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Biomedical subjects

H Kronenberg

Publications and source records attributed to H Kronenberg.

At least 55 records · Page 3Linked to original sources

Neonatal alloimmune thrombocytopenia caused by an antibody to the Bak(a) antigen.

A 31 year old woman was assessed following delivery of her second child affected by neonatal alloimmune thrombocytopenia (NAIT). Antiplatelet antibodies with specificity for Bak(a) were identified in the woman's serum and her platelets were typed as Bak(a) negative whilst her husband's were Bak(a) positive. Unlike the majority of reported anti-Bak(a) antibodies in the literature, this patient's serum contained no contaminating anti-HLA antibodies. This is the first report of NAIT caused by an anti-Bak(a) without co-existing anti-HLA antibodies. An anti-Bak(a) antibody has not previously been reported in Australia. The current status of this antigen system is reviewed.

Adult↗

Immunophenotypic analyses of cultured hemopoietic mast cells.

Immunophenotypic analyses of immature stage (day 19-23), intermediate stage (day 28-32), mature stage (day 34-37), and older stage (day 42-44) human hemopoietic mast cells from colonies grown in semi-solid agar cultures were performed to study the ontogeny and identity of this cell type and its relationship to other leukocytes. Intermediate to mature stage mast cells were positive with the YB5.B8 mouse monoclonal antibody, (McAb) specific for human mast cells, whereas the reactivity of immature mast cells with this McAb was inconsistent and older cells were generally negative. Mast cells at all stages of maturation were strongly positive for IgE receptor sites and negative with the Bsp-1 McAb, specific for human basophils. Mast cells at all stages of maturation were also strongly positive with the monocyte McAbs RPA-M1 (CD11), positive with the monocyte McAb OKM5 and the monocyte/granulocyte McAbs BMA-210 and MY7 (CD13), strongly positive with the B-cell markers J5 (CD10) and anti-IgM, and positive with the plasma cell marker PCA-1 and to a lesser extent with the activated B-cell marker CD23. The mast cells were also strongly positive with anti-CD45 to the common leukocyte antigen and positive with an antibody to HLA-DR and an antibody to FVIIIC. They were negative for specific T-cell markers. The diversity of this phenotype supports the current concept that mast cells originate from the pluripotential progenitor cells in the bone marrow.

Antibodies, Monoclonal↗

Human cardiolipin as the antigen in an ELISA to detect anticardiolipin antibodies.

Human cardiolipin was purified from cadaver heart tissue and used as the antigen in an enzyme-linked immunoassay (ELISA) for anticardiolipin antibodies. The correlation between assays using human and bovine cardiolipin was r = 0.90. Of the lupus anticoagulant positive patients 88% had antibodies to the human antigen and 75% had antibodies to the bovine antigen. Six of 45 samples contained antibodies which only reacted with the human antigen. All six samples remained positive when retested with a different human cardiolipin preparation and were negative when tested against a preparation of sheep cardiolipin. These studies suggest that there was increased specificity when human cardiolipin was used as the phospholipid antigen.

Animals↗

Very high dose intravenous gammaglobulin in thrombocytopenia of pregnancy.

A 22-year-old woman with severe idiopathic thrombocytopenic purpura, complicating pregnancy, was unresponsive to high-dose corticosteroids and three separate infusions of high-dose intravenous immunoglobulin using the conventional schedule of 400 mg/kg/d for five days. A dramatic albeit transient, elevation of her platelet count followed a six day course of very high dose immunoglobulin (1000 mg/kg/d) thus allowing elective lower segment cesarean section to be performed without complications and with the delivery of a live, female infant. Two months later a further course of very high dose gammaglobulin was again effective in raising the patient's platelet count prior to elective splenectomy. No adverse reactions were seen to either infusion.

Adult↗

Serum thymidine kinase as a marker of disease activity in patients with multiple myeloma.

Serum thymidine kinase (STK) levels have recently been used to detect tumour regression and progression in a number of hematological malignancies. In this study, patients with myeloma were monitored longitudinally for STK and several other potentially useful tumour markers to determine which laboratory parameters are the most useful for differentiating between stable and progressive disease. STK was determined by radioenzyme assay, lymphocyte surface markers were analysed by flowcytometry, plasma cell labelling index (LI) by immunofluorescence with anti BU-1, serum B2-microglobulin (SB2M) by radioimmunoassay and M proteins by radial immunodiffusion. Detailed multiparameter longitudinal investigations of 5 patients and ongoing studies of 70 other patients suggest that STK is a more reliable marker of progressive disease than either SB2M, LI, M-protein or CD10 positive lymphocytes. A rise in STK during the emergence of progressive disease at least paralleled and usually preceded any change in the other parameters which often did not change at all. All samples from patients with progressive disease (n = 29) had a STK above the normal range (0-5U/l) whereas 76% of patients in clear stable disease had a STK within the normal range. All samples (n = 34) from patients with light chain isotype suppression (LCIS) had STK values of less than 12 U/L and 82% of samples (n = 33) from patients without LCIS had a STK above the normal range (0-5U/L). The correlation between STK and LI was r = 0.65; p less than 0.001 (n = 21). The radioenzyme assay for STK is simple, reproducible and a valuable tool for monitoring patients with myeloma and when used in conjunction with other clinical and laboratory investigations, aids in the separation of patients with stable myeloma from patients whose disease is progressive.

Antigens, Differentiation↗

Immune hemolysis after an ABO mismatched renal transplant.

We describe a case of immune hemolysis due to anti-B occurring in a blood group B patient 16 days after a cadaveric renal transplantation from a blood group O donor. Transfusional support was initially required and the direct antiglobulin test (DAT) remained positive for 80 days. Cyclosporin A (CSA), which was used for rejection prophylaxis in this case, has unique immunosuppressive capabilities which protects transplanted organs from rejection, but which might permit this type of 'graft versus host' reaction.

ABO Blood-Group System↗

A randomised trial of empirical antibiotic therapy in febrile neutropenic patients with hematological disorders: ceftazidime versus azlocillin plus amikacin.

One hundred and two patients with neutropenia (less than 1 x 10(9)/L) secondary to primary hematological disorders or chemotherapy for hematological malignancies were prospectively randomised, upon the development of fever or other signs of infection, to receive empirical antibiotic treatment with either ceftazidime (+/- flucloxacillin) (n = 52) or azlocillin plus amikacin (+/- flucloxacillin) (A&A, n = 50). The two groups were equivalent with respect to clinical and laboratory parameters prior to antibiotic therapy and flucloxacillin was added to approximately 25% of the patients in each group on the clinical suspicion of Gram positive infection. When assessed at 96 hours, the complete response rates were 59.6% for the ceftazidime treated patients and 44% for A&A treated patients. Partial response rates were 17% and 20% respectively. This difference was not statistically significant. Eight patients died whilst on the trial, three of those initially randomised to ceftazidime and five initially randomised to A&A. Moderate to severe hypokalemia was encountered significantly less often in the ceftazidime treated group (p less than 0.01), whilst other parameters of toxicity were equivalent. No primary or acquired resistance to ceftazidime was encountered. Separate analysis of those patients who did not receive flucloxacillin yielded identical results. We conclude that ceftazidime (+/- flucloxacillin) is as efficacious as azlocillin plus amikacin (+/- flucloxacillin) in the empirical antibiotic management of such patients and is associated with a lower incidence of moderate to severe hypokalemia.

Adolescent↗

Gallium scanning in the management of mediastinal Hodgkin's disease.

Gallium-67 scanning was performed pre- and post-therapy in 25 patients with Hodgkin's disease and a mediastinal mass. At restaging after therapy, radiographs (or CT scans) did not predict the presence of active disease whereas gallium scans did with a high degree of accuracy. Gallium-67 determined disease activity in those patients who had a residual mediastinal mass predicting outcome in 11 out of 12 patients; one had a late relapse at 7 years. In patients without a residual mass gallium scanning was again accurate, predicting outcome in 11 of 13 patients. Two patients with negative gallium scans but subsequent active disease were scanned too soon after chemotherapy. The results suggest that gallium scanning has an important role in the management of mediastinal Hodgkin's disease and is superior to all current methods of assessing disease activity irrespective of the presence of a residual mediastinal mass.

Adolescent↗

A family exhibiting the cis-AB genotype.

Studies on blood samples from a 30-year-old woman of Korean origin, her husband and children, showed the presence of the cis-AB genotype in the mother and one child. The cis-AB red cells showed abnormal reactions with both polyclonal and monoclonal anti-B reagents and an elevated level of H antigen. The serum contained weak anti-B that reacted with normal B antigen but not with that on cis-AB cells. Normal levels of A substance but reduced levels of B and H substances were present in the saliva. Conversely, the serum showed reduced A and normal B and H blood group transferase activity.

ABO Blood-Group System↗

A molecular marker associated with mild hemoglobin H disease.

The clinical spectrum of HbH disease varies from a benign disorder to a severe anemia which is blood-transfusion dependent. Heterogeneity at the clinical level is now being understood in terms of the underlying molecular defects. In this study a mild phenotype found in a group of patients with HbH disease is associated with two types of alpha-thalassemia. These are: alpha+-thalassemia (-alpha 3.7/) and alpha 0-thalassemia (--SEA/). In contrast, a second group with more severe HbH disease has a non-deletional alpha-thalassemia defect instead of alpha+-thalassemia (genotype alpha alpha T/--SEA). In the majority of cases, the basis for non-deletional alpha-thalassemia is Hb Constant Spring.

Adolescent↗

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↗

Clinical response of hairy-cell leukaemia to interferon-alpha: results of an Australian study.

Twelve patients with documented, progressive hairy-cell leukaemia were treated with human lymphoblastoid interferon-alpha. All patients initially received a three-month course of interferon-alpha (3 x 10(6) U each day) which resulted in two complete remissions and 10 partial remissions. All eight patients who were dependent upon packed red-cell transfusions became independent of them and the three patients with the most severe, pretreatment pancytopenia also became independent of platelet transfusions. The histological appearance of the bone marrow improved in all patients; in three patients, a complete resolution of the leukaemic infiltrate was recorded. Adverse reactions occurred in 10 patients, but these were mild and did not interrupt treatment in seven patients. Moderate reactions that required a temporary reduction in the dose of interferon-alpha were seen in three patients. Ten patients subsequently received maintenance therapy with interferon-alpha (3 x 10(6) U, three times a week). A haematological improvement continued to be seen in all patients, and the results, with a minimum of one year of follow-up, are presented.

Adult↗

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↗

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↗