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Biomedical subjects

C H Frith

Publications and source records attributed to C H Frith.

At least 37 records · Page 2Linked to original sources
PubMed1990

Spontaneous primary astrocytoma in the spinal cord of a mouse and a rat.

A spontaneous astrocytoma was observed as an incidental finding in the thoracic spinal cord of a control Charles Rivers CD-1 female mouse from a 2 yr oncogenicity study. An astrocytoma was also observed in the lumbar spinal cord of a Charles Rivers Sprague-Dawley control, female rat from a 2 yr oncogenicity study. The mouse was clinically normal and was sacrificed at the end of the 2 yr study. The rat was killed at 512 days of age because of posterior paralysis.

Animals↗
PubMed1988

Neurochemical and neurohistological alterations in the rat and monkey produced by orally administered methylenedioxymethamphetamine (MDMA).

MDMA is an amphetamine analog prescribed by some health professionals in the field of psychotherapy and used as a recreational drug by the general public. In recent reports, investigators have suggested that MDMA produces acute neurotoxicity when administered by subcutaneous injection. In order to determine if MDMA produces lasting neurochemical alterations after oral administration, groups of six rats (adult male Sprague-Dawley) were dosed by gavage with either 40 or 80 mg/kg of MDMA or saline vehicle once every 12 hr for 4 days. These rats were terminated 2 weeks after the first dose along with an additional group of rats (80 mg/kg) terminated 4 weeks after the first dose. Brain regions including the hippocampus (H), caudate nucleus (CN), hypothalamus (HY), frontal cortex (FC), and brain stem (BS) were analyzed by HPLC with electrochemical detection for concentrations of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and norepinephrine (NE). In the CN, 40 mg/kg MDMA produced no change in DA, DOPAC, or HVA, but a 50-60% decrease in 5-HT and 5-HIAA concentrations was observed at 2 weeks. Similar effects were observed at 80 mg/kg at both 2 weeks and 4 weeks. A temporary decrease was also seen in DA (21%) and in HVA (34%) 2 weeks but not 4 weeks after the 80 mg/kg dose regimen. In the H, MDMA (40 or 80 mg/kg) produced no change in NE, but a 50-60% decrease was seen in 5-HT and 5-HIAA concentrations at 2 weeks. Concentrations of 5-HT and 5-HIAA were significantly decreased in the HY and FC by all MDMA treatments, but DA and DOPAC concentrations were not altered as compared to vehicle controls. BS was least affected by treatment with no change in DA, DOPAC, or 5-HIAA concentrations and only a slight decrease in 5-HT (19-33%) concentrations at 2 weeks but not at 4 weeks. To determine the sensitivity of the nonhuman primate to MDMA, a total of nine rhesus monkeys were dosed with vehicle or 5 or 10 mg/kg MDMA (n = 3) by gastric intubation twice per day for 4 days. One month after MDMA dosing, a dose-related reduction from vehicle control values for 5-HT and 5-HIAA was observed. These results indicate that the monkey may be more sensitive than the rat to the persistent serotonergic neurotoxicity of MDMA.(ABSTRACT TRUNCATED AT 400 WORDS)

3,4-Methylenedioxyamphetamine↗
PubMed1988

Morphologic classification and incidence of hematopoietic neoplasms in the Sprague-Dawley rat.

Hematopoietic and related neoplasms were morphologically studied in a total of 1,765 male and 1,765 female Sprague-Dawley rats from 6 chronic toxicity studies conducted at a large toxicology testing laboratory. The most common types of lymphoid neoplasms seen included the lymphoblastic lymphoma (0.65%) and the large granular lymphocyte lymphoma (LGL, Fischer or mononuclear cell leukemia) (0.60%). The most common type of nonlymphoid neoplasm with morphologic features similar to lymphoid tumors was histiocytic sarcoma (1.1%). A small number of cases of myelogenous leukemia were also seen. Additional work is needed in the classification of hematopoietic neoplasms in rats including refined immunomorphological studies.

Animals↗
PubMed1988

Neuropathological evaluation by combined immunohistochemistry and degeneration-specific methods: application to methylenedioxymethamphetamine.

To best interpret the significance of neurological alterations produced by chemicals, the changes in morphological as well as neurochemical parameters must be measured and compared to each other. We have devised an approach to readily label microscopic sections for multiple antigens (neurotransmitters, enzymes, peptides, etc.) as well as for the demonstration of degenerating structures by silver impregnation. Here, we applied silver-staining together with immunolabelling of 5-HT and tyrosine hydroxylase (the rate-limiting enzyme for dopamine synthesis) to study neurohistological alterations produced by methylenedioxymethamphetamine (MDMA), a hallucinogenic stimulant previously used as an adjunct to psychotherapy and now a popular recreational drug ("Ecstasy"). Single oral doses of 40 or 80 mg/kg MDMA doubled the density of silver-impregnated (degenerating) fiber terminals in the caudate nucleus compared to controls, when rats were sacrificed 18 hours after treatment. Four months after two 40 mg/kg oral doses per day for four days, rats had a reduced neurochemical content of 5-HT in the hippocampus, and fewer immunostainable 5-HT axons per unit area in the hippocampal stratum lacunosum but no change in brain-stem neurochemical 5-HT content or in the numeric density of 5-HT-positive cell bodies in the dorsal raphe nucleus. The neurohistology suggests interpreting the changes in neurochemical content of serotonin produced by MDMA as due to degeneration followed by subsequent loss of 5-HT axons, rather than a decrease in the rate of neuronal 5-HT synthesis or a toxicity directed toward 5-HT cell bodies. The combination of neurohistological and neurochemical evaluation will continue to prove useful in comprehensive evaluation of the neurological effects of chemical exposure.

3,4-Methylenedioxyamphetamine↗
PubMed1987

Toxicity of methylenedioxymethamphetamine (MDMA) in the dog and the rat.

Methylenedioxymethamphetamine (MDMA) was administered to dogs and rats orally once a day for a 28-day period to evaluate the morphological and neuropathological effects. Major clinical signs associated with the administration of MDMA in the dog included circling, depression, dilated pupils, hyperactivity, rapid breathing, and salivation. Major clinical signs in the rat included hyperactivity, excitability, piloerection, exophthalmos, and salivation. Gross observations at necropsy in the dog possibly related to administration of the test article included reduced testicular size (one high and one medium dose) and prostatic enlargement in two high-dose animals. No gross lesions were seen in the rats at necropsy. The medium- and the high-dose groups in both sexes in both the rats and the dogs gained significantly less weight than the control and low-dose groups. Food consumption decreased the first week for the high- and medium-dose groups, but a significant reversal toward more normal consumption was noted in the following weeks in both the rats and the dogs. Hematologic, clinical chemistry, and urinalysis values did not appear to be affected by the administration of the test article in the dog. In the rat clinical pathology variables showing a trend to decrease with dose included urinary pH, blood urea nitrogen, glucose, creatinine (females), lactate dehydrogenase (LDH) (females), and chloride. Clinical pathology variables showing a trend to increase with dose included total white blood cell count and phosphorus. Microscopically, testicular atrophy was present in one medium-dose and two high-dose male dogs. Prostatic hyperplasia was present in two high-dose male dogs. No test article-related lesions were seen in the brains of either species.

3,4-Methylenedioxyamphetamine↗
PubMed1987

Tumorigenic responses to lindane in mice: potentiation by a dominant mutation.

Obese mottled yellow Avy/a, lean pseudoagouti Avy/a and lean black a/a (YS X VY) F-1 hybrid female mice were fed diet containing 160 p.p.m. lindane (gamma-hexachlorocyclohexane) for 6, 12, 18 or 24 months. Clara cell hyperplasia was present in a majority of the mice after six months of lindane ingestion; however, more yellow mice (77%) than pseudoagouti (50%) or black (56%) mice had developed this lesion. Continued ingestion of lindane increased the incidence of Clara cell hyperplasia and resulted in similar prevalences in the three phenotypes. Lung tumors associated with lindane ingestion for 24 months were found only in yellow (19%) and pseudoagouti (14%) mice but not in the black mice. Prevalences of hepatocellular adenomas and carcinomas were very low (less than 10%) in untreated pseudoagouti and black mice. Lindane ingestion for 24 months resulted in an hepatocellular adenoma prevalence of 12% in pseudoagouti mice and 3% in black mice; comparable hepatocellular carcinoma prevalences were 5% and 1%. Among yellow mice fed lindane diet for 24 months, adenoma prevalence was 35% (9% among untreated controls) but carcinoma prevalence was only 17% (13% among controls). The tumorigenic responses evoked by lindane feeding in the lean pseudoagouti Avy/a mice but not in the black a/a mice indicate, for the first time, that the Avy gene itself, in the absence of obesity, sensitizes cells to transformation. The greater prevalence of hepatocellular adenomas in obese yellow Avy/a than in lean pseudoagouti Avy/a mice implicates obesity-associated factors in tumor promotion. Similarly, the increased prevalence of hepatocellular carcinomas in untreated obese yellow Avy/a mice, as compared to lean pseudoagouti mice, implicates obesity-associated factor as favoring histiotypic progression of liver tumors. Thus, the Avy gene not only sensitizes cells to respond to tumorigenic stimuli but also, by the induction of obesity, enhances promotion and progression of transformed cells.

Adenoma↗
PubMed1986

Scanning and transmission electron microscopic observations of the acute morphological response of the mouse urinary bladder to 4-ethylsulfonylnaphthalene-1-sulfonamide.

A total of 75 BALB/cStCrlfC3H/Nctr male weanling mice were administered either 0 or 250 ppm of 4 ethylsulfonylnaphthalene-1-sulfonamide (ENS) in the diet for periods up to 14 days to evaluate the early morphological changes of the transitional epithelium of the urinary bladder with scanning (SEM) and transmission (TEM) electron microscopy. Primary TEM changes included hyperplasia of the epithelium, loosening of the intercellular junctions, autophagic vacuoles and electron dense granules in the mitochondria. Primary SEM changes included sloughing of epithelial cells, irregularity in the size and shape of the transitional epithelial cells and the presence of microvilli. Although pleomorphic microvilli were present after only three days of treatment with ENS, it appears that they are a transient observation in a series of morphological changes. The reversibility or transient nature of the pleomorphic microvilli may indicate that they are an acute toxic response and may not necessarily indicate a preneoplastic change.

Animals↗
PubMed1986

Contributions of recent research to the classification of spontaneous lymphoid cell neoplasms in mice.

The present review focuses on the mouse as an experimental immunopathologic model for non-Hodgkins' lymphomas and related leukemias. Immunomorphologic evidence will be presented which demonstrates that B and T cell subtypes of mouse lymphoid cell neoplasms resemble and are analogous to B and T cell subtypes of human lymphoid cell neoplasms. The many experimental advantages of the mouse system will be stressed with a particular emphasis on the concept that this newly defined immunomorphologic approach should be effectively combined with biologic, molecular, and cytogenetic parameters.

Animals↗
PubMed1985

Morphological observations on the epithelium of the developing urinary bladder of the mouse and rat.

Bladders from fetal and neonatal BALB/cStCrlfC3H/Nctr mice and Sprague-Dawley rats were studied to establish the sequence of events in their morphological development by using scanning electron, transmission electron and light microscopy. On fetal day 18 or 19 the epithelium from the mouse and the rat displayed 2 or 3 distinct cell layers. With transmission electron microscopy a star-like contraction of the cell surface of the mouse bladder occurred which was not seen in the developing rat bladder. In both the mouse and the rat, some of the superficial cells sloughed between fetal day 18 or 19 and the day of birth. On the day of birth, the epithelium was composed of only 2 layers. The nuclei of both the superficial and basal layers contained prominent euchromatin, and mitotic figures were often present in the basal layer. By the 5th postnatal day, some of the superficial cells contained autophagic vacuoles, and the epithelium was still 2 cell layers thick. One week after birth the epithelium consisted of 2 to 3 cell layers. Three weeks after birth the epithelium was 3 cell layers thick and appeared as the adult pattern with both transmission and scanning electron microscopy. The study demonstrated that the fetal and neonatal mouse and rat urinary bladders undergo a series of rapid developmental changes and suggest that the fetal and neonatal urinary bladder may be a target organ susceptible to toxic insult.

Animals↗
PubMed1984

Morphological classification and incidence of thyroid tumors in untreated aged mice.

The authors reviewed a total of 83 thyroid neoplasms in several strains of untreated mice. The 83 thyroid neoplasms consisted of 76 adenomas and 7 carcinomas. The adenomas and carcinomas were divided into the following three morphological types: papillary, follicular, and solid. The papillary adenoma was the most common type. The tumors were more common in female than male mice. The incidence ranged from 0.13% in BALB/c females to 8.6% in C3H-MTV females.

Adenoma↗
PubMed1984

A morphologic classification of brain tumors found in several strains of mice.

Brain tumors were found in 42 mice from a total study population of 77,410 mice, which included several strains (BALB/c, C3H, C57BL/6, and hybrids of these strains). The brain tumors were classified on the basis of the new World Health Organization classification of human brain tumors. Tumors originated from neuroepithelial and meningeal tissues, blood vessels, and germ cells. The youngest animal with a tumor was 111 days of age. The tumor incidence was low, being 0.054% of the total study population, with 0.067% in controls and 0.052% in treated mice. Lipomas were the most common type of tumor diagnosed, and they were considered to represent hamartomas rather than true neoplasms. There were 27 brain tumors other than lipomas, the majority (16) of which occurred in BALB/c mice, whereas meningeal tumors (6) were confined to C3H and hybrid strains of mice. The morphologic characteristics of each tumor type are presented.

Animals↗
PubMed1984

The role of urinary physiological changes in the genesis of urothelial lesions in mice given 4-ethylsulfonylnaphthalene-1-sulfonamide, acetazolamide, and oxamide.

BALB/c female mice were administered several compounds, including 4-ethylsulfonylnaphthalene-1-sulfonamide, acetazolamide, and oxamide, in the diet for six weeks. Fresh urine samples were analyzed three times per week for pH, osmolality, micro-crystals, and protein; and a histopathological evaluation was made of the urothelium at the end of the six weeks test. Incidences of hyperplasia, nodular hyperplasia, vacuolization, ulceration and acute inflammation of the bladder urothelium appeared to be related to the osmolality of the urine and the micro-crystalluria experienced by the mice. Correlation coefficients between lesions and urinary osmolality or crystals were -0.69 (p less than 0.0001) and 0.31 (p less than 0.03), respectively, at the 5% significance level.

Acetazolamide↗
PubMed1984

Urothelial lesions in mice given 4-ethylsulfonylnaphthalene-1-sulfonamide, acetazolamide, and oxamide.

4-Ethylsulfonylnaphthalene-1-sulfonamide, acetazolamide and oxamide were administered in the diet to female BALB/c mice for varying periods of time from three to eighty weeks. All three compounds induced lesions in the urothelium. In the bladder, these included simple hyperplasia, nodular hyperplasia, inflammation and calculi. Similar lesions were observed in the ureter and urethra, along with a novel lesion, diverticulum, in the ureter. The diverticular lesions existed as down-growths of the transitional epithelium which often extended from the mucosa through the muscle layers to the adventitial surface. The etiology of the lesions appeared to be related to urinary physiological alterations (crystalluria, calculi, hypoosmolality) caused by administration of the compounds.

Acetazolamide↗
PubMed1983

Incidence of hepatic metastases for various neoplasms in several strains of mice.

The incidence of hepatic metastases for a variety of spontaneous and carcinogen-induced malignant neoplasms was studied in several strains of mice. Forty percent of osteogenic sarcomas metastasized to the liver in C57BL/6 female mice. Fourteen percent of mesotheliomas metastasized to the liver in C3H mice and 11.5% of alveolar/bronchiolar carcinomas metastasized to the liver in BALB/c male mice. All other malignant neoplasms metastasized to the liver at a rate of less than 10% and most at less than 5%.

Animals↗
PubMed1983

Medullary thyroid carcinoma in female BALB/c mice. A report of 3 cases with ultrastructural, immunohistochemical, and transplantation data.

Medullary thyroid carcinoma (MTC) is a neoplasm derived from thyroidal C cells. This tumor occurs spontaneously in several animal species and is relatively common in certain strains of rats. Descriptive reports of such neoplasms in mice, however, have not been published. From several studies using female BALB/c mice, 3 animals were identified that had thyroid neoplasms histologically compatible with MTC. All three primary neoplasms and a first generation transplant from one of them contained calcitonin. Somatostatin was identified in two of three primary thyroidal neoplasms and in the first-generation transplant. Ultrastructurally, the neoplastic cells of the first-generation transplant contained membrane-bound dense-core granules that resembled those seen in normal mouse C cells. Intracisternal Type A retrovirus particles were also identified in neoplastic cells in this case. Transplantation of one of the neoplasms yielded subcutaneous masses averaging 2 cm in diameter by 3 months following transplantation in the second-generation recipients. These neoplasms resemble MTCs of man, rat, and other species and may prove of value for comparative morphologic and endocrinologic studies of C cell neoplasms and for studies of factors that regulate the synthesis and secretion not only of calcitonin but also of a variety of regulatory peptides, including somatostatin.

Animals↗
PubMed1983

Immunomorphologic classification of spontaneous lymphoid cell neoplasms occurring in female BALB/c mice.

WIth the use of a recently proposed, combined immunomorphologic classification (Pattengale-Taylor, 1981) for murine lymphomas and related leukemias, 70 spontaneously occurring lymphoid cell neoplasms from female BALB/cStCrl mice were evaluated and classified and then compared to the earlier Dunn classification (Dunn, 1954). The predominant lesion (i.e., 60% total incidence) in female BALB/c mice [previously called "reticulum cell sarcomas (neoplasm)", type B, by Dunn] was a lymphoid cell neoplasm derived from follicular center cells (i.e., follicular center cell [FCC] lymphoma). The B-cell nature was further confirmed in the majority (76%) of these FCC lymphomas by means of immunoperoxidase techniques that demonstrated the presence of cytoplasmic immunoglobulin (Clg). Smaller percentages of B-lymphoblastic (10% total incidence) and B-immunoblastic (7% total incidence) lymphomas were also observed. In addition, FCC, B-lymphoblastic, and B-immunoblastic lymphomas occurred in female BALB/c mice over 20 months of age. In contrast, Clg-negative lymphoblastic lymphomas involving the anterior mediastinum (and presumably T-cell in origin) occurred with a bimodal incidence in both young (13% total incidence at a mean age less than 6 mo) and old (10% total incidence at a mean age greater than 21 mo) female mice.

Animals↗