Proliferating cell nuclear antigen (PCNA) expression in Hodgkin's disease.

Previous studies of the proliferating cell fraction in Hodgkin's disease (HD) have been directed towards the classical Hodgkin and Reed-Sternberg cells (HRS) to the exclusion of the background population and have not included cases of nodular lymphocyte predominant Hodgkin's disease (NLPHD). Using an antibody to proliferating cell nuclear antigen (PCNA), we have determined the growth fraction of HRS cells and L&H cells in paraffin sections of 15 cases of classical HD [12 nodular sclerosis (NS), 3 mixed cellularity (MC)] and eight cases of NLPHD. By double staining with anti-PCNA and antibodies to B cells (CD20) and T cells (CD45RO), we also determined the growth fraction and immunophenotype of the background population in each case. In classical HD, 50.4 per cent of HRS cells were PCNA-positive and judged to be proliferating, which is comparable to previous studies, while in NLPHD 76.9 per cent of L&H cells were PCNA-positive. In both classical HD and NLPHD, the majority of PCNA-positive cells in the background were T cells, which showed a growth fraction of 57.8 and 68.5 per cent, respectively; in comparison, only 4 per cent of B cells were PCNA-positive in each type of HD. L&H cells are widely accepted to be B cells and there is growing evidence that HRS cells are also B cell-derived. Our results underline a relationship between classical HD and NLPHD and suggest that the characteristic histological features of both diseases may be caused by the production and release of cytokines from altered B cells.     

Familiäre Karzinome der Schilddrüse

Approximately 5% of differentiated thyroid carcinomas with follicular cell differentiation, papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) and 25–30% of medullary thyroid carcinoma (MTC) are hereditary. They occur either as part of a defined syndrome or are confined to the thyroid gland. Compared to their sporadic non-hereditary counterparts hereditary thyroid carcinomas generally develop earlier and regularly show multifocal tumour growth. With the exception of familial MTC, which is preceded by neoplastic C cell hyperplasia, no precursor lesions of hereditary thyroid carcinoma are known. In strong correlation with the localisation of the germline mutation of the RET protooncogene, familial MTC shows a distinct clinical course which allows precise clinical decision-making for prophylactic thyroidectomy to prevent invasive MTC. According to current knowledge prophylactic thyroidectomy of all other types of hereditary thyroid carcinoma is not justified.     

Setting out the frame conditions for feasible use of FFPE derived RNA

Introduction

The usage of formalin-fixed paraffin embedded (FFPE) tissue is characterized by its long shelf-life and simple handling. Therefore it is the most commonly available tissue specimen in routine diagnostics and histological studies. Formaldehyde fixation may result in RNA degradation and cross linking with proteins, while storage conditions also affect RNA integrity. The present study was designed to investigate the influence of these factors on RNA analysis.

Biology-Driven Approaches to Prevent and Treat Relapse of Myeloid Neoplasia after Allogeneic Hematopoietic Stem Cell Transplantation

The curative potential of allogeneic hematopoietic cell transplantation (allo-HCT) in the treatment of acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) relies mainly on the graft-versus-leukemia effect. Relapse after allo-HCT occurs in a considerable proportion of patients and has a dismal prognosis, with still very limited curative potential. This review provides an overview of the established and evolving approaches to preventing or treating relapse of AML and MDS after allo-HCT, in the context of novel insight into the biology of relapse. Established prophylactic measures to prevent relapse include optimized conditioning and graft-versus-host disease (GVHD) prophylaxis, as well as donor lymphocyte infusion (DLI) for high-risk patients; novel immunomodulatory interventions and maintenance approaches are still experimental. Improved diagnostics can detect persistent or recurring disease at a molecular level, enabling early preemptive interventions. Established options include hypomethylating agents and DLI. Standard treatments for hematologic relapse include chemotherapy, cessation of immunosuppressive treatment, and DLI. Experimental approaches include molecular targeted therapies, novel immunomodulatory treatments, and second allo-HCT. For all interventions, the potential risks, including occurrence of GVHD, must be weighed against the benefits individually in each patient. Concurrently, prevention and treatment of relapse after allo-HCT remain challenging and unmet medical needs.     

Evidence for a respiration-modulated cholinergic action on the activity of medullary respiration-related neurons in the rabbit

Effects of the iontophoretically administered cholinergic agonists acetylcholine, bethanechol and DMPP on the activity of medullary respiration-related neurons were examined in urethane-anaesthetized rabbits. Inhibitory effects prevailed over excitatory effects. Analysis of cholinergic effects by cycle-triggered averaging revealed three major types of neuronal responses: (i) constant alterations of spike-density throughout the whole period of activity ("constant effects"), (ii) effects increasing during the progression of the burst of discharge or effects restricted to a particular fraction of the burst ("phasic effects") and (iii) effects which were characterized by an excitation during one respiratory phase and an inhibition during the other phase ("bi-phasic effects"). The latter type of effects was observed in phase-spanning respiration-related neurons. Phasic effects were mainly observed in inspiration-related neurons which were predominantly inhibited by stimulation of muscarinic receptors. Inspiratory R beta-neurons in no case were phasically affected by cholinergic agents. The mean muscarinic inhibition of inspiration-related neurons increased with the progression of inspiration. The mean nicotinic inhibition of expiration-related neurons decreased with the progression of expiration. Results suggest that the efficacy of (i) a central inspiration terminating mechanism and (ii) the onset of discharge of expiratory neurons is modulated by acetylcholine.     

Bone marrow examination in patients with AIDS and AIDS-related complex (ARC). Morphologic and in situ hybridization studies

Bone marrow examinations were performed on 20 patients with acquired immune deficiency syndrome (AIDS) and 39 with AIDS-related complex (ARC). Fever of unknown origin and thrombocytopenia were common in ARC, but anemia and leukopenia were most frequent in AIDS. Changes in stromal cells and perivascular cuffing of plasma cells were found significantly more often in patients with AIDS than in those with ARC. Malignancies were common in both groups. Human immunodeficiency virus (HIV) nucleic acids were detected with the use of a 3H-labeled cDNA probe with an in situ hybridization method in 11 bone marrow samples (three ARC and eight AIDS). Most commonly positive cells were mononucleated, resembling lymphocytes and histiocytes. Endothelial cells, interdigitating reticulum cells, nucleated red blood cells, and immature myeloid cells also had positive results in some instances. The number of HIV-positive cells was not related to the size of the bone biopsies or the clinical diagnoses. The authors postulate that changes in the peripheral blood and bone marrow of these patients may be related to latent persistent infection with HIV.     

Na,K-ATPase expression in the mouse cochlea is not dependent on the mineralocorticoid receptor

This study was performed in order to test the hypothesis that the mineralocorticoid hormone stimulates the expression of Na,K-ATPase in the cochlea of the mouse. Immunohistochemistry was used to investigate the distribution of the mineralocorticoid receptor (MR) in the cochlea of the C57Bl/J6 mouse at different ages between gestational day 19 and postnatal day 30, and the occurrence and distribution of Na,K-ATPase in the inner ear of a mouse with a null mutation of the MR. Adult patterns of staining for MR were found as early as on gestational day 19 in the cochlea, with small changes thereafter. MR was detected in the same structures in the cochlea as Na,K-ATPase in earlier studies, where the amount of Na,K-ATPase increased after postnatal day 4. Thus there is latency between the increase of MR and the increase of Na,K-ATPase. In the cochlea of the MR deficient mouse, antibody labelling of Na,K-ATPase showed no significant difference as compared to the control wild type mouse. The hypothesis that mineralocorticoid hormone alone via MR stimulates the formation of Na,K-ATPase in the inner ear could not be confirmed by this study, and other regulating mechanisms must be considered.     

Oxytocin and its receptor in the process of parturition

OBJECTIVE: To review the potential roles of oxytocin (OT) and its receptor (OTR) in the regulation of parturition. METHODS: We reviewed the literature to describe the molecular aspects of the mechanisms of action and the regulation of OT and its receptor, particularly in relation to changes that occur at parturition. RESULTS: The literature provides strong support for a role for the OT/OTR system in the regulation of human parturition. Paracrine rather than endocrine mechanisms might be more important, and the regulation of the receptor might be more important than the ligand. The system is regulated by a wide variety of chemical and physical factors, including sex steroids, orphan receptors, uterine stretch, and many others. There also might be important interactions with the immune system. CONCLUSION: The OT/OTR system provides a potentially important therapeutic target for regulating the timing of human birth.