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Biomedical subjects

H Kronenberg

Publications and source records attributed to H Kronenberg.

At least 19 recordsLinked to original sources
PubMed1992

Autoantibodies to thrombomodulin: development of an enzyme immunoassay and a survey of their frequency in patients with the lupus anticoagulant.

In order to investigate the possibility that autoantibodies to thrombomodulin (TM) may exist in patients with the lupus anticoagulant (LA) and perhaps be implicated in the pathogenesis of recurrent thrombosis seen in such patients, we developed an enzyme-immunoassay to screen serum samples for anti-human TM activity. The major technical problem encountered in developing this assay was to reduce the non-specific binding of serum components from both the LA positive and the negative population. Considerable reduction of non-specific binding was achieved by use of a phosphate/citrate buffer at pH 8.0 and the use of an optimal sample dilution of 1/40. In addition, samples were always tested in parallel in blank wells and results are expressed as an OD ratio. Samples from 113 patients with the LA were assayed and compared to 78 patients referred for LA testing but found to be negative. The mean OD values for the LA positive patients (+/- SD) was 1.36 (0.44) with a range of 0.78-2.57. This was virtually identical to the values for the LA negative population (1.38 +/- 0.40, range 0.76-2.77). The results of this study indicate that there is no evidence for the presence of a significant autoantibody activity to TM in patients with the LA when compared to LA negative patients. If such autoantibodies do exist their frequency must be quite low.

Autoantibodies↗
PubMed1992

Cytosine arabinoside and etoposide (CARE) in relapsed and refractory non-Hodgkin's lymphoma.

Twelve patients with relapsed or refractory non-Hodgkin's lymphoma (NHL) were treated with a 5 day protocol of high dose cytosine arabinoside 3 g/m2 and etoposide 200 mg/m2 (CARE) daily for 4 days for either 1 or 2 cycles together with alternating intrathecal cytosine arabinoside and methotrexate. Seven men and 5 women aged 18 to 65 years (median age 47.5 years) have received a total of 19 cycles. Six patients had Stage III and 6 had Stage IV disease, all with marrow involvement. Three patients had diffuse small lymphocytic NHL, 3 had diffuse large cell NHL, 3 had diffuse small cleaved NHL and 3 remaining patients had diffuse mixed small and large cell NHL, lymphoblastic NHL and Burkitt's. Six patients (50%) achieved complete remission (3-44 months), four of whom subsequently underwent successful autologous bone marrow transplantation and a fifth has had marrow harvested in preparation for ABMT. One patient achieved partial remission and 5 patients had no response to CARE. Ten patients had nadir granulocyte counts less than 0.5 x 10(9)/l and all required red cell (range 2-11 units) and platelet (range 6-130 units) transfusions. The platelet nadir was less than 20 x 10(9)/l in all patients. One patient with refractory disease succumbed to pulmonary haemorrhage while three other patients developed reversible toxicity with serve mucositis, prolonged diarrhoea and acute renal failure. One patient with refractory disease died with a progressive neuropathy.

Adolescent↗
PubMed1992

The rational use of homologous blood in elective surgery.

The supply of homologous blood in Australia is limited, but the demand for blood and blood products is steadily increasing. Elective surgery is a major part of this demand. In many institutions the blood ordering practices for elective surgery have been haphazard. This study was undertaken to document current patterns of blood use in a major city teaching hospital. A retrospective analysis of blood ordering and transfusion for elective surgical procedures was carried out over a 12 month period. As in several previous studies, an inefficient use of blood was demonstrated. Possible strategies to rationalize the use of blood in elective surgery have been proposed. These include the use of a 'group and screen' procedure instead of a full cross-match when transfusion is unlikely to be necessary, and ordering according to a 'maximum blood order schedule' when transfusion is usually required for a procedure.

Australia↗
PubMed1992

PRAD1 (cyclin D1): a parathyroid neoplasia gene on 11q13.

Hyperparathyroidism is a central component of multiple endocrine neoplasia type 1 (MEN 1), and both sporadic and familial forms of parathyroid disease may share certain pathogenetic features. We recently identified a gene that is clonally rearranged with the PTH locus in a subset of sporadic parathyroid adenomas. This candidate oncogene, PRAD1 (previously D11S287), appears to contribute to parathyroid tumorigenesis in a fashion analogous to activation of C-MYC or BCL-2 by rearrangement with tissue-specific enhancers of the immunoglobulin genes in B-lymphoid neoplasia. The PRAD1 gene maps to 11q13 and has been linked to the BCL-1 breakpoint locus, although not to the most tightly linked MEN 1 markers, by pulsed field gel electrophoresis. PRAD1 may, in fact, be the long-sought BCL-1 lymphoma oncogene. PRAD1 encodes a novel type of cyclin protein and thus may normally function in controlling the cell cycle, perhaps through direct interaction with cdc2 or a related kinase. PRAD1's possible primary, or more likely secondary, involvement in the pathogenesis of MEN 1-related tumors is unknown and under investigation.

Amino Acid Sequence↗
PubMed1991

Full-length chicken parathyroid hormone. Biosynthesis in Escherichia coli and analysis of biologic activity.

Chicken parathyroid hormone (cPTH) has been reported to stimulate adrenal steroidogenesis and to have unusual potency on traditional PTH target tissues. To evaluate these properties, chicken PTH-(1-88) has been expressed in Escherichia coli using a plasmid encoding a fusion protein which links together growth hormone, a factor Xa recognition site, and chicken PTH-(1-88). The growth hormone-cPTH fusion protein required the presence of 0.02% sodium dodecyl sulfate to remain in solution and be cleaved by factor Xa. The high performance liquid chromatography-purified recombinant cPTH-(1-88) and chemically synthesized cPTH-(1-34) had similar potency in rat osteosarcoma (ROS 17/2.8) cells, opossum kidney (OK) cells, and dispersed primary chicken kidney cells. The biologic potencies of cPTH-(1-34) and cPTH-(1-88) in radioreceptor binding and cAMP generation in both bone- and kidney-derived cell lines were less than those of human (h)PTH-(1-34). In dispersed chicken kidney cells, cAMP production by cPTH-(1-34) and cPTH-(1-88) was similar to that stimulated by human PTH-(1-34). No stimulation of steroidogenesis could be detected when recombinant chicken PTH-(1-88) was added to dispersed chicken adrenal cells. The biologic activity of recombinant chicken PTH-(1-88) purified from E. coli was comparable with that of chicken PTH-(1-88) expressed by mammalian COS cells. Thus, the full-length chicken PTH did not exhibit enhanced potency, when compared with human PTH in ROS 17/2.8, OK cell lines, and dispersed chicken kidney cells and did not demonstrate the novel steroidogenic action previously reported in adrenal cells. The successful production of chicken PTH-(1-88) will enhance our understanding of the structure-activity relationships for PTH, particularly the sequence-dependent metabolism of the hormone.

Animals↗
PubMed1991

Analysis of N-ras gene mutations in acute myeloid leukemia by allele specific restriction analysis.

N-ras gene activation occurs via single base substitutions in codons 12, 13, and 61. We have developed a rapid screening method, termed allele specific restriction analysis (ASRA), for detection of N-ras mutations at these three critical codons in acute myeloid leukemia (AML). Patient DNA samples are amplified by the polymerase chain reaction (PCR) by using primers that induce restriction sites in normal but not mutant N-ras alleles. We have used ASRA to identify 5 point mutations in four out of 19 patients at initial presentation of de novo AML. Three patients had one mutation at codon 12, 13, or 61 respectively, while a fourth patient had concurrent mutations at codons 12 and 13. N-ras mutations were more common in patients over 65 years of age (P less than 0.04), but did not correlate with FAB classification, attainment of complete remission, disease free survival, or overall survival. ASRA can also be used as the first step in a more sensitive approach to the detection of ras mutations. When ASRA was combined with allele specific oligonucleotide (ASO) hybridization the sensitivity and specificity of these assays were increased. This allowed identification of additional low level mutations in two patients. The data presented here constitute the first complete analysis of N-ras mutations in leukemia by ASRA and include the first identification of three concurrent N-ras mutations in a single leukemic patient. By facilitating sensitive sequential studies, ASRA should contribute to our understanding of the role of N-ras mutations in leukemogenesis.

Acute Disease↗
PubMed1991

Aseptic meningitis associated with high dose intravenous immunoglobulin therapy.

Two cases of aseptic meningitis occurred in temporal association with high dose intravenous immunoglobulin therapy to treat thrombocytopenia. In neither case was any other aetiological agent identified and both patients completely recovered within a few days. This phenomenon has been reported in only one previous paediatric case.

Adult↗
PubMed1991

Hb Geelong [beta 139(H17)Asn----Asp].

Hb Geelong [beta 139(H17)Asn----Asp] was detected in a German woman of Polish-Russian descent. It is an unstable variant which appears to increase the severity of a beta (+)-thalassemic phenotype in the propositus. The electrophoretic properties of Hb A and Hb Geelong are similar on cellulose acetate in both acidic and alkaline conditioning. The electrophoretic mobility and the amino acid analysis of beta XT-14 indicated the substitution Asn----Asp at beta 139. The sequence of beta XT-14 was confirmed by dansyl-Edman degradation. The slight increase observed in the P50 of whole blood is not intrinsic to the beta 139 substitution, but is thought to result from an increased 2,3-diphosphoglycerate level in response to anemia. No family studies were possible to investigate the mode of inheritance of either beta (+)-thalassemia or Hb Geelong in the propositus. Synthetic globin chain ratios suggest that impaired synthesis of the variant globin chain is partially responsible for the low level of Hb Geelong in peripheral blood.

2,3-Diphosphoglycerate↗
PubMed1990

Etoposide in acute nonlymphocytic leukemia. Australian Leukemia Study Group.

Previously untreated patients with acute nonlymphocytic leukemia (ANLL) aged 15 to 70 years were randomized to either cytosine arabinoside 100 mg/m2/d continuous intravenous (IV) infusion days 1 through 7, daunorubicin 50 mg/m2/d IV days 1 through 3 (7-3), or the same drugs intensified with etoposide 75 mg/m2/d IV days 1 through 7 (7-3-7) as induction therapy. Patients achieving complete remission (CR) received two courses of consolidation therapy (5-2 or 5-2-5) followed by maintenance therapy. Of 264 eligible patients, CR occurred in 56% of 7-3 and 59% of 7-3-7 patients; 7-3-7 significantly improved remission duration (P = .01). The median remission duration was 12 months for 7-3 and 18 months for 7-3-7. Survival was similar when the two arms were compared overall. Subset analysis performed to identify patients with the most benefit showed that etoposide significantly prolonged remission duration in younger patients (less than 55 years) with a median of 12 months for 7-3 and 27 months for 7-3-7 (P = .01). Survival appeared to be prolonged with 7-3-7 in patients aged less than 55 years, with a median of 9 months for 7-3 as compared with 17 months for 7-3-7 (P = .03). In older patients (aged greater than or equal to 55 years), 7-3-7 was more toxic, with significantly more severe [World Health Organization (WHO) grade 3 or 4] stomatitis (P = .02) and no additional clinical benefit. Hematologic toxicity for induction courses was similar, with granulocytopenia less than 0.5 x 10(9)/L for a median of 16 days per course for 7-3 and 15 days for 7-3-7. Hematologic toxicity was more severe for 5-2-5 consolidation courses (P = .003). Induction and consolidation therapy intensified with etoposide resulted in significantly improved remission duration but not survival.

Adolescent↗
PubMed1990

Red cell folate assays: some answers to current problems with radioassay variability.

Red cell folate specimens were added to the Quality Assurance Program (QAP) of the Royal College of Pathologists of Australasia in 1986. The interlaboratory variation in the results of these red cell folate surveys has been persistently unsatisfactory. This study reports an investigation into the factors contributing to the wide variation of results reported in QAP surveys. Survey results were studied, replies to a questionnaire regarding methods sent to all participants were assessed and some new experimental studies were performed. Factors contributing to the poor QAP results include variation in dilution and diluent, calculation errors, failure to freeze the hemolysate prior to assay and to follow the kit manufactorer's instructions, stability of dithiothreitol, and variations in kit methods, especially in the release of bound folate by "boil" and "no-boil" methods. Photodecomposition and the form and concentration of ascorbate may also be significant. Adequate preparation of the hemolysate sample should ensure release of all protein-bound red cell folate with the reduction of all folates to a single form. Kit manufactures, users and the QAP committee can all contribute in all attempt to rectify current sources of error.

Ascorbic Acid↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

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↗