Increased thymic B cells but maintenance of thymic structure, T cell differentiation and negative selection in lymphotoxin-alpha and TNF gene-targeted mice

TNF, lymphotoxin (LT) and their receptors are expressed constitutively in the thymus. It remains unclear whether these cytokines play a role in normal thymic structure or function. We have investigated thymocyte differentiation, selection and thymic organogenesis in gene targeted mice lacking LTalpha, TNF, or both (TNF/LTalpha-/-). The thymus was normal in TNF/LTalpha-/- mice with regard to cell yields and stromal architecture. Detailed analysis of alphabeta and gammadelta T cell-lineage thymocyte subsets revealed no abnormalities, implying that neither TNF nor LT play an essential role in T cell differentiation or positive selection. The number and distribution of thymic CD11c+ dendritic cells was also normal in the absence of both TNF and LTalpha. A three-fold increase in B cell numbers was observed consistently in the TNF/LTalpha-/- thymus. This phenotype was due entirely to the LTalpha deficiency and associated with changes in the hemopoietic compartment, rather than the thymic stromal compartment of LTalpha-/- mice. Finally, specific Vbeta8+ T cell deletion within the thymus following intrathymic injection of staphylococcal enterotoxin B (SEB) was TNF/LT independent. Thus, despite the presence of these cytokines and their receptors in the normal thymus, there appears no essential role for either TNF or LT in development of organ structure or for those processes associated with T cell repertoire selection.     

Effect of sleep on the electrographic manifestations of epilepsy

Alterations in the level of arousal have profound predictable effects on the electrographic manifestations of epileptogenic abnormalities. The changes produced by sleep are dramatic in patients with generalized epilepsy as compared to patients with partial epilepsy. The epileptiform complexes associated with the generalized epilepsies show changes in spatial distribution, voltage, temporal sequencing, and waveform morphology. The changes are qualitatively similar in the different types of generalized seizure disorders but vary in the degree to which they are expressed in proportion to the "severity" of the seizure disorder. The presence of a generalized epileptogenic abnormality may result in alteration of K-complex waveform morphology. Multifocal spikes occurring in conjunction with bilateral synchronous discharges are frequently represented by a spatial field distribution consistent with a "horizontal dipole," during sleep especially in children.     

Iterative reconstruction algorithms

In this paper a survey of recent results on iterative reconstruction algorithms is given. These results, many of which have not yet appeared elsewhere, are applicable to a very general formulation of the reconstruction problem based on the series expansion approach. A set of optimization criteria and a number of iterative reconstruction algorithms are stated, together with theorems on the convergence of the algorithms to optimum images. The efficacy of the algorithms is compared to that of the convolution method. In particular, the falseness of the claim that ART and the backprojection method are the same is demonstrated.     

Histiocytic and t-cell rich b-cell lymphoma (TCRBCL) of the stomach

Although stomach is a frequent site of extranodal lymphomas, histiocyte-rich TCRBCL has not yet been described there. Even histology of repeated gastrobiopsies of this uncommon, diffuse, large B-cell lymphoma may be inconclusive and partial gastrectomy cannot be avoided. It is only immunohistology (CD20, CD43, CD68) of the paraffin blocks from the resection specimen that can lead to the final diagnosis of intermediate grade malignant lymphoma.     

In vitro antitumor activity of MIC2 protein-doxorubicin conjugates

The pseudoautosomal encoded MIC2 glycoprotein is a tumor-associated antigen of Ewing's sarcoma (ES) and closely related tumors of unknown function. To investigate the use of this protein as selective drug carrier recombinant MIC2 was coupled to doxorubicin by a two step glutaraldehyde method (molar ratio DOX/MIC2 of 32 and 16). The conjugates showed dose-dependent cytostatic activity against the ES cell line SK-ES1, the peripheral neuroectodermal line KAL and the prostate cancer cell line PC-3 concurrent with reduced toxicity against normal lymphoblasts. In comparison to free doxorubicin the MIC2-doxorubicin conjugates exhibited highest activity against the PC-3 cell line. Confocal microscopy showed intracellular accumulation of MIC2 conjugates.     

Inhibitory effect of antagonists of bombesin and growth hormone-releasing hormone on orthotopic and intraosseous growth and invasiveness of PC-3 human prostate cancer in nude mice.

PURPOSE: To determine whether antagonists of growth hormone-releasing hormone (GHRH) and bombesin/gastrin-releasing peptide (BN/GRP) can inhibit the orthotopic and metastatic growth of PC-3 human androgen-independent prostate cancers. EXPERIMENTAL DESIGN: The effects of administration of GHRH antagonist MZ-J-7-118, BN/GRP antagonist RC-3940-II, and their combination on the growth and metastatic spread of PC-3 tumors implanted orthotopically into nude mice were evaluated. The efficacy of this treatment on PC-3 tumors implanted intratibially and s.c. was also determined. RESULTS: Treatment with MZ-J-7-118, RC-3940-II, or their combination significantly inhibited the growth of PC-3 tumors implanted orthotopically, intraosseously, and s.c. The combination of the two antagonists had the greatest effect, inhibiting orthotopic tumor growth by 77%, intratibially implanted tumors by 86%, and s.c. tumors by 86%. The therapy with BN/GRP and GHRH antagonists, especially in combination, also reduced the local tumor spread and distant metastases in animals bearing orthotopic tumors. Combination therapy was likewise the most effective in reducing the incidence and severity of tibial osteolytic lesions and pathologic fractures in intraosseously implanted tumors. High-affinity binding sites for BN/GRP and GHRH were found in s.c. and orthotopic PC-3 tumor samples. MZ-J-7-118, RC-3940-II, and the combination of both compounds inhibited in vitro growth of PC-3 cells. CONCLUSIONS: Our findings show the efficacy of BN/GRP antagonists and GHRH antagonists for the treatment of advanced prostate cancer in preclinical metastatic models. As BN/GRP antagonists are already in clinical trials and GHRH antagonists are effective in androgen-independent prostate cancer models, these analogues could be considered for the management of advanced prostate carcinoma.     

Birth outcomes of patients with isolated anorectal malformations: A population‐based case‐control study

In most patients affected by isolated anorectal malformation (IARM) the etiology is largely unknown. Thus, the aim of our project was to analyze possible risk factors for IARM. In the first step, birth outcomes of cases with IARM were analyzed on the basis of maternal socio‐demographic variables, and these data are presented in this paper. Gestational age at delivery, birthweight, preterm birth, low birthweight and small for gestational age of cases with IARM were evaluated in the function of maternal age, birth/pregnancy order, marital and employment status of mothers in the population‐based large dataset of the Hungarian Case‐Control Surveillance of Congenital Abnormalities, 1980–1996. The study samples included 231 live‐born cases with IARM, 361 matched and 38 151 population controls without any defect. IARMs are more frequent in males, twins and newborn infants with low birthweight and small‐for‐gestational‐age, the latter being the consequence of intrauterine growth restriction. In addition, mothers of cases were younger but with higher birth order, and had lower socio‐economic status. These maternal variables are characteristic for the gypsy population in Hungary. The higher proportion of gypsy women among the mothers of cases with IARM was confirmed during the home visits of the study. Male sex and intrauterine growth restriction of cases, in addition to low socioeconomic status and gypsy origin of mothers may have a role in the risk of IARMs.