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Biomedical subjects

M J Tarr

Publications and source records attributed to M J Tarr.

54 records · Page 3Linked to original sources

Enhancement of murine mixed lymphocyte response by 1,1-dimethylhydrazine: characterization and possible mechanism.

Treatment of mice with 1,1-dimethylhydrazine (UDMH) resulted in enhancement of the one-way mixed lymphocyte response (MLR); this effect was seen when both responder and stimulator mice were treated as well as when just the stimulator or just the responder mice were treated. Experiments in which splenocytes were exposed to UDMH in vitro indicated that exposure of the stimulator cells alone resulted in an enhanced MLR; exposure of the responder cells alone had no effect; and addition of UDMH to the assay (exposure of both populations) resulted in suppression of the response at higher concentrations. A possible mechanism for the enhancement of the MLR by UDMH was suggested by further experiments showing that UDMH inhibited prostaglandin E2 production by adherent splenocytes.

Animals↗

Expression, release, and characterization of soluble human T-lymphotropic virus-I (HTLV-I) antigens from an infected cell line.

The Human T-lymphotropic virus type I (HTLV-I) infected cell line MT-2 was studied to obtain HTLV-I or related proteins for the purpose of producing an effective vaccine for HTLV-I infection. The cells were characterized as to HTLV-I antigen expression during the cell cycle and antigens released into the culture fluids. MT-2 cell grown in fetal calf supplemented media produced more HTLV-I related antigens during the G2/M phase of the cell cycle. To determine the conditions for maximal release and harvest of HTLV-I associated proteins, the MT-2 cells were grown in RPMI 1640 medium supplemented with serum-free medium. Cell- and virus-free supernatants were collected on day 4, lyophilized, and concentrated 50-fold. The proteins in these supernatants were characterized using SDS-PAGE and western blot using rabbit anti-HTLV-I sera and human adult T-cell leukemia sera. The western-blot analysis indicated that the supernatants obtained from the MT-2 cells grown in serum-free supplemented medium contained detectable amounts of proteins which reacted with human ATL and rabbit anti-HTLV-I sera. The molecular weights of these proteins observed are 68kd, 46kd, 28kd, 24kd, 19kd, and 15kd indicating that gag, env, and pX gene products are present.

Blotting, Western↗

Clinicopathologic findings associated with chronic renal disease in cats: 74 cases (1973-1984).

The historic, physical, laboratory, and histologic findings for 74 cats with chronic renal disease were reviewed. Most cats were older, and no breed or sex predilection was detected. This most common clinical signs detected by owners were lethargy, anorexia, and weight loss. Dehydration and emaciation were common physical examination findings. Common laboratory findings were nonregenerative anemia, lymphopenia, azotemia, hypercholesterolemia, metabolic acidosis, hyperphosphatemia, and isosthenuria. The most common morphologic diagnosis was chronic tubulointerstitial nephritis of unknown cause. The other pathologic diagnoses were renal lymphosarcoma, renal amyloidosis, chronic pyelonephritis, chronic glomerulonephritis, polycystic renal disease, and pyogranulomatous nephritis secondary to feline infectious peritonitis.

Animals↗

Serological and virological evidence of human T-lymphotropic virus in systemic lupus erythematosus.

We present evidence that systemic lupus erythematosus (SLE) patients, but not other mixed connective tissue disease patients, have been exposed to a retrovirus similar or identical to known human T-lymphotropic viruses (HTLV). Serological studies demonstrated a high incidence of seropositivity in SLE patients to HTLV-I antigens by indirect immunofluorescence and Western blot analysis, and to HTLV-III by Western blot analysis. Furthermore, peripheral blood mononuclear cells from four patients with SLE cultivated in vitro expressed HTLV-I antigens after 3 days or more in culture, and reverse transcriptase activity was detected in supernatants from short-term cultures.

Antibodies, Viral↗

Dietary estrogens--a probable cause of infertility and liver disease in captive cheetahs.

The cheetah in the wild is "racing towards extinction" mostly due to habitat destruction. Its survival will probably depend on accelerated captive breeding. At this time, however, reproductive failure and liver disease threaten the future of the captive cheetah population. Histopathological evaluation of more than 100 cheetah livers identified venocclusive disease as the main hepatic lesion responsible for liver disease in this species. Analysis of the commercial feline diet by high-performance liquid chromatography and gas-liquid chromatography-mass spectrometry revealed large amounts of two phytoestrogens identified as daidzein and genistein. These compounds were found to be derived from a soybean product that was a component of the cheetah diet, and their concentrations both ranged from 18 to 35 micrograms/g diet. The adult cheetah consequently consumes approximately 50 mg/day of these weak estrogens. When extracts of the diet were tested for estrogenicity using a bioassay, a dose-related increase in uterine weight was observed. In 4 cheetahs studied, withdrawal of this feline diet by substitution with a chicken diet resulted in an improvement in conventional liver function tests and a normalization in the appearance of hepatic mitochondria. We conclude that the relatively high concentrations of phytoestrogens from soybean protein present in the commercial diet fed to captive cheetahs in North American zoos may be one of the major factors in the decline of fertility and in the etiology of liver disease in this species. The survival of the captive cheetah population could depend upon a simple change of diet by excluding exogenous estrogen.

Acinonyx↗

Tissue distribution of amyloid deposits in Abyssinian cats with familial amyloidosis.

The tissue distribution of amyloid deposits was studied in 15 related Abyssinian cats with familial amyloidosis. There was interstitial medullary amyloidosis in the kidneys of all 15 cats but only 11 had detectable glomerular involvement. The thyroid glands, stomach and colon were affected in all cats examined. Most of the cats also had amyloid deposits in the small intestine, spleen, heart, adrenals, pancreas, liver, lymph nodes and bladder. In 50 per cent or fewer of the cats examined, there was involvement of the parathyroids, lung and gonads. The central nervous system was not involved in any of the 3 cats evaluated. In 8 of the cats, no concurrent inflammatory disease could be detected. The tissue distribution of amyloid deposits resembled that found in other breeds of domestic cats with systemic amyloidosis. Despite the wide tissue distribution of amyloid deposits, clinical signs were related to renal amyloidosis. Familial amyloidosis in the Abyssinian cat may represent a valuable spontaneous animal model for the study of Familial Mediterranean Fever in man and the pathogenesis of reactive amyloidosis in general.

Amyloid↗

Feline leukemia vaccine: efficacy, contents and probable mechanism.

An effective subunit vaccine against feline leukemia virus infection and related diseases has been developed. The source of the vaccine immunogen is feline retrovirus persistently infected cells that continuously synthesize and shed virus polypeptides. Western blot analysis identifies FeLV-gp70, p27, p15, p12, and p10 in the subunit vaccine preparation. Cats immunized with the vaccine developed antibodies to a 70,000 MW protein of the vaccine that seems to be distinct from, but related to the FeLV-gp70 polypeptide.

Animals↗

Oncogenic viruses of domestic animals.

The objective of this article is to review the relevant oncogenic viruses of small animals. Basic scientific principles that have been discovered by research into feline leukemia and other animal cancer viruses have enhanced our understanding of oncogenesis and have led to practical methods of cancer control and prophylaxis.

Animals↗

Hemodialysis of a dog with acute renal failure.

A dog with oliguric acute renal failure presumed to have been caused by ethylene glycol ingestion was treated by hemodialysis for 1 month. Hemodialysis was effective in controlling azotemia, hyperphosphatemia, and hyperkalemia when performed on a daily or alternate-day basis. The major complications during treatment were infection and severe weight loss. Serial renal biopsies disclosed a progression from initial acute tubular necrosis to severe diffuse interstitial fibrosis and mononuclear cell inflammation. Infection, cachexia, development of end-stage renal lesions, and terminal hyperkalemia contributed to the eventual death of the dog.

Acute Kidney Injury↗

In vivo and in vitro effects of 1,1-dimethylhydrazine on selected immune functions.

The in vivo phase of the experiments reported here include the evaluation of immune function after short-or long-term treatment of mice with 1,1-dimethylhydrazine (UDMH). Long-term exposure (3 injections/week for 14 weeks) resulted in increased numbers of Jerne plaque-forming cells, a trend toward decreased induction of suppressor cell activity by concanavalin A (Con A), and no effects on mitogen-induced lymphocyte blast transformation (LBT), compared to saline-treated control mice. These effects were greatest at doses of 10 or 50 mg/kg, while higher doses had less of an effect. In vitro experiments were performed by adding UDMH to normal murine splenocytes in the LBT assay and con A-induced suppressor cell assay. The UDMH induced a significant enhanced response to lipopolysaccharide (LPS) at 10 and 50 micrograms/ml, and a suppressed response to both Con A and LPS at higher concentrations. The UDMH also caused a decrease in suppressor cell activity at 25 micrograms/ml. Selective abrogation of suppressor activity or alteration of the suppressor cell-helper ratio were suggested as possible mechanisms for the enhancement effect associated with UDMH.

Animals↗

Suppression of mitogen-induced blastogenesis of feline lymphocytes by in vitro incubation with carcinogenic nitrosamides.

Effects of brief in vitro incubation with nitrosamides on the lymphocyte blast transformation (LBT) response of feline peripheral blood mononuclear cells (PMC) to concanavalin A (con A) was studied. Incubation for 1/2 hr with 10--100 microgram/ml methylnitrosourea (MNU) or 0.1-2.01 microgram/ml methyl-N-nitrosoquanidine (MNNG) caused marked suppression of the normal LBT response. This effect was not due to cytotoxicity, since viability experiments showed no significant decrease in viability for any concentration of either MNU or MNNG. MNU caused suppression when added to PMC cultures 24 hr, but not 48 hr, after initiation of stimulation with con A. Biologically inactivated MNU also caused suppression of the LBT response, similar in magnitude to active MNU. Finally, serum from cats immunologically suppressed by MNU did not cause suppression of the LBT response of normal feline PMC. It was concluded that the immunosuppressive properties of MNU previously noted in vivo are probably due to a direct suppressive effect on lymphocytes and/or macrophages, and that the decreased LBT response to con A of MNU-treated PMC is an accurate reflection of the immunosuppression seen in vivo.

Animals↗

The effects of methylnitrosourea on the immune system and hematopoietic system of adult specific pathogen free cats.

The effects of a single non-carcinogenic dose of 15 mg/kg methylnitrosourea (MNU) on the immune and hematopoietic systems of adult specific-pathogen-free (SPF) cats were determined. The cell-mediated-immune (CMI) system was markedly suppressed, as evidenced by: (i) Prolonged cutaneous allograft retention time (41-84 days); (ii) Decreased lymphocyte blast transformation response to mitogens (2% of pretreatment response to pokeweed mitogen or concanavalin A) and antigen (12% of untreated control cat response to keyhole limpet hemocyanin); (iii) Reduced number of absolute erythrocyte-rosetting T-cells in the peripheral blood. This immunosuppression lasted at least 3 months, the duration of the experiment. Suppression of the hematopoietic system was also noted as evidenced by: (i) Peripheral lymphopenia lasting 3 months and neutropenia lasting 3 weeks; (ii) Bone marrow hypocellularity lasting 3 weeks; (iii) Hypoplasia of neutrophilic precursors lasting 3 weeks and erythroid precursors lasting 4 days. It was concluded that a single non-carcinogenic dose of MNU induces a prolonged suppression of the CMI system and a brief suppression of hematopoiesis in adult SPF cats. The immunosuppression may in part be responsible for the previously observed increased susceptibility to feline leukemia virus infection and disease of adult SPF cats treated with MNU.

Animals↗

Erythrocyte rosette formation of equine peripheral blood lymphocytes.

Erythrocyte rosette (ER) formation of equine peripheral blood lymphocytes (PBL) was characterized. Guinea pig and, to a lesser extent, human erythrocytes formed ER; cat, cow, dog, hamster, mouse, rat, and sheep erythrocytes showed negligible rosetting properties. Conditions of the assay were varied to determine which procedure allowed the largest percentage of rosette formation. The PBL from 20 normal horses were then assayed, averaging 38 +/- 2% ER. To characterize the erythrocyte receptor as being on T or B cells, equine thymocytes from 6 foals were assayed; the thymocytes formed an average of 66 +/- 5% ER. Mixed ER and erythrocyte-antibody-complement rosette assays showed no PBL which bound both ER and erythrocyte-antibody-complement rosettes. The PBL which was stimulated with phytohemagglutinin formed more rosettes (69 +/- 2%) than nonstimulated, control PBL (42 +/- 3%).

Animals↗

Effect of 1,1-dimethylhydrazine on lymphoproliferation and interleukin 2 immunoregulatory function.

The studies reported here suggest that the immunomodulatory effects of 1,1-dimethylhydrazine (UDMH) are associated, in part, with interference with interleukin 2 (IL-2) regulatory action. Concanavalin A (Con A)-stimulated DNA synthesis in murine splenocytes was inhibited from 18.6 to 44.1% at sub-toxic concentrations of UDMH (10 to 50 micrograms/ml) and IL-2-dependent DNA synthesis in CTLL-20 cells was inhibited from 11.3 to 41.58% at sub-toxic concentrations of UDMH (10 to 50 micrograms/ml). In addition, UDMH suppressed phorbol myristic acetate (PMA)-stimulated IL-2 production in EL-4 cells by up to 30% and slightly suppressed IL-2 production by Con A-stimulated murine splenocytes. In all cases, inhibition was evident at sub-toxic UDMH concentrations and was demonstrated to be independent of inactivation of IL-2 or interference with IL-2 absorption. It is suggested that UDMH has the potential to modify immune function through interference with IL-2 production and especially the lymphoproliferative response to IL-2.

Animals↗

How are three-dimensional objects represented in the brain?

In this report we discuss a variety of psychophysical experiments that explore different aspects of the problem of object recognition and representation in human vision. In all experiments, subjects were presented with realistically rendered images of computer-generated 3D objects, with tight control over stimulus shape, surface properties, illumination, and viewpoint, as well as subjects' prior exposure to the stimulus objects. Contrary to the predictions of the paradigmatic theory of recognition, which holds that object representations are viewpoint invariant, performance in all experiments was consistently viewpoint dependent, was only partially aided by binocular stereo and other depth information, was specific to viewpoints that were familiar, and was systematically disrupted by rotation in depth more than by deforming the 2D images of the stimuli. The emerging concept of multiple-views representation supported by these results is consistent with recently advanced computational theories of recognition based on view interpolation. Moreover, in several simulated experiments employing the same stimuli used in experiments with human subjects, models based on multiple-views representations replicated many of the psychophysical results concerning the observed pattern of human performance.

Cues↗

Species variation in susceptibility to methylnitrosourea-induced immunosuppression.

Methylnitrosourea (MNU) was shown to suppress the cell-mediated immune system of mice. Cutaneous allografts were retained longer than controls in mice treated with 25 or 50 mg/kg MNU. The lymphocyte blast transformation (LBT) responses to the mitogens concanavalin A (con A) and lipopolysaccharide (LPS) of splenocytes from treated mice were also suppressed three days following treatment. By 7 and 42 days, however, the LBT responses to con A were higher than the controls for the 10 and 25 mg/kg dose groups. The rebound in the response to LPS was not nearly so pronounced and at 7 and 42 days was still suppressed for the 50 mg/kg dose group. In additional experiments, the LBT response of normal murine splenocytes to con A and LPS were significantly suppressed after exposure to 25 micrograms/ml MNU, and the LBT response of human lymphocytes to con A was suppressed after exposure to 60 micrograms/ml MNU. The results of these studies were compared to previous experiments in cats. It was concluded that cats are more immunosuppressed by MNU than mice, and suppression of the LBT response following exposure of normal lymphocytes to MNU is in the order cats greater than mice greater than humans.

Animals↗