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Biomedical subjects

T Conway

Publications and source records attributed to T Conway.

At least 19 recordsLinked to original sources

BRCA1 testing in families with hereditary breast-ovarian cancer. A prospective study of patient decision making and outcomes.

OBJECTIVES: To identify predictors of utilization of breast-ovarian cancer susceptibility (BRCA1 gene) testing and to evaluate outcomes of participation in a testing program. DESIGN: Prospective cohort study with baseline interview assessment of predictor variables (eg, sociodemographic factors, knowledge about hereditary cancer and genetic testing, perceptions of testing benefits, limitations, and risks). BRCA1 test results were offered after an education and counseling session in a research setting. Outcome variables (including depression, functional health status, and prophylactic surgery plans [follow-up only]) were assessed at baseline and 1-month follow-up interviews. PARTICIPANTS: Adult male and female members (n=279) of families with BRCA1-linked hereditary breast-ovarian cancer (HBOC). RESULTS: Of subjects who completed a baseline interview (n=192), 60% requested BRCA1 test results (43% of all study subjects requested results). Requests for results were more frequent for persons with health insurance (odds ration [OR], 3.74; 95% confidence interval [CI], 2.06-6.80); more first-degree relatives affected with breast cancer (OR, 1.59; 95% CI, 1.16-2.16); more knowledge about BRCA1 testing (OR, 1.85; 95% CI, 1.36-2.50); and indicating that test benefits are important (OR, 1.45; 95% CI, 1.13-1.86). At follow-up, noncarriers of BRCA1 mutations showed statistically significant reductions in depressive symptoms and functional impairment compared with carriers and nontested individuals. Individuals identified as mutation carriers did not exhibit increases in depression and functional impairment. Among unaffected women with no prior prophylactic surgery, 17% of carriers (2/12) intended to have mastectomies and 33% (4/12) to have oophorectomies. CONCLUSIONS: Only a subset of HBOC family members are likely to request BRCA1 testing when available. Rates of test use may be higher in persons of a higher socioeconomic status and those with more relatives affected with breast cancer. For some high-risk individuals who receive test results in a research setting that includes counseling, there may be psychological benefits. More research is needed to assess the generalizability of these results and evaluate the long-term consequences of BRCA1 testing.

Adult

The internist's role in addressing violence. A review of current recommendations and a model for intervention.

Approximately 25,000 people die in the United States each year as the result of intentional homicide, and many millions more suffer the physical and emotional consequences of nonfatal interpersonal violence. Violence affects everybody's quality of life. The cost to the health care system is in the billions of dollars annually. Over the past 2 decades epidemiologic studies have defined risk factors for violence, and a number of physicians and medical groups have made recommendations for preventive action. As the largest physician group in the United States, internists have a clear role to play in carrying out the medical responsibility to help prevent violence. Internists should be aware of the signs and symptoms of violence in patients and be prepared to assist victims. To facilitate action against violence, a model for intervention is proposed that involves screening, counseling, and treatment for patients at greatest risk.

Adolescent

Cloning and expression of the Zymomonas mobilis "production of ethanol" genes in Lactobacillus casei.

This study describes the expression of the Zymomonas mobilis genes coding for pyruvate decarboxylase (pdc) and alcohol dehydrogenase (adh) in Lactobacillus casei 686. To promote transcription, the promoter and ribosome binding site (RBS) from the Lactococcus lactis subsp. lactis-derived vector, pMGE36e, were inserted upstream of the pdc gene. The former sequences were positioned such that translation of pdc was coupled to translation of an 81-base pair open reading frame terminating within the pdc initiation site. The recombinant plasmid (pRSG02) was electroporated into L. casei, and transformants were obtained. Northern analysis confirmed the production of a 3. 1-kb transcript corresponding to the predicted size of the PET operon. Western blot analyses revealed that the recombinant strain expressed both enzymes. The recombinant produced more than twice the ethanol produced by the parental L. casei strain.

Alcohol Dehydrogenase

The gntP gene of Escherichia coli involved in gluconate uptake.

The gntP gene, located between the fim and uxu loci in Escherichia coli K-12, has been cloned and characterized. Nucleotide sequencing of a region encompassing the gntP gene revealed an open reading frame of 447 codons with significant homology to the Bacillus subtilis gluconate permease. Northern (RNA) blotting indicated that the gntP gene was monocistronic and was transcribed as an mRNA with an apparent molecular size of 1.54 kb. The transcriptional start point was determined by primer extension analysis. The gntP gene was found to be under catabolite repression and was not induced by gluconate. Also, expression seemed to be stringently controlled. Several observations indicated that the GntP protein is an inner membrane protein; it contains characteristic membrane-spanning regions and was isolated predominantly from the inner-membrane fraction of fractionated host cells. A topology analysis predicted a protein with 14 membrane-spanning segments. The inability of a mutant strain to grow on gluconate minimal medium could be relieved by introduction of a plasmid encoding the gntP gene. Finally, the kinetics of GntP-mediated gluconate uptake were investigated, indicating an apparent Km for gluconate of 25 microM.

Amino Acid Sequence

Cloning and molecular genetic characterization of the Escherichia coli gntR, gntK, and gntU genes of GntI, the main system for gluconate metabolism.

Three genes involved in gluconate metabolism, gntR, gntK, and gntU, which code for a regulatory protein, a gluconate kinase, and a gluconate transporter, respectively, were cloned from Escherichia coli K-12 on the basis of their known locations on the genomic restriction map. The gene order is gntU, gntK, and gntR, which are immediately adjacent to asd at 77.0 min, and all three genes are transcribed in the counterclockwise direction. The gntR product is 331 amino acids long, with a helix-turn-helix motif typical of a regulatory protein. The gntK gene encodes a 175-amino-acid polypeptide that has an ATP-binding motif similar to those found in other sugar kinases. While GntK does not show significant sequence similarity to any known sugar kinases, it is 45% identical to a second putative gluconate kinase from E. coli,gntV. The 445-amino-acid sequence encoded by gntU has a secondary structure typical of membrane-spanning transport proteins and is 37% identical to the gntP product from Bacillus subtilis. Kinetic analysis of GntU indicates an apparent Km for gluconate of 212 microM, indicating that this is a low-affinity transporter. Studies demonstrate that the gntR gene is monocistronic, while the gntU and gntK genes, which are separated by only 3 bp, form an operon. Expression of gntR is essentially constitutive, while expression of gntKU is induced by gluconate and is subject to fourfold glucose catabolite repression. These results confirm that gntK and gntU, together with another gluconate transport gene, gntT, constitute the GntI system for gluconate utilization, under control of the gntR gene product, which is also responsible for induction of the edd and eda genes of the Entner-Doudoroff pathway.

Amino Acid Sequence

Effects of dietary calcium and phosphorus on vitamin D metabolism and calcium absorption in hamster.

We studied the following responses to restriction of dietary calcium and phosphorus in the growing hamster: (i) serum concentrations of calcium, inorganic phosphorus, magnesium, and vitamin D metabolites; and (ii) calcium transport by ileum. Diets fed were normal calcium with normal or low phosphorus or low calcium with normal or low phosphorus. We found serum 1 alpha,25-dihydroxycalciferol (1,25-[OH]2D) concentration did not differ significantly among the diet groups. Calcium absorption, measured as serosal/mucosal calcium concentration ratio produced by everted ileal sac, was greater in the low calcium, normal phosphorous group than in all other groups. The other groups did not differ from one another in calcium absorption. Feeding the low calcium, normal phosphorus diet increased inorganic phosphorus and magnesium but decreased calcium concentration in serum in comparison with the three other diets. Both low phosphorus diets were without effect on serum calcium, but the low calcium, low phosphorus diet increased serum inorganic phosphorus and magnesium above that of the normal calcium, low phosphorus diet. Ileal calcium absorption in hamster (i) was independent of serum 1,25-(OH)2D concentration; (ii) increased in response to low dietary calcium if dietary phosphorus was normal; and (iii) was independent of dietary calcium, if dietary phosphorus was low. Despite increased calcium absorption, serum calcium was decreased in the low calcium-normal phosphorus group as compared with all other groups. Feeding low calcium diets increased serum inorganic phosphorus and magnesium as compared with feeding the corresponding normal calcium diets (i.e., independently of whether dietary phosphorus content was normal or low). These studies demonstrate that the interrelationships between calcium absorption and vitamin D and mineral metabolism in hamster differ from other mammals.

Absorption

Single-run separation and detection of multiple metabolic intermediates by anion-exchange high-performance liquid chromatography and application to cell pool extracts prepared from Escherichia coli.

A method is described for analysis of the intracellular concentrations of metabolic intermediates of the Embden-Meyerhof-Parnas pathway, the Entner-Doudoroff pathway, the pentose phosphate pathway, and the tricarboxylic acid cycle in cell pool extracts of Escherichia coli. A single anion-exchange HPLC run of 40 min allowed resolution of 27 anionic metabolite standards. Detection limits of 0.1 nmol per injection were achieved by use of a conductivity detector equipped with an anion self-regenerating suppressor and a uv detector. A boiling water extraction procedure was used to prepare cell pool extracts. Cochromatography of cell pool extracts and metabolite standards was used to confirm the identities of metabolites in the cell pool. As many as 16 metabolites could be detected and quantified in the cell pool extracts by using the described HPLC method. An analysis of metabolite concentrations in E. coli showed the dynamics of glucose metabolism during a 2-min transition from starvation to steady-state metabolism following addition of glucose. The ease and power of this method suggests general utility for in vivo metabolite analysis in a variety of experimental systems.

Carbohydrates

Breast cancer and importance of zygosity determination in triplet sisters.

This study is the first to examine the genetic risk in a breast cancer-prone family wherein two of three triplet sisters and their mother manifested breast cancer. The unaffected triplet, the proband, was found to be monozygotic with her deceased sister through DNA testing of tumor blocks and dizygotic to her living affected sister. Genetic counseling implications are discussed.

Adult

Characterization of the Zymomonas mobilis glucose facilitator gene product (glf) in recombinant Escherichia coli: examination of transport mechanism, kinetics and the role of glucokinase in glucose transport.

Zymomonas mobilis is known to transport glucose by a facilitated diffusion process. A putative glucose facilitator gene (glf), closely related to a large family of glucose transporters, is located in a cluster of genes that code for enzymes of glucose metabolism. The Z. mobilis glf gene is able to complement glucose transport in an Escherichia coli strain that is defective in native glucose transport and glucokinase. In this study, the recombinant E. coli was shown to be capable of influx counterflow when preloaded with glucose and had an apparent Km for glucose of approximately 1.1-2.9 mM, consistent with the function of Glf as a low-affinity glucose facilitator. The ability of glucokinase mutants expressing glf to transport glucose made it clear that glucokinase activity was not required for Glf-dependent glucose transport. The possibility that glucokinase can interact with Glf to improve the affinity for glucose was not supported since expression of the Z. mobilis glucokinase gene, in addition to glf, did not affect the Km of Glf for glucose in recombinant E. coli. The inability of various sugars to compete with glucose during glucose transport by recombinant E. coli expressing glf indicated that Glf is specific for glucose. While the results of fructose transport assays did not completely rule out the possibility of very low affinity for fructose, the apparent specificity of Glf for glucose makes it possible that Z. mobilis utilizes a different transporter(s) for fructose.

Bacterial Proteins

Violence victims' perception of functioning and well-being: a survey from an urban public hospital walk-in clinic.

This study assessed the health perceptions of self-reported violence victims in an urban minority population attending a walk-in clinic by using an anonymous, 1-week, cross-sectional survey. The Medical Outcome Study Short-Form (MOS SF-20) was used to assess functioning/well being, including the dimensions of physical functioning, role functioning, social functioning, mental health, health perceptions, and pain. Health perception main scores were calculated for each of the six health dimensions in the following four groups: patient-victims, patient-nonvictims, visitor-victims, and visitor-nonvictims. Odds ratios (OR) were calculated to assess the association of violence victimization and functioning/well-being. The mean scores of health status were consistently better among nonvictims for all of the six health concepts measured; patients who were victims showed lower mean scores than nonvictim patients. A similar pattern also was found in visitors' health status scores when victims were compared to nonvictims. The strongest association was found between violence victimization and mental health, and the least association was between the pain score and violence victimization. This study showed a substantial association between poor health and violence victimization in the patient population studied. Intervention is needed to prevent and decrease violence in order to minimize the impact of violence on the health of victims.

Chicago

The Wisconsin Diabetes Control Program: a health systems and community-based approach.

The Wisconsin Diabetes Control Program will address the health needs of people with diabetes by working closely with the Wisconsin Affiliate of the American Diabetes Association and other diabetes health professionals in the state. The 5-year program will use both health systems and community-based approaches to coordinate prevention, detection, and control activities required to reduce the burden of this chronic condition. This program represents a major shift in focus from previous diabetes control programs supported by the CDC, and is designed to establish the program as a key component of an evolving health care environment.

Community Health Services

Psychological aspects of monitoring high risk women for breast cancer.

BACKGROUND: There is a paucity of knowledge pertaining to the attitudes, feelings, and emotions of women who are at increased familial risk for breast cancer and how these concerns will affect their surveillance behavior. A review of the literature shows an unevenness in the conclusions about these matters, with some reports indicating that anxiety aroused in the familial cancer setting may abet surveillance behavior, whereas other data indicates a negative effect. METHODS: The authors reported anecdotal accounts of such behavior in women from hereditary breast and hereditary breast-ovarian cancer prone families. RESULTS: Although these responses of fear, anxiety, and apprehension about cancer risk are not unique to this hereditary cohort, they nevertheless must have been tempered by often life-long exposure of cancer occurrences that may have decimated their families. CONCLUSIONS: All accounts agree with the need to devote more research to the special needs--psychological, social, insurance, and general public health measures--of these high risk women.

Adoption

Prevalence of violence victimization among patients seen in an urban public hospital walk-in clinic.

OBJECTIVES: To study the prevalence of serious physical interpersonal violence and to identify the types of perpetrators, the frequency of occurrence, the time since the violence occurred, the risk profiles, and other factors related to victimization. METHODS: One-week survey of all consecutively registered patients and their visitors in an urban public hospital adult walk-in clinic, using an anonymous self-administered questionnaire. RESULTS: Of the 1,504 patients, 1,041 (69.2%) completed the questionnaire. The reported experience of serious physical violence victimization for the whole study population, both patients (n = 1,041) and visitors (n = 155), was 47.9% (573/1,196). A violence victim was more likely to be male [odds ratio (OR) = 1.41, 95% confidence interval (CI): 1.11, 1.78], African-American (OR = 1.27, 95% CI: 0.98, 1.63), aged 45 years or younger (OR = 1.55, 95% CI: 1.19, 2.03), and single (OR = 1.47, 95% CI: 1.16, 1.86). Alcohol use and drug use were clearly associated with violence victimization, with prevalence ORs of 2.26 (95% CI: 1.80, 2.85) for alcohol and 3.68 (95% CI: 2.66, 5.09) for drugs. CONCLUSION: A history of serious physical violence victimization is common in inner-city hospital walk-in clinic patients. Walk-in clinics in urban areas of high violence, therefore, may prove to be important places for intervention and prevention of violence.

Adult

Familial aggregation of carcinoma of the endometrium.

OBJECTIVE: Our purpose was to describe histologically verified endometrial carcinoma and other cancer types manifested through three generations in a pedigree, where these findings do not fit any classic hereditary cancer syndrome. STUDY DESIGN: Our family study protocol used detailed patient interviews whenever possible and questionnaires with permission forms that, when signed, enabled retrieval of pertinent medical-genetic and pathologic study documents. RESULTS: Endometrial carcinoma was histologically verified in five women through three consecutive generations. The triad of obesity, hypertension, and diabetes mellitus was not observed. Primary carcinomas of both the endometrium and ovary and endometrium and lymphoma were documented in two relatives in the direct genetic lineage of the pedigree. CONCLUSION: An aggregation of endometrial carcinoma in families, even when classic hereditary cancer syndrome identification is lacking, nevertheless merits surveillance and management strategies targeted to putative high-risk family members.

Endometrial Neoplasms

Attitudes, knowledge, and skills of internal medicine residents regarding pre-conception care.

BACKGROUND: A questionnaire was designed based on current recommendations for pre-conception care and care of women at the time of diagnosis of pregnancy to evaluate internal medicine residents' attitudes, knowledge, and clinical management skills in the pre-conception care of healthy women and women who have chronic diseases during their reproductive years. METHOD: In early 1991, a self-administered questionnaire was distributed to 104 internal medicine residents at Cook County Hospital, a large, inner-city public hospital. Statistical analysis included the use of chi-square comparison, Pearson correlation, and Student's t-test. RESULTS: Seventy-nine of the residents completed questionnaires. Their levels of knowledge and management skills regarding pre-conception care were relatively low compared with standard recommendations. The residents' attitudes, however, were favorable toward the importance of the topic. Residency training did not appear to improve the residents' management skills, as there was no significant difference in skills among the first-, second-, and third-year residents. CONCLUSION: That the residents' levels of knowledge and management skills were low (despite their favorable attitudes) suggests that the current curriculum for primary care training in internal medicine needs to be revised to improve the readiness of residents to take care of women of reproductive age.

Attitude of Health Personnel

Reconstruction of glucose uptake and phosphorylation in a glucose-negative mutant of Escherichia coli by using Zymomonas mobilis genes encoding the glucose facilitator protein and glucokinase.

Expression of the Zymomonas mobilis glf (glucose facilitator protein) and glk (glucokinase) genes in Escherichia coli ZSC113 (glucose negative) provided a new functional pathway for glucose uptake and phosphorylation. Both genes were essential for the restoration of growth in glucose minimal medium and for acid production on glucose-MacConkey agar plates.

Bacterial Proteins