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Biomedical subjects

B Goldman

Publications and source records attributed to B Goldman.

At least 73 records · Page 4Linked to original sources
PubMed1996

Epidermal growth factor promotes a cardiomyoblastic phenotype in human fetal cardiac myocytes.

Peptide growth factors likely play an important role in cardiac development, but growth factors which inhibit or prevent differentiation in cardiac myocytes are largely unknown. Using immunocytochemistry, Western and Northern blotting, and RNase protection assays, we demonstrate that epidermal growth factor (EGF) significantly inhibits differentiation and promotes proliferation in cultured human fetal ventricular cardiac myocyte cell lines. In enriched cell lines and in a pure myocyte cell strain, EGF inhibited increases in immunoreactive sarcomeric actin and sarcomeric myosin heavy chain (SMHC) normally seen after serum withdrawal. In the pure myocyte strain, EGF induced a cardiomyoblastic phenotype; i.e., it caused a complete loss of detectable sarcomeric proteins in the majority of cells; it was also mitogenic. EGF inhibited expression of cardiac alpha-actin and SMHC mRNAs, but inhibition of SMHC expression was predominantly of the beta-MHC isoform. Removal of EGF was followed by reexpression of sarcomeric proteins. Blocking the EGF receptor (EGFR) with monoclonal anti-receptor antibody completely abolished the dedifferentiating effects of EGF and also significantly reduced the mitogenic effect of the peptide. The results indicate that activation of the EGFR both inhibits differentiation and promotes proliferation of human fetal ventricular myocytes in vitro. These findings suggest an important role for EGF in human cardiac differentiation and development.

Actins↗
PubMed1996

Effect of gravidity on maternal serum markers for Down's syndrome.

The effect of gravidity on maternal serum alpha-fetoprotein (AFP), unconjugated oestriol (uE3), and human chorionic gonadotrophin (hCG) levels was investigated in 27,592 women being screened for Down's syndrome. There was no difference in the median AFP level in primigravid and multigravid women, but the median hCG level in multigravid women was 5.9 per cent lower than in those tested in their first pregnancy (P < 0.0001) and the median uE3 level was 3.9 per cent lower (P < 0.0001). Among multigravid women, there was no material difference in hCG levels according to the number of previous pregnancies or livebirths, whereas uE3 levels declined steadily with increasing numbers. Both markers declined with advancing maternal age: for hCG this was an independent effect, but for uE3 it was due to the correlation between age and gravidity. Allowing for these effects will not greatly alter the Down's syndrome screening detection and false-positive rates.

Adult↗
PubMed1996

Second-trimester ultrasonographic diagnosis of segmental vertebral abnormalities associated with neurological deficit: a possible new variant of occult spinal dysraphism.

Sonographic evaluation of the fetal spine in a second-trimester, low-risk patient revealed segmentary, low thoracic vertebral abnormalities, including hemi- and butterfly vertebrae, resulting in severe fetal scoliosis with fetal paraplegia and bilateral club-feet. X-ray and magnetic resonance imaging studies of the abortus confirmed the prenatal vertebral findings in addition to rib defects and transection of the spinal cord. We believe that these findings which, to the best of our knowledge, have not been previously reported, represent a new variant of occult spinal dysraphism.

Adult↗
PubMed1996

Down's syndrome screening marker levels following assisted reproduction.

Maternal serum alpha-fetoprotein (AFP), human chorionic gonadotrophin (hCG), and unconjugated oestriol (uE3) levels were examined in 1632 women who had ovulation induction and 327 who had in vitro fertilization. There was a highly statistically significant increase in hCG and reduction in uE3 among those with ovulation induction. The median levels were respectively 1.09 and 0.92 multiples of the normal gestation-specific median (MOM) based on a total of 34582 women. Ovulation induction appeared to have no material effect on the median AFP level but this masked a significant increase when treatment was with Clomiphene (1.05 MOM) and a significant decrease when Pergonal was used (0.93 MOM). There was a highly statistically significant reduction in uE3 among women having in vitro fertilization with a median level of 0.92 MOM. Those fertilized with a donor egg (21) had significantly higher AFP and uE3 levels than when their own egg was used. Our results were confounded by differences in gravidity, but formally allowing for this factor did not materially change the findings. None of the observed effects is great enough to warrant routine adjustment of marker levels to allow for them. Moreover, women with positive Down's syndrome screening results can be reassured that this is unlikely to be due to them having had assisted reproduction.

Biomarkers↗
PubMed1996

A novel mutation of presenilin 1 in familial Alzheimer's disease in Israel detected by denaturing gradient gel electrophoresis.

Germline mutations in the presenilin 1 (PS1) gene apparently account for the majority of early-onset, familial Alzheimer's disease (AD). Using a mutation-screening strategy (denaturing gradient gel electrophoresis; DGGE), we analyzed a large family with early onset AD and seizures. The patients in this family showed a novel missense mutation in exon 5 of the PS1 gene (A to T change in codon 120, altering glutamine to aspartic acid). This novel mutation is located within the second hydrophilic domain of the molecule, a region not particularly involved in previously described germline mutations, and is of unknown biological significance. These results also demonstrate that DGGE can be used effectively to screen for mutations within this gene.

Alzheimer Disease↗
PubMed1996

Hyperechogenic fetal bowel and elevated serum alpha-fetoprotein: a poor fetal prognosis.

OBJECTIVE: To evaluate the clinical significance of increased fetal bowel echogenicity in women with elevated maternal serum alpha-fetoprotein (MSAFP) during the second trimester. METHODS: The study group comprised six pregnant women with elevated second-trimester MSAFP (greater than 2.5 multiples of the median), whose ultrasonographic evaluations indicated hyperechogenic fetal bowel. They were compared with six pregnant women whose fetuses, during routine second-trimester ultrasonographic screening for fetal anomalies, were found to have a hyperechogenic bowel without elevated MSAFP, according to natural history, pregnancy outcome, and associated features. RESULTS: All six fetuses with the combination of elevated MSAFP and echogenic bowel were growth-restricted; four died in utero and one of the two live-born infants died during the neonatal period. The single survivor in this group was born prematurely; necrotizing enterocolitis was diagnosed at 30 days of life and surgery was performed. None of the cases had associated congenital anomalies. Only one of the six controls had associated anomalies (trisomy 21), and this pregnancy was terminated. The pregnancy course of the remaining five fetuses was normal; all were appropriate for gestational age and were delivered at term. No perinatal mortality occurred in this group; however, in one infant, cerebral palsy was diagnosed at 10 months of age. CONCLUSION: Fetal bowel hyperechogenicity found in women with elevated second-trimester MSAFP levels is associated with poor fetal outcome, particularly fetal growth restriction with fetal and neonatal death, and should be considered an ominous prenatal finding.

Adult↗
PubMed1996

Prenatal ultrasonographic diagnosis of fetal hepatic hyperechogenicities: clinical significance and implications for management.

The clinical significance of sonographically detected fetal hepatic hyperechogenicities has not been fully established. The aim of this study was to assess various aspects of fetal hepatic hyperechogenicities detected in utero, including natural history, prenatal investigation and pregnancy outcome. In a retrospective survey of pregnant women presenting to the ultrasonographic unit, five fetuses with a mean gestational age of 20 weeks (range 14-24 weeks) were antenatally diagnosed as having hepatic hyperechogenicities. All cases underwent extensive investigation to establish the etiology and to determine the spectrum of ultrasonographic presentation. In three fetuses, only parenchymal lesions were found, while two had combined lesions: parenchymal and peritoneal. The earliest prenatal ultrasonographic diagnosis was made at 14 weeks' gestation in a fetus with combined hyperechogenic lesions, which, at 12 weeks' gestation, demonstrated unexplained fetal ascites. Associated abnormalities were found in only one fetus in which a solitary parenchymal lesion was associated with direct communication of the intrahepatic portion of the umbilical vein with the right atrium, and high output cardiac failure. In this case, termination of pregnancy confirmed ischemic hepatic necrosis. In the other four cases, no direct etiology could be determined, and all four pregnancies continued to term with normal neonatal follow up until 12 months of age. The present data suggest that in cases of fetal hepatic hyperechogenicities, where apparent intrauterine infection or neoplasia can be ruled out, a vascular disruption phenomenon is a putative etiology. If there are no associated morphological abnormalities or abnormal karyotypes, the prognosis may be favorable.

Adult↗
PubMed1995

Cytokines and growth factors modulate cell growth and insulin-like growth factor binding protein secretion by the human salivary cell line (HSG).

The human salivary cell line (HSG) was investigated for the effect of various growth factors and cytokines on cellular proliferation and on the production of insulin-like growth factor binding proteins (IGFBPs). IGF-I increased cell growth by approximately 25%, and induced the appearances of three distinct protein bands on ligand blot of the cell culture. Two bands with molecular weights of 43 and 45 Kda, respectively, proved to be IGFBP-3 using a specific antibody, and the third was a 24 Kda species (probably, IGFBP-4). Similar IGFBPs were released by the cells following stimulation by EGF and insulin as well as following incubation with the IGF-I receptor antibody alpha IR3. Retinoic acid had an inhibitory effect (50%) on IGF-I-induced cellular proliferation and an attenuative effect on the 24 Kda band when it was combined with IGF-I, and to a lesser effect EGF; however, it enhanced IGFBP-3 production when incubated with IGF-I. The IGF-I receptor antibody had an agonistic effect on IGFBPs production when applied alone or together with IGF-I. TNF-alpha and INF-gamma had minimal effects on cell growth when added alone but when applied in combination, a marked inhibition of cellular proliferation was noted. These cytokines caused increased accumulation of IGFBP-3, -4, and -5. Addition of IGF-I to these cytokines enhanced the expression of these bands. These data demonstrate that growth factors and cytokines which modulate HSG cell growth, induce specific IGFBPs which may play a role in their effects on cell growth.

Cell Division↗
PubMed1995

GM2 gangliosidosis B1 variant: biochemical and molecular characterization of hexosaminidase A.

The biochemical properties of hexosaminidase A (HexA) and the coding sequence of the alpha-subunit were examined in a patient of Syrian ancestry with the B1 form of Tay-Sachs disease (TSD). The biochemical characteristics of the variant HexA suggest that both active sites are affected by the mutation(s). Kinetic studies with the beta-subunit specific substrate, 4-methylumbelliferyl-beta-D-N-acetylglucosamine (MUG), revealed a significant difference between the Km values. of normal and variant HexA, while no difference was found when the sulfated substrate MUG-6-sulfate (MUGS), which is specific for the alpha-subunit active site, was used. The Vmax values for both substrates were significantly lower in extracts from B1 variant cells than in control extracts, implying a reduced enzyme level in the variant cells. A noncompetitive inhibitor of the reaction with MUGS, N-acetylglucosamine (NAG), induced a significant inhibition (30%) in the mutant cells only. When MUG was used as substrate, variant HexA was found to be more heat stable (T50 = 170 min) than normal HexA (T50 = 65 min). Furthermore, the mutant cell preparation differed from control in the relation between Hex thermosensitivity and protein concentration in the reaction. Two new mutations were identified in exon 5 of the HexA gene: a C496 to G transversion, which produced an Arg166 -->Gly alteration and a deletion of C498 which generated a shift in the reading frame. The patient was a heterozygote for both mutations even though her parents are first cousins. There is no evidence as yet which of these mutations accounts for the B1 phenotype.

Base Sequence↗
PubMed1995

Down syndrome prevention program in a population with an older maternal age.

OBJECTIVE: To investigate the effect of a relatively high proportion of pregnant women 35 years and older on the efficacy of prenatal screening for Down syndrome. METHODS: We obtained information on normal and abnormal cytogenetic and maternal serum marker studies for 1990 and 1992 from all 11 public and two private cytogenetic laboratories operating in Israel. RESULTS: In the Jewish Israeli population, 16.2-17.1% of all pregnant women are at least 35 years old. Thus, prenatal testing of all pregnant women at least 35 years old could have identified 62.8-66.5% of all Down syndrome cases. Screening by maternal serum markers would classify 9.28% of pregnancies as being at high risk for Down syndrome (greater than 1:386 at birth). The percentage of Down syndrome cases detected prenatally increased from 78 of 147 (53%) to 123 of 163 (75%) as a result of the increased use of prenatal testing from 11.3% to 19.4% of all pregnancies in 1990 and 1992, respectively. CONCLUSIONS: In a population with a high proportion of mothers at least 35 years old, as in the Jewish population in Israel, screening by maternal serum markers instead of by maternal age alone would leave the Down syndrome detection rate unchanged, but would lower the amniocentesis rate from 16.2-17.1% to 9.28%. In addition to the reduction in the expected fetal loss as a result of post-amniocentesis spontaneous abortion, this policy would also pay the cost of maternal serum marker testing of the entire pregnant population.

Adult↗
PubMed1995

Placenta accreta encountered during dilation and evacuation in the second trimester.

OBJECTIVE: To assess the frequency of placenta accreta encountered during dilation and evacuation (D&E) in the second trimester. METHODS: Among 16,827 second-trimester D&E procedures performed at our hospitals and clinics, seven cases of placenta accreta, either suspected clinically or proven histologically, were encountered. These cases were analyzed for history of prior cesarean delivery, placenta localization, and histology of hysterectomy specimens. RESULTS: Six of the seven cases suspected clinically were confirmed histologically. All placenta accreta patients had at least one cesarean delivery (mean 1.7), and five had a preoperative sonogram demonstrating some form of placenta previa. The prevalence of clinical placenta accreta encountered during D&Es in the second trimester was 0.04%, the same as that reported for placenta accreta diagnosed clinically in the third trimester. CONCLUSION: Placenta accreta can be a potential complicating factor in the patient undergoing D&E in the second trimester.

Abortion, Induced↗
PubMed1995

Pre-marital genetic counselling to consanguineous couples: attitudes, beliefs and decisions among counselled, noncounselled and unrelated couples in Israel.

Semi-structured interviews were conducted with 65 Israeli subjects who received genetic counselling while considering marriage to a close relative, 40 subjects married to a close relative who did not receive pre-marital genetic counselling, and 125 controls married to a nonrelative and never having considered marrying a relative. It was found that 72% of the consanguineous couples who received pre-marital genetic counselling proceeded with their plans and married their relative; 86% of them reported that the counselling influenced their final decision to some degree. Counsellees' appraisals of genetic counselling revealed unfulfilled expectations to obtain more definitive answers, and mixed reactions to the nondirective approach applied by the counsellors. Comparisons between consanguineous and control couples revealed different views about consanguinity in general, and genetic risks in particular. Consanguineous couples, unlike controls, perceived consanguinity as an ordinary form of marriage, and had more favorable attitudes towards it. Compared to the noncounselled consanguineous group, consanguineous couples who received pre-marital genetic counselling had fewer children, estimated their genetic risk as lower but its subjective significance as higher, and perceived genetic disorders as more severe. The implications of these results are discussed from both theoretical and practical standpoints.

Attitude to Health↗
PubMed1995

Fetal lung hyperechogenicity: prenatal ultrasonographic diagnosis, natural history and neonatal outcome.

The ultrasonographic appearance of fetal lung hyperechogenicity is most commonly associated with congenital bronchopulmonary abnormalities, such as cystic adenomatoid malformation or pulmonary lobar sequestration. Spontaneous disappearance of echogenic lung lesions has rarely been reported, mainly due to in utero resolution of cystic adenomatoid malformation. We describe four fetuses with echogenic lungs detected prenatally, none of them having been proved to have adenomatoid malformation or pulmonary sequestration of the lungs. Color Doppler sonography was used prenatally in all cases to rule out pulmonary sequestration. Three of the four fetuses showed complete resolution of the lung lesions during gestation, with normal neonatal outcome, but in one where the lesion decreased in size, intrauterine demise occurred at 28 weeks' gestation before complete resolution, and pneumonia was found at autopsy. We suggest that fetal lung hyperechogenicity may result from in utero bronchial tree obstruction with retention of mucoid fluid distal to the obstruction. With advancing gestation, in some cases the relative obstruction may be relieved, and the sonographic appearance of the lungs may return to normal. A retention of mucus in the bronchial tree should be added to the differential diagnosis of hyperechogenic lung lesions detected by antenatal ultrasound examination.

Adult↗