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Biomedical subjects

R Aston

Publications and source records attributed to R Aston.

At least 55 records · Page 3Linked to original sources
PubMed1985

Monoclonal antibodies to human growth hormone can distinguish between pituitary and genetically engineered forms.

Monoclonal antibodies (MABs) prepared against human pituitary growth hormone (hGH) have been compared for their binding to pituitary-derived and genetically engineered methionyl growth hormone (met-hGH). The antibodies bind to four non-overlapping epitopes of which two are completely shared with human choronic somatomammotropin (hCS). The determinant defined by MAB NA27 was expressed on met-hGH to a lesser degree than on hGH of pituitary origin. However, another antibody, QA68, which binds to a determinant closely related to NA27, failed to discriminate between hGH and met-hGH. A further two MABs (EB1 and NA71) were similarly ineffective in distinguishing between the two forms of the hormone. The determinant recognized by antibody EB2 was equally represented on hGH and met-hGH when assessed by a liquid-phase radioimmunoassay: however, measurement of the binding in a solid-phase assay resulted in a two-four-fold lower binding to met-hGH. Bioactivity assessed by both an in vitro cell proliferation assay and an in vivo cartilage sulphation bioassay failed to distinguish between the two hormones. It is therefore concluded that the NH2-terminal methionine on bacterially derived growth hormone results in altered antigenicity of the hormone without any measurable effect on bioactivity.

Animals↗
PubMed1985

Monoclonal antibody-mediated enhancement of growth hormone activity in vivo.

This work demonstrates that complexing hGH with monoclonal antibody EBl (MAB-EBl) can produce a striking potentiation of the somatogenic actions of hGH in vivo in Snell dwarf mice. In short-term experiments significant increases in cartilage metabolism and body weight were noted; these responses were dose-dependent for both MAB-EBl and hGH concentration. Increased growth was also observed in long-term experiments. In marmosets where MAB-EBl cross-reacts with endogenous GH, MAB-EBl alone enhanced the actions of endogenous GH. A new perspective may be necessary to incorporate these results into the current concept of antibody action.

Animals↗
PubMed1984

Identification of Mr variants of prolactin with monoclonal antibodies.

Monoclonal antibodies ( QB01 and 1200) prepared against human prolactin (hPRL) have helped define a variant form of the hormone. This variant is of apparently higher molecular mass (26 kDa) than the predominant form of the hormone (24 kDa) and its presence does not appear to be species-restricted. The demonstration of the 26 kDa form of hPRL in fresh pituitary tissue and amniotic fluid suggests it may retain some specific function.

Amniotic Fluid↗
PubMed1984

Drug abuse. Its relationship to dental practice.

Drug abuse appears destined to become an exacerbating cultural phenomenon despite intrinsic dangers to the abuser and accelerating costs to society. Dentists cannot afford to ignore the problem or its sequelae either in terms of their personal involvement or in terms of the clinical implications of such a practice for their patients. Abuse of agents, such as opioids and amphetamines, by the dental practitioner leads to devastating personal, social, and professional consequences. The abuser jeopardizes his or her reputation, family relationships, professional practice, and, not uncommonly, his or her very life through accidental overdose of drugs or by suicide. Nitrous oxide abuse is particularly prevalent among dentists and, although producing no psychological dependence, may result in long-term myeloneuropathy and physical disability making continued dental practice impossible. The dentist's responsibilities in this area lie within clinical and social domains. Clinically, the dentist must (1) learn to detect those physical and behavioral signs in patients that are indicators of drug abuse; (2) become familiar with tactics employed by drug abusers to obtain drugs for themselves or for further criminal diversion, and be prepared to defend against such tactics; (3) understand and make clinical allowance for therapeutic complications that may arise in the treatment of drug-abuse patients. The dentist's social role as an informed, concerned, and empathic counselor in matters of drug abuse must be assumed as a personal imperative and not viewed as an intellectual abstraction. Whenever we are made aware of the drug-related devastation or death of a friend, colleague, or student, we discern the immediacy of an ethical responsibility of social dimensions, so eloquently expressed over 350 years ago, by John Donne in his "Devotions XVII": "No man is an island, ... Any man's death diminishes me, because I am involved in Mankind; And therefore never send to know for whom the bell tolls; It tolls for thee".

Amphetamines↗
PubMed1983

Antigenic, receptor-binding and mitogenic activity of proteolytic fragments of human growth hormone.

Analysis of the subtilisin-digested, two-chain form of human growth hormone (hGH) and its constituent polypeptide fragments has been aided by the use of monoclonal antibodies which bind specifically to four distinct epitopes on the native hormone. Using the SDS-polyacrylamide immunoblotting technique, it was shown that one epitope (shared with human chorionic somatomammotropin) detected by EB1 (or EB3) antibody was expressed to a similar extent by both the N-terminal (15 K) and C-terminal (7 K) polypeptides. This epitope is unique in that it represents a repeating determinant within the single chain structure of the hormone. Another three epitopes detected by monoclonal antibodies QA68/NA27, NA71 or NA39/EB2 were absent from the 7-K fragment but were expressed on the 15-K fragment to a similar extent to that on unmodified growth hormone. Binding of NA71 antibody was demonstrated only by radioimmunoassay since this, presumably conformational epitope could not be detected by immunoblotting. The functional importance of the 15-K peptide was demonstrated by its ability to bind specifically to hormone receptors on IM9 human lymphoblastoid cells and by its retention of mitogenicity for the NB2 rat lymphoma cell line. However, all tested monoclonal antibodies inhibited the binding of [125I]15-K to IM9 cell receptors by either steric hindrance or by an allosteric mechanism and therefore could not be further related topographically to the receptor-binding moiety of hGH.

Animals↗
PubMed1983

Update: midazolam maleate, a new water-soluble benzodiazepine.

It appears that midazolam maleate with its short half-life, water solubility, lack of venous irritation, lack of serious side effects, and benign cardiovascular, respiratory, and CNS effects, may become a useful drug in the dental profession, especially in the field of oral and maxillofacial surgery.

Anesthesia, Dental↗
PubMed1983

Definition of species specific and cross-reactive antigenic determinants of Mycobacterium leprae using monoclonal antibodies.

Four soluble antigens of Mycobacterium leprae have been identified using 12 murine monoclonal antibodies. Their specificity, taxonomic distribution and molecular nature were analysed by radioimmunoassays and by immunoblotting from polyacrylamide electrophoresis gels. A protein antigen MY1 (12K) reacted with one antibody (ML06) without demonstrable cross-reactivity for any of the other 20 tested species of mycobacteria. Another four antibodies which identified antigen MY2 revealed only a marginal degree of cross-reactivity with three other species of mycobacteria. Two antigens shared by several other mycobacteria species were: MY3 represented by five protein bands (35-70K) and a subtilisin resistant molecule MY4 (40-50K) with two distinct determinants and presumably of polysaccharide nature. The described monoclonal antibodies may represent novel valuable diagnostic reagents as well as tools for the purification of antigens which could be explored towards prophylactic or therapeutic immunization against leprosy.

Antibodies, Monoclonal↗
PubMed1981

Cyclic AMP mediated morphological changes in a hybrid cell line.

A hybrid cell line (PCM 3) obtained from a fusion between Chinese hamster fibroblasts and a mamalignant lymphoma has the unusual property of converting from a monolayer of flat spindle-shaped cells to one of spherical cells on treatment with agents which elevate intracellular cAMP. This dose dependent changes is not accompanied by a loss of adhesion and is enhanced by phosphodiesterase inhibitors. The morphological change has been found to be energy dependent and is similar to that induced by cytochalasin B, although the changes has been found to be energy dependent and is similar to that induced by cytochalasin B, although the changes in plasma membrane proteins are not of a similar nature. Furthermore, it has been shown that specific serum factors can inhibit this cAMP induced cell rounding.

Alprostadil↗
PubMed1980

Prolonged succinylcholine-induced apnea caused by atypical cholinesterase: report of case.

A case of prolonged apnea after administration of succinylcholine in a patient homozygous for the dibucain variant cholinesterase (genotype E1aE1a) has been presented. Knowledge of the patient's medical history, preoperative laboratory tests, and the length of apnea enabled the surgical team to eliminate liver disease, carcinoma, and malnutrition from the differential diagnosis. This, in addition to the patient's failure to respond to an anticholinesterase agent, led to the belief that the patient had an atypical cholinesterase response to succinylcholine and not one secondary to a decreased production of cholinesterase enzyme from an impaired liver or prolonged paralysis for the nondepolarizing agent, pancuronium. Treatment consisted of maintaining adequate pulmonary ventilation nitrous oxide sedation to diminish anxiety until the patient regained spontaneous respiration. Anticholinesterase agents were used after the patient had progressed to a phase II depolarization block. After a cholinesterase assay of the family's serum, all members having the atypical allele were instructed to obtain medical alert identification.

Adult↗
PubMed1973

Mechanisms contributing to barbiturate intolerance in rats.

1. Female rats, 3 weeks after pretreatment with 200 or 400 (mg/kg)/day barbitone for 2 or 30 days, exhibited a prolonged sleeping time and a reduced awakening barbiturate brain level when challenged with either barbitone or pentobarbitone. After 3 additional weeks, the latter responses had returned, or were returning to, control values.2. Barbitone pretreatment schedules had no residual effect upon in vitro hepatic pentobarbitone-metabolizing activity measured 3 or 6 weeks later, except in one instance, when hepatic enzyme activity was significantly enhanced 3 weeks after 30 daily doses of 200 mg/kg barbitone. In this case, however, an enhanced barbiturate sleeping time, together with a reduced awakening barbiturate brain level, were observed.3. It is concluded that barbitone administered intraperitoneally in doses of 200 to 400 (mg/kg)/day for 2 or 30 days induces a non-hepatogenic intolerance to barbiturates, related to an increased sensitivity of the central nervous system to these drugs. This central intolerance is seen 3 weeks, but not 6 weeks, after pretreatment. Furthermore, this central intolerance has been observed to co-exist with an hepatic tolerance, a situation which could result in a reduced LD(50) coupled with an increase in ED(50).

Animals↗