Characterization of an antigen secreted by Chlamydia-infected cell culture.

A soluble genus-specific chlamydial antigen has been isolated from the supernatants of cultures infected with Chlamydia trachomatis and from other sources. The antigen is a glycolipid that is secreted during the infective cycle. This exoglycolipid can be hydrolysed and fractionated into polysaccharide and lipid components. Both fractions retain antigenic activity. An immunodominant antigenic determinant of the lipid component contains fatty acids of C17 and C18:1. The polysaccharide immunodominant epitope gives rise to gulose when derivatives are formed. The secretion of the antigen into the media supernatant, the presence of gulose and the observed molecular weight are consistent with properties of alginate secreted by Gram-negative bacteria. Chemical analyses and SDS-PAGE indicate that the exoglycolipid is markedly different from LPS.     

Analysis of quantal content and quantal conductance in two populations of neurons in the avian ciliary ganglion

The avian ciliary ganglion contains two populations of parasympathetic cells, termed the ciliary and choroid neurons. We have estimated the quantal contents of nicotinic excitatory postsynaptic potentials in both populations of neurons by several methods. The singly innervated ciliary neurons have quantal contents of 15–30. In contrast, the multiply innervated choroid cells have quantal contents of 4–7. Quantal conductance was also determined, using a parallel conductance model which takes into account the capacitance of the cell membrane. This analysis indicates that in both populations of neurons one quantum activates approximately 100 postsynaptic receptors.

It is concluded that in autonomie ganglia singly innervated cells demonstrate a larger quantal content, consistent with a higher safety factor for neurotransmission, while quantal content in multiply innervated cells is generally much lower, allowing for considerable summation of presynaptic inputs. Further, in autonomic neurons many fewer postsynaptic receptors are activated by a single quantum than is the case at the neuromuscular junction.     

Threshold effect of urinary glycosaminoglycans and the walk test as indicators of disease progression in a survey of subjects with Mucopolysaccharidosis VI (Maroteaux-Lamy syndrome)

A cross-sectional survey in individuals affected with the lysosomal storage disease Mucopolysaccharidosis VI (MPS VI) was conducted to establish demographics, urinary glycosaminoglycan (GAG) levels, and clinical progression of the disease. The survey evaluated 121 bona fide MPS VI-affected individuals over the age of 4 years from 15 countries across the Americas, Europe, and Australasia representing greater than 10% of the estimated world prevalence of the disease. A medical history, complete physical exam, urinary GAG determination, and assessment of several clinical measures related to physical endurance, pulmonary function, joint range of motion, strength, and quality of life were completed for each participant. Although a wide variation in clinical presentation was observed, several general findings were obtained reflecting progression of the disease. Impaired physical endurance, as measured by the distance achieved in a 6-min walk, could be demonstrated across all age groups of MPS VI-affected individuals. High urinary GAG values (>200 mug/mg creatinine) were associated with an accelerated clinical course comprised of age-adjusted short stature and low body weight, impaired endurance, compromised pulmonary function, and reduced joint range of motion. An unexpected result was the predominance of urinary GAG values <100 mug/mg creatinine for those participants over the age of 20 years. Pending the collection of longitudinal data, these results suggest that urinary GAG levels predict clinical morbidity, and longer-term survival is associated with urinary GAG levels below a threshold of 100 mug/mg creatinine.     

Leiomyosarcoma of the breast: a pathologic and comparative genomic hybridization study of two cases

Leiomyosarcoma is an extremely rare form of primary breast sarcoma. We present the pathologic and genetic findings of two cases of leiomyosarcoma of the breast. The patients were 44 and 52 years of age and they presented with circumscribed masses of 3.0 and 4.5 cm, (greatest dimension) respectively. Microscopically, the two tumors showed diffuse proliferation of spindle cells with oval and blunt-ended nuclei arranged in short fascicles or bundles. There was moderate cytologic atypia in both cases, and 6 and 12 mitotic figures per 10 high power fields, respectively. No epithelial component was identified. The tumor cells were strongly immunoreactive for markers of smooth-muscle differentiation, including desmin, muscle-specific actin, and smooth-muscle actin. Comparative genomic hybridization analysis showed losses of 10q (two of two cases), 13q (two of two cases), 17p (one of two cases), and gains of 1q (one of two cases) and 17p (one of two cases). The patterns of chromosomal imbalances identified in leiomyosarcoma of the breast are similar to those reported in leiomyosarcoma of soft tissue and uterus and are different from those reported for leiomyoma, indicating that these alterations may be important for development of malignant smooth-muscle tumors regardless of site or organ of origin.     

Arterial myogenic properties of the spontaneously hypertensive rat

When subject to a transmural pressure gradient resistance arteries develop a spontaneous, intrinsically initiated contraction which varies according to the pressure stimulus and occurs in the absence of vasoconstrictor agonists. Such pressure-dependent active changes in vascular tone are indicative of the vascular myogenic response and contribute to autoregulation and the setting of total peripheral resistance and hence blood pressure regulation. The myogenic behaviour of blood vessels provides the background tone upon which other vasomotor influences act. Hypertension is associated with a raised vascular resistance and in this article the evidence for increased myogenic activity contributing to the raised vascular resistance is reviewed. Although there are some cases that provide evidence for exaggerated myogenic responsiveness in resistance arteries taken from hypertensive animals it is not possible to conclude that enhanced myogenic contractile responses within normal pressure ranges contribute to the raised total peripheral resistance. However, the myogenic tone of the resistance arteries of the various vascular beds is subject to differing modulatory influences in hypertensive animals and their normotensive controls which may contribute to the aetiology of hypertension.     

Cluster-Randomized Controlled Trial of An Athletic Trainer-Directed Spit (Smokeless) Tobacco Intervention for Collegiate Baseball Athletes: Results After 1 Year

Context: Athletes in the United States are at high risk for using spit (smokeless) tobacco (ST) and incurring its associated adverse health effects.Objective: To examine whether an athletic trainer-directed ST intervention could decrease initiation and promote cessation of ST use among male collegiate baseball athletes.Design: Stratified, cluster-randomized controlled trial.Setting: Fifty-two California colleges.Patients or Other Participant(s): A total of 883 subjects in 27 intervention colleges and 702 subjects in 25 control colleges participated, as did 48 certified athletic trainers.Intervention(s): For college athletic trainers and associated dental professionals, a 3-hour video conference, and for collegiate athletes, an oral cancer screening with feedback and brief counseling during the preseason health screenings, athletic trainer support for cessation, and a peer-led educational baseball team meeting.Main Outcome Measure(s): The subjects' ST use over 1 year was assessed by self-report. At the end of the study, the certified athletic trainers were mailed a survey assessing their tobacco use and perceptions and behavior related to tobacco control in the athletic environment. We used multivariable logistic regression models for clustered responses (generalized estimating equations) to test the difference between groups in ST-use initiation and cessation and to identify significant overall predictors of noninitiation and cessation of ST use.Results: Of the 1585 athletes recruited, 1248 (78.7%) were followed up at 12 months. In addition, 48 of the 52 athletic trainers (92%) responded to the 1-year follow-up survey. The ST-use initiation (incidence) was 5.1% in intervention colleges and 8.4% in control colleges (generalized estimating equation odds ratio = 0.58, 95% confidence interval = 0.35-0.99). Predictors of ST noninitiation were low lifetime tobacco and monthly alcohol use (odds ratio = 1.98, 95% confidence interval = 1.40- 2.82) and athletic trainers' report that the baseball coach supported ST-use prevention activities (odds ratio = 1.43, 95% confidence interval = 1.11-1.83). Although at 1 year, cessation of ST use was relatively high in both groups (36%), we noted no significant difference between the groups (odd ratio = 0.94, 95% confidence interval = 0.70-1.27).Conclusions: The intervention was significantly effective in preventing incident ST use but did not significantly increase cessation beyond that seen in the control group. The latter finding is inconsistent with previous studies and may be explained by spillover of the intervention to control colleges, other anti-tobacco activity in control colleges, and/or the small sample of dependent ST users enrolled in the study.     

Induction of PGE2 by estradiol mediates developmental masculinization of sex behavior

Adult male sexual behavior in mammals requires the neuronal organizing effects of gonadal steroids during a sensitive perinatal period. During development, estradiol differentiates the rat preoptic area (POA), an essential brain region in the male copulatory circuit. Here we report that increases in prostaglandin-E(2) (PGE(2)), resulting from changes in cyclooxygenase-2 (COX-2) regulation induced by perinatal exposure to estradiol, are necessary and sufficient to organize the crucial neural substrate that mediates male sexual behavior. Briefly preventing prostaglandin synthesis in newborn males with the COX inhibitor indomethacin permanently downregulates markers of dendritic spines in the POA and severely impairs male sexual behavior. Developmental exposure to the COX inhibitor aspirin results in mild impairment of sexual behavior. Conversely, administration of PGE(2) to newborn females masculinizes the POA and leads to male sex behavior in adults, thereby highlighting the pathway of steroid-independent brain masculinization. Our findings show that PGE(2) functions as a downstream effector of estradiol to permanently masculinize the brain.