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Biomedical subjects

A O Martin

Publications and source records attributed to A O Martin.

At least 37 records · Page 2Linked to original sources
PubMed1987

Studies of cystic fibrosis in Hutterite families by using linked DNA probes.

Several multigenerational S-leut Hutterite families with cystic fibrosis (CF) were ascertained. Linkage studies with DNA marker loci MET and pJ3.11 (D7S8) were performed to determine whether (1) the CF gene in this inbred population is linked to DNA markers on chromosome 7, as it is in outbred populations of European origins, and (2) ancestral origin(s) of the CF gene could be determined. Our results indicate that the CF gene in Hutterite families segregates with chromosome 7 markers, identified by probes metH and pJ3.11. Thus, the CF mutation in Hutterites is likely to be either at the same locus as or at one closely linked to that reported in outbred populations. Heterozygous carriers could be distinguished from normal homozygous sibs of affected individuals. In the families studied, three different chromosome 7 haplotypes carried the CF mutation, raising the possibility that the CF gene may have been introduced into this population by as many as three different ancestors.

Chromosomes, Human, Pair 7↗
PubMed1986

Maternal serum alpha-fetoprotein screening: low and high values for detection of genetic abnormalities.

In initiating a maternal serum alpha-fetoprotein screening program, we pursued not only elevated values for the detection of neural tube defects but also low values to detect trisomic fetuses. We detected neural tube defects (0.2%) as expected but were surprised by the efficacy with which low serum alpha-fetoprotein values identified aneuploid fetuses. In 1421 pregnant women, 132 (9.3%) showed maternal serum alpha-fetoprotein values less than 0.4 multiple of the median. After repeat sampling, 57 women still had low values. These 57 women and six others who were too anxious for repeat sampling underwent level I ultrasound examination with the following results: gestational age overestimated by 2 weeks (n = 8), fetal death (n = 1), and no explanation (n = 54). Of the 54, 49 underwent amniocentesis with detection of three aneuploid fetuses: trisomy 18 (n = 2) and trisomy 21 (n = 1); maternal ages were 27, 29, and 31 years, respectively. Autosomal aneuploidy did not occur in other women screened. We conclude that low maternal serum alpha-fetoprotein values could efficiently detect aneuploid fetuses, perhaps with greater sensitivity than previously predicted.

Adult↗
PubMed1986

Chorionic villus sampling in continuing pregnancies. I. Low fetal loss rates in initial 109 cases.

Among the first 150 women who agreed to have chorionic villus sampling after receiving counseling and giving informed consent, 41 proved ineligible. In six (5.5%) of the remaining 109 cases in which chorionic villus sampling was performed, we were unsuccessful in obtaining an adequate amount of villi to permit diagnostic testing. In the single loss, fetal viability was confirmed 2 weeks after sampling; however, fetal death became evident 3 weeks later. In four (3.7%) cases the pregnancies were terminated because of abnormal results, and in one (0.9%) case the pregnancy was electively terminated after normal results. Among the 41 completed pregnancies no anomalies were evident in the infants. There were two premature deliveries; one of these two infants died shortly after birth following premature rupture of the membranes at 29 weeks' gestation. All undelivered cases were progressing normally at the time of submission.

Abortion, Induced↗
PubMed1986

Chorionic villus sampling in continuing pregnancies. II. Cytogenetic reliability.

Cytogenetic analysis was performed on 103 chorionic villus samples. Analysis of the 103 samples revealed six abnormalities. In three of the six the abnormalities were confirmed in fetal or neonatal tissue (47,XY, + 13; 46,XY, t(13q13q); 45,X). In three samples the abnormalities detected were not confirmed; in two of the three the abnormalities were detected only in long-term cultures, whereas in the other samples the abnormality was restricted to direct analysis of the villi after overnight incubation. Our initial experience leads us to conclude that certain abnormalities in chorionic villus sampling may not be indicative of fetal abnormalities; 45,X/46,XX or 45,X/46,XY mosaicism is such a complement. Discrepancies between cytogenetic analysis of intact villi processed soon after sampling and of cells grown in culture can be managed by adhering to several suggested guidelines and by liberal use of confirmatory amniocentesis.

Amniocentesis↗
PubMed1986

Gestational diabetes mellitus: a syndrome with phenotypic and genotypic heterogeneity.

One hundred ninety-nine gravida with gestational diabetes mellitus (GDM) defined as "carbohydrate intolerance of varying severity with onset or first recognition during pregnancy" have been stratified into subgroups on the basis of fasting plasma glucose and evaluated for further phenotypic and genotypic heterogeneity. A significantly greater proportion of the women in all our groups were older and heavier than in a "control" population of 148 consecutive gravida with documented normal oral glucose tolerance. After correction for age and weight by covariate analysis, absolute insulinopenia in response to oral glucose could be demonstrated in all GDM groups, although exceptions were present in each. The incidence of diabetes in the mothers of our patients with GDM was 8-fold greater than in controls; the incidence in fathers did not deviate from control patterns. HLA-DR3 and DR4 antigens were more frequently present in GDM and the increase was statistically significant in blacks. At the time of diagnosis, cytoplasmic islet cell antibodies (ICA) were significantly more common in GDM associated with elevated fasting plasma glucose than in controls; the frequency of ICA was 18.4% (7/38) in women with fasting plasma glucose greater than or equal to 130 mg/dl. Our findings indicate that GDM entails genotypic as well as phenotypic diversity and may include patients with slowly-evolving Type I diabetes mellitus, as well as patients with Type II diabetes mellitus, and women with asymptomatic diabetes which antedated the pregnancy (i.e. pregestational diabetes mellitus). Appreciation of this heterogeneity should be incorporated into any evaluation of intervention strategies for women with GDM or into prognoses concerning their postpartum metabolic status.

Adult↗
PubMed1986

Outcome after prenatal detection of a sporadic, unstable translocation t(5;21).

Amniotic fluid cultures from a 37 year old woman showed a sporadic 46,XX,t(5;21)(5qter----5p13 or p14::5pter----5p13 or p14::21p12----21qter) complement. In the majority of metaphases the 5p fragment was attached to the stalks of chromosome 21; however, in 9% of metaphases, the fragment was loosely attached by a 'thread' and in 6% it was completely detached. Silver staining and in situ hybridisation with a homologous ribosomal gene probe, which localises to stalk regions (nucleolar organisers, NOR) of human acrocentric chromosomes, failed to show a reciprocal exchange. Prognosis was uncertain because the possibility that the 5p fragment might have been lost in some cell lines could not be excluded. Nonetheless, the parents elected to continue the pregnancy. The translocation was confirmed in blood specimens obtained both at birth and at 1 year of age and showed similar instability. However, the proband shows no anomalies and is developing normally at 1 year.

Adult↗
PubMed1986

Hypermodal cells, hypomodal cells, and repetitive abortions.

The frequency of neither hypermodal cells (2N = 47) nor hypomodal cells (2N = 45) differed between lymphocytes of individuals experiencing repetitive spontaneous abortions (N = 429) and controls (N = 90). The same conclusion held when data were analyzed according to chromosome involved (sex chromosome, autosome) or other variables (e.g., prior reproductive outcome). A study of this relatively large sample failed to confirm findings of smaller and sometimes uncontrolled studies. Hypermodal cells do not necessarily serve as a clue to meiotic instability and in turn probably do not identify couples at risk for recurrent aneuploidy.

Abortion, Habitual↗
PubMed1985

Ultrasound effects.

In a listing of the new foreign associates of the National Academy of Sciences (News and Comment, 17 May, p. 826), the name of Pierre Chambon, Biochemistry, Institut de Chimie Biologique, Faculté de Médecine, Strasbourg, France, was inadvertently omitted.

Humans↗
PubMed1985

Chorionic villus sampling for first-trimester prenatal diagnosis: Northwestern University program.

We present our initial experience in developing a chorionic villus sampling program at Northwestern University. In phase 1, we performed chorionic villus sampling in 58 patients prior to elective first-trimester abortion, assessing the reliability and reproducibility of obtaining adequate villus samples and performing cytogenetic analysis by means of both the direct and culture methods. Specimens were categorized according to quality: class I, multiple identifiable villi (n = 20); class II, few villi or villi mixed with decidua (n = 15); class III, no villi (n = 23). There was a positive trend between operator experience, amount of villi obtained, and quality of cytogenetic preparations. In March, 1984, we received Institutional Review Board approval to perform chorionic villus sampling in continuing pregnancies (phase 2). Among the first 20 cases we found two abnormalities (47,XY, + 13; 45,X). The remaining 18 pregnancies were continuing. Recommendations are made for developing a chorionic villus sampling program.

Adolescent↗
PubMed1985

Frequency of diabetes mellitus in mothers of probands with gestational diabetes: possible maternal influence on the predisposition to gestational diabetes.

Interviews for genetic histories were conducted prior to delivery in 166 pregnant diabetic probands and 83 control gravidas with normal carbohydrate metabolism throughout gestation. A significant association was observed between parental diabetic phenotypes and type of diabetes in the probands (chi 2(12)) = 32.413; p less than 0.001). In particular a higher than expected number of mothers with diabetes was encountered in 91 probands with gestational diabetes mellitus. The findings are examined in relationship to the hypothesis that vulnerability to gestational diabetes may be increased by exposure to an abnormal environment during intrauterine development.

Adult↗
PubMed1985

Silver staining in clinical cytogenetics.

Silver staining of human chromosomes at prometaphase or metaphase identifies variants in the stalk (nucleolar organizing) regions of acrocentric chromosomes (Nos. 13, 14, 15, 21, 22). Variants are defined by size, number, and morphology of silver staining areas. They are heritable polymorphisms and have not been associated with clinical abnormalities. However, these variants are useful in clinical cytogenetics, specifically in studies attempting to determine whether genetic material has been gained or lost in chromosomal rearrangements, the origin of chromosomal aberrations, the origin of cells in tissue culture, the chromosomal location of single genes, clonal origin of tumors, the zygosity of twins, and paternity. Some chromosomal aberrations require silver staining for their definition. Because loss of the stalk regions per se is apparently not deleterious, demonstration that chromosomal breaks occurred within this region without concomitant loss or gain of genetic material essential for normal human development provides basis for a good prognosis for the individual with the chromosomal rearrangement resulting from such breakage. The principle underlying most of the other applications is to determine whether variants being compared are identical or dissimilar, and to make inferences from these results (e.g., variants in monozygotic twins should all be identical, whereas in dizygotic twins they are as similar as in any pair of sibs). Silver staining is a valuable technique for special questions in clinical analysis.

Chromosome Aberrations↗
PubMed1985

Adverse effects of human leukocyte antigen-DR sharing on fertility: a cohort study in a human isolate.

To elucidate further the reproductive effects of human leukocyte antigen (HLA) sharing among spouses, we have been investigating prospectively the relationship between HLA-A, -B, and -DR sharing and reproductive outcome in the Hutterites, a religious isolate that proscribes contraception. For the first time the reproductive effects of HLA-DR sharing in a fertile population is reported in this article. Median intervals from marriage to first through fifth births were longer among couples who shared more than one HLA-A, -B, or -DR antigen. Longer intervals were associated with increased spontaneous abortion rates among couples who shared HLA-DR antigens (27%), compared with couples who shared only HLA-A or -B antigens (9%) and couples who shared no antigens (12%). Median completed family sizes were 5.0, 8.5, and 8.0 among the groups, respectively. However, some couples who shared HLA-DR antigens experienced no spontaneous abortions, despite ten or more pregnancies. Therefore, although HLA-DR compatibility, per se, is not deleterious, our data suggest a potentially important role for undefined HLA-linked genes in normal pregnancy.

Abortion, Spontaneous↗
PubMed1984

Sister chromatid exchanges after exposure to ultrasound and mitomycin C.

A pilot study was designed to determine whether a synergistic ability to produce sister chromatid exchanges exists between ultrasound and mitomycin C, an alkylating agent known to induce sister chromatid exchanges. Bromodeoxyuridine-containing cells from human lymphocyte cultures were randomized into one of four exposures: (1) unexposed controls, (2) 20 minutes of pulsed ultrasound (3.5 MHZ), (3) mitomycin C alone, or (4) mitomycin C and 20 minutes of pulsed ultrasound. The mean sister chromatid exchange frequencies were 6.7 control cells, 7.5 cells exposed only to ultrasound, 8.1 cells treated with both ultrasound and mitomycin C, and 10.4 cells treated with mitomycin C alone. Neither X2 tests for differences in the four distributions nor analysis of variance for interaction between ultrasound and mitomycin C was significant. Our results suggest that individuals receiving alkylating agents are not likely to be highly susceptible to any deleterious effects of ultrasound. However, these results remain tentative pending repetition of studies and development of more appropriate in vitro exposure systems.

Adult↗
PubMed1984

A statistical test for detection of ancestral genetic contributions to disease occurrence in finite populations.

We have been investigating cancer patterns in the Hutterites, a religious isolate residing on communal farms [Martin et al, 1980a,b,c]. Advantages of this population include extensive and accurate genealogies, essentially complete case ascertainment, and relatively uniform environmental background with regard to geographic location, lifestyle, and diet. However, application of the common epidemiological approach to familial risk assessment based on incidence in relatives of index cases [Haenszel, 1959] posed difficulties because all cases are probands. We also planned to employ matching to control for important confounders and thus had to deal with the problems of the matching of cases and controls as well as the existence of complex inbreeding [Hauck and Martin, 1982]. Our basic approach was to compare coefficients of kinship (Fm, a measure of coancestry) of cases with each other to coefficients between cases and matched controls drawn from the same population. We have developed a paired t-type statistic to assess the significance of observed differences. We present, as examples, application of our methods to the analysis of Hutterite data on neurofibromatosis, known to be inherited in autosomal dominant fashion, and on cancer. Neurofibromatosis showed significant familial aggregation, as expected. Breast, colon-rectal, and stomach cancer did not. We then show how to evaluate power and to determine appropriate sample sizes for detecting specified increases in kinship.

Biometry↗
PubMed1984

Increased sister chromatid exchanges in human cell lines characterized by monosomy X or structural abnormalities of the X chromosome.

In the present investigation we test the hypothesis that deficiencies of the X chromosome affect sister chromatid exchange (SCE) frequencies in human fibroblast cell lines. Our results show increased mean SCE frequencies in cell lines with abnormalities of the X chromosome: 45,X; 46,X,del(X) (q13), 46,X,del(X)(p11), and 46,X,i(Xq); control cell lines were 46,XX. In only one abnormal line [46,X,del(X)(p11)] was the increase not significant after correcting for multiple comparisons. If SCE formation is replication-dependent, the increased SCE frequencies might merely reflect the prolonged cell cycle we reported previously in cell lines with X chromosome abnormalities (Simpson and LeBeau 1981). Other explanations for differences between cell lines are possible, e.g., that deleted loci on the X chromosome affect cellular uptake of bromodeoxyuridine (BrDU). However, specific mechanisms were not explored directly.

Adult↗
PubMed1984

Use of a newly established human cell line (SU-CCS-1) to demonstrate the relationship of clear cell sarcoma to malignant melanoma.

A new tumor cell line, designated SU-CCS-1, was established from the malignant pleural effusion of a 16-year-old Caucasian girl with clear cell sarcoma. Morphological studies at the light- and electron-microscopic levels revealed similar features between the SU-CCS-1 cells and the primary tumor. Ultrastructural and cytochemical techniques showed that both the SU-CCS-1 cell line and the original tumor were amelanotic in nature. The malignant derivation of the SU-CCS-1 cell line was demonstrated by intracranial and s.c. heterotransplantation in the nude, athymic mouse and by cytogenetic analysis which showed that the cell line had a hypodiploid chromosome number and several karyotypic abnormalities. Live-cell radioimmunoassay procedures using a large panel of monoclonal antibodies directed against tumor-associated antigens revealed that, phenotypically, SU-CCS-1 closely resembled melanoma tumor cell lines. Immunological assays for the detection of neuroendocrine-associated peptides, hormones, and enzymes revealed that, like melanoma, the SU-CCS-1 cell line was actively producing alpha-melanotropin, S-100 antigen, and nerve growth factor. A notable difference between these tumor types was the capacity of SU-CCS-1 to produce bombesin, an active neuropeptide whose synthesis has been found in cell lines from patients with small cell carcinoma of the lung. From these studies, we concluded that the SU-CCS-1 cell line is phenotypically similar to melanoma, yet displays unique characteristics which distinguishes it from other sarcomas. The availability of an established clear cell sarcoma cell line will greatly facilitate further studies aimed at uncovering the histogenesis of this rare cancer.

Adolescent↗
PubMed1983

The development of a profile scoring system for early identification and severity assessment of pregnancy-induced hypertension.

Two commonly encountered problems in the management of patients with pregnancy-induced hypertension (PIH) or pregnancy-aggravated hypertension (PAH) are (1) a delay in early recognition of disease, and (2) imprecise assessment of the severity of the disease. Gravid women suffering from PIH may present in a protean manner which can be misleading to the clinician who relies strictly upon classic clinical parameters in the management of the patient. Many hematologic changes associated with PIH have been documented. However, a comprehensive evaluation of these changes, as depicted by simultaneous laboratory testing, has not been reported. The purpose of this study was twofold: (1) to formulate a profile scoring system in which clinical parameters and laboratory tests were utilized in concert, not as a predictor, but as a standardized method of early recognition of PIH, and (2) to evaluate the profile scoring system's accuracy in assessing the severity of the disease. Empirically, a "profile" was developed that included five clinical parameters (rollover test, mean arterial blood pressure, ocular arteriolar vasospasm, hand and facial edema, patellar reflexes) and eight laboratory tests (urine protein, serum urate, urea nitrogen, creatinine, albumin, total proteins, platelet count, and plasma fibrinogen). Values for each parameter and test were categorized into the accepted normal and abnormal ranges for pregnancy. On the basis of the degree of abnormality, weighted numerical scores of increasing magnitude were arbitrarily assigned to the respective value ranges. For a given patient, the sum of the individual parameter and test scores constituted the profile score. The sample population consisted of 108 patients with "at risk" characteristics or clinical manifestations of PIH. From one to six profile scores per patient were obtained between 24 weeks' gestation and the onset of labor. Simultaneously, the clinical status of the patient was evaluated and assigned to one of four categories: (1) no PIH, (2) incipient PIH, (3) mild PIH, and (4) severe PIH. Of the 108 sample patients, 14 did not develop clinical PIH (no PIH), 17 developed mild gestational or intrapartum hypertension only (incipient PIH), 45 manifested mild preeclampsia (mild PIH), and 32 demonstrated severe preeclampsia (severe PIH), four of whom were eclamptic. Profile scores +/- standard error of the mean (SEM) relative to the patient's clinical status were as follows: no PIH = 7.1 +/- 0.5, incipient PIH = 10.7 +/- 0.4; mild PIH = 15.5 +/- 0.4; and severe PIH = 28.3 +/- 0.9. On the basis of our study data, we believe that profile scoring is an effective system for the early identification of PIH. Also, we believe that, when patients with clinically overt PIH are evaluated, this approach enhances our ability to quantitate the severity of the disease objectively.

Blood Pressure↗