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Biomedical subjects

D E Joshua

Publications and source records attributed to D E Joshua.

At least 55 records · Page 3Linked to original sources
PubMed1989

Multiple myeloma: evidence that light chains play an immunoregulatory role in B-cell regulation.

Supernatants from human lymphoblastoid and plasma cell lines were added to cultures of normal cells stimulated with pokeweed mitogen (PWM) with the aim of providing an in vitro model for light chain isotype suppression (LCIS). Supernatants from the kappa-secreting cell line LICR-LON-HMY2 were specifically able to block the secretion of kappa-associated immunoglobulin and supernatants from the lambda-secreting cell line U266 were specifically able to block the secretion of lambda-associated immunoglobulin without any effect on the secretion of the other light chain isotype. Supernatant from a human leukemia line, HL60, did not block either kappa or lambda immunoglobulin secretion. Purging studies where kappa or lambda light chains were removed from supernatants of these cell lines suggest that this is a direct effect of light chain and not due to any other nonspecific inhibitory material which may be present.

B-Lymphocytes↗
PubMed1988

Fulminant postsplenectomy sepsis.

The vital role of a normally-functioning spleen in a host's defence against circulating microorganisms has been realized for many years. The fulminant clinical course that characterizes infection with encapsulated microorganisms in asplenic patients is highlighted in these cases of severe pneumococcal sepsis in two patients, 10 and 13 years after splenectomies for idiopathic thrombocytopenic purpura. Approaches to the acute management of septic episodes and preventive measures are discussed. Pneumococcal vaccination reduces the incidence of infection effectively in asplenic patients and has a low complication rate. Penicillin by mouth is also efficacious in this situation, but patient compliance is low. Our current practice is to offer pneumococcal vaccination to all patients who have undergone splenectomy in the past and to administer the vaccine two weeks before elective splenectomies. Asplenic patients should be educated about the potential dangers of a septic episode and should be urged to seek an early medical consultation when this occurs.

Acute Disease↗
PubMed1988

Multiple myeloma: relationship between light chain isotype suppression, labelling index of plasma cells, and CD38 expression on peripheral blood lymphocytes.

In this study we have investigated the relationship between the labelling index of plasma cells, the expression of CD38 positive lymphocytes in the peripheral blood, and light chain isotype suppression. This study confirms the relationship between plateau-phase disease and light chain isotype suppression (LCIS) and documents an inverse relationship between LCIS and CD38 positive lymphocytes (.001 less than P less than .01), which is similar to the relationship we have described with the expression of CD10 positive lymphocytes. PCA-1 is rarely expressed in the peripheral blood of patients with myeloma and does not fulfill a role as a marker of active vs. stable disease. There is no relationship between the labelling index of plasma cells and LCIS, because many patients can enter a stage of progressive disease and yet have a labelling index of less than 1% at that time, although a labelling index less than 1% is present in the majority of patients with LCIS. beta-2-microglobulin (beta 2M) also fails to differentiate these two phases of disease in myeloma and does not have a relationship with LCIS, CD38 expression, or CD10 expression. These data suggest that myeloma, like chronic granulocytic leukemia (CGL), can be considered as having two phases of disease: a stable or chronic phase disease, as identified by the presence of LCIS, the absence of CD10 and CD38 positive lymphocytes in the peripheral blood, and a low labelling index, and progressive disease, which is associated with the loss of LCIS and of, CD10 and CD38 positive lymphocytes in the peripheral blood and a high labelling index, although in many cases of progressive disease, the labelling index may also be low. beta 2M does not differentiate between these states.

ADP-ribosyl Cyclase↗
PubMed1988

Post bone marrow transplant sera and persisting mast cell colonies.

Serum samples were collected from eight recipients of allogeneic bone marrow transplants (BMT) following the normalization of peripheral blood counts. Three patients (11 samples) were in the early engraftment period (less than 6 months post-BMT) and still receiving cyclosporin A or methotrexate and the remaining five patients (18 samples) were in stable engraftment (12-84 months post-BMT) and not on immunosuppressive therapy. All post-BMT serum samples supported the growth of increased numbers of mast cell colonies in long-term agar cultures when compared with normal controls (p less than 0.025-0.005), irrespective of the time from BMT or the presence of clinical graft-versus-host disease (GVHD). In contrast, the numbers of neutrophil, monocyte and eosinophil colonies were equivalent in test and control groups. It is proposed that post-BMT sera contain higher levels of a mast cell stimulating activity(s) than does normal sera. Such increased levels might be associated with clinical or subclinical GVHD.

Blood Physiological Phenomena↗
PubMed1987

Immunoregulation and prognosis in myeloma.

In patients in the plateau phase of myeloma, expression of the light-chain isotype concordant with the malignant paraprotein on peripheral-blood lymphocytes is suppressed. This light-chain-isotype suppression (LCIS) is lost when the disease becomes progressive. LCIS is identified by quantifying kappa and lambda cells in peripheral blood in an indirect immunofluorescence assay. In 27 patients presenting with myeloma, the prognosis was significantly better for patients with LCIS at presentation than for those without. Bone-marrow mononuclear cells, studied in 7 patients with myeloma and LCIS in peripheral blood, did not show LCIS.

B-Lymphocytes↗
PubMed1987

Multiple myeloma: the relationship between CALLA (CD10) positive lymphocytes in the peripheral blood and light chain isotype suppression.

This study describes the presence of small numbers of common acute lymphocytic leukaemia antigen (CALLA, CD10)-positive lymphocytes in the peripheral blood of patients with multiple myeloma. A significant correlation (0.001 less than P less than 0.01) was found between the lack of light chain isotype suppression (LCIS), which is characteristic of progressive myeloma, and the presence of CALLA-positive lymphocytes. Sixty patients with multiple myeloma, four with benign monoclonal gammopathy (BMG) and seven with solitary plasmacytoma (SP) were monitored in this study. Nineteen of the patients with multiple myeloma demonstrated LCIS, of which only three were found to have CALLA-positive lymphocytes. Of the 41 patients with multiple myeloma who did not have LCIS, 20 (49%) had CALLA-bearing lymphocytes. None of the patients with BMG or SP demonstrated LCIS or were found to have CALLA-bearing lymphocytes in their blood. Forty-four of the patients with multiple myeloma were also monitored for serum beta-2-microglobulin (SB2M levels. There was no correlation between the SB2M and either LCIS or CALLA-positivity. Detection of CALLA-positive lymphocytes in the blood of patients with multiple myeloma may be an early marker of the onset of progressive disease. The correlation of CALLA expression on lymphocytes with lack of LCIS provides further evidence for the operation of immunoregulatory systems in these patients.

Antigens, Neoplasm↗
PubMed1987

Multiple myeloma: light chain isotype suppression--a marker of stable disease at presentation.

Prognosis in multiple myeloma (MM) is related to the establishment of an immunologically and kinetically characteristic plateau phase. Patients who present with this state may not benefit from immediate chemotherapy. We assessed 20 patients with MM who were staged according to the Salmon and Durie classification at diagnosis and monitored throughout the course of their disease. Patients with a lambda paraprotein and a kappa/lambda lymphocyte ratio in the blood greater than 4.0 were considered to demonstrate light chain isotype suppression (LCIS). Similarly, patients with a kappa paraprotein and a kappa/lambda ratio of less than 0.55 were also considered to have LCIS (1). 14 patients had LCIS; of these, 6 were classified as stage IA, 2 as stage IB, 3 as stage IIA, and 3 as stage IIIA. 6 patients did not have LCIS; 3 were classified as stage IIA, 1 as stage IIIA and 2 as stage IIIB. 10 patients with LCIS were assessed for treatment benefit following administration of melphalan and prednisone, as defined by a fall in the serum paraprotein level of greater than 50% over 6 months. In 8 patients the serum paraprotein levels did not fall, and the patients remained in good health without clinical deterioration. Thus LCIS at presentation may indicate patients in whom treatment can be safely deferred or in whom aggressive therapy is not indicated.

Antibodies, Monoclonal↗
PubMed1986

Early supradiaphragmatic Hodgkin's disease. High-dose gallium scanning obviates the need for staging laparotomy.

Experience with 16 sequential patients with Stage IA/IIA supradiaphragmatic Hodgkin's disease who had no evidence of intra-abdominal disease using high-dose gallium and computerized tomography scanning is reported. Subsequent staging laparotomy also was negative in all these patients and did not alter management decisions. It is suggested that high-dose, whole-body gallium scanning and other noninvasive staging procedures give reliable data for therapeutic decisions.

Adult↗
PubMed1986

A phase I-II study of cytosine arabinoside, daunorubicin, and VP16-213 in adult patients with acute non-lymphocytic leukemia.

The combination cytosine arabinoside (ara-C), daunorubicin, and VP 16-213 was studied in 28 patients with acute non-lymphocytic leukemia to define the toxicity of the combination and assess its efficacy. Of 21 previously untreated patients, 16 (76%) achieved a complete response (CR) with the median remission duration not reached but exceeding 25 weeks. For CR patients, the median number of days with neutrophils less than 500/microliter was 19. The median survival for patients with CR is 60 weeks. Two of seven previously treated patients achieved CR for 11 weeks and in excess of 36 weeks, respectively. At the initial VP16-213 dose of 100 mg m-2 per day for seven days, severe stomatitis was seen in 38% of courses but was less with dose reduction to 75 mg m-2 per day for seven days. Other toxicity was similar to previous experience with ara-C and daunorubicin alone.

Acute Disease↗
PubMed1986

Complications associated with indwelling venous Hickman catheters in patients with hematological disorders.

During a 28 month period, 77 Hickman catheters were inserted in 66 patients with hematological disorders. Complete follow-up was possible for 72 catheter insertions. Catheters remained in situ for a median period of 77 days (range 5-474 days). Fourteen (19%) catheters required removal because of complications which included sepsis, blockage, or displacement. Catheter-related infection was the major complication and Staphylococcus epidermidis and diphtheroids (Corynebacterium species) were the organisms most commonly isolated.

Adolescent↗
PubMed1985

Some studies with a monoclonal antibody directed against human fibrinogen.

Some properties of a monoclonal antibody generated against the fibrinogen component of a factor VIII preparation were investigated. The antibody bound with equal affinity in solid phase radioimmunoassays to fibrinogens isolated from both normal patients and patients with von Willebrand disease. It reacted in a sensitive immunoassay of plasma fibrinogen. The specificity of the antibody was confined to the parent molecule with no significant inhibition of fibrinogen binding by the fibrinogen degradation products (FDPs) X, Y, D, or E. The antibody had no significant effect on the activated partial thromboplastin time and prothrombin time of normal plasma. However, it prolonged the thrombin time as determined by the Clauss chronometric fibrinogen method. During fibrinogen lysis by plasmin immunoreactivity of fibrinogen to the antibody was lost at the same rate as the clottable fibrinogen content determined by the Clauss assay. The lack of reactivity of the antibody with FDPs makes it a suitable reagent for investigating plasmin activity as well as studying fibrinogen and fibrin. These findings suggest that the epitope of the antibody lies within the polar protruberance of the carboxy terminal end of the A alpha chain of fibrinogen and is destroyed by plasmin cleavage.

Antibodies, Monoclonal↗
PubMed1985

Rapidly progressive fatal pulmonary infiltration by lymphoma.

Two patients with diffuse lymphoma, one diffuse large cell and the other diffuse mixed, large and small cell, developed an illness characterised by a high swingeing fever and a pulmonary infiltrate. In both patients there was clinical evidence of chemotherapy-induced tumour response elsewhere at the time lung infiltrates progressed. Blood and sputum cultures, bronchial washings, and, in one case, trans-bronchial lung biopsy did not establish a diagnosis and there was progressive clinical deterioration. Post mortem examination showed widespread involvement of both lungs with lymphoma. The differential diagnosis of fever and pulmonary infiltrates in patients with diffuse lymphoma is discussed, in particular the possibility of this being due to rapidly progressive lymphoma.

Adult↗
PubMed1985

Idiopathic myelofibrosis complicated by lymphoma. Report of two cases.

2 cases of diffuse large-cell non-Hodgkin's lymphoma developing in conjunction with idiopathic myelofibrosis are described. In neither case could any predisposition to neoplastic transformation be discerned. The possible pathogenetic implications of this association are discussed, and a brief literature review of the relationship between myeloproliferative and lymphoproliferative disease is presented.

Adult↗