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Biomedical subjects

W L Martin

Publications and source records attributed to W L Martin.

17 recordsLinked to original sources

Isolation of fetal trophoblasts and nucleated erythrocytes from the peripheral blood of pregnant women for prenatal diagnosis of fetal aneuploides.

We present the results of a study of fetal cell isolation from the peripheral blood of 46 women in the first trimester of pregnancy. The trophoblasts were sorted with paramagnetic beads labelled with a novel monoclonal antibody 340 (Mab340) (Durrant et al., Prenat. Diagn., 14 (1994) 131). This was followed by triple density gradient enrichment to remove maternal lymphocytes and red blood cells. Nucleated red blood cells (NRBC) were sorted by incubation with ferromagnetic particles coated with Mab CD71, an antitransferrin receptor monoclonal antibody, and separation on a mini-MACS column. Sorted cells were sexed using nested PCR for the Y chromosome and the results compared with the karyotypic analysis of the CVS. The sensitivity in determining a male pregnancy with NRBC alone was 38% and with trophoblasts alone was 39%. Sorting for both cell types correctly predicted a male pregnancy in 10/18 or 56%. Of the 10 males correctly identified, 3 were diagnosed on NRBC alone, 3 on trophoblast alone and 4 with both cell types. As there are very few fetal cells in maternal blood, sorting for both will increase the yield and improve diagnosis. However the technique requires further development to improve sensitivity.

Aneuploidy

The cytochrome P450 2D6 (CYP2D6) enzyme polymorphism: screening costs and influence on clinical outcomes in psychiatry.

OBJECTIVES: This study examined factors that affect cost, reliability, and the value of determining the cytochrome P450 2D6 (CYP2D6) polymorphism in clinical practice. STUDY DESIGN: The method of deoxyribonucleic acid isolation, sample preparation, oligonucleotide primers, and polymerase chain reaction procedures were scrutinized for their effect on CYP2D6 genotyping efforts. The determination of the CYP2D6 A, B, D, E, and T alleles was used to identify the deficiency in CYP2D6 expression in 161 individuals phenotyped for CYP2D6 activity with dextromethorphan. The CYP2D6 genotype was assessed in 74 outpatients who had received diagnoses of depression. Eighteen of these patients were screened because of an adverse response to a tricyclic or antidepressant known or suspected to be a CYP2D6 substrate. RESULTS: The CYP2D6 A, B, C, D, E, and T alleles could be detected in 13 hours at a cost of $84 per sample by judicious selection of conditions and procedures. The genotype provided an accurate predictor of CYP2D6 expression in all 134 subjects who expressed the enzyme and in all 27 unrelated individuals phenotyped as deficient in CYP2D6 activity. In the patient group that experienced adverse effects, 44% of all CYP2D6 gene copies contained the A, B, D, E, or T allele(s) associated with inactive CYP2D6 expression. This was more than twice the rate for the occurrence of mutant alleles in the other 56 psychiatric patients (21%) and in 80 random subjects from the general population (20%; p < 0.05). CONCLUSIONS: Screening psychiatric patients for CYP2D6 expression may distinguish metabolic-based therapeutic problems from drug sensitivity caused by other mechanisms.

Antidepressive Agents, Tricyclic

Cloning of a mineral phosphate-solubilizing gene from Pseudomonas cepacia.

We have recently shown that the ability of some gram-negative bacteria to dissolve poorly soluble calcium phosphates (Mps+ phenotype) is the result of periplasmic oxidation of glucose to gluconic acid via the quinoprotein glucose dehydrogenase (GDH), a component of the direct oxidation pathway. Escherichia coli K-12 derivatives synthesize apo-GDH but not the cofactor pyrroloquinoline-quinone (PQQ) essential for formation of the holoenzyme. Therefore, in the absence of exogenous PQQ, these strains do not produce gluconic acid and are Mps-. Evidence is presented to show that expression of a single 396-base Pseudomonas cepacia open reading frame (designated gabY) in E. coli JM109 (a K-12 derivative) was sufficient to induce the Mps+ phenotype and production of gluconic acid. We present the nucleotide sequence of this open reading frame which coded for a protein (GabY) with a deduced M(r) of 14,235. Coupled transcription-translation of a plasmid (pSLY4 or pGAB1) carrying gabY resulted in production of a protein with an M(r) of 14,750. Disruption of the open reading frame of gabY via site-directed mutagenesis changed the phenotype to Mps- and eliminated gluconic acid production. The deduced amino acid sequence of gabY has no apparent homology with those of previously cloned direct oxidation pathway genes but does share regions highly homologous with the histidine permease system membrane-bound protein HisQ as well as other proteins in this family. In the presence of 1 microM exogenous PQQ, both JM109(pSLY4) and JM109(pGAB1) produced 10 times as much gluconic acid as was seen with either the plasmid or exogenous PQQ alone.(ABSTRACT TRUNCATED AT 250 WORDS)

ATP-Binding Cassette Transporters

Cognitive performance on the Alzheimer's Disease Assessment Scale: effect of education.

The cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog) is used to monitor disease progression and treatment efficacy in clinical trials of Alzheimer's disease (AD). Using data from a 12-week drug trial, we retrospectively studied the effect of education on ADAS-Cog performance in a group of 444 patients with AD. The effect of education was statistically significant on baseline ADAS-Cog total scores. This effect remained statistically significant after controlling for age, gender, and dementia severity. Education effects were also statistically significant at week 12 for ADAS-Cog total and 10 of 11 subitem scores in 138 AD patients in the placebo arm of the trial. Post hoc analysis showed that non-high school graduates performed worse than those with greater educational levels across a broad range of cognitive domains. Our results, in conjunction with reports linking lower educational level with a higher risk for AD, suggest that educational level of patients be given consideration in the design and interpretation of cognitive tests in AD drug trials.

Aged

Reversal of female sterilisation: outcome of 210 referrals.

AIMS: To determine the outcome of request for reversal of sterilisation and to compare demographic and social factors of women who subsequently withdrew their request with those who proceeded with the reversal assessment and operation. METHODS: Information relating to the sterilisation and regret intervals were sought from 210 women. Demographic and social factors were recorded and the outcome of the reversal request determined. Patients who withdrew or were deferred/declined were compared on relevant factors with the group who proceeded to, or are still planning, the reversal operation. RESULTS: Ninety-two (44%) withdrew before or during the assessment phase. Another 13 withdrew after laparoscopy identified a poor prognosis. Three declared their intention not to conceive after they underwent the reversal operation. To date, 83 have had surgery with the cumulative intrauterine pregnancy rate at 1, 2 and 3 years being 0.46, 0.62 and 0.78 respectively. In comparing those women who proceeded and withdrew, there were no differences in mean age at referral, age at sterilisation, the number of living children nor marital status. The regret interval prior to referral was significantly longer in the women who proceeded (27.9 and 19.5 months respectively, p = 0.03). Those who were highly motivated in their reversal request were also more likely to proceed (p = 0.003). CONCLUSIONS: There is a large dropout rate of women who seek a reversal of sterilisation. Women who regret sterilisation may have sought sterilisation as a solution to problems that were psychosocial rather than contraceptive in nature. We stress the importance of counselling for both sterilisation and its reversal, since in the latter many developmental personality and relationship problems remain unresolved.

Adult

Human stereopsis.

This paper reviews much of the basic literature on stereopsis for the purpose of providing information about the ability of humans to utilize stereoscopic information under operational conditions. This review is organized around five functional topics that may be important for the design of many stereoscopic display systems: geometry of stereoscopic depth perception, visual persistence, perceptual interaction among stereoscopic stimuli, neurophysiology of stereopsis, and theoretical considerations. The paper concludes with the presentation of several basic ideas related to the design of stereoscopic displays.

Animals

Performance on a reciprocal tapping task with variations in intertapping interval.

Fitts' law was investigated in a study of the effect of the index of difficulty (ID) and intertapping interval upon reaction time (RT) and movement time (MT) for a reciprocal tapping task. ID showed its well-established relationship with MT as described by Fitts' law: MT = aID + b. Improvement in the linearity of this relationship was, however, demonstrated by expressing MT in logarithmic units. While ID had an unsubstantial (though significant) effect on RT, increases in intertapping interval from zero to any level of discrete tapping led to significant increases in RT of about 135 msec. The results are interpreted as lending support to Fitts' thesis that RT and MT reflect independent phases of information processing.

Humans

Normal pressure hydrocephalus: a case presentation.

There are presently no successful medical treatments available for most of the chronic dementias. For this reason it is most important to diagnose potentially reversible syndromes such as Normal Pressure Hydrocephalus and to determine if that patient is a candidate for neurosurgical treatment. A typical clinical case exemplifying the most common features of this syndrome is presented. This is followed by a discussion of the physiology, etiology, signs and symptoms, methods of diagnosis, and treatment of this illness. Material for this discussion was obtained from personal clinical experience and a review of the medical literature.

Aged