Search PubMed⌕ Search

Biomedical subjects

J McGill

Publications and source records attributed to J McGill.

At least 37 records · Page 2Linked to original sources
PubMed1999

Origins of accessory small ring marker chromosomes derived from chromosome 1.

Three patients with accessory small ring chromosomes derived from chromosome 1 are presented together with additional clinical details and cytogenetic analyses of a previously reported patient. Cytogenetic analysis was undertaken by FISH using a reverse painting probe generated from one of the patients by microdissection of the r(1) chromosome and with a BAC923C6 which maps to 1p12. Results indicated that patients with r(1) chromosomes consisting of 1q12 heterochromatin and short arm pericentric euchromatin which extends to at least the BAC923C6 were associated with a normal or mild phenotype. Patients with abnormal phenotypes possessed two types of rings. One patient had evidence for contiguous pericentric short arm euchromatin which extended from the centromere to beyond the BAC923C6. Two patients showed molecular cytogenetic results which were compatible with non-contiguous chromosome 1 euchromatin. The diversity of origin of r(1)s will hamper attempts to define phenotype/genotype relationships.

Abnormalities, Multiple↗
PubMed1998

Role of orlistat in the treatment of obese patients with type 2 diabetes. A 1-year randomized double-blind study.

OBJECTIVE: Obesity is an important risk factor for type 2 diabetes. Weight loss in patients with type 2 diabetes is associated with improved glycemic control and reduced cardiovascular disease risk factors, but weight loss is notably difficult to achieve and sustain with caloric restriction and exercise. The purpose of this study was to assess the impact of treatment with orlistat, a pancreatic lipase inhibitor, on weight loss, glycemic control, and serum lipid levels in obese patients with type 2 diabetes on sulfonylurea medications. RESEARCH DESIGN AND METHODS: In a multicenter 57-week randomized double-blind placebo-controlled study, 120 mg orlistat or placebo was administered orally three times a day with a mildly hypocaloric diet to 391 obese men and women with type 2 diabetes who were aged > 18 years, had a BMI of 28-40 kg/m2, and were clinically stable on oral sulfonylureas. Changes in body weight, glycemic control, lipid levels, and drug tolerability were measured. RESULTS: After 1 year of treatment, the orlistat group lost 6.2 +/- 0.45% (mean +/- SEM) of initial body weight vs. 4.3 +/- 0.49% in the placebo group (P < 0.001). Twice as many patients receiving orlistat (49 vs. 23%) lost > or = 5% of initial body weight (P < 0.001). Orlistat treatment plus diet compared with placebo plus diet was associated with significant improvement in glycemic control, as reflected in decreases in HbA1c (P < 0.001) and fasting plasma glucose (P < 0.001) and in dosage reductions of oral sulfonylurea medication (P < 0.01). Orlistat therapy also resulted in significantly greater improvements than placebo in several lipid parameters, namely, greater reductions in total cholesterol, (P < 0.001), LDL cholesterol (P < 0.001), triglycerides (P < 0.05), apolipoprotein B (P < 0.001), and the LDL-to-HDL cholesterol ratio (P < 0.001). Mild to moderate and transient gastrointestinal events were reported with orlistat therapy, although their association with study withdrawal was low. Fat-soluble vitamin levels generally remained within the reference range, and vitamin supplementation was required in only a few patients. CONCLUSIONS: Orlistat is an effective treatment modality in obese patients with type 2 diabetes with respect to clinically meaningful weight loss and maintenance of weight loss, improved glycemic control, and improved lipid profile.

Adult↗
PubMed1997

Familial glaucoma iridogoniodysplasia maps to a 6p25 region implicated in primary congenital glaucoma and iridogoniodysgenesis anomaly.

Familial glaucoma iridogoniodysplasia (FGI) is a form of open-angle glaucoma in which developmental anomalies of the iris and irido-corneal angle are associated with a juvenile-onset glaucoma transmitted as an autosomal dominant trait. A single large family with this disorder was examined for genetic linkage to microsatellite markers. A peak LOD score of 11.63 at a recombination fraction of 0 was obtained with marker D6S967 mapping to chromosome 6p25. Haplotype analysis places the disease gene in a 6.4-cM interval between the markers D6S1713 and D6S1600. Two novel clinical appearances extend the phenotypic range and provide evidence of variable expressivity. The chromosome 6p25 region is now implicated in FGI, primary congenital glaucoma, and iridogoniodysgenesis anomaly. This may indicate the presence of a common causative gene or, alternatively, a cluster of genes involved in eye development/function.

Chromosome Mapping↗
PubMed1997

Small simulated polyps in pig colon: sensitivity of CT virtual colography.

PURPOSE: The authors evaluated computed tomographic (CT) virtual colography for the detection of simulated polyps under ideal conditions, as well as the effects on lesion conspicuity of (a) collimation, (b) table pitch, and (c) orientation of the colon lumen with respect to the gantry. MATERIALS AND METHODS: Pig colon was resected and cleansed, and polyps with diameters of 3, 7, and 10 mm were created. Each specimen was scanned with collimation of 5 and 7 mm and table pitch of 1.0, 1.6, and 2.0 at angles of 0 degrees, 45 degrees, and 90 degrees to the gantry. The initial two-dimensional (2D) images were reconstructed at 1-mm intervals (2D reconstructions), from which three-dimensional (3D) virtual colography images were generated. Polyp conspicuity on the initial and reconstructed 2D images and the 3D reconstructions was evaluated on a three-point scale: 0 = polyp not depicted, 1 = polyp faintly depicted, and 2 = polyp clearly depicted. RESULTS: The 10-mm-diameter polyp was clearly depicted (grade 2 conspicuity) on every initial and reconstructed 2D image and 3D reconstruction without regard to collimation, table pitch, or angle to the gantry. The 7-mm-diameter polyp was clearly depicted (grade 2 conspicuity) on every initial and reconstructed 2D image, but conspicuity on 3D reconstructions varied as the imaging parameters varied. The 3-mm-diameter polyp was faintly depicted (grade 1 conspicuity) on the initial and reconstructed 2D images and 3D reconstructions, but conspicuity varied on the 3D reconstructions as the imaging parameters varied. CONCLUSION: CT virtual colography helped detection of small mucosal polyps regardless of the angle of the colon lumen to the gantry at which they were obtained.

Animals↗
PubMed1997

Rapid testing for the MCAD G583A mutation, by PCR-mediated site directed mutagenesis, in an Australian population of SIDS patients.

Medium Chain Acyl CoA Dehydrogenase (MCAD) deficiency is the most common genetic disorder of fatty acid metabolism and has been reported as a cause of sudden death in infants. We investigated the incidence of a rare MCAD mutation (G583A) in a large population of SIDS patients. A method utilising PCR mediated site directed mutagenesis and restriction enzyme digestion was devised to enable rapid and simple testing of large numbers of samples. The G583A mutation was not detected in 413 SIDS patients tested suggesting the mutation is not an important cause of sudden death in infants. The prevalence of this mutation in the general population was estimated to be between 0 and 0.89%.

Acyl-CoA Dehydrogenase↗
PubMed1996

An alpha 1(II) Gly913 to Cys substitution prevents the matrix incorporation of type II collagen which is replaced with type I and III collagens in cartilage from a patient with hypochondrogenesis.

A heterozygous mutation in the COL2A1 gene was identified in a patient with hypochondrogenesis. The mutation was a single nucleotide transition of G3285T that resulted in an amino acid substitution of Cys for Gly913 in the alpha 1(II) chain of type II collagen. This amino acid change disrupted the obligatory Gly-X-Y triplet motif required for the normal formation of a stable collagen triple helix and prevented the deposition of type II collagen into the proposita's cartilage, which contained predominantly type I and III collagens and minor amounts of type XI collagen. Biosynthetic analysis of collagens produced and secreted by the patient's chondrocytes cultured in alginate beads was consistent with the in vivo matrix composition, demonstrating that the main products were type I and III collagens, along with type XI collagen. The synthesis of the cartilage-specific type XI collagen at similar levels to controls indicated that the isolated cartilage cells had re-differentiated to the chondrocyte phenotype. The chondrocytes also produced small amounts of type II collagen, but this was post-translationally overmodified and not secreted. These data further delineate the biochemical and phenotypic consequences of mutations in the COL2A1 gene and suggest that cartilage formation and bone development can take place in the absence of type II collagen.

Adult↗
PubMed1996

Predictors of the progression of renal insufficiency in patients with insulin-dependent diabetes and overt diabetic nephropathy. The Collaborative Study Group.

We designed a prospective, double-blind controlled trial to determine predictors of loss of renal function in patients with insulin dependent diabetes and established nephropathy. A total of 409 insulin-dependent diabetic patients with established nephropathy enrolled in a trial on the effect of Captopril on the rate of progression of renal disease. Baseline demographic, clinical (history and physical) and laboratory parameters were analyzed as risk factors for time to progression. Dichotomous characteristics were compared by Fisher's exact test and continuous characteristics with the Wilcoxon rank-sum test. Univariate proportional hazards regression analysis was used to estimate relative risk of nephropathy progression, and bivariate proportional hazard regression to identify interactions with the treatment group assignment. Multivariate proportional hazard regression was employed to determine which characteristics were independent risk factors. We found that a number of demographic and clinical characteristics were significantly associated with nephropathy progression even after adjustment for treatment group. However, after multivariate analysis, the risk factors that independently predicted progression were onset of IDDM later in life, parental diagnosis of IDDM, the presence of edema, increased mean arterial pressure, and an abnormal electrocardiogram. Likewise, a number of laboratory characteristics were also predictive of nephropathy progression. A low hematocrit, high blood sugar, and higher protein excretion predicted nephropathy progression as did a higher serum creatinine, particularly in the face of a normal serum albumin. In conclusion, this study identifies a number of clinical and laboratory risk factors that can predict which patients with insulin-dependent diabetes with established nephropathy are more likely to sustain a clinically important decrease in renal function over a median follow-up of three years.

Adolescent↗
PubMed1996

Clinical features in 27 patients with Angelman syndrome resulting from DNA deletion.

We report the clinical features in 27 Australasian patients with Angelman syndrome (AS), all with a DNA deletion involving chromosome 15(q11-13), spanning markers from D15S9 to D15S12, about 3 center dot 5 Mb of DNA. There were nine males and 18 females. All cases were sporadic. The mean age at last review (end of 1994) was 11 center dot 2 years (range 3 to 34 years). All patients were ataxic, severely retarded, and lacking recognisable speech. In all patients, head circumference (HC) at birth was normal but skewed in distribution, with 62 center dot 5% at the 10th centile. At last review HC was around the 50th centile in three patients (12 center dot 5%) while 15 had poor postnatal head growth. Short stature was not invariable, 5/26 (19%) were on or above the 50th centile. Hypotonia at birth was recorded in 15/24 (63%) and neonatal feeding difficulties were recorded in 20/26 (77%). Epilepsy was present in 26/27 (96%) with onset by the third year of life in 20 patients (83%). Improvement in epilepsy was reported in 11/16 patients (69%) with age. An abnormal EEG was reported in 25/25 patients. Hypopigmentation was present in 19/26 (73%). One patient had oculocutaneous albinism. Five patients could not walk independently. Of the remaining 22 who could walk, age of onset of walking ranged from 2 to 8 years. Disrupted sleep patterns were present in 18/21 patients (86%), with improvement in 9/12 patients (75%) over 10 years of age. The clinical features in this group of deletional AS patients were similar to previous reports, but these have not separated patients into subgroups based on DNA studies. In our group of deletional cases, 100% showed severe mental retardation, ataxic movements, absent language, abnormal EEG, happy disposition (noted in infancy in 95%), normal birth weight and head circumference at birth, and a large, wide mouth. These features occurred with a higher frequency than in AS patients as a whole. Our study also provided information on the evolution of the phenotype. The data can act as a benchmark for comparisons of AS resulting from other genetic mechanisms.

Adolescent↗
PubMed1994

Distinct phenotype in maternal uniparental disomy of chromosome 14.

We report on the occurrence of maternal uniparental disomy for chromosome 14 (mUPD14) in a 4-year-old girl with a de novo Robertsonian translocation, 45,XX,t (13q,14q). The child has arrested hydrocephalus, short stature, minor anomalies, small hands with hyperextensible joints, and mild to moderate developmental delay. Comparison of her phenotype with those of three previously described individuals show some common distinct traits which suggest a mUPD14 syndrome.

Abnormalities, Multiple↗
PubMed1994

Pure cutting current for loop excision of squamous intraepithelial lesions.

Clear margins are critical to the identification of complete excision of premalignant lesions on the cervix. Large loop excision of the transformation zone aids the pathologic evaluation of the excised specimen while it causes minimal thermal damage. Prior studies of loop excision were performed with a cutting current blended with a coagulating waveform to aid hemostasis. Blended current has higher voltage, which may cause tissue to stick to the electrode and produce thermal damage to the cervix. In this series, pure cutting current was used to excise the cervical transformation zone in 20 patients. The depth of thermal damage was studied in 6 patients; the average endocervical zone of damage was 0.47 mm and that of the exocervical zone, 0.43 mm. The base of the cervix could be examined with the colposcope for the presence of glands. None of our procedures was complicated by intraoperative or delayed bleeding. The preoperative injection of a vasoconstrictor into the cervical stroma is thought to aid the surgery by its hemostatic properties.

Carcinoma, Squamous Cell↗
PubMed1993

Cloning of the human taurine transporter and characterization of taurine uptake in thyroid cells.

A cDNA clone encoding a taurine transporter, designated HTAU, has been isolated from human thyroid. It contains an open reading frame encoding a protein of 619 amino acids with a calculated molecular weight of 69,675 Da. The predicted amino acid sequence of HTAU is highly homologous to those of dog kidney and rat brain. The HTAU mRNA was detectable in various human tissues examined. Transient expression of HTAU in COS-7 cells conferred a higher taurine uptake. The taurine uptake in FRTL-5 cells appears to be regulated by thyrotropin through cAMP. Finally, a higher taurine uptake may be associated with a higher proliferation rate in some cultured cell lines.

Amino Acid Sequence↗
PubMed1993

Regulation of membrane chloride currents in rat bile duct epithelial cells.

This study examines the conductive properties of the plasma membrane of cells isolated from the intrahepatic portion of bile ducts. Membrane Cl- conductance was measured in single cells using whole-cell patch clamp recording techniques and in cells in short-term culture using 36Cl and 125I efflux. Separate Ca(2+)- and cAMP-dependent Cl- currents were identified. Ca(2+)-dependent Cl- currents showed outward rectification of the current-voltage relation, time-dependent activation at depolarizing potentials, and reversal near the equilibrium potential for Cl-. Ionomycin (2 microM) increased this current from 357 +/- 72 pA to 1,192 +/- 414 pA (at +80 mV) in 5:7 cells, and stimulated efflux of 125I > 36Cl in 15:15 studies. Ionomycin-stimulated efflux was inhibited by the Cl- channel blocker 4,4'-diisothiocyano-2,2'-stilbene disulfonic acid (DIDS) (150 microM). A separate cAMP-activated Cl- current showed linear current-voltage relations and no time dependence. Forskolin (10 microM) or cpt-cAMP (500 microM) increased this current from 189 +/- 50 pA to 784 +/- 196 pA (at +80 mV) in 11:16 cells, and stimulated efflux of 36Cl > 125I in 16:16 studies. cAMP-stimulated efflux was unaffected by DIDS. Because the cAMP-stimulated Cl- conductance resembles that associated with cystic fibrosis transmembrane conductance regulator (CFTR), a putative Cl- channel protein, the presence of CFTR in rat liver was examined by immunoblot analyses. CFTR was detected as a 150-165-kD protein in specimens with increased numbers of duct cells. Immunoperoxidase staining confirmed localization of CFTR to bile duct cells but not hepatocytes. These findings suggest that Ca(2+)- and cAMP-regulated Cl- channels may participate in control of fluid and electrolyte secretion by intrahepatic bile duct epithelial cells, and that the cAMP-regulated conductance is associated with endogenous expression of CFTR. Abnormal ductular secretion may contribute to the pathogenesis of cholestatic liver disease in cystic fibrosis.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1992

A controlled clinical trial of angiotensin-converting enzyme inhibition in type I diabetic nephropathy: study design and patient characteristics. The Collaborative Study Group.

A placebo-controlled, double-blind clinical trial has been initiated to determine whether angiotensin-converting enzyme inhibitor (ACEI) therapy with captopril (25 mg three times daily) slows the progressive loss of renal function in patients with type 1 diabetes mellitus. Entry criteria include; (1) ages 18 to 50 yr; (2) onset of insulin-dependent diabetes before the age of 30 yr, insulin dependent for at least 7 yr; (3) 24-h urine protein excretion > 500 mg, plus: (a) diabetic retinopathy or (b) if no retinopathy, a renal biopsy diagnosis of diabetic nephropathy; (4) serum creatinine (SCr) < 2.5 mg/dL; (5) informed consent. Patients follow strict medical management protocols. Systemic blood pressure is controlled to predefined goals (< 140-90 mm Hg). The primary outcome of the Study is a doubling of the patients' entry SCr to at least 2 mg/dL confirmed by a > 50% decrease in GFR by radioactive iothalamate clearance technique. Baseline characteristics of the cohort at entry into the Study are (mean +/- SD): male/female, 52%/48%; age, 35 +/- 8 yr; duration of diabetes, 21 +/- 7 yr; duration of proteinuria, 2.8 +/- 3.3 yr; duration of retinopathy, 4.5 +/- 4.1 yr; 50% of cohort presented with hypertension, duration, 4 +/- 4.7 yr; blood pressure, 139/86 +/- 19/12; SCr, 1.35 +/- 0.44 mg/dL; GFR 78 +/- 32 mL/min; BUN, 24 +/- 11 mg/dL; proteinuria, 3.1 +/- 3.3 g/day; cholesterol, 236 +/- 50 mg/dL; total glycosylated hemoglobin, 11.1 +/- 2.1%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Preclinical leads for innovative uses for etoposide.

Amplification of oncogenes in human tumors has been associated with a poor prognosis. Microscopically visible amplified oncogenes can be located either within chromosomes in homogeneously staining regions, or in an extrachromosomal compartment in double minutes (DMs). The DMs are composed of submicroscopic circular DNA (episomes), which have multimerized to form the microscopically visible DMs. When amplified oncogenes are located in an extrachromosomal location, they are vulnerable to loss from the cell. In this study we have found that the topoisomerase II inhibitor etoposide, in concentrations easily achievable clinically, causes a significant decrease in the number of DM-containing amplified oncogenes in three different human tumor cell lines. The elimination of amplified oncogenes from the cell could be accompanied by less aggressive tumor behavior.

DNA, Circular↗