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Biomedical subjects

T R Poskitt

Publications and source records attributed to T R Poskitt.

At least 19 recordsLinked to original sources
PubMed1987

IgD myeloma with malignant pleural effusion.

We have described a patient with IgD myeloma and pleural effusions in whom biopsy and postmortem examination demonstrated myelomatous pleural involvement with IgD-positive plasma cells. Despite the presence of two uniformly poor prognostic features (IgD type and malignant effusion) at presentation, this patient survived for two years. This is the first case of IgD myeloma with documented malignant pleural effusion reported in the English literature.

Adult↗
PubMed1987

Radiation therapy and the role of red blood cell transfusion.

Based on a survey of fifty radiation therapy departments in this country revealing that a majority transfuse anemic cancer patients to a predetermined hemoglobin level prior to and during radiotherapy, a review of the literature was undertaken to assess whether the potential benefits of such a practice outweigh the very real risks (especially non-A, non-B hepatitis) associated with transfusions. Although the intent of transfusion is to increase tumor oxygenation and thereby reduce the number of radioresistant hypoxic cells, studies in laboratory animals do not support a relationship between the hemoglobin level and the percentage of hypoxic tumor cells in normovolemic anemia, both acute and chronic. Several large studies of carcinoma of the cervix agree that anemia is a poor prognostic feature at presentation and correlates with shorter survival and poorer control of local disease in those patients treated solely with radiation. These findings have been interpreted by many to reflect impairment of tumor oxygenation directly attributable to anemia in the poor responders and has been used to support the recommendation of blood transfusion. An alternative explanation for which considerable supporting data exist is that carcinoma of the cervix associated with anemia is, by nature, a biologically more aggressive subtype and portends a poorer prognosis for reasons other than anemia-related tumor hypoxia. It is concluded that the practice of routinely transfusing all chronically anemic cancer patients prior to radiation therapy is not justified.

Anemia↗
PubMed1986

Simultaneous bilateral ocular metastases from a gastric carcinoma.

Metastatic tumors are the most common intraocular neoplasms. A rare case of adenocarcinoma of the stomach with simultaneous presentation of bilateral intraocular metastases is reported with a review of the literature. The prompt improvement in vision that occurred in this patient following radiation therapy underscores its important role in reducing the visual morbidity of patients with metastatic intraocular tumors.

Adenocarcinoma↗
PubMed1985

Lack of association of rheumatoid factor with either circulating immune complexes or tumor burden in cancer patients.

The frequency of rheumatoid factor (RF) seropositivity and the frequency of association of RF with immune complex (IC) elevation were determined in 72 patients with a variety of solid tumors, in 78 patients with IC-associated diseases, 27 patients with non-IC-associated diseases, and in 31 normal healthy controls. The frequency of RF positivity in cancer patients (31%) was virtually identical to that in patients with IC-associated diseases (28%), and did not differ significantly from that seen in patients with non-IC-associated disease (15%). Whereas IC elevation was clearly related to tumor progress, RF was not. RF and IC status also appeared to be unrelated to each other, not only in cancer patients, but in patients with other diseases as well. The results do not support the concept that RF reflects progressive tumor growth or an immune response to IgG-containing immune complexes.

Antigen-Antibody Complex↗
PubMed1985

Thrombocytopenia of sepsis. The role of circulating IgG-containing immune complexes.

Platelet-associated IgG (PAIgG), circulating IgG-containing immune complexes (ICs), plasma beta-thromboglobulin (beta-TG), and platelet factor 4 (PF-4) levels were assayed in 33 consecutive patients with culture-proved bacteremia. Thrombocytopenia occurred in 18%, and no correlation was seen between platelet count and PAIgG, beta-TG, or PF-4. In contrast, when patients were assigned to groups on the basis of rising or stable counts vs falling counts, a significant increase in the frequency of elevated PAIgG was seen in those with falling platelet counts. Elevated ICs did not correlate with PAIgG, platelet count, beta-TG, or PF-4. The results of this study of patients with uncomplicated bacteremia, although clearly demonstrating intravascular platelet activation and suggesting a pathologic role for elevated PAIgG, do not support the hypothesis that platelet-bound serum ICs are responsible for either phenomenon.

Antigen-Antibody Complex↗
PubMed1985

The automated complete blood cell count. Use of the red blood cell volume distribution width and mean platelet volume in evaluating anemia and thrombocytopenia.

The availability of automated blood cell analyzers that provide an index of red blood cell volume distribution width (RDW) and a mean platelet volume (MPV) has led to new approaches to patients with anemia and thrombocytopenia. The RDW, which measures heterogeneity of the red blood cell population, complements the mean corpuscular volume in the differential diagnosis of anemia based on peripheral blood analysis. The MPV varies inversely but nonlinearly with the platelet count in normal individuals and is of value in assessing platelet production in the thrombocytopenic patient. The clinical applications of the RDW and MPV, which are currently reported on most routine blood cell counts, are discussed.

Anemia↗
PubMed1985

Spurious thrombocytopenia produced by the interaction of rheumatoid factor with antiplatelet antibody.

A patient had spurious thrombocytopenia resulting from a mechanism not previously described. Whereas in prior reports the in vitro phenomenon of platelet clumping has been effected by either EDTA-dependent or temperature-dependent antibodies capable of direct platelet agglutination, neither the IgG nor the IgM fractions of this patient's serum demonstrated such activity. However, agglutination was produced by incubating allogeneic platelets with the IgG fraction followed by a room temperature incubation with the rheumatoid factor-positive IgM fraction. The data support a new mechanism for spurious thrombocytopenia resulting from the interaction of a cold-reactive rheumatoid factor with antiplatelet antibody.

Autoantibodies↗
PubMed1982

Absence of circulating IgG immune Complexes in C57Bl/6 mice with age-associated renal IgG deposits.

The L1210 enzyme-linked immunoassay (ELIA) for circulating immune complexes, previously developed for use in humans, has been adapted for use in mice. The assay detected elevated levels of immune complexes in 100% of NZB/W female mice (6-10 months old) with age-related immune complex-mediated glomerulonephritis. Application of the assay to the serum of one year old C57Bl/6 male mice failed to demonstrate elevated levels of serum immune complexes in spite of the routine finding of renal deposition of IgG plus proteinuria in aged mice of this strain. Since the L1210 ELIA detects all IgG-containing immune complexes, regardless of size or complement fixing capacity, these results suggest that the renal IgG deposits seen in aged C57Bl/6 mice are not derived from circulating IgG immune complexes.

Aging↗
PubMed1981

Immune complexes in hemophilia.

Circulating immune complexes (ICs), assayed by the L1210 enzyme-linked immunoassay, were detected in 48% of patients with hemophilia. A, 50% of patients with von Willebrand's disease, and in none of our patients with hemophilia B. Eighty-five % of the hemophilia A and B patients had mild to moderate disease with only one patient demonstrating a circulating inhibitor. No correlation was found between IC levels and hepatitis B infection, SGOT, disease severity, total quantity of factor VIII or IX infused, time interval from list infusion, or rheumatoid factor positivity. Although the nature of the ICs is not known, the similarity of IC levels between hemophilia A and von Willebrand's disease is discussed with regard to antibodies generated to non-procoagulant portions of the factor VIII molecule.

Adolescent↗
PubMed1981

A quantitative enzyme-linked immunoassay for serum immune complexes.

A sensitive, quantitative, non-complement dependent enzyme-linked immunoassay (ELIA) for human serum immune complexes has been developed utilizing the L1210 murine leukemia cell and peroxidase-conjugated anti-IgG. At end-point O-dianisidine dihydrochloride method was developed which detects as little as 16.45 x 10(-5) purpurogallin units of horse radish peroxidase. The L1210 ELIA requires only five microliters of serum and reproducibly quantitates as little as 55 nanograms of an artificial immune complex standard (heat aggregated IgG). The validity of using aggregated IgG as a standard was demonstrated by the fact that it produced a dose dependent inhibition of binding of a known immune complex (peroxidase-anti-peroxidase) to the L1210 cells whereas monomeric IgG showed no inhibition. Results of the L1210 ELIA are similar to those of the L1210 radioimmune assay (RIA) which we have previously reported. There was no significant difference in mean immune complex levels between the ELIA and the RIA when serums from normal healthy blood donors were tested. A strong correlation (rs equals +0.787) of immune complex levels as determined by the ELIA and the RIA was found in 17 serum samples from patients with disease associated with elevated levels of circulating immune complexes.

Animals↗
PubMed1979

The L1210 assay for immune complexes: application in cancer patients and correlation with disease progress.

Immune complexes (ICs) were determined by the non-complement-dependent L1210 radioimmune assay on 132 serum samples collected from 53 patients with a variety of cancers. Both the mean IC levels and frequency of positive tests were significantly greater in cancer patients (mean = 96 +/- 100 microgram/ml, 46% positive) than in a control group of 67 normal healthy blood donors (mean = 39 +/- 15, 3% positive). When cancer patients were assorted into groups by disease progress, those with large or progressing tumors had significantly higher mean values (136 +/- 129) and frequency of positives (75%) than those with small or regressing tumors (58 +/- 18, 22% positive). In lung cancer patients, IC levels showed a strong inverse correlation (rs = -0.903) with survival time in patients who died, and appeared to be a better prognostic indicator than performance status (Karnofsky scale) at time of diagnosis. Serial IC measurements taken on several patients showed a decrease in levels concomitant with a favorable response to cytoreductive therapy, sustained normal levels during periods of prolonged remission, and a rise to elevated levels with (and sometimes preceding) documentation of new metastases.

Animals↗
PubMed1979

Temperature dependent activation of the alternate complement pathway by an IgG cryoglobulin.

A patient with chronic membranoproliferative glomerulonephritis is presented whose serum contains a monoclonal IgG3 cryoglobulin. The presence of persistent hypocomplementemia suggested the possibility that the cryoglobulin, upon cold-induced precipitation, was capable of activating the complement system. Because visible cryoprecipitation commenced in vitro at 30 degrees C, the patient's serum and normal serum had been added the isolated cryoglobulin were repeatedly cooled to 30 degrees C and rewarmed to 37 degrees C. This reproduction of the in vivo counterpart of blood circulating through an extremity exposed to the cold resulted in activation of C3-proactivator (properdin factor B), C3 cleavage, and a 78% reduction in total hemolytic complement. This study demonstrates that IgG is capable of activating complement via the alternate pathway and reveals a mechanism through which this can occur in vivo; namely, by means of temperature dependent polymerization. In addition, we postulate that episodic complement activation initiated by the cryoglobulin contributed to the development of glomerulonephritis in this patient.

Aged↗
PubMed1978

The L1210 radioimmune assay for detecting circulating immune complexes.

A radioimmune assay for the detection and quantitation of circulating immune complexes has been developed which employs the L1210 murine leukemia cell. The assay is based upon the binding of immune complexes to the L1210 through its Fc receptor followed by quantitation of the complexes with an 125I-labelled anti-IgG. The radioactivity of the cell pellet is referred to a standard curve generated by incubating the L1210 with known amounts of heat aggregated IgG (AIgG). 7S IgG of three species (human, canine, murine) do not bind significantly to the L1210 in contrast to the respective AIgG. The assay readily distinguishes between sera of healthy individuals and sera of individuals (human and canine) with diseases known to be associated with circulation immune complexes (i.e., systemic lupus erythematosus, HBAg positive acute hepatitis). The L1210 radioimmune assay is capable of detecting as little as 5 micrograms of immune complexes per ml of serum in all three species tested. The assay possesses several advantages over those currently employed, the most notable being the ability of the L1210 cell to detect immune complexes irrespective of their complement fixing properties.

Animals↗
PubMed1976

Release into culture medium of membrane-associated, tumor-specific antigen by B-16 melanoma cells.

Serum-free supernatant fluids from monolayer cultures of B-16 mouse melanoma cells were found to contain a soluble membrane associated tumor-specific antigen. The 100,000 g supernatant of the culture fluid induced an antibody response to the B-16 cells both in rabbits and in the mouse strain of origin (C57Bl/6J). Similar supernatant fluids derived from an unrelated cell line (L-929) or from normal C57Bl/6 fibroblasts did not contain the B-16 specific material. Preliminary results indicate that the B-16 specific material is a protein of low molecular weight which is released into the culture fluid chiefly by living cells and, to a lesser extent, by autolysing cells.

Animals↗
PubMed1974

Renal deposition of soluble immune complexes in mice bearing B-16 melanoma. Characterization of complexes and relationship to tumor progress.

Histologic and immunofluorescence studies of the kidneys of mice bearing a progressive melanoma show a proliferative glomerulonephritis associated with immune complex deposition in the mesangium and along the glomerular basement membrane This immune complex disease is distinct from the age-associated disease of the C57BL/6J host strain and the complexes can be shown to consist of soluble tumor antigen and antitumor antibody. Furthermore, the intensity of IgG complex deposition correlates directly with tumor progress (size and metastases) and inversely with mononuclear leukocyte infiltration of the tumor. In vitro assays for lymphocyte cytotoxicity and humoral antibody were found to be less reliable indicators of tumor progress. The possible role of circulating soluble tumor antigen in modifying the immune response to tumors is discussed.

Age Factors↗