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Biomedical subjects

R C Young

Publications and source records attributed to R C Young.

At least 19 recordsLinked to original sources
PubMed2001

Human papilloma virus (HPV)-E6/E7 and epidermal growth factor receptor (EGF-R) protein levels in cervical cancer and cervical intraepithelial neoplasia (CIN).

BACKGROUND: About 90% of cervical cancers and advanced cervical intraepithelial neoplasia (CIN II/III) are squamous epithelial cells with mRNA for human papillomavirus (HPV)16 and 18 and up-regulated epidermal growth factor receptor (EGF-R). Since presence of proteins rather than mRNA may be truly indicative of active infection or disease progression, establishing reliable methods for quantifying these proteins in cervical biopsies is important. METHOD: We have established an objective semi-quantitative immunofluorescent antibody assay to reliably assess the levels of HPV-E6/E7 and EGF-R proteins in the cervical biopsies from 12 normal women, five women with CIN I, 15 with CIN II/III and ten with cervical cancer. RESULTS: HPV-E6/E7 and EGF-R, when present, were specific to para-basal, basal and squamous epithelial cells (negative in stromal cells). Nine of ten women with cervical cancer and 15 (14 CIN II/III; 1 CIN I) of 20 women with CIN were positive for HPV-E6/E7. All 12 controls were HPV-negative. The controls and six women with CIN (four with CIN I) negative for HPV had low levels of EGF-R. The only exception was one woman with cervical cancer negative for HPV, with high levels of EGF-R. Levels of HPV-E6/E7 and EGF-R were significantly higher (P < 0.001 vs. controls) in women with advanced CIN II and III (P< 0.05 vs. controls in CIN I) and cervical cancer. The HPV-E6/E7 and EGF-R levels correlated significantly (r = 18.98; P < 0.001, by linear regression analysis). CONCLUSION: We have established a highly specific and sensitive semi-quantitative immunofluorescent antibody assay for measuring levels of HPV-E6/E7 proteins and EGF-R in archival cervical biopsies. Our data suggest an association between HPV-E6/E7 and EGF-R.

Carcinoma, Squamous Cell↗
PubMed2001

Just teasing: a conceptual analysis and empirical review.

Drawing on E. Goffman's concepts of face and strategic interaction, the authors define a tease as a playful provocation in which one person comments on something relevant to the target. This approach encompasses the diverse behaviors labeled teasing, clarifies previous ambiguities, differentiates teasing from related practices, and suggests how teasing can lead to hostile or affiliative outcomes. The authors then integrate studies of the content of teasing. Studies indicate that norm violations and conflict prompt teasing. With development, children tease in playful ways, particularly around the ages of 11 and 12 years, and understand and enjoy teasing more. Finally, consistent with hypotheses concerning contextual variation in face concerns, teasing is more frequent and hostile when initiated by high-status and familiar others and men, although gender differences are smaller than assumed. The authors conclude by discussing how teasing varies according to individual differences and culture.

Cultural Characteristics↗
PubMed2001

Intracellular calcium gradients in cultured human uterine smooth muscle: a functionally important subplasmalemmal space.

The plasma membrane contains the key elements for the control of coupling excitation to contraction in smooth muscle. The superficial calcium buffer barrier, initially proposed by van Breemen for vascular smooth muscle, may participate in the regulation of calcium entry in other smooth muscle types. To investigate the relationship between the sarcoplasmic reticulum (SR) and the plasma membrane in myometrial smooth muscle cells, we performed experiments using videofluorescence imaging and cell-attached electrophysiology. The cell-attached patch was used as a reporter for the free calcium in the subplasmalemmal space by monitoring openings of the Maxi-K channel. Calcium green-1 was used to simultaneously monitor changes of the deep cytosolic calcium concentrations. The cell with the patch attached was stimulated via an intercellular calcium wave from an adjacent cell. In this fashion, release of SR calcium was accomplished with minimal disturbance of the plasma membrane and the subplasmalemmal space of the cell studied. With physiological bathing solution, six of seven calcium waves activated Maxi-K channels. Surprisingly, the Maxi-K channels began opening 6.3 +/- 4.7s (range 2.6-15.0s) after the wave passed the pipette location. When plasma membrane calcium fluxes were inhibited with 100 microM lanthanum, no Maxi-K channel openings were observed in six of seven experiments. These results are best explained by a subplasmalemmal space in which the calcium concentration is largely controlled by store-operated channels. These results suggest the superficial buffer barrier as merely one aspect of subplasmalemmal regulation of calcium dynamics, and emphasize the importance of store-operated calcium channels during dynamic calcium changes.

Calcium↗
PubMed2001

The mechanism of propagation of intracellular calcium waves in cultured human uterine myocytes.

OBJECTIVE: The primary goal of this work was to determine the relative importance of sarcoplasmic reticulum inositol 1,4,5-triphosphate receptors and ryanodine receptors in the mechanism of intracellular calcium wave propagation in human uterine myocytes. A secondary goal was to identify the rate-determining step of calcium wave propagation. STUDY DESIGN: Pregnant human myometrium was obtained at the time of cesarean delivery, enzymatically dispersed, and cultured through several passages. Intracellular calcium wave velocities were measured with video fluorescence microscopy and the calcium-dependent fluorescent dye calcium green 1. Experimental conditions were modified by exposure of the cells to ruthenium red (blocked ryanodine receptor), ryanodine (locked open ryanodine receptor), oxytocin (increased inositol-1,4,5-triphosphate), sodium butyrate (intracellular acidification), ammonium chloride (intracellular alkalinization), and elevation of temperature (from 19 degrees C to 30 degrees C). RESULTS: Wave velocities were found to be the same for spontaneously occurring (9.6 +/- 2.6 microm/s) and oxytocin-stimulated (10.3 +/- 3.4 microm/s) waves. Advance treatment of the cells with ryanodine or ruthenium red failed to change oxytocin-stimulated wave velocities from control values. The temperature dependence of calcium wave velocities was studied across the range 19 degrees C to 30 degrees C. Plots of wave velocities versus the inverse of the temperature yielded apparent activation energies that were the same for spontaneous (13.2 +/- 0.3 kcal/mol) and oxytocin-induced (14.3 +/- 1.6 kcal/mol) waves. After intracellular acidification by treatment with butyrate (20 mmol/L) wave velocities increased by 44%. Wave velocities decreased by 35% after treatment with ammonium chloride (20 mmol/L). CONCLUSION: Propagation of intracellular calcium waves in cultured human uterine myocytes exhibited mechanisms of sarcoplasmic reticulum calcium release that could use either inositol 1,4,5-triphosphate receptors alone or ryanodine receptors alone, or both together. The rate-determining step for calcium wave propagation was diffusion of calcium though a highly buffered cytoplasm.

Ammonium Chloride↗
PubMed2001

Differing mechanisms of inhibition of calcium increases in human uterine myocytes by indomethacin and nimesulide.

OBJECTIVE: Indomethacin, an inhibitor of cyclooxygenase types 1 and 2, and nimesulide, a cyclooxygenase 2 selective inhibitor, are both well-known inhibitors of prostaglandin production. It has been assumed that the tocolytic mechanism of nimesulide and indomethacin is only through decreased prostaglandin production. The purpose of this study was to test the hypothesis that either nimesulide or indomethacin, or both, has a mechanism of action on human myocytes other than inhibition of prostaglandin production. STUDY DESIGN: Human uterine myometrium was obtained from consenting patients during cesarean deliveries. Myocytes were cultured, plated, and loaded with a calcium-dependent fluorescent dye, calcium green 1. The relative concentrations of intracellular free calcium were determined by measurement of time-dependent fluorescence changes by means of a video fluorimeter. In all experiments, cells were stimulated with prostaglandin F2alpha, 30 micromol/L. Experiments were performed without pretreatment (control) or with pretreatment consisting of indomethacin, 10 micromol/L, or nimesulide, 30 micromol/L. The percentages of cells demonstrating calcium increases were counted and compared by means of the Fisher exact test. A P value =.05 was considered significant. RESULTS: After prostaglandin F2alpha exposure, 33% of cells showed an increase in intracellular free calcium under control conditions. When pretreated with nimesulide, 39% of cells responded to prostaglandin F2alpha (P =.59). When pretreated with indomethacin, only 16% of cells responded to prostaglandin F2alpha (P =.019). CONCLUSIONS: Pretreatment with nimesulide failed to reduce the fraction of cells that responded to prostaglandin F2alpha. In contrast, pretreatment with indomethacin significantly reduced the fraction of responding cells. These data suggest that, in vitro, indomethacin exhibits a mechanism of tocolysis other than inhibition of prostaglandin synthesis.

Calcium↗
PubMed2001

Standards for assessment of lung function and respiratory health in minority populations: some challenges linger into the new millennium.

Results of pulmonary function tests (as an indicator of respiratory health) are from 11 to 13 percent lower in African Americans and other racial ethnic populations than in Caucasians when controlled for gender, age, and height. Environmental factors influencing these indices are circadian variation, altitude, air pollutants, technology, state of nutrition, smoking history, and other indicators of lifestyle. A combination of subtle, genetically determined anthropometric variants may also be operative, the extent of which is controversial. Population-based, population-specific standards are required to avoid erroneous diagnosis of cardiorespiratory disease, erroneous assessment of operative risk, unfair hiring practices when lung function tests are used for preemployment evaluation in dusty occupations, and unfair labeling when workers apply for disability compensation. Tailoring of statistical prediction standards from simple linear to more complex polynomial regression models will increase the accuracy of population prediction standards for pulmonary function variables into the 21st century.

Adult↗
PubMed2000

Executive dysfunction and long-term outcomes of geriatric depression.

BACKGROUND: This study investigated the relationship of executive and memory impairment to relapse, recurrence, and course of residual depressive symptoms and signs after remission of geriatric major depression. METHODS: Fifty-eight elderly subjects remitted from major depression received continuation nortriptyline treatment (plasma levels 60-150 ng/mL) for 16 weeks and then were randomly assigned to either nortriptyline maintenance therapy or placebo for up to 2 years. Diagnosis was made using the Research Diagnostic Criteria and the DSM-IV criteria after an interview using the Schedule for Affective Disorders and Schizophrenia. Executive dysfunction and memory were assessed with the Dementia Rating Scale, disability and social support were rated with the Philadelphia Multiphasic Instrument, and medical burden was assessed with the Cumulative Illness Rating Scale. RESULTS: Abnormal initiation and perseveration scores, but not memory impairment, were associated with relapse and recurrence of geriatric depression and with fluctuations of depressive symptoms in the whole group and in subjects who never met criteria for relapse or recurrence during the follow-up period. Memory impairment, disability, medical burden, social support, and history of previous episodes did not significantly influence the outcome of depression in this sample. CONCLUSIONS: Executive dysfunction was found to be associated with relapse and recurrence of geriatric major depression and with residual depressive symptoms. These observations, if confirmed, will aid clinicians in identifying patients in need of vigilant follow-up. The findings of this study provide the rationale for investigation of the role of specific prefrontal pathways in predisposing or perpetuating depressive syndromes or symptoms in elderly patients.

Age Factors↗
PubMed2000

Age and nortriptyline concentrations in plasma ultrafiltrate.

OBJECTIVES: Since plasma protein binding of tricyclic antidepressants may be relevant to treatment effects and can be influenced by age-associated factors, we examined both plasma ultrafiltrate and total concentrations of nortriptyline (NT) in patients and compared these to age. We hypothesized negative associations with age of both ultrafiltrate NT and the ratio of ultrafiltrate NT to total plasma NT. METHODS: Patients with major depression at a psychiatric service treated with a stable dose of NT were studied. Trough plasma ultrafiltrate NT concentrations and total plasma NT concentrations were measured by high performance liquid chromatography. Concentrations were corrected for dose. RESULTS: Eighty-seven patients aged 26 - 88 years were studied. Ultrafiltrate NT concentrations and the ratio of ultrafiltrate NT to total NT concentrations were both significantly negatively associated with age. Total NT concentrations were not significantly associated with age. CONCLUSIONS: Relatively low ultrafiltrate NT concentrations in older patients may reflect lower tissue exposure at a given total plasma NT concentration. This could be relevant to toxic and therapeutic effects. Studies of relationships between non-bound drug concentrations and NT treatment outcomes across the age span are needed.

Adult↗
PubMed2000

Up-regulation of epidermal growth factor-receptors (EGF-R) by nicotine in cervical cancer cell lines: this effect may be mediated by EGF.

PROBLEM: Over-expression of epidermal growth factor-receptors (EGF-R) has been described in a variety of cancers, including cervical cancer. Nicotine may increase cellular proliferation rates through a mechanism involving EGF or EGF-R. In this study, we ascertain the effect of EGF antibodies on nicotine-enhanced proliferation rates in two cervical cancer cell lines. METHOD OF STUDY: We studied (a) nicotine-induced increase in the cellular expression of EGF-R in human papillomavirus (HPV)-positive ME-180 and HPV-negative HT-3 cervical cancer cell line cultures, using a semi-quantitative immunofluorescent antibody assay; (b) alterations in cellular proliferation in association with changes in EGF-R levels; and (c) the EGF-R mediation by EGF. RESULTS: Nicotine exposure at physiologically attainable plasma concentrations caused increased expression of EGF-R in both cervical cancer cell lines. Up-regulation of EGF-R was associated with increased cellular proliferation. Decreased expression of EGF-R was associated with decreased cellular proliferation. These data were consistent with EGF-R expression as a mechanism for the control of proliferation of the cervical cancer cells. The action of nicotine was abrogated when antibodies to EGF were added, implying that nicotine up-regulation of EGF-R may be mediated by EGF. CONCLUSIONS: Our data show that nicotine-induced proliferation of cervical cancer cells is mediated through EGF-R over-expression and that this action of nicotine utilizes EGF.

Cell Division↗
PubMed2000

Cervical epidermal growth factor-receptor (EGF-R) and serum insulin-like growth factor II (IGF-II) levels are potential markers for cervical cancer.

PROBLEM: To ascertain if cervical epithelial epidermal growth factor receptor (EGF-R) and serum insulin-like growth factor II (IGF-II) levels are potential markers for cervical cancer. METHOD OF STUDY: We tested cervical biopsies obtained from 18 controls, 3 women with cervical intraepithelial neoplasia (CIN) I, 17 women with CIN II and III, and 12 women with cervical cancer for EGF-R using a quantitative immunofluorescent antibody assay. We measured serum IGF-II levels using an enzyme-linked immunosorbent assay in 20 controls, 26 CIN patients, 12 with cervical cancer before therapy, 5 with cervical cancer for < 1 year, and 9 others > 1 year after therapy. RESULTS: The levels of cervical EGF-R in women with CIN and cervical cancer were significantly higher (P<0.05 for CIN I; P<0.001 for patients with CIN II and III or cervical cancer) than in controls. Women with cervical cancer (P<0.001 vs. controls) or advanced CIN (P = 0.03) had elevated levels of serum IGF-II, while the women with CIN I had levels similar to controls. Women with cervical cancer in the post-therapy period had significantly lower serum IGF-II levels than the women with cervical cancer before therapy (P<0.001). CONCLUSION: Cervical epithelial EGF-R and serum IGF-II levels may be used for the diagnosis and prognosis of cervical cancer.

Biomarkers, Tumor↗
PubMed2000

Fox Chase Network: Fox Chase Cancer Center's community hospital affiliation program.

Fox Chase Cancer Center developed a format for affiliation with community providers in 1986. Fox Chase Network was formed to establish hospital-based community cancer centers to increase access to patients involved in clinical research. Under this program, the Fox Chase Network now contributes 500 patients per year to prevention and clinical research studies. As relationships with community providers form, patient referrals have increased at Fox Chase Cancer Center and for each Fox Chase Network member. A dedicated staff is required to operate the central office on a day-to-day basis as well as at each affiliate. We have found this to be a critical element in each program's success. New challenges in the cancer business-increasing volumes with declining revenue-have caused us to reconfigure the services offered to affiliates, while maintaining true to our mission: to reduce the burden of human cancer.

Cancer Care Facilities↗
PubMed2000

Three cycles versus six cycles of adjuvant paclitaxel (Taxol)/carboplatin in early stage ovarian cancer.

The optimal management of early stage ovarian cancer with poor prognostic features remains controversial. On the basis of results of studies in advanced ovarian cancer, paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in combination with a platinum agent has become part of adjuvant chemotherapy trials in early stage disease. Because the optimal number of chemotherapy cycles has not been determined, the Gynecologic Oncology Group is conducting a study comparing three cycles with six cycles of adjuvant paclitaxel/carboplatin in high-risk patients with early stage ovarian cancer. At a median follow-up period of 3 years, 290 (88%) of the 331 evaluable patients on both arms of the trial were alive and recurrence free. Regimen B (treatment groups have not yet been unblinded) was associated with a somewhat higher incidence of grade 3/4 leukopenia and a markedly higher frequency of grade 2-4 neurologic toxicity. Final results from this study will reveal any difference in overall or progression-free survival between the two regimens.

Adult↗
PubMed2000

Automated oxyhemoglobin dissociation curve construction to assess sickle cell anemia therapy.

Oxyhemoglobin dissociation curves measure the most important function of red blood cells - the affinity for oxygen and its delivery to the tissues. This function may be deranged in sickle cell anemia and some other hemoglobinopathies. An automated oxyhemoglobin dissociation curve analyzer constructed dissociation curves in 55 patients with hemoglobinopathies and in 24 control subjects while maintaining constant temperature and pH. Sigmoid curves were converted to rectilinear ones using the Hill equation. Oxygen affinity of red cells was assessed by calculation of P50 (the PO2 at which hemoglobin is half saturated). Results revealed separation of oxyhemoglobin dissociation Hill plots according to phenotype but with wide variability. Mean oxygen affinity of fetal hemoglobin was greatest, whereas that of sickle hemoglobin was least. Other hemoglobins were intermediate. A positive correlation between decreased oxygen affinity and carboxyhemoglobin confirmed the decreased oxygen affinity of sickle hemoglobin and decreased oxygen affinity and increased diphosphoglycerate in red cells. Hill plots are less sensitive discriminators of oxygen affinity than traditional sigmoid dissociation curves and offer no particular advantage. Serial studies in a subset of three sickle cell anemia patients treated conservatively suggest automated oxyhemoglobin dissociation curves may be useful in assessment of effectiveness of newer therapies of sickle cell anemia after refinement of the method and studies of larger populations.

Adult↗
PubMed1999

Brain computed tomography in geriatric manic disorder.

BACKGROUND: Excess brain changes in geriatric manic patients have been hypothesized. Few neuroimaging studies are available. METHODS: Brain computed tomography scans in geriatric patients with manic disorder (n = 30) were compared to those in same-age control subjects (n = 18). Ratings of cortical sulcal widening (CSW), lateral ventricle-brain ratio (VBR), and related linear measures were determined. RESULTS: Patients had greater CSW scores (Exact p = .002) and VBR (t = 2.51, df = 46, p < .02) compared to control subjects. CSW was positively associated with age at illness onset (rs = .46, p < .01) and age at first manic episode (rs = .53, p < .005). VBR was poorly correlated with CSW and was not associated with these indices of illness course. CONCLUSIONS: These findings support the need for further investigation of relationships between brain structure and clinical features in geriatric mania.

Aged↗
PubMed1999

Three-dimensional structure of the smooth muscle in the term-pregnant human uterus.

OBJECTIVE: To identify the structural elements and describe the three-dimensional microanatomy of the term-pregnant human uterus. METHODS: Biopsy specimens were taken from the funduses and the lower uterine segments of two term-pregnant uteri. Tissue was sectioned serially and stained with Masson trichrome. Microscope images were captured with a digital camera, aligned, and computer-processed. Computer-assisted three-dimensional reconstruction of structures was performed. RESULTS: Five structures were identified: 1) fasciculus-the macroscopic organization of myocytes and connective tissue, 2) cylindric bundle-300+/-100-microm diameter cylinder of densely packed myocytes, 3) sheet-like bundle-densely packed sheet of myocytes, 4) fiber bundle-a loosely packed bundle of small numbers of myocytes, and 5) communicating bridge-a large cylindric bundle that bridges adjacent fasciculi. The cylindric bundles merged, dichotomized, and intertwined with each other and with sheet-like bundles. Essentially all myocytes except those in fiber bundles were contiguous. CONCLUSION: The microanatomy of the term-pregnant human uterus contains clearly defined structural elements. These structures merge with each other and potentially form an interlacing network, connecting the vast majority of the myocytes of the uterus in a contiguous pathway.

Female↗
PubMed1999

Calcium-calmodulin mediates bradykinin-induced MAPK phosphorylation and c-fos induction in vascular cells.

The vasoactive peptide bradykinin (BK) has been implicated in the pathophysiology of a number of vascular wall abnormalities, but the cellular mechanisms by which BK generates second messengers that alter vascular function are as yet undefined. Exposure of vascular smooth muscle cells (VSMC) to BK (10(-7) M) produced a rapid and transient rise in intracellular calcium, which preceded an increase in tyrosine phosphorylation of mitogen-activated protein kinase (MAPK). MAPK activation by BK was observed as early as 1 min, peaked at 5 min, and returned to baseline by 20 min. Treatment of cells with the intracellular calcium chelator EGTA-acetoxymethyl ester inhibited BK-stimulated MAPK activation, suggesting that intracellular calcium mobilization contributes to the activation of MAPK. The calmodulin inhibitor W-7 also markedly inhibited BK-induced MAPK phosphorylation in the cytoplasm as well as in the nucleus. Moreover, the BK-induced increase in c-fos mRNA levels was significantly inhibited by the calmodulin inhibitor, indicating that calmodulin is required for BK signaling leading to c-fos induction. These results implicate the calcium-calmodulin pathway in the mechanisms for regulating MAPK activity and the resultant c-fos expression induced by BK in VSMC.

Animals↗
PubMed1999

On and off the playing field: ethics in medicine.

The sportscasters' metaphor, "on and off the playing field," is used to describe the altruistic demeanor of good ethical and moral behavior and empathy toward patients that is required of medical students and physicians. It has been noted that these altruistic qualities often compete unsuccessfully with scientific skills and scholarly pursuits. Many schools hold the "White Coat Ceremony" annually and host a chapter of the Honor Medical Society to instill these traits in students. Teaching of altruistic demeanor is most successful using a combination of techniques, which include philosophy, virtue theory, small-group discussions using case vignettes, and the structured objective clinical examination with "standardized patients." On the playing field, current major issues are intellectual honesty, mandatory testing/treatment for HIV/AIDS, abortion, end-of-life issues, and gene therapy. Off the playing field, family, religion, community service, and leadership will immortalize medical students in the mythical Health Care Hall of Fame.

Altruism↗