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Biomedical subjects

S A Carter

Publications and source records attributed to S A Carter.

At least 37 records · Page 2Linked to original sources
PubMed1996

Enhanced cytochemical detection of viral proteins and RNAs using double-sided labeling and light microscopy.

We have developed a double-sided labeling technique for detecting viral proteins or RNAs in plastic-embedded leaf tissue by immunocytochemistry or in situ hybridization, respectively, and light microscopy. The signal from the target was enhanced by double-sided labeling when compared with single-sided labeling because sections were submerged in labeling solutions with both sides accessible to antibodies or complementary RNAs. The additional label was visible during microscopic analysis. Background signal was decreased since the tissue was probed and washed under conditions where folds and creases in the tissue were minimized. This technique uses the same equipment and chemicals as for single-sided labeling, and thus adjustments for reagent expenditures are not necessary. The procedure should be applicable to animal and plant tissue.

Animals↗
PubMed1994

Linkage analyses in British pedigrees suggest a single locus for Darier disease and narrow the location to the interval between D12S105 and D12S129.

Darier disease is a dominantly inherited skin disorder in which there appears to be abnormal adhesion between keratinocytes. We and others have shown that the disease in some British pedigrees is closely linked to markers mapping to 12q23-q24.1. In the present study we have defined crossovers that enable us to narrow the location of the disease gene to the interval between the D12S105 and the D12S129 markers. This interval may be expected to be on the order of about 4 cM on the basis of linkage data obtained using the primary CEPH reference families. Our data provide further evidence for locus homogeneity: each of four large British pedigrees, two of which have previously been subjected to preliminary characterization, shows statistically significant evidence for linkage to markers mapping to 12q23-q24.1.

Chromosome Mapping↗
PubMed1994

Germline mutations in the neurofibromatosis type 2 tumour suppressor gene.

The recent identification of the NF2 tumour suppressor gene has enabled large scale screening for pathological mutations in the gene. We have sought germline mutations in the NF2 gene by SSCP and heteroduplex analysis of cDNA and genomic DNA samples followed by cloning and sequencing of mutant alleles. In the present report we describe 11 putative pathological mutations, including five nonsense mutations, three short insertions or deletions causing frameshifts and three missense mutations. Most stop mutations and frameshift mutations were found in individuals expressing a severe phenotype while one of the three missense mutations was associated with a mild phenotype. Four unrelated NF2 patients of the 93 tested were found to have identical nonsense mutations caused by a C to T transition (C169) in a CpG dinucleotide, which is a potential mutational hotspot in the NF2 tumour suppressor gene.

Base Sequence↗
PubMed1994

A mutation in the neurofibromatosis type 2 tumor-suppressor gene, giving rise to widely different clinical phenotypes in two unrelated individuals.

We have sought mutations in the recently identified neurofibromatosis type 2 (NF2) tumor-suppressor gene in a large panel of NF2 patients, using PCR-based SSCP and heteroduplex analysis, followed by cloning and sequencing of appropriate PCR products. Two unrelated NF2 patients were found to have identical nonsense mutations caused by a C-to-T transition in a CpG dinucleotide that is a potential mutational hot spot in the NF2 tumor-suppressor gene. Unexpectedly, the two individuals had widely different clinical phenotypes, representing the severe Wishart and mild Gardner clinical subtypes. Analysis of DNA samples from different tissues of the mildly affected patient suggests that he is a somatic mosaic for the mutation.

Adolescent↗
PubMed1993

Outcome criteria in patients with peripheral arterial disease.

To adequately evaluate patients with chronic occlusive arterial disease several factors will need to be taken into account and documented. These include associated diseases such as diabetes mellitus. When surgical or endovascular therapy is applied, analysis of outcome must include the symptomatic status of the patient, the anatomic evidence of patency of the procedure and of the proximal and distal disease, the hemodynamic result, limb preservation, and mortality. All of these factors will provide a better global picture of the disease and information on how it can be best treated.

Arm↗
PubMed1993

A new locus for autosomal dominant retinitis pigmentosa on chromosome 7p.

Autosomal dominant retinitis pigmentosa (adRP) is known to result from mutations in two different retinal genes--rhodopsin and peripherin--while a third locus has been implicated by linkage data. However, families have been reported in which all three known loci have been excluded. We report linkage of adRP in one such family to two microsatellite markers on chromosome 7p. D7S435 has previously been localized to 7p13-15.1; D7S460, previously only localized to chromosome 7, maps to within 2 cM of D7S435 with a lod score of 12.15. Two point linkage analysis between these markers and adRP gave lod scores of 5.65 (theta = 0) and 4.19 (theta = 0.046) for D7S460 and D7S435, respectively. Multipoint analysis gave a maximum lod score of 8.22. These data strongly suggest a new adRP locus on chromosome 7p.

Base Sequence↗
PubMed1993

Tissue penetration of clindamycin in diabetic foot infections.

Serum and tissue samples were obtained during surgery from four diabetics with neuropathy who underwent debridement or amputation for foot infections while receiving clindamycin 600 or 900 mg iv. Clindamycin concentrations were assayed by radioimmunoassay. Clindamycin was detected in all serum and tissue samples (range: 0.04-2.8 mg/kg in tissues and 1.1-11.1 mg/L in serum). In nine of the eleven tissue samples the clindamycin concentration exceeded the MICs reported for many pathogens commonly involved in such infections. In only a single instance was the ratio of tissue to serum concentration < 0.13.

Adipose Tissue↗
PubMed1993

Elective foot surgery in limbs with arterial disease.

Surgical correction of foot deformities is generally indicated to relieve the disability. The presence or suspicion of arterial disease may lead to the reluctance to operate because of the concern that healing might not occur, however. Twenty-three patients were referred for vascular assessment before elective foot surgery. There was little or no evidence of arterial disease in 15 limbs. In eight limbs there was unequivocal evidence of complete obstruction in the main limb artery. Contrary to what might be expected, healing after surgery occurred without difficulties in the limbs with arterial obstruction. The arterial disease as assessed by laboratory methods was not severe. The results indicate that elective foot surgery can be safely undertaken in some limbs. Simple laboratory methods for assessment of arterial circulation include measurements of distal blood pressure, skin temperature, transcutaneous oxygen tension, and assessment of digital pulsatility. A useful approach for estimating the chances of healing after elective surgery in limbs with arterial obstruction is formulated on the basis of the clinical and laboratory assessment.

Aged↗
PubMed1992

Exclusion of chromosome 6 and 8 locations in nonrhodopsin autosomal dominant retinitis pigmentosa families: further locus heterogeneity in adRP.

Genetic studies have revealed that 25 to 30% of autosomal dominant retinitis pigmentosa (adRP) families have mutations in the rhodopsin gene, while the remainder do not. More recently linkage data and mutation detection have demonstrated two further loci implicated in adRP, at an as yet unidentified gene on chromosome 8p and at the human gene homologue of the mouse Rds (Retinal Degeneration Slow) gene on chromosome 6p. We have previously reported exclusion of adRP from the rhodopsin locus on 3q in two large adRP families. We now report exclusion data for both families, on chromosomes 6 and 8, demonstrating that the adRP phenotype results from mutations in at least four locations.

Chromosome Mapping↗
PubMed1992

The effect of body heating and cooling on the ankle and toe systolic pressures in arterial disease.

Although changes in body temperature alter limb blood flow, little information exists on the effect of body heating and cooling on systolic pressures in limbs with arterial disease. Ten patients with stable claudication were studied. Mean ankle systolic pressure index during body cooling (0.79 +/- 0.04) exceeded (p less than 0.01) both the value during routine test (0.69 +/- 0.03) and during heating (0.65 +/- 0.04). The individual, paired difference in ankle systolic pressure index between cooling and heating exceeded 0.15 in seven limbs and between cooling and routine test in five. Mean toe systolic pressure index during heating, but not during cooling, was lower than during routine test (p less than 0.01). There was no significant difference in the mean toe systolic pressure index between heating and cooling. However, compared with heating, toe systolic pressure index increased with cooling in 12 limbs and decreased in eight, including three with loss of measurable pressure. The paired difference in toe systolic pressure index between cooling and heating exceeded 0.15 in 10 limbs and between cooling and routine test in eight; whereas between heating and routine test the paired difference was within 0.15 in all but three limbs. The results indicate that changes in body temperature have significant effects on distal pressures in arterial disease. Preliminary warming in routine tests should improve reproducibility.

Aged↗
PubMed1992

Effect of temperature on digital systolic pressures in lower limb in arterial disease.

BACKGROUND: Toe pressures correlate with the chances of healing of skin lesions and with the risk of amputation and mortality. They are not affected by incompressibility of the tibial vessels, which may render ankle pressures inaccurate and reflect the overall arterial obstruction down to the digits. Digital pressures, however, may be affected by temperature. METHODS AND RESULTS: Measurements under routine laboratory conditions were compared with those at controlled temperatures in 77 limbs with arteriosclerosis obliterans. The desired local temperatures were attained by perfusing water through the cuffs for 7 minutes before the measurements while the flow was interrupted by a tourniquet to allow equilibration of the toe and water temperatures. Mean toe pressure of 34 +/- 4 mm Hg at 10 degrees C was significantly lower (p less than 0.001) than the values during routine measurements (57 +/- 4 mm Hg) and at 30 degrees C (69 +/- 4 mm Hg). The pressure at 30 degrees C was 10 +/- 3 mm Hg higher than during routine measurements when initial digit temperature was below 30 degrees C (p less than 0.01) but not when it was higher. Measurements at 3 degrees C increments from 27 degrees C to 39 degrees C showed progressive increase in pressure (p less than 0.01). CONCLUSIONS: Pressures at 36 degrees C and 39 degrees C were the highest but were not significantly different from each other. When toe temperature is low under routine conditions, the measured pressure may be falsely low, probably because of an effect on the main digital arteries that leads to delayed opening during deflation of the cuffs. Measurements at warm local temperature will increase the accuracy of the assessment of the severity of the arterial obstruction and may improve prediction of spontaneous healing of skin lesions.

Aged↗
PubMed1991

The effect of cooling on toe systolic pressures in subjects with and without Raynaud's syndrome in the lower extremities.

The effect of changes in local and body temperature on the toe systolic pressures was studied in 20 subjects with and 30 without Raynaud's syndrome in the toes. The pressures were significantly lower in the group with Raynaud's syndrome under all experimental conditions (P less than 0.01). The pressures were significantly lower during body cooling than during body warming in both groups (P less than 0.01). The mean decrease with body cooling was 58 mmHg in the group with Raynaud's syndrome and 24 mmHg in the control subjects (P less than 0.01). During body cooling pressures fell to less than 30 mmHg in 70% of subjects with Raynaud's syndrome and in 3% of the controls. Local cooling from 30 to 10 degrees C during body cooling resulted in a significant mean decrease in pressure of over 40 mmHg in both groups (P less than 0.01) and the pressure fell below 30 mmHg in over 90% of the group with and in 26% of those without Raynaud's attacks. The results indicate the importance of body cooling and local temperature in the mechanism of vasospasm in the toes. They are also relevant to the diagnosis of Raynaud's syndrome in the lower limbs and have implications for the testing of patients with arteriosclerotic occlusion since erroneously low pressure values could be obtained in tests when the feet are cold.

Adolescent↗
PubMed1989

A case study of the Tenwek hospital community health programme in Kenya.

Tenwek mission hospital, situated in the west-central highlands of Kenya, initiated a community health programme in 1984. This paper describes the major features of the programme and assesses the impact on a number of health and family planning practices after 3 years of implementation. Comparison of the results in the programme areas with the baseline survey and with control areas show significant changes in several indicators. It is concluded that Tenwek hospital demonstrated the impact a hospital can have on health of communities by effectively moving into community-based health care.

Community Health Services↗
PubMed1989

Walking ability and ankle systolic pressures: observations in patients with intermittent claudication in a short-term walking exercise program.

Walking ability and limb hemodynamics were studied in 56 patients with intermittent claudication in an exercise program. Patients walked 1 hour 3 times a week for 3 to 6 months. Ankle and brachial pressures were measured at rest and after a standard walk, and walking ability on the treadmill and during free walking was determined. Average maximal distance on the treadmill increased from 0.59 to 1.00 km after training (p less than 0.0001). Also, after training 84% of patients were able to walk continuously more than 2 km without severe discomfort. The attained walking ability of individual patients could not be predicted from pressure measurements. Small pressure changes after training suggested that factors other than increased development of collateral vessels were important in determining walking ability. Practically useful walking ability was achieved in patients with aortoiliac and femoropopliteal arterial obstruction in the presence or absence of coronary disease and in patients taking beta-blockers. The results indicate that walking exercise is a valuable treatment for many patients with claudication who are not candidates for arterial reconstruction.

Ankle↗
PubMed1988

Preferred conformational state of the N-terminus section of a bovine growth hormone fragment (residues 96-133) in water is an omega loop.

The solution structure of a 38-amino-acid-residue, biologically active fragment of bovine growth hormone (bGH96-133) was investigated with a combined nuclear magnetic resonance (NMR) and computer modeling approach. With the distance geometry program DISGEO and distance constraints derived from nuclear Overhauser enhancement (NOE) experiments, it was found that residues Ser-100 to Tyr-110 circumscribe and omega-loop, a recently categorized feature of nonregular secondary protein structure.

Amino Acid Sequence↗
PubMed1988

Training to vasodilate in a cooling environment: a valid treatment for Raynaud's phenomenon?

While many reports indicate that voluntary modification of skin temperature is possible and may be useful in the treatment of Raynaud's phenomenon, little attention has been paid to the ecological validity of training skin temperature increases when a considerable amount of vasodilation of digital vessels may already exist (room temperature, 22-24 degrees C). Patients with Raynaud's vasospastic attacks may benefit from learning to avoid attacks when they are impending by voluntarily vasodilating the vessels of their digits under conditions when vasoconstriction has begun. The results in 14 patients with primary and secondary Raynaud's phenomenon indicated that (a) patients learned to voluntarily increase digital skin temperatures in a "cooling" environment during documented vasoconstriction, and (b) there was a 31% decrease in the occurrence of vasospastic attacks following such learning. These data suggest that a new methodology may be useful in the biofeedback treatment of Raynaud's phenomenon, but further research is needed to determine the specific mechanism(s) involved, and the limits to its usefulness.

Adult↗
PubMed1988

Apparent finger systolic pressures during cooling in patients with Raynaud's syndrome.

Despite considerable research, the mechanisms responsible for the vasospasm associated with Raynaud's syndrome are not well understood and there is no reliable diagnostic test. In the present studies, measurements of systolic pressure in locally cooled fingers were used to address these issues. We found that local cooling produced a marked decrease or loss of the apparent finger systolic pressure in patients with Raynaud's syndrome in whom a standardized vasoconstriction had been induced by body cooling. Abnormal responses were encountered in 109 of 125 patients with secondary Raynaud's syndrome, in 21 of 37 patients with primary Raynaud's disease or the syndrome of uncertain cause, and in two of 63 subjects without symptoms of Raynaud's. These data suggest a high accuracy of the test in patients with secondary Raynaud's syndrome and lower accuracy in those with disease of primary or uncertain cause. We studied responses of systolic pressures to alterations in body and local temperatures in fingers with and without low pressures secondary to proximal arterial obstruction. Our data show that although local cooling has a small independent effect that increases vascular tone: (1) sympathetic vasoconstriction induced by body cooling is necessary to produce vasospasm and often produces it without local cooling, (2) high local temperature (30 degrees C) protects from vasospasm, and (3) low finger blood pressure predisposes to it. Delayed opening of the vessels observed after sudden deflation of blood pressure cuffs suggests that abnormal responses of finger systolic pressure to cold represent combined effects of high vascular tone, delayed opening, and local blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗