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Biomedical subjects

M G Beale

Publications and source records attributed to M G Beale.

At least 19 recordsLinked to original sources
PubMed1986

Familial abnormalities of lymphocyte function in a large Sjögren's syndrome kindred.

A large kindred (32 members), whose proband had primary Sjögren's syndrome, was investigated to ascertain whether abnormalities of lymphocyte function were present in family members of patients with Sjögren's syndrome. Ten members of the kindred with autoimmune diseases, 17 blood relatives, 5 spouses, and 32 matched controls were studied. Concanavalin A induced suppression of pokeweed mitogen stimulated immunoglobulin synthesis was decreased in patients and blood relatives both with and without autoimmune diseases. Elevations of the mean T4/T8 ratio, due to decreased numbers of suppressor/cytotoxic lymphocytes, were present in both the disease group and the blood relatives. These abnormalities occurred independently of HLA and were not necessarily associated with autoantibodies.

Autoimmune Diseases↗
PubMed1985

The influence of autologous cell interactions on spontaneous and pokeweed mitogen-induced immunoglobulin production.

Both helper- and suppressor-T-cell activities are generated in the autologous mixed lymphocyte reaction and in pokeweed mitogen (PWM)-stimulated cultures. The addition of low numbers of irradiated non-T cells enhance while high numbers suppress spontaneous and PWM-stimulated IgG synthesis by autologous cells. Monocytes are the principal inducers of suppression and exert their influence within the first 24 hr of culture. Suppression in association with PWM stimulation is nonspecific in nature, T-cell mediated, partially radiosensitive, and resistant to hydrocortisone. Neither indomethacin nor dibutyryl cyclic AMP reverses monocyte-related suppression. These findings suggest that the outcome of in vitro Ig synthesis assays is critically dependent upon monocyte-T-cell interaction.

Antibody Formation↗
PubMed1983

Synthesis and secretion of IgA, IgM, and IgG by peripheral blood mononuclear cells in human disease states, by isolated human intestinal mononuclear cells, and by human bone marrow mononuclear cells from ribs.

We have examined the secretion of IgA, IgM, and IgG by isolated human intestinal MNC, human bone marrow MNC from rib specimens, and peripheral blood MNC from patients with CD, UC, SLE, and HSP. "Normal" control intestinal MNC exhibited high spontaneous secretion of IgA, whereas intestinal MNC from UC and CD patients exhibited only modest increases in IgA secretion. Peripheral blood MNC from patients with CD, UC, SLE, and HSP exhibited markedly elevated spontaneous secretion of immunoglobulins in general and IgA in particular. Pure human bone marrow MNC exhibited high spontaneous secretion of IgA with modest amounts of IgG and normal IgM being secreted. The addition of PWM to cultures in which high spontaneous synthesis and secretion of immunoglobulins was seen, resulted in no further enhancement, and in some instances suppression, of antibody secretion. In patients with autoimmune disease, there appeared to be dual immunoregulatory defects, one involving a lack of normal T-suppressor cell functional capabilities for spontaneous antibody synthesis, and the other the presence of PWM activable T-suppressor cells. In human bone marrow, we have identified MNC that secrete suppressor factors in the presence of PWM and that are capable of inhibiting antibody synthesis and secretion. Column separation using Sephacryl S-300 revealed that the IgA secreted by "normal" control intestinal MNC is predominantly dimeric, whereas the IgA secreted by human bone marrow MNC is predominantly monomeric. Furthermore, mucosal MNC from patients with CD and uninvolved intestine from patients with UC exhibited patterns similar to control intestinal MNC, being predominantly dimeric IgA with some monomeric IgA secreted. By contrast, intestinal MNC from patients with UC had a decreased proportion of dimeric IgA and increased proportion of monomeric IgA, thus indicating that IgA precursor B-cells may have migrated into the intestine from extraintestinal sites, or that the normal dimeric IgA-secreting cells in the intestine had begun secreting increased proportion of monomeric IgA as well. These studies indicate that homing patterns and/or immunoregulation of IgA-secreting cells are altered in human intestine, bone marrow, and autoimmune disease states.

Antibody-Producing Cells↗
PubMed1983

Immunoglobulin synthesis by peripheral blood mononuclear cells in minimal change nephrotic syndrome.

The spontaneous and pokeweed mitogen (PWM)-induced immunoglobulin synthesizing activities of circulating mononuclear cells (MNC) from minimal change nephrotic syndrome systemic (MCNS) patients in relapse (N = 13) were compared with those of patients in remission (N = 9), patients with active systemic lupus erythematosus (SLE, N = 9), and healthy controls (N = 17). Cumulative amounts of IgM, IgG, and IgA secreted over a 12-day culture period were determined in a solid phase radioimmunoassay. Mean levels of spontaneous immunoglobulin production in control cultures did not exceed 370 ng/ml. In contrast unstimulated IgM, IgG, and IgA synthesis among MCNS patients in relapse averaged 588, 1258, and 2665 ng/ml, respectively. The majority of patients exhibited synthetic activities that equalled or exceeded those of patients with active SLE. Spontaneous immunoglobulin production declined by 80 to 97% in three patients restudied in stable remission. A fourth patient with frequent relapses maintained high rates of synthesis in remission as well as in relapse. PWM stimulation increased immunoglobulin production in patients in remission and controls but failed to increase or suppressed immunoglobulin secretion in SLE patients and patients in relapse. These results suggest that MNC from MCNS patients in relapse are reversibly activated in vivo.

Adolescent↗
PubMed1982

A rapid miniaturized solid-phase radioimmunoassay technique for secreted immunoglobulins, employing microtiter plates, antibody bound to polyacrylamide beads, and filter strip harvesting.

We have developed a solid-phase radioimmunoassay technique, which allows a large number of samples to be assayed, while minimizing amounts of reagents and technician time. The assay is run in microtiter plates, which results in improved organization, shorter assay set-up time and advantageous miniaturization. On the first day only 3 reagents are required: sample or standard, a 125I-labeled antigen, and an antibody attached to a polyacrylamide bead. After on overnight incubation period, the assay is harvested using a commercial microharvesting apparatus (24 samples/2 min) and placed directly into a gamma counter for counting. In the present study, we have developed the assay to measure secreted IgG, IgM and IgA, and we have compared our results with those of a standard radioimmunoassay technique. This rapid, simple, economical approach should be applicable to the radioimmunoassay of other substances as well.

Acrylic Resins↗
PubMed1982

Pulse methylprednisolone therapy in diffuse proliferative lupus nephritis.

The prognosis of patients with diffuse proliferative lupus nephritis is generally poor, and the majority of patients with this lesion develop progressive deterioration in renal function. Intravenous "pulses" of methylprednisolone have been advocated for the treatment of severe nephritis. In this study, 15 patients with biopsy-proven diffuse proliferative lupus nephritis were treated with oral high-dose prednisone therapy, initially 2 mg/kg/day. They were compared with seven patients with similar renal pathology treated with six daily pulses of methylprednisolone (30 mg/kg/day, not to exceed 1 gm/day), followed by prednisone orally, initially 2 mg/kg/day. There were no deaths in either group and the side effects of therapy were similar in the two groups. Pretreatment GFRs for the pulse and high-dose groups were similar. There was a more rapid improvement in GFR following pulse therapy, but the long-term effects on renal function for the two modes of therapy were the same.

Administration, Oral↗
PubMed1980

Immunosuppressive effects of low doses of glucocorticoids: effects on autologous and allogeneic mixed leukocyte reactions.

The effects of single oral doses of 10, 15, or 30 mg of prednisone on circulating mononuclear cells, autologous MLR, mitogen responses, and allogeneic MLR were studied in healthy volunteers. Doses as low as 10 mg were immunosuppressive, causing diminution of circulating T cells and monocytes, and significant reduction in autologous but not allogeneic MLR responses. These effects were maximal 6 hr after drug administration and gone by 24 hr. Autologous MLR responses were particularly sensitive to the effects of prednisone being significantly and consistently suppressed 2 hr after drug administration, before significant cell redistribution had occurred. Macrophage-enriched stimulating cells were more easily suppressed than responding T cells. Since the autologous MLR may be important in in vivo regulation of immune responses, its reduction by low-dose glucocorticoids may be of clinical relevance. This suppressive effect must be considered in studies of the autologous MLR in patients receiving glucocorticoid therapy.

Adult↗
PubMed1980

Inhibitory factors of lymphocyte transformation in sera from patients with minimal change nephrotic syndrome.

This study was undertaken to establish the specificity and relation to disease activity of serum inhibitors of lymphocyte function in minimal change nephrotic syndrome (MCNS). Sera from 21 children with MCNS were evaluated for their effect on blast transformation of normal human lymphocytes after stimulation with E-PHA, ConA, PWM or allogeneic cell surface antigens (mixed lymphocyte cultures;MLC). Sera from patients in relapse on no medication (n = 12), in relapse on steroids (n = 5), and in remission on steroids (n = 7) were significantly more inhibitory than sera from patients in late remission off steroids (n = 14 both in mitogen induced blast transformation and in MLC. Sera from eight children with other forms of nephrotic syndrome exhibited the same degree of inhibition of E-PHA, ConA, and PWM induced mitogenesis but significantly less inhibition of MLC when compared to 12 MCNS patients in untreated relapse. Thus serum inhibition of mitogen induced blast transformation is not specific for MCNS but occurs in other forms of nephrotic syndrome as well. Conversely, sera from MCNS patients does selectively inhibit MLC. Finally, the inhibitory activity of MCNS sera for both mitogen and cell surface antigen stimulation correlates with the course of the disease.

Adolescent↗
PubMed1979

Congenital glomerulosclerosis and nephrotic syndrome in two infants. Speculations and pathogenesis.

The incidental finding of hyalinized glomeruli in otherwise normal infant kidneys is referred to as congenital glomerulosclerosis. Two infants had extensive glomerulosclerosis manifested by nephrotic syndrome, severe oliguria, and progressive renal failure. Both patients were believed to have had intrauterine infections. These two cases have unequivocally identified congenital glomerulosclerosis as one of the causes of nephrotic syndrome in infancy. In addition, they suggest that extensive glomerulosclerosis in some cases may be a result of congenital infections.

Female↗
PubMed1976

Vitamin D: the discovery of its metabolites and their therapeutic applications.

Our understanding of the role of vitamin D in calcium-phosphorus metabolism has changed considerably in the last decade. Studies performed in tissue culture, animal, and man have firmly established that the natural compound requires hydroxylation in the liver at the C-25 position and in the kidney at the C-1 position to form the biologically active derivative 1,25-(OH)2D3. These hydroxylation reactions are finely regulated to maintain normal calcium-phosphorus homeostasis: We now regard 1,25-(OH)2D3 as a hormone which is released by the kidney during periods of hypocalcemia. This hormone acts on the intestinal mucosa to facilitate calcium absorption and on bone to increase calcium mobilization. Its function in other tissues is still being evaluated. The active metabolites of vitamin D and several closely related analogs have been synthesized. It has been clearly demonstrated that 1,25-(OH)2D3 and 1alpha-OH-D3 promote healing in uremic bone disease. Administration of small amounts of these compounds has corrected the biochemical disturbances in vitamin D-dependency and hypoparathyroidism. Limited clinical experience with 25-OH-D3 and 1,25-(OH)2D3 in children with familial hypophosphatemia has failed to show convincing evidence of a therapeutic effect. Further clinical studies are needed to fully evaluate the therapeutic potential of this new family of compounds.

Animals↗