Search PubMed⌕ Search

Biomedical subjects

C Legum

Publications and source records attributed to C Legum.

At least 37 records · Page 2Linked to original sources
PubMed1995

Solar activity cycle and the incidence of foetal chromosome abnormalities detected at prenatal diagnosis.

We studied 2001 foetuses during the period of minimal solar activity of solar cycle 21 and 2265 foetuses during the period of maximal solar activity of solar cycle 22, in all women aged 37 years and over who underwent free prenatal diagnosis in four hospitals in the greater Tel Aviv area. There were no significant differences in the total incidence of chromosomal abnormalities or of trisomy between the two periods (2.15% and 1.8% versus 2.34% and 2.12%, respectively). However, the trend of excessive incidence of chromosomal abnormalities in the period of maximal solar activity suggests that a prospective study in a large population would be required to rule out any possible effect of extreme solar activity.

Adult↗
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↗
PubMed1994

Relatively low proportion of dystrophin gene deletions in Israeli Duchenne and Becker muscular dystrophy patients.

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are allelic disorders caused by mutations in the X-linked dystrophin gene. The most common mutations in western populations are deletions that are spread non-randomly throughout the gene. Molecular analysis of the dystrophin gene structure by hybridization of the full length cDNA to Southern blots and by PCR in 62 unrelated Israeli male DMD/BMD patients showed deletions in 23 (37%). This proportion is significantly lower than that found in European and North American populations (55-65%). Seventy-eight percent of the deletions were confined to exons 44-52, half of these to exons 44-45, and the remaining 22% to exons 1 and 19. There was no correlation between the size of the deletion and the severity of the disease. All the deletions causing frameshift resulted in the DMD phenotypes.

Blotting, Southern↗
PubMed1994

Autosomal recessive colobomatous microphthalmia.

Colobomatous microphthalmia was studied in multiple relatives of 5 families. In these families, the disorder was an autosomal recessive trait as opposed to the usual autosomal dominant form of the disorder. A relatively high incidence of this recessive allele is found in the Iranian Jewish community.

Adult↗
PubMed1994

A molecular survey of Israeli Duchenne and Becker muscular dystrophy patients.

Duchenne (DMD) and Becker (BMD) muscular dystrophy are allelic X-linked recessive diseases caused by a mutation in the dystrophin gene located on the short arm of chromosome X (Xp21). The dystrophin gene is the largest gene known in humans, extending over 2300 kb and containing more than 70 exons coding for a 420 KD protein comprising 3685 amino acids. The gene is highly unstable, with a high percentage of deletions and rearrangements. A third of dystrophin mutations are new mutations. The frequency of DMD is 1:3500 liveborn males, and that of BMD 1:10000. These dystrophies are severe, progressive, and lethal. BMD/DMD patients and 2/3 of female carriers have high levels of creatine phosphokinase (CK). During the past 5 years, 169 families with patients affected by progressive muscular dystrophy were examined and counselled. We were able to exclude the diagnosis of DMD/BMD in 49 families on the basis of clinical symptoms and signs, normal dystrophin on biopsy (11 families) and/or the absence of linkage to chromosome X by analysis of RFLP derived haplotypes. Molecular analysis was performed on 111 DMD/BMD families (five BMD and 106 DMD) with 81 available probands. This study resulted in the establishment in Israel of an integrated diagnostic protocol for DMD/BMD, employing genetic, biochemical and molecular techniques. Molecular analysis provided most of the families with new and essential information.

DNA, Complementary↗
PubMed1994

Prenatal testing for Down syndrome in the Jewish and non-Jewish populations in Israel.

The present work evaluated the efficacy of a prenatal diagnosis program in which amniocentesis and chorionic villus sampling were offered free of charge to all pregnant women in Israel aged > or = 37 years. The number of Down syndrome (DS) live births that occurred during the period of the program (1978-92) was correlated to the prevalence of old maternal age (> 35 years) and the utilization of prenatal test in the Jewish and non-Jewish populations in 1990 and 1992. It was noted that in the Jewish population, there was a slight increase in the DS live birth rate, from 1.05 in 1978, to 1.37 DS cases/1,000 live births in 1987, which corresponded to an increase in the prevalence of older pregnant women, from 8.0% in 1978 to 14.8% in 1987. Thereafter, however, there was a continuous decline, to 0.71 DS cases/1,000 live births in 1992, as a result of increased acceptance of prenatal testing by women > or = 37 years (67%) and, recently, also by younger women (from 5.6% in 1990 to 14% in 1992). In the non-Jewish population, there has been a very low acceptance rate of prenatal testing (23.3-16.1% in women > or = 37 years and 0.36-0.63% in women < 37 years). As a result, a very low prenatal detection rate (8-16% of all DS cases) and a high prevalence of DS live births (1.4 cases/1,000 live births) were observed. We suggest that a unique genetic counseling approach is required in the non-Jewish population to improve prenatal DS prevention in Israel.

Adult↗
PubMed1993

Detection of Duchenne muscular dystrophy gene products in amniotic fluid and chorionic villus sampling cells.

We have examined the expression of several Duchenne muscular dystrophy (DMD) gene products in amniotic fluid (AF) and chorionic villus sampling (CVS) cells. Variable amounts of dystrophin could be detected in most CVS and AF samples by immunoprecipitation followed by Western blot analysis. PCR analysis demonstrated the presence of the muscle type dystrophin mRNA in all AF cell cultures. The brain type dystrophin mRNA was also detected in some of these cultures. These DMD gene transcripts are of fetal origin and are produced by most or all clonable AF cells. The results may facilitate the development of a method for prenatal diagnosis of DMD, based on the expression of the gene in AF and CVS cells.

Amniotic Fluid↗
PubMed1993

The correlation between the frequency of sister-chromatid exchange and human reproductive hormones.

Different frequencies of sister-chromatid exchanges (SCEs) during various stages of the menstrual cycle have previously been observed. We tested the hypothesis that sex hormones, particularly steroids, influence the frequency of SCEs in women undergoing ovulation induction for in vitro fertilization treatment. These women undergo extreme hormonal changes and therefore serve as a good model for testing the rate of genetic damage due to these changes. As controls, we tested fertile women with regular menstrual cycles who received no hormonal treatment. Peripheral lymphocytes were obtained during different stages of the normal and treated cycles. We examined SCE frequency as related to the different hormones of the reproductive cycle at each of the stages. In general, an increased SCE frequency was observed around ovulation time in the controls, and around the time of human chorionic gonadotropin administration in the group undergoing ovulation induction. However, in the latter group, SCE frequency was significantly higher. SCE frequency was positively correlated with the level of testosterone and FSH in the ovulation induction group, and positively correlated with the estradiol level in both groups.

Adult↗
PubMed1992

Use of dystrophin genomic and cDNA probes for solving difficulties in carrier detection and prenatal diagnosis of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) results from mutations in the X-linked gene coding for the muscular protein dystrophin. The isolation of genomic and cDNA probes for this gene has greatly facilitated the detection of DMD carriers, which previously relied mainly on measurements of serum creatine kinase (CK), and has enabled prenatal diagnosis of this disease. However, the relatively large size of the gene and the high frequency of recombination and mutation events within the dystrophin locus continue to pose difficulties in the genetic counselling and prenatal diagnosis of DMD, and render the conclusions of molecular analysis less clear cut. This communication presents examples of two such difficulties: the distinction between sporadic and inherited cases in families with a single patient and normal CK levels in all females, and the distinction between mutant and normal dystrophin alleles in families in which the patients have died. The combined use of genomic and cDNA probes allows one to make these distinctions. An additional complicating factor, gonadal mosaicism, is demonstrated.

Clinical Enzyme Tests↗
PubMed1991

Bloom's syndrome in an Iranian Jewish male.

Bloom's syndrome is described in an Iranian Jewish male who subsequently developed myocardial disease. This may represent the first definitely non Ashkenazi Jewish patient in the literature and the only one to develop this complication.

Bloom Syndrome↗
PubMed1991

Krabbe disease in Israel.

Over a period of 15 years, 18 infants affected with Krabbe disease were diagnosed in Israel. None of the patients were Jews. Six were Druze from a large kindred in which a very high incidence of the disease was previously reported. The 12 other patients were Moslem Arabs; 7 were from two adjacent villages and most of them were found to be related, originating from a large kindred in which the incidence of the disease is 1/130 live births. Three other patients were from a third large kindred that also had a high incidence of Krabbe disease. Israel's population includes communities in which a high incidence of lysosomal diseases has been found. The incidence of these diseases in Israel may be reduced by delineating the populations at risk. With respect to Krabbe disease, as reported here, the tests for heterozygote detection are not sufficiently accurate for a screening of the populations at risk. Prevention is possible only by prenatal diagnosis in the families at risk.

Female↗
PubMed1990

Prenatal diagnosis of vitamin D-dependent rickets, type II: response to 1,25-dihydroxyvitamin D in amniotic fluid cells and fetal tissues.

Vitamin D-dependent rickets type II (VDDR-II; hereditary resistance to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]), an autosomal recessive genetic disease that results from a failure to respond to 1,25-(OH)2D3, is characterized by severe rickets, hypocalcemia, growth retardation, and high prevalence of alopecia. We used amniotic fluid cells in the 17th week of gestation to detect VDDR-II in fetuses at risk for the defect. First, we demonstrated in cells obtained from 15 control pregnancies the presence of a specific high affinity 1,25-(OH)2D3 receptor (Kd = 0.3 x 10(-11) mol/L; maximal number of binding sites, 6.1 fmol/mg protein) and 1,25-(OH)2D3-induced 25-hydroxyvitamin D3-24-hydroxylase activity (up to 30-fold increase). Amniotic fluid cells from a woman who had already given birth to a child with VDDR-II contained receptors that bound [3H]1,25-(OH)2D3 normally and responded to 1,25-(OH)2D3 stimulation with a 10-fold increase in 24-hydroxylase activity. The fetus was, therefore, judged unaffected, and a normal baby girl was born. At the age of 16 months she did not demonstrate clinical or biochemical features of VDDR-II. Amniotic fluid cells from another mother of a child with VDDR-II were unable to bind [3H]1,25-(OH)2D3, and the hormone failed to stimulate 24-hydroxylase activity. VDDR-II in this fetus was confirmed after termination of pregnancy by the total inability of 1,25-(OH)2D3 to stimulate 24-hydroxylase activity in tissue explants and cell cultures prepared from the fetus's kidney and skin. In contrast, tissues from dead control fetuses responded to stimulation by 1,25-(OH)2D3 with a 3- to 10-fold increase in 24-hydroxylase activity. Fetal kidney and skin explants and cell cultures also synthesized a [3H]1,25-(OH)2D3-like metabolite from [3H]25-OHD3 as early as the 17th week of gestation. 1,25-(OH)2D3 (10 nM) decreased the in vitro synthesis of the [3H]1,25-(OH)2D3-like metabolite in tissues from dead control fetuses, but not from the affected fetus. Thus, human fetuses at midgestation already have the regulatory mechanisms responsive to 1,25-(OH)2D3 present postnatally. The prenatal diagnosis of VDDR-II is now possible and is indicated in a high risk family.

Adult↗
PubMed1989

Prenatal diagnosis of Lesch-Nyhan syndrome: experience with three fetuses at risk.

Our experience with the prenatal detection of the Lesch-Nyhan syndrome (LNS; hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency) in three fetuses at risk is reported. Enzyme activities were measured in cultured amniocytes in two pregnancies, and in tissues and cultures obtained from chorionic villus sampling (CVS) in a third pregnancy. In all tissues the specific activities of HGPRT and adenine phosphoribosyltransferase (APRT) were determined and APRT/HGPRT ratios were calculated. In addition to the enzyme assays, the rate of purine synthesis de novo was assessed in the two amniocyte cultures, and the rate of [14C]hypoxanthine incorporation into nucleotides and sensitivity to azaguanine were measured in one of the amniocyte cultures. We report the diagnosis of normal fetuses by study of amniocytes in two pregnancies and of LNS using CVS in one pregnancy. In all three cases the diagnosis was confirmed.

Adenine Phosphoribosyltransferase↗
PubMed1988

Enzyme analysis of amniotic fluid for prenatal diagnosis of cystic fibrosis in high-risk pregnancies.

We determined the activity concentrations of alkaline phosphatase (ALP), ALP isoenzymes, gamma-glutamyltransferase (GGT), and alpha-glucosidase (AGL) in 1200 unselected amniotic fluids and in amniotic fluids from 40 pregnancies at high risk for cystic fibrosis (CF). From the results we established the normal range and CF-predictive cutoff values for these enzymes in the second trimester of pregnancy. In all predicted normal pregnancies that went to term, normal children were born. Among the predicted affected pregnancies, 14 were terminated and two went to term, one resulting in a CF-affected child and the other in a healthy child. Evidence for CF was found in all 13 aborted fetuses examined (the parents of one refused to allow autopsy). We noted no differences in the amniotic fluid enzyme activities for the Arab and various Jewish ethnic groups living in Israel. We conclude that prenatal diagnosis of CF among the Israeli population at risk for CF is feasible by means of a reliable, fast, and economic test in the second trimester of pregnancy.

Alkaline Phosphatase↗
PubMed1987

Familial colon cancer in the Tel-Aviv area and the influence of ethnic origin.

The family history of colon cancer was investigated in 38,823 individuals (2,129 families) who comprised a control and an oncology patient series from Tel-Aviv and nearby areas. A significant increased risk for colon cancer was observed among first-degree relatives of colon cancer patients when compared to controls. When the patient sample was divided into two groups based on country and continent of birth--European (Ashkenazim) and other (nonAshkenazim)--the relatives of the nonAshkenazi subjects showed a greater relative risk for colon cancer (P less than 0.05). Colon cancer was found to be less frequent in nonAshkenazim than in Ashkenazim controls. These findings suggest that although the colon cancer frequency in the nonAshkenazi group is lower, the genetic component may be more important than for the Ashkenazi sample. The nonAshkenazi Jews may represent distinct subgroups that differ with respect to either primary genetic susceptibility to colorectal cancer and/or they may have been subjected to peculiar, environmental carcinogenic exposures when compared to their Ashkenazim brethren.

Adult↗
PubMed1987

Family history of colorectal cancer as a marker of potential malignancy within a screening program.

Epidemiologic studies have shown that asymptomatic adult relatives of colorectal cancer patients are at increased risk for developing this tumor. A prospective, published pilot study confirmed this added risk and demonstrated the importance of the family history of cancer as a marker of potential malignancy. The study group was enlarged to include 471 asymptomatic adult, first degree relatives of patients having large bowel neoplasia (cancer or adenomatous polyps) but without polyposis syndromes. These first degree relatives were screened by fecal occult blood examinations and flexible sigmoidoscopy, followed by colonoscopy when indicated. Adenomatous polyps or cancer were found in 8.1% of the study group as compared with 3.7% in a comparison group of screens, not having the same family history of neoplasia and undergoing similar screening tests. Of the study group the age-adjusted rate for colorectal adenomas or cancer increased threefold (P less than 0.001) for subjects older than 40 years and an even higher fivefold relative risk was found for large bowel cancer only (P = 0.01). This was true even if there was only one relative with colorectal neoplasia (P less than 0.01) but was even more pronounced among those having more than one affected relative. The results confirm the usefulness of the family history, of even one member with large bowel neoplasia, in isolating a group at high risk for these lesions. This group would most likely benefit from regular cancer and adenomatous polyp screening particularly when older than 40 years.

Adenomatous Polyposis Coli↗