Characteristics of peripheral blood lymphoid subpopulations of shigellosis patients

Chelyabinsk Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR A. D. Ado.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 113, No. 3, pp. 299–301, March, 1992.     

Endothelial Apoptosis and Chronic Transplant Vasculopathy: Recent Results, Novel Mechanisms

Chronic transplant vasculopathy (CTV) is a progressive form of vascular obliteration affecting the arteries, arterioles and capillaries of solid organ transplants. It is characterized by intimal accumulation of mononuclear cells, vascular smooth muscle cells (VSMC), myofibroblasts and connective tissue. Mounting evidence, based on animal models and human biopsy results, suggests that acute and persistent rejection triggering apoptosis of endothelial cells (EC) plays a pivotal role in CTV. The precise mechanisms that underlie the induction of fibroproliferative changes in association with endothelial apoptosis have yet to be clearly delineated. Recent observations in the field of apoptosis research provide some important mechanistic clues. First, endothelial apoptosis creates a state of hyperadhesiveness for mononuclear cells, thus facilitating sustained leukocyte infiltration. Second, phosphatidylserine-dependent engulfment of apoptotic cells by infiltrating mononuclear leukocytes promotes transforming growth factor-beta1 production. Third, apoptosis of EC triggers extracellular matrix (ECM) proteolysis thus initiating the production of fibroproliferative/fibrogenic ECM fragments. The relative importance of these mechanisms in the pathophysiology of CTV will need to be addressed in vivo. Yet, these recent developments provide a new mechanistic framework that will help better define the importance of immune-mediated EC apoptosis in the regulation of vascular repair.     

Myoelectrical activity and intraluminal flow in human sigmoid colon

Myoelectric spike bursts were recorded in the sigmoid colon by means of an intraluminal silastic tube equipped with 3 Ag–AgCl ring electrodes fixed 15 cm apart on the tube that was introduced by flexible sigmoidoscopy. In six subjects, the tube was also equipped with three catheters whose tip opened 1 cm aborad from each electrode, for pressure recordings. In six other subjects, the tube was equipped with both electrodes and a catheter opening at the tip of the probe for infusing fluids at a rate of 12 ml/min into the colonic lumen. The fluid was collected with another tube inserted in the rectum and the volume was measured at 1-min intervals. Colonic spiking activity was made of rhythmic stationary bursts (RSB) and of sporadic bursts that were either propagating (SPB) or not propagating (SNPB). All sporadic bursts were associated with intraluminal pressure waves whose amplitude was significantly higher than that associated with rhythmic bursts. In the infusion experiments, the volume of fluid collected did not change significantly whether rhythmic bursts were present or not (3.9±1.7 ml/min and 3.3±1.9 ml/min respectively) (mean±sd). However, the volume was significantly higher when sporadic nonpropagating bursts were present (9.4±4.1 ml/min), and even higher when the sporadic bursts were propagating (21.6±8.8 ml/min). These results indicate that (1) the occurrence of sporadic bursts, particularly when propagating, is associated with intraluminal pressure waves that lead to significant propulsive movements; and (2) rhythmic bursts do not seem to be involved in colonic propulsive activity.This work was supported by the grant DG282 from the Medical Research Council of Canada.     

Modulation of immune response to Lol p I by pretreatment with anti-idiotypic antibody is not restricted to the idiotypic expression.

To study the role of anti-idiotypic antibodies in the regulation of the immune response to Lol p I (the major allergenic component of rye grass pollen), we have recently generated a panel of three MoAbs directed against distinct epitopes of Lolp I and an anti-idiotypic MoAb directed against the idiotype borne by one of the anti-Lol p I MoAbs (290A-167). The effects of pretreatment with this anti-idiotypic MoAb in BALB/c mice before immunization with the antigen have been examined. The anti-idiotypic MoAb or unrelated MoAb were given weekly for 8 weeks intraperitoneally. Mice then received the antigen (2 micrograms) adsorbed with alum (2 mg) at weeks 9, 11 and 13. Serum anti-Lol p I antibodies (IgG or IgE) and specific idiotypic responses were measured. Anti-Lol p I IgG antibodies could be detected before immunization with Lol p I only in mice pretreated with anti-idiotypic MoAb. Immunization with Lol p I induced an anti-Lol p I IgG response in both groups, but this response was higher in mice that received anti-idiotypic MoAb. Similar profiles were seen for specific IgE antibodies and idiotypic responses. Surprisingly, idiotypes borne by other anti-Lol p I MoAbs (539A-6 and 348A-6) had also been enhanced after pretreatment with the anti-290A-167 MoAb. These observations suggested that the pretreatment with this anti-idiotypic MoAb modulates not only the expression of the respective idiotype, but also affects other idiotype responses.     

Mutations in activation-induced cytidine deaminase in patients with hyper IgM syndrome

Recent studies have shown that mutations in a newly described RNA editing enzyme, activation-induced cytidine deaminase (AID), can cause an autosomal recessive form of hyper IgM syndrome. To determine the relative frequency of mutations in AID, we evaluated a group of 27 patients with hyper IgM syndrome who did not have defects in CD40 ligand and 23 patients with common variable immunodeficiency. Three different mutations in AID were identified in 18 patients with hyper IgM syndrome, including 14 French Canadians, 2 Lumbee Indians, and a brother and sister from Okinawa. No mutations were found in the remaining 32 patients. In the group of patients with hyper IgM syndrome, the patients with mutations in AID were older at the age of diagnosis, were more likely to have positive isohemagglutinins, and were less likely to have anemia, neutropenia, or thrombocytopenia. Lymphoid hyperplasia was seen in patients with hyper IgM syndrome and normal AID as well as the patients with hyper IgM syndrome and defects in AID.     

Mechanics of porcine coronary arteries<Emphasis Type="Italic">ex vivo</Emphasis> employing impedance planimetry: A new intravascular technique

Our objective was to evaluate methodological aspects of impedance planimetry, a new balloon catheter-based technique, for the investigation of coronary artery mechanical wall properties. We used a four ring-electrode electrical impedance measuring system that was located inside a balloon. Two of the electrodes were used for excitation and connected to a generator producing a constant alternating current of 250 mA at 5 kHz. The other two electrodes for detection were placed midway between the excitation electrodes. The balloon was distended with electrically conducting fluid through an infusion channel. The vessel cross-sectional area (CSA) was measured according to the field gradient principle by measuring the impedance of the fluid inside the balloon. Impedance planimetry was applied in the three major branches of the coronary arteries of seven extracted porcine hearts to assess luminal CSAs in response to internal pressurization. The biomechanical wall properties were evaluated by computing the strain [(r?r ₀)·r ₀ ^?1, wherer is the vessels inner radius computed as (CSA · π^?1)^½ andr ₀ is the radius of the vessel at a minimal distension pressure], the tension [(r·dP), wheredP is the transmural pressure difference], and the pressure elastic modulus (ΔP·r·Δr ^?1). We found thatin vitro testing demonstrated that impedance planimetry was accurate and reproducible. The technique has controllable sources of crror. Measurements were performed with consecutively increasing pressures in the range 1–25 kPa (8–188 mmHg, 0.01–0.25 atm). The CSAs increased nonlinearly and were significantly larger in the left anterior descendent coronary artery (LAD) (1 kPa, mean 5.0 mm²; 25 kPa, mean 21.8 mm²) than in both the left circumflex (Cx) (4.5–16.0 mm²) and the right coronary artery (RCA) (2.8–15.6 mm²) (analysis of variance,P<0.001 for both). The circumferential wall tension-strain relation showed exponential behavior. For a given strain, tension values for LAD were significantly lower than those of Cx (P<0.01). The pressure elastic modulus-strain relation also was exponential, and values for Cx were significantly lower than values for LAD (P<0.001) and RCA (P<0.05). Impedance planimetry was applied to the study of coronary artery biomechanicsex vivo. The LAD had the largest CSA, and the Cx was the least compliant. Methodological aspects of anin vivo introduction of the method require additional evaluation.     

30 years of campylobacters: biochemical characteristics and a biotyping proposal for Campylobacter jejuni.

Several biochemical test systems were studied for their potential usefulness for the examination of strains of Campylobacter species. Most (81%) of the C. jejuni strains hydrolyzed sodium hippurate, but strains of C. fetus, C. sputorum, and C. fecalis did not. Some (46%) of the C. jejuni strains and all of the C. sputorum subsp. sputorum, C. sputorum subsp. bubulus, and C. fecalis strains hydrolyzed DNA, but the C. fetus and C. sputorum subsp. mucosalis strains did not. Strains of all species of Campylobacter grew on charcoal-yeast extract agar, but 47% of the C. jejuni strains did not. Alkaline phosphatase activity was recorded for some strains of C. jejuni, but all other species were negative for this activity. Aryl sulfatase activity was detected in 7% of the C. jejuni, 15% of the C. fetus subsp. fetus, and all of the C. sputorum subsp. sputorum, C. sputorum subsp. bubulus, and C. fecalis strains, but it was not detected in the C. fetus subsp. venerealis and C. sputorum subsp. mucosalis strains. Most (93%) of the C. jejuni but none of the other Campylobacter strains contained lactobacillic acid when examined for cellular fatty acids. On the basis of results from three of these tests (hippurate hydrolysis, DNA hydrolysis, and growth on charcoal-yeast extract agar), clinical strains of C. jejuni were placed in eight biotypes.     

Regional brain distribution of noradrenaline uptake sites, and of alpha1-alpha2- and beta-adrenergic receptors in PCD mutant mice: a quantitative autoradiographic study

The mouse "Purkinje cell degeneration" (pcd) is characterized by a primary loss of Purkinje cells, as well as by retrograde and secondary partial degeneration of cerebellar granule cells and inferior olivary neurons; this neurological mutant can be considered as an animal model of human degenerative ataxia. To determine the consequences of this cerebellar pathology on the noradrenergic system, noradrenaline transporters as well as alpha1-, alpha2- and beta-adrenergic receptors were evaluated by quantitative ligand binding autoradiography in adult control and pcd mice using, respectively, [3H]nisoxetine, [3H]prazosin, [3H]idazoxan and [3H]CGP12177. In cerebellar cortex and deep nuclei of pcd mutants, [3H]nisoxetine labelling of noradrenaline transporters was higher than in control mice. However, when binding densities were corrected by surface area, they remained unchanged in the cerebellar cortex but associated with 25% and 40% lower levels of labelling of alpha1 and beta receptors, as well as a very important increase (275%) of alpha2 receptors. In deep cerebellar nuclei, surface corrections did not reveal any changes either in transporter or in receptor densities. Higher densities of [3H]nisoxetine labelling were found in several regions related with the cerebellum, namely inferior olive, inferior colliculus, vestibular, reticular, pontine, raphe and red nuclei, as well as in primary motor and sensory cerebral cortex; they may reflect an increased noradrenergic innervation related to motor adjustments for the cerebellar dysfunction. Increased [3H]nisoxetine labelling was also measured in vegetative brainstem regions and in dorsal hypothalamus, implying altered autonomic functions and possible compensation in pcd mutants. Other changes found in extracerebellar regions affected by the mutation, such as thalamus and the olfactory system implicated both noradrenaline transporters and adrenergic receptors. In contrast to the important alterations of the noradrenergic system in cerebellar cortex, the lack of receptor changes in deep cerebellar nuclei suggests that local adaptations may be sufficient to minimize the consequence of the cerebellar atrophy on motor control. An intense labelling by [3H]idazoxan of the inner third of the molecular layer was a novel, albeit unexplained finding, and could represent a postsynaptic subset of alpha2-adrenergic receptors.