The Q-tip test correlation with urethroscopic findings in urinary stress incontinence.
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Adult↗
Biomedical subjects
R L Young
Publications and source records attributed to R L Young.
Evolution of sex-biased maternal effects in birds: I. Sex-specific resource allocation among simultaneously growing oocytes.
Females in species that produce broods of multiple offspring need to partition resources among simultaneously growing ova, embryos or neonates. In birds, the duration of growth of a single egg exceeds the ovulation interval, and when maternal resources are limited, a temporal overlap among several developing follicles in the ovary might result in a trade-off of resources among them. We studied growth of oocytes in relation to their future ovulation order, sex, and overlap with other oocytes in a population of house finches (Carpodacus mexicanus) where strongly sex-biased maternal effects are favoured by natural selection. We found pronounced differences in growth patterns between oocytes that produced males and females. Male oocytes grew up to five times faster and reached their ovulation size earlier than female oocytes. Early onset and early termination of male oocytes' growth in relation to their ovulation resulted in their lesser temporal overlap with other growing ova compared with female oocytes. Consequently, ovulation mass of female but not male oocytes was strongly negatively affected by temporal overlap with other oocytes. In turn, mass of male oocytes was mostly affected by the order of ovulation and by maternal incubation strategy. These results provide a mechanism for sex-biased allocation of maternal resources during egg formation and provide insights into the timing of the sex-determining meiotic division in relation to ovulation in this species.
Animals↗
Complexity and integration in sexual ornamentation: an example with carotenoid and melanin plumage pigmentation.
Sexual ornaments often consist of several components produced by distinct developmental processes. The complexity of sexual ornaments might be favoured by mate choice of individual components in different environments which ultimately results in weak interrelationships (integration) among the developmental processes that produce these components. At the same time, sexual selection for greater exaggeration of individual components favours their stronger co-dependence on organismal resources. This should ultimately produce stronger condition-mediated integration among ornaments' components in individuals with the most exaggerated ornamentation. Here we distinguish between these two sources of integration by examining the relationship between integration and elaboration of sexual ornamentation in three bird species: two with carotenoid-based sexual ornamentation (the house finch, Carpodacus mexicanus and common redpoll, Carduelis flammea) and a species with melanin-based sexual ornamentation (house sparrow, Passer domesticus). We found that integration of components varied with elaboration of carotenoid-based ornamentation but not of melanin ornamentation. In the house finches, integration was the highest in individuals with small ornaments and decreased with ornament elaboration whereas the pattern was the opposite in common redpolls. These results suggest that in these species integration and complexity of carotenoid-based ornamental components are due to shared condition-dependence of distinct developmental pathways, whereas integration and complexity of the melanin ornamentation is due to organismal integration of developmental pathways and is largely condition- and environment-invariant. Thus, functionally, ornamentation of the house sparrows can be considered a single trait, whereas complexity of the house finch and redpoll ornamentation varies with ornament elaboration and individual condition.
Animals↗
Successful vaccine immunotherapy. An exciting novel approach to cancer treatment.
Global cancer spread to pandemic proportions, has reinforced the importance of disease surveillance and prevention programs, and has provided the stimulus for greater resources in vaccine development. Many reports from phase I or II trials indicate that both partial and complete responses have been observed, with little or no toxicity, in a small proportion of vaccine recipients. Future prospects will be to increase basic knowledge of immunogenic tumor antigens to vaccine administration, which will make the cancer patient develop an immune response able to induce tumor regression. Clinical trials already under way in patients with malignant diseases may yield more definitive conclusions.
Cancer Vaccines↗
Left ventricular aneurysm repair in rats: structural, functional, and molecular consequences.
OBJECTIVES: This study examined the effects of aneurysm repair in a rat model of myocardial infarction on functional indices and on the spatiotemporal distribution of cardiac contractile protein and natriuretic peptide messenger RNA. METHODS: In a rat infarct model, expanded left ventricular aneurysms were plicated 4 weeks after infarction. At 30 weeks, transverse heart sections were taken at 4 levels (apex [level 1] through base [level 4]) and assessed by in situ hybridization histochemistry to determine regional messenger RNA levels of pre-pro-atrial natriuretic peptide, cardiac alpha-actin, skeletal alpha-actin, myosin light chain-2v, and beta-myosin heavy chain. RESULTS: Rats with plicated left ventricular aneurysms had reduced left ventricular endocardial circumference (19%, P <.005), lower heart weight ratio (31%, P <.05), left ventricular end-diastolic pressures (51%, P <.05), and increased +/-dP/dt (34%-38%, P <.05). Cardiac messenger RNA levels of pre-pro-atrial natriuretic peptide were reduced in the septum (levels 2 and 3), and skeletal alpha-actin levels were reduced in the septum and left ventricular free wall of plicated rats (level 3). beta-Myosin heavy chain levels were markedly reduced in peri-infarct regions of the left ventricular free wall, septum, and right ventricle in plicated rats at level 4, whereas myosin light chain-2v levels were reduced at levels 2 and 4 in the left ventricular free wall and at level 4 in the right ventricle. CONCLUSIONS: Plication of left ventricular aneurysm after infarction in the rat significantly reduced cardiac hypertrophy, improved cardiac function, and reduced the upregulation of pre-pro-atrial natriuretic peptide and both fetal and adult contractile protein isoforms associated with cardiac hypertrophy.
Actins↗
GABA(B) receptors on vagal afferent pathways: peripheral and central inhibition.
To investigate GABA(B) receptors along vagal afferent pathways, we recorded from vagal afferents, medullary neurons, and vagal efferents in ferrets. Baclofen (7-14 micromol/kg i.v.) reduced gastric tension receptor and nucleus tractus solitarii neuronal responses to gastric distension but not gastroduodenal mucosal receptor responses to cholecystokinin (CCK). GABA(B) antagonists CGP-35348 or CGP-62349 reversed effects of baclofen. Vagal efferents showed excitatory and inhibitory responses to distension and CCK. Baclofen (3 nmol i.c.v. or 7-14 micromol/kg i.v.) reduced both distension response types but reduced only inhibitory responses to CCK. CGP-35348 (100 nmol i.c.v. or 100 micromol/kg i.v.) reversed baclofen's effect on distension responses, but inhibitory responses to CCK remained attenuated. They were, however, reversed by CGP-62349 (0.4 nmol i.c.v.). In conclusion, GABA(B) receptors inhibit mechanosensitivity, not chemosensitivity, of vagal afferents peripherally. Mechanosensory input to brain stem neurons is also reduced centrally by GABA(B) receptors, but excitatory chemosensory input is unaffected. Inhibitory mechano- and chemosensory inputs to brain stem neurons (via inhibitory interneurons) are both reduced, but the pathway taken by chemosensory input involves GABA(B) receptors that are insensitive to CGP-35348.
Afferent Pathways↗
GABA(B)R expressed on vagal afferent neurones inhibit gastric mechanosensitivity in ferret proximal stomach.
GABA(B)-receptor (GABA(B)R) agonists reduce transient lower esophageal sphincter relaxation (TLESR) and reflux episodes through an action on vagal pathways. In this study, we determined whether GABA(B)R are expressed on vagal afferent neurones and whether they modulate distension-evoked discharge of vagal afferents in the isolated stomach. Vagal mehanoreceptor activity was recorded following distensions of the isolated ferret proximal stomach before and after perfusion with the GABA(B)R-selective agonists baclofen and 3-aminopropylphosphinic acid (3-APPiA). Retrograde labeling and immunohistochemistry were used to identify GABA(B)R located on vagal afferent neurones in the nodose ganglia. Vagal afferent fibers responded to isovolumetric gastric distension with an increase in discharge. The GABA(B)-receptor agonists baclofen (5 x 10(-5) M) and 3-APPiA (10(-6) to 10(-5) M) but not muscimol (GABA(A)-selective agonist: 1.3 x 10(-5) M) significantly decreased afferent distension-response curves. The effect of baclofen (5 x 10(-5) M) was reversed by the GABA(B)-receptor antagonist CGP 62349 (10(-5) M). Over 93% of retrogradely labeled gastric vagal afferents in the nodose ganglia expressed immunoreactivity for the GABA(B)R. GABA(B)R expressed on vagal afferent fibers directly inhibit gastric mechanosensory activity. This is likely a contributing mechanism to the efficacy of GABA(B)-receptor agonists in reducing TLESR and reflux episodes in vivo.
Animals↗
Peritoneal adhesions: etiology, pathophysiology, and clinical significance. Recent advances in prevention and management.
AIM: To summarize the most common etiologic factors and describe the pathophysiology in the formation of peritoneal adhesions, to outline their clinical significance and consequences, and to evaluate the pharmacologic, mechanical, and surgical adjuvant strategies to minimize peritoneal adhesion formation. METHODS: We performed an extensive MEDLINE search of the internationally published English literature of all medical and epidemiological journal articles, textbooks, scientific reports, and scientific journals from 1940 to 1997. We also reviewed reference lists in all the articles retrieved in the search as well as those of major texts regarding intraperitoneal postsurgical adhesion formation. All sources identified were reviewed with particular attention to risk factors, pathophysiology, clinical manifestations, various methods, and innovative techniques for effectively and safely reducing the formation of postsurgical adhesions. RESULTS: The formation of postoperative peritoneal adhesions is an important complication following gynecological and general abdominal surgery, leading to clinical and significant economical consequences. Adhesion occur in more than 90% of the patients following major abdominal surgery and in 55-100% of the women undergoing pelvic surgery. Small-bowel obstruction, infertility, chronic abdominal and pelvic pain, and difficult reoperative surgery are the most common consequences of peritoneal adhesions. Despite elaborate efforts to develop effective strategies to reduce or prevent adhesions, their formation remains a frequent occurrence after abdominal surgery. CONCLUSIONS: Until additional information and findings from future clinical investigations exist, only a meticulous surgical technique can be advocated in order to reduce unnecessary morbidity and mortality rates from these untoward effects of surgery.
Abdomen↗
Previous cesarean section. A contraindication to vaginal hysterectomy?
OBJECTIVE: To compare surgical outcomes of vaginal hysterectomy between women who have had one or more cesarean deliveries and those who have not. STUDY DESIGN: A retrospective, chart review study was performed on women undergoing vaginal hysterectomy during a four-year period. Of 275 women who met the study criteria, 104 had a history of previous cesarean deliveries, and 171 did not. The groups were compared for indications for surgery, operative time, length of hospitalization and surgical complications. RESULTS: Previous cesarean delivery did not affect hemoglobin loss, hospital stay or operative time among women undergoing vaginal hysterectomy. The complication rate (either operative or postoperative) was 12.3% among women without a history of cesarean section, 6.8% among those with one, 3.7% among those with two and 11.1% among those with three or more (chi 2 = 2.8, P = .4). The odds for surgical complications were not significantly different between women with one or more prior cesarean deliveries as compared to those without after adjustment for possible confounders. CONCLUSION: Surgical complications with vaginal hysterectomy do not appear to be higher among women with a prior cesarean section as compared to those without a history of such operation.
Adult↗
Effects of low-dose monophasic levonorgestrel with ethinyl estradiol preparation on serum lipid levels: A twenty-four month clinical trial.
OBJECTIVE: The aim of this 24-cycle study was to evaluate the effects on serum lipid concentrations of an oral contraceptive preparation containing 100 microg levonorgestrel and 20 microg ethinyl estradiol. STUDY DESIGN: Forty-two healthy women were enrolled in a study designed to evaluate the effects on serum lipid concentrations of an oral contraceptive containing 100 microg levonorgestrel and 20 microg ethinyl estradiol. Lipid data were evaluated for 28 women who completed 24 cycles of treatment with a preparation of 100 microg levonorgestrel with 20 microg ethinyl estradiol for 21 days followed by placebo for 7 days. Concentrations of triglycerides, total cholesterol, high-density lipoprotein cholesterol, high-density lipoprotein cholesterol subfractions 2 and 3, low-density lipoprotein cholesterol, and apolipoproteins A-I and B were analyzed. Mean percentage changes from baseline were tested for significance by means of paired Student t tests. RESULTS: Total cholesterol, high-density lipoprotein cholesterol, high-density lipoprotein subfraction 2, and apolipoprotein A-I concentrations were not significantly changed from baseline. Neither was the ratio of high-density lipoprotein subfraction 2 to high-density lipoprotein subfraction 3. Mean percentage increases in concentrations of triglyceride, high-density lipoprotein subfraction 3, apolipoprotein B, and low-density lipoprotein cholesterol and increases in the ratios of total cholesterol to high-density lipoprotein cholesterol, low-density lipoprotein cholesterol to high-density lipoprotein cholesterol, and apolipoprotein B to apolipoprotein A-I were significant (P <.05) at >/=1 cycle. By cycle 24, however, only the concentration of high-density lipoprotein subfraction 3 remained significantly elevated. CONCLUSION: Changes in the plasma lipid profiles among women receiving monophasic 100 microg levonorgestrel with 20 microg ethinyl estradiol were similar to those seen with other low-dose oral contraceptives, but by cycle 24 only 1 of 7 mean values remained significantly different from baseline.
Adult↗
Toxic megacolon associated with Campylobacter jejuni colitis.
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Campylobacter Infections↗
Timing of subsequent pregnancy following treatment of molar pregnancy.
OBJECTIVE: To assess the practice habits and recommendations of members of American Society of Gynecologic Oncologists (ASGO) dealing with follow-up management of molar pregnancy. MATERIALS AND METHODS: A questionnaire was mailed to ASGO members requesting their recommended waiting period for subsequent pregnancy following treatment of molar pregnancy. Year of Fellowship completion was determined for each respondent. RESULTS: Only 36.8% still recommended the traditionally accepted 12-month waiting period, and 31.3% recommended 6 months. The trend was toward shorter waiting periods among younger, more recently trained oncologists, although differences were not statistically significant. CONCLUSION: It appears time to review the recommendation of a 12-month waiting period. A reduction of at least down to 6 months may be appropriate, but needs further investigation.
Female↗
The Ig heavy chain 3' end confers a posttranscriptional processing advantage to Bcl-2-IgH fusion RNA in t(14;18) lymphoma.
The chromosomal translocation t(14;18) in lymphoma leads to an overproduction of the Bcl-2 protein on the basis of increased Bcl-2 mRNA levels. Whereas the juxtaposition of Bcl-2 with the Ig heavy chain locus causes a transcriptional activation, 70% of the lymphomas also produce Bcl-2-Ig fusion RNAs with Ig 3' ends. Using S1 nuclease protection assays that can discriminate between nuclear RNA precursors and spliced mRNA, we found that the fusion RNAs in t(14;18) cell lines exhibit an additional posttranscriptional processing advantage. Transfection experiments with artificial genes containing various Bcl-2 or Ig 3' ends show that this effect is (1) related to RNA splicing and/or nucleocytoplasmic transport; (2) independent of transcriptional activation by the heavy chain enhancer; (3) dependent on the presence of the JH-CH and C-gamma1 Ig introns; and (4) tissue specific for B cells. This constitutes a novel mechanism of oncogene deregulation unrelated to transcriptional activation or half-life prolongation. The data further support the existence of a tissue-specific posttranscriptional pathway of Ig regulation in B cells.
Actins↗
Altered cardiac hormone and contractile protein messenger RNA levels following left ventricular myocardial infarction in the rat: an in situ hybridization histochemical study.
OBJECTIVES: Cardiac remodeling secondary to myocardial infarction is associated with hypertrophy of surviving myocardium and altered cardiac gene expression. The present study examined the spatiotemporal expression of cardiac contractile protein and peptide hormone mRNA following left ventricular myocardial infarction (LVMI) in the rat heart. METHODS: LVMI was produced in Wistar rats by ligation of the left anterior descending coronary artery and mRNA levels of cardiac alpha-action (sACT), ventricular myosin light chain-2(MLC-2v), beta-myosin heavy chain (beta-MHC) and pre-proatrial natriuretic peptide (ppANP) were examined at 24 h, 1 and 4 weeks) post-LVMI by in situ hybridization histochemistry with 35S-labeled oligonucleotide probes. RESULTS: Infarct size, determined at 1 week post-LVMI, was 44.5 +/- 2.7% of the combined left ventricular epi- and endocardial surface area. Myocyte fiber width, reflecting cellular hypertrophy, was increased in left ventricular, mid-septal and mid-right ventricular muscle fibers by 11-20% at 1 week post-LVMI (P < 0.05) and by 24-29% at 4 weeks (P < 0.05). At 24 h, 1 and 4 weeks post-LVMI, heart- and lung/body weight ratios were significantly elevated compared to sham-operated rats (1.3-1.8-fold, P < 0.01 and 1.6-2.9-fold, P < 0.005, respectively). PpANP mRNA levels in the left ventricle were increased 3.8- and 3.3-fold at 1 and 4 weeks (P < 0.05), with highest levels in the epicardium, papillary muscle, infundibulum and apex of the chamber. Septal and right ventricular ppANP mRNA levels were highest at 24 h post-LVMI (2.1- and 2.6-fold increase, P < 0.05) and remained elevated at 4 weeks, with maximum levels at the left endocardial surface of the septum and apex of the chambers. Atrial levels of cACT mRNA were increased 1.9-fold at 1 week post-LVMI (P < 0.05) and remained elevated at 4 weeks. Skeletal ACT mRNA, not normally expressed in the adult rat heart, was induced as early as 24 h post-LVMI in both atria, the septum and right ventricle, with discrete hybridization signal detected at the apex of the chambers and in the right ventricular free-wall, and later (1 week) in the left ventricular epicardium. MLC-2v mRNA levels were unaltered post-LVMI, except for a transitory loss of expression at 24 h in the left atria, ventricle and apical septum. In contrast, ventricular beta-MHC mRNA was markedly induced in regions containing increased ppANP mRNA, with a maximal 3.0- and 4.0-fold induction (P < 0.05) seen at 1 and 4 weeks in the left ventricle and a 3.7-fold induction at 4 weeks in the septum and right ventricle (P < 0.05). CONCLUSION: The regional increases in induced cardiac hormone and contractile protein mRNA in similar subchamber regions of the rat heart post-LVMI implies mutual activation by mechanical and/or neuroendocrine stimuli in the transcriptional response to myocardial overload.
Actins↗
Practical clinical considerations in the use of estrogen/androgen therapy. A case-based forum.
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Adult↗
Physiologic estradiol replacement therapy and cardiac structure and function in normal postmenopausal women: a randomized, double-blind, placebo-controlled, crossover trial.
OBJECTIVE: To assess the effect of estradiol (E2) replacement therapy on cardiac structure and function in healthy postmenopausal women. METHODS: We conducted a randomized, double-blind, placebo-controlled, crossover study of 31 healthy postmenopausal female volunteer study subjects (55-65 years) using 12 weeks of micronized E2 replacement therapy (2 mg/day). Echocardiography and Doppler techniques were used to assess the cardiac effects of E2 at rest and during graded bicycle ergometry. RESULTS: Crossover analysis demonstrated no carryover effects of estrogen treatment (which increased serum E2 15-fold to 37.6 pmol/L) on the cardiac characteristics measured. Estradiol treatment did not affect measurements of systolic function, diastolic function, left ventricular mass, or pulmonary artery pressure at rest or during bicycle ergometry. Left ventricular end-diastolic volume at rest was slightly higher with E2 treatment (P = .03). However, this change was not reflected by changes in stroke volume, ejection fraction, or cardiac output. CONCLUSIONS: Estrogen replacement therapy, which results in physiologic serum concentrations, does not affect cardiac structure or function in normal postmenopausal women after 12 weeks of treatment.
Aged↗
In normal postmenopausal women physiologic estrogen replacement therapy fails to improve exercise tolerance: a randomized, double-blind, placebo-controlled, crossover trial.
OBJECTIVE: Our purpose was to test whether estrogen replacement therapy could increase exercise tolerance in postmenopausal women. STUDY DESIGN: A randomized, double-blind, placebo-controlled, crossover study in 31 healthy postmenopausal women who received 12 weeks of physiologic estrogen replacement therapy (micronized estradiol, 2 mg/day) and were evaluated with modified Balke exercise treadmill tests. RESULTS: Serum estradiol levels increased significantly during replacement therapy in this cohort of female volunteers with a mean age of 59 years, and resting heart rate was lower in women receiving estrogen replacement (p < 0.05). However, neither the heart rate nor the blood pressure responses to exercise was different, nor was the total exercise time, rate of oxygen uptake, or maximal oxygen uptake increased after estradiol treatment. Similarly, ventilatory parameters were unaffected by estradiol. The slope of the respiratory exchange ratio was slightly but significantly different (p < 0.05) while volunteers received estrogen replacement therapy. CONCLUSION: Estrogen replacement therapy, which achieves serum estradiol concentrations in the physiologic range for 12 weeks, fails to increase exercise tolerance or improve cardiovascular response to exercise in postmenopausal women.
Cross-Over Studies↗
The conserved box 1 motif of cytokine receptors is required for association with JAK kinases.
The JAK2 tyrosine kinase is known to associate with the receptors for growth hormone (GH) and erythropoietin (EPO) and with the interleukin-6 receptor signal transducing protein, gp130. Here we demonstrate that chimeric cytokine receptors which contain the cytoplasmic domain of the receptors for GH and EPO or for gp130 can form complexes with JAK2 when transiently co-expressed in HeLa cells. Mutational analyses of chimeras for the the GH and EPO receptors and gp130 demonstrated that box 1, a motif critical for cytokine receptor signal transduction, was required for the association of JAK2. Although JAK2 was capable of associating with all three of the chimeras, JAK1 co-precipitated only with the gp130 chimera. Association of JAK1 and JAK2 with cytokine receptor proteins, therefore, requires the highly conserved box 1 domain, but other sequences within the receptor proteins may influence the specificity of JAK binding. Mutational analysis of JAK2 revealed that multiple or complex protein sequences within JAK2 are required for association with cytokine receptors.
Animals↗