B cell lymphoma (BCL) comprises a biologically and clinically heterogeneous group of tumors deriving from different stages of B cell development. The immunoglobulin (Ig) variable heavy chain (VH) gene rearrangement is unique for each BCL and can be used to reveal cellular origin, to study signs of antigen selection and to quantify tumor cell load. The normal counterpart of mantle cell lymphoma (MCL) has been postulated to be a naïve B cell and in hairy cell leukemia (HCL) it is considered to be a post-germinal centre B cell. We analyzed the VH gene rearrangements in 110 MCLs and 32 HCLs by PCR amplification and sequencing. Most MCLs (84%) displayed VH genes lacking somatic hypermutation (SHM), thus correlating to a naïve cell origin, whereas a subgroup (16%) showed SHM, implying derivation from a more differentiated B cell. In HCL, a majority of cases (84%) displayed SHM with signs of intraclonal heterogeneity and 16% had unmutated VH genes, thus questioning the cell of origin in HCL. Biased usage of particular VH genes was detected in both HCL (VH3-30) and MCL (VH3-21 and VH4-34), which indicates that antigen selection may be involved in lymphoma development. Furthermore, VH3-21+ MCLs showed a highly restricted Vλ3-19 gene use and they also had a superior outcome compared to other MCLs. Rearrangement analysis of 67 VH3-21+ chronic lymphocytic leukemia (CLL) cases from three different countries verified, regardless of geographical origin, the short and highly homologous complementarity determining region 3s and the strikingly biased usage of the Vλ2-14 gene (75%), as previously reported in CLL. This further supports that antigen selection by a common antigenic epitope may have occurred in VH3-21+ CLLs. In an autologous transplantation study of 30 multiple myeloma patients, we quantified the tumor content in the autografts before and after stem cell selection using clone-specific PCR. We conclude that stem cell selection reduced the number of clonal cells linearly, but purging could not totally eliminate the tumor cells from the graft, thus increasing the risk of a relapse. Altogether, our data allowed us to define new BCL subsets and to gain insights into the potential role of antigen selection in BCL development as well as the monitoring of tumor cell load using Ig gene rearrangements analysis.

published_or_final_version / Paediatrics and Adolescent Medicine / Master / Master of Medical Sciences

Tyrimo objektas. Celiakija yra labai dažna virškinimo trakto liga. Jos paplitimas Europoje ir Šiaurės Amerikoje 1 iš 100-300 suaugusių ir vaikų. Lietuvoje duomenų apie celiakijos paplitimą nėra, ši liga diagnozuojama tik pavieniais atvejais [29]. Sergantieji imumoglobulino A (IgA) deficitu 10 kartų dažniau serga celiakija negu sveikieji. Viršutinių kvėpavimo takų ir virškinimo trakto infekcijos, autoimuninės ligos ir onkologiniai susirgimai taip pat dažnesni sergantiesiems IgA deficitu [143, 163-168]. Lietuvoje duomenų apie IgA deficito paplitimą nėra [29]. Darbo tikslas. Nustatyti Vilniaus miesto 11-13 m. vaikų celiakijos ir IgA deficito paplitimą. Tyrimo medžiaga ir metodai. Gavus Lietuvos bioetikos komiteto leidimą nuo 2009 metų sausio mėnesio iki 2010 metų kovo mėnesio ištirta 1000 vaikų nuo 11 iki 13 metų amžiaus, kurie mokėsi šešiose lietuviškose Vilniaus miesto mokyklose. Mokyklos pasirinktos atsitiktiniu atrankos būdu. Jose buvo išdalintos asmens informavimo formos (tėvams priedas nr. 1 ir vaikams priedas nr. 2), kuriose buvo aprašytas biomedicininis tyrimas, jo eiga ir nauda. Vaikams, kurių tėvai sutiko atlikti celiakijos tyrimą, buvo nustatomi audinių transgliutaminazės IgA klasės (aTG IgA) antikūnai ir bendras IgA kiekis kapiliarinio kraujo laše. Tyrimo metu buvo naudojami Biocard TM celiakijos testai (Ani Biotech OY, Suomija). Tyrimo atsakymas buvo gaunamas ir įvertinamas po 5 min. Nustačius aTG IgA klasės antikūnus, vaikai buvo nukreipti į Vilniaus universitetinę... [toliau žr. visą tekstą] / Object. Coeliac disease is one of the most prevalent gastrointestinal disorder. It‘s prevalence in Europe and North America is 1 of 150-300 adults and children. In Lithuania there are no data on prevalence of coeliac disease but it‘s seems that there is hypodiagnosis [29]. IgA-deficient individuals have a tenfold risk for coeliac disease compared with the general population. Patients with IgA deficiency have a tendency to develop recurrent sinopulmonary and gastrointestinal infections, allergies, autoimmune diseases and malignancies [148-154]. There are no data on the prevalence of IgA deficiency in Lithuania [29]. The aim. To determine the prevalence of coeliac disease and IgA deficiency among 11-13 years children in Vilnius. Material and methods. From January 2009 to March 2010 we investigated 1000 children (11-13 years of age) for coeliac disease and immunoglobulin A (IgA) deficiency from six Vilnius secondary schools. We examined capillary blood for tissue transglutaminase IgA class antibodies (tTG IgA) and total IgA with Biocard TM test (Ani Biotech OY, Finland) for children whose parents agreed to do this test. The results were evaluated after 5 min. Children with positive test results (tTG IgA positive or total IgA deficiency) underwent small bowel endoscopy with biopsies at Vilnius University Children Hospital to confirm or deny the diagnosis of coeliac disease. We get permission for this study from Lithuanian Bioethics Committee. Results. Two of 1000 children were... [to full text]

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Texas Southwestern Medical Center at Dallas, 2001. / Vita. Bibliography: 146-193.

Thesis (Ph. D.)--West Virginia University, 2006. / Title from document title page. Document formatted into pages; contains x, 202 p. : ill. (some col.). Includes abstract. Includes bibliographical references.

O câncer colorretal (CCR) pode ocorrer em qualquer parte do cólon ou do reto e representa o terceiro câncer mais comum no mundo em ambos os sexos. As células Natural Killer (NK) fazem parte do sistema imune inato reconhecendo moléculas de HLA de classe I em células alvo, através de seus receptores de membrana killer cell immunoglobulin-like receptors (KIR). O objetivo deste estudo foi avaliar a associação entre os genes KIR e os ligantes HLA em pacientes com câncer colorretal e controles saudáveis. Examinamos o polimorfismo de 16 genes KIR e seus ligantes HLA em 154 pacientes caucasóides com CCR e 216 controles saudáveis pela técnica de PCR-SSO e PCR-SSP. Quando comparamos os dois grupos, não foram encontradas diferenças significativas para os ligantes HLA e os genes KIR após correção de Bonferroni. Entretanto, o grupo de genótipos Bx (heterozigoto e homozigoto para o haplótipo B) foi mais frequente nos controles, quando comparados com os pacientes. Estes achados sugerem que altos níveis de ativação de sinais KIR aparecem como proteção para o câncer colorretal. / Colorectal cancer (CRC) can occur anywhere in the colon or rectum and represents the third most common cancer in the world in both sexes. Natural killer cells (NK) are part of the innate immune system recognizing class I HLA molecules on target cells through their membrane receptors, called killer cell immunoglobulin-like receptors (KIR). The aim of our study was to evaluate the association between the KIR genes and HLA ligands in patients with colorectal cancer and healthy controls. We examined the polymorphism of 16 KIR genes and their HLA ligands in 154 caucasoid CRC patients and 216 healthy controls by PCR-SSO and PCR-SSP. When both groups were compared, no significant differences were found for HLA ligands and KIR genes after Bonferroni correction. However, the Bx group genotypes (heterozygous and homozygous for the haplotype B) were more frequent in controls, when compared with patients. These findings suggest that individuals with Bx genotypes could have some protection to colorectal cancer. These findings suggest that higher levels of activating KIR signals appear as protective to colorectal cancer.

La dermatite atopique est une dermatose inflammatoire apparaissant préférentiellement avant l’âge de cinq ans, et évoluant naturellement vers la guérison après l’adolescence dans plus de 90% des cas. L’origine de cette amélioration spontanée n’est pas clairement établie dans cette dermatose multifactorielle dont l’étiopathogénie reste encore à déterminer (maturation du système immunitaire ?). Les liens de cette pathologie avec le psychisme sont certains : retentissement psychologique important avec altération de la qualité de vie, aggravation voire déclenchement des poussées par le stress, amélioration des lésions par psychothérapie. L’observation de la nature de la structure d’attachement est importante dans le domaine de la psychopathologie. Elle est encore peu réalisée dans le domaine da la pathologie organique. Nous avons étudié la structure d’attachement de 80 adultes ayant présenté dans l’enfance une dermatite atopique, 40 d’entre eux ayant une guérison de celle-ci depuis l’adolescence, 40 autres présentant une pérennisation des crises d’eczéma. L’évaluation de l’attachement a été réalisée avec un autoquestionnaire (CAMIR de PIERREHUMBERT) et la cotation de l’entretien d’attachement avec la méthode Q-SORT selon KOBAK. Nous avons également mesuré les symptômes psychopathologiques associés avec l’échelle SCL90-R, le niveau d’anxiété avec l’inventaire trait-état de SPIELBERGER (STAIY) et le coping avec le WCC-R de VITALIANO. Les IgE totales ont été dosées. Les sujets avec dermatite atopique ayant débutée avant trois ans ne sont pas plus insécures que ceux avec un début plus tardif de leur dermatose. Ceci fait évoquer la possibilité d’une absence de retentissement sur la structure d’attachement d’une dermatite atopique apparaissant dans les premiéres années de vie, contrairement à ce qui est noté dans toute pathologie chronique d’apparition précoce. Il est alors supposé un effet positif des soins cutanés sur la nature de la relation de la dyade mère-enfant. Par contre, le retentissement ultérieur de la dermatite atopique chez l’adulte est important, avec augmentation d’une insécurité préoccupée en termes de représentations d’attachement, une augmentation des scores de toutes les dimensions psychopathologiques mesurées et une recherche anxieuse de soutien à l’extérieur. Ce retentissement est d’autant plus important que les IgE sont élevées, ceci n’étant pas uniquement le reflet de la gravité de la maladie. Les adultes présentant une dermatite atopique pérennisée sont structurellement plus insécures que ceux qui ont guéris : si nous considèrons l’aspect stable dans le temps de la structure d’attachement, ces résultats positionneraient celle ci en tant que possible facteur dispositionnel prédictif dans l’évolution de la dermatite atopique. Le score de sécurité des patients guéris est d’autant plus élevé que les IgE sont normales. Un phénomène d’interaction entre le système d’attachement et le système adaptatif au stress, à dépendance développementale commune sur certains aspects, est évoqué. Le rôle des IgE reste à déterminer. En termes de psychologie de la santé, la structure d’attachement pourrait être considérée comme un facteur dispositionnel susceptible d’influer l’évolution de la dermatite atopique. / Atopic dermatitis is an inflammatory skin disorder which usually appears before the age of five, and heals naturally little by little after adolescence in over 90% of cases. Why this spontaneous improvement occurs is not clearly established for this multi-factor skin disorder, for which the etiopathology has yet to be determined (immune system maturity?).There is a clear relationship between this pathology and the psyche: major psychological repercussions affecting the quality of life, aggravation or triggering of skin reactions due to stress, alleviation of lesions using psychotherapy. Observation of patterns of attachment is important in the field of psychopathology, but is not often undertaken in the domain of organic pathology. We studied the patterns of attachment for 80 adults having suffered from atopic dermatitis during childhood, 40 of them had been cured since adolescence, the other 40 continued to suffer from outbreaks of eczema. Attachment was evaluated using a self-completion questionnaire (CAMIR by PIERRE HUMBERT) and the attachment interview was graded using the Q-SORT method, by KOBAK. We also measured the associated psychopathological symptoms using the SCL90-R scale, level of anxiety using SPIELBERGER’s state-trait-anxiety inventory (STAIY), and coping measurement using the WCC-R scale devised by VITALIANO. Total IgE was measured. Patients suffering from atopic dermatitis that began before the age of 3 years are not more insecure than patients whose skin disorder started later in life. This meant that there were possibly no repercussions on the pattern of attachment for cases of atopic dermatitis that had appeared in the first years of life, contrary to all reports regarding a chronic pathology appearing early in life. This implies that caring for the skin has a positive effect on the mother-child relationship. On the other hand, adults suffer from major repercussions of atopic dermatitis later on in life: increased sense of preoccupied insecurity in terms of representations of attachment, increased scores in all the psychopathological dimensions measured, and an anxious need for outside support. These repercussions are even more serious when IgE is high, but this is not solely connected with the gravity of the illness. Adults suffering from persistent atopic dermatitis are basically more insecure than those who are cured: if long-term stability in the pattern of attachment is considered, this study could place pattern of attachment as a possible predictive disposition factor in the evolution of atopic dermatitis. The security score of cured patients is all the greater when IgE is normal. The existence of an interaction between the attachment pattern and the system for adapting to stress has been suggested, since they are both dependent on development. The role played by IgE remains to be determined. In terms of health psychology, the pattern of attachment could be considered as a disposition factor likely to influence the evolution of a skin disorder.

O câncer de próstata é o segundo câncer mais comum entre homens, uma vez que tanto a incidência como a mortalidade aumentam exponencialmente após a idade de 50 anos. As células Natural Killer (NK) fazem parte do sistema imune inato e reconhecem moléculas de HLA de classe I na célula alvo, através de seus receptores de membrana, chamados killer immunoglobulin-like-receptors (KIR). O objetivo desse estudo foi avaliar a associação entre os genes KIR e HLA em pacientes com câncer de próstata e grupo controle. Genotipamos 200 pacientes com diagnóstico de câncer de próstata e 185 pacientes saudáveis para os genes KIR e HLA classe I por PCR-SSP. Quando comparados os grupos, não foram encontradas diferenças significativas para HLA-C do grupo 1 e do grupo 2, HLA-Bw4, HLA-A3 e A11. Nenhuma diferença foi observada na frequência dos genes KIR nos pacientes com câncer de próstata e nos controles. Esses resultados sugerem que não há potencial papel para o sistema dos genes KIR no câncer de próstata. / Prostate cancer is the second most common cancer among men, since both incidence and mortality exponentially increases in men over fifty years of age. Natural killer cells (NK) are part of the innate immune system recognizing class I HLA molecules on target cells through their membrane receptors, called killer immunoglobulin-like receptors (KIR). The aim of our study was to evaluate the association between the KIR genes and HLA alleles in patients with prostate cancer and healthy controls. Two hundred prostate cancer patients and 185 healthy controls were typed for HLA class I and KIR genes by PCR-SSP. When both groups were compared, no significant differences were found for HLA-C group 1 and group 2, HLA-Bw4, HLA-A3 and A11. No difference was seen either in KIR frequency between patients with prostate cancer and controls. In conclusion, our data suggests no potential role for the KIR gene system in prostate cancer.

O objetivo desse trabalho foi avaliar a concentração de imunoglobulina G (IgG), a sobrevivência e o ganho de peso de leitões com baixo peso ao nascimento durante a lactação, de acordo com a quantidade de colostro ingerida com ou sem um suplemento proteico-energético (SPE). Leitões com peso ao nascimento variando de 800 a 1200 g (média de 1025,2 ± 8,15 g) foram submetidos, nas primeiras 24 h, a diferentes tratamentos: CM (n=30) e CMS (n=30) compostos por leitões que ficaram com suas mães biológicas em baias convencionais, sem e com SPE, respectivamente; D120 (n=30) e D120S (n=30) compostos por leitões que receberam 120 mL (30 mL a cada 6 horas) de colostro por sonda orogástrica em um deck de alimentação, sem e com SPE, respectivamente; D200 (n=29) e D200S (n=27) formados por leitões que receberam 200 mL (50 mL a cada 6 horas) de colostro por sonda orogástrica em um deck de alimentação, sem e com SPE, respectivamente. Os leitões dos tratamentos CMS, D120S e D200S receberam 4 mL do SPE nas primeiras 24 horas. Os leitões foram selecionados de fêmeas de ordem de parto (OP) 2 a 7 (média de 3,9 ± 0,11), e o intervalo médio entre o nascimento e a ingestão ou fornecimento de colostro foi 100,3 ± 3,6 minutos. Os leitões dos tratamentos D120, D120S, D200 e D200S foram alimentados com colostro procedente de um pool de colostro. Os leitões foram colocados para mamar em mães adotivas de ordem de parto (OP) 2 a 5 (média de 3,0 ± 0,08), em leitegadas contendo dois leitões de cada tratamento, perfazendo um total de 12 leitões. Os leitões foram pesados individualmente ao nascimento, 24h após e, também, aos 7, 14 e 20 dias de vida. A duração média da lactação foi de 20,4 ± 0,06 dias. A concentração de IgG no soro dos leitões D200 e D200S foi superior à dos leitões CM, D120 e D120S (P<0,05), enquanto que os leitões CMS e D200 tiveram concentração de IgG similar (P>0,05). O maior ganho de peso nas primeiras 24 h foi observado no tratamento CMS, ao passo que os tratamentos D120 e D120S tiveram perda de peso neste período (P<0,05). O ganho de peso diário durante o período de lactação e o peso aos 7, 14 e 20 dias foram semelhantes entre os tratamentos (P>0,05). Os leitões D120 apresentaram maior taxa de mortalidade durante a lactação do que os leitões CMS, D120S, D200 e D200S (P<0,05). O fornecimento de 200 mL de colostro ou de suplemento proteico-energético são alternativas que garantem maior concentração de IgG sérica, ganho de peso nas primeiras 24 h de vida e maior sobrevivência. / The aim of this study was to evaluate the concentration of immunoglobulin G (IgG), survival and weight gain of low birth weight piglets according to the amount of colostrum intake and the supplementation of an oral protein and energy supplement (OPES). Piglets with an range birth weight of 800 to 1200 g (average of 1025.2 ± 8.15 g) were submitted during the first 24 h to one different treatments: WS (n=30) and WSS (n=30) consisted of piglets suckling in their mothers in conventional farrowing crates, with or without OPES, respectively; D120 (n=30) and D120S (n=30) consisted of piglets fed 120 mL (30 mL every 6 hours) of colostrum by orogastric tube in a feeding deck, with or without OPES, respectively; D200 (n=29) and D200S (n=27) consisted of piglets fed 200 mL (50 mL every 6 hours) of colostrum by orogastric tube in a feeding deck, with or without OPES, respectively. The piglets on WSS, D120S and D200S received 4 mL of OPES on the first 24 hours after birth. Piglets were selected from sows of parity 3.9 ± 0.11 (range of 2 to 7), and the average time lapse between birth and first colostrum intake or gavage was 100.3 ± 3.6 minutes. Piglets of treatments D120, D120S, D200 and D200S received colostrum from a colostrum pool. All animals were individually weighed at birth and after the first 24 h of life. They were cross-fostered for suckling in foster mothers parity order (OP) range of 2 to 5 (average OP 3.0 ± 0.08), and each litter remained with 12 piglets, two of each treatment. Piglets were weighed again at 7, 14 and 20 days of life, and lactation length was of 20.4 ± 0.06 days. Serum concentration of IgG in the piglets was greater in D200 and D200S than in CM, D120 and D120S treatments (P<0.05), whereas CMS and D200 piglets had similar (P>0.05) IgG concentration. The greatest weight gain during the first 24 h was observed in CMS piglets, whereas D120 and D120S piglets lost weight (P<0.05). The average daily gain during lactation, as well as body weight at 7, 14 and 20 days were similar (P>0.05) among treatments. Piglets from the D120 treatment showed higher mortality rate during lactation than CMS, D120S, D200 and D200S piglets (P<0.05). Hence, the supply of 200 mL of colostrum or an energy and protein supplement are options which assure greater IgG concentration, weight gain in the first 24 h of life, and higher survival.