HIV-1 gp41 heptad repeat 2 (HR2) possesses an amino acid domain that resembles the allergen domain in <Emphasis Type="Italic">Aspergillus fumigatus Asp f1</Emphasis> protein: review,hypothesis and implications

Enfuvirtide (ENF, T-20, Fuzeon) is the first synthetic peptide to be modeled according to the amino acid sequence of HIV-1 heptad repeat 2, which was used to treat cohorts of HIV-1-infected individuals who had failed to respond to treatment with the anti-HIV-1 cocktail HAART. It was reported that when injected subcutaneously, Enfuvirtide reduced viral RNA in patients’ blood by 1.96 log₁₀, leading to a subsequent increase in the number of CD4⁺ T cells in the blood. The drug treatment caused adverse effects at the injection site in a small number of treated individuals, and a gradual increase in IgE in the blood during prolonged treatment. Enfuvirtide was approved for treatment of HIV-1 patients who developed resistance to HAART. The present review attempts to explain the adverse effects of Enfuvirtide at the skin site of injection, and the gradual increase in IgE in patients’ blood during treatment. These phenomena were reported to resemble the effect of allergens that cause asthma in humans. It is hypothesized that since the amino acid domain of the Asp f1 allergen from Aspergillus fumigatus was identified in the N-terminus of an 18 kDa protein, it may be useful to compare Asp f1 peptide aa 7–22 from the β-hairpin sequence to the β-hairpin sequence of the heptad repeat 2 of HIV-1 gp41. The comparison revealed that the amino acid sequence resembles part of the Asp f1 aa 7–22 allergenic domain. The heptad repeat 1 of gp41 also resembles the fungal allergen. It is suggested that the Enfuvirtide peptide be tested experimentally to determine if ENF peptide is capable of binding to IgE antibodies from Enfuvirtide-treated, HIV-1-infected patients, and whether the HR2-derived peptide is capable of inducing basophils that were isolated from healthy individuals and from ENF-treated and untreated HIV-1 patients to release histamine and IL-4.     

Early-life factors and adult anti-Müllerian hormone levels

Journal of Assisted Reproduction and Genetics - This study aims to examine whether early-life factors are associated with adult ovarian reserve, measured by anti-Müllerian hormone (AMH)...     

Familial aggregation of red blood cell membrane fatty acid composition: the Kibbutzim Family Study

The fatty acid composition of membranes plays an important role in health and diseases. Whether genetic factors play a role in interindividual variability in membrane fatty acid levels has received limited attention. Using variance decomposition methods, we estimated the heritability of red blood cell (RBC) membrane fatty acids in an unselected population sample of 80 families (205 male and 212 female subjects) living in kibbutz settlements in Israel. Fatty acid levels were measured by gas chromatography. We estimated that polygenes explained 40% to 70% of the sex- and age-adjusted interindividual variability in all RBC fatty acids: saturated, monounsaturated, and polyunsaturated. The heritability estimates remained very similar after further adjustment for smoking, alcohol consumption, physical activity, lipoproteins, body mass index, waist to hip ratio, education, and religiosity. In bivariate genetic analyses, we observed positive genetic correlations for the fatty acid pairs 20:4n6-22:6n3 and 20:5n3-22:6n3, and negative genetic correlations for the pairs 16:0-20:4n6, 16:0-22:6n3, 18:1n9-20:3n6, 18:2n6-20:4n6, 18:2n6-24:0, and 20:3n6-20:4n6, suggesting that shared effects of the same sets of loci account for 12% to 30% of the additive genetic variance in these pairs of fatty acids. This study suggests a considerable polygenic component for all RBC membrane fatty acids and provides evidence that shared genetic effects account for the additive genetic variance in various fatty acid pairs. Future studies are needed to map the genes underlying the interindividual variation in these inherited phenotypes.     

Dissociation of cognitive from affective components of theory of mind in schizophrenia

Patients suffering from schizophrenia show impaired emotional and social behavior, such as misinterpretation of social situations and lack of theory of mind. However, there is conflicting evidence regarding their ability to perform on theory of mind tasks. Based on previous findings with patients suffering from prefrontal damage, the present study suggests that the behavioral deficit of schizophrenic patients may be due to impaired 'affective theory of mind' abilities, rather than to a general impairment in theory of mind. To test this hypothesis we assessed the ability of 22 schizophrenic patients and 55 age-matched healthy controls, to judge first and second order affective vs. cognitive mental state attribution, based on eye gaze. The relationships between negative and positive symptoms of schizophrenia, and affective and cognitive theory of mind were also assessed. Results indicated that while healthy controls made fewer errors on affective as compared to cognitive theory of mind conditions, schizophrenic patients showed a less prominent trend. Although the pattern of reaction time did not differ significantly between groups, the patients made significantly more errors in the affective conditions, as compared to controls. Furthermore, correlation analysis indicated that impaired affective theory of mind in these patients correlated with their level of negative symptoms. These results indicate that individuals with high level of negative symptoms of schizophrenia may demonstrate selective impairment in their ability to attribute affective mental states. These findings offer new insight into the affective facets of social behavior that may underlie the profound behavioral disturbances observed in schizophrenia.     

Reversible Inhibition of Herpes Simplex Virus Replication by Hydroxyurea

Hydroxyurea, at a concentration of 5 x 10(-2) M, inhibits the replication of herpes simplex deoxyribonucleic acid (DNA) in the nuclei of infected cells. As a result, the synthesis of infectious virus progeny was prevented. The presence of parental viral DNA genomes in inhibited cells led to the synthesis of the viral structural peptides. The inhibitory effect of hydroxyurea was reversible; after washing the cells free from hydroxyurea, virus progeny appeared after a lag of 3 h. Upon resumption of viral DNA replication, the content of radioactive viral structural peptides gradually increased in parallel with the increase in mature virions. It is concluded that the information for the synthesis of viral structural peptides is transcribed from the parental DNA genomes.     

Cardiac abnormalities in the Bardet-Biedl syndrome: Echocardiographic studies of 22 patients

The Bardet-Biedl syndrome is an autosomal recessive disorder of polydactyly, obesity, tapetoretinal degeneration, mental retardation, hypogenitalism, and renal involvement. A high incidence of congenital and acquired heart disease was reported in the former “Laurence-Moon-Biedl-Bardet” syndrome. However, since the establishment of the Bardet-Biedl syndrome as a separate clinical entity, cardiac involvement has not been evaluated in this disorder. We have performed echocardiographic studies on 22 patients with the Bardet-Biedl syndrome from three extended, highly inbred Bedouin families. In addition to previously reported congenital heart defects we have observed hypertrophy of the interventricular septum and dilated cardiomyopathy. Our findings of cardiac involvement in 50% of the cases suggest that echocardiographic examination should be included in the clinical evaluation and follow-up of patients with Bardet-Biedl syndrome. © 1994 Wiley-Liss, Inc.     

Fatal pneumococcal sepsis following flexible bronchoscopy in an immunocompromised infant

A 5-month-old boy who suffered from a leukocyte chemotactic defect underwent flexible bronchoscopy for persistent right upper lobe atelectasis and tachypnea. Ten hours after the procedure he developed fulminant sepsis, and he died 16 hrs after bronchoscopy. Streptococcus pneumoniae (serotype 23) grew from the bronchoalveolar lavage fluid and from the blood culture taken during the sepsis work-up. We, therefore, suggest administering prophylactic antimicrobial therapy immediately following bronchoscopy to immunosuppressed children, even when an acute respiratory infection is not suspected, in order to prevent bacteremia and sepsis. Pediatr Pulmonol. 1998; 25:390–392. © 1998 Wiley-Liss, Inc.