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Biomedical subjects

C Richardson

Publications and source records attributed to C Richardson.

At least 109 records · Page 6Linked to original sources
PubMed1995

Factors affecting illicit and licit drug use among adolescents and young adults in Greece.

A cross-sectional survey on psychosocial issues, drug use, alcohol and health was carried out in Greece, with a nationwide probability sample of 2448 respondents aged 12-17 and 18-24. Factors potentially associated with illicit and unprescribed licit drug use were tested by logistic regression analysis. Several predictors were revealed. Sex and age were related to a higher lifetime use of illicit drugs, the male young adults reported a higher lifetime use of illicit drugs than the females. Positive attitudes toward hashish use, systematic smoking and use of drugs by close friends were more closely related to illicit than to unprescribed licit drug use. In addition "low self-esteem, family members using tobacco and alcohol" and "problematic drinking" were found only to predict illicit drug use. Other variables, "family members using drugs with or without a doctor's prescription", "being dissatisfied with social life" and "suffering from anxiety, depression and depersonalization symptoms" were found to be significantly associated with licit but unprescribed drug use.

Adolescent↗
PubMed1995

Clinical use of cyclosporin in rheumatoid arthritis.

Rheumatoid arthritis is a chronic immune-mediated disease characterised by an inflammatory synovitis and extra-articular manifestations. There is an expanding body of evidence to indicate that the activation of T lymphocytes is central in the initiation and perpetuation of this disease. Cyclosporin is an immunomodulator and a highly specific inhibitor of T-lymphocyte function, and has demonstrated disease-modifying properties in clinical studies in patients with rheumatoid arthritis. A concern with the use of cyclosporin has been the development of dose-dependent adverse effects, in particular renal dysfunction. Cyclosporin is lipophilic by nature and the conventional oral formulation (Sandimmun) was subject to incomplete and highly variable absorption, resulting in substantial inter- and intrasubject variations in peak concentrations and systemic bioavailability. A microemulsion-based formulation of cyclosporin (Neoral) has recently been developed, and possesses more predictable and improved absorption with a consequent increased peak concentration and systemic bioavailability. The improved predictability of absorption, and hence blood concentrations, facilitates the ability to 'tailor' therapy to an individual patient, which, in theory, could translate into an improved efficacy and safety profile.

Antirheumatic Agents↗
PubMed1995

Costs of antifungal prophylaxis after bone marrow transplantation. A model comparing oral fluconazole, liposomal amphotericin and oral polyenes as prophylaxis against oropharyngeal infections.

We used a costs model to compare alternative modes of prophylaxis against oropharyngeal fungal infections in patients with leukaemia or myeloma who had undergone bone marrow transplantation (BMT). We compared 2 innovative pharmaceutical options (oral fluconazole and intravenous liposomal amphotericin) with existing standard practice (oral polyenes). Costs were measured over a 12-week treatment period, and were compared with the 2 effectiveness measures: (i) the avoidance of colonisation or infection; and (ii) the patients' ability to continue with prophylaxis in an uninfected state. The costs and effectiveness of BMT itself were not considered in this evaluation. The costs per successfully treated patient over a 12-week period were 28,956 pounds (1 pound = $US1.60, June 1995) for oral fluconazole, 53,225 pounds for liposomal amphotericin and 32,768 pounds for oral polyenes. Sensitivity analysis showed that the costs of liposomal amphotericin always exceeded those of the oral comparators, reflecting its high acquisition, preparation and administration costs.

Amphotericin B↗
PubMed1995

Home health agencies: targets of anti-fraud and abuse investigations.

Increased health care fraud and abuse investigations could result in home health agencies, and other targets, becoming politically acceptable casualties of war in the battle to balance the federal budget. To protect themselves, home health agencies would be well advised to conduct internal fraud and abuse audits on an annual basis and to develop corporate compliance plans (see Newsletter, Vol. 9, No. 7, July 1994, at 16, and next month's issue, which will discuss corporate compliance programs as well as the OIG's new voluntary disclosure program). In addition, purchasers of home health agencies should be especially vigilant of fraud and abuse problems during the due diligence phase of the acquisition and, if problems are discovered, should consider whether voluntary disclosure to the OIG and settlement of any resulting claims is an appropriate condition of closing.

Aged↗
PubMed1994

Transfer and expression of the human multiple drug resistance gene in human CD34+ cells.

The human multiple-drug resistance (MDR1) gene has been transferred into human hematopoietic progenitors using retroviral gene transfer. Human bone marrow cells and isolated CD34+ cells isolated from marrow were exposed to growth factors interleukin-3 (IL-3), IL-6, and stem cell factor for 48 hours and then to two changes of MDR retroviral supernatants over the next 24 hours. Progenitor assays in methylcellulose at this time showed that 18% to 70% of BFU-E and 30% to 60% of CFU-GM contain the transferred MDR gene by polymerase chain reaction analysis. Up to 11.2% of the progeny of these cells express increased amounts of MDR glycoprotein on their surface by fluorescence-activated cell sorter (FACS) analysis. In addition, transduced cells are enriched in high MDR-expressing cells after exposure to taxol as assessed by FACS analysis, and by resistance of BFU-E to taxol (Bristol-Myers Squibb, Princeton, NJ). These studies indicate the feasibility of using MDR gene transfer as a means of enriching marrow for MDR-transduced cells. They also provide the basis of a phase 1 clinical protocol in patients with advanced cancers not involving the bone marrow for the use of MDR gene transfer as a means of protecting marrow cells, which normally express low levels of MDR, from the myelosuppressive effects of drugs like taxol.

Antigens, CD↗
PubMed1994

Mouse fetal liver cells lack functional amphotropic retroviral receptors.

We have been transducing mouse hematopoietic cells with the human MDR1 (MDR) gene in retroviral vectors to determine the optimal conditions for retroviral gene transfer as a model system for potential human gene therapy. In these studies, we have demonstrated transduction and expression of the human MDR gene using ecotropic and amphotropic MDR-retroviral producer lines. To obtain more mouse hematopoietic cells for detailed study, mouse fetal liver cells (FLC) have been used for MDR transduction and expression, and to reconstitute the ablated marrows of live adult mice. FLC contain hematopoietic cells that have a reconstituting capacity comparable to that of adult mouse bone marrow cells. However, to our surprise, FLC can only be transduced with ecotropic retrovirus and not with amphotropic virus. This restriction of transduction of FLC cannot be overcome by higher titer virus. The resistance to amphotropic transduction by FLC may be part of a changing developmental program that results in a different antigen repertoire on FLC as compared with adult bone marrow cells.

Animals↗
PubMed1994

Changing cognitive functioning in rehabilitation of schizophrenia.

A three-factor model is proposed for clinical assessment of cognitive and neuropsychological impairments in schizophrenia. The first factor is stable, pervasive and vulnerability-linked. The second and third include executive, memory and conceptual abilities and are episode-linked. The third factor may be amendable to psychosocial treatment.

Cognition Disorders↗
PubMed1994

Characterization of a cleavage mutant of the measles virus fusion protein defective in syncytium formation.

Membrane fusion caused by measles virus (MV) is a function of the fusion (F) protein. This process is essential for penetration into the host cell and subsequent initiation of the virus replicative cycle. The biological activity of the MV F protein is generated by endoproteolytic cleavage of a precursor protein (F0) into a large F1 subunit and a smaller F2 subunit held together by disulfide bonds. The cleavage site consists of a cluster of five basic amino acids (amino acids 108 to 112) within the predicted primary structure of the F protein. To investigate the role of the arginine residue at the carboxy terminus of the F2 subunit (arginine 112), site-directed mutagenesis was used to construct a cleavage mutant of the MV F protein in which this arginine residue was changed to a leucine residue. The mutated F gene, encoding four out of the five basic amino acids at the cleavage site, was inserted into the genome of vaccinia virus. The resulting recombinant virus was used to study expression of the mutant F protein in infected cells. Analysis of the Leu-112 mutant protein made in infected cells demonstrated that this single-amino-acid substitution resulted in a reduced rate of transport of the mutant protein to the cell surface, despite its efficient cleavage to yield F1 and F2 subunits. However, the electrophoretic mobilities of the Leu-112 polypeptides suggested that the protein was cleaved incorrectly. This aberrant cleavage appears to have abolished the ability of the F protein to cause syncytium formation. The data indicate that the arginine 112 residue is critical for the correct proteolytic cleavage that is required for the membrane fusion activity of the MV F protein.

Amino Acid Sequence↗
PubMed1994

Functional analysis of N-linked glycosylation mutants of the measles virus fusion protein synthesized by recombinant vaccinia virus vectors.

The role of N-linked glycosylation in the biological activity of the measles virus (MV) fusion (F) protein was analyzed by expressing glycosylation mutants with recombinant vaccinia virus vectors. There are three potential N-linked glycosylation sites located on the F2 subunit polypeptide of MV F, at asparagine residues 29, 61, and 67. Each of the three potential glycosylation sites was mutated separately as well as in combination with the other sites. Expression of mutant proteins in mammalian cells showed that all three sites are used for the addition of N-linked oligosaccharides. Cell surface expression of mutant proteins was reduced by 50% relative to the wild-type level when glycosylation at either Asn-29 or Asn-61 was abolished. Despite the similar levels of cell surface expression, the Asn-29 and Asn-61 mutant proteins had different biological activities. While the Asn-61 mutant was capable of inducing syncytium formation, the Asn-29 mutant protein did not exhibit any significant cell fusion activity. Inactivation of the Asn-67 glycosylation site also reduced cell surface transport of mutant protein but had little effect on its ability to cause cell fusion. However, when the Asn-67 mutation was combined with mutations at either of the other two sites, cleavage-dependent activation, cell surface expression, and cell fusion activity were completely abolished. Our data show that the loss of N-linked oligosaccharides markedly impaired the proteolytic cleavage, stability, and biological activity of the MV F protein. The oligosaccharide side chains in MV F are thus essential for optimum conformation of the extracellular F2 subunit that is presumed to bind cellular membranes.

Animals↗
PubMed1993

Mutation of glutamate 309 to glutamine alters one Ca(2+)-binding site in the Ca(2+)-ATPase of sarcoplasmic reticulum expressed in Sf9 cells.

Sf9 cells infected with a baculovirus vector containing SERCA1 cDNA expressed immunoreactive rabbit fast-twitch muscle Ca(2+)-ATPase at levels up to 3 mg/liter. The microsomal fraction isolated from infected Sf9 cells catalyzed Ca2+ transport at rates 6-fold above control values. To obtain direct evidence for the postulate (Clarke, D. M., Loo, T. W., Inesi, G., and MacLennan, D. H., et al. (1989) Nature 339, 476-478) that Glu309 contributes to a Ca(2+)-binding site in the transmembrane sector of the Ca(2+)-ATPase, Ca2+ binding to wild type and mutant (Glu309 to Gln) Ca(2+)-ATPases was measured. The wild type Ca(2+)-ATPase, expressed in Sf9 cells and purified using a monoclonal antibody bound to Sepharose beads, bound approximately 1.6-1.7 mol Ca2+/mol of enzyme at 2 microM Ca2+ in a buffer favoring the E1 conformation of the enzyme and at 10 microM Ca2+ in a buffer favoring the E2 conformation. Under identical conditions, the mutant Ca(2+)-ATPase bound less than 0.1 mol of Ca2+/mol of enzyme in E1 buffer, but 0.8 mol Ca2+/mol in the E2 buffer. In spite of the ability of the Glu309 to Gln mutant enzyme to bind about 1 mol of Ca2+/mol of enzyme, E2P formation was not inhibited by up to 100 microM Ca2+, and E1P formation from ATP and Ca2+ was not observed with up to 100 microM Ca2+ in intact microsomal vesicles from Sf9 cells. Nevertheless, with detergent-solubilized and purified mutant Ca(2+)-ATPases, E2P formation was inhibited with a K0.5 of 2 microM Ca2+. These observations are consistent with the view that a single intact Ca(2+)-binding site is present in the mutant Ca(2+)-ATPase, which is accessible to Ca2+ only from the lumenal side and only in the E2 conformation. Transition from E2 to E1-Ca2+ may occur during or following Ca2+ binding, accounting for the relatively high Ca2+ affinity and inhibition by Ca2+ of phosphorylation from Pi.

Animals↗
PubMed1993

Effects of different types of mechanical load on the duration of the initial agonist pulse.

Ten right-hand-dominant subjects completed a series of unsighted, goal-directed, arm flexion movements under three different mechanical loading conditions: an inertial load, an elastic spring load, and a stretched-spring load. Subjects completed a series of inertial load training trials followed by random application of one of the three loads. Three time intervals of the first agonist pulse were considered for analysis: the time from initiation of agonist activity to the onset of movement, the interval from movement initiation to the end of the agonist pulse, and the duration of the entire agonist pulse. Analyses revealed that load type did not affect the duration of any of the time intervals studied. The results suggest the presence of a regulatory control process which temporally organizes an invariant agonist pulse even when the movement is perturbed by external loads possessing different mechanical characteristics.

Electromyography↗
PubMed1993

Factors associated with HIV seropositivity in European injecting drug users. The European Community Study Group on HIV in Injecting Drug Users.

OBJECTIVE: To study factors associated with HIV seropositivity among European injecting drug users (IDU). METHODS: Data on behavioural and other factors potentially associated with HIV status were collected retrospectively by personal interview with IDU (n = 2330) in a multicentre cross-sectional survey conducted in 12 European countries from 1989 to 1990. HIV status tested at the time of the survey was examined in relation to demographic data, history of imprisonment, travel to foreign countries, high-risk drug-using practices in the previous 6 months (re-using other IDU's injecting equipment without effective disinfection) and high-risk sexual behaviour in the last 6 months (multiple partners, unless none was IDU and condoms were always used). Analysis excluded IDU who claimed to be seropositive from previous testing. RESULTS: Imprisonment was significantly associated with current HIV status [odds ratio (OR), 1.70; 95% confidence interval (CI), 1.2-2.87]. High-risk drug-use practices were significantly associated with current HIV status in respondents not previously tested (OR, 2.86; 95% CI, 1.09-7.35) but not in respondents claiming to be seronegative. No significant association was found for high-risk sexual behaviour. CONCLUSIONS: Our experience supports the validity of retrospective investigation of behaviour in a population that is notoriously difficult to study. However, any interpretation of the apparently different associations of HIV status with high-risk sexual behaviour and high-risk drug-use practices must consider that factors tending to attenuate the correlations may operate differently in these two areas.

Adolescent↗
PubMed1993

Measurement of hemoglobin flow and blood flow by near-infrared spectroscopy.

A noninvasive method of measuring hemoglobin flow through an organ by near-infrared spectroscopy (NIRS) is described that allows blood flow to be calculated. The method is derived from the Fick principle and uses a small change in arterial oxyhemoglobin concentration (brought about by a change in the fractional inspired O2 concentration) as an intravascular tracer. Changes in deoxyhemoglobin and oxyhemoglobin concentrations are quantified by monitoring variations in the absorption of near-infrared light in the organ, thus providing a measure of tracer accumulation. The tracer input function is calculated from the change in arterial O2 saturation, measured by pulse oximetry. The method was used to determine hemoglobin flow in the forearms of six healthy young adults on 10 occasions. Forearm hemoglobin flow ranged from 22.5 to 82.6 mumol.l-1.min-1. Calculated forearm blood flow ranged from 1.01 to 4.01 ml.100 g-1.min-1. For comparison, forearm blood flow was measured by venous occlusion plethysmography, and the relation between flow calculated by NIRS (y) and plethysmography (x) was y = 0.93x + 0.30 (r2 = 0.95). The mean difference between the methods was 0.14 ml.100 g-1.min-1. The technique may be widely applicable.

Adult↗
PubMed1993

Control of goal-oriented, rapid arm movements by individuals with diabetes mellitus.

Diabetic subjects completed a series of rapid, goal-directed arm movements under two conditions of unexpected external loading. Evaluation of electromyographic (EMG) patterns revealed that cocontraction and triphasic activity were predominantly associated with inertial and spring loading, respectively. During inertial load responses some EMG patterns indicated a modified cocontraction pattern. Response accuracy was unaffected by type of load but movement time was greater for the inertial load condition.

Arm↗
PubMed1993

Acid secretion and serum gastrin in normal subjects and patients with duodenal ulcer: the role of Helicobacter pylori.

OBJECTIVES: To compare gastric secretory function in patients with duodenal ulcer and in healthy volunteers with and without Helicobacter pylori infection. METHODS: Basal acid output, peak acid output, meal-stimulated acid output, fasting and meal-stimulated serum gastrin concentrations were measured in 136 healthy volunteers (63 H. pylori positive, 73 H. pylori negative) and 52 duodenal ulcer patients, all but one of whom were H. pylori positive. RESULTS: By multivariate linear regression analysis, H. pylori infection was a significant negative predictor of basal acid output and a positive predictor of fasting and meal-stimulated gastrin concentrations. When compared to truly normal (i.e., H. pylori-negative) control subjects, duodenal ulcer patients had elevated basal acid output, peak acid output, fasting and meal-stimulated gastrin concentrations. CONCLUSIONS: Our results show that in patients with duodenal ulcer disease, hypergastrinemia is largely related to gastric H. pylori infection, whereas acid hypersecretion is due to factors other than H. pylori.

Adult↗
PubMed1993

Use of gene therapy to induce human-mouse xenogeneic chimerism.

BACKGROUND: Bone marrow transplantation (BMT) has been used in the laboratory to overcome the immunologic barriers to xenotransplantation and results in chimerism and specific tolerance to donor antigens in lethally irradiated mice. Clinically, BMT carries the considerable risks of graft-versus-host disease and graft failure. Retrovirus-mediated gene transfer could provide a means of introducing foreign major histocompatibility (MHC) genes into host bone marrow cells (BMC) and thus accomplish the immunologic goals of BMT, without the associated risks. METHODS: Using a Moloney virus-based vector, a replication defective retrovirus was constructed that contained a complementary DNA encoding the human MHC antigen HLA-A2. Three million C57BL/6 mouse BMC were cocultured for 48 hours with 1 x 10(6) HLA-A2 virus "producer" cells in the presence of 15% WEHI supernatant (interleukin-3) and 200 units/ml interleukin-6. Putatively infected BMC were then used at 2 to 3 x 10(6) BMC/animal to reconstitute lethally irradiated syngeneic mice. RESULTS: Twelve days after reconstitution, spleen colonies were found to have integrated the full-length retroviral sequences. Thirty days after BMT, the introduced DNA could be found in the bone marrow, thymus, and spleen, and approximately 5% of T cells in the spleen expressed the HLA-A2 surface antigen. CONCLUSIONS: These data show that xenogeneic MHC genes can be introduced and expressed in mouse hematopoietic cells in vivo and indicate that gene therapy potentially may be used in the future to manipulate the immune system to induce transplantation tolerance.

Animals↗