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.

Assessment of the estrogenic activity of phytoestrogens isolated from bourbon and beer.

Phytoestrogenic substances have previously been isolated and identified in two alcoholic beverages: bourbon and beer. To delineate the relative potencies of the estrogenic substances of plant origin thus far identified in these commonly consumed alcoholic beverages, we evaluated the ability of biochanin A, beta-sitosterol, genistein, and daidzein to bind to cytosolic estrogen receptor binding sites. The in vitro studies demonstrated that each of the contained substances was capable of effectively competing for cytosolic estrogen receptor binding sites of rat liver and uterus. Further, the two phytoestrogenic constituents of bourbon, beta-sitosterol and biochanin A, were less potent than those present in beer. Given the high concentration of beta-sitosterol in bourbon, we chose to evaluate the estrogenicity of beta-sitosterol in vivo using ovariectomized rats. beta-sitosterol was administered either daily or intermittently at 3 doses, based on amounts previously determined to be present in bourbon. The in vivo studies demonstrated that beta-sitosterol is capable of producing a weak estrogenic effect only at the lowest dose (6.2 micrograms/dl) administered intermittently. These responses suggest that beta-sitosterol may be weakly estrogenic at low doses, but is unable to maintain such an effect at higher doses.

Isolation and identification of phytoestrogens from beer.

Two estrogenic substances of plant origin have been identified in beer using gas chromatography/mass spectrometry. These phytoestrogens, daidzein and genistein, have previously been shown to be biologically active in animals. Confirming the presence of biologically active phytoestrogens in beer and their possible presence in other beverages, suggests that there may be clinically significant effects related to sustained exposure to phytoestrogens contained in alcoholic beverages.

Quantitation of beta-sitosterol in bourbon.

Four phytoestrogens have previously been isolated and identified in alcoholic beverages. Before studies to evaluate the degree of estrogenicity of these substances can be performed, it is necessary to determine appropriate doses to be administered to experimental animals. Because beta-sitosterol is the most plentiful, being present in bourbon at microgram/dl quantities, we have chosen to begin our quantitation work with this compound. The variability of the amount of beta-sitosterol contained in various brands of bourbon and in different lots of the same brand of bourbon have been assessed using combined gas chromatography/mass spectrometry (GC/MS) for quantitation following a simplified procedure to extract compounds of interest from bourbon.

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.

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.

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.

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.

Biologically active phytoestrogens are present in bourbon.

The nonethanol congeners of bourbon have been found to possess estrogenic activity when tested using an in vivo oophorectomized rat bioassay, as well as an in vivo estrogen receptor assay system. The phytoestrogen, biochanin A, as well as the plant sterol, beta-sitosterol, were identified in the bourbon preparation using gas chromatography/mass spectrometry. These findings, using three methodological approaches, demonstrate that bourbon contains at least one biologically active phytoestrogen and suggest that the effects of alcoholic beverage use or abuse, particularly as they relate to endocrine systems, should not be viewed as resulting solely from exposure to ethanol.

Discriminant validity of the Crown-Crisp Experiential Index.

The discriminative power of the CCEI subscales was examined. Several approaches were undertaken on the responses from subjects in three neurotically disturbed groups and a normal control group. Analyses indicated that simple cut-off points could discriminate effectively an 'adjusted-neurotic' dimension; simple cut-off points were relatively more difficult to develop for discrimination among the three neurotically disturbed groups. Discriminant analysis of the CCEI subscales indicated that approximately 74 per cent of all subjects could be classified correctly. The OBS and HYS subscales were not found to be effective discriminators among the four groups. While that finding may question the utility of those scales, an alternative explanation was proposed in terms of the characteristics of the present samples.

Separation and identification of phytoestrogenic compounds isolated from bourbon.

There is considerable evidence that several plant metabolites have estrogenic properties. Given that many alcoholic beverages are made from plants which have been shown to possess estrogenic activity, we considered the possibility that alcoholic beverages may contain estrogenically active substances. To evaluate this hypothesis we first extracted and then used gas chromatography/mass spectrometry to identify two phytoestrogens, biochanin A and beta-sitosterol in the bourbon extracts. Based on these findings we suggest that the feminization observed in chronic male alcoholics with liver disease may reflect, at least in part, the presence of biologically active phytoestrogens in the alcoholic beverages they consume.

Effect of hypobaric oxygen and oleic acid on respiration of Staphylococcus aureus.

The effect of hypobaric oxygen, with oleic acid in the nutrient substrate, on respiration and slime production by a pulmonary isolate of Staphylococcus aureus was investigated. Under hypobaric, but not normal oxygen pressure, the addition of oleic acid to the nutrient broth caused the bacteria to drastically diminish their demand for oxygen and initiate the secretion of extrapolymeric substances (slime). The decrease in oxygen demand was found to result from impairment of the capacity to reduce and oxidize the coenzyme NAD. Prior to the initiation of slime production, the rate of oxidation exceeded the rate of reduction of the coenzyme, whereas with slime production the rate of reduction was greatest. This could result in elevation of the cellular NADH, which could stimulate gluconeogenesis and thereby increase the synthesis of the carbohydrate component of the slime. The results suggest that staphylococcal infections, such as those of the pulmonary tract in cystic fibrosis and essential fatty acid deficiency, may occur in response to a peculiar chemical environment.

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.

Vitamin K (menaquinone) biosynthesis in bacteria: purification and probable structure of an intermediate prior to o-succinylbenzoate.

The first aromatic intermediate in the menaquinone biosynthetic pathway is o-succinylbenzoate (OSB); it is formed from chorismate/isochorismate and 2-ketoglutarate. Cell-free extracts of menD+ E. coli strains synthesize an intermediate, "X", which is converted to OSB by extracts of menC+ cells. "X" has been purified to near homogeneity by HPLC. On treatment with acid, it yields both OSB and succinylbenzene (SB). This and other data, suggest that "X" has the structure, 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate (I).

A factorial analysis of BDI scores.

Undertook a factorial analysis of the BDI on a sample of 214 male cardiac outpatients. The factor structure yielded three psychologically distinct dimensions interpreted as negative self-attitudes, physiological symptoms and sadness. The sample was divided into depressed and nondepressed subgroups in order to investigate whether the BDI factor structure is dependent on the range of BDI scores selected. While the first two factors from the nondepressed group's scores mimicked those for the full sample, in general the subgroups' factor structures provided no clear interpretation.

A statistical audit of the clinical utility of the 168 version of MMPI.

Measured MMPI protocols from 347 female and 563 male psychiatric patients according to the standard form and the 168 version. Clinical scales were derived and profiles were classified using the procedure of Marks, Seeman, and Haller (1978). Approximately 50% agreement between MMPI-168 and full scale profiles was obtained. Most disagreements tended to be clinically important. On a simple psychopathology/nonpsychopathology dichotomy, between 75 and 80% agreement occurred.

Face validity vs. item subtlety in the MMPI D scale.

The distinction between item subtlety and face validity ( Holden & Jackson, 1979) provided the basis to reevaluate findings for subtle items in the MMPI D scale (N = 214). Results indicated that the inclusion of nonpathological items in the D scale did not lead to greater predictive validity of depression criteria. The need for substantive considerations in scale construction was emphasized further.