THE RELATIONSHIP BETWEEN SODIUM INFLUX AND VOLUME FLOW INTO THE CEREBRAL VENTRICLES OF CATS

Abstract— The relationship between sodium ion (Na⁺) influx and vol. flow of fluid into the cerebral ventricles was measured during ventriculocisternal perfusion with sucrose solutions of various concentrations. The vol. flow of fluid into the ventricles of cats varied linearly from 0 to 90 μl/min with sucrose solutions of 6 to 780 mOsm/l. In the vol. flow range of 0 to 35 μl/min, Na⁺ influx was essentially constant independent of vol. flow rate with a mean value of 6.95 μEq/min. In the vol. flow range of 25 to 90 μl/min, Na⁺ influx increased linearly with flow rate. Under all conditions, Na⁺ influx was greater than that corresponding to newly formed fluid with a normal spinal fluid Na⁺ concentration. The virtual Na⁺ concentration of nascent fluid was effectively infinite when vol. flow was zero and had an asymptotic minimum value of 109 mEq/l as vol. flow increased above normal. These results demonstrate that Na⁺ influx into the ventricles may occur by diffusion from the surrounding brain and also with vol. flow of nascent fluid.     

Orientation of Intermediates in the Bleaching of Shear-Oriented Rhodopsin

Cattle rhodopsin can be highly oriented by shearing a wet paste of digitonin micelles of this visual pigment between two quartz slides. This orients the rhodopsin micelles so that their chromophores lie mainly parallel to the direction of shear. In such preparations the orientation of rhodopsin and intermediates of its bleaching by light have been measured with plane-polarized light from -195°C to room temperature. The chromophore maintains essentially the same orientation as in rhodopsin in all the intermediates of bleaching: bathorhodopsin (prelumirhodopsin), lumirhodopsin, and metarhodopsins I and II. When, however, the retinaldehyde chromophore is hydrolyzed from opsin in the presence of hydroxylamine, the retinaldehyde oxime that results rotates so as to lie mainly across the direction of shear. That is, the retinal oxime, though free, orients itself upon the oriented matrix of the opsin-digitonin micelles. These experiments show the rhodopsin-digitonin micelle to be markedly asymmetric, with the chromophore lying parallel to its long axis. The asymmetry could originate in the formation of the micelle, in rhodopsin itself, or by its linear polymerization under the conditions of the experiment. If rhodopsin itself is markedly asymmetric, for which there is some evidence, then, since in the rod outer segments its chromophores lie parallel to the disk membranes, the molecules themselves must lie with their long axes parallel to the membranes.     

Association between Atherosclerotic Diseases and Carboxyhaemoglobin Levels in Tobacco Smokers

In a cross-sectional study carboxyhaemoglobin (COHb) levels in tobacco smokers were found to provide a better indication of a person''s risk of having developed certain atherosclerotic diseases, including ischaemic heart disease, than the smoking history. In the age group 30-69 years a person with a COHb level of 5% or more was found to be 21 times (lower 95% confidence limit 3·3 times) as likely to be affected by these diseases as another person of the same age and sex with similar smoking history and current smoking habits but with a COHb level of less than 3%.     

Recruited vs. nonrecruited molecular signatures of brown, "brite," and white adipose tissues

Mainly from cell culture studies, a series of genes that have been suggested to be characteristic of different types of adipocytes have been identified. Here we have examined gene expression patterns in nine defined adipose depots: interscapular BAT, cervical BAT, axillary BAT, mediastinic BAT, cardiac WAT, inguinal WAT, retroperitoneal WAT, mesenteric WAT, and epididymal WAT. We found that each depot displayed a distinct gene expression fingerprint but that three major types of depots were identifiable: the brown, the brite, and the white. Although differences in gene expression pattern were generally quantitative, some gene markers showed, even in vivo, remarkable depot specificities: Zic1 for the classical BAT depots, Hoxc9 for the brite depots, Hoxc8 for the brite and white in contrast to the brown, and Tcf21 for the white depots. The effect of physiologically induced recruitment of thermogenic function (cold acclimation) on the expression pattern of the genes was quantified; in general, the depot pattern dominated over the recruitment effects. The significance of the gene expression patterns for classifying the depots and for understanding the developmental background of the depots is discussed, as are the possible regulatory functions of the genes.     

Gender differences in clinical presentation and outcomes of epidemic Kaposi sarcoma in Uganda

Introduction

The incidence of Kaposi sarcoma (KS) has increased dramatically among women in sub-Saharan Africa since the onset of the HIV pandemic, but data on KS disease in women are limited. To identify gender-related differences in KS presentation and outcomes, we evaluated the clinical manifestations and response in men and women with AIDS-associated KS in Uganda.

Methods and Findings

HIV-infected adults with KS attending the Infectious Diseases Institute (IDI) and Uganda Cancer Institute (UCI) in Kampala, Uganda between 2004 and 2006 were included in a retrospective cohort. Evaluation of KS presentation was based on the clinical features described at the initial KS visit. Response was evaluated as the time to “improvement”, as defined by any decrease in lesion size, lesion number, or edema. The cohort consisted of 197 adults with HIV and KS: 55% (108/197) were women. At presentation, the median CD4 T-cell count was significantly lower in women (58 cells/mm³; IQR 11–156 cells/mm³) than men (124 cells/mm³; IQR 22–254 cells/mm³) (p = 0.02). Women were more likely than men to present with lesions of the face (OR 2.8, 95% CI, 1.4, 5.7; p = 0.005) and hard palate (OR 2.0, 95% CI, 1.1, 3.7; p = 0.02), and were less likely than men to have lower extremity lesions (OR 0.54, 95% CI, 0.3, 0.99; p = 0.05). Women were less likely than men to demonstrate clinical improvement (HR = 0.52, CI 0.31, 0.88; p = 0.01) in multivariate analysis.

Conclusions

The clinical presentation and response of KS differs between men and women in Uganda. These data suggest that gender affects the pathophysiology of KS, which may have implications for the prevention, diagnosis, and treatment of KS in both men and women. Prospective studies are needed to identify predictors of response and evaluate efficacy of treatment in women with KS, particularly in Africa where the disease burden is greatest.     

Estimating the Impact of Plasma HIV-1 RNA Reductions on Heterosexual HIV-1 Transmission Risk

Background

The risk of sexual transmission of HIV-1 is strongly associated with the level of HIV-1 RNA in plasma making reduction in HIV-1 plasma levels an important target for HIV-1 prevention interventions. A quantitative understanding of the relationship of plasma HIV-1 RNA and HIV-1 transmission risk could help predict the impact of candidate HIV-1 prevention interventions that operate by reducing plasma HIV-1 levels, such as antiretroviral therapy (ART), therapeutic vaccines, and other non-ART interventions.

Methodology/Principal Findings

We use prospective data collected from 2004 to 2008 in East and Southern African HIV-1 serodiscordant couples to model the relationship of plasma HIV-1 RNA levels and heterosexual transmission risk with confirmation of HIV-1 transmission events by HIV-1 sequencing. The model is based on follow-up of 3381 HIV-1 serodiscordant couples over 5017 person-years encompassing 108 genetically-linked HIV-1 transmission events. HIV-1 transmission risk was 2.27 per 100 person-years with a log-linear relationship to log₁₀ plasma HIV-1 RNA. The model predicts that a decrease in average plasma HIV-1 RNA of 0.74 log₁₀ copies/mL (95% CI 0.60 to 0.97) reduces heterosexual transmission risk by 50%, regardless of the average starting plasma HIV-1 level in the population and independent of other HIV-1-related population characteristics. In a simulated population with a similar plasma HIV-1 RNA distribution the model estimates that 90% of overall HIV-1 infections averted by a 0.74 copies/mL reduction in plasma HIV-1 RNA could be achieved by targeting this reduction to the 58% of the cohort with plasma HIV-1 levels ≥4 log₁₀ copies/mL.

Conclusions/Significance

This log-linear model of plasma HIV-1 levels and risk of sexual HIV-1 transmission may help estimate the impact on HIV-1 transmission and infections averted from candidate interventions that reduce plasma HIV-1 RNA levels.