Peroxisomal proliferator activated receptor-γ deficiency in a Canadian kindred with familial partial lipodystrophy type 3 (FPLD3)

Background  

Familial partial lipodystrophy (Dunnigan) type 3 (FPLD3, Mendelian Inheritance in Man [MIM] 604367) results from heterozygous mutations in PPARG encoding peroxisomal proliferator-activated receptor-γ. Both dominant-negative and haploinsufficiency mechanisms have been suggested for this condition.     

Cortical dendritic pathology in human immunodeficiency virus encephalitis.

Previous neuropathological and morphometric studies of the cerebral cortex of patients with human immunodeficiency virus encephalitis (HIVE) have shown a decrease in the population of large neurons, moderate loss in synaptophysin immunoreactivity, and pathological changes in dendrites. To further characterize and quantify alterations in the dendritic tree of neocortical pyramidal neurons, we performed a modified Golgi impregnation technique on Formalin fixed blocks from the frontal cortex of 5 HIVE cases, 5 human immunodeficiency virus seropositive control cases without encephalitis, and 5 human immunodeficiency virus seronegative controls. Apical dendrites of HIVE cases were dilated, vacuolated, and tortuous with decreased length and branching. Basal and oblique dendrites also showed these alterations, but to a lesser extent. Some dendrites presented lacunae and filopodia consistent with remodeling. Computer aided quantification of HIVE cases showed a 40-60% decrease in spine density throughout the entire length of dendrites. Laser confocal imaging of Golgi impregnated sections displayed aberrant spines in regions of abnormal second order dendritic branches. These observations support the role of primary dendritic damage in HIVE in contrast to other neurodegenerative disorders where the primary pathology is presynaptic.     

Storage of thawed cryoprecipitated AHF is better at room temperature than at 1 degree C to 6 degrees C for factor VIII content

Before November 1989, both the American Association of Blood Banks and the Food and Drug Administration required that thawed cryoprecipitated antihemophilic factor (AHF) should be used immediately or be stored at room temperature and administered within 6 hours. However, in November 1989, the American Association of Blood Banks changed the requirement for storage of thawed cryoprecipitated AHF from room temperature to 1 degree C to 6 degrees C, while the Food and Drug Administration still required thawed cryoprecipitated AHF to be stored at room temperature. The present study was designed to measure and compare the factor VIII activity in 10 bags of thawed cryoprecipitated AHF that were split into aliquots and stored at room temperature and at 1 degree C to 6 degrees C. At 6 and 24 hours after thawing, the mean factor VIII activities (% of normal) of the room temperature-stored cryoprecipitated AHF were 741% and 680% vs 650% and 608% for the 1 degree C- to 6 degrees C-stored cryoprecipitated AHF (P less than .05 at 6 hours and P = .11 at 24 hours). The storage of thawed cryoprecipitated AHF at 1 degree C to 6 degrees C also resulted in precipitation of both factor VIII and fibrinogen. These data show that it is better to store thawed cryoprecipitated AHF at room temperature vs 1 degree C to 6 degrees C for factor VIII activity. These data also suggest that adequate levels of factor VIII are maintained in thawed cryoprecipitated AHF that has been stored at room temperature for up to 24 hours.     

Evaluation of United States-licensed human immunodeficiency virus immunoassays for detection of group M viral variants

Six Food and Drug Administration (FDA)-licensed human immunodeficiency virus type 1 (HIV-1) and HIV-1/2 immunoassays, including five enzyme immunoassays and one rapid test, were challenged with up to 250 serum samples collected from various global sites. The serum samples were from individuals known to be infected with variants of HIV-1 including group M subtypes A, B, B', C, D, E, F, and G and group O. All immunoassays detected the vast majority of samples tested. Three samples produced low signal over cutoff values in one or more tests: a clade B sample, an untypeable sample with a low antibody titer, and a group O sample. It is concluded that HIV-1 immunoassays used in the United States are capable of detecting most HIV-1 group M variants.     

Embryo donation: attitudes toward donation procedures and factors predicting willingness to donate

BACKGROUND: The aim of the study was to assess infertile couples' attitudes toward the procedures of embryo donation (ED) and to identify factors predicting interest in donation. METHODS: Fifty-one couples who had received IVF treatment and had subsequently had embryos cryopreserved for >3 years were located and sent written information about the procedures for ED and possible implications of donation. A total of 49 couples agreed to participate in the study with 36 women and 31 men subsequently returning questionnaires describing their reasons for not claiming unused embryos and attitudes towards ED. RESULTS: Patients were supportive of donor screening procedures, but less comfortable sharing non-identifying information. Comfort levels declined as information became increasingly personal. Support for unconditional (i.e. the donation of embryos without conditions attached) and conditional (i.e. where couples could limit the donation of their embryos to persons/couples according to their preferences) models of donation was highly polarized and a substantial minority expressed strong opposition to each model. Willingness to donate was associated with greater comfort about disclosing personal information, a desire to know the outcome of donation and willingness to have future contact with a child, but not with current family size. CONCLUSIONS: Comfort in sharing information with a recipient couple is more important than acceptance of screening procedures, or attainment of family size goals in predicting willingness to donate embryos. Offering the option of conditional donation could increase the acceptability of ED for some patients.     

Detecting Candida albicans in human milk

Procedures for diagnosis of mammary candidosis, including laboratory confirmation, are not well defined. Lactoferrin present in human milk can inhibit growth of Candida albicans, thereby limiting the ability to detect yeast infections. The inhibitory effect of various lactoferrin concentrations on the growth of C. albicans in whole human milk was studied. The addition of iron to the milk led to a two- to threefold increase in cell counts when milk contained 3.0 mg of lactoferrin/ml and markedly reduced the likelihood of false-negative culture results. This method may provide the necessary objective support needed for diagnosis of mammary candidosis.     

Absence of demonstrable phospholipid turnover in B cells stimulated by low mitogenic concentrations of dextran-anti-immunoglobulin conjugates.

Previously we have demonstrated that when anti-immunoglobulin (Ig) is conjugated to high molecular weight dextran (Dex) it stimulates B cell activation at pg/ml concentrations in the absence of detectable phosphoinositide hydrolysis or increases in intracellular ionized calcium. To study carefully whether anti-Ig-Dex recruited a phosphoinositide-dependent pathway of activation, we stimulated B cells that were labeled with 32P and [3H]glycerol with anti-Ig-Dex conjugates at concentrations ranging from 1-1 x 10(-4) micrograms/ml. Thirty seconds to thirty minutes after stimulation lipids were extracted and analyzed by thin layer chromatography and spots correlating with known lipid standards were isolated and counted. There was a four- and tenfold increase in the ratio of 32P/3H incorporated into phosphatidic acid (a metabolite of diacylglycerol) and phosphatidylinositol, respectively, when cells were stimulated with 0.1-1.0 microgram/ml of anti-Ig-Dex for 30 min. Below 1 ng/ml there was no detectable increase in the turnover of these metabolites despite the fact that in parallel cultures B cells were stimulated to proliferate by this concentration of anti-Ig-Dex. To determine whether a cAMP-dependent pathway was recruited by low concentrations of conjugates, we evaluated cAMP levels from B cells that were stimulated with anti-Ig-Dex for 5-60 min using a radioimmunoassay. While cholera toxin stimulated a 50-100-fold increase in the levels of cAMP, we observed no alteration in cAMP in anti-Ig-stimulated cells. These results support and extend our previous findings by demonstrating that B cell activation that is induced by cross-linking of surface Ig may not stimulate phosphoinositide-dependent or cAMP-dependent pathways of activation. Possible alternative mechanisms of activation will be discussed.     

Psychophysiological Predictors of Attentional Dysfunction in Children with Congenital Heart Defects

Cardiac responses to non-signal stimuli and to signal stimuli in a vigilance task were examined in children born with congenital heart defects (CHD), and in normal and attention deficit disordered (ADD) subjects. Overall task performance was lower in subjects with heart defects and in the ADD group. Cardiac measures revealed that normal children displayed significantly larger heart rate deceleration to the target stimuli than did either of the clinical groups. Moreover, although no group differences were observed in the cardiac response to non-signal auditory stimuli, exaggerated heart rate deceleration was observed to vibrotactile stimuli in both the clinical groups. Regression analyses revealed that the magnitude of the cardiac response to somatosensory stimuli was predictive of task performance (both within and between subject groups), with larger responses associated with higher error rates and lower perceptual sensitivity. Results were suggestive of a predictive relationship between somatosensory reactivity and neuropsychological maturation.     

Characterization of a single base-pair deletion in neurofibromatosis type 1

The gene which is responsible for neurofibromatosis type 1 (NF1)is located on chromosome 17 (17q11.2). The NF1 gene is approximately350 kilobases (kb) long and exhibits an extremely high mutationrate; therefore, most patients are expected to have unique mutations.To date, relatively few mutations have been well characterized.We report here a de novo single base pair (bp) deletion in oneNF1 allele in a patient diagnosed with NF1 and leukemia. Wefurther characterized this mutation at the RNA level by allele-specificoligonucleotide (ASO) hybridization which demonstrated thatthe mutant allele is transcribed.