Genetische Mechanismen der Antikörperbildung

Zusammenfassung Mutation und Selektion sind die Faktoren, die der Entwicklung spezifischer Strukturen in Antikörpermolekülen zugrunde liegen. Sie wirken ständig modifizierend auf die im genetischen Code der kompetenten Zelle des Immunsystems weitergegebene Information ein. Durch den Vergleich der Primärstruktur homologer Polypeptide sind Hypothesen über den genetischen Mechanismus möglich, der zur Entstehung der Antikörpervariabilität führt.Die wichtigsten dieser Hypothesen werden dargestellt.

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Summary Mutation and selection are the factors on which the development of the specific structures in antibody molecules are based. They act continuously and modify the genetic information which is transmitted by the immune competent cell. Hypotheses on the genetic mechanisms leading to antibody variability are possible by a comparison of amino acid sequences of immunoglobulin polypeptides. Appropriate for investigations of this kind are the Bence-Jones proteins, which are excreted in the urine of men, mouse and rabbit in myelomatosis. These proteins resemble immunoglobulin light chains and are sufficiently homogeneous for chemical analysis (monoclonal proteins). They exist in two different types, designated and . Since the amino acid sequence of four Bence-Jones proteins is known completely and stretches of the sequence of about 30 other light chain proteins are known comparisons between homologous proteins are possible. It appeared that all - and -polypeptides consist of a variable half (v) and a constant half (c). The v-region comprises the N-terminal residues 1–117, whereas the c-region comprises the C-terminal residues 108–214. Within a given light chain type all c-halves are identical in their amino acid sequence with exception of the residue No. 191 in -chains and No. 190 in -chains. These positions correspond to the allotypic specifities Inv and Oz.The variability of individual light chains is confined to that part of the molecule which carries the antibody combining site. It follows that amino acid sequence studies of the v-region of the immunoglobulin molecule provide us with information about the structural basis of antibody specifity and — at the same time — enables us to test hypotheses on the genetic mechanisms of the antibody variability. Two categories of hypotheses are distinguishable: 1. the multiple gene hypotheses and 2. the somatic mutation hypotheses.The multiple gene hypotheses postulate as many genes as specific antibodies exist. Somatic mutation hypotheses on the other hand are based on the assumption that recombinations between homologous genes occur during the individual development of the immune system. Advantages and disadvantages of some of the somatic mutation hypotheses are discussed. The conclusions to be drawn from the observed mutations in immunoglobulin light chain proteins were considered with respect to the coding problem.

     

Olfactory and auditory event-related potentials in Huntington's disease

The influence of Huntington's disease (HD) on the olfactory event-related potential (OERP), an electrophysiological measure of olfactory information processing, has not been reported to date. In the present study, olfactory and auditory event-related potentials (ERPs) were recorded monopolarly from Fz, Cz, and Pz electrode sites in 8 patients with HD and 8 age- and gender-matched control participants. Results demonstrated that individuals with HD were delayed compared with controls on the P3 component of the OERP (p<.001), with a trend toward a significant delay on the auditory ERP P3 (p<.06). The effect size for OERP P3 latency (pi(2)=.72) was larger than that for the auditory P3 (pi(2)=.24), which has previously been shown to be delayed in HD. Patients performed significantly worse than controls did on all neuropsychological measures. These measures significantly correlated with several components of the OERP. These findings extend the understanding of olfactory deficits in HD.     

Recall discriminability: utility of a new CVLT-II measure in the differential diagnosis of dementia.

Memory tests that are in a recall format have almost universally measured accuracy in terms of the number of target items reported by the examinee. However, this traditional scoring method can, in certain cases, result in artificially inflated memory accuracy scores. That is, just as a "yes" response bias and high false-positive rate on recognition testing can artificially inflate a patient's hit rate, so, too, a liberal response bias and high intrusion rate on recall testing can artificially inflate a patient's level of target recall. Recognition tests correct for this problem by using a discriminability measure that provides a single score of hit rate relative to false-positive rate; however, recall tests rarely provide a single score of recall accuracy that corrects for intrusion rate. In the present study, we examined the utility of a new recall discriminability measure that analyzes target recall relative to intrusion rate. Patients with Alzheimer's disease (AD) or Huntington's disease (HD) were administered the CVLT-II, which provides both the traditional measure of target recall and a new measure of recall discriminability. The results indicate that the new recall discriminability measure was superior to the traditional level of target recall measure in distinguishing the recall performance of AD and HD patients. Implications of these results for clinical practice and theories of memory disorder in dementia are discussed.     

Treatment of unresectable lung metastases with transpulmonary chemoembolization: preliminary experience

Transpulmonary chemoembolization (TPCE) was evaluated as a new treatment for unresectable lung metastases. Institutional review board approval and patient consent were obtained. In 23 patients, 26 lung metastases of different origins were treated locally by using a transpulmonary approach. After femoral vein puncture, tumor-supplying pulmonary arteries were selectively explored, and 5-10 mg mitomycin C and 5-10 mL iodized oil and microsphere particles were applied with balloon protection. Diagnosis and follow-up (3-month intervals) were performed with unenhanced and contrast material-enhanced computed tomography (CT). Treatment was well tolerated in all patients, with no major side effects or complications. As indicated by using morphologic criteria, volume regression of embolized areas was achieved in eight patients, while stable disease was revealed at follow-up in six patients. In nine patients, progression of treated intrapulmonary metastases was recorded. TPCE could be a well-tolerated palliative treatment option in patients with pulmonary metastases.     

Effects of low-intensity laser therapy on the orthodontic movement velocity of human teeth: a preliminary study

BACKGROUND AND OBJECTIVES: Low-intensity laser therapy (LILT) has been studied in many fields of dentistry, but to our knowledge, this is the first time that its effects on orthodontic movement velocity in humans are investigated. STUDY DESIGN/PATIENTS AND METHODS: Eleven patients were recruited for this 2-month study. One half of the upper arcade was considered control group (CG) and received mechanical activation of the canine teeth every 30 days. The opposite half received the same mechanical activation and was also irradiated with a diode laser emitting light at 780 nm, during 10 seconds at 20 mW, 5 J/cm2, on 4 days of each month. Data of the biometrical progress of both groups were statistically compared. RESULTS: All patients showed significant higher acceleration of the retraction of canines on the side treated with LILT when compared to the control. CONCLUSIONS: Our findings suggest that LILT does accelerate human teeth movement and could therefore considerably shorten the whole treatment duration.     

Medical informatics at Heidelberg/Heilbronn: status-evaluation-new challenges in a specialised curriculum for medical informatics after thirty years of evolution

After reporting on characteristics, structure and contents of the specialised informatics-based curriculum for medical informatics (MI) at the University of Heidelberg/University of Applied Sciences Heilbronn, the paper describes the development during the last 5 years, and in particular a complementary health care oriented postgraduate program in 'Health Information Management' (IM). Furthermore, it outlines results of a study among the MI graduates, which aims to assess their job situation and to evaluate the curriculum from their viewpoint and so establishes a summary of 30 years of experience with the program. Finally, the paper discusses new challenges of the program, considering the results of the study, perspectives of health care provision in the next decade, content changes to be focused on and the growing competition in the field of programs for medical informatics.     

A paradigm for measuring the olfactory event-related potential in the clinic

Recent research on the olfactory event-related potential (OERP) using inter-stimulus intervals (ISIs) of 90 s and shorter has revealed a marked decrease in component amplitude after the first trial, with a leveling off for the remaining trials. Studies manipulating the ISI in olfactory and other modalities demonstrate an association between higher amplitudes and longer ISIs, suggesting that habituation occurs at short time intervals between each stimulus presentation. The present study attempted to reduce the effects of habituation by using a 10-min ISI and fewer trials. OERPs were recorded monopolarly at the Fz, Cz and Pz electrode sites in ten subjects (five males, five females), for three trials using a 10-min ISI. Results demonstrated no significant reduction in component amplitudes across trials and no significant difference in latencies over trials, indicating no habituation effect at this ISI. These results indicate that with a 10-min ISI and three trial recordings, a complete reduction in habituation can be achieved. These findings may prove to be clinically useful to physicians who can implement this technique to assess olfactory functioning in cognitively impaired individuals or to assess malingering.     

Oxygen radical production in neutrophils interacting with platelets and surface-immobilized plasma proteins: role of tyrosine phosphorylation

The interaction between neutrophil granulocytes and platelets is considered to play an important role in the inflammatory process induced by an implanted foreign material. However, the cellular mechanisms involved remain incompletely understood. We used a luminol-dependent chemiluminescence (CL) technique to analyze the generation of reactive oxygen species (ROS) in human neutrophils interacting with different plasma protein-coated surfaces in the presence or absence of unstimulated or stimulated platelets. The role of tyrosine phosphorylation in the regulation of NADPH oxidase activity was evaluated with quantitative fluorescence microscopy and the specific tyrosine kinase inhibitor genistein. We found that the ROS-production is 2 to 3 times higher in neutrophils on immunoglobulin G (IgG)-coated surfaces than in cells interacting with albumin- or fibrinogen-coated surfaces. Incubation with superoxide dismutase and catalase revealed that about 45% of the ROS was released extracellularly on IgG surfaces whereas corresponding values were 90% and 85% in neutrophils interacting with albumin and fibrinogen, respectively. The presence of platelets markedly increased the extracellular generation of ROS, mainly in neutrophils interacting with IgG- or fibrinogen-coated surfaces whereas the intracellular production was only modestly affected. Quantitative fluorescence microscopy of neutrophils stained with FITC-conjugated anti-phosphotyrosine antibodies showed a correlation between tyrosine phosphorylation, cell spreading, and ROS production. Platelets markedly amplified the anti-phosphotyrosine staining on both fibrinogen- and IgG-coated surfaces whereas the low level of tyrosine phosphorylation in neutrophils on albumin-coated surfaces was not further elevated by platelets. Furthermore, the tyrosine kinase inhibitor genistein inhibited both extra- and intracellular ROS production in neutrophils regardless of the presence of platelets. We demonstrate that plasma protein coating and the presence of platelets are crucial for the inflammatory response of adhering neutrophils and that the oxidative response correlates with the extent of tyrosine phosphorylation of proteins in focal contacts.