A possible mechanism for host-specific pathogenesis ofSalmonellaserovars

We have identified the complement receptors on human and murine macrophages involved in the recognition ofSalmonellaserovars, and investigated their relevance to the intracellular survival.S. typhiwas capable of surviving within human monocyte-derived macrophages, whereasS. typhimuriumwas not. Conversely,S. typhimurium, but notS. typhi, resisted intracellular killing by murine macrophages, demonstrating that the intracellular survival ofSalmonellaserovars is host-dependent. In the presence of serum opsonin, human monocyte-derived macrophages recognizedS. typhiandS. typhimuriumvia complement receptor type 1 (CR1) and type 3 (CR3), respectively. In contrast, murine macrophages recognizedS. typhiandS. typhimuriumvia CR3 and CR1, respectively. These findings demonstrate that the intracellular fate ofSalmonellaserovars following phagocytosis may depend on the type of complement receptors involved in their recognition, in that CR1-mediated recognition is closely correlated to subsequent intracellular survival. The Tn5 insertion mutant ofS. typhimuriumwhich lacks the ability to interact with CR1 was sensitive to intracellular killing by murine macrophagesin vitro, and was much less virulent to micein vivo, confirming the relevance of CR1-mediated bacterial recognition to the pathogenicity ofS. typhimuriumfor mice. These results suggest that selective recognition ofSalmonellaserovars through CR1 may lead to their subsequent intracellular survival, and is responsible for the host-specific pathogenesis ofSalmonellaserovars.     

Effect of hypoxia on dynamics of changes in hexokinase activity in subcellular fractions of neonatal rat tissues

Hexokinase (HK) activity in the total homogenate and cytoplasmic and mitochondrial fractions of the brain, heart, and liver of newborn rats was studied in relation to the severity of exposure to hypoxia. With a mild form of hypoxic hypoxia an increase in the activity of the mitochondrial-bound form of the enzyme was observed in the brain and liver tissue accompanied by a decrease in cytoplasmic HK activity and, in the brain, by a marked increase in the rate of glucose phosphorylation. Deep hypoxia led to a decrease in HK activity in the total homogenate and in both subcellular fractions in all tissues investigated. The results point to a disturbance of certain mechanisms in the tissues of newborn rats after exposure to a severe degree of hypoxia.Laboratory of Clinical Biochemistry, Scientific-Research Institute of Pediatrics, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR M. Ya. Studenikin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 1, pp. 21–24, January, 1977.     

Role of injury in the appearance of “activated” smooth muscle cells

In experiments on rats the ultrastructure of the muscle tissue of the inferior vena cava after disturbance of the outflow of blood, of the muscular coat of the stomach after resection of 50% of its fundus, and of the muscular coat of the cecum after constriction of its ascending portion was studied. Activation of smooth muscles was shown to reflect the phase of injury to the ultrastructure of the cells, followed by processes of intracellular regeneration. Analysis of the ratio between DNA-synthesizing and activated cells showed the local origin of the latter from differentiated myocytes.Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR. No. 4 Main Board, Ministry of Health of the USSR. Institute of Human Morphology, Academy of Medical Sciences of the USSR. Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. P. Avtsyn.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 84, No. 7, pp. 112–115, July, 1977.     

Neuropeptide Y regulates rat renal tubular Na,K-ATPase through several signalling pathways

Neuropeptide Y (NPY) has at least three receptors (Y₁, Y₂ and Y₃) through which it influences different mechanisms in many cell types. Previous data suggest that the Y₂ receptor may be divided into prejunctional and postjunctional subgroups. We have examined the intracellular signalling pathways of the postjunctional Y₂ receptor in rat renal proximal tubules. The results indicate that NPY regulates Na⁺,K⁺-ATPase through several signalling pathways: (1) In proximal tubule (PT) cells NPY increased intracellular calcium. The response was blocked by removing extracellular calcium and was also blocked by using nifedipine. This suggests that calcium was increased by influx from the extracellular space through L -type calcium channels. (2) NPY increased Na⁺,K⁺-ATPase activity in PT segments and this effect was also blocked by nifedipine. CaMKII-Ala²⁸⁶[281–302] a blocker of Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) inhibited the NPY-stimulated Na⁺,K⁺-ATPase activity. This implies that increased intracellular calcium activates CaMKII which subsequently increases Na⁺,K⁺-ATPase activity. CaMKII thus appear to act similar to what has been proposed for protein phosphatase 2B. (3) Calphostin C, an inhibitor of protein kinase C (PKC), did not inhibit NPY-stimulated Na⁺,K⁺-ATPase activity. PKC is, therefore, unlikely to be involved. (4) Y₂ receptors are negatively coupled to the cAMP pathway. NPY attenuated forskolin-stimulated cAMP production in renal tubules and exogenous cAMP counteracted the NPY-stimulated Na⁺,K⁺-ATPase activity. This illustrated the importance of NPY for the regulation of renal sodium handling. We also propose that the renal tubule cell is a good model for studying the function and mechanisms of postjunctional Y₂ receptors.     

Blood pressure analysis

SUMMARY  Arterial blood pressure is influenced by sleep-related breathing disorders. As cardiovascular consequences can be diagnosed by an accurate recording and analysis of blood pressure, new recording methodologies and an approach to analysis are presented here. Invasive continuous blood pressure recording is the common reference for all methodologies. As blood pressure varies rapidly in parallel with sleep-related breathing disorders it is indispensible to record blood pressure continuously. To introduce non-invasive methodology the Finapres system was used during sleep studies; a validation study showed severe limitations. This study was followed by the validation of an improved system called Portapres, which is portable, has two finger cuffs and a hydrostatic height compensation.
Analysis of continuous blood pressure in patients with sleep apnoea is carried out to detect mechanisms which influence the cardiovascular risk. Spectrum analysis of systolic blood pressure showed two different major oscillations present in patients with obstructive sleep apnoea. One oscillation (<0.06 Hz) occurs in parallel with each apnoeic episode and the other oscillation (0.2-0.4 Hz) occurs in parallel with the obstructive efforts during each apnoea and in parallel with respiration during periods of snoring. These two oscillations were so specific that the use of non-invasive continuous blood pressure recording allowed an estimation of the extent of underlying breathing disorders, and assessment of cardiovascular risk in a patient with obstructive apnoea in terms of hypertension and on the basis of ambulatory monitoring.     

Characterization of a whole-cell Ca2+-blockable monovalent cation current in isolated ectodermal cells of chick embryo

The presence of a Ca²⁺-blockable monovalent cation current is demonstrated in isolated ectodermal cells of the chick embryo using the whole-cell patch-clamp method. In the absence of any stimulation, the whole-cell current is time independent and rectifies outwardly at membrane potentials higher than +40 mV The outward current is neither carried by Cl^– channels nor by K⁺ channels. Application of a Ca²⁺-free solution containing 1 mmol/l ethylenediaminetetraacetic acid (EDTA) elicits a large inward current and increases the outward current. The inward current can be carried by extracellular Li⁺, Na⁺, K⁺ and Cs⁺, but notN-methyl-d-glucamine. The Ca²⁺-blockable monovalent cation channel discriminates very poorly among these cations. The estimated number of channels per cell is around 2000. Extracellular protons block the inward Na⁺ current in the absence of extracellular Ca²⁺. The apparent negative logarithm of the dissociation constant for proton (pK _H) at –100 mV is 5.8. Among 12 potential channel modulators, including verapamil and nifedipine, only quinine decreases the current. Quinine blocks this current with a dissociation constant,K _d, equal to 0.18 mmol/l, independent of the membrane potential. This study demonstrates the presence of a whole-cell Ca²⁺-blockade monovalent cation current in dissociated chick ectodermal cells with permeation properties similar to those observed at the single-channel level. Contrary to studies made of other tissues, we did not observe any blocking effect of verapamil and nifedipine on the Ca²⁺-blockable monovalent cation current.     

Another Look at the Relationship of Electrodermal Activity to Electrode Contact Area

The present study was undertaken lo reexamine the hypothesis that the relationship between skin conductance and electrode size is monotonic and linear. Skin conductance activity was recorded from 48 right-handed male subjects using 6 different sixes of electrode collars ranging in exposed surface area from .131 cm² to .786 cm². The dependent measures were skin conductance level (SCL); skin conductance response (SCR) amplitude to a series of 8 loud tones; latency, rise time, and recovery half-time of the first tone elicited response; (he largest self-generated SCR; and the number of nonspecific responses. The results indicated a significant linear relationship between contact area and SCL, stimulus and self-generated SCR amplitude, and the number of nonspecific responses. Latency was not affected by electrode size although the other time-based measures were. Differences in skin conductance activity were found among different palmar recording sites. The observed linear relationship between electrode size and electrodermal measures has implications for current models of electrodermal activity and for the comparison of results across studies in which different electrode contact areas are used.     

Possible mechanisms of the concentration-dependent action of substance P to induce histamine release from rat peritoneal mast cells and the effect of extracellular calcium on mast-cell activation

Rat peritoneal mast cells purified on a Percoll gradient were loaded with the fluorescent Ca²⁺ indicator fura-2 and were challenged with different concentrations of substance P (SP), and intracellular calcium concentrations ([Ca²⁺]_i) were measured by a spectrofluorometric assay. SP at 5 × 10⁻⁶ mol/1 and 10⁻⁵ mol/1 caused a significant histamine release with a significant increase in [Ca²⁺]_i in a dose-dependent manner. However, SP at 10⁻⁸-10⁻⁶ mol/1 did not induce either histamine release or increase in [Ca²⁺]_i. Extracellular calcium at 0.9 mM inhibited the histamine release with a significant reduction of [Ca²⁺]ⁱ compared with that of the cells in a nominally calcium-free condition. These results indicate that the action of SP on rat mast cells relies upon [Ca²⁺]_i to induce histamine release.     

Pattern electroretinogram plus visual evoked potential: A decisive test in patients suspected of malingering

Along the processing chain in the visual pathway the pattern electroretinogram (PERG) is a better indicator of the peripheral function than the visual evoked potential (VEP). Therefore the PERG and the VEP will be impaired equally by disturbances before the ganglion cell layer (e.g., blurred image or retinal disease) and differently by further centrally located diseases (e.g., tumor compression of the optic nerve). Thus in patients complaining of reduced visual acuity who show disturbed VEP but a normal PERG, malingering can be definitely ruled out. Representative combinations of PERG and VEP findings are described.     

Vagally Mediated Gut-Brain Relationships in Appetite Control-Insights from Porcine Studies

Signals arising from the upper part of the gut are essential for the regulation of food intake, particularly satiation. This information is supplied to the brain partly by vagal nervous afferents. The porcine model, because of its sizeable gyrencephalic brain, omnivorous regimen, and comparative anatomy of the proximal part of the gut to that of humans, has provided several important insights relating to the relevance of vagally mediated gut-brain relationships to the regulation of food intake. Furthermore, its large size combined with the capacity to become obese while overeating a western diet makes it a pivotal addition to existing murine models, especially for translational studies relating to obesity. How gastric, proximal intestinal, and portal information relating to meal arrival and transit are encoded by vagal afferents and their further processing by primary and secondary brain projections are reviewed. Their peripheral and central plasticities in the context of obesity are emphasized. We also present recent insights derived from chronic stimulation of the abdominal vagi with specific reference to the modulation of mesolimbic structures and their role in the restoration of insulin sensitivity in the obese miniature pig model.