bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oxindole alkaloids from Uncaria tomentosa induce apoptosis in proliferating, G0/G1‐arrested and bcl‐2‐expressing acute lymphoblastic leukaemia cells
Authors: Bacher Nicole , Tiefenthaler Martin , Sturm Sonja , Stuppner Hermann , Ausserlechner Michael J. , Kofler Reinhard , Konwalinka Günther 
Published: December 2005

SummaryNatural products are still an untapped source of promising lead compounds for the generation of antineoplastic drugs. Here, we investigated for the first time the antiproliferative and apoptotic effects of highly purified oxindole alkaloids, namely isopteropodine (A1), pteropodine (A2), isomitraphylline (A3), uncarine F (A4) and mitraphylline (A5) obtained from Uncaria tomentosa, a South American Rubiaceae, on human lymphoblastic leukaemia T cells (CCRF‐CEM‐C7H2). Four of the five tested alkaloids inhibited proliferation of acute lymphoblastic leukaemia cells. Furthermore, the antiproliferative effect of the most potent alkaloids pteropodine (A2) and uncarine F (A4) correlated with induction of apoptosis. After 48 h, 100 μmol/l A2 or A4 increased apoptotic cells by 57%. CEM‐C7H2 sublines with tetracycline‐regulated expression of bcl‐2, p16ink4A or constitutively expressing the cowpox virus protein crm‐A were used for further studies of the apoptosis‐inducing properties of these alkaloids. Neither overexpression of bcl‐2 or crm‐A nor cell‐cycle arrest in G0/G1 phase by tetracycline‐regulated expression of p16INK4A could prevent alkaloid‐induced apoptosis. Our results show the strong apoptotic effects of pteropodine and uncarine F on acute leukaemic lymphoblasts and recommend the alkaloids for further studies in xenograft models.
Involvement of 4-1BB (CD137)−4-1BBligand interaction in the modulation of CD4+ T cell-mediated inflammatory colitis
Authors: Maerten P , Kwon B S , Shen C , De Hertogh G , Cadot P , Bullens D M A , Overbergh L , Mathieu C , Van Assche G , Geboes K , Rutgeerts P , Ceuppens J L 
Published: December 2005

Summary4-1BB ligand (4-1BBL) expressed on antigen-presenting cells interacts with 4-1BB on activated T cells (especially CD8+ cells) and co-stimulates the latter to secrete cytokines and to proliferate. The role of 4-1BB−4-1BBL interaction was studied here in a model of colitis based on naive CD4+ T cell transfer to SCID mice, a disease model in which CD8 cells do not take part. We found that CD4+ T cells from 4-1BB-deficient mice, after transfer in SCID mice, proliferated more rapidly compared to wild-type CD4+ T cells. Mice reconstituted with naive CD4+ T cells from 4-1BB-deficient mice developed colitis, however, with a mixed Th1/Th2 response, in contrast to the Th1-type response in mice reconstituted with wild-type naive CD4+ T cells. Importantly, this altered cytokine response did not temper colitis severity. Although it has been reported previously that 4-1BB co-stimulation may contribute to regulatory T cell functioning, we found that CD4+CD25+ regulatory T cells from 4-1BB-deficient mice were perfectly able to prevent naive CD4+ T cell-induced colitis. In conclusion, our data provide evidence that 4-1BB−4-1BBL interaction modulates the effector CD4+ T cell-driven immune response and cytokine production in experimental colitis without affecting regulatory T cell function.
Immunomodulation using the recombinant monoclonal human B7-DC cross-linking antibody rHIgM12
Authors: Van Keulen V P , Ciric B , Radhakrishnan S , Heckman K L , Mitsunaga Y , Iijima K , Kita H , Rodriguez M , Pease L R 
Published: December 2005

Summary
A patient with Waldenstrom’s macroglobulinaemia expresses a high titre IgM antibody in serum that binds both mouse and human dendritic cells (DC) in a B7-DC (PD-L2)-dependent manner. We have reported previously that purified antibody from patient serum activates immature and mature DC in vitro, enhancing the ability of these professional antigen-presenting cells to activate naive T cells, take up antigen, resist a cytokine-depleted environment and secrete immunomodulatory cytokines, such as interkeukin (IL)-6 and tumour necrosis factor (TNF)-α. Systemic treatment of experimental animals with this antibody induces potent anti-melanoma immunity and modulates protectively the recall response against antigen challenge through the airway in an experimental model of inflammatory airway disease. Here we describe a monoclonal IgM antibody derived from this serum immunoglobulin that recapitulates each of these earlier observations, providing direct evidence that M protein from the Waldenstrom’s patient mediates these potent immunomodulatory effects. Furthermore, cell lines expressing this recombinant form of the human antibody provide the basis for developing this reagent for clinical application.
Oral administration of CpG-ODNs suppresses antigen-induced asthma in mice
Authors: Kitagaki K , Businga T R , Kline J N 
Published: December 2005

SummaryOligodeoxynucleotides containing CpG motifs (CpG-ODNs) can protect against eosinophilic airway inflammation in asthma. Previously we have found that parenteral or mucosal administration of CpG-ODNs is effective in preventing (as well as reversing established) disease. In this study, we examined the effect of oral CpG-ODNs on the development of immune tolerance. Using an ovalbumin (OVA)-induced murine model of asthma, we found that CpG-ODNs, administered orally around the time of sensitization, prevented eosinophilic airway inflammation in a dose-dependent manner. Although oral co-administration of CpG-ODNs with OVA (known to induce tolerance) did not significantly change the inhibition of OVA-induced airway eosinophilia, it did modulate OVA-specific immunoglobulin responses: oral administration of OVA alone suppressed OVA-specific IgG1 production, but only mice that received CpG-ODNs demonstrated enhanced levels of OVA-specific IgG2c. Finally, we examined whether oral administration of CpG-ODNs, alone or with OVA, could reverse established eosinophilic airway inflammation. Again, neither OVA nor CpG-ODNs alone modulated established eosinophilic airway inflammation, but a combination of the OVA and CpG-ODNs successfully desensitized the mice. This desensitization was associated with suppression of OVA-specific IgE and enhancement of OVA-specific IgG2c production. These findings provide the first indication that oral administration of CpG-ODNs is effective in preventing and reversing antigen-induced eosinophilic airway inflammation. CpG-ODNs may be useful as a component of oral immunotherapy to promote tolerance in established asthma.
NK cells, displaying early activation, cytotoxicity and adhesion molecules, are associated with mild dengue disease
Authors: Azeredo E L , De Oliveira-Pinto L M , Zagne S M , Cerqueira D I S , Nogueira R M R , Kubelka C F 
Published: December 2005

SummaryDuring the innate immune response against infections, Natural Killer (NK) cells are as important effector cells as are Cytotoxic T lymphocytes (CTL) generated after antigenic stimulation in the adaptative response. NK cells increase in numbers, after viral infection or vaccination. We investigated the NK cell and CD8 T lymphocyte status in 55 dengue infected patients. The NK (CD56+CD3-) and CD56+ T cell (CD56+CD3+) rates rise during the acute phase of disease. The majority of NK cells from dengue patients display early markers for activation (CD69, HLA-DR, and CD38) and cell adhesion molecules (CD44, CD11a) during the acute phase of disease. The intracellular cytotoxic granule, TIA-1, is also up-regulated early in NK cells. Most of these markers appear also on CD8+ T lymphocytes but during the late acute phase. Circulating IL-15 is elevated in a significant number of patients during early acute infection and its values were statistically correlated with NK frequencies and cytotoxic markers on NKs. We have therefore shown that dengue virus infection is very likely stimulating a cytotoxic response that may be efficient in controlling the virus in synergism with CD8+ T lymphocytes. Interestingly, the heightened CD56+CD3-, CD56+CD3+, CD56+TIA-1+ and CD56+CD11a+ cell rates are associated with mild dengue clinical manifestations and might indicate a good prognosis of the disease.
Age dependency and mutual relations in T and B lymphocyte abnormalities in common variable immunodeficiency patients
Authors: Vlková M , Thon V , Šárfyová M , Bláha L , Svobodník A , Lokaj J , Litzman J 
Published: December 2005

SummaryCommon variable immunodeficiency (CVID) is primary hypogammaglobulinaemia with an unknown aetiopathogenesis. Although various abnormalities of T and B cells have been described, their pathogenetic roles are unclear. We determined T and B lymphocyte subsets known to be abnormal in CVID in order to disclose possible relations between numerical abnormalities in those cells. Markers associated with B cell development (CD21, CD27, IgM, IgD) were determined on B lymphocytes (CD19+); T lymphocyte development (CD45RA, CD45RO, CD62L) and activation markers (CD25, CD27, CD28, CD29, CD38, CD57, HLA-DR) were determined on CD4+ and CD8+ T lymphocytes in 42 CVID patients and in 33 healthy controls. Abnormalities in CD4+ T lymphocyte activation markers (increase in CD29, HLA-DR, CD45RO, decrease in CD27, CD62L, CD45RA) were observed particularly in patients with a decreased number of memory (CD27+) and mature (CD21+) B cells (group Ia according to the Freiburg group’s classification), while abnormalities observed in CD8+ cells (increase in CD27 and CD28 and decrease in HLA-DR, CD57 and CD38) did not depend upon grouping patients together according to B lymphocyte developmental subpopulations. We observed correlations between immature B cells (IgM+ CD21–) and expression of CD27, CD62L, CD45RA, CD45RO and HLA-DR on CD4+ T cells in CVID patients but not in the control group. The expression of CD27 and CD45RA on CD4+ T lymphocytes, such as the percentage of IgD+ CD27– and IgD+ CD27+ cells in B lymphocytes, showed age dependency to be more significant than in the control group. Our study demonstrates that T and B lymphocyte abnormalities in CVID are partially related to each other. Some of those abnormalities are not definite, but may evolve with age of the patient.
Assessing the benefits of frugivory for seed germination: the importance of the deinhibition effect
Authors: ROBERTSON A. W. , TRASS A. , LADLEY J. J. , KELLY D. 
Published: December 2005

SummaryMany studies have examined the effects of frugivores on the germination of seeds of fleshy fruited plants. However, three key issues are rarely addressed: the need to measure germination of seeds in intact fruits; the effect of germination conditions on results; and the distinction between deadvsdormant seeds.A literature review including 51 plant species from 28 families found that the often‐measured scarification effect (germination of bird‐defecatedvshand‐cleaned seeds) is significantly smaller than the rarely‐measured deinhibition effect (germination of hand‐cleaned seedsvsthose in intact fruits).Both the literature review and new experimental data show that germination conditions affect germination. In particular, seeds in intact fruits have much lower germination percentages in Petri dishes than in the field. Poor germination from intact fruits in Petri dishes may be an artefact.A field experiment with three New Zealand species showed variable effects of non‐removal of the fruit pericarp. The retention of the pericarp had no effect on germination inNestegis cunninghamii; increased the proportion of seeds entering dormancy inMelicytus lanceolatus; and greatly increased seed mortality inPennantia corymbosa.Germination experiments must be designed carefully to evaluate accurately the risks for plants of frugivory mutualism failures.
A clinicopathological study of nodal marginal zone B‐cell lymphoma. A report on 21 cases
Authors: Traverse‐Glehen A , Felman P , Callet‐Bauchu E , Gazzo S , Baseggio L , Bryon P A , Thieblemont C , Coiffier B , Salles G , Berger F 
Published: December 2005

Aims : To report the clinicopathological findings of 21 cases of primary nodal marginal zone B‐cell lymphoma (NMZL). NMZL is a recently characterized lymphoma and few series have been published.Methods and results : The clinical data were characteristic of a disseminated disease at presentation: presence of peripheral and abdominal lymph nodes, bone marrow involvement (62%), disease stage III and IV (76%), elevated lactate dehydrogenase (LDH) (48%). Other features included peripheral blood involvement (23%), anaemia (24%), thrombocytopenia (10%) and presence of serum M component (33%), while the previously reported association with hepatitis C virus and cryoglobulinaemia was not found. Relapses were frequent but the majority of patients receiving chemotherapy had a good initial response. Morphological features were heterogeneous and there were some differences compared with other marginal zone B‐cell lymphomas (MZL). Pure monocytoid B‐cell lymphomas were rare (10%) but a minor component of monocytoid B cell was observed more frequently (23%). Plasmacytoid or plasmacytic differentiation was a very common feature (61%). Large cells and a high mitotic count were also frequent (57%).Conclusion : NMZL can be distinguished from splenic MZL and extranodal MZL by its aggressive morphology and disseminated disease at presentation.
Prevalence of hepatitis C virus infection in cases of B‐cell lymphoma in Japan
Authors: Takeshita M , Sakai H , Okamura S , Higaki K , Oshiro Y , Uike N , Yamamoto I , Shimamatsu K , Muranaka T 
Published: December 2005

Aims : To determine the prevalence of hepatitis C virus (HCV) infection in B‐cell lymphoma in Japan. HCV infection and type II (monoclonal IgM) cryoglobulinaemia (CG) may be involved in the pathogenesis of low‐grade B‐cell lymphoma (ML) in southern Europe.Methods and results : Forty‐five (11.3%) of 400 B‐cell ML cases were HCV antibody (Ab) positive, which was significantly (P < 0.01) higher than the blood donors (2.5%). Among them, 28 diffuse large B‐cell lymphoma (DLBCL) cases were included. In the primary sites, 10 (47.6%) of 21 splenic DLBCL and seven (23.3%) of 30 gastric DLBCL were HCV Ab positive, which were significantly (P < 0.05) higher than the myeloma cases (4.9%). HCV infection was rarely (4.2%) detected in 24 lymphoplasmacytic and salivary gland low‐grade B‐cell ML cases. Type II CG was detected in one myeloma case (3.5%) of 29 HCV+ B‐cell ML. By real‐time polymerase chain reaction, HCV RNA was detected in fresh tumour tissues of all 11 B‐cell ML cases examined. Lymphoma cells were positive for the envelope HCV non‐structural (NS)3 and envelope (E2) proteins in six of eight examined B‐cell ML cases.Conclusions : The rare incidence of type II CG is characteristic of Japanese HCV+ ML patients and may influence the low incidence of low‐grade B‐cell ML. HCV infection may play a role in lymphomagenesis of splenic and gastric DLBCL.
Persistent nodules at injection sites (aluminium granuloma)—clinicopathological study of 14 cases with a diverse range of histological reaction patterns
Authors: Chong H , Brady K , Metze D , Calonje E 
Published: December 2005

Aims : To assess and document the spectrum of histological appearances of persistent swellings which occur at injection sites following vaccination or allergen desensitization.Methods and results : Fourteen cases were studied. Four overlapping histological reaction patterns were evident. Ten cases showed at least focal fibrosis, fat necrosis and a mixed inflammatory cell infiltrate mainly in the subcutis, giving rise to the features of a non‐specific septal and lobular panniculitis. The appearance of three cases, in addition to the non‐specific panniculitis pattern, also included prominent lymphoid follicles with germinal centres and a prominent perifollicular infiltrate resembling a lymphoma (pseudolymphoma pattern). A single case mimicked lupus profundus, with a perivascular and periadnexal infiltrate in the dermis and hyaline fat necrosis. Three cases showed a predominantly palisaded histiocytic infiltrate surrounding eosinophilic necrobiosis, in a pattern closely resembling deep granuloma annulare or rheumatoid nodule. The remaining case partly showed this appearance, but in combination with panniculitis, thus demonstrating an overlap of patterns. A common feature in all 14 cases was the focal presence of histiocytes with abundant violaceous granular cytoplasm. These were shown to contain aluminium on energy dispersive X‐ray microanalysis.Conclusion : Persistent swellings at injections sites show a variety of overlapping patterns, which mimic other conditions. Identification of characteristic histiocytes with violaceous granular cytoplasm is the key distinctive feature allowing the correct diagnosis to be reached.
Cytosolic overexpression of p62 sequestosome 1 in neoplastic prostate tissue
Authors: Kitamura H , Torigoe T , Asanuma H , Hisasue S‐I , Suzuki K , Tsukamoto T , Satoh M , Sato N 
Published: December 2005

Aims : To investigate the expression of p62 in various prostatic tissues, and to demonstrate different immunohistochemical patterns of p62 expression in distinct pathological entities of the prostate. The p62 sequestosome 1 (SQSTM1) gene product is a multifunctional protein with ubiquitous expression in normal adult tissue.Methods and results : Overexpression of p62 was detected in prostate cancer cell lines and tissues by reverse transcriptase‐polymerase chain reaction. Immunohistochemical staining for p62 was performed on 73 cases of paraffin‐embedded prostatic tissue. p62 was negative or weakly positive only in the nucleus (pattern N) of prostatic gland epithelium in nine normal and hyperplastic prostate specimens, whilst most cancerous tissue showed intense, uniform staining for p62 in the cytoplasm (pattern C). Of the prostate cancer specimens, 91% showed positive pattern C immunoreactivity. Of the cases with high‐grade prostatic intraepithelial neoplasia (PIN) around cancer, 77% showed pattern C. However, in specimens from the patients without prostate cancer PIN displayed pattern C in only 32% of cases. Western blot analysis showed that all cancer cell lines expressed p62 in the cytoplasm but there was little nuclear expression.Conclusion : Cytosolic overexpression of p62 is a novel immunohistochemical characteristic in prostatic adenocarcinoma and high‐grade PIN, suggesting that p62 might be a novel marker for prostatic malignancy.
Influence of obesity on timing of puberty
Authors: BIRO FRANK M. , KHOURY PHILIP , MORRISON JOHN A. 
Published: December 2005

SummaryTiming of normal pubertal maturation has received increased attention over the past several years. Age of menarche showed a dramatic decrease in the first half of the 20th century in Western nations; since 1960, the decrease in age of menarche has slowed and, in some societies, has actually increased. More recently, age of onset of pubertal maturation appears to have decreased, especially in girls. Multiple studies have demonstrated that childhood levels of obesity and ponderosity are associated with earlier menarche in girls. Earlier maturation in boys, however, is associated with lower adiposity and ponderosity. Secular changes in the United States as well as around the world have noted increases in prevalence as well as extent of overweight. Factors contributing to these changes include increases in calories and fast food consumption, decreases in physical activity, and increases in television viewing. There appear to have been selective advantages to lower metabolic rate (the ‘thrifty’ gene hypothesis), and earlier maturation. However, changes in caloric consumption, caloric density and physical activity, combined with greater lifespan, may allow expression of the adverse consequences of these adaptations, such as the metabolic syndrome or cancers.
The roe deer as a model for studying seasonal regulation of testis function
Authors: KLONISCH THOMAS , SCHÖN JENNIFER , HOMBACH‐KLONISCH SABINE , BLOTTNER STEFFEN 
Published: December 2005

SummaryIn mature male seasonal breeders, the circannual cycles of testicular growth and involution involve significant changes in structure and function of both the tubular and interstitial testicular compartment. Roe deer (Capreolus capreolus) are seasonal breeders with a short defined rutting season from mid‐July to mid‐August and represent a unique non‐rodent model for studying testicular functions during the course of a complete reproductive cycle with naturally changing photoperiod. Germ cells and Sertoli cells of the seminiferous tubules and the interstitial Leydig cells all display significant morphological and physiological alterations during the seasonal changes. In contrast to the germ cell population, Sertoli and Leydig cells persist as a numerically constant cell population in the roe deer testis. This report emphasizes the intricate relationship between seasonal cellular differentiation, intratesticular growth factor networks and their impact on the functional dynamics during the seasonal changes in roe deer testis.
Trends in testicular cancer incidence in the Nordic countries, focusing on the recent decrease in Denmark
Authors: JACOBSEN RUNE , MØLLER HENRIK , THORESEN STEINAR Ø. , PUKKALA EERO , KJÆR SUSANNE KRÜGER , JOHANSEN CHRISTOFFER 
Published: December 2005

SummaryTesticular cancer is the most frequent malignancy among young men, and there have been steady increases in its incidence in most western countries for many decades. Recently, a decrease was seen in some countries, including Denmark. Here, we report recent trends in testicular cancer incidence in the Nordic countries. We address the hypothesis that the causal factors for testicular cancer in Denmark are related to birth cohort and that non‐seminoma and seminoma tumours have a common aetiology. An overall increase in testicular cancer incidence was found in the Nordic countries, corresponding to increases with each consecutive birth cohort in each country. In Denmark, a decline in incidence was observed during the past 5 years, and men born around 1943 and around 1968 showed lower incidences than men born just before or just after these dates. These birth‐cohort effects were seen both for seminoma and non‐seminoma tumours. This descriptive study confirms the hypothesis that birth cohort has a major influence on the incidence pattern of testicular tumours and suggests that seminoma and non‐seminoma have common aetiological factors.