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Biomedical subjects

S Oldfield

Publications and source records attributed to S Oldfield.

At least 37 records · Page 2Linked to original sources

Hypogammaglobulinaemia in nephrotic rats is attributable to hypercatabolism of IgG.

The effect of the nephrotic syndrome induced by puromycin aminonucleoside (PA) in rats on specific antibody responses to 2,4 dinitrophenyl (DNP) conjugated to either spider crab haemocyanin (MSH), a T cell-dependent antigen, or hydroxyethyl starch (HES), a T cell-independent type 2 antigen were studied. The serum IgG anti-DNP levels following immunization with both antigens were reduced in nephrotic animals compared with controls while IgM anti-DNP antibody titres were higher. The half-life of IgG anti-DNP antibodies passively transferred into non-immunized nephrotic rats was markedly reduced while the half-life of anti-DNP antibodies of the IgM class was comparable to that in controls. Low serum IgG and elevated IgM levels were seen in nephrotic animals compared to controls. Antibody-forming cells specific for DNP were demonstrated by immunohistology on rat spleens and the numbers of both IgG and IgM-producing cells were found to be significantly increased (P less than 0.05) in nephrotic animals in response to both DNP-HES and DNP-MSH. These data indicate that in nephrotic rats the alteration seen in the serum immunoglobulin levels is not attributable to reduced antibody production but increased catabolism of serum IgG antibodies.

Agammaglobulinemia↗

Newly produced virgin B cells migrate to secondary lymphoid organs but their capacity to enter follicles is restricted.

The migration of recirculating B cells was compared with that of newly produced virgin B cells following passive cell transfer between congenic strains of rats differing in their kappa immunoglobulin light chain (kappa) allotype. The number and location of donor B cells in the secondary lymphoid organs was determined at intervals following transfer by immunohistology using monoclonal antibodies specific for rat kappa allotypes. Recirculating B cells were obtained from thoracic duct lymph while bone marrow from rats depleted of recirculating cells was used as a source of newly produced virgin B cells. B cells from both sources gained immediate access to extrafollicular areas of secondary lymphoid organs rich in interdigitating cells and T cells. However, in lymph nodes extrafollicular B cells were found adjacent to lymphatics and not in the central paracortex. By 8 h after transfer most B cells from thoracic duct lymph were found in follicles. However, the capacity of the bone marrow B cells to enter follicles was very limited. These results are interpreted in relation to previous observations concerning (a) the timing of virgin B cell recruitment into T cell-dependent antibody responses, and (b) the role of B cells in antigen presentation.

Animals↗

Effect of acetazolamide on blood gases and 2,3 DPG during ascent and acclimatization to high altitude.

Blood gases and red cell 2,3 DPG concentrations were measured during ascent and a stay for 6 days at 4846 m in 20 subjects. Acetazolamide improved Pa,O2 and reduced pH and Pa,CO2. 2,3 DPG concentrations were lower in the acetazolamide group during ascent and at high altitude. However, 2,3 DPG concentrations were significantly greater at high altitude in both the acetazolamide and placebo groups compared with low altitude. The acetazolamide group remained different from the placebo group during the stay at high altitude with higher Pa,O2, lower PaCO2, lower pH and lower 2,3 DPG concentrations.

2,3-Diphosphoglycerate↗

Differences in the recruitment of virgin B cells into antibody responses to thymus-dependent and thymus-independent type-2 antigens.

The bone marrow of mammals generate large numbers of B cells throughout life. Most of these have a short life span. The subject of this report is to investigate the extent to which newly formed virgin B cells can be activated by thymus-dependent (TD) and thymus-independent type 2 (TI-2) antigens carrying the hapten 2,4-dinitrophenyl. The experimental approach used chimeras made between congenic rats of different kappa immunoglobulin light chain allotype. Host (kappa la) rats were depleted of peripheral B cells by whole body irradiation but had B lymphopoietic capacity conserved by shielding the hind limbs. Their peripheral B cell pool was reconstituted by transfer of kappa lb thoracic duct lymphocytes from donors immunized previously with the TD carrier. This provides test animals where newly produced virgin B cells only express kappa la but where initially most peripheral B cells are kappa lb. The TD antigen tested was able to activated both virgin and memory B cells in the period immediately following immunization. However, long-term antibody production was attributable to repeated activation of memory B cell clones without further virgin B cell recruitment. By contrast, antibody evoked by the TI-2 antigen initially was almost exclusively due to activation of donor peripheral B cells. However, over a period following TI-2 immunization there was a progressive increase in the amount of host antibody produced with corresponding decline of the donor component of the response so that the host response was dominant by six weeks. Control experiments were conducted to show that these effects could not be explained by allotype or isotype-directed suppression. The cellular basis of these differences was investigated further by studying the rate of repopulation of different B cell compartments in these chimeras by newly formed host and mature donor B cells. The results indicate that the onset of host antibody production to the TI-2 antigen closely correlated with the appearance of host B cells in the marginal zones of the spleen, whereas good TD host anti-2,4-dinitrophenyl responses antedated the appearance of host B cells in this compartment. These results are discussed in relation to other data implicating marginal zone B cells in responses to TI-2 antigens.

Animals↗

Conflict between classifications based on free thyroxine and thyroid stimulating hormone concentrations in thyroxine-treated patients.

The use of free thyroxine assay as the basis for monitoring patients on thyroxine replacement therapy was assessed. Patients with normal free thyroxine levels were divided into sub-groups on the basis of serum TSH levels. Of these, patients with normal TSH levels had higher serum free thyroxine and free 3,5,3'-triiodothyronine concentrations than patients with elevated TSH levels. No significant differences were seen in the level of duration of replacement therapy. Patients were almost equally divided between the high and normal TSH sub-groups. It was concluded that free thyroxine assay had little role to play in the monitoring of these patients.

Humans↗

Class and subclass anti-pneumococcal antibody responses in splenectomized patients.

Antibody titres against pneumococcal capsular and cell wall antigens and the immune response to polyvalent pneumococcal vaccine were measured in 21 splenectomized patients and 12 healthy controls. Most individuals possessed anti-pneumococcal capsular polysaccharide antibodies of IgG, IgA and IgM classes. The anti-capsular IgG was predominantly of the IgG1 and IgG2 subclasses; only occasional individuals had any detectable titre in IgG3 or IgG4 subclass. Most individuals responded to immunization with Pneumovax. There was no clear difference between groups of control and splenectomized subjects, although three of the splenectomized patients had undetectable pre-immunization anti-capsular titres in one or more subclass which failed to rise following immunization. All subjects tested had anti-phosphocholine antibodies in IgG, IgA and IgM classes with the exception of a single splenectomized patient who lacked detectable anti-phosphocholine IgM. Pre-immunization titres where similar in healthy controls and splenectomized patients. There was no demonstrable rise in anti-phosphocholine titre following immunization with Pneumovax.

Adult↗