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Biomedical subjects

M Gray

Publications and source records attributed to M Gray.

At least 19 recordsLinked to original sources

High-frequency DNA sequence polymorphisms in the insulin receptor gene detected by denaturing gradient gel blots.

A limiting factor in the study of genetic determinants of human disorders is the availability of informative DNA markers. In this report, we describe an application of the denaturing gradient gel blot method for detecting high-frequency DNA sequence polymorphisms in the human insulin receptor locus. Using two restriction enzymes and cDNA probes for the insulin receptor, we found five DNA polymorphisms. The probe that contained exons 4-10 of the insulin receptor gene detected two two-allelic polymorphisms in HinfI digests, one at denaturant concentrations of 38%/39% and the other at 46%/48%. The probe that contained exons 14-22 detected three two-allelic polymorphisms in Sau96I digests, the first at denaturant concentrations of 34%/35%, the second at 38%/39%, and the third at 46%/47%. All these DNA polymorphisms segregated in families in a Mendelian fashion, and the allelic distribution for each of them did not deviate from Hardy-Weinberg equilibrium. The identified polymorphisms were in linkage equilibrium and provided sufficient genetic information to determine parental haplotypes at the insulin receptor locus in small two-generation families. The denaturing gradient gel blot method is a very sensitive technique for identifying sequence polymorphisms in genomic DNA; its application will facilitate the search for genes involved in the development of many inherited disorders.

DNA

The value of urodynamics and bladder management in predicting upper urinary tract complications in male spinal cord injury patients.

A review of 160 male patients admitted to the Shepherd Spinal Center was completed to determine the influence of urodynamic findings and choice of bladder management program on the risk of developing upper urinary tract distress following acute spinal injury. Within the context of this investigation, upper urinary tract distress was defined as presence of hydronephrosis, febrile urinary tract infection, urolithasis or vesicoureteral reflux. Three groups were identified according to the urodynamic findings and the bladder management program. Thirty-four subjects with preservation of detrusor function managed their bladders by spontaneous voiding. Seventy patients with detrusor areflexia managed their bladders via intermittent catheterization; and 56 males who had detrusor hyperreflexia on urodynamics were managed by a reflex voiding program with condom drainage. None of the subjects with preservation of spontaneous voiding function experienced upper tract distress. Seven percent of those on intermittent catheterization and 32% of those managed by a reflex voiding program experienced upper tract distress. The presence of detrusor hyperreflexia with or without vesicosphincter dyssynergia influenced the likelihood that subjects would experience upper urinary tract distress following spinal injury. While traditional urodynamics failed to distinguish patients managed by a reflex voiding program who experienced upper tract distress from those who did not, calculation of a new urodynamic variable, the urethral pressure gradient, was found to assist in this prediction.

Adult

Multicenter randomized clinical trial of home uterine activity monitoring for detection of preterm labor.

Home uterine activity monitoring has been described as an effective means of detecting uterine contractions, but controversy exists whether it is home uterine activity monitoring or increased nursing support in conjunction with it that contributes to earlier detection of preterm labor. In this study 377 women at risk for preterm labor from three centers were prospectively, randomly assigned to high-risk prenatal care alone (not monitored) or to the same care with twice-daily home uterine activity monitoring without increased nursing support (monitored). The two groups were medically and demographically similar at entry into the study. Routine visits, nonroutine visits, and gestational age at diagnosis of preterm labor were similar in both groups. Preterm labor occurred in 41 of 198 monitored and 39 of 179 not monitored patients. Mean cervical dilatation was 1.4 cm in 41 monitored compared with 2.5 cm for 37 not monitored (p = 0.0006); 73.1% of monitored and 27.5% of not monitored had preterm labor detected before 2 cm dilatation (p = 0.00009). Neonatal outcome of singleton pregnancies showed greater birth weight, fewer days in the neonatal intensive care unit, and fewer babies requiring oxygen therapy and mechanical ventilation in the monitored group. The better outcomes are probably due to the increased likelihood of diagnosis of preterm labor before advanced cervical dilatation with home uterine activity monitoring, thus providing the clinician with a better chance to initiate tocolytic therapy directed at improving pregnancy outcome.

Birth Weight

Mapping point mutations in the Drosophila rosy locus using denaturing gradient gel blots.

Mutations within the rosy locus of Drosophila were mapped using blots of genomic DNA fragments separated on denaturing gradient gels. DNA sequence differences between otherwise identical small rosy DNA fragments were detected among the mutants as mobility shifts on the blots. Mutations were mapped to within a few hundred base pairs of rosy sequence in 100 of 130 mutants tested--a 77% detection rate. The sequence changes in 43 rosy mutations are presented; all but six of these were single base changes. Thirty-four of 36 sequenced mutations induced by the alkylating agents N-ethyl-N-nitrosourea and ethyl methanesulfonate were transitions. All of the mutations mapped in the rosy transcription unit. Twenty-three of the 43 sequenced mutations change the predicted rosy gene polypeptide sequence; the remainder would interrupt protein translation (17), or disrupt mRNA processing (3).

Animals

ABO-incompatible marrow transplants.

Seventeen patients with aplastic anemia or acute leukemia received transplants from donors who had major ABO incompatibilities. Antibody titers were decreased by plasma and whole blood exchanges prior to marrow infusion. All 17 patients were successfully engrafted, and there was one possible rejection in the patient with the highest pretransplant anti-A IgG titer. Nine of 17 patients are currently alive. A review was carried out of transplants performed in Seattle between HLA-matched siblings with aplastic anemia and leukemia. Two hundred forty-six evaluable patients with ABO-compatible donors were compared with 46 with minor ABO-incompatible donors. There was no effect of minor ABO incompatibility on graft rejection, incidence and severity of graft-versus-host disease, or survival.

ABO Blood-Group System

Competency assurance: applying the concept.

The purpose of this paper is to increase understanding of the concept of competency assurance; to encourage associations of health professionals to develop a competency assurance program; and to motivate health care personnel to participate in a competency assurance program. The concept of competency assurance as defined by Wilson is used and its application and usefulness for a national association and its members are illustrated.

Humans

Laboratory diagnosis of latent human papillomavirus infection.

The etiologic association of human papillomavirus (HPV) with uterine cervical cancer has prompted the need for improved laboratory diagnosis of this virus. The application of conventional hybridization technology, including filter in situ hybridization (FISH) and Southern-blot analysis, has revealed that the detection and typing of the virus is inconsistent between sequential specimens from the same individual. To determine whether the polymerase chain reaction (PCR) can be used to provide a more accurate assessment of infection status, two exfoliated cervical cell specimens obtained sequentially from a cohort of 30 women without clinical evidence of cervical abnormalities were analyzed in parallel by FISH and PCR at 6-month intervals. Neither of the procedures provided consistent findings with two sequential specimens suggesting that multiple analyses are necessary to assess infection accurately. However, PCR was less subjective in interpretation and demonstrated greater specificity than did FISH. With the increased sensitivity inherent to PCR, our findings indicated that PCR is more likely to identify latent HPV infection with a single specimen.

Base Sequence