A second isolate of HTLV-II associated with atypical hairy-cell leukemia.
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Aged↗
Biomedical subjects
A Jacobs
Publications and source records attributed to A Jacobs.
Prognostic importance of hypodiploid hemopoietic precursors in myelodysplastic syndromes.
It has been suggested that a poor prognosis and the development of leukemia in patients with myelodysplasia may be related to chromosomal abnormalities. We measured the DNA content of bone marrow cells with flow cytometry in 19 hematologically normal subjects and in 70 patients who had recently been diagnosed as having myelodysplasia. Thirty-four of the patients were found to have aneuploidy. This was not related to the percentage of blast cells in the bone marrow, and there was no demarcation in terms of DNA content between patients with a high percentage of blast cells and those with a low percentage of such cells. Patients with hypodiploid marrow cells had a significantly shorter survival time than other patients (P = 0.001). Patients with hyperdiploid marrow and those whose marrow had a normal DNA content had similar survival times. Hypodiploidy appears to be a better indicator of poor survival than the marrow blast-cell count. Patients with sideroblastic anemia invariably had cells with a normal or high DNA content; none of these patients died during the study. Our data suggest that there is a relation between the loss of chromosomal material and progression toward a leukemic phenotype. It is tempting to speculate that this process may involve a loss of negative regulatory genes ("anti-oncogenes").
Aneuploidy↗
Trial of strategy for reducing the use of laboratory tests.
Clinical guidelines and a weekly review of medical records were introduced into a medical unit in a teaching hospital to promote a more discriminating use of laboratory tests. This strategy resulted in an immediate reduction in the average number of requests each week from 74 to 27 haematological tests (64%) and 158 to 58 biochemical tests (64%). During a period of 10 weeks after the strategy was introduced (the intervention period) the mean number of haematological tests for each person decreased from 2.0 during the baseline period to 1.1 (45% reduction; p less than 0.01) and the mean number of biochemical tests decreased from 4.4 to 2.7 (39%; p less than 0.0001). The decrease in the number of repeat requests was greater than that for new requests and accounted for half the reduction in use. There was no significant change in the number of tests requested from an adjacent medical unit that was not exposed to the interventions. This strategy is worthy of trial in other specialties and hospitals, but attention will have to be paid to possible difficulties in sustaining reductions in use over long periods of time.
Clinical Laboratory Techniques↗
Measurement of 5-aminolevulinic acid synthase activity in whole and fractionated human bone marrow: effect of myeloid cell lysis by monoclonal antibody.
A sensitive radiochemical assay for the measurement of bone marrow and erythroblast 5-aminolevulinic acid (ALA) synthase (EC 2.3.1.37) was developed and optimized with respect to sample preparation and reagent concentration. Succinylacetone (4,6-dioxoheptanoic acid) was used to prevent ALA utilization during the incubation period. Sample purification on a Sep-Pak cartridge (Waters Associates) followed by reverse-phase high-performance liquid chromatography (HPLC) allowed rapid isolation of pure ALA-pyrrole, free from radioactive succinate and other contaminants. ALA synthase activity was measured in unfractionated bone marrow and in samples from which myeloid cells had been removed by monoclonal antibody-mediated cell lysis. Myeloid-derived ALA synthase was calculated and found to contribute approximately half of the total unfractionated marrow enzyme activity. This suggests that results from previous studies using unfractionated bone marrow which have assumed that myeloid cells are an insignificant source of ALA synthase require reappraisal.
5-Aminolevulinate Synthetase↗
Serum levels of CA-125 in patients with endometriosis: a preliminary report.
Seven out of 8 patients with endometriosis demonstrated levels of CA-125 antigen above 35 U/ml. None of 15 patients with other benign gynecologic diagnoses demonstrated elevated levels. This antigen has been proposed as a tumor marker for epithelial carcinoma and other gynecologic neoplasms. However, it cannot be used to differentiate clinically between cancer and endometriosis.
Adolescent↗
The ferritin content of normoblasts and megaloblasts from human bone marrow.
Erythroblasts were enriched from human bone marrow samples and fractionated on Percoll gradients according to maturity. Heart-type and spleen-type ferritin was measured in each fraction by an immunoradiometric assay. In normal marrow, heart-type ferritin content was higher in the early erythroblast fractions and fell with maturation. Spleen-type ferritin content showed no such consistent change. Megaloblastic erythroblasts had a significantly higher ferritin content.
Bone Marrow↗
Iron uptake and ferritin synthesis in human erythroblasts.
The erythroblasts from four normal bone marrows were enriched by using an anti-myeloid monoclonal antibody (TG-1), and a polyclonal antibody against mononuclear cells to effect complement mediated lysis of unwanted cells. The erythroblasts were cultured for 2 h in medium containing [59Fe]transferrin and [3H]-leucine, then fractionated on Percoll gradients according to their density. Whole cell iron uptake by early erythroblasts was greater than in the dense late erythroblasts. In all marrows, iron uptake into ferritin was highest in fractions containing the earliest erythroblasts and decreased with increasing erythroblast maturity. In three of the four marrows this paralleled the pattern of ferritin synthesis. It seems likely that apoferritin is synthesized in response to the amount of iron taken into the cell and this iron is incorporated within the protein shell to form ferritin.
Bone Marrow↗
Eosinophilic infiltration with flame figures. A distinctive tissue reaction seen in Wells' syndrome and other diseases.
We report five cases, all male, of diverse clinical findings of scattered erythematous, violaceous, or centrally blue plaques. Eight biopsies from the five patients showed nodular or diffuse dermal and subcutaneous infiltration, predominantly of eosinophils and histiocytes, with "flame figures" composed of granules of eosinophils that surround collagen bundles, whose staining quality is thereby altered. Two patients were children, the younger only 18 months old. Three patients initially presented clinical evidence of insect bites, and in one of these the biopsy showed cutaneous pseudolymphoma underlying dermal changes of eosinophilic cellulitis. Eosinophilic infiltration with flame figures is a distinctive reaction to various stimuli. It may be seen in a wide variety of clinical conditions and is not confined solely to patients with Wells' syndrome, which may be an acceptable term for clinically typical cases. Eosinophilic infiltration with flame figures is preferred descriptively to identify the microscopic changes in Wells' syndrome and in other cases like that of our patient with pseudolymphoma, in which the cutaneous reaction may be secondary to some other disease.
Adult↗
Primary acquired sideroblastic anaemia.
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Anemia, Sideroblastic↗
DNA content and cell cycle analysis of bone marrow cells in myelodysplastic syndromes (MDS).
DNA distribution in bone marrow cells from 10 normal subjects and 34 patients with MDS (24 with refractory anaemia (RA) and 10 with excess blasts (RAEB] was determined by flow cytometry using a FACS III. DNA histograms were resolved into G0/1, S and G2/M compartments by fitting Gaussian distributions and the DNA content of G0/1 cells, expressed as DNA index (DI), was determined. In 19 MDS patients the DI was outside the normal range, those with RA tending to be hyperdiploid. Two patients with RAEB had a second G0/1 peak. In five cases of RA the number of cells in G0/1 was below the normal range and the mean value was significantly lower than normal for this group as a whole (P = 0 X 018). Eleven (RA) patients had a higher percentage of cells in G2/M than normal (P = 0 001). In RAEB patients there is a suggestion of increased numbers in G0/1 and a decrease in S phase and G2/M cells. All three of the deaths amongst RA patients and four out of the five deaths in RAEB patients since the beginning of this study were associated with an abnormal DI at the initial investigation.
Bone Marrow↗
Increased alpha:non-alpha globin chain synthesis ratios in myelodysplastic syndromes and myeloid leukaemia.
Globin chain synthesis ratios (alpha:beta + gamma) in leucocyte free reticulocytes from six of 11 patients with various myelodysplastic syndromes were high, ranging from 1.28 to 2.43. High ratios were also found for reticulocytes from two of four patients with acute myeloblastic leukaemia. Of the eight cases in which high ratios were found, seven were in patients who were either undergoing leukaemic transformation or who had already transformed. The reason for these findings is not known, but an understanding of the mechanism may give us further insight into the process of leukaemic transformation.
Aged↗
Diagnostic methods for iron status.
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Clinical Laboratory Techniques↗
Alpha-2 interferon therapy of hairy-cell leukemia: a multicenter study of 64 patients.
Sixty-four patients with hairy-cell leukemia (HCL) (61 had undergone prior splenectomy) were treated with alpha-2 interferon (Intron A, Schering Corp, Kenilworth, NJ) subcutaneously three times per week at a dosage of 2 X 10(6) U/m2. Three patients (5%) demonstrated a complete response (CR) with apparent eradication of hairy cells from the bone marrow, 45 patients (70%) showed a partial response (PR) defined as normalization of all three blood counts associated with decreased involvement in the bone marrow, and nine patients (14%) showed a minor response that included improvement in at least one blood count. Three patients had no response, three patients died before completing 1 month of therapy, and one patient refused further therapy after 1 month of therapy. The median platelet count returned to normal by the second month of treatment. The median hemoglobin returned to greater than 12 mg/dL by the fourth month of treatment, and the median granulocyte count to greater than 1,500/mu by the fifth month of treatment. Bone marrow biopsy analysis during interferon therapy demonstrated a decrease in median hairy-cell index by more than half. Transfusion of both RBCs and platelets were decreased within 4 months of initiating treatment. Serious infections, which averaged four per month in 16 of the 64 patients before interferon therapy, were rarely observed after the first month of treatment. Treatment-induced toxicity was mild, consisting primarily of influenza-like symptoms, fatigue, and minor skin disorders. Alpha-2 interferon therapy is highly effective in reversing the course of progressive HCL and should be considered the treatment of choice for a minimum of 12 months in patients who have progressive disease post-splenectomy.
Adult↗
EMG biofeedback training, relaxation training, and placebo for the relief of chronic back pain.
24 patients with chronic low back pain were randomly assigned to three treatment conditions: EMG biofeedback, relaxation training, and a placebo condition. Patients were seen for eight sessions and were evaluated before Session 1 and after Session 8. Eight analyses of covariance which were adjusted for age and pretest scores were computed on the final scores to find which variables could detect significant difference between treatments. Age was included as a covariate because the differences in age between conditions were significant. Four variables with significant and nearly significant differences were chosen for analysis. The second set of analyses identified the nature of the differences among the three conditions. These included a priori planned comparisons among conditions, and paired t tests. Relaxation-trained subjects were significantly superior to subjects in the placebo condition, in decreasing pain during the function test, increasing relaxation, and decreasing Upper Trapezius EMG. They were superior to EMG Biofeedback training in increasing reported activity. Both Relaxation and EMG trained subjects were able to reduce Upper Trapezius EMG by Session 8. Relaxation-trained subjects showed significant change on eight of the 14 possible comparisons for each treatment condition. EMG biofeedback training showed significant favorable results in only one condition; the placebo condition showed no significant results. Relaxation training gave better results in reducing EMG and pain, and in increasing relaxation and activity than either EMG biofeedback alone or a placebo condition.
Back Pain↗
Ferritin expression in transformed human haemopoietic cell lines.
Isoferritins found in a number of human haemopoietic cell lines do not correspond to the isoferritins found widely distributed in normal tissues. It is suggested that these proteins may result from the expression of otherwise silent genes known to be present in the human genome.
Amino Acid Sequence↗
Triclonal gammopathy in a patient with plasma cell dyscrasia.
A triclonal gammopathy is an immunoglobulin abnormality in which three discrete monoclonal subpopulations of immunoglobulin molecules are present in a patient's serum. Monoclonal and biclonal gammopathies have been studied extensively, but relatively little is known about the much rarer triclonal gammopathies. The case described below illustrates some of the difficulties that this condition can present to the clinician and the clinical laboratory.
Humans↗
Pathogenesis and clinical variations in the myelodysplastic syndromes.
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Aged↗
Peripheral blood granulocyte-macrophage progenitors in patients with the myelodysplastic syndromes.
Peripheral blood (PB) granulocyte-macrophage progenitor (CFU-GM) growth was measured in 47 normal subjects and, together with bone marrow CFU-GM and blast cell numbers, in 45 newly diagnosed patients with myelodysplastic syndromes (MDS). Both PB colony and cluster numbers were significantly reduced in MDS patients. In patients with greater than 5% marrow blasts there was a negative correlation between blast cell numbers and PB colony growth. Bone marrow and PB colony growth were also well correlated in this group. Poor growth of PB CFU-GM appears to be more closely related to prognosis than does bone marrow progenitor growth.
Bone Marrow Cells↗