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A O Martin

Publications and source records attributed to A O Martin.

At least 19 recordsLinked to original sources
PubMed2001

Gap junctions mediate electrical signaling and ensuing cytosolic Ca2+ increases between chromaffin cells in adrenal slices: A role in catecholamine release.

In adrenal chromaffin cells, a rise in cytosolic calcium concentration ([Ca(2+)]i) is a key event in the triggering of catecholamine exocytosis after splanchnic nerve activation. Action potential- or nicotine-induced [Ca(2+)]i transients are well described in individual chromaffin cells, but whether they remain spatially confined to the stimulated cell or propagate to adjacent cells is not yet known. To address this issue, the spatiotemporal organization of electrical and associated Ca(2+) events between chromaffin cells was investigated using the patch-clamp technique and real-time confocal imaging in rat acute adrenal slices. Spontaneous or electrically evoked action potential-driven [Ca(2+)]i transients were simultaneously detected in neighboring cells. This was likely attributable to gap junction-mediated electrotonic communication, as shown by (1) the bidirectional reflection of voltage changes monitored between cell pairs, (2) Lucifer yellow (LY) diffusion between cells exhibiting spontaneous synchronized [Ca(2+)]i transients, and (3) the reduction of LY diffusion using the uncoupling agent carbenoxolone. Furthermore, transcripts encoding two connexins (Cx36 and Cx43) were found in single chromaffin cells. This gap junctional coupling was activated after a synaptic-like application of nicotine that mediated synchronous multicellular [Ca(2+)]i increases. In addition, nicotinic stimulation of a single cell triggered catecholamine release in coupled cells, as shown by amperometric detection of secretory events. Functional coupling between chromaffin cells in situ may represent an efficient complement to synaptic transmission to amplify catecholamine release after synaptic stimulation of a single excited chromaffin cell.

Action Potentials↗
PubMed1993

A critical review of the genotoxic potential of electric and magnetic fields.

55 published articles were identified which reported results of tests of ELF (extremely low frequency) or static electric or magnetic fields for genotoxic effects. The biological assays used spanned a wide range, including microbial systems, plants, Drosophila, mammalian and human cells in vitro and in vivo. Experimental results were grouped into four exposure categories: ELF Electric; ELF Magnetic; Static Electric; and Static Magnetic. The internal electric fields present in media (for in vitro experiments) and in the torso and extremities (for in vivo experiments) were estimated, providing an index of comparison. All experiments were critically analyzed with respect to basic data quality criteria. Experiments within each exposure category were then compared to determine if results reinforced or contradicted one another. The preponderance of evidence suggests that neither ELF nor static electric or magnetic fields have a clearly demonstrated potential to cause genotoxic effects. However, there may be genotoxic activity from exposure under conditions where phenomena auxiliary to an electric field, such as spark discharges, electrical shocks, or corona can occur. In addition, two unconfirmed reports suggest the genotoxic potential of certain chemical mutagens or ionizing radiation may be affected by co-exposure to electric or magnetic fields. Certain exposure categories are not represented or are under-represented by tests in some genotoxicity test systems that are usually included in minimal test batteries as specified by EPA for chemicals. It is suggested that consideration be given to whether additional genotoxicity testing is warranted to fill these gaps.

Animals↗
PubMed1992

Oculoauriculovertebral anomaly: segregation analysis.

Seventy-four families of probands with oculoauriculovertebral anomaly were evaluated, including 116 parents and 195 offspring. Relatives were examined to identify ear malformations, mandibular anomalies, and other craniofacial abnormalities. For segregation analysis using POINTER, selection of the sample was consistent with single ascertainment. Different population liabilities were used for probands and relatives, because affection was narrowly defined for probands and broadly defined for relatives. The hypothesis of no genetic transmission was rejected. The evidence favored autosomal dominant inheritance; recessive and polygenic models were not distinguishable.

Adult↗
PubMed1991

Method of cavitation-suppressed exposure of cells and explant mouse embryos to clinical real-time and pulsed Doppler ultrasound.

An apparatus and procedure for well-controlled exposure of cells or explant mouse embryos to clinical real-time ultrasound are described. Cells or embryos to be exposed are suspended in media made sufficiently viscous through inclusion of methylcellulose that cavitation is suppressed but thermal effects remain negligible. During exposure, the scanning beam is precisely centered in a 2 mm x 20 mm slot in a 20 cm diameter agar disc containing the suspension. The high viscosity causes the cells to remain distributed uniformly throughout the exposure; this fact, along with precision beam alignment, ensures that exposure is well defined. Exposure data are acquired with a 0.6 mm diameter hydrophone.

Animals↗
PubMed1991

Diagnostic ultrasound is unable to enhance the rate of neoplastic transformation in cultured mammalian cells.

The ability of diagnostic pulsed ultrasound to induce heritable genetic damage of the type that could result in neoplasia was assayed using BHK21/cl 13 hamster cells or normal human fibroblasts as targets. Using an exposure apparatus carefully designed to minimize beam attenuation and reflection, cavitation, and heating, cells were exposed from 20 seconds to 40 minutes either to clinical machines operating at maximum power, or to a highly focused nonclinical transducer at 2900 W/cm2, or to 200 shocks from a lithotripter. No evidence of an increase in the frequency of neoplastically transformed BHK cells or in the frequency of mutant human cells was seen over those found in matched sham-exposed controls.

Animals↗
PubMed1991

The role of preimplantation sonographic exposure in postimplantation development and pregnancy outcome.

To determine what, if any, effects exposure to ultrasonic beams has on preimplantation embryos we isolated mouse blastocysts and assessed resorption rate, pregnancy rate, decidual swelling volume, and live birth rate after in vitro exposure with subsequent transfer to surrogate mothers. The blastocyst stage embryos were isolated by flushing the uteri of pregnant animals with a phosphate buffered medium. Blastocysts at a discrete stage of development were pooled and transferred to a PB1-methylcellulose medium. This medium is specifically designed to maintain the embryos in a high viscosity solution during the sonographic exposure to prevent microcavitation. After the exposure, the embryos were washed free of methylcellulose and transferred to the uteri of pseudopregnant surrogate mothers. A total of 660 blastocyst stage embryos were distributed among seven treatment groups. After exposure, the embryos were transferred to 54 surrogate mothers. A total of 199 embryos were implanted successfully for postimplantation evaluation. An additional 427 blastocysts were distributed among four treatment groups and transferred to 46 surrogate mothers to assess the effect of sonographic exposure on birth rate. The results indicate possible deleterious effects (decreased implantation rate, increased resorption rate, decreased decidual swelling volume, and increased stillbirth rate) of short ultrasonic exposures (1 min and 5 min) on mouse blastocyst function.

Animals↗
PubMed1991

Sister chromatid exchange analysis of human cells exposed to diagnostic levels of ultrasound.

Lymphocyte and lymphoblastoid cells were exposed in vitro to diagnostic levels of ultrasonic beams delivered by a Hewlett-Packard CE 30001 and a GE system with a 5 MHz linear transducer for 20 sec, 1 min, 5 min, and 20 min. Temperature and cavitation effects were controlled and there were matched sham exposures. The synergistic effects of theophylline with ultrasonography also were investigated. Small increases in sister chromatid exchange levels were observed after ultrasonic exposure, but increases were so small as to be unlikely to have clinical relevance. Theophylline was found to have no effect and ultrasonography had no effect on cell viability.

Adult↗
PubMed1990

Stylized chromosome images.

Stylized chromosome images 1) serve as a format to test effects of preprocessing algorithms used in automated karyotyping; 2) enhance the ability of humans to perform quantitative analysis of chromosomal aberrations; 3) provide an alternative format for karyotype hard copies produced by automated systems. Stylized chromosomes are two-dimensional computer-generated images based on information extracted from one-dimensional width and density profiles. These profiles correspond to what cytogeneticists observe through the microscope as the shape and banding patterns of stained chromosomes. Stylized presentation sharpens chromosome band boundaries and perimeters, reduces "noise," and enhances gray level variations, which are difficult to distinguish by humans on photographic or computer generated karyotypes. Karyotyping accuracy using stylized images was used to detect difficult areas for automated chromosome identification. Landmark bands sufficient to classify chromosomes were identified; shapes of chromosomes reflected in width profiles were said to aid classification. A two-step automated karyotyping strategy proposed is: 1) classify chromosomes by landmarks, minimum information needed for identification; 2) subsequently employ the full banding pattern with maximum resolution to detect aberrations. Stylized images of abnormal chromosomes have potential for testing hypothesis regarding breakpoints and quantitative analysis, but improvements are needed in homologue normalization and definition of termini of chromosomes.

Algorithms↗
PubMed1990

Cytogenetic results of chorionic villus sampling: high success rate and diagnostic accuracy in the United States collaborative study.

Cytogenetic results of first-trimester chorionic villus sampling are reported from seven U.S. medical centers. For 6033 patients who had a successful chorionic villus sampling procedure, the rate for obtaining a cytogenetic diagnosis was 99.6% with the direct method, long-term culture, or both. There were no incorrect sex predictions and no diagnostic errors involving trisomies 21, 18, or 13, sex chromosome aneuploidies, or structural abnormalities. There were no cases of normal cytogenetic diagnosis followed by birth of a cytogenetically abnormal infant. Three cases of unusual aneuploidies (tetraploidy, trisomy 16, and trisomy 22) detected by the direct method only were not confirmed by cytogenetic follow-up. Mosaic cytogenetic abnormalities were observed in 0.83% of all cases in which chorionic villus sampling was done but were confirmed by amniocentesis or in fetal tissues in only 7 of 30 cases (23.3%). Maternal cell contamination occurred in 1.9% of long-term cultures, although this did not present any cytogenetic diagnostic difficulties. Overall, a very high degree of laboratory success and diagnostic accuracy was observed with either cytogenetic method, although fewer predictive errors were observed with the long-term culture method and none were observed when both methods were used.

Amniocentesis↗
PubMed1990

Maternal serum alpha-fetoprotein levels in pregnancies complicated by diabetes: implications for screening programs.

Maternal serum alpha-fetoprotein may be reduced in diabetic pregnancies, but the association with elevated glycosylated hemoglobin has been controversial. We tested the hypothesis that reductions in maternal serum alpha-fetoprotein may reflect the same phenomena that can also impair normal rates of embryo growth in the presence of poorly compensated maternal diabetes. If so, associations would be expected among maternal serum alpha-fetoprotein, embryo rates of growth, and levels of glycosylated hemoglobin reflective of regulation of maternal diabetes during the period of organogenesis. We found maternal serum alpha-fetoprotein levels in 93 pregnant patients with diabetes to be negatively associated with the earliest (4 to 12 weeks) glycosylated hemoglobin determinations. At glycosylated hemoglobin values greater than 9.6% (which approximates the upper quartile), all maternal serum alpha-fetoprotein values fell below the median for patients without diabetes (below 0.8 multiple of the median after weight adjustment). Moreover, there was a trend for pregnancies with lower maternal serum alpha-fetoprotein levels and higher glycosylated hemoglobin values to also demonstrate early fetal growth delay as measured by ultrasonography.

Embryo, Mammalian↗
PubMed1989

On the selection of systems for automated cytogenetic analysis.

Impressive technological advances in systems for automated metaphase location and cytogenetic analysis have resulted in a proliferation of commercially available systems offering a variety of performance and price options. Based on the numbers of systems sold, it appears as if automation is becoming an accepted component of cytogenetic laboratories. To address the question of whether automation is useful and, if so, to identify the advantages and disadvantages of some of the systems, we have supplemented our own laboratory experience using the Magiscan routinely for clinical cytogenetic analysis, with information obtained during an on-site survey of other clinical cytogenetic facilities using automated systems (Genetiscan, Karyotype Image Editor, Metachrome, Cytoscan). Some systems provide both metaphase-locating and karyotyping capabilities--some only the latter. The basic structure of all systems is similar: microscope with camera, image processor, mechanism for operator interaction with the computer, hard copy printer. Metaphases are digitized, analyzed, and converted to permanent images. Metaphase-locating systems (Cytoscan, Magiscan, Metachrome) require, in addition, motorized slide-scanning stages. The biggest time savings resulting from use of automation is in the karyotyping steps, especially the production of a hard copy. Consequently, laboratories making many karyotypes will benefit most from such systems. The optimum choice of system will depend on specific laboratory parameters: number and type of specimens processed; operational preferences, e.g., number of bands per metaphase; number of metaphases counted; and karyotypes prepared per case. Laboratories processing chorionic villus specimens and/or bone marrows, where much slide area must be searched, will benefit from fast metaphase locators with multislide stages.(ABSTRACT TRUNCATED AT 250 WORDS)

Computers↗
PubMed1989

Microtia and associated anomalies: statistical analysis.

Terms such as oculoauriculovertebral dysplasia, Goldenhar syndrome, and hemifacial microsomia have been used to describe microtia with specific combinations of other craniofacial anomalies. Microtia is also observed with anomalies of postcranial structures. Statistical studies were performed on 297 patients with microtia and other anomalies to identify subgroups of patients representing previously described or new associations. Analysis identified 15 subgroups of patients with specific patterns of anomalies. Log-linear analyses of cranial and postcranial variables demonstrated a positive association between mandibular hypoplasia and cervical spine fusion, which was, in turn, positively associated with other spine anomalies (P less than .02) and other skeletal anomalies (P less than .001). Although unilateral microtia was commonly observed with mandibular hypoplasia, mandibular hypoplasia was negatively associated with bilateral microtia. Many of the associated anomalies were of structures not derived from the 1st and 2nd branchial arch neural crest. However, most associated anomalies were of structures derived from migratory cell populations or populations undergoing differentiation prior to migration between the 19th and 24th day post-fertilization (neural crest, ectodermal placode, mesoderm, surface ectoderm). These findings suggest that many different cell populations may be disturbed in the pathogenesis of microtia in association with other anomalies. The timing of the pathogenetic event may determine the specific pattern of associated anomalies.

Abnormalities, Multiple↗
PubMed1989

Translocations are infrequent among couples having repeated spontaneous abortions but no other abnormal pregnancies.

During the years 1977 to 1986, cytogenetic studies were performed on 342 women and 297 men whose reproductive history included one or more first trimester spontaneous abortions. Thirty-nine women and 35 men experienced not only early fetal losses but also one or more stillborn infants, liveborn anomalous infants, or early neonatal deaths. Among the 303 women and 262 men evaluated solely because of repetitive abortions, only 1 woman and 1 man showed a translocation. Two translocations were detected among the 39 women and 35 men having not only repetitive abortions but also a stillborn infant, anomalous liveborn, or unexplained neonatal death. Only among the 25 women having abortions and other abnormal perinatal events was the frequency of translocations high (2/25 or 8%). Our data continue to indicate that balanced chromosomal translocations are relatively infrequent in individuals having repeated abortions but no other adverse perinatal outcome.

Abortion, Habitual↗
PubMed1989

Genetic analysis of HLA in the U.S. Schmiedenleut Hutterites.

The Hutterites are an Anabaptist population, highly inbred, with large family sizes and extensively documented pedigrees. As part of genetic-epidemiologic studies of the impact of HLA on fertility, HLA-A, -B, -C, -DR, and -DQ typing was performed on a total of 650 Schmiedenleut Hutterities in South Dakota. An extraordinary degree of homogeneity was found. HLA-A1, -A2, -A3, -A24, and -A26 accounted for 83%, HLA-B8, -B27, -B35, -B51, -Bw60, and -Bw62 for 75%, and HLA-DR1, -DR2, -DR3, and -DR4 for 66% of the antigens at the respective HLA-A, -B, and -DR loci. All Hutterites characterized for HLA were descendants of no more than 78 ancestors. However, family analysis identified only 45 unique HLA haplotypes thought to reflect the original gene pool. Eight haplotypes were particularly frequent, accounting for nearly 50% of all observed haplotypes; four of these were consistent with a European ancestry. Coefficients measuring linkage disequilibrium were computed from haplotypes identified by family analysis. Overall, HLA analysis portrayed the Schmiedenleut Hutterities as a homogeneous and unique population, with disequilibrium among particular alleles and a spectrum of common and uncommon European haplotypes.

Alleles↗
PubMed1988

Prenatal detection of 46,XY,rec(5),dup q, inv(5)(p13q33) using DNA analysis, flow cytometry, and in situ hybridization to supplement classical cytogenetic analysis.

Distinguishing between balanced and unbalanced chromosome complements segregating from parental rearrangements may be difficult using only classical cytogenetic techniques if banding morphology is similar under both expectations. In these situations, supplementing cytogenetic analysis with molecular genetic techniques and flow cytometry may provide increased diagnostic accuracy. To illustrate this, we present a case in which similar band pattern morphology would be expected for both the balanced carrier (heterozygote) and the recombinant dup q chromosome complements segregating from a mother with a balanced inversion [46,XX,inv(5)(p13q33)]. The parents came to Northwestern for consultation after receiving conflicting interpretations of their first amniotic fluid cultures. An ultrasound examination was said to be normal. They inquired whether there were ways to increase their confidence that the complement was unbalanced. Their reluctance to terminate the pregnancy was due to a 6-year history of infertility. After extensive counselling, the couple elected repeat amniocentesis. Further cytogenetic analysis of repeat amniotic fluid cultures by G-banding and R-banding, molecular genetic analysis with highly polymorphic DNA probes, and quantitative flow cytometry were performed. Results agreed that an unbalanced fetal complement was present. Southern blot analysis with a 5p marker definitively demonstrated a lack of maternal 5p material in the fetus, and in situ hybridization showed a 5q marker at either end of the recombinant chromosome. Flow cytometry was consistent with this interpretation. Because of the advanced gestational age, the parents elected to terminate based on cytogenic results of the second amniocentesis, rather than to wait another 1-2 weeks for results of other methods.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Growth disadvantage of 45,X and 46,X,del(X)(p11) fibroblasts.

We have previously shown that cell generation time (CGT) is prolonged in 45,X and certain X-deletion fibroblast lines (Simpson & Le Beau 1981). A consequence of that finding should be that cells with 45,X or an X-structural abnormality are at a competitive disadvantage when cocultivated with 46,XX cells. To test this hypothesis we prepared 15 minutes of cells from combinations of 9 different cell lines: four 45,X; one 46,Xdel(X)(p11); and four 46,XX. Each culture was monitored cytogenetically at frequent passage intervals for the percentage of the two cell lines. Significant differences were found between normal and abnormal lines in culture predominance, in the order predicted by our hypothesis (p less than 0.01). The specific mechanism by which absence of an X chromosome confers growth disadvantage is unknown, but is consistent with prolongation of CGT. Prolongation of CGT could also be responsible for the embryonic lethality, intrauterine growth retardation, short stature, and somatic anomalies commonly observed in individuals with absent or aberrant X chromosomes.

Cell Division↗
PubMed1987

Oculoauriculovertebral dysplasia and variants: phenotypic characteristics of 294 patients.

Here we describe the phenotypic characteristics of a single craniofacial clinic population of 294 individuals affected with oculoauriculovertebral dysplasia (OAV) and variants. To our knowledge, this is the largest population so described in the literature. The study population was divided into five subgroups based on the presence of combinations of minimal diagnostic criteria: microtia, mandibular hypoplasia, anomalies of the cervical spine and/or epibulbar or lipodermoids. The following data were recorded: sex (M:F 191:103); race (78% Caucasian); the presence of unilateral or bilateral microtia (193 unilateral, 98 bilateral); the presence of symmetric microtia in bilateral cases (34/98); the presence of mandibular hypoplasia ipsilateral or contralateral to the microtic ear or most severely microtic ear in bilateral cases (135/137 were ipsilateral in unilateral cases, 55/62 were ipsilateral in bilateral cases); the number of individuals with no other congenital anomaly in addition to the minimal diagnostic criteria (154/294), with only one other congenital anomaly (51/294), and with two or more other congenital anomalies (89/294); and the type of other congenital anomalies. Finally, we compared our results with other studies. Findings from our study include: mandibular asymmetry should be expected in patients with unilateral or bilateral microtia; bilateral involvement is frequent in patients with microtia; other malformations are seen frequently in all subgroups; anomalies of the cervical spine are more likely to be associated with other anomalies; and other malformations are seen in all systems and should be searched for to provide optimal management.

Adolescent↗