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Biomedical subjects

C Mullins

Publications and source records attributed to C Mullins.

36 records · Page 2Linked to original sources
PubMed1996

A gene from human chromosomal band 3p21.1 encodes a highly conserved arginine-rich protein and is mutated in renal cell carcinomas.

We have identified a gene, called ARP for Arginine-rich protein, in human chromosomal band 3p21. It is approximately 600 Kb telomeric to the ACY1 locus (Miller et al., 1989) and encodes a previously unidentified 234 amino acid long, highly basic protein. This gene is highly conserved at the DNA and RNA level. It is found in all species including hamster, rat, mouse, bovine and yeast. We have detected a point mutation (ATG50 to AGG) or deletion of ATG50 in 10 of 21 sporadic renal cell carcinomas. The mutable region is in an imperfect trinucleotide repeat in the coding region which is non-polymorphic among 50 normal individuals examined. The point mutation (ATG50 to AGG) or deletion of codon 50 removes a methionine and increases the stretch of arginines encoded by the AGG repeats in the ARP gene.

Amino Acid Sequence↗
PubMed1996

Endovascular stent placement for pulmonary venous obstruction after Mustard operation for transposition of the great arteries.

Stenting of the left pulmonary venous baffle obstruction was successfully performed in a 6 year old girl after the Mustard operation for transposition of the great arteries. She also had stent implantation in both the superior vena cava and inferior vena cava baffle junctions. These procedures were followed by sustained clinical improvement. Angiography showed that all three stents were fully patent a year after the procedure.

Child↗
PubMed1995

A mutation affecting signal peptidase inhibits degradation of an abnormal membrane protein in Saccharomyces cerevisiae.

Signal peptidase removes amino-terminal signal peptides from precursor proteins during or immediately following their translocation to the lumen of the endoplasmic reticulum (ER) and may participate in ER degradation, a poorly defined process whereby abnormal proteins are rapidly degraded early in the secretory pathway. Here, the involvement of signal peptidase in ER degradation is examined through the use of two chimeric membrane proteins that lack amino-terminal signal peptides: A189invHD, which contains sequences derived from arginine permease and histidinol dehydrogenase, and AHDK2, containing the ER-resident protein Kar2p fused to the carboxyl terminus of A189invHD. Degradation of approximately 95% of A189invHD is observed in yeast cells expressing enzymatically active signal peptidase, whereas only 60% undergoes rapid degradation in a sec11 mutant bearing a temperature-sensitive mutation in the gene encoding the 18-kDa subunit (Sec11p) of the signal peptidase complex. AHDK2 is proteolyzed in a reaction yielding at least two fragments in wild-type cells and in the sec11 mutant containing a plasmid bearing the SEC11 gene. The proteolytic reaction is catalyzed in a temperature-dependent manner in the sec11 mutant, with AHDK2 remaining stable at the nonpermissive temperature. Using conditional mutants defective in protein translocation into and out of the ER and in vitro protease protection studies, the site of degradation for AHDK2 is localized to the ER lumen. The data therefore indicate (i) A189invHD is degraded through both signal peptidase-dependent and independent processes; (ii) signal peptidase, specifically the Sec11p subunit, is required for the proteolysis of AHDK2; and (iii) the Kar2 fragment at the carboxyl terminus of AHDK2 permits detection of proteolytic intermediates.

Alcohol Oxidoreductases↗
PubMed1995

Natural protection against HIV-1 infection provided by HIV-2.

Significant differences have been observed in the rates of transmission and disease development in human immunodeficiency virus (HIV) types 1 and 2. Because many HIV-2-infected people remain asymptomatic for prolonged periods, the hypothesis that HIV-2 might protect against subsequent infection by HIV-1 was considered. During a 9-year period in Dakar, Senegal, the seroincidence of both HIV types was measured in a cohort of commercial sex workers. Despite a higher incidence of other sexually transmitted diseases (STDs), HIV-2-infected women had a lower incidence of HIV-1 than did HIV-seronegative women, with a relative risk of 0.32 (P = 0.008). An understanding of the cross-protective mechanisms involved may be directly relevant to HIV-1 vaccine development.

AIDS Vaccines↗
PubMed1995

Precise localization of aphidicolin-induced breakpoints on the short arm of human chromosome 3.

The common fragile site at 3p14.2 (FRA3B) has been described as the most active fragile site in the human genome. This locus may predispose chromosome 3 to specific losses due to deletions and translocations that have been associated with several malignancies, including hereditary renal cell carcinoma. We have previously described induction of breakage around FRA3B using aphidicolin in a somatic cell hybrid whose only human component was a single intact chromosome 3. That work led to the isolation of hybrids with breakpoints in the 3p13-p21.1 region with loss of all sequences distal to their respective breakpoints. In this report we describe the further characterization of the breakpoints in many of these cell lines using newly available molecular markers. We also report the identification of YAC clones that span the breakpoints present in many of these hybrids.

Aphidicolin↗
PubMed1994

Balloon dilatation of complete obstruction of the superior vena cava after Mustard operation for transposition of great arteries.

Balloon dilatation was successfully performed in two patients with complete obstruction of the superior vena cava baffle junction after a Mustard operation for transposition of the great arteries. Evidence for complete relief of obstruction in the first patient, aged 4 years, was obtained by angiography, which showed improved calibre at the site of obstruction and improved haemodynamic pressure measurement after the balloon dilatation. In the second patient, aged 14 years, the relief was incomplete; in this patient a 3 cm long 3 mm diameter Palmaz stent was successfully implanted.

Adolescent↗
PubMed1992

Structure-function analyses for aminoglycoside 3'-phosphotransferase II (APH(3')-II).

Mutant strains containing APH(3')-II were constructed via site-directed mutagenesis of the cloned gene and by random mutagenesis of a strain containing the APH(3')-II gene on a conjugative plasmid. Substitutions at highly conserved amino acid residues produced APH(3') enzymes which in general showed reduced activity and conferred reduced levels of resistance to their substrates. Substitutions at Tyr 218 altered substrate specificity for the enzymes. Random mutagenesis produced plasmid-borne mutations conferring amikacin resistance. Two of these mutations appeared to be localized to the APH(3')-II structural gene.

Amino Acid Sequence↗
PubMed1991

Molecular characterization of PKU allele prevalent in southern Europe and Ireland.

A novel substitution has been characterized in the phenylalanine hydroxylase (PAH) gene that is linked exclusively to mutant haplotype 6, which is prevalent in southern Europe but rare in northern and eastern Europe. It is a G-to-A transition in intron 10, 11 bases from exon 11. This substitution creates an additional AG dinucleotide, which may serve as a cryptic splice acceptor site. Individuals who bear this substitution in the homozygous state have a severe PKU phenotype with pretreatment serum phenylalanine levels over 1200 mumol/liter. The frequency and distribution of this substitution among European populations suggests two possible founding populations, one being Middle Eastern and the other Roman. The use of this substitution as a marker to identify PKU chromosomes will be an invaluable aid to carrier screening and prenatal diagnosis in populations where mutant haplotype 6 is prevalent.

Alleles↗
PubMed1988

[Percutaneous transluminal balloon dilatation of discrete membranous subvalvular aortic stenosis].

Discrete membranous subaortic stenosis (DMSS) which is localized immediately subvalvular and can be differentiated from fibromuscular stenosis of the left ventricular outflow tract, represents theoretically a well-suited lesion for uncomplicated balloon dilatation. The practical use of balloon dilatation for treatment of DMSS has been reported by two groups [6, 10]. In this overview, we will report our experience with balloon dilatation of DMSS in six children. Between June, 1986 and June, 1987, balloon dilatation of DMSS was carried out in six male children ranging in age from four to ten years (Table 2). In one child, coarctation of the aorta had been present and was previously treated successfully with balloon dilatation. In two children, the aortic valve was thickened with or without stenosis. All children had mild aortic regurgitation. After transvenous right heart catheterization and transarterial left heart catheterization including levocardiography and supraaortic angiography, 50 units of heparin per kilogram of body weight were administered and a guidewire advanced to the left ventricle for positioning of the balloon catheter in the left ventricular outflow tract. The choice of balloon diameter was based on measurement of the angiographically-determined aortic ring diameter (Table 1). Pressure measurements were obtained by means of a diagnostic catheter after the dilatation. No complications were observed either during or immediately after the intervention. After the dilatation, all children were discharged from the hospital to go home. Pressure in the left ventricle was reduced from 225 +/- 55 to 116 +/- 29 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Stenosis, Subvalvular↗
PubMed1988

[Percutaneous transvenous antegrade balloon angioplasty in aortic isthmus stenosis].

Balloon angioplasty of native or postoperative coarctation of the aorta has been recommended as an alternative method to surgical treatment. On use of the retrograde approach via the femoral artery, after introduction of the catheter into a vessel of narrow lumen, not infrequently, injury or obstruction was observed. This overview summarizes our experience primarily on use of antegrade balloon angioplasty for coarctation of the aorta, the first description of which was published as a case report in 1986. Between December, 1985, and September, 1987, balloon angioplasty was carried out for native coarctation of the aorta in seven neonates, age two to 30 days. Concomitant cardiovascular anomalies included ventricular septal defect in five, patent ductus arteriosus in five, mitral valve atresia in two and transposition of the great arteries with and without double outlet right ventricle in two (Table 1). Prior to balloon angioplasty for coarctation, in four neonates therapeutic balloon atrial septostomy had been performed. For balloon angioplasty, via the right femoral vein, an end-hole catheter was advanced into the right ventricle. In five neonates, the catheter could be advanced into the ascending aorta directly from the right ventricle or through a ventricular septal defect. In the two other neonates, the catheter was advanced via the foramen ovale and the mitral valve into the left ventricle and the ascending aorta. Pressure was measured by the end-hole catheter as well as in the femoral artery after direct puncture.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Coarctation↗
PubMed1983

Decision-making among emergency room residents: preliminary observations and a decision model.

Emergency room residents face a range of clinical decisions and often call on senior residents or faculty members for help. The individual clinical decision process has frequently been analyzed, but little attention has been given to the social process in clinical decision-making. Based on data from interviews and over 100 hours of direct observation at two large urban general hospitals with busy emergency rooms staffed by medical and surgical residents, the authors suggest there are five basic decision situations. In each situation, the residents appeared to follow implicit decision patterns about involving other medical and surgical staff in the final clinical decision. The decision situations are nonacute, routine acute, nonroutine acute, multispecialty acute, and crisis. These situations call for individual, consultive, or consensual patterns in making decisions. The consequences of these patterns are explored. Improving residents' decision-making should contribute to improved understanding of the resident's role, better resident supervision, and better emergency room functioning.

Critical Care↗
PubMed1980

Screening for congenital hypothyroidism in the Republic of Ireland.

A national pilot study for detecting congenital hypothyroidism by radioimmunoassay of thyroid-stimulating hormone concentrations in dried blood was incorporated into the newborn screening programme in Ireland on 1 August 1979. The programme has been monitored by a steering committee and follows the guidelines set by the European Society of Paediatric Endocrinologists. During the first 12 months 76 224 infants were screened and 19 cases confirmed, giving an incidence of 1:4012. Fifty infants (0.07%) were recalled for a serum sample, though most of the recalls (31; 0.04%) occurred during the first three months, before the methodology had become established. No case was detected clinically. At recall only three of the 19 affected infants had obvious features, and nine inconspicuous features. Organisation was directed at early diagnosis and treatment, the mean age at beginning treatment being 15 days. These results confirm the efficacy of screening for congenital hypothyroidism and suggest that capital and running costs will be offset by savings in maintenance treatment of untreated patients. Screening does not, however, remove the need for continued vigilance, and clinicians should request thyroid-function tests in any suspected case.

Age Factors↗
PubMed1978

Oral propranolol treatment in infants and children.

To determine the effectiveness of oral propranolol in children, we administered 0.5 to 4.0 mg/kg/day of the drug to 64 children (age one day to 20 years); 41 with cardiac dysrhythmias, six with isiopathic hypertrophic subaortic stenosis, and 17 with paroxysmal hypoxemic spells associated with right ventricular infundibular obstruction. A new liquid form of propranolol (10 mg/ml) was administered to 37 of the younger patients, and tablets were given to the other 27. Propranolol improved the dysrhythmia in 31 of 41 patients, being notably effective in supraventricular tachycardia and ventricular tachycardia associated with a prolonged QT interval. The drug also eliminated symptoms attributed to IHSS in six of six patients and abolished hypoxemic spells in 12 of 17. The liquid and tablets were equally effective; and the liquid had the advantage of allowing for accurate dose changes in younger children. We conclude that oral propranolol is an excellent drug for use in pediatric patients with certain types of cardiac disease.

Adolescent↗