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Biomedical subjects

R Hall

Publications and source records attributed to R Hall.

At least 379 records · Page 21Linked to original sources

Nuclear morphology and morphometry of B-lymphocyte transformation. Implications for follicular center cell lymphomas.

One of the major tenets of current non-Hodgkin's lymphoma classifications is the relationship of morphologic subtypes to stages in the sequence of normal B-lymphocyte transformation occurring in the germinal follicle. To test this hypothesis, quantitative morphometric image analysis was carried out on in vivo and in vitro samples of mouse splenic lymphocytes in which transformation was induced by bacterial lipopolysaccharide (LPS), a specific B-cell mitogen. The results were compared with a similar analysis of germinal center lymphocyte populations of normal human spleen. In the in vivo mouse model, initial stages of B-cell transformation were detectable as early as 4 hours after LPS injection, and the process was essentially fully developed by 48-72 hours. Quantitative evaluation revealed that the majority of nuclear profiles were nearly spherical or only slightly eccentric and that no major alteration in nuclear contour occurred during any phase of the progressive increase in nuclear size following mitogen-induced lymphocyte transformation. In fact, in this system, B lymphocytes with a nuclear profile cleft of greater than or equal to 0.4 mu accounted for only 3% of the combined unstimulated and LPS-activated population assessed (N = 9936). This compared with normal human spleen, in which 16% of germinal center lymphocyte populations had similarly cleft nuclear profiles. Sequential alterations in the organization of condensed chromatin occurred concomitant with gradual nuclear enlargement during mitogen-induced mouse spleen lymphocyte transformation. A comparative morphologic and morphometric assessment of nuclear profiles of lymphocyte populations in germinal centers of normal human spleen provides indirect evidence for a similar pattern of nuclear alterations in human B lymphocytes. Autoradiographic data obtained from LPS-activated mouse splenic lymphocytes indicate that nuclear morphologic aspects of the transformation process can occur entirely within the G1 phase of the cell cycle. The results of this study suggest that subtypes of non-Hodgkin's lymphoma largely composed of neoplastic lymphocytes with extensively convoluted or cleft nuclei do not reflect a morphologic stage in the transformation of normal lymphocytes. In addition, the heterogeneous nuclear forms of follicular center cell lymphocytes would appear to result from parallel transformation processes involving cleaved and noncleaved nucleated lymphocytes and not the sequential pathway proposed by Lukes and Collins.

Animals↗

Thyroglobulin uptake and presentation by macrophages in experimental autoimmune thyroiditis.

Macrophage uptake and presentation of thyroglobulin (TG) were investigated in rats with experimental autoimmune thyroiditis induced by immunization with TG and adjuvant. Peritoneal macrophages were shown to take up radiolabelled TG and this did not depend on the presence of thyroiditis in the animal or on the strain of rat used. Cell-associated antigen was largely unaffected by trypsin. Macrophages primed in vitro with TG produced a rise in the circulating TG autoantibody levels of convalescent animals when given intravenously (unlike free antigen), but did not induce disease in virgin animals. These findings show that macrophages can bind and present TG and suggest that this process may perpetuate otherwise transient autoimmune reactions.

Animals↗

A short-term-culture ELISA system to detect IgG and autoantibody synthesis by human lymphocytes.

A simple combined culture and assay system for small numbers of human lymphocytes is described which permits rapid detection of immunoglobulin adherent to 96-well plates after 18 h culture, by means of an enzyme-linked immunosorbent assay (ELISA). The method is capable of detecting thyroglobulin antibody secreted by cells obtained from fine needle aspiration of the thyroid and therefore allows investigation of B cells activated in vivo from different sites by quantitation of the amount of immunoglobulin or antibody secreted.

Antibody Affinity↗

Reduced dopaminergic inhibition of thyrotrophin release in states of physiological hyperprolactinaemia.

We have tested the hypothesis that physiological puerperal hyperprolactinaemia may be secondary to reduced hypothalamic dopaminergic inhibition of prolactin (PRL) release. Nine post-partum females with physiological hyperprolactinaemia (aged 19-40 years; mean basal PRL +/- SE, 2099 +/- 257 mU/1, range 1002-3762 mU/1) were studied and results compared with fourteen normoprolactinaemic females (basal PRL less than 400 mU/1; aged 18-36 years). Puerperal hyperprolactinaemic females showed a reduced TSH response to dopamine (DA) receptor blockade with metoclopramide (10 mg i.v.) compared with normal females over a 60-min period following drug administration (total incremental TSH change, mean +/- SE, mU/1; 0.5 +/- 0.3 v. 3.1 +/- 1.0 P less than 0.005). This finding of reduced dopaminergic inhibition of TSH release in females with physiological puerperal hyperprolactinaemia supports the view that an overall reduction in hypothalamic dopaminergic tone may contribute towards hyperprolactinaemia in post-partum women.

Adult↗

Hyperprolactinaemia in men-response to bromocriptine therapy.

Men with hyperprolactinaemia present with large tumours. Conventional therapy with surgery and/or irradiation is unsatisfactory, with up to 100% of patients remaining hyperprolactinaemic (or subsequently developing pituitary insufficiency). In view of reports of bromocriptine-induced regression of prolactinomas, eight consecutive male hyperprolactinaemic patients with impotence and/or symptoms related to local tumour effects were treated with bromocriptine 20 mg daily as sole therapy for 3-11 months. Symptoms were relieved partly or completely in seven patients and serum prolactin was restored to normal or near normal in all men. Serum thyroxine and plasma cortisol response to hypoglycaemia became normal in two men who had subnormal values before therapy. Mean serum growth hormone response to hypoglycaemia rose significantly as did plasma testosterone concentrations. Evidence of tumour regression, sometimes massive, was seen in the six patients who underwent repeat radiology. The symptomatic relief and biochemical and radiological improvement in these patients indicate that bromocriptine therapy may now be the treatment of choice for hyperprolactinaemic men with large tumours.

Adult↗

Inpatient treatment of prolapsing piles: cryosurgery versus Milligan-Morgan haemorrhoidectomy.

A comparative retrospective study, based on clinical assessment and questionnaire analysis, of 97 patients treated by cryosurgical haemorrhoidectomy and 99 patients treated by Milligan-Morgan haemorrhoidectomy, at 4-year average follow-up, has shown that 70 per cent of patients in each group derived complete and lasting relief from their symptoms. Two patients in each group required further treatment. There was no significant difference between the numbers who remembered severe, moderate or mild pain, or in its duration, although fewer cryosurgical patients required opiates. Postoperative discharge ceased in 70 per cent of patients within 2 weeks. When skin tags remained, they were usually inconsequential. Anal stenosis following cryohaemorrhoidectomy did not occur, and has not been reported. Cryohaemorrhoidectomy gave results equal to Milligan-Morgan haemorrhoidectomy in patients with prolapsing piles, with fewer complications, and has the economic advantages of less time in hospital (P less than 0.01) and less time off work (P less than 0.01).

Cryosurgery↗

Effects of dopaminergic nucleus accumbens lesions on the acquisition of schedule induced self injection of nicotine in the rat.

Data from recent experiments show that dopaminergic depletion of the nucleus accumbens septum (NAS) decreases the frequency of schedule induced drinking and wheel running. In the present experiment a group of 8 rats with 6-OHDA lesions in the NAS showed a significantly lower rate of schedule induced nicotine self injection than sham operated controls. These findings extend the number of schedule induced behaviors which appear to depend for their occurrence on an intact dopamine system in the NAS.

Animals↗

Phorbol myristate acetate inhibits immunoglobulin synthesis by human peripheral blood lymphocytes.

Phorbol myristate acetate (PMA), a known lymphocyte mitogen, has been shown to inhibit immunoglobulin synthesis by human peripheral blood lymphocytes. This effect occurs with low concentrations of the agent and following only 12 h contact with the lymphocytes. PMA was also capable of preventing pokeweed mitogen stimulation of lymphocytes. These experiments suggest that PMA prevents the complete differentiation of B-cells into plasma cells capable of secreting immunoglobulin.

B-Lymphocytes↗

Evidence that the porcine thyrotropin (TSH) receptor contains an essential disulphide bridge.

The effects of reducing agents on membrane bound and detergent solubilised porcine TSH receptors have been investigated. Both 2-mercaptoethanol and dithiothreitol appeared to inhibit the TSH-binding activity by a direct effect on the TSH receptor itself and Scatchard analysis suggested that this was primarily due to an alteration in TSH-binding capacity. In addition, some binding activity could be recovered by reoxidation of reduced receptor preparations. These results suggest therefore that the porcine TSH receptor contains an essential disulphide bridge.

Animals↗

Salivary cortisol assays for assessing pituitary-adrenal reserve.

Cortisol concentrations were determined in matched samples of plasma and saliva from patients and healthy volunteers throughout the course of standard tests of pituitary and adrenal reserve. During insulin tolerance tests the percentage incremental changes in cortisol concentrations in saliva were strictly comparable with those in plasma and showed less inter-subject variance. The clinical decision taken with regard to the integrity of the pituitary-adrenal axis was the same whether plasma or salivary cortisol was measured. In the short tetracosactrin test changes in salivary cortisol reflected those in plasma and patients with loss of adrenal responsiveness would have been diagnosed as such using either measurement. In normal subjects, the circadian rhythm in salivary cortisol concentrations exactly paralleled that in plasma. Absence of the circadian rhythm in cases of hypercortisolism was seen as well in saliva as in plasma. Assays for salivary cortisol therefore provide information which is as clinically useful as that of plasma determinations. Since salivary cortisol concentrations were shown to reflect the free, biologically active fraction in plasma, salivary assay may, in selected cases, provide results of greater diagnostic significance than plasma total concentrations.

Adult↗

Childhood acromegaly successfully treated with interstitial irradiation using yttrium-90.

A child with a growth hormone producing tumour presented at the age of 4 1/2 years. The onset of the disease was at 18 months of age. Treatment was given with three doses of interstitial irradiation using yttrium-90 implants. There were no local complications from the procedures. Now, 11 years after diagnosis, she is asymptomatic, of normal appearance, and her height and the size of the pituitary fossa are normal. Growth hormone levels are almost normal, thyroid function is intact, and she is maintained on prednisone and sex hormones.

Adenoma, Acidophil↗

Coeliac disease, splenic function, and malignancy.

Blood films from 41 cases of coeliac disease complicated by malignancy were examined and evidence of hyposplenism found in 12 cases (29%). This is similar to the proportion of adult coeliacs without malignancy who have hypoplenism and it is concluded that impaired splenic function is not associated with the development of malignancy in coeliac disease.

Adult↗