Search PubMed⌕ Search

Biomedical subjects

W B Lawson

Publications and source records attributed to W B Lawson.

At least 37 records · Page 2Linked to original sources
PubMed1985

Increased urine volume in chronic schizophrenic patients.

Polydipsia and polyuria have a long association with schizophrenia. To assess the prevalence of polydipsia and polyuria in schizophrenia, urine volume was examined in medication-free chronic schizophrenic patients, normal controls, and nonschizophrenic patients. Mean urine volume was significantly higher in the schizophrenic patients (2319 +/- SD 2052 ml/24 hours) than in the other two groups (1054 +/- SD 471 ml/24 hours for nonschizophrenic patients and 1265 +/- SD 613 ml/24 hours for normals). Seven of 35 patients with schizophrenia but 0/7 nonschizophrenics had urine volumes greater than any normal control. Polyuria was associated with a good premorbid history and a positive neuroleptic response. Among polyuric patients, those with hyponatremia may represent a different, distinct subgroup. Neuroleptic treatment was associated with a further, significant increase in urine volume. Hence, polydipsia and polyuria appear to be relatively common in schizophrenia.

Adult↗
PubMed1985

Transition-state inhibition of thrombin and trypsin by amidinophenylpyruvates.

The interactions of human thrombin and bovine trypsin with 4-amidinophenylpyruvate (p-APPA), 3-amidinophenylpyruvate (m-APPA) and benzamidine were studied by equilibrium binding and by stopped-flow kinetics with proflavin displacement. The excellent inhibitory properties of p-APPA with both enzymes are explained by a two-step transition-state mechanism in which the initial Michaelis complex E.I reacts rapidly to form a fairly stable, chemically bonded complex E-I, in which the keto group of p-APPA forms a hemiketal with the gamma-O-atom of Ser195 at the active site. The hemiketal complex of thrombin and p-APPA may be further stabilized by a hydrogen bond between a carboxylate oxygen of p-APPA and the N tau-atom (= N epsilon 2) of His57, as was previously shown for the trypsin-p-APPA complex by X-ray crystal structure analysis by J. Walter and W. Bode. m-APPA is apparently sterically incapable of forming a hemiketal with Ser195 O gamma; it does not bind to thrombin or trypsin in a time-dependent manner, and it displays KI values with both enzymes close to those obtained for benzamidine itself. In the p-APPA-thrombin reaction the overall binding constant KI (E-I) is 1.3 microM, while the initial binding displays a KM (E.I) estimated at least 100-fold higher (700 microM). The half-time for the formation of E-I is about 0.6 s at a p-APPA concentration of 1 microM.

Animals↗
PubMed1985

Polydipsia and chronic hyponatremia in schizophrenic inpatients.

The occasional presence of polydipsia in psychiatric patients, at times progressing to hyponatremia with severe medical complications, has been previously noted. The clinical history and laboratory data from eight chronically hyponatremic psychiatric inpatients were examined. Common characteristics were a diagnosis of chronic undifferentiated schizophrenia, an early age of onset of their illness, extended hospitalizations with minimal response to neuroleptic medications, heavy tobacco use, and a relatively high frequency of tardive dyskinesia and brain scan abnormalities. Water loading in three patients showed responses consistent with inappropriate secretion of antidiuretic hormone. Potential pathophysiologic mechanisms and treatment considerations are discussed.

Adult↗
PubMed1984

Race, violence, and psychopathology.

The frequency of violent behavior among inpatients on an acute psychiatric unit for veterans was examined. Violent behavior was assessed using a modified Lion scale in 93 white and 24 black consecutively admitted inpatients receiving a fixed dose of neuroleptic. Blacks were significantly less violent according to the Lion scale. Item analysis revealed that whites made more violent threats, committed more violent acts against self, and were more likely to be secluded or restrained. Blacks were less likely to commit multiple acts against others, although the actual numbers of violent episodes were not significantly different. No racial differences were seen in serum neuroleptic level, psychopathology as measured by the BPRS, or admission status. The same racial differences in violence were seen when either schizophrenics alone or paranoid schizophrenics were considered.

Black or African American↗
PubMed1982

Essential roles of alkylammonium and alkylguanidinium ions in trypsin-catalyzed hydrolysis of acetylglycine esters: enhancement of catalytic efficiency analyzed by the use of "inverse substrates".

An "inverse substrate" for trypsin, p-amidinophenyl acetylglycinate, has been synthesized and applied to mechanistic studies of tryptic hydrolysis. The compound reacts to form the intermediate acetylglycyl trypsin in a very specific manner, analogous to the reactions of p-amidinophenyl alkanoates with trypsin to give alkanoyl trypsins (Tanizawa, K., Kasaba, Y., & Kanaoka, Y. (1977) J. Am. Chem Soc. 99, 4485). The effects of alkylammonium and alkylguanidinium ions on tryptic hydrolysis of this "inverse substrate" have been investigated, and all alkylamines and alkylguanidines tested behaved as activators. n-Propylamine, n-propylguanidine, and n-butylguanidine, which have been reported to inhibit tryptic hydrolysis of ethyl or p-nitrophenyl acetylglycinate, were activators with p-amidinophenyl acetylglycinate. The activating properties of these amines and guanidines were demonstrated for the first time by making use of the specific characteristics of this inverse substrate. Tryptic mechanisms proposed in the literature are discussed in the light of these observations.

Catalysis↗
PubMed1982

Studies on the inhibition of human thrombin: effects of plasma and plasma constituents.

The effects of blood plasma and some plasma constituents on several types of thrombin inhibitors were quite varied. Two active esters were rapidly destroyed by serum albumin; one of these reacted initially with Lys-199, the residue that is also acylated by aspirin. Of two sulfonyl fluorides one was unaffected by albumin, and the other bound reversibly to albumin; this binding was greater with albumin acetylated at Tyr-411 near the binding site for medium-chain fatty acids. The effects of a chloromethyl ketone were inhibited, apparently reversibly, by albumin but were practically abolished by glutathione. Of two potent reversible inhibitors one was unaffected by plasma constituents, while the other was over 10-fold less potent in plasma than in fibrinogen. The effect of plasma could be partially explained by binding to albumin and lipoproteins.

Benzoates↗
PubMed1979

Taste detection and preferences in diabetics and their relatives.

In order to determine whether a generalized defect in glucose recognition exists in diabetes, taste detection and preference were measured in adult onset diabetics (AOD), juvenile onset diabetics (JOD), and healthy first-degree relatives of diabetics (NR). Controls (C) were age and sex matched nondiabetics without first-degree diabetic relatives. The AOD and NR gorups showed significantly higher glucose thresholds than their controls. In contrast, glucose threshold in JOD was not different from C. The AOD group also demonstrated a higher sucrose threshold than C. This difference was not present for JOD or NR groups. No difference in salt detection was seen in any of the groups. Taste preference was assessed by two choice situations and ratings of test solutions of varying concentrations. No significant difference in glucose or sucrose preference were noted, but both the AOD and NR groups preferred lower salt concentrations than C. These findings indicate that thery may be a widespread impariment of cellular glucose recognition in AOD and their relatives, while JOD have a specific beta cell defect.

Adolescent↗
PubMed1972

Comparative studies of the specificities of -chymotrypsin and subtilisin BPN'. Studies with flexible substrates.

A series of arylalkanoate esters and alpha-acetamidoarylalkanoate esters were tested as substrates for alpha-chymotrypsin and subtilisin BPN'. Chymotrypsin hydrolysed N-acetyl-l-phenylalanine methyl ester and methyl 4-phenylbutyrate faster than their respective higher and lower homologues, whereas methyl 2-acetamido-6-phenylhexanoate and methyl 6-phenylhexanoate were better substrates for subtilisin than their lower homologues. N-Acetyl-l-tryptophan methyl ester and its analogue, N-acetyl-3-(1-naphthyl)-alanine methyl ester, were hydrolysed 23 times faster by chymotrypsin than by subtilisin. These results indicate that the binding site of alpha-chymotrypsin is roughly 1.1nm (11A) long and curved, whereas that of subtilisin is a longer system and less curved. The stereo-specificity during the hydrolysis of typical substrates by both enzymes was found to vary over a wide range. The enhancing effect of the alpha-acetamido group in the l-series of substrates and the detrimental effect in the d-series of substrates also varies considerably.

Binding Sites↗
PubMed1972

Comparative studies of the specificities of -chymotrypsin and subtilisin BPN'. Studies with flexible and 'locked' substrates.

Subtilisin BPN' hydrolysed N-acetyl-l-3-(2-naphthyl)-alanine methyl ester, N-acetyl-l-leucine methyl ester and N-acetyl-l-valine methyl ester, faster than alpha-chymotrypsin. Of eight ;locked' substrates tested, only methyl 5,6-benzindan-2-carboxylate was hydrolysed faster by subtilisin, whereas the other esters were better substrates for chymotrypsin. Compared with the values for chymotrypsin, the stereospecific ratios during the hydrolysis of the optically active locked substrates by subtilisin were decreased by one and two orders of magnitude for bi- and tri-cyclic substrates respectively. The polar groups adjacent to the alpha-carbon atom of locked substrates did not contribute significantly to the reactivity of the more active optical isomers, but had a detrimental effect on the less active antipodes during hydrolysis by both the enzymes. These studies show that the binding site of subtilisin BPN' is longer and broader than that of alpha-chymotrypsin.

Binding Sites↗