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Biomedical subjects

G Burke

Publications and source records attributed to G Burke.

At least 19 recordsLinked to original sources
PubMed1992

Random digit dialing in Chicago CARDIA: comparison of individuals with unlisted and listed telephone numbers.

Young adult blacks and whites aged 18-30 years of both low and high educational levels were recruited through random digit dialing to participate in the Chicago, Illinois, portion of a longitudinal study, Coronary Artery Risk Development in Young Adults (CARDIA). Overall, 31% of randomly selected persons eligible to participate had unlisted telephone numbers--about 50% of black men and women and 11% and 17% of white men and women, respectively. There was no difference in proportions of numbers unlisted by educational level, except for white men, who were more likely to have unlisted numbers at a low educational level than at a high educational level. There was no consistent pattern of differences in rates of participation across race, sex, or education subgroups for unlisted and listed numbers, and there were no significant differences for selected health measures, except smoking. The findings suggest that in Chicago, there is a potential bias in estimates of sociodemographic characteristics from the exclusion of unlisted numbers, but it is likely to be insignificant if recruitment is stratified according to race, sex, and education. Within strata, there was little bias with respect to the attributes measured. Ideally, to guard against possible bias, random digit dialing is recommended as the preferred way to select a representative population-based sample.

Adolescent↗
PubMed1992

Cross-species reactivity of the anti-idiotype anti-OKT3 cascade between mice and humans.

The administration of murine mAb specific for the CD3 epsilon subunit of the TCR complex (OKT3) has been demonstrated to engender in humans an anti-OKT3 idiotypic cascade. This study used murine-derived anti-OKT3 (Ab2) as a bioreagent to determine whether this Ab2 and polyclonal anti-(anti-OKT3) (Ab3) generated in some human kidney transplant patients are idiotypically connected. Two anti-OKT3 mAbs G-880 (IgG1) and M-12 (IgM) were derived by immunizing BALB/c mice with the OKT3-secreting hybridoma. The two mAbs exhibited specificity for OKT3 F(ab)'2 idiotypic determinants. Both mAbs were tested for their ability to inhibit OKT3 induced mitogenesis and to block FITC-OKT3 binding to cell surface CD3 epsilon chain. The M-12 mAb inhibited OKT3-induced mitogenesis and blocked (approximately 60%) the binding of OKT3 to peripheral blood (PBL) T-cell CD3 epsilon chain in flow cytometry. In contrast, the G-880 mAb did not inhibit mitogenesis and only weakly blocked OKT3 binding to CD3 epsilon chain (approximately 12%). Sera of kidney transplant recipients who received OKT3 antirejection therapy and who developed antiidiotypic anti-OKT3 antibodies could be divided into two subgroups exhibiting anti-OKT3 activity: (a) those who had similar specificity as M-12 and failed to enhance the M-12 inhibition of OKT3 binding to PBL T-cell CD3 epsilon chain when added as a third component (n = 3), and (b) those with anti-OKT3 antibodies with idiotype specificity dissimilar to M-12 and who were able to increase the (maximum 60%) inhibition obtained with M-12 in the OKT3 to T-cell CD3-binding assay (n = 4). From these observations, we conclude that M-12 had the characteristics of an Ab2 beta and G-880 that of an Ab2 alpha. Additionally, there was an idiotypic connectivity of mouse-derived M-12 anti-OKT3 (Ab2) and OKT3-engendered human polyclonal anti-(anti-OKT3) (Ab3), in that three of seven patients examined had human serum IgG antibodies that specifically recognized M-12 idiotypic determinants as demonstrated in ELISA.

Animals↗
PubMed1992

Severe cerebral edema in a patient with anasarca and hypernatremia.

We describe a woman whose fatal post-liver transplantation cerebral edema was unexpected and of unusual pathogenesis. Her severe cerebral edema is of considerable pathophysiologic interest: 1) it developed in the setting of marked anasarca and persistent hypernatremia, and 2) although hepatic function was poor, it was not considered sufficiently deranged to induce cerebral edema. Furthermore, there was no histologic evidence of hepatic rejection or antemortem hepatic necrosis. We postulate that an impairment of the blood brain barrier in association with a degree of hepatic dysfunction insufficient by itself to cause cerebral edema permitted the brain interstitial fluid volume to increase pari passu with ECF expansion. Cytotoxic cerebral edema and vascular engorgement may also have contributed to a life-threatening increase in intracranial pressure.

Adult↗
PubMed1991

Factors affecting the ten-year outcome of human renal allografts. The effect of viral infections.

Long-term (10-year) results of kidney transplantation have been analyzed from this center with respect to several variables. In this report the influence of viral disease was added in studying the effect of cadaver versus living-related donor, recipient race, and compliance. Over all, 10-year actuarial patient and graft survival were 68% and 48%, respectively. Cytomegalovirus, hepatitis B and C, and HIV-1 were studied for their effects, and survival curves analyzed statistically. Although cadaver and living-related donor, recipient race, and compliance were 3 main variables influencing graft survival, these 4 viruses were not selective in their effects on any of them. Hepatitis B surface antigen positivity and hepatitis C antibody positivity did not influence overall mortality or graft survival. Only cytomegalovirus seronegative status was important (as opposed to seropositive status, which was not). Of seronegative patients only those receiving a kidney from a seropositive donor were adversely affected. The presence of HIV-1 antibody had an adverse effect on graft survival, but the question remains as to whether overall mortality in HIV seropositive patients is any worse than those receiving dialysis therapy.

Cadaver↗
PubMed1991

The effects of tissue-associated and MHC class II antigen presentation on in vitro lymphoproliferative responses against canine liver and kidney cell subpopulations.

Purified hepatocytes (LH), Kupffer cells (LKu), and intrahepatic biliary duct cells (LD) were isolated from canine livers, as well as tubular cells from canine kidneys, by enzymatic digestion, gradient centrifugation, and tissue culture techniques. Incubation of LH, LKu, and LD for 48 hr in a two-compartment diffusion chamber opposite two-way mixed lymphocyte cultures, or with canine gamma interferon purified and standardized in our laboratory, resulted in a significant increase in class II expression. This was detected in the cell analyzer with directly fluoresceinated B1F6, a monoclonal antibody (mab) generated in our laboratory vs. a canine class II monomorphic epitope. An amplification of the allogeneic mixed lymphocyte liver cell cultures (MLLC) of at least 2-fold was observed by preinduction of canine class II expression with IFN-gamma on LKu and LD cells, but an autologous reaction could not be elicited. However, an autologous as well as allogeneic lymphoproliferation against kidney tubular cells (MLKC) could be easily observed without IFN-gamma and amplified with IFN-gamma to stimulation indices of at least 3 times that of noninduced cultures. Dependence of the allogeneic MLLC and allogeneic and autologous MLKC on class II gene expression was also evidenced by blocking of 3H-thymidine uptake seen by incubation with 5 micrograms of B1F6. Another mab, I1F6, generated against tubular cells and inhibiting the autologous and allogeneic MLKC, had no blocking effect on lymphoproliferation with any of the liver cell preparations. No such tissue-specific mab (analogous to I1F6) has thus far been found in response to mouse immunization with LH, LKu, or LD. In the absence of accepted defined molecular probes in the dog as yet, we conclude that, in contrast to kidney tubular cells, cells of the normal canine liver do not readily stimulate a primary lymphoproliferative autoimmune reaction in vitro despite class II amplification. Thus autoreactivity (as opposed to alloreactivity) is much less prominent in immune recognition of purified cellular components of nondiseased liver tissue than of kidney tissue in which tissue-associated epitopes are more operative.

Animals↗
PubMed1991

Evidence that antibodies to cytomegalovirus and the T cell receptor (TCR)/CD3 complex may have common ligands.

Immunoglobulins derived from sera containing anti-antiidiotypic antibodies (Ab2) generated in renal transplant recipients after OKT3 monoclonal antibody therapy, as reported in our previous study (1), have now been proved to bind to several bands of T cell membrane lysates (TCML) in immunoblotting analyses ranging in molecular weight from 40 to 55 KD. These sera also blocked the expression of the ligand binding to WT31 in flow cytometry. WT31 is a MAb that recognizes a common determinant on the T cell receptor (TCR). Immunoglobulins from these sera suppressed the activation of normal peripheral blood T lymphocytes (PBT) induced by OKT3. All patients (7/32) who developed this Ab2 had distinct culture-proved cytomegaloviral infections. In further immunoblotting studies, alpha F1, another MAb recognizing the framework of the TCR alpha chain, more deeply inserted in the T cell membrane, also showed binding to protein bands of cytomegalovirus pellet lysates derived from virus-infected embryonic fibroblasts. In addition, alpha F1 showed positive binding to several ligands in the membrane lysate of CMV-infected, but not noninfected MRC-5 cells. An anti-CMV MAb recognizing late nuclear antigen (LAb), also strongly bound to a approximately 50 KD band of TCML and several bands (approximately 34, approximately 40, and approximately 50 KD) of H33HJAJ1 (human T leukemia) cell lysate. Furthermore, alpha F1 immunoprecipitated a approximately 96 KD ligand of CMV-infected MRC5 lysate that had the same electrophoretic mobility as one of the proteins precipitable with LAb. Both LAb and alpha F1 also showed positive binding to paraformaldehyde-fixed and Triton X-100-permeabilized PBT in flow cytometry. Sera containing Ab2 blocked alpha F1 binding to acetone-fixed cytofuged PBT preparations on slides. Moreover, both alpha F1 and LAb inhibited mitogen-stimulated lymphocyte activation in vitro. These data support the notion that T cell functional abnormalities associated with CMV infection observed after treatment of transplant recipients with anti-T cell monoclonals might be caused by binding to T cell ligands by a variety of crossreacting human Igs operative in a regulatory network. Confirmatory evidence is the effect of MAbs generated against CMV virion epitopes crossreacting with T cell ligands, and vice versa.

Antibodies, Monoclonal↗
PubMed1991

Commentary concerning demonstration of safety and efficacy of investigational anticancer agents in clinical trials.

Expeditious clinical development and approval of new drugs that are beneficial to patients are matters of high priority. There has been a great deal of discussion within the oncology community about what should constitute evidence of effectiveness of new anticancer agents for purposes of drug approval. This commentary is intended to illustrate a variety of end points that can lead to approval of new anticancer agents for specific clinical situations. Although the ultimate hope of antineoplastic therapy is prolongation of life, there are other effects of anticancer drugs that constitute clear clinical benefit and represent evidence of effectiveness. The guiding principle is that the beneficial effects obtained from a new drug should sufficiently outweigh the adverse effects such that the potential risk:benefit ratio achieved by an individual patient is favorable. The assessment of a new drug should flexibly evaluate safety and efficacy in the context of the specific clinical condition being treated. Early discussions with the Food and Drug Administration (FDA) and the National Cancer Institute (NCI) are recommended to identify prospectively the end points and trial designs needed to demonstrate effectiveness of a new drug. The general principles discussed will likely apply to the drug approval process for other medical disciplines as well.

Antineoplastic Agents↗
PubMed1990

Non-histone chromatin proteins in beef thyroid: distinct phosphorylation patterns of several protein kinases.

Non-histone chromatin protein (NHCP) fractions were extracted from purified beef thyroid nuclear preparations and tested for the presence of protein kinase activities using several known mediators of thyroid regulation, as well as potential phosphotransferase substrates using purified or partially purified protein kinase activities. The addition of cAMP/3-isobutyl-1-methylxanthine had no effect on NHCP histone kinase activity; the addition of 10 micrograms of the heat-stable cAMP-dependent protein kinase A inhibitor, however, resulted in a 47% reduction in histone H1 kinase activity. Nuclear casein kinase II activity was present in the NHCP fractions as evidenced by the capacity of spermine to stimulate (ED50 = 0.19 mM) and heparin to inhibit (ID50 = 0.09 microgram/ml) the phosphorylation of casein; further, the phosphotransferase activity could be purified by sequential casein-agarose and spermine-agarose affinity chromatography. Neither calcium-calmodulin nor calcium/phosphatidylserine/diolein had an effect on NHCP casein kinase or histone kinase activities, respectively. The addition of cAMP-dependent protein kinase A catalytic subunit, nuclear casein kinase II, calcium-activated calmodulin-dependent protein kinase and diacylglycerol-activated calcium/phospholipid-dependent protein kinase C activities exhibited distinct phosphorylation patterns when NHCP were used as substrates and analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and autoradiography. We conclude that NHCP fraction from beef thyroid: 1) contains both cAMP-dependent protein kinase A catalytic subunit and nuclear casein kinase II and 2) substrates for cAMP-dependent protein kinase A, calcium-activated calmodulin-dependent protein kinase, protein kinase C, and nuclear casein kinase II.

Animals↗
PubMed1990

Is intrauterine growth retardation with normal umbilical artery blood flow a benign condition?

OBJECTIVE: To determine whether intrauterine growth retardation associated with normal umbilical artery blood flow is a benign condition. DESIGN: A prospective comparative study of growth retarded fetuses with normal and abnormal umbilical artery blood flow. SETTING: The fetal assessment clinic of a large maternity hospital in Ireland. PATIENTS: 179 Women with singleton pregnancies in which the fetal abdominal circumference, measured by ultrasonography, was below the fifth centile for gestation. MAIN OUTCOME MEASURES: Perinatal deaths, fetal distress requiring caesarean section, preterm delivery, cerebral irritation. RESULTS: Of 124 fetuses with normal flow, all physically normal fetuses survived but one baby had cerebral irritation; there were six preterm deliveries and four caesarean sections for fetal distress. Among 55 women with abnormal flow there were two midtrimester abortions, three perinatal deaths, and one case of cerebral irritation in physically normal fetuses. CONCLUSIONS: Intrauterine growth retardation associated with normal umbilical blood flow is a different entity from that associated with abnormal flow, normal flow being largely benign and abnormal flow carrying a serious risk of adverse outcome.

Cesarean Section↗
PubMed1990

True rupture/scar dehiscence in delivery following prior section.

Fear of uterine rupture has led to the widespread practice of 'Once a section, always a section'. Between 1972 and 1982, 1498 patients with one or more previous cesarean sections were delivered at University College Hospital, Galway. Trial of labor was undertaken in 844 patients, while the remaining 654 patients underwent repeat elective section because they had two or more prior sections. Eight true ruptures and 22 scar dehiscences were found. Regional analgesia and oxytocin did not significantly affect the rate of true rupture. The mean parity with uterine rupture was five, and it occurred most frequently in the initial trial of labor. There were four perinatal deaths associated with true rupture. Failure to detect the already compromised fetus before labor and delivery, rather than the method of delivery, was responsible for fetal demise in some instances. Five true ruptures were found in the trial of labor group (i.e. a ratio of 1:169), with the loss of three babies. A further baby was stillborn in a mother who ruptured a classical scar before labor. There were no maternal deaths in trial-of-labor patients and one in the elective section group. Two patients with true rupture had their uterus repaired, and were subsequently delivered by section. Another two patients with bloodless dehiscence and no repair, had two subsequent elective repeat sections each, and the unrepaired scar dehiscence was not evident.

Cesarean Section↗
PubMed1990

Alcohol intake and blood pressure in young adults: the CARDIA Study.

Associations between self-reported average daily alcohol intake and blood pressure were assessed in 5031 black and white men and women ages 18-30 from the Coronary Artery Risk Development in Young Adults Study (CARDIA). In general, intake was positively but weakly related to both systolic and diastolic blood pressure. Associations with systolic pressure were generally stronger than those with diastolic pressure. With average daily alcohol intake categorized as none, 0.1-9.9 ml, 10.0-19.9 ml, 20.0-29.9 ml, and 30.0+ ml, mean systolic pressure, adjusted for age, body mass index, education, smoking, and physical activity, increased progressively with increasing intake in black and white men and in white women. Mean diastolic pressure increased progressively with increasing intake only in white men and women, but was highest for those averaging 30.0+ ml per day in black women as well as white men and women. Mean pressures were also compared for those averaging 75.0+ ml per day (men) or 50.0+ ml per day (women) vs those reporting no intake. Differences in adjusted mean pressures for white men were 3.2 mmHg (95% confidence limits (CL) -0.3, 6.8) for systolic pressure and 1.7 mmHg (-1.6, 5.0) for diastolic pressure. In black men differences were 4.4 mmHg (1.4, 7.4) and 3.4 mmHg (0.6, 6.3), respectively. Differences in white women were 1.4 mmHg (-2.5, 5.3) for systolic pressure and 0.9 mmHg (-2.7, 4.5) for diastolic pressure and for black women, -0.2 mmHg (-4.3, 3.8) and 1.9 mmHg (-1.9, 5.8). Separate analyses in smokers and nonsmokers of the associations between alcohol intake and blood pressure suggested that associations may differ by smoking status in some sex-race groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

An unusual case of pulmonary emboli.

The authors present an interesting case of pulmonary embolus serendipitously diagnosed during an evaluation for a presumed metastatic pulmonary nodule.

Diagnosis, Differential↗