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Biomedical subjects

C R Robinson

Publications and source records attributed to C R Robinson.

At least 37 records · Page 2Linked to original sources
PubMed1994

Hydrostatic pressure reverses osmotic pressure effects on the specificity of EcoRI-DNA interactions.

To characterize the role of water in protein-DNA interactions, we have studied the specificity of the EcoRI restriction endonuclease as a function of osmotic and hydrostatic pressure. The extent of cleavage by the enzyme at noncanonical ("star") sites is shown to depend uniquely upon the osmotic pressure in the reaction as controlled by the addition of a wide variety of neutral solutes. Alteration of cleavage specificity ("EcoRI* activity") is not uniformly correlated with any other colligative solvent property such as dielectric constant, viscosity, or water concentration. The application of hydrostatic pressure reverses the effects of osmotic pressure, restoring the natural selectivity of the enzyme for its canonical site GAATTC. This combination of observations provides compelling evidence that the site-specific recognition of canonical site DNA by EcoRI is mediated by discretely bound water molecules and that the release of these waters induces a fundamental change in the specificity of the interaction, leading to cleavage at alternative sites. This comprehensive analysis of solvent effects facilitates the unambiguous identification of structurally and functionally specific waters involved in macromolecular recognition events.

DNA↗
PubMed1993

Molecular recognition mediated by bound water. A mechanism for star activity of the restriction endonuclease EcoRI.

Many restriction endonucleases such as EcoRI lose some specificity for their recognition sequence under certain buffer conditions. The cause of this disruption of accurate protein-DNA recognition has never been explained. By cleaving DNA with EcoRI in the presence of several osmolytes, we show that the extent of this EcoRI "star activity" depends strongly upon osmotic pressure. The loss of specificity accompanying decreased water activity implies a role for one or more water molecules in recognition of specific sequences of DNA. Water mediation may constitute a general motif for sequence-specific DNA recognition by restriction enzymes and other DNA-binding proteins.

Binding Sites↗
PubMed1993

Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis.

BACKGROUND: Familial adenomatous polyposis is an autosomal dominant disorder characterized by the formation of hundreds of colorectal adenomas and eventual colorectal cancer. Administration of the nonsteroidal antiinflammatory drug sulindac has been followed by regression of polyps in patients with this disorder, but no controlled trial of this drug in patients who have not had surgery has been reported. METHODS: We conducted a randomized, double-blind, placebo-controlled study of 22 patients with familial adenomatous polyposis, including 18 who had not undergone colectomy. The patients received sulindac at a dose of 150 mg orally twice a day for nine months or identical-appearing placebo tablets. The number and size of the polyps were evaluated every three months for one year. RESULTS: A statistically significant decrease in the mean number of polyps and their mean diameter occurred in patients treated with sulindac, as compared with those given placebo. When treatment was stopped at nine months, the number of polyps had decreased to 44 percent of base-line values and the diameter of the polyps to 35 percent of base-line values (P = 0.014 and P < 0.001, respectively, for the comparison with the changes in the group given placebo). No patient had complete resolution of polyps. Three months after treatment with sulindac was stopped, both the number and the size of the polyps increased in sulindac-treated patients but remained significantly lower than the values at base line. No side effects from sulindac were noted. CONCLUSIONS: Sulindac reduces the number and size of colorectal adenomas in patients with familial adenomatous polyposis, but its effect is incomplete, and it is unlikely to replace colectomy as primary therapy.

Adenomatous Polyposis Coli↗
PubMed1993

Electrostatic stabilization in four-helix bundle proteins.

Charge substitutions generated by site-directed mutagenesis at the termini of adjacent anti-parallel alpha-helices in a four-helix bundle protein were used to determine a precise value for the contribution of indirect charge-charge interactions to overall protein stability, and to simulate the electrostatic effects of alpha-helix macrodipoles. Thermodynamic double mutant cycles were constructed to measure the interaction energy between such charges on adjacent anti-parallel helices in the four-helix bundle cytochrome b562 from Escherichia coli. Previously, theoretical calculations of helix macrodipole interactions using modeled four-helix bundle proteins have predicted values ranging over an order of magnitude from 0.2 to 2.5 kcal/mol. Our system represents the first experimental evidence for electrostatic interactions such as those between partial charges due to helix macrodipole charges. At the positions mutated, we have measured a favorable interaction energy of 0.6 kcal/mol between opposite charges simulating an anti-parallel helix pair. Pairs of negative or positive charges simulating a parallel orientation of helices produce an unfavorable interaction of similar magnitude. The interaction energies show a strong dependence upon ionic strength, consistent with an electrostatic effect. Indirect electrostatic contacts do appear to confer a limited stabilization upon the association of anti-parallel packing of helices, favoring this orientation by as much as 1 kcal/mol at 20 mM K phosphate.

Apoproteins↗
PubMed1993

Racial differences in the relationship between blood pressure and risk of retinopathy among individuals with NIDDM.

OBJECTIVE: To assess whether the prevalence of retinopathy differs between blacks and whites with diabetes and to examine differences between blacks and whites in the relationship between risk factors for and prevalence of retinopathy. Population data suggest diabetic retinopathy is either more prevalent or more severe in blacks than in whites. RESEARCH DESIGN AND METHODS: We analyzed data from a screening study for retinopathy among patients with diabetes, conducted in Maryland from 1986-1990. RESULTS: After adjusting for age, duration of diabetes, type of treatment for diabetes, and presence or absence of high blood pressure, black men with NIDDM were approximately 23% more likely to have retinopathy than other race-sex groups (not statistically significant). We also found a different relationship between systolic blood pressure and retinopathy prevalence in blacks than in whites among individuals with NIDDM. Among blacks, the risk increased as systolic blood pressure increased, even within the normal range, and reached statistical significance at > 150 mmHg. Among whites, the risk was increased only among those with high systolic blood pressure (> 140 mmHg) and did not reach statistical significance. CONCLUSIONS: Our data are consistent with the hypothesis that differences exist between blacks and whites in risk of diabetic retinopathy, and that the effect of blood pressure on risk of retinopathy differs between blacks and whites.

Adult↗
PubMed1992

Physiological nursing research in dyspnea: a paradigm shift and a metaparadigm exemplar.

Dyspnea, the primary activity-limiting symptom in chronic obstructive pulmonary disease, is associated with respiratory muscle mechanisms. This leads to a paradigm shift from pulmonary processes to respiratory muscle function. Within the context of an integrative metaparadigm, basic and clinical nursing science are developed: to better understand physiological processes associated with dyspnea as presented in three physiological models of dyspnea, to identify respiratory muscle mechanisms associated with current treatment strategies for dyspnea, to eventuate clinical assessments of exercise endurance, and to generate treatment strategies in the promotion of positive life processes. The basic knowledge developed within this program provides a foundation for the generation of strategies to assess patients, to promote normal functioning of life processes, and to enhance positive coping with responses to illness. Thus, this research program provides a model for the development of substantive physiological and clinical knowledge for nursing practice.

Clinical Nursing Research↗
PubMed1989

Differential effects of acetylsalicylic acid and acetaminophen on sleep abnormalities in a rat chronic pain model.

We studied the effects of two non-steroidal anti-inflammatory analgesics (NSAIAs), acetylsalicylic acid (ASA) and acetaminophen, on sleep patterns in rats with adjuvant-induced arthritis. We found that in the normal rat both NSAIAs reduced non-rapid eye movement (NREM) sleep. In arthritic rats ASA and acetaminophen had opposite effects on sleep. ASA increased wakefulness and decreased all sleep stages and acetaminophen decreased wakefulness and increased NREM sleep and paradoxical sleep during the light hours (the hours of maximal sleep in the normal rat). When the effects of severity of arthritis were factored out, both drugs still had large and significant effects on sleep and wakefulness. Thus, two prostaglandin synthetase inhibitors showed differential effects on sleep and wakefulness in the normal rat and in rats experiencing chronic pain. Although ASA is important in the treatment of pain in rheumatic diseases, it may contribute to abnormal sleep patterns.

Acetaminophen↗
PubMed1989

Body temperature and heart rate rhythms in acutely head-injured patients.

This descriptive pilot study investigated the circadian (24-hour) rhythms of heart rate and temperature in acutely head-injured patients and the relationships between these variables. The convenience sample consisted of 10 patients who were admitted to the hospital with the diagnosis of acute head injury. Patel's Method of Partition was used to estimate rhythmicity. Only one patient demonstrated circadian rhythms for body temperature and heart rate with the peaks occurring at appropriate times. While three other patients had significant rhythms for these variables, the rhythms had cycles of less than 24 hours and peaks occurring at inappropriate times. Although significant correlations were found between body temperature and heart rate rhythms, they were low.

Adult↗
PubMed1989

Decreased slow-wave and paradoxical sleep in a rat chronic pain model.

Diurnal sleep-wake patterns in the normal and the adjuvant arthritic rat were measured during the first 3 h of both light and dark periods. During the hours of maximal sleep in the normal rat, arthritic rats showed a significant increase in wakefulness (Wake), a shift to non-rapid-eye-movement (NREM) stages with lower amplitudes (LS and HS1), and a large reduction of NREM sleep with the highest-amplitude (HS2) and paradoxical sleep. Arthritic rats also showed marked sleep fragmentation manifested by more episodes of Wake, LS, and HS1 and shorter episodes of HS2 during both the light and the dark periods. Thus, arthritic rats cannot sustain long periods of sleep. In contrast to control rats, arthritic rats lacked a diurnal variation in Wake, total sleep, and electroencephalographic (EEG) delta activity. They also showed a decrease in overall EEG amplitude. In addition, there was a positive correlation between the severity of arthritis and the percentages of NREM sleep with low (LS) and moderate (HS1) amplitude. Thus, the decline in EEG amplitude could indicate a deficit of EEG generating mechanisms or some aspect of disease severity, such as pain.

Animals↗
PubMed1989

Adrenal lipoma: a rare tumour of the adrenal gland.

We report a case of an adrenal lipoma, a very rare lesion first described in 1899 and of which a total of six cases have previously been reported (Lange 1966, Page, De Lellis & Hough 1986). Five of these cases were found incidentally at post mortem. In one case an acute hypertensive episode intra-operatively simulated the signs of phaeochromocytoma and contributed directly to the patient's death (Lange 1966). Intra-operative hypertension also occurred in our patient.

Adrenal Gland Neoplasms↗
PubMed1984

Localized amyloidosis of the ureter.

The deposition of amyloid fibril proteins as localized tumor-like masses (amyloid tumors) is a relatively rare phenomenon in the spectrum of amyloid-related disease. These tumors have a particular tendency to occur in the genitourinary tract and are often mistaken clinically for malignancies. We report a case of primary amyloidosis of the ureter. A cause for the amyloid deposition could not be identified.

Aged↗
PubMed1984

Low-grade clear cell eccrine carcinoma.

Two patients had facial tumors that had a distinctive microscopic appearance. Each consisted of multiple nests of glycogen-filled clear cells dispersed in the dermis and associated with a hyalinized, collagenous stroma. There were also ductular features suggestive of eccrine differentiation. The lesions had a locally infiltrative microscopic appearance, and one involved the subcutaneous fat and skeletal muscle. Although neither tumor has recurred following excision, we believe that they are low-grade eccrine carcinomas and that they may represent a distinctive, albeit rare, subtype of adnexal neoplasm.

Aged↗
PubMed1977

Occlusion of the subclavian vein associated with cephalic vein pacemaker electrodes.

Thrombosis and occlusion of major veins have been described following the use of transvenous pacing electrodes for the establishment of permanent cardiac pacing. The frequency of such complications is, however, not well known. A series of 125 patients was therefore reviewed, all of whom had been paced with permanent transvenous electrodes through a cephalic vein. There was clinical and venographic evidence of subclavian vein occlusion in only 3 of these patients. A further 20 of these patients were also subjected to venography and showed no radiographic evidence of venous occlusion although minor thrombosis associated with the pacemaker electrode was found in one patient. It is concluded that the convenience of using the cephalic vein as a route for the insertion of transvenous pacing electrodes outweighs the small risk of major venous occlusion.

Adult↗