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Biomedical subjects

M Carey

Publications and source records attributed to M Carey.

At least 127 records · Page 7Linked to original sources

Efficacy of induction therapy in cadaveric renal transplantation comparing rabbit antithymocyte serum and Minnesota antilymphoblast globulin.

From August 1986 to July 1989, 98 patients receiving primary cadaveric kidney transplants received either RATS (n = 50) or MALG (n = 48) during the induction phase of a quadruple immunosuppressive protocol. Patient groups were well matched. The duration of RATS and MALG treatment and the time of CyA induction were equivalent. Serum creatinine and rejection episodes up to 1 year were not statistically different. Hematologic side effects resulted in dose reduction of MALG in 42% of patients without adverse rejection results. In the RATS group, no dosage reductions were required. One-year patient survivals (96% to 100%), and 1-year graft survival (82% to 85%) were not significantly different in the 2 groups. Infectious complications were 30% higher in the MALG group and a significant factor in 2 deaths. Monitoring of lymphocyte subsets revealed insignificant differences in the percent of decrease of each cell population between MALG and RATS groups during induction.

Adult↗

Markers of hepatitis B virus infection in schoolchildren in the Kimberley, Western Australia.

In 1986 the Aboriginal community in Western Australia was identified as a high-risk group for hepatitis B virus infection. An immunization programme was commenced in 1988 but concerns were expressed about horizontal transmission, especially in schools, to the low-risk Caucasian group and whether they should also be included in the vaccination programme. To estimate the extent of this occurrence, a survey of schoolchildren from two district high schools in Broome and Derby in the Kimberley Region of Western Australia was carried out in March 1989. A total of 607 students aged 4 to 19 years were included in the study. None of the 300 Caucasian students had any serological markers of hepatitis B virus infection (95% confidence interval (CI) upper limit, 1.3%). Eighteen children were found to be seropositive for hepatitis B surface antigen (HBsAg); 17 were Aboriginal and one Asian. In addition, 61 Aboriginal students and one Asian had hepatitis B surface antibody (antiHBs). The hepatitis B virus infection rate in these Aboriginal children is 28.2% (95% CI, 23.2%-33.7%) with a carrier rate of 6.1% (95% CI, 3.9%-9.6%). This study demonstrates that Caucasian students have a very low risk of infection with hepatitis B virus in this community, and there is therefore no need to extend the hepatitis B vaccination programme beyond the already identified high-risk groups.

Adolescent↗

How different eukaryotic transcriptional activators can cooperate promiscuously.

A striking characteristic of many different eukaryotic transcriptional activators is their ability to activate gene expression synergistically. Thus, for example, the rat glucocorticoid receptor and the yeast activator GAL4 cooperatively activate transcription of a mammalian gene bearing binding sites for each of the proteins: activation by both activators is greater than the sum of the effects of each working alone. It would seem unlikely that these two proteins from such different organisms directly interact; rather, the idea has been suggested that these and at least some other eukaryotic activators can work synergistically by simultaneously touching some part of the transcriptional machinery. An important prediction of this idea is that synergy between two such activators would be seen under conditions where each is present at concentrations sufficiently high to saturate its site on DNA. In this paper we use transcription in vitro to confirm that prediction using a derivative of the yeast activator GAL4 and the mammalian transcription factor ATF. The accompanying paper describes a similar conclusion comparing the effects of singly and multiply bound GAL4 molecules.

Activating Transcription Factors↗

A mechanism for synergistic activation of a mammalian gene by GAL4 derivatives.

In prokaryotes and eukaryotes many gene activators work synergistically. For example, two dimers of lambda repressor interact to promote binding of these proteins to DNA, a reaction that is crucial at the repressor concentrations found in lysogens. In this case one of the bound dimers activates transcription, evidently by touching RNA polymerase. In another example, the yeast transcriptional activator GAL4, which can stimulate transcription in many eukaryotes, binds to multiple sites on DNA to activate transcription synergistically; the presence of two such sites can elicit a level of transcription more than twice that found with a single site. In this paper we show that synergistic activation by each of several GAL4 derivatives involves a mechanism different from that illustrated by the lambda repressor: multiple activator molecules can work synergistically under conditions in which their binding sites on DNA are saturated. The accompanying paper shows that under similar conditions of activator excess, GAL4 derivatives work synergistically with a heterologous mammalian gene activator. These results support the idea that eukaryotic activators can cooperate not by directly interacting but by simultaneously touching some component(s) of the transcriptional machinery.

Binding Sites↗

A potent GAL4 derivative activates transcription at a distance in vitro.

Transcription of a typical eukaryotic gene by RNA polymerase II is activated by proteins bound to sites found near the beginning of the gene as well as to sites, called enhancers, located a great distance from the gene. According to one view, the primary difference between an activator that can work at a large distance and one that cannot is that the former bears a particularly strong activating region; the stronger the activating region, the more readily the activator interacts with its target bound near the transcriptional start site, with the intervening DNA looping out to accommodate the reaction. One alternative view is that the effect of proteins bound to enhancers might require some special aspect of cellular or chromosome structure. Consistent with the first view, an activator bearing an unusually potent activating region can stimulate transcription of a mammalian gene in a HeLa nuclear extract when bound as far as 1.3 kilobase pairs upstream or 320 base pairs downstream of the transcriptional start site.

Activating Transcription Factors↗

An amino-terminal fragment of GAL4 binds DNA as a dimer.

GAL4 is a yeast transcriptional activator protein that binds to specific 2-fold rotationally symmetric sites on DNA and stimulates transcription of the genes required for galactose catabolism. The DNA binding region of the protein is located within the first 74 amino acids and contains a "zinc finger" sequence motif. We show that a polypeptide comprising the first 147 amino acids of GAL4, designated GAL4 (1-147), binds DNA as a dimer in vitro. Although a protein containing only the first 74 amino acids, designated GAL4 (1-74), binds DNA specifically, its affinity is reduced relative to GAL4 (1-147). Addition of the strong dimerization domain of lambda repressor to GAL4 (1-74) generates a protein that binds as tightly as GAL4 (1-147). GAL4 (1-147) makes rotationally symmetric contacts with its recognition site when assayed by DNase I, exonuclease III and hydroxyl radical footprinting and by phosphate ethylation interference. Binding of GAL4 (1-147) in vitro requires either zinc or cadmium.

Amino Acids↗

A prospective trial of prophylactic intravenous immune globulin for the prevention of infections in severely burned patients.

A prospective randomized double-blind study evaluated the efficacy of i.v. immune globulin in preventing infectious complications in severely burned patients. Fifty patients were randomized to receive either i.v. immune globulin or placebo. Each group of patients was treated with twice weekly infusions for either 5 weeks or until the patients' wounds were covered. Patients treated with the immune globulin had an immediate correction of their depressed serum IgG levels, however there was no change in the infection or mortality rates. No adverse effects were noted with the immune globulin treatments. One potential weakness of this study was the greater burn surface area and a higher incidence of inhalation injury in adult patients treated with i.v. immune globulin compared to controls.

Adolescent↗

Activation of yeast polymerase II transcription by herpesvirus VP16 and GAL4 derivatives in vitro.

Fusion proteins known to activate transcription in vivo were tested for the ability to stimulate transcription in vitro in a recently developed Saccharomyces cerevisiae RNA polymerase II transcription system. One fusion protein, whose activation domain was derived from the herpesvirus transcriptional activator VP16, gave more than 100-fold stimulation in the in vitro system. The order of effects of the various proteins was the same for transcription in vitro and in vivo, suggesting that the natural mechanism of activation is preserved in vitro.

Base Sequence↗

Evaluating an enteral nutrition formulary.

Two hundred registered dietitians in health care facilities in the United States were surveyed to ascertain practices in enteral nutrition formulary management. A random selection of members of the Clinical Nutrition Management Dietetic Practice Group of The American Dietetic Association comprised the sample population. The response rate was 74%. The facilities were typically private, nonprofit, acute-care, with a capacity of 201 to 500 beds. Dietetic departments were primarily responsible for procuring, preparing, and distributing enteral nutrition formulas, Physicians, however, primarily initiated orders for formulas. Approximately 15% of hospitalized patients required enteral nutrition formulas, yet modular formulas were rarely used. More than 75% of the facilities utilized enteral nutrition formularies. Ninety-five percent of dietitians believed that establishing objective criteria for evaluating enteral nutrition formulas was important. Cost-containment through decreased product duplication, staff education, inventory management, and quantity ordering advantages were cited as motivating factors in criteria development. Osmolarity, lactose content, and product availability were identified as being the most important criteria in enteral product evaluation. The costs of enteral formulas were included in the standard room rate when the dietetics department was responsible for procuring and supplying enteral formulas. Patients were billed directly when the pharmacy department was responsible for purchasing or supplying enteral products. This study provides data from which a model may be developed to guide health care professionals in enteral formulary decision making.

Dietetics↗

The objective evaluation of alternative treatment plans: I. Images of regret.

An innovative approach to treatment planning is described in which a planned dose distribution is evaluated in terms of prescribed limits of acceptability, and any discrepancies (referred to as "regions of regret") are displayed in the form of a contour diagram in which colors are used to represent different types and degrees of regret. A commercial treatment planning system has been modified to display images of regret in addition to conventional isodose plots, and is used for the comparison of alternative plans in terms of adequate target coverage and minimal irradiation of sensitive organs. Required tumor dose levels and organ-specific tolerance doses are prepared in advance by the clinician for each site and stored in a prescription file for use in the planning process. The method is found to expedite the optimization procedure, is objective and reproducible, and provides clear documentation of the selection process.

Computer Graphics↗

Treatment planning using images of regret.

The lack of well-defined criteria for evaluating alternative treatment plans introduces a degree of subjectivity into the planning process. The complexity of conventional isodose charts causes further difficulty in making rapid and reliable evaluations of a plan. An objective method is described, using a prescription file to define the clinician's requirements in terms of the area of each organ which may be treated to predefined tolerance doses. The computer program OSCAR then compares the predicted dose distribution with the prescribed limits, and displays regions of noncompliance as colored "areas of regret." In addition, score functions are used to provide a quantitative measure of the acceptability of dose distributions within the target and each organ at risk. An example is described in which a plan for the treatment of ca esophagus is evaluated using both images of regret and score functions.

Esophageal Neoplasms↗

Influence of nutritional factors on calcium-regulating hormones and bone loss.

UNLABELLED: The relationships between nutritional factors, calcium regulating hormones, and bone density were evaluated in three groups of normal subjects in rural southeast Kansas. Dietary intake of calcium (Ca), phosphorous (P), protein, and vitamin D; and serum 25OHD, Ca, P, parathyroid hormone (iPTH), and bone density (distal 1/3 radius) were measured in 29 elderly women, 35 elderly men, and 50 perimenopausal women. Measurements were repeated 5 years and 4 years later respectively in 16 elderly women and 15 elderly men. The r values for significant regression correlations for each group were as follows: perimenopausal: bone density and dietary Ca:P--r = .29, iPTH and 25OHD--r = -.38; elderly women: 25OHD and dietary Vitamin D(D)--r = .58, change in bone density (delta BD) and initial bone density (BDI)--r = -.71, delta BD and serum 25OHD--r = -.60, serum calcium and age--r = -.42; elderly men: Serum 25OHD and D--r = .61, iPTH and 25OHD--r = -.43, iPTH and serum phosphorous--r = .59. CONCLUSIONS: The more adequate the state of vitamin D nutriture, the lower the serum iPTH in perimenopausal women and elderly men and the less bone loss in elderly women. The Ca:P ratio in the diet may be important in maintaining bone density in perimenopausal women.

Adult↗

Infertility surgery for pelvic inflammatory disease: success rates after salpingolysis and salpingostomy.

Eighty-seven patients with infertility due to pelvic inflammatory disease were retrospectively studied to determine pregnancy rates after infertility surgery. Patients were divided into two groups on the basis of the type of surgical procedure: group 1, lysis of adhesions only (22 patients); group 2, terminal salpingostomy with lysis of adhesions (65 patients). A significantly greater number of patients in group 1 (nine of 22, 41%) than in group 2 (12 of 65, 18%) (p less than 0.05) achieved intrauterine pregnancy. The incidence of ectopic pregnancy was 23% in group 1 (five of 22) and 9% in group 2 (six of 65) (p = 0.12). Almost all pregnancies that were conceived more than 16 months after operation were ectopic gestations. Patients were classified according to severity of disease on the basis of several factors. Although few patients with severe pelvic inflammatory disease conceived after operation, the effect of disease severity on the likelihood of successful operation was not statistically significant.

Adult↗

Employment considerations of AIDS in dental institutions.

Acquired immunodeficiency syndrome (AIDS) has become one of the most pressing public health issues of this decade. As a member of the health care team, dental professionals are increasingly confronted with the responsibilities of treating AIDS victims, preventing the transmission of HIV and other infectious agents, and being nondiscriminatory employers. Guidelines are currently available to help the dental profession in these first two responsibilities. However, policies governing the employment of health care workers with AIDS have not been established firmly. Therefore, this article focuses on the AIDS employment issue facing dental practitioners, administrators, and educators today. Background information on the current medical status, transmission, epidemiology, and populations-at-risk is reviewed. Legal considerations of AIDS in the work place are addressed as to HIV testing, employee rights to gain and/or retain employment, economic considerations, and confidentiality issues.

Acquired Immunodeficiency Syndrome↗