine-treated group, and 25.5 months versus 10 month in the colchicine-treated group). The study suggests that colchicine has improved the life expectancy in AL amyloidosis. Although it is not a specific therapy, it may be a reasonable form of adjunctive treatment in this complex disorder.

Amyloidosis↗
PubMed1987

Diagnosis of amyloidosis by abdominal fat aspiration. Analysis of four years' experience.

Abdominal fat aspiration samples from 443 consecutive patients were examined for amyloid after Congo red and hematoxylin staining. Of the aspirates from 83 patients known to have systemic amyloid disease prior to the biopsy, 70 (84 percent) were found to yield positive results. The results for four aspirates from patients with localized amyloid disease were negative. Of the aspirates from 356 patients of unknown clinical status referred for analysis by outside physicians, 26 (7 percent) yielded positive results for amyloid. On review of the clinical records of these 26 patients, 11 had proved systemic amyloidosis demonstrated on biopsy of another site; all had a clinical course consistent with amyloid disease. In no case was amyloid found in a fat aspiration sample from a patient without clinical evidence suggestive of systemic amyloid disease. This study supports the proposal that abdominal fat aspiration is the diagnostic procedure of choice in the evaluation of amyloidosis since it requires no specialty consultation or technical expertise, causes minimal patient discomfort, and is accompanied by virtually no risk of morbid complication. A positive result has a high predictive value of amyloid disease in patients of unknown clinical status.

Abdomen↗