PubMed Health⌕ Search

Biomedical subjects

A Cunningham

Publications and source records attributed to A Cunningham.

At least 73 records · Page 4Linked to original sources
PubMed1992

Long-term symptomless HIV-1 infection in recipients of blood products from a single donor.

There have been reported cases of long-term symptomless human immunodeficiency virus type 1 (HIV-1) infection, but it is not clear whether the benign course of infection was due to host, viral, or other unknown factors. During follow-up of subjects with transfusion-acquired HIV-1 infection in New South Wales, Australia, we identified a group of 6 subjects who had been infected through a single common donor. We were therefore able to study the contributions of various factors to the course of infection. Throughout follow-up (range 6.8-10.1 years after infection), 5 of the recipients and the donor (last follow-up 10.2 years after infection of the first recipient) remained clinically free of symptoms, with normal CD4 cell counts and no p24 antigenaemia. HIV-1 was isolated from only 1 recipient; the isolate did not induce syncytia in a SUPT1 co-culture assay and had a limited in-vitro host range. 1 infected recipient (who had received extensive immunosuppressive treatment for systemic lupus erythematosus) developed Pneumocystis carinii pneumonia and died 4.3 years after infection. The frequency of progression to AIDS or a CD4 cell count below 0.50 x 10(9)/l was significantly lower among the 6 subjects with a common donor (1/6) than among 101 other HIV-infected transfusion recipients for whom data from 7 years of follow-up were available (94/101; p less than 0.0001). These findings suggest that the subjects were infected by a less virulent strain of HIV-1. The identification of this group of subjects should stimulate a search for other similar groups, which will provide important information on the immunopathogenesis of HIV-1 disease.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Molecular cloning and primary structure of the avian Thy-1 glycoprotein.

We have previously characterised, both biochemically and immunohistochemically, a 23 kDa putative avian Thy-1 protein homologue. In this report we have examined the carbohydrates present on the protein and determined the partial protein sequence of enzymatically and CNBr-produced peptides. The protein sequences enabled us to clone an essentially full-length (1854 bp) cDNA using PCR and colony screening of an embryonic day (ED) 18 forebrain pUEX-1 cDNA library. Analysis of deduced amino acid sequence shows the 23 kDa protein to be 110 amino acids in length compared to mouse (112) and human and rat (111) while still retaining the conserved cysteine residues. The N-glycosylation site at position 61 is the same as that in the human protein, but is different from that in the rodent (position 75). Northern blot analysis of Thy-1 mRNA expression in the forebrain, cerebellum and tectum show that all three tissues have low levels at ED4 (forebrain and tectum) and ED8 (cerebellum), rising most rapidly between ED16 and the first few days post-hatch. Analysis of various tissues at hatch and adult show expression to be predominantly neuronal with very low levels in some other organs, mainly at hatch, indicating the possibility of subsets of cells, which we have also seen in histological sections, in these tissues expressing Thy-1 mRNA. Bone marrow and blood cells were also negative for Thy-1 protein.

Aging↗
PubMed1992

Acute phenobarbital intoxication.

Phenobarbital is a long-acting barbiturate often prescribed for seizure disorders. It has a high abuse potential and was commonly used in suicide attempts in the past. Although benzodiazepines are now more frequently used in suicide attempts, barbiturate intoxications are still occasionally seen and constitute a medical emergency. The management of phenobarbital overdose includes cardiac and respiratory support, cathartics, activated charcoal, and alkaline diuresis. In severely compromised patients, hemodialysis and hemoperfusion can be used to enhance drug clearance.

Drug Overdose↗
PubMed1991

Mechanism and pathway of penicillopepsin-catalyzed transpeptidation and evidence for noncovalent trapping of amino acid and peptide intermediates.

Penicillopepsin acting on Nph-Ala2-amide (where Nph = p-nitrophenylalanyl) catalyzes a transpeptidation reaction which leads to the formation of Nph2-Ala2-amide, which arises from condensation of the substrate with enzyme-bound Nph, as the first product released from the enzyme. This is followed by a stage during which Nph3 and Ala2-amide are the major products. A small amount of Nph4 is also formed during this time. Nph and Nph2, formed during the reactions, are tightly, but probably not covalently, bound to the enzyme. They appear as free products only as a result of the cleavage of Nph3 and Nph4 and after most of the substrate Nph-Ala2-amide has been used up. They act as acceptors for the substrate and for Nph2-Ala2-amide. Nph3-Ala2-amide, formed by condensation of Nph-Ala2-amide or of Nph2-Ala2-amide with enzyme-bound Nph2 or Nph, respectively, is also released but is cleaved rapidly to give Nph3 and Ala2-amide. Incorporation of 18O from [18O]water into the carbonyl oxygens of the products is extensive and shows that release of the intermediates is slower than peptide bond cleavage and peptide bond formation. Hence the rate-limiting step in these reactions is product release. No 18O is incorporated into the initial substrate. We propose that Nph and Nph2 as intermediates are held in the active site by hydrogen bonds and by two strong electrostatic interactions.

Amino Acids↗
PubMed1991

Hepatitis C virus infection in haemodialysis patients.

Antibody to hepatitis C has been variously detected in 1-20% of haemodialysis patients in recent studies from overseas. To determine the frequency of antibodies to the C100-3 protein of the hepatitis C virus (anti-HCV) a cross-sectional study was performed in 60 patients on maintenance haemodialysis in Western Sydney. Six patients (10%) were anti-HCV seropositive. Four of the six anti-HCV positive patients were also hepatitis B core antibody positive, compared with nine of 54 anti-HCV negative patients (p less than 0.05). All anti-HCV positive patients had received multiple blood transfusions. Serum alanine aminotransferase (ALT) was not useful as a screening test. Recent evidence suggests that anti-HCV seropositivity underestimates infectivity.

Antigens, Viral↗
PubMed1990

Rate-determining steps in penicillopepsin-catalysed reactions.

The hydrolysis of Ac-(Ala)2-Lys-Nph-(Ala)2-amide (II) by penicillopepsin is characterized by a solvent isotope effect of 2.11, whereas the hydrolysis of Ac-Lys-Nph-amide (I) shows no solvent isotope effect. The dependence of the isotope effect on the concentration of D2O in H2O for substrate II is not linear and suggests that two or more protons are involved in its rate-determining step. We propose that for substrate I the rate-determining step is the distortion of the scissile bond towards a tetrahedral configuration, and for substrate II a conformational change induced by the occupation of the S3 pocket in the enzyme.

Amino Acid Sequence↗
PubMed1990

A ligand-induced, temperature-dependent conformational Change in penicillopepsin. Evidence from nonlinear Arrhenius plots and from circular dichroism studies.

The effect of temperature on the rate constants of hydrolysis of various substrates by penicillopepsin is dependent on the length of the substrate. For the series Ac-(Ala)m-Lys-Nph-(Ala)n-amide (where Ac- is acetyl- and Nph- is p-nitrophenylalanyl-), where m and n = 0-2, substrates lacking both P'2 and P3 residues give linear Arrhenius plots with an energy of activation of about 55 kJ.mol-1. The Arrhenius plots of substrates in which an alanine residue occupies P'2 show a sharp break at an average transition temperature of 10.5 degrees C. The activation energies are approximately 90 kJ.mol-1 below and approximately 54 kJ.mol-1 above the transition temperature, respectively. For substrates in which P3 is occupied, the average transition temperature is 14.2 degrees C. In this case, the activation energies are 66 kJ.mol-1 below and from 26 to 39 kJ.mol-1 above the transition point. The most probable explanation of these phenomena is that substrate interaction at subsites S3 and/or S'2 of the enzyme induces a temperature-dependent conformational change. Physical evidence for this comes from the observation that the temperature dependence of a CD absorption band at 242 nm of a penicillopepsin-pepstatin complex shows a sharp break that corresponds to those observed in the Arrhenius plots of substrates with alanine at P'2 and P3, whereas the same CD band in the free enzyme is linearly dependent on temperature.

Amino Acid Sequence↗
PubMed1990

Participation effect from water projects on EPI.

It has been hypothesized that in addition to the direct health and amenity benefits of an improved water supply, there are other, more subtle, benefits to communities who participate in community-based water supply projects. A detailed empirical comparison of villages with and without community-based water projects in Indonesia and Togo suggests that such indirect benefits are substantial. Between 25 and 30% more children are immunized in villages with community-based water projects than in comparison villages which either have benefitted from non-participatory water projects, or have had no water project. From a comparison between the activities of villagers and workers in external agencies involved in water projects in the two countries, it is concluded that successful participatory water projects are best characterized as a partnership between the community and the external agency. Such projects require substantial inputs of time, resources, skill and persistence from both the community and the external agency. These inputs must be sustained by both parties in all phases--planning, construction and maintenance--if this partnership is to result in lasting improvements in water supply and other aspects of community life.

Child, Preschool↗
PubMed1989

Homoeopathy.

Explore the source record for details and available documents.

Animals↗
PubMed1989

National survey of critical-care pharmaceutical services.

The results of a national survey of critical-care pharmaceutical services are reported. A questionnaire was mailed on March 8, 1988, to 1500 of the 6800 U.S. hospitals with more than 100 beds. The questionnaire was divided into four sections: (1) critical-care pharmaceutical services; (2) critical-care clinical pharmacy activity; (3) critical-care pharmacy standards; and (4) general information on the hospital, including pharmaceutical services provided to patients who are not critically ill. A total of 613 usable questionnaires were returned, for a response rate of 41%. Respondents from 124 hospitals reported having a critical-care satellite pharmacy. Critical-care beds served by satellite pharmacies were more likely to have unit dose drug distribution services than were critical-care beds not served by satellite pharmacies. The level of clinical and educational services provided to critical-care patients was significantly lower for intensive-care unit (ICU) pharmacists practicing in satellite pharmacies than it was for ICU pharmacists not associated with satellite pharmacies. There were no differences between satellite and nonsatellite ICU pharmacists in either the percentage of a typical day spent providing clinical services to critical-care patients or the percentage of critical-care patients receiving those services. Respondents expected their hospitals to add 301 full-time-equivalent critical-care pharmacists to their staffs during the next two years, for a 39% increase. Respondents strongly favored establishing 24-hour unit dose drug distribution and i.v. admixture services, providing inservice education to nurses and physicians, and providing written pharmacokinetic consultations.(ABSTRACT TRUNCATED AT 250 WORDS)

Critical Care↗
PubMed1988

Effect of secondary substrate binding in penicillopepsin: contributions of subsites S3 and S2' to kcat.

The kinetic parameters kcat, KM, and kcat/KM were determined at 25 degrees C and pH 4.5, 5.5, and 6.0 for the series of penicillopepsin substrates Ac-Alam-Lys-(NO2)Phe-Alan-amide, where (NO2)Phe is p-nitrophenylalanine and m and n equal 0-3. KM values at pH 6.0 were the same for all 12 peptides and averaged 0.088 +/- 0.02 mM but increased to different degrees at lower pH. In contrast, kcat values increased with increasing chain length. At pH 6 and at the pH optimum of kcat, the largest increases (about 37-fold on average) were obtained when alanine residues were added in positions P2' and P3. Only 1-2-fold increases were observed for positions P2, P3', P4, and P4'. These results show that occupation of subsites S2' and S3 is largely responsible for the rate enhancements caused by secondary substrate interactions with this series of peptides. Additional support for an important role of subsite S3 comes from the observation that the two peptides where m = 1 and n = 1 or 2, respectively, are cleaved not only between lysine and p-nitrophenylalanine but also between the latter and alanine, suggesting that occupation of subsite S3 by the N-terminal alanine overcomes the unfavorable interaction of alanine in subsite P1'. Subsite S3 is also important in the binding of pepstatin analogues and in transpeptidation reactions. It is proposed that the roles of subsites S3 and S2' are to facilitate the conversion of the first enzyme-substrate complex into a productive complex and to assist in the distortion of the scissile bond.(ABSTRACT TRUNCATED AT 250 WORDS)

Aspartic Acid Endopeptidases↗
PubMed1988

Visual evoked potentials and changes in serum glycine concentration during transurethral resection of the prostate.

Visual evoked potentials were recorded in 10 patients undergoing transurethral prostatectomy under subarachnoid anaesthesia. They were compared with those obtained in a control group (n = 5) having other operative procedures also under spinal anaesthesia. Serum concentrations of glycine, ammonia, glucose and sodium, and osmolality, were determined during the perioperative period. The prostatectomy group demonstrated a significant prolongation of visual evoked potential P2 latency in the postoperative period when compared with preoperative values (P less than 0.01). No significant changes in latency occurred in the control group when measured at similar times. The prostatectomy group demonstrated a significant increase in serum glycine concentration (P less than 0.01); changes in serum ammonia and sodium concentrations and osmolality were not significant. There was no correlation between visual evoked potential latency and changes in serum glycine concentration. Changes in visual evoked potential during transurethral prostatectomy may be the result of an accumulation of a metabolite of glycine.

Aged↗
PubMed1988

Neonatal myotonic dystrophy.

Six cases of congenital myotonic dystrophy are described. Only two survived the neonatal period. There were seven neonatal deaths in the immediate families and six reported miscarriages. Of the two survivors one is moderately retarded and the other at 9 months is at the developmental level of 5-6 months. Facial diplegia and depressed deep tendon reflexes are clues to the presence of neonatal myotonic dystrophy and the diagnosis is confirmed by examining the mother who will show some of the features of the disorder. Infants may also present with non-specific respiratory problems, hypotonia and poor sucking.

Diagnosis, Differential↗