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Ronit Haimov-Kochman

Publications and source records attributed to Ronit Haimov-Kochman.

17 recordsLinked to original sources
PubMed2006

Gene expression profiling of the human maternal-fetal interface reveals dramatic changes between midgestation and term.

Human placentation entails the remarkable integration of fetal and maternal cells into a single functional unit. In the basal plate region (the maternal-fetal interface) of the placenta, fetal cytotrophoblasts from the placenta invade the uterus and remodel the resident vasculature and avoid maternal immune rejection. Knowing the molecular bases for these unique cell-cell interactions is important for understanding how this specialized region functions during normal pregnancy with implications for tumor biology and transplantation immunology. Therefore, we undertook a global analysis of the gene expression profiles at the maternal-fetal interface. Basal plate biopsy specimens were obtained from 36 placentas (14-40 wk) at the conclusion of normal pregnancies. RNA was isolated, processed, and hybridized to HG-U133A&B Affymetrix GeneChips. Surprisingly, there was little change in gene expression during the 14- to 24-wk interval. In contrast, 418 genes were differentially expressed at term (37-40 wk) as compared with midgestation (14-24 wk). Subsequent analyses using quantitative PCR and immunolocalization approaches validated a portion of these results. Many of the differentially expressed genes are known in other contexts to be involved in differentiation, motility, transcription, immunity, angiogenesis, extracellular matrix dissolution, or lipid metabolism. One sixth were nonannotated or encoded hypothetical proteins. Modeling based on structural homology revealed potential functions for 31 of these proteins. These data provide a reference set for understanding the molecular components of the dialogue taking place between maternal and fetal cells in the basal plate as well as for future comparisons of alterations in this region that occur in obstetric complications.

Female↗
PubMed2006

Duration not severity of the climacteric syndrome predicts resumption of hormone therapy after discontinuation: a prospective cohort study.

BACKGROUND: Predictive factors of women who are unable to quit prolonged hormonal therapy (HT) are largely unknown. We sought to identify predictors for the resumption of HT after the discontinuation of treatment. METHODS: A cohort prospective study was conducted allocating menopausal women treated with HT for over 3 years. Menopausal symptoms were monitored periodically after HT cessation by the Greene climacteric scale. RESULTS: Eighty-two women participated in the study. Age, the age of menopause, BMI, HT duration, the type of regimen, reasons cited to discontinue HT and the method of discontinuation did not differ between the subjects who successfully discontinued HT and those who failed to quit HT. Only the prevalence of vasomotor symptoms when HT was first prescribed significantly differed between the groups (P = 0.03). Comparable maximal Greene score was recorded in both groups. Over time, the subjects who returned to HT had higher Greene score [Hazard ratio 1.25, confidence interval (CI) 95% (1-1.07)] and significantly higher vasomotor score [Hazard score 1.22, CI 95% (1.02-1.46)]. CONCLUSIONS: The history of hot flashes and the duration of menopausal symptoms upon HT discontinuation predict the resumption of HT. Thus, the return to HT is expected in individuals who are intolerant of prolonged climacteric syndrome.

Aged↗
PubMed2006

Are there second thoughts about the results of the WHI study?

The publication of the Women's Health Initiative (WHI) study had significant impact on the attitude of physicians and patients towards the use of hormones in the menopause. It has been estimated that 40-83% of patients using hormones ceased treatment on their own initiative following publication of the WHI results. While in the pre-WHI period, use of hormones in the menopause was termed 'hormone-replacement therapy' (HRT) with an emphasis on replacement; 'HRT' has now been replaced with the term 'hormone therapy' (HT), focusing on the therapy's status as a treatment with defined risks and benefits. Following the publication of the WHI study, many caregivers concluded that HT had absolutely no role in clinical practice. However, the decision to begin HT for the symptomatic, healthy, newly postmenopausal woman should be based on whether the WHI study addresses all the issues that must be taken into consideration before initiation of HT, whether there are effective alternatives available to relieve climacteric symptoms, and also whether HT is better able to prevent cardiovascular disease (CVD) and Alzheimer's disease (AD) than to halt atherosclerotic lesions. Every postmenopausal woman should have an individual risk-benefit evaluation to determine whether HT suits her needs. Until the effectiveness of HT for primary prevention of CVD and AD is established or disproved, there is no justification for HT use in the asymptomatic postmenopausal woman. However, symptomatic newly menopausal women might experience relief of their climacteric symptoms following HT use without exposing themselves to unreasonable risks.

Alzheimer Disease↗
PubMed2005

Reproduction concepts and practices in ancient Egypt mirrored by modern medicine.

The treasured ancient papyri provide a glimpse into understanding of common concepts and practices in ancient Egypt. The Kahun gynecological papyrus and other texts unveil the traditions of reproduction, conception and delivery. This article addresses the rationale of beliefs and practices of that era. Frequently, the reason for common traditions exercised at the time is based on medical knowledge of female anatomy and physiology during pregnancy. Surprisingly some of the remedies commonly used in ancient Egypt were recently explored and found intriguing. This paper was aimed to look at the reflection of archaic practices and concepts of ancient Egypt by the modern mirror of evidence-based medicine.

Contraception↗
PubMed2005

Expression and regulation of Sprouty-2 in the granulosa-lutein cells of the corpus luteum.

Growth factor signalling has important modulatory roles in the process of human follicular growth, oocyte maturation and corpus luteum (CL) formation. Recently, Sprouty-2, an inhibitor of receptor tyrosine kinase (RTK) signalling pathway was advocated as a marker of oocyte competence in the bovine ovary. We sought to study Sprouty-2 expression and regulation in the human ovary. RT-PCR was used to detect Sprouty-2 mRNA in human granulosa-lutein cells (GLC) collected from follicular aspiration of IVF patients. The effect of epidermal and fibroblast growth factors (EGF and FGF) on Sprouty-2 mRNA expression in GLC was studied using quantitative real-time PCR. Immunohistochemistry was performed on cultured GLC, human CL and stimulated rat ovary sections. Sprouty-2 mRNA was expressed in human GLC. EGF and basic FGF, but not FGF4 and FGF10, increased Sprouty-2 mRNA expression in GLC. The Sprouty protein was localized to GLC of early and late human CL but not to the theca cell layer. Immunostaining of developing rat CL confirmed the temporal and spatial expression of Sprouty in humans. The detection of Sprouty-2 mRNA and protein in human GLC may suggest a role for Sprouty-2 during the final stages of follicle maturation and CL formation.

Adolescent↗
PubMed2005

Spatiotemporal expression of heparanase during human and rodent ovarian folliculogenesis.

Heparanase (HPSE) is an endoglycosidase that cleaves heparan sulfate proteoglycans (HSPGs), major components of the basement membrane (BM) and extracellular matrix (ECM). Heparanase activity results in release of HSPG-bound molecules, including basic fibroblast growth factor (FGF2). Structural and functional development of the corpus luteum (CL) involves tissue remodeling, active angiogenesis, and steroid production. Heparanase-induced ECM and BM breakdown as well as FGF2-stimulated endothelial proliferation may have an important role in the regulation of luteal function. Heparanase mRNA was detected by reverse-transcription-polymerase chain reaction in granulosa cells recovered from follicular fluid of in vitro fertilization patients. Using sulfate-labeled ECM, heparanase enzymatic activity was determined in human luteinized granulosa cells. Employing immunohistochemistry, heparanase protein was localized predominantly in the theca interna cell layer of the mature antral follicle, whereas in human corpora lutea, both luteinized granulosa and theca cells were immunostained for heparanase. During luteolysis, heparanase was identified in macrophages surrounding the forming corpus albicans. In serially sectioned ovaries from unstimulated rats as well as from eCG-treated rats, expression of heparanase was noted exclusively in the ovarian steroid-producing interstitial tissue. Following an ovulatory dose of hCG, heparanase was immunostained also in lutein cells of the forming corpora lutea. Temporal expression of heparanase in granulosa cells during the luteal phase and in macrophages during luteal regression supports the hypothesis that heparanase plays a role in human ovarian ECM remodeling and may potentiate cellular migration and growth factor bioavailability.

Adolescent↗
PubMed2005

In vitro fertilization-intracytoplasmic sperm injection success rates with cryopreserved sperm from patients with malignant disease.

OBJECTIVE: To describe the success rate of intracytoplasmic sperm injection (ICSI) using thawed cryopreserved sperm in male cancer patients. DESIGN: Retrospective consecutive study. SETTING: IVF unit in a tertiary university hospital. PATIENT(S): Twenty-one couples treated by ICSI using the frozen-thawed sperm of husbands treated for cancer. INTERVENTION(S): Follow-up of all treatments by ICSI. MAIN OUTCOME MEASURE(S): Pregnancy rate, sperm count, and fertilization rate. RESULT(S): Male patients being treated for cancer froze between one and 29 sperm samples. Post-thaw sperm count ranged from 1 x 10(5) to 106 x 10(6). The mean fertilization rate by ICSI was 60% (range, 33%-100%), and the pregnancy rate was 42%. Twenty-six pregnancies were obtained resulting in 23 children (13 singleton and 10 twins) and eight spontaneous abortions (31%). Delivery was obtained in 12 of the 21 treated couples (57%). The lowest total motile sperm count that resulted in a pregnancy was 1 x 10(5). CONCLUSION(S): Male cancer patients should be encouraged to freeze numerous sperm samples even when sperm count and motility are poor. In these cases, ICSI is a powerful technique compared with intrauterine injection since thawed sperm samples with poor parameters can produce relatively high fertilization rates resulting in normal pregnancies and deliveries. The possibility to repeat treatments even in the face of a limited number of sperm samples appears to be of importance.

Adult↗
PubMed2005

Hot flashes revisited: pharmacological and herbal options for hot flashes management. What does the evidence tell us?

BACKGROUND: Hot flashes are the most frequent symptoms of menopause and the most common reason for climacteric women seeking medical advice. Estrogen therapy is by far the most effective therapy. However, fears of side-effect of estrogen therapy urged many patients to seek alternative modalities for symptomatic relief. METHODS: The MEDLINE database for the years 1975-2004 was searched for clinical placebo-controlled trials for the treatment of hot flashes with alternative therapy. Articles reporting the use of progesterone, alpha adrenergic agonists, anti-depressants, anti-convulsants, soy products, black cohosh (BC), red clover, dong quai, ginseng root, evening primrose oil, vitamin E, and wild yam were included. RESULTS AND CONCLUSIONS: A critical review of the literature shows that progesterone may have an independent effect on relieving hot flashes. New nonhormonal agents such as selective serotonin-uptake-inhibitor anti-depressants and a new anti-convulsant gabapentin yielded promising results on small well-conducted studies. Isoflavone's effect on hot flashes is variable and inconsistent, and only modest and delayed improvement of symptoms could be expected by BC and vitamin E. There are insufficient data on the other herbal alternative therapies at this time. Well-designed large studies are needed to further explore new modalities of treatment.

Adrenergic alpha-Agonists↗
PubMed2005

[Fetal programming--the intrauterine origin of adult morbidity].

Many epidemiological studies have demonstrated an association between low birth weight and the subsequent development of hypertension, insulin resistance, type 2 diabetes and cardiovascular disease. This association appears to be independent of classic lifestyle risk factors such as smoking, overweight, social class, alcohol consumption and lack of exercise, which are additive to the effect. The association holds for the full range of birth weights, including those within the normal range. In addition, it was suggested that faster postnatal catch-up growth may also predict later risk of cardiovascular disease. 'Fetal programming' has been proposed as a mechanism underlying the link related to low birth weight, rapid neonatal growth and adult disease. The fetal programming hypothesis suggests that the intrauterine environment during critical periods of organogenesis and tissue growth may permanently alter organ structure and function in an epigenetic manner. Indeed, evidence from both human and animal studies suggests that diseases of adult life are induced by the fetal environment. This review describes epidemiological and physiological evidence that the programming phenomenon is a major factor in determining later life diseases. Better management of pregnancy in the present will have long term wide-scale effects on the health of our society.

Cardiovascular Diseases↗
PubMed2003

CXCL12 expression by invasive trophoblasts induces the specific migration of CD16- human natural killer cells.

In the maternal decidua, natural killer (NK) cells, characterized by lack of CD16, are found in direct contact with the fetal extravillous trophoblasts (EVTs). It is yet unknown which factors contribute to the specific homing of this unique NK subset to the decidua. In this study we analyze the chemokine receptor repertoire on various NK populations derived from the peripheral blood and decidua. We show that CXCR4 and CXCR3 receptors are preferentially expressed on CD16- NK subsets derived either from the peripheral blood or the decidua and that these receptors are involved in migration of all NK subsets to their ligands. We further demonstrate in vivo that invading EVTs that eventually perform endovascular invasion express CXCL12, the ligand for CXCR4, but not ligands for CXCR3. Indeed, specific accumulation of the CD16- NK cells at the expense of CD16+ cells was observed only when in vitro migration was performed with ligands for CXCR4. Finally, incubation of the peripheral blood CD16- NK cells with cytokines present in the decidua, especially interleukin 15 (IL-15), resulted in the expression of chemokine receptor repertoire similar to that observed on decidual NK cells, suggesting an additional important regulatory effect of local decidual cytokines.

Blood Vessels↗
PubMed2003

Intraperitoneal levonorgestrel-releasing intrauterine device following uterine perforation: the role of progestins in adhesion formation.

BACKGROUND: Intrauterine contraception is a widely used, highly effective means of birth control. Uterine perforation is a serious, albeit rare, complication of intrauterine device (IUD) use. Although uterine perforation by levonorgestrel-releasing (20 micro g/day) intrauterine system (LNG-IUS) has already been reported, the peritoneal adhesion potential of this IUD is unknown. METHODS: The medical files of all patients diagnosed with an intra-peritoneal IUD between the years 1990-2002 at Hadassah Medical Center were reviewed. Histopathological study of peritoneal adhesion tissue adjacent to levonorgestrel medicated IUD was conducted in one case. RESULTS: Eight cases of dislocated IUDs were found. Four cases used LNG-IUS and four other cases used copper-IUD. Laparoscopy for IUD removal disclosed mild local peritoneal adhesions between omentum and pelvic organs in all cases. No difference was noted in the appearance of the peritoneum in the presence of either a copper-IUD or LNG-IUS. Histological examination of peritoneal tissue encasing the levonorgestrel-intrauterine system revealed loose connective tissue with aggregates of submesothelial cells with a pseudo-decidual change. Immunohistochemical staining for progesterone receptor was negative. CONCLUSIONS: The peritoneal adhesions potential of LNG-IUS is low, similar to that of the copper-bearing IUD.

Adult↗
PubMed2003

Management of a perforated levonorgestrel-medicated intrauterine device--a pharmacokinetic study: case report.

Intrauterine contraception is a widely used, highly effective method of birth control. Uterine perforation is a serious albeit rare complication with the use of an intrauterine device (IUD). Although uterine perforation by the levonorgestrel-releasing intrauterine system (LNG-IUS) has already been described, no plasma LNG concentrations in this setting were reported. Neither has the management of LNG-IUS been commented on to date. Two months after insertion of an LNG-IUS into a 33-year-old woman, it was noted to be in the peritoneal cavity. Laparoscopy for IUD removal was conducted 5 months after insertion. LNG and sex hormone-binding globulin plasma concentrations were measured prior to and following the laparoscopic removal of the IUD. Intra-peritoneal dislocated LNG-IUS resulted in plasma LNG levels 10 times higher (4.7 nmol/l) than the plasma level of LNG observed with LNG-IUS placed in utero. This high plasma LNG level suppresses ovulation. Therefore a misplaced LNG-IUS should be removed when pregnancy is desired.

Adult↗
PubMed2002

Localization of heparanase in normal and pathological human placenta.

Degradation of extracellular matrix (ECM) components is critical for invasion. Heparan sulphate proteoglycans are abundant in the ECM of the placenta and the decidua, hence their degradation may disassemble the matrix and facilitate placentation and trophoblast invasion. This study investigates the expression of heparanase in normal and pathological placentation using RT-PCR, in-situ hybridization and immunohistochemistry analysis to detect heparanase in specific cells of the placenta and at the fetal-maternal interface throughout pregnancy. Heparanase was observed in villous cytotrophoblasts (CT), syncytial trophoblasts (ST) and in intermediate trophoblast cell columns in normal first trimester, molar and ectopic pregnancies. The heparanase protein was preferentially expressed in the endothelium of fetal capillaries, and to a much lesser extent in larger fetal vessels. Extravillous trophoblasts (EVT) invading the decidua and the maternal vessels were also heparanase positive. In the second and third trimesters, villous CT remained heparanase positive whereas ST showed variable heparanase expression. EVT invading the placental implantation site were also positively stained. A similar pattern was observed in samples obtained from pre-eclamptic placentae and from placenta accreta. Our results indicate consistent expression of heparanase in normal and abnormal placenta, in small fetal vessels and in a variety of trophoblast subpopulations with different invasive potentials.

Female↗
PubMed2002

[Review of risk factors for breast cancer--what's new?].

Breast cancer is the most common malignancy in women and constitutes 18% of all cancers in women. Female gender, age and country of birth are the strongest determinants of disease risk. Family history and mutations in tumor suppressor genes BRCA1 and BRCA2 are important correlates of lifetime risk. Genetic polymorphisms associated with estrogen synthesis and metabolism are viewed as major factors in breast cancer prevalence in specific populations. Atypical hyperplasia and ductal/lobular carcinoma in situ although uncommon, are considered as pre-malignant conditions as well as markers for invasive breast cancer. Lately, increased bone density and high breast tissue density on mammogram in postmenopausal women have been reported in association with increased risk of breast carcinoma, probably attributable to increased levels of endogenous estrogen. Serum estrogen levels are higher in breast cancer cases as compared with controls. Current use of oral contraceptives and prolonged, current or recent use of postmenopausal hormonal replacement therapy are also considered as risk factors for breast cancer. Tamoxifen and raloxifene, selective estrogen receptor modulators, were shown to reduce breast cancer risk among high-risk women. Various nutrients were evaluated for their possible effect on breast cancer risk but further studies are needed. High socioeconomic status is found to be associated with increased risk of breast malignancy for as yet unestablished reasons. Studying breast cancer risk factors and further research into the molecular etiology of the disease will enable early diagnosis and detection of high-risk women and ultimately improve prognosis.

Breast Neoplasms↗
PubMedDate not supplied

Gradual discontinuation of hormone therapy does not prevent the reappearance of climacteric symptoms: a randomized prospective study.

OBJECTIVE: To investigate the recurrence and severity of climacteric symptoms after two methods of discontinuation of prolonged hormone therapy. DESIGN: Postmenopausal women treated with hormone therapy for more than 3 years and opting to discontinue therapy were randomly assigned to two treatment groups. Hormone therapy was discontinued either abruptly (group 1) or gradually (group 2). Symptoms in both groups were monitored with the Greene climacteric scale at 1, 3, 6, 9, and 12 months. RESULTS: Ninety-one women aged 48 to 73 years (mean age 56.8 +/- 4.2 years) participated in the study. The mean therapy duration was 8.8 +/- 3.8 years. No differences were noted between the two groups regarding age at menopause, body mass index, reasons to start therapy, hormone therapy duration, type of regimen, and reasons cited for hormone treatment discontinuation. After cessation of therapy, a similar percentage of patients in each group resumed hormone therapy. Climacteric syndromes, specifically vasomotor dysfunction, were more severe in group 1 than in group 2 during the first 3 months after hormone therapy withdrawal. However, by 6 months vasomotor symptoms were worse in group 2. By 9 to 12 months, no difference was noted between groups. No differences were observed in the percentage of weight gain, vaginal bleeding, and atrophy after discontinuation of therapy by either method. CONCLUSIONS: Our specific regimen of gradual discontinuation of hormone therapy merely postponed, and neither prevented nor minimized, the reappearance of vasomotor symptoms, mood deterioration, and sexual dysfunction, and the resulting discomfort.

Aged↗