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R Harris

Publications and source records attributed to R Harris.

At least 217 records · Page 12Linked to original sources
PubMed1992

A genetic study of type 2 neurofibromatosis in the United Kingdom. II. Guidelines for genetic counselling.

The major defining features, age at onset of symptoms, and survival in 150 patients with type 2 neurofibromatosis (NF2) have been studied. The mean age at onset was 21.57 years (n = 110) and no cases presented after 55 years of age. Patients presented with symptoms attributable to vestibular schwannomas (acoustic neuroma), cranial meningiomas, and spinal tumours. In 97 cases studied personally by the authors, skin and eye examination were found to be useful to detect early signs of the condition. Examination of the skin is likely to assist in early diagnosis in at least 10% of cases and examination of the eye for a lens opacity or cataract in at least as many again. There are marked interfamilial differences in disease severity and tumour susceptibility. Vestibular schwannomas are not fully penetrant, but the condition is usually expressed in another way. Alteration to the current diagnostic criteria is advocated to cover the lack of provision for new mutations. A screening protocol is proposed and the effect of disease heterogeneity on management is discussed.

Adolescent↗
PubMed1992

Measuring the use of mammography: two methods compared.

Population studies often estimate mammography use using women's self-reports. In one North Carolina county, we compared self-report surveys with a second method--counting mammograms per population--for 1987 and 1989. Estimates from self-reports (35% in 1987, 55% in 1989) were considerably higher than those from mammogram counts (20% in 1987, 36% in 1989). We then confirmed 66% of self-reports in the past year. Self-reported use is more accurate regarding whether a woman has had a mammogram than when she had it, but self-reports accurately measure change over time.

Aged↗
PubMed1992

AIDS and Trojan horses.

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Acquired Immunodeficiency Syndrome↗
PubMed1992

Genetics in the reformed health service. Changes for the better?

The practical value of medical genetics, in particular the development of molecular genetics complemented by clinical diagnosis and counselling, is widely recognised. There is strong independent support from government and patient organisations for augmenting genetics services in all health regions; this support gives much reason for optimism. But there appears to be a hiatus following the reform of the Health Service: no genetics centre has, as yet, adequate resources and there has been no increase in clinical genetic manpower in the last two years. Even worse, Wales and at least one English region have devolved genetic services to districts, which appears to be contrary to government policy for genetic services. These factors have inevitably limited the implementation of many opportunities for improved patient care and the prevention of genetic disease. However, medical geneticists, assisted by the Royal College of Physicians and others, want to respond positively to the changes in the Health Service. Recommendations are made for strategies which promise to maintain integrated regional clinical and laboratory services and to achieve well evaluated developments.

Career Mobility↗
PubMed1992

A clinical study of type 2 neurofibromatosis.

The clinical features, age at onset of symptoms and survival of 150 patients with type 2 neurofibromatosis were studied. The mean age at onset was 21.57 years (n = 110) and no patients presented after 55 years of age. Patients presented with symptoms attributable to vestibular schwannomas (acoustic neuroma), cranial meningiomas and spinal tumours. In 100 patients studied personally by the authors 44 per cent presented with deafness and this was unilateral in the majority (35/44). Deafness was accompanied by tinnitus in a further 10 per cent and muscle weakness or wasting was the first symptom in 12 per cent. Less common presenting symptoms were seizures (8 per cent), vertigo (8 per cent) numbness and tingling (2 per cent) and blindness (1 per cent). Eleven patients were diagnosed asymptomatically through screening. Café au lait spots occurred in 43 per cent (n = 43) but only one case had six. Skin tumours were detected in 68 per cent (68/100) and 38 per cent (34/90) had an identifiable lens opacity or cataract. The mean age at death in 40 cases was 36.25 years and all but one death was a result of a complication of neurofibromatosis. There are marked inter-family differences in disease severity and tumour susceptibility.

Adult↗
PubMed1992

Arterial emboli of venous origin.

In a small but significant group of patients with documented systemic emboli, a source is never determined. It is in this group of patients that an arterial embolus of venous origin should be considered. During the past 20 years, we identified four patients who fulfilled the diagnostic criteria for an arterial embolus of venous origin. In each, the diagnosis was made during life. In addition, we reviewed the 40 additional patient reports in the literature that appeared to meet the criteria for the diagnosis of venous origin arterial emboli. Noninvasive methods were useful in determining the presence of thrombus in the venous system, and right to left shunting across an intracardiac defect. We conclude that treatment with heparin is the mainstay of therapy, and that caval interruption should be used only on a selective basis.

Adult↗
PubMed1991

Medical genetics.

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Coronary Disease↗
PubMed1991

Regulation of the F plasmid traY promoter in Escherichia coli K12 as a function of sequence context.

TraJ and SfrA are, respectively, plasmid and host (Escherichia coli)-encoded proteins normally required for F plasmid traY promoter function. Beginning with plasmids in which a traY-lacZ fusion gene, designated phi (traY'-'lacZ)hyb, and lacY are expressed from the F plasmid traY promoter, we isolated mutants in which lac gene expression was SfrA or TraJ-independent. A total of 45 of 50 SfrA-independent isolates obtained after 2-aminopurine mutagenesis proved to have chromosomal mutations, whereas four out of four isolates obtained without mutagenesis had plasmid mutations. All of 17 isolates selected for TraJ-independent expression after mutagenesis had plasmid mutations. By restriction endonuclease digestions, 25 of 26 SfrA-independent and TraJ-independent plasmid mutations were insertions. Four of the former and three of the latter were examined further. By sequence analysis, all seven proved to be IS1 or IS2 insertions defining five insertion sites between base-pairs -49 and -82 with respect to the major traY transcription initiation site. In two cases, the same insertion allele was obtained from the two selection schemes. All three of the mutants selected for TraJ-independent gene expression manifested SfrA-independent expression as well, and levels of beta-galactosidase in different plasmid mutant strains lacking TraJ and SfrA were indistinguishable. By primer extension analysis, transcription initiation sites for traY mRNA synthesis were unaltered by the mutations. Replacing the tra sequence upstream from base-pair -78, without genetic selection, increased beta-galactosidase activity in the absence of TraJ and SfrA greater than tenfold. Activity increased two- to threefold more in a traJ+ sfrA mutant strain, and fivefold more in a traJ+ sfrA+ strain. Activity was unaltered in an sfrA+ strain without TraJ. By primer extension analysis, the traY promoter was utilized under all conditions. The data indicate that regulation of traY promoter activity is strongly dependent on sequence context.

Alleles↗
PubMed1991

Regulation of the F plasmid traY promoter in Escherichia coli by host and plasmid factors.

F plasmid DNA transfer (tra) gene expression in Escherichia coli is regulated by chromosome- and F-encoded gene products. To study the relationship among these regulatory factors, we constructed low-copy plasmids containing a phi(traY'-'lacZ)hyb gene that couples beta-galactosidase and Lac permease synthesis to the F plasmid traY promoter. Wild-type transformants maintained high levels of beta-galactosidase over a broad range of culture densities. Primer extension analysis of tra mRNA from F'lac and phi(traY'-'lacZ)hyb strains indicated very similar, though not identical, transcription initiation sites. Moreover, phi(traY'-'lacZ)hyb gene expression required both TraJ and SfrA, as does tra gene expression in F+ strains. beta-Galactosidase activity was reduced approximately 30-fold in the absence of TraJ, which could be supplied in cis or in trans. In a two-plasmid system in which TraJ was supplied in trans by a lac-traJ operon fusion, phi(traY'-'lacZ)hyb expression was a linear, saturable function of traJ expression. Enzyme activity was reduced approximately tenfold in sfrA mutants. That reduction could not be attributed to an effect on the TraJ level. Several other cellular or environmental variables had only a modest effect on phi(traY'-'lacZ)hyb expression. Hyperexpression was observed at high cell density (twofold) and in anaerobic cultures (1.2- to 1.5-fold). In contrast, expression was reduced twofold in integration host factor mutants.

Aerobiosis↗
PubMed1991

Extended MHC haplotypes and CYP21/C4 gene organisation in Irish 21-hydroxylase deficiency families.

We have analysed fifteen classical 21-hydroxylase deficiency families from throughout Southern Ireland and report the serologically defined HLA-A, HLA-B, HLA-Cw, HLA-DR, C4A and C4B polymorphisms that characterize the inferred disease haplotypes. Additionally, we have used a combination of short and long range restriction mapping procedures in order to characterize the CYP21/C4 gene organization associated with individual serologically defined haplotypes. The results obtained indicate that disease haplotypes are characterized by a high frequency (33%) of CYP21B gene deletion and 8 out of 10 such deletion haplotypes are represented by the extended haplotype HLA-DR1, C4BQo, C4A3, HLA-B40(w60), HLA-Cw3, HLA-A3. Large scale length polymorphism in the CYP21/C4 gene cluster was found to conform strictly to a variable number of tandem repeats model with 4 alleles being detected. Disease haplotypes in which defective CYP21B gene expression is inferred to result from pathological point mutations show extensive diversity of associated HLA markers and include two examples of the extended HLA haplotype HLA-DR3, B8, Cw7, A1 haplotype, which has previously been reported to be negatively associated with 21-hydroxylase deficiency. One unusual disease haplotype has two CYP21 + C4 units, both of which appear to contain CYP21B-like genes.

Adrenal Hyperplasia, Congenital↗
PubMed1991

New DNA markers in the Huntington's disease gene candidate region.

The search for the Huntington's disease (HD) gene has prompted construction of a complete long-range restriction map of a 2.5-Mb candidate region, distal to the DNA marker D4S10. To facilitate the procurement of cloned DNA from this candidate region, we have augmented the existing regional mapping panel of somatic cell hybrids with hybrid HHW1071 containing a t(4p16;12) chromosome from a patient with Wolf-Hirschhorn syndrome. This translocation maps between D4S180 and D4S127, subdividing the HD candidate region and setting a proximal limit to the Wolf-Hirschhorn syndrome region. Using the expanded mapping panel, we have regionally assigned 14 independently cloned cosmids, five proximal to the t(4;12) breakpoint in the same region as D4S10 and nine distal to the breakpoint. By a combination of overlap with previously mapped cosmids and pulsed-field gel analysis, each of these cosmids has been positioned on the long-range restriction map of 4p16.3, increasing the clone coverage of the candidate region to approximately 40%. Single-copy probes from mapped cosmids were used to identify eight new DNA polymorphisms spanning the HD candidate region. These new DNA markers should prove valuable for analysis of recombination and linkage disequilibrium in HD, as well as for preclinical diagnosis of the disorder.

Alleles↗
PubMed1991

Freeze-substitution of gram-negative eubacteria: general cell morphology and envelope profiles.

Freeze-substitution was performed on strains of Escherichia coli, Pasteurella multocida, Campylobacter fetus, Vibrio cholerae, Pseudomonas aeruginosa, Pseudomonas putida, Aeromonas salmonicida, Proteus mirabilis, Haemophilus pleuropneumoniae, Caulobacter crescentus, and Leptothrix discophora with a substitution medium composed of 2% osmium tetroxide and 2% uranyl acetate in anhydrous acetone. A thick periplasmic gel ranging from 10.6 to 14.3 nm in width was displayed in E. coli K-12, K30, and His 1 (a K-12 derivative containing the K30 capsule genes), P. multocida, C. fetus, P. putida, A. salmonicida, H. pleuropneumoniae, and P. mirabilis. The other bacteria possessed translucent periplasms in which a thinner peptidoglycan layer was seen. Capsular polysaccharide, evident as electron-dense fibers radiating outward perpendicular to the cell surface, was observed on E. coli K30 and His 1 and P. mirabilis cells. A more random arrangement of fibers forming a netlike structure was apparent surrounding cells of H. pleuropneumoniae. For the first time a capsule, distinct from the sheath, was observed on L. discophora. In all instances, capsular polysaccharide was visualized in the absence of stabilizing agents such as homologous antisera or ruthenium red. Other distinct envelope structures were observed external to the outer membrane including the sheath of L. discophora and the S layers of A. salmonicida A450 and C. crescentus CB15A. We believe that the freeze-substitution technique presents a more accurate image of the structural organization of these cells and that it has revealed complex ultrastructural relationships between cell envelope constituents previously difficult to visualize by more conventional means of preparation.

Cell Membrane↗
PubMed1991

Von Hippel-Lindau disease: a genetic study.

Genetic aspects of von Hippel-Lindau (VHL) disease were studied in familial and isolated cases. Complex segregation analysis with pointers was performed in 38 kindreds with two or more affected members. Dominant inheritance with almost complete penetrance in the highest age classes (0.96 at 51 to 60 and 0.99 at 61 to 70 years) was confirmed and there was no evidence of heterogeneity between families ascertained through complete and incomplete selection. The point prevalence of heterozygotes in East Anglia was 1.89/100,000 (1/53,000) persons with an estimated birth incidence of 2.73/100,000 (1/36,000) live births. Reproductive fitness was 0.83. Direct and indirect estimates of the mutation rate were 4.4 (95% CI 0.9 to 7.9) x 10(-6)/gene/generation and 2.32 x 10(-6)/gene/generation respectively. There was no significant association between parental age or birth order and new mutations for VHL disease.

Adult↗