Alexithymia in Holocaust Survivors with and Without PTSD

Alexithymia was measured in non-treatment seeking, community-dwelling Holocaust survivors using the Toronto Alexithymia Scale—Twenty Item Version (TAS-20). Scores of survivors with (n = 30) and without (n = 26) posttraumatic stress disorder (PTSD) were compared, and associations among alexithymia, severity of trauma, and severity of PTSD symptoms were determined. Survivors with PTSD had significantly higher scores on the TAS-20 compared to survivors without PTSD. TAS-20 scores were significantly associated with severity of PTSD symptoms, but not with severity of trauma. This study adds to our knowledge of the relationship between alexithymia and trauma by demonstrating that this characteristic is related to the presence of posttraumatic symptoms and not simply exposure to trauma.     

Western blot analysis of immune response to Legionella bozemanii antigens.

The immune response to individual major antigens of Legionella bozemanii was studied in 67 sera from 26 inpatients with febrile disease using immunoblotting techniques. All the patients had fever of unknown origin and showed strong serological reactions to L bozemanii that cross-reacted with Rickettsia typhi, as determined by a standard indirect microimmunofluorescence assay. Sera analysed by western blotting reacted with 12-14 molecular components of L bozemanii with apparent molecular weights ranging from 14,000 to 94,000 daltons. These reactions compared well with a reference system using antisera of rabbits immunised with the same strain of Legionella. The three major cross-reactive components of R typhi were polypeptide antigens of 94,000, 67,000 and 43,000 daltons. It is concluded that western blotting can help in the differential diagnosis of patients with fever of unknown origin whose sera cross-react to L bozemanii and R typhi.     

Multiple sclerosis: genetic versus environmental aetiology: epidemiology in Israel updated

The incidence and prevalence of multiple sclerosis (MS) were compared, controlling for age, in native-born Israelis of different origins and in immigrants to Israel. This comparison was carried out in two populations, countrywide and in Jerusalem. In the countrywide population, ascertainment was based mainly on hospitalizations; it included 252 patients who were native-born and 150 who had immigrated from Africa-Asia (AA immigrants). The 89 MS patients of Jerusalem also included patients diagnosed in outpatient clinics. In native-born Israelis whose father was born in Europe-America (I-EA), the incidence and prevalence of MS were found to be as high as or even higher than that found previously in immigrants from Europe-America. Among native-born Israelis whose father was born in Africa or Asia (I-AA), the yearly age-adjusted incidence and prevalence rates were found to be 1.4- to 1.8-fold higher than among AA immigrants, pointing to environmental factors. The incidence and prevalence rates in the I-EA were 1.2- to 1.6-fold higher than in the I-AA, pointing to genetic factors. These results seem to point to both environmental and genetic factors in the aetiology of MS. Further research is needed, however, to disentangle the genetic factors from possible environmental differences in the two ethnic groups.     

Expression and functional activity of CXCR-4 and CCR-5 chemokine receptors in human thymocytes

In this paper we addressed the expression of the HIV co-receptors CXCR-4 and CCR-5 in human thymocytes by phenotypic, molecular and functional approaches. Cytofluorimetric analysis disclosed that CXCR-4 was constitutively expressed by freshly isolated thymocytes (~10 000 molecules/cell in about 30% of thymocytes); the receptor was endowed with functional activity, as it mediated polarization, migration and intracellular Ca2+ increase in response to its ligand, SDF-1. On the contrary, CCR-5 expression in freshly isolated thymocytes was significantly lower (<4000 molecules/cell in less than 5% of the cells), and no functional response to CCR-5 agonists could be documented. Northern blot analysis of freshly isolated thymocytes showed high CXCR-4 mRNA levels, whereas the message for CCR-5 was barely detectable. On the other hand, a modest increase in the expression of CCR-5 was associated with in vitro thymocyte stimulation, and CCR-5 density at the cell surface attained CXCR-4 figures in most cases. None the less, no functional response to CCR-5 agonists could be documented in in vitro stimulated thymocytes. In vitro infection of thymocytes by CAT-expressing recombinant HIV bearing the envelope glycoproteins from different isolates showed that T-tropic strains, which use CXCR-4 as a co-receptor, were more efficient in infecting thymocytes than M-tropic strains, which preferentially use CCR-5. Altogether, these data indicate that expression of the major co-receptors involved in infection by M-tropic HIV strains is very poor in human thymocytes, and would suggest that thymocyte infection by M-tropic HIV strains may be a rare event in vivo.     

Histocompatibility Determinants in Israeli Jewish Patients with Multiple Sclerosis

The distribution of 24 HLA antigens of the A and B loci was investigated in 197 Israeli Jewish patients with multiple sclerosis (MS) from various Jewish ethnic origins including central and eastern Europe, countries bordering the Mediterranean, the Middle East and from native-born Israelis. The results were compared with the HLA antigen frequencies in a control sample of 455 unrelated individuals representing the general Jewish population. The frequency of HLA-Bw40 among all MS patients (15%) was significantly greater (P less than 0.001) than among the controls (7%). In contrast to the findings in MS patients from other populations, there was no increased frequency of A3 and B7 and Dw2 was present in only one out of 28 patients. The study showed a similar distribution of HLA-A and -B locus antigens, especially of Bw40, in Jews of diverse ethnic origins represented in the control group.     

Inheritance of idiopathic torsion dystonia among Jews.

Idiopathic torsion dystonia (ITD) has long been considered to be genetically determined, but the pattern of inheritance has been unclear. It has been suggested that inheritance may differ in Jews and non-Jews. In the present study, data gathered in a nationwide survey of ITD in Israel were analysed. Between 1969 and 1980, 47 patients were collected, of whom 40 were of European origin. In these European Jews, the ITD frequency was about 1:23 000 live births, which was five-fold greater than in Jews of Afro-Asian origin. Assuming that all cases fit the same genetic model, an X linked or a simple autosomal recessive model of inheritance did not agree well with our data. An autosomal dominant model with low penetrance could have accounted for our observations and would yield an ITD gene frequency in European Jews of 3 to 4:100 000. In view of the increased ages of their fathers, the isolated cases may have included some new mutations. Multifactorial inheritance was also possible. However, it may be inappropriate to assume that all cases have the same genetic basis, or even that all are inherited.     

Evidence for the genetic role of human leukocyte antigens in low frequency DRB1*1501 multiple sclerosis patients in Israel

A strong association exists between multiple sclerosis (MS) and the DRB1*1501 haplotype, in most populations. Linkage of Multiple Sclerosis (MS) with the MHC or HLA region on chromosome 6p21 has previously been observed in DRB1*1501 positive MS families. A group of 13 Israeli multiplex MS families with a very low frequency of DRB1*1501 haplotype were examined in this study. Association and a linkage test were performed in order to identify a non-DRB1*1501 effect of HLA on susceptibility for MS. MS multiplex families and healthy controls were molecularly typed for six highly polymorphic markers located within the MHC region: DRB1, DQA1 and DQB1, BAT-2, MIB and D6S248. Data analyses included: (a) an association study comparing the patient group with both healthy relative, and healthy control groups (b) a transmission test for linkage disequilibrium (TDT) of the MS-associated alleles in the multiplex families, and (c) multipoint non-parametric linkage (NPL) and parametric LOD score analyses using the GENEHUNTER program. The DRB1*1303 allele was significantly more frequent among the MS patients. There was a trend towards transmission disequilibrium of DRB1*1303, but was not statistically significant. Allele sharing and LOD score analyses revealed no evidence for linkage. The high frequency of DRB1*1303 observed in our family patients provides evidence to support the association with this allele that previously described in sporadic non-Ashkenazi MS patients. Thus, DRB1*1303 may serve as genetic risk factor for MS. Our study exemplifies the genetic heterogeneity in MS as there is a genetic effect of HLA on MS susceptibility in our low frequency DRB1*1501 patients.     

Serum insulin‐like growth factor (IGF)‐I and IGF binding protein‐3 in relation to terminal duct lobular unit involution of the normal breast in Caucasian and African American women: The Susan G. Komen Tissue Bank

Lesser degrees of terminal duct lobular unit (TDLU) involution, as reflected by higher numbers of TDLUs and acini/TDLU, are associated with elevated breast cancer risk. In rodent models, the insulin‐like growth factor (IGF) system regulates involution of the mammary gland. We examined associations of circulating IGF measures with TDLU involution in normal breast tissues among women without precancerous lesions. Among 715 Caucasian and 283 African American (AA) women who donated normal breast tissue samples to the Komen Tissue Bank between 2009 and 2012 (75% premenopausal), serum concentrations of IGF‐I and binding protein (IGFBP)‐3 were quantified using enzyme‐linked immunosorbent assay. Hematoxilyn and eosin‐stained tissue sections were assessed for numbers of TDLUs (“TDLU count”). Zero‐inflated Poisson regression models with a robust variance estimator were used to estimate relative risks (RRs) for association of IGF measures (tertiles) with TDLU count by race and menopausal status, adjusting for potential confounders. AA (vs. Caucasian) women had higher age‐adjusted mean levels of serum IGF‐I (137 vs. 131 ng/mL, p = 0.07) and lower levels of IGFBP‐3 (4165 vs. 4684 ng/mL, p < 0.0001). Postmenopausal IGFBP‐3 was inversely associated with TDLU count among AA (RR_T3vs.T1 = 0.49, 95% CI = 0.28–0.84, p‐trend = 0.04) and Caucasian (RR_T3vs.T1=0.64, 95% CI = 0.42–0.98, p‐trend = 0.04) women. In premenopausal women, higher IGF‐I:IGFBP‐3 ratios were associated with higher TDLU count in Caucasian (RR_T3vs.T1=1.33, 95% CI = 1.02–1.75, p‐trend = 0.04), but not in AA (RR_T3vs.T1=0.65, 95% CI = 0.42–1.00, p‐trend = 0.05), women. Our data suggest a role of the IGF system, particularly IGFBP‐3, in TDLU involution of the normal breast, a breast cancer risk factor, among Caucasian and AA women.     

Pathophysiology of fibroid disease: angiogenesis and regulation of smooth muscle proliferation

Uterine fibroids are the most common tumours presenting in women. The pathophysiology of fibroids is poorly understood, but disordered angiogenesis and altered smooth muscle cell proliferation are believed to play a role. In this review, current knowledge of both of these processes will be summarized. Differences between 'normal' adjacent myometrium and fibroid tumours within the same uterus are outlined. Exploiting these differences represents one of the best opportunities for the development of medical treatments that target fibroid tissue selectively.