The effect of immunization route on rat serum and tear antibody responses to Chlamydia trachomatis

Using reliable displacement radiobinding assay (RBA) and ELISA, the existence of anti-human growth hormone autoantibodies (hGHAA) was confirmed in idiopathic hypopituitary patients with growth impairment. Six of 35 hypopituitary patients (17.1%) and 1/85 (1.2%) control children proved positive for hGHAA by RBA (>control mean + 3 SD). IgG isotype-hGHAA by ELISAIgG (> control mean + 3 SD) were positive for 6/34 (17.7%) and 3/85 (3.5% hypopituitary and control children, respectively. Due to an asymmetry to the right of the ELISAIgG distribution, an alternative cutoff based on a nonparametric method was obtained, and positive results for hypopituitary children increased to 10/34 (29.4%). Three of 34 hypopituitary patients but no control children were positive for hGHAA of IgM isotype. The hGHAA were detected in children with or without perinatal problems. These autoantibodies may represent markers of a major autoimmune process involving a portion of the anterior pituitary and may contribute to the development of hypopituitarism in over 15% of hypopituitary children.     

Brain-derived neurotrophic factor rapidly enhances phosphorylation of the postsynaptic N-methyl-D-aspartate receptor subunit 1

Although neurotrophins have traditionally been regarded as neuronal survival factors, recent work has suggested a role for these factors in synaptic plasticity. In particular, brain-derived neurotrophic factor (BDNF) rapidly enhances synaptic transmission in hippocampal neurons through trkB receptor stimulation and postsynaptic phosphorylation mechanisms. Activation of trkB also modulates hippocampal long-term potentiation, in which postsynaptic N-methyl-D-aspartate glutamate receptors play a key role. However, the final common pathway through which BDNF increases postsynaptic responsiveness is unknown. We now report that BDNF, within 5 min of exposure, elicits a dose-dependent increase in phosphorylation of the N-methyl-D-aspartate receptor subunit 1. This acute effect occurred in hippocampal synaptoneurosomes, which contain pre- and postsynaptic elements, and in isolated hippocampal postsynaptic densities. Nerve growth factor, in contrast, caused no enhancement of phosphorylation. These results suggest a potential mechanism for trophin-induced potentiation of synaptic transmission.     

Protective effect of calcitonin gene-related peptide against caerulein-induced pancreatitis in rats

The stimulation of sensory nerves by capsaicin exhibits the protective effect against caerulein-induced pancreatitis whereas deactivation of these nerves aggravates pancreatic damage evoked by overdose of caerulein. Calcitonin-gene related peptide (CGRP) has been identified as the prominent mediator of sensory nerves. The aim of the present study was to examine the influence of CGRP on the course of caerulein-induced pancreatitis (CIP). CIP led to a significant decrease in DNA synthesis and pancreatic blood flow (PBF) by 48% and 50% respectively, as well as a significant increase of pancreatic weight, plasma amylase concentration and development of the histological signs of pancreatic damage expressed as edema, leukocyte infiltration and vacuolization. Treatment with CGRP (2 x 10 micrograms/kg s.c.) attenuated the pancreatic tissue damage in caerulein-induced pancreatitis and completely reversed the deleterious effect of the ablation of sensory nerves on caerulein-induced pancreatitis. We conclude that CGRP exerts protective effect against caerulein-induced pancreatitis and is able to reverse the damage caused by deactivation of sensory nerves. Vasodilatation and preservation of pancreatic blood flow are involved in this effect.     

Robust, but transient expression of adeno-associated virus-transduced genes during human T lymphopoiesis

Recombinant adeno-associated viruses (rAAV) have been proposed to be gene transfer vehicles for hematopoietic stem cells with advantages over other virus-based systems due to their high titers and relative lack of dependence on cell cycle for target cell integration. We evaluated rAAV vector containing a LacZ reporter gene under the control of a cytomegalovirus (CMV) promoter in the context of primary human CD34+CD2- progenitor cells induced to undergo T-cell differentiation using an in vitro T-lymphopoiesis system. Target cells from either adult bone marrow or umbilical cord blood were efficiently transduced, and 71% to 79% CD2+ cells expressed a LacZ marker gene mRNA and produced LacZ-encoded protein after exposure to rAAV-CMV-LacZ. The impact of transgene expression on the differentiation of T cells was assessed by sequential quantitation of immunophenotypic subsets of virus-exposed cells and no alteration was noted compared with control. The durability of transgene expression was assessed and found to decay by day 35 with kinetics dependent on the multiplicity of infection. In addition, vector DNA was absent from CD4 or CD8 subselected CD3+ cells by DNA-polymerase chain reaction. These data suggest that rAAV vectors may result in robust transgene expression in primitive cells undergoing T-cell lineage commitment without toxicity or alteration in the pattern of T-cell differentiation. However, expression is transient and integration of the transgene unlikely. Recombinant AAV vectors are potentially valuable gene transfer tools for the genetic manipulation of events during T-cell ontogony but their potential in gene therapy strategies for diseases such as acquired immunodeficiency syndrome is limited.     

Fos protein expression in the circadian clock is not associated with phase shifts induced by a nonphotic stimulus, triazolam

A mutant human lysozyme, designated as C77A-a, in which glutathione is bound to Cys95, has been shown to mimic an intermediate in the formation of a disulfide bond during folding of human (h)-lysozyme. Protein disulfide isomerase (PDI), which is believed to catalyze disulfide bond formation and associated protein folding in the endoplasmic reticulum, attacked the glutathionylated h-lysozyme C77A-a to dissociate the glutathione molecule. Structural analyses showed that the protein is folded and that the structure around the disulfide bond, buried in a hydrophobic core, between the protein and the bound glutathione is fairly rigid. Thioredoxin, which has higher reducing activity of protein disulfides than PDI, catalyzed the reduction with lower efficiency. These results strongly suggest that PDI can catalyze the disulfide formation in intermediates with compact structure like the native states in the later step of in vivo protein folding.     

Embryonic origin of preimplantation factor (PIF): biological activity and partial characterization

Preimplantation factor (PIF) is detected in the serum of women shortly after fertilization; its origin, however, has not been established. In this study, the embryonal origin of PIF was investigated and partial characterization of the factor was carried out. Culture media from viable human 2-8-cell stage embryos and mouse 2-cell-blastocyst stage embryos were analysed using the lymphocyte/platelet binding assay (LPBA). The assay was performed by combining culture media with donor O+ type blood-derived lymphocytes/platelets, complement and an antibody against CD2. Increased autorosette formation between lymphocytes and platelets (> 9%) was an indication for the presence of PIF. In addition, the effect of platelet-activating factor (PAF) and chaperonin 10 on PIF activity was determined. Partial purification of PIF was carried out using gel filtration and reverse-phase high purification liquid chromatography (HPLC), followed by mass spectrometry. Culture media of single human viable fertilized oocytes were negative for PIF; however, the 10-fold concentrated medium was positive for PIF. In medium in which five or more mouse embryos were cultured, PIF activity was observed starting at the morula stage and was higher by the blastocyst stage. Addition of PAF or chaperonin 10 to the PIF assay did not elicit a specific effect on PIF activity. Chromatographic data suggest that PIF activity is due to low molecular weight proteins. PIF appears to be a low molecular weight protein which is derived from viable preimplantation embryos. It is different from PAF or chaperonin 10. Its final characterization will be valuable for better understanding of maternal recognition of pregnancy and implantation.     

Adenocarcinoma of the esophagus and gastroesophageal junction

The experimental work discussed here supports the hypothesis that in the pathogenesis of MG the initial and essential steps take place within the thymus. Most if not all thymuses of MG patients contain B cells capable of producing AChR specific autoantibody along with appropriate stroma elements. Hyperplastic thymuses characteristically contain germinal centers with cellular complexes of AChR-producing MC and surrounding interdigitating dendritic cells. In thymomas, the source of the myasthenogenic autoantigen is less obvious. There are data suggesting that thymoma epithelium expresses a protein sharing certain peptide epitopes with the AChR alpha chain, although there is no further molecular similarity. A unique type of 'molecular self-mimicry' cold be involved in the initiation of thymoma-associated MG.     

Myopathy associated with human immunodeficiency virus infection: report of a case

This paper explores nursing's current fascination with defining and exploring the term 'caring'. Fear of caring is proposed as the reason for this fascination. Factors at the root of this fear are identified and an expanded definition of caring (one which arises from the dispelling of such fear) is proposed. This expanded definition is given a new label--loving. For, as this author contends, has not loving always been at the heart of nursing?