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Biomedical subjects

G Stevenson

Publications and source records attributed to G Stevenson.

11 recordsLinked to original sources
PubMed1992

4-Amido-2-carboxytetrahydroquinolines. Structure-activity relationships for antagonism at the glycine site of the NMDA receptor.

trans-2-Carboxy-5,7-dichloro-4-amidotetrahydroquinolines, evolved from the lead 5,7-dichlorokynurenic acid, have been synthesized and tested for in vitro antagonist activity at the glycine site on the N-methyl-D-aspartate (NMDA) receptor. Optimization of the 4-substituent has provided antagonists having nanomolar affinity, including the urea trans-2-carboxy-5,7-dichloro-4[[(phenylamino)carbonyl]amino]-1,2,3, 4-tetrahydroquinoline (35; IC50 = 7.4 nM vs [3H]glycine binding; Kb = 130 nM for block of NMDA responses in the rat cortical slice), which is one of the most potent NMDA antagonists yet found. The absolute stereochemical requirements for binding were found to be 2S,4R, showing that, in common with other glycine-site NMDA receptor ligands, the unnatural configuration at the alpha-amino acid center is required. The preferred conformation of the trans-2,4-disubstituted tetrahydroquinoline system, as shown by X-ray crystallography and 1H NMR studies, places the 2-carboxyl pseudoequatorial and the 4-substituent pseudoaxial. Modifications of the 4-amide show that bulky substituents are tolerated and reveal the critical importance for activity of correct positioning of the carbonyl group. The high affinity of trans-2-carboxy-5,7-dichloro-4-[1-(3-phenyl-2-oxoimidazolidinyl)]- 1,2,3,4-tetrahydroquinoline (55; IC50 = 6 nM) suggests that the Z,Z conformer of the phenyl urea moiety in 35 is recognized by the receptor. Molecular modeling studies show that the 4-carbonyl groups of the kynurenic acids, the tetrahydroquinolines, and related antagonists based on N-(chlorophenyl)glycine, can interact with a single putative H-bond donor on the receptor. The results allow the establishment of a three-dimensional pharmacophore of the glycine receptor antagonist site, incorporating a newly defined bulk tolerance/hydrophobic region.

Aminoquinolines↗
PubMed1992

Comparative efficiencies of bispecific F(ab'gamma)2 and chimeric mouse/human IgG antibodies in recruiting cellular effectors for cytotoxicity via Fc gamma receptors.

The three forms of Fc gamma receptor carried by monocytes (Fc gamma RI, II) and natural killer (NK) cells (Fc gamma RIII) are all capable of mediating cell lysis. Here we compare the use of F(ab'gamma)2 bispecific antibodies, specifically targetting individual Fc gamma R, and chimeric IgG mouse/human antibodies which are capable of targetting all Fc gamma R, for their ability to mediate target cell destruction. The derivatives are prepared by linking hinge sulphydryl residues via tandem thioether bonds, using a bismaleimide crosslinker: Fab' from an anti-Fc gamma R mAb linked to Fab' from a common anti-target mAb (BsAb), or Fab' from the common anti-target mouse antibody linked to human Fc gamma (FabFc or bisFabFc). All the derivatives targetting chick red blood cells gave efficient lysis, although different effector cell donors yielded differences in both the lytic levels achieved and the comparative efficiencies of derivatives. In contrast, significant lysis of the guinea pig lymphoblastic leukaemia, L2C, regularly resulted only via the anti-Fc gamma RIII BsAb and the chimeric derivatives. These results suggest that the chimeric, Fc-containing derivatives mediate tumour cell lysis principally through Fc gamma RIII on NK cells. This is in contrast to the situation with the chick red blood cells where the chimeric derivatives appear capable of lysing erythrocytes by utilizing either monocytes or NK cells, because significant (approximately 50%) lysis occurred with effector cell populations magnetically depleted through either Fc gamma RII or Fc gamma RIII. A major difference between these two types of antibody derivative was their ability to function in the presence of high concentrations of normal human Fc gamma. The lysis mediated by BsAb reactive with Fc gamma RI or II was unaffected by the presence of human Fc gamma at 2.5 mg/ml (a concentration comparable with that yielded by IgG in plasma) whereas the BsAb recognizing Fc gamma RIII and all the Fc-containing derivatives were completely inhibited.

Animals↗
PubMed1992

Safety and efficacy of high kV biliary lithotripsy: preliminary experience.

Despite intense interest in laparoscopic cholecystectomy, biliary lithotripsy (BL), by avoiding the need for general anesthesia, could remain a useful alternative in approximately 10% of patients with symptomatic gallstones. The poor stone clearance rates reported by the Dornier National Biliary Lithotripsy Study has led to disenchantment with biliary lithotripsy. However, the results may reflect the relatively low kV (18.7 +/- 1.7) used. We have compared symptomatic gallbladder stone/cholecystolithiasis patients with one to five stones of aggregate diameter < 60 mm treated with one to three sessions on an MPLS 9000 (Dornier) lithotripter at moderate kV (22.7 +/- 1.7 kV; mean number of shocks 1473 +/- 356) with a similar group treated with high kV (26 kV, mean number of shocks 1357 +/- 507). Ultrasound stone diameter measurements were made pre- and post-BL; 12-wk results are reported. Treatment safety was assessed by recording adverse experiences and serum, urine, hematology, and chemistry. For patients with single stones, the high kV treatment took significantly (p < 0.05) less time (74 +/- 30 min) than moderate kV treatment (118 +/- 33 min). At 3 months, the moderate kV-treated single-stone group had a residual maximum fragment size of 3.2 +/- 3.3 mm versus 1.8 +/- 2.3 mm in the high kV-treated single-stone group. The 3-month stone-free rate for patients with single stones treated at high kV was 44% compared with 46% for the moderate kV-treated group (NS). At 1 wk, 11 patients had microscopic or macroscopic hematuria and six patients had mildly elevated liver function tests. At 6 wk, however, all urine and hematological measurements had returned to normal. Two patients suffered pancreatitis, one in each group. High kV BL appears to be safe and, for patients with single stones, gives better fragmentation and takes less time to administer than moderate kV. Whether a high kV treatment protocol can achieve improved long-term stone-free rates remains to be assessed.

Cholelithiasis↗
PubMed1991

The cps gene cluster of Salmonella strain LT2 includes a second mannose pathway: sequence of two genes and relationship to genes in the rfb gene cluster.

We report the presence in Salmonella enterica strain LT2 (serovar thyphimurium) of duplicate genes for two steps in the synthesis of GDP-mannose. The previously known genes, rfbK (phosphomannomutase) and rfbM (mannose-1-phosphate guanyltransferase), are part of the gene cluster for the O antigen. The two new genes, cpsB and cpsG, respectively, are thought to be part of the gene cluster for the M antigen capsular polysaccharide, present in many Enterobacteriaceae. The two genes have been sequenced and have a GC content of 0.61, suggesting an origin outside of Salmonella. Comparison of the inferred protein sequences for cpsB and rfbM shows 57% identity of amino acids whereas for cpsG and rfbK there is only 19% identity. It is suggested that the greater divergence between cpsG and rfbK may be due to a period of accelerated evolution, perhaps precipitated by transfer of the genes from another species.

Amino Acid Sequence↗
PubMed1979

Changing patterns of neonatal necrotizing enterocolitis.

In a 4 year and 4 month period 80 patients with necrotizing enterocolitis were treated. Review of the mode of clinical presentation, radiological features, management, mortality, and complications showed that there have been considerable changes over this period. The disease is now frequently diagnosed clinically prior to the development of paralytic ileus. Scalloping of the bowel wall and separation of the bowel loops are probably the earliest radiological signs. The management has become a more aggressive medical approach with more limited and well-defined surgical indications. These changes have been associated with a marked decrease in mortality and a concomitant increase in the number of late complications.

Enterocolitis, Pseudomembranous↗
PubMed1978

Laws of motion in the for-profit health industry: a theory and three examples.

The dynamics generated in the for-profit health industry by the drive for accumulation combine with the life cycle of a product to produce, within a given political framework, tendencies toward certain types of industry structure. The evolution of this structure is characterized by increased concentration of economic activity in diversified multinational corporations which combine health and non-health products. Three industries representing different stages of product and market development are analyzed in this article. The pharmacological industry is a mature industry dominated by large diversified multinational corporations which grow mainly through expansion abroad and diversification. The medical and dental instruments and supplies industry is newer, smaller, and faster growing. Its growth potential is attracting many companies an; increasing competition. The newest industry, investor-owned hospitals and hospital chains, is characterized by rapidly growing but still relatively small companies. The appendix, included to illustrate certain social, economic, and political issues, focuses on Medtronics, a highly scientific, fast-growing firm which produces electronic pacemakers.

Delivery of Health Care↗
PubMed1978

Social relations of production and consumption in the human service occupations.

This paper presents a Marxist analysis of human service occupations. As the forces of monopoly capitalism increased the need for human services and destroyed the social institutions which previously satisfied those needs, employment in the human service industries grew rapidly, and may now exceed that in manufacturing. The nature of human services is discussed: production and consumption occur simultaneously; the social relations of consumption and production are closely related; and service workers play a direct social control role. These characteristics generate contradictions between service and control in service work, and between service workers' roles as both oppressed workers and oppressors. Discussions of the ideologies impacting on the relationships between workers and "clients," the dynamics of these relationships, and the struggles to which they give rise conclude the paper.

Consumer Behavior↗
PubMed1978

Profits in medicine: a context and an accounting.

The U.S. health care industry is composed of a dynamic mixture of profit and non-profit entities. These sectors sometimes compete in the same activities and may have virtual monopolies over other activities. Estimates of the relative and absolute sizes and growth trends of the profit and non-profit sectors are developed in this article. These estimates show that approximately 39 percent of total health care expenditures in the U.S. in 1975 went to for-profit institutions, generating $3.3 billion in profit. This represented 7 percent of for-profit and 2.8 percent of total expenditures. Some for-profit subsectors grew more rapidly and others less rapidly than total health care expenditures. As a whole, the for-profit sector grew faster than the non-profit sector before and after Medicare and Medicaid were introduced as well as during the period when price controls were in effect. The relative growth of the for-profit sector was greatest right after the introduction of Medicare and Medicaid. The true significance of profit lies not in numbers, but in the effects that the drive for profit have on the nature and quality of health and health care. This is discussed in the final section.

Delivery of Health Care↗
PubMed1977

The distribution of gastric ulcers: double contrast barium meal and endoscopy findings.

One thousand consecutive double contrast barium meals and 424 consecutive upper gastrointestinal endoscopic examinations have been reviewed. 70 gastric ulcers were found radiologically in 56 patients and 82 gastric ulcers endoscopically in 70 patients. 55% of radiological and 53.6% of endoscopic ulcers were located in the mid or upper body of the stomach. The distribution is contrary to previous radiological findings with the traditional barium meal. Age did not seem to be a major factor. The double contrast meal and in particular the left anterior oblique view with the head elevated, display en face the lesser curve of the upper body around the cardia where many benign ulcers and carcinomas arise.

Adolescent↗