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Mucus secretion in hypertrophic, hypersecretory, protein-losing gastropathy.

A 48-year-old man presented with giant folds of the gastric mucosa, hypoalbuminemia, and hypersecretion of acid. In vivo labeling of plasma proteins by 51CrCl3 disclosed an abnormal gastric protein clearance. Mucus secretion, evaluated by the output of dry matter, mucosubstance constituents (hexosamine and fucose), protein (by the method of Lowry), and sodium were five to eight times those in nine healthy volunteers, but were normalized by the histamine-H2-receptor antagonist cimetidine. The proportion of dry matter and protein was the same in the patient and in healthy subjects, indicating that the loss of plasma protein into the stomach probably occurred as part of an abnormally great secretion of mucus.

Cimetidine↗

Vascular injury compared to ageing of normal rabbit aorta. Biochemical and histochemical studies on time-dependent alterations of vascular connective tissue.

Male albino rabbits of the Danish country strain, 5 months of age, were divided into two groups. One group of animals was killed 180 days after a single mechanical dilatation injury of the thoracic aorta. A second group of untreated controls was killed at ages of 150, 165, 180, 210, 330, and 450 days. Glycosaminoglycans, uptake of 35S-sulphate, collagen, uptake of 125I-albumin, and vascular histochemistry and morphology were analyzed in the thoracic aorta. In the injured aortae the dry weight and the total amounts of hexosamine, hyaluronic acid, chondroitin-4,6-sulphate, dermatan sulphate, heparan sulphate, and hydroxyproline were increased. The concentration of hyaluronic acid decreased, whereas the concentration of dermatan sulphate increased. The concentrations of chondroitin-4,6-sulphate and heparan sulphate were unchanged. The total uptake of 35S-sulphate into the sulphated proteoglycans as well as the uptake of 125I-albumin were increased. The light microscopical examination showed thickening of the intima, medial changes with fibrosis, accumulations of proteoglycans, calcifications, formation of cartilage, and ossified tissue with haematopoiesis. In the uninjured thoracic aorta the only significant change during ageing was an increase in the total amount of hyaluronic acid and a decrease of the 35S-sulphate incorporation into the chondroitin-4,6-sulphate in the aorta. No morphological or histochemical alterations were observed during ageing. Spontaneous lesions were observed in 2 out of 55 aortas. It may be concluded that injury and ageing are reflected quite differently in the thoracic aorta of the rabbits. The observations may be of relevance to the interpretation of the alterations in human arterial diseases involving processes of injury and repair as well as ageing.

Aging↗

[Studies on the glycopeptides of canine prothrombin].

After degradation of canine prothrombin by the complex of Streptomyces griseus proteases four glycopeptides were obtained. Each of them contained aspartic acid, hexosamines, mannose, galactose and sialic acids. Canine prothrombin contains two or three carbohydrate chanins, which are bound to aspartic (asparagine) residues. Microheterogenity of the carbohydrate chains of canine prothrombin was found.

Animals↗

Penicillin immunogenicity in the presence of different pharmaceutical adjuvants.

Preliminary results in the variations of the penicillin immunogenicity in the presence of aminosugars, polysaccharides and terpenic substances are presented and the decreasings of the potential antigenicity of the penicillin molecule appeared in the presence of hexosamine molecules are estimated. It might be possible as a consequence of modifications in the early immunogenic interactions between antibiotic and serum proteins of the hipersensitive animals.

Adjuvants, Pharmaceutic↗

Immunological activity of the peptidoglycan.

Studies on the immunology of peptidoglycan received impetus from the initial observation that the rabbit Group A-variant streptococcal antisera were a rich source of antibodies to peptidoglycan. Indeed, quantitative precipitin studies revealed concentrations as high as 7-10 mg/ml of antiserum. The amount of antibody after Group A-variant streptococcal immunization is much greater than the amount in the sera following immunization of rabbits with the Group A or C streptococci. Furthermore, earlier studies had shown that the purified peptidoglycan obtained as a residue following extraction of streptococcal cell walls with hot formamide was a poor antigen. Both the hexosamine polymer and the peptide moiety are antigenic. Use of the solid phase synthesized pentapeptide L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala and related similar peptides facilitated the determination of the fine structure of the immunodominant site of pentapeptide. The evidence points to the C-terminal D-Ala-D-Ala as the immunodominant determinant. Because of the similarity of the peptidoglycans of a number of different bacteria, it would be anticipated that they would cross-react immunologically, and this has been shown to be the case. The biological and medical significance of antibodies to peptidoglycan has yet to be determined. Certainly the exposure to this ubiquitous substance which occurs in all the indigenous bacteria of the respiratory and the gastrointestinal tract must mean that from an early age and through advancing years there is a constant stimulation of the immune response to peptidoglycan. Because the immunochemistry of these substances is now firmly established, there is a scientific basis for proceeding with the medical and biological implications of peptidoglycan immunity.

Antibodies, Bacterial↗

The mechanical strength of the growth plate under the influence of sex hormones.

As sex hormones are considered to play a role in the etiology of the slipped upper femoral epiphysis, the influence of sex hormones on the mechanical strength of the epiphyseal plate was investigated in 310 female and 70 male rats. Ovariectomy weakened the strength of the growth plate while orchiectomy strengthened it. Estrogen given after ovariectomy, markedly strengthened the plate. Histologic examination revealed that the width of the growth plate was narrower in the mechanically stronger group. Hydroxyproline content increased and hexosamine content decreased in the epiphyseal plates of the mechanically stronger group. These observations confirm the view that sex hormones, especially estrogen, regulate the mechanical, morphologic, and biochemical functions of the growth plate.

Animals↗

Changes in hepatic collagen metabolism in rats produced by chronic ethanol feeding.

The effect of ethanol feeding for a period of 6 months on parameters of hepatic collagen metabolism was studied in the rat. Ethanol feeding resulted in small increases in the fibrous and ground substance components of hepatic collagen as measured by increases in collagen-bound hydroxyproline and hexosamine, respectively. Liver histology revealagen proline hydroxylase and the incorporation of labeled proline into collagen by liver slices, both of which are associated with collagen synthesis, were not changed. Ethanol feeding resulted in increases in the concentration of protein and deoxyribonucleic acid in the Kupffer cells, but in no changes in collagenase activity. An increase in collagen degradation was suggested, however, by the increase in the urinary excretion of hydroxyproline and glycosaminoglycans found after 2 and 6 months of ethanol feeding, respectively. This study demonstrates that fatty infiltration of the liver in the rat, after prolonged ethanol feeding, is associated with increased deposition of chemically detectable collagen and evidence of increased collagen degradation, although no significant changes in parameters associated with hepatic collagen synthesis were found.

Alcoholism↗

[Chemical composition and degradation of the cells walls of a wild-type and of a white mutant of the mushroom Drechslera sorokiniana].

The cell walls of the fungus Drechslera sorokiniana and an albino mutant have been studied to determine if disappearance of pigment also involves an important modification of the chemical structure. The albino mutant has lost, besides the pigment, pentose, xylose, and part of galactose and mannose. The protein contents as well as those of hexosamine and chitin are not modified. After treatments of the walls with 2 M NaOH-0.5 M H2SO4 and with ethylenediamine identical compounds are isolated from the two walls; however, cell walls of the mutant are more easily and more extensively degraded than those of the wild type. This difference in resistance is not only due to the presence of pigment but also to a different architectural structure of the two cell walls.

Amino Acids↗

Mouse virulent strain of Staphylococcus epidermidis. Relation of antiphagocytic activity to the protection-inducing antigen.

Using 10(9) or 10(7) colony-forming units of a strain of Staphylococcus epidermidis (strain 1142) in saline or 5% mucin, respectively, 90 to 100% of mice died within 24 to 48 hr after intraperitoneal challenge infection. These organisms gradually multiplied in the peritoneal cavity when injected intraperitoneally into mice, while the mouse avirulent strain (strain 1124) rapidly decreased and no organisms were found there 20 hr after injection. This strain was capable of inducing resistance against challenge with homologous strains. The resistance appeared as early as the first week and disappeared the 4th week after the immunization. However, no resistance was induced with strain 1124 against challenge with strain 1142. Also, hyperimmune rabbit serum prepared with strain 1142 passively protected against challenge with homologous strain in mice. The protective antibody was absorbed out with homologous organisms but not with strain 1124. Subsequently, a surface substance was obtained from strains 1142 or 1124 by the method of Morse. The 1142 surface substance was capable of inducing a resistance against challenge with the homologous strain but not with the 1124 surface substance. Also, this substance absorbed the protective antibody in hyperimmune rabbit serum prepared with the homologous strain but not with the 1124 surface substance nor with the Smith surface antigen extracted from the Smith strain of Staphylococcus aureus. Conversely, the protective antibody in rabbit anti-Smith strain serum against challenge with the homologous strain was absorbed with the Smith surface antigen but not with the 1142 surface substance. In the agar diffusion test, the 1142 surface substance and the Smith surface antigen produced single precipitin lines only against homologous antisera. Biochemical analysis of the 1142 surface substance showed that the substance contained neither nucleic acids nor proteins but is composed of hexosamine, glycerol, phosphorus, alanine, glycine and phenylalanine.

Amino Acids↗

[The role of vitamin K in the metabolism of connective tissue biopolymers (review)].

Metabolism of connective tissue biopolymers was studied under conditions of various content of vitamin K in the body. The data obtained suggest the existence of a new metabolic effect of vitamin K--its participation as an allosteric activator in regulation of glucosamine synthetase (EC 5.3.1.19). The anabolic effect of vitamin K on connective tissue is apparently related to an increase in the rate of biosynthesis of glucosamine-6-phosphate--general precursor of glycosaminoglycans, glycoproteins and hexosamine-containing glycolipids.

Animals↗

A study on topographical change of proteoglycans in human lumbar disc.

Proteoglycan aggregates, the binding of disc proteoglycan to hyaluronate, chondroitin sulfate chain length, hexosamine and amino acid compositions were measured in different regions of the L1/L2 and L4/L5 intervertebral discs from 3 spines aged 35, 49, and 60 years. The results were as follows: proteoglycan aggregates and the binding of disc proteoglycan to hyaluronate were shown to increase from the nucleus pulposus to the outer annulus, while only small differences were observed among the anterior, posterior and lateral regions in either the inner or the outer annulus within a given disc. Changes in chondroitin sulfate chain length were observed with aging. However, within a given disc, and furthermore, within a given spine, chondroitin sulfate chains were similar in length. Glucosamine/galactosamine molar ratios of disc proteoglycan were higher in the L1/L2 disc than the L4/L5 disc. Changes with age were also observed. Nevertheless, only minor differences among the anterior, posterior and lateral regions of the annulus fibrosus were found within a given disc. The amino acid compositions showed small differences when proteoglycans from various regions of a disc were compared. All of them had a high content of aspartic acid, threonine, serine, glutamic acid, proline and glycine. The results indicate that it seems there are only minor differences among the anterior, posterior and lateral regions of the annulus fibrosus in a number of the experimented parameters.

Adult↗

Presence and functional significance of sulphates in the submandibular glands of growing rabbits.

A heteropolysaccharide formed by hexoses, hexosamines, fucose, sialic acid, uronic acids and sulphates was isolated from submandibular glands of rabbits during postnatal development. The presence of sulphates in the submandibular glands of growing animals and their absence in the submandibular glands of adult animals is rather difficult to explain. This biochemical investigation and preliminary results obtained by light and electron microscopy on the sublingual gland seem to suggest a substitutive role of the submandibular gland during the neonatal period.

Aging↗

Growth plate cartilage metabolism, morphology and biochemical composition in over- and underfed horses.

Weanling Thoroughbred horses were fed diets providing 70%, 100%, or 130% of their daily energy and protein requirements for eight months. Biopsy specimens of growth plate cartilage were taken from the distal right radius at this time. Tissues from both overfed and underfed horses exhibited significantly decreased protein, hydroxyproline and hexosamine contents (on a dry tissue weight basis), increased DNA content and decreased LDH activity, compared to tissues taken from the animals fed 100% of their daily requirements. Growth plate thickness was proportional to diet level. The reserve and hypertrophic zones were enlarged in the overfed horses. The hypertrophic cartilage from the overfed horses lost the usual columnar organization of lacunae and remained unpenetrated by metaphyseal capillaries. Longitudinal growth rates of the upper forelegs were reduced by under-nutrition and were unaffected by overfeeding. The similarities between the lesions accompanying chronic overfeeding and those of equine hypothyroidism suggest endocrine involvement linking dietary excess to developmental osteochondrosis.

Animal Nutritional Physiological Phenomena↗

[Metabolism of glycosaminoglycans and glycoproteids with experimental fractures].

Biochemical studies of the glycosaminoglycanes and glycoproteids metabolism in the callus, liver and blood serum of rabbits with extremty fractures showed that different stages of reparative osteogenesis are accompanied by considerable changes in metabolism of these substances in the callus, fragments adjoining it and the bone tissue of the intact extremty. At the early stages of the knitting consolidation an increase in the level of hyaluronic acid in the callus relatively to the total of glycosaminoglycanes is combined with a rise in the hyaluronidase activity. The rise in the content of carbohydrates bound with proteins: neuraminic acid, hexosamines, hexoses, in the callus, liver and blood serum is also established to be different in different periods of reparative osteogenesis. Comparison of the results of the studies showed a significant role of glycosaminoglycanes and glycoproteids metabolism in the processes knitting consolidation. The data obtained make it possible to specify the role of the bone tissue and liveer as sources of serum glycoproteids under considitions of experimental injury and to recommend the determination of the content of carbohydrate-protein compounds in blood serum as an additional criterion for the course of knitting consolidation.

Animals↗

Supersaturated bile from obese patients without gallstones supports cholesterol crystal growth but not nucleation.

Cholesterol crystal formation was studied in gallbladder bile samples collected from 18 patients with cholesterol gallstones, 6 patients with black pigment stones, and 14 obese patients without gallstones. In the absence of seed crystals, bile from patients with cholesterol stones showed a much greater tendency to form cholesterol crystals in vitro than bile of similar cholesterol saturation from patients without cholesterol stones. The ability to form crystals was not related to the biliary hexosamine concentration, an indicator of mucin content. When small seed crystals of cholesterol monohydrate were added to each bile, the seed crystals dissolved in all biles (n = 8) with a cholesterol saturation index less than 0.76. In contrast, 29 of 30 biles with a cholesterol saturation index greater than 0.76 supported crystal growth, even when collected from patients without gallstones. These results indicate that the difference between supersaturated biles in the ability to form cholesterol crystals resides at the nucleation, rather than the growth, stage of crystal formation.

Adult↗

[Effect of 1-(chloromethyl)silatrane on biochemical indices in the tissue of experimental gastric ulcer].

It has been demonstrated in rats with experimental gastric ulcer that 1-(chloromethyl) silatrane intensifies the development of granulation-fibrous tissue and favours optimization of the ratio of collagens and glycosaminoglycans, the main connective tissue biopolymers. Furthermore, 1-(chloromethyl) silatrane produces a more pronounced effect on hexosamine-containing glycoproteins in the ulcer tissue as compared with methyluracil and oxyferriscorbon. At the same time, judging by the time course of sialoproteins, the antiulcerous drugs, methyluracil and oxyferriscorbon, are much more effective antiinflammatory agents than 1-(chloromethyl)silatrane.

2,3-Diketogulonic Acid↗

Isolation of a chondroitin sulfate proteoglycan from a rat yolk sac tumor and immunochemical demonstration of its cell surface localization.

A proteoglycan was isolated from ascites fluid produced by a rat yolk sac tumor. The glycosaminoglycan chains of the proteoglycan are all sensitive to digestion with chondroitinase ABC and about 90% are sensitive to chondroitinase AC. The proteoglycan contains 5% protein. Amino acid analysis revealed a high content of serine and glycine which together constitute 37% of the amino acids. Glutamic acid (glutamine) and aspartic acid (asparagine) are also abundant. Galactosamine accounts for 97% of the hexosamine and the remainder is glucosamine. These characteristics indicate that the glycosaminoglycan side chains of this proteoglycan are predominantly chondroitin sulfate with a smaller amount of dermatan sulfate. Antibodies to the proteoglycan were prepared by immunization of a rabbit with purified alkali-treated proteoglycan. Affinity-purified antibodies from the antiserum immunoprecipitated (35S)sulfate-labeled radioactivity from culture media of the yolk sac tumor cells known to contain chondroitin sulfate proteoglycan. This binding was inhibited by the intact purified proteoglycan but not by proteoglycan treated with papain, suggesting dependence of the reactivity of the antibodies on integrity of the protein part of the proteoglycan. Immunofluorescence of the cultured yolk sac tumor cells revealed localization of immune reactive proteoglycans at the cell surface.

Amino Acids↗

The effect of lysophosphatidylcholine on gallbladder function in the cat.

The effects of lysoPC on gallbladder net fluid transport and motility were investigated by a perfusion technique in the anesthetized cat. It was found that addition of 1 mumol/ml lysoPC to the buffer perfusate resulted in an immediate contraction of the gallbladder and also a change in net fluid transport from a basal absorption of 0.71 ml/hr to a secretion of 0.34 ml/hr. An increased output of hexosamine and protein from the gallbladder accompanied the lysoPC treatment. Indomethacin--a prostaglandin synthetase inhibitor--at a dose of 2 mg/kg caused a relaxation of the gallbladder and abolished the secretion but did not return the gallbladder to its original rate of basal absorption. LysoPC, when added to bile, had a similar effect on net fluid transport but did not induce a contraction of the gallbladder. The results indicate that the effect of lysoPC on gallbladder function could be of importance in acute cholecystitis and that endogenous prostaglandin synthesis may play a part in this lysoPC-induced inflammatory response.

Animals↗