Cation channels,cell volume and the death of an erythrocyte

Similar to a variety of nucleated cells, human erythrocytes activate a non-selective cation channel upon osmotic cell shrinkage. Further stimuli of channel activation include oxidative stress, energy depletion and extracellular removal of Cl^–. The channel is permeable to Ca²⁺ and opening of the channel increases cytosolic [Ca²⁺]. Intriguing evidence points to a role of this channel in the elimination of erythrocytes by apoptosis. Ca²⁺ entering through the cation channel stimulates a scramblase, leading to breakdown of cell membrane phosphatidylserine asymmetry, and stimulates Ca²⁺-sensitive K⁺ channels, thus leading to KCl loss and (further) cell shrinkage. The breakdown of phosphatidylserine asymmetry is evidenced by annexin binding, a typical feature of apoptotic cells. The effects of osmotic shock, oxidative stress and energy depletion on annexin binding are mimicked by the Ca²⁺ ionophore ionomycin (1 µM) and blunted in the nominal absence of extracellular Ca²⁺. Nevertheless, the residual annexin binding points to additional mechanisms involved in the triggering of the scramblase. The exposure of phosphatidylserine at the extracellular face of the cell membrane stimulates phagocytes to engulf the apoptotic erythrocytes. Thus, sustained activation of the cation channels eventually leads to clearance of affected erythrocytes from peripheral blood. Susceptibility to annexin binding is enhanced in several genetic disorders affecting erythrocyte function, such as thalassaemia, sickle-cell disease and glucose-6-phosphate dehydrogenase deficiency. The enhanced vulnerability presumably contributes to the shortened life span of the affected erythrocytes. Beyond their role in the limitation of erythrocyte survival, cation channels may contribute to the triggering of apoptosis in nucleated cells exposed to osmotic shock and/or oxidative stress.     

Isolation of two H1N2 influenza viruses from swine in France

Summary Samples collected in 1987 and 1988 in Brittany from influenzainfected swine made it possible to isolate and antigenically characterize two H1N2 recombinant viruses (Sw/France/5027/87 and Sw/France/5550/88). The former virus was cloned and reinoculated to swine to allow reproduction of the disease and reisolation of a strain similar to the original one. The serodiagnostic tests carried out on both the original sera and those from the experimentally infected animals confirmed that the virus was actually type Sw/H1N2.     

Quantitative Bestimmung von Pregnandiol

Ohne Zusammenfassung     

Comparison of GB virus C, HIV, and HCV infection markers in hemophiliacs exposed to non-inactivated or inactivated factor concentrates.

BACKGROUND: Until the mandatory introduction of viral inactivation techniques of blood plasma products in the early 1980s many recipients of these products were infected with various viral pathogens. OBJECTIVES: To determine the rate of transmission of GB virus C/hepatitis G virus (GBV-C/HGV) HCV, and HIV through non-virus-inactivated clotting factor concentrates in hemophiliacs, as well as the relation between amount of administered clotting factor and risk for GBV-C/HGV infection. STUDY DESIGN: In this cross-sectional study, we determined retrospectively the rates of infection markers for GBV-C/HGV, HCV, and HIV in a German cohort of hemophiliacs treated with documented amounts of non-virus-inactivated clotting factor concentrates (group A) and in a second group of hemophiliacs who were treated exclusively with virus-inactivated clotting factor (group B). The presence of anti-virus antibodies was determined by ELISA. Viral RNA was detected by RT-PCR. Markers for viral infections were compared to amounts of administered non-virus-inactivated clotting factor. RESULTS: Among hemophiliacs treated with documented amounts of non-virus-inactivated clotting factor the prevalence for GBV-C/HGV, HCV, and HIV was 40.3%, 98.6%, and 56.3%, respectively. In contrast to HIV, the rate of GBV-C/HGV infections did not increase with increasing amounts of consumed non-inactivated clotting factor. Even in the subgroup of heavily treated hemophiliacs the rate of GBV-C/HGV infection markers did not exceed 45%. CONCLUSIONS: The amount of non-virus-inactivated clotting factor is not predictive for the risk of GBV-C/HGV infection in hemophiliacs. Despite repeated parenteral exposure more than 55% of hemophiliacs were not infected with GBV-C/HGV. Our findings indicate a high frequency of host factors preventing parenteral transmission of GBV-C/HGV.     

Do children with focal cerebellar lesions show deficits in shifting attention?

More recent findings suggest a possible role of the cerebellum in nonmotor functions. Disability of individuals with cerebellar damage in rapidly shifting attention is one frequently used example to support cerebellar involvement in mental skills. The original proposal was based on findings in five children with chronic surgical lesions of the cerebellum and a young adult with a degenerative disorder. The aim of the present study was to repeat Akshoomoff and Courchesne's initial findings in a larger group of children with focal cerebellar lesions. Ten children with cerebellar lesions and 10 age- and sex-matched controls were tested. Neocerebellar areas were affected in all children with cerebellar damage except one based on detailed analysis of MRI scans. Subjects had to perform a focus and a shift attention task. Two visual and two auditory stimuli were presented in a pseudorandom order. An ellipse and a high-pitched tone were presented less frequently than a circle and a low-pitched tone. Rare stimuli were presented at five different time intervals. In the focus tasks, subjects had to react to the same rare stimulus of one of the two modalities. In the shift task, subjects had to switch between the two rare stimuli. Motor deficits based on reaction times were small in cerebellar children compared with controls. The ability of target detection did not significantly differ in the children with cerebellar lesions compared with the control children in both the focus and the shift attention task. In particular, children with cerebellar damage showed no significant impairment in rapid (<2 s) shifts of attention. The present findings indicate that the cerebellum may be less critical in attention related processes than suggested previously.     

Interstitial deletion in the long arm of chromosome no. 5

A case of a male infant with several congenital anomalies combined with an interstitial deletion of the long arm of chromosome no. 5 is presented. The symptoms of the infant were compared to five previous reported cases with similar interstitial deletions in 5q.     

Abnormal courtship conditioning in males mutant for the RI regulatory subunit of Drosophila protein kinase A

The previously described site-selected P-element mutagenesis of a Drosophila gene encoding the regulatory subunit of cAMP-dependent protein kinase generates mutants that have defective behavior in the olfactory learning test. Here we describe the effect of the same mutations in a courtship conditioning assay. Wild-type males can distinguish between virgin females (which they court vigorously), and fertilized females (which they court less vigorously). After exposure to fertilized females, wild-type males modify their behavior by decreasing courtship to subsequent target virgins, an effect that may last for many hours. Like wild-type males, PKA-RI mutant males are also able to distinguish between virgin and fertilized females. PKA-RI males also modify their behavior towards virgin females after prior exposure to a fertilized female, but such an effect is short-lived, suggesting a defect in memory rather than learning. We also show that under these conditions the behavior of PKA-RI males is similar to that of amnesiac, dunce and rutabaga males.     

Epitrochlearis muscle. I. Mechanical performance, energetics, and fiber composition

An in vitro rat muscle preparation is described that can contract at rates of 12-240 twitches/min. Maximum dF/dt paralleled maximum twitch tension, their ratio being constant at approximately 8 ms for contraction rates of 12-120 twitches/min. Time to peak tension was 8-13 ms, time to peak dF/dt 5-8 ms, and half-relaxation time 4 ms. These parameters were unaffected by rate of contraction or duration of isometric work. Differential ATPase staining demonstrated that 60-65% of the fibers were fast-twitch white, 20% fast-twitch red, and 15% slow-twitch red. The preponderance of fast-twitch fibers correlated with the observed mechanical performance of the muscle. Muscles contracting for 60 min at rates up to 48 twitches/min maintained total adenine nucleotide content (ATP, ADP, AMP) at near resting levels. At higher twitch rates (72-240 twitches/min), total adenine nucleotide content decreased 40%, reflecting exclusively a fall in ATP in the presence of adequate phosphocreatine stores. Adequate oxygenation was reflected by lactate-to-pyruvate ratios in the range of 11-15 at all rates of contraction.     

Role of the blue mechanism in wavelength discrimination

The role of blue cones as well as the pathways they supply (collectively called the "blue mechanism") is evaluated by comparing ordinary wavelength discrimination functions with those obtained using two methods designed to inhibit the blue mechanism selectively. These methods use a just-noticeable-border criterion (JNB), instead of the usual one of just-noticeable-difference, and a yellow preadapting field to induce transient tritanopia. Without transient tritanopia, the data obtained using the just-noticeable-border criterion reveal a small contribution of the blue mechanism to wavelength discrimination. Transient tritanopia, with JNB, produces an additional selective loss of wavelength discrimination in a spectral region flanking 460 nm, which yields a function resembling those for tritanopes previously examined.