Griscelli Syndrome Type 3: Two New Cases and Review of the Literature

A 3‐year‐old Arab boy with a history of hypoplastic left heart syndrome was referred to the pediatric dermatology clinic at Sheba Medical Center for evaluation of hypomelanosis, manifested by fair skin pigmentation and silvery‐grey hair, eyebrows, and eyelashes. The child had one older brother with similar hypopigmentation and another older brother who had died of congenital heart disease. The child had no history of neurologic deficits or immunodeficiency and no additional findings on clinical evaluation.     

The home-self and out-of-home placement: The home concept among adults educated in their childhood at a residential care setting

This study proposes to examine the phenomenology of home among 46 Israeli adults who had been deemed "at-risk children" and removed from their home by court order in their childhood on the grounds of parental mistreatments, such as abuse and neglect. For a comprehensive understanding of the long-term impact of out-of-home placement, adults of different ages were interviewed. The research findings reflect the close connection between home concept and self-concept, a long-standing internal dialectic between the home that did not exist and the home (as an internal-emotional space) that the adults would have liked to have. Furthermore, our findings reveal what we term the life career of the home concept, that is, the various diachronic phenomenological definitions that adults grant to the home-self in childhood, anchored in the family home, during their time in a residential care setting, their adolescence, and their adulthood. The discussion addresses the unique self-concept and home concept of care leavers.     

Switching yeast from meiosis to mitosis: double-strand break repair, recombination and synaptonemal complex

Background:

When Saccharomyces cerevisiae cells that have begun meiosis are transferred to mitotic growth conditions (‘return-to-growth’, RTG), they can complete recombination at high meiotic frequencies, but undergo mitotic cell division and remain diploid. It was not known how meiotic recombination intermediates are repaired following RTG. Using molecular and cytological methods, we investigated whether the usual meiotic apparatus could repair meiotically induced DSBs during RTG, or whether other mechanisms are invoked when the developmental context changes.

Results:

Upon RTG, the rapid disappearance of meiotic features—double-strand breaks in DNA (DSBs), synaptonemal complex (SC), and SC related structures—was striking. In wild-type diploids, the repair of meiotic DSBs during RTG was quick and efficient, resulting in homologous recombination. Kinetic analysis of double-strand breakage and recombination indicated that meiotic DSB formation precedes the commitment to meiotic levels of recombination. DSBs were repaired in RTG in dmc1, but not rad51 mutants, hence repair did not occur by the usual meiotic mechanism which requires the Dmc1 gene product. In haploids, DSBs were also repaired quickly and efficiently upon RTG, showing that DSB repair did not require the presence of a homologous chromosome. In all strains examined, SC and related structures were not required for DSB repair or recombination following RTG.

Conclusions:

At least two pathways of DSB repair, which differ from the primary meiotic pathway(s), can occur during RTG: One involving interhomologue recombination, and another involving sister-chromatid exchange. DSB formation precedes commitment to recombination. SC elements appear to prevent sister chromatid exchange in meiosis.

     

Expression of human CD81 in transgenic mice does not confer susceptibility to hepatitis C virus infection

We previously demonstrated that hepatitis C virus (HCV) binds to human CD81 through the E2 glycoprotein. Therefore, expression of the human CD81 molecule in transgenic mice was expected to provide a new tool to study HCV infection in vivo, as the chimpanzee is the only species currently available as a laboratory animal model that can be infected with HCV. We produced transgenic mice expressing the human CD81 protein in a wide variety of tissues. We confirmed binding of recombinant E2 glycoprotein to the liver tissue as well as to thymocytes and splenic lymphocytes in the transgenic mice. We inoculated chimpanzee plasma infected with HCV into these animals. None of these transgenic animals showed evidence of viral replication. Furthermore, human CD81 transgenic mice that lack expression of endogenous mouse CD81 were also resistant to HCV infection. We conclude that expression of human CD81 alone is insufficient to confer susceptibility to HCV infection in the mouse. The presence of additional possible factors for HCV infection is discussed.     

HLA and alopecia areata in Jerusalem

A study of 46 patients with Alopecia areata in Jerusalem showed a significant increase in the frequency of HLA-B18 (23.9%) as compared to the control population (7.4%) with a relative risk of 3.9%. This association of HLA-B18 with AA was independent of the origin of patients, sex, age of onset and type of alopecia areata.     

HLA–DRw4 in Pemphigus Vulgaris Patients in Israel

Pemphigus vulgaris (PV) is relatively common in Jews. Three HLA antigens were significantly more frequent in 39 Israeli Jewish PV patients than in controls: A26 – 59% vs 20%; Bw38 – 61% vs 20%; and DRw4 – 90% vs 38%. The joint occurrence of A26–Bw38–DRw4 was observed in 46% of PV patients and in 10% of controls. Similar results were recently reported for Jews in the Los Angeles area. Yet, when our patient sample was grouped into Ashkenazi and non-Ashkenazi Jews, it was evident that each of the three antigens had a higher frequency both in Ashkenazi patients and controls as compared to non-Ashkenazim. The relative risk for DRw4 in Ashkenazim was 33.8 as compared to 14.4 in the total sample of Israeli PV patients. The phenotype A26–Bw38–DRw4 was present in 57% of Ashkenazi patients and in 13% of controls. Ashkenazi Jews have the highest prevalence of PV, and HLA associations were strongest with Ashkenazi PV patients. These associations were with three antigens, all of high frequency in that group.     

The mechanism of action of soluble lymphocytic mediators: I. A pulse exposure test for the measurement of macrophage migration inhibitory factor

Culture supernatants containing macrophage migration inhibitory factor (MIF) were obtained by incubating lymphocytes of guinea-pigs, immunized with Freund's complete adjuvant (FCA), with tuberculin PPD in vitro. Exposure of normal peritoneal macrophages to MIF-containing supernatants for 2 hours at 37° (pulse exposure), followed by suspension in culture medium and transfer to capillaries, resulted in inhibition of migration in vitro for the next 24 hours. No inhibition was seen when macrophages were incubated with MIF at 4°. On the other hand when exposure to MIF at 4° was followed by incubation of the cells for 2 hours at 37° in culture medium, in the absence of MIF, inhibition of migration was obtained. These results indicate that: (a) macrophages possess a specific receptor able to bind MIF at either 4° or 37°, and (b) inhibition of migration by receptor bound MIF requires a temperature-dependent active process, the nature of which remains unknown.

Passage of lymphocytes through columns of glass beads resulted in a population of cells with intact or heightened MIF-forming ability, as assessed by both conventional and pulse exposure techniques.

     

Treatment variables in relation to oocyte maturation: Lessons from a clinical micromanipulation-assisted in vitro fertilization program

Objective: In an effort to understand the mechanism underlying the improved pregnancy rate observed in IVF cycles when gonadotropin-releasing hormone analogues (GnRH-a) are applied, we investigated a possible relationship between treatment variables and oocyte-nuclear maturity. Design: Nuclear maturity was retrospectively assessed in cumulus-free, denuded oocytes, obtained from women undergoing micromanipulation-assisted IVF treatment following controlled ovarian hyperstimulation with GnRH-a and menotropins. Setting: The setting was the infertility and IVF unit of a tertiary academic medical center. Participants: Two hundred twenty-one patients underwent 435 treatment cycles. Main Outcome Measure: This was the proportion of germinal vesicle-intact immature (GVII) oocytes. Results: One hundred fifty-four of the 3520 oocytes studied (4.4%) were in the GVII stage. These oocytes were found in 66 of the treatment cycles (15.2%) and in 54 of the patients (24.4%). Cycles in which GVII oocytes were detected did not differ from those in which all the aspirated oocytes were mature in the following respects: patient age, type and duration of infertility, controlled ovarian hyperstimulation protocol and time of ovum pickup. However, the GVII group was characterized by a significantly higher peak estradiol level, as well as a higher number of mature follicles visualized sonographically (diameter, >14 mm) and oocytes retrieved. Conclusions: Comparing the present findings with previously published data, it appears that the inclusion of GnRH-a in the stimulation regimen is associated with a lower proportion of immature oocytes. A higher occurrence of oocyte-nuclear immaturity is apparently associated with a significantly better ovarian response to stimulation. The high incidence of immature oocytes observed in patients with normospermic partners and low fertilization rates in previous cycles may suggest that the fertilization failure in some of these cases is due to oocyte, rather than sperm, dysfunction.