Impact of blood transfusions and HLA on cyclosporine-treated renal transplant recipients.
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Azathioprine↗
Biomedical subjects
R M Lewis
Publications and source records attributed to R M Lewis.
A retrospective analysis of long-term renal allograft function associated with cyclosporine-prednisone immunosuppressive therapy.
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Azathioprine↗
Cloning of cDNA for DARPP-32, a dopamine- and cyclic AMP-regulated neuronal phosphoprotein.
A cDNA clone for the mRNA of bovine DARPP-32 (dopamine- and adenosine 3',5'-monophosphate-regulated phosphoprotein, Mr = 32,000) was isolated from a modified Okayama-Berg plasmid library. Transformed Escherichia coli colonies were screened by in situ colony hybridization with 2 different oligonucleotide probes corresponding to a region unusually rich in glutamate within the protein. Three positive clones were isolated and shown to encode DARPP-32 by an in situ immunoblot assay of their fusion protein products with beta-galactosidase. The results of the sequence analysis of the longest cDNA clone, pTKD7 (1771 nucleotides), revealed a 606-nucleotide-long coding region, in exact agreement with the bovine DARPP-32 amino acid sequence (Williams et al., 1986). Southern blot analysis of total bovine genomic DNA showed that there is a single gene coding for DARPP-32. Northern blot analysis of caudate nucleus RNA using antisense RNA derived from the clone pTKD7 demonstrated the existence of 2 abundant mRNA species, corresponding to 1.8 and 1.65 kilobase in length. The high concentration of DARPP-32 mRNAs in the caudate nucleus is in agreement with the known distribution of this protein.
Amino Acid Sequence↗
Clinicopathologic, renal immunofluorescent, and light microscopic features of glomerulonephritis in the dog: 41 cases (1975-1985).
In a 10-year retrospective study, we evaluated the clinicopathologic features and renal immunofluorescence patterns of glomerulonephritis in 41 dogs. On the basis of results of histologic examinations, the dogs were segregated into 3 groups, including membranous (n = 12), mesangioproliferative (n = 15), or membranoproliferative glomerulonephritis (n = 14). No significant differences existed among groups in regard to age or duration of illness. Most dogs had been ill for one month or longer. The proportion of dogs with azotemia, anemia, and hyperphosphatemia were not different among the disease groups. Proportion of dogs with hypoalbuminemia and the severity of hypoalbuminemia were not different among groups. Highest urine protein losses and 24-hour urine protein/creatinine ratios developed in dogs with membranous glomerulonephritis. Although hypoalbuminemia and hypercholesterolemia were common (49%), the formation of edema or ascites was not (15%) and, therefore, few dogs had all of the classic features of the nephrotic syndrome. Few dogs suffered thromboembolic complications. Antinuclear antibody titers developed in 11 dogs, the highest titers developing in dogs with polyarthritis and systemic lupus erythematosis. Cellulose acetate electrophoresis detected alpha 2 and beta 1 globulin spikes in most dogs (87%). Results of renal immunofluorescence testing were positive in 36 dogs, using polyvalent antisera for immunoglobulins (Ig)G, IgA, IgM, and/or antisera for complement factor C3. When monovalent antisera for IgG, IgA, and IgM, and fibrinogen were used, immunofluorescence was not observed as often. The major fluorescent pattern was discrete multifocal segmental granular glomerular fluorescence, consistent with immune-complex deposition. Two dogs had linear glomerular staining patterns; however, antibodies directed against normal glomerular basement membrane were not found via elution studies. A high prevalence of glucocorticoid excess (treatment with glucocorticoids and spontaneous hyperadrenocorticism) (34%), chronic inflammatory skin disease (27%), neoplasia (17%), polyarthritis (12%), and systemic lupus erythematosis (7%) were observed as clinical problems concurrent with glomerulonephritis. In 5 dogs, treatment of glomerulonephritis with prednisolone (0.5 to 1.1 mg/kg) did not result in beneficial effects and in fact appeared to be detrimental, leading to azotemia and worsening proteinuria and physical condition in some of the dogs.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Differentiation of a human monocytic cell line associated with increased production of Rift Valley fever virus by infected cells.
Rift Valley fever (RVF) virus is a cause of significant human and animal disease in many parts of Africa. In some cases, it causes a hemorrhagic fever, which is frequently fatal. Prior studies have shown that RVF virus productively infects peritoneal macrophages from susceptible rat strains. The U937 human monocytic cell line was used to determine the effect of monocytic cell differentiation on the degree of viral production by cell cultures infected with RVF virus. Differentiation of U937 cells to more mature monocytic cells by phorbol ester resulted in production of 10 times more infectious virions in comparison with undifferentiated cells. These studies imply that monocytic cell differentiation increases permissiveness for RVF virus production.
Bunyaviridae↗
Comparative pathology of canine hereditary nephropathies: an interpretive review.
Hereditary nephropathies in dogs represent multiple complex clinicopathological entities which cause renal failure in juvenile, adolescent, and young adult dogs. To date, nephropathies believed to have a genetic basis have been described in 11 breeds. These disorders represent a variety of developmental, degenerative, and metabolic defects. Many canine hereditary nephropathies are analogous to childhood nephropathies in man. Review of the veterinary literature, comparative pathology, and avenues of future research are discussed.
Animals↗
Juvenile renal disease in the Doberman Pinscher: ultrastructural changes of the glomerular basement membrane.
Ten cases of juvenile renal disease in Doberman Pinschers were examined by light microscopy and 8 of them additionally by electron microscopy. Two distinct basic ultrastructural lesions of the glomerular basement membrane (GBM) were observed. One is characterized by lamellation of the lamina densa with intramembranous focal areas of lucency containing electron-dense particles, the second by diffuse attenuation of the lamina densa with intramembranous and/or subendothelial deposition of matrix entrapping cross-banded fibres (collagen). Based on similar ultrastructural changes in other hereditary nephropathies in man and dogs, a metabolic or biochemical basis for the structural lesions is suspected.
Aging↗
The effects of d-amphetamine on food competition in male rats.
Male Wistar rats were tested in 3 competitive situations to determine the effects of d-amphetamine (AMP) on competitive behavior. Subjects were initially tested in a fixed-pair food competition paradigm. Based on the percentage of pellets obtained, a winner and loser were defined for each pair. AMP (2.0 and 4.0 mg/kg) was then administered to one or both members of pair, and the effects of the drug on the defined winners and losers were determined. AMP did not significantly alter the percentage of pellets obtained by losers except when only the winners were administered AMP (4.0 mg/kg). Subjects were then tested in a round-robin competition paradigm in which each subject was paired with every other subject. The animals were ranked according to the percentage of pellets obtained out of a possible 450 pellets. AMP (2.0 mg/kg) decreased pellet acquisition in higher ranking subjects, whereas pellet acquisition was increased in lower ranking subjects. The effects of AMP were also evaluated in a "worker-parasite" paradigm. Subjects were individually conditioned to press a lever using an FI schedule for presentation of a food pellet. When the lever was located on the wall opposite the food hopper, a worker and parasite were defined for each pair. The worker was the subject that made the most responses on the lever while obtaining fewer reinforcements. Subjects that were defined as winners in the fixed pair food competition emerged as the workers in this situation. AMP (0.8 mg/kg) given concurrently to both subjects resulted in a reversal of roles; the parasites now emitted the majority of responses and obtained less pellets. The data indicate that AMP has a differential effect on participants in competitive situations when all subjects in the situation are treated.
Animals↗
Long-term cultivation of canine keratinocytes.
The growth characteristics and morphology of canine keratinocytes grown in vitro were studied. Keratinocytes from canine oral mucosa, ear skin, and ventral abdominal skin were grown in culture either as explants or as dispase/trypsin-derived suspensions in the absence of a feeder cell layer. Cholera toxin and epidermal growth factor were essential to the successful long-term growth and propagation of the cells during multiple passages. Keratinocytes from all tissue sources, either as primary cultures or subcultivated for up to 10 passages, had growth characteristic and morphology similar to that reported in other species. The use of cultured canine keratinocytes should provide a suitable model for comparative in vitro studies of the pathogenesis of dermatologic diseases.
Abdomen↗
Ultrastructural and phenotypic changes in Langerhans cells induced in vitro by contact allergens.
Ultrastructural changes of murine Langerhans cells (LC) were examined following exposure of crude epidermal cell suspensions to the contact allergens dinitrochlorobenzene, nickel sulphate and lead nitrate at various concentrations and for various incubation times. An immunogold labelling technique was employed to study changes in surface expression of MHC Class II (Ia) molecules. In all cases, activation of LC was evident after as little as 15 min exposure and was characterized by a marked increase in surface expression of Ia molecules, prominent rough endoplasmic reticulum and numerous ribosomes and lysosomes. Degenerative changes in LC were apparent to varying degrees depending on the allergen, its concentration and the time of incubation. Degenerative changes included swollen mitochondria, membrane disruption or rupture, loss of density of the cytoplasm (cytolysis), loss of dendritic processes and decreased expression of Ia molecules. In the case of dinitrochlorobenzene, degenerative changes were present and usually severe at concentrations greater than 10 micrograms/ml, while exposure to nickel sulphate and lead nitrate was associated with only mild degenerative changes. These observations indicate that contact allergens have a variety of direct effects on LC, including activation and degeneration, which are dose- and time-dependent. Since these alterations of LC were observed in the absence of other immunologically active cells, peripolesis cannot be involved in these events.
Allergens↗
Microscopic features of canine renal dysplasia.
Forty-five cases of renal dysplasia in dogs are examined. Microscopic lesions of dysplasia include asynchronous differentiation of nephrons, persistent mesenchyme, persistent metanephric ducts, atypical tubular epithelium, and dysontogenic metaplasia. These may be distinguished from secondary lesions including compensatory hypertrophy and hyperplasia of the nephron and a variety of degenerative and inflammatory lesions. Although morphological features of renal dysplasia in dogs differ somewhat from those in man, microscopic criteria used in the diagnosis of human dysplasia may be useful when applied to the dog.
Animals↗
Purification and identification of murine epidermal dendritic cells: flow cytometry and immunogold labeling.
We report on application of flow cytometric and immunogold labeling techniques to purify and identify two types of murine epidermal dendritic cells: Langerhans cells (LC) and Thy-1-positive dendritic epidermal cells (Thy 1+-dEC). After density centrifugation of epidermal cell (EC) suspensions through Ficoll gradients. IA-positive LC and Thy 1+-dEC are labeled with monoclonal antibodies (fluorescein-conjugated anti-IAd for LC and anti-Thy 1.2-biotin, followed by avidin-phycoerythrin, for Thy 1+-dEC). The fluorescence-activated cell sorter (FACS) is then used to obtain 95-98% pure populations of these dendritic cells with a yield of 2-4 X 10(6) cells and a viability of 80-90%. A post-fixation, pre-embedding immunogold labeling technique using 15 nm and 40 nm colloidal gold particles is employed to identify LC and Thy 1+-dEC, respectively, to confirm the purity of the sorting and to estimate the number of IA antigenic sites per LC. With transmission electron microscopy, ultrastructural morphology of sorted LC is preserved; however, Birbeck granules are markedly diminished compared to the pre-sorted population of LC. In contrast, characteristic dense-core granules are readily visualized in sorted Thy 1+-dEC. Purification of epidermal dendritic cells by flow cytometry may be a useful technique to employ in functional studies of epidermal dendritic cells.
Animals↗
Studies of the coagulation system in arenaviral hemorrhagic fever: experimental infection of strain 13 guinea pigs with Pichinde virus.
Significant coagulation abnormalities were associated with experimental infection of strain 13 guinea pigs with Pichinde virus, an arenavirus related to the virulent human pathogens Junin, Machupo, and Lassa viruses. Infected animals developed decreased activity of multiple coagulation factors, decreased antithrombin III levels, high levels of fibrin-fibrinogen degradation products, impaired platelet function, and thrombocytopenia. Testing for the presence of a coagulation inhibitor revealed a pattern consistent with factor deficiency. Fibrin thrombi were not found at necropsy. The findings of high fibrin-fibrinogen degradation product levels and decreased antithrombin III levels, in association with decreased activity of multiple coagulation factors and thrombocytopenia, suggest that intravascular coagulation is a feature of this experimental infection. The demonstration of abnormal platelet function is also significant, as this could contribute to defective hemostasis despite the moderate thrombocytopenia which usually occurs in arenaviral disease.
Animals↗
Monoclonal antibodies: cell surface markers for canine keratinocytes.
Plasma membranes were isolated from cultured canine keratinocytes by paraformaldehyde-induced membrane vesiculation. The isolated plasma membrane vesicles retained cell surface antigens (eg, a pemphigus vulgaris antigen). These membrane vesicles were used as an antigen source for the production of monoclonal antibodies. Eight antibodies that had specific reactivity to the cytoplasmic membrane of keratinocytes on frozen sections of canine esophagus were identified by use of an indirect immunoperoxidase method. The stratified squamous epithelium of the esophageal mucosa had 4 staining patterns. When applied to frozen sections of canine skin, lip, and tongue, the antibodies had different tissue specificities for differing stratified squamous epithelia. Using sodium dodecyl sulfate polyacrylamide-gel electrophoresis and the western blot technique, one of the antibodies was specific for a 60-kD cell surface molecule. Therefore, such monoclonal antibodies may be useful in defining heterogeneity between different stratified squamous epithelia, in identifying biologically important surface antigens, or in the diagnosis of tumors.
Animals↗
Factors determining renal transplant outcome at the University of Texas at Houston.
CsA-Pred therapy yields equivalently good patient survival for LRD and 2 degrees CAD versus 1 degree CAD transplants. There is a long-term graft survival advantage for LRD versus 1 degree CAD transplants (5 years; 83% vs 58%). 2 degrees CAD transplants have inferior graft survival when compared with 1 degree CAD grafts (one year; 78% vs 67%). Multiple donor factors adversely affecting graft outcome include increased warm and cold ischemia times, pulsatile perfusion, use of pressors or diuretics in the donor, donor age less than 10 years, donor blood transfusions, and kidneys shipped from other centers. Recipient factors adversely affecting graft outcome include retransplantation and CMV infection as well as noncompliance with therapy. HLA-matching and pretransplant blood transfusions have not contributed in a statistically significant way to graft outcome although they may affect the quality of graft function at this center. Immunosuppressive therapy with CsA-Pred must be tailored to the individual patient. Continuous IV CsA infusion in the preoperative period and slow steroid taper impact favorably on graft outcome. The complications of CsA therapy include neuroectodermal toxicity, hepatotoxicity, and most importantly, nephrotoxicity. Other problems unique to CsA-Pred therapy include hypertension, delayed graft thrombosis, and de novo hemolytic uremic syndrome. Hepatotoxicity may eventuate in biliary and pancreatic complications necessitating surgical therapy. The overall incidence of infection and neoplasm remains low with CsA-Pred therapy. The use of therapeutic trough CsA level monitoring, as well as pharmacokinetic and pharmacodynamic analyses may assist in clinical decision making regarding administered doses, dosing interval, and discrimination between rejection and nephrotoxicity.
Adolescent↗
PROBFIND: a computer program for selecting oligonucleotide probes from peptide sequences.
Synthetic oligonucleotides have proven to be extremely useful probes for screening cDNA and genomic libraries. Selection of the appropriate probe can be more easily and accurately achieved with the use of the computer program PROBFIND. The user enters the amino acid sequence from a file or from the keyboard, selects the minimum length allowed for the probe and the maximum allowable degeneracy. The computer prints a list of the sequences of potential probes which meet these minimum specifications and the location of the corresponding sequence in the protein to the screen and to a file. The user may modify the specifications for length and degeneracy at any time during the output of data, which allows for rapid selection of the desired probe. The program is interactive, accepts any file format with only a single modification of the file, is written in BASIC, and requires less than 6 kbytes of memory. This makes the program easy to use and adaptable even to unsophisticated microcomputers.
Amino Acid Sequence↗
Myocardial ischemia: platelet and thromboxane concentrations in cardiac lymph and the effects of ibuprofen and prostacyclin.
Blood platelets have been implicated in several mechanisms leading to and/or modifying myocardial ischemia. Cardiac lymph examination allows insight into the extracellular fluid that is in equilibrium with the capillary blood. In order to obtain an index of platelet activation during coronary artery events in the awake chronic animal, we wished to ascertain whether evaluation of cardiac lymph would detect changes in platelet activation resulting from a vascular occlusion. The study used conscious dogs in which cardiac lymph vessels had been previously cannulated by open-chest surgical protocol. The concentrations of immunoreactive thromboxane B2 and platelet counts were assessed in the cardiac lymph during the control period, the 10-60 minute occlusions, and the reperfusion periods. The same protocols were effected on another series of dogs after infusion of ibuprofen or prostacyclin. Initially, immunoreactive thromboxane B2 concentrations in the systemic blood and cardiac lymph were identical. A three-fold increase in immunoreactive thromboxane B2 concentrations occurred in untreated animals and was accompanied by a fall in platelet count in the lymph. The infusion of ibuprofen or prostacyclin, which inhibit platelet aggregation by different mechanisms, prevented both the decrease in platelets and the increase in immunoreactive thromboxane B2. In this study, intravascular events resulting from coronary occlusion invoke a rapid rise of immunoreactive thromboxane B2 in the extravascular fluid. A decrease in platelet escape into the extravascular compartment is interpreted as a result of intravascular aggregation promoting decreased platelet numbers. Thus, examination of continuously flowing cardiac lymph allows rapid detection of intravascular activation of platelets in the awake animal in the absence of surgical trauma.
Animals↗
Immunopathology of laboratory animals.
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Animals↗