Cholinergic stimulation of ouabain-sensitive respiration in rat submandibular gland

Oxygen consumption of slices of rat submandibular gland was monitored with an oxygen electrode method. Carbachol stimulated an immediate increase in tissue respiration that was inhibitable by ouabain. The stimulation required the presence of calcium in the incubation medium and was blocked by atropine. The calcium ionophore A23187 also stimulated ouabain-sensitive oxygen consumption in the tissue slices. The results show that the mechanism using the extra energy during cholinergic stimulation is the sodium pump. Amiloride at a 1, 10, or 100 microM concentration had no effect on stimulation of ouabain-sensitive respiration by carbachol. Since amiloride, which is known to block the sodium reabsorption process in the ductal segment, has no effect on the stimulation, the increased sodium pump activity is probably located in the acinar region and is associated with the primary fluid secretion process.     

Ribosomal binding sites on poliovirus RNA

Eucaryotic ribosome binding sites on type 1 poliovirus RNA were obtained by isolation of T1 RNase-resistant RNA fragments from 80 S ribosomes that had been bound under conditions specific for initiation of translation and prevented from translocation with sparsomycin. The fragments were analyzed by two-dimensional polyacrylamide gel electrophoresis. Three ribosome-protected (RP) oligonucleotides and several non-ribosomal-protein-protected (NP) oligonucletides were analyzed. Secondary T1 digestion of the RP fragments revealed that at least three separate species existed. By comparison of these secondary digests to T1 digests of RNaseIII fragments mapped on the polio RNA, and by electron microscopic observation of ribosomes bound to polio RNA, preferred ribosome binding sites were localized to near 115 bases from the 5′ end, just to the 3′ side of midgenome, and 780 bases from the 3′ end.     

Impaired Microvascular Function in Normal Children: Effects of Adiposity and Poor Glucose Handling

Clustering of cardiovascular risk factors is thought to occur early in life. The endothelium is an important regulator of microvascular function. We investigated the relationship between microvascular function and cardiovascular risk factors in 145 normal, healthy children aged 11-14 years. Skin microvascular responses, measured using laser Doppler imaging, to iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP), were negatively correlated with percentage body fat ( r =−0.20, P < 0.05 and r =−0.18, P < 0.05, respectively). Subjects were stratified into quintiles based on 2-h, post-feeding glucose levels. Subjects in the upper glucose quintile (range 7.4-11.4 mmol l⁻¹) showed significantly lower vasodilatation to both ACh (   P < 0.005  ) and SNP (   P < 0.02  ) than those in the lower quintile (range 3.9-4.9 mmol l⁻¹). Waist-to-hip ratio and the fasting insulin resistance index were significantly greater in subjects in the upper quintile than those in the lower quintile ( P < 0.001 and P < 0.05, respectively). Additionally, in subjects in the upper glucose quintile, fasting triglyceride correlated with fasting insulin ( r = 0.59, P < 0.001) and with the fasting insulin resistance index ( r = 0.49, P < 0.009), and plasma levels of cholesterol and 2-h glucose were also correlated ( r = 0.40, P < 0.05). In a cross-section of normal children, microvascular function was negatively associated with adiposity. Additionally, in a subgroup of subjects, there was a clustering of high post-feeding glucose, impaired microvascular function, increased insulin resistance and higher central fat distribution. These findings suggest that risk factors for adult cardiovascular disease begin to cluster in normal children, which might have important consequences for development of atherosclerosis later in life.     

The relationship between social anxiety disorder and alcohol use disorders: a critical review

Epidemiological studies have demonstrated a significant co-morbidity between social anxiety disorder (SAD) and alcohol use disorders (AUDs). Despite the fact that many studies have demonstrated strong relationships between SAD and AUD diagnoses, there has been much inconsistency in demonstrating causality or even directionality of the relationship between social anxiety and alcohol-related variables. For example, some studies have showed a positive relationship between social anxiety and alcohol-related variables, while others have shown a negative relationship or no relationship whatsoever. In an attempt to better understand the relationship between social anxiety and alcohol, some researchers have explored potential moderating variables such as gender or alcohol expectancies. The present review reports on what has been found with regard to explaining the high co-morbidity between social anxiety and alcohol problems, in both clinical and non-clinical socially anxious individuals. With a better understanding of this complex relationship, treatment programs will be able to better target specific individuals for treatment and potentially improve the efficacy of the treatments currently available for individuals with co-morbid SAD and AUD.     

Comparison of in vitro and in vivo alpha/beta ratios for prostate cancer

Parallel in vitro and in vivo studies provide insight into the relationship between clinical response and intrinsic cellular radiosensitivity and may aid in the development of predictive assays. Compilations of radiosensitivity parameters from in vitro experiments can also be used to examine the potential effectiveness of alternative or new treatment plan designs until enough clinical data become available to directly estimate the requisite radiosensitivity parameters. In this work, survival data for six prostate cancer cell lines (ten datasets total) have been extracted from the literature and re-analysed using the linear-quadratic (LQ) survival model. The paired bootstrap technique for regression is used to compute 95% confidence intervals for the estimated radiosensitivity parameters. LQ radiosensitivity parameters derived from the in vitro data are then compared to radiosensitivity parameters derived from clinical data for prostate cancer. Estimates of alpha range from 0.09 to 0.35 Gy(-1) (all cell lines), and the alpha/beta ratio ranges from 1.09 to 6.29 Gy (all cell lines). Point estimates of the repair half-time (PPC-1, TSU-Pr1, PC-3 and DU-145 cell lines) range from 5.7 to 8.9 h (95% confidence interval from 0.26 h to 10.7 h). Differences in the radiosensitivity parameters determined from the data reported by different laboratories are as large as or larger than the differences in radiosensitivity parameters observed among the various prostate cell lines. The reported studies demonstrate that even seemingly small corrections for dose rate effects, such as those expected in high dose rate (HDR) experiments, can sometimes have a significant impact on estimates of alpha and alpha/beta. By neglecting dose rate effects in the analysis of HDR experiments, estimates of the alpha/beta, ratio may be too high by factors as large as 1.3 to 6.2. The half-time for repair derived from the in vitro experiments appears significantly larger (slower repair rate) than estimates derived from the clinical data. However, the prostate radiosensitivity parameters alpha and alpha/beta may be approximately the same in vitro and in vivo. Most of the in vitro data are consistent with an alpha/beta ratio for prostate cancer less than 3 or 4 Gy.     

Adeno-associated virus vector gene transfer and sarcolemmal expression of a 144 kDa micro-dystrophin effectively restores the dystrophin-associated protein complex and inhibits myofibre degeneration in nude/mdx mice

Duchenne muscular dystrophy is a severe life-threatening X-linked recessive disorder, caused by mutations in the dystrophin gene, for which currently there is no effective treatment. Because of the large size of the dystrophin cDNA (14 kb) this precluded it from being used in early adenovirus- or retrovirus-based gene therapy vectors. However, some therapeutic success has been achieved in mdx mice using adenovirus- and retrovirus-mediated transfer of a 6.3 kb recombinant mini-dystrophin cDNA. Despite this, problems with immunogenicity and inefficient transduction of mature myofibres make these vectors less than ideal for gene transfer to skeletal muscle. Adeno-associated viral (AAV) vectors overcome many of the problems associated with other vector systems. However, AAV vectors can only accommodate <5 kb of foreign DNA. For this reason we have produced a micro-dystrophin cDNA gene construct that is <3.8 kb. This construct, driven by a CMV promoter, was introduced into the skeletal muscle of 12-day-old nude/mdx mice using an AAV vector, resulting in specific sarcolemmal expression of micro-dystrophin in >50% of myofibres up to 20 weeks of age, and effective restoration of the dystrophin-associated protein (DAP) complex components. Additionally, evaluation of central nucleation indicated a significant inhibition of degenerative dystrophic muscle pathology. We have therefore shown that the current micro-dystrophin gene delivered in vivo using an AAV vector is not only capable of restoring sarcolemmal DAP complexes, but can also ameliorate dystrophic pathology at the cellular level.     

An autosomal dominant syndrome of acromegaloid facial appearance and generalised hypertrichosis terminalis.

We report a family in which a phenotype of acromegaloid facial appearance (AFA) and generalised hypertrichosis terminalis segregates through three generations. Congenital hypertrichosis terminalis and AFA have been previously reported as independent autosomal dominant traits. This is the first report to delineate an autosomal dominant transmission of the combined phenotype.     

A history of personal violence and postpartum depression: is there a link?

Summary Background: A link between violence and depression has been shown, but not a link between violence and postpartum depression. This study sought to determine if there is an association between a history of abuse (physical, sexual, emotional as a child or adult) and postpartum depression (PPD). Method: 200 postpartum women were recruited from 6 hospitals. At 8–10 weeks postpartum, a telephone interviewer asked women about physical, emotional or sexual abuse as an adult or child and sociodemographic, obstetrical and personal medical history. PPD was assessed using the Edinburgh Postnatal Depression Scale (EPDS, score of ≥12). Abuse was determined by the Conflict Tactics Scale or the Abuse Assessment Screen. Chi-square and logistic regression were used to determine the relationship between violence and PPD. Results: 11% of women had EPDS scores of ≥12. Rates of childhood (6.5%), or adult (6.5%) physical abuse; and childhood (13%) or adult (14%) sexual abuse were reported by respondents. Emotional abuse in the current relationship (29.6%) exceeded that of childhood abuse (3.5%). Overall 43.2% of respondents had at least one form of abuse. Having a history of depression (OR = 3.3 (95% CI, 1.3–8.7)), panic attack during pregnancy (OR = 5.4 (1.6–19.0)), maternal complications (OR = 5.0 (1.7–15.1)), low social support (OR = 3.3 (1.3–8.7)) and emotional abuse (OR = 2.8 (1.1–7.4) were associated with PPD. Conclusion: Emotional abuse but not physical or sexual abuse was found to be associated with PPD. A possible explanation for this relationship may be that being in an abusive situation puts one at risk for depression and in turn, postpartum depression.