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Biomedical subjects

C Carmack

Publications and source records attributed to C Carmack.

14 recordsLinked to original sources
PubMed2001

Phylogenetic footprinting of transcription factor binding sites in proteobacterial genomes.

Toward the goal of identifying complete sets of transcription factor (TF)-binding sites in the genomes of several gamma proteobacteria, and hence describing their transcription regulatory networks, we present a phylogenetic footprinting method for identifying these sites. Probable transcription regulatory sites upstream of Escherichia coli genes were identified by cross-species comparison using an extended Gibbs sampling algorithm. Close examination of a study set of 184 genes with documented transcription regulatory sites revealed that when orthologous data were available from at least two other gamma proteobacterial species, 81% of our predictions corresponded with the documented sites, and 67% corresponded when data from only one other species were available. That the remaining predictions included bona fide TF-binding sites was proven by affinity purification of a putative transcription factor (YijC) bound to such a site upstream of the fabA gene. Predicted regulatory sites for 2097 E.coli genes are available at http://www.wadsworth.org/resnres/bioinfo/.

Base Sequence↗
PubMed1998

Mediating variable framework in physical activity interventions. How are we doing? How might we do better?

INTRODUCTION: Behavioral science provides the foundation for physical activity interventions. The mediating variable framework is used to assess the status of physical activity interventions and the roles that are, or could be played, by behavioral theory. METHODS: Twenty-five physical activity intervention studies and 45 physical activity correlational studies were found in the literature, tabulated, and included in the analysis. RESULTS: Behavioral interventions for promoting physical activity have worked primarily when participants were motivated enough to volunteer or when a school-based physical education program changed. In most cases, behavioral or psychosocial theory accounted for 30% or less of the variability in physical activity behaviors. Most intervention studies do not measure mediating variables, and when they do, they do not systematically effect changes in all the mediating variables on which they are predicated. DISCUSSION: To increase the effectiveness of physical activity interventions, more physical activity research should focus on a better understanding of the predictors of physical activity and toward interventions demonstrated to effect change in these predictors of physical activity. CONCLUSION: Changing the focus to basic behavioral and social science and mediator change research should provide a more systematic and cost-effective approach to increasing the effectiveness of physical activity interventions.

Adult↗
PubMed1993

The health status and health care utilization of deaf and hard-of-hearing persons.

OBJECTIVE: To evaluate whether health habits, self-reported health status, and communication with physicians play a role in the known altered health care utilization patterns of deaf and hard-of-hearing persons. DESIGN: A cross-sectional survey. Respondents were given the choice of completing either a self-administered written survey or an American Sign Language interview-administered survey. POPULATION: Eighty-seven deaf and hard-of-hearing members of various organizations serving this population in southeastern Michigan and 88 hearing patients from a family practice clinic in the same area. RESULTS: Deaf and hard-of-hearing persons visit physicians more frequently (P = .01), have a lower incidence of ever smoking tobacco (P < .0006) and of alcohol use (P = .04), have more difficulties communicating with physicians (P < .001), have trouble understanding physicians (P < .001), and feel less comfortable with physicians (P < .001). Lower current tobacco use among deaf and hard-of-hearing persons was only seen in persons who were not educated beyond high school. Increased frequency of physician visits for deaf and hard-of-hearing persons was especially noticeable in the group of persons 60 years of age and older. Our finding that use of interpreters is associated with increased utilization and decreased understanding suggests deaf and hard-of-hearing patients presenting with interpreters warrant more focused attention from physicians. Reasons for seeing physicians did not explain the difference in frequency of physician visits between the two groups. CONCLUSIONS: Deaf and hard-of-hearing persons report a lower subjective health status and higher physician utilization, as well as substantial communication difficulties with physicians. They also report better health-related behaviors, namely less use of tobacco and alcohol. The use of interpreters did not decrease physician utilization or improve the understanding of physicians by these persons. Overall, our results underscore the fact that deaf and hard-of-hearing persons constitute a minority population that experiences considerable difficulties in the patient-physician relationship.

Adult↗
PubMed1991

Expression of anti-DNA immunoglobulin transgenes in non-autoimmune mice.

Self-reactive B cells can be regulated by either deletion or inactivation. These manifestations of self-tolerance have been dramatically shown in transgenic mice in which the number of self-reactive cells has been artificially expanded. We have now extended these models to ask if B-cell tolerance as described for non-disease-associated antigens also operates for the targets of autoimmunity. The target we have chosen is DNA. Anti-DNA antibodies are diagnostic of certain autoimmune syndromes in humans and are a characteristic of the murine model of systemic autoimmunity, the MRl/lpr mouse. Antibodies to both single-stranded and double-stranded DNA have been implicated in disease. By generating anti-DNA transgenic mice, we have addressed the question of whether DNA-specific B cells are regulated in normal (non-autoimmune) mice. We indeed found that most transgenic B cells bind DNA, yet we failed to detect secreted anti-DNA. We suggest that as a consequence of their self-reactivity these B cells are developmentally arrested.

Animals↗
PubMed1984

Mesotrypsin: a new inhibitor-resistant protease from a zymogen in human pancreatic tissue and fluid.

We have isolated and identified a new zymogen in human pancreatic tissue and fluid. It is secreted as a minor component of pancreatic juice and resembles the two known trypsinogen variants in many properties. Its electrophoretic mobility and isoelectric pH lie between those of the cationic and anionic trypsinogen variants, and we propose the name "mesotrypsinogen" for the new enzyme precursor. It is activated by enteropeptidase or trypsin, and the free enzyme possesses a substrate specificity similar to that of the trypsins. Its pH optimum is at 8.2, and it appears to require Ca2+ for full enzymatic activity. The molecular weight of the new enzyme is approximately 25,000, similar to that of the known trypsin variants. Its stability resembles that of anionic trypsin extending over a pH range of 4-8.5. Activity is lost gradually at pH 2. The enzyme is inactivated rapidly by diisopropylfluorophosphate, but in contrast to the trypsins, it reacts only slowly with tosyllysine chloromethylketone. Immunologically, it is different from the cationic trypsin variant with which it does not cross-react. The most remarkable property of mesotrypsin is its almost total resistance to biological trypsin inhibitors, such as pancreatic trypsin inhibitor, soybean, lima bean, ovomucoid inhibitor, alpha 1-antitrypsin, etc. It is capable of activating trypsinogen in the presence of excess pancreatic trypsin inhibitor and thus inducing activation of other pancreatic zymogens, but it also possesses the ability to degrade trypsinogen rapidly to inert products. The physiological or pathophysiological role of this unique enzyme remains to be explored.

Animals↗
PubMed1983

Pancreatic secretory profiles of protein, digestive, and lysosomal enzymes in Syrian golden hamster. Effect of secretin and cholecystokinin.

Profiles of pancreatic secretory proteins (zymogens, lysosomal enzymes) were studied in Syrian golden hamsters after sequential stimulation of the pancreas with secretin and cholecystokinin-octapeptide (CCK). The flow rate of pancreatic juice after secretin (0.2 CU/100 g) was approximately 2.7 microliters/min/100 g animal (about 55% of that in human subjects). The half-life of the secretin effect was about 60 min. The initial concentration of protein in pancreatic juice (minute-to-minute collection) in response to secretin was over 10 times larger than that in human subjects and the "wash-out" phase required greater than 1 hr vs less than 10 min in humans. CCK (4 ng/100 g) in minute-to-minute collections of juice produced an approximately eightfold increase in concentration of secretory products over baseline values, and the half-life of its effect was about 2 min, similar to that found in human subjects. Digestive as well as lysosomal enzyme activities in hamster pancreatic juice were 10-15 times higher than those found in human pancreatic secretions. This species difference may be relevant to the susceptibility of the hamster pancreas to carcinogens.

Animals↗
PubMed1983

Pancreatic secretory abnormalities precede appearance of tumors of the pancreas in hamsters treated with bis-(2-oxopropyl)-N-nitrosamine.

The possibility that pancreatic secretory abnormalities might precede the appearance of pancreatic neoplasms and thus provide clues to early detection of this malignancy has been investigated in an animal model. Syrian golden hamsters were treated with bis-(2-oxopropyl)-N-nitrosamine on two successive weeks (2 mg/100 g body weight/week). Pancreatic secretions from treated and untreated control animals were studied at approximately monthly intervals. The animals were anesthetized, their pancreatic ducts cannulated, and basal pancreatic juice collected for 30 min. Pancreatic secretion was then stimulated by sequential intravenous injection of secretin (50 ng/100 g) and C-terminal octapeptide of cholecystokinin (4 ng/100 g) 1 hr later. Four consecutive 15-min collections of fluid were made following secretin stimulation and four additional collections after CCK administration. Each collection was examined for volume, total protein, trypsin, chymotrypsin, elastase, arylsulfatase, beta-D-glucuronidase, alpha-D-glucosidase, and leucine naphthylamidase. In addition two trypsinogen variants present in pancreatic secretions were determined. The pancreas and other organs were removed and examined histologically at the end of each experiment. Cytological atypia appeared 3 months, ductal hyperplasia 4 months, and pancreatic neoplasms 6 months after the last injection of carcinogen. Striking decreases in flow rate and output of trypsin and chymotrypsin were observed several months prior to the appearance of histologically recognizable pancreatic tumors. By contrast, output of beta-D-glucuronidase and alpha-D-glucosidase in pancreatic juice increased markedly in the last 2 months preceding the emergence of neoplasms. The diagnostic significance of these premalignant abnormalities is illustrated most dramatically in the form of ratios of lysosomal to digestive enzymes, such as beta-D-glucuronidase-trypsin or alpha-D-glucosidase-chymotrypsin. Highly significant increases in these ratios were observed consistently, not only in hamsters with pancreatic neoplasms, but also in animals with preneoplastic lesions (ductular hyperplasia) which preceded malignancies by about 2 months.

Age Factors↗
PubMed1979

Trypsinogen variants in pancreatic juice of healthy volunteers, chronic alcoholics, and patients with pancreatitis and cancer of the pancreas.

Polyacrylamide gel electrophoresis of pure pancreatic juice from 14 healthy normal subjects, 11 chronic alcoholics without detectable pancreatic disease, 15 patients with pancreatitis, and two with cancer of the pancreas consistently demonstrated the presence of two variants of trypsinogen with different electrophoretic mobilities. In healthy normal subjects the proportion of cationic to anionic trypsinogen was invariably greater than 1 and averaged about 2. In chronic alcoholics, patients with pancreatitis or cancer of the pancreas, this ratio, with a single exception, was below one and averaged about 0.45. The extraordinary consistency of these findings suggests that the quantitative relationship between cationic and anionic trypsinogen in human pancreatic juice may be a very sensitive indicator of incipient or existing pancreatic pathology. The most acceptable explanation for the reversal of the normal zymogen ratio in pancreatic disease is a selective increase in the synthesis of the anionic variant relative to that of the cationic species. Total trypsinogen concentrations differed widely from one another in the three patient groups, but the ratio of cationic to anionic trypsinogen exhibited little change and remained below 1. Our results also demonstrate for the first time a specific effect of chronic alcohol abuse on the secretory profile of a pancreatic enzyme in human subjects. A newly discovered minor, trypsinogen-like component of human pancreatic juice was found to be significantly increased in pancreatic juice of chronic alcoholics, decreased in pancreatic secretions of patients with pancreatitis, and barely detectable in those of two patients with cancer of the pancreas.

Adult↗
PubMed1976

Lymphocyte effector molecules: an vitro production method for obtaining liter volumes of supernatants from mitogen-stimulated human lymphocytes.

An in vitro method has been developed utilizing phytohemagglutinin (PHA) activated lymphocytes obtained from human tonsils and adenoids which permit the accumulation of multi-liter quantities of cell-free supernatants containing lymphotoxin and other lymphocyte effector molecules (LEM). An enriched media is employed which contains a large molecular weight, heat stable bovine serum fraction which supports lymphoid cell activation and levels of LEM secretion equal to that of cultures maintained in medium supplemented with whole serum. Elimination of whole serum from the media greatly reduces overall protein concentrations and facilitates concentration and purification studies. Various technical aspects of these cultures have been examined, i.e.: 1) cell concentration, 2) kinetics of LT production over a ten-day period, 3) mitogen dosage, and 4) types of media. Supernatants can be harvested repeatedly from a single culture over the ten day period, thus doubling the yield of LEM collected from a single culture.

Cell Survival↗
PubMedDate not supplied

A possible zymogen self-destruct mechanism preventing pancreatic autodigestion.

Incubation at 37 degrees C of human cationic trypsinogen purified by PAGE electrophoresis, results in development of proteolytic activity (enzyme Y) capable of rapidly degrading cationic and anionic trypsinogens to inert products. Enzyme Y appears to be a serine protease with a molecular weight of about 20,000 daltons and is different from any of the known pancreatic enzymes. The active enzyme may be derived from trypsinogen itself or a hitherto unrecognized precursor contaminating the trypsinogen fraction used in this work. Appearance of enzyme Y activity seems to be associated with the presence of traces of free trypsin. Enzyme Y possesses insignificant or no activity when tested with a variety of synthetic trypsin, chymotrypsin and other protease substrates. It is not inactivated by the specific trypsin and chymotrypsin inhibitors TLCK and TPCK, but its activity is reduced gradually by increasing concentrations of pancreatic secretory trypsin inhibitor. Ca2+ concentrations greater than 3 mM strongly inhibit enzyme Y, and diisopropylfluorophosphate completely inactivates it. The enzyme is stable when incubated at pH 1.9 and 37 degrees C for 30 min and its activity is not abolished by treatment with Hg2+. When added to pancreatic juice with low inhibitor content it causes rapid inactivation of zymogens without significant release of active enzymes or reduction of pancreatic trypsin inhibitor. Its physiological role may be perceived as a second line of defense against premature intrapancreatic activation of zymogens. Enzyme Y activity may be generated when trypsin inhibitor, the first line of defense, is sufficiently depleted by complex formation with inappropriately released trypsin to permit dissociation of a small amount of trypsin from this complex. This in turn may lead to activation of enzyme Y and inactivation of the zymogens of pancreatic proteases.

Autolysis↗