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At least 631 records · Page 35Linked to original sources
PubMed2002

Strategy of Escherichia coli for crossing the blood-brain barrier.

A major contributing factor to high mortality and morbidity associated with bacterial meningitis is the incomplete understanding of the pathogenesis of this disease: It is unclear how circulating bacteria cross the blood-brain barrier (BBB). Recent studies with Escherichia coli K1 show that successful traversal of the BBB requires a high degree of bacteremia, invasion of brain microvascular endothelial cells (BMEC), host cell actin cytoskeleton rearrangements and related signaling pathways, and traversal of the BBB as live bacteria. Several microbial determinants such as the K1 capsule, OmpA, Ibe proteins, AslA, TraJ, and CNF1 contribute to BMEC invasion. Of interest, E. coli K1 trafficking mechanisms differ from those of other meningitis-causing bacteria such as Listeria monocytogenes and group B streptococcus. Complete understanding of bacteria-BMEC interactions contributing to translocation of the BBB should assist in developing novel strategies to prevent bacterial meningitis.

Animals↗
PubMed1988

Human repetitive and unique sequences coexist in a large circulating DNA species found in cryoprecipitates from SLE patients.

Cryoprecipitates from systemic lupus erythematosus (SLE) patients with high levels of anti DNA antibodies show a sharply migrating large circulating DNA species of about 17-20 kb (M. Rieber et al., Clin. exp. Immunol. (1986) 66, 61). We have now used Southern blot analysis of circulating DNA from different individuals to analyse the relative cross-hybridization of circulating DNA from different individuals, as well as their homology with genomic DNA from different species. Molecular hybridization showed significant homology of the various circulating DNA examined, only with human genomic DNA, but limited cross-reactivity among circulating DNA from different individuals. This suggests that the circulating DNA is composed of sequences repeated in human genomic DNA and by specific sequences unique to circulating DNA from some individuals. Our data suggests the possibility of using probes derived from the specific sequences now reported in the circulating DNA, in gene typing and in the analysis of susceptibility to disease.

Base Sequence↗
PubMed1982

Circulating antithrombins in pregnancy.

In a cross-sectional study circulating levels of antithrombins, antithrombin III, alpha 1-antitrypsin and alpha 2-macroglobulin were measured in groups of 20 women before pregnancy, during each trimester and post partum. Blood levels of antithrombin III were significantly lower, alpha 1-antitrypsin higher and alpha 2-macroglobulin no different when compared with those of the non-pregnant and puerperal states. These findings suggest that there may be not only an increase in total antithrombin production, but also a qualitative change in antithrombin 'activity', the principal protein during pregnancy being alpha 1-antitrypsin.

Alpha-Globulins↗
PubMed1994

Effect of diaspirin cross-linked hemoglobin and norepinephrine on systemic hemodynamics and regional circulation in rats.

Diaspirin cross-linked hemoglobin (DCLHb) (400 mg/kg, i.v.) produced a pressor effect that was equal to that produced by norepinephrine (NE) (25 micrograms/kg/min i.v. infusion). Total peripheral resistance was increased by DCLHb and more significantly by NE. Heart rate was not affected by DCLHb but was significantly increased by NE. The cardiac output and stroke volume were insignificantly increased by DCLHb but were significantly decreased by NE. DCLHb and NE produced a significant increase in blood flow to the heart. The vascular resistance in the heart was not affected by DCLHb but was decreased by NE. DCLHb did not affect the renal and brain circulation, but NE in kidneys decreased the blood flow and increased the vascular resistance, whereas in the brain it increased the blood flow and decreased the vascular resistance. DCLHb increased the blood flow to the stomach and small intestine. The vascular resistance was not affected by DCLHb in the gastrointestinal tract. NE did not affect the blood circulation in the gastrointestinal tract. Blood flow to the spleen was increased by DCLHb, and there was no change in the vascular resistance. NE insignificantly decreased the blood flow to the spleen and significantly increased the vascular resistance. The blood circulation to the mesentery and pancreas was not affected by DCLHb, whereas NE increased the blood flow without affecting the vascular resistance. DCLHb produced a significant increase in the blood flow to the skin without affecting the vascular resistance, whereas NE did not affect the blood flow but increased the vascular resistance. DCLHb did not affect the blood flow to the musculo-skeletal system but increased the vascular resistance, whereas NE decreased the blood flow and increased the vascular resistance. In summary, although the pressor effect of DCLHb and NE at the doses studied is equal, DCLHb did not decrease the blood flow to any organ, whereas NE produced significant decreases in blood flow to several organs. It is concluded that the blood flow to most of the organs is either increased or not affected by DCLHb.

Animals↗
PubMed1994

Effect of stroma-free hemoglobin and diaspirin cross-linked hemoglobin on the regional circulation and systemic hemodynamics.

The effects of unmodified stroma-free hemoglobin (SFHb) and diaspirin cross-linked hemoglobin (DCLHb) on the regional blood circulation and systemic hemodynamics were studied in rats using a radioactive microsphere technique. SFHb and DCLHb increased mean arterial blood pressure without affecting heart rate. SFHb produced a 24.9% decrease in the cardiac output while DCLHb produced an 44.8% increase in the cardiac output. Stroke volume was decreased (-27.3%) by SFHb and increased (+36.4%) by DCLHb. Total peripheral resistance increased with both SFHb and DCLHb. DCLHb increased blood flow to the heart, spleen, stomach, small intestine and skin, and had no effect on blood flow to the brain, kidneys, liver, mesentery, pancreas, caecum, large intestine and musculo-skeletal system. In contrast, in animals infused with SFHb, blood flow decreased to the kidneys, liver and spleen, increased to the heart, small intestine and skin, and had no effect to the brain, caecum, large intestine and musculo-skeletal system. DCLHb had no effect on vascular resistance in any organ except for an increase in the musculo-skeletal system. In contrast, SFHb increased vascular resistance in the kidneys, liver, spleen, skin, mesentery and pancreas, and had no effect on vascular resistance in the musculo-skeletal system, brain, heart, stomach, small intestine, caecum and large intestine. SFHb had no effect on distribution of cardiac output to the brain, gastrointestinal tract (GIT), kidneys, skin, musculo-skeletal and portal system, while DCLHb significantly decreased the percent cardiac output to the musculo-skeletal system. DCLHb did not affect the distribution of cardiac output to the brain, GIT, kidneys, skin and portal system. SFHb and DCLHb increased the percent cardiac output to the heart. It is concluded that similar concentrations and doses of DCLHb and SFHb produce different effects on the regional blood circulation and systemic hemodynamics.

Animals↗
PubMedDate not supplied

Use of artificial circulation in resuscitation of drowned dogs.

The effectiveness of artificial circulation by the method of Bryukhonenko and his colleagues in the resuscitation of dogs that had died from drowning in fresh- or salt-water was studied. Eight out of ten dogs were revived after freshwater drowning 'death' lasting from 10.5 to 21 min, when a variant of the artificial circulation method, dog donor with a venous pump of the artificial heart, was used. Resuscitated dogs remained alive from 3 to 72 h and died from pulmonary oedema. Artificial circulation appeared to be more effective in resuscitation of dogs drowned in saltwater. Their clinical 'death' lasted up to 31.5 min; clinically signs of pulmonary oedema were not observed in any of them, though some signs of oedema were revealed by histological studies. Of the 42 dogs in this series, all the main functions of the central nervous system were restored in 18 with clinical 'death' for up to 25 min. Resuscitation was performed by one of two methods, either the dog donor plus venous pump of the artificial heart, or the method of Bryukhonenko. The effectiveness of artificial circulation for resuscitation of dogs from drowning was demonstrated.

Animals↗
PubMed1994

[Changes in the immunological indices of patients with obstructive jaundice and liver cirrhosis during the extracorporeal connection of a pig spleen].

The immunologic indices were studied in 29 patients with hepatic cirrhosis and obstructive jaundice, who had the porcine spleen been connected according to the conventional technique, and in 17 patients of the control group. The blood was collected in dynamics. The positive effect of the method on the immune status of the patients, which manifested itself in activation of a T-link of immunity, normalization of the indices of B-link, decrease in the severity of intoxication due to elimination of the middle molecular mass peptides and circulating immune complexes, was noted.

Animals↗
PubMed1990

New renin--angiotensin from plasma prorenin?

Within 24 h of binephrectomy in rats, plasma prorenin (activated by trypsin) rose well above normal levels while renin disappeared. This rise in prorenin may be attributed to enhanced secretion by an unidentified extrarenal source and the lack of any renin formation from it suggests that nephrectomy abolishes any systemic "convertase" mechanism that exists for its activation. Within 48 h of adrenalectomy in rats, plasma prorenin levels dropped below normal, while renin rose sharply, suggesting enhanced activation of prorenin to renin, resulting in prorenin depletion, and/or the release of a higher proportion of renin: prorenin by the kidneys. To test for enhanced convertase activity, we crosscirculated adrenalectomized (high convertase) and nephrectomized (low convertase) rats and observed a rapid drop in prorenin with an increase in renin in their shared blood. This was also observed after mixing their bloods in vitro, without crosscirculation, indicating that renal convertase activity was in the bloodstream and not just in the kidneys. Acute nephrectomy of previously adrenalectomized rats lowered renin and raised prorenin within 15 min suggesting a rapid loss of kidney-derived convertase. These results could not be attributed to changes in renin-substrate concentration. The new renin (from activated extrarenal prorenin) was blocked by a monoclonal antibody effective against normal rat plasma renin. It also generated immunoreactive angiotensin I, indicating immunological and biological coidentity with renal renin. The blood of normal control rats did not exhibit convertase activity in vivo or in vitro. These data point to a secretory (endocrine) source of extrarenal prorenin which is stimulated by nephrectomy and to a renal prorenin convertase mechanism which is abolished by nephrectomy and stimulated by adrenalectomy. Thus, in a high renin state, active renin may arise by activation of circulating prorenin (renal and extrarenal) as well as by direct renal release.

Adrenalectomy↗
PubMed2003

Standardization of an isolated pig heart preparation with parabiotic circulation: methodological considerations.

In the present study we standardized an experimental model of parabiotic circulation of isolated pig heart. The isolated heart was perfused with arterial blood from a second animal as support and submitted to regional ischemia for 30 min, followed by total ischemia for 90 min and reperfusion for 90 min. Parameters for measurement of ventricular performance using different indices measured directly or indirectly from intraventricular pressure were defined as: maximum peak pressure, final diastolic pressure, pressure developed, first derivative of maximum pressure (dP/dt max), first derivative of minimum pressure (dP/dt min), systolic stress of the left ventricle (sigmas), and maximum elastance of the left ventricle. Isolated hearts subjected to regional and global ischemia presented significant worsening of all measured parameters. Less discriminative parameters were dP/dt max and dP/dt min. Elastance was the most sensitive parameter during the reperfusion period, demonstrating an early loss of ventricular function during reperfusion. The model proved to be stable and reproducible and permitted the study of several variables in the isolated heart, such as ischemia and reperfusion phenomena, the effects of different drugs, surgical interventions, etc. The model introduces an advantage over the classical models which use crystalloid solutions as perfusate, because parabiotic circulation mimics heart surgery with extracorporeal circulation.

Analysis of Variance↗
PubMed1993

Antigens pre-bound to the primate erythrocyte complement receptor via cross-linked bispecific monoclonal antibody heteropolymers are rapidly cleared from the circulation.

We have used cross-linked, bispecific monoclonal antibody heteropolymers, specific for primate erythrocyte (E) complement receptor (CR1) and target antigen (Ag), to attach 125I-labeled Ag to 51Cr-labeled monkey erythrocytes (E) in vitro. Injection of these sensitized E into monkeys leads to rapid clearance from the circulation of several different 125I-labeled Ag with little, if any sequestration, lysis, or clearance of the E. It should now be possible, in principle, to use the heteropolymer-E system to facilitate the clearance of blood-borne pathogens from the circulation.

Animals↗
PubMed2000

[Neurovascular cross-compression syndromes of the cerebellopontine angle].

Neurovascular cross-compression syndromes involve the Vth, VIIth, VIIIth, and IXth cranial nerves. They share in common the same physiopathologic mechanism and are demonstrated by T2 volumetric MR explorations (CISS 3D and 3D TSE sequences) and 3D TOF MRA sequences of the posterior circulation. The cross compression is located at the root entry zone. Arterial loops are the classical offenders while venous compressions are less frequently encountered.

Adult↗
PubMed2002

Platelet-endothelial cell adhesion molecule-1-directed immunotargeting to cardiopulmonary vasculature.

Therapeutic molecules conjugated with antibodies to the platelet-endothelial cell adhesion molecule-1 (PECAM-1) accumulate in the pulmonary endothelium after i.v. injection in mice. In this study, we characterized PECAM-directed targeting to the lung and heart after local versus systemic intravascular administration in a large animal model, pigs. Radiolabel tracing showed that 1 h post-i.v. injection, 35% of anti-PECAM versus 2.5% of control IgG had accumulated in the lungs. Infusion of anti-PECAM via a catheter placed in the right pulmonary artery (RPA) resulted in a 3-fold elevation of the uptake in the right lower lobe and 2-fold reduction of uptake in the left lobes in the lung. Cardiac uptake of anti-PECAM was negligible after i.v. and RPA infusion. In contrast, delivery with a catheter placed in the right coronary artery (RCA) resulted in a 4-fold elevation of cardiac uptake of anti-PECAM, but not IgG, compared with i.v. injection. To estimate the targeting of an active reporter enzyme, streptavidin-conjugated beta-galactosidase (beta-Gal) was coupled to anti-PECAM or IgG (anti-PECAM/beta-Gal and IgG/beta-Gal) and injected into the RCA. Beta-Gal activity was markedly elevated in the heart and lungs (5- and 25-fold increased, respectively) after injection of anti-PECAM/beta-Gal, but not IgG/beta-Gal. Image analysis confirmed endothelial targeting of anti-PECAM/beta-Gal in the heart and lung. In summary, anti-PECAM antibody conjugates deliver agents to the pulmonary endothelium regardless of injection route, whereas local arterial infusion permits targeting to the cardiac vasculature. This paradigm may be useful for drug targeting to endothelium in lungs, heart, and possibly other organs.

Animals↗
PubMed2002

Circulating amyloid-beta peptide crosses the blood-brain barrier in aged monkeys and contributes to Alzheimer's disease lesions.

1. We studied cerebrovascular sequestration and blood-brain barrier (BBB) permeability to [125I]- or [123I]-labeled amyloid-beta peptides (A beta) in aged rhesus and aged squirrel monkey, the nonhuman primate models of cerebral beta-amyloidosis and cerebrovascular amyloid angiopathy (CAA), respectively. 2. In aged rhesus, the half-time of elimination of [125I]A beta 1-40, t1/2e, was faster by 1.34 h, the systemic clearance, Clss, increased by 4.21 ml/min/kg and the mean residence time of intact peptide in the circulation shortened by 2 h. 3. Cerebrovascular sequestration of [125I]A beta 1-40 was significant in aged squirrel monkey (20.8 ml/g x 10(2)), but undetectable in the rhesus. 4. The permeability surface area product, PS, for [14C]inulin was low in both species (0.11-0.18 ml/g/s x 10(6)) indicating an intact barrier. 5. The BBB permeability to A beta 1-40 was 34.8- and 13.7-fold higher than for [14C]inulin in aged squirrel and rhesus, respectively, suggesting a specialized A beta transport across the BBB. 6. The single photon computed emission tomography studies confirmed a saturable [123I]A beta 1-40 transport at the BBB in primates (Km = 40 nM). 7. Brain autoradiographic analysis of [125I]A beta 1-42 or [125I]A beta 1-40 after intracarotid infusions of radiotracers confirmed co-localization of the signal with A beta-immunoreactive plaques in rhesus monkeys. 8. Metabolism of [125I]A beta 1-40 in brain and plasma was slower in aged squirrel compared to aged rhesus, by 2.9- and 2.6-fold, respectively. 9. Thus, transport of circulating A beta across the BBB contributes to brain parenchymal accumulation of amyloid in aged nonhuman primates. Negligible capillary binding, rapid systemic and brain degradation, and accelerated body elimination of blood-borne A beta, may prevent the development of CAA in rhesus in contrast to squirrel monkeys.

Adolescent↗
PubMed1979

Genetic regulation of CFA expression in interspecific avian hybrids and somatic cell hybrids.

Chicken fetal-leukemic antigen (CFA) is an oncodevelopmental antigen present on embryonic and neonatal chicken peripheral red blood cells (RBCs) but is not restricted to fetal stages of development in other avian species. Crosses between white Leghorn chickens and Japanese quail resulted in adult hybrids whose peripheral RBCs were positive for CFA. Of the four CFA determinants normally found in adult quail RBCs, only two were present on quail-chicken hybrid RBCs. Adult quail--chicken hybrid RBCs also possessed on CFA determinant associated with early development in both quail and chicken and one chicken-specific CFA determinant. Evidence is presented for the possible association of CFA-positive adult peripheral RBCs and the level of circulating reticulocytes. Crosses between pheasant and turkey (both with CFA-positive adult RBCs) resulted in hybrid adult RBCs expressing only a portion of the parental CFA determinants. Through the formation of somatic cell hybrids between adult chicken and embryonic Japanese quail RBCs, it was possible to induce the appearance of CFA determinants normally restricted to embryonic chicken RBCs. Approximately 50% of the hybrid cells showed reexpression of CFA, and this induction was both time and temperature dependent. Hybridization between RBCs of adult chicken and those of either adult Japanese quail or adult turkey failed to elicit the reexpression of chicken-specific CFA.

Animals↗
PubMed1992

Target organ susceptibility and autoantibody production in an animal model of spontaneous autoimmune thyroiditis.

F1-hybrids of Obese strain (OS) chickens, afflicted with spontaneous autoimmune thyroiditis (SAT), and normal, inbred CB chickens, do not develop severe thyroiditis. About 50% of these crosses show circulating autoantibodies to thyroglobulin (TgAAb), but the thyroid glands are only slightly infiltrated, suggesting that the target organ is not susceptible to autoimmune attack. In the present study we show that despite this mild infiltration TgAAb are only synthesized by lymphoid cells within the thyroid gland. Furthermore, we demonstrate that immunization with chicken thyroglobulin (Tg) in complete Freund's adjuvant causes severe experimental autoimmune thyroiditis (EAT) in F1(OSxCB) hybrids.

Animals↗
PubMed1976

Mechanisms of blood vessel constriction during hemorrhage.

The contributions of sympathetic nerves, circulating hormones, and passive vascular recoil to vasoconstriction and transcapillary fluid reabsorption in skin and skeletal muscle were examined in the forelegs of 55 pentobarbitalized dogs by using a combined gravimetric and segmental resistance technique. Hemorrhage elicited large increases in forelimb segmental vascular resistances and in the rate of extravascular fluid reabsorption. Only a small part of these responses could be attributed to the passive effects of reducing forelimb perfusion pressure.

Animals↗