Search PubMed⌕ Search

Biomedical subjects

K Sanders

Publications and source records attributed to K Sanders.

At least 19 recordsLinked to original sources
PubMed2006

The role of NADPH oxidase in carotid body arterial chemoreceptors.

O(2)-sensing in the carotid body occurs in neuroectoderm-derived type I glomus cells where hypoxia elicits a complex chemotransduction cascade involving membrane depolarization, Ca(2+) entry and the release of excitatory neurotransmitters. Efforts to understand the exquisite O(2)-sensitivity of these cells currently focus on the coupling between local P(O2) and the open-closed state of K(+)-channels. Amongst multiple competing hypotheses is the notion that K(+)-channel activity is mediated by a phagocytic-like multisubunit enzyme, NADPH oxidase, which produces reactive oxygen species (ROS) in proportion to the prevailing P(O2). In O(2)-sensitive cells of lung neuroepithelial bodies (NEB), multiple studies confirm that ROS levels decrease in hypoxia, and that E(M) and K(+)-channel activity are indeed controlled by ROS produced by NADPH oxidase. However, recent studies in our laboratories suggest that ROS generated by a non-phagocyte isoform of the oxidase are important contributors to chemotransduction, but that their role in type I cells differs fundamentally from the mechanism utilized by NEB chemoreceptors. Data indicate that in response to hypoxia, NADPH oxidase activity is increased in type I cells, and further, that increased ROS levels generated in response to low-O(2) facilitate cell repolarization via specific subsets of K(+)-channels.

Animals↗
PubMed2006

Wrong and missing sire information affects genetic gain in the Angeln dairy cattle population.

In the present study, molecular genetic markers were used to help estimate the degree of wrong sire information in the German Angeln dairy cattle population. Sixteen polymorphic microsatellite markers were genotyped on 5 different paternal half-sib families with a total of 805 daughters. For the genotyping process, blood samples of the daughters and semen samples of the sires were used. Allelic frequencies and exclusion probabilities were estimated. The simultaneous effect of wrong (WSI) and missing sire information (MSI) on the reliability of estimated breeding values and on the genetic gain was investigated using deterministic simulations. For these simulations, different values for the number of daughters per sire, heritability, WSI, and MSI were chosen. The estimated proportion of the WSI was 7% in the German Angeln dairy cattle population. The combined impact of WSI and MSI on the genetic gain was relatively large, especially in the case of small progeny size per sire and low heritability. The impact of WSI was more harmful than MSI on response to selection.

Alleles↗
PubMed2006

Characterization of the DGAT1 mutations and the CSN1S1 promoter in the German Angeln dairy cattle population.

The identification of quantitative trait loci (QTL) and genes with influence on milk production traits has been the objective of various mapping studies in the last decade. In the centromeric region of Bos taurus autosome (BTA) 14, the acyl-CoA:diacylglycerol acyltransferase1 gene (DGAT1) has been identified as the most likely causative gene underlying a QTL for milk fat yield and content. Recently, a second polymorphism in the promoter of DGAT1 emerged as an additional source of variation. In this study, the frequencies and the effects of alleles at the DGAT1 K232A and at the DGAT1 promoter variable number of tandem repeat (VNTR) locus on BTA14, and of alleles at the CSN1S1 (alpha(S1)-casein-encoding gene) promoter on BTA6 in the German Angeln dairy cattle population were investigated. Analyzed traits were milk, fat, protein, lactose, and milk energy yield, fat, protein, lactose, and milk energy content and somatic cell score. The lysine variant of the DGAT1 K232A mutation showed significant effects for most of the milk production traits. A specific allele of the DGAT1 promoter VNTR showed significant effects on the traits lactose yield and content, milk energy content, and SCS compared with the other alleles. Additionally, a regulation mechanism between the DGAT1 K232A mutation and the DGAT1 promoter VNTR was found for fat yield and content, which could be caused by an upper physiological bound for the effects of the DGAT1 gene. At the CSN1S1 promoter, 2 of 4 alleles showed significant allele substitution effects on the milk yield traits.

Alleles↗
PubMed2005

Effect of p47phox gene deletion on ROS production and oxygen sensing in mouse carotid body chemoreceptor cells.

Membrane potential in oxygen-sensitive type I cells in carotid body is controlled by diverse sets of voltage-dependent and -independent K(+) channels. Coupling of Po(2) to the open-closed state of channels may involve production of reactive oxygen species (ROS) by NADPH oxidase. One hypothesis suggests that ROS are produced in proportion to the prevailing Po(2) and a subset of K(+) channels closes as ROS levels decrease. We evaluated ROS levels in normal and p47(phox) gene-deleted [NADPH oxidase knockout (KO)] type I cells using the ROS-sensitive dye dihydroethidium (DHE). In normal cells, hypoxia elicited an increase in ROS, which was blocked by the specific NADPH oxidase inhibitor 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF, 3 mM). KO type I cells did not respond to hypoxia, but the mitochondrial uncoupler azide (5 microM) elicited increased fluorescence in both normal and KO cells. Hypoxia had no effect on ROS production in sensory and sympathetic neurons. Methodological control experiments showed that stimulation of neutrophils with a cocktail containing the chemotactic peptide N-formyl-Met-Leu-Phe (1 microM), arachidonic acid (10 microM), and cytochalasin B (5 microg/ml) elicited a rapid increase in DHE fluorescence. This response was blocked by the NADPH oxidase inhibitor diphenyleneiodonium (10 microM). KO neutrophils did not respond; however, azide (5 microM) elicited a rapid increase in fluorescence. Physiological studies in type I cells demonstrated that hypoxia evoked an enhanced depression of K+ current and increased intracellular Ca2+ levels in KO vs. normal cells. Moreover, AEBSF potentiated hypoxia-induced increases in intracellular Ca2+ and enhanced the depression of K+ current in low O(2). Our findings suggest that local compartmental increases in oxidase activity and ROS production inhibit the activity of type I cells by facilitating K+ channel activity in hypoxia.

Animals↗
PubMed2002

Aerosolized pentamidine prophylaxis for Pneumocystis carinii pneumonia after allogeneic marrow transplantation.

Pneumocystis carinii pneumonia (PCP) poses a serious risk to allogeneic bone marrow transplant (BMT) patients, who are often intolerant of trimethoprim-sulfamethoxazole (TMP-SMX), the traditional first-line prophylactic agents. There are limited published data supporting the use of aerosolized pentamidine (AP) prophylaxis in the BMT population. We assessed the effectiveness of AP in BMT recipients by reviewing the experience at our center. We divided our review into four time periods from January 1990 to March 2000, during which approximately 700 BMTs were performed. The first period includes patients receiving AP treatments from January 1990 to July 1997 (baseline), the second from August 1997 to July 1998 (pre-outbreak), the third from August 1998 to October 1999 (outbreak), and the fourth from November 1999 to March 2000 (post-outbreak). At our center, TMP-SMX is the first-line agent for PCP prophylaxis, which is routinely continued for at least one year, or for the duration of enhanced immunosuppression. During the baseline period, 505 BMTs were performed and 192 patients (38%) received AP for part of their time at risk. Six patients (3%) experienced toxicities requiring discontinuation of AP. Three cases of PCP were diagnosed over 1114 patient-months of treatment in the baseline period. During the last 42 months of the baseline period, 2/154 patients receiving AP and 2 of an estimated 293 patients receiving exclusively oral prophylaxis developed breakthrough PCP (p = 0.61). During the outbreak period, 9 of 180 patients receiving AP developed PCP compared to none in the group receiving exclusively oral prophylaxis. Either changes in our AP protocol during the pre-outbreak period or pentamidine resistance may have led to this failure of prophylaxis. There were no further cases during the 5-month post-outbreak period. Our observed overall breakthrough rate was 12 cases out of 439 patients (2.7%). Our study shows that AP is an effective and well-tolerated second-line agent in preventing PCP post BMT and we recommend its continued use in this regard. However, it should be administered using a well-studied protocol, and only when TMP-SMX is not tolerated.

Administration, Inhalation↗
PubMed2002

Characteristics of carotid body chemosensitivity in NADPH oxidase-deficient mice.

Various heme-containing proteins have been proposed as primary molecular O(2) sensors for hypoxia-sensitive type I cells in the mammalian carotid body. One set of data in particular supports the involvement of a cytochrome b NADPH oxidase that is commonly found in neutrophils. Subunits of this enzyme have been immunocytochemically localized in type I cells, and diphenyleneiodonium, an inhibitor of the oxidase, increases carotid body chemoreceptor activity. The present study evaluated immunocytochemical and functional properties of carotid bodies from normal mice and from mice with a disrupted gp91 phagocytic oxidase (gp91(phox)) DNA sequence gene knockout (KO), a gene that codes for a subunit of the neutrophilic form of NADPH oxidase. Immunostaining for tyrosine hydroxylase, a signature marker antigen for type I cells, was found in groups or lobules of cells displaying morphological features typical of the O(2)-sensitive cells in other species, and the incidence of tyrosine hydroxylase-immunopositive cells was similar in carotid bodies from both strains of mice. Studies of whole cell K(+) currents also revealed identical current-voltage relationships and current depression by hypoxia in type I cells dissociated from normal vs. KO animals. Likewise, hypoxia-evoked increases in intracellular Ca(2+) concentration were not significantly different for normal and KO type I cells. The whole organ response to hypoxia was evaluated in recordings of carotid sinus nerve activity in vitro. In these experiments, responses elicited by hypoxia and by the classic chemoreceptor stimulant nicotine were also indistinguishable in normal vs. KO preparations. Our data demonstrate that carotid body function remains intact after sequence disruption of the gp91(phox) gene. These findings are not in accord with the hypothesis that the phagocytic form of NADPH oxidase acts as a primary O(2) sensor in arterial chemoreception.

Animals↗
PubMed2001

Optimizing nitrogen management in food and energy production and environmental protection: summary statement from the Second International Nitrogen Conference.

Human efforts to produce food and energy are changing the nitrogen (N) cycle of the Earth. Many of these changes are highly beneficial for humans, while others are detrimental to people and the environment. These changes transcend scientific disciplines, geographical boundaries, and political structures. They challenge the creative minds of natural and social scientists, economists, engineers, business leaders, and decision makers. The Second International Nitrogen Conference was designed to facilitate communications among all stakeholders in the "nitrogen community" of the world. The Conference participants" goal in the years and decades ahead is to encourage every country to make optimal choices about N management in food production and consumption, energy production and use, and environmental protection. Scientific findings and recommendations for decision makers that emerged from the Conference are presented.

Agriculture↗
PubMed2001

Double primary cancers of the breast and thyroid in women: molecular analysis and genetic implications.

Multiple primary cancers are characteristic of hereditary cancer syndromes. A familial association between breast and thyroid cancer has been suggested, but a genetic basis for this association has not yet been established. To determine the extent to which double primary cancers of the breast and thyroid are due to common hereditary factors, we conducted a registry- and hospital-based study in Ontario and Quebec. We obtained family histories of 74 women diagnosed with both cancer of the breast and thyroid before 70 years of age. Cancer histories were obtained for the 533 first- degree relatives of these women. The observed cancer rate in the relatives was compared with the expected number, based on age- standardized Canadian cancer incidence rates, and relative risks were estimated. A total of 87 cancers were observed in the relatives, compared to 93.7 expected cancers, giving a relative risk of 0.9 (95% confidence interval (CI): 0.7-1.1). The risk for breast cancer was 1.1 (95% CI: 0.6-1.7) and the risk for thyroid cancer was 0.7 (95% CI: 0-3.8). Blood samples were collected on 53 patients for mutational analysis of the BRCA1, BRCA2, and PTEN genes. One woman was found to be a carrier of a BRCA1 mutation (exon 11 3227delT). Our findings do not support the hypothesis that a significant proportion of double primary cancers of the breast and thyroid are due to hereditary factors.

Adult↗
PubMed2001

Increased risk for nonmedullary thyroid cancer in the first degree relatives of prevalent cases of nonmedullary thyroid cancer: a hospital-based study.

The genetic basis for nonmedullary forms of thyroid cancer (NMTC) is less well established than that of medullary thyroid cancer. However, epidemiological and family studies suggest that a proportion of NMTC may be due to inherited predisposition. To estimate the familial risk of thyroid cancer, we conducted a hospital-based case-control study at the Princess Margaret Hospital in Toronto, Ontario, Canada, and at 2 university hospitals in Montréal, Québec, Canada. We obtained pedigrees from 339 unselected patients diagnosed with NMTC and from 319 unaffected ethnically matched controls. Family histories of cancer were obtained from the cases and controls for 3292 first degree relatives of cases and controls. Seventeen cases (5.0%) and 2 controls (0.6%) reported at least one first degree relative with thyroid cancer. In relatives of patients with thyroid cancer, the incidence of any type of cancer (including NMTC) was 38% higher than in relatives of controls (incidence rate ratio, 1.4; 95% confidence interval, 1.1-1.7). The relative risk for thyroid cancer was 10-fold higher in relatives of cancer patients than in controls (incidence rate ratio, 10.3; 95% confidence interval, 2.2-47.6). Our findings suggest that hereditary or other familial factors are important in a small proportion of NMTC. Molecular studies are needed to determine the genetic basis of cancer susceptibility in these families.

Adolescent↗
PubMed2000

Attitudes of clinical faculty about career progress, career success and recognition, and commitment to academic medicine. Results of a survey.

OBJECTIVE: To assess attitudes about career progress, resources for career development, and commitment to academic medicine in physician faculty at an academic medical center who spend more than 50% of their time in clinical care. DESIGN: Faculty survey. SETTING: Academic medical center and associated Veterans Affairs medical center. RESULTS: A total of 310 physician faculty responded to the survey. Half of the faculty reported spending 50% or less of their time in clinical care (mean, 31% of time) (group 1) and half reported spending more than 50% of their time in clinical care (mean, 72% of time) (group 2). Group 2 faculty had one third of the time for scholarly activities, reported slower career progress, and were less likely to be at the rank of professor (40% and 16% for groups 1 and 2, respectively; P<.001) or to be tenured (52% and 26%, respectively; P<.001) despite similar age and years on faculty. Group 2 faculty were 50% more likely to report that tenure and promotion criteria were not reviewed at their annual progress report (P =.003) and that they did not understand the criteria (P<.001). Group 2 faculty valued excellence in patient care over scholarship and national visibility. Group 2 faculty reported greater dissatisfaction with academic medicine and less commitment to a career in academic medicine. CONCLUSIONS: Physician faculty who spend more than 50% of their time in clinical care have less time, mentoring, and resources needed for development of an academic career. These obstacles plus differences in their attitudes about career success and recognition contribute to significant differences in promotion. These factors are associated with greater dissatisfaction with academic medicine and lower commitment to academic careers.

Academic Medical Centers↗
PubMed2000

Correlation of p53 and the proto-oncogene eIF4E in larynx cancers: prognostic implications.

p53 abnormalities constitute the most frequent genetic alterations identified in larynx cancers. p53 overexpression in histologically "tumor-free" surgical margins correlates with a high recurrence rate. However, only 50-60% of tumors overexpress p53. The tumor marker eIF4E is overexpressed in 100% of larynx cancers, and overexpression of eIF4E in histologically "tumor-free" margins predicts a significantly higher recurrence. We undertook this study to correlate the expression of p53 and eIF4E in the tumors and surgical margins of squamous cell cancers of the larynx and to determine their prognostic value. A retrospective analysis was performed on 54 patients who underwent surgery for squamous cell cancers of the larynx. Patient and tumor characteristics were reviewed, and the time to recurrence was noted. Paraffin-embedded sections from the tumors and surgical margins were immunostained with antibodies to eIF4E and p53, and a qualitative analysis was performed. All 54 patients (100%) overexpressed eIF4E in the primary tumor, whereas 25 of 53 patients (47%) were p53 positive. Thirty-two of the 54 patients (59%) had eIF4E-positive margins. All 6 of 53 patients (11%) with p53-positive margins also overexpressed eIF4E in the margins. There was a significant correlation between p53 and eIF4E being positive in the margins (Spearman's correlation coefficient, P = 0.03). Twenty-one of the 25 patients (84%) that recurred, including the 6 patients with p53-positive margins, had eIF4E-positive margins. Hence, although the univariate analysis showed that nodal status and both eIF4E and p53 expression in the margins were significant predictors of recurrence (P < 0.05), in the multivariate analyses only nodal status (P < 0.001) and eIF4E in the margins (P < 0.001) were significant predictors of recurrence. Kaplan-Meier analysis demonstrated that the disease-free intervals for eIF4E-positive margins were significantly shorter than eIF4E-negative margins (P = 0.0007). There was no additional effect to the combination of positive p53 and eIF4E margins (P = 0.21). The overexpression of eIF4E in the margins appears to be a more sensitive indicator of recurrence and may be an earlier event in the process of tumorigenesis than p53.

Analysis of Variance↗
PubMed2000

Obstacles to promotion? Values of women faculty about career success and recognition. Committee on the Status of Women and Minorities, Virginia Commonwealth University, Medical College of Virginia Campus.

PURPOSE: To assess attitudes of female faculty about career progress, resources for career development, and values related to academic success and recognition. METHOD: In 1997, the authors surveyed all faculty at Virginia Commonwealth University School of Medicine and its associated Veterans Affairs Medical Center. RESULTS: Of 918 faculty, 567 (62%) responded to the survey; 33% of the respondents were women. Compared with men, women faculty were less likely to be tenured or at the level of professor, spent more time in clinical activities, had less time for scholarly activity, and reported slower career progress. Women were more likely to report that promotion and tenure criteria had not been reviewed with them. Significant differences were found between female physicians and non-physician faculty; female physicians reported the least time for scholarly activities and poorest understanding of promotion and tenure criteria. When the authors asked faculty how they valued certain indicators of career success, women were less likely to value leadership than were men. Female physicians were less likely to value scholarship and national recognition as indicators of their career success. CONCLUSION: This survey found important differences in career progress of male and female faculty, with women reporting less time for career development. In addition, there were differences in values related to career success and recognition, which were most pronounced for female physicians. These differences may have an important impact on promotion for women in general and particularly for female physicians.

Adult↗
PubMed1999

Adult nutrient intake as a risk factor for Parkinson's disease.

BACKGROUND: This population-based case-control study evaluated nutrient intake as a risk factor for Parkinson's disease (PD) among people aged > or =50 years in metropolitan Detroit. METHODS: Cases (n = 126) were diagnosed between 1991 and 1995 and neurologist-confirmed. Controls (n = 432) were frequency-matched for sex, age (+/-5 years) and race. Using a standardized food frequency questionnaire, subjects reported the foods they ate within the past year. RESULTS: Estimating the association between PD and risk of being in the highest versus the lowest intake quartile, there were elevated odds ratios for total fat (OR 1.94, 95% confidence interval [CI] : 1.05-3.58), cholesterol (OR 2.11, 95% CI: 1.14-3.90), lutein (OR 2.52, 95% CI: 1.32-4.84) and iron (OR 1.88, 95% CI: 1.05-3.38). CONCLUSIONS: These results suggest an association of PD with high intake of total fat, saturated fats, cholesterol, lutein and iron.

Aged↗
PubMed1999

Mastectomy or lumpectomy? Helping women make informed choices.

PURPOSE: To develop an instrument to help clinicians inform their patients about surgical treatment options for the treatment of breast cancer and to evaluate the impact of the instrument on the clinical encounter. METHODS: We developed an instrument, called the Decision Board, to present information regarding the benefits and risks of breast-conserving therapy (lumpectomy plus radiation therapy) and mastectomy to women with early-stage breast cancer to enable them to express a preference for the type of surgery. Seven surgeons from different communities in Ontario administered the instrument to women with newly diagnosed clinical stage I or II breast cancer over an 18-month period. Patients and surgeons were interviewed regarding acceptability of the instrument. The rates of breast-conserving surgery performed by surgeons before and after the introduction of the instrument were compared. RESULTS: The Decision Board was administered to 175 patients; 98% reported that the Decision Board was easy to understand, and 81% indicated that it helped them make a decision. The average score on a true/false test of comprehension was 11.8 of 14 (84%) (range, 6 to 14). Surgeons found the Decision Board to be helpful in presenting information to patients in 91% of consultations. The rate of breast-conserving surgery decreased when the Decision Board was introduced (88% v 73%, P =.001) CONCLUSION: The Decision Board is a simple method to improve communication and facilitate shared decision making. It was well accepted by patients and surgeons and easily applied in the community.

Adult↗
PubMed1998

Effects of a split keyboard design and wrist rest on performance, posture, and comfort.

The purpose of this study was to examine differences in experienced typists' performance, posture, and musculoskeletal pain when using a split, adjustable (SA) computer keyboard and when using a standard flat keyboard. In addition, the use of a wrist rest was examined for performance, posture, and musculoskeletal pain effects. Eighteen participants were exposed to the SA keyboard and a flat keyboard in a laboratory study of text typing for four consecutive hours on five days. The results indicated that after just 2 h of orientation and practice, the participants could perform as well on the SA keyboard as on the flat keyboard. The SA keyboard provided advantages for reduced wrist/hand pronation. There was no difference between the keyboards in the level of musculoskeletal pain reported by participants after typing. However, they reported increased pain in the back, neck, shoulders, and wrists from the beginning to the end of each of the experimental periods for both keyboards.

Adolescent↗
PubMed1997

Case-control study of phyto-oestrogens and breast cancer.

BACKGROUND: Phyto-oestrogens are a group of naturally occurring chemicals derived from plants; they have a structure similar to oestrogen, and form part of our diet. They also have potentially anticarcinogenic biological activity. We did a case-control study to assess the association between phyto-oestrogen intake (as measured by urinary excretion) and the risk of breast cancer. METHODS: Women with newly diagnosed early breast cancer were interviewed by means of questionnaires, and a 72 h urine collection and blood sample were taken before any treatment started. Controls were randomly selected from the electoral roll after matching for age and area of residence. 144 pairs were included for analysis. The urine samples were assayed for the isoflavonic phyto-oestrogens daidzein, genistein, and equol, and the lignans enterodiol, enterolactone, and matairesinol. FINDINGS: After adjustment for age at menarche, parity, alcohol intake, and total fat intake, high excretion of both equol and enterolactone was associated with a substantial reduction in breast-cancer risk, with significant trends through the quartiles: equol odds ratios were 1.00, 0.45 (95% CI 0.20, 1.02), 0.52 (0.23, 1.17), and 0.27 (0.10, 0.69)--trend p = 0.009--and enterolactone odds ratios were 1.00, 0.91 (0.41, 1.98), 0.65 (0.29, 1.44), 0.36 (0.15, 0.86)--trend p = 0.013. For most other phytoestrogens there was a reduction in risk, but it did not reach significance. Difficulties with the genistein assay precluded analysis of that substance. INTERPRETATION: There is a substantial reduction in breast-cancer risk among women with a high intake (as measured by excretion) of phyto-oestrogens-particularly the isoflavonic phyto-oestrogen equol and the lignan enterolactone. These findings could be important in the prevention of breast cancer.

4-Butyrolactone↗
PubMed1997

High labial incisions for genioplasty.

Clinical experience in genioplasty has shown that high labial incisions heal with fewer scar bands than conventional deep labial incisions. In a prospective randomized trial, we compared 18 high labial curvilinear incisions with 27 high labial W-shaped ('royal') incisions for access and visibility during chin osteotomy. Both incisions were 3 cm wide. Maximal incision lengthening between two skin hooks was recorded with a ruler before closure, and there was no significant difference between the two. The maximum wound area between three skin hooks was photographed and computed, and showed a mean difference of 188.75 mm2 (t-test, P < 0.001), which corroborated the clinical findings that access and visibility were superior in the W-shaped incision group. Complications were few in both groups. We now use the high labial royal incision about 3.5 cm wide, with 90 degrees limb angle for complicated chin osteotomies and ostectomies. A smaller curvilinear high labial incision is used for simple advancement osteotomies.

Adult↗