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Biomedical subjects

T T Brown

Publications and source records attributed to T T Brown.

At least 55 records · Page 3Linked to original sources
PubMed1985

Dose-response studies of gentamicin nephrotoxicity in rats with experimental renal dysfunction. II. Polyvinyl alcohol glomerulopathy.

Animal studies involving concurrent pathophysiologic states, including experimental renal dysfunction, are useful for a proper understanding of the mechanisms of gentamicin nephrotoxicity and acute renal failure. This study examined gentamicin nephrotoxicity in a model of glomerular dysfunction in rats. Administration of medium molecular weight polyvinyl alcohol (PVA) produced a glomerulopathy, with characteristic accumulation of macromolecular PVA in the glomerular mesangium without altering glomerular filtration or causing proteinuria. Subsequent daily doses of gentamicin ranging from 0 to 120 mg/kg elicited a dose-response nephrotoxicity in both control and PVA-pretreated rats after 6 or 12 days of drug. Based on statistical analysis of renal clearances of creatinine, urea, sodium, and potassium; serum creatinine and urea nitrogen; urinary N-acetyl-beta-D-glucosaminidase excretion (6 days only); in vitro renal cortical transport of tetraethylammonium (TEA) (6 days); and quantified light-microscopic data (12 days), PVA induced an early (6 days) sensitivity to gentamicin nephrotoxicity. By 12 days, there were no differences in the responses of control and PVA rats to gentamicin. Single-dose gentamicin clearance, volume of distribution, and half-life were not altered by PVA and renal concentrations at 6 days were generally lower in these rats. Results of TEA transport studies tend to rule out PVA-induced metabolic lesions in the proximal tubular epithelium as the mechanism for the early sensitivity. This investigation demonstrates altered gentamicin nephrotoxicity in rats with an otherwise benign glomerulopathy and, combined with similar conclusions from a related study in subtotally nephrectomized rats, presents further evidence that the underlying pathophysiologic state of the kidney is an important factor in the renal response to nephrotoxins.

Animals↗
PubMed1985

Dexamethasone and indomethacin modify endotoxin-induced respiratory failure in pigs.

We studied the porcine pulmonary response to endotoxemia before and after administration of nonsteroidal antiinflammatory drugs (NSAID, i.e., indomethacin or flunixin meglumine) or dexamethasone (DEX). Escherichia coli endotoxin was infused intravenously into anesthetized 10- to 12-wk old pigs for 4.5 h. In endotoxemic pigs, the phase 1 (i.e., 0-2 h) increases in pulmonary arterial pressure, pulmonary vascular resistance (PVR), and alveolar-arterial O2 gradient and the decreases in cardiac index (CI) and lung dynamic compliance (Cdyn) were blocked by NSAID. Thus phase 1 changes were cyclooxygenase dependent. Furthermore, these effects were blocked or greatly attenuated by DEX. During phase 2 of endotoxemia (i.e., 2-4.5 h), the increased PVR and decreased CI and Cdyn were not blocked by NSAID but were attenuated by DEX, suggesting the presence of cyclooxygenase-independent metabolites. Both NSAID and DEX blocked the endotoxin-induced increases in lung water, bronchoalveolar lavage (BAL) neutrophil, and BAL albumin content. The fall in plasma proteins persisted in NSAID but not DEX-treated pigs. We conclude that endotoxemia in the pig causes severe acute respiratory failure largely mediated by cyclooxygenase and possibly lipoxygenase products of arachidonic acid metabolism.

Animals↗
PubMed1985

Effects of endotoxemia on lung water and hemodynamics in conscious calves.

The effects of endotoxemia on cardiovascular and pulmonary parameters were determined in conscious, 4- to 6-week-old calves. Escherichia coli endotoxin was infused continuously (4 micrograms/kg/hr, IV) for 5 hours. During endotoxemia, pulmonary vascular resistance and mean pulmonary artery pressure increased, and cardiac index, central plasma volume, and mean systemic arterial pressure decreased. Neutrophil, lymphocyte, and platelet counts also decreased. During the first hour of endotoxemia PaO2 decreased, and alveolar-arterial O2 gradient and shunt fraction increased. Lung extravascular thermal volume was increased from 2 to 5 hours. Postmortem extravascular lung water/extravascular dry weight ratio, bronchoalveolar lavage albumin, and poly morphonuclear cell content did not change. Microscopically, the septal capillaries of endotoxemic calves were dilated and engorged with erythrocytes, accompanied by focal accumulations of neutrophils. Intraalveolar edema and hemorrhage were not seen.

Animals↗
PubMed1983

Development of a nonneuronal cell line derived from porcine spinal ganglia.

A cell line from porcine spinal ganglion (PSPG) tissue was initiated and characterized. The PSPG cell line contained epithelioid, fibroblast-like, and stellate-like cells. There were numerous intercellular communications between cells in the culture. Neuronal cells were not present in the PSPG cell line. The PSPG cell line was aneuploid at the 5th and 45th subculture levels. Seven porcine viruses replicated in cultures of PSPG cells, and 2 pseudorabies virus strains infected the cells after being diluted 10(-7).

Animals↗
PubMed1981

Laboratory evaluation of selected disinfectants as virucidal agents against porcine parvovirus, pseudorabies virus, and transmissible gastroenteritis virus.

Of a variety of disinfectants evaluated, only sodium hypochlorite and sodium hydroxide inactivated porcine parvovirus (PPV) after a 5-minute incubation period. After the same incubation time, pseudorabies and transmissible gastroenteritis viruses were inactivated by all of the disinfectants tested. When the incubation time was increased to 20 minutes, 2% glutaraldehyde and a double-strength concentration of a commercial formaldehyde preparation also inactivated PPV. Formaldehyde vapor and ultraviolet radiations inactivated PPV also, but relatively long exposure times were required.

Animals↗
PubMed1980

Transplacental infection and embryonic death following maternal exposure to porcine parvovirus near the time of conception.

Each of 20 gilts (principals) from a commercial swine herd free of antibody for porcine parvovirus (PPV) was exposed intranasally and orally to PPV at the onset of gestation. The gilts were killed and necropsied 22 +/- 1 days later to determine the effect of the virus on their embryos. An equal number of gilts (controls of the same status, from the same herd, and bred to the same boars, were treated similarly except for exposure to PPV. The following data were obtained at necropsy and from subsequent laboratory tests. Principals had 223 corpora lutea (8 to 16/gilt) and 203 embryos (6 to 16/litter). Porcine parvovirus-infected embryos (1 to 9/litter) were detected in 12 (60 per cent) of the 20 litters. Of the 203 embryos of principals, 169 were alive and 34 were dead and in various stages of decomposition and resorption. Both virus and viral antigen were detected in 7 of the live embryos (1, 1, 2, and 3 in 4 litters) and in 32 of the dead embryos. With 1 exception, infected live embryos were next to infected dead littermates in the uterus suggesting the beginning of intrauterine spread of the virus. Controls had 234 corpora lutea (9 to 15/gilt) and 217 embryos (9 to 14/litter). None of their embryos were infected with PPV and all but 3 were alive.

Animals↗
PubMed1980

Porcine fetuses with pulmonary hypoplasia resulting from experimental swine influenza virus infection.

Porcine fetuses between 51 and 57 days of gestation were inoculated intraallantoically with swine influenza virus and examined 3, 7, 13, 28 and 58 days after inoculation. At 3 and 7 days, severe epithelial necrosis was seen in most bronchial buds and there was moderate epithelial necrosis in more fully differentiated major bronchi. As a result of the epithelial injury, bronchial buds did not develop further and the surrounding mesoderm failed to differentiate. By 28 days, the lungs of inoculated fetuses were about one-half the size of the normal control lungs. Microscopically, the lungs of the inoculated fetuses were composed of major bronchi surrounded by multiple islands of cartilage, medium to large arteries and a few small, incompletely developed lobules. Influenza virus was isolated most consistently and in greatest quantity from the lung, trachea and chorion of inoculated fetuses. Influenza viral antigen was shown in the epithelium of bronchial buds, bronchi and the trachea by direct fluorescent antibody staining. Hemagglutination inhibiting antibodies to influenza virus were first found in the serum of an inoculated fetus at 13 days and in the sera of all inoculated fetuses at 28 and 58 days.

Animals↗
PubMed1980

Response of conventionally raised weanling pigs to experimental infection with a virulent strain of porcine parvovirus.

Conventionally raised 6-week-old pigs were inoculated intranaslly and orally with porcine parvovirus. The pigs remained clinically normal for up to 17 days. They were viremic between 2 and 6 days after inoculation and had detectable hemagglutination-inhibiting titers to porcine parvovirus at 5 or 6 days after inoculation. Virus was isolated from multiple tissues of pigs killed between 3 and 17 days after inoculation. Viral antigen was demonstrated mainly in lymphoid tissues of these pigs. Gross and microscopic examination of tissues failed to reveal any notable pathologic changes. The numbers of thymus- and bone marrow-derived lymphocytes did not differ significantly in inoculated and noninoculated control pigs, and the response of peripheral blood lymphocytes to selected mitogens was not altered by infection.

Animals↗
PubMed1980

Effect of vaccinal and passive immunity on experimental infection of pigs with porcine parvovirus.

One group of 5 pigs was vaccinated twice at 6 and 8 weeks of age with an inactivated porcine parvovirus (PPV) vaccine. A 2nd group of 5 pigs was passively immunized at 9 weeks of age, and a 3rd group of 5 pigs served as nonimmunized controls. The immunity of all pigs was challenged with live PPV at 10 weeks of age. Four vaccinated pigs with hemagglutinating-inhibiting (HI) antibody titer of 160 to 640 and 3 passively immunized pigs with HI titer of 80 to 160 were resistant to PPV infection. Neither infective virus nor viral antigen was detected in their tissues. However, virus replicated in tissues of 1 vaccinated and 2 passively immunized pigs with HI titers of 80, and viral antigen was detected in their lymphoid tissues. There was a 4-fold increase of HI titer in 1 passively immunized pig. Viremia and viral excretion were not detected in any of the vaccinated or passively immunized pigs. In contrast, PPV replicated in the tissues of nonimmunized pigs; both virus and viral antigen were detected in their tissues, and they produced HI antibodies to PPV. All nonimmunized pigs developed viremia and shed virus in oral secretions and feces. Our data show that a high level of humoral antibodies is required for protection from PPV infection.

Animals↗
PubMed1979

Serological response of the bovine fetus to bovine viral diarrhea virus.

Susceptible pregnant heifers were inoculated with bovine viral diarrhea virus at 150 days of gestation and earlier. Fetuses were surgically collected at selected times after inoculation. Serum immunoglobulins were quantitated, and the presence of specific antibodies was determined. In fetuses from heifers inoculated at 150 days, immunoglobulin M (IgM) appeared approximately 2 weeks after inoculation and was followed in 7 days by IgG1. Later IgG2 was detected in the sera of three fetuses. Serum-neutralizing and complement-fixing antibodies were first detected in a fetus taken at 206 days of gestation. Fetuses taken at later times also had specific serum antibodies. Possible explanations for the appearance of serum immunoglobulin substantially before specific bovine viral diarrhea antibodies include the viral alteration of host tissues rendering them antigenic viral activation of polyclonal B cells, and viral modulation of virus-specific lymphocytes causing specific interference with the appearance of antiviral antibodies. In one of the fetuses having IgG2, the serum also contained IgA. Placental leakage of material immunoglobulins was thought to be responsible for the presence of IgA and IgG2 in this fetus. Small quantities of IgM were found in the serum of two fetuses taken from heifers inoculated between 65 and 95 days of gestation, but specific antibodies were found in none.

Animals↗
PubMed1979

Replication of porcine parvovirus in peripheral blood lymphocytes, monocytes, and peritoneal macrophages.

Porcine peripheral blood lymphocytes (PBL), peripheral blood monocytes, and peritoneal macrophages were examined for their ability to support porcine parvovirus (PPV) replication. The cell cultures were infected with the NADL-2 strain of PPV at 0.1 multiplicity of infection. PBL cultures were stimulated with the following phytomitogens: phytohemagglutinin M, concanavalin A, and pokeweed mitogen. Unstimulated PBL cultures infected with PPV and uninfected PBL stimulated with phytomitogens served as controls. All cultures were examined daily for PPV-specific immunofluorescence and hemagglutinin. PPV replicated in PBL cultures stimulated with all phytomitogens. Both viral hemagglutinin in culture fluids and nuclear immunofluorescence in cells were detected. In contrast, unstimulated PBL did not support viral replication; however, PPV antigen was detected in the cytoplasm. PPV persisted in unstimulated PBL for 21 days (duration of the experiment) without replication, but replicated each time with the addition of phytohemagglutinin M at 0, 3, 7, 14, and 21 days after infection. Uninfected PBL stimulated with phytomitogens lacked both viral hemagglutinin and immunofluorescence. Simultaneous detection of lymphocyte surface marker and viral antigens in pokeweed mitogen-stimulated PBL revealed that both T and non-T cells (B and null cells) are able to support PPV replication. Peripheral blood monocytes and peritoneal macrophages phagocytized PPV but did not support virus replication.

Animals↗
PubMed1979

Efficacy of an inactivated virus vaccine for prevention of porcine parvovirus-induced reproductive failure.

Gilts vaccinated IM either once (4 gilts) or twice (2 gilts) with an acetylethyleneimine-inactivated porcine parvovirus (PPV) vaccine before they were bred were subsequently exposed intranasally and orally to virulent PPV at about the 40th day of gestation (from 37 to 43 days). At 2 weeks after vaccination, all had hemagglutination-inhibiting (HI) titers for PPV (from 20 to 80) which decreased by the time the immunity was challenged with virulent virus (from 10 to 40), but increased thereafter (from 160 to 1,280). Titers of singly and doubly vaccinated gilts were similar throughout the experiment. The gilts were killed at about the 84th day of gestation (from 80 to 87 days), and their litters were examined. Litters were comprised of 68 live fetuses and 1 dead fetus (7 to 14 fetuses/litter). Neither viral antigen, PPV, nor homologous HI antibody was found in any of the fetuses. In addition, 4 gilts were kept in contact with the vaccinated gilts and were treated similarly except for vaccination. These 4 gilts remained free of HI antibody until after they were exposed to virulent PPV during gestation. At the time the gilts were killed the titers were 1,280 to 2,560. Their litters were comprised of 11 live fetuses and 26 dead fetuses (8 to 11 fetuses/litter). Virus was isolated from fetuses of all litters. Viral antigen was found in 24 of the dead fetuses and 10 of the live fetuses. All infected live fetuses also had HI antibody for PPV. The 2 boars used to breed vaccinated and nonvaccinated gilts (usually each gilt was bred to each of the 2 boars), but not exposed to virulent PPV, remained free of HI antibody for PPV.

Animals↗
PubMed1978

Cerebrospinal parelaphostronglylosis in llamas.

Four of 11 llamas (Lama guanicoe) from a ranch near Houston, Texas developed clinical signs of a neurologic disease. Tissues from 2 of the 4 llamas were submitted for microscopic examination. Lesions in the central nervous system of both llamas appeared to have been caused by a migrating parasite. An adult nematode having morphologic features of the meningeal worm (Parelaphostrongylus tenuis) was found in the brain of one llama. The findings suggest that the neurologic disease in the llamas were caused by P. tenuis.

Animals↗
PubMed1976

Male pseudohermaphroditism, cryptorchism, and Sertoli cell neoplasia in three miniature Schnauzers.

A syndrome of male pseudohermaphroditism, cryptorchidism, and testicular neoplasia was diagnosed in 3 Miniature Schnauzers. The dogs had clinical signs of hyperestrogenism and were either unilateral or bilateral cryptorchids. At surgery, it was discovered that the dogs were male pseudohermaphrodites, having intra-abdominal testes containing Sertoli cell tumors and uteri that had undergone endometrial cystic hyperplasia.

Animals↗
PubMed1976

Fetal and adult bovine interferon production during bovine viral diarrhea virus infection.

Levels of interferon in adult bovine serum and in fetal bovine serum and tissues were examined during the course of transplacental bovine viral diarrhea virus infection. The cows produced circulating interferon between 2 and 9 days after viral inoculation, with mean peak levels in the serum on day 4. Interferon could be routinely detected in fetal tissues (e.g., thymus, spleen, and kidney) between days 4 and 21 after viral inoculation of the cows at 149 to 150 days of gestation (mid-second trimester) and in fetal serum from day 13 through day 21. Interferon was also detectable in the serum and tissues of fetuses from dams infected at day 95 of gestation (the beginning of the second trimester). In general, no differences were found between the ability of the adult and fetus to produce interferon. Fetal lamb kidney cells were more sensitive to the antiviral effects of bovine interferon than were fetal bovine kidney cells. The antiviral substance from the fetal and adult animals was characterized as interferon by standard criteria.

Age Factors↗