Membrane biophysical studies of lymphocytes and erythrocytes in manic-depressive illness

Recent research suggests that manic-depressive illness is associated with a membrane abnormality which is detectable in peripheral tissues. Using fluorescence spectroscopy, the cellular membrane dynamics of intact erythrocytes and lymphocytes from manic-depressive patients and controls were studied in a double blind fashion. A cross-sectional analysis of membrane dynamics was obtained by using fluorescent probes with known affinity for specific regions of erythrocyte membranes. This preliminary study demonstrates alterations in the hydrocarbon region of erythrocyte membranes and the cell surface of lymphocytes in patients with manic-depressive illness. These abnormalities appear to be independent of clinical symptomatology and medication. The membrane abnormality demonstrated by fluorescence spectroscopy may provide clues to the molecular pathophysiology in manic-depressive illness, as well as a method of diagnosis in presymptomatic patients.     

Skin testing to detect penicillin allergy

Skin testing for penicillin allergy with penicillin G (Pen G), penicilloic acid (PA), and penicilloyl poly-L-lysine (PPL) was performed on 740 subjects, and the results were assessed from epidemiologic and immunologic perspectives. Approximately 95% of these patients had histories of apparent allergic reactions to beta-lactam antibiotics, and 63% were skin-test positive. The prevalence of positive skin tests was related to the time that had elapsed between clinical reactions and skin testing. Ninety-three percent were skin-test positive 7 to 12 mo after reactions, and 22% were positive 10 yr or more after reactions. Patients under 30 yr of age had a prevalence of positive skin tests 1.7-fold higher than older patients. Testing with PPL, PA, and Pen G detected 76.3%, 55.3%, and 57.1% of the positive patients, respectively. Omission of PPL, PA, or Pen G would have led to a failure to detect 25.6%, 7.2%, and 6.2% of the positive patients, respectively. Subjects with skin tests positive to penicillin often reacted to skin tests with other beta-lactam antibiotics; 73% (41 of 56) reacted to ampicillin and 51% (38 of 74) reacted to cephalothin. No serious allergic reactions were provoked by testing. None of the 83 skin test--negative patients treated with beta-lactam antibiotics immediately after testing experienced acute allergic reactions. Two patients developed mild urticaria beginning 3 and 5 days into therapy. One skin test--negative patient experienced urticaria 3 hr after receiving oral penicillin 6 mo after skin testing. This patient's skin-test status immediately before therapy was unknown. These results support the position that testing with PPL, PA, and Pen G is a rapid, safe, and effective method for identifying patients at risk, or not at risk, for allergic reactions to penicillin.     

Differential effects of cognitive therapy and pharmacotherapy on depressive symptoms

Patterns of symptom change were examined in 35 unipolar depressed outpatients treated with either cognitive therapy or pharmacotherapy (imipramine HCI). Cross-lagged panel analyses were used to evaluate the temporal relationships among changes in views of the self, hopelessness, mood, motivation and vegetative symptoms during treatment weeks 1–4.During cognitive therapy improvements in hopelessness, views of the self and mood generally preceded changes in vegetative and motivational symptoms. On the other hand, no consistent pattern of change was associated with pharmacotherapy. While these results are compatible with the notion that cognitive therapy initially alters negative thinking and mood, which secondarily leads to improvements in vegetative and motivational symptoms, further studies with a placebo or wait-list group are needed to determine if this is a unique effect of cognitive therapy.     

Diagnosis of Latent Mycobacterium tuberculosis Infection in the Era of Interferon Gamma Release Assays

Mycobacterium tuberculosis (MTB), an acid-fast bacterium, is a leading cause of respiratory illness and death worldwide. Individuals can be latently infected and can harbor the organism without clinical evidence of disease for years. Screening and treatment of numerous populations, including health care workers, recent contacts of actively infected individuals, immunocompromised individuals, children, and immigrants from countries where MTB is endemic, is essential to eradicate the infection by 2050, as the World Health Organization envisions. Detection of active and latent infection historically has utilized tuberculin skin tests and other clinical findings. Interferon gamma release assays can test whether a patient has had MTB exposure with improved sensitivity and specificity over tuberculin skin testing. This article reviews the history of MTB testing, compares available interferon gamma release assays, and discusses the new developments related to latent-MTB infection testing.     

Near-haploid cell line in the blastic crisis of chronic myelogenous leukemia: A possible marker for lymphoid malignancy

The blast cells of a 14-year-old patient in the blastic phase of chronic myelogenous leukemia (CML) were studied. Cellular morphology, presence of the enzyme terminal deoxynucleotidyl transferase (TdT), and reactivity to the common acute lymphoblastic leukemia antiserum (CALLA) substantiated a lymphoid blast cell line. Immunologic surface markers were nonreactive for E-rosette (T) cells and immunoglobulin-bearing (B) cells. Cytogenetic studies revealed persistance of the Philadelphia chromosome and a near-haploid cell line, i.e., 28,XY,t(9;22),+14,+15,+21,+22(GTG).The patient responded to chemotherapy with vincristine, prednisone, and l-asparaginase, first line drugs used for remission-induction of acute lymphoblastic leukemia in childhood. We suggest that severe hypodiploidy or near-haploidy, along with TdT and CALLA, may provide more accurate prognostic information in patients with CML and the lymphoid blastic crisis.     

Segregation of three recently identified HLA specificities in an American Black family

Three recently identified HLA specificities have been detected in a ten-member American Black family using 8th International Histocompatibility Testing Workshop and local antisera. Independent segregation of the two principal components of 8w59 (Bu and SV) was demonstrated. An Aw19-related specificity also segregated in the family.     

A grading system for bone marrow cytogenetics and its use as a standard for quality control

A grading system has been developed to assess the quality of the results of bone marrow cytogenetic procedures. The results of 3 1/2 years use of this grading system are reported. This grading system is a satisfactory internal standard for quality control and is adaptable for use as an external standard. The use of such an internal standard will improve the performance of the cytogenetics laboratory and will validate the quality of the results of cytogenetic examination. The use of an external standard will stimulate the standardization and improvement of cytogenetic laboratory techniques and may be used to develop performance standards for accreditation of both bone marrow and other cytogenetic laboratories. Internal and external quality controls have been used in general medical laboratories for many years, and their use should be instituted by cytogenetic laboratories as well.     

A human c-src gene resides on the proximal long arm of chromosome 20 (cen----q131)

A molecular clone of v-src, the oncogene of Rous sarcoma virus, was used to detect and regionally localize a human c-src proto-oncogene on chromosome #20. The human c-src gene, detected as either a 28-kbp EcoRI DNA fragment or as a 15.4-kbp BglII DNA fragment, was localized to 20 cen----q131 by filter hybridization analysis of DNAs from human-rodent somatic cell hybrids. The results indicate that c-src is on the same chromosome arm as aberrations associated with myeloproliferative disease, although the possible involvement of c-src in these aberrations is unknown.     

The aniridia-Wilms tumor association: The critical role of chromosome band 11p13

The role of del (11)(p13) as a cause of aniridia, with and without Wilms tumor, is strengthened by demonstration of this chromosome aberration in 3 patients: monozygous twin girls, both of whom have aniridia and mental retardation and one of whom has a Wilms tumor; and an unrelated boy with aniridia and ambiguous genitalia. The break points defining the interstitial deletion for the twins are 11p13 and 11p15.1, while for the boy they are 11p1302 and 11p14.1. These patients and their karyotypes substantiate the critical importance of chromosome band 11p13 (or its hemizygous representation) in the development of aniridia and an associated Wilms tumor diathesis, as had been suggested previously (Riccardi VM, Sujansky E, Smith AC, Francke U, (1978): Pediatrics 61, 604-610).     

Conversion of nonfusing mumps virus infections to fusing infections by selective proteolysis of the HN glycoprotein

Mumps virus strains differ in their ability to induce cell fusion following an infection: strains with activeneuraminidase (NANase) fail to cause cell fusion, while strains with less active NANases cause cell fusion. When chymotrypsin is added to infected cells, cell fusion is amplified in a concentration-dependent manner for all mumps virus strains. Virions produced in such infections do not express HN glycoprotein-associated activities. Chymotrypsin treatment of purified mumps virus in vitro results in sequential cleavage into two glycopolypeptides, HNc1 (32K) and HNc2′ (41K), with concomitant loss of hemagglutinating and NANase activities, and infectivity. Further incubation with chymotrypsin causes complete degradation of HNc1 and digestion of HNc2′ to HNc2 (13K–19K). Both HNc2′ and HNc2 contain the [³H]palmitic acid label found in the HN polypeptide, which suggests that these fragments are associated with the viral membrane. Analyses of infected cells and released virions indicate that chymotrypsin acts similarly on HN exposed at the cell surface. Exogenous NAnase does not abolish the protease-augmented cell fusion though it does reduce cell fusion of untreated fusing strain infections. These results confirm that mumps virus HN glycoprotein is critically linked to cell fusion cytopathology and show that cyrptic cell fusion activity in nonfusing strain infections can be unmasked by the proteolytic removal of the HN glycoprotein.     

Leukemia with a novel 4q11q rearrangement

Translocation (4;11)(q21;q23) is characteristic of a distinct acute leukemic syndrome. We report an 8-wk-old male patient with the clinical features ascribed to t(4;11), but with an unusual chromosome rearrangement consisting of an insertion of the 11q23 band into the q21 region of chromosome #4.     

Chromosomal anomaly of 6q in chronic myelogenous leukemia (CML)

Anomalies of chromosome 6q, along with other chromosomal anomalies, are described in the bone marrow cells of two patients with chronic myelogenous leukemia (CML). One patient, a 14-year-old male, developed the karyotype 46,XY,t(1;6)(p36;q15),del(3)(q25),del(17)(p11),? inv(17)(q12q24) during blastic crisis of his disease. The other patient, a 24-year-old male, had the karyotype 46,XY,del(6)(q13),t(9;22)(q34;q11) during the early phase of his disease and evolution of i(17q) in the karyotype late in the disease.     

The immune response to (T,G)-A-L and GAT in man: an association of nonresponsiveness to (T,G)-A-L with HLA-DRw8

The response of human lymphocytes to synthetic polypeptides has been measured by sensitizing cells in vitro followed by restimulation with the sensitizing antigen or with cross-reacting antigens. It was found that there was considerable individual heterogeneity in the specific response and the cross-reaction obtained with the antigens (T,G)-A-L, GAT, GT, and GA. In spite of this heterogeneity, it is possible to define three different response patterns using nonresponsiveness to (T,G)-A-L and the failure of (T,G)-A-L to cross-restimulate GAT sensitized cells as discriminating criteria. The nonresponders to (T,G)-A-L show a significant association with HLA-DRw8 and it is suggested that this might represent a dominant HLA associated immune response gene involved in the regulation of the response to (T,G)-A-L. We further show that the individuals whose cells respond to (T,G)-A-L form a heterogeneous group which may explain the conflicting results previously published on the genetic control of the immune response to (T,G)-A-L in man.