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Biomedical subjects

H Kronenberg

Publications and source records attributed to H Kronenberg.

At least 73 records · Page 4Linked to original sources

Red cell ferritin and iron stores in patients with chronic disease.

Serum and red cell ferritin were determined in a heterogeneous group of 59 patients with chronic disease undergoing a bone marrow biopsy. There was very little correlation between serum and red cell ferritin (r = 0.53). Although serum ferritin increased in relation to increased bone marrow iron stores, only 1 out of 8 patients with absent marrow iron stores and none of 8 patients with reduced marrow iron stores had a decreased serum ferritin. In contrast, 6 of 8 patients with absent iron stores had a reduced red cell ferritin concentration. There was no significant difference between the mean red cell ferritin of the patients with reduced, normal and mild-moderately increased marrow iron stores (30, 26 and 34 ag/cell). Red cell ferritin was decreased in 78% of a group of 32 patients with a low mean cell volume. In the patients studied, red cell ferritin was a better indicator of absent iron stores than serum ferritin. However, red cell ferritin did not detect a reduction in the iron status until the marrow iron stores were completely depleted. Apparently, during normal erythropoiesis the primitive erythroblasts continue to take up iron irrespective of the amount of iron available in the stores.

Adolescent↗

von Willebrand's disease characterized by increased ristocetin sensitivity and the presence of all von Willebrand factor multimers in plasma: a new subtype.

The clinical and laboratory features of a patient with a recently recognized new variant of von Willebrand's disease are presented. The importance of this variant is that it is associated with a clinically significant bleeding diathesis but with a normal skin bleeding time, PTTK, factor VIIIc and platelet aggregation with 1 mg/ml ristocetin. The distinctive laboratory features are increased platelet sensitivity to low concentrations of ristocetin, and the presence of all plasma von Willebrand factor multimers, but in reduced amounts. The need for thorough investigation of patients with significant bleeding history despite apparently normal screening tests is emphasized.

Adult↗

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↗

Identification and characterization of human hemopoietic mast cell colonies.

Persisting mast cell colonies from human bone marrow and cord blood cells grown in semisolid agar cultures for over 56 days have been positively identified and characterized using morphology and cytochemistry. Mast cells demonstrated the following features: Cytoplasmic granules frequently contained the specific and characteristic papyrus rolls (transmission electron microscopy); mature cells were positive to the mouse monoclonal antibody YB5.B8 specific for human mast cells (raised against acute myeloid leukemia cells) and RPA-M1 specific for human monocytes but negative to the human basophil monoclonal antibody Bsp-1; morphologically the cells were large (diameter 20-25 micron), deeply basophilic, and contained granules that measured up to 2 micron in diameter (May-Grünwald-Giemsa stain); the presence of heparin by the thrombin clotting time and positive staining with toluidine blue and alcian blue; the presence of histamine by a positive fluorescent o-phthalaldehyde stain; the presence of IgE receptor sites with human IgE and a rabbit anti-human IgE second antibody; and a unique zone of lysis around mast cell colonies occurred when cultured on peripheral blood feeder layers in agar plates that was not present around monocytic, neutrophilic, or eosinophilic colonies under the same culture conditions. Our results identify the cells in persisting colonies as mast cells and describe some specific characteristics that distinguish these cells from basophils.

Bone Marrow Cells↗

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↗

Persisting colonies in agar cultures containing serum from patients with CML in blastic transformation.

Addition of serum from patients with chronic myeloid leukemia (CML) in both chronic phase and blastic transformation, to agar cultures of normal human marrow cells stimulated the growth of persisting colonies (day 35) containing either eosinophils or mast cells. Chronic phase serum stimulated an 800% increase in the total number of these colonies of which only 16% were mast cells. Serial studies using serum from 2 patients demonstrated that the proportion of mast cells increased during the progression to blastic transformation. The emergence of a greater proportion of persisting mast cell colonies and a decrease in absolute number of eosinophil colonies in agar cultures of normal marrow cells containing serum from patients with CML coincides with the emergence of blastic transformation and suggests that a significant change occurs in the absolute and relative concentration of hemopoietic growth factors in these patients.

Bone Marrow Cells↗

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↗

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↗

Chronic lymphocytic leukaemia complicated by recurrent Bell's palsy.

A patient who presented with a transient right-sided Bell's palsy (lower motor neurone lesion of the facial nerve) and chronic lymphocytic leukaemia (CLL) is described. During the following 5 years whilst receiving intermittent treatment for her CLL, the patient experienced two further episodes of Bell's palsy, one on the right side and the other left-sided. Each episode completely resolved. This is the first reported case of recurrent Bell's palsy complicating CLL.

Facial Paralysis↗

DNA changes during blastic transformation in chronic granulocytic leukemia.

Immunoglobulin and T cell receptor gene mapping were undertaken in 10 patients during both chronic and blastic phases of chronic granulocytic leukemia. Twenty percent were shown to undergo lymphoblastic transformation. DNA changes did not predict blastic transformation or those who would respond favourably to treatment with vincristine and prednisone.

Adolescent↗

Evaluation of the Technicon H-1 hematology analyser.

The Technicon H-1 is a new, random-access hematology instrument performing a full blood count with leukocyte differential including eosinophils and basophils. Technical assessment showed good linearity and precision. Comparison with a Coulter S-PLUS (II) showed close correlation for all full blood count parameters except MPV and MCHC on 149 unselected hospital inpatients over a wide clinical range. No significant carry-over was detected in hemoglobin, red cell, white cell and platelet estimations. Differentials agreed closely with Technicon H6000 results for neutrophils, lymphocytes, monocytes and eosinophils. Poorer correlation with 100-cell manual differentials for all cell types except neutrophils probably reflects the relative lack of precision in manual methods. Technological innovations on the H-1 include a laser-based optical system from which several new hematological parameters are derived. The contribution they make towards improved patient care awaits assessment.

Blood Cell Count↗