Hemoglobin M equon beta 41 (C7) phenylalanine leads to tyrosine

A severe hemolytic crisis was observed in a 34-yr-old female of English- Irish extraction following a viral illness treated with acetaminophen. Heinz bodies and heat instability were present only during a transient hemolytic event. A challenge dose of acetaminophen caused no detectable hematologic abnormality. Structural studies of the hemoglobin during hemolysis and again after complete recovery localized the abnormality to tryptic peptide beta Tp-5, and automated sequencing of I 125-labeled beta chains indicated a replacement of phenylalanine (C7) beta 41 by tyrosine. Substitution of the next residue, phenylalanine (CD1) beta 42 by serine (Hb Hammersmith), has resulted in chronic severe Heinz body hemolytic anemia. The lack of chronic anemia in the present disorder may reflect the different relationships of beta41 and beta 42 and/or the similarities in volume and hydrophobicity of tyrosine and phenylalanine. It is suggested that substitution of tyrosine for phenylalanine in Hb Mequon may disturb the critical environment around the heme group and render it susceptible to oxidative denaturation in the presence of infections and/or drugs.     

Apoptosis and macrophage-mediated deletion of precursor B cells in the bone marrow of E mu-myc transgenic mice

Transgenic mice expressing the c-myc proto-oncogene under the control of the Ig heavy chain enhancer (E mu-myc) all eventually develop clonal pre-B- or B-cell tumors. The preneoplastic period is characterized by increased polyclonal proliferation of pro-B and pre-B cells in the bone marrow (BM) associated with a reduced number of B cells, suggesting a high degree of B-cell loss. To examine the mechanisms of this cell loss, we have identified B220+ B-lineage cells within the BM of pretumorous E mu-myc transgenic mice by in vivo radiolabeling and electron microscope radioautography. Large mitotic B220(+)-labeled cells form prominent clusters in the extravascular compartment of the BM. Some B220+ small lymphocytes, as well as large lymphoid cells, enter BM sinusoids. However, in addition, large numbers of B220+ cells exhibit nuclear chromatin condensation, fragmentation, and other morphologic features characteristic of apoptotic cell death. Propidium iodide staining and flow cytometry of BM cells from pretumorous E mu- myc transgenic mice, as well as agarose gel electrophoresis of DNA, confirm extensive apoptosis. Many B220+ apoptotic cells are closely associated with the extensive processes of prominent macrophages that contain numerous B220+ apoptotic bodies and complex lysosomal systems. These results suggest that the constitutive expression of c-myc oncogene in BM B-lineage cells, which increases the proliferation of precursor B cells, also leads to increased apoptotic cell death and rapid elimination by resident macrophages. Further mutations may be needed to block these protective mechanisms and permit surviving c-myc- dysregulated cells to leave the BM and to initiate tumorigenesis.     

The spine: changes in T2 relaxation times from disuse

Magnetic resonance imaging of the spine was performed in six healthy male volunteers before and after 5 weeks of continuous bed rest. Imaging studies consisted of a single 1-cm sagittal section obtained with a spin-echo technique through the center of the spinal column. The T2s of the lumbar vertebral body and nucleus pulposus and the area of the latter were measured. In both vertebrae and disks, there was a significant decrease in T2 after bed rest. The nucleus pulposus also decreased in size with bed rest. The decrease in relaxation time of the lumbar vertebrae could be explained by the replacement of hematopoietic marrow by fatty marrow, a known consequence of paralytic immobilization. The decreases in size and T2 of the disks probably represent loss of water. The significance of these changes to the mechanical integrity of these structures after immobilization or space flight is not known but will depend in part on whether changes are progressive with increasing length of immobilization and on the rate and extent that they are reversed after reambulation. These results indicate that relaxation times can be altered by simple disuse, which often accompanies the underlying disease.     

Critical analysis of radiologist-patient interaction

A critical incident interview technique was used to identify features of radiologist-patient interactions considered effective and ineffective by patients. During structured interviews with 35 radiology patients and five patients' parents, three general categories of physician behavior were described: attention to patient comfort, explanation of procedure and results, and interpersonal sensitivity. The findings indicated that patients are sensitive to physicians' interpersonal styles and that they want physicians to explain procedures and results in an understandable manner and to monitor their well-being during procedures. The sample size of the study is small; thus further confirmation is needed. However, the implications for training residents and practicing radiologists in these behaviors are important in the current competitive medical milieu.     

The relationship between objective sleep variables and subjective sleep estimation in schizophrenia

AIM: Few investigations of sleep structure in schizophrenia have concentrated on the relationship between objective and subjective sleep variables. The aim of this study was to assess objective sleep variables and subjective estimation of sleep duration and sleep quality. METHODS: Polysomnography was performed in 20 chronic patients with schizophrenia during three consecutive nights. After final awakenings subjects answered questions concerning subjective estimations of sleep duration, sleep latency, number of awakenings, and sleep depth. Pearson correlations between ranged subjective reports and objective sleep variables were performed. RESULTS: The results showed a high positive correlation between objective sleep latency and its subjective estimation; a positive correlation between subjective estimation of sleep depth and percentage of slow wave sleep (SWS%); a positive correlation between eye movement (EM) density and subjective estimation of wakefulness during the night; and a negative correlation between EM density and dream reports. CONCLUSION: We concluded that objective sleep variables are related to subjective sleep estimation in schizophrenic patients. In these patients, EM activity in REM sleep is related to the subjective feeling of wakefulness. (Int J Psych Clin Pract 2000; 4:63-67)     

Screening tests for blood donors presumed to have transmitted the acquired immunodeficiency syndrome

We investigated 18 sets of blood donors from 12 to 50 months after they donated blood to recipients who subsequently developed the acquired immunodeficiency syndrome (AIDS). Within each donor set, only one donor was suspected of having transmitted the disease (ie, member of an AIDS risk group). The other donors (n = 189) were not risk group members and served as controls. A number of laboratory tests distinguished suspected from nonsuspected donors, including determination of T helper/T suppressor cell ratio, antibody to hepatitis B core antigen, and immune complexes, but none of these was as sensitive and specific as tests for antibody to the human retrovirus, HTLV-III/LAV.     

SYSTOLIC MURMURS IN APPARENTLY HEALTHY INDIVIDUALS

Presence of a systolic murmur is not always indicative of organic heart disease or abnormality, especially so in asymptomatic individuals. We studied 210 young adults (192 males, 18 females) of the age group 16 to 23 years with systolic murmurs to evaluate the utility of noninvasive tests in ascertaining the presence or absence of heart disease. Each case was categorized after clinical evaluation and again after noninvasive investigations (chest radiogram, 12 lead ECG, and echocardiography) into 3 groups. Based on clinical evaluation alone, 190 (90.5%) cases had no evidence of heart disease (group A), 16 (7.6%) cases had definite heart disease (group C) and in 4 (1.9%) cases the presence of heart disease could not be ruled out definitely (group B). The recategorization after investigations did not alter the initial diagnosis in any of the subjects from groups A and C (98.1%). Two cases from group B (0.95%) changed groups whereas in the remaining 2 cases (0.95%) from group B no definite conclusions could be reached even after echocardiography.KEY WORDS: Heart disease, Heart murmurs, Echocardiography, Diagnosis