Biomedical subjects

V E Valli

Publications and source records attributed to V E Valli.

At least 55 records · Page 3Linked to original sources

PubMed1992

Production of anti-NC1 antibody by affected male dogs with X-linked hereditary nephritis: a probe for assessing the NC1 domain of collagen type IV in dogs and humans with hereditary nephritis.

Some patients with hereditary nephritis (HN) who have received a renal transplant have been shown to form antibody with specificity for the NC1 domain of collagen type IV, a major constituent of glomerular basement membranes (GBM). We attempted to duplicate this phenomenon in a family of dogs with X-linked HN, a model for human X-linked HN, by immunizing affected male dogs with normal dog NC1 domain. A collagenase digest was prepared from normal dog GBM, the NC1 domain was separated into dimer (approximately 50 kDa) and monomer (24 kDa and 26 kDa) components by SDS-PAGE, and injected into two affected male dogs. Antisera obtained from both dogs contained antibody which reacted with the NC1 domain of dog and human GBM by a plate-binding radioimmunoassay, bound to the dimer and 26 kDa monomer bands by Western blotting, and staining dog and human GBM by immunofluorescence (IF). The affected male dog antiserum reacted equally by radioimmunoassay with the NC1 domain isolated from GBM of unaffected, affected male, and carrier female dogs in the family with X-linked HN, and bound by Western blotting to dimers and the 26 kDa monomer band of the NC1 domain of GBM in each group of dogs. However, the affected male dog antiserum differentiated these dogs by IF; it produced global staining of GBM of unaffected dogs, failed to stain GBM of affected male dogs, and produced segmental staining of GBM of carrier female dogs. Absorption of the affected male dog antiserum with normal dog NC1 domain eliminated the staining of dog GBM by IF, whereas staining persisted after absorption with affected male dog NC1 domain. The abnormal staining patterns of GBM seen by IF in the affected male and carrier female dogs and the results of the absorption studies imply an abnormality of one or more determinants in the 26 kDa monomer band of the NC1 domain of their GBM. Amino acid sequencing of this band identified the alpha 1(IV) chain of collagen type IV, a finding that has implications for the pathogenesis of canine X-linked HN. Absent and segmental staining respectively were also seen by IF in GBM of a male and female patient with HN, using the affected male dog antiserum. Thus, the results obtained in affected male and carrier female dogs with X-linked HN may also be relevant to patients with this disease.

Amino Acid Sequence↗

PubMed1992

Systemic toxicity of the heavy fraction of a coal coprocessing product in male rats following subchronic dermal exposure.

The systemic toxicity of a coal coprocessing product [heavy gas oil II (HGOII)] following subchronic, dermal exposure in male Sprague-Dawley rats was investigated. HGOII was applied to the dorsal skin daily at doses of 8.7, 20.8, 50.0, or 120.0 mg/kg body weight (bw) for 13 weeks. Another group of rats treated with a medium boiling coal liquefaction product (CLP) served as positive controls. Growth suppression and decreased food consumption were noted in the groups exposed to HGOII at 20.8 mg/kg and higher, and to CLP starting at the third week of treatment. Relative liver, kidney, and brain weights in the 20.8 mg/kg HGOII group and up were higher than those of the control. Increased spleen weight was observed in all HGOII-treated groups. CLP treatment also caused increased relative kidney and brain weights. Serum cholesterol was elevated in the HGOII-treated groups starting at 8.7 mg/kg while increased uric acid and lactate dehydrogenase were observed at 20.8 mg/kg and up. Decreased erythrocyte, hemoglobin, and platelet counts were observed at 20.8 mg/kg and higher. All HGOII-treated groups had elevated reticulocytes. These biochemical and hematological changes were not observed in the CLP-treated group. Mild to marked histological changes were observed in the thyroid, thymus, liver, spleen, and bone marrow of HGOII groups. In contrast, morphological changes were relatively mild in CLP-treated animals. Data from the present study demonstrated that the hematological endpoints were sensitive to the liquid fuels and that HGOII was more toxic than CLP.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗

PubMed1992

Classification of 1,198 cases of bovine lymphoma using the National Cancer Institute Working Formulation for human non-Hodgkin's lymphomas.

A retrospective histologic study was made of 1,198 cases of bovine lymphoma using the National Cancer Institute Working Formulation for human non-Hodgkin's lymphoma. This classification scheme was found to be readily applicable to bovine lymphoma. Most of the cell types described in the National Cancer Institute Working Formulation occurred in this series of bovine lymphomas, but the distribution of cell types varied markedly compared to that of human beings. Eighty-nine percent (1,067/1,198) of bovine lymphomas were high-grade tumors. The diffuse large cell type and its cleaved variant comprised 65.9% of all bovine lymphomas. Similar to the dog, but in marked contrast to human beings where at least 34% of non-Hodgkin's lymphomas were follicular, follicular tumors were found to be extremely rare in cattle (0.3% or 4/1,198). The prevalence of cell types varied significantly between the enzootic and sporadic lymphomas. The cleaved variant of the diffuse large cell type constituted 38% (406/1,072) of enzootic lymphomas versus 14% (18/126) of sporadic lymphomas. The mitotic index (100 x oil immersion field, 175 microns in diameter) of enzootic lymphomas (3.72 +/- 0.06, mean +/- standard error) was significantly greater than the mitotic index of sporadic lymphomas (2.82 +/- 0.17). We concluded that the cleaved variant of the diffuse large cell type with high mitotic index is characteristic of enzootic lymphoma. This characteristic high-grade cell type may be a consequence of the viral etiology of the enzootic form of bovine lymphoma.

Age Factors↗

PubMed1992

Evidence for bovine leukemia virus infection of peripheral blood monocytes and limited antigen expression in bovine lymphoid tissue.

Bovine leukemia virus (BLV) infection of cattle is a common but inapparent retrovirus infection from which less than 5% of infected cattle manifest clinically with lymphoma. During the course of life-long infection, cattle maintain a high anti-BLV titer during an apparent latent infection of B cells from which proviral DNA but not transcripts can be detected. To investigate if BLV infection is truly latent and restricted only to B lymphocytes, peripheral blood leukocytes were purified from cattle with naturally acquired BLV infection with various stages of subclinical and clinical disease. These cells were purified into populations of polymorphonuclear cells, monocytes and subsequently B cells and T cells by fluorescent-activated cell sorting. Southern blot analysis revealed the presence of provirus in monocytes and B cells but not T cells. Secondly, the ability of provirus containing cell types to express BLV antigens was then confirmed by mitogen stimulation in vitro. Subsequently, the pattern of expression of BLV antigens was studied in situ in tissue sections to determine the location of BLV antigen expressing cells in vivo. Antigen expressing cells were infrequent and solitary in intrafollicular and marginal zone cells of architecturally normal lymph nodes of chronic, BLV-infected cattle. These results demonstrate that BLV persists in cells of the monocyte/macrophage lineage in addition to B lymphocytes and that expression of BLV antigens in cattle doses occur but rarely in lymph nodes of BLV infected cattle. The high frequency of provirus containing cells and infrequent expression of BLV antigen in vivo suggests that BLV expression is not truly latent but highly regulated, possibly triggered by rare events in host lymphoid tissue.

Animals↗

PubMed1992

Proviral detection and serology in bovine leukemia virus-exposed normal cattle and cattle with lymphoma.

Twenty-seven cattle with lymphoma and 46 cows from a known bovine leukemia virus (BLV)-infected herd were tested for anti-BLV antibody by the agar gel immunodiffusion (AGID) test and an enzyme-linked immunosorbent assay (ELISA). The polymerase chain reaction (PCR) and Southern hybridization were used to detect BLV provirus in the tumor DNA of the 27 cattle with lymphoma. The PCR was used to detect BLV provirus in the peripheral blood mononuclear cell DNA of the 46 normal known-exposed cattle. Two presumed false negative AGID test results compared to ELISA were found. Of ten cattle three years of age or less with "sporadic" forms of lymphoma, four had BLV provirus in tumor DNA, detectable by PCR. In two of these four, BLV provirus was clonally integrated based on digestion of tumor DNA with restriction enzymes followed by Southern hybridization. The BLV provirus was not detected by PCR in 5 of 17 cattle with "enzootic" lymphoma and two of these five were seronegative. Among normal BLV-exposed cows, 6.5% (3 of 46) were serologically positive and PCR negative; serologically negative and PCR positive cows occurred with the same frequency. Serological and PCR test results, when considered in all cattle (n = 73), had a concordance rate of 83.6%. Discordant test results occurred with approximately equal frequency between serologically positive and PCR negative (7 of 73, 9.6%) and serologically negative and PCR positive (5 of 73, 6.8%) groups. These data suggest that the role of BLV in some "sporadic" bovine lymphomas, previously unassociated with BLV, should be reexamined. The BLV provirus was not demonstrable in the tumor DNA from five adult cattle with lymphoma, suggesting that BLV may not be the etiological agent in all adult bovine lymphomas. The findings of persistently seronegative PCR positive and seropositive PCR negative cattle indicate that further work is needed to more fully understand the host-virus interaction. Present serological screening methods may not have sufficient sensitivity for determining BLV status in some circumstances.

Animals↗

PubMed1992

Detection of multiple retroviral infections in cattle and cross-reactivity of bovine immunodeficiency-like virus and human immunodeficiency virus type 1 proteins using bovine and human sera in a western blot assay.

Bovine antibovine immunodeficiency-like virus (BIV) antibodies were detected by Western blot analysis (WBA) using a chemiluminescence protocol. Bovine sera with anti-BIV activity, obtained from cows in two dairy herds, had antibodies directed against a variety of BIV-specific antigens indicating chronic infections. These sera were also tested for serological reactivity against bovine leukemia virus (BLV) and bovine syncytial virus (BSV). Cows most commonly had anti-BSV antibodies (12 of 39). Evidence for infection with BSV and BIV or BSV and BLV occurred with almost equal frequency (5 of 39 and 4 of 39, respectively) while only one instance of BIV and BLV coseropositivity was detected. The high prevalence of BSV seropositivity is consistent with a relatively infectious virus, which, as is known, may be transferred congenitally. Similar rates of coseropositivity of BIV or BLV with BSV in this population suggest that BIV is no more infectious than BLV and probably requires prolonged close contact for transmission. Seven of nine cows with anti-BIV antibodies detected primarily human immunodeficiency virus type 1 (HIV-1) p51 and p63 antigens by WBA using an alkaline phosphatase detection system, suggesting that HIV-1 proteins have potential usefulness in screening cattle for BIV seropositivity. Six human sera that showed strong reactivity against multiple HIV-1 proteins and the serum from one of three patients considered to be an "indeterminate" HIV-1 reactor, cross-reacted primarily with BIV p26. This is the first report of human sera with antibody to BIV-specific proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

The use of an implantable central venous (Hickman) catheter for long-term venous access in dogs undergoing bone marrow transplantation.

Methods were developed for the insertion and maintenance of long-term central venous catheters in dogs in order to provide reliable venous access during bone marrow transplantation. Single-lumen, 9.6 Fr Hickman catheters with a VitaCuff were used. The catheter was inserted into the jugular vein via a surgical cut-down, and tunnelled subcutaneously to exit over the thoracic spine. Fluoroscopic guidance was necessary to ensure proper positioning of the catheter tip in the right atrium. The catheter was secured at the venous entrance site with a grommet and at the cutaneous exit site with a finger-cuff suture. The exit site was bandaged; dressings were changed daily. Five dogs were studied. Catheter insertion and maintenance techniques were developed using two dogs. For the other three dogs, which developed 7 wk of profound myelosuppression induced by total body irradiation, the catheters were used for blood sampling and infusions of antibiotics, fluids, and blood products. For these three dogs there were 261 total catheter-days. Complete catheter obstruction did not occur. Partial obstruction (inability to withdraw blood) occurred for 13 days with one catheter. The tip of this catheter was in the cranial vena cava. One irradiated dog had a staphylococcal exit site infection for several days after catheter insertion, which resolved with antibiotic therapy. Infections of the subcutaneous tunnel, and catheter associated bacteremia, were not identified. Infectious and hemorrhagic complications of myelosuppression were less severe than in six other dogs where intermittent venipuncture was used for vascular access during radiation induced myelosuppression. In conclusion, long-term central venous catheterization is feasible in dogs during profound myelosuppression and markedly facilitates patient management.

Animals↗

PubMed1991

Production and related variables in bovine leukaemia virus-infected cows.

A newly developed milk dot blot test was used to detect anti-bovine leukaemia virus (BLV) antibody in milk samples from 2079 lactating adult cows from among 61 herds. The milk dot blot test was highly repeatable; the concordance rate, compared with the agar gel immunodiffusion test performed on serum, was 83.5%. All herds contained BLV-positive cows; the prevalence rate was 36%. BLV-positive cows tended to come from larger herds and were older and more often later in lactation. Fourteen production and related variables (herd size, age, days open, days in milk, milk somatic cell count, milk, fat, and protein produced in the current lactation, projected production of milk, fat, and protein, and breed class average deviations for milk, fat, and protein) were compared between BLV-positive and BLV-negative cows. Although somatic cell count, milk produced, and projected production of milk and protein were related significantly to BLV status using simple tests of association, once the variables herd size, age and days in milk were controlled, these differences were removed. Further analyses using logistic (outcome: individual cow BLV status) and least-squares regression (outcome: herd proportion of BLV-positive cows) failed to show an association between any of the measured production or related variables and BLV-positivity. We concluded that the effect of BLV on production and related variables in dairy cows was below the sensitivity of our analytical techniques or was non-existent.

Animals↗

PubMed1991

Short-term dermal toxicity and mutagenicity of coal coprocessing products in the rat.

The present study was conducted to determine the dermal toxicity of coal coprocessing products and to assess their potential health hazards. Groups of 10 male and 10 female Sprague-Dawley rats were administered dermally coal coprocessing products (light gas oil, LGO; heavy gas oil I, HGOI; heavy gas oil II, HGOII) at 1 g/kg body weight/d for 14 d. The control and positive control groups received normal saline and a coal liquefaction product (CLP) at the same dose level, respectively. Treatment with either the three fractions of coprocessing products or CLP caused decreased growth rate and food consumption in animals of both sexes. Liver enlargement occurred in groups treated with HGOI, HGOII, and CLP. Decreased serum glucose was observed in animals of both sexes treated with the three fractions and CLP. Treatment with HGOI and CLP caused an elevation of hepatic microsomal ethoxyresorufin deethylase activity in the rat of both sexes. The three fractions and CLP caused mild anemia. Mild treatment-related histological changes were observed in the liver, spleen, thyroid, bone marrow, and kidney. All three fractions of coprocessing products were tested for their mutagenicity in five strains of Salmonella typhimurium: TA98, TA100, TA1535, TA1537, and TA1538. HGOI, after metabolic activation, was found to be mutagenic in the strains of TA98, TA100, and TA1538. In contrast, HGOII was mutagenic in the five strains with or without metabolic activation. These data indicate that HGOI and HGOII are more toxic than LGO, and should be subjected to further studies to determine their long-term effects.

Administration, Topical↗

PubMed1991

Renal disease in carrier female dogs with X-linked hereditary nephritis. Implications for female patients with this disease.

Male dogs with X-linked hereditary nephritis (HN) serve as a model for studying male patients with this disease. In the present study, carrier female dogs were found to resemble female patients in showing a broad range of renal dysfunction. Of 37 carrier female dogs studied, all were healthy up to 5 years of age; however, all had proteinuria develop at 2 to 3 months, and focal segmental glomerulosclerosis (FSGS) was detected after 7 months. After 5 years, 4 of 13 dogs remained healthy and showed mild FSGS on renal biopsy; 4 had mild renal dysfunction develop and their kidneys showed extensive FSGS; 5 died prematurely of renal failure with end-stage kidneys. By immunofluorescence, using antibody to the NC1 domain of collagen type IV, segmental staining of glomerular basement membranes (GBM) was seen in all dogs before 3 to 4 years, and lesions of FSGS were negative. Thereafter, a transition to global staining of GBM was noted and lesions of FSGS became positive. Lens capsule and basement membranes in lung and choroid plexus showed discontinuous staining in two young carrier female dogs and continuous staining in one older carrier female dog. By electron microscopy, multilaminar splitting of some GBM was seen up to 4 years, and thereafter, splitting took on a compressed appearance, with the layers becoming apposed though still detectable. The authors conclude that: 1) carrier female dogs with X-linked HN are mosaics for an abnormality in the NC1 domain of GBM and other basement membranes; 2) FSGS develops in all carrier female dogs in glomerular capillary loops that possess an abnormal NC1 domain, and progresses to a variable extent in different dogs; and 3) the abnormality of NC1 in GBM of carrier female dogs appears to diminish with age, but this does not prevent progression of renal disease. Similar conclusions may apply to females with X-linked HN.

Animals↗

PubMed1991

Dietary modification reduces splitting of glomerular basement membranes and delays death due to renal failure in canine X-linked hereditary nephritis.

Affected male (AM) Samoyed dogs with X-linked hereditary nephritis (HN) demonstrate splitting of all of their glomerular basement membranes (GBM) and rapidly develop renal failure within the first year of life, features reminiscent of those seen in male patients with X-linked HN. In contrast, carrier female (CF) dogs with X-linked HN show only isolated foci of splitting of GBM, and renal failure is never seen at such an early age. In the present study, we assessed whether a diet designed for dogs in renal failure could modify the changes seen in GBM of AM and CF dogs and improve the clinical outcome in the AM dogs. Beginning at 35 days of age, one group of dogs (unaffected, AM, and CF) was fed a regular diet, while a second group was fed a modified diet (i.e., restricted in protein, lipid, calcium, and phosphorus). AM dogs fed the modified diet showed less of a reduction in glomerular filtration rate than AM dogs fed the regular diet, indicative of a delay in the onset and a decrease in the severity of renal damage. Nevertheless, all of the AM dogs eventually died of renal failure regardless of diet. However, the onset and progression of renal failure were delayed and the severity of splitting of GBM was reduced in the AM dogs fed the modified diet; these dogs lived 53% longer than AM dogs fed the regular diet. CF dogs fed the modified diet also showed a reduced severity of splitting of GBM. In addition, when two CF dogs on the modified diet were switched to the regular diet, splitting of their GBM increased, indicating that continual administration of the modified diet was required to maintain the reduced rate of splitting. These studies indicate that dietary modification is beneficial in canine X-linked HN, and suggest that similar benefits (i.e., reduction in severity of splitting of GBM and delay in development of renal failure) might be observed in patients with HN who are treated with an appropriately modified diet.

Animals↗

PubMed1990

A teratological assessment of coal liquefaction products in the rat.

Teratogenicity of coal liquefaction products (CLP) was assessed in the pregnant rat. Three product streams of CLP (medium, hydrotreated medium and heavy fractions) were each administered dermally on Sprague-Dawley rats at doses of 125, 250 or 500 mg kg-1 day-1 from Day 6 through to Day 15 of gestation. Depressed maternal weight gain and reduced number of fetuses resulting from an increased resorption rate, decreased fetal weight and retarded ossification were observed in the group treated with the heavy fraction at a dose of 500 mg kg-1 day-1. The heavy fraction at 500 mg kg-1 day-1 also caused anaemia and increased liver and spleen weights in dams. The dams exposed to the highest dose of three CLP fractions had mild and adaptative hepatic changes consisting of increased cytoplasmic eosinophilia and nuclear anisokaryosis. No treatment-related histological changes were observed in fetuses. None of the fractions demonstrated any teratological effects.

Abnormalities, Drug-Induced↗

PubMed1990

Subchronic oral toxicity of triethyl lead in the male weanling rat. Clinical, biochemical, hematological, and histopathological effects.

This study was designed to ascertain the effects of low level exposure of triethyl lead (3EL) to the male weanling rat. Groups of 20 animals were administered by gavage 3EL at 0.05, 0.10, 0.20, 0.50, and 1.00 mg/kg body wt for 91 days, 5 days/week. Lead acetate (PbHOAC) at 200 mg/kg body wt/day was given as a positive control. Weight gain was reduced in those animals receiving 1.0 3EL. Spleen and kidney weights were elevated in the PbHOAC group. Residues of 3EL and its metabolites diethyl lead (2EL) and lead (Pb) accumulated in a dose-dependent manner in blood, liver, kidney, and brain; 3EL accumulated preferentially in the liver while inorganic lead accumulated in the kidney. Dose-dependent changes occurred in serum calcium which was decreased and in phosphorus which was elevated for all dose groups. Serum cholesterol was elevated in the three highest 3EL groups as was alkaline phosphatase. LDH was lowered in the PbHOAC-treated group but microsomal aniline hydroxylase was elevated. Hematological changes consisted of elevated platelet counts in the 1.0 3EL group and decreased mean corpuscular hemoglobin content and mean corpuscular volume in the PbHOAC-treated group. Treatment related histopathological changes were seen in thyroid, liver, kidney, and bone marrow. Based on these data a no observed adverse effect level for 3EL was set at 0.10 mg/kg/body wt.

Administration, Oral↗

PubMed1990

Clinical management of the cancer patient. Taking a biopsy.

Good biopsy protocol depends on excellent interaction with diagnostic pathologists. This article reviews the essentials of diagnostic appraisal, specimen preparation, biopsy interpretation, proper reporting, and implementation of biopsy results in case management. The emphasis is on biopsy of malignancy.

Animals↗

PubMed1990

Toxicological assessment of chlorinated diphenyl ethers in the rat, Part II.

Chlorinated diphenyl ethers (CDE's) are environmental contaminants that have been found in Great Lakes fish. Because of the paucity of toxicity data and potential for human exposure, the present short-term study was conducted to assess their potential toxic effects. Groups of 10 male and 10 female rats were administered the three CDE congeners (2,2',4,4',5-pentachlorodiphenyl ether (PCDE), 2,2',4,4',5,5'-hexachlorodiphenyl ether (HCDE), 2,2',3,4,4',6,6'-heptachlorodiphenyl ether (HPCDE] in diets at levels of 0.5, 5.0, 50 or 500 ppm for a period of 4 weeks. Decreased food consumption was observed with male and female rats fed the diet containing 500 ppm HPCDE. Treatment with the three isomers at the highest dose level produced an increase in liver weight in both sexes. While administration of PCDE produced an increase in hepatic aminopyrine demethylase activity, HCDE caused a significant increase in aminopyrine demethylase, aniline hydroxylase and ethoxyresorufin de-ethylase activities. HPCDE caused a significant increase in ethoxyresorufin de-ethylase activity. HPCDE at the highest dose level also caused a significant reduction in circulating lymphocytes in male rats. The 3 CDE's produced mild and adaptative histological changes in the liver and thyroid, but only HPCDE elicited mild changes in the thymus, bone marrow, and spleen. The above data indicate that HPCDE is immunosuppressive and that all three CDE isomers are considered to be moderately toxic in rats. The no-observable effects levels appear to be between 5-50 ppm in diet (0.36-3.0 mg/kg b.w.) for the three CDE's.

Animals↗

PubMed1990

Transformed phenotype of enzootic bovine lymphoma reflects differentiation-linked leukemogenesis.

Detailed genotypic and phenotypic characteristics of enzootic bovine lymphoma were defined to determine if tumor cell characteristics were consistent with the etiologic agent of this disease. Lymphoid tumors from cattle with serologic evidence of bovine leukemia virus (BLV) infection were examined by Southern blot analysis to confirm the presence and copy number of integrated BLV. All cases of enzootic bovine lymphoma examined contained 1 to 4 BLV proviral copies in tumor DNA and revealed immunoglobulin gene rearrangement (Ig). Tumors were further characterized immunohistochemically with a panel of 8 monoclonal antibodies to bovine lymphocyte determinants and B cell differentiation markers. The majority of cases examined expressed Ia/DR, 11 of 17 cases also expressed surface IgM, frequently with another Ig isotype. To definitively characterize the stage of B cell differentiation represented in the transformed phenotype, genotypic evidence of isotype switching was examined in these tumors. Our results demonstrated that enzootic bovine lymphomas are tumors of mature B cells with common characteristics, suggesting that pressures associated with BLV infection which favor tumor development are manifested late in B cell ontogeny, possibly during the isotype switch period.

Animals↗

PubMed1990

Effects of dietary supplementation with n-3 fatty acids on kidney morphology and the fatty acid composition of phospholipids and triglycerides from mice with polycystic kidney disease.

The DBA/2FG-pcy strain of mouse has been developed as an animal model for adult polycystic kidney disease and we have determined the effects of feeding an n-3 fatty acid-enriched diet on kidney morphology and the fatty acid compositions of the constituent phospholipid and triglyceride fractions in this strain. Twelve male and female DBA/2FG-pcy mice were fed lab chow or semi-purified diets containing sunflower seed oil (SO) or a n-3 fatty acid-enriched concentrate (MaxEPA) for 60 days. At necropsy, blood and urine samples were taken and the kidneys processed for examination by light microscopy. Gas-liquid chromatography of the fatty acids in the kidney lipids was also performed. Male and female mice fed the MaxEPA-based diet tended to have lower mean kidney weights. Hematocrits, blood urea, and serum creatinine levels were similar among the lab chow-, SO- and MaxEPA-fed groups. All the groups exhibited a moderate hematuria; the incidence of this symptom was lowest in the MaxEPA-fed male animals. Extensive tubular dilatation was apparent in the cortices and medullae from the lab chow-fed animals; these lesions were slightly less severe in the SO-fed group and least severe in kidneys from the MaxEPA-fed animals. By morphometry, the renal area occupied by cysts was also lowest in the male Max-EPA-fed group; females fed the MaxEPA-based diet did not show a marked decrease in the proportion of kidney area occupied by cysts. Fatty acid compositions of the total phospholipid and triglyceride fractions from kidneys of male mice fed the MaxEPA-based diet showed a reciprocal replacement of the n-6 fatty acids with the n-3 fatty acids compared to kidneys from males fed the SO-based diet.

Animals↗

PubMed1990

Long-term culture of canine marrow: cytogenetic evaluation of purging of lymphoma and leukemia.

We established and maintained long-term cultures of marrow from normal dogs and dogs with lymphoma or leukemia by single inoculations of mononuclear cell suspensions. Media containing only horse sera (as opposed to horse and fetal calf sera) and catalase (for antioxidative effect) supported improved culture viability, as indicated by increased recovery of progenitor cells (granulocyte-macrophage colony-forming units, CFU-GM) and the release of abundant erythroid cells in the cultures for up to 3 weeks. CFU-GM were maintained for at least 3-4 weeks of culture. Culture appearance, cell counts, and assays of CFU-GM were used to compare the culture kinetics of tumor-involved marrow to normal marrow specimens. Cultures of marrow with extensive tumor involvement tended to be less viable, apparently due to a relative lack of competent progenitors. To investigate whether canine long-term marrow culture provided a purging effect similar to the loss of tumor cells noted in human long-term cultures of marrow from patients with chronic myelogenous leukemia (CML) or acute myelogenous leukemia (AML), we established long-term marrow cultures from 28 dogs with histologically confirmed untreated lymphoma or leukemia. Eleven of these dogs had cytogenetically marked tumor cells in the marrow at the initiation of culture. In six dogs with lymphoma and one dog with acute monocytic leukemia (AMoL) French-American-British classification (FAB) M4 leukemia, we could detect no cytogenetic evidence for persistence of the tumor clones in individually plucked or pooled CFU-GM grown from 3-week-old long-term cultures. In one case of AML (FAB M2), 80% of CFU-GM recovered from long-term cultures at 4 weeks still contained an extra metacentric marker chromosome associated with the continued presence of the leukemic clone in the cultures. Our documentation of a purging effect for some tumors supports the use of this canine model system in the investigation of autologous marrow transplantation with long-term cultured cells for humans with lymphoma and leukemia.

Animals↗