B-cell function in patients with chronic lymphocytic leukemia

Summary Using a reverse hemolytic protein A plaque assay, spontaneous and pokeweed mitogen (PWM)-induced immunoglobulin (Ig) secretion was determined in peripheral blood from 22 patients with B₁-chronic lymphocytic leukemia (CLL), one patient with B₂-CLL, and one patient with suppressor T-CLL. Diagnoses were established by cytological and histological criteria as well as several marker analyses. Lymphocytes from B₁- and B₂-CLL patients were unable to secrete Ig either spontaneously or after PWM stimulation. In T-CLL lymphocytes, spontaneous Ig secretion was suppressed very probably by the OKT-8-positive leukemic population, since, after cultivation with PWM, a normal Ig secretion could be demonstrated which was paralleled by a decrease in the OKT-8-positive cells. Cocultivation experiments with freshly isolated, unseparated lymphocytes from normal subjects and lymphocytes from patients were of no informational value, since isolated normal B-cells alone already showed a high rate of Ig secretion. However, coculture experiments with separated subpopulations after PWM stimulation revealed an intrinsic B-cell defect in lymphocytes from B₁-CLL patients, whereas their T-lymphocytes were found to be normal helper cells.

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Abbreviations CLL Chronic lymphocytic leukemia - PWM Pokeweed mitogen - ISC Immunoglobulin-secreting cells - Ig Immunoglobulin(s) Supported by the Deutsche Forschungsgemeinschaft (Ru 215/2)     

Über die Behandlung idiopathischer Ödeme mit Bromocriptin

Zusammenfassung Die Therapie idiopathischer Ödeme mit Diuretica ist problematisch, da sie die Symptome nicht beseitigt, sondern einen sekundären Hyperaldosteronismus induziert, der die Ödembildung unterhält. Die Beobachtung einer verminderten Dopaminausscheidung bei Patientinnen mit idiopathischen Ödemen läßt einen Behandlungsversuch mit dem oral wirksamen Dopaminagonisten Bromocriptin als sinnvoll erscheinen.Wir behandelten daher neun Patientinnen mit idiopathischen Ödemen mit typischer Symptomatik und mehrjähriger Anamnese mit 2 × 2,5 mg/die Bromocriptin (Pravidel®). Der Therapieerfolg wurde nach der Normalisierung der circadianen Gewichtsschwankungen und dem subjektiven Befinden beurteilt. Sieben Patientinnen zeigten einen guten, eine nur einen unsicheren Therapieerfolg, und eine Patientin brach die Therapie wegen Nausea ab.Vor und während Bromocriptinbehandlung sind Serumelektrolyte, Blutdruck, Plasmareninaktivität und Aldosteron normal. Bromocriptin normalisiert die circadianen Gewichtsschwankungen, ohne das morgendliche Körpergewicht zu senken. Die Ergebnisse der vorliegenden Pilotstudie legen nahe, daß Bromocriptin bei einigen Patientinnen mit idiopathischen Ödemen eine wirksame Alternative zur herkömmlichen diuretischen Therapie sein kann. Es bleibt offen, ob die Bromocriptinwirkung durch einen Dopaminmangel zu erklären ist, oder ob Bromocriptin eine rein symptomatische Behandlung darstellt.     

Presentation of cytosolic antigens via MHC class II molecules

Major histocompatibility (MHC) class II molecules function to present antigenic peptides to CD4 T lymphocytes. The pathways by which these molecules present exogenous antigens have been extensively studied. However by contrast, far less is known about the processing and trafficking of cytosolic antigens, which can also serve as an alternative source of ligands for MHC class II molecules. Self-proteins, tumor antigens, as well as viral proteins found within the cytosol of cells, can be presented via MHC class II molecules, resulting in the activation of specific CD4 T cells. Studies have begun to reveal unique steps as well as some similarities in the pathways for cytosolic and exogenous antigen presentation. Recent developments in this area are summarized here.     

Initial validation of the SLEEP-50 questionnaire

Initial psychometric properties of the SLEEP-50 questionnaire, designed to detect sleep disorders as listed in the Diagnostic and Statistical Manual of Mental Disorders (4th ed., Text Revision), were examined. The sample consisted of 377 college students, 246 sleep patients, 32 nightmare sufferers, and 44 healthy volunteers. The internal consistency was high (Cronbach's alpha = .85); test-retest correlations fell between .65 and .89. Principal component analysis with a direct oblimin rotation revealed a factor structure that closely matched the designed structure. Sensitivity and specificity scores were promising for all sleep disorders; the agreement between all clinical diagnoses and SLEEP-50-classifications was substantial (kappa = .77). These initial findings indicate that the SLEEP-50 seems able to detect a variety of sleep disorders. The SLEEP-50 can aid in screening for common sleep disorders in the general population.     

Fractal system — A time domain approach

A method to analyze the fractal system in the time domain is presented so that the dynamic behavior of the system can be studied. The fractal system is represented by a set of linear time-varying differential equations whose order depends on the order of the system under non-fractal condition. Four different types of fractal system are considered and their solutions in the time domain are presented. These analyses show that the fractal system is dynamically more stable with smooth changes of magnitude and less oscillatory than the non-fractal system. Examples of the physiological system of the conduction pathways in the heart and also the polarization phenomena of noble metal are presented to illustrate the phonomena.     

Functionality of chimeric Rev proteins of HIV/SIV

Studies on functional compatibility of various Rev proteins derived from all known human and simian immunodeficiency virus subgroups have shown that this essential gene product is not always exchangeable among the viruses. In an attempt to map the region of Rev proteins responsible for the observed nonreciprocal complementation, hybrid genomic Rev expression vectors were constructed by exchanging the first and second exons ofrev genes, and were examined for their abilities to activate reporter clones by transfection. With one exception, the second coding exon ofrev gene determined the functional specificity of Rev proteins.     

Plasma cystine concentration and redox state in aging and physical exercise

Because redox-regulated signalling pathways are often modulated by the thiol/disulfide redox state (REDST), changes in plasma REDST may possibly account for pathological processes. We, therefore, investigated the mechanisms that account for changes in the plasma REDST as derived in first approximation from the cystine and acid soluble thiol (mainly cysteine) concentrations. Elderly subjects (studies A) and younger subjects after intensive physical exercise (IPE) (study B) i.e. subjects in conditions typically associated with decreased insulin responsiveness, showed, on the average, an increase in the plasma total free amino acid (TAA) concentration to approximately 3000 microM, including an increase in cystine but no increase in the thiol concentration if compared with controls. The REDST was decreased accordingly. A study on the postabsorptive amino acid exchange rates across the lower extremities (study C) indicated that a TAA level > or =2800 microM supports a balanced net protein synthesis even under conditions of weak insulin stimulation, suggesting that high TAA levels may prevent the release of cysteine into the blood in the postabsorptive state. Collectively, these studies indicate that the age-related oxidative shift in plasma REDST may result from the decrease in amino acid clearance capacity and may be aggravated by excessive physical exercise.     

Reliability of life event assessments: test-retest reliability and fall-off effects of the Munich Interview for the Assessment of Life Events and Conditions

This paper presents the findings of two independent studies which examined the test-retest reliability and the fall-off effects of the Munich Life Event List (MEL). The MEL is a three-step interview procedure for assessing life incidents which focuses on recognition processes rather than free recall. In a reliability study, test-retest coefficients of the MEL, based on a sample of 42 subjects, were quite stable over a 6-week interval. Stability for severe incidents appeared to be higher than for the less severe ones. In the fall-off study, a total rate of 30% fall-off was noted for all incidents reported retrospectively over an 8-year period. A more detailed analysis revealed average monthly fall-off effects of 0.36%. The size of fall-off effects was higher for non-severe and positive incidents than for severe incidents. This was particularly evident for the symptomatic groups. Non-symptomatic males reported a higher overall number of life incidents than females. This was partly due to more frequent reporting of severe incidents. The findings of the fall-off study do not support the common belief that the reliability of life incident report is much worse when the assessment period is extended over a period of several years as compared to the traditional 6-month period.     

Pituitary pathology in erdheim-chester disease

Pituitary morphologic changes in patients with Erdheim-Chester disease have not been described in detail. We report here the histologic and immunohistochemical findings in the autopsy obtained pituitary of a 35-yr-old woman with extensively disseminated Erdheim-Chester disease. The posterior lobe was completely replaced by xanthogranulomatous infiltrates, providing an explanation for the patient’s diabetes insipidus. The anterior lobe was intact and immunohistochemistry demonstrated expression of GH, TSH, FSH, LH, and alpha subunit within the normal range. A clinically observed decrease of anterior pituitary function was interpreted as hypothalamic in origin due to massive destruction of the hypophysial stalk and compression of the hypothalamus. Prolactin immunoreactive cells were numerous, consistent with the view that prolactin cell hyperplasia resulted from the loss of hypothalamic dopaminergic inhibition. Massive Crooke’s hyalinization in the ACTH-producing cells was considered unrelated to Erdheim-Chester disease and was the consequence of treatment with pharmacologic doses of glucocorticoid hormones. It can be concluded that prolactin cell hyperplasia may be the only finding in the adenohypophysis of patients with disseminated Erdheim-Chester disease. It appears that in our patient the clinically apparent anterior hypopituitarism was not due to the lack of storage but rather to insufficient release of adenohypophysial hormones caused by the defect in hypothalamic regulation.