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Biomedical subjects

A Koestner

Publications and source records attributed to A Koestner.

At least 37 records · Page 2Linked to original sources
PubMed1987

Dieldrin inhibition of gap junctional intercellular communication in rat glial cells as measured by the fluorescence photobleaching and scrape loading/dye transfer assays.

Application of the fluorescence-recovery after photobleaching (FRAP analysis) technique and scrape loading/dye transfer assay was made to measure the presence of gap junctional communication in primary rat glial cells in vitro in the presence and absence of the neurotoxicant and tumor promoter dieldrin, a chlorinated insecticide. Results demonstrate that primary rat glial cells are able to exhibit gap junctional intercellular communication and that dieldrin at noncytotoxic concentrations can modulate gap junctional communication as early as 10 min after exposure to the chemical and that the effect is reversible after 4 hr recovery from the dieldrin exposure. Both the FRAP analysis and the scrape loading/dye transfer assay have validated the observation that dieldrin inhibits gap junctional communication in other cell types using different techniques to measure gap junction function. These results were interpreted as an indication that inhibition of gap junctional communication might contribute to the cellular mechanism of dieldrin's neurotoxicity.

Animals↗
PubMed1986

The brain-tumour issue in long-term toxicity studies in rats.

Problems arise in the measurement of the neurocarcinogenic potential of chemical substances in chronic toxicity studies because of the spontaneous occurrence of neoplasms in the brain and other organs of rats from the age of about 2 yr. Statistical analysis may be equivocal and must be accompanied by a thorough biological analysis, to determine the presence or absence of the following characteristic effects of neurocarcinogenic agents: a reliable and consistent increase in brain-tumour incidence beyond the expected control level, a decrease in the age at which tumours appear and/or in survival, a dose-effect relationship, a greater effect on embryonal and foetal brain cells than on those of adults, a shift to more anaplastic types of tumour and the finding of preneoplastic lesions. These criteria have been met in chronic tests on the neurocarcinogens ethyl- and methylnitrosourea and some have been met in results obtained with the weak carcinogen methyl methanesulphonate. However, none of these criteria were met in the case of a test compound subjected to two 2-yr studies (one involving transplacental exposure), although brain tumours occurred in the controls and in all the experimental groups. The test substance is not considered to be a neurocarcinogenic agent.

Age Factors↗
PubMed1985

Chronic toxicity/carcinogenicity study of FD & C Blue No. 2 in rats.

FD & C Blue No. 2 was fed to rats in the diet in a long-term toxicity/carcinogenicity study. The study included an in utero phase in which the compound was administered to groups of 60 male and 60 female Charles River CD albino rats at levels of 0.5, 1.0 and 2.0%. Two concurrent control groups, each containing 60 rats of each sex, received the basal diet. After random selection of the F1 animals, the long-term phase was initiated at the same dietary levels, with 70 rats of each sex in each dose group and in each of two control groups. Maximum exposure was 30 months. No consistent compound-related biologically adverse effects were noted. There were random statistically significant differences from the controls with respect to body weight, food consumption and clinical chemistry tests. Food consumption by the test groups showed a dose-related increase. This was probably due to the non-nutritive character of the colouring. A statistically significant increase in gliomas in the high-dose male rats was not found to be biologically significant, since none of the criteria for determining the neurocarcinogenic potential of chemical substances was met. The overall brain-tumour incidence in this study was within the range typical for 2-yr-old CD rats. Under the conditions of this study, FD & C Blue No. 2 did not produce evidence of any toxicity, including carcinogenicity.

Animals↗
PubMed1985

Prognostic role of cell morphology of animal tumors.

The purpose of this presentation is to determine the prognostic role of cellular morphology in animal neoplasia. With some exceptions, cellular morphology is the single most accurate predictor of the prospective behavior of neoplasms. There is generally a positive correlation between the degree of malignancy and prognosis. The exceptions are a) morphologically malignant-appearing tumors following a benign course (e.g., canine histiocytoma, canine seminoma, equine sarcoid) and b) morphologically differentiated tumors exhibiting an unpredictable prognosis (e.g., canine pericytoma, acanthomatous epulis, myxoma, follicular thyroid cell carcinoma, etc.). Anaplasia, an important characteristic of most malignant neoplasms, may be less stable than generally assumed. Sodium butyrate may reverse it intermittently and anaplastic gliomas may loose all morphologic and cytokinetic characteristics of anaplasia following sodium butyrate exposure. Host factors, such as nerve growth factor, have similar and more lasting effects upon anaplastic cells derived from the neural crest. Such factors may act as reverse transformation agents and may represent prospective therapeutic agents for anaplastic tumors.

Anaplasia↗
PubMed1985

Testicular (Sertoli's cell)-like tumors of the ovary induced by N-ethyl-N-nitrosourea (ENU) in rats.

N-ethyl-N-nitrosourea (ENU) administered intraperitoneally or transplacentally to Sprague-Dawley (CD) and BD-IV (Berlin Druckrey IV) rats increased the incidence (26.6%) of an uncommon ovarian tumor with testicular characteristics compared either to controls (3.0%) or rats administered diethylnitrosamine (3.3%). The induced tumors were composed of tubular structures that resembled seminiferous tubules lined by Sertoli's-like cells. The abundant electron-lucent cytoplasm of the tumor cells contained polyribosomes, lipid bodies, and mitochondria but few additional organelles. Sertoli's cell-like tumors appeared to develop from the ovarian stroma in the hilar region of the ovary. They usually were benign and resulted in unilateral enlargement of the ovary. The mean serum concentrations of testosterone, estrone, and estradiol in selected rats with ovarian tumors were elevated above mean serum values in controls. There was not a consistent direct correlation between tumor diameter and circulating hormone level. Ethyl nitrosourea-induced ovarian tumors composed of testicular (Sertoli's-like) cells will provide a reproducible animal model to investigate the histogenesis and hormone secreting properties of this unique gonadal neoplasm.

Animals↗
PubMed1984

Spinal cord medulloepithelioma in a dog.

Medulloepithelioma, an embryonal neural tumor, was diagnosed in a 6-month-old Bullmastiff. Clinical signs of incomplete, upper motor neuron, transverse myelopathy involving the hindlimbs were observed on examination. Myelography was required to identify the cause of clinical abnormality. The tumor involved the L1 spinal cord segment.

Animals↗
PubMed1984

The effect of nerve growth factor and antibodies to nerve growth factor on ethylnitrosourea-induced neoplastic proliferation in rat trigeminal nerves.

Sprague-Dawley (CD) rats were injected intravenously with ethylnitrosourea at a dose of 20 mg/kg on day 20 of gestation. This exposure resulted in early neoplastic proliferation or development of a neurinoma of the trigeminal nerve in 58% of the offspring at 90 days of age. Implantation of osmotic microinfusion pumps containing 2.5S nerve growth factor prior to ethylnitrosourea administration significantly reduced the incidence of early neoplastic proliferation. Postnatal implantation of microinfusion pumps containing 2.5S nerve growth factor also resulted in a significant but less pronounced reduction of early neoplastic proliferation. Immunoglobulin G directed against nerve growth factor (anti-nerve growth factor) did not influence the incidence of early neoplastic proliferation when administered via microinfusion pumps implanted on day 15 postnatally. These findings suggest that nerve growth factor has a protective effect on the developing nervous system against ethylnitrosourea-induced carcinogenesis.

Animals↗
PubMed1984

Diverse spectrum of tumors in male Sprague-Dawley rats following single high doses of N-ethyl-N-nitrosourea (ENU).

In this study, 30-day-old male Sprague-Dawley rats, were inoculated intraperitoneally with a single dose of 45, 90, and 180 mg/kg of N-ethyl-N-Nitrosourea (ENU). A wide spectrum of neoplasms occurred. The most common tumors were those of the mammary gland and of the nervous system. Although the incidence of mammary tumors was highest in the two high-dose groups (90 and 180 mg/kg ENU), the incidence of neurogenic tumors was highest in the 45 mg/kg dose group. Mammary tumor development led to early death and precluded development of tumors of the nervous system, which require a longer latency period. A variety of neoplasms of other organs have been associated particularly with high doses of ENU, including ameloblastic tumors, carcinomas of the thyroid, prostate, kidney, pancreas, intestine, and lung, hemilymphatic tumors, and sarcomas. It is concluded that large doses of ENU are capable of expanding the tumor spectrum in young male rats beyond the target organs generally affected with lower doses, as described in earlier reports.

Animals↗
PubMed1983

Characterization of N-ethyl-N-nitrosourea--induced mammary tumors in the rat.

A single intraperitoneal inoculation of 180 mg/kg N-ethyl-N-nitrosourea (ENU) into 30-day-old outbred Sprague-Dawley (CD) rats resulted in an 90% incidence of mammary tumors (MTs) after an average latent period of 93 days, with an 85% rate of malignancy. The incidence, induction period, number of tumors per rats, and the rate of malignancy were reduced in rats ovariectomized prior to or shortly after (5 days) ENU exposure. Over 70% of the ENU-induced MTs regressed following ovarioectomy. The malignant MTs developed from nodules located in the terminal end buds (TEB), which are believed to contain the most susceptible cell population for chemical carcinogens. The serum calcium was elevated above control values in 92% of intact rats evaluated with MTs in the absence of bone metastases. No correlation was demonstrated between the volume of MTs or total number of MTs and the serum calcium level. The ENU-induced MT is a reproducible animal model that can be used in the investigation of the early changes in mammary cells (especially TEB) and the interrelationships between the carcinogen and ovarian hormones associated with neoplastic transformation.

Adenofibroma↗
PubMed1983

Potential factors in carcinogenesis and tumor regression.

Known and unknown host factors determine the individual susceptibility to carcinogenic agents. Such factors may interact with either the phase of transformation (initiation) or with the phase of proliferation (promotion). Some of these factors have been recognized as potential determinants of the degree of susceptibility or resistance to cancer. Transformation may be impeded by a low rate of absorption of carcinogenic agents (barrier effect), by the availability of deactivating enzymes operative at several steps of the metabolism of carcinogenic agents, and by a high repair capability of DNA damage. Proliferation of transformed cells may be impeded or prevented by immune defense mechanisms and by maturation factors such as nerve growth factor (NGF), glia maturation factor, fibroblast growth factor, and others. NGF has already been shown to be capable of maturing anaplastic glioma cells (clone F98) and reducing their rate of growth. Rats treated with NGF following implantation of anaplastic glioma cells had a significantly decreased tumor growth rate and increased survival time. NGF administration to pregnant rats preceding exposure to ethylnitrosourea (ENU) (50 mg/kg, 21st day of gestation) or to offspring transplacentally exposed to ENU resulted in reduction of neurinoma development. The importance of NGF as a suppressing agent of neoplastic proliferation and as a prospective tumor therapeutic needs further exploration.

Absorption↗
PubMed1982

Experimental canine distemper encephalomyelitis in neonatal gnotobiotic dogs. A sequential ultrastructural study.

The ultrastructural morphogenesis of neuronal degeneration and necrosis and patterns of associated myelin and axonal degeneration were studied in gnotobiotic dogs neonatally infected with neurovirulent R252 strain of canine distemper virus (CDV-R252). Distemper virus-infected neurons underwent a distinct sequence of ultrastructural changes culminating in direct viral-induced necrosis beginning after 21 days post inoculation (DPI). Viral-induced neuronal cytolysis occurs apparently independently of anti-viral immune mechanisms of immunologic destruction. Viral nucleocapsid aggregates in postsynaptic axosomatic and axodendritic complexes and in structurally intact axons provided morphologic evidence for viral-induced functional modulation of synaptic transmission and possible trans-synaptic interneuronal viral spread. There were secondary degenerative axonal and myelin changes, particularly in heavily myelinated tracts. There was no evidence of primary demyelination. Active phagocytosis of degenerating axons and myelin debris in foci of virus-associated necrosis was apparently restricted to CDV-containing macrophages. Demonstration of a productive CDV infection of choroid plexus epithelium 10 DPI and thereafter was identified as an intracranial source of free infectious virus.

Animals↗
PubMed1982

Acute encephalitis and hydrocephalus in dogs caused by canine parainfluenza virus.

Gnotobiotic puppies were inoculated intracerebrally with a strain of canine parainfluenza virus (CPI-78-238). Four of eight dogs developed histological evidence of acute encephalitis. Clinical signs of encephalitis were seen in two of these four dogs; one had signs and lesions of interstitial pneumonia. Of six inoculated dogs observed for six months after infection, five developed internal hydrocephalus. Virus was reisolated from two dogs with acute encephalitis but not from dogs with hydrocephalus. Hemagglutination-inhibition antibodies persisted throughout the observation period of six months at high levels in the serum and cerebrospinal fluid of hydrocephalic dogs.

Acute Disease↗
PubMed1982

Ultrastructural evaluation of the acute encephalitis and hydrocephalus in dogs caused by canine parainfluenza virus.

Intracranial infection of neonatal dogs with canine parainfluenza virus (strain 78-238) progressed from an acute phase of encephalitis to a chronic phase of internal hydrocephalus. Acute encephalitis was characterized ultrastructurally by laminar cortical necrosis, neuronal degeneration, neocapillary formation, reactive gliosis, and ependymitis. Viral nucleocapsids were seen in the cytoplasm of neurons. Ultrastructural lesions in hydrocephalic dogs were restricted to ventricular surfaces. The earliest light microscopic change in ependymal cells occurred four weeks post-infection and consisted of segmental loss of ependymal cells. Dogs killed at three and six months post-infection had quantitatively similar ultrastructural alterations in ependymal cells regardless of the extent and severity of hydrocephalus. The shape of these cells changed from cuboidal to squamous. There was progressive loss of cilia and cell organelles along with a concomitant increase of cytoplasmic filaments. Viral nucleocapsids and inflammatory cells were not present in convalescent hydrocephalic dogs. These results suggested that virus-associated hydrocephalus can occur in the absence of obvious viral persistence in ependymal cells and in the absence of inflammation in the ventricular system.

Acute Disease↗
PubMed1982

Identification of rat T and B lymphocytes by surface marker analysis.

The majority of thymocytes in suspension (72.1%) formed nonimmune rosettes with guineapig erythrocytes but not with erythrocytes from sheep, cats, dogs, pigs, or man. In contrast, only a minority of cells form lymph node (2.1%) or spleen (1.4%) rosetted with guineapig erythrocytes. Treatment of guineapig erythrocytes with neuraminidase of 2-S-aminoethyl-isothiouronium bromide did not enhance rosette formation. Adherence of the erythrocytes to tissue sections was achieved in the thymic cortex and T-cell-dependent areas of lymph node and spleen. Absorbed equine anti-rat antithymocyte serum bound 98% thymocytes and 70.0, 35.1 and 44.6% lymphocytes from peripheral blood, spleen and lymph nodes respectively. Surface immunoglobulin was demonstrated on 2.2% thymocytes, 35% peripheral-blood lymphocytes and 43 and 51% cells from lymph nodes and spleen respectively, Complement receptors were determined in suspension with erythrocyte-antibody-complement complexes. Rosetting was observed in 44% splenic, 29% lymph node and 3% thymocyte cellular suspension. The presence of Fc receptors for IgG was assessed by determining the pattern of binding of erythrocyte-antibody complexes to frozen tissue sections. For rats, antithymocyte serum is the method of choice for T cells, whereas SIg determination is the most reliable B-cell marker.

Animals↗