1,066 research outputs found
Erythrocytic inclusions in clinical and experimental toxicology
The author reviews the results of his studies of erythrocytic inclusions carried out at the Institute in the last twenty years. The importance of these inclusions and their role in clinical and experimental toxicology are pointed out. This year-long work has embraced principal non-parasitic inclusions, i. e. the structures within erythrocytes and their precursors cells that are morphological manifestations of intracellular biochemical processes: stippled cells, Heinz bodies, Schmauch bodies, and siderotic granules of Grüneberg and Pappenheimer. Evidence has been obtained of the myelogenic origin of stippled cells, of a morphologic resemblance and biological difference between Heinz and Schmauch bodies, and of the existence of the two variants of siderotic granulations
Role of villus microcirculation in intestinal absorption of glucose: coupling of epithelial with endothelial transport
Effect of arterial pressure on arterial and venous resistance of intestine
The effect of local alteration of arterial pressure on arterial and venous resistance of the intestine was investigated by means of the Pappenheimer isogravimetric technique. Reduction of arterial pressure caused a decrease in total vascular resistance in 70% of the experiments (autoregulation). This response was localized to the arterial portion of the circuit, specifically to vessels less than 0.5 mm o.d. Also associated with the reduction in arterial pressure was an increase in venous resistance. Venous resistance increased threefold as arterial pressure was reduced from 100 to 30 mm Hg. This venous response was seen in all preparations tested. It is suggested that both the venous response and autoregulation of arterial vessels aid in maintenance of a normal capillary pressure. Submitted on November 6, 1961 </jats:p
Adherence and invasive properties of Corynebacterium diphtheriae strains correlates with the predicted membrane-associated and secreted proteome
Background:
Non-toxigenic Corynebacterium diphtheriae strains are emerging as a major cause of severe pharyngitis and tonsillitis as well as invasive diseases such as endocarditis, septic arthritis, splenic abscesses and osteomyelitis. C. diphtheriae strains have been reported to vary in their ability to adhere and invade different cell lines. To identify the genetic basis of variation in the degrees of pathogenicity, we sequenced the genomes of four strains of C. diphtheriae (ISS 3319, ISS 4060, ISS 4746 and ISS 4749) that are well characterised in terms of their ability to adhere and invade mammalian cells.
Results:
Comparative analyses of 20 C. diphtheriae genome sequences, including 16 publicly available genomes, revealed a pan-genome comprising 3,989 protein coding sequences that include 1,625 core genes and 2,364 accessory genes. Most of the genomic variation between these strains relates to uncharacterised genes encoding hypothetical proteins or transposases. Further analyses of protein sequences using an array of bioinformatic tools predicted most of the accessory proteome to be located in the cytoplasm. The membrane-associated and secreted proteins are generally involved in adhesion and virulence characteristics. The genes encoding membrane-associated proteins, especially the number and organisation of the pilus gene clusters (spa) including the number of genes encoding surface proteins with LPXTG motifs differed between different strains. Other variations were among the genes encoding extracellular proteins, especially substrate binding proteins of different functional classes of ABC transport systems and ‘non-classical’ secreted proteins.
Conclusions:
The structure and organisation of the spa gene clusters correlates with differences in the ability of C. diphtheriae strains to adhere and invade the host cells. Furthermore, differences in the number of genes encoding membrane-associated proteins, e.g., additional proteins with LPXTG motifs could also result in variation in the adhesive properties between different strains. The variation in the secreted proteome may be associated with the degree of pathogenesis. While the role of the ‘non-classical’ secretome in virulence remains unclear, differences in the substrate binding proteins of various ABC transport systems and cytoplasmic proteins potentially suggest strain variation in nutritional requirements or a differential ability to utilize various carbon sources
Plasma protein osmotic pressure equations and nomogram for sheep
The equations developed by Landis and Pappenheimer (Handbook of Physiology. Circulation, 1963, p. 961–1034) for calculating the protein osmotic pressure of human plasma proteins have been frequently used for other animal species without regard to the fractional albumin concentration or correction for protein-protein interaction. Using an electronic osmometer, we remeasured the protein osmotic pressure of purified sheep albumin and sheep plasma partially depleted of albumin. We measured protein osmotic pressures of serial dilutions over the concentration range 0–180 g/l for albumin and 0–100 g/l for the albumin-depleted proteins at room temperature (26 degrees C). Using a nonlinear least squares parameter-fitting computer program, we obtained the equation of best fit for purified albumin, and then we used that equation together with the measured albumin fraction to obtain the best-fit equation for the nonalbumin proteins. The equation for albumin is IIcmH2O,39 degrees C = 0.382C + 0.0028C2 + 0.000013C3, where C is albumin concentration in g/l. The equation for the nonalbumin fraction is IIcmH2O,39 degrees C = 0.119C + 0.0016C2. Up to 200- and 100-g/l protein concentration, respectively, these equations give the least standard error of the estimate for each of the virial coefficients. The computed number-average molecular weight for the nonalbumin proteins is 222,000. Using the new equations, we constructed a nomogram, based on the one of Nitta and co-workers (Tohoku J. Exp. Med. 135: 43–49, 1981). We tested the nomogram using 144 random samples of sheep plasma and lymph from 31 sheep. We obtained a correlation coefficient of 0.99 between the measured and nomogram estimates of protein osmotic pressure. </jats:p
Hematocrit Ratio of Blood Within Mammalian Kidney and Its Significance for Renal Hemodynamics
Evidence is presented indicating that the dynamic hematocrit of intra-renal blood is normally about one-half that in blood entering or leaving the kidney. The hematocrit ratio of intrarenal blood, relative to that in arterial blood, varies with the corpuscular concentration in arterial blood and inversely with the renal arterial blood pressure. When the blood pressure is reduced from 140 to 50 mm Hg, the vascular volume of the kidney decreases from 24% to 19% of the kidney volume and the kidney weight decreases by a like amount (i.e. 5%). Owing to the increased intrarenal hematocrit, however, the absolute quantity of red cells in kidneys removed at low pressure is usually greater than in their contralateral controls removed at high pressure. A theory is advanced to take account of the low dynamic hematocrit ratio in intrarenal blood and its variations with arterial pressure and corpuscular concentration. The theory supposes that red cells are progressively separated from plasma by a process of plasma skimming in the interlobular arteries. The deeper glomeruli are supplied primarily with plasma, leaving a highly viscous, cell-rich component of the blood to supply the terminal arterioles. After traversing the efferent arterioles, the cell-rich moiety of the blood is presumed to pass through a short circulation (preferential channels for red cells) bypassing the peritubular capillary network. The energy for the separation process is presumed to be supplied by the kinetic energy of renal arterial blood; the separation process is therefore dependent upon velocity and cell concentration. Applications of the theory to the following topics in renal physiology are discussed: a) the dynamic hematocrit of intrarenal blood; b) autoregulation of the renal circulation as a function of arterial pressure and corpuscular composition; c) afferent and efferent arteriolar resistance and the mechanism of regulation of glomerular filtration rate; d) renal extraction of PAH and Diodrast; e) oxygen supply of the kidney and its variation with blood flow. </jats:p
Observation of new Xi(0)(c) baryons decaying to lambda K-+(c)-
The
Λ
+
c
K
−
mass spectrum is studied with a data sample of
p
p
collisions at a center-of-mass energy of 13 TeV corresponding to an integrated luminosity of
5.6
fb
−
1
collected by the LHCb experiment. Three
Ξ
0
c
states are observed with a large significance and their masses and natural widths are measured to be
m
[
Ξ
c
(
2923
)
0
]
=
2923.04
±
0.25
±
0.20
±
0.14
MeV
,
Γ
[
Ξ
c
(
2923
)
0
]
=
7.1
±
0.8
±
1.8
MeV
,
m
[
Ξ
c
(
2939
)
0
]
=
2938.55
±
0.21
±
0.17
±
0.14
MeV
,
Γ
[
Ξ
c
(
2939
)
0
]
=
10.2
±
0.8
±
1.1
MeV
,
m
[
Ξ
c
(
2965
)
0
]
=
2964.88
±
0.26
±
0.14
±
0.14
MeV
,
Γ
[
Ξ
c
(
2965
)
0
]
=
14.1
±
0.9
±
1.3
MeV
, where the uncertainties are statistical, systematic, and due to the limited knowledge of the
Λ
+
c
mass. The
Ξ
c
(
2923
)
0
and
Ξ
c
(
2939
)
0
baryons are new states. The
Ξ
c
(
2965
)
0
state is in the vicinity of the known
Ξ
c
(
2970
)
0
baryon; however, their masses and natural widths differ significantly
Carbon metabolism of enterobacterial human pathogens growing in epithelial colorectal adenocarcinoma (Caco-2) cells.
Analysis of the genome sequences of the major human bacterial pathogens has provided a large amount of information concerning their metabolic potential. However, our knowledge of the actual metabolic pathways and metabolite fluxes occurring in these pathogens under infection conditions is still limited. In this study, we analysed the intracellular carbon metabolism of enteroinvasive Escherichia coli (EIEC HN280 and EIEC 4608-58) and Salmonella enterica Serovar Typhimurium (Stm 14028) replicating in epithelial colorectal adenocarcinoma cells (Caco-2). To this aim, we supplied [U-(13)C(6)]glucose to Caco-2 cells infected with the bacterial strains or mutants thereof impaired in the uptake of glucose, mannose and/or glucose 6-phosphate. The (13)C-isotopologue patterns of protein-derived amino acids from the bacteria and the host cells were then determined by mass spectrometry. The data showed that EIEC HN280 growing in the cytosol of the host cells, as well as Stm 14028 replicating in the Salmonella-containing vacuole (SCV) utilised glucose, but not glucose 6-phosphate, other phosphorylated carbohydrates, gluconate or fatty acids as major carbon substrates. EIEC 4608-58 used C(3)-compound(s) in addition to glucose as carbon source. The labelling patterns reflected strain-dependent carbon flux via glycolysis and/or the Entner-Doudoroff pathway, the pentose phosphate pathway, the TCA cycle and anapleurotic reactions between PEP and oxaloacetate. Mutants of all three strains impaired in the uptake of glucose switched to C(3)-substrate(s) accompanied by an increased uptake of amino acids (and possibly also other anabolic monomers) from the host cell. Surprisingly, the metabolism of the host cells, as judged by the efficiency of (13)C-incorporation into host cell amino acids, was not significantly affected by the infection with either of these intracellular pathogens
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