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Biomedical subjects

E Gruys

Publications and source records attributed to E Gruys.

At least 145 records · Page 8Linked to original sources

Amyloid enhancing factor in hamster.

An amyloid enhancing factor (AEF) was extracted from spleens and livers of casein-treated hamsters. It shortened the induction time of experimental amyloidosis in recipient hamsters from 14 days to 4 days. Sepharose-4B gel filtration resolved the extract into 4 different fractions, with molecular weights of: higher than IO(7) (Vo-fraction), about 280 000, 59 000 and 12 000 respectively. In all 4 fractions AEF was present, indicating that AEF is probably a low molecular weight substance that easily aggregates, or associates with other compounds present in the spleen extract. AEF was precipitable at 50% ammonium sulphate saturation. On anion exchange chromatography in PBS (pH 7.2) of this precipitate, AEF was found in the fraction eluting at high NaCl concentration. This fraction did not show any relation to hamster protein AA, IgG or albumin with double immunodiffusion. Ultraviolet absorption spectrophotometry indicated nucleotide-like material, suggesting AEF to be related to nucleoproteins.

Ammonium Sulfate↗

Pharmacokinetic and therapeutic activity of polyinosinic-polycytidylic acid stabilized with poly-L-lysine in carboxymethylcellulose [poly(I,C)-LC].

Polyinosinic-polycytidylic acid stabilized with poly-L-lysine in carboxymethylcellulose [poly(I,C)-LC] significantly augmented natural killer (NK) cell activity in several tissues. Macrophage (M phi) tumoricidal activity was also markedly increased. Both effector cells were active for 9 days. Poly(I,C)-LC also increased effector cell response in vitro. Injections of poly(I,C)-LC resulted in elevated effector cell responses in four of five routes tested. Treatment with poly(I,C)-LC led to an earlier reconstitution of bone marrow cells, NK cell activity, and M phi effector cell activity in mice pretreated with cyclophosphamide (Cytoxan). Combined treatment of MBL-2 tumor cells with cytoreductive chemotherapy and poly(I,C)-LC resulted in an enhanced therapeutic response.

Animals↗

Immunohistochemical identification and crossreactions of amyloid-A fibril protein in man and eleven other species.

Antisera were prepared in rabbits, sheep or chicken against purified amyloid fibril protein AA from man, mouse, stone marten, dog, cow and hamster. These antisera were tested by immunodiffusion against all purified antigens and applied to tissue sections containing amyloid from man, mouse, hamster, guinea pig, rabbit, cat, dog, mink, stone marten, pine marten, cow and horse. The binding of the antibodies to amyloid in tissue sections was assessed by the indirect immunoperoxidase method. The strongest reactions in the immunodiffusion and immunohistochemical methods were found between amyloid deposits of members of a given species and an antibody raised against protein AA from the same species. In contrast to the lack of cross-reactivity in immunodiffusion (except in the mouse-man relationship), extensive cross-reactions were observed immunohistochemically in phylogenetically related species, e.g. between stone marten, pine marten and mink, or between hamster and mouse. However, cross-reactions were also observed in combinations such as man-mouse, man-dog, man-cat, mouse-horse, and dog-cow. In addition, individual antisera showed variations in immunohistochemical reactivity with amyloid deposits of different members of one given species. Moreover, antisera prepared in rabbits reacted more restrictedly than those prepared in sheep, while rabbit antisera against any AA-protein did not react with rabbit amyloid. Finally, the widest degree of cross-reactivity including almost all mammalian species investigated was observed with a chicken antiserum to human amyloid AA protein.

Amyloid↗

A second component in bovine AA amyloid fibrils not identical with protein AA is essential for AA amyloid fibrillogenesis.

Amyloid fibrils were isolated from the renal papillae and glomeruli of cows with spontaneous AA amyloidosis. The fibrils were solubilized by treatment with guanidine hydrochloride (Gu HCl) and subjected to gel filtration on Sephacryl S-200. Two other fractions were obtained beside the void volume and the AA fractions. Reaggregation studies were performed by dialysing the fractions, separately or in combinations, against Gu-HCl-free solutions. Protein AA alone (about 10 kd) appeared not to precipitate. The other fractions alone and the combinations of fractions tested formed precipitates. The precipitates containing all fractions (including protein AA) or protein AA plus a fraction containing a 19- and a 23-kd protein revealed congophilic green birefringent fibrillar material. Dialysis against acidic and calcium-containing solutions gave the best results. Amyloid fibril-like material was visible on electron microscopic examination. The amino acid composition of the 19 + 23-kd material appeared to be slightly different from protein AA and evidently unlike SAP. On immunofluorescence-absorbance studies the 19 + 23-kd material appeared evidently unlike protein AA and SAP. From these findings it is concluded that for spontaneous formation of AA amyloid fibrils other non-AA proteins are necessary.

Amino Acids↗

Spontaneous hypertension and hypertensive renal disease in the fawn-hooded rat.

The fawn-hooded (FH) rat, a strain characterized by a platelet storage-pool disease, developed focal and segmental glomerulosclerosis at the age of 2-3 months (males) and approximately 6 months (females). Male animals died spontaneously at 11-13 months, and females at 15 months of age, both with overt malignant nephrosclerosis. During the first half year of life focal glomeruli showed depositions of IgG, IgA, IgM, C3 and fibrinogen in a segmental pattern and mainly in mesangial areas. Mesangial IgG and IgA were already demonstrable at the age of 5 weeks. On electron microscopy no electron-dense deposits suggestive of immune complexes were found. Mean arterial blood pressure in 5.5-month-old male FH rats was increased compared with that of matched Wistar rats. One-year-old FH rats had severe hypertension. The presumed relationship between the hypertension, the renal lesions and the blood platelet defect is discussed.

Animals↗

Amyloid deposits in bioprosthetic cardiac valves after long-term implantation in man. A new localization of amyloidosis.

Congo red staining with microscopic examination under polarized light was performed in 30 porcine bioprosthetic cardiac valves and one autologous fascia lata valve explanted from 31 patients in order to detect the presence of amyloid. Microdeposits of amyloid were present in the sewing ring of the fascia lata valve and in 10 porcine bioprostheses, and this finding was confirmed by transmission electron microscopy in 3 porcine bioprostheses. All amyloid-laden porcine valves had been implanted for at least 33 months before removal, and all except two showed dysfunction and/or severe degeneration of cuspal tissue. Statistical analyses failed to establish any correlation between the presence of amyloid and patient-related factors. In a majority of porcine bioprostheses amyloid was permanganate-sensitive and tryptophan-positive. The pathogenesis of this new form of heart valve amyloidosis might consist in penetration of human macrophages in deteriorated bioprosthetic cusps and their interaction with blood-borne amyloid precursors.

Adolescent↗

Isolation and characterization of C-reactive protein from the dog.

Using calcium-dependent affinity chromatography on Sepharose-bearing, covalently-coupled pneumococcal C-polysaccharide, a protein was isolated from the serum of dogs that had undergone general anaesthesia and major surgery. This protein was confirmed as the canine analogue of C-reactive protein (CRP) in other species by virtue of its electron microscopic appearance, subunit composition and behaviour as an acute phase reactant. Dog CRP had an apparent molecular weight of approximately 100,000 and was composed of five subunits of approximately 20,000 MW each. Two of the five subunits in each molecule were glycosylated. Negatively stained preparations had the typical cyclic pentameric disc-like structure of proteins of the pentraxin family, and in some preparations had a tendency to form stacks. Serum from normal healthy dogs of various strains usually contained less than 5 mg/l of CRP but, following the stimulus of major surgery, an increase in the CRP concentration was first detected at 4 hr.

Animals↗

Amyloid A proteins in different species.

Amyloid A (AA) proteins were purified from canine and bovine idiopathic amyloid and casein-induced hamster amyloid. The molecular weights of these proteins were in the same range (8,000-10,000) as those reported for AA proteins from man and other animal species. The amino acid compositions were comparable as well. Antisera against human, bovine, canine and hamster protein AA were tested with the indirect immunoperoxidase antiperoxidase (PAP) method and the indirect immunofluorescence technique on amyloid-containing human, bovine, canine and hamster tissue sections. Antihuman protein AA serum did not cross-react with hamster protein AA. In all the other combinations, cross-reactions were observed. Because of the high similarity of these different AA proteins, the amyloid diseases in the species mentioned can serve as interchangeable models to investigate the pathogenesis of AA amyloidosis.

Amino Acids↗

Porcine Parvovirus infection: review and diagnosis in a sow herd with reproductive failure.

In a commercial swine herd a rise was noted during the summer of 1981 in the number of repeat breeders, mostly four to eight weeks after serving. During the autumn there was a decrease in the litter size at birth and an increase in the number of stillborn and mummified piglets. Several gilts and sows showed a seroconversion against Porcine Parvovirus (PPV), determined by the Haemagglutination Inhibition test (HI-test). Characteristic pathological findings were seen in some maturely stillborn and neonatally decreased piglets (up to an age of 28 days); hepatic congestion and necrosis, accummulation of fluid in body cavities, myocarditis, and encephalitis were the most prominent features. Serological tests for antibodies in blood samples of one sow and body fluids of two stillborn piglets were suggestive of Porcine Parvovirus as the aetiological agent.

Animals↗

Urinary protein loss in the dog: nephrological study of 29 dogs without signs of renal disease.

In 29 dogs without any sign of renal disease, the total daily urinary protein loss was measured and related to renal morphology. The daily urinary protein loss was less than 10 mg/kg bodyweight in most dogs (24 out of 29). The median value of the protein loss in dogs with and without lesions differed significantly, as well as the median values of the ages of dogs with and without lesions. Polyacrylamide gel electrophoresis of urinary protein revealed the presence of albumin, high molecular weight and low molecular weight proteins. With immunofluorescence, especially, the presence of IgA (21 out of 28) and IgM (17 out of 28) was shown. In 12 out of 14 dogs with glomerular lesions IgA deposits were demonstrated (graded as +/- in two dogs and as + in 10 dogs), whereas in nine out of 14 dogs without glomerular lesions IgA deposits were demonstrated (graded as +/- in four dogs and as + in five dogs). The presence of IgA was significantly related to the presence of glomerular lesions (P less than 0.05). Fibrinogen degradation products were not detectable in urine from 15 of 23 dogs.

Albuminuria↗

Dubious effect of dimethylsulphoxide (DMSO) therapy on amyloid deposits and amyloidosis.

Data from the literature on DMSO therapy for amyloidosis in laboratory animals and man are reviewed and found to be inconclusive. In hamsters with casein-induced amyloidosis, as well as in dogs with spontaneous amyloidosis, therapeutic experiments with DMSO were performed. In these investigations no effect of DMSO on amyloid and amyloidosis was found.

Amyloid↗

Demonstration of multiple phenotypic diversity in a murine melanoma of recent origin.

The purpose of these studies was to examine whether the metastatic heterogeneity that is frequently found in serially transplanted neoplasms could be observed in a murine melanoma of recent origin. The primary K-1735 melanoma that arose in an inbred C3H/HeN murine mammary tumor virus-negative (C3H-) mouse was transplanted once into an immunosuppressed recipient and then established in culture. Cells from the fifth in vitro passage were used to produce clones. The parent K-1735 and 22 cloned lines were tumorigenic in syngeneic and outbred N:NIH(S) nude mice. Metastatic properties were assessed by observing the ability of the cells to produce pulmonary and extrapulmonary lesions after they were injected iv into 6-week-old C3H- mice. The number of metastases produced, their relative size, and pigmentation varied dramatically among the clones. Only 2 of 22 clones were indistinguishable from the parent tumor. Most of the nonmetastatic (but tumorigenic clones) were also nonmetastatic in 3-week-old nude mice, which suggests that the absence of metastasis formation was not merely due to their immunologic rejection by the normal C3H- mouse. Control subcloning experiments demonstrated that the procedure of cloning in vitro was not responsible for the variability among the clones. The clones did not differ in their karyotype or cell size, but they did differ in their growth rate in vitro. These phenotypes, however, did not correlate with metastatic propensity. In conclusion, the K-1735, a murine melanoma of most recent origin, is heterogeneous and contains subpopulations of cells with diverse biologic behavior.

Animals↗

[Hereditary lysosomal storage diseases (author's transl)].

The literature on hereditary lysosomal storage diseases occurring in man and various domestic animals is reviewed. These forms of disease are usually recessively autosomally heritable and are reflected in partial or total deficiency of a lysosomal enzyme, resulting in accumulation of metabolites. The majority of these lysosomal storage diseases show a predilection for localization in the nervous system. As a rule, the main clinical features are neurological symptoms. The first symptoms are usually observed at an early age and the disease is marked by the fact that it is familial in character. Heterozygotes may be identified by controlled haematological studies in a number of these diseases. In domestic animals, these forms of disease may serve as models for human pathology and some may be of economic importance, such as mannosidosis of Angus cattle in New Zealand and GM1 gangliosidosis of Friesian cattle in Ireland.

Animals↗

[Renal failure caused by mercury and lead poisoning in the calf (author's transl)].

The renal lesions in three calves with mercury poisoning (phenylmercuric acetate) and two calves with lead poisoning are described. In addition of slight tubular degeneration, glomerulonephritis occurred in the animals with mercury poisoning. Moreover, uraemia, oedema and haemorrhages were present. Lesions of the brain not were found. In the animals with lead poisoning, chronic renal tubular changes and characteristic intranuclear inclusion bodies in the proximal tubular cells were observed. The juxtamedullary glomeruli showed proliferative mesangial lesions. In one calf, the cerebral cortex showed oedema, necrosis of neurons and an increase in glial cells.

Animals↗

Nephrogenic diabetes insipidus in a dog with renal medullary lesions.

Antidiuretic hormone (ADH) administration to a polyuric Miniature Poodle did not alter diuresis. Plasma ADH concentrations were high, and urine osmolality remained low during water deprivation. From these findings, it was concluded that the polyuria was of renal origin. In addition, the glomerular filtration rate was found to be high. Electron microscopic examination of the renal medulla revealed vacuoles containing myelinic figures and fingerprint structures in the cells of the Henle loops, blood vessels, and interstitium, similar to those in lysosomal lipid storage disease. Their absence in collecting duct epithelium indicated that the defect in concentrating ability was due to a disturbance of the counter-current multiplier mechanism rather than to a defect in ADH receptors.

Animals↗

Deposition of amyloid in the liver of hamsters: an enzyme-histochemical and electron-microscopical study.

In induced amyloidosis the amyloid was first deposited in the portal areas, then in the centre of the lobule and disseminated through it in the spaces of Disse. No intracellular amyloid was found in the predeposit phase. In the hepatic lobule both mononuclear phagocytes and hepatocytes showed a topographic relationship to the first deposits of amyloid. Some macrophages showed invaginations or vacuoles containing amyloid fibrils. Between the microvilli of hepatocytes, parallel amyloid fibrils occurred. Between the amyloid fibrils were 30-50 nm membrane-bounded spherical particles which may have been lipoprotein aggregates. There was no large-scale phagocytosis of amyloid during the induction period or after survival without casein treatment up to 18 weeks. Lysosomal enzyme activity was seen in the deposits of extracellular amyloid.

Amyloid↗