PubMed Health⌕ Search

Biomedical subjects

W Lawton

Publications and source records attributed to W Lawton.

8 recordsLinked to original sources

Proteinmorphosis: a mechanical model for protein conformational changes.

Proteinmorphosis is a physically-based interactive modeling system for simulating large or small conformational changes of proteins and protein complexes. It takes advantage of the cross-linked one-dimensional nature of protein chains. The user can, based on her chemical knowledge, pull pairs of points (lying either on a single protein or on different molecules) together by specifying geometric distance constraints. The resulting conformation(s) of the molecule(s) of interest is computed by an efficient finite element formalism taking into account elasticity of the protein backbone, van der Waals repulsions, hydrogen bonds, salt bridges and the imposed distance constraints. The conformational change is computed incrementally and the result can be visualized as an animation; complete interactivity is provided to position and view the proteins as desired by the user. Physical properties of regions on the protein can also be chosen interactively. The conformational change of calmodulin upon peptide binding is examined as a first experiment. It is found that the result is satisfactory in reproducing the conformational change that follows on peptide binding. We use Proteinmorphosis to study the cooperative hemoglobin oxygen binding mechanism in a second, more sophisticated, experiment. Different modeling strategies are designed to understand the allosteric (cooperative) binding process in this system and the results are found to be consistent with existing hypotheses.

Calmodulin↗

Renal clearances of oxypurinol and inulin on an isocaloric, low-protein diet.

In previous studies a low-calorie, low-protein diet caused a sustained reduction in both oxypurinol and uric acid renal clearances (CLR). With the hypothesis that the decrease in CLR was due to the low-protein and not the low-caloric content of the diet, we studied the CLR of oxypurinol, uric acid, creatinine, and inulin in normal subjects during isocaloric (2600 calories per 70 kg per day), normal-protein (150 gm per day), and low-protein (19 gm per day) diets. There were three major findings: (1) the CLR of oxypurinol declined from 26.6 +/- 1.8 ml/min on the normal-protein diet to 13.5 +/- 1.4 ml/min on the isocaloric low-protein diet (p less than 0.05); (2) the CLR of inulin and creatinine fell 14% and 20%, respectively, on the low-protein diet compared with the normal-protein diet (both p less than 0.05); and (3) there was a diurnal variation in the CLR of oxypurinol. We conclude that the decreased CLR of oxypurinol was the result of the reduced protein content of the diet and the CLR of both inulin and creatinine were decreased on the low-protein diet.

Adult↗

Increased detection of prolylaminopeptidase in Neisseria meningitidis by Identicult-Neisseria.

Identicult-Neisseria (Scott Laboratories, Inc., Fiskeville, R.I.), a rapid enzymatic method with chromogenic substrates, was tested in our laboratories for the identification of Neisseria gonorrhoea, Neisseria meningitidis, and Neisseria lactamica. The test correlated very highly in its identification of pathogenic Neisseria spp. with modified New York City fermentation medium. Identicult-Neisseria appeared to be more sensitive in its detection of prolylaminopeptidase activity in N. meningitidis than most of the currently available systems.

Aminopeptidases↗

Urinary kallikrein in postobstructive diuresis.

We studied urinary kallikrein excretion in the rat during unilateral release of 24-hr bilateral ureteral ligation (BUL). In six rats studied after 24 hr of BUL, the glomerular filtration rate was 20 per cent of that in the five sham-operated controls. In the BUL group, the urine flow rate was 5 fold greater, fractional sodium excretion 100 times greater, and fractional potassium excretion 5 times greater than in controls. Urinary kallikrein excretion in the BUL group was one-half that of the controls. However, urinary kallikrein excretion per functioning nephron was increased 3 fold in the BUL group. Five of six BUL rats with increased fractional sodium and water excretion also showed increased urinary kallikrein excretion/GFR when compared to controls. Our study suggests that after 24 hr of BUL in the rat, urinary kallikrein excretion is increased in relation to the remaining, functioning nephrons and suggests a role for the kallikrein-kinin system in the postobstructive salt and water losses.

Animals↗

A solitary functioning osseous metastasis from a malignant pheochromocytoma of the organ of Zuckerkandl.

A case of a malignant phenochromocytoma of the organ of Zuckerkandl is reported. There was a solitary functional metastasis in the left femur, which was treated by hip disarticulation after removal of the primary. The patient is asymptomatic and free of further metastases after 3 years. Other reported cases of solitary metastases from malignant pheochromocytomas are cited. These occurred most frequently in the skeleton system, which is the most common site of distant metastases in malignant pheochromocytoma. The reported case and the review of the literature indicate that solitary or limited metastatic lesions should be treated surgically by partial or, when possible, complete resection.

Adolescent↗

The effects of therapy for mild hypertension on circulating level of dopamine beta-hydroxylase.

Circulating dopamine beta-hydroxylase levels and norepinephrine excretion were measured in 76 mild hypertensive patients. Levels of dopamine beta-hydroxylase, norepinephrine excretion and blood pressure were obtained both before and after the initiation of therapy. Data from 20 patients exhibiting a diastolic blood pressure decrease of 10 mmHg or more were compared with data from 10 normotensive individuals. Changes in dopamine beta-hydroxylase levels were similar for the two groups and were not related to blood pressure changes. Intra-individual variation was small in both groups. There were no detectable functional relationships between diastolic pressure and urinary norepinephrine, norepinephrine and dopamine beta-hydroxylase or dopamine beta-hydroxylase and diastolic pressure. It dose not seem likely that dopamine beta-hydroxylase levels can replace urinary catecholamines as a commonly used index of sympathetic activity.

Blood Pressure↗