Biomedical subjects

J R Krause

Publications and source records attributed to J R Krause.

At least 37 records · Page 2Linked to original sources

PubMed1990

Multiple lineage reactivity in childhood leukemia.

The leukemia cells from 63 children with acute leukemia were evaluated by flow cytometry with a panel of monoclonal antibodies that included lymphoid and myeloid lineage-specific antigens. Surface markers from patients with acute lyphocytic leukemia (ALL) did not correlate with their FAB classification except for L3 leukemia. Myeloid leukemias of FAB class M1-M4 were positive for CD13 and CD33, whereas CD14 and MY8 were only detected in FAB class M4 leukemia. Mixed leukemias were subclassified as intralineage (B+T+) or interlineage (B+ or T+/M+). Interlineage leukemias represented 5.6% of ALLs, and all patients are alive after treatment with ALL protocols. Interlineage mixed leukemias represent 7.9% of all leukemias occurring in 3.7% of ALLs and 33% of acute myeloid leukemias (AMLs). All children with mixed interlineage leukemias are alive after treatment with the protocol for the dominant leukemia; however, follow-up periods are too short to predict final outcome. The high proportion of mixed interlineage leukemias in AMLs supports Greaves' theory of lineage promiscuity, that is, there is a normal period of hematopoietic development when individual cells co-express multiple lineage antigens on the cell surface.

Acute Disease↗

PubMed1990

Quality control in flow cytometry for diagnostic pathology. I. Cell surface phenotyping and general laboratory procedures.

Flow cytometric analyses have become commonplace in the clinical laboratory for determining cell lineage and for quantitation of cells bearing a given phenotype. Because these assays are being conducted to support diagnoses or assist in determining therapy, it is crucial to ensure that these tests are highly accurate and reproducible within a laboratory and among laboratories involved in similar endeavors. This quality assurance has been slow evolving in clinical flow cytometry for a variety of reasons: the exquisite sensitivity and delicacy of the instrumentation that recognize previously undetectable variations in staining; the constant improvement of the hardware and software; the rapid development of new techniques and reagents of clinical interest; and the failure of any existing specialty or subspecialty to encompass all aspects of flow cytometry. This article provides an overview of quality assurance necessary for the flow cytometric analysis of cell surface markers. Practical experience, published studies, and suggested guidelines from accreditation agencies have been combined to develop the text.

Cell Separation↗

PubMed1990

Automated differentials in the hematology laboratory.

The white blood cell differential continues to be one of the most widely performed clinical laboratory procedures. However, its clinical usefulness is affected by sampling error and, to some extent, by classification criteria. It is also labor intensive and expensive to perform. Automated leukocyte differential instrumentation addresses many of the sources of error that occur with the manual differential. Current state-of-the-art instrumentation will give results that equal or exceed the routine manual differential. Because these instruments also examine red blood cell and platelet parameters, as well as providing white blood cell information, they can better screen for significant abnormalities as well as greatly reduce the expensive and time-consuming manual differential procedures.

Automation↗

PubMed1989

Three infants with acute megakaryoblastic leukemia simulating metastatic tumor.

The diagnosis of acute megakaryoblastic leukemia (AMKL) (M7, French-American-British [FAB] classification) has rarely been made in children due, in part, to its pleomorphic morphology and ability to mimic other malignancies common in the pediatric age group. Three infants are described who had thrombocytopenia and the classical criteria of metastatic solid tumor in the bone marrow: patchy infiltration by cohesive clusters of cells with high nuclear cytoplasmic ratio and myelofibrosis in the bone marrow biopsy infiltrated area. This finding prompted clinical evaluation for solid tumor. The megakaryocytic lineage was ascertained by immunocytochemical studies and/or electron microscopic examinations of the bone marrow aspirates. The blasts in all three patients showed cytogenetic abnormalities that also were demonstrated by quantitative DNA analysis. None of the infants had Down's syndrome. Two of the patients are alive; one is off of therapy and the other is in remission. The third patient was transferred to another institution and lost to follow-up. Two children had wheezing that disappeared in remission. It is proposed that the clinical symptoms may be due to a substance produced, stored, or released by the leukemic cells.

Adolescent↗

PubMed1989

Immunophenotyping in the classification of acute leukemia in adults. Interpretation of multiple lineage reactivity.

Fifty-nine adult patients with acute leukemia were classified using a combination of the French-American-British (FAB) criteria and characterization by immunophenotyping using flow cytometric study. The authors identified 51 patients with acute myeloblastic leukemia and eight with acute lymphoblastic leukemia. This procedure permitted lineage assignment in leukemias that otherwise might have been unclassifiable. In addition, the authors demonstrated that the leukemic blasts of 29% of patients with myeloblastic disease exhibited one or more T-cell antigens on their surface. The use of immunophenotyping has greatly enhanced the authors' ability to correctly identify the lineage of acute leukemias. The data, however, must be interpreted with caution with respect to diagnosing acute mixed lineage leukemias and must be integrated with the morphologic and cytochemical evaluation of traditional classification schemes. The possible significance of T-cell markers in myeloblastic leukemia is discussed.

Adult↗

PubMed1989

Microgranular promyelocytic leukemia: a multiparameter examination.

Six cases of microgranular variant acute promyelocytic leukemia (M3v) were studied by use of a multiparameter approach including morphology, cytochemistry, flow cytochemistry, flow cytometry, cytogenetics, and gene rearrangement. Three of six cases demonstrated both myeloid and monocytoid associated surface markers by flow cytometry. One of six cases had strong alpha-naphthyl-butyrate esterase (alpha-NBE) activity in addition to myeloperoxidase activity. There was no correlation between percentage of positive monocytoid surface markers and intensity of cytoplasmic alpha-NBE activity. Four of six cases also had a T-cell-associated surface antigen. Further studies indicated that the T-cell markers appeared to be on the promyelocytes and that the T-B receptor gene was not rearranged. Similarly, cytogenetics studies indicated only one clonal abnormality t(15q+; 17q-). Whether these cases represent true "lineage infidelity" remains to be answered. Future important studies are needed on normal hematopoietic progenitor cells at early stages of development and childhood to study lineage-specific characteristics and to determine whether co-expression normally exists during early development.

Adult↗

PubMed1989

Detection of the ras p21 gene product in human leukemias by flow cytometry.

To date, the detection of oncogene products in human neoplasms has relied primarily upon immunoblot analysis of specimen homogenates. Herein are reported the results of a study using flow cytometry to evaluate the expression of the ras p21 gene product in both fresh and cryopreserved specimens of human acute leukemias. Cell lines known to express ras p21 were used as positive controls and normal peripheral blood was used as a negative control. Intensity of staining for ras p21 (Ip21) was expressed as the ratio of the peak channel numbers of the peak generated by staining with anti-ras p21 to the peak obtained by staining with an isotype control. Using this method, 21 out of 32 clinical specimens of acute leukemia were found to express ras p21 in elevated amounts compared to normal peripheral blood. Flow cytometry appears to be a practical method for routine screening of clinical specimens for the expression of oncogene products on individual cells rather than cell homogenates.

Flow Cytometry↗

PubMed1989

Regulation of total leukocyte, neutrophil and lymphocyte concentrations in human blood by major effectors.

Commingling analysis of total leukocyte, neutrophil and lymphocyte concentrations in human blood suggested the effect of major regulatory factors affecting each type of white blood cells. Our results showed two distributions for the total leukocyte and lymphocyte concentrations. The values of the low and high phenotypes were 5.8 and 8.4 x 10(9)/l of total leukocytes and 2.0 and 4.6 x 10(9)/l of total lymphocytes. On the other hand, the neutrophil concentration in blood is probably regulated by equally penetrant factors. The means of the three phenotypes were 2.6, 4.2 and 6.5 x 10(9)/l. The evidence of two or three phenotypes, although consistent with the effect of a single-factor hypothesis (genetic or environmental), must be confirmed by segregation analysis of families.

Adolescent↗

PubMed1988

Immunogold staining in bone marrow aspirate for the study of surface markers in acute lymphoblastic leukemia.

The diagnostic value of phenotyping acute lymphoblastic leukemia (ALL) of childhood using the immunogold staining method (IGS) was assessed in 34 consecutive new ALL patients seen at Children's Hospital of Pittsburgh during a 14-month period. IGS proved to have considerable value in the diagnosis and classification of ALL. It allowed a sharp and clear identification of surface antigens, documented surface antigen heterogeneity in normal and abnormal cells, and provided a permanent record. The combination with cytochemistries allowed further cytoplasmic identification and correlation. This method does not require sophisticated equipment and can be performed in any laboratory, thus enabling results from different institutions to be more readily compared.

Adolescent↗

PubMed1988

Flow cytometry in the diagnosis of acute leukemia.

Fifty cases of acute leukemia were analyzed by means of flow cytometry. The results obtained were correlated with morphology and routine cytochemistries. The panel selected was useful in classifying an acute leukemia as acute lymphocytic (ALL) or acute nonlymphocytic (ANLL), which is of primary importance for therapeutic considerations. Common ALL (CALLA) (J5) was a good marker for classifying the leukemia as ALL. Monoclonal antibodies (MoAbs) T1 and/or T11 further delineated the lymphoid leukemia as T-cell ALL while MoAbs B4 or B1 delineated the lymphoid leukemia as non-T-cell ALL. Eighteen cases of ALL were diagnosed and consisted of five cases of T-cell ALL and 13 cases of non-T-cell ALL. Both the T-cell ALL cases and non-T-cell ALL cases were found to be heterogeneous and could be further subgrouped by phenotypic expression with additional MoAbs in the panel. A monoclonal antibody panel consisting of My4, My7, My9, Mo1, and Mo2 was useful in characterizing an acute leukemia as ANLL. This panel was less useful in distinguishing myeloid from monocytic subtypes although My4, Mo1, or Mo2 when present, appeared to favor a monocytic component. Of interest, a case of biclonal leukemia with two distinct blast populations on the flow cytogram was discovered. Morphology alone was successful in diagnosing ALL from ANLL in 35 cases (70%). It was not useful in distinguishing non-T-ALL cases from T-ALL cases. The ambiguous cases could be resolved by cytometric means. Flow cytometry has much to offer as a diagnostic aid in the evaluation of acute leukemia.

Acute Disease↗

PubMed1988

Effect of simulated altitude erythrocythemia in women on hemoglobin flow rate during exercise.

The effect of simulated altitude erythrocythemia on hemoglobin flow rate and maximal O2 uptake (VO2max) was determined for nine women sea-level residents. Test conditions included normoxia and normobaric hypoxia (16% O2-84% N2). Cycle tests were performed under normoxia (T1-N) and hypoxia (T1-H) at prereinfusion control and under hypoxia 48 h after a placebo infusion (T2-H) and 48 h after autologous infusion of 334 ml of erythrocytes (T3-H). Hematocrit (38.1-44.9%) and hemoglobin concentration (12.7-14.7 g.dl-1) increased from control to postreinfusion. At peak exercise, VO2max decreased from T1-N (2.40 l.min-1) to T1-H (2.15 l.min-1) then increased at T3-H (2.37 l.min-1). Maximal arterial-mixed venous O2 difference decreased from T1-N to T1-H and increased at T3-H. Cardiac output (Q), stroke volume, heart rate, and total peripheral resistance during maximal exercise were unchanged from T1-N through T3-H. Hemoglobin flow rate (Hb flow) at maximum did not change from T1-N to T1-H but increased at T3-H. When compared with submaximal values for T1-N, VO2 was unchanged at T1-H and T3-H; Q increased at T1-H and decreased at T3-H; arterial-mixed venous O2 difference decreased at T1-H and increased at T3-H; Hb flow did not change at T1-N but increased at T3-H. For young women, simulated altitude erythrocythemia increased peak Hb flow and decreased physiological altitude (227.8 m) but did not affect maximum cardiac output (Qmax).

Adult↗

PubMed1988

The bone marrow in nutritional deficiencies.

The overwhelming majority of nutritional deficiencies that affect the bone marrow and blood are due to the lack of vitamin B12, folic acid, or iron or combinations thereof. The two vitamins are closely related in DNA synthesis, whereas iron is the most abundant heavy metal in the body and is chiefly utilized for hemoglobin synthesis. Concomitant conditions of vitamin B12 and/or folate deficiency along with iron deficiency are not infrequent, and one type of anemia may mask the other. It is important to establish the correct diagnoses, as therapy directed at the wrong deficiency may hide the real deficiency with disastrous results. Specific diagnostic tests are now available to determine definitive diagnoses, and specific therapy is readily available to restore and maintain a normal nutrient status.

Anemia, Hypochromic↗

PubMed1988

Biclonal IgM gammopathy in chronic lymphocytic leukemia.

The association of chronic lymphocytic leukemia (CLL) with serum paraproteinemia (ie, monoclonal immunoglobulin production and secretion) is well known. We, however, could find only three previous reports of CLL where multiple serum paraproteins were encountered. We describe a case of biclonal gammopathy in CLL, involving IgM/kappa and IgM/lambda, with each paraprotein reaching serum levels of approximately 10 g/L (1 g/dL). Using immunohistochemical techniques, we identified two morphologically similar lymphocyte populations, which could be stained for either mu and kappa or mu and lambda. The peripheral blood contained a majority of mu/kappa-containing cells (kappa/lambda = 17.5:1), while the bone marrow only contained a modest excess of cells staining for mu/kappa (kappa/lambda = 2.4:1). The clinical significance and prognosis of biclonal IgM gammopathies is uncertain, since so few cases have been reported. Our patient has now been followed up for more than four years.

Aged↗

PubMed1988

Use of the Technicon H-1 in the characterization of leukemias.

The Technicon H-1 is a hematology analyzer that performs a complete blood cell count and white blood cell differential using both cytochemistry and flow technology. Two white blood cell cytograms are produced based on peroxidase activity and nuclear characteristics of the cells. Ninety cases of leukemia were studied. The 25 cases of acute lymphocytic leukemia (ALL) could be distinguished from the 39 cases of acute nonlymphocytic leukemia as the lymphocyte percentage was greater than 50% in the ALL cases and the mean peroxidase index value was 0 in 80% of the cases. The ALL cases and the chronic lymphocytic leukemia cases also had different cytogram patterns. Subtypes of acute nonlymphocytic leukemia could not be absolutely distinguished, although promyelocytic leukemias (M3) had characteristic cytograms and a monocyte percentage above 15% suggested a monocytic component (M4 or M5). Chronic myelogenous leukemia likewise seemed to have a recognizable pattern. Since a sample takes only 60 s to process, information is readily available. The unique data available from this instrument should provide a significant advancement in the automated hematology field.

Adolescent↗

PubMed1987

Search for eosinopenia in hospitalized patients with normal blood leukocyte concentration.

Hospitalized patients were studied prospectively in an attempt to determine whether idiopathic eosinopenia in the absence of other major changes in blood cells is rare or is more frequent than is commonly recognized. Strict criteria for eosinopenia were used; patients with more than 10.0 X 10(9)/liter total leukocyte count, or less than 4.0, as well as those with any form of hematologic cancer, or those receiving any form of cancer chemotherapy, were excluded from the study. With those criteria and exclusions, only 24 patients with eosinopenia were found among 24,300. Twenty were receiving some form of adrenal glucocorticosteroid (steroid) and of the other four, three had serious organic diseases for which they were receiving various drugs. The remaining patient, whose primary problem was depression, could have had drug-induced eosinopenia. Thus, unexpected eosinopenia appears to be a very rare event or syndrome. A normal range for eosinophils was defined from studies of 740 medical students, which was 0.015 to 0.65 X 10(9)/liter and was quite similar to previously reported values. The effect of acute or chronic steroid administration on eosinophils in normal human subjects was studied. Confirming studies reported for man and many other mammals, eosinopenia developed promptly, but disappeared within hours unless repeated doses were given. Literature on various types of eosinopenia was reviewed.

Eosinophils↗

PubMed1987

Simultaneous evaluation of terminal deoxynucleotidyl transferase and myeloperoxidase in acute leukemias using an immunocytochemical method.

The classification of acute leukemia is important for the selection of optimal therapy. Classification often rests on morphologic, cytochemical, and immunologic criteria, and the marker enzyme terminal deoxynucleotidyl transferase (TdT) has been considered to be a reliable indicator of lymphoblastic leukemias. Because TdT-positive cells sometimes are seen in leukemias otherwise identified as myeloblastic, the authors evaluated blasts identified as myeloid by the presence of myeloperoxidase (MPO) for the simultaneous expression of TdT. The blasts in the bone marrow aspirate or peripheral blood of unselected patients with hematologic malignancies were evaluated and 60 cases are shown. The French-American-British system and, in some patients, cytochemical and immunologic studies were used to classify the leukemias. The authors demonstrated that blasts simultaneously contained MPO and TdT in 29% of patients with acute myeloblastic leukemia and 3% of patients with acute lymphocytic leukemia (ALL). This finding supports the hypothesis that TdT is an expression of cell primitivity rather than a marker for lymphoblastic cells.

Adolescent↗

PubMed1987

Interleukin-2 receptor levels are increased in blood of heart transplant patients during infections.

Increased levels of soluble interleukin-2 (IL-2) receptor were found in plasma of six patients after the heart transplantation. The levels peaked the first week after transplantation and then gradually decreased to normal levels. The moderate episodes of heart transplant rejection did not affect the IL-2 receptor levels in comparison to transplant recipients without the rejection episodes. However, the transplant patients with pneumonia had the IL-2 receptor levels ten times higher than healthy controls. Hence, the IL-2 receptor levels in plasma might be a valuable indicator of the dynamics of the acute infection in heart transplant recipients.

Fever↗

PubMed1987

Multiple myeloma in two young postpartum women.

Multiple myeloma is an uncommon disease before age 30 years. We recently encountered two cases of myeloma in women, aged 29 and 30 years, respectively. Aside from their young age, another unusual feature of these cases was that each woman had been pregnant and had a normal delivery, three and four months prior to diagnosis. A literature search revealed only 35 reported cases of multiple myeloma at or before the age of 30 years. Of these, only 14 were thought to be clear-cut or highly suggestive of myeloma by the authors. The relationship of multiple myeloma and pregnancy is discussed. Although the number of cases is small, the occurrence of myeloma in the younger individual does not appear to impart a worse prognosis or survival.

Adult↗