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Biomedical subjects

N J MacLachlan

Publications and source records attributed to N J MacLachlan.

At least 91 records · Page 5Linked to original sources
PubMed1988

Equivalent potency and pharmacokinetics of recombinant human growth hormones with or without an N-terminal methionine.

Two forms of human GH (hGH) have been produced by recombinant DNA technology. One form has an amino acid sequence identical to that of the natural pituitary hormone (rhGH) and the other form has an additional N-terminal methionine (Met-hGH). The biological potencies of these 2 polypeptides have been compared in hypophysectomized rats in a multidose study measuring body weights and several long bone growth parameters. The pharmacokinetic profiles after iv and sc injection were determined in cynomolgus monkeys in a 4-period cross-over study. All of the measured parameters in all the studies indicated that there was no difference in the two forms of hGH. Measurements taken after 27 daily injections of rhGH or Met-hGH (30-500 micrograms/kg.day) indicated that femur length and width of the proliferative zone in the tibial epiphysis showed dose-related effects for both forms of hGH but no difference between them. The relative potency, based on body weight gain, was calculated using a parallel line bioassay. Weight gain after 8 daily injections in the 5-dose long bone growth study indicated a rhGH potency of 0.80 (95% confidence interval, 0.5-1.23) relative to Met-hGH. It was concluded that the presence of an N-terminal methionine on hGH has no effect on potency in this model. The pharmacokinetic parameters after iv administration were estimated by fitting serum concentration-time data to a 2-compartment model. Parameters after sc injection were computed by compartment-independent methods. Met-hGH and rhGH had very similar pharmacokinetic profiles after both routes of administration. Comparison of the pharmacokinetic parameters indicated that the clearance after iv administration (rhGH, 15 ml/min; Met-hGH, 13 ml/min) and the sc bioavailability (rhGH, 0.72 +/- 0.21; Met-hGH, 0.59 +/- 0.21) were not significantly different for the 2 forms of hGH. It was concluded that rhGH and Met-hGH have equivalent bioavailability and pharmacokinetics in cynomolgus monkeys.

Amino Acid Sequence↗
PubMed1988

Neodymium:yttrium, aluminum, and garnet laser energy delivered transsclerally to the ciliary body of dogs.

Using a hand-held optical fiber, a surgical neodymium:yttrium, aluminum, and garnet laser was used transsclerally on the left ciliary body of 25 dogs. Dogs were assigned to groups and were given low (100 J) and high (238 J) energy levels. In 12 dogs given 100-J energy, the intraocular pressure decreased a mean value of 6 mm of Hg below that in the untreated right eye. However, intraocular pressure returned to the pretreatment value 1 week after treatment. Intraocular lesions were not found by histologic examination 28 days later. In the second group of 13 dogs treated with 238-J energy, 6 were euthanatized 7 days after treatment and 7 were euthanatized 28 days after treatment. A mean decrease in intraocular pressure of 10 mm of Hg in the treated left eye, relative to the untreated right eye, persisted throughout the evaluation period. In eyes examined histologically 7 days after treatment, ciliary hemorrhage and necrosis were prominent. Other histologic changes were minimal and consisted principally of iris stromal hemorrhage. Of 7 dogs examined for 28 days after treatment, 6 remained sighted; in 1 dog, extensive intraocular hemorrhage occurred, eventually resulting in phthisis bulbi. Ciliary atrophy and fibrosis were the important histologic lesions observed 28 days after treatment. Laser energy delivered transsclerally by this optical system effectively induced ciliary necrosis and may be an effective treatment for canine glaucoma.

Animals↗
PubMed1987

Ovarian disorders in domestic animals.

The histologic appearance of the ovaries and persistence of corpora lutea vary considerably among domestic animals, particularly between spontaneous and induced ovulators. The seasonally polyestrous mare has a variety of unique characteristics in ovarian structure and general reproductive function. Among the anomalies of ovarian development is the bovine freemartin with gonads containing a mixture of male and female elements. A variety of ovarian cysts occur in domestic animals, and persistent corpora lutea with associated reproductive perturbations occur in several species. Ovarian tumors are relatively uncommon in domestic animals, with most examples described in dogs, cats, and horses. These ovarian neoplasms are generally classified as epithelial, germ cell, or sex cord-stromal tumors.

Aging↗
PubMed1987

Humoral immune response of calves to bluetongue virus infection.

Humoral immune responses of 7 calves to bluetongue virus (BTV) infection were evaluated by plaque-reduction assay and immunoblotting. Most readily interpretable results were obtained with the immunoblot assay when colostrum-deprived calves were used, and sera were reacted with proteins in partially purified extracts of BTV. Viremia persisted in calves for 35 to 56 days, and BTV coexisted in blood for several weeks with virus-specific neutralizing antibody. Calves developed antibody to virus protein 2, the major determinant of virus neutralization, at 14 to 28 days after inoculation; this time interval also coincided with the appearance of neutralizing antibody in serum. Virus clearance in BTV-infected calves did not coincide with humoral immune responses to protein 2 or other virion proteins.

Animals↗
PubMed1986

Genetic stability in calves of a single strain of bluetongue virus.

Newborn calves were inoculated IV with highly plaque-purified bluetongue virus (BTV), serotype 10. The electrophoretic migration patterns of RNA segments and proteins of viruses isolated from calves at intervals after inoculation were compared. In addition, sera collected from calves at intervals after inoculation were compared for their abilities to neutralize several virus isolates from the same calf. Viremia persisted in calves for up to 56 days. Differences were not detected in the electrophoretic migration pattern of RNA segments or proteins of any of the BTV isolates. All calves produced high titers of neutralizing antibody to the original BTV inoculum by 28 days after inoculation, and significant (greater than or equal to 4-fold) differences were not detected in the neutralizing titers of sera to viruses collected at intervals after inoculation. The plaque-purified strain of BTV appeared to be stable genetically in infected calves, and failure to demonstrate antigenic variation among isolates indicated that antigenic shift was not the mechanism that allowed viremia to persist in BTV-infected calves.

Animals↗
PubMed1986

Effect of recombinant DNA-derived bovine alpha-1 interferon on transmissible gastroenteritis virus infection in swine.

Recombinant DNA-derived bovine interferon alpha 1-1 (BoIFN) inhibited replication of both vesicular stomatitis virus and transmissible gastroenteritis virus in cultures of swine testicular cells. Newborn pigs were orally inoculated with BoIFN and subsequently had interferon in their gastric contents and serum; however, interferon was found only occasionally in intestinal washings. Incubation of BoIFN with gastric contents from a newborn suckling pig did not affect antiviral activity, whereas intestinal (small intestine) contents from the same animal inactivated BoIFN within 1 minute. Beginning at 6 hours of age, newborn, colostrum-deprived pigs were given 1 mg of BoIFN orally every 12 hours. These pigs were not protected against challenge exposure to virulent transmissible gastroenteritis virus at 48 hours of age; disease and mortality were similar for these pigs and for control pigs not given BoIFN prior to challenge exposure. The BoIFN did not impair growth rate of pigs and did not cause obvious disease or lesions.

Administration, Oral↗
PubMed1985

Bluetongue virus-induced interferon in cattle.

Calves were inoculated IV with bluetongue virus (BTV), serotype 10. Titers of interferon (IFN) in serum and BTV in peripheral blood were determined. All inoculated calves produced circulating IFN that persisted for 2 to 4 days. Highest titers of BTV in peripheral blood were present after serum IFN was no longer detected. The persistence of BTV in peripheral blood, as compared with the transient IFN response, indicated that IFN was most important in the initial antiviral response of cattle to BTV infection. Bluetongue virus is probably not a suitable model inducer of circulating IFN in cattle because the profound neutropenia that accompanied BTV infection may predispose cattle to infections with other agents.

Animals↗
PubMed1985

Orbivirus infection of the bovine fetus.

Direct inoculation of 85-125 day bovine fetuses with 4 serotypes of bluetongue virus (BTV) or 1 serotype of epizootic hemorrhagic disease virus (EHDV) resulted in either fetal death or teratogenesis. Three serotypes of BTV, and 1 of EHDV caused a similar cavitating encephalopathy, the severity of which likely reflected gestational age of the fetus at infection. Virus-specific antibody was readily detected in precolostral serum samples from all inoculated fetuses that survived until term, whereas, virus was not recovered from any of these calves. Calves with severe Orbivirus induced cerebral malformations would have poor viability, and they could not be expected to have any significance as virus reservoirs.

Animals↗
PubMed1985

Comparison of tissue reactions produced by Haemophilus pleuropneumoniae vaccines made with six different adjuvants in swine.

Tissue damage caused by six different adjuvants incorporated in a Haemophilus pleuropneumoniae vaccine was compared in swine. The adjuvants compared were four mineral oil compounds, one peanut oil compound and aluminum hydroxide. Inoculations were given in the neck, quadriceps and semitendinosus muscles. The mineral oil adjuvants were highly irritant and caused extensive areas of granulomatous inflammation that were present at eight weeks after injection. The aluminum hydroxide produced smaller lesions that also persisted for eight weeks. Only the peanut oil adjuvant did not produce significant lesions at the site of injection. At two and four weeks, but not at eight weeks postinoculation, lesions in the quadriceps and semitendinosus muscles were approximately twice as extensive as those in the muscles of the neck.

Adjuvants, Immunologic↗
PubMed1984

Lymphocyte blastogenesis in bluetongue virus or Mycobacterium bovis-inoculated bovine fetuses.

Bovine fetuses were inoculated with Mycobacterium bovis, bluetongue virus or placebo at approximately 125 days of gestation, and blastogenic responses of peripheral blood lymphocytes and lymph node cells were determined at various time intervals after inoculation. Lymphocytes from all fetuses were stimulated by phytohemagglutinin, concanavalin A, and pokeweed mitogen, and peripheral blood lymphocytes gave consistently greater stimulation indices than did prescapular lymph node cells. Bluetongue virus infection did not consistently suppress mitogen induced lymphocyte blastogenesis. Lymphocytes taken from fetuses at 20 or 50 days after Mycobacterium bovis inoculation were not stimulated by purified protein derivative (PPD), whereas lymphocytes taken from adult cattle at similar intervals after Mycobacterium bovis inoculation were stimulated by PPD. Although lymphocytes from bovine fetuses may be stimulated by mitogens, antigen specific blastogenesis to a known inducer of cellular immunity was not detected by 175 days of gestation.

Animals↗
PubMed1983

Bluetongue virus-induced hydranencephaly in cattle.

Direct inoculation of bluetongue virus into 125-day bovine fetuses resulted in development of hydranencephaly. The earliest lesions after virus inoculation were a severe necrotizing encephalitis, which was most prominent in the cerebrum, and an associated nonsuppurative meningitis. At birth, the brains of infected fetuses had thin-walled cerebral hemispheres, dilated lateral ventricles, and cerebral cysts. No gross lesions were observed in the brain stem or cerebellum. Two morphologically different lesions were present in the brain of a fetus sacrificed 20 days after virus inoculation. There were discrete foci of hemorrhagic cerebral necrosis that resembled infarcts and widespread microcavitations of the intermediate and subventricular zones. Changes consistent with vascular damage were present in the brains of fetuses sacrificed 12 and 20 days after virus inoculation. Calves with bluetongue virus-induced hydranencephaly would have poor viability, but they would not be expected to have any significance as virus reservoirs.

Anencephaly↗
PubMed1982

Ontogeny of the immune system.

Cellular and humoral aspects of the immune response develop sequentially in the fetus. Although there is evidence of immunologic activity to some antigens, many of the nonimmune effector systems are neither developed nor fully functional in the fetus. The lack of fully functional systems make the fetus a highly susceptible candidate for invading bacteria and viruses. Often, infection prior to immune competence may lead to abortion, malformation, and in some instances, viral persistence and immune tolerance. On the other hand, immune responses tend to elevate immunoglobulin values and cause specific antibody that may be used for diagnostic purposes. Little work has been done to appreciate fully the immunologic and nonimmune effector systems' role in normal development or during congenital infections.

Adenoviridae Infections↗