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Biomedical subjects

R Field

Publications and source records attributed to R Field.

At least 19 recordsLinked to original sources
PubMed1999

A fully human antibody neutralising biologically active human TGFbeta2 for use in therapy.

Phage display provides a methodology for obtaining fully human antibodies directed against human transforming growth factor-beta (TGFbeta) suitable for the treatment of fibrotic disorders. The strategy employed was to isolate a human single chain Fv (scFv) fragment that neutralises human TGFbeta2 from a phage display repertoire, convert it into a human IgG4 and then determine its TGFbeta binding and neutralisation properties and its physical characteristics. Several scFv fragments binding to TGFbeta2 were isolated by panning of an antibody phage display repertoire, and subsequent chain shuffling of the selected V(H) domains with a library of V(L) domains. The three most potent neutralising antibodies were chosen for conversion to IgG4 format. The IgG4 antibodies were ranked for their ability to neutralise TGFbeta2 and the most potent, 6B1 IgG4, was chosen for further characterisation. 6B1 IgG4 has a high affinity for TGFbeta2 with a dissociation constant of 0.89 nM as determined using the BIAcore biosensor and only 9% cross-reactivity with TGFbeta3 (dissociation constant, 10 nM). There was no detectable binding to TGFbeta1. 6B1 IgG4 strongly neutralises (IC50 = 2 nM) the anti-proliferative effect of TGFbeta2 in bioassays using TF1 human erythroleukaemia cells. Similarly, there was strong inhibition of binding of TGFbeta2 to cell surface receptors in a radioreceptor assay using A549 cells. 6B1 IgG4 shows no detectable cross-reactivity with related or unrelated antigens by immunocytochemistry or ELISA. The 6B1 V(L) domain has entirely germline framework regions and the V(H) domain has only three non-germline framework amino acids. This, together with its fully human nature, should minimise any potential immunogenicity of 6B1 IgG4 when used in therapy of fibrotic diseases mediated by TGFbeta2.

Amino Acid Sequence↗
PubMed1997

Clinical improvement in chronic fatigue syndrome is not associated with lymphocyte subsets of function or activation.

The relationship between markers of immune function and chronic fatigue syndrome (CFS) is controversial. To examine the relationship directly, 43 subjects with CFS entering a randomized controlled trial of a nonpharmacological treatment for CFS gave samples for immunological analysis before and after treatment. Percentage levels of total CD3+ T cells, CD4 T cells, CD8 T cells, and activated subsets did not differ between CFS subjects and controls. Naive (CD45RA+ RO-) and memory (CD45RA- RO+) T cells did not differ between subjects and controls. Natural killer cells (CD16+/CD56+/CD3-) were significantly increased in CFS patients compared to controls, as was the percentage of CD11b+ CD8 cells. There were no correlations between any immune variable and measures of clinical status, with the exception of a weak correlation between total CD4 T cells and fatigue. There was a positive correlation between memory CD4 and CD8 T cells and depression scores and a negative correlation between naive CD4 T cells and depression. No immune measures changed during the course of the study, and there was no link between clinical improvement as a result of the treatment program and immune status. Immune measures did not predict response or lack of response to treatment. In conclusion, we have been unable to replicate previous findings of immune activation in CFS and unable to find any important associations between clinical status, treatment response, and immunological status.

Adult↗
PubMed1997

Tenderness variation among loin steaks from A and C maturity carcasses of heifers similar in chronological age.

Fifty-two Angus x Gelbvieh rotationally crossed virgin, ovariectomized, or single-calf heifers were slaughtered after 100 d on a high-concentrate diet. Heifers from each treatment were approximately 31, 33, or 35 mo of age, and they produced 31 A, 5 B, and 16 C maturity carcasses. Because of the small number, B maturity carcasses were not included in this study. Number of A maturity carcasses decreased as age increased. No differences (P > .05) in slaughter weight, total weight gain, dressing percentage, longissimus muscle area, or kidney fat percentage existed between carcass maturity groups, but C maturity heifers had 3.56 mm more fat (P < .01) over the longissimus muscle than A maturity heifers. Marbling scores of slight79 and small0 for A and C maturity carcasses, respectively, did not differ (P > .05). The A and C maturity heifers had similar amounts of collagen and hydroxylysyl-pyridinium crosslinks in metacarpal bone cortex and in longissimus muscle. Neither means for panel tenderness nor Warner-Bratzler shear values differed (P > .05) between maturity groups. Coefficients of variation for tenderness were slightly higher in steaks from C maturity carcasses, but CV for shear values between A and C maturity groups were similar. Because inconsistent meat tenderness is a recognized problem in the beef industry, more research on tenderness variability within maturity and marbling groups is needed. This information, in addition to pooled SEM and differences between means, should aid in finding ways to reduce beef tenderness variability.

Aging↗
PubMed1996

Growth, carcass, and tenderness characteristics of virgin, spayed, and single-calf heifers.

Fifty-three Angus/Gelbvieh rotationally crossed heifers were slaughtered after 100 d on a high-concentrate diet. The average slaughter age for each of three different groups was 31, 33, or 35 mo, which falls within the USDA's 30- to 42-mo age range for animals producing "B" maturity carcasses. Each age group consisted of five or six heifers that had never been bred (virgin), six heifers ovariectomized at 1 yr of age (spayed), and six heifers that had weaned calves approximately 120 d postpartum (single-calf). Slaughter weight was higher (P < .05) for the virgin heifers but total weight gain in the feedlot was similar among the three groups. Single-calf heifers fed 100 d after weaning calves tended to be fatter than virgin or spayed heifers. Carcass maturity scores for the single-calf, virgin, and spayed heifers were different (P < .05); single-calf heifers produced carcasses that appeared older and spayed heifers produced carcasses that appeared younger. Maturity scores coupled with lighter and shorter metacarpal bone weights indicated single-calf heifers matured earlier (P < .05) than the other groups. Panel tenderness and Warner-Bratzler (WB) shear values of rib roasts from virgin, spayed, and single-calf heifers were determined. No differences among groups of heifers existed but scores within each group varied greatly. Marbling score was correlated (P < .05) with panel tenderness and shear force and the hydroxylysylpyridinium (HP) crosslink of muscle collagen was correlated (P < .05) with shear values. Because no significant (P < .05) correlation existed between HP in bone collagen or HP or WB shear values in muscle, we concluded that collagen maturation processes in muscle and bone occur independently. With the exception of differences in bone maturity scores, few meaningful differences in characteristics of virgin, spayed, and single-calf heifers existed, but these maturity differences could change carcass grade and influence value.

Amino Acids↗
PubMed1992

Detection and disinfection of pathogens in storm-generated flows.

The disease-producing potential of recreational waters is currently estimated through the use of certain bacterial indicators that are believed to be positively correlated with the presence of fecal contamination. In general, these indicators and their recommended limiting values have been adopted for use from existing standard methods for the analysis of sanitary waste water. However, no indicator currently in use today exists solely in the feces of man and not also elsewhere, e.g., in soils, vegetation, and the feces of animals. Storm-water runoff is often rich in bacteria originating from these nonhuman sources and can contain high densities of indicator bacteria; however, existing epidemiological studies of recreational waters receiving storm-water runoff have reported little correlation between current indicator densities and the incidences of swimming illnesses. In addition, microbial analyses of storm-water runoff have revealed a predominance of nonenteric disease-causing bacteria and viruses that have been linked to respiratory illnesses and skin infections. Fecal-based indicators in use today provide no information on the risks resulting from body contact with these nonenteric pathogens. Consequently, for receiving waters containing discharges that originate primarily from separate storm drainage systems, current bacterial indicators are ill suited to accurately assess the water's total illness-producing capabilities. This paper briefly reviews the development of current bacterial standards and evaluates their adoption in the field of storm-water testing. The unique disinfection requirements of storm-generated runoff are discussed, and advanced disinfection practices are reviewed. The need for additional epidemiological studies that address the disease-causing potential of nonhuman and nonenteric pathogens commonly found in storm-water runoff from urban, agricultural, and rural watershed areas is emphasized in order to determine the actual health risks associated with storm water runoff contact.

Animals↗
PubMed1984

Structure-affinity relationships between several new benzodiazepine derivatives and 3H-diazepam receptor sites.

Several new benzodiazepines were studied with respect to their ability to bind specifically to benzodiazepine receptor sites in rat cerebral cortex membrane fraction. The IC50 values of new benzodiazepines were compared to that of diazepam. A group of triazolo-[1,4] benzodiazepines displaced 3H-diazepam very effectively. The most potent of this group was brotizolam . Its potency was about ten times higher than that of diazepam. In this study, camazepam, which differs from diazepam in its C-3 substitution, had the lowest affinity to the benzodiazepine receptor site. This potency was about 0.006 that of diazepam. CM 7116 bound with the highest affinity to the benzodiazepine receptor site among the metabolites of CM 6912. The length of the side chain at the C-3 position of this compound is shorter than that of the other metabolites of CM 6912. These results indicated that the long side chain at the C-3 position might inhibit a close interaction between the receptor site and the substrate molecule, thereby leading to low-affinity binding.

Animals↗
PubMed1982

Pneumococcal polysaccharide immunization of children with sickle cell disease. II. Serologic response and pneumococcal disease following immunization.

One-hundred seventy-four children with sickle cell disease (SCD) were immunized with a single dose of tetradecavalent pneumococcal vaccine. Preimmunization and postimmunization antibody against 13 of the 14 pneumococcal capsular antigens was measured by indirect hemagglutination (IHA). The ability of each antigen to stimulate antibody following immunization was characterized by one of three types of responses: (1) poor antibody response regardless of the age at immunization (capsular types 6A, 14, and 19F); (2) improving antibody response with advancing age at immunization (capsular types 1, 4, 9N, 12F, 18C, and 23F); and (3) good antibody response regardless of age at immunization (capsular types 2, 3, 7F, and 8). An increase in antibody following immunization was significantly correlated (P less than 0.0005) with an increasing level of preimmunization antibody titer for all 13 antigens. Through the first 24 months of study, two episodes of pneumococcal sepsis caused by group 23 pneumococci were documented in two children immunized prior to 24 months of age (incidence rate, 4.40/100 patient-years in children less than 5 years of age), and one additional episode caused by a group 23 pneumococcus occurred in a 5 7/12-year-old child (incidence rate, 0.66/100 patient-years in children greater than 5 years of age). These observations suggest that anamnestic immune response significantly contributed to the enhanced antibody response observed in older children and adults. Only modest vaccine efficacy may be expected among children with SCD who receive a single dose of pneumococcal vaccine.

Adolescent↗
PubMed1978

Role of cardiovascular disease in the pathogenesis of rhegmatogenous retinal detachments.

In 100 patients with fresh rhegmatogenous retinal detachments complete ocular and physical examinations including electrocardiograms were carried out. The incidence of coronary artery disease and systemic hypertension in these patients with retinal detachments was much greater than that found in the general population of similar age and sex. A vascular theory is proposed to explain these findings in light of our current concepts of the pathogenesis of retinal detachments. It is also suggested that retinal detachments may be one element of a generalized vasculopathy that involves the coronary arteries, the pulmonary vasculature, and perhaps the renal circulation in patients with systemic hypertension.

Adolescent↗