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Biomedical subjects

A O Martin

Publications and source records attributed to A O Martin.

At least 55 records · Page 3Linked to original sources
PubMed1983

Diabetes in pregnancy, Northwestern University series (1977-1981). I. Prospective study of anomalies in offspring of mothers with diabetes mellitus.

Offspring of mothers with diabetes mellitus were examined prospectively with the use of a detailed checklist. Diabetic women were usually identified in the late first or early second trimester and thereafter rigorously managed in hopes of achieving euglycemia. The frequency of infants with major anomalies was higher (9/106, 8.5%) in White Classes B to F than in either the general population or in a small group of concurrently gathered control subjects (1/41, 2.4%). The frequency of anomalies in Class A diabetes was 3/76 (3.9%), a rate that may or may not be increased. Of the 12 major anomalies observed in diabetic offspring, six involved the heart and three involved the skeletal system. No pattern of minor anomalies appeared to exist. Limited data failed to reveal a specific HLA type that conferred increased risk for anomalies, and chromosomal abnormalities were not increased in frequency. If hyperglycemia is indeed the mechanism responsible for anomalies in offspring of mothers with diabetes mellitus, our observations suggest that rates will be reduced only by achieving optimal control in the first trimester.

Congenital Abnormalities↗
PubMed1983

Relationship between Y-chromosome length and first-trimester spontaneous abortions.

The hypothesis that variation in Y-chromosome length is associated with repetitive fetal wastage was tested. Chromosome lengths were objectively quantitated by scanning photographic negatives of metaphases with a computer programmed to (1) select boundary thresholds and (2) construct and measure centerlines with a cubic spline-fitting algorithm. Variation in Y length among cells of different individuals was standardized by use of the ratio of the length of the Y to the average of the lengths of the No. 20s (20) in the same cell. Three groups were studied: (1) men whose wives had three or more spontaneous abortions and no live-born infants, (2) men whose wives had both abortions and normal live-born infants, and (3) control men whose wives had normal live-born infants only. Although central tendencies were similar in the three groups, the distributions of Y lengths among the three groups were significantly different (chi 2(6) = 15.33, 0.025 greater than p greater than 0.010). This difference was primarily because more of the subjects with only repetitive loss had Y lengths in the "tails" of the distribution rather than in the center. Our observations suggest the existence of an optimal Y length with respect to reproductive performance.

Abortion, Habitual↗
PubMed1983

Enhancement of a fra(16)(q22) with distamycin A: a family ascertained through an abnormal proposita.

A family in which a fragile site at 16q22 was segregating was ascertained through a newborn infant with multiple anomalies. The same fragile site was present in the phenotypically normal father and in a brother with cleft palate. The fra(16)(q22) was similar in appearance, and in response to culture conditions, to that reported by other investigators, including increased breakage in media supplemented with distamycin A. Sampling variation in the frequency of breakage over time may be considerable in some individuals. No pattern of anomalies was found to be associated with the fragile site. However, the reproductive history of the family we report (two livebirths with major congenital anomalies and one stillbirth) suggests caution in concluding fra(16)(q22) is not deleterious.

Abnormalities, Multiple↗
PubMed1983

Clinical implications of chromosomal inversions. A pericentric inversion in No. 18 segregating in a family ascertained through an abnormal proband.

Chromosomal inversions are being detected in humans with increasing frequency due to the application of chromosomal banding techniques. Inversions have occurred in all chromosomal groups. These structural aberrations may lead to infertility, reproductive loss, or abnormal offspring. To illustrate their clinical significance, we report a family in which an inversion in chromosome No. 18 is segregating. This family was ascertained through a proband whose anomalies were consistent with the deletion 18q syndrome. The chromosomal imbalance originated by recombination within the parental inversion during meiosis. Consideration of this family and 6 others with similar breakpoints (18p11 and 18q12 or q21) suggests that the risk of unbalanced (recombinant) livebirths may be higher for female inv(18) heterozygotes than for males. The paucity of male carriers detected could be due to prenatal selection or chance. Overall, there may be preferential segregation for the aberrant chromosomes (inversions plus recombinants). Amniocentesis and cytogenetic analysis of pregnancy losses is recommended for families in which inversions are detected.

Abnormalities, Multiple↗
PubMed1983

Linkage analysis in von Willebrand disease.

We studied a 3-generation kindred to determine whether the gene responsible for one form of von Willebrand disease (vWD) is linked to 1) the HLA locus, or 2) a polymorphic locus for a serum enzyme or red cell antigen. HLA haplotypes were determined in 12 affected family members, in 10 cases by direct analysis and in 2 cases by deduction. Seven of 12 affected individuals were A2, B7, as compared to 0 of 9 unaffected. However, the maximum lod score was only 0.41 at a recombination frequency of 0.2. Of the 17 serum red cell and plasma protein markers studied, 5 (Kell, ADA, AK1, BF, GC) did not segregate, and 12 (ABO, Rh, JK, Fy, P, PGM1, ACP1, ESD, GLO1, MN, HP, GPT) gave lod scores less than + 1.0. We conclude that there is no strong evidence for linkage between the locus for vWD and any of the markers studied.

Blood Proteins↗
PubMed1983

Shared HLA antigens and reproductive performance among Hutterites.

Shared histocompatibility antigens between spouses may affect reproductive outcome adversely as a result of prenatal selection against compatible fetuses. Evidence from both animal and human studies suggest that histocompatible fetuses may not initiate a maternal immunologic response that prevents rejection of the embryo. Therefore, parents sharing HLA antigens may produce compatible fetuses and consequently experience a greater frequency of early fetal losses and show poorer reproductive outcome than couples not sharing antigens. In the Hutterites, an inbred human isolate that proscribes contraception, we tested the hypothesis that couples sharing HLA antigens have poorer reproductive outcomes than couples who do not. The Hutterites are characterized by high fertility and large family sizes. Couples that share zero (no. = 21), one (no. = 15), and more than one (no. = 10) HLA-A or HLA-B antigens were compared for reproductive performance. Median intervals between births were larger among couples that share more than one antigen in eight of 11 intervals examined. In addition, the median intervals from marriage to first, fifth, and tenth birth were consistently larger among couples that share more than one antigen. Differences among the groups appear to become larger with increasing parity, suggesting that the effect of histocompatibility on reproductive performance becomes more evident in later pregnancies. These differences in reproductive performance between couples that share zero, one, or more than one HLA-A or HLA-B antigens may have significant evolutionary consequences. However, our results demonstrate that sharing HLA antigens does not preclude normal pregnancy and caution should be exercised before concluding that shared HLA antigens are solely responsible for repeated fetal losses.

Birth Intervals↗
PubMed1982

Hypermodal cells in amniotic fluid cultures: frequency, interpretation, and clinical significance.

Specimens of amniotic fluid were studied to assess the frequency of hypermodal cells and their significance. Multiple cultures were initiated on each specimen, and thorough cytogenetic analysis was performed routinely. Of 1,000 specimens, 59 (5.9%) contained a total of 64 hypermodal cells. However, true fetal mosaicism was not detected. An additional structurally abnormal chromosome accounted for 32 of the 64 hypermodal cells, and, in each case, cytogenetic analysis offered an explanation that obviated clinical concern. In 17 of the 32 cases, hypermodality was only apparent, the result of a single chromosome broken into two parts to produce a spuriously elevated count; in the other 15 cases, the extra chromosome was an unidentified fragment. In the 32 other hypermodal cells, an additional morphologically normal chromosome was present; however, in each case, failure to detect similar aberrations in other cultures initiated from the same specimen minimized the possibility that such cells reflected true fetal mosaicism. Indeed, clinical outcome was normal in all cases. Thus, for clinical purposes, routine banding techniques and analysis of multiple cultures seem to be adequate to exclude fetal mosaicism; laborious in situ methodology seems to be unnecessary. Future cytogenetic efforts should emphasize processing of more specimens of amniotic fluid, rather than more detailed analysis of individual specimens.

Amniocentesis↗
PubMed1982

The cytogenetic response of Fanconi's anemia lymphoblastoid cell lines to various clastogens.

Cytogenetic damage was investigated in long term lymphoid cell lines derived from normal individuals, patients with Fanconi's anemia (FA), ataxia telangiectasia (AT), xeroderma pigmentosum (XP), and FA heterozygotes. The cell lines were exposed to various concentrations of four chemical clastogens, including the alkylating agents diepoxybutane, mitomycin C, and nitrogen mustard, as well as the antitumor glycopeptide bleomycin. The FA cells exhibited chromosomal hypersensitivity to all four clastogens and could be distinguished from the other genotypes. AT cells were identified by bleomycin, while FA heterozygotes could not be reliably detected. Discriminant function analysis was used to describe the cytogenetic response to the various clastogens. This method might prove useful for evaluation and classification of multivariate chromosome breakage studies.

Adult↗
PubMed1982

The identification of fanconi anemia genotypes by clastogenic stress.

Clastogen-induced chromosome damage was investigated in peripheral lymphocytes of five patients with Fanconi anemia (FA), 10 obligate heterozygotes, 25 normal controls, and four individuals with some clinical manifestations of FA. The two agents used were diepoxybutane (DEB) and mitomycin C (MMC), previously reported to be specific for the induction of increased chromosome breakage in FA cells. Following clastogenic stress, two of the five FA patients did not exhibit the expected increase in chromosomal damage while three of the four "non-FA" individuals did. In this series of subjects, the possibility of misdiagnosis is considerable when based on either clinical delineation or cytogenetic results alone. Therefore, the integration of both laboratory data and physical findings is essential before reaching a diagnosis. Furthermore, the broad range of response in both the control group and the parents of FA patients yields overlapping results, making reliable heterozygote detection impractical by these procedures.

Adolescent↗
PubMed1982

A family study of spontaneous sister chromatid exchange frequency.

The frequency of spontaneous sister chromatid exchanges (SCEs) was determined in PHA-stimulated peripheral lymphocytes of 52 individuals, comprising 12 complete 2-generation pedigrees. Neither intraindividual variation between replicate cultures established from the same blood sample nor variation among samples from the same individual initiated at different times was significant. However, familial factors affecting mean SCE frequencies were indicated by detection of significant differences among, but not within, families. Although sample sizes were small, a genetic contribution to the SCE frequency was suggested by the observed pattern of familial correlations.

Adolescent↗
PubMed1981

Cancers of the breast and female genital system: search for recessive genetic factors through analysis of human isolate.

To investigate the importance of recessive genes in female breast and genital cancers, we have conducted investigations in the Hutterites, a highly inbred genetic isolate in North America. The homogeneous life style of this group, which lives on communal farms, also facilitates distinction between shared environmental and genetic factors. We ascertained 177 cases of cancer (all organ systems) through Canadian and United States cancer registries, field trips, and searches of death certificates. Breast cancer and endometrial cancer mortalities were those expected for 1970 United States whites, but no deaths due to squamous cervical carcinoma were ascertained in this monogamous population. Inbreeding coefficients (F) for cases were higher than means for matched controls for each of the four cases of breast cancers that occurred in younger women (less than 45 years of age), for four of five cases of endometrial cancer, and for the single cases of uterine leiomyosarcoma, dysgerminoma, and ovarian adenocarcinoma. By contrast, in cases of breast cancer that occurred in women 45 years of age or older, only four of 15 F's were above those for controls. There is a significant difference between the two breast cancer age groups with respect to the likelihood that the F of cases was higher than the F of controls (chi 2 = 6.99, p less than 0.01). However, grouping cases by type, none of the F distributions were significantly different from those of their matched controls. These preliminary genetic investigations thus conform certain concepts concerning breast and female genital cancer but also suggest the desirability of further studies to elucidate the role of genetic factors in premenopausal breast cancer.

Adult↗
PubMed1981

Chromosome analysis of ectopic human conceptuses.

Maternal factors (e.g. salpingitis) are known to be associated with ectopic gestations; however, few studies have considered the chromosomal complements or morphologic features of ectopic conceptuses. We studied 23 ectopic conceptuses removed from fallopian tubes during surgical resection. The chromosomal complements were normal (four with 46,XY; four with 46,XX) in all cases in which an intact embryo was identified, as well as in the single case characterized by disorganized embryonic tissue. Ten of the 14 ectopic conceptuses in which only a gestational sac and placental villi were identified also show normal chromosomal complements (seven with 46,XX; three with 46,XY); in the remaining four cases, variations from the normal chromosomal complement were found (46,XX/47,XX,+9; 45,X/46,XX; 46,XX/47,XX,+mar; and 92,XXXX). The former two probably signify underlying fetal abnormalities; however, the latter two could have reflected, respectively, in vitro aberrations or tetraploidy characteristic of normal amnion. Pooled data from this study and two previous reports indicate that ectopic conceptuses probable have no higher frequency of chromosomal abnormalities than in utero conceptuses of comparable embryonic ages.

Adolescent↗
PubMed1981

Genetic counseling and genetic services in obstetrics and gynecology: implications for educational goals and clinical practice.

Analysis of genetic counseling and antenatal diagnostic services offered by a genetics unit in a women's hospital was undertaken to identify genetic needs of the obstetrician-gynecologist. For similar reasons we tabulated findings derived from a genetic questionnaire administered routinely to obstetric registrants. Certain well-defined indications for genetic referral were identified, allowing specific educational objectives to be formulated. Potential chromosomal abnormalities constitute the most common indications for referral, particularly advance maternal age and repetitive abortions. A wide range of mendelian and polygenic/multifactorial disorders was encountered, albeit many individually rare. This suggests that the obstetrician-gynecologist should become familiar with principles of these modes of inheritance. However, educational objectives need not stress specific details of rare disorders but rather should emphasize the relatively few disorders that the obstetrician-gynecologist is likely to encounter. Realistic suggestions are offered to achieve these objectives.

Female↗
PubMed1981

The S-leut anthropometric traits: genetic analysis.

Genetic analyses were conducted on 51 anthropometric measurements and on four factors derived from them by factor analysis. These variables were obtained on 784 members of a religious isolate, the S-leut. Correlations were computed between relatives, and heritabilities were estimates using information on extended families. Longitudinal measurements generally exhibited the highest heritabilities. The test for fit of a major gene model was significant for 13 of the 55 variables, the circumferential and breadth measurements giving the strongest evidence for major gene control. In another approach to establishment of genetic control, linkage analysis was performed between the anthropometric variables and blood group and serum protein polymorphisms. Several traits showed some evidence for linkage but none achieved statistical significance.

Adolescent↗
PubMed1981

Ultrasonic induction of sister chromatid exchanges in human lymphocytes.

We analyzed sister chromatid exchange (SCE) frequencies as an indicator of DNA damage induced in human lymphocytes by 'real-time' ultrasound. A range of exposure times and intensities was tested in a series of blind, randomized, in vitro experiments under spatial and sonographic conditions simulating exposure of a gravid abdomen and uterus. Our studies showed small but consistent effects of ultrasound on SCE frequencies, for each experiment. Differences between matched control and exposed means were significantly different from zero. chi 2 tests for homogeneity indicated no significant differences among either the means or the total distributions of the controls, nor among each of the separate dose levels. Consequently, experiments were pooled, and chi 2 analysis indicated significant differences both among distributions and among means of SCE frequencies for controls versus exposed cells (P less than 0.001). The pooled control mean was also significantly different from each of the pooled dose means. Correcting for multiple comparisons gave identical results for the paired comparisons of means except for the 20-min level which was borderline (0.025 less than P less than 0.01). We conclude that the well-established value of clinical ultrasonography warrants its continued use; however, minimizing the numbers and lengths of exposure per patient would seem prudent, pending further information on clinical implications of our results.

Adult↗
PubMed1981

XY gonadal dysgenesis: genetic heterogeneity based upon clinical observations, H-Y antigen status and segregation analysis.

Clinical observations and segregation analysis indicate that XY gonadal dysgenesis is characterized by genetic heterogeneity. In addition to the type inherited in X-linked recessive fashion, segregation analysis of other families suggested another type by revealing that the proportion of affected sibs did not differ from that expected on the basis of a male-limited autosomal recessive inheritance. Further heterogeneity may be deduced on the basis of coexisting campomelic dwarfism or possibly also renal parenchymal abnormalities. These observations of genetic heterogeneity must be considered when interpreting studies in which individuals with XY gonadal dysgenesis may or may not show H-Y antigen.

Alleles↗