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Biomedical subjects

J Clayton

Publications and source records attributed to J Clayton.

At least 73 records · Page 4Linked to original sources
PubMed1990

Pharmacokinetic studies of passively administered ovine anti-testosterone antibodies given to cattle by the subcutaneous and intravenous routes.

Passive immunization of cattle with ovine anti-testosterone antiserum can result in an increased ovulation rate, but the effect is variable and may be influenced by the route of administration. Investigations were made into the pharmacokinetics of these antibodies in cattle when given intravenously (i.v.), subcutaneously (s.c.) or via a combination of these two routes. Serum levels of free residual binding sites were measured by testosterone radioimmunoassay, whilst total circulating ovine IgG was determined using a specific enzyme-linked immunosorbent assay which shows no cross-reactivity with bovine IgG. The biological half-life of the administered antibodies was longer when it was calculated by measuring titre than when it was calculated by measuring IgG. Subcutaneous injection resulted in a significantly longer half-life of IgG than intravenous injection or the combined route, with a concomitant increase in the area under the curve. No significant differences between the half-lives as measured by titre were noted following the various routes of administration, but the mean value following s.c. injection was longest. The choice of route of administration of antiserum for passive immunization can be used to control the timing and duration of effective antibody levels. The results of the present study suggest that the s.c. or combined i.v. and s.c. routes are the preferred methods of passive immunization if an effect of long duration is required. It may be that it is the period over which the maximum level is maintained, rather than the absolute maximum level, which is important for successful immunomodulation of ovulation rate.

Animals↗
PubMed1989

Encephalitogenic T cells in the B10.PL model of experimental allergic encephalomyelitis (EAE) are of the Th-1 lymphokine subtype.

T helper cells reactive to myelin basic protein are clearly implicated in the pathogenesis of murine EAE. We have developed a T cell line, BML-1 that (1) is reactive to the encephalitogenic amino terminal nonapeptide (1-9NAC) of MBP, (2) is I-Au restricted, and (3) induces relapsing EAE in B10.PL (H-2u) mice. Measurement of the lymphokine profile of BML-1 revealed secretion of IL-2, interferon-gamma and lymphotoxin but not IL-4. This profile is consistent with the Th1/DTH subtype. Coculture of BML-1 with MBP-primed B cells shows that BML-1 does not provide significant helper function in vitro. In addition, BML-1 secretion of interferon-gamma was found to inhibit LPS-induced anti-MBP antibody responses. This suggested that anti-MBP antibodies may not be necessary for induction of EAE. Sera from mice, in which severe disease was induced with the 1-9NAC peptide and Bordetella pertussis, showed no development of serum antibodies to MBP. These data show that MBP-reactive Th cells of the Th-1/DTH subtype can induce EAE and do not provide Th function for anti-MBP responses and that serum anti-MBP antibodies are not found in peptide 1-9NAC-induced disease. T cell lines specific for encephalitogenic epitopes and characterized for lymphokine secretion will provide a useful tool for understanding the role of T cells in the induction of EAE.

Animals↗
PubMed1989

Vitamin D metabolism in myeloma.

We measured serum concentrations of vitamin D metabolites in 27 patients with myeloma, 16 of whom were hypercalcaemic. Serum values were compared with values from normal controls. Serum concentrations of calcitriol (1.25-dihydroxyvitamin D; 1.25(OH)2D3) were decreased in both hyper- and normocalcaemic patients, but more markedly so in hypercalcaemia. These findings were not solely due to impaired renal function nor due to an inadequate supply of 25-hydroxyvitamin D, and in hypercalcaemic patients were reversed by diphosphonate treatment. We conclude that hypercalcaemia in myeloma is not mediated by abnormalities in vitamin D metabolism. Decreased serum concentrations of 1.25(OH)2D3 may adversely affect both skeletal and tumour metabolism.

Adult↗
PubMed1989

Physiological growth hormone secretion and response to growth hormone treatment in children with short stature and intrauterine growth retardation.

Physiological growth hormone (GH) secretion was examined in 31 children (8 girls, 23 boys) with short stature secondary to intrauterine growth retardation (IUGR). Seventeen (4 girls, 13 boys) had dysmorphic features of Russell-Silver syndrome. Four of the 31 children had GH insufficiency with peak GH levels of less than 20 mU/l during the night. Nine of the patients (8 of whom had Russell-Silver syndrome) had a single nocturnal GH pulse. Twenty-three children (6 girls, 17 boys) were randomized into two groups treated with either 15 or 30 U/m2/week of GH by daily subcutaneous injections. Age, sex distribution, pretreatment height velocity SD score (SDS), and distribution of dysmorphic and non-dysmorphic children were similar in both groups. The group treated with 15 U/m2/week for a mean of 0.82 years showed an increase in mean height velocity SDS from -0.61 to +1.09, and the group treated with 30 U/m2/week for a mean of 0.92 years showed an increase in mean height velocity SDS from -0.69 to +3.48. The results suggest that physiological GH insufficiency is probably common in children with Russell-Silver syndrome and that both dysmorphic and non-dysmorphic children with short stature secondary to IUGR will respond to GH treatment. Initial evidence suggests that the increase in short-term growth velocity does not result in an improved final height prognosis.

Body Height↗
PubMed1988

Restricted use of T cell receptor V genes in murine autoimmune encephalomyelitis raises possibilities for antibody therapy.

Experimental allergic encephalomyelitis (EAE) is a paralytic autoimmune disease induced in susceptible animals by active immunization with myelin basic protein (MBP) or by passive transfer of MBP-specific T helper (TH) lymphocytes. We have analyzed the T cell receptor genes of 33 clonally distinct TH cells specific for a nonapeptide of MBP inducing EAE in B10.PL (H-2u) mice. All 33 TH cells used two alpha variable gene segments (V alpha 2.3, 61%; V alpha 4.2, 39%), the same alpha joining gene segment (J alpha 39), and two V beta and J beta gene segments (V beta 8.2-J beta 2.6, 79%; V beta 13-J beta 2.2, 21%). The anti-V beta 8 monoclonal antibody F23.1 was found to block completely recognition of the nonapeptide by V beta 8 TH cells in vitro and to reduce significantly the susceptibility of B10.PL mice to peptide-induced EAE.

Animals↗
PubMed1988

A bovine monoclonal antibody to oestrone/oestradiol prepared by a (murine x bovine) xbovine interspecies fusion.

A heterohybridoma was produced by the fusion of sensitized peripheral blood lymphocytes (PBLs) with a previously derived heteromyeloma, generated by the fusion of bovine PBLs with murine myeloma cells. The sensitized bovine PBLs were collected from a steer immunized with an oestradiol-ovalbumin conjugate. The cell lines resulting from the fusion were screened for the production of bovine antibodies to oestradiol. A stable heterohybridoma was isolated which secreted a bovine IgG1 to oestrone/oestradiol. The use of sensitized PBLs together with heteromyeloma fusion partners has proved to be a reliable and simple way of producing monoclonal antibodies against specific haptens.

Animals↗