Showing papers by "Charité published in 1993"

Is alopecia areata an autoimmune-response against melanogenesis-related proteins, exposed by abnormal MHC class I expression in the anagen hair bulb?

Abstract: The etiology of alopecia areata (AA), a putative autoimmune disease characterized by sudden hair loss, has remained obscure. It is not understood, how the characteristic inflammatory infiltrate that selectively attacks anagen hair follicles in AA is generated. We hypothesize that this reflects an unexplored form of autoimmunity, a cytotoxic T cell attack on rhythmically synthesized autoantigens normally sequestered by a lack or very low level of MHC class I (MHC I)-expression, and suggest the following mechanism of AA pathogenesis: Microtrauma, neurogenic inflammation, or microbial antigens cause a localized breakdown of MHC I-"negativity" in the proximal anagen hair bulb via proinflammatory cytokines. This exposes autoantigens derived from melanogenesis-related proteins (MRP-DP), which are only generated during anagen, and triggers two successive waves of autoimmune responses: CD8+ cytotoxic T cells initiate AA after recognizing MRP-DP abnormally presented by MHC I molecules on hair matrix melanocytes and/or keratinocytes; a secondary attack, carried by CD4+ T cells and antigen presenting cells, is then mounted against MHC class II--presented additional autoantigens exposed by damaged melanocytes and keratinocytes. The latter causes most of the follicular damage, and extrafollicular disease, and depends greatly on the immunogenetic background of affected individuals. This unifying hypothesis explains the clinical heterogeneity and all salient features of AA, and argues that only the unlikely coincidence of multiple predisposing events triggers AA. The suppression of MHC I--expression and synthesis of MRP in the hair bulb, and the "tolerization" of MRP-DP autoreactive CD8+ T cells may be promising strategies for treating AA.

APO‐1 mediated apoptosis or proliferation in human chronic B lymphocytic leukemia: Correlation with bcl‐2 oncogene expression

Abstract: We studied induction of apoptosis in several human malignant B cells from chronic lymphocytic leukemias (BCLL) by triggering the APO-1 antigen. The APO-1 antigen was found to be expressed on the surface of malignant B cells. In BCLL cells from most patients, APO-1 antigen expression increased following in vitro activation by Staphylococcus aureus Cowan I (SAC) or interleukin-2 (IL-2). In certain cases of BCLL co-stimulation with SAC plus IL-2 resulted in a synergistic up-regulation of the APO-1 antigen on the cell surface and prepared BCLL cells for monoclonal antibody anti-APO-1 mediated apoptosis. Interestingly, bcl-2 mRNA expression decreased upon stimulation with SAC plus IL-2, whereas SAC or IL-2 alone did not affect the level of bcl-2 expression. Thus, in these BCLL cells induction of anti-APO-1-mediated apoptosis appeared to be correlated with bcl-2 mRNA down-regulation. One informative BCLL, however, with a similar pattern of APO-1-antigen expression, did not show SAC plus IL-2-dependent bcl-2 down-regulation. Surprisingly, these cells proliferated in response to anti-APO-1 only when cells were co-stimulated with SAC plus IL-2. Our data suggest that down-regulation of bcl-2 prepares BCLL cells for induction of APO-1-mediated apoptosis. In addition they demonstrate that triggering of the APO-1 antigen may also lead to the induction of proliferation in special cases of BCLL.

Comparison of Recalled and Validated Oral Contraceptive Histories

Abstract: From a case-control study of the relation between oral contraceptives and breast cancer carried out in East Germany during 1982-1986, the authors obtained information on oral contraceptive use through interviews of study subjects and from the records of prescribing gynecologists. The degree of agreement regarding information from these two sources was assessed for 234 breast cancer cases and 524 controls who had ever used oral contraceptives. Agreement between information obtained from medical records and that from interviews on total duration of use, number of episodes of use, and time since first and last use was reasonably good, and levels of agreement did not differ appreciably between cases and controls. Lower levels of agreement were observed for individual brand names and the duration of use of specific brands. Attempts should be made to obtain information on specific brands from medical records when investigating the effects of individual preparations.

Water and ion distribution profiles in human skin.

Abstract: Bulk sample x-ray microanalysis (XRMA) of human gluteal skin was performed to provide data on water and ion profiles over the epidermal cross section. All samples were analyzed both in the frozen hydrated state and in the frozen dried state. This allows, for the first time, a quantitative determination of the local water content in different strata of the skin. A steep water gradient was found in the stratum corneum towards the stratum granulosum, while the water content was constant in all deeper layers of the skin, including the papillary dermis. Previously demonstrated distributions over the epidermis of the monovalent ions sodium (Na), potassium (K) and chlorine (Cl) given in concentrations per unit dry weight were confirmed, as were the distributions of phosphorus (P) and sulfur (S). Combining the water and ion distributions, our data indicate the major monovalent ions Na, K and Cl to be in equilibrium between the stratum corneum and the dermis if the assumption is that all monovalent ions are in solution and that all the water of the tissue is available as solvent for the ions. This result does not disprove the existence of an ion transport gradient in the epidermis but sets significant bounds to it.

Changes of telomere lengths in human intracranial tumours

Abstract: The termini of human chromosomes comprise stretches of G-rich repeats that are about 5–20 kilobase (kb) in length. The size of the telomeres can be determined by hybridization with probes specific for these (ttaggg)n sequences after digestion of chromosomal DNA with appropriate restriction enzymes and electrophoretic separation of the fragments. Here, probing with the 32P-labelled synthetic (TTAGGG)3 oligonucleotide revealed length changes of the telomeres occurring in intracranial tumours. Among 60 samples analysed, 41.7% showed telomere elongation, and 21.7% telomere reduction, whereas 36.7% of the tumours exhibited equal lengths compared with the patients' peripheral blood leukocytes. Most of the elongated glioma telomeres exceeded in length those of untransformed astrocytes derived from human fetal tissue.

Hereditärer Morbus Parkinson: Bericht über drei Familien mit autosomal-dominantem Erbgang

Abstract: We have studied three families who ancestors immigrated to North America from contiguous regions of northern Germany and southern Denmark. The pedigrees contain 77,206 and 376 individuals spanning 6, 7 and 8 generations with 7,7 and 11 affected members, respectively. Autosomal dominant inheritance pattern is present in two families and probable in the third. Typical L-dopa-responsive parkinsonism with bradykinesia, rigidity, resting tremor, and impaired postural reflexes uniformly develop in affected individuals from all three families. Further research on these three families, including genetic, pathologic and clinical examinations is planned.

Role of Influenza Vaccination in the Elderly during an Epidemic of A/H1N1 Virus in 1988–1989: Clinical and Serological Data

Abstract: During a winter epidemic of A/H1N1 influenza virus, we evaluated the protection conferred by vaccination of 285 residents of a nursing home. Fifteen of 204 members of the nursing staff were also vaccinated. Serological determinations were performed before and after vaccination using radial hemolysis (RH) and neuraminidase inhibition (NI) tests. In the outbreak period, only one influenza case was noted in the vaccinated elderly and none among the vaccinated nursing staff. On the other hand, 38 cases (20%) occurred in the unvaccinated hospital personnel. Twenty-one percent of the elderly people exhibited seroconversion to the vaccinal strain by RH and NI while 27 and 20% of the vaccinated nursing staff seroconverted by the same tests, respectively. Thus, the clinical protection conferred by influenza vaccination was excellent and much greater than expected from serological results.

Cellular bound β-carotene quenches singlet oxygen in man

Abstract: It is often postulated that a major role of carotenoids in biology and medicine involves their ability to quench a toxic form of oxygen, known as singlet oxygen, although direct observations of such mechanisms do not exist. Using β-carotene, bound to lymphocytes taken from human blood, we have used a direct, pulsed laser, physical chemical technique and, separately, a biological method to show a particularly efficient quenching reaction of singlet oxygen by carotene in a cellular environment.

Relevance of tumour necrosis factor-α and interleukin-1-α in the pathogenesis of hypoxia-related organ failure

Abstract: Tumour necrosis factor-alpha (TNF) and Interleukin-1-alpha (IL-1) are both cytokines which are known to be released by stimulated macrophages during septic events. Because of their influence on the function of the vascular endothelium, TNF and IL-1 contribute to the pathogenesis of hypoperfusion and organ dysfunction. The finding of elevated cytokine levels in patients with hypoxic organ failure, suggesting a relation between systemic oxygen supply and humoral mechanisms, led us to perform laboratory investigations on the relevance of TNF and IL-1 for the pathogenesis of hypoxia-related deterioration of the microcirculation. In vivo studies with anaesthetized rats demonstrated a synergism between hypoxaemia and endotoxaemia on the development of lethal organ failure. In vitro studies with human monocytes showed that a hypoxic atmosphere was not able to induce synthesis or release of TNF and IL-1, whereas re-oxygenation after hypoxia initiated a significant increase in TNF and IL-1 synthesis, probably mediated by oxygen radicals. Finally, experiments with human endothelial cells established that hypoxia is able to induce high affinity receptors for TNF in a time- and dose-dependent manner. These studies demonstrate that hypoxia influences humoral mechanisms which are known to contribute to the pathogenesis of vessel dysfunction, probably through a cytokine-dependent pathway of hypoxia-related organ dysfunction.

Studies of the etiology and pathogenesis of motor neuron diseases: III. Magnetic cortical stimulation in patients with lathyrism

Abstract: Neurophysiological assessments of central motor pathways were conducted of 11 Spanish subjects with varying degrees of spastic paraparesis (lathyrism). The disease has been induced more than 40 years ago by subsistance on the neurotixic chick pea Lathyrus sativus. Patient evolution was carried out by magnetic cortical and electric spinal stimulations and recordings of the contralateral muscle responses. Central motor conduction times corresponding to lower limbs were clearly more prolonged in those severely affected patients with marked difficulty walking (Stages 4 and 3). Central conduction times corresponding to upper limbs were delayed in only 1 patient. Taken together with clinical and published neuropathological data, these findings suggest that established lathyrism is essentially a central motor system disorder primarily affecting corticospinal tracts regulating the lower limbs.

Is there a relationship between malnutrition, inflammation, and post-vaccinal antibody response to influenza viruses in the elderly?

Abstract: This study was designed to explore the relationship between malnutrition, inflammation, and the specific antibody response after influenza vaccination in the elderly. Eighty-two aged subjects, immunized annually against influenza with a trivalent inactivated vaccine, were evaluated for 9 protein markers (albumin, thyroxin-binding prealbumin, transferrin, immunoglobulins (Ig) G, M, and A, orosomucoid, haptoglobin, and C reactive protein) and for their antibody response to influenza viruses in comparison to 29 younger adults who received the same vaccine and 21 unvaccinated adults. IgM and nutritional markers were significantly reduced in the aged as compared to controls, while the opposite pattern was seen for IgA and inflammatory markers. No difference was observed between the elderly and the controls with regard to the antibody response to influenza virus after vaccination. Reciprocally, influenza immunization had no influence on the levels of the protein variables. These results suggest that the protein status does not play an important role in the antibody response to influenza vaccination in the elderly, a fact which could be related to the slight involvement of cellular immunity in the defense against influenza reinfection.

Establishment and characteristics of two new human mammary carcinoma lines serially transplantable in nude mice.

Abstract: Two human mammary carcinomas of postmenopausal women were successfully transplanted into nude mice. Both tumours were classified as epidermal-growth-factor-, oestradiol- and progesterone-receptor-negative and c-erbB2-protein-positive. Histological studies of the primary tumours (4000 and 4151) revealed ductal invasive mammary carcinomas. In the first passages the precondition for the growth of breast carcinoma 4000 were pretreatments of the nude mice with oestradiol and peanut oil before transplantation. The mammary carcinomas 4000 and 4151 described here are suitable for in vivo testing of antineoplastic substances and for biological studies.

Intracellular interactions under oxidative stress and aging: a hypothesis.

Abstract: Oxygen-derived free radicals may result from various reactions, both intra- and extracellularly, but generation of oxygen free radicals from electrons escaping from the electron transport chain in mitochondria is by far the predominant process during the lifetime of a "normal", healthy cell. There is clear evidence that mitochondria are also an important target for oxygen-derived free radicals, and the resulting mitochondrial malfunction has long been suggested as the intracellular basis of aging. Moreover, there is clear evidence that free radical-dependent reactions lead to lipofuscin formation and its accumulation in Lysosomes of post-mitotic cells. Lipofuscin accumulation was demonstrated to be dependent on the probability of iron-catalyzed Fenton reactions. A hypothesis is presented which assumes free radical dependent reactions in mitochondria and lysosomes to be interdependent. Production of hydrogen peroxide in mitochondria and its subsequent diffusion in the cytoplasm, and Fenton reactions in lysosomes, transferring hydrogen peroxide intra-lysosomally to the highly cytotoxic hydroxyl radical, are thought to be necessary intermediary steps in the generation of mitochondrial damage. On the other hand, damage to mitochondria increases both mitochondrial output of hydrogen peroxide and lipofuscin accumulation.

A homogeneous immunological detection system for soman using the in vitro protection of acetylcholinesterase by a monoclonal antibody

Abstract: In this study a monoclonal antibody (MAb) based soman detection system was investigated. Since the MAb F71D7 recognizes the pinacolyl group of soman, non-toxic soman analogues are also detected when using an indirect competitive ELISA. This can lead to falsely positive results. The toxic effect of soman is, however, independent of the pinacolyl group. In the described homogeneous enzyme immunoassay (EIA), the inhibitory effect of soman on acetylcholinesterase (AChE) was combined with its specific binding to the MAb F71D7 in order to minimize false positive results and enhance the specificity of the detection system. In this rapid EIA no incubation or washing steps are necessary, so only time for pipetting and reaction have to be considered. Soman could be detected in concentrations of 1.6–25 nM using the EIA. This corresponds to 8 pg soman per 25 μl sample and means that compared to other ELISA systems, besides enhanced specificity, the limit of detection could be improved by 3 orders of magnitude.

Percentile curves of functional residual capacity of newborn infants

Abstract: BACKGROUND Helium dilution or nitrogen washout techniques are commonly used to measure the functional residual capacity (FRC) in newborn babies. For both techniques equipment is available. Its clinical application, however, was difficult since there were no FRC reference ranges for the different weight groups of newborn infants; reference studies are very time consuming and cause several technical and ethical problems. METHODS Statistical methods were used to evaluate several results from the literature and to exclude significantly differing data of some authors. Measured values of FRC were related to body weight, and the percentiles of FRC/kg were estimated by the smoothed cumulative distribution function of the pooled data. RESULTS No significant differences were found between the results of helium dilution and nitrogen washout techniques. The distribution of 178 results showed a significant skewedness (x5% = 18.3 ml/kg; x50% = 27.5 ml/kg x95% = 42.8 ml/kg), which could also be seen in the percentile curves calculated approximately, assuming a linear development of functional residual capacity with body weight. CONCLUSION Percentile curves describe best the development and interindividual variability of FRC in newborn babies as our evaluation could show. We conclude that the nonparametric estimation of percentiles is more adequate for the description than the use of simple regression models.

Prenatal diagnosis of the acute form of proximal spinal muscular atrophy: Experience on the acceptance of linkage analyses by the families

Abstract: The acute form of proximal spinal muscular atrophy (SMA) is a severe autosomal recessive inherited neuromuscular disorder. It has been mapped to chromosome 5q 11.2-13.3. Using restriction fragment length polymorphisms (RFLPs) or (CA)n repeats of DNA probes in this region, prenatal diagnosis is, in principle, possible. Misdiagnosis can be due to incorrect diagnosis in the index patient, and crossing-over events. Using the DNA probes D5S6, D5S112, D5S39, and D5S78, we cover a region of 10.4 mega-base pairs (Mbp) of partially NotI-digested genomic DNA without overlap of fragments. The DNA probes D5S6 and D5S112, most likely flanking the SMA gene, cover a distance of about 6.6 Mbp. This corresponds to the genetic distance of 6 cM (Morrison et al., 1992; Daniels et al., 1992). But since the precise localization of the SMA gene is still unknown (Simard et al., 1992), a 10 per cent risk of misdiagnoses due to crossing-over events cannot be excluded. The acceptance of this 10 per cent risk for prenatal diagnoses differs in SMA families. We observed a case in which a woman accepted a 25 per cent risk because RFLPs and (CA)n repeats were both uninformative. In contrast, another family did not accept the minimal 10 per cent risk and the pregnancy was terminated. In two families, we performed prenatal diagnosis by linkage analysis. One child predicted to be healthy has been born in the meantime and has shown no indication of SMA during her first 8 months.

Circulatory changes in local and segmental use of shortwave diathermy

Abstract: 6 healthy volunteers were examined for dose-effect relations, with a view to obtaining substantiated information for dosage in medical short-wave therapy. Venous occlusion plethysmography was used to measure total blood flow in the legs. So-called segmental treatment was checked, in addition to locally delimited high-frequency action. Low, medium, and high amounts of energy were therapeutically applied to the probands for 5, 10 and 20 minutes. Close correlations were found to exist between magnitude of blood flow, length of treatment and therapeutic intensity. The 20-minute variant proved to be the most effective application which differed from the literature according to which maximum intensification of blood flow was recorded at 10 minutes. The medium level of energy application was considered to be a highly favorable approach in terms of intensity. While higher doses usually provide the highest increase in blood flow, they may well cause discomfort. Blood flow remained increased after termination of therapy, usually for up to 60 minutes, in response to 20-minute medium-intensity short-wave treatment. Segmental high-frequency application likewise resulted in increased blood flow in both legs, though intensity values thus achieved were below results of locally delimited calf treatment.

Techniques and clinical application of capnography in newborn infants and infants

Abstract: Capnography has not yet achieved wide application as a noninvasive method for monitoring and optimizing assisted ventilation in neonatological intensive care medicine. The development of new equipment will probably make it possible for capnography to find its place as a routine examination. The aim of this work is to evaluate the existing methods for CO2-analysis in newborns and infants using data from existing literature. A mainstream capnograph (Novametrix 7000) was used to demonstrate typical capnographic curves in newborns and prematurely born children. The results offer new possibilities for the optimization of assisted ventilation.

Estimation of steady-state flux rates in metabolic systems by computer simulations of radioactive tracer experiments.

Abstract: The dynamics of radioactive tracers in metabolic systems can be mathematically modelled by coupled systems of differential equations for both the concentrations and the specific radioactivities of the metabolites involved. Computer simulations, i.e. direct fitting of numerical solutions of these equations to observed time-courses of metabolites and specific radioactivities, enables one to estimate unknown kinetic parameters of the system. The theoretical fundamentals of this approach and the main steps towards the quantitative assessment of flux rates in stationary metabolic systems are outlined. An application of the method to the purine nucleotide metabolism of Ehrlich ascites tumor cells is given based on a simplified model of this pathway. The obtained steady-state flux rates indicate a marked increase in the metabolism of the adenine nucleotides during the proliferating phase in comparison to the resting phase of tumor growth.

Analysis of Haemoglobin Variants Using Immobilized pH Gradients

Abstract: We present a new method for analysis of haemoglobin variants in immobilized pH gradients. The isoelectric fractionation is performed in polyacrylamide gels with copolymerized pH gradients between pH 7.0 and 8.0. The common haemoglobin variants (HbA, HbF, HbS, HbC, HbE and HbA2) are clearly resolved within this pH range. The high resolving power and reproducibility of immobilized pH gradients combined with extremely short separation times make this fractionation technique superior to all electrokinetic procedures used for haemoglobin analysis. At present, isoelectric focusing in immobilized pH gradients is a complementary tool for haemoglobin analysis when classical electrophoretic techniques do not provide sufficient resolution. We hope that in the future this technique will gain the popularity it deserves.

Implantation of vena cava filters in acute pulmonary embolism

Abstract: The long-term results of 222 patients (pts) with transvenously implanted vena cava filters are critically reviewed. A total of 98 pts were given a Mobin-Uddin filter, 102 pts a Gunther filter, and 16 pts a LGM filter. Among the serious complications observed during long-term follow-up were vena cava occlusions and increasing symptoms ranging from congestion of the deep leg veins, perforations into ureters, fractures and embolizations of the filters in up to 40% of the patients, if Gunther filters were implanted.

Multi-Valued Demand and Rational Choice in the two- Commodity Case

Abstract: We show that the weak and strong congruence axioms for consumer demand correspondences are equivalent if there are only two commodities. This result generalizes a well-known analogous equivalence theorem that applies to single-valued demands.

Fetale Gastroschisis und Omphalozele: Sectio oder vaginale Entbindung?

Abstract: Seit die pranatale Diagnose angeborener Bauchwanddefekte moglich ist, stellt sich die Frage nach den geburtshilflichen Konsequenzen. Unumstritten ist, das die Entbindung in einem Perinatalzentrum stattfinden sollte. Uber den besten Entbindungsmodus und -zeitpunkt wird jedoch seit Jahren kontrovers diskutiert.

Die Transvaginale Rekanalisation des proximalen Tiibenverschlusses unter Ultraschallbeobachtung

Abstract: Als histologisches Korrelat der Tubenpathologie finden sich nach Operationen eines proximalen Tubenverschlusses in vielen Fallen weder Tubenwand- noch Epithelveranderungen, sondern Storungen der Lumenverhaltnisse. Diese werden durch amorphes Material im Tubenlumen, zarte Adhasionen oder lediglich durch einen Muskelspasmus hervorgerufen. Was liegt in der Konsequenz naher als der Versuch, auf vaginalem Wege die Tube zu erreichen und mittels Katheterisierung die einfache Lumenverlegung zu beseitigen.