Interleukin-1 treatment increases neutrophils but not antioxidant enzyme activity or resistance to ischemia-reperfusion injury in rat kidneys

Hearts from rats treated with interleukin-1 (IL-1) intraperitoneally developed a rapid (6 h after IL-1), transient increase in neutrophils, tissue hydrogen peroxide (H₂O₂), and oxidized glutathione (GSSG) levels, and a subsequent (36 h after IL-1) increase in myocardial glucose-6-phosphate dehydrogenase (G6PD) activity and tolerance to ischemia-reperfusion. In the present investigation, we found that rats treated similarly with IL-1 had increased numbers of neutrophils in their kidneys, which were comparable to myocardial neutrophil increases, but did not develop increased renal tissue H₂O₂ or GSSG levels acutely (6 h after IL-1) or increased G6PD activity or resistance to ischemia-reperfusion injury later (36 h after IL-1). Our findings indicate that IL-1 treatment increased neutrophil accumulation in rat kidneys but did not increase oxidative stress, antioxidant enzyme activity, or resistance to ischemia-reperfusion injury. We conclude that organ-to-organ differences exist with respect to IL-1-induced tolerance.     

Characterization of an antigen secreted by Chlamydia-infected cell culture.

A soluble genus-specific chlamydial antigen has been isolated from the supernatants of cultures infected with Chlamydia trachomatis and from other sources. The antigen is a glycolipid that is secreted during the infective cycle. This exoglycolipid can be hydrolysed and fractionated into polysaccharide and lipid components. Both fractions retain antigenic activity. An immunodominant antigenic determinant of the lipid component contains fatty acids of C17 and C18:1. The polysaccharide immunodominant epitope gives rise to gulose when derivatives are formed. The secretion of the antigen into the media supernatant, the presence of gulose and the observed molecular weight are consistent with properties of alginate secreted by Gram-negative bacteria. Chemical analyses and SDS-PAGE indicate that the exoglycolipid is markedly different from LPS.     

Mitochondrial antigens as targets of cellular and humoral auto-immunity in primary biliary cirrhosis

Several factors point toward an auto-immune pathogenesis for primary biliary cirrhosis (PBC), mostly based on the presence of serum auto-antibodies to mitochondrial antigens (AMAs) and autoreactive T cells (both helper and cytotoxic). Interestingly, epitopes recognized by AMA and T-cell clones are located within overlapping areas of the antigens. Moreover, a role for an imbalance in cytokine pattern and for natural-killer lymphocytes has also been proposed. Despite several experimental reports, no clear evidence is available regarding the interaction of these factors leading to bile duct destruction. This article reviews the current reports regarding the auto-immune reaction against mitochondrial auto-antigens in PBC.     

Analysis of quantal content and quantal conductance in two populations of neurons in the avian ciliary ganglion

The avian ciliary ganglion contains two populations of parasympathetic cells, termed the ciliary and choroid neurons. We have estimated the quantal contents of nicotinic excitatory postsynaptic potentials in both populations of neurons by several methods. The singly innervated ciliary neurons have quantal contents of 15–30. In contrast, the multiply innervated choroid cells have quantal contents of 4–7. Quantal conductance was also determined, using a parallel conductance model which takes into account the capacitance of the cell membrane. This analysis indicates that in both populations of neurons one quantum activates approximately 100 postsynaptic receptors.

It is concluded that in autonomie ganglia singly innervated cells demonstrate a larger quantal content, consistent with a higher safety factor for neurotransmission, while quantal content in multiply innervated cells is generally much lower, allowing for considerable summation of presynaptic inputs. Further, in autonomic neurons many fewer postsynaptic receptors are activated by a single quantum than is the case at the neuromuscular junction.     

Sodium and calcium currents shape action potentials in immature mouse inner hair cells

Before the onset of hearing at postnatal day 12, mouse inner hair cells (IHCs) produce spontaneous and evoked action potentials. These spikes are likely to induce neurotransmitter release onto auditory nerve fibres. Since immature IHCs express both α1D (Ca_v1.3) Ca²⁺ and Na⁺ currents that activate near the resting potential, we examined whether these two conductances are involved in shaping the action potentials. Both had extremely rapid activation kinetics, followed by fast and complete voltage-dependent inactivation for the Na⁺ current, and slower, partially Ca²⁺-dependent inactivation for the Ca²⁺ current. Only the Ca²⁺ current is necessary for spontaneous and induced action potentials, and 29 % of cells lacked a Na⁺ current. The Na⁺ current does, however, shorten the time to reach the action-potential threshold, whereas the Ca²⁺ current is mainly involved, together with the K⁺ currents, in determining the speed and size of the spikes. Both currents increased in size up to the end of the first postnatal week. After this, the Ca²⁺ current reduced to about 30 % of its maximum size and persisted in mature IHCs. The Na⁺ current was downregulated around the onset of hearing, when the spiking is also known to disappear. Although the Na⁺ current was observed as early as embryonic day 16.5, its role in action-potential generation was only evident from just after birth, when the resting membrane potential became sufficiently negative to remove a sizeable fraction of the inactivation (half inactivation was at −71 mV). The size of both currents was positively correlated with the developmental change in action-potential frequency.     

Resistance exercise training and the orthostatic response

Resistance exercise has been suggested to increase blood volume, increase the sensitivity of the carotid baroreceptor cardiac reflex response (BARO), and decrease leg compliance, all factors that are expected to improve orthostatic tolerance. To further test these hypotheses, cardiovascular responses to standing and to pre-syncopal limited lower body negative pressure (LBNP) were measured in two groups of sedentary men before and after a 12-week period of either exercise (n = 10) or no exercise (control, n = 9). Resistance exercise training consisted of nine isotonic exercises, four sets of each, 3 days per week, stressing all major muscle groups. After exercise training, leg muscle volumes increased (P?P = 0.00) by 2.0 (0.5)?kg, leg compliance and BARO were not significantly altered, and the maximal LBNP tolerated without pre-syncope was not significantly different. Supine resting heart rate was reduced (P = 0.03) without attenuating the heart rate or blood pressure responses during the stand test or LBNP. Also, blood volume (¹²⁵I and ⁵¹Cr) and red cell mass were increased (P?相似文献   

Genotype-phenotype relationship in human ATP6i-dependent autosomal recessive osteopetrosis

Autosomal-recessive osteopetrosis is a severe genetic disease caused by osteoclast failure. Approximately 50% of the patients harbor mutations of the ATP6i gene, encoding for the osteoclast-specific a3 subunit of V-ATPase. We found inactivating ATP6i mutations in four patients, and three of these were novel. Patients shared macrocephaly, growth retardation and optic nerve alteration, osteosclerotic and endobone patterns, and high alkaline phosphatase and parathyroid hormone levels. Bone biopsies revealed primary spongiosa lined with active osteoblasts and high numbers of tartrate-resistant acid phosphatase (TRAP)-positive, a3 subunit-negative, morphologically unremarkable osteoclasts, some of which located in shallow Howship lacunae. Scarce hematopoietic cells and abundant fibrous tissue containing TRAP-positive putative osteoclast precursors were noted. In vitro osteoclasts were a3-negative, morphologically normal, with prominent clear zones and actin rings, and TRAP activity more elevated than in control patients. Podosomes, alphaVbeta3 receptor, c-Src, and PYK2 were unremarkable. Consistent with the finding in the bone biopsies, these cells excavated pits faintly stained with toluidine blue, indicating inefficient bone resorption. Bone marrow transplantation was successful in all patients, and posttransplant osteoclasts showed rescue of a3 subunit immunoreactivity.     

Helicobacter pylori does not require Lewis X or Lewis Y expression to colonize C3H/HeJ mice

Helicobacter pylori strains frequently express Lewis X (Le(x)) and/or Le(y) on their cell surfaces as constituents of the O antigens of their lipopolysaccharide molecules. To assess the effect of Le(x) and Le(y) expression on the ability of H. pylori to colonize the mouse stomach and to adhere to epithelial cells, isogenic mutants were created in which fucT1 alone or fucT1 and fucT2, which encode the fucosyl transferases necessary for Le(x) and Le(y) expression, were deleted. C3H/HeJ mice were experimentally challenged with either wild-type 26695 H. pylori or its isogenic mutants. All strains, whether passaged in the laboratory or recovered after mouse passage, colonized the mice well and without consistent differences. During colonization by the mutants, there was no reversion to wild type. Similarly, adherence to AGS and KatoIII cells was unaffected by the mutations. Together, these findings indicate that Le expression is not necessary for mouse gastric colonization or for H. pylori adherence to epithelial cells.