Activation of neurons projecting to the paraventricular hypothalamic nucleus by intravenous lipopolysaccharide

The central nervous system interacts with the immune system to coordinate several components of the acute phase response, although the specific neuroanatomical pathways that mediate these responses are still uncharacterized. However, neurons in both the autonomic and endocrine components of the paraventricular hypothalamic nucleus (PVH) are characteristically activated in different models of immune stimulation. In the current study, we have used intravenous administration of lipopolysaccharide (LPS; 5 or 125 micrograms/kg) to induce the acute phase response. We subsequently coupled immunohistochemistry for Fos (as a marker of neuronal activation) with retrograde transport of the neuroanatomical tracer cholera toxin-b from the PVH. Several of the activated cell groups directly projected to the paraventricular nucleus, including the visceromotor (infralimbic) cortex, median preoptic nucleus, ventromedial preoptic area, bed nucleus of the stria terminalis, parabrachial nucleus, ventrolateral medulla, and nucleus of the solitary tract. These findings indicate that immune system stimulation activates cell groups from multiple nervous system levels that project to the paraventricular nucleus. We hypothesize that the activation of specific autonomic and endocrine elements of the PVH may be due to the activity of distinct afferents that converge on the PVH from multiple components of the central autonomic control system. Our results are consistent with the hypothesis that the PVH plays a key role in integrating diverse physiological cues into the varied manifestations that constitute the cerebral component of the acute phase response.     

The avian chB6 (Bu-1) alloantigen can mediate rapid cell death

The control of cell death is critical in the immune system. T and B lymphocytes must be censored during their development to remove nonfunctional or self-reactive lymphocytes. However, the molecules controlling cell deletion during lymphopoiesis have not been defined. B cells removed from the avian bursa of Fabricius rapidly undergo cell death in culture. We screened bursal B cells with a panel of Abs and lectins to identify molecules affecting their viability. Abs to the chB6 alloantigen caused a rapid loss of cell viability as measured by staining with propidium iodide. ChB6 Abs also cause adhesion between B cells. Transfection of cDNA encoding chB6 reconstituted the allele-specific cell death and adhesion effects in avian cell lines. These effects can be separated by binding cells onto Ab-coated plastic dishes. In these experiments, cells were killed in the absence of cell:cell contact. The ability of chB6 cross-linking to evoke cell aggregation and cell death is also observed when chB6 is expressed in growth factor-dependent mammalian cells. In these cells growth factor can almost completely prevent cell death but not cell aggregation. This suggests that known cell survival stimuli can suppress the cell death brought about by chB6 cross-linking. These results show that chB6 may have an important role in controlling cell survival and/or adhesion during avian B cell development.     

Biologic implications of genetic changes in head and neck squamous cell carcinogenesis

Cytogenetic techniques for the analysis of genetic changes common in head and neck squamous cell carcinogenesis show complex patterns of chromosomal deletions, translocations, and amplifications. Powerful molecular biologic techniques have recently made possible the investigation of these abnormalities at the DNA level. Tumour suppressor gene loss and oncogene activation can now be recognized in tumours. Multiple genetic loci are implicated in the carcinogenesis process, while much evidence points to the existence of yet to be recognized tumour suppressor genes. An overview of the genetic changes commonly seen in head and neck squamous cell carcinogenesis and the possible implications of these are presented.     

Identification of the peptides that stimulate the phosphoinositide hydrolysis in lymphocyte cell lines from peptide libraries

Peptides which stimulate the formation of inositol phosphates (InoPs) in lymphocyte cell lines were identified by screening synthetic peptide libraries composed of random sequences of hexapeptides. The peptides containing the consensus sequence XKYX(P/V)M were found to be most active in the phospholipase C (PLC)-mediated formation of InoPs in a human B myeloma cell line, U266. The peptides also stimulated the phosphoinositide hydrolysis and the release of [Ca2+]i in HL60 and U937 cell lines. On the other hand, these peptides showed no effect in the following cell lines: NIH3T3, PC12, Daudi, Sp2, Jurkat, H9, Molt-4, SupT-1, K562, and RBL-2H3. The result suggests the possibility that the peptides may have cell type specificity. Experiments with one of the active peptides, WKYMVM-NH2 showed that its action mimics the effect of AlF4- which is a G-protein activator in the InoPs generation, and pertussis toxin partially blocked the InoPs accumulation and [Ca2+]i release induced by the peptide in the U266 cells. Binding assays with the peptide labeled with 125I showed that U266 cells have a saturable number of binding sites for the peptide. Taken together, these results suggest that the peptides could activate PLC-mediated signal transduction via a pertussis toxin-sensitive G-protein coupled receptor in certain cell types.     

Nitric oxide donors induce ripening of the human uterine cervix: a randomised controlled trial

OBJECTIVE: To determine whether nitric oxide donors can induce cervical ripening before surgical termination of pregnancy in the first trimester. DESIGN: Prospective, randomised controlled trial. SETTING: Department of Obstetrics and Gynaecology, Royal Infirmary, Glasgow. PARTICIPANTS: Forty-eight primigravid women undergoing surgical termination of pregnancy before 12 weeks of gestation. METHODS: The women were randomised to receive per vaginam before surgery either the nitric oxide donor isosorbide mononitrate, the nitric oxide donor glyceryl trinitrate, the prostaglandin analogue gemeprost, or no treatment. MAIN OUTCOME MEASURES: The cumulative force required to dilate the cervix to 8 mm was measured objectively and the cervical diameter before surgical dilatation was recorded. RESULTS: Following isosorbide mononitrate or gemeprost, a lower cumulative force was required to dilate the cervix to 8 mm and a higher cervical diameter before dilatation was recorded. Pretreatment with glyceryl trinitrate reduced the cumulative force required to dilate the cervix but had no effect on cervical diameter. CONCLUSIONS: Like the prostaglandin analogue gemeprost, the nitric oxide donors isosorbide mononitrate and glyceryl trinitrate can effect cervical ripening. Nitric oxide donors may provide an alternative to prostaglandins for cervical ripening before surgical procedures in the first trimester.