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Biomedical subjects

U Giger

Publications and source records attributed to U Giger.

At least 109 records · Page 6Linked to original sources
PubMed1980

Induction of drug-metabolizing enzymes by phenobarbitone: structural and biochemical aspects.

Two aspects of the induction of microsomal monooxygenases by phenobarbitone have been investigated. First, structural associations between mitochondria and single cisternae of rough endoplasmic reticulum (mitochondria--RER complexes) may operate as functional units in the biosynthesis of cytochrome P-450. This was deduced from (i) studies on the subcellular distribution of the phenobarbitone-induced incorporation of leucine into microsomal proteins including apocytochromes P-450 and (ii) the incorporation of labelled delta-aminolaevulinic acid into the haem prosthetic group of cytochrome P-450. Secondly, in hepatocytes from chick embryo in primary monolayer culture, induction of cytochrome P-450-haemoproteins was markedly influenced by changes in the proliferative activity of hepatocytes. Inducibility of cytochrome P-450 by phenobarbitone and by beta-naphthoflavone was decreased in cultures with 'spontaneous' or experimentally increased proliferative activity of hepatocytes. Treatment with inhibitors of DNA synthesis increased the induction response.

Aminolevulinic Acid↗
PubMedDate not supplied

Frequency and inheritance of A and B blood types in feline breeds of the United States.

Using a simple hemagglutination assay to determine A and B blood types, we surveyed 1,072 domestic short- and longhair (DSH/DLH) cats and 1,100 purebred cats in the United States. Data from 234 matings with 552 offspring were consistent with the hypothesis that feline blood types A and B are due to the action of two different alleles at the same gene locus and that A is completely dominant over B. Neither an AB nor an O type cat was encountered. No type B cats were found in the Siamese and related breeds or in American Shorthair and Norwegian Forest cats. Among the breeds with type B blood, the proportion was lowest in DSH/DLH cats (0.0028) and variably higher in Abyssinian, Birman, British Shorthair, Devon Rex, Himalayan, Persian, Scottish Fold, and Somali, ranging from 0.15 to 0.59. Since all type B cats have strong, naturally occurring anti-A alloantibodies, fatal neonatal isoerythrolyses occur in type A offspring of type B mothers bred to type A males. The gene frequency of the B allele and the proportion of mating at risk of neonatal isoerythrolysis were estimated in a number of breeds. In most breeds, the frequency of the B allele was less than 0.5. Since the kittens at risk for neonatal isoerythrolysis always have the genotype AB, there is constant natural selection against heterozygotes. Heterozygote disadvantage in the cat AB system represents an unusual form of negative selection, similar to that in Rh blood group incompatibility in humans.

Alleles↗
PubMedDate not supplied

Feline adult beta-globin polymorphism reflected in restriction fragment length patterns.

Adult domestic cats (Felis catus) appear to have the most polymorphic beta-globin system of any species. Reversed-phase high-performance liquid chromatography (RP-HPLC) revealed one alpha-chain and six different beta-globin chains. Each cat may have one to four different beta-globins, and a total of 17 different beta-globin patterns were identified. Based on family studies, a beta-globin gene region with two linked beta-globin gene loci and two to five alleles was proposed. In order to further define the molecular basis of this polymorphism we performed Southern blot analysis of the beta-globin gene region from 25 cats with 13 different HPLC patterns. Genomic DNA was digested with five restriction endonucleases (BamHI, BglII, EcoRI, HindIII, and PstI) and blots were hybridized with a human beta-globin probe. Restriction fragment length polymorphisms (RFLPs) with one to five fragments of 2.2-23 kb in size were found with BglII, EcoRI, HindIII, and PstI. Cats with specific HPLC beta-globin patterns had a unique DNA restriction pattern. The similarly sized BamHI and HindIII fragments of 4.6 kb suggest the presence of two closely linked genes. Furthermore, family studies suggest an autosomal codominant mode of inheritance of the beta-globin chains with seven haplotypes. Thus the RFLP data analyzed in the context of the HPLC haplotypes provide evidence at the DNA level for a feline beta-globin gene region with two closely linked gene loci and two to five alleles.

Animals↗
PubMedDate not supplied

Congenital myotonic myopathy in the miniature schnauzer: an autosomal recessive trait.

Myotonia is a clinical sign characterized by a delay in skeletal muscle relaxation following electrical or mechanical stimulation. A series of related miniature schnauzer dogs with congenital myotonic myopathy were studied. A composite pedigree of six affected litters and the results of a planned breeding between two affected animals are consistent with an autosomal recessive mode of inheritance.

Animals↗
PubMedDate not supplied

Inheritance, biochemical abnormalities, and clinical features of feline mucolipidosis II: the first animal model of human I-cell disease.

Mucolipidosis II (ML II), also called I-cell disease, is a unique lysosomal storage disease caused by deficient activity of the enzyme N-acetylglucosamine-1-phosphotransferase, which leads to a failure to internalize enzymes into lysosomes. We report on a colony of domestic shorthair cats with ML II that was established from a half-sibling male of an affected cat. Ten male and 9 female kittens out of 89 kittens in 26 litters born to clinically normal parents were affected; this is consistent with an autosomal recessive mode of inheritance. The activities of three lysosomal enzymes from affected kittens, compared to normal adult control cats, were high in serum (11-73 times normal) but low in cultured fibroblasts (9-56% of normal range) that contained inclusion bodies (I-cells), reflecting the unique enzyme defect in ML II. Serum lysosomal enzyme activities of adult obligate carriers were intermediate between normal and affected values. Clinical features in affected kittens were observed from birth and included failure to thrive, behavioral dullness, facial dysmorphia, and ataxia. Radiographic lesions included metaphyseal flaring, radial bowing, joint laxity, and vertebral fusion. In contrast to human ML II, diffuse retinal degeneration leading to blindness by 4 months of age was seen in affected kittens. All clinical signs were progressive and euthanasia or death invariably occurred within the first few days to 7 months of life, often due to upper respiratory disease or cardiac failure. The clinical and radiographic features, lysosomal enzyme activities, and mode of inheritance are homologous with ML II in humans. Feline ML II is currently the only animal model in which to study the pathogenesis of and therapeutic interventions for this unique storage disease.

Animals↗
PubMedDate not supplied

Carrier detection of ovine hemophilia A using an RFLP marker, and mapping of the factor VIII gene on the ovine X-chromosome.

Ovine hemophilia A is an X-linked recessive bleeding disorder. For diagnostic purposes, restriction fragment length polymorphism (RFLP) analysis in the region of the factor VIII (F-VIII) gene was carried out using human F-VIII gene probes. The probe St14, known to detect a highly polymorphic region that is closely linked to the F-VIII gene in humans, hybridized nonspecifically with DNA from sheep. Searching for intragenic RFLPs, the entire 9.0-kb coding sequence of the human F-VIII was used as a probe. Using the 1.8-kb SstI/KpnI F-VIII cDNA probe for hybridization, an MspI-RFLP with allelic bands of 5.8 kb (A1) and 4.2 kb (A2) was detected. A1 was in linkage phase with the mutated allele responsible for hemophilia A. The F-VIII locus in the sheep genome was assigned to the long arm of the X-chromosome in the region Xq24-q33, using in situ hybridization with a 3-kb human F-VIII cDNA probe to QFQ banded sheep metaphase chromosomes.

Animals↗
PubMedDate not supplied

Neuronal-visceral GM1 gangliosidosis in Portuguese water dogs.

Three female siblings in a litter of seven Portuguese Water dogs (PWDs) showed clinical signs of ataxia and/or lameness at 5 months of age. Signs of cerebellar dysfunction (intention tremors, ataxia, widebased stance, dysmetria, and/or nystagmus) and mild limb weakness developed rapidly. Results of hemograms (three dogs), blood chemistry profiles (two dogs), urinalyses (two dogs), electroencephalograms (two dogs), and radiographs of the limbs or pelvis (three dogs), vertebrae (two dogs), and skull (one dog) were unremarkable except for an absolute lymphocytosis in one dog. Routine cerebrospinal fluid (CSF) analyses were normal in all three dogs. However, the CSF creatine kinase concentration was elevated in the one dog in which it was measured. Mucopolysacchariduria was present in all three dogs. Due to the rapid progression of clinical signs and a poor prognosis, all three dogs were euthanatized between 6 and 7 months of age. Histopathologic and electron microscopic studies showed neuronal cytoplasmic inclusions, vacuolated hepatocytes, and vacuolated renal tubular epithelial cells, compatible with the diagnosis of a storage disease. Beta-galactosidase activities in leukocytes, serum, and brain homogenates were reduced when compared with that in normal dogs and the stored product was identified as GM1 ganglioside, confirming GM1 gangliosidosis.

Animals↗
PubMedDate not supplied

Acute hemolytic transfusion reaction in an Abyssinian cat with blood type B.

After receiving a transfusion with unmatched blood, an anemic Abyssinian cat developed an acute hemolytic transfusion reaction. Similar to many other purebred cats, the recipient had type B blood with strong serum anti-A alloantibodies, whereas the donor had blood type A. Subsequent transfusions with type B blood proved effective and without adverse reactions. This case of a clinical A-B incompatibility reaction emphasizes the need for blood typing and/or crossmatching prior to transfusing cats.

ABO Blood-Group System↗
PubMedDate not supplied

Anemia of chronic renal failure in dogs.

Seventeen dogs with chronic renal failure (CRF) were studied to evaluate the incidence, type, and etiology of anemia in CRF. A nonregenerative, normochromic, normocytic anemia was seen in 12 of 17 dogs (70.6%). There was a direct correlation between the degree of anemia and the extent of CRF as assessed by serum creatinine concentrations (P = .0386, r = .50923). Erythrocyte concentrations of 2,3-diphosphoglycerate (DPG) were significantly increased in anemic animals and showed a close correlation to the degree of anemia. The high DPG concentrations may compensate for the anemia by decreasing the hemoglobin-oxygen affinity and thereby facilitating tissue oxygenation at low hematocrits. Serum concentrations of erythropoietin (Epo) were in the low to normal range, despite mild to moderate anemia, documenting a deficiency of Epo in dogs with CRF. The nonregenerative nature of the anemia supports impaired hematopoiesis as a significant etiologic factor. Other factors, such as increases in serum parathyroid hormone and phosphorus, were not found to correlate significantly with the degree of anemia, although there were significant differences between their concentrations in anemic compared with non-anemic dogs. There was no change in erythrocyte osmotic fragility with uremia. The documentation of a nonregenerative, normochromic, normocytic anemia, with failure of an appropriate increase in Epo production, supports the therapeutic use of Epo in the management of the anemia seen in CRF in the dog.

2,3-Diphosphoglycerate↗
PubMedDate not supplied

Hemolytic transfusion reactions in a dog with an alloantibody to a common antigen.

Alloantibodies to high-frequency red cell antigens, defined as inherited traits occurring in 92% to 99% or more of the general population, are recognized as a cause of hemolytic transfusion reactions in humans. Here we describe a dog (dog erythrocyte antigen [DEA] 1.2- and DEA 4-positive) sensitized by prior blood transfusion, for which a compatible blood donor could not be found; transfusion of DEA 1.1-negative blood resulted in hemolytic transfusion reactions. Patient serum from days 1 (before first transfusion) and 16 was available for further testing; using 4 dogs with different blood types as potential donors, the major crossmatches were compatible using serum from day 1. However the crossmatches were all incompatible with serum from day 16, indicating that the patient was sensitized to an antigen after the first transfusion. The presence of an alloantibody against DEA 1.1 was not ruled out in this patient, but the incompatibility reactions of patient serum with red cells from donors negative for DEA 1.1 indicated that an alloantibody against a red cell antigen other than DEA 1.1 or any other known DEA for which typing reagents were available (DEA 3, 5, and 7) was present. Subsequently, red cells from 1 of the patient's siblings (DEA 1.2-, 4-, and 7-positive) were found not to agglutinate when incubated with patient's serum from day 16, ruling out the presence of an anti-DEA 7 antibody, and suggesting that an alloantibody against a common red cell antigen missing in the patient and sibling was responsible for the blood incompatibility reactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Agglutination Tests↗
PubMedDate not supplied

Vaccine-associated immune-mediated hemolytic anemia in the dog.

Vaccination has been incriminated as a trigger of immune-mediated hemolytic anemia (IMHA) in dogs and in people, but evidence to support this association is lacking. In a controlled retrospective study, idiopathic IMHA was identified in 58 dogs over a 27-month period. When compared with a randomly selected control group of 70 dogs (presented for reasons other than IMHA) over the same period, the distribution of cases versus time since vaccination was different (P < .05). Fifteen of the dogs (26%) had been vaccinated within 1 month (mean, 13 days; median, 14 days; range, 1 to 27 days) of developing IMHA (P < .0001), whereas in the control group no marked increase in frequency of presentation was seen in the first month after vaccination. The dogs with IMHA were divided into 2 groups based on time since vaccination: the vaccine IMHA group included dogs vaccinated within 1 month of developing IMHA; the nonvaccine IMHA group included dogs that developed IMHA more than 1 month after vaccination. The recently vaccinated dogs with IMHA (vaccine IMHA group) had significantly lower platelet counts (P < .05) and a trend towards increased prevalence of intravascular hemolysis and autoagglutination when compared with the nonvaccine IMHA group. Similar mortality rates were seen in teh vaccine IMHA group (60%) and the nonvaccine IMHA group (44%), with the majority of fatalities (> 75%) occurring in the first 3 weeks after presentation. Persistent autoagglutination was a negative prognostic indicator for survival in both groups (P < .05). Presence of icterus and hyperbilirubinemia were negative prognostic indicators for survival in the nonvaccine IMHA group (P < .0001 and P < .01, respectively) but not in the vaccine IMHA group. In the recently vaccinated dogs, combination vaccines from various manufacturers against canine distemper, adenovirus type 2, leptospirosis, parainfluenza, and parvovirus (DHLPP) were involved in each case. Vaccines against rabies virus, Bordetella spp, coronavirus, and Lyme Borrelia were administrated concomitantly to some dogs. This study provides the first clinical evidence for a temporal relationship of vaccine-associated IMHA in the dog.

Anemia, Hemolytic↗
PubMedDate not supplied

Sry-negative XX sex reversal in a family of Norwegian Elkhounds.

Two related female Norwegian Elkhounds were evaluated at 6 and 8 months of age for enlarged clitori. Both had a 78 XX karyotype. Histology of their internal reproductive tracts demonstrated 1 to be an XX true hermaphrodite with bilateral ovotestes and the other to be an XX male with bilateral aspermatogenic testes. Polymerase chain reaction-based tests of genomic DNA showed that both dogs lacked Sry, the testis-determining gene. Pedigree analysis was consistent with an autosomal recessive mode of inheritance, as has been reported in the American Cocker Spaniel and the German Shorthaired Pointer. This is the 1st reported case of familial Sry-negative XX sex reversal in the Norwegian Elkhound. A summary of 34 previously unreported cases of dogs with masculinized external genitalia and a normal 78 XX karyotype seen from 1980 to 1997 is given.

Animals↗
PubMedDate not supplied

Familial protein-losing enteropathy and protein-losing nephropathy in Soft Coated Wheaten Terriers: 222 cases (1983-1997).

Records and pedigrees of Soft Coated Wheaten Terriers (SCWT) with protein-losing enteropathy (PLE) or protein-losing nephropathy (PLN) were studied retrospectively. Criteria for inclusion were defined based on analysis of blood (panhypoproteinemia for PLE, hypoalbuminemia for PLN) and urine (proteinuria for PLN) and histopathologic examination of tissue. Two hundred twenty-two affected dogs (female:male ratio = 1.6, P < .001) were clinically identified. Dogs were diagnosed with PLE earlier (P < .005; mean +/- SD age: 4.7+/-2.6 years, n = 76) than with PLN (6.3+/-2.0 years, n = 84) or with both diseases (5.9+/-2.2 years, n = 62). Clinical signs included vomiting, diarrhea, weight loss, pleural and peritoneal effusions, and less commonly thromboembolic disease. Dogs with PLE generally had panhypoproteinemia and hypocholesterolemia; intestinal lesions included inflammatory bowel disease, dilated lymphatics, and lipogranulomatous lymphangitis. Dogs with PLN generally had hypoalbuminemia, proteinuria, hypercholesterolemia, and azotemia; renal lesions typically showed chronic glomerulonephritis/glomerulosclerosis, and less commonly endstage renal disease. Dogs with combined PLE/PLN had intermediate mean values (P < .001) for serum total protein, albumin, globulin, and cholesterol but had a higher mean urine protein:creatinine ratio than did PLN dogs (P < .05); intestinal and renal lesions in these dogs were similar to those in the other groups. Two dogs had incidental mild renal dysplasia. Pedigree analysis from 188 dogs demonstrated a common male ancestor, although the mode of inheritance is unknown. Both PLE and PLN are common diseases in this small breed population. The prognosis is poor. Compared with previously reported intestinal and renal diseases in dogs, a new, distinctive familial predisposition for both PLE and PLN has been recognized in the SCWT breed.

Animals↗
PubMedDate not supplied

Serum erythropoietin values in polycythemic cats.

Serum erythropoietin (EPO) concentrations and clinicopathological features were evaluated in 31 cats with absolute polycythemia (i.e., packed cell volume [PCV], 52% to 84%). Five cats had high serum EPO values and were classified as having secondary polycythemia. The remaining 26 cats had EPO values in the low or normal range. Four of these 26 cats had clinical evidence of secondary polycythemia and therefore were classified as having secondary polycythemia. In the remaining 22 cases, no signs of secondary polycythemia could be found, and primary polycythemia was diagnosed. A low or normal serum EPO value in a polycythemic cat is consistent with primary polycythemia, but does not exclude secondary polycythemia.

Animals↗
PubMedDate not supplied

Canine red blood cell transfusion practice.

Red blood cell (RBC) transfusions in 307 dogs were reviewed. A total of 658 units of RBCs, including 474 (72%) units of packed red blood cells (PRBCs) and 184 (28%) units of whole blood (WB), were administered. Reasons for transfusion included hemorrhage (n = 222), hemolysis (n = 43), and ineffective erythropoiesis (n = 42). The mean pretransfusion packed cell volume (PCV) of dogs with hemolysis (13%) was significantly lower (p less than 0.0001) than the mean pretransfusion PCVs of dogs with hemorrhage (21%) or ineffective erythropoiesis (18%). The mean total volume of PRBCs transfused was significantly greater (p less than 0.03) in dogs with hemolysis. Overall, 187 (61%) of 307 dogs were discharged from the hospital. Cause of anemia, pretransfusion PCV, and total volume of blood administered did not appear to influence survival. However, the mean adjusted posttransfusion PCV of dogs with hemorrhage was significantly higher (p less than 0.001) in dogs that survived. Possible adverse events were observed during or shortly after RBC transfusion in 10 (3.3%) dogs; all reactions were mild and self-limiting, and none were hemolytic.

Anemia↗