Simplifying the molecular mechanisms of human papillomavirus

Human papillomaviruses are a common human pathogen responsible for diseases varying in severity from warts to cervical cancer. This article examines the functions of the viral gene products and how they interact with cellular factors to replicate themselves and cause disease.     

Anomalies in coral reef community metabolism and their potential importance in the reef CO2 source-sink debate

It is not certain whether coral reefs are sources of or sinks for atmospheric CO2. Air-sea exchange of CO2 over reefs has been measured directly and inferred from changes in the seawater carbonate equilibrium. Such measurements have provided conflicting results. We provide community metabolic data that indicate that large changes in CO2 concentration can occur in coral reef waters via biogeochemical processes not directly associated with photosynthesis, respiration, calcification, and CaCO3 dissolution. These processes can significantly distort estimates of reef calcification and net productivity and obscure the contribution of coral reefs to global air-sea exchange of CO2. They may, nonetheless, explain apparent anomalies in the metabolic performance of reefs close to land and reconcile the differing experimental findings that have given rise to the CO2 debate.     

Effects of proteins, blood cells and glucose on the viscosity of cerebrospinal fluid

It has long been assumed that cerebrospinal fluid (CSF) is a newtonian fluid with viscosity similar to water, yet high protein content, has been postulated to increase the viscosity of CSF in vivo. Such an increase in viscosity may have serious implications for the effectiveness of surgical shunts implanted to re-establish the CSF flow in cases of abnormal CSF circulation. In this study, glucose content, total protein content and blood cell count in the CSF of 23 patients undergoing brain surgery were measured. Viscosity measurements were performed on duplicate CSF samples over a range of shear strain rates of 25-1,460 s-1. The results indicated that high protein or high cell concentration in CSF does not significantly affect the viscosity of the cerebral fluid at those shear rates. CSF is clearly newtonian, and its viscosity at 37 degreesC is in the range of 0.7-1 mPa.s.     

Consequences of depression during adolescence: marital status and marital functioning in early adulthood

In previous studies, depression has been associated with both marital status and marital distress. Unfortunately, given the cross-sectional design of most of this research, the temporal nature of these associations is unclear. The authors examined the marital functioning of young adults as a function of whether they received psychiatric diagnoses of major depressive disorder or nonaffective psychiatric disorder during adolescence. Depression during adolescence was found to predict higher rates of marriage among younger women and subsequent marital dissatisfaction. This pattern of results appears to be specific to depression: The presence during adolescence of a nonaffective psychiatric disorder was unrelated to subsequent marital functioning. These findings highlight the potentially adverse consequences of depression in adolescence and underscore the importance of prevention and early treatment efforts.     

Substitution mutations in the myosin essential light chain lead to reduced actin-activated ATPase activity despite stoichiometric binding to the heavy chain

Myosin essential light chain (ELC) wraps around an alpha-helix that extends from the myosin head, where it is believed to play a structural support role. To identify other role(s) of the ELC in myosin function, we have used an alanine scanning mutagenesis approach to convert charged residues in loops I, II, III, and helix G of the Dictyostelium ELC into uncharged alanines. Dictyostelium was used as a host system to study the phenotypic and biochemical consequences associated with the mutations. The ELC carrying loop mutations bound with normal stoichiometry to the myosin heavy chain when expressed in ELC-minus cells. When expressed in wild type cells these mutants competed efficiently with the endogenous ELC for binding, suggesting that the affinity of their interaction with the heavy chain is comparable to that of wild type. However, despite apparently normal association of ELC the cells still exhibited a reduced efficiency to undergo cytokinesis in suspension. Myosin purified from these cells exhibited 4-5-fold reduction in actin-activated ATPase activity and a decrease in motor function as assessed by an in vitro motility assay. These results suggest that the ELC contributes to myosin's enzymatic activity in addition to providing structural support for the alpha-helical neck region of myosin heavy chain.     

Clostridium difficile infection in patients with reactive arthritis of undetermined etiology

BACKGROUND: Multiple sensory neuropeptides are present in human airways and may contribute to diseases such as asthma. This study quantified and characterised substance P (SP), neurokinin A (NKA), and calcitonin gene related peptide (CGRP) immunoreactivity in bronchoalveolar lavage fluid in asthmatic and normal subjects. METHODS: Using specific radioimmunoassay (RIA), SP, NKA and CGRP were measured in bronchoalveolar lavage fluid from asthmatic subjects (n = 5), normal subjects (n = 5), atopic non-asthmatic subjects (n = 6), and asthmatic subjects four hours after allergen challenge (n = 12). Peptide immunoreactivity was characterised using high performance liquid chromatography (HPLC) and RIA. RESULTS: No SP or CGRP immunoreactivity was detected in any of the fractions from samples after extraction, HPLC, and RIA. Non-specific binding resulted in spurious SP immunoreactivity being detected in bronchoalveolar lavage fluid when no extraction process was employed. NKA was detected in significant amounts in asthmatic (median 550, range 425-625 pg/ml) and normal subjects (median 725, range 350-1425 pg/ml). The level of NKA was significantly higher in the asthmatic subjects after allergen challenge (median 750, range 350-1250 pg/ml) than in unchallenged asthmatic subjects (median 600, range 425-600 pg/ml, p < 0.01). CONCLUSIONS: Extraction and characterisation of peptides from bronchoalveolar lavage fluid must be performed to ensure that the measured immunoreactivity represents target peptide. NKA is present in bronchoalveolar lavage fluid in high concentrations and is the predominant tachykinin. The concentrations of NKA are similar in normal subjects and subjects with mild asthma.     

Toward quantitative fetal heart rate monitoring

Continuous electronic fetal heart rate (FHR) monitoring during labor is motivated by the clinical experience that fetal distress causes loss of FHR variation and the occurrence of decelerations late during uterine contraction. This practice is of uncertain clinical benefit, perhaps because the interpretation is qualitative. We have developed new quantitative measures and analyzed cardiotocograph records from 148 consecutive patients, 44 of whom had at least one "nonreassuring" epoch. In multivariate regression models, measures of deceleration and variability were significantly associated with the obstetrician's diagnosis (receiver operating characteristic area 0.84, p < 0.05). This approach may be useful clinically.     

Nucleolar organizer regions in lymphomas: a quantitative study

Using a silver staining technique, nucleolar organizer region-associated proteins (Ag-NORs) have been studied in paraffin sections of 76 non-Hodgkin's lymphomas, five normal lymph nodes, and five lymph nodes. The mean number of nucleolar organizer regions per nucleus was 1.19 (SD:0.09) for normal lymphocytes, 3.04 (SD:0.14) for reactive lymph nodes, 2.79 (SD:0.44) for low-grade lymphomas, 6.33 (SD:1.58) for intermediate-grade lymphomas, and 10.53 (SD:1.97) for high-grade lymphomas. There were highly significant differences in Ag-NOR counts among the groups (p < 0.001). The Ag-NOR regions were often observed in nuclei in areas where nucleoli themselves were invisible. It is suggested that this method is useful in diagnostic histopathology and in differentiation of the grade of lymphomas.     

Application of physicians' predictions of meal and exercise effects on blood glucose control to a computer simulation

Our aim was to develop a computer simulator program that allows patients to practise insulin dose and dietary adjustment on a day of planned exercise, and shows the resulting blood glucose response in an average diabetic patient. The degree of blood glucose change predicted by the program was determined from changes predicted by five local specialists in seven hypothetical scenarios involving exercise +/- dietary or insulin dose adjustments. The program was then tested against 18 outside specialists' responses in 7 different scenarios. The program simulates the 24 h glycaemic response after 45 min mild or moderate exercise starting 2 h after meals, as well as changes to this response induced by alterations in dietary carbohydrate and/or insulin dose. Coefficients of variation of specialists' blood glucose predictions were greater for exercise (35% local, 31% outside specialists) than dietary change (7% local, 10% outside specialists; p = 0.002-0.04). The program's predicted change in blood glucose levels in the seven scenarios correlated well with the outside specialists' corresponding mean predictions (r = 0.97; p = 0.0001). We conclude that specialists are less consistent in predicting glycaemic change with exercise than with dietary alteration. Nevertheless it is possible to represent their predictions in a computerized simulator for diabetic patient education.