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עמוד בית
Mon, 06.04.26

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August 2006
I. Goldberg Cohen, G. Beck, A. Ziskind and J. Itskovitz-Eldor
 Embryonic stem cells, derived from the inner cell mass of embryos in the blastocyst stage, are cells capable of perpetual self-renewal and long-term propagation and hold the potential to differentiate to progeny of the three embryonic germ layers. Since their derivation approximately two decades ago, exploration of mouse ES cells made major advances in ES cell differentiation research and in the successful development and propagation of various cell types. The subsequent derivation of ES cells from human embryos allows detailed study of early developmental events practically unreachable in early human embryos, and the potential derivation of a variety of adult cell types differentiated from the ES cells holds immense therapeutic promise. Recently, the study of ES cell-derived teratomas identified the partial presence of human ES cell-derived premature vessels within the teratoma, and a preliminary protocol for the in vitro derivation of a vascular progenitor was developed based on the study with the mouse ES cells. Furthermore, genetic profiling identified a pattern of expression of various endothelial and vascular smooth muscle cell genes that provide additional Information on the degree of vascular development that ES cells undergo. Finally, the clinical application of ES cells in transplantation medicine is closer than ever following the affirmation that human ES cell-derived endothelial progenitors conferred increased neovascularization in transplanted engineered skeletal muscle. This review summarizes these recent advances in vascular development from human ES cells and their potential clinical applications.

July 2006
D. Rimar, Y. Rimar and Y. Keynan
 Today, more than 10 years and 2000 articles since human herpesvirus 8 was first described by Chang et al., novel insights into the transmission and molecular biology of HHV-8[1] have unveiled a new spectrum of diseases attributed to the virus. The association of HHV-8 with proliferative disorders – including Kaposi's sarcoma, multicentric Castleman disease and primary effusion lymphoma – is well established. Other aspects of HHV-8 infection are currently the subject of accelerated research. Primary HHV-8 infection may manifest as a mononucleosis-like syndrome in the immunocompetent host, or in various forms in the immunocompromised host. The association of HHV-8 with primary pulmonary hypertension was observed by Cool et al. in 2003, but six clinical trials evaluating the role of HHV-8 in pulmonary hypertension have not been able to replicate this intriguing observation. It has been speculated that HHV-8 may secondarily infect proliferating endothelium in patients with pulmonary hypertension. HHV-8 epidemiology, modes of transmission, new spectrum of disease and treatment are presented and discussed.







[1] HHV-8 = human herpesvirus 8


May 2006
H. Joffe, E. Bamberger, S. Nurkin, E. Kedem, Z. Kra-Oz, S. Pollack and I. Srugo

Background: The co-morbidity of human immunodeficiency virus and other sexually transmitted diseases in Israel has not been established. 

Objectives: To compare the prevalence of STDs [1]among HIV[2]-positive patients to HIV-negative patients visiting an STD clinic in northern Israel. 

Methods: Between December 2000 and December 2001, 176 HIV-positive individuals (53% males) were screened and compared to 200 HIV-seronegative individuals (76% males). Demographics, symptomatology and risk factors were obtained via questionnaire. First-void urine samples were tested for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae. Serum was tested for type-specific herpes simplex virus-2, hepatitis B and syphilis. 

Results: Relative to the seronegative STD patients, HIV-positive patients exhibited significantly greater risk-reducing sexual behaviors such as consistent condom use [29/86 (33.7%) vs. 16/187 (8.6%), P < 0.001], and abstinence in the previous 6 months [43/125 (34%) vs. 7/185 (3.8%), P < 0.001]. Nevertheless, STD prevalence was higher among HIV-positive than HIV-negative patients (79.5% vs. 37.5%, P < 0.001). HSV[3]-2, syphilis and HBV[4] were more common among HIV-positive than HIV-negative patients [120/175 (68.8%)] vs. 18/200 (9%), P < 0.001)], [43/161 (26.7%) vs. 0%, P < 0.001)], [13/171 (7.6%) vs. 3/200 (1.5%), P < 0.01)], respectively. In contrast, Chlamydia and gonorrhea were more commonly found in HIV-negative patients than HIV-positive patients [3/176 (1.7%) vs.13/200 (6.5%), P < 0.05] vs. [0% vs.5/200 (2.5%), P < 0.05], respectively. 

Conclusion: Despite the low risk sexual behavior of Israeli HIV patients, they had a high prevalence of chronic STDs (e.g., HSV-2, HBV and syphilis). The lower prevalence of Chlamydia and gonorrhea among HIV-immunosuppressed patients may be attributed to routine antibiotic prophylaxis against opportunistic infections. Nevertheless, as advocated by international health organizations, it appears prudent to recommend the routine screening of these asymptomatic HIV-positive patients for STD pathogens. 


 




[1] STD = sexually transmitted diseases

[2] HIV = human immunodeficiency virus

[3] HSV = herpes simplex virus

[4] HBV = hepatitis B virus


March 2006
O. Caspi and L. Gepstein

The adult human heart has limited regenerative capacity and, therefore, functional restoration of the damaged heart presents a great challenge. Despite the progress achieved in the pharmacological and surgical treatment of degenerative myocardial diseases, they are still considered a major cause of morbidity and mortality in the western world. Repopulation of the damaged heart with cardiomyocytes represents a novel conceptual therapeutic paradigm but is hampered by the lack of sources for human cardiomyocytes. The recent derivation of pluripotent human embryonic stem cell lines may provide a solution for this cell sourcing problem. This review will focus on the derivation of the hESC[1] lines, their mechanism of self-renewal, and their differentiation to cardiomyocytes. The possible signals and cues involved in the commitment and early differentiation of cardiomyocytes in this model will be discussed as well as the molecular, structural and electrophysiologic characteristics of the generated hESC-derived cardiomyocytes. Finally, the hurdles and challenges toward fully harnessing the potential clinical applications of these unique cells will be described.

 






[1] hESC = human embryonic stem cells


February 2006
T. Ben-Hur

Human embryonic stem cells may serve as a potentially endeless source of  transplantable cells to treat various neurologic disorders. Accumulating data have shown the therapeutic value of various neural precursor cell types in experimental models of neurologic diseases. Tailoring cell therapy for specific disorders requires the generation of cells that are committed to specific neural lineages. To this end, protocols have been developed recently for the derivation of dopaminergic neurons, spinal motor neurons and oligodendrocytes from hESC[1]. These protocols recapitulate normal development in culture conditions. However, a novel concept emerging from these studies is that the beneficial effect of transplanted stem cells is not only via cell replacement in damaged host tissue, but also by trophic and protective effects, as well as by an immunomodulatory effect that down-regulates detrimental brain inflammation.






[1] hESC = human embryonic stem cells


August 2005
S. Berger-Achituv, T. Shohat and B-Z. Garty
 Background: The rate of breast-feeding in Israel has increased over the last two decades but is still lower than rates in other developed countries that have taken an active role in promoting breast-feeding.

Objective: To determine breast-feeding patterns and the association between sociodemographic characteristics and breast-feeding in the Tel Aviv district.

Methods: The mothers of infants aged 2, 4, 6 and 12 months, attending 59 well-baby clinics in the Tel Aviv district, were interviewed by telephone. Singleton infants who weighed less than 2,000 g and multiple-gestation infants were excluded from the study. The questions covered background data, sociodemographic characteristics of the family, and breast-feeding practices. Stepwise logistic regression was used to analyze the association between breast-feeding and various sociodemographic characteristics.

Results: Altogether, 78.5% of the mothers (1,307/1,665) initiated breast-feeding. The rate of breast-feeding at 2, 4, 6 and 12 months was 55.8, 36.8, 29.9 and 11.8%, respectively. Only 35.8% of the infants at 2 months and 11.2% at 6 months were exclusively breast-fed. The mean duration of breast-feeding was 5.2 ± 0.2 months. Grand multiparas (≥5 children) had a significantly higher rate of breast-feeding than women with one to four children (P < 0.001). More likely to breast-feed for 2 weeks or longer were women married to Yeshiva students (odds ratio = 5.3), women with ≥13 years education (OR[1] = 2.1), and women on maternity leave (OR = 1.6). The predictors for breast-feeding for 6 months or longer were similar.

Conclusions: Although the rate of breast-feeding initiation in central Israel was 78.5%, only 29.9% of the mothers continue to breast-feed for 6 months. Already at a young age, an appreciable number of breast-fed infants receive infant formula. Breast-feeding promotion should focus on less educated women, homemakers, and families with one to four children.


 



[1] OR = odds ratio


June 2005
April 2005
E. Magen, D. Elbirt and Z. Sthoeger
Highly active antiretroviral therapy has dramatically improved the quality of life and life expectancy of patients with human immunodeficiency virus. However, the prolonged use of HAART[1] leads to severe metabolic adverse events. Both HIV[2]infection and HAART can cause changes in lipid and glucose metabolism as well as elevation of blood pressure, promoting the development of atherosclerosis. Cardiovascular diseases have become a major cause of mortality among HIV-infected subjects who respond well to antiretroviral therapy. Nevertheless, a proper lifestyle and pharmacologic intervention can improve cardiovascular risk factors in the HIV-treated population and significantly reduce healthcare investments in the treatment of future cardiovascular complications in this population. In this review we summarize the current knowledge of CVD[3] prevention and treatment in HIV patients.

________________

[1] HAART = highly active antiretroviral therapy

[2] HIV = human immunodeficiency virus

[3] CVD = cardiovascular disease
April 2004
A. Ya'ari, C.L. Jaffe and B-Z. Garty

Background: Visceral leishmaniasis was first reported in Israel (then Palestine) in 1929. In the 1960s and 1970s, it was endemic to northern Israel, but only partial data about the disease have been gathered since then.

Objective: To investigate the epidemiologic trends of visceral leishmaniasis in Israel from 1960 to 2000, and to delineate some clinical features of the infection.

Methods: Data were collected from hospital charts, scientific publications, and reports of the Ministry of Health and the Kuvin Center for the Study of Infectious and Tropical Diseases.

Results: During the last four decades, 87 cases of visceral leishmaniasis were diagnosed in Israel, 76 of them (87%) in children. All 54 patients diagnosed in the 1960s occurred in the northern part of the country. The rate of infection declined significantly in the 1970s (5 cases) and then increased slightly in the 1980s (11 cases) and 1990s (17 cases). More than 50% of the cases in the 1990s were in central Israel. Children accounted for 100% of cases in the 1960s but only 58% in the 1990s. The main clinical features of the patients diagnosed in the last decade were fever, weight loss, hepatosplenomegaly and pancytopenia. Three of the adults were co-infected with human immunodeficiency virus.

Discussion: The decline in the incidence of visceral leishmaniasis in the 1970s and the slight increase in the 1980s and 1990s can be attributed to changes in the animal reservoir and vectors, and in the immunity status of part of the population exposed to Leishmania.

Conclusions: Visceral leishmaniasis has reemerged in Israel. This mandates better control of the animal reservoir and vectors and increased awareness of this infection.

December 2003
J-L. Touraine, K. Sanhadji and R. Sembeil

Background: The humanized SCID mouse model is an attractive tool for testing gene therapy to combat human immunodeficiency virus infection in vivo.

Objectives: To devise a more specific gene therapy directed against HIV, replacing the formerly used interferon with either soluble CD4 molecule immunoadhesin (sCD4-IgG) and/or anti-gp41 monoclonal antibody (2F5), or negative transdominants (Tat, Rev).

Methods: Human monocytoid cell line (U937) was transfected with IFNa[1], b or g genes. 3T3 murine fibroblastic cell line was transfected with sCD4-IgG or 2F5, or both genes, and a human T4 cell line (CEM) was grafted to SCID mice. Negative transdominant genes (Tat, Rev or both) were also transduced in CEM T cell line. Animals were then challenged with HIV-1[2]. Viral load was followed.

Results: IFNa or b were potent anti-HIV, reducing viral load in vivo and inhibiting reverse transcriptase activity in human-removed cells from animals. sCD4-IgG immunoadhesin and gp41 monoclonal antibody resulted in a dramatic reduction of HIV-1 cellular and plasmatic viral load in humanized SCID mice. The simultaneous introduction of negative Tat and Rev genes resulted in a synergistic inhibition of HIV-1 replication in vivo.

Conclusions: Despite the marked reduction of HIV-1 propagation by IFN genes or by negative Tat and Rev transdominants, the gene therapy using soluble CD4 immunoadhesin or anti-gp41 was a more efficient preventive treatment against HIV infection.






[1] IFN = interferon



[2] HIV = human immunodeficiency virus


September 2003
D. Nitzan Kaluski and A. Leventhal

Only one case of a cow infected with bovine spongiform encephalopathy has been reported in Israel. Its publication, in 2002, caused both public and professional concern. The inevitable health policy question raised was whether or not to recommend against consuming beef and what public health measures should be taken. In this article we describe the prion diseases among animals and humans, their interaction and the precautionary procedures that were carried out by the state Veterinary Services and the Ministry of Health since 1988. The BSE[1] case (a 10 year old dairy cow) is believed to be the result of local consumption of infected food with mammalian meat and bone meal more than a decade earlier. The risk assessment took into consideration that no cases of vCJD (a new variant of Creutzfeldt-Jacob disease) have ever been diagnosed in Israel, as well as the low risk of contamination of the meat due to the religious method of slaughtering performed in the country. The policy decision was to implement a contingency plan prepared in advance. Israel was reclassified from the level II category of geographic risk where BSE is unlikely but not excluded in the herds, to level III, where BSE is likely but not confirmed, or confirmed at a lower level. No undue damage to the meat industry has occurred. By the end of 2002, despite the examination of more than 3,800 brains from slaughtered cows older than 3 years, no other cases of BSE have been detected.

 







[1] BSE = bovine spongiform encephalopathy


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