ABSTRACT
A set of experimental model systems were designed to investigate (a) the inter-relationship between growth of two human cancer cell lines (SK-CO-1, HT-29) and carcino-embryonic antigen (CEA) kinetics; and (b) whether neoplastic growth or CEA concentration is modulated by human growth hormone (hGH). We found that increasing CEA concentration depended on tumour burden. SK-CO-1 cells had the lowest growth rates but the highest rates of CEA production. The rate of CEA increase exceeded the growth rate of both SK-CO-1 and HT-29. hGH modulated neither neoplastic growth nor CEA production. In conclusion, our results suggest that experimental models may be useful for investigating the role of serological markers as monitors of increasing tumour burden. It will be of interest to investigate the performance of those model systems in examining the effect of cytotoxic agents in neoplastic growth.
Subject(s)
Adenocarcinoma/pathology , Carcinoembryonic Antigen/metabolism , Colonic Neoplasms/pathology , Neoplasm Proteins/metabolism , Adenocarcinoma/metabolism , Animals , Colonic Neoplasms/metabolism , Growth Hormone/pharmacology , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Transplantation , Transplantation, Heterologous , Tumor Cells, CulturedABSTRACT
Transgenic mice with tissue-specific expression of the human insulin gene in the beta cells of the pancreas do not produce insulin-specific antibodies when injected with human insulin. Tolerant transgenic mice injected with human or porcine insulin reflect the clinical situation. When injected with bovine insulin the transgenic mice produce antibodies. The potential immunogenicity of 12 recombinant human insulin analogues has been tested in this transgenic model. The analogues were designed either to prevent hexamer formation or to improve chemical stability or both. The analogues have amino acid substitutions or deletions at residue 8, 10 and 21 in the A-chain and residue 3, 9, 27 and 28 in the B-chain. The results show that substitution of single amino acids in the A-chain loop of human insulin for the corresponding amino acids in bovine insulin at residues A8 or A10 is sufficient to elicit an antibody response in responder mice. Only human insulin analogues with substitutions at residues 8 or 10 in the A-chain elicit antibody formation in the transgenic mice, whereas non-transgenic control groups respond to insulin and all analogues. Antibodies developed against the human insulin analogues are cross reactive with recombinant human insulin. Antibodies developed against an immunogenic analogue could therefore neutralize both the analogue and the native insulin and thereby aggravate the patient's condition. This transgenic mouse immunogenicity model should be useful as an in vivo model to map immunogenic areas of recombinant proteins.
Subject(s)
Insulin Antibodies/biosynthesis , Insulin/genetics , Insulin/immunology , Proinsulin/genetics , Amino Acid Sequence , Animals , Antibody Formation , Base Sequence , Cattle , Crosses, Genetic , DNA Primers , Female , Humans , Insulin/analogs & derivatives , Insulin/biosynthesis , Macromolecular Substances , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Inbred DBA , Mice, Inbred Strains , Mice, Transgenic , Molecular Sequence Data , Polymerase Chain Reaction , Sequence Homology, Amino Acid , SwineABSTRACT
Inherited coagulation disorders have been diagnosed in many breeds of dogs as well as in mongrels and cats. This article presents the different coagulation factor deficiencies that are known to exist in small animals. A description is given of each coagulation factor along with the relevant clinical signs, inheritance, and the breeds affected. Suggestions are also given for the diagnosis and therapy of these deficiencies.
Subject(s)
Blood Coagulation Disorders/veterinary , Cat Diseases/genetics , Dog Diseases/genetics , Afibrinogenemia/genetics , Afibrinogenemia/veterinary , Animals , Blood Coagulation Disorders/genetics , Cats , Dogs , Factor VII Deficiency/genetics , Factor VII Deficiency/veterinary , Factor X Deficiency/genetics , Factor X Deficiency/veterinary , Factor XI Deficiency/genetics , Factor XI Deficiency/veterinary , Factor XII Deficiency/genetics , Factor XII Deficiency/veterinary , Hemophilia A/genetics , Hemophilia A/veterinary , Hemophilia B/genetics , Hemophilia B/veterinary , Hypoprothrombinemias/genetics , Hypoprothrombinemias/veterinaryABSTRACT
Classical hemophilia, hemophilia A, is the most common coagulation disorder in dogs. This article presents a comprehensive study of this disease in German Shepherd dogs in Denmark. Emphasis is placed on pathophysiology, diagnosis, genetics, therapy, and prophylaxis. Furthermore, a scheme for a rational elimination of the causative gene from the population is presented.
Subject(s)
Dog Diseases/genetics , Hemophilia A/veterinary , Animals , Breeding , Denmark , Dog Diseases/diagnosis , Dog Diseases/therapy , Dogs , Female , Hemophilia A/diagnosis , Hemophilia A/genetics , Hemophilia A/therapy , MaleABSTRACT
Clinical data, pedigrees, screening tests (APTT, PT and TT) and specific tests (VIII:C, VIIIC:Ag, VIIIR:Ag and IX:C) were used to diagnose hemophilia A (classical hemophilia) in two colonies of German Shepherd dogs in Denmark. The affected individuals in both colonies were males, and they descended from a common, hemophilic ancestor. All observations were in accordance with X-linked, recessive inheritance. Therapeutic and prophylactic measures are discussed.
Subject(s)
Dog Diseases/blood , Hemophilia A/veterinary , Animals , Blood Transfusion , Dogs , Female , Hemophilia A/prevention & control , Hemophilia A/therapy , Male , PedigreeABSTRACT
A review is given of the history and distribution of hemophilia in dogs. The current knowledge of Factor VIII relative to hemophilia A and von Willebrand's Disease is presented. The tests required for distinguishing between hemophilia A, hemophilia B, von Willebrand's Disease, and various disorders caused by other factor defects in the coagulation cascade are described. X-linked, recessive inheritance of hemophilia A is illustrated in genealogical diagrams. The precautions required in connection with blood sampling for diagnostic tests are emphasized.
Subject(s)
Dog Diseases/blood , Hemophilia A/veterinary , Animals , Blood Specimen Collection , Denmark , Diagnosis, Differential , Dogs , Factor VIII/physiology , Female , Hemophilia A/genetics , Hemophilia A/physiopathology , Male , Mammals , PedigreeSubject(s)
Cell Line , Neoplasms, Experimental/pathology , Animals , Bone Neoplasms/pathology , Breast Neoplasms/pathology , Carcinoma/pathology , Cell Differentiation , Female , Head and Neck Neoplasms/pathology , Humans , Lung Neoplasms/pathology , Male , Mice , Mice, Nude , Neoplasm Transplantation , Sarcoma, Experimental/pathology , Transplantation, Heterologous , Uterine Cervical Neoplasms/pathologyABSTRACT
Subcutaneous inoculation of 87 human tumors into athymic nude mice, including gastrointestinal (non-colon) tumors, germ cell-primitive cell tumors, kidney tumors, lower urinary tract tumors, malignant melanomas and several metastases from unknown primary sites, resulted in growth in primary transplants in 32 cases (36.8%). Take rates varied among the tumor categories, from 56% for malignant melanomas to 13% for lower urinary tract tumors. They also differed among recurrent tumors (50%), metastases (41%) and tumors of primary site (28%). 23 tumor lines were established, including five lines each from renal cell adenocarcinomas and malignant melanomas, two each from adenocarcinoma of the pancreas and Wilms' tumors and only line each from various tumors of the gastrointestinal, germ cell-primitive cell, lower urinary tract and primary site unknown categories. The frequency of line establishment was greater for recurrent tumors and metastases than for primary tumors. Tumor lines have been carried continuously up to passage 17 in one case. Time in primary transplant varied from 3 to 29 weeks for the individual tumors and the average primary transplant time varied from 5.8 to 14.7 weeks for the six tumor categories. The average time in passage varied among the established lines from 2.3 to 10.6 weeks. The average passage time for all tumor lines was 5.3 weeks, with those of recurrent tumor origin showing the shortest average (4.0 weeks) followed by lines of metastatic origin (5.4 weeks) and those of primary tumor origin (5.8 weeks).
Subject(s)
Cell Line , Mice, Nude , Neoplasm Transplantation , Adenocarcinoma/pathology , Animals , Female , Gastrointestinal Neoplasms/pathology , Humans , Kidney Neoplasms/pathology , Male , Melanoma/pathology , Mice , Neoplasm Metastasis , Urologic Neoplasms/pathologyABSTRACT
One hundred and twenty-seven cultured human tumor cell lines produced tumors after sc inoculation of 1-20 million cells into nude mice. They included 56 carcinoma lines, 14 sarcoma lines, and 57 lines from miscellaneous tumors and were all glucose-6-phosphate dehydrogenase type B. Twenty-nine percent of the lines produced tumors of 1 cm3 size within 1 month and 41% in the second month after inoculation. The histopathology correlated with the human tumor of origin in all cases.
