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Biomedical subjects

P Cullen

Publications and source records attributed to P Cullen.

At least 91 records · Page 5Linked to original sources
PubMed1994

Complex segregation analysis provides evidence for a major gene acting on serum triglyceride levels in 55 British families with familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCHL) was first described as an autosomal dominant inherited trait with primary action on triglyceride levels and secondary effects on cholesterol metabolism. This conclusion has since been questioned by several groups despite subsequent supportive biochemical and metabolic studies. To reexplore the genetics of FCHL, we assembled 55 families from the United Kingdom comprising 559 persons ascertained through probands with both hypercholesterolemia and hypertriglyceridemia. The results of univariate complex segregation analysis were consistent with a major gene acting on triglyceride and explaining two thirds of the genetic variability and 20% of the phenotypic variance in triglyceride levels. Univariate analysis did not identify a major genetic component acting on cholesterol levels. Bivariate segregation analysis rejected a major gene model. We also reexamined the original FCHL pedigrees collected by Goldstein et al and obtained results similar to those in the UK families. The prospects for mapping putative major genes determining triglyceride levels in FCHL patients by linkage analysis are discussed.

Family Health↗
PubMed1993

Association of familial Duane anomaly and urogenital abnormalities with a bisatellited marker derived from chromosome 22.

We report a spectrum of defects that were found in an 18-year-old girl who presented for investigation of primary amenorrhea. The patient was found to have Duane anomaly, left renal agenesis, absent uterus, bilateral sensorineural deafness, and bilateral preauricular skin tags and sinuses. Investigation of her family showed that her brother also had Duane anomaly, right renal agenesis, sensorineural deafness, and preauricular skin tags and that their father had preauricular skin tags. Cytogenetic analysis, including in situ hybridisation of peripheral blood lymphocytes, demonstrated a supernumerary bisatellited marker chromosome derived from the region of chromosome 22pter-q11 in the affected individuals. Our findings indicate that a gene or genes located in the region of chromosome 22pter-q11 may be associated with the Duane anomaly and the development of the urogenital tract.

Adolescent↗
PubMed1993

Stable isotopes show a direct relation between VLDL apoB overproduction and serum triglyceride levels and indicate a metabolically and biochemically coherent basis for familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCHL) may be genetically and metabolically more heterogeneous than previously thought. A consistent feature is an increase in circulating very-low-density lipoprotein (VLDL) apolipoprotein (apo) B, which could be due to either an increase in apoB production or a decrease in its catabolism. Therefore, we directly measured VLDL apoB production in the postabsorptive state in seven FCHL subjects (four male, three female) and seven normal control subjects (three male, four female) by using L-[1-13C]leucine as an endogenous label. Mean age and body mass index did not differ significantly between the two groups. The mean total cholesterol levels were 4.7 +/- 0.8 and 8.8 +/- 1.6 mmol/L (+/- SD, P < .01) and the mean triglyceride levels were 0.84 +/- 0.14 and 3.30 +/- 1.10 mmol/L (+/- SD, P < .01) in the control and FCHL groups, respectively. Although the fractional production rate of VLDL apoB was 38% lower in the FCHL group than in the control subjects (0.11 +/- 0.03 versus 0.18 +/- 0.02 pool/h; mean +/- SD, P < .01), its absolute production rate was 2.7 times greater (534 +/- 193 micrograms/kg per hour in FCHL versus 196 +/- 71 micrograms/kg per hour in control subjects; mean +/- SD, P < .01). There was a linear relation (r = 0.8, P = .03) between triglyceride levels and the VLDL apoB production rate in FCHL, the slope of which indicated a similar VLDL triglyceride-to-apoB ratio in the FCHL and control groups. We conclude that FCHL is a metabolically coherent disorder and that the increase in circulating apoB and triglyceride levels in FCHL is due to secretion of an increased number of VLDL particles, each containing, on average, a normal amount of triglyceride and one molecule of apoB.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Familial combined hyperlipidaemia linked to the apolipoprotein AI-CII-AIV gene cluster on chromosome 11q23-q24.

Familial combined hyperlipidaemia (FCHL) is a common inherited disorder of lipid metabolism with a prevalence of 0.5-2.0% (refs 1, 2). It is estimated to cause 10% of premature coronary heart disease. The underlying metabolic and genetic defects in FCHL have not been identified, but a population study has suggested an association between FCHL and an XmnI restriction fragment length polymorphism (RFLP) within the apolipoprotein AI-CIII-AIV gene cluster. Here we confirm this association and show that it results from linkage disequilibrium between FCHL and the 6.6-kilobase (kb) allele of the XmnI RFLP. Subsequent analysis in seven FCHL families, ascertained through a proband carrying the 6.6 kb XmnI allele, demonstrated linkage to the AI-CIII-AIV cluster on 11q23-q24, zeta = 6.86 with no recombinants. This assignment will facilitate the identification of the mutation that causes hyperlipidaemia in these families.

Apolipoprotein A-I↗
PubMed1991

Restriction fragment length polymorphism of ovine casein genes: close linkage between the alpha s1-, alpha s2-, beta- and kappa-casein loci.

Restriction fragment length polymorphism (RFLP) of ovine casein genes was investigated. Genomic DNA from 56 rams was digested with 10 restriction endonucleases and Southern blots probed with the four ovine casein cDNAs (alpha s1-, beta-, alpha s2- and kappa-Cn). Five enzymes, namely, BglI, PvuII, RsaI, TaqI and HindIII revealed nine different RFLPs. The inheritance of six of these polymorphisms was studied by segregation analysis of gametes in nine rams' families, and each of them could be related to the existence of alleles at the relevant casein locus. A close linkage between the four ovine casein genes was demonstrated since no recombination within the four pairs of loci examined, alpha s1-beta-Cn, alpha s1-kappa-Cn, beta-kappa-Cn and alpha s2-kappa-Cn, was observed in the progeny of double heterozygous rams. The casein genes are thus clustered in the ovine species as in the case of other mammals.

Alleles↗
PubMed1987

Demonstration of residual contrast medium in renal parenchyma using computerized tomography.

Residual contrast medium in the renal parenchyma was demonstrated by computerized tomography in 11 patients with renal trauma, inflammatory renal disease, infarction and a large renal cyst. The contrast medium (10 to 100 ml.) was administered intravascularly 30 minutes to 48 hours before the computerized tomography scan. In each patient the scan demonstrated residual contrast medium (either initially or after a second scan with additional contrast enhancement) in a variety of parenchymal zones that frequently appear to be normal with other imaging techniques. After a suitable interval for accumulation of residual contrast medium, computerized tomography appears to provide better visualization of the renal parenchyma than conventional modes of examination. Persistent retention of contrast medium in the renal parenchyma is believed to represent cortical damage.

Adult↗
PubMed1987

Mitotic activity of corneal endothelial cells in organ culture with recombinant human epidermal growth factor.

Recombinant human epidermal growth factor (EGF) was assessed for its capacity to stimulate proliferation of human corneal endothelial cells in vitro in organ culture with 87 human corneas. The EGF in defined serum-free (S-F) media was able to stimulate endothelial cell mitosis (t test P less than 0.01) in matched transected human corneas after a four-day incubation period as judged by histologic studies. Clearly defined endothelial mitotic figures were seen in all stages of cell division throughout the endothelial cell layer. The implication of increasing corneal endothelial cell numbers in donor corneas before transplantation using a human growth factor, potentially available in pure form in unlimited quantities, is discussed.

Adolescent↗
PubMed1987

Dose requirements of propofol by infusion during nitrous oxide anaesthesia in man. II: Patients premedicated with lorazepam.

The infusion rate of propofol required to supplement 67% nitrous oxide in oxygen to maintain surgical anaesthesia was determined in 72 patients premedicated with lorazepam. Following an induction dose of propofol 2 mg kg-1, groups of eight patients received an infusion of propofol varying from 60 to 200 micrograms kg-1 min-1. Probit analysis was used to determine the ED50 (130 micrograms kg-1 min-1; 95% confidence limits: 106-167 micrograms kg-1 min-1) and ED95 (348 micrograms kg-1 min-1; 95% confidence limits: 233-1296 micrograms kg-1 min-1) for propofol infusion. Whole blood propofol concentrations at the time of surgical incision correlated strongly with the infusion rate, giving an EC50 value of 2.5 micrograms ml-1, and an EC95 value of 5.92 micrograms ml-1. There was no significant correlation between the rate of infusion of propofol, or the total propofol dose, and the times to response to command, or to recall of birthdate.

Adolescent↗
PubMed1986

Primary malignant melanoma of the esophagus.

We report the case of a 74-year-old woman who was admitted to hospital with progressive dysphagia. Further examinations revealed a tumor in the esophagus in which the macroscopic aspect and the histological work-up showed a primary malignant melanoma. The histogenesis of primary malignant melanoma in the esophagus is discussed, and a short review of the literature presented.

Aged↗
PubMed1985

Ocular fluid dynamics response to topical RU486, a steroid blocker.

A steroid antagonist applied to one eye of 18 young pigmented rabbits during a 10-week period caused a statistically significant fall in IOP, but no statistically significant nor clinically relevant change in the rate of aqueous humor turnover. The pressure change is therefore ascribed to an alteration in outflow channels. No changes occurred in a parallel group of 5 animals in which one eye was treated with vehicle and the contralateral eye was untreated. The drug effects became evident after two weeks of application, suggesting that a slow turnover pathway is involved.

Administration, Topical↗
PubMed1981

The human cytotoxic T cell response to influenza A vaccination.

The human cytotoxic T lymphocyte (CTL) response to challenge with influenza A vaccine was studied. Six of eight volunteers given killed whole influenza virus A/USSR (H1N1) vaccine showed substantial increases on the level of CTL memory 1 month after immunization. The CTL measured at this time showed complete cross-reactivity in their specificity for influenza A/USSR (H1N1) and A/X31 (H3N2) infected cells and also showed HLA restriction. The level of CTL memory increased in only three out of nine donors given subunit vaccine and showed no change in those not given vaccine. If cytotoxic T cells are important in influenza prophylaxis, killed whole virus vaccine should offer better protection than subunit vaccine.

Antibody Formation↗