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The farmed blue fox (Alopex lagopus) is particularly susceptible to congenital infections of the microsporidian species Encephalitozoon cuniculi. This report is based on an outbreak of the disease in Finland with high mortality. Five pups (four males and one female) with prolonged disease were examined. The pups had moderate pathological alterations in the kidneys and mild lesions were found in the brains, hearts, salivary and prostatic glands. Diagnosis of E. cuniculi infection was made from serological tests (ELISA, CIA, IFAT), and by in vitro isolation of the parasite from the brain of all five pups investigated. The identity was confirmed by molecular means as E. cuniculi strain II ('mouse strain'). Novel histopathological lesions not described as yet in fox encephalitozoonosis are presented. These include cerebral infarction and necrotizing inflammation of the renal pelvis. The sources and mechanisms of spreading of E. cuniculi to blue foxes are discussed.

A severe hyperlipemia in mink, with a pattern that suggested recessive inheritance, was observed at a farm in Norway. On a normal mink diet, affected animals had grossly elevated levels of plasma triglycerides which decreased towards normal on a low-fat diet. Normal minks had the main part of their plasma cholesterol in the HDL fraction. Affected minks, although severely hypertriglyceridaemic, had almost normal levels of both LDL and HDL. Affected minks frequently had lipogranulomas in the mesentery and the pancreas. The lipogranulomatous tissue contained spaces filled with an amorphous, sudanophilic substance with many foamy macrophages in the fibrous tissue between the lesions. Separation of postheparin plasma on heparin-agarose revealed that the affected minks had no detectable lipoprotein lipase activity but normal activity of hepatic lipase. Both normal and affected minks had inactive lipoprotein lipase protein in pre- and post-heparin plasma. This protein, which eluted before the active lipase from heparin-agarose, probably corresponds to lipase monomers. The presence of lipoprotein lipase mass in the affected minks, but no activity, indicates that there might be a point mutation in the lipase gene. The minks provide a new animal model for studies on pancreatitis induced by hypertriglyceridemia and on lipoprotein metabolism in the lipoprotein lipase-deficient state and show features similar to those found in human hyperlipoproteinemia type I.

Summary Bovine kidney material with advanced glomerular deposits of amyloid was studied immunohistochemically using the avidin biotin complex immunoperoxidase method, with rabbit antihorse AA serum as primary antibody. Severely affected glomeruli consisted of strongly reacting positive material, obscuring all cellular structures. Transmission electron microscopy revealed that the amyloidotic areas, with evident amyloid fibrils, also contained a considerable admixture of cellular remnants. In this investigation it was found that such material was more abundant in the bovine glomerular amyloid masses than in amyloid laden organs from other animal species, and it is discussed to what extent this observation may explain the varying tinctorial properties of amyloid deposits in bovine tissues, and the relative high content of histones in bovine amyloid proteins.

Bovine serum amyloid A (SAA) was isolated from the acute phase high density lipoprotein (HDL) fraction of a cow suffering from acute mastitis. The elucidated primary structure revealed a protein consisting of 112 amino acid residues. Compared with SAA proteins from other species, the bovine protein was shown to have an insertion of nine amino acid residues between positions 69 and 70. No microheterogeneity could be observed in the protein. Amyloid fibrils extracted from the kidneys were found to contain at least three subspecies of protein AA, consisting of 68, 81 and about 110 amino acid residues. The amino acid sequences established for the protein AA subspecies revealed no microheterogeneity, and were identical to that elucidated for protein SAA.

Six calves were infected per os with Salmonella dublin and killed nine hours to seven days later. Early changes included occlusion of capillaries with a hyaline material, particularly in the ileal Peyer's patch (PP). Central areas of the follicles contained hemorrhages and edema. In later stages the follicle-associated epithelium (FAE) of both the jejunal and ileal PP was fused with the adjacent epithelium and the follicles were collapsed. As judged from 5'nucleotidase histochemistry, follicles were depleted of lymphocytes whereas reticular cells were retained. Carbonic anhydrase (CA) histochemistry showed a decreased reaction in the ileal FAE and a reduced amount of CA reactive material in the follicles of the ileal PP, indicating loss of FAE differentiation and function. Hyaline material and fibrinous thrombi were seen occluding the blood capillaries and the lymphatics, respectively. The villi were atrophied and covered with thick fibrin deposits. Using antifibrinogen antibodies, immunoperoxidase stained fibrin in the lymphatics and the lumenal deposits but not the hyaline material in the capillaries. Reaction for CA indicated that this hyaline material originated from erythrocytes. Factors contributing to the follicle atrophy may include anoxia due to stasis in the microcirculation with the formation of erythrocyte thrombi, and reduced lymphopoiesis due to a decrease in the stimulating factors provided by the FAE.

Mussel samples from four locations along the Norweigian coast were extracted by methods for diarrheic shellfish toxins (DST) and tested by chemical and biological methods, including histopathology. All samples had previously been found to be highly toxic in mice, with symptoms indicating the presence of non-diarrheagenic toxins in the mouse bioassay. Chemical analysis revealed that the DST okadaic acid (OA) and dinophysistoxin-1 (DTX1) were present each one in one sample, but only a minor part of the total toxicity could be attributed to these toxions. In the other two samples, OA and DTX1 were absent. Incubation of the mussel extracts from all four samples with freshly prepared hepatocytes indicated the presence of unknown toxin(s) which may not be classified within the DST complex. Purified mussel samples were given to baby mice both via intraperitoneal (i.p.) injections and by oral intubation. Oral toxicity was about 25-50 times lower than toxicity obtained by i.p. injections, a result in accordance with acute toxic properties of many toxins. Risk assessment of the unknown toxin(s) requires chemical identification, but the preliminary results obtained indicate a large margin of safety, based on the large amounts of mussel extracts necessary to yield toxic effects in the intestine and liver in experimental animals upon oral exposure versus human intake.

A severe hyperlipemia in mink, with a pattern that suggested recessive inheritance, was observed at a farm in Norway. On a normal mink diet, affected animals had grossly elevated levels of plasma triglycerides which decreased towards normal on a low-fat diet. Normal minks had the main part of their plasma cholesterol in the HDL fraction. Affected minks, although severely hypertriglyceridaemic, had almost normal levels of both LDL and HDL. Affected minks frequently had lipogranulomas in the mesentery and the pancreas. The lipogranulomatous tissue contained spaces filled with an amorphous, sudanophilic substance with many foamy macrophages in the fibrous tissue between the lesions. Separation of postheparin plasma on heparin-agarose revealed that the affected minks had no detectable lipoprotein lipase activity but normal activity of hepatic lipase. Both normal and affected minks had inactive lipoprotein lipase protein in pre- and post-heparin plasma. This protein, which eluted before the active lipase from heparin-agarose, probably corresponds to lipase monomers. The presence of lipoprotein lipase mass in the affected minks, but no activity, indicates that there might be a point mutation in the lipase gene. The minks provide a new animal model for studies on pancreatitis induced by hypertriglyceridemia and on lipoprotein metabolism in the lipoprotein lipase-deficient state and show features similar to those found in human hyperlipoproteinemia type I.

Two-dimensional electrophoresis and N-terminal analysis were used to study serum amyloid A protein (SAA) from humans, mink, fox, goat and rabbit. Previously uncharacterized SAA variants were demonstrated in fox, goat and rabbit, and considerable interspecies homology was seen. In rabbit, two novel SAAs were characterized, and SAA1 and SAA2 were demonstrated in mink and rabbit sera. The results confirm previous cDNA studies and indicate that SAA do possess an important function also in fox and goat.

A Norwegian Canine Cancer Registry, covering four of 19 counties, has been operative since March 1990. Until the end of April 1994 about 6,000 tumours have been registered, more than 50% of these being manifestly or potentially malignant. Among 14 selected breeds the relative risk ratio for all tumours varies with factor 35 from boxer to dunker, the boxer having the highest tumour risk. The percentage distribution of specified tumour types also varies greatly between breeds, mammary cancer constituting 59% of all neoplasms in the dachshund, but only 4% in the Bernese mountain dog. Because of the genetic diversity between breeds the dog is a suitable species for differentiation between genetically determined predisposition and environmental influences in the etiology of cancer. Epidemiological surveillance of cancer morbidity in dogs may be a useful instrument for tracing carcinogens, even in the surroundings of man.

Summary An abattoir survey of renal lesions in Norwegian slaughter pigs demonstrated the presence of a macroscopic evident nephropathy characterised by pale, slightly enlarged and fibrotic kidneys in 143 out of 668 (21.4%) examined carcasses. At light microscopy fibrotic kidneys revealed glomerular lesions characterised by a diffuse mesangial proliferative glomerulopathy. Immunohistochemical examination demonstrated mesangial and paramesangial immune complex deposition containing IgM and C3, and to a lesser degree IgA and IgG in the glomeruli of fibrotic kidneys. Our observation of glomerular lesions caused by immune complex depositions in fibrotic pig kidneys are compared with mesangial nephropathies in man.

About 50 years ago crystalline deposits of a substance representing approximately 7 per cent wet tissue weight and believed to be hentriacontane or a mixture of similar long-chain n-alkanes (30-34 carbon atoms) were detected in two discoloured and swollen cow livers. Stored purified extracts from these livers were recently reanalysed using gas chromatography and mass spectrometry. They were found to contain about equal amounts of nonacosane and hentriacontane with a small admixture of tritriacontane and other long carbon-chain alkanes. On the basis of histological findings, five additional cases of "paraffin liver" in cows have been recorded. In the discussion comparison is made with the only known case of a similar disorder in a human, visceral accumulation of the same three alkanes as in the cows, which was recently described in the literature. Concerning the origin of the deposits, importance is given to the fact that the long-chain alkanes with odd carbon numbers identified both in cattle and man predominate in the cuticular waxes of many dietary plants. The very large quantities of the abnormal substance in the cow livers indicate low toxicity, and evidently accumulation over long periods of time.

Summary Six hundred and sixty-eight consecutive carcasses of slaughtered swine were examined for renal lesions at meat inspection. The macroscopic lesions were divided into 7 categories: D1 = depressions of the external surface and partial persistence of fetal lobation; D2 = focal leukolymphocytic nephritis (acute focal tubulo-interstitial nephritis); D3 = cysts; D4 = interstitial fibrosis; D5 = infarct-like lesions; D6 = fatty degeneration, and D7 = hydronephrosis. 396 (59.3 %) of the examined carcasses were diagnosed as having one or more of these renal lesions. Two hundred and seventy-two (40.7%) of the carcasses were macroscopically judged as having normal kidneys. A selected material of 250 kidneys representative for each group of lesions based on macroscopic examination and 50 normal kidneys were prepared for histological examination. In the group of kidneys with the macroscopic diagnosis interstitial fibrosis (D4), an accompanying histological finding was proliferative glomerular changes with fatty degeneration of the proximal tubules. Cortical infarct-like lesions (D5) were observed in the absence of thrombo-embolic disease and were considered to have developed in association with local arterial alterations similar to polyarteritis nodosa.

The elution pattern obtained when amyloid fibrils from amyloid-laden bovine kidneys were subjected to gel filtration under dissociating conditions revealed a larger amount of non-AA material (eluting between the void volume and protein AA) than usually seen in other species. SDS-PAGE of this non-AA fraction yielded several Coomassie blue stained bands. The most distinctive ones gave estimated molecular masses of 15 kDa, 18 kDa, 33 kDa and 43 kDa. These molecular species were electroblotted onto PVDF membranes, and were further characterized by amino acid composition analyses, cyanogen bromide cleavage and N-terminal analyses. The results revealed that the intermediate 'non-AA' fraction consisted of histones H2B, H3 and H4 in addition to protein AA also found in this fraction.

Serum activities of gamma-glutamyl transferase (GGT), alkaline phosphatase (AP), aspartate aminotransferase (AST), and concentrations of total bilirubin and total bile acids were screened during a 5 year period in 27 horses used for production of hyperimmune serum. The horses investigated were regularly immunized with live cultures of the endotoxin-releasing bacteria Escherichia coli or Pasteurella multocida, the individual animals having undergone such treatment for periods varying from 2 weeks to 10 years. In a majority of the horses, GGT-activity had increased within 6 to 7 years of first having undergone immunization. Constantly high values seemed to co-incide with the presence of advanced liver amyloidosis, as demonstrated by histopathological examination after slaughter. The AP activity was also increased but only moderately compared with GGT. Individual values more than 10-fold greater than the upper reference limit were recorded for GGT, while the highest AP values were less than double the upper reference limit. Activity of AST and bilirubin concentrations remained unaffected, whereas the concentration of total bile acids rose after 6 to 7 years of immunization compared to the baseline value. It is concluded that the determination of serum activities of GGT may serve as a practical routine test for the evaluation of liver amyloidosis status in serum horses.

The elution pattern obtained when amyloid fibrils from amyloid-laden bovine kidneys were subjected to gelfiltration under dissociating conditions, revealed a larger amount of non-AA material than usually seen from other species. SDS-PAGE of this non-AA fraction yielded several Coomassie blue stained bands. The most distinctive ones gave estimated molecular weights of 15 kDa, 18 kDa, 33 kDa and 43 kDa. These molecular species were further characterised by electroblotting, cyanogen bromide cleavage and N-terminal analysis. The results revealed that the non-AA fraction consisted of histones H2B, H3 and H4 in addition to protein AA.

When Northern blot analysis of LPS stimulated mink liver RNA was performed using a SAA specific probe, several signals were found. Nucleotide sequence analysis of two clones from a cDNA library was performed. Deduced amino acid sequence of the longer one, SAA1 (776 bp), indicates that it represents a SAA isotype found only in serum, while the shorter one, SAA2 (552 bp), corresponds to an isotype found both in serum and degraded to protein AA in secondary amyloid. These results show that the situation in mink is the same as in mice, where only one out of at least two SAA isotypes has been shown to be amyloidogenic. Northern blot analysis also showed that almost all SAA mRNA was found in the liver, while only minor amounts of SAA1 and SAA2 mRNA was found in the brain and the lungs. No signals could be detected in amyloid prone organs like intestine and spleen. In the liver a SAA specific signal was found corresponding to 2.2 kb, and after in vitro translation a protein SAA band corresponding to 28,000 Daltons was detected, indicating that a SAA isotype with high molecular weight exists in this animal.

The goal of this work was to determine the complete covalent structures of the bovine proteins SAA and AA. Protein AA was isolated from the amyloid fibrils extracted from the kidneys. Three molecular species of protein AA was characterised and were found to consist of 68, 81 and about 112 amino acid residues, respectively. The protein SAA isolated from acute phase HDL was composed of 112 amino acid residues. The amino acid sequence elucidated for the protein AA subspecies was identical to that determined for protein SAA. No microheterogeneity could be detected in the amino acid sequence of protein SAA or of protein AA subspecies. The data thus suggest the existence of only one molecular species of protein SAA and that this species is amyloidogenic. As shown for the equine protein SAA, an insertion of several amino acid residues between positions 68 and 69 could be established.

Alveld is a hepatogenous photosensitization disease seen in lambs grazing Narthecium ossifragum pastures in Norway. Mycotoxins, possibly sporidesmin, have been suspected to cause the liver damage in alvled as in facial eczema. The histological changes in the liver of alveld cases and in lambs photosensitized after experimental sporidesmin intoxication were compared. The liver damage, characterized by necrosis in single centrilobular hepatocytes, was of the same type in both conditions. Minor to moderate portal fibroplasia and bile duct proliferation were almost always present. Accumulated glycogen was seen in hepatocytes in the centrilobular areas. This was significantly correlated to the enzymatically measured glycogen content and there was good correlation between parenchymal damage and glycogen accumulation. The glucose-6-phosphatase and glycogen phosphorylase activities were normal. These findings indicate that parenchymal damage, rather than obstruction of the bile ducts, caused the retention of phylloerythrin both in alveld cases and in experimentally sporidesmin-intoxicated lambs. The accumulation of glycogen could not be explained.

Six calves were infected per os with Salmonella dublin and killed nine hours to seven days later. Early changes included occlusion of capillaries with a hyaline material, particularly in the ileal Peyer's patch (PP). Central areas of the follicles contained hemorrhages and edema. In later stages the follicle-associated epithelium (FAE) of both the jejunal and ileal PP was fused with the adjacent epithelium and the follicles were collapsed. As judged from 5'nucleotidase histochemistry, follicles were depleted of lymphocytes whereas reticular cells were retained. Carbonic anhydrase (CA) histochemistry showed a decreased reaction in the ileal FAE and a reduced amount of CA reactive material in the follicles of the ileal PP, indicating loss of FAE differentiation and function. Hyaline material and fibrinous thrombi were seen occluding the blood capillaries and the lymphatics, respectively. The villi were atrophied and covered with thick fibrin deposits. Using antifibrinogen antibodies, immunoperoxidase stained fibrin in the lymphatics and the lumenal deposits but not the hyaline material in the capillaries. Reaction for CA indicated that this hyaline material originated from erythrocytes. Factors contributing to the follicle atrophy may include anoxia due to stasis in the microcirculation with the formation of erythrocyte thrombi, and reduced lymphopoiesis due to a decrease in the stimulating factors provided by the FAE.

The concentration of the amyloid AA-related serum protein (SAA) was markedly increased after endotoxin injections in mink, mouse, rabbit, and man. It was particularly studied during the development of endotoxin-induced amyloidosis of the mink. Protein SAA was markedly elevated in all mink 24 h after the first endotoxin injection but had fallen to relatively low levels before the onset of amyloidosis at about 4 wk. These results are consistent with SAA being a circulating precursor of the amyloid fibril protein, AA. However, both proteins may be derived by proteolysis from a common precursor.

The serum proteins in Sapphire mink from the experimental and control groups in 2 endotoxin experiments and in a group of normal mink of the Standard type, were separated electrophoretically on cellulose acetate membranes. In experiment No. 1, in which the experimental mink were given repeated injections of endotoxin, and the controls were untreated, significantly increased total protein and significantly decreased albumin concentrations in the experimental group compared to the normal group were demonstrated. The concentration of the alpha(1)-globulin was significantly elevated and the alpha(2)-globulin significantly reduced in the experimental and the control groups compared to the normal group. Significant differences between the gamma-globulin concentrations in the various groups were not found. In experiment No. 2, all the animals were inoculated intraperitoneally with a crude tissue suspension containing the plasmacytosis agent 10 days before the experimental animals received the first of a series of injections with endotoxin. Significantly increased concentrations of total protein and gamma-globulin and significantly decreased albumin concentrations were, compared with the normal group, demonstrated in sera collected from the experimental group on the 94th, 201st and 254th day after the first injection of endotoxin. In the control group, compared with the normal group, significantly elevated concentrations of total protein, alpha(2)-, beta- and gamma-globulins and significantly reduced albumin- and alpha(1)-globulin were found but only in the second set of samples, while significantly decreased albumin- and significantly increased gamma-globulin concentrations were found in the third set. The results showed no significant differences between the gammaglobulin concentrations or between the other serum fractions in the experimental and the control groups in the 2 experiments. A possible explanation may be that there is no direct interrelationship between hypergammaglobulinaemia and amyloidosis, and that a common basic mechanism may stimulate related stem cells which thereafter differentiate in different ways.

The amyloid-related serum protein SAA has been isolated by gel filtration in 10% formic acid from three animal species: mink, mouse, and rabbit. Sera used in the isolation procedure were obtained from animals in which high concentrations of SAA had been induced by treatment with LPS. The isolated SAA proteins had a subunit size similar to that of human SAA, with m.w. values ranging from 10,000 to 11,700 (estimated by gel filtration in 6 M guanidine-HCl) or 12,400 to 15,000 (estimated by SDS-PAGE). The m.w. studies and amino acid sequence data indicated that SAA and the amyloid fibril protein AA in the mouse, and probably also the mink, are related in the same way as in man, the two proteins having common NH2-terminal amino acid sequences and SAA being extended by 20 to 40 residues at the COOH-terminal end of the molecule.

An outbreak of endometritis and septicaemia in farms that raise Arctic blue foxes is described. Eleven animals from eight different farms were examined, most of them pregnant or with newly delivered litters. Pathological examination indicated inflammation of the uterus, and focal necrotic changes in the liver. In some animals evidence of hemorrhaging was found in the anterior part of the small intestine. Bacteriological examination revealed abundant growth from different organs of the animals of a pure culture of a small, slender, Gram-variable, sporeforming rod, which was identified phenotypically as aerotolerant Clostridium carnis. This identification was confirmed by DNA hybridization. The organism caused death in mice 1–2 days after intraperitoneal inoculation, and killed an Arctic blue fox which was inoculated intracervically. Two foxes, pretreated with diethyl-stilboestrol, became seriously ill after intrauterine inoculation, but survived. The spontaneous outbreak of the disease was characterized by sudden onset of septicaemia with few or no clinical symptoms before the animals succumbed.

Amyloid was extracted from the liver of a horse that had developed amyloidosis after being used for several years for the production of antibodies to bacterial antigens. The amyloid fibrils were shown to be of the AA type. Two AA proteins with molecular weights of 9000 and 11,000 and with identical partial N-terminal amino acid sequences were identified. Marked structural homology with AA from other species including man was seen, although clear species-related antigenic specificity was observed. SAA isolated from an acute phase (septic abortion) horse serum was identical to AA with respect to antigenicity and the 10 first N-terminal amino acid residues that have been studied up to now. The bulk of SAA was present in the high-density lipoprotein complex in serum. Also SAA was heterogeneous with respect to size, most molecules having a molecular weight of 11,000, and a minority 9000.

Intravascular hemolysis and ultrastructure of erythrocytes from liver sinusoids were studied during and after infusion of Escherichia coli endotoxin in Labrador retriever dogs. Endotoxin infusion caused hemoconcentration, and induced disseminated intravascular coagulation (DIC), characterized by a rapid drop of platelet numbers, a gradual consumption of coagulation factors and activation of fibrinolysis. Advanced DIC and circulatory shock gradually developed, and the animals died after 7-15 h. Plasma hemoglobin concentrations did not rise for several hours, but late in the experimental period a significant intravascular hemolysis was constantly found. Circulating adenosine diphosphate (ADP) did not appear. During shock, liver biopsies revealed accumulation of erythrocytes often disintegrated within distended sinusoidal lumina. In advanced shock the fragmented erythrocyte seemed to form occlusive masses within the vessels. A fibrin-like material frequently appeared adjacent to the red cells. However, it did not have the periodicity characteristic for fibrin, and the ultrastructure of the material was very similar to that inside the erythrocytes. None of these changes were induced by saline infusion in control animals. The lack of fibrin formation and the late development of intravascular hemolysis indicate that red cell breakdown was of little importance for the initiation and progress of DIC.

During recent years, nosematosis (syn. encephalitozoonosis) has caused serious losses among young blue foxes (Alopex lagopus) in Norway; the causative organism is considered to be Nosema (syn. Encephalitozoon) cuniculi. Descriptions of clinical symptoms and patho-morphological changes on which the diagnosis is based have been given in previous papers (Nordstoga 1972, Nordstoga et al 1974, Nordstoga & Westbye 1976). The disease, as a rule, is restricted to certain litters, in which several or all pups are affected, a pattern which indicates a congenital infection. In a previous report we presented experimental evidence for transplacental transmission, after oral infection of the dam (Mohn et al. 1974). Although we feel that oral exposure, resulting in subclinical infection, is the most common way in which the dams are infected, field observations indicate that the organisms, in rare cases, may be transmitted from the male during matins.

Serum amyloid A protein (SAA) was isolated from mink, horse, and human serum by ultracentrifugation and gel filtration and characterized by two-dimensional gel electrophoresis, Western blotting followed by autoradiography and N-terminal amino acid analysis. SAA was found in similar quantities in the high density lipoprotein (HDL) fraction of serum from a patient suffering from systemic juvenile rheumatoid arthritis (JRA) and mink stimulated with lipopolysaccharide (LPS), and in somewhat smaller quantities in serum from horses stimulated with Escherichia coli cultures. Only very small quantities were present in normal human controls and not detectable in normal mink and horse. Striking similarities were found between human and mink SAA with respect to molecular weight, isoelectric point and degree of heterogeneity, while the molecular weight of horse SAA seemed to be somewhat lower, and no obvious heterogeneity could be demonstrated in this protein using two-dimensional gel electrophoresis. Immunologic cross-reactivity between SAA from the three species was not found. In contrast to human and horse HDL, mink HDL was found not to contain apoA-II and only minute amounts of apoC proteins. Normal horse HDL also contained additional apoproteins not present in HDL from the other species. N-terminal amino acids analysis of SAA from mink and horse demonstrated the same similarity with the corresponding AA protein as previously reported for human SAA/AA.

A survey of polyarteritis nodosa in domestic animals is presented, including a description of the patho-morphological lesions and a discussion on the causal factors. This vascular disease occurs in domestic animals in association with both viral infections (infectious plasmacytosis in mink), bacterial infections (erysipelas in swine), and protozoan infections (nosematosis in blue foxes). The conclusion is drawn that the observations in domestic animals support the view that immunological disturbances are involved as pathogenetic mechanisms. Nosematosis is dealt with in more detail; the infecting agent (fig. 1), Nosema cuniculi (Encephalitozoon cuniculi), is a widespread mamalian parasite, which causes cerebral and renal lesions in blue foxes of the same type as in animals of other species. In addition, the vascular system throughout the body is affected, resulting in patho-morphological alterations corresponding to classical polyarteritis nodosa (Fig. 2). In the early stages of involvement, masses of parasitic organisms are regularly found within the walls of affected arteries (Fig. 3). This disease is frequently lethal, and always accompanied by elevated values of gamma globulins. Both the hypergammaglobulinemia and the tissue lesions, seem at times, at least in part, to be reversible.

The clinical features of a case of granulosa cell tumour in the blue fox (Alopex lagopus) are described. The associated hormonal changes are discussed in relation to present knowledge of the regulation of the oestrous and furring cycles in this species.

The serum proteins in 1 group of healthy breeders, 1 group of healthy pups and 4 groups of foxes suffering from various diseases were separated electrophoretically on cellulose acetate membranes. In most of the sera, the proteins were separated into 1 albumin fraction and 5 globulin fractions designated alpha(1), alpha(2), alpha(3), beta and gamma. The mean concentrations of the total proteins and the various serum fractions in the disease groups were compared statistically with the mean values of the normal groups. A nosematosis group was characterized by a distinct hypergammaglobulinaemia together with an increase in the total protein — and a decrease in the albumin concentrations. However, in 2 cubs recovering from nosematosis the hypergammaglobulinaemia was shown to be reversible. In a feed intoxication group the concentration of albumin was found to be lower and the alpha(3)-globulin higher than the corresponding values in the healthy group. A virus hepatitis group was characterized by a decrease in the concentrations of albumin and beta-globulin and an increase in the alpha(1)- and alpha(3)-globulins. In the toxoplasmosis group the total protein and alpha(1)- and alpha(3)-globulins showed concentrations below the normal values.

The patho-morphological alterations in porcine intestinal adenomatosis were studied by light- and electron microscopy, and the pathogenetic mechanisms leading to the adenomatous lesions were discussed. The intestinal changes were partly interpreted as degenerative modifications, partly as hyperplastic processes. In some areas there seemed to be an uncontrolled proliferation of poorly differentiated crypt epithelium, resulting in adenomatous changes. These lesions were associated with intracellular location of bacteria. It was assumed that the epithelial hyperplasia in areas with normal differentiation of crypt cells was an expression of a regenerative reaction. It was further assumed that the faulty regeneration of intestinal mucosa occurred in areas where the mesenchymal destruction was too advanced to allow complete morphological restoration.

Newborn and young pups up to the age of 15 days were exposed to E. cuniculi, either by keeping the pups in cages together with orally inoculated foster-mothers and their offspring, or by oral inoculation with E. cuniculi spores. A majority of pups appeared sero-positive to E. cuniculi with the india-ink immuno-reaction from 35 to 87 days post exposure; spores of E. cuniculi were detected in organs of some of the animals. The non-inoculated pups kept together with the orally inoculated pups became seropositive from 49 to 129 days after the oral inoculations. However, the exposure of newborn and young pups failed to induce clinical encephalitozoo-nosis, and when killed at the time of pelting the body weights and fur quality appeared to be within the normal range in all exposed foxes. No macroscopic lesions were detected in the various organs. Histologically focal interstitial nephritis occurred in the great majority of the seropositive animals. Meningoencephalitis was seen in some of the foxes, whereas slightly thickened walls of some arteries, mainly in the myocardium, were found in a few animals. The lesions of the brain and kidneys seem to be very similar to those seen in chronic cases of rabbit encephalitozoonosis. Polyarteritis nodosa and severe encephalitis and interstitial nephritis with extensive proliferations of plasma cells, which are almost constant findings in cases of clinically diseased foxes, were not detected in any of the subclinically infected animals. Various factors that might be of significance in the pathogenesis of the disease are discussed, and it is concluded that intrauterine infection of the pups via the transplacental route appears to be an essential supposition for the establishment of clinical fox encephalitozoonosis.

Investigations concerning the effect on fur-bearing animals of large doses of vitamin D3 were carried out. The material comprised 62 animals in all--10 silver foxes, 17 blue foxes and 35 mink (Table II). Daily doses of 5 IU vitamin D3/g body weight for two months did not produce clinical symptoms in the foxes. However, a short while after the dose was increased to 10 IU, the animals showed loss of appetite, had difficulty in moving, were apathetic and developed dark coloured faeces. Analysis of blood serum showed markedly raised calcium values (Table III). Calcium deposits were demonstrated in the kidneys and in some cases also in the musculature, gastric mucosa, bronchi and the larger blood vessels. No abnormal signs were shown by 30 mink which received 0.6--0.7 IU vitamin D3/g body weight for five months. PM findings were normal.

1. 1. Serum amyloid A protein (SAA) was isolated from mink and human serum by ultracentrifugation and gel filtration and characterized by two-dimensional gel electrophoresis and Western blotting followed by autoradiography. 2. 2. SAA was found in similar quantities in the high density lipoprotein (HDL) fraction of serum from a patient suffering from systemic juvenile rheumatoid arthritis (JRA) and mink stimulated with lipopolysaccharide (LPS). Only very small quantities were present in normal human controls and not detectable in normal mink. 3. 3. Striking similarities were found in molecular weight, isoelectric point and degree of heterogeneity for human and mink SAA, while immunologic cross-reactivity between the two species was not found. 4. 4. In contrast to human HDL, mink HDL was found not to contain apoA-II and only minute amounts of apoC proteins.

The investigation comprised sexual organs from 25 gilts and 97 sows culled because of repeat breeding. Among the gilts 24.0 per cent and among the sows 25.8 per cent had endometritis. The following germs were present in uterus from gilts and sows with signs of endometritis: Staphylococcus aureus, Corynebacterium pyogenes, alpha-hemolytiske streptococcer, Escherichia coli, Pasteurella sp., Aeromonas sp., Acinetobacter sp. and Citrobacter sp. Among gilts and sows with germs present in uterus 40.9 per cent had endometritis. The corresponding per cent among gilts and sows without germs present was 25.0.

Spores of Encephalitozoon cuniculi were recovered from foetal and placental tissues from blue fox females orally inoculated with the parasite. The results provided evidence for transplacental transmission of the causative agent of fox encephalitozoonosis.

Experimental amyloidosis was induced in mink by repeated injections with endotoxin. Amyloid fibrils extracted from liver and spleen were fractionated by gel filtration after treatment with guanidine-hydrochloride and a reducing agent, dithiothreitol. An elution profile very similar to that of human amyloid fibrils, having protein AA as a major component, was obtained. The mink amyloid protein eluted at a position similar to that of human protein AA was by amino acid composition and partial sequence studies shown to be very similar to the latter protein and was called mink protein AA. In addition, a protein AA-related component (protein SAA) was found in increased amounts in serum of amyloidotic mink, providing further evidence of the homology with human amy-loidosis. Experimental amyloidosis in mink represents a suitable model for studying amyloid proteins and related serum components.

Hemorrhagic necrosis of the gastric and colonic mucosa with capillary thrombosis were induced in pigs experimentally infected with Salmonella cholerae-suis when an additional intravenous supply of disintegrated cells of Salmonella cholerae suis or hemolytic Escherichia coli was administered. Except for the gastrointestinal lesions, the necropsy findings were almost identical with the picture found in acute septicemic salmonellosis. The gastrointestinal changes were interpreted as a special gastroenteric effect of endotoxins of Gramnegative bacteria during the development of septicemic salmonellosis.