Vaccine-associated varicella and rubella infections in severe combined immunodeficiency with isolated CD4 lymphocytopenia and mutations in IL7R detected by tandem whole exome sequencing and chromosomal microarray.

In areas without newborn screening for severe combined immunodeficiency (SCID), disease-defining infections may lead to diagnosis, and in some cases, may not be identified prior to the first year of life. We describe a female infant who presented with disseminated vaccine-acquired varicella (VZV) and vaccine-acquired rubella infections at 13 months of age. Immunological evaluations demonstrated neutropenia, isolated CD4 lymphocytopenia, the presence of CD8(+) T cells, poor lymphocyte proliferation, hypergammaglobulinaemia and poor specific antibody production to VZV infection and routine immunizations. A combination of whole exome sequencing and custom-designed chromosomal microarray with exon coverage of primary immunodeficiency genes detected compound heterozygous mutations (one single nucleotide variant and one intragenic copy number variant involving one exon) within the IL7R gene. Mosaicism for wild-type allele (20-30%) was detected in pretransplant blood and buccal DNA and maternal engraftment (5-10%) demonstrated in pretransplant blood DNA. This may be responsible for the patient's unusual immunological phenotype compared to classical interleukin (IL)-7Rα deficiency. Disseminated VZV was controlled with anti-viral and immune-based therapy, and umbilical cord blood stem cell transplantation was successful. Retrospectively performed T cell receptor excision circle (TREC) analyses completed on neonatal Guthrie cards identified absent TREC. This case emphasizes the danger of live viral vaccination in severe combined immunodeficiency (SCID) patients and the importance of newborn screening to identify patients prior to high-risk exposures. It also illustrates the value of aggressive pathogen identification and treatment, the influence newborn screening can have on morbidity and mortality and the significant impact of newer genomic diagnostic tools in identifying the underlying genetic aetiology for SCID patients.

How valine deprivation and its reversal affect fatty acid metabolism in HeLa cells.

A protocol based on radio gas chromatography demonstrates that when HeLa cells are deprived of valine for short periods of time (6-7.5 h), their overall fatty acid biosynthetic activity is depressed after a latency of a few hours. The transfer of newly synthesized fatty acyl units to phospholipids is curtailed much faster than their transfer to triacyglycerols. Despite the cut-back in fatty acid biosynthesis, valine deprivation causes a lipid accumulation in the cells. Valine deprivation appears to affect de novo synthesis of fatty acid units from acetate more rapidly than desaturation and elongation. When valine is returned to the valine-deprived culture, overall fatty acid biosynthesis is resumed well within 2 h. Newly synthesized fatty acyl units are transferred to both the phospholipids and the 1,2-diacylglycerols of the cells but not initially to the triacylglycerols.

Influence of valine deprivation and its reversal on fatty acid metabolism in HeLa cells.

The effects that amino acid starvation and re-supplementation have on fatty acid metabolism in HeLa cells have been studied using radio gas chromatographic techniques. Deprivation of valine for 13.5 h caused fatty acid de novo biosynthesis, elongation and desaturation to cease. This effect was reversed within 5 h by adding valine back to the culture. During deprivation accumulation of triacylglycerol occurred. The return of valine to the culture caused compositional changes in the triacylglycerols and phosphatidylcholines.

Abnormal fatty acid composition and impaired oxygen supply in cystic fibrosis patients.

Impaired oxygen supply and deteriorating health, in cystic fibrosis patients, correlates with abnormal changes in the fatty acid composition of blood lipids. As the proportion of oleates increases and that of linoleates decreases, erythrocyte membrane interference with the formation of intracellular oxyhemoglobin increases and arterial oxygen pressure decreases. The physical-chemical basis for these changes seems to be that oleic and linoleic acid differ in their ability to undergo reversible oxygenation in response to changes in oxygen pressure. The oxygen complex of linoleic acid dissociates at relatively high pressures, whereas that of oleic dissociates only at low pressures. Accordingly, excessive substitution of oleic for linoleic acid in membrane lipids would be expected to decrease the intracellular oxygen pressure to a level where hemoglobin oxygenation and any other oxygen-requiring processes would be impaired.

Is social skills performance a correlate of schizophrenia subtypes?

53 inpatients with a DSM-III diagnosis of schizophrenia were assessed in the week prior to discharge from hospital on measures of social skills performance and on severity of positive and negative symptoms. A cluster analysis based on the total positive and negative symptom scores resulted in three groups. The group with the least negative symptoms exhibited the best social skills performance. The findings add a further dimension to the validity of the subtyping of schizophrenia on the basis of positive and negative symptoms.

Negative symptoms and social skills performance in schizophrenia.

The present study aimed to determine whether the negative symptoms of patients with schizophrenia were better predictors of social competence than a range of other variables pertaining to demographics, illness, hospitalization, and premorbid functioning. Independent raters assessed social skills performance on a video-taped role-play test and 5 min conversation in 53 inpatients with a DSM-III diagnosis of schizophrenia. Patients' social skills were also assessed by ward nurses. Project clinicians assessed depression, medication side effects and positive and negative symptoms. Multiple-regression analyses demonstrated that, generally, negative symptoms were the best predictors of social skills performance.

Assessment of articulated thoughts in social anxiety: modification of the ATSS procedure.

In the present study an assessment strategy was developed which adapted the Articulated Thoughts during Simulated Situations (ATSS) paradigm devised by Davison, Robins & Johnson (1983). That strategy was applied to the assessment of social anxiety. Responses of 10 socially anxious and 10 non-anxious males were compared as they imagined themselves participating in videotaped simulations of heterosocial interactions. Each time the subject was aware of a reaction to the events depicted, he stopped the videotape, and then articulated his thoughts. Consistent with cognitive conceptualizations of social anxiety, the articulated thoughts of anxious males were distinguished by a greater focus upon the self in general and by a concentration upon irrational concerns in particular. In contrast, non-anxious males provided larger proportions of thoughts directed towards the environment and in particular, provided more positive thoughts both about other persons and their interactions in general. The theoretical and methodological implications of the data are discussed.

The role of interpersonal perception in dyadic adjustment.

The discrepancy between the way individuals perceive themselves and the way they are perceived by their partners has been proposed as an indicator of dyadic adjustment. The present study employed the CPI to investigate the relation of interpersonal perception within dyads and real similarity of spouses to marital satisfaction. The subjects were 20 married couples. Support was provided for the use of the real similarity-assumed similarity-accuracy paradigm in studies of interpersonal perception. No sex differences were found in the ability of individuals to predict their spouse's responses on the CPI. Accuracy of prediction was correlated significantly with scores on the Hogan Empathy scale for males, but not for females. Conversely, accuracy was related significantly to dyadic adjustment in the case of females, but not males. Real similarity also was correlated positively with dyadic adjustment. Avenues for further research are suggested.

A manifest anxiety scale from the MMPI-168.

An established measurement of anxiety that uses MMPI items is Taylor's Manifest Anxiety Scale (MAS). Because the items on the MAS are distributed over the entire MMPI, this measure is not available from a popular short form, the MMPI-168. A new composite anxiety scale that comprises items on the MMPI-168 is described, together with relevant normative statistics and its relationship with other MMPI scales.

Disposition of Mycophenolic Acid, Brevianamide A, Asperphenamate, and Ergosterol in Solid Cultures of Penicillium brevicompactum.

When Penicillium brevicompactum was grown between layers of dialysis membrane on Czapek-Dox agar for 3 days, no synthesis of mycophenolic acid, brevianamide A, asperphenamate, or ergosterol occurred. After removal of the uppermost membrane layer, aerial mycelium developed and all four metabolites were formed. The bulk of the mycophenolic acid that was formed was excreted into the medium, the bulk of the brevianamide A and asperphenamate was found in the aerial hyphae, and ergosterol was found in both vegetative and aerial mycelia.

Vesicle surface charge and polylysine modification of ultraviolet absorption by the olefinic bonds in charged lipid.

The results of electrical conductivity and ultraviolet absorption studies on bilayer vesicles, composed of various mixtures of saturated dipalmitoylphosphatidylcholine (DPPC)and unsaturated bovine brain phoaphatidylserine (PS), in the presence and absence of polylysine indicate the following. (i) The two kinds of lipid maintain a strong transbilayer segregation over a wide range of proportions. The charged lipid (PS) preferentially locates in the inner, at PS proportions of 33% or less, and in the outer layer of the membranes when its proportion is increased to 50%. (ii) At PS proportions of 33% of less, where DPPC is the major component of the outer layer, the ability of polylysine to modify ultraviolet absorption by the olefinic bonds in the PS depends on the fluidity of the phosphatidylcholine. At higher PS proportions, where PS preferentially locates in the outer layer, modification of the ultraviolet absorption spectrum of the lipid by polylysine occurs only when the surface charge of the vesicles is diminished by the addition of bivalent metal ions. (iii) The polylysine-induced change in the ultraviolet absorption spectrum of the olefinic bonds in the vesicles was found to be very similar to that induced by dispersing unsaturated fatty acids in water rather than dissolving them in a nonpolar solvent. This suggests that polylysine modification of the vesicles spectrum may be the result of deep hydrophobic penetration by the polypeptide causing hydration and(or) parallel alignment of the dipole moments of the absorbing chromophores.

Labelled acetone and levulinic acid are formed when [14C]acetate is being converted to mycophenolic acid in Penicillium brevicompactum.

Evidence is presented that is compatible with the hypothesis that the farnesyl unit involved in the biosynthesis of mycophenolic acid in Penicillium brevicompactum is degraded by two successive oxidative cleavages at the double bonds distal from the phthalide nucleus. Acetone and levulinic acid are two non-aromatic degradation products.

The effect of polypeptide-lipid interactions on the ultraviolet spectrum of the olefinic bonds of the lipid.

The effect of associating acidic and basic polypeptides with dilute suspensions of vesicles composed of various unsaturated phospholipids was assessed with regard to optical density and ultraviolet absorption. Associating basic polypeptides with phosphatidylserine, phosphatidylethanolamine, and phosphatidylglycerol vesicles, or acidic polypeptide with phosphatidylcholine vesicles, caused an increase in the optical density of the preparations, with no measurable effect on the intensity of the ultraviolet spectrum of the olefinic bonds of the lipid. Associating basic polypeptides with phosphatidylcholine vesicles, in addition to causing similar increases in optical density, resulted in a large decrease in the intensity of ultraviolet absorption by the olefinic bonds. This implies that the interaction between the basic polypeptides and phosphatidylcholine vesicles results in major alterations in the microenvironment of the olefinic bonds, which would require intimate association of the polypeptide with the ninth carbon region of the acyl chains. These observations support the conclusion, drawn from our earlier studies, that the association of basic polypeptides and liquid crystalline phase phosphatidylcholine vesicles is peculiar in that it involves a major hydrophobic component.

Naphthalenone production in Aspergillus parvulus.

The naphthalenones asparvenone and its 6-O-methyl ether are produced by Aspergillus parvulus during vegetative growth in batch-mode, shaken cultures in a glucose-glycine-salts medium. The secondary metabolites first appear around the time when hyphae of developing spores begin to make contact with each other, i.e. at a very early stage of culture development. Resuspension in new medium of mycelium that is producing the naphthalenones fails to inhibit production. When A. parvulus is grown in parallel on a glucose-glycine-salts medium and on a glucose-malt-peptone medium, the naphthalenones appear first in the richer medium despite the fact that biomass proliferation is relatively unrestricted in that medium. Radiolabelled [1-14C]-acetate is taken up quickly by the fungus (k = 0.09 min-1) and is incorporated effectively into the naphthalenones.

Reversible cryogenic alteration of the ultraviolet absorption spectra of the olefinic bonds in lipid membranes.

In earlier studies it was found that the association of basic polypeptides with lipid vesicles drastically altered ultraviolet absorption by the olefinic bonds of the lipid. Such an effect suggested that the polypeptide was increasing the polarity of the chromophore environment by either direct interaction with the acyl chains or by inducing their hydration. It is reported here that freeze-thaw cycling, which was expected to allow hydration of the olefinic-bond region of the membranes, caused the same spectral alteration as vesicle interaction with basic polypeptides. When these vesicles were subsequently placed under conditions that would be expected to accelerate the escape of water entrapped within the membranes (i.e., by placing them under vacuum or adding sucrose to establish a high osmotic gradient to their exterior), the absorption spectrum was rapidly restored to that for olefinic bonds in a nonpolar environment. Since placing the polylysine- dioleoylphosphatidylcholine (DOPC) vesicle interaction product under the same conditions restored the spectral intensity, at 190 nm, to between 80 and 85% of that for the lipid in a nonpolar environment, it seems that a major effect of polylysine on DOPC membranes may be though induction of hydration of their interior.

Composition of the saturated and monounsaturated fatty acids of Mycobacterium phlei.

Combined gas-liquid chromatography-mass spectrometry has been used to identify unusual fatty acids of Mycobacterium phlei. In addition to many normal saturated and monounsaturated fatty acids, series of iso, anteiso, 10-methyl, and (n-8)-methyl substituted fatty acids have been found and identified. These mid-chain branched acids may arise by methylation of monounsaturated acids followed (if necessary) by chain elongation.

Mass spectral discrimination between monoenoic and cyclopropanoid, and between normal, iso, and anteiso fatty acid methyl esters.

Measurement of the ratio of the intensity of the parent molecular ion to that of the parent molecular ion minus 32 (the mass of methanol) can distinguish between monoenoic and cyclopropanoid fatty acid methyl esters with the same carbon number. A similar technique can be used to distinguish between isomeric normal, iso, and anteiso fatty acid methyl esters.