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Biomedical subjects

A Jonas

Publications and source records attributed to A Jonas.

At least 145 records · Page 8Linked to original sources

Disturbed fat absorption following infectious gastroenteritis in children.

Fat absorption was studied in 10 patients recovering from an episode of acute infectious gastroenteritis who failed to gain weight despite adequate caloric intake. Three patients restudied after clinical improvement and three other infants with failure to thrive, unrelated to gastrointestinal problems, served as control subjects. Fat balance studies during the ingestion of a formula containing long-chain fatty acids demonstrated significant degrees of steatorrhea in patients (mean CFA 70.6 +/- 10.7 compared to 90.3 +/- 2.4 in control subjects). The administration of a test meal demonstrated a marked deficiency of duodenal bile acid concentration and of fat incorporation into the micellar phase in patients. Fecal bile acid excretion was significantly increased in patients (mean 33.9 +/- 11.6 microM/kg/day) as compared to control subjects (mean 13.5 +/- 3.1 microM/kg/day). Bacterial overgrowth and abnormalities of the small intestinal mucosa were not constant. Ileal dysfunction and associated bile acid loss are possible causes of disturbed fat assimilation following acute intestinal infection in children.

Acute Disease↗

Oral fat loading test: a reliable procedure for the study of fat malabsorption in children.

Oral triglyceride (TG) loading tests were performed in four groups of children: normal controls, patients with chronic nonspecific diarrhoea (CND), biopsy-proved mucosal pathology (MP), and disturbed intraluminal fat malabsorption (IFM). The rise of plasma TG levels greater than or equal to 55 mg/100 ml (greater than or equal to 0.6 mmol/l) can discriminate between patients with gastrointestinal disease and normal controls or patients with functional disturbances. The postmeal plasma TG rise correlates well with the coefficient of fat absorption (CFA) in normal subjects, patients with CND, and patients with IFM, but not in patients with MP who showed a disproportionally low plasma TG rise compared with their CFA. This test can serve as a useful tool in diagnosis and clinical evaluation for children with gastrointestinal disorders.

Adolescent↗

Interaction of bovine serum high density lipoprotein with mixed vesicles of phosphatidylcholine and cholesterol.

The interaction of sonicated, small vesicles of egg phosphatidylcholine and cholesterol (2:1, mol/mol) with bovine high density serum lipoproteins was examined in terms of lipid transfer between both types of particles and the resulting changes in lipoprotein structure. Saturation of high density lipoprotein preparations with vesicle lipids gave final lipoprotein particles with essentially unchanged protein content and composition, unchanged cholesterylester and nonpolar lipid content, but with markedly increased phospholipid content (59% increas by weight) and moderately increased cholesterol content (20% increase by weight). The lipoproteins enriched in lipid were relatively uniform, spherical particles, 110 +/- 3.6 A in diameter (6 A larger than the original lipoproteins); they had a markedly decreased intrinsic protein fluorescence, a red-shifted fluorescence wavelength maximum, and more fluid lipid domains. These results indicate that the direct addition of excess lipids from membranes or other lipoproteins is a possible mechanism for lipid transfer to high density lipoproteins. Also they suggest a structural flexibility of high density lipoproteins that allows the addition of significant amounts of surface components.

Animals↗

Etiology of acute gastroenteritis in children in Israel: role of human reoviruslike agent and bacterial pathogens.

A study of acute gastroenteritis in children was carried out with the aim of establishing the prevalence of human reoviruslike agent (HRLA) and its relation to other enteric pathogens in Israel. The stools of 384 children with acute diarrhea referred to a pediatric emergency service were screened for HRLA by counterimmunoelectroosmorphoresis (CIEOP) and for pathogenic bacteria. Evidence of HRLA infection was found in 65 patients (17%). The highest infection rate prevailed during the cool season (25%), with a peak prevalence (41%) in November, when both the temperature and humidity were low. A very high proportion of HRLA was found in children younger than 36 months and no HRLA infection was observed in those older than nine years. The highest prevalence occurred in infants younger than six months, a situation rarely encountered in other countries. The main clinical features of HRLA infection were fever, vomiting, dehydration, signs of upper respiratory infection and carbohydrate intolerance. Bacterial pathogens accounted for 45% of enteric infections. Shigella species predominated (28%) during the summer season, especially in older children. In 38% of the study group, no etiologic agent could be detected. None of the 50 control subjects showed evidence of viral or bacterial pathogens in stools.

Acute Disease↗

Incorporation of excess cholesterol by high density serum lipoproteins.

Excess cholesterol was added to human HDL3 and to bovine mammalian high density serum lipoprotein (HDL) by incubating aqueous lipoprotein solutions with solid dispersions of [4-(14)C]cholesterol on Celite. Lipoprotein cholesterol complexes were isolated by centrifugation and filtration through a Sepharose 4B column. The pure complexes were analyzed for protein and lipid content and composition and were subsequently investigated by physical methods (analytical ultracentrifugation, circular dichroism, and fluorescence spectroscopy), in order to detect any structural changes induced by added cholesterol. The rates of cholesterol uptake varied as an inverse function of the intrinsic cholesterol present in the native lipoproteins. The maximum cholesterol taken up by human HDL3 increased the free cholesterol content from 3--4% (initial) up to 22% of the total lipoprotein weight. Bovine HDL was observed to increase its free cholesterol content from 2--4% (initial) up to 11--17% of the total lipoprotein weight, before denaturation. At maximum levels of added cholesterol, both lipoproteins had increased molecular weights and sedimentation velocity coefficients corresponding to the increased mass of the particles. No major changes in the hydrodynamic properties were observed. At the molecular level, the protein components only showed a 15--20% decrease in fluorescence intensity, possibly a consequence of a modified environment of the aromatic amino acid residues. In the human HDL3, added cholesterol increased the microviscosity of the lipid domains by 1.2 P at 25 degrees C (from 3.4 to 4.6 P), but did not affect the fluidity of bovine HDL lipids (5.9 P).

Animals↗

Pathogenesis of mucosal injury in the blind loop syndrome.

Bacterial extracts were prepared from cultures originating in chronic self-filling intestinal blind loops in rats. Their ability to remove active maltase molecules from isolated brush border membranes was studied in vitro. Twelve strains in 51 tested, belonging to one of three species, Bacteroides fragilis, Clostridium perfringens, and Streptococcus fecalis, possessed maltase-releasing activity. The ability to remove maltase correlated well with the ability to hydrolyze p-nitrophenyl-tert-butyloxycarbonyl-l-alaninate (NBA), an ester substrate rapidly hydrolyzed by elastase, but not with substrated favored by tryhsin and chymotrypsin. Maltase-releasing activity from C. perfringens was strongly inhibited by soybean trypsin inhibitor and to a lesser extent by lima bean trypsin inhibitor. Of four chloromethylketone active-site directed inhibitors tested with specificities for elastase, trypsin, and chymotrypsin, inhibition was maximal with elastase-specific inhibitors. In two species, activity was shown to be heat sensitive, and to be inhibited by concentration of the extract. In one species maltase-releasing activity was shown to be due to an enzyme of molecular weight at least 66,000 with the capacity to remove lactase, sucrase, and alkaline phosphatase, as well as maltase. The results indicate that anaerobic or facultatively anaerobic species, previously identified with the pathology of of the blind loop syndrome, contain proteases which are capable of removing components of the intestinal surface membrane. These proteases appear to have elastase-like substrate specificity and may be involved in the etiology of disaccharidase deficiency in bacterial overgrowth syndromes.

Animals↗

Interaction of human and bovine A-1 apolipoproteins with L-alpha-dimyristoyl phosphadicylcholine and L-alpha-myristoyl lysophosphatidylcholine.

The major protein components from human and bovine high density serum lipoproteins (apo-A-I proteins) were investigated in their interactions with L-alpha-myristoyl lysophosphatidylcholine and L-alpha-dimyristoyl phosphatidylcholine. Complex formation was followed by 25 degrees by observing changes in fluorescence polarization, rotational relaxation times (ph), and CD spectra of the proteins, covalently labeled with fluorescent dimethylaminonaphthalene sulfonyl groups. Monomeric human apo-A-I and initially oligomeric bovine apo-A-I interact with similar efficiency with the same amphiphiles. During binding of L-alpha-myristoyl lysophosphatidylcholine and L-alpha-dimyristoyl phosphatidylcholine, the structure of both proteins changes drastically, exhibiting about 35% increases in secondary structure with the phospholipid and about 20% increases with the lysophospholipid. Simultaneously, regions of the proteins adjacent to the fluorescent probes become more mobile. With the bovine protein, binding of both amphiphiles results in changes in the oligomeric structure: dissociation with L-alpha-myristoyl lysophosphatidylcholine and dissociation or rearrangement with L-alpha-dimyristoyl phosphatidylcholine. The complexes formed in the presence of excess L-alpha-myristoyl lysophosphatidylcholine are flexible structures with considerable rotational freedom. The largest rotational unit in these complexes has ph = 60 ns for both proteins; by comparison, the monometic human apo-A-I has a ph = 73.5 ns. Interactions of both proteins with the lysophospholipid take place well above its critical micelle concentration, but probably involve binding of monomeric lipid. With L-alpha-dimyristoyl phosphatidylcholine the complexes are different from those formed with the lysophospholipid. They have limiting ph values of 250 +/- 50 and 280 +/- 60 ns with the human and bovine proteins, respectively. These ph values are consistent with particles of the general size of human high density lipoprotein rather than of liposomes and indicate the formation of distinct, relatively small structures upon interaction of the self-associated lipid with the apo-A-I-proteins.

Animals↗

Physical properties of isolated complexes of human and bovine A-I apolipoproteins with L-alpha-dimyristoyl phosphatidylcholine.

Human or bovine A-I apolipoproteins in solution form complexes with sonicated L-alpha-dimirystoyl phosphatidylcholine at 23 and 37 degrees, but not at 8 degrees, suggesting a strong dependence of the interaction on the physical state of the lipid (phase transition temperature 23 degrees). Complexes were isolated by gel filtration on a Sepharose 4B column and were subsequently analyzed for protein and lipid content, molecular weight, and physical state of the lipid portion. The average stoichiometry of all complexes, regardless of the initial concentrations or ratios of protein and lipid, was constant: 90 +/- 20 mol of phospholipid/mol of protein monomer, suggesting a highly cooperative interaction. Sedimentation equilibrium experiments indicated homogeneous macromolecular preparations and gave molecular weights around 235,000 (+/- 15%) for the complexes, with the human and bovine apo-A-I proteins contributing 77,000 (+/- 10%), i.e. about three protein subunits per complex. The lipid portion of the complexes retained some characteristics of a bilayer: it had a broad phase transition with a midpoint at 25.5 degrees as reported by the fluorescence polarization of the lipophilic probe diphenylhexatriene. Above the phase transition temperature the mobility of the phospholipids in the complexes with both apo-A-I proteins was considerably decreased relative to the pure L-alpha-dimyristoyl phosphatidylcholine dispersion; below the phase transition temperature the opposite was true, i.e. the protein fluidized the lipids. The results indicate that apol-A-I proteins interact stoichiometrically with L-alpha-dimyristoyl phosphatidylcholine vesicles above the gel to liquid-crystalline transition temperature of the lipid, promoting the destruction of vesicles and the formation of well defined particles of the general size of high density serum lipoproteins.

Animals↗

Pathogenesis of mucosal injury in the blind loop syndrome. Brush border enzyme activity and glycoprotein degradation.

The effect of intestinal bacterial over-growth on brush border hydrolases and brush border glycoproteins was studied in nonoperated control rats, control rats with surgically introduced jejunal self-emptying blind loops, and rats with surgically introduced jejunal self-filling blind loops. Data were analyzed from blind loop segments, segments above and below the blind loops, and three corresponding segments in the nonoperated controls. Rats with self-filling blind loops had significantly greater fat excretion than controls and exhibited significantly lower conjugated:free bile salt ratios in all three segments. Maltase, sucrase, and lactase activities were significantly reduced in homogenates and isolated brush borders from the self-filling blind loop, but alkaline phosphatase was not affected. The relative degradation rate of homogenate and brush border glycoproteins was assessed by a double-isotope technique involving the injection of d-[6-(3)H]glucosamine 3 h and d-[U-(14)C]glucosamine 19 h before sacrifice, and recorded as a (3)H:(14)C ratio. The relative degradation rate in both homogenate and brush border fractions was significantly greater in most segments from rats with self-filling blind loops. In the upper and blind loop segments from rats with self-filling blind loops, the (3)H:(14)C ratios were higher in the brush border membrane than in the corresponding homogenates, indicating that the increased rates of degradation primarily involve membrane glycoproteins. Incorporation of d-[6-(3)H]glucosamine by brush border glycoproteins was not reduced in rats with self-filling blind loops, suggesting that glycoprotein synthesis was not affected. Polyacrylamide gel electrophoresis of brush border glycoproteins from the contaminated segments indicated that the large molecular weight glycoproteins, which include many of the surface hydrolases, were degraded most rapidly. Brush border maltase, isolated by immunoprecipitation, had (3)H:(14)C ratios characteristic of the most rapidly degraded glycoproteins. The results indicate that bacteria enhance the destruction of intestinal surface glycoproteins including disaccharidases. Since alkaline phosphatase, a glycoprotein, is not affected, the destruction is selective and presumably involves only the most exposed membrane components.

Animals↗

Interaction of phosphatidylcholine with bovine serum albumin. Specificity and properties of the complexes.

Phosphatidylcholine dispersed on Celite was rapidly solubilized by neutral bovine serum albumin solutions. Stable protein-lipid complexes were isolated by Agrose gel filtration or by ultracentrifugal flotation in high density solvents, and the physicochemical properties of the complexes were investigated in terms of the stoichiometry of binding, effect of fatty acid ligands on phosphatidylcholine binding, effect of high ionic strength on the stability of the complexes, intrinsic fluorescence and circular dichroism spectra, and sedimentation velocity coefficients. Complexes containing from 2 to 30 phosphatidylcholine molecules per protein molecule were observed; however, no saturation of binding sites could be detected in this range of molar ratios. Oleic acid binding by serum albumin prevents interaction of the protein with phosphatidylcholine, indicating possible competition of these ligands at low contents of the phospholipid. For molar ratios of up to 10 phosphatidylcholine molecules per serum albumin, binding is primarily due to hydrophobic interactions that have no effect on the overall shape and secondary structure of the native protein except for local modifications at tryptophan residues, whose fluorescence becomes quenched and blue shifted on phosphatidylcholine binding. Similar phosphatidylcholine uptake experiments performed with a series of globular proteins indicated that the lipid extraction from Celite surfaces is a non-specific process, accelerated by several other proteins (e.g. aldolase, egg albumin, chymotrypsinogen, soybean trypsin inhibitor, and the major apolipoprotein from bovine serum high density lipoprotein). Formation of stable protein-lipid complexes, however, was only observed with bovine serum albumin, which in contrast to the other proteins is known to have affinity binding sites for anions with hydrophobic side chains.

Animals↗

Microviscosity of lipid domains in human serum lipoproteins.

Microviscosities for the hydrophobic lipid regions of human serum lipoproteins and for dispersions of lipids extracted from the lipoproteins have been determined using fluorescence polarization measurements with 1,6-diphenyl-1,3,5-hexatriene, a rod-like molecule, as the main fluorescent probe. Additional microviscosity measurements were carried out on LP-X, an abnormal human lipoprotein characteristic of cholestasis. Perylene, a disc-shaped fluorescent probe, was used with intact human lipoproteins in order to confirm relative microviscosity values measured with 1,6-diphenyl-1,3,5-hexatriene and to estimate the anisotropy of the lipid domains. Logarithmic plots of microviscosity against the inverse of absolute temperature, over the range of 0-40 degrees C, gave no indication of phase transitions and yielded activation energy values for all human lipoproteins and for the isolated lipids. The microviscosity results at 25 degrees C range from a high value of 6.1 +/- 0.9 P for low density lipoprotein down to 1.0 +/- 0.2P for chylomicrons, when 1,6-diphenyl-1,3,5-hexatriene is used as the probe. Activation energies vary from 9 kcal per mol to 6 kcal per mol for the intact lipoproteins. In contrast, isolated lipids have microviscosities from 2.4 +/- 0.3P for low density lipoprotein lipids to 1.0 +/- 0.2P for chylomicron lipids, with activation energies around 6 kcal per mol. The absolute microviscosity values indicate fluid yet viscous and anisotropic lipid domains in higher density lipoproteins, and more fluid and disordered states for isolated lipids and chylomicrons. Differences in microviscosities between the intact lipoproteins and isolated lipids can be attributed to the effects of proteins in restricting the mobility of lipids, these effects are strongest for low density lipoproteins, followed by high density lipoproteins, LP-X, very low density lipoproteins, and chylomicrons. Flow activation energies are throught to reflect intermolecular interactions, and are again higher for the higher density lipoproteins than for isolated lipids, or for chylomicrons.

Benzene Derivatives↗

[Results in the implantation of total or partial prosthesis in the knee joint].

A report of the results achieved by treating of corrosive diseases of knee joint by partial and total endoprosthesis. A total of 74 knee joints were operated on. Improvement of movement and stress capability was achieved in 93% of all cases. Complications are presented and discussed. Follow-up and summary of all cases reveals that the total endoprosthesis is increasingly indicated. The replacement of a sliding endoprosthesis by a total endoprosthesis has since become necessary in three cases and resulted in marked improvement of function. One patient is not free of complaints, and an exchange operation is indicated. The indications for implantation of a sliding endoprosthesis will in the future surely be much more closely drawn. Follow-up reveales that increasing reactive changes of the knee joint cause pain of increasing measure. An initially painless interval is followed by a period of increasing pain. Results of follow-uthesis may be extended. The continued pain that totally operated patients in part by the high-grade and progressive changes in the femoro-patellar joint.

Aged↗