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J Gamble

Publications and source records attributed to J Gamble.

At least 109 records · Page 6Linked to original sources

A receptor for antibody on B lymphocytes. III. Relationship to immunoglobulin and ia determinants.

The physicochemical structure of the receptor for antibody (FcR) on B cells and its interrelationship with Ig and H-2 gene complex associated antigens were examined. FcR were found to be sensitive to treatment with phospholipase C and pronase, but resistant to neuraminidase, phospholipase A and chymotrypsin. They would therefore appear to be composed of phospholipoproteins. Several lines of evidence indicated that FcR and Ig receptors were discrete entities: thus, FcR (1) were resistant to chymotrypsin; (2) capped independently of Ig, as demonstrated by means of Fab fragments of anti-Ig, and (3) were closely associated with at least some Ia determinants, which are known to be distinct from Ig determinants. The relationship between FcR and H-2 gene complex associated antigens was confirmed by demonstrating inhibition of binding of aggregates by anti-Ia serum and vice versa. If, however, FcR were capped, anti-Ia serum applied under non-capping conditions was still found to bind diffusely to the great majority of B cells. Although this could be explained in part by the presence of residual FcR, some Ia determinants appeared to be distinct from FcR. The finding of residual FcR after capping with aggregates or immune complexes implied that FcR are a more integral part of the cell membrane than Ig receptors and could therefore act as proreceptors for the latter. Consistent with this was the demonstration of a significant polar distribution of Ig on B cells capped for FcR and then labelled under non-capping conditions with anti-Ig.

Animals↗

H-2 gene complex restricts transfer of delayed-type hypersensitivity in mice.

Sensitized lymphocytes can transfer a state of delayed-type hypersensitivity to soluble protein antigens to naive mice only if donor and recipient share the I-A region of the H-2 gene complex. Identity at the K or D region is not essential. The restriction is unlikely to result from ineffective homing of the injected cells or from their early destruction. It is thought to reflect a requirement for an Ir-gene controlled mechanism which governs effective interaction between sensitized T lymphocytes and antigen presented on the surface of macrophages.

Animals↗

The association of vinyl chloride exposures with morbidity symptoms.

A mail-out questionnaire examined symptoms previously associated with vinyl chloride exposure. Assessment of exposure levels was made by analytical measurement and observation. The resulting statistical analysis revealed a dose-response type of relationship between exposure and certain morbidity symptoms.

Air Pollutants, Occupational↗

A radioisotopic method to measure delayed type hypersensitivity in the mouse. I. Studies in sensitized and normal mice.

Delayed type hypersensitivity (DTH) lesions have been difficult to evaluate objectively in the mouse because they are usually assessed in terms of an increase in footpad swelling or ear thickness. We have developed a radioisotopic method which not only reduces the observer's error but also gives an objective measurement of the cellular activity in the lesions. In brief, 10 mul of the test antigen is injected intradermally into the left pinna and either nothing or the same volume of a control solution into the right. 10 h later, a 2-muCi pulse of 5-iodo-2'deoxyuridine-125I is given intravenously, the ears cut off at the hairline 16 h later and the radioactivity counted in a gamma spectrometer. The following was obtained as evidence that the increased radioactivity of the left pinna over the right was a measure of the extent of a DTH response: (1) the ear reaction was delayed in mice without serum antibodies becoming maximum at 24 h; (2) there was a mononuclear cell infiltration in the left pinna and autoradiographs revealed radioactive label bound to these cells; (3) athymic mice could not develop a 24-hour ear reaction, and (4) antigens known not to activate T cells did not elicit the ear response. Cell transfer studies will be described in a subsequent paper. Different sensitization regimes were required with different antigens in order to obtain the highest levels of DTH as tested by the ear response, and the maximal ear reaction occurred at different days. The ear reaction showed the specificity expected of a DTH response.

Animals↗

A radioisotopic method to measure delayed type hypersensitivity in the mouse. II. Cell transfer studies.

Sensitized lymphoid cells could transfer to normal non-sensitized (naive) mice by 24-48 h after antigen challenge in the ear, the capacity to incorporate, at the site of antigen deposition, 5-iodo-2'deoxyuridine-125I in amounts significantly above those obtained in control mice. This was associated with a mononuclear cell infiltration in the pinna. In contrast to lymphoid cells, serum antibodies were unable to transfer a 24- or 48 hour ear reaction. The cells responsible were T lymphocytes as demonstrated by successful transfer following enrichment for T lymphocytes, and abrogation of transfer following treatment with anti-theta serum and complement. Transfer was achieved whether the naive recipients were normal, T-cell deprived, pretreated with cyclophosphamide, or lightly irradiated but not when they were heavily irradiated. Adoptive transfer of the 24-hour ear response was demonstrated with three different antigenic systems. The time-response curves were different with each system although peak reactions were obtained 5 days after sensitization of the donors in all cases. The specificity patterns of the 24-hour ear reaction on transfer were similar to those obtained in the sensitized donors. The results of these studies indicate that the radioisotopic ear method can, under defined conditions, demonstrate the existence of a state of delayed type hypersensitivity in the donors.

Animals↗

A subpopulation of T cells bearing Fc receptors.

A wide range of cell populations were examined for Fc receptor (FcR)-bearing T cells: thymus, spleen, peritoneal cells, and T cells activated to H-2 antigens in spleen (ATC spleen) and in thoracic duct lymph (T-TDL). In addition, B lymphocytes from thoracic duct lymph of athymic nude mice and a Thy-1-positive, FcR-positive thymoma served as control cell populations. Reagents used were aggregates of human gamma-globulin and of various mouse myeloma proteins (IgG1, IgG2a, IgG2b), radioiodinated antigen-antibody complexes, and sheep erythrocyte antibody rosettes. Labeling techniques involving radioautography and immunofluorescence were used to demonstrate FcR by one of the above reagents and to identify T cells either by staining with anti-Thy-1.2 or by a specific rabbit anti-mouse T cell serum, or by failure to stain with anti-mouse immunoglobulin. In some experiments phagocytic cells were removed whereas in others they were identified by their capacity to engulf latex particles. Approximately 25% of cells with T cell markers were FcR-bearing cells in thymus, normal spleen, and peritoneal cavity, and 17% in ATC spleen. FcR on T cells in peripheral lymphoid tissues were detectable by aggregates of HGG and myeloma proteins and by radioiodinated immune complexes. Those on T cells in thymus were revealed only by aggregates of HGG. Circulating T cells (T.TDL) failed to display FcR: a) despite the use of a wide range of the above labeling techniques, each of which was shown to detect FcR on other T cells, thymoma cells, and B cells, and b) even after removal of Ig associated with their cell membranes. In contrast to B cell FcR which bound IgG1 preferentially, those on T cells bound both IgG1 and IgG2, raising the possibility that the FcR on T cell is distinct from that on B cell. It is concluded that FcR-bearing T cells represent a subpopulation of cells within the thymus and the secondary lymphoid tissues.

Animals↗

Frequency-dependent differences in the responses of the capsular and vascular smooth muscle of the spleen of the dog to sympathetic nerve stimulation.

1. The responses of the capsular and vascular smooth muscle to splenic nerve stimulation have been studied simultaneously in the isolated blood-perfused dog's spleen.2. Low frequencies of splenic nerve stimulation (below 1.0 Hz) caused pronounced contraction of the splenic capsule but little or no constriction of the splenic vascular bed.3. Splenic contraction reached a maximum at stimulation frequencies of 1-2 Hz; maximum vasoconstriction occurred at frequencies of 7-10 Hz.4. The separation of responses of the capsular and vascular smooth muscle was mimicked by close arterial infusions of either adrenaline or noradrenaline.5. The maximum responses of the splenic vascular smooth muscle to nerve stimulation, adrenaline and noradrenaline were not significantly different.6. The maximum reduction in spleen volume to sympathetic nerve stimulation was significantly greater than the maximum response to close arterial noradrenaline.7. The maximum contractions of the spleen to adrenaline and noradrenaline were not significantly different. At concentrations producing submaximal responses adrenaline was more potent than noradrenaline.8. It is suggested that the frequency dependent separation of smooth muscle responses to sympathetic nerve stimulation is due to a different sensitivity of the capsular and vascular smooth muscle to the chemical transmitter noradrenaline.9. The results are discussed in the context of the function of the dog's spleen.

Animals↗

Capillary filtration coefficient in type II (non-insulin-dependent) diabetes.

Changes in microvascular permeability may be important in the pathogenesis of diabetic microangiopathy. In order to assess microvascular fluid permeability, the capillary filtration coefficient was determined in the forearm of 24 normotensive type II diabetic patients with minimal evidence of microangiopathy and satisfactory glycemic control, and 24 age- and sex-matched control subjects, using a sensitive strain gauge plethysmographic system. The median capillary filtration coefficient was not significantly different in the type II diabetic patients and control subjects [5.3 (3.2 - 9.1) x 10(-3) mL.min-1.100 g tissue-1.mm Hg-1 versus 5.4 (3.5 - 8.0) x 10(-3) mL.min-1.100 g tissue-1.mm Hg-1, p = 0.98)]. There were no correlations between capillary filtration coefficient and age, blood pressure, body mass index, duration of diabetes, glycemic control, or the presence of microvascular complications. These findings contrast with type I diabetes, where capillary filtration coefficient is elevated at an early stage in the disease, and lend support to the theory that there are differences in early microvascular functional abnormalities between type I and type II diabetes.

Adult↗

Prevalence of cyclic changes in limb volume (volumotion) of male patients with knee injury and the effects of ischemia/reperfusion due to tourniquet.

During surgery of limbs tourniquet up to a maximum of 2 h is frequently applied which may cause ischemia/reperfusion injury (IRI). During this condition the presence of vasomotion may have consequences for the perfusion and nutritive state of the tissues. We used a noninvasive plethysmographic method to investigate periodic changes in limb circumference (volumotion) in healthy male patients (n = 24) undergoing surgery for knee injury. To facilitate surgery a tourniquet was applied to the thigh, which caused an IRI of the leg. Results are given as mean of all values +/- SEM. Immediately after tourniquet release (duration 57.75 +/- 5.19 min) blood lactate levels in the femoral vein increased significantly from 1.40 +/- 0.08 to 2.59 +/- 0.20 mmol/l (p < 0.001) and pH fell from 7.39 +/- 0.01 to 7.32 +/- 0.01 (p < 0.001). Preoperatively 10 out of 24 patients (42%) showed signs of volumotion on the injured leg with a periodicity ranging from 0.8 to 6.9 cycles/min, whereas none showed volumotion in the control leg (p < 0.001). In the second measurement, taken after surgery and reperfusion while peripheral sympathetic nerves were blocked, 7 out of 18 patients (39%) showed volumotion on the injured leg and 0 on the control leg (p < 0.004). 6 h after IRI, volumotion was observed in 11 out of 17 patients (65%) on the injured leg and in 1 patient (6%) on the control leg (p < 0.001). The mean volume change in the patients with volumotion on the injured leg was 0.057 +/- 0.007 ml/100 ml tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A trouble shared.

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Adaptation, Psychological↗