Biomedical subjects

U Giger

Publications and source records attributed to U Giger.

At least 37 records · Page 2Linked to original sources

PubMed2000

Anemia, splenomegaly, and increased osmotic fragility of erythrocytes in Abyssinian and Somali cats.

OBJECTIVE: To determine clinical and clinicopathologic features of a chronic intermittent severe hemolytic anemia characterized by erythrocyte osmotic fragility in Abyssinian and Somali cats. DESIGN: Case series. ANIMALS: 13 Abyssinian and 5 Somali cats. PROCEDURES: History, pedigree information, and results of routine laboratory tests, special erythrocyte studies, and histologic evaluation of splenic and hepatic specimens were analyzed. RESULTS: Age at which clinical signs of anemia were first apparent ranged from 6 months to 5 years. Ten cats had splenomegaly. Most often, the PCV was between 15 and 25%, but it was as low as 5% at some times. The anemia was characterized by macrocytosis and mild to moderate reticulocytosis, but no poikilocytosis. Hyperglobulinemia, lymphocytosis, mild hyperbilirubinemia, and high hepatic enzyme activities were common findings. Results of Coombs tests and tests for infectious diseases were negative. The erythrocytic osmotic fragility was high in affected cats (mean osmotic fragility, 0.66 to 0.78%), compared with healthy cats (0.48 to 0.58). No specific membrane protein abnormality, erythrocyte enzyme deficiency, or hemoglobinopathy was identified. Histologic evaluation of splenic and hepatic specimens revealed extramedullary hematopoiesis and hemosiderosis. Four of the 5 Somali cats were closely related. CONCLUSIONS AND CLINICAL RELEVANCE: On the basis of results of pedigree analyses, the apparent breed predilection, and the exclusion of other known causes of anemia in cats, we believe that the hemolytic anemia in these cats was likely a result of a novel hereditary erythrocyte defect. A genetic predisposition to immune-mediated destruction of erythrocytes could not be ruled out.

Anemia, Hemolytic, Autoimmune↗

PubMed2000

Canine cystinuria: polymorphism in the canine SLC3A1 gene and identification of a nonsense mutation in cystinuric Newfoundland dogs.

Cystinuria is an inherited renal and intestinal disease characterized by defective amino acid reabsorption and cystine urolithiasis. Different forms of the disease, designated type I and non-type I in cystinuric humans, can be distinguished clinically and biochemically, and have been associated with mutations in the SLC3A1 (rBAT) and SLC7A9 genes, respectively. Type I cystinuria is the most common form and is inherited as an autosomal recessive trait in humans. Cystinuria has been recognized in more than 60 breeds of dogs and a severe form, resembling type I cystinuria, has been characterized in the Newfoundland breed. Here we report the cloning and sequencing of the canine SLC3A1 cDNA and gene, and the identification of a nonsense mutation in exon 2 of the gene in cystinuric Newfoundland dogs. A mutation-specific test was developed for the diagnosis and control of cystinuria in Newfoundland dogs. In cystinuric dogs of six other breeds, either heterozygosity at the SLC3A1 locus or lack of mutations in the coding region of the SLC3A1 gene were observed, indicating that cystinuria is genetically heterogeneous in dogs, as it is in humans. The canine homologue of human type I cystinuria provides the opportunity to use a large animal model to investigate molecular approaches for the treatment of cystinuria and other renal tubular diseases.

Amino Acid Sequence↗

PubMed2000

Persistent cobalamin deficiency causing failure to thrive in a juvenile beagle.

A six-month-old beagle was presented with a three-month history of failure to gain weight, lethargy, intermittent vomiting and seizures. Hypoglycaemia, portosystemic shunt, lead intoxication, gastrointestinal diseases and hereditary metabolic disorders were considered. Laboratory test results of low serum cobalamin (Cbl) concentrations, anaemia, leucopenia and methylmalonic aciduria while the dog was receiving a balanced commercial canine diet were suggestive of a congenital selective Cbl malabsorption. Treatment with repeated injections of parenteral cyanocobalamin (CN-Cbl) at 50 microg/kg every two weeks corrected the Cbl-deficient state and reversed all the clinical abnormalities. Selective Cbl malabsorption has previously been described in giant schnauzers and border collies and represents a unique readily treatable hereditary metabolic disorder.

Anemia↗

PubMed1999

A missense mutation in canine C1C-1 causes recessive myotonia congenita in the dog.

Myotonia congenita is an inherited disorder of sarcolemmal excitation leading to delayed relaxation of skeletal muscle following contractions. Mutations in a skeletal muscle voltage-dependent chloride channel, CIC-1, have been identified as the molecular genetic basis for the syndrome in humans, and in two well characterized animal models of the disease: the myotonic goat, and the arrested development of righting (adr) mouse. We now report the molecular genetic and electrophysiological characterization of a canine CIC-1 mutation that causes autosomal recessive myotonia congenita in miniature Schnauzers. The mutation results in replacement of a threonine residue in the D5 transmembrane segment with methionine. Functional characterization of the mutation introduced into a recombinant CIC-1 and heterologously expressed in a cultured mammalian cell line demonstrates a profound effect on the voltage-dependence of activation such that mutant channels have a greatly reduced open probability at voltages near the resting membrane potential of skeletal muscle. The degree of this dysfunction is greatly diminished when heterodimeric channels containing a wild-type and mutant subunit are expressed together as a covalent concatemer strongly supporting the observed recessive inheritance in affected dog pedigrees. Genetic and electrophysiological characterization of the myotonic dog provides a new and potentially valuable animal model of an inherited skeletal muscle disease that has advantages over existing models of myotonia congenita.

Amino Acid Sequence↗

PubMed1999

Evaluation of the association between medial patellar luxation and hip dysplasia in cats.

OBJECTIVE: To investigate the association between hip dysplasia (HD) and medial patellar luxation (MPL) in cats. DESIGN: Cross-sectional prevalence study. ANIMALS: 78 cats. PROCEDURE: A complete history was obtained. Cats were examined to detect MPL and HD. Radiographs of the stifle and hip joints were obtained. Hip joints were evaluated by use of Norberg angle, distraction index, and scoring consistent with that established by the Orthopedic Foundation for Animals. RESULTS: There were 43 male and 35 female cats mean age, 2.5 years). Eleven cats had clinical signs of disease in the pelvic limbs. Medial subluxation of the patella (subgrade 1) was seen in 31 of 33 cats with otherwise normal stifle joints. Medial patellar luxation was found in 45 of 78 (58%) cats, and 35 of 45 (78%) had grade-1 MPL. Bilateral MPL was seen in 32 of 45 (71%) cats. A weak association existed between MPL and HD, because cats were 3 times more likely to have HD and patellar luxation than to have either condition alone. Concurrent MPL and HD were detected in 19 of 78 (24%) cats, and HD was diagnosed radiographically in 25 of 78 (32%) cats (19 mild, 4 moderate, 2 severe). Eighteen of the 25 cats with HD had bilateral HD. CONCLUSIONS AND CLINICAL RELEVANCE: Clinically normal cats may have a certain degree of laxity in the stifle joint, evident as medial patellar subluxation (< grade 1). There is a weak association between MPL and HD, and both conditions may develop, alone or in combination, more frequently than has been reported.

Animals↗

PubMed1999

Molecular basis of feline beta-glucuronidase deficiency: an animal model of mucopolysaccharidosis VII.

A family of domestic cats was found that exhibited clinical and biochemical abnormalities consistent with mucopolysaccharidosis VII, an autosomal recessive lysosomal storage disorder caused by beta-glucuronidase deficiency. beta-Glucuronidase activity was undetectable in affected cat fibroblasts and restored by retroviral gene transfer of rat beta-glucuronidase cDNA. beta-Glucuronidase mRNA was normal in affected cat testis by Northern blot analysis. Normal feline beta-glucuronidase cDNA was cloned and characterized, and amplified from affected cat fibroblasts by reverse transcription coupled polymerase chain reaction. There was a G-to-A transition in the affected cat cDNA that predicted an E351K substitution, destroyed a BssSI site, and eliminated GUSB enzymatic activity in expression studies. Multiple species comparison and the crystal structure of human beta-glucuronidase indicated that E351 is a highly conserved residue most likely essential in maintenance of the enzyme's conformation. BssSI digestion of polymerase chain reaction products amplified from genomic DNA indicated that affected cats were homozygous and cats with half-normal beta-glucuronidase activity were heterozygous for the missense mutation. Carriers identified in this manner produced affected kittens in prospective breedings, and a feline MPS VII breeding colony has been established.

Amino Acid Sequence↗

PubMed1999

In vivo determination of altered hemoglobin saturation in dogs with M-type phosphofructokinase deficiency.

Muscle-type phosphofructokinase (M-PFK) deficiency causes an exertional myopathy and chronic hemolysis in affected humans and dogs, the only animal model available. Deficient individuals have impaired glycolytic metabolism, impaired oxidative metabolism, and increased hemoglobin-oxygen (HbO2) affinity as a result of low 2,3-diphosphoglycerate (2,3-DPG) levels. The purpose of this study was to determine if PFK-deficient muscle has abnormal oxygen saturation during exercise. Oxygen saturation of hemoglobin/myoglobin was measured noninvasively in skeletal muscle during progressive muscle activation using near-infrared spectroscopy (NIRS). Muscle metabolites were also measured using magnetic resonance spectroscopy (MRS). PFK-deficient and normal dogs were anesthetized and the cranial tibial muscles stimulated for 6 min at each of four different rates (1, 2, 4, and 8 Hz). With increasing stimulation, muscles from normal dogs showed progressive decrease in hemoglobin saturation. In contrast, PFK-deficient dogs exhibited either an increase in hemoglobin saturation or an initial decrease with no further change. PFK-deficient muscles accumulated 11.1 +/- 3.5 mmol/L of sugar phosphate which was not seen in normal muscle and had higher calculated [ADP] levels at each stimulation level, indicating impaired oxidative metabolism. These findings are consistent with the hypothesis that these animals have impaired oxidative metabolism and impaired muscle O2 extraction from hemoglobin due to increased HbO2 affinity. NIRS appears to be a useful noninvasive method of monitoring tissue oxygen saturation in normal or disease conditions.

Adenosine Diphosphate↗

PubMed1999

The AB blood group system in wild felids.

The blood type of 131 non-domesticated felids belonging to 26 felid species was surveyed in this study. Based upon a tube hemagglutination assay established for domestic cats, 80% of felids had type-A, 18% type-B, and 2% type-AB blood. Felids in the Puma group and African and Asian golden cats had blood type B, whereas all other species were found to have blood type A. Two cheetahs and one bobcat had type-AB blood. Red cell glycolipids analysed by high performance thin layer chromatography revealed a similar ganglioside pattern in wild cats as reported in domestic cats. Independent of the AB blood group system, incompatible blood crossmatch reactions were detected between different felid groups. In conclusion, wild felids display the same AB-erythrocyte antigens as domestic cats, and the same blood typing procedures can be applied for wild and domestic felids.

Animals↗

PubMed1999

Correlation of haemostatic abnormalities with tumour stage and characteristics in dogs with mammary carcinoma.

Sixty female dogs with untreated mammary carcinoma, comprising equal numbers of dogs in tumour stages I to IV, were evaluated for haemostatic abnormalities using the following tests: platelet count, prothrombin time, activated partial thromboplastin time, thrombin time, plasma activity of factor V, VIII and X, plasma concentration of fibrinogen, fibrin monomers and fibrinogen degradation products, and plasma antithrombin III activity. Two-thirds of all dogs had one or more haemostatic test abnormality of which the likelihood and frequency was increased in those with stage III and IV neoplasia. Haemostatic abnormalities were more frequently observed in dogs which had mammary tumours with distant metastases, extended tumour necrosis, inflammatory carcinomas, tumours fixed to underlying structures, or tumours in which there was penetration of the tumour capsule by tumour cells. As in humans with mammary carcinoma, these haemostatic abnormalities might be used as prognostic indicators, but their clinical importance remains unknown.

Adenocarcinoma↗

PubMed1999

Genomic screening for fucosidosis in English Springer Spaniels.

OBJECTIVE: To develop a robust molecular genetic test for alpha-L-fucosidosis in English Springer Spaniels and to screen dogs from the United Kingdom and United States for the mutant allele. ANIMALS: 35 English-bred English Springer Spaniels, 60 American-bred English Springer Spaniels, and 1 affected dog and its parents from a family of English Springer Spaniels in Colorado. PROCEDURE: Polymerase chain reaction analysis was used to amplify the mutated region in the gene encoding alpha-L-fucosidase. High guanine-cytosine (GC) content of the region required use of an amplification buffer with high pH. Mutant and normal alleles were separated by polyacrylamide gel electrophoresis. Molecular genetic test results were compared with enzyme data. RESULTS: A 262-bp PCR product was amplified from normal dogs and compared with a 248-bp product from affected dogs. Carriers had 1 copy of each allele, distinguishable by the 14-bp size difference. Two carriers among the English-bred dogs were identified by use of enzyme and genomic DNA analyses. The molecular defect in dogs from Colorado was proven to be the same as that in British and Australian dogs. None of the other 60 American-bred dogs carried the mutant allele. CONCLUSIONS AND CLINICAL RELEVANCE: A PCR method that can be used to identify dogs affected with or carriers of the autosomal recessive disease fucosidosis was established. Amplification was achieved within a GC-rich region, using a method that may be useful in overcoming amplification problems in GC-rich areas within other genes. Using this test, fucosidosis can be controlled and ultimately eradicated from the English Springer Spaniel population.

Animals↗

PubMed1999

Identification of a 6 base pair insertion in West Highland White Terriers with erythrocyte pyruvate kinase deficiency.

OBJECTIVE: To define the disease-causing mutation in West Highland White Terriers (WHWT) with erythrocyte pyruvate kinase (R-PK) deficiency and to design a genetic test capable of recognizing affected (homozygous) and carrier (heterozygous) dogs. ANIMALS: 3 anemic WHWT littermates and 1 unaffected littermate; 16 dogs from the same kennel, including 4 unrelated, phenotypically normal dogs (control dogs), and 12 for which PK activity was not known; 2 PK-deficient Basenjis; 2 PK-deficient Beagles; 4 unaffected English Springer Spaniels; and 1 mixed-breed dog. PROCEDURES: cDNA was cloned and sequenced, and cDNA sequences were compared with the published sequence for canine R-PK cDNA to identify the putative disease-causing mutation. Genomic DNA spanning the affected region was cloned and sequenced to verify the mutation. Subsequently, polymerase chain reaction primers were designed to amplify the section of the gene containing the mutation from DNA in blood or buccal swab samples. Gel electrophoresis allowed assignment of genotypes on the basis of allele separation. RESULTS: 4 single base polymorphisms attributable to sequencing errors in the published sequence were identified, along with a 6 base pair (bp) insertion in exon 10 that was recognized as a putative disease-causing mutation. An identical insertion was found in genomic DNA. Amplification of genomic DNA yielded a 117 bp product for genotypically normal dogs and a 123 bp product for WHWT homozygous for PK deficiency. Carriers had 1 copy of each allele and variable heteroduplex structures. CONCLUSIONS AND CLINICAL RELEVANCE: A 6 bp insertion in the C domain of R-PK was identified in WHWT with PK deficiency. Affected and carrier dogs could be distinguished with a genetic test.

Animals↗

PubMed1998

Relationship between degenerative joint disease and hip joint laxity by use of distraction index and Norberg angle measurement in a group of cats.

OBJECTIVE: To determine the relationship between degenerative joint disease (DJD) and passive laxity of the hip joint in a group of cats. DESIGN: Prospective study. ANIMALS: A select (nonrandomized) group of 78 cats. PROCEDURE: Standard hip-extended radiographic views and compression and distraction views of the pelvis were obtained from cats during sedation. Radiographs were evaluated, using an Orthopedic Foundation for Animals (OFA)-like scoring system for dogs. Passive joint laxity was measured, using Norberg angle (NA) and distraction index (DI). Hip laxity in cats with DJD was compared with hip laxity in cats without DJD. RESULTS: Hip dysplasia (HD) was subjectively diagnosed radiographically in 25 of 78 (32%) cats using the OFA-like scoring system. Nineteen cats had mild HD 4 had moderate HD, and 2 had severe HD. Fifteen of the 25 cats with HD had DJD. The NA ranged from 56 to 105. The mean NA in cats with DJD was (84 degrees) significantly lower than in cats without DJD (95 degrees). The DI ranged from 0.2 to 0.84. The mean DI for cats with DJD was (0.6) significantly higher than that for cats without DJD (0.49). Cats with a DI < 0.4 did not have DJD. Cats had an increased likelihood of having DJD with increased laxity in the coxofemoral joint, as measured by NA or DI. CLINICAL IMPLICATIONS: The mean NA for radiographically normal cats (92.4 degrees) was lower than that in radiographically normal dogs (103 degrees). The overall mean DI for cats in this group (0.51) is similar to dogs of breeds with high joint laxity, such as the Labrador Retriever (0.5). As in dogs, there is a relationship between DJD and laxity in the hip joint of cats.

Animals↗

PubMed1998

Seroprevalence of Babesia equi among horses in Israel using competitive inhibition ELISA and IFA assays.

Sera from 361 horses were tested by indirect immunofluorescence antibody test (IFA) and by competitive inhibition ELISA (cELISA), to detect antibodies to Babesia equi. The concordance between the assays was 95.7%. Application of a cutoff based on a calculated percent inhibition of < 20% gave a total of 22 discrepant results, while only 8 sera negative by the cELISA were found positive by the IFA when a cutoff of > 20% inhibition was used. Approximately one-third of all the horses tested were found serologically positive to B. equi, with more horses testing positive from northern Israel. Among horses raised with access to pasture there was a significant difference in the percentage of seropositive reactors (76.6% in the north and 20.1% in the central region), compared with horses without access to pasture (14.3 and 10.3%, respectively). Nineteen percent of stallions were found to be positive, which was significantly less than the proportions of seropositive mares and geldings: 38 and 42%, respectively. No significant association was found between the mean age of horses and seroreactivity to B. equi.

Animals↗

PubMed1998

Sulfamidase deficiency in a family of Dachshunds: a canine model of mucopolysaccharidosis IIIA (Sanfilippo A).

Mucopolysaccharidosis IIIA (MPS IIIA or Sanfilippo A, McKusick 25290) was diagnosed in two adult wire-haired Dachshund littermates. Clinical and pathologic features paralleled the human disorder; both dogs exhibited progressive neurologic disease without apparent somatic involvement. Pelvic limb ataxia was observed when the dogs were 3 y old and progressed gradually within 1-2 y to severe generalized spinocerebellar ataxia. Mentation remained normal throughout the course of the disease. A mucopolysaccharide storage disorder was indicated in both dogs by positive toluidine blue spot tests of urine. The diagnosis of MPS IIIA was confirmed by documentation of urinary excretion and tissue accumulation of heparan sulfate and decreased sulfamidase activity in fibroblasts and hepatic tissue. Mild cerebral cortical atrophy and dilation of the lateral ventricles were grossly evident in both dogs. Light microscopically, fibroblasts, hepatocytes, and renal tubular epithelial cells were vacuolated. Within the nervous system, cerebellar Purkinje cells, neurons of brainstem nuclei, ventral and dorsal horns, and dorsal ganglia were distended with brightly autofluorescent, periodic acid-Schiff-positive, sudanophilic material. Ultrastructurally, visceral storage presented as membrane-bound vacuoles with finely granular, variably electron-lucent contents. Neuronal storage appeared as membranous concentric whorls, lamellated parallel membrane stacks, or electron-dense lipid-like globules. This represents the first reported animal disease homolog of the human Sanfilippo A syndrome.

Animals↗

PubMed1998

Polymorphism of feline beta-globins studied by reversed-phase high-performance liquid chromatography.

OBJECTIVE: To characterize the feline beta-globin system with respect to the number and genetics of adult beta-globin chains. ANIMALS: 84 domestic and purebred cats (9 breeds), 14 cats were mildly to severely anemic. For genetic analyses, 12 litters with 1 to 5 offspring for a total of 29 kittens. PROCEDURE: Feline globins from erythrocyte lysates were separated by reversed-phase high-performance liquid chromatography and analyzed on the basis of retention time and area of each beta-globin peak. Mixing studies with half the amount of hemoglobin (Hb) from 2 cats were performed to assign the beta-globin peaks in each cat. The Hb from 60 cats were also separated by standard isoelectric focusing methods. RESULTS: Heme and alpha- and beta-globins were effectively separated by high-performance liquid chromatography. Although there was only 1 alpha-globin, a total of 6 beta-globins (I through VI) were identified, with each cat having 1 to 4 beta-globin chains. From analysis of the number of beta-globins, their relative amounts, and Hb mixing studies, 17 beta-globin patterns were observed. The beta-globin pattern in healthy and anemic cats was identical. Family studies documented an autosomal codominant mode of inheritance of the adult beta-globins and a linkage of 2 beta-chains forming haplotypes. CONCLUSIONS: Biochemical and genetic evidence for the greatest polymorphism of adult beta-globins thus far described in any species is provided. A feline beta-globin gene region with 2 linked beta-globin gene loci and 2 and 5 alleles is proposed. CLINICAL RELEVANCE: Better understanding of feline Hb will likely be helpful for diagnosis of hemoglobinopathies in anemic cats.

Alleles↗

PubMed1998

Chrono-lume and magnesium potentiate aggregation of canine but not human platelets in citrated platelet-rich plasma.

The effects of Chrono-lume (CL) and magnesium sulfate (Mg2+), a component of this luciferin-luciferase reagent, on platelet aggregation were studied in platelet-rich plasma (PRP) obtained from blood anticoagulated with sodium citrate from humans, dogs, cats, horses, and cows. The final added Mg2+ concentration of both solutions ranged from 0.75-3.7 mM. CL and Mg2+ had no effect on maximum aggregation of platelets from humans induced by sub-threshold concentrations of collagen and ADP. In contrast, addition of CL or Mg2+ to canine PRP resulted in a dose-dependent and equal potentiation of platelet aggregation in response to sub-threshold concentrations of collagen, ADP, and thrombin in normal and thrombopathic dogs. The effect of CL on platelet aggregation induced by sub-threshold concentrations of agonists was less pronounced and varied in other species according to the agonist. The reason for the marked difference in sensitivity of human and canine platelets to CL or Mg2+ is not clear, although a difference in releasable cation pools of the platelets from these two species has been recognized. Platelet aggregation studies of animals with suspected thrombopathias should be performed without CL to prevent masking of a platelet function defect.

Animals↗

PubMed1997

[Von Willebrand factor concentrations in blood plasma of Bernese mountain dogs].

Many Bernese Mountain dogs have been found to exhibit an increased hemorrhagic tendency of unknown etiology. Since other bleeding disorders have been excluded by routine tests and Bernese Mountain dogs have been listed to have von Willebrand's disease (vWD), we analyzed the plasma concentration of the von Willebrand Factor (vWF) in 160 Bernese Mountain dogs that were used for breeding in Switzerland in 1992. We also evaluated the suitability of the commercial Asserachrom vWF test kit to quantitate vWF in canine plasma by comparing the plasma vWF determination with validated vWF ELISA test. The vWF plasma concentration in Bernese Mountain dogs ranged from 13% to 162%, with the Asserachrom test kit (normal range 67% to 124%). Similar values were obtained with the research vWF ELISA kit (10% to 166%), and there was a close correlation between the two test methods. In 8 of the 9 Bernese Mountain dogs with initially low vWF concentration (< 60%), the determination was repeated on another sample. Since the values were well within the normal range, a problem with the collection of blood for the first determination is suspected. We conclude that vWD does not appear to be a clinical issue in Bernese Mountain dogs in Switzerland and is, therefore, not likely to be the cause of the observed bleeding tendency. The commercially available Asserachrom vWF test kit seems suitable for the determination of canine vWF plasma concentrations. It is recommended that low vWF values will be confirmed by the determination in second samples.

Animals↗

PubMed1997

Feline colostrum--friend or foe: maternal antibodies in queens and kittens.

The transfer of immunoglobulins (Ig) by colostrum from the queen to the neonatal kitten not only provides protection from infection, but may also cause serious illness. Neonatal isoerythrolysis may occur when kittens of blood type A or AB receive colostral anti-A alloantibodies from a type B queen. In contrast to other species, Ig concentrations in milk and colostrum did not differ markedly. Gastrointestinal absorption of IgG was limited to the first day of life. The half-lifes of maternally derived IgG and IgA in kittens were shorter than in puppies. In conclusion, milk from another queen may be given as a replacement for colostrum to neonatal kittens. Kittens at risk of neonatal isoerythrolysis must be removed from their type B queen during the first day of life and may safely receive milk or colostrum from a type A queen.

ABO Blood-Group System↗