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Biomedical subjects

D Robinson

Publications and source records attributed to D Robinson.

At least 271 records · Page 15Linked to original sources

Estrogen replacement therapy and memory in older women.

OBJECTIVE: To study the relationship between estrogen hormone replacement therapy and recall of proper names and words in cognitively intact older women. DESIGN: A case-control study using subjects matched on age and education. PARTICIPANTS: From a group of 278 older (age range 55 to 93 years) community-dwelling women volunteers for memory research, 72 older women taking estrogen replacement therapy were matched on age and education with a group of 72 women not taking estrogen. MEASUREMENTS: Dependent measures were performances on: a proper name recall test and a word recall test. RESULTS: Proper name recall was significantly better in those receiving estrogen (mean = 4.3; SD = 3.3) than in those not receiving estrogen (mean = 3.1; SD = 2.5), P = 0.01. There was also significantly greater variance in the name recall scores of the group taking estrogen than in the group not taking estrogen. For word recall, there was no significant difference between those subjects taking estrogen (mean = 6.4; SD 3.8) and those not taking estrogen (mean = 5.8; SD 3.7), P > 0.10. CONCLUSIONS: Estrogen use was associated with enhanced recall of proper names. Previous failures to find differences associated with estrogen use may reflect the memory measures used or an increased inter-individual variability of the estrogen-taking group, as was observed in the present study. Interpretation of these results should be tempered by their retrospective nature.

Aged↗

Correlation between response to acyclovir and foscarnet therapy and in vitro susceptibility result for isolates of herpes simplex virus from human immunodeficiency virus-infected patients.

In vitro susceptibility testing of herpes simplex virus (HSV) isolates will play an increasingly important role in guiding the clinical management of immunocompromised hosts who have lesions that are poorly responsive to therapy with standard antiviral agents. We assessed the correlation between the in vitro susceptibility result using a plaque reduction assay in Vero cells and the response to antiviral therapy with acyclovir or foscarnet for 243 clinical isolates of HSV collected from 115 human immunodeficiency virus-infected patients. The in vitro results and clinical responses were highly associated for both acyclovir and foscarnet (P < 0.001 and P < 0.001, respectively). The predictive values of a susceptible result (50% effective concentrations, < 2 micrograms/ml for acyclovir and < 100 micrograms/ml for foscarnet) for complete healing of lesions were 62% for acyclovir and 82% for foscarnet; the predictive values of a resistant result for failure to heal were 95% for acyclovir and 88% for foscarnet. Thus, in vitro testing has clinical utility in guiding therapy, although the 1 to 2 weeks required to derive a definitive result by the plaque reduction assay is a major limitation.

Acyclovir↗

Membrane-binding domains and cytopathogenesis of the matrix protein of vesicular stomatitis virus.

The membrane-binding affinity of the matrix (M) protein of vesicular stomatitis virus (VSV) was examined by comparing the cellular distribution of wild-type (wt) virus M protein with that of temperature-sensitive (ts) and deletion mutants probed by indirect fluorescent-antibody staining and fractionation of infected or plasmid-transfected CV1 cells. The M-gene mutant tsO23 caused cytopathic rounding of cells infected at permissive temperature but not of cells at the nonpermissive temperature; wt VSV also causes rounding, which prohibits study of M protein distribution by fluorescent-antibody staining. Little or no M protein can be detected in the plasma membrane of cells infected with tsO23 at the nonpermissive temperature, whereas approximately 20% of the M protein colocalized with the membrane fraction of cells infected with tsO23 at the permissive temperature. Cells transfected with a plasmid expressing intact 229-amino-acid wt M protein (M1-229) exhibited cytopathic cell rounding and actin filament dissolution, whereas cells retained normal polygonal morphology and actin filaments when transfected with plasmids expressing M proteins truncated to the first 74 N-terminal amino acids (M1-74) or deleted of the first 50 amino acids (M51-229) or amino acids 1 to 50 and 75 to 106 (M51-74/107-229). Truncated proteins M1-74 and M51-229 were readily detectable in the plasma membrane and cytosol of transfected cells as determined by both fluorescent-antibody staining and cell fractionation, as was the plasmid-expressed intact wt M protein. However, the expressed doubly deleted protein M51-74/107-229 could not be detected in plasma membrane by fluorescent-antibody staining or by cell fractionation, suggesting the presence of two membrane-binding sites spanning the region of amino acids 1 to 50 and amino acids 75 to 106 of the VSV M protein. These in vivo data were confirmed by an in vitro binding assay in which intact M protein and its deletion mutants were reconstituted in high- or low-ionic-strength buffers with synthetic membranes in the form of sonicated unilammelar vesicles. The results of these experiments appear to confirm the presence of two membrane-binding sites on the VSV M protein, one binding peripherally by electrostatic forces at the highly charged NH2 terminus and the other stably binding membrane integration of hydrophobic amino acids and located by a hydropathy plot between amino acids 88 and 119.

1,2-Dipalmitoylphosphatidylcholine↗

Hormonal regulation of the gene for the type C ecotropic retrovirus receptor in rat liver cells.

The infectibility of the regenerating rat liver by ecotropic retroviruses was studied relative to the expression of the gene coding for the ecotropic retrovirus receptor (Ecor) that functions as a cationic amino acid transporter. It is known that the gene for the receptor is expressed in primary hepatocytes and hepatoma cells but is absent in adult liver cells. Isolation of a 2.85-kb cDNA for the rat Ecor suggested that the rat viral receptor is 97% homologous to the mouse viral receptor and that it contains the envelope-binding domain that determines the host range of ecotropic murine retroviruses. This explains the efficient infection of rat cells by ecotropic retroviruses. Since cell division is required for liver cells to be infected, we determined the susceptibility of the regenerating rat liver to infection at different time points after partial hepatectomy (0 to 24 h) in relation to the presence of receptor mRNA. Infection of the liver occurred only when the liver was exposed to virus 4 h after partial hepatectomy. This time course of infection paralleled expression of the gene for the Ecor, which was rapidly induced between 2 and 6 h during liver regeneration. However, expression of the dormant receptor gene in quiescent liver cells can be induced by insulin, dexamethasone, and arginine, indicating that cell division is not required for expression of the receptor gene in liver cells. A diet high in carbohydrate (low in protein) significantly increased the concentration of receptor mRNA in liver cells, indicating that hormones play a role in the regulation of expression of this gene in vivo. We conclude that the gene for the viral receptor is expressed in the regenerating and quiescent liver when the urea cycle enzymes are down regulated. The infection of the regenerating rat liver by ecotropic retroviruses at the time point of expression of the receptor gene supports the requirement of expression of this transporter for infection.

Amino Acid Sequence↗

Polylactide/polyglycolide antibiotic implants in the treatment of osteomyelitis. A canine model.

Osteomyelitis with Staphylococcus aureus was established in the tibiae of twenty-six adult mongrel dogs. After confirmation of infection at four weeks, all animals had operative débridement and were then divided into three treatment groups. Group 1 (eight animals [sixteen tibiae]) was treated with parenteral administration of gentamicin (three milligrams per kilogram of body weight per day) every eight hours for four weeks. Group 2 (nine animals [nine tibiae]) was treated with a polymethylmethacrylate implant containing 100 milligrams of gentamicin that was placed in the tibia for six weeks. Group 3 (nine animals [nine tibiae]) was treated with a polylactide/polyglycolide implant containing 100 milligrams of gentamicin that was placed in the tibia for six weeks. All animals were killed at the end of treatment. At that time, specimens of tissue were obtained for quantitative culture as well as for antibiotic immunoassay. In the groups that had been treated with an implant, serum was obtained for the measurement of serum drug levels after débridement; after the implantation; four, seven, and twenty-one days postoperatively; and immediately before the animals were killed. The infection was eradicated in ten of the sixteen tibiae in Group 1, in eight of the nine tibiae in Group 2, and in all nine tibiae in Group 3.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Changes in femur dimensions in asymptomatic non-cemented hip arthroplasties. 20 cases followed for 5-8 years.

We assessed changes in proximal femur diameter during 5-8 years follow-up of 20 clinically successful press-fit cementless isoelastic implants. Total bone diameter, medullary diameter and cortical thickness were measured over the distal half of the prosthesis and just beyond the prosthesis tip. During the follow-up period total bone diameter did not change. However, cortical thickness declined by an average of 1 mm, while the size of the medullary canal increased by the same amount. As the patients remained asymptomatic during this period, the phenomenon observed did not appear to be related to loosening. We concluded that age-related changes in bone diameter can lead to widening of the tight interface between the stem and the femur.

Adult↗

Measurement of prostate-specific antigen in serum using four different immunoassays.

This paper summarises the results of a comparison of the Serono SR1, Ciba Corning ACS 180, Abbott IMx and Hybritech Tandem-R prostate-specific antigen assays. One hundred serum pools were assayed using the four methods. Linear regression analysis of the data showed that, although overall correlations were good, different assays gave different prostate-specific antigen concentrations. Tandem-R and SR1 assays gave very similar prostate-specific antigen values; in general, the ACS assay gave higher prostate-specific antigen values than the IMx assay gave lower prostate-specific antigen values than the established Tandem-R assay. Following fractionation of serum from prostate cancer patients, all immunoassays detected several immunoreactive prostate-specific antigen forms. The major immunoreactive form (> 88% of immunoreactivity) had an apparent molecular size of M(r) approximately 100,000 and is likely to be a complex of prostate-specific antigen with alpha 1-antichymotrypsin; two minor forms had apparent molecular sizes of M(r) approximately 30,000 (probably free prostate-specific antigen) and 200,000 (probably prostate-specific antigen complexed to high molecular mass anti-proteases). From this study there is no evidence that polyclonal/monoclonal antibody immunoassays are to be preferred to monoclonal/monoclonal antibody immunoassays for the determination of free prostate-specific antigen in serum.

Antibodies, Monoclonal↗

Adhesion characteristics of chondrocytes cultured separately and in co-cultures with synovial fibroblasts.

The present study was designed to investigate the adherence mechanism(s) and behaviour of cultured chondrocytes under various culturing conditions, co-culturing with fibroblasts, or growth in the presence of conditioned medium either of fibroblasts or chondrocytes. The findings obtained indicate that chondrocyte time-adhesion curves and the final percentiles of attached cells to a plastic substrate are much slower and lower respectively than those of anchorage dependent cell types. The poorest adhesion occurs employing chondrocytes originated from suspension cultures, as compared to chondrocytes grown in monolayers. No interference with chondrocyte adhesion was found by inhibiting the production of proteoglycan (PG). Puromycin and to a lesser degree actinomycin but not cytosine arabinoside interfered with chondrocyte adhesion, suggesting the importance of protein synthesis in this process. The nature of proadhesion modifying molecules in synoviocytes conditioned media and antiadhesive agents in chondrocyte conditioned media suggests that both substances are heat labile, non-dialyzable, protein containing factors.

Animals↗

In vitro construction of cells-containing implants for articular cartilage regeneration.

Regeneration of destroyed articular cartilage can be induced by transplantation of cartilage cells into the defects. The best results are obtained by the use of either fetal allogeneic cells or autogenic ones. Induction of chondrogenesis in residual mesenchymal cells is optimal for obtaining large amounts of autogenic chondrocytes. Further modification of the technique is needed to reconstruct large defects. The cells are grown on biodegradable scaffolds and are later implanted into joint defects.

Animals↗

Seasonal variation in serum cholesterol levels in health screening populations from the U.K. and Japan.

We have performed time series analyses on data from 140,000 men and 32,000 women in the U.K. and 30,000 men and 12,000 women in Japan, seen over periods ranging from 4 to 6 1/2 years, in order to test for seasonal variation in serum cholesterol levels. In both countries and both sexes we found a strong seasonal effect, with mean cholesterol levels being some three to five percent higher in winter than in summer. Mean monthly cholesterol levels were negatively correlated with mean monthly air temperatures (r = -0.60 to -0.71). The seasonal differences observed were independent of changes in body weight, and have important implications both for long-term epidemiological or follow-up studies, and for the interpretation of patient data.

Cholesterol↗

Activation of CD4+ T cells, increased TH2-type cytokine mRNA expression, and eosinophil recruitment in bronchoalveolar lavage after allergen inhalation challenge in patients with atopic asthma.

BACKGROUND: We have examined whether the local eosinophilia provoked by inhalational allergen challenge of patients with atopic asthma is associated with the appearance, in vivo, of activated TH2-type T helper lymphocytes. METHODS: Fifteen patients with atopic asthma had bronchial wash and bronchoalveolar lavage (BAL) 24 hours after allergen or diluent challenge separated by at least 21 days. RESULTS: There was an increase in eosinophils in both bronchial wash (p = 0.01) and BAL (p = 0.02) after allergen challenge but not after diluent challenge. Activation of CD4+ BAL T cells was suggested by an increase in the expression of CD25 shown by flow cytometry after allergen challenge, when compared with diluent (p = 0.02). There was no evidence of activation of CD8 T cells. By in situ hybridization after allergen challenge as compared with diluent, increases were shown in the numbers of cells expressing mRNA for interleukin-4 (IL-4) (p = 0.005), IL-5 (p = 0.01), and granulocyte-macrophage colony-stimulating factor (p = 0.03) but not IL-3, IL-2, or interferon-gamma. In situ hybridization of BAL cells after immunomagnetic separation of CD2-positive and CD2-negative cell populations showed that IL-4 and IL-5 mRNAs were associated with T lymphocytes after allergen challenge. BAL and bronchial wash eosinophilia closely correlated with maximal late fall in forced expiratory volume in 1 second after allergen challenge. CONCLUSION: Cytokines produced by activated TH2-type CD4+ T cells in the airway may contribute to late asthmatic responses by mechanisms that include eosinophil accumulation.

Administration, Inhalation↗

Multiple-dose phase I study of transnasal butorphanol.

The safety, tolerance, and pharmacokinetics of transnasal butorphanol were evaluated in a double-blind, multiple-dose phase I study. A total of 18 subjects received either placebo (n = 6) or a single transnasal dose of 2 mg butorphanol tartrate on the first day and 1, 2, and 4 mg doses of butorphanol tartrate every 6 hours on days 2 through 6, 7 through 11, and 12 through 16, respectively. Safety assessment was performed on days 7, 12, and 17. Serial blood samples were collected on days 1, 6, 11, and 16, and the plasma was analyzed for unchanged butorphanol by a validated and specific radioimmunoassay. Butorphanol was rapidly absorbed and peak levels in plasma were generally attained within 1 hour after the nasal administration. The values of maximum concentration, minimum concentration, and area under the concentration versus time curve from time zero to the dosing interval [AUC(0-tau)] increased as the administered dose increased in a dose-proportional manner. The values of AUC from time zero to infinity after a single dose of 2 mg butorphanol tartrate, 10.9 ng.hr/ml, were identical to the values of AUC(0-tau) after a multiple administration of 2 mg dose, 10.4 ng.hr/ml. Mean elimination half-life value was 5.45 hours. Steady state was reached in fewer than eight doses when given every 6 hours. Transnasal butorphanol was well tolerated by all subjects. After repeated administration of transnasal butorphanol, no significant changes were observed in the nasal examination, which included evaluation of color, wetness, and thickness of nostril membrane, air flow, airway patency, and general nasal conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗