O relacionamento fraterno na presença da deficiência

This research was developed during four years, in different regions of the country. Its purpose was to better understand the possible influences that handicapped siblings have on the development of non- handicapped siblings. Participated in the study 80 siblings, with ages ranging between 14 and 26 years. There were 20 siblings of physical handicapped (PH), 20 siblings of auditory handicapped (AH), 20 of mental handicapped (MH), and 20 of non handicapped, in number and ages equivalent.The participants answered a questionnaire containing “characteristics of handicapped person”, “characteristics of respondent sibling”, “characteristics of family”, a questionnaire with eleven closed questions and one open, but for the control group there was on less question. The phenomena studied in this research in some situations present themselves differently for each group of respondent sibling (ex: greater concern of the parents with the MH sibling, calling attention more for siblings of PH and MH, more responsibility in the family, taking care of the handicapped sibling, fear of having handicapped children, and the perception of (in) dependency of the handicapped sibling) and in others present themselves in similar manner (ex: more concern of the parents with the brother with PH, nature of the relationship, to feel or not ashamed of the sibling, talking about the sibling development). In conclusion, some phenomena, so far socially perceived as causing differences in sibling relations and attributed to de presence of a handicap are not, since between siblings of non handicapped these same phenomena present themselves in a similar way. Differently from the control group, siblings of handicapped need correct information, as well as therapeutic support to elaborate feelings of fear, anger, shame that they may have due to their condition. It is important to stress, also, the need that these siblings have to be themselves without the stigma of sibling of handicapped.

Scanning Electron Microscopy of Male Terminalia and Its Application to Species Recognition and Phylogenetic Reconstruction in the Drosophila saltans Group

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

As condições de vida e saúde de pessoas acima de 50 anos com deficiência e seus cuidadores em um município paulista

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Atrichia, abnormal EEG, epilepsy and mental retardation in two sisters

Two daughters of a nonconsanguineous couple are described. Both present mental retardation, epileptic seizures, congenital atrichia, histologically anomalous skin and abnormal EEG pattern. From a discussion of the literature on atrichia, the forms without involvement of teeth, nails and hidrosis, among which recessive inheritance prevails, are distinguished from each other. None of them coincide with the syndrome described here.

Interação entre irmãos em situação de cuidados formais

Este trabalho teve como objetivo descrever as principais características de famílias onde os filhos mais velhos são responsabilizados pela execução das tarefas domésticas e pelo cuidado aos irmãos menores, durante a ausência dos pais. Participaram deste estudo vinte famílias residentes à Vila Paranoá, Distrito Federal, com filhos de um a dezesseis anos de idade. Os dados foram colhidos através de entrevistas e sessões de observação sistemática do comportamento em ambiente natural, realizadas durante o período de almoço. A análise se deteve na organização familiar, desempenho em tarefas domésticas e interação entre irmãos, tendo sido possível classificar as famílias em três grupos qualitativamente distintos. Os resultados são discutidos em termos da necessidade de se considerar fatores de ordem social na análise do grupo familiar.

The Effects of Ornamentation on Wolf Spider Foraging

ABSTRACT: As a secondary sexual trait that can increase reproductive success, ornamentation is believed to be costly for organisms to acquire and possess. This study investigates possible costs of ornamentation on wolf spider foraging by comparing foraging abilities of two male forms that differ in ornamentation upon maturation. The two male forms, found syntopically in a mixed population in Mississippi, USA, resemble two sibling species: Schizocosa ocreata, in which males develop large black brushes on their forelegs upon maturation, and Schizocosa rovneri, in which males lack ornamentation following maturation. Individuals of both forms participated in foraging trials as penultimates (juveniles) and as matures. Analyses were conducted to compare behaviors and determine changes in foraging abilities between male forms (non-ornamented vs. brush-legged) and between age groups (penultimate vs. mature). Most foraging behaviors of the two male forms during immaturity were similar with the exception that brush-legged males attacked more frequently than non-ornamented males. Brush-legged males attacked less, spent more time moving, and improved capture abilities as matures, while non-ornamented males retained similar trends for these behaviors with age. Additionally, while capture abilities improved with age among brush-legged males, killing abilities remained constant. This disparity was due to increased escapes made by captured prey items, possibly due to hindrances caused by brush presence preventing secure holds onto crickets. In summary, differences in foraging exist between brush-legged and non-ornamented males prior to sexual maturation, and the development of/presence of brushes appears to influence adult male foraging efficiency.

Impact of FLT3 Internal Tandem Duplication on the Outcome of Related and Unrelated Hematopoietic Transplantation for Adult Acute Myeloid Leukemia in First Remission: A Retrospective Analysis

Purpose Patients with acute myeloid leukemia (AML) and FLT3/internal tandem duplication (FLT3/ITD) have poor prognosis if treated with chemotherapy only. Whether this alteration also affects outcome after allogeneic hematopoietic stem-cell transplantation (HSCT) remains uncertain. Patients and Methods We analyzed 206 patients who underwent HLA-identical sibling and matched unrelated HSCTs reported to the European Group for Blood and Marrow Transplantation with a diagnosis of AML with normal cytogenetics and data on FLT3/ITD (present: n = 120, 58%; absent: n = 86, 42%). Transplantations were performed in first complete remission (CR) after myeloablative conditioning. Results Compared with FLT3/ITD-negative patients, FLT3/ITD-positive patients had higher median leukocyte count at diagnosis (59 v 21 x 10(9)/L; P < .001) and shorter interval from CR to transplantation (87 v 99 days; P = .04). Other characteristics were similar in the two groups. At 2 years, relapse incidence (RI; +/- standard deviation) was higher (30% +/- 5% v 16% +/- 5%; P = .006) and leukemia-free survival (LFS) lower (58% +/- 5% v 71% +/- 6%; P = .04) in FLT3/ITD-positive compared with FLT3/ITD-negative patients. In multivariate analyses, FLT3/ITD led to increased RI (hazard ratio [HR], 3.4; 95% CI, 1.46 to 7.94; P = .005), as did older age, female sex, shorter interval between CR and transplantation, and higher number of chemotherapy courses before achieving CR. FLT3/ITD positivity was associated with decreased LFS (HR, 0.37; 95% CI, 0.19 to 0.73; P = .002), along with older age and higher number of chemotherapy courses before achieving CR. Conclusion FLT3/ITD adversely affected the outcome of HSCT in the same direction it does after chemotherapy; despite this, more than half of the patients harboring this mutation who received transplants were alive and leukemia free at 2 years. To further improve the results, use of FLT3 inhibitors before or after HSCT deserves investigation.

Clinical features of obsessive-compulsive disorder with hoarding symptoms: A multicenter study

Background: Factor analyses indicate that hoarding symptoms constitute a distinctive dimension of obsessive-compulsive disorder (OCD), usually associated with higher severity and limited insight. The aim was to compare demographic and clinical features of OCD patients with and without hoarding symptoms. Method: A cross sectional study was conducted with 1001 DSM-IV OCD patients from the Brazilian Research Consortium of Obsessive-Compulsive Spectrum Disorders (CTOC), using several instruments. The presence and severity of hoarding symptoms were determined using the Dimensional Yale-Brown Obsessive-Compulsive Scale. Statistical univariate analyses comparing factors possibly associated with hoarding symptoms were conducted, followed by logistic regression to adjust the results for possible confounders. Results: Approximately half of the sample (52.7%, n = 528) presented hoarding symptoms, but only four patients presented solely the hoarding dimension. Hoarding was the least severe dimension in the total sample (mean score: 3.89). The most common lifetime hoarding symptom was the obsessive thought of needing to collect and keep things for the future (44.0%, n = 440). After logistic regression, the following variables remained independently associated with hoarding symptoms: being older, living alone, earlier age of symptoms onset, insidious onset of obsessions, higher anxiety scores, poorer insight and higher frequency of the symmetry-ordering symptom dimension. Concerning comorbidities, major depressive, posttraumatic stress and attention deficit/hyperactivity disorders, compulsive buying and tic disorders remained associated with the hoarding dimension. Conclusion: OCD hoarding patients are more likely to present certain clinical features, but further studies are needed to determine whether OCD patients with hoarding symptoms constitute an etiologically discrete subgroup. (C) 2012 Elsevier Ltd. All rights reserved.

Transmission of Human Herpesvirus Type 8 Infection Within Families in American Indigenous Populations From the Brazilian Amazon

Background. The intrafamilial dynamics of endemic infection with human herpesvirus type 8 (HHV-8) in Amerindian populations is unknown. Methods. Serum samples were obtained from 517 Amerindians and tested for HHV-8 anti-latent nuclear antigen (anti-LANA) and antilytic antibodies by immunofluorescence assays. Logistic regression and mixed logistic models were used to estimate the odds of being HHV-8 seropositive among intrafamilial pairs. Results. HHV-8 seroprevalence by either assay was 75.4% (95% confidence interval [CI]: 71.5%-79.1%), and it was age-dependent (P-trend<.001). Familial dependence in HHV-8 seroprevalence by either assay was found between mother-offspring (odds ratio [OR], 5.44; 95% CI: 1.62-18.28) and siblings aged >= 10 years (OR 4.42, 95% CI: 1.70-11.45) or siblings in close age range (<5 years difference) (OR 3.37, 95% CI: 1.21-9.40), or in families with large (>4) number of siblings (OR, 3.20, 95% CI: 1.33-7.67). In separate analyses by serological assay, there was strong dependence in mother-offspring (OR 8.94, 95% CI: 2.94-27.23) and sibling pairs aged >= 10 years (OR, 11.91, 95% CI: 2.23-63.64) measured by LANA but not lytic antibodies. Conclusions. This pattern of familial dependence suggests that, in this endemic population, HHV-8 transmission mainly occurs from mother to offspring and between close siblings during early childhood, probably via saliva. The mother to offspring dependence was derived chiefly from anti-LANA antibodies.

Scorpiodinipora costulata (Canu & Bassler, 1929) (Bryozoa, Cheilostomata), a taxonomic and biogeographic dilemma: complex of cryptic species or human-mediated cosmopolitan colonizer?

Despite implausible cosmopolitanism, the species Scorpiodinipora costulata (Canu & Bassler, 1929) has been attributed with reservations to small encrusting colonies with similar morphological features whose known distribution is scattered in tropical and subtropical seas: Pacific Ocean (Philippines), Indian Ocean (Oman), Red Sea, SE Mediterranean, SE Atlantic (Ghana) and SW Atlantic (Brazil). This material raised questions about its generic assignment. The genus Scorpiodinipora Balavoine, 1959 is redescribed with Schizoporella costulata Canu & Bassler, 1929, from the Philippines as the type species, as Balavoine misidentified the specimens to define the genus as Cellepora bernardii Audouin, 1826. Moreover, SEM examination of the cotypes of S. costulata showed that Canu & Bassler confused two genera among them. A lectotype and paralectorype were thus chosen from Canu & Bassler's syntypes corresponding with the present morphotype. Hippodiplosia ottomuelleriana var. parva Marcus, 1938, from Brazil, which presents the same morphotype, is provisionally considered as the junior synonym of S. costulata. Considering the broad allopatric distribution of this morphotype across the oceans and the low capacity of dispersal of species with short-lived larvae, it is likely that this material includes several sibling species. However, the role of man-mediated dispersal is not excluded, at least in regions with high shipping activity, such as that comprising the Suez Canal.

Effect of acute and chronic GVHD on relapse and survival after reduced-intensity conditioning allogeneic transplantation for myeloma

We evaluated the effect of acute and chronic GVHD on relapse and survival after allogeneic hematopoietic SCT (HSCT) for multiple myeloma using non-myeloablative conditioning (NMA) and reduced-intensity conditioning (RIC). The outcomes of 177 HLA-identical sibling HSCT recipients between 1997 and 2005, following NMA (n = 98) or RIC (n = 79) were analyzed. In 105 patients, autografting was followed by planned NMA/RIC allogeneic transplantation. The impact of GVHD was assessed as a time-dependent covariate using Cox models. The incidence of acute GVHD (aGVHD; grades I-IV) was 42% (95% confidence interval (CI), 35-49%) and of chronic GVHD (cGVHD) at 5 years was 59% (95% CI, 49-69%), with 70% developing extensive cGVHD. In multivariate analysis, aGVHD (>= grade I) was associated with an increased risk of TRM (relative risk (RR) = 2.42, P = 0.016), whereas limited cGVHD significantly decreased the risk of myeloma relapse (RR = 0.35, P = 0.035) and was associated with superior EFS (RR = 0.40, P = 0.027). aGVHD had a detrimental effect on survival, especially in those receiving autologous followed by allogeneic HSCT (RR = 3.52, P = 0.001). The reduction in relapse risk associated with cGVHD is consistent with a beneficial graft-vs-myeloma effect, but this did not translate into a survival advantage. Bone Marrow Transplantation (2012) 47, 831-837; doi:10.1038/bmt.2011.192; published online 26 September 2011

Age-adjusted recipient pretransplantation telomere length and treatment-related mortality after hematopoietic stem cell transplantation

Telomere attrition induces cell senescence and apoptosis. We hypothesized that age-adjusted pretransplantation telomere length might predict treatment-related mortality (TRM) after hematopoietic stem cell transplantation (HSCT). Between 2000 and 2005, 178 consecutive patients underwent HSCT from HLA-identical sibling donors after myeloablative conditioning regimens, mainly for hematologic malignancies (n = 153). Blood lymphocytes' telomere length was measured by real-time quantitative PCR before HSCT. Age-adjusted pretransplantation telomere lengths were analyzed for correlation with clinical outcomes. After age adjustment, patients' telomere-length distribution was similar among all 4 quartiles except for disease stage. There was no correlation between telomere length and engraftment, GVHD, or relapse. The overall survival was 62% at 5 years (95% confidence interval [CI], 54-70). After a median follow-up of 51 months (range, 1-121 months), 43 patients died because of TRM. The TRM rate inversely correlated with telomere length. TRM in patients in the first (lowest telomere length) quartile was significantly higher than in patients with longer telomeres (P = .017). In multivariate analysis, recipients' age (hazard ratio, 1.1; 95% CI, .0-1.1; P = .0001) and age-adjusted telomere length (hazard ratio, 0.4; 95% CI; 0.2-0.8; P = .01) were independently associated with TRM. In conclusion, age-adjusted recipients' telomere length is an independent biologic marker of TRM after HSCT. (Blood. 2012;120(16):3353-3359)

The Integrated European Project "GEHA - GEnetics of Healthy Aging": recruitment, health status assessment and survival of the Italian 90+ sibpairs

The present study is part of the EU Integrated Project “GEHA – Genetics of Healthy Aging” (Franceschi C et al., Ann N Y Acad Sci. 1100: 21-45, 2007), whose aim is to identify genes involved in healthy aging and longevity, which allow individuals to survive to advanced age in good cognitive and physical function and in the absence of major age-related diseases. Aims The major aims of this thesis were the following: 1. to outline the recruitment procedure of 90+ Italian siblings performed by the recruiting units of the University of Bologna (UNIBO) and Rome (ISS). The procedures related to the following items necessary to perform the study were described and commented: identification of the eligible area for recruitment, demographic aspects related to the need of getting census lists of 90+siblings, mail and phone contact with 90+ subjects and their families, bioethics aspects of the whole procedure, standardization of the recruitment methodology and set-up of a detailed flow chart to be followed by the European recruitment centres (obtainment of the informed consent form, anonimization of data by using a special code, how to perform the interview, how to collect the blood, how to enter data in the GEHA Phenotypic Data Base hosted at Odense). 2. to provide an overview of the phenotypic characteristics of 90+ Italian siblings recruited by the recruiting units of the University of Bologna (UNIBO) and Rome (ISS). The following items were addressed: socio-demographic characteristics, health status, cognitive assessment, physical conditions (handgrip strength test, chair-stand test, physical ability including ADL, vision and hearing ability, movement ability and doing light housework), life-style information (smoking and drinking habits) and subjective well-being (attitude towards life). Moreover, haematological parameters collected in the 90+ sibpairs as optional parameters by the Bologna and Rome recruiting units were used for a more comprehensive evaluation of the results obtained using the above mentioned phenotypic characteristics reported in the GEHA questionnaire. 3. to assess 90+ Italian siblings as far as their health/functional status is concerned on the basis of three classification methods proposed in previous studies on centenarians, which are based on: • actual functional capabilities (ADL, SMMSE, visual and hearing abilities) (Gondo et al., J Gerontol. 61A (3): 305-310, 2006); • actual functional capabilities and morbidity (ADL, ability to walk, SMMSE, presence of cancer, ictus, renal failure, anaemia, and liver diseases) (Franceschi et al., Aging Clin Exp Res, 12:77-84, 2000); • retrospectively collected data about past history of morbidity and age of disease onset (hypertension, heart disease, diabetes, stroke, cancer, osteopororis, neurological diseases, chronic obstructive pulmonary disease and ocular diseases) (Evert et al., J Gerontol A Biol Sci Med Sci. 58A (3): 232-237, 2003). Firstly these available models to define the health status of long-living subjects were applied to the sample and, since the classifications by Gondo and Franceschi are both based on the present functional status, they were compared in order to better recognize the healthy aging phenotype and to identify the best group of 90+ subjects out of the entire studied population. 4. to investigate the concordance of health and functional status among 90+ siblings in order to divide sibpairs in three categories: the best (both sibs are in good shape), the worst (both sibs are in bad shape) and an intermediate group (one sib is in good shape and the other is in bad shape). Moreover, the evaluation wanted to discover which variables are concordant among siblings; thus, concordant variables could be considered as familiar variables (determined by the environment or by genetics). 5. to perform a survival analysis by using mortality data at 1st January 2009 from the follow-up as the main outcome and selected functional and clinical parameters as explanatory variables. Methods A total of 765 90+ Italian subjects recruited by UNIBO (549 90+ siblings, belonging to 258 families) and ISS (216 90+ siblings, belonging to 106 families) recruiting units are included in the analysis. Each subject was interviewed according to a standardized questionnaire, comprising extensively utilized questions that have been validated in previous European studies on elderly subjects and covering demographic information, life style, living conditions, cognitive status (SMMSE), mood, health status and anthropometric measurements. Moreover, subjects were asked to perform some physical tests (Hand Grip Strength test and Chair Standing test) and a sample of about 24 mL of blood was collected and then processed according to a common protocol for the preparation and storage of DNA aliquots. Results From the analysis the main findings are the following: - a standardized protocol to assess cognitive status, physical performances and health status of European nonagenarian subjects was set up, in respect to ethical requirements, and it is available as a reference for other studies in this field; - GEHA families are enriched in long-living members and extreme survival, and represent an appropriate model for the identification of genes involved in healthy aging and longevity; - two simplified sets of criteria to classify 90+ sibling according to their health status were proposed, as operational tools for distinguishing healthy from non healthy subjects; - cognitive and functional parameters have a major role in categorizing 90+ siblings for the health status; - parameters such as education and good physical abilities (500 metres walking ability, going up and down the stairs ability, high scores at hand grip and chair stand tests) are associated with a good health status (defined as “cognitive unimpairment and absence of disability”); - male nonagenarians show a more homogeneous phenotype than females, and, though far fewer in number, tend to be healthier than females; - in males the good health status is not protective for survival, confirming the male-female health survival paradox; - survival after age 90 was dependent mainly on intact cognitive status and absence of functional disabilities; - haemoglobin and creatinine levels are both associated with longevity; - the most concordant items among 90+ siblings are related to the functional status, indicating that they contain a familiar component. It is still to be investigated at what level this familiar component is determined by genetics or by environment or by the interaction between genetics, environment and chance (and at what level). Conclusions In conclusion, we could state that this study, in accordance with the main objectives of the whole GEHA project, represents one of the first attempt to identify the biological and non biological determinants of successful/unsuccessful aging and longevity. Here, the analysis was performed on 90+ siblings recruited in Northern and Central Italy and it could be used as a reference for others studies in this field on Italian population. Moreover, it contributed to the definition of “successful” and “unsuccessful” aging and categorising a very large cohort of our most elderly subjects into “successful” and “unsuccessful” groups provided an unrivalled opportunity to detect some of the basic genetic/molecular mechanisms which underpin good health as opposed to chronic disability. Discoveries in the topic of the biological determinants of healthy aging represent a real possibility to identify new markers to be utilized for the identification of subgroups of old European citizens having a higher risk to develop age-related diseases and disabilities and to direct major preventive medicine strategies for the new epidemic of chronic disease in the 21st century.

Artbildung via Wirtsrassen bei Tephritis conura (Diptera: Tephritidae)

Tephritis conura parasitiert verschiedene Kratzdistel-Arten (Cirsium sp.), darunter Cirsium heterophyllum und C. oleraceum. Vorhergehende Studien hatten gezeigt, dass T. conura auf diesen Wirten zumindest partiell reproduktiv isolierte Wirtsrassen ausgebildet hat. Ziel der vorliegenden Arbeit war es durch die Kombination von genetischen und morphometrischen Analysen mit direkten Untersuchungen von potentiellen Isolationsbarrieren einerseits, und die Einbeziehung verschiedener Verbreitungsmuster der Wirtspflanzen andererseits, die Artbildungsprozesse bei T. conura besser zu verstehen. Der Genfluss zwischen Heterophyllum- und Oleraceum-Fliegen wird durch eine Reihe von Isolationsbarrieren eingeschränkt: Habitatspräferenzen und Unterschiede im Zeitpunkt der sexuellen Aktivität wirken als präzygotische Barrieren, mangelnde Adaptation der Larven an den Alternativwirt sowie möglicherweise genomische Inkompatibilitäten bei Hybriden stellen postzygotische Barrieren dar. Das Maß der genetischen Differenzierung (Allozyme und mtDNA) lässt den Schluss zu, dass diese Barrieren in einer nahezu kompletten reproduktiven Isolation resultieren, so dass Heterophyllum- und Oleraceum-Fliegen eher als eigene Arten denn als Wirtsrassen angesehen werden können. Die mtDNA-Daten deuten darauf hin, dass C. heterophyllum der ursprüngliche Wirt gewesen ist und dass der Wirtswechsel im Laufe der letzten Eiszeit stattgefunden hat. Dabei scheint ein peripatrisches Szenario am wahrscheinlichsten, bei dem die relative Häufigkeit der Wirte für den Differenzierungsprozess die entscheidende Rolle spielte.

Untersuchungen zur Lymphozytotoxizität gegen Tumoren in Nierenzellkarzinom-Patienten und HLA-kompatiblen gesunden Spendern

In der vorliegenden Arbeit wurden Blutlymphozyten, die aus allogenen, serologisch HLA (humanes Leukozytenantigen)-identischen gesunden Geschwisterspendern von Nierenzellkarzinom (RCC, engl. renal cell carcinoma)-Patienten isoliert wurden, auf ihre antitumorale Reaktivität in vitro untersucht. Dazu war die vorangehende Generierung von stabil in vitro wachsenden Tumorzelllinien der Patienten zwingende Voraussetzung. Insgesamt wurden aus primärem Tumorgewebe von 65 Nierenzellkarzinom-Patienten Tumorzellen isoliert und daraus Zellkulturen angelegt. In 28 % der Fälle gelang es, eine konstant in Zellkultur wachsende Tumorzelllinie zu etablieren. Daneben wurden aus 56 Tumorpatienten auch die aus dem angrenzenden Nierengewebe gewonnenen nicht-malignen Nierenzellen über wenige Zellkultur-Passagen expandiert. In vier Patienten mit stabil in vitro wachsender Tumorzelllinie war ein allogener HLA-identischer Geschwisterspender verfügbar. In diesen Modellsystemen wurden in gemischten Lymphozyten-Tumorzell-Kulturen (MLTCs, engl. mixed lymphocyte tumor cell cultures) die Blutlymphozyten der Patienten und der gesunden Geschwisterspender mit der jeweiligen Nierenzellkarzinom-Zelllinie stimuliert und tumorreaktive CD8+ zytotoxische T-Lymphozyten (CTLs, engl. cytotoxic T-lymphocytes) generiert. Wenn möglich wurden aus den so gewonnenen „Responder“-Massenkulturen CD8+ T-Zellklone isoliert und hinsichtlich ihrer Funktionalität in IFN-γ-ELISpot-Assays und 51Chrom-Zytotoxizitätstests untersucht. Durch Blockade der HLA-Moleküle mit monoklonalen Antikörpern wurden die HLA-Restriktionselemente sowie weitere an der Erkennung beteiligte Oberflächenmoleküle analysiert. Kreuzreaktivitätsuntersuchungen mit einem breiten Zielzell-„Panel“ gaben Aufschluss über die Reaktivität der CTLs gegen RCC, nicht-maligne Nierenzellen, hämatopoetische Zielzellen von Patient und Geschwisterspender und weitere Tumorzelllinien aus Nierenzellkarzinomen und anderen Tumorentitäten. Interessanterweise zeigten die Geschwister-MLTC-„Responder“-Lymphozyten im Vergleich zu den autologen MLTC-„Responder“-Lymphozyten eine stärkere Proliferation und Zytotoxizität nach Stimulation mit Tumorzellen. Die allogenen tumorreaktiven „Responder“-Lymphozyten entstammten der CD8+ CD62L(high)+ Subpopulation, die naive Vorläufer- und „central memory“-T-Zellen enthält. Im Gegensatz zu autologen MLTC-Lymphozyten und tumorinfiltrierenden Lymphozyten konnte aus nahezu allen allogenen MLTCs mithilfe des Grenzverdünnungsverfahrens ein breites Spektrum an tumorreaktiven CTL-Klonen expandiert werden. Diese lysierten entweder ausschließlich die autologe RCC-Zelllinie oder kreuzreagierten mit autologen nicht-malignen Nierenzellen. Eine Minderheit der CTL-Klone erkannte außerdem hämatopoetische Zellen des Patienten oder allogene Tumorzellen. Als HLA-Restriktionselemente der allogenen tumorreaktiven CD8+ CTL-Klone wurden HLA-A2, -A3, -A11, -A24 und -B7 identifiziert. Weiterhin wurden in einem Modellsystem bisher unbekannte, stark proliferierende CD3+ CD16+ CD57+ CTL-Klone mit nicht-HLA-restringierter Tumorreaktivität isoliert. Zusammenfassend zeigt diese Arbeit erstmals, dass allogene Blutlymphozyten von HLA-identischen gesunden Geschwistern eine Vielfalt von tumorreaktiven CD8+ CTL-Klonen enthalten. Im direkten Vergleich mit autologen Blutlymphozyten der betroffenen Patienten besitzen allogene Blutlymphozyten der Geschwister eine stärkere proliferative und zytotoxische Tumorreaktivität. Die Ergebnisse dieser Arbeit ermutigen weitere Bemühungen, tumorreaktive T-Zellen aus dem Blut von HLA-identischen gesunden Geschwisterspendern in vitro zu generieren. Solche T-Zellen wären in zweierlei Hinsicht von Interesse: Zum einen ermöglichen sie die Identifizierung der Zielantigene, die von T-Zellen aus gesunden Individuen auf Tumoren erkannt werden und als Zielstrukturen von antigenspezifischen Immuntherapien (z. B. Vakzination) dienen könnten. Zum anderen könnten diese T-Zellen möglicherweise für eine adoptive Immuntherapie der betroffenen Tumorpatienten verwendet werden.