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Nathan Rojansky

Publications and source records attributed to Nathan Rojansky.

At least 19 recordsLinked to original sources
PubMed2006

Inhibition of leiomyoma cell proliferation in vitro by genistein and the protein tyrosine kinase inhibitor TKS050.

OBJECTIVE: To determine the potency of TKS050, a new epidermal growth factor receptor (EGFR) inhibitor and genistein, a naturally occurring protein tyrosine kinase inhibitor, to inhibit leiomyoma cell proliferation in vitro. DESIGN: Establishment of paired cultures of leiomyoma and normal myometrial samples. SETTING: University clinical research laboratory. PATIENT(S): Hysterectomy specimens from premenopausal women affected by uterine leiomyomas. INTERVENTION(S): The suppressive effect of TKS050 and genistein on the cells, before and after steroidal hormone treatment, was examined. MAIN OUTCOME MEASURE(S): Cell proliferation, recovery after treatment, cell cycle analysis, and immunochemical analysis of relevant proteins were performed. RESULT(S): TKS050 (2 micromol/L) and genistein (50 micromol/L) completely suppressed leiomyoma cell proliferation, and the cells did not recover after cessation of treatment. TKS050 induced cell cycle arrest and apoptosis in a dose- and time-dependent manner. Cells accumulated in the G(0)/G(1) phase of the cell cycle at the expense of the S and G(2)+M phases. Treatment of cells with TKS050 resulted in a dose-dependent inhibition of EGFR autophosphorylation and of phosphorylated signal transducer and activator of transcription 3 (Stat3). Genistein inhibited the phosphorylated Stat3 but did not affect EGFR autophosphorylation. The inhibitory effects of TKS050 or genistein were unaffected by the presence of physiologic concentrations of estradiol-17beta. CONCLUSION(S): Leiomyoma cell growth is effectively blocked by TKS050 and genistein. The inhibitory action of newly developed and natural inhibitors derived from diet may be useful as a possible alternative therapy for leiomyomas.

Antineoplastic Agents↗
PubMed2006

LDL induces Saos2 osteoblasts death via Akt pathways responsive to a neutral sphingomyelinase inhibitor.

Atherosclerosis is epidemiologically associated with postmenopausal osteoporosis (OP) presumably by common etiologic factors, reflecting a state of co-morbidity in aging. Osteoblasts make a significant facet of this co-morbidity state. Since oxidized low-density lipoprotein (oxLDL) is a major factor in generation of vascular wall pathology, we examined the ability of native LDL (nLDL) and oxLDL to induce Saos2 osteoblasts growth arrest. OxLDL induced Saos2 cell death with morphological features of apoptosis that was inhibited mainly by caspase-9 and partially by caspase-3 but not by caspase-8 inhibitors. nLDL, like oxLDL, has induced cell death, where 60% (P = 0.00033) and 30% (P = 0.075, ns) of the cell death, respectively, could be inhibited by scyphostatin (a neutral sphingomyelinase [nSMase] inhibitor). Upon similar condition, nLDL inhibited the phosphorylation of Akt and two of its downstream targets, fork head receptor (FKHR) and glycogen synthase kinase-3 (GSK3). This is a pathway that stimulates cell survival and proliferation. nLDL has also induced an increase in the proapoptotic Bcl-Xs and it has diminished the potential antiapoptotic Src kinase activity. At the 4 h time-point, upon a substantial decrease in nLDL-induced Akt phosphorylation, scyphostatin has inhibited the reduction in FKHR and GSK3 phosphorylation but inexplicably not that of Akt. Scyphostatin has also corrected the reduction in Src kinase activity. Taken together, the results indicate that nLDL has induced apoptosis in Saos2 osteoblasts by inactivation of the pathway downstream to Akt using nSMase, and by involvement of Src kinase. Inferring that caspase-9 was the main executioner (rather than caspase-8 and-3) in Saos2 cell death, indicates that the nSMase-induced release of ceramide, directly activated the intrinsic mitochondrial apoptotic pathway. With regard to the Akt inactivation by nLDL, Saos2 osteoblasts responded in an opposite fashion to the response reported by others, in macrophages.

Amides↗
PubMed2006

Preparation of low density lipoprotein from large apheresis cartridges for induction of cell death in Saos2 osteoblasts.

Atherosclerosis is epidemiologically associated with postmenopausal osteoporosis presumably by common etiologic factors, reflecting a state of comorbidity in aging. Osteoblasts make a significant facet of this comorbidity state. The present study shows that LDL (native and oxidized) separated by conventional density ultracentrifugation induces osteoblast cell growth arrest in culture. Since the density unltracentrifugation is a tedious procedure we examined, in the present study, the option of LDL purification by ionic strength elution from LDL-apheresis cartridges. We tested the ability of LDL and oxidized LDL (oxLDL) from apheresis columns to induce apoptosis in human Saos2 osteoblasts. Isotonic NaCl effluent washed from LDL-apheresis columns (before starting elution of LDL) induced cell proliferation. In some of the effluent fractions that stimulated Saos2 osteoblasts, up to 15% of the stimulation levels could be significantly inhibited with antilipoprotein A antibodies. After the isotonic washing (150 mM NaCl), upon elution with high ionic strength, 0.2-0.3 M NaCl, some front-runner LDL eluate fractions also induced cell growth and others did not inhibit Saos2 cell growth. This indicates that these fractions might have been contaminated with apolipoprotein A or with other mitogenic compounds. In contrast, the late-to-elute (last 1/3) LDL portion, with a mean density of 1.042 g/mL, killed the cells as expected. This suggests that only the very last one third of LDL eluted by high ionic strength (0.3-0.5 M) is free of osteoblast-mitogenic compounds or lipoprotein-A containing particles. This approach to LDL purification might serve as a convenient and economic method for studying the composition of individual LDL particles and their interaction with cells in culture.

Apoptosis↗
PubMed2005

Intensive management and early delivery reduce antenatal mortality in monoamniotic twin pregnancies.

BACKGROUND: Intensive management and elective delivery between 32 and 35 weeks of monoamniotic twin pregnancies were suggested as improving perinatal outcome. We sought to evaluate this management as viewed by the outcome of monoamniotic twin pregnancies in our population. METHODS: A retrospective systematic chart review of all monoamniotic twin pregnancies, diagnosed from January 1986 to June 2002, was performed in three medical centers. Demographics, pregnancy course, and perinatal outcome were evaluated. The management and outcome were compared between the group of survivors and the groups of intrauterine fetal demise (IUFD) and miscarriage. RESULTS: Thirty-three pairs of monoamniotic twins were identified. Excluded were three women, who chose to terminate the pregnancy. Total survival rate was 60% (of 60 fetuses, 36 were born alive, but one neonate died due to sepsis). None of the IUFD occurred in hospitalized patients, and two pairs of twins died after 32 weeks. In the 10 twin pairs who died in utero, cord entanglement was documented in eight (80%). There were two cases of twin discordance and two cases of twin-to-twin transfusion syndrome. One twin of the live-born group had congenital transposition of the great arteries. Furthermore, one of the hospitalized patients was delivered by means of an emergency cesarean section because of a non-reassuring non-stress test at 30 weeks. CONCLUSIONS: Women with monoamniotic twin pregnancies should be advised about the very high mortality and morbidity rate. Early diagnosis, close in-hospital antenatal surveillance starting at fetal viability, and elective delivery at 32 weeks would reduce the antenatal mortality.

Adult↗
PubMed2005

Behçet's disease and pregnancy.

BACKGROUND: Behçet's disease (BD) is a multisystem inflammatory chronic disorder, which is characterized by relapsing oral and genital ulceration and iridocyclitis. While being of unknown etiology, vasculitic changes of possible autoimmune origin are common to all involved organs, and thrombotic complications, which may adversely affect gestation, are frequently seen. Very little is known to date about the reciprocal influence of BD and pregnancy. We have undertaken to explore the mutual effect of BD and pregnancy with emphasis on maternal and fetal complications. METHODS: In this case-control study, we have evaluated pregnancies that occurred in women suffering from BD, who were treated in our institution during the last 25 years. All records were reviewed, and data were confirmed by a telephone interview and compared with a matched control group. To review the current knowledge, a Medline search together with a manual search of selected articles was performed. RESULTS: Thirty-one Behçet's patients who had 135 pregnancies were studied. Remissions were significantly more frequent during both pregnancy and postpartum periods, while exacerbations were observed only in one-sixth of the patients (P < 0.001). Pregnancy complications (P < 0.001), cesarean section (P < 0.001), and miscarriage (P < 0.02) rates, however, were significantly higher in the study group. CONCLUSIONS: Our study suggests that pregnancy does not have a deleterious effect on the course of BD and may possibly ameliorate its course. However, it seems that BD may adversely affect pregnancy. The miscarriage rate was higher, and the pregnancy complications and cesarean section rates were significantly elevated.

Abortion, Spontaneous↗
PubMed2005

Rudimentary horn pregnancy: first-trimester prerupture sonographic diagnosis and confirmation by magnetic resonance imaging.

OBJECTIVE: Two cases of rudimentary horn pregnancy diagnosed in the first trimester by sonography and confirmed by magnetic resonance imaging (MRI) are reported. We suggest criteria for early, prerupture sonographic diagnosis of this rare condition. METHODS: We report a case in which pregnancy in a rudimentary horn was suspected on routine sonographic examination. In the second case, sonographic examination at 11 weeks' gestation revealed a right unicornuate uterus and a noncommunicating left rudimentary horn containing a gestational sac. In both cases, MRI clearly confirmed the sonographic diagnosis, showing an empty cavity of the uterine body and a pregnant uterine horn without an endometrial communication to the uterine body. RESULTS: Both patients underwent surgery, and the pregnant rudimentary horns were resected with no complications. CONCLUSIONS: We suggest the following criteria for sonographic diagnosis of rudimentary horn pregnancy: (1) a pseudopattern of a asymmetrical bicornuate uterus, (2) absent visual continuity tissue surrounding the gestational sac and the uterine cervix, and (3) the presence of myometrial tissue surrounding the gestational sac. Typical hypervascularization of placenta accreta may support the diagnosis. Additionally, MRI can be used to confirm the diagnosis before an invasive procedure is undertaken.

Adult↗
PubMed2005

Reproduction and ulcerative colitis: a review.

Ulcerative colitis is a chronic inflammatory bowel disease. The onset peaks at age 15-30 years and coincides with the reproductive period. We screened and summarized the relevant English-language publications (Entrez-PubMed) on ulcerative colitis, fertility and pregnancy. The presence of ulcerative colitis per se does not seem to significantly alterfertility in young women. However, associated conditions, such as active disease, surgical interventions and medication, may interfere with reproduction. It is difficult to draw conclusions regarding the effect of ulcerative colitis on pregnancy outcome in terms of pregnancy loss, intrauterine growth restriction, low birth weight, preterm labor, stillbirth and perinatal mortality. Nevertheless, it appears that major complications do not occur in ulcerative colitis patients more frequently than in healthy women. The rate of exacerbation is probably the same for pregnant and nonpregnant women. Disease control during pregnancy is of the utmost importance. Fortunately, most drugs can by used safely during pregnancy.

Adolescent↗
PubMed2005

[Prevention of venous thromboembolism in obstetric & gynecology--an update].

BACKGROUND: Thromboembolic events are quite common in obstetrics and gynecology and constitute a significant cause for morbidity and mortality. Recently, a decline in complication rates has been observed following the implementation of effective preventive measures. OBJECTIVE: This article aims to review the different prevention and treatment methods and to evaluate their efficiency. Furthermore, the article strives to forge a structured approach and form appropriate protocols for our population. RESULTS: Many studies have shown that the extensive use of preventive treatment is safe, clinically effective and valuable from the cost-benefit perspective. Nevertheless, most surveys performed around the world showed that the number of surgeons that use prophylactic treatment is lower than expected. In our department, we have engaged in a discussion with our hematologist and created protocols with simple and clear flow-charts for DVT and PE prevention, both in gynecological operations and in obstetrics. CONCLUSION: The implementation of a clear departmental policy will increase the awareness and the use of preventive treatment and will potentially decrease morbidity and mortality from thromboembolic events.

Female↗
PubMed2004

How often are endometrial polyps malignant?

OBJECTIVE: Endometrial polyps are a frequent pathology encountered during pelvic sonography and diagnostic hysteroscopies. The true incidence of malignant endometrial polyps is unknown. The estimations range from 0.5 to 4.8%. The objective of this study was to investigate the frequency of malignant endometrial polyps, and to characterize the hysteroscopic image of these polyps. METHODS: The study included 300 consecutive women with endometrial polyps who underwent hysteroscopic polypectomy. Patients' characteristics, operative findings, and pathology reports were analyzed. RESULTS: Four of the 300 endometrial polyps removed by operative hysteroscopy were malignant (1.3%). Patients with malignant polyps were symptomatic peri- or postmenopausal women. All asymptomatic polyps in this series were found to be benign. We could not identify any distinct hysteroscopic feature of malignancy. CONCLUSIONS: Our study shows that about 1.5% of endometrial polyps may be malignant. This finding reinforces the indication for removal of symptomatic endometrial polyps, preferably by a hysteroscopic procedure. The significance of asymptomatic uterine polyps has still to be determined.

Adult↗
PubMed2004

Prelabor rupture of the membranes at term: when to induce labor?

OBJECTIVES: To determine the significant predictors of clinical chorioamionitis and neonatal infection in patients with prelabor rupture of the membranes at term, and to apply this information to determination of optimal timing of labor induction. STUDY DESIGN: A retrospective case control series of women at > or =37 weeks' with prelabor rupture of the membranes. The study group consisted of women with evidence of maternal or neonatal infection. Controls had no evidence of infection. Three types of management were compared. (1) Immediate induction of labor, (2) expectant management up to 24 h followed by induction of labor if still necessary, or (3) expectant management for over 24 h. Univariate and multivariate analyses were performed by stepwise logistic regression (SPSS software package). The size of the study and the control groups was calculated for a 90% power with two sided P value of 0.05 in order to demonstrate an odds ratio of 2 for expectant management (two groups: early and late) versus immediate induction of labor (132 and 279 women in the study and the control groups, respectively). RESULTS: The rate of expectant management for over 24 h versus expectant management until 24 h followed by induction of labor when still necessary, was higher among cases than among controls ( OR = 1.84; P < 0.017; 95% CI, 1.127-3.003). Conversely, the rate of immediate induction of labor versus expectant management until 24 h followed by induction of labor when still necessary, was also higher among cases ( OR = 2.66; P < 0.001; 95% CI, 0.222-0.644). CONCLUSION: In women with prelabor rupture of the membranes at term, the best approach is to induce labor if spontaneous labor has not begun after 24 h.

Adult↗
PubMed2004

The AG1478 tyrosine kinase inhibitor is an effective suppressor of leiomyoma cell growth.

BACKGROUND: Uterine leiomyomas are the most common benign smooth muscle cell tumours in women. Formation of leiomyomas, still not completely understood, is viewed as a multistep process, with involvement of ovarian steroid hormones, cytokines and growth factors. Our study aimed to identify tyrosine kinase inhibitors as potential 'signal transduction therapeutics' for leiomyomas, underlying the effect of ovarian steroidal hormones. METHODS: The selective epidermal growth factor (EGF) receptor blocker AG1478 was evaluated as a potential target, since EGF has been shown to mediate estrogen action and to play a crucial role in regulating leiomyoma growth. Paired cultures of leiomyoma and normal myometrium samples were established and the suppressive effect of AG1478 on the cells prior and subsequent to steroidal hormone treatment was examined: cell proliferation, recovery after treatment, cell cycle analysis and immunochemical analysis of relevant proteins. RESULTS: Leiomyoma cell growth is effectively blocked by AG1478 and is unaffected by the presence of physiological concentrations of progesterone and estradiol. AG1478 (10 microM) completely suppressed proliferation and the cells did not recover after cessation of treatment. CONCLUSION: The growth-arresting properties of AG1478, unaffected by ovarian steroidal hormones, identify it as a potential lead agent for the non-surgical management of uterine leiomyomas.

Adult↗
PubMed2004

Perinatal outcome of pregnancies complicated by placenta accreta.

OBJECTIVE: The purpose of the study was to characterize the perinatal outcome of pregnancies complicated by placenta accreta. METHODS: We conducted a case-control analysis of all deliveries between the years 1990 and 2000 that were complicated by placenta accreta. Perinatal variables included in the analysis were gestational age at delivery, birth weight, Apgar scores, and perinatal mortality. Statistical analysis was performed using both the unpaired and paired approach. P <.05 was considered significant. RESULTS: The study encompassed 34,450 deliveries, from which 310 cases of placenta accreta were diagnosed (0.9%) and compared with 310 matched controls. In the pregnancies complicated by placenta accreta, we found a statistically significant increase in preterm deliveries (10.7% versus 1%, P <.001, odds ratio 12.1, 95% confidence interval 3.7-39.9) and small-for-gestational-age babies (27.3% versus 14%, P <.001, odds ratio 5.05, 95% confidence interval 1.46-3.28). CONCLUSION: Pregnancies complicated by placenta accreta are at increased risk for perinatal adverse outcome. We speculate that these findings may arise from pathological implantation of the placenta, resulting in interference with normal fetal growth.

Adult↗
PubMed2003

Inhibitors that target protein kinases for the treatment of ovarian carcinoma.

OBJECTIVE: Ovarian cancer is the leading cause of death from gynecologic malignancies in the United States. In an attempt to develop drugs that suppress ovarian cancer cells, we examined the effect of selective inhibitors of protein tyrosine kinases-tyrphostins, which are likely to play a role in ovarian cancer cells. STUDY DESIGN: We examined the cellular and biochemical effects of tyrphostins AG1478, PP2, AGL2592, and AG490 from four different families on the ovarian carcinoma cell line OV1063. RESULTS: We found that the AG1478, PP2, AGL2592, and AG490 tyrphostins suppressed cell proliferation and altered cell cycle distribution of the OV1063 cells in a dose- and time-dependent manner. Immunoblotting analysis indicated that AG1478 effectively inhibited epidermal growth factor receptor autophosphorylation, that AG490 decreased the level of Jak2 and phosphorylated Stat3, and that PP2 decreased the level of pp60Src protein. AGL2592 decreased the level of constitutive activated epidermal growth factor receptor and pStat3, but its molecular targets have not been identified completely. CONCLUSION: The growth-arresting properties of these tyrphostins identify them as possible candidates for signal transduction therapy.

Antineoplastic Agents↗
PubMed2003

Septate uterus with cervical duplication: rethinking the development of müllerian anomalies.

We present a case of a septate uterus with duplication of the cervix and a vaginal septum, which challenges the embryologic concept of unidirectional caudad to cephalad müllerian ducts fusion. This unique case is, to the best of our knowledge, the seventh reported case of this müllerian anomaly. It challenges the classic theory of unidirectional caudad to cephalad fusion of the müllerian ducts, and might be additional evidence to support the hypothesis suggested by Musset et al. Accurate diagnosis and reports of such cases are important not only for the benefit of treatment, but to reflect the true incidence of this anomaly, and consolidate the embryologic concept.

Adult↗
PubMed2002

IUD use and the risk of endometrial cancer.

OBJECTIVE: Although the intrauterine device (IUD) is one of the most widely used forms of contraception throughout the world, its potential long-term effects on the uterus have not been thoroughly evaluated. This paper reports the long-term results of IUD use on the incidence of endometrial cancer. STUDY DESIGN: The data is part of a nationwide case-control, pilot study that was undertaken in order to evaluate the possible influence of ovulation induction drugs on the risk of endometrial cancer. The study included 128 living women 35-64 years old, with a histologically confirmed diagnosis of endometrial carcinoma. The controls were 255 women from the same dialing areas selected by random digit dialing. A multivariate logistic model, controlling for age, was used to assess the independent effects of factors found to be significantly associated with endometrial cancer on univariate analysis. RESULTS: The following parameters were found to be independently associated with endometrial cancer controlling for age: nulliparity OR=2.7 (95% CI 1.1-6.5, P=0.03); history of infertility OR=1.8 (95% CI 1.0-3.3, P=0.05); BMI>/=27 OR=2.3 (95% CI 1.4-3.8, P=0.001). The use of oral contraceptives and IUD were found to be protective; OR=0.29 and 0.37, respectively, (95% CI 0.14-0.61, P=0.001, 0.19-0.70, and 0.003, respectively). CONCLUSIONS: IUD use may have a protective effect on endometrial cancer risk. The protective effect of IUD may be either, through the intense inflammatory response that leads to other lisosomal and inflammatory actions, which may include cells responsible for early elimination of hyperplastic endometrial epithelial cells or, the more complete shedding of the endometrium associated with IUD use may decrease hyperplasia of the endometrium, a known risk factor for endometrial carcinoma.

Adult↗
PubMed2002

Hysteroscopic treatment of intrauterine lesions in premenopausal and postmenopausal women.

STUDY OBJECTIVE: To compare the safety and efficacy of hysteroscopic surgery in the management of intrauterine lesions in premenopausal and postmenopausal women and, in particular, to investigate whether glycine absorption is different between these populations. DESIGN: Comparative study (Canadian Task Force classification II-2). SETTING: Tertiary care university hospital. PATIENTS: Thirty postmenopausal and 78 premenopausal women with intrauterine polyps or myomas. INTERVENTION: Hysteroscopic myomectomy or polypectomy. MEASUREMENTS AND MAIN RESULTS: One hundred eight procedures were completed successfully by hysteroscopy; in two cases myomectomy was completed in a second operation for a deeply embedded myoma. No major complications occurred in either group. Median operating time, mean glycine absorption, and median postoperative hospital stay were not significantly different between groups. During mean follow-up of 15 months (range 1-39 mo), four women underwent hysterectomy (1 for endometrial cancer, 1 for complex hyperplasia with atypia, 2 for pelvic pain and menorrhagia). CONCLUSION: Hysteroscopic surgery is an effective and safe therapeutic option for intrauterine lesions regardless of a woman's menopausal status.

Adult↗
PubMed2002

Extreme caudal agenesis. Possible drug-related etiology?

BACKGROUND: Caudal regression syndrome (CRS) is a rare anomaly of the lower body pole that represents a continuum of congenital malformations ranging from isolated sacral agenesis to absence of the lumbosacral spine and major visceral anomalies. While the exact etiology of this syndrome is unclear, maternal diabetes, genetic factors, teratogens and vascular anomalies altering blood flow have been hypothesized to play a role in its pathogenesis. CASE: A fetus had extreme hypotrophy of the caudal body pole, aplasia of the lower spine and complete renal agenesis diagnosed in the second trimester by ultrasound. Maternal history revealed the use of minoxidil solution for preventing hair loss for four years prior to and during gestation. Also, the mother had taken trimethoprim-sulfamethoxazole during the first trimester for treatment of upper respiratory disease. No maternal diabetes or history of familial genetic diseases was evident. CONCLUSION: In an extreme form of CRS consisting of complete aplasia of the lower body pole and viscera and additional malformations, a possible drug-related etiology was suggested but should be confirmed by more studies.

Abnormalities, Multiple↗