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Biomedical subjects

C Stewart

Publications and source records attributed to C Stewart.

At least 19 recordsLinked to original sources

The transport of airborne trace elements copper, lead, cadmium, zinc and manganese from a city into rural areas.

The fluxes of the elements lead, zinc, copper, cadmium and manganese have been measured in the insoluble component of bulk deposition derived from Christchurch, New Zealand. Lead, zinc, copper and cadmium fluxes follow approximately exponential decay curves away from the city whereas manganese deposition showed little spatial variation. A similar composite source originating in the city is indicated for the lead zinc, copper and cadmium and a different major source occurs for manganese. In the city and nearby rural areas soil is not a major source of atmospheric lead, zinc, copper and cadmium, whereas at remote sites atmospheric levels of these elements are mostly soil derived. Seasonal variations in the bulk deposition are large within the city, and at upwind rural sites. The variations are controlled by meteorological conditions, in particular wind speed and the height of the mixing layer. Compared with overseas studies, the proportion of the metals occurring in the soluble fraction of the bulk deposition is low. This may be due to the relatively dry climate of the area.

Air Pollutants

Congenital bilateral absence of the vas deferens. A primarily genital form of cystic fibrosis.

OBJECTIVE: Almost all males with cystic fibrosis (CF) have absent vasa deferentia. It has been suggested that otherwise healthy males with congenital bilateral absence of the vas deferens (CBAVD), previously considered a distinct genetic entity, have an increased frequency of CF gene mutations. This study examined the genetic commonality of these two disorders. DESIGN: We typed six common CF gene mutations in 25 patients with CBAVD. Additional rare mutations were sought using single-stranded conformation polymorphisms and direct DNA sequencing. When rare mutations were found, they were sought in a large sample of both CF patients and obligate CF carriers to exclude them as polymorphisms. SETTING: All the patients presented to a male infertility clinic of a teaching hospital. SUBJECTS: Twenty-five unselected, unrelated azoospermic men with CBAVD, most of them of Northern European ancestry. RESULTS: Sixteen (64%) of the 25 men with CBAVD had at least one detectable CF mutation, 16 times the expected frequency (P less than .001). Moreover, we have thus far determined that three of these 16 men are compound heterozygotes, one of whom has a mutation not previously described. Analyses continue on patients who have yet to yield a detectable mutation. CONCLUSIONS: Some, if not all, otherwise healthy men with CBAVD reflect a newly recognized, primarily genital, phenotype of CF. Prior to sperm aspiration to remedy infertility, CF mutation analysis should be recommended for them and their partners, as well as for their relatives.

Adult

Typing of HLA-DQA1 and DQB1 using DNA single-strand conformation polymorphism.

The technique of single-strand conformation polymorphism (SSCP), which is capable of distinguishing DNA sequence variability, was adapted to the identification of the HLA-DQA1 and DQB1 alleles. Eight DQA1 alleles and 12 DQB1 alleles were distinguished by amplifying the second exon of the genes in the presence of radioactive deoxynucleotide, denaturing the products with heat, and separating the single strands by electrophoresis in nondenaturing gels. For DQA1, it was possible to distinguish the eight alleles with standard bis-acrylamide or with a Hydrolink gel matrix. Twelve DQB1 alleles were identified by a protocol employing a combination of oligohybridization and SSCP using products amplified by specific DQB1 primers.

Alleles

Alternate cardiovascular baseline assessment techniques: vanilla or resting baseline.

The accurate evaluation of cardiovascular reactions to psychological challenge requires stable baselines against which change can be evaluated. When more than one challenge is employed, the recovery of this baseline becomes important in order to avoid carryover effects. Resting periods, even those of 20 min or more, do not guarantee baseline stability. We compared a 20-min resting condition and a new form of baseline condition in 48 college men using video tasks as the psychological challenges. The new form was a minimally demanding color detection task, termed the "vanilla" baseline condition. A 10-min version and a 20-min version of this condition were tested. Comparisons to 10-min resting baselines were made using our prior work and values from the literature. Vanilla baseline conditions were shown to be equal to or better than resting baseline conditions using criteria of between- and within-baseline stability, amplitude and significance of responsivity, and generalizability between sessions on separate days. Ten-minute resting baselines also showed acceptable stability, questioning the value of lengthy baselines. The good performance of the 10-min vanilla baseline in initial and replication samples supported its utility for estimating baselines for many purposes.

Adolescent

Cardiac conduction abnormalities and rhythm changes after neonatal anatomical correction of transposition of the great arteries.

Seventy three infants who underwent neonatal anatomical correction for transposition of the great arteries with or without a ventricular septal defect were reviewed for evidence of conduction and rhythm abnormalities on preoperative and postoperative 12 lead electrocardiograms and during 24 hour Holter monitoring. There was a partial right bundle branch block pattern in 47% (29/62) of all patients and in 60% (24/40) of those with simple transposition. Complete right bundle branch block was noted in 21% including 5% with simple transposition. Holter monitoring showed sinus rhythm in all patients except three: one had episodes of supraventricular tachycardia, another an intermittent second degree heart block, and a third a complete heart block. Atrial extrasystoles were noted in 47% (29/62) of patients but were frequent in only three patients. Occasional unifocal ventricular extrasystoles were encountered in 37% (23/62) of patients and were frequent in a further 3% (2/62). Only one patient (2%) developed multifocal ventricular extrasystoles. The frequency of important cardiac arrhythmias after neonatal anatomical correction of transposition of the great arteries was 5%, significantly less than that reported after atrial inflow diversion for the same malformation.

Arrhythmias, Cardiac

Abductor laryngeal dystonia: a series treated with botulinum toxin.

Abductor laryngeal dystonia (LD) is characterized by a hoarse voice quality which is broken up by breathy or whispered portions. Botulinum toxin injection (Botox) has been a safe and effective treatment for adductor laryngeal dystonia and is currently accepted medical therapy. As an extension of the established treatment program, in 1989 treatment of abductor LD was initiated. Thirty-two patients have been treated by sequential percutaneous electromyogram-guided (EMG) injections of the posterior cricoarytenoid (PCA) muscles. Most patients required treatment of both PCA muscles and improved to an average of 70% of normal voice. Patients who had a preexisting tremor, evidence of dystonia in other muscle groups, vocal tremor, or respiratory dysrhythmia had less improvement. Ten patients also required injection of the cricothyroid muscles and/or type I laryngoplasty.

Adolescent

Linkage mapping of the human CSF2 and IL3 genes.

Interleukin 3 (encoded by the IL3 gene) and granulocyte-macrophage colony-stimulating factor (encoded by the CSF2 gene) are small secreted polypeptides that bind to specific cell surface receptors and regulate the growth, gene expression, and differentiation of many of the hematopoietic cell lineages, particularly nonlymphoid cells. The IL3 and CSF2 genes have been cloned and mapped to human chromosome bands 5q23-31. Only 10 kilobases of DNA separates the two genes, suggesting that they have a common origin and/or regulation. We have cloned 70 kilobases of genomic DNA that includes the IL3 and CSF2 genes, as well as flanking sequences, and report a physical map of this region. Several unique-sequence DNA segments have been identified in this region, and one of these fragments detects two restriction fragment length polymorphisms in DNA from unrelated Caucasians. Segregation of these DNA polymorphisms was followed in the Centre Etudé du Polymorphisme Humaine (CEPH) panel of 40 large three-generation pedigrees, and linkage was detected with 17 genetic markers previously typed in these families. Multipoint linkage analysis permits the placement of the region containing the IL3 and CSF2 structural genes on the recombination-genetic linkage map of chromosome 5q and thereby allows the role of these genes in leukemogenesis to be more critically examined.

Base Sequence

Experimental oral foreign body reactions: vegetable materials.

Foreign bodies and tissue reactions to foreign materials are commonly encountered in the oral cavity. Exogenous materials most commonly causing foreign body reactions are metallic in origin (usually amalgam). Of the nonmetallic materials seen during biopsies, suture materials and vegetable matter are most often observed. Since many foodstuff foreign materials are unidentifiable histologically, common vegetables were experimentally implanted subcutaneously in rats to assess local host responses and to characterize the nature of these materials microscopically. The histologic characteristics of these vegetable foreign body reactions are detailed herein. The implanted materials correspond to reactions seen in human subjects.

Animals

Detection of three rare frameshift mutations in the cystic fibrosis gene in an African-American (CF444delA), an Italian (CF2522insC), and a Soviet (CF3821delT).

We have identified three new frameshift mutations in the CFTR gene in patients with cystic fibrosis (CF). The first one involves the deletion of an adenine nucleotide in exon 4 in an African-American patient (CF444delA), the second involves the insertion of a cytosine nucleotide in exon 13 in an Italian patient (CF2522insC), and the third results from the deletion of a thymidine nucleotide in exon 19 in a Soviet patient (CF3821delT). Each mutation is predicted to result in premature termination of the CFTR protein.

Adult

Type III glycogen storage disease: an adult case with mild disease but complete absence of debrancher protein.

A 54-yr-old woman who presented with chest pain and elevated serum creatine kinase levels was found to have type III glycogen storage disease. Except for a history of hepatomegaly in childhood, she was healthy and lived a normal life. There was no hypoglycemia, seizure disorder or growth retardation. Muscle weakness was not apparent until the sixth decade. Despite the mild clinical course, debranching enzyme activity was not detectable by biochemical assay, and immunoblot analysis using a polyclonal antibody showed a complete absence of debrancher protein. Thus, mild clinical manifestations in this patient could not be explained by the residual debrancher enzyme and/or activity.

Creatine Kinase

Tumour suppression associated with expression of human insulin-like growth factor II.

Recent circumstantial evidence has implicated Insulin-like growth factor II in the genesis of several tumour types, notably developmental tumours (Scott et al., 1985; Schofield & Tate, 1987; Wilkins et al., 1989). This type of tumour, thought to originate during the defective differentiation of organ precursors (Miereau et al., 1987), often expresses greatly elevated levels of mRNA for IGF-II, a known mitogen for these cells and abundantly expressed in their presumed normal counterparts (Scott et al., 1985; Schofield & Tate, 1987; Gray et al., 1987). It has been proposed that continued, inappropriate expression of this gene drives tumour growth by an autocrine mechanism. In order to examine the potential role of IGF-II in the growth of tumour cells an IGF-II cDNA was introduced into a retroviral expression vector, and used to infect a cloned fibroblast cell line. Expression of IGF-II conferred a degree of serum independence of growth in cell culture, however, when cells were injected into nude mice as subcutaneous grafts, clones expressing IGF-II from the retrovirus were found to have a greatly increased (five fold) latency of sarcoma formation. After a prolonged lag all cell lines eventually gave rise to tumours in which the introduced IGF-II genes had either been lost or inactivated, suggesting that in this system IGF-II acts as a tumour suppressor gene.

Animals

Epidermal growth factor receptors (EGFR) in human ovarian cancer.

Epidermal growth factor receptor can be used as a biological marker in tumours. We examined 199 samples from 150 patients with ovarian cancer first by using a single point screen, then by full Scatchard analysis, over a concentration range between 0.086-16.6 nM. Taking as positive those samples which showed a 20% difference between total binding and non specific binding, the EGFR was present in 39.7% of samples ranging from 36.4% in those tumours which were classified as being mucinous to 47.7% in the undifferentiated group. Thirty-six samples had a low affinity component (Kd greater than 1 nM), 27 had a high affinity component (Kd less than 1 nM) and 16 had both high and low affinity components to the EGFR. There was no statistical difference between degree of differentiation of the tumour and the presence of the EGFR nor between stage of the disease and EGFR presence.

ErbB Receptors

Growth factors in ovarian cancer.

Epidermal growth factor and transforming growth factor alpha are two peptides which bind to the epidermal growth factor receptor. One hundred and seventy-four samples from 133 patients with ovarian cancer were examined for EGF and TGF alpha. EGF was detected in only 27.6% of samples while TGF alpha was present in 88.5%. The median values for TGF alpha presence were at least 10-fold greater than those of EGF. There was no statistical difference between either TGF alpha or EGF levels and degree of differentiation of the tumours. There was no statistical difference between stage three and four in relation to concentration of either peptide. Median concentration did not differ significantly among the histological sub-groups.

Carcinoma