Biomedical subjects

C M Wilson

Publications and source records attributed to C M Wilson.

At least 37 records · Page 2Linked to original sources

PubMed2000

Marijuana use among HIV-positive and high-risk adolescents: a comparison of self-report through audio computer-assisted self-administered interviewing and urinalysis.

The validity of self-report of drug use has been found to vary widely. Moreover, previous research has focused on samples of adults. In 1996-1998, human immunodeficiency virus (HIV)-infected adolescents and high-risk, noninfected adolescents (n = 182) were recruited at 16 locations in 13 US cities into the Reaching for Excellence in Adolescent Care and Health (REACH) project, to the authors' knowledge, the first national study of disease progression among HIV-positive adolescents who were infected through sexual behavior or injection drug use. Self-report of marijuana use was assessed through audio computer-assisted self-administered interviewing (ACASI). Urines were tested for marijuana at a certified laboratory by using the enzyme-multiplied immunoassay technique. Conditional kappas for 2-, 5-, and 7-day self-reports were 0.57, 0.71, and 0.69, respectively. Maximum sensitivity was obtained from a combination of ACASI and urine drug testing. Contrary to previous studies, the data suggest that if a single evaluative instrument is to be used for prevalence, ACASI is more sensitive than urine drug testing for marijuana overall, but particularly for HIV-infected adolescents.

Adolescent↗

PubMed2000

Pivotal role of calnexin and mannose trimming in regulating the endoplasmic reticulum-associated degradation of major histocompatibility complex class I heavy chain.

We have established a mammalian semipermeabilized cell system that faithfully reconstitutes the proteasome-mediated degradation of major histocompatibility complex Class I heavy chain. We show that degradation required unfolding of the protein and was cytosol- and ATP-dependent and that dislocation and degradation required proteasome activity. When the interaction of heavy chain with calnexin was prevented, the rate of degradation was accelerated, suggesting that an interaction with calnexin stabilized heavy chain. Stabilization of heavy chain to degradation was also achieved either by preventing mannose trimming or by removal of the N-linked glycosylation site. This demonstrates that glycosylation and mannose trimming are required to ensure degradation of heavy chain. When degradation or mannose trimming was inhibited, heavy chain formed a prolonged interaction with immunoglobulin heavy chain binding protein, ERp57, and protein disulfide isomerase. Taken together, these results indicate that calnexin association and mannose trimming provide a mechanism to regulate the folding, assembly, and degradation of glycoproteins entering the secretory pathway.

Amino Acid Substitution↗

PubMed2000

Relationship of CD4+ T cell counts and HIV type 1 viral loads in untreated, infected adolescents. Adolescent Medicine HIV/AIDS Research Network.

The REACH Project (Reaching for Excellence in Adolescent Care and Health) of the Adolescent Medicine HIV/AIDS Research Network was designed as a study of an adolescent cohort composed of HIV-1-infected and -uninfected subjects. The goal of the analysis presented was to examine the relationship of CD4+ T cell counts and HIV-1 plasma viral loads in adolescents. The CD4+ T cell counts of 84 HIV+ subjects who were 13 to 19 years of age were measured at the clinical sites, using ACTG standardized techniques. HIV-1 viral loads in frozen plasma were determined by the NASBA/NucliSens assay at a central laboratory. Past and current treatment with antiretroviral drugs was determined by medical record abstraction and interview data. The slope of the line generated by regressing log10 HIV-1 RNA (copies/ml) versus CD4+ T cell counts of REACH subjects who are antiretroviral drug naive was negative and significantly different than zero. A negative association has also been reported for antiretroviral drug-naive, adult males in the Pittsburgh Men's Study, a component of MACS (Pitt-MACS) (Mellors J, et al.: Science 1996;272:1167). These data show that in adolescents, as in adults, HIV-1 RNA concentrations are correlated with corresponding absolute CD4+ T cell count. The slopes of the lines generated with data from each cohort were different (p = 0.003). In addition to age, there are sex and racial differences in the makeup of the two cohorts. Any or all of these differences may affect the slopes of the lines.

Adolescent↗

PubMed2000

Prevalence of and risks for cervical human papillomavirus infection and squamous intraepithelial lesions in adolescent girls: impact of infection with human immunodeficiency virus.

CONTEXT: Data suggest that in adults, human papillomavirus (HPV) infections and their sequalae, squamous intraepithelial lesions (SILs), occur more commonly among human immunodeficiency (HIV)-infected women because of the HIV-associated CD4+ T-cell immunosuppression. Since adolescents are more likely to be early in the course of HIV and HPV infections, the study of both infections in this age group may help elucidate their initial relationship. OBJECTIVE: To examine the prevalence of and risks for cervical HPV infection and SILs by HIV status in a population of adolescent girls. PARTICIPANTS: Subjects recruited at each of the 16 different US sites participating in a national study of HIV infection in adolescents. MAIN OUTCOME MEASURES: Cervical HPV DNA findings using polymerase chain reaction detection techniques and Papanicolaou smear from baseline visits. Infection with HPV was categorized into low- (rarely associated with cancer) and high- (commonly associated with cancers) risk types. RESULTS: Of 133 HIV-infected girls, 103 (77.4%) compared with 30 (54.5%) of 55 noninfected girls were positive for HPV (relative risk [RR], 1.4; 95% confidence interval [CI], 1.1-1.8). The risk was for high-risk (RR, 1.8; 95% CI, 1.2-2.7) but not low-risk (RR, 1.2; 95% Cl, 0.4-3.9) HPV types. Among the girls with HPV infection, 21 (70.0%) of the non-HIV-infected girls had normal cytologic findings compared with only 29 (29.9%) of the HIV-infected girls (P<.001). Multivariate analysis showed that HIV status was a significant risk for HPV infection (odds ratio [OR], 3.3; 95% CI, 1.6-6.7) and SIL (OR, 4.7; 95% CI, 1.8-14.8), but CD4 cell count and viral load were not associated with infection or squamous intraepithelial lesions. Only 9 girls had a CD4+ T-cell count of less than 0.2 cell X 10(9)/L. CONCLUSIONS: High prevalence of HPV infection in both groups underscores the risky sexual behavior in this adolescent cohort. Rates of HPV infection and SILs were higher among HIV-infected girls, despite similar sexual risk behaviors and the relatively healthy state of our HIV-infected group. Infection with HIV may enhance HPV proliferation through mechanisms other than CD4 immunosuppression, particularly early in the course of HIV infection.

Adolescent↗

PubMed2000

The prevalence of anergy in human immunodeficiency virus-infected adolescents and the association of delayed-type hypersensitivity with subject characteristics.

PURPOSE: To examine the prevalence of anergy in HIV-infected adolescents and factors associated with its occurrence. METHODS: Anergy was defined as less than 2mm induration to each of three intradermally applied antigens (Candida albicans, tetanus toxoid, and mumps) between 24 and 96 hours in a population of HIV-infected adolescents aged 12-18 at entry in a national multicenter study of HIV disease progression. CD4(+) T-cell counts and plasma HIV-1 RNA were measured in quality controlled laboratories. Factors associated with the probability of anergy were examined with contingency table comparisons, tree-structured classification, and logistic regression analyses. RESULTS: Overall prevalence of anergy in this clinic-based population of 167 was 11% [7% in males and 12% in females (p = 0.57)]. The sole significant predictor of anergy was decreased CD4(+) T-cell count (p = 0.005). CONCLUSION: The prevalence of anergy is low in this HIV-infected population compared to older infected cohorts. The occurrence of differential rates of anergy in particular age and sex groupings that may be related to intrinsic immunologic differences requires further study.

Adolescent↗

PubMed2000

Does pretreatment with progestogen or oral contraceptive pills in low responders followed by the GnRHa flare protocol improve the outcome of IVF-ET?

PURPOSE: Women undergoing in vitro fertilization with low ovarian reserve and poor response to controlled ovarian hyperstimulation (COH) present a management dilemma. In a retrospective observational study, we compared the pretreatment use of the gestogen medroxyprogesterone acetate (10 mg twice daily from day 15 of the cycle for a minimum of 2 weeks) with an oral contraceptive pill (one tablet daily from day 4 of the cycle for a minimum of 3 weeks). METHODS: The criteria for inclusion in the study included one or more of the following: abandoned cycles due to poor response, fewer than four oocytes retrieved following a standard COH protocol, age > 39 years, and elevated basal serum follicle-stimulating hormone (FSH). Thirty-eight women received pretreatment with gestogen, and a similar number of women received pretreatment with the pill. The flare protocol was used in all treatment cycles combined with an individualized dose of human menopausal gonadotropin (hMG) (4-8 ampoules/day of 75 units FSH/ampoule) depending on previous response, age, and early follicular serum FSH level. Both groups were similar in mean age, duration of infertility, early follicular FSH levels, and the distribution of various aetiologies. RESULTS: Twenty-nine cycles were abandoned before oocyte retrieval, 15 (39.5%) in the pill group and 14 (36.8%) in the gestogen group, because of an inadequate ovarian response. The mean (+/- SD) number of ampoules (75 IU FSH/ampoule) of hMG used per cycle was similar in the pill and gestogen groups (59.7 +/- 19.3 vs. 70.2 +/- 29.4, respectively). There also was no difference seen in the numbers of oocytes retrieved (4.4 +/- 2.3 vs. 4.2 +/- 2.5), total number of embryos (2.5 +/- 2.4 vs. 2.2 +/- 1.1), or the number of embryos transferred (1.8 +/- 1.2 vs. 2.1 +/- 1.0) in the pill and gestogen groups, respectively. One pregnancy in each group resulted following embryo transfer in 22 women in the pill group and in 24 women in the gestogen group. CONCLUSIONS: We conclude that pre-IVF treatment with oral contraceptive pill or gestogen combined with the flare protocol in women at high risk of or with a history of poor ovarian response, as defined in this study, did not appear to result in an improvement in outcome of IVF-embryo transfer.

Adult↗

PubMed2000

Increased left ventricular mass is not associated with impaired left ventricular diastolic filling in normal individuals.

BACKGROUND: Hypertensive left ventricular (LV) hypertrophy has been associated with diastolic dysfunction. However, the underlying physiological relationship between LV size and diastolic function remains to be clarified. The aim of this study was to evaluate the relationship between several measures of diastolic filling and LV mass in a population sample. METHODS: We used M-mode and Doppler echocardiography to compare left ventricular mass index (LVMI) and wall thickness with five measures of ventricular diastolic filling (ratio of the peak early mitral inflow velocity to the peak atrial mitral inflow velocity, deceleration time of early mitral inflow, isovolumetric relaxation time, ratio of the peak pulmonary venous systolic to diastolic flow and difference between the durations of the pulmonary venous and mitral inflow atrial waves) in 159 healthy volunteers. RESULTS: LVMI was significantly (P< 0.0001) greater in men (81.3 g/m2, interquartile range: 67-94) than women (59.7 g/m2, interquartile range: 49-74), but no gender differences were observed in diastolic filling. Higher age, blood pressure and heart rate showed significant correlation with diminished diastolic filling. However, no measure of diastolic filling correlated with LVMI or wall thickness in either univariate or multiple regression analyses that adjusted for relevant covariates. CONCLUSIONS: LVMI does not explain physiological differences in diastolic filling. The significant decline in diastolic filling with age reflects changes in the quality rather than the quantity of myocardial tissue.

Adult↗

PubMed2000

Seroprevalence and risk factors of hepatitis B, hepatitis C, and human cytomegalovirus among HIV-infected and high-risk uninfected adolescents: findings of the REACH Study. Adolescent Medicine HIV/AIDS Research Network.

BACKGROUND AND OBJECTIVES: In adolescents and young adults, multiple studies have identified sexual activity and behaviors as significant risk factors for acquiring both human cytomegalovirus (HCMV) and hepatitis B virus (HBV). However, there are no reports on the prevalence or risk factors for infection of these viruses and hepatitis C virus (HCV) in an adolescent population with sexually acquired HIV. GOALS: To examine the seroprevalence and risk factors of HBV, HCV, and HCMV infection in a population of HIV-infected male and female adolescents and in an age- and risk behavior-matched HIV-uninfected cohort. STUDY DESIGN: A cross-sectional analysis of HBV, HCV, and HCMV infections in a cohort of HIV-infected and HIV-uninfected adolescents. RESULTS: Adolescent males infected with HIV were more likely to have evidence of HBV and HCMV infection than HIV-uninfected males (23.7% versus 0%, respectively, for HBV, P = 0.008; 79.7% versus 50%, respectively, for HCMV, P = 0.004). HIV-infected females were more likely to have evidence of HCMV infection (78.5% versus 61.4%, P = 0.003) than HIV-uninfected females. No significant difference was found for HBV infection in the two groups of females. The rate of HCV infection (1.6%) was too small to make comparisons between the groups. To determine whether the differences in infection rates for HBV and HCMV could be explained by factors other than HIV status, a variety of possible risk factors were examined using univariate and multivariate analyses. A significant risk factor for HBV and HCMV infections for males was a homosexual or bisexual orientation. For females, a risk factor for HBV infection was having more than 10 lifetime sexual partners; for HCMV infection, HIV infection was the only risk factor. In addition, in the HIV-infected cohort, 15% of females and 36% of males who were seropositive for HBV had evidence of active HBV infection. CONCLUSIONS: These results emphasize the need for continued development of primary and secondary prevention programs and clinical screening and treatment for HBV and HCMV in adolescents.

Adolescent↗

PubMed1999

The adenosine transporter of Toxoplasma gondii. Identification by insertional mutagenesis, cloning, and recombinant expression.

Purine transport into the protozoan parasite Toxoplasma gondii plays an indispensable nutritional function for this pathogen. To facilitate genetic and biochemical characterization of the adenosine transporter of the parasite, T. gondii tachyzoites were transfected with an insertional mutagenesis vector, and clonal mutants were selected for resistance to the cytotoxic adenosine analog adenine arabinoside (Ara-A). Whereas some Ara-A-resistant clones exhibited disruption of the adenosine kinase (AK) locus, others displayed normal AK activity, suggesting that a second locus had been tagged by the insertional mutagenesis plasmid. These Ara-A(r) AK+ mutants displayed reduced adenosine uptake capability, implying a defect in adenosine transport. Sequences flanking the transgene integration point in one mutant were rescued from a genomic library of Ara-A(r) AK+ DNA, and Southern blot analysis revealed that all Ara-A(r) AK+ mutants were disrupted at the same locus. Probes derived from this locus, designated TgAT, were employed to isolate genomic and cDNA clones from wild-type libraries. Conceptual translation of the TgAT cDNA open reading frame predicts a 462 amino acid protein containing 11 transmembrane domains, a primary structure and membrane topology similar to members of the mammalian equilibrative nucleoside transporter family. Expression of TgAT cRNA in Xenopus laevis oocytes increased adenosine uptake capacity in a saturable manner, with an apparent K(m) value of 114 microM. Uptake was inhibited by various nucleosides, nucleoside analogs, hypoxanthine, guanine, and dipyridamole. The combination of genetic and biochemical studies demonstrates that TgAT is the sole functional adenosine transporter in T. gondii and a rational target for therapeutic intervention.

Adenosine↗

PubMed1999

Insertional tagging of at least two loci associated with resistance to adenine arabinoside in Toxoplasma gondii, and cloning of the adenosine kinase locus.

A genetic approach has been exploited to investigate adenylate salvage pathways in the protozoan parasite Toxoplasma gondii, a purine auxotroph. Using a new insertional mutagenesis vector designed to facilitate the rescue of tagged loci even when multiple plasmids integrate as a tandem array, 15 independent clonal lines resistant to the toxic nucleoside analog adenine arabinoside (AraA) were generated. Approximately two-thirds of these clones lack adenosine kinase (AK) activity. Parallel studies identified an expressed sequence tag (EST) exhibiting a small region of weak similarity to human AK, and this locus was tagged in several AK-deficient insertional mutants. Library screening yielded full-length cDNA and genomic clones. The T. gondii AK gene contains five exons spanning a approximately 3 kb locus, and the predicted coding sequence was employed to identify additional AK genes and cDNAs in the GenBank and dbEST databases. A genomic construct lacking essential coding sequence was used to create defined genetic knock-outs at the T. gondii AK locus, and AK activity was restored using a cDNA-derived minigene. Hybridization analysis of DNA from 13 AraA-resistant insertional mutants reveals three distinct classes: (i) AK-mutants tagged at the AK locus; (ii) AK- mutants not tagged at the AK locus, suggesting the possibility that another locus may be involved in regulating AK expression; and (iii) mutants with normal AK activity (potential transport mutants).

Adenosine Kinase↗

PubMed1999

Peripheral blood mononuclear cell markers in antiretroviral therapy-naive HIV-infected and high risk seronegative adolescents. Adolescent Medicine HIV/AIDS Research Network.

OBJECTIVE: To examine potential hematologic and immunologic markers for healthy adolescents and for adolescents infected with HIV. DESIGN: The REACH Project (Reaching for Excellence in Adolescent Care and Health) of the Adolescent Medicine HIV/AIDS Research Network (AMHARN) recruits HIV-infected and high-risk HIV-uninfected adolescents, aged at least 13 but less than 19 years. The study evaluates biomedical and behavioral features of HIV infection as observed while under medical care for HIV infection and adolescent health. METHODS: Blood samples were collected from HIV-infected and HIV-uninfected subjects at 16 clinical sites. Cell phenotypes were determined using standard single, dual or three-color flow cytometry. RESULTS: This report includes data at enrollment for 94 HIV-positive adolescents who had never received antiretroviral therapy (ART) (mean age, 17.4 +/- 1.0 years for males and 16.5 +/- 1.3 years for females) and 149 HIV-negative adolescents (mean age, 16.7 +/- 1.2 years for males and 16.6 +/- 1.2 years for females); this is the antiretroviral therapy-naive subset drawn from 294 HIV-positive and 149 HIV-negative adolescents enrolled in the REACH Cohort. The total leukocyte count was significantly reduced in the HIV-positive females in comparison with the HIV-negative females (P < 0.001). There was a reduction in natural killer cells (P < 0.05) in HIV-positive females (mean, 140.6 +/- 104.2 x 10(6) cells/l) in comparison with HIV-negative females (184.3 +/- 142.5 x 10(6) cells/l), whereas no differences were found between the two groups of males. The reduction in the total CD4 cell count in HIV-positive males and females in comparison with the HIV-negative subjects was the consequence of a decrease in both the naive CD4 and memory CD4 components. There was a striking increase in the mean number of CD8 memory cells in HIV-positive compared with HIV-negative adolescents, and a corresponding increase in the percentage of these cells. In contrast, naive CD8 cells were present in increased numbers but their percentage was decreased. CONCLUSIONS: These studies of adolescents provide normative data for high-risk healthy adolescents as well as baseline immunologic data for a cohort of ART-naive HIV-positive adolescents. This comparison suggests that this untreated, recently infected group had relatively intact immunologic parameters.

Adolescent↗

PubMed1999

Intravenous buscopan for analgesia following laparoscopic sterilisation.

Following reports that tubal smooth muscle spasm may contribute to pelvic pain following laparoscopic sterilisation, we studied the effect of buscopan (an anticholinergic agent used to relieve smooth muscle spasm) on 45 patients undergoing general anaesthesia for day-case laparoscopic sterilisation. Patients were randomly allocated to receive either buscopan 20 mg or saline placebo after induction of anaesthesia. There were no significant differences in pain scores or postoperative analgesic requirements between the two groups. We conclude that intravenous buscopan confers no benefit in day-case laparoscopic sterilisation.

Adult↗

PubMed1999

Discrepancies between echocardiographic measurements of left ventricular mass in a healthy adult population.

Increased left ventricular (LV) mass is associated with increased cardiovascular morbidity and mortality. LV mass is commonly estimated from echocardiography according to the Penn or ASE (American Society of Echocardiography) conventions. No formal statistical test of agreement between these methods has been published. Therefore we compared M-mode echocardiographic LV mass estimates by the Penn and ASE methods in a normal adult population. M-mode echocardiographic tracings were obtained in 169 healthy volunteers and used to calculate LV mass using the Penn and ASE methods. Median values of the estimates were similar [Penn, 126 g (interquartile range 96-170 g); ASE, 129 g (105-164 g); P=0.08] and were highly intercorrelated (r=0.98, P<0.0001). However, the Bland-Altman analysis of agreement revealed significant inconsistencies between Penn and ASE LV mass values. The difference between Penn and ASE values was correlated significantly with heart size (P<0.0001), such that, for small hearts, the Penn LV mass was lower than the ASE LV mass; in contrast, for large hearts, Penn estimates were greater than ASE values. In the upper 5% of the LV mass distribution, the median value for the Penn LV mass index was 132.4 g/m(2), compared with 116.5 g/m(2) for ASE values (2P=0.017). Thus the two most common methods of echocardiographic estimation of LV mass differ significantly at the upper and lower ends of the heart size distribution. These results have important implications for both cardiac research and clinical evaluation.

Adult↗

PubMed1998

Dexamethasone inhibits insulin-stimulated recruitment of GLUT4 to the cell surface in rat skeletal muscle.

To test the hypothesis that glucocorticoids reduce insulin-stimulated skeletal muscle glucose transport by inhibiting the recruitment of GLUT4 glucose transporters to the cell surface, we determined the effect of glucocorticoid treatment on cell-surface GLUT4 using the impermeant glucose transporter photolabel, 2-N-4-(1-azi-2,2,2-trifluoroethyl)benzoyl-[2-3H]1,3-bis-(D-mann os-4-yloxy)-2-propylamine (ATB-[2-3H]BMPA), and GLUT4 immunoprecipitation. Male Sprague-Dawley rats were treated with dexamethasone ([Dex] 0.9 mg/kg for 2 days) and compared against pair-fed controls. 2-[3H]deoxyglucose (2-[3H]DG) uptake in isolated soleus muscles was measured under conditions in which uptake reflects glucose transport activity. In control muscles, 2-[3H]DG uptake was stimulated eightfold by insulin (20 nmol/L). Dex treatment reduced maximal insulin-stimulated 2-[3H]DG uptake by 48% +/- 4% (mean +/- SEM) and decreased cell-surface (ATB-[2-3H]BMPA-photolabeled) GLUT4 by 48% +/- 3%, despite an increase in total muscle GLUT4 content of 26% +/- 7%. These findings indicate that glucocorticoid-induced inhibition of insulin-stimulated glucose transport in muscle is due to impaired recruitment of GLUT4 to the cell surface.

Animals↗

PubMed1998

The REACH Project of the Adolescent Medicine HIV/AIDS Research Network: design, methods, and selected characteristics of participants.

PURPOSE: To describe the Reaching for Excellence in Adolescent Care and Health (REACH) Project of the Adolescent Medicine Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) Research Network, a unique collaborative effort to conceive and implement a research design intended to examine HIV pathogenesis, pubertal hormonal variation, and the effects of sexually transmitted disease comorbidity in HIV-infected youth to improve their health care. METHODS: This multidisciplinary team has drawn on basic science and clinical experience to produce a study design with relevant and feasible study aims and testable hypotheses. Particular attention has been paid to centralized training and quality control practices. Standardized measurements include direct and computer interviews, physical examination, laboratory analysis, and medical chart abstraction. The protocol has been approved by local institutional review boards. RESULTS: A highly standardized and quality control monitored protocol has been implemented at 16 sites throughout the United States collecting historical, observational, and laboratory data in a group of HIV-infected adolescents and HIV-negative controls. Preliminary data collected on subjects are consistent with published reports of the sociodemographic and clinical characteristics of the HIV epidemic in sexually active youth, thus supporting the integrity of the protocol development process. The study population is, for the most part, in older adolescence, predominantly minority and female, and with publicly financed or no health insurance. CONCLUSIONS: The REACH Project is positioned to address questions about the clinical course, immunologic profile, and viral dynamics in HIV-positive youth, and thus is able to inform drug development and management strategies for this understudied population.

Acquired Immunodeficiency Syndrome↗

PubMed1998

Do children need to be monitored after electric shocks?

OBJECTIVE: To determine whether cardiac monitoring is required in children sustaining electric shock at Australian household voltage. METHODOLOGY: Records of patients admitted via the Emergency Department of Princess Margaret Hospital for Children, Perth, Australia, for the period 1968-96 were retrospectively reviewed. The initial ECG findings of patients with an electric shock were recorded, and the development of any arrhythmia. RESULTS: Forty-four patients were identified, 40 of whom had sustained a household electrical injury. One patient had an abnormal ECG on admission, none developed an arrhythmia and all survived. CONCLUSIONS: Routine cardiac monitoring is not required after exposure to Australian household electricity supply if the child is asymptomatic and has a normal ECG on presentation.

Adolescent↗

PubMed1998

Concentrations of placental protein 14 in uterine flushings from infertile women: validation of the collection technique and method of expression of results.

Concentrations of various proteins in uterine flushings have been described as a direct method for assessment of the secretory activity of the endometrium. We investigated levels of the endometrial protein known as placental protein 14 (PP14) in flushings obtained from 271 infertile women. Under transvaginal ultrasonographic control, 2 ml of 0.154 M sodium chloride solution were injected into the uterine cavity and re-aspirated, five times. In contrast to previous studies the recovered volume of each flushing was not consistent (range: 0.05-2.1 ml); the volume varied significantly between serial samples obtained from an individual (P = 0.02, one-way ANOVA), different cycle days (P < 0.0001, one-way ANOVA) and women with bilaterally blocked versus patent Fallopian tubes (P < 0.05, Student's t-test). Concentrations of PP14 showed a better correlation with protein content (r = 0.506, P < 0.0001) than with the recovered volume (r = 0.087, P = 0.095). We therefore corrected PP14 concentrations for total protein content as an indicator of the efficiency of the flushing process. Corrected PP14 concentrations varied significantly relative to time since the onset of menstruation (P = 0.001, Kruskal Wallis ANOVA) with higher levels on days 1-8, as previously observed in plasma samples. No significant difference in PP14 levels was found with different causes of infertility. This study shows that uterine flushing is not a consistent process in women with differing physical characteristics and at varying times throughout the menstrual cycle.

Adult↗

PubMed1998

Endothelin-1, delayed rectifier K channels, and pulmonary arterial smooth muscle.

Sarafotoxin S6c [STXS6c; a selective endothelin-B (ETB) receptor agonist] causes constriction of isolated pulmonary arteries. In perforated-patch experiments on pulmonary arterial myocytes, ET-1 and STXS6c induced a gradual inhibition of the delayed rectifier K current (IKV), the profile of which resembled that carried by Kv1.5. Reverse-transcriptase polymerase chain reaction (RT-PCR) experiments revealed mRNA encoding this channel, and immunolocalization experiments demonstrated expression of the channel protein in pulmonary arterial smooth muscle. It is tempting to speculate that ETB receptor coupling to Kv1.5 may be implicated in contraction after stimulation of these receptors.

Animals↗