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Biomedical subjects

Michael Hirsch

Publications and source records attributed to Michael Hirsch.

6 recordsLinked to original sources

An estimate of fetal autonomic state by time-frequency analysis of fetal heart rate variability.

In this study we present a noninvasive method that enables the investigation of the fetal heart rate (FHR) fluctuations. The objective was to design a quantitative measurement to assess the fetal autonomic nervous system and to investigate its development as a function of the gestational age. Our Medical Physics group has developed a complex algorithm for online beat-to-beat detection of the fetal ECG (FECG), extracted from the maternal abdominal ECG signal. We used our previously acquired FECG data, which includes noninvasive recordings of 200 maternal abdominal ECG signals. From these, we chose 35 cases of healthy pregnancies that we divided into three groups according to gestational age: Group 1, 23 +/- 2 wk; Group 2, 32 +/- 1 wk; and Group 3, 39 +/- 1 wk. The FHR variability was analyzed by a time-frequency decomposition based on a continuous wavelet transform. We showed that, independent of the gestational age, most of the FHR power is concentrated in the very-low-frequency range (0.02-0.08 Hz) and in the low-frequency range (0.08-0.2 Hz). In addition, there is power in the high-frequency range that correlates with the frequency range of fetal respiratory motion (0.4-1.7 Hz). In the intermediate-frequency range (0.2-0.4 Hz), the power is significantly smaller. The changes in the average power spectrum in relation to gestation time were carefully and quantitatively examined. The results imply that there is a neural organization during the last trimester of the pregnancy, and the sympathovagal balance is reduced with the gestational age.

Algorithms↗

Use of various contraceptive methods and time of conception in a community-based population.

AIMS: To investigate the association between method of contraception and time to conception in a normal community-based population. DESIGN: Prospective, cross-sectional, survey. SETTING: Large comprehensive ambulatory women's health center. PATIENTS AND METHODS: One thousand pregnant women at their first prenatal obstetrics visit were asked to complete a self-report questionnaire. The return to fertility was analyzed by type of contraceptive method, duration of use, and other sociodemographic variables. RESULTS: Response rate was 80% (n=798). Mean age of the patients was 29.9+/-5 years. Seventy-five percent had used a contraceptive before trying to conceive: 80% oral contraceptives, 8% intrauterine device, and 7% barrier methods. Eighty-six percent conceived spontaneously. Contraceptive users had a significantly higher conception rate than nonusers in the first 3 months from their first attempt at pregnancy. Type of contraception was significantly correlated with time to conception. Pregnancy rates within 6 months of the first attempt was 60% for oral contraceptive users compared to 70 and 81% for the intrauterine device and barrier method groups, respectively. There was no correlation between time to conception and parity or duration of contraceptive use. Other factors found to be significantly related to time to conception were older age of both partners and higher body mass index. CONCLUSIONS: Contraception use before a planned pregnancy does not appear to affect ease of conception. Type of method used, although not duration of use, may influence the time required to conceive.

Adult↗

NuRD complex component Mi-2beta binds to and represses RORgamma-mediated transcriptional activation.

RORgamma is a nuclear receptor that binds to DNA motifs as a monomer to constitutively activate target genes. RORgamma plays an important role in thymocyte development and lymph node organogenesis, while the regulation of RORgamma-mediated transcriptional activation is currently unclear. The purpose of this study was to identify other nuclear proteins that interact with RORgamma. A yeast two-hybrid screen with Y190 yeast cells under stringent conditions resulted in the identification of CHD4, also known as Mi-2beta, as a RORgamma-interacting protein. This interaction was confirmed by GST pull-down assays. This interaction occurred within the middle regulatory region (amino acids 719-1164) of Mi-2beta. Transfection of Gal4-RORgamma into HeLa cells resulted in constitutive transactivation of the MH100-tk-luc reporter. The addition of Mi-2beta resulted in a dramatic 50% decrease in Gal4-RORgamma-mediated transactivation. These data demonstrate that RORgamma forms a protein-protein interaction with the regulatory region of Mi-2beta, resulting in inhibition of RORgamma transcriptional activity. These results may provide evidence as to how RORgamma-mediated transactivation is regulated by other nuclear proteins.

Animals↗

Improved RGF method to find saddle points.

The predictor-corrector method for following a reduced gradient (RGF) to determine saddle points [Quapp, W. et al., J Comput Chem 1998, 19, 1087] is further accelerated by a modification allowing an implied corrector step per predictor but almost without additional costs. The stability and robustness of the RGF method are improved, and the new version in addition reduces the number of gradient and Hessian calculations.

Journal Article↗

Determination of energy minima and saddle points using multireference configuration interaction methods in combination with reduced gradient following: the S(0) surface of H(2)CO and the T(1) and T(2) surfaces of acetylene.

The implementation of the reduced gradient following (RGF) method into the COLUMBUS quantum-chemical program system is reported using the newly developed analytic MR-CISD/AQCC gradient feature. By this combination a very useful tool has been developed for general searches of stationary points on ground- and excited-state energy surfaces. This procedure is applied to the S(0) surface of H(2)CO and the T(1) and T(2) surfaces of acetylene. For H(2)CO we investigated three minima (formaldehyde, s-trans, and s-cis hydroxycarbene) and five saddle points. For the T(1) and T(2) states of acetylene the cis- and trans-minima and the planar and nonplanar saddle points were computed.

Journal Article↗

Tofupill/Femarelle (DT56a): a new phyto-selective estrogen receptor modulator-like substance for the treatment of postmenopausal bone loss.

OBJECTIVE: To evaluate the efficacy of Tofupill/Femarelle (DT56a), a novel phyto-selective estrogen receptor modulator (SERM), in preserving bone mineral density (BMD) in postmenopausal women. DESIGN: The study sample consisted of 98 healthy, postmenopausal women who were randomly allocated, on a double-blind basis, to receive either 644 mg/d DT56a (study group) or 344 mg/d DT56a supplemented with calcium (low-dose group) for 12 months. Each participant was assessed with a comprehensive health questionnaire, a detailed physical, and laboratory and pelvic sonogram examinations at entry and every 3 months thereafter. BMD was assessed by dual-energy x-ray absorptiometry (Lunar) of the lumbar spine and femoral neck before the study began and after 12 months of treatment. RESULTS: After 12 months of treatment, BMD had increased in the study group by 3.6% in the lumbar spine (P = 0.039) and by 2.0% in the femoral neck (NS). In the low-dose group, BMD had decreased in the lumbar spine by 0.6% (NS) and by 0.6% in the femoral neck (NS). Comparison of the change in bone density between the groups yielded a significant difference for the lumbar spine (P = 0.037). Neither group showed a change in endometrial thickness and sex hormone levels nor reported any side effects of treatment. CONCLUSIONS: Tofupill treatment in postmenopausal women increases BMD without unwanted estrogenic effect. Tofupill appears to be a promising phyto-SERM for the prevention of postmenopausal osteoporosis.

Bone Density↗