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Biomedical subjects

R George

Publications and source records attributed to R George.

At least 163 records · Page 9Linked to original sources

A diagnostic adjunct in treatment planning for the dentofacial deformity patient.

The purpose of this article is to elucidate individual facial relationships using the concepts of the proportionate analysis as described by Moorrees and others. Diagnosis and treatment must be based upon dynamic orofacial and masticatory muscles as well as occlusal and temporomandibular joint functions in concert with esthetic considerations of the soft-tissue configuration. The Moorrees mesh offers a practical means for the study of proportionate relationships rather than linear and angular measurements.

Cephalometry↗

Lipid modulation of the activity and temperature dependence of the purified (Na+ + Mg2+)-ATPase from Acholeplasma laidlawii B membranes.

The influence of lipid composition on the activity and temperature dependence of the purified (Na+ + Mg2+)-ATPase from Acholeplasma laidlawii B membranes has been investigated. The reconstituted enzyme requires liquid-crystalline lipid for full activity. However, phosphatidylcholines with fatty acids varying considerably in chemical structure and chain length all support comparable levels of activity at temperatures above their gel to liquid-crystalline phase transition temperatures, indicating that the specific activity of this ATPase is not dependent on membrane lipid fluidity. Phosphatidylethanolamines also effectively reconstitute this enzyme but anionic phospholipids do not, and in fact inhibit enzyme activity when mixed with zwitterionic phospholipids. The incorporation of cholesterol into phosphatidylcholine vesicles had no effect on ATPase activity except at high concentrations, where some inhibition occurs. Cholesterol also affects the temperature dependence of this enzyme somewhat, probably through its effect on the phase state of the phospholipids.

Acholeplasma laidlawii↗

Dengue haemorrhagic fever in Malaysia: a review.

The historical background, epidemiology and changing pattern of clinical disease as seen in Malaysia is reviewed. The preliminary results of the longitudinal study of epidemiology of dengue in Malaysia is also presented. Studies led by Rudnick et al. over some 18 years have established that the disease is endemically transmitted by both Aedes aegypti and Aedes albopictus causing illnesses ranging from mild febrile episodes through classical dengue fever, dengue haemorrhagic fever and the dengue shock syndrome. The first epidemic occurred in 1962 in Penang, and the second major epidemic in 1974 in Selangor. From then on epidemics seem to occur every 4 years, i.e. 1978, and then in 1982. With increasing number of cases being seen from the end of 1985 and in 1986, and with the increasing numbers of positive virus isolates, another epidemic may occur this year. Though in the early years, mainly children were affected, recently more cases are being seen in 16-30 years age group. There is also a changing pattern in the clinical presentation of the cases. The clinician has to be aware of the various modes of presentation of this sinister disease. A high index of suspicion is needed for early diagnosis, as management is mainly symptomatic and there is no specific drug as yet to combat the shock and bleeding manifestations.

Adolescent↗

A model hypocholinergic syndrome produced by a false choline analog, N-aminodeanol.

N-aminodeanol is an analog of choline that serves as a less effective substrate in all of its known enzymatic and transport mechanisms. It was utilized to test the hypothesis that the selective vulnerability of cholinergic neurones in Alzheimer's disease is due to competition for the available choline between pathways for acetylcholine and phospholipid synthesis. Rats placed on a choline free diet containing an equivalent amount of N-aminodeanol develop a model hypocholinergic state comprising hyperreactivity, hyperalgesia, aggressive behavior and a deficit in learning and memory. These effects are associated with a progressive replacement of free and lipid-bound choline and acetylcholine with N-aminodeanol and its corresponding esters. Choline acetyltransferase is reduced in some brain regions, suggesting a loss of cholinergic neurones. We propose that this represents a potentially useful animal model of Alzheimer's disease which deserves further investigation.

Alzheimer Disease↗

Structure-function investigations of the membrane (Na+ + Mg2+)-ATPase from Acholeplasma laidlawii B: studies of reactive amino acid residues using group-specific reagents.

The purified, lipid-reconstituted (Na+ + Mg2+)-ATPase from Acholeplasma laidlawii B was treated with a variety of reagents which specifically modify various amino acid residues on the enzyme. In all cases reaction of this enzyme with any of the reagents tested results in at least a partial inactivation of its activity. The modification of one reactive lysine by dinitrofluorobenzene, of one reactive arginine by phenylglyoxal, or of two tyrosine residues by 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole or fluorosulfonylbenzoyl adenosine results in a complete inactivation of the enzyme. Partial inactivation of enzymatic activity with N-ethylmaleimide, p-chloromercuribenzene sulfonic acid, dicyclohexylcarbodiimide, and Woodward's reagent K suggests an indirect involvement of sulfhydryl and carboxylic acid groups in the maintenance of enzymatic activity, although inhibition by these reagents may also be the result of nonspecific effects such as subunit crosslinking. These studies also show that all of the subunits of the ATPase can be labeled by aqueous-phase reagents directed at amino groups and phenolic groups, and provide evidence for a specific affinity labeling of the alpha subunit of the enzyme by a nucleotide analog directed at phenolic and/or sulfhydryl groups.

4-Chloro-7-nitrobenzofurazan↗

The effects of the acute administration of phencyclidine hydrochloride (PCP) on the release of corticosterone, growth hormone and prolactin in the rat.

There is little information on the neuroendocrine effects of PCP. The present study examined the effects of the acute subcutaneous administration of PCP on serum levels of corticosterone, growth hormone and prolactin in the male rat. PCP increased serum levels of corticosterone, decreased serum levels of prolactin and failed to affect growth hormone levels. The results indicate that, like other drugs of abuse, PCP alters neuroendocrine function.

Animals↗

Determination of protein by Coomassie dye-binding in agarose gels.

A variation of the Coomassie dye-binding assay for proteins is described. Protein samples were pipetted to the surface of agarose plates in uniformly sized spots and stained with Coomassie Blue G-250. The bound dye was determined by densitometric scanning using double wavelength and flying spot facilities. The response curves were linear in an about 10-fold concentration range with a lower detection limit of 0.5 microgram. No background correction was necessary because unbound dye and most substances known to interfere with other protein assays were removed during the staining and destaining of the agarose gels. Membrane proteins could be analyzed since the samples were applied as solutions in 1% sodium dodecyl sulfate.

Animals↗

Reconstitution and photolabeling of the purified (Na+ + Mg2+)-ATPase from the plasma membrane of Acholeplasma laidlawii B with phospholipids containing a photosensitive fatty acyl group.

The purified membrane (Na+ + Mg2+)-ATPase of Acholeplasma laidlawii B was reconstituted into vesicles composed of phospholipids containing a photoactivatable aryl nitrene-generating fatty acyl group. The reconstitution with phospholipid resulted in an enhancement of ATPase activity and a reduction in the sensitivity of the enzyme to radiation inactivation. The incorporation of the enzyme into the lipid vesicles results in a broadening of the gel-to-liquid-crystalline phase transition of the photolabeled phospholipid and the appearance of two partially resolved endotherms in the calorimetric traces. The temperatures and the total enthalpy of these overlapping transitions are higher than in the absence of incorporated enzyme. After photolysis of the lipid-reconstituted ATPase and separation of the polypeptide subunits by sodium dodecyl sulfate (SDS) gel electrophoresis, a significant labeling of the alpha-subunit of the enzyme was demonstrated. These results indicate that at least the alpha-subunit of this ATPase must penetrate into or traverse the phospholipid bilayer.

Acholeplasma laidlawii↗

Cryptosporidium and diarrhoea in southern Indian children.

Cryptosporidium was detected more frequently in stool samples from southern Indian children with acute diarrhoea than from matched controls. It was seldom the only pathogen detected and was not associated with clearcut clinical features. The frequency of the protozoon in children under six months of age was higher in controls than in patients with acute diarrhoea. These features suggest that Cryptosporidium is unlikely to be a major cause of acute diarrhoea in this population. Frequency of Cryptosporidium was higher in children who had been given antibiotics and in those with prolonged episodes of diarrhoea. Administration of antibiotics may lead to conditions within the intestinal lumen that favour colonisation by the organism and prolongation of diarrhoeal episodes.

Acute Disease↗

The effects of the acute administration of buprenorphine hydrochloride on the release of anterior pituitary hormones in the rat: evidence for the involvement of multiple opiate receptors.

Multiple opiate receptor agonists and antagonists have been found to produce different patterns of anterior pituitary hormone release. The present studies examined the pattern of anterior pituitary hormone release produced by buprenorphine. The effects of the kappa agonist ethylketocyclazocine on thyroid stimulating hormone release were also examined. Following buprenorphine, serum levels of corticosterone and luteinizing hormone were not changed while growth hormone release was stimulated in a dose-dependent manner. Prolactin release was stimulated after the lowest dose of buprenorphine while the highest dose induced a fall in serum prolactin. Similar biphasic effects on thyroid stimulating hormone were seen after either buprenorphine or ethylketocyclazocine. The results provide support for the role of multiple opiate receptors in opiate-induced changes in anterior pituitary hormone release.

Animals↗

Affinity labeling of the (Na+ + Mg2+)-ATPase from Acholeplasma laidlawii B membranes by the 2',3'-dialdehyde derivative of adenosine 5'-triphosphate.

The (Na+ + Mg2+)-ATPase of the Acholeplasma laidlawii B plasma membrane was inactivated by the 2',3'-dialdehyde derivative of ATP (oATP). oATP behaved as a reversible competitive inhibitor of this ATPase and was slowly hydrolyzed by the enzyme. In addition, oATP induced an irreversible inactivation of the enzyme. A 62% inactivation of the enzyme correlated with the binding of 16 moles of oATP per mole of the enzyme. In the presence of 5'-adenylyl imidodiphosphate, a non-hydrolyzable substrate analogue, the stoichiometry was 8 moles oATP per mole of ATPase. By SDS-polyacrylamide gel electrophoresis, [U-14C]oATP was found to bind covalently to four of the five subunits of the enzyme, but specific labeling was highest for the gamma-subunit of the ATPase.

Acholeplasma laidlawii↗

Identification of multiple opiate receptors through neuroendocrine responses. I. Effects of agonists.

The effects of the systemic administration of three prototypic multiple opiate receptor agonists, morphine sulfate (MS), ethylketocyclazocine methanesulfonate (EKC) and N-allylnormetazocine hydrochloride (NANMT), on the release of anterior pituitary hormones were studied in the rat. The serum levels of corticosterone, growth hormone, prolactin and luteinizing hormone were measured by radioimmunoassay 30 min after s.c. injection of the drugs. The three opiate compounds elicited different patterns of release of the four hormones. MS, EKC and NANMT elicited rises in the serum levels of corticosterone whereas only MS and EKC induced elevations in growth hormone. MS stimulated but NANMT inhibited the release of prolactin. The administration of the lowest dose of EKC stimulated the release of prolactin whereas higher doses were without effect suggesting biphasic dose-response relationship. The administration of MS, EKC and the highest dose of NANMT elicited a fall in serum luteinizing hormone levels suggesting that NANMT possesses agonist activity at the receptor mediating luteinizing hormone release. The data support the hypothesis that multiple opiate receptors are involved in the mechanism of action of opiate-induced changes in anterior pituitary hormone release.

Animals↗

Identification of multiple opiate receptors through neuroendocrine responses. II. Antagonism of mu, kappa and sigma agonists by naloxone and WIN 44,441-3.

The effects of the administration of naloxone hydrochloride (NX) or WIN 44,441-3 (WIN), administered either alone or prior to the subsequent administration of the three prototypic multiple opiate receptor agonists morphine sulfate (MS), ethylketocyclazocine methanesulfonate (EKC) and N-allylnormetazocine hydrochloride (NANMT), on the release of anterior pituitary hormones were studied in the rat. Serum levels of corticosterone, growth hormone, prolactin and luteinizing hormone were measured by radioimmunoassay. The administration of WIN alone produced a pattern of hormone release similar to that seen following the administration of NX. Pretreatment with either NX or WIN blocked the MS-induced rise in serum levels of corticosterone whereas neither the EKC nor the NANMT-induced rises were blocked. Pretreatment with WIN blocked the EKC-induced rise in serum growth hormone but failed to block the MS-induced increase. Both antagonists blocked the rise in serum levels of prolactin induced by either MS or EKC but also blocked the NANMT-induced fall. The administration of either NX or WIN blocked the inhibition of luteinizing hormone release induced by either MS or NANMT and partially blocked the EKC-induced fall. The data indicate that multiple opiate receptors are involved in opiate-induced changes in anterior pituitary hormone release and suggest that the patterns of hormone release induced by various opiate agonists as well as their interaction with antagonists may be useful in classifying drugs with respect to their activity toward specific receptors.

Animals↗

Endocrine influences on the actions of morphine: IV. Effects of sex and strain.

The antinociceptive and temperature responses to morphine were compared in male and female rats from two different strains. Males of both the Sprague-Dawley and Wistar-Furth strains were slightly more responsive to the acute actions of morphine than were females of the same strain. However, Wistar-Furth animals required approximately twice the dose of morphine to display equivalent antinociceptive responses and four times the dose of display equivalent hypothermic responses when compared with Sprague-Dawley animals. During chronic morphine treatment, the development of tolerance was slightly more rapid in males than in females and in Sprague-Dawley animals than in Wistar-Furth animals. Gonadal hormones also influenced morphine responses. Ovariectomized rats were significantly more responsive acutely to morphine and developed tolerance less rapidly than estradiol-treated females. However, alterations of gonadal hormones in males did not affect morphine responses. These results indicate that morphine responses vary considerably between strains of animals and are influenced by gonadal hormones of females, but not of males.

Animals↗

A clinical database management system.

The processing of Case Report Form data collected in clinical trials is a data processing task unlike any other. Conventional systems approaches to clinical data management are not responsive to user demands and require excessive amounts of manpower to support. The Clinical Data Management System implemented at Merck utilizes Infodata 's Inquire database management software, IBM's CICS communications software, IBM's VSAM file management software, and SAS Institute's SAS software. System flexibility was the paramount consideration when the CDMS was designed. Clinical data at Merck is now processed on a system that provides on-line ad hoc retrieval capabilities through a user friendly query language, and allows for drug specific database designs coupled with a common update and retrieval mechanism.

Clinical Trials as Topic↗