Search PubMed⌕ Search

Biomedical subjects

H Karle

Publications and source records attributed to H Karle.

At least 91 records · Page 5Linked to original sources

Cell proliferation and protein synthesis in human leukaemic myeloblasts after cytosine arabinoside therapy.

The effect of a single intravenous bolus injection of cytosine arabinoside (ARA-C) on the cytokinetics and 3H-leucine uptake of leukaemic myeloblasts in bone marrow and blood was studied at intervals up to 96 h after ARA-C in five patients with previously untreated acute myelogenous leukaemia. An early decrease in mitotic index and in 3H-thymidine labelling was observed in four of five patients and pretreatment values were reached again within the observation period. Changes suggesting synchronization were not observed. ARA-C induced a marked decrease in protein synthesis in the leukaemic myeloblasts as estimated from either a decrease in the 3H-leucine labelling index or the mean grain count of 3H-leucine labelled cells. It is suggested that ARA-C is incorporated also by cell which are not in S-phase and has a prolonged biochemical effect on the leukaemic cells.

Adult↗

Nuclear DNA-polymerase estimation in human leukaemic myeloblasts.

A technique which detects the presence of DNA-polymerase in cell nuclei by measuring the incorporation of 3H-thymidine-5-triphosphate (3H-TTP) has been used to estimate the proportion of leukaemic myeloblasts which contains DNA-polymerase and DNA capable of acting as primer-template. In six cases of previously untreated acute myeloid leukaemia the 3H-TTP labelling index (3H-TTP LI) was much larger than the fraction in DNA synthesis. After a single 'flash' injection of cytosine arabinoside a pronounced decline was observed in the 3H-TTP LI, which can be explained by a direct inhibition of NDA-polymerase. No change was observed in the fraction of cells labelled with 3H-thymidine. A decrease in 3H-TTP LI was also observed after a single i.v. dose of methotrexate.

Bone Marrow↗

Serum lysozyme in Crohn's disease and ulcerative colitis.

Serum lysozyme (muramidase) was determined in 72 patients with Crohn's disease or ulcerative colitis. Serum lysozyme was elevated in both disease groups. The mean enzyme level was significantly higher in Crohn's disease than in ulcerative colitis, but there was a considerable overlapping between the groups, which makes serum lysozyme determination of dubious value in the differential diagnosis between Crohn's disease and ulcerative colitis. No correlation was found between the serum lysozyme concentration and the activity of the diseases.

Adolescent↗

Neutrophilic granulocytes in acute bacterial infection. Sequential studies on lysozyme, myeloperoxidase and lactoferrin.

The changes in intraneutrophilic and plasma concentrations of the three antibacterial proteins lysozyme, lactoferrin, and myeloperoxidase were studied sequentially during acute bacterial infection in nine patients. Intraneutrophilic concentrations of the three proteins were decreased by more than 50% during the 1st week of infection, followed by a slow increase over the following 2 weeks. Nadir values coincided with maximal toxic granulation of the neutrophils. The data suggest that neutrophilic granulocytes are deficient during early bacterial infection, possibly because of deficient synthesis of antibacterial proteins in the bone marrow, and that neutrophil toxic granulation is the visual counterpart of this defect. The plasma concentrations of the three proteins showed considerable differences: whereas plasma lysozyme did not show any sequential changes, plasma myeloperoxidase was high at the start of infection and quickly decreased towards normal values, and plasma lactoferrin, high in the first samples, showed a secondary peak 1 week after onset of disease, before normalization was seen. These differences may result from differences in the signals are specific for the individual antibacterial protein and not for the different types of neutrophil granules.

Adult↗

Sequential studies of lymphocyte responsiveness and antibody formation in acute bacterial meningitis.

Lymphocyte transformation responses in vitro were studied in eight patients with acute bacterial meningitis (in five due to Neisseria meningitidis). Sequential studies were done from 24--48 hr after the first symptoms of infection to complete recovery. In all cases lymphocyte transformation was depressed during the acute phases of illness. The responses to microbial antigens were more affected than the responses to mitogens. The course of the lymphocyte responses to the causative micro-organism showed no difference from the responses to other microbial species. A moderate shift towards increased sensitivity of the lymphocytes to lower doses of the causative micro-organism was observed during the course of illness in three cases. In N. meningitidis infection, a rapid rise was seen in the serum titres of complement-fixing antibodies and in the number of precipitating antibodies, whereas the rise in immunoglobulin concentrations was more prolonged. Characteristic patterns of elevation and return towards normal were found in the serum concentrations of the acute-phase reactants alpha1-antitrypsin, haptoglobin, and orosomucoid. It is concluded that the lymphocyte transformation responses in vitro during severe bacterial infection are largely governed by non-specific factors, and that studies of lymphocyte responses to micro-organisms should always include other microbial species as controls.

Antibody Formation↗

Neutrophil defect in multiple myeloma. Studies on intraneutrophilic lysozyme in multiple myeloma and malignant lymphoma.

Intracellular lysozyme concentration was measured in neutrophilic granulocytes from 25 patients with multiple myeloma. At diagnosis intraneutrophil lysozyme activity was significantly reduced (mean reduction 50%). During clinical remission after 1-4 months of intensive chemotherapy values were normalized. In 18 cases studied at various stages of the disease from 6 to 70 months after diagnosis there was a significant negative correlation between the duration of the disease and neutrophil lysozyme concentration. The decrease in neutrophil lysozyme concentration was significantly correlated to clinical disease activity and the percentage of plasma cells in bone marrow aspirates, whereas there was no correlation between the concentration of M-protein in serum and the neutrophil lysozyme concentration. Plasma lysozyme concentration was normal. In contrast, neutrophil lysozyme concentration was normal in 18 patients with stage III-IV malignant lymphoma. Plasma lysozyme in this group was significantly higher than normal. The difference in neutrophil lysozyme patterns between multiple myeloma and malignant lymphoma supports the hypothesis that the defect in neutrophil maturation seen in malignant blood disorders is directly related to the infiltration of the bone marrow by pathologic cells.

Antineoplastic Agents↗

Fever and haemolysis in Hodgkin's diseases.

One hundred and four patients with Hodgkin's disease have been studied retrospectively in order to evaluate the relationship between fever associated with the disease (Pel-Ebstein type) and the development of anaemia. In the material 19 episodes of fever were found to be of this type. The mean loss of Hb during a fever period was 14% (range 2-33). From the rate of decrease in Hb it was deduced that this was at least partly caused by an increased destruction of erythrocytes. There was a significant correlation between the thermal exposure (expressed either as the duration of fever, the maximum body temperature during the fever period, or the sum of the temperature maxima) and the degree of erythrocyte loss. The loss of Hb was self-limited in spite of persistent fever. Furthermore, there seemed to be an inverse relationship between the degree of preexisting anaemia and the fever-induced relative loss of Hb. A possible explanation is that the older part of the erythrocyte population is more sensitive to the effect of fever.

Erythrocytes↗

Neutrophil kinetics in corticosteroid induced neutrophilia measured by plasma lysozyme.

A single dose of prednisone (2 mg/kg orally) resulted in a mean rise in neutrophil counts to 2.3 (range 1.5-3.6) and a mean decrease in plasma lysozyme to 0.73 (range 0.50-0.87) times the value before the steroid was given in 10 haematologically normal persons. There was no change in the intraneutrophilic lysozyme activity. It is concluded that the decrease in plasma lysozyme is compatible with a reduction in the egress of neutrophils to the tissues and a decrease in the neutrophil turnover rate.

Adult↗

Lysozyme turnover in man.

Lysozyme turnover studies with (125)I-labeled human lysozyme were carried out on 22 patients, viz. nine control patients, seven nephrological patients with varying degrees of renal insufficiency, including three bilaterally nephrectomized patients, and six hematological patients with disturbed turnover of the neutrophilic granulocytes. It was found that plasma lysozyme has a rapid turnover with a fractional catabolic rate of 76%/hr of the plasma content. Lysozyme catabolism varied with the endogenous creatinine clearance; in addition however, extrarenal sites of catabolism were demonstrated since lysozyme could be broken down in the anephric patients, although only at a rate amounting to about 15% of the rate found in persons with intact kidneys. In the uremic patients the increased plasma lysozyme concentration was due to decreased rates of catabolism; in the hematological patients the increased plasma lysozyme level was due to increased rates of synthesis which supports the hypothesis that plasma lysozyme mainly stems from disintegrating neutrophilic granulocytes. Furthermore, it was shown that in the nonhematological patients examined, the rate of synthesis varied with the endogenous creatinine clearance.

Adolescent↗