Circannual variation in lymphocyte subsets, revisited

BACKGROUND: Circadian and circannual variations in lymphocyte subsets, especially CD8+ T-lymphocytes, have been reported. This study focuses on CD4+ T-lymphocyte seasonal variation over a 6-year 8-month period. STUDY DESIGN AND METHODS: Lymphocyte subsets were quantitated monthly for four healthy individuals from 1986 through 1992 as part of a flow cytometry quality-control program. RESULTS: In general, there were no significant seasonal changes in the total number of white cells or in total lymphocyte counts. The absolute numbers of CD4+ T-lymphocytes were lowest in summer when the CD8+ T-lymphocytes were highest. Mean CD4+ T-lymphocyte counts were 846, 967, 618, and 695 per microL for Subjects 1 through 4, respectively, in winter and 432, 670, 355, and 766 per microL, respectively, in summer. Two healthy subjects had CD4+ T-lymphocyte counts lower than 300 per microL on one or more occasions during the study period. In three of the four subjects, the percentage of B-lymphocytes in winter was almost double that in summer. In one of the four subjects, no circannual rhythm was observed in these lymphocyte subpopulations. CONCLUSION: The seasonal variation in CD4+ T- lymphocyte counts demonstrated in three healthy individuals over almost 7 years is again of interest in light of renewed consideration of using surrogate tests, such as CD4+ T-lymphocyte counts, to screen for AIDS- like diseases that may be in the blood supply.     

The family history in family practice: a questionnaire study

OBJECTIVES: Our aims were to investigate family medical history taking in general practice, and to evaluate the value attached to the family medical history as an aid to decision making in general practice. METHOD: A postal questionnaire survey was conducted among all 291 GPs working within the Calderdale and Kirklees Health Authority area. Each questionnaire was followed by a reminder. The main outcome measures were answers to questions on routine and opportunistic family history taking and a question about transmitting knowledge about genetic risk to other members of the family. Questions were also posed about the value attached to the family medical history as an aid to decision making. RESULTS: A total of 193 GPs returned the questionnaire (response rate 66.3%). On registration, 94.3% of GPs indicated that enquiries were made about a family history of coronary heart disease. Breast and colorectal cancer were specifically asked about by 48.4% and 30.7% of GPs, respectively. One-fifth of respondents indicated that they asked a general question about family medical history. A little over one-quarter of respondents indicated that they made opportunistic enquiries about the family history or suggested that the patient should inform other members of the family about possible risks. In the scenarios highlighted in this study, the majority of respondents felt that the family medical history had value as an aid to decision making. This was particularly the case for checking a patient's cholesterol (92.1%) and for initiating referrals in younger patients with possible cancer-related symptoms (three-quarters of respondents). CONCLUSION: GPs value the family medical history as an aid to decision making. Unfortunately, apart from enquiries about coronary heart disease, routine or opportunistic family history taking is not occurring in practice. Mechanisms need to be sought to extract information from the family medical history so that it can be more effectively used by GPs.      

The role of hemagglutinins in the midgut extracts of two lines of Aedes aegypti in their susceptibility to Dengue-2 virus

Hemagglutinin activity (HA) was studied in the midgut extracts from highly (h) and lowly susceptible strains of Aedes aegypti mosquitoes to Dengue-2 virus (DEN-2). HA in the midgut extracts from these two isofemale strains of mosquitoes was high in as compared to (h) mosquitoes. HA was found to be higher with chicken red blood cells (RBCs) than with rabbit and human RBCs of O group. Larval midgut extracts showed higher activity than those from adult female mosquitoes. Exposure of midgut extracts to 100 degrees C for 10 mins destroyed the activity. The activity was observed between pH 6 and pH 10. HA in midgut extracts was also studied using twenty different carbohydrates; five of them showed an inhibition of HA. The inhibitory carbohydrates, when incorporated into DEN-2-infected bloodmeal, showed a reduction in the susceptibility of mosquitoes to the virus as compared to the control ones fed on the virus alone. Similarly, when these carbohydrates were incorporated in the DEN-2-infected inoculum, the inoculated mosquitoes showed a reduction in the susceptibility to the virus. HA in the virus-infected midgut extracts was higher than that in the uninfected controls. These results suggest that the presence of HA in the midgut may be one of the factors that affect the susceptibility of Ae. aegypti mosquitoes to DEN-2.     

Remote Echography between a Ground Control Center and the International Space Station Using a Tele-operated Echograph with Motorized Probe

Echography is the most appropriate imaging modality for investigating astronauts. Unfortunately, it requires a great deal of training to perform ultrasound examinations, which can be difficult and time consuming, especially if the astronaut does not have a medical background. We designed a new echography system with motorized probes that allows for the majority of exam functions to be controlled by a ground-based sonographer. Using tele-operation, the sonographer controls the orientation of the transducer (tilt, rotation) and echograph settings (gain, depth, freeze) and triggers ultrasound functions (pulsed wave color Doppler, 3-D capture, radiofrequency data collection, elastography). With this system, astronauts are required to hold the motorized probe only at the locations indicated, with the remainder of the exam being conducted by the ground-based sonographer. During spaceflight, ultrasound imaging of the carotid artery, jugular vein, thyroid, liver, gallbladder, biliary tract and portal vein (2-D, 3-D, color, pulsed wave, radiofrequency) were successfully performed.     

cDNA cloning and complete sequence of porcine choline acetyltransferase: in vitro translation of the corresponding RNA yields an active protein.

A cDNA clone encoding the complete sequence of porcine choline acetyltransferase (ChoAcTase; acetyl-CoA: choline O-acetyltransferase, EC 2.3.1.6.) has been identified. A cDNA library, constructed from poly(A)+ RNA of ventral spinal cord, was screened with a mixture of eight oligonucleotides corresponding to the N-terminal sequence of pig brain ChoAcTase. Among five positive clones, one, pChAT-1, was identified as a ChoAcTase cDNA clone based on the following criteria. (i) This clone has an open reading frame coding for a protein of the size expected for ChoAcTase (640 amino acids). (ii) The amino acid composition deduced from the nucleotide sequence of this open reading frame matches that of purified porcine ChoAcTase. (iii) When subcloned in the T7 expression system, the corresponding RNA directs the synthesis in the rabbit reticulocyte lysate of a protein that is specifically immunoprecipitated by antibodies raised against ChoAcTase. (iv) Finally and most important, this corresponding RNA, when translated in the reticulocyte lysate, as well as in the Xenopus oocyte system, directs the synthesis of a protein displaying ChoAcTase activity. This activity is inhibited by the specific ChoAcTase inhibitor 4-(1-naphthylvinyl)pyridine. Comparison of porcine ChoAcTase sequence with that of Drosophila reveals 32% identity between these proteins, when the sequences are suitably aligned. pChAT-1 probe hybridizes with a porcine mRNA species that is at least 7000 nucleotides long, whereas the equivalent rat mRNA species is 3700 nucleotides long.     

Fingolimod, a sphingosine-1 phosphate receptor modulator, increases BDNF levels and improves symptoms of a mouse model of Rett syndrome

The functional relevance of brain-derived neurotrophic factor (BDNF) is beginning to be well appreciated not only in mice, but also in humans. Because reduced levels typically correlate with impaired neuronal function, increasing BDNF levels with well-tolerated drugs diffusing into the central nervous system may help in ameliorating functional deficits. With this objective in mind, we used the sphingosine-1 phosphate receptor agonist fingolimod, a drug that crosses the blood-brain barrier. In addition, fingolimod has recently been introduced as the first oral treatment for multiple sclerosis. In cultured neurons, fingolimod increases BDNF levels and counteracts NMDA-induced neuronal death in a BDNF-dependent manner. Ongoing synaptic activity and MAPK signaling is required for fingolimod-induced BDNF increase, a pathway that can also be activated in vivo by systemic fingolimod administration. Mice lacking Mecp2, a gene frequently mutated in Rett syndrome, show decreased levels of BDNF, and fingolimod administration was found to partially rescue these levels as well as the size of the striatum, a volumetric sensor of BDNF signaling in rodents. These changes correlate with increased locomotor activity of the Mecp2-deficient animals, suggesting that fingolimod may improve the functional output of the nervous system, in addition to its well-documented effects on lymphocyte egress from lymph nodes.