Hemoglobin Ohio (beta 142 Ala replaced by): a new abnormal hemoglobin with high oxygen affinity and erythrocytosis

Hemoglobin Ohio [beta 142 (H20) Ala replaced by Asp] was found in three members of a white family, all of whom showed erythrocytosis. The variant hemoglobin has a high oxygen affinity, a reduced Bohr effect, and diminished cooperativity. The functional abnormalities of Hb Ohio are explained by the proximity of the substituent beta 142 residue, both to beta 143 His, which is involved in the DPG binding site of hemoglobin, and to the critical C terminal region of the beta chain, which participates in the stabilization of the deoxy (T) conformation.     

Influence of exercise training frequency on cardiac and hepatic oxidative stress in rats

The present study investigated the influence of different frequencies of moderate exercise (13 weeks of treadmill running at 60% of maximal oxygen consumption) on oxidative stress in the heart and liver in rats. Oxidative stress was evaluated by chemiluminescence and lipid peroxidation (LPO) through thiobarbituric acid reactive substances. Activities of superoxide dismutase (SOD), glutathione peroxidase (GHPx) and catalase (CAT) were also measured. The animals were divided into four groups: control (C), acute ([A], only one exercise session at the end of 13 weeks), low frequency ([LF], one session a week for 13 weeks) and high frequency ([HF], five sessions a week for 13 weeks). Chronic exercise promoted cardiac hypertrophy in the HF group. Myocardial LPO in groups A and LF was increased, whereas in the HF group, it was decreased when compared with group C. The HF group demonstrated decreased myocardial SOD and GHPx activities and increased CAT activity. All exercise groups exhibited an increase in LPO in the liver compared with group C. SOD activity in liver was lower in the HF group and higher in the LF group as compared with group C. GHPx activity was higher in group A in relation to group C. Hepatic CAT activity was higher in groups A, LF and HF. It is suggested that chronic exercise training at a submaximal level is better than infrequent exercise bursts to promote metabolic adaptations that minimize oxidative stress.     

Detection of sickle alpha- or beta0-thalassemia by studies of globin biosynthesis

Globin synthesis studies are useful in the analysis of thalassemia syndromes. We have applied globin synthesis and free alpha-chain pool studies of peripheral blood to characterize hematologic disorders where alpha- or beta-thalassemia was present in combination with HbS or HbC. In 60 non-thalassemic controls, the beta/alpha specific activity ratio was 1.01 +/- 0.06 (SD). In three patients with HbS-beta0-thalassemia, the (betas + gamma)/alpha ratios were 0.48-.067. In four patients with HbSS-alpha-thalassemia, the (BETAS/ALPHA RATIO was 1.26 +/- 0.18 (1.13- 1.53). The radioactive free alpha-chain pool in three patients with HbS- beta0-thalassemia was elevated (35.1%-53.0%), while three patients with HbSS-alpha-thalassemia had decreased free radioactive alpha-chain pools (3.2%-6.4%); both were significantly different from the mean (15.1% +/- 2.6%) of the 17 iron-sufficient controls. Simultaneous studies of the fraction of newly synthesized alpha chain contained in the free alpha- chain pool in peripheral blood and bone marrow demonstrated that this fraction was larger in peripheral blood than in marrow, and that the differences between thalassemia patients and controls previously found in bone marrow using these methods were also present in peripheral blood. The results indicate that even when family studies are not possible, patients with HbS in combination with alpha- or beta0- thalassemia can be differentiated from those with homozygous sickle cell disease by globin synthesis and free alpha-chain pool studies using peripheral blood.     

Terminal deoxynucleotidyl transferase-containing cells in peripheral blood: implications for the surveillance of patients with lymphoblastic leukemia or lymphoma in remission

An indirect immunofluorescence assay was used to quantitate TdT- containing (TdT+) cells in the mononuclear leukocyte fraction of peripheral blood from normal subjects and patients with acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LL). In normal children (10) and adults (10), 0.036% +/- 0.014% (mean +/- SD) and 0.030% +/- 0.015% TdT+ cells were found. In peripheral bloods from 10 children receiving chemotherapy for tumors other than ALL or LL, 0.040% +/- 0.039% TdT+ cells were found. Serial determinations were performed on 15 patients with ALL or LL who were in clinical remission. Eight of these patients remained in continuous remission and always had fewer than 0.11% TdT+ cells in their peripheral blood. Three patients who developed systemic relapse were found to have progressively rising numbers of TdT+ cells in their peripheral blood prior to clinical evidence of relapse. All 3 of these patients had greater than 0.1% TdT+ cells in their peripheral blood from 3 to 8 wk prior to clinical relapse. In 3 other patients, localized extramedullary relapse developed, but no trend was found on serial TdT determinations. Thus, the indirect immunofluorescence assay for TdT detects a small population of cells in normal peripheral blood. In patients with ALL, progressive increases above this normal level were associated with subsequent bone marrow relapse.     

Establishment and characterization of a primary effusion (body cavity- based) lymphoma cell line (BC-3) harboring kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) in the absence of Epstein-Barr virus

The recently identified Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8), has been found to be consistently associated with an unusual subset of acquired immunodeficiency syndrome-related lymphomas, the so-called body cavity- based lymphomas (BCBL) or primary effusion lymphomas (PEL). These lymphomas are characterized by a unique spectrum of morphologic and molecular characteristics, and grow as lymphomatous effusions without an identifiable contiguous tumor mass. Until now, efforts to delineate the role of KSHV in the pathogenesis of PELs have been hampered by the lack of appropriate model systems and the concomitant presence of Epstein-Barr virus (EBV) in nearly all cases examined, and in all previously established cell lines. We now report the establishment and characterization of a novel PEL cell line, BC-3, which is KSHV+ by polymerase chain reaction (PCR) but EBV- as assessed by a variety of methods including PCR for EBER, EBNA-2, and EBNA-3C. This cell line was established from a lymphomatous effusion obtained from an HIV- patient, and has immunophenotypic and molecular features consistent with the diagnosis of PEL, including an indeterminate immunophenotype with a B- cell immunogenotype and lack of c-myc proto-oncogene rearrangements. Pulsed-field gel electrophoresis shows an intact KSHV genome of about 170 kb both in the cell line and in the viral isolate, whereas herpesvirus-like capsids are visible by electron microscopy. Consequently, the BC-3 cell line represents an invaluable tool as a source of KSHV, for both the evaluation of the pathogenic potential of this virus and the mechanistic characterization of its role in the development of Kaposi's sarcoma and malignant lymphoma.     

Durability of responses to interferon alfa-2b in advanced hairy cell leukemia

Previous studies have demonstrated that significant hematologic improvement occurs in the majority of patients with hairy cell leukemia (HCL) treated with partially purified or recombinant interferon (IFN). Fifty-three patients received IFN alfa-2b for at least 3 months in a dose of 2 X 10(6) U/m2 subcutaneously thrice weekly. Of the 49 patients evaluable for response (at least 6 months of IFN therapy), there were ten complete responses and 29 partial responses for a total response rate of 80%. The peripheral blood counts and bone marrow continued to improve over the course of a full year of therapy. IFN was well tolerated, with no patients discontinuing therapy because of toxicity. Transient myelosuppression occurred in most patients during the first 1 to 2 months of therapy, occasionally precipitating a transfusion requirement. After IFN treatment was discontinued, there was a marked decrease in normal marrow elements and a relative increase in marrow hairy cells. This was associated with a transient increase in normal elements in the peripheral blood. Only one of 24 patients followed after receiving IFN for a median of 8.5 months (range, 3 to 16 months) has required further therapy. We conclude that low-dose IFN alfa-2b is highly effective in advanced HCL; responding patients should be treated for at least 1 year. The decision to initiate a second course of IFN therapy should be based primarily on peripheral blood counts and the clinical status of the patient rather than on the bone marrow.     

Transduction of hematopoietic cells by foamy virus vectors

Foamy viruses are retroviruses of the spumavirus family that are often isolated from primary cultures of primate cells. We previously constructed vectors based on human foamy virus (HFV) and found that they were able to transduce a wide variety of vertebrate cells by integration of the vector genome. Here we show that several types of hematopoietic cells are efficiently transduced by an HFV vector that encodes alkaline phosphatase (AP). These cell types include transformed cell lines and primary hematopoietic progenitors from mice, baboons, and humans. The transduction rates of HFV vectors compare favorably with those obtained by murine leukemia virus vectors, which suggests that HFV vectors may be effective in the treatment of hematologic diseases by gene therapy.     

Coordinate glycosylation and cell surface expression of glycophorin A during normal human erythropoiesis

The expression of two epitopes on glycophorin A (GPA) during erythroid development was examined on normal human bone marrow using quantitative flow cytometry. The highly correlated binding of two monoclonal antibodies, one sensitive and the other insensitive to glycosylation, indicated that the two epitopes were coordinately expressed during erythroid development. Both antigens reached a maximum expression during the early normoblast stage and were maintained at a constant amount per cell throughout further maturation to erythrocytes. These data suggest that glycosylation of GPA, as detected by antibodies recognizing blood group (M) and (N) antigens, does not increase during erythroid maturation.     

Donor room personnel attitudes toward autologous donors

Patients with serious illnesses who donate their blood for autologous use create anxiety for many phlebotomists. Donor room staff were surveyed at three donor centers, using confidential questionnaires, to identify their concerns and to evaluate factors associated with reduced anxiety toward autologous donors. Among respondents (n = 93), 58 percent had patient care experience within the last 5 years, which correlated with diminished concern about phlebotomizing cardiac patients (r = .21; p = 0.04). Fifty-seven percent of respondents had drawn blood from greater than 50 autologous donors. Surprisingly, the experience of drawing blood from relatively large numbers of autologous donors did not correlate with increased confidence in phlebotomizing pediatric, cardiac, and elderly patients (r = -.04; p = 0.75). Those respondents who felt that they had adequate medical support agreed with more liberal donor criteria and were more confident about phlebotomizing pediatric, cardiac, and elderly patients (r = -.32; p = 0.001). Those respondents who believed most strongly in the benefits of autologous transfusion had the least anxiety toward donors who were medically more complex (r = .39; p = 0.0001). It is concluded that, contrary to what might be expected, phlebotomizing large numbers of autologous donors does not reduce the anxiety of staff members when they encounter donors with complex medical problems. Factors that do reduce anxiety include dependable physician and other medical support services, previous experience in direct patient care, and knowledge of the benefits of autologous transfusion.     

Advanced Pacemaker Diagnostic Features in the Characterization of Atrial Fibrillation: Impact on Preventive Pacing Algorithms

YANG, A., et al .: Advanced Pacemaker Diagnostic Features in the Characterization of Atrial Fibrillation: Impact on Preventive Pacing Algorithms. Pacing algorithms to prevent PAF are mainly based on the suppression of premature atrial complexes (PACs), which play an important role in its initiation. In contrast to 24-hour ambulatory electrocardiograms, advanced pacemaker (PM) diagnostic features are capable of recording AF episodes during long follow-up periods and of characterizing AF in a detailed fashion. For the specific use of these algorithms, a detailed characterization of AF was performed in 91 dual chamber PM recipients with histories of AF. Fifteen patients with episodes of oversensing due to far-field signals or frequent episodes of "2:1-undersensing" of atrial flutter were excluded. The remaining 76 patients had high recurrence rates of AF (median 0.8 episodes/day), however, the majority of episodes lasted <7 minutes. Despite frequent PACs (median 10.8/hour) during sinus rhythm, a median of 66.4% of the AF episodes were preceded by <2 PACs/min before onset. In conclusion, frequent, short-lived AF episodes seem best suited for AF preventive pacing therapies. However, the small number of PACs preceding many AF episodes may limit the efficacy of PAC suppressing algorithms. (PACE 2003; 26[Pt. II]:310–313)