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Biomedical subjects

R A Herbert

Publications and source records attributed to R A Herbert.

At least 19 recordsLinked to original sources
PubMed1999

Osmotically induced intracellular trehalose, but not glycine betaine accumulation promotes desiccation tolerance in Escherichia coli.

Trehalose considerably increased the tolerance of Escherichia coli to air drying, whether added as an excipient prior to drying or accumulated as a compatible solute in response to osmotic stress. The protective effect of exogenously added trehalose was concentration dependent, up to a threshold value of 350 mM. However, trehalose alone cannot explain the intrinsically greater desiccation tolerance of stationary compared to exponential phase E. coli cells, although their tolerance was also enhanced by exogenous or endogenously accumulated trehalose. In contrast, glycine betaine whether added as an excipient or accumulated intracellularly had no influence on desiccation tolerance. These data demonstrate that the protection provided by compatible solutes to cells subjected to desiccation differs from that during osmotic stress, due to the much greater reduction in available cell water. The protective effects of trehalose during desiccation appear to be due to its stabilising influence on membrane structure, its chemically inert nature and the propensity of trehalose solutions to form glasses upon drying, properties which are not shared by glycine betaine.

Adaptation, Biological↗
PubMed1999

Nitrogen cycling and community structure of proteobacterial beta-subgroup ammonia-oxidizing bacteria within polluted marine fish farm sediments.

A multidisciplinary approach was used to study the effects of pollution from a marine fish farm on nitrification rates and on the community structure of ammonia-oxidizing bacteria in the underlying sediment. Organic content, ammonium concentrations, nitrification rates, and ammonia oxidizer most-probable-number counts were determined in samples of sediment collected from beneath a fish cage and on a transect at 20 and 40 m from the cage. The data suggest that nitrogen cycling was significantly disrupted directly beneath the fish cage, with inhibition of nitrification and denitrification. Although visual examination indicated some slight changes in sediment appearance at 20 m, all other measurements were similar to those obtained at 40 m, where the sediment was considered pristine. The community structures of proteobacterial beta-subgroup ammonia-oxidizing bacteria at the sampling sites were compared by PCR amplification of 16S ribosomal DNA (rDNA), using primers which target this group. PCR products were analyzed by denaturing gradient gel electrophoresis (DGGE) and with oligonucleotide hybridization probes specific for different ammonia oxidizers. A DGGE doublet observed in PCR products from the highly polluted fish cage sediment sample was present at a lower intensity in the 20-m sample but was absent from the pristine 40-m sample station. Band migration, hybridization, and sequencing demonstrated that the doublet corresponded to a marine Nitrosomonas group which was originally observed in 16S rDNA clone libraries prepared from the same sediment samples but with different PCR primers. Our data suggest that this novel Nitrosomonas subgroup was selected for within polluted fish farm sediments and that the relative abundance of this group was influenced by the extent of pollution.

Ammonia↗
PubMed1998

Carcinogenesis studies of tetrahydrofuran vapors in rats and mice.

Tetrahydrofuran (THF) is a widely used industrial solvent and was selected for carcinogenesis studies by the National Toxicology Program (NTP) because of its potential for widespread occupational exposure in humans and a lack of information on animal toxicity and carcinogenicity. Groups of 50 male and 50 female F344/N rats and B6C3F1 mice were exposed to 0, 200, 600, or 1800 ppm THF by inhalation, 6 h per day, 5 days per week, for 105 weeks. Survival and mean body weights of male and female rats exposed to THF were comparable to that of the controls. No clinical findings or nonneoplastic lesions related to THF exposure were observed in male or female rats. The incidences of renal tubule epithelial adenoma or carcinoma (combined) in exposed male rats occurred with a positive trend, and in males exposed to 600 and 1800 ppm exceeded the historical range for controls in 2-year NTP inhalation studies. There were no other neoplastic lesions related to THF exposure observed in male or female rats. After week 36, the survival of male mice exposed to 1800 ppm was significantly lower than that of the controls. Mean body weights of male and female mice exposed to THF were similar to those of the controls throughout the study. Male mice exposed to 1800 ppm were observed in a state of narcosis during and up to 1 h after the exposure periods. Nonneoplastic lesions related to THF exposure were not observed in male or female mice. The neoplastic lesions related to THF exposure were seen in female mice only. In female mice exposed to 1800 ppm, the incidences of hepatocellular neoplasms were significantly greater than those in the controls. In conclusion, there was some evidence of carcinogenic activity of THF in male F344/N rats due to increased incidences of adenoma or carcinoma (combined) of the kidney at the 600 and 1800 ppm exposure levels. There was clear evidence of carcinogenic activity in female B6C3F1 mice based on increased incidences of hepatocellular neoplasms at the 1800 ppm exposure level. THF was not carcinogenic in female rats or male mice exposed at 200, 600, or 1800 ppm.

Animals↗
PubMed1998

Toxicity and carcinogenicity studies of oxazepam in the Fischer 344 rat.

Oxazepam and related benzodiazepines are used in the treatment of anxiety. Carcinogenicity studies of oxazepam were performed with the F344 rat because of marked differences in tumor responses observed in NTP studies with B6C3F1 and Swiss-Webster mice compared to the results of Sprague-Dawley rat studies submitted to the FDA by a manufacturer to support registration of the drug. Groups of 50 male and 50 female F344/N rats were fed diets containing 0, 625, 2500, or 5000 ppm oxazepam for up to 105 weeks. A stop-exposure group of 50 males and 50 females received 10,000 ppm oxazepam in diet for 26 weeks, after which animals received control diet. All 5000- and 10, 000-ppm stop-exposure males died before the end of the study. Survival of 2500-ppm males and females was lower than that of controls. Body weight gains of 2500- and 5000-ppm males and females were less than those of controls. Male rats exposed to 2500 ppm had an increased incidence of renal tubule adenoma and hyperplasia. In addition, the incidences of renal tubule adenoma and hyperplasia were increased in the 10,000-ppm stop-exposure group. The incidences of nephropathy in exposed females were greater than those in controls, and the severity of nephropathy increased in exposed males. Epithelial hyperplasia and chronic inflammation of the nonglandular stomach were increased in males given 2500 and 5000 ppm and the incidence of ulcers of the nonglandular stomach in 2500-ppm males was also greater than that in controls. In males exposed to 5000 ppm, mineralization of the glandular stomach and erosion of the duodenum were observed. In females exposed to 2500 ppm, the incidences of epithelial hyperplasia, chronic inflammation, and ulcers of the nonglandular stomach and the incidence of erosion in the glandular stomach were increased. The incidences of centrilobular hepatocyte hypertrophy in males and females given 2500 and 5000 ppm were greater than those in controls. In summary, there was equivocal evidence of carcinogenicity in males based on increased renal tubule adenomas in groups which also had significantly enhanced nephropathy. There was no evidence of carcinogenicity of oxazepam in females given a diet containing 625, 2500, or 5000 ppm for 2 years or 10,000 ppm for 6 months.

Adenoma↗
PubMed1998

Lung tumor induction by inhalation exposure to molybdenum trioxide in rats and mice.

Inhalation studies of molybdenum trioxide (MoO3) were conducted because of its wide use in industry, human exposure, and lack of data on carcinogenicity. Groups of 50 male and 50 female F344/N rats and B6C3F1 mice were exposed to MoO3 by inhalation at 0, 10, 30, or 100 mg/m3, 6 h/day, 5 days/week, for 2 years. In both rats and mice, survival and mean body weights of exposed groups of males and females were similar to those of their respective controls. There were significant exposure-dependent increases in blood molybdenum concentration in exposed rats and mice. There were no toxicological differences in bone density or curvature between exposed animals and their respective controls. In rats, dose-dependent increases in incidence of hyaline degeneration in the nasal olfactory epithelium and squamous metaplasia of the epithelium lining the base of the epiglottis were observed. The incidence of alveolar/bronchiolar adenoma or carcinoma (combined) was marginally increased in males but not in females compared with controls. In mice, the incidences of squamous metaplasia of the epithelium lining the base of the epiglottis, hyperplasia of the laryngeal epithelium, and metaplasia of the alveolar epithelium were significantly increased in all exposed males and females compared with controls. The incidence of alveolar/bronchiolar adenoma or carcinoma (combined) in exposed groups of males and females was significantly greater than that in the control groups.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1998

Theophylline-induced mesenteric periarteritis in F344/N rats.

The toxicity and carcinogenic potential of theophylline (an alkaloid bronchodilator drug) was investigated in male and female F344/N rats in 16-day, 14-week, and 2-year gavage and feeding studies. In 16-day studies, rats were fed diets containing 0, 500, 1000, 2000, 4000, and 8000 ppm of theophylline or given 0, 12.5 (twice daily), 25 (once daily), 50 (once daily), 50 (twice daily), 100 (once daily), 200 (once daily), 200 (twice daily), and 400 (once daily) mg theophylline/kg body weight in corn oil by gavage. In 14-week studies, rats were fed diets containing 0, 1000, 2000, and 4000 ppm theophylline or given 0, 37.5, 75, and 150 mg/kg body weight theophylline in corn oil by gavage. In 2-year gavage studies, rats were given 0, 7.5, 25, and 75 mg/kg body weight in corn oil. In 16-day gavage studies, treatment-related periarteritis occurred in arteries of the pancreas and adjacent to the mesenteric lymph nodes of early death male and female rats given 400 mg/kg once daily. In the 14-week studies, treatment-related periarteritis occurred at similar sites and in male rats exposed to 75 and 150 mg/kg, and in all exposed female rats (gavage studies), in females exposed to 1000 ppm, and in both sexes exposed to 2000 and 4000 ppm (feeding studies). In the 2-year study, chronic periarteritis was significantly increased only in the males receiving 75 mg/kg of theophylline. The adventitia, media and intima of medium- and large-sized mesenteric arteries were involved. Similar to other vasodilator chemicals, the pathogenesis of theophylline-induced vascular lesions may be a consequence of hemodynamic changes induced in the vascular wall.

Administration, Oral↗
PubMed1998

Effect of retinoid analogues on mammary cancer in transgenic mice with c-neu breast cancer oncogene.

Breast cancer is one of the most common cancers and is a leading cause of mortality in women. The TG.NK transgenic mouse line expresses the c-neu breast cancer oncogene under the control of an MMTV promoter and appears to be a useful animal model for evaluation of intervention strategies to delay/prevent breast cancer. Fiber-rich nonpurified diet (NTP-2000), as compared to a purified diet (AIN-76A), has previously been shown to significantly delay the development of mammary cancer in the TG.NK model. Four-week old hemizygous TG.NK female mice with MMTV/c-neu oncogene were fed NTP-2000 diet containing the retinoid analogue 4-hydroxyphenyl retinamide (4-HPR) at 5 mM/kg or an arotinoid Ro 40-8757 at 2 and 3 mmol/kg for 26 weeks. The 4-HPR at 5 mmol/kg diet delayed the development of palpable tumors up to 24 weeks, but by 26 weeks, the incidence was not significantly different from the NTP-2000 diet control group. However, the 4-HPR diet markedly decreased the average weight of the tumors at 26 weeks. The 4-HPR diet also caused a significant increase in body weight without an increase in food consumption. Arotinoid Ro-40-8757 at both doses inhibited the development of mammary tumors for the duration of the study. However, the Ro 40-8757 at 3 mmol/kg appeared to be toxic as indicated by a significant depression of the average body weight with alopecia and skin scaling in some mice. Our observations with TG.NK transgenic mouse and fiber-rich diet (NTP-2000) indicate that the arotinoid Ro 40-8757 has a markedly higher inhibitory effect on the development of mammary cancer than 4-HPR. Studies to evaluate genetic changes and expression of hormonal receptors and growth factors associated with the inhibition of mammary cancer development by the retinoid analogues are in progress.

Animals↗
PubMed1997

Influence of diet on mammary cancer in transgenic mice bearing an oncogene expressed in mammary tissue.

Breast cancer is one of the most common cancers in women. The laboratory rat treated with strong carcinogen is the most commonly used animal model for study of breast cancer. Transgenic mouse lines with homologues of human breast cancer oncogenes have been developed. The transgenic mouse line TG.NK with c-neu, the human breast cancer oncogene homologue of erbB2, was evaluated to determine its suitability for study of intervention strategies to delay/prevent the development of breast cancer. There were no palpable mammary tumor masses up to 22-weeks of age, and almost all mice fed a purified diet developed palpable mammary tumors by 28-weeks of age. Nonpurified diets decreased the incidence and multiplicity, and delayed the development of mammary tumors as compared to a purified diet. Increasing the fiber content of nonpurified diet decreased the tumor incidence further. There is approximately a 19-week interval between weaning and development of palpable mammary masses to evaluate intervention strategies to delay or prevent the development of mammary cancer in the TG.NK mouse model. Fiber from nonpurified cereal ingredients appears to be highly beneficial in delaying the development of mammary cancer in TG.NK mice, and this observation is in agreement with human epidemiological findings. Therefore, the TG.NK transgenic mouse with oncogene c-neu (erbB2), appears to be a useful animal model for evaluation of dietary intervention strategies.

Animals↗
PubMed1995

Subchronic feeding study of the mycotoxin fumonisin B1 in B6C3F1 mice and Fischer 344 rats.

Fumonisin B1 (FB1) is a mycotoxin produced by Fusarium moniliforme, a common fungus which occurs naturally on corn, and other Fusarium species. FB1 and other fumonisins are now recognized as having potentially important animal and human health implications. However, few toxicological data are currently available. Male and female B6C3F1 mice and Fischer 344 rats were fed diets containing 0, 1, 3, 9, 27, or 81 ppm FB1 (> or = 98% purity) for 13 weeks. No differences in behavior or appearance, body weight or food consumption between control and FB1-fed groups were found. In mice, hepatopathy and altered serum chemical profiles indicative of hepatotoxicity were found in females fed the 81 ppm diet. No adverse effects were found in female mice fed < or = 27 ppm FB1 or in male mice at any dietary level studied. In rats, nephrosis involving the outer medulla was found in males fed > or = 9 ppm and, to a lesser degree, in females fed 81 ppm FB1, while decreased kidney weight was found in both sexes at dietary levels > or = 9 ppm FB1. Although the liver is a target organ of FB1 in rats, hepatotoxicity was not found in rats fed diets containing up to 81 ppm FB1 for 90 days. Thus, FB1 was toxic to both species following subchronic oral exposure, although significant interspecies differences in the no observed effect levels and organ-specific responses were found.

Adrenal Glands↗
PubMed1995

Long-term toxicity studies of ozone in F344/N rats and B6C3F1 mice.

The toxicity and carcinogenicity of ozone was evaluated in Fischer 344/N rats and B6C3F1 mice exposed to 0, 0.12 (2 years only), 0.5 or 1.0 ppm ozone by inhalation for 2-year and lifetime exposures. A 2-year cocarcinogenicity study (male rats only) included the subcutaneous administration of 0, 0.1 or 1.0 mg/kg/body wt. of 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) for the first 20 weeks along with inhalation exposure to 0 or 0.5 ppm ozone followed by additional 84 weeks of ozone exposure alone. Ozone exposure in rats did not cause an increased incidence of lung neoplasms. In the cocarcinogenicity study, ozone exposure did not have an additive carcinogenic effect. Lifetime and 2-year ozone exposure was associated with a marginal increase in lung tumors in male B6C3F1 mice and a more pronounced increase in females. Unique mutations in the K-ras gene were found in the mouse lung neoplasms from the ozone-exposed mice.

Animals↗
PubMed1995

Increased frequency of K-ras mutations in lung neoplasms from female B6C3F1 mice exposed to ozone for 24 or 30 months.

The National Toxicology Program recently completed long-term ozone inhalation studies in B6C3F1 mice and F344/N rats. Mice and rats were exposed to 0, 0.5 or 1.0 p.p.m. ozone by inhalation for 24 or 30 months. There was an increased incidence of lung neoplasms in B6C3F1 mice. However, there was no evidence of carcinogenicity in F344/N rats. The objectives of this study were to (i) evaluate benign and malignant lung neoplasms from B6C3F1 mice for mutations in the K-ras gene at codons 12, 13 and 61, (ii) determine if the frequency and spectra of K-ras mutations were unique for ozone-induced lung neoplasms, (iii) determine if specific K-ras mutations were associated with the size and morphological patterns of lung neoplasms or ozone exposure concentrations and (iv) screen lung neoplasms by immunohistochemical methods for the p53 protein. K-ras mutations were detected by single-strand conformation analysis and identified by direct sequencing of polymerase chain reaction-amplified DNA isolated from formalin-fixed, paraffin-embedded neoplasms. K-ras mutations were detected in 73% of ozone-induced neoplasms, as compared with 33% of lung neoplasms from controls. The predominant mutations consisted of A-->T transversions at codon 61 (8/19) and G-->T transversions at codon 12 (7/19). Specific K-ras mutations in lung neoplasms were not associated with various morphological patterns. Our data suggests that ozone may cause direct and/or indirect DNA damage in the K-ras proto-oncogene of B6C3F1 mice.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1994

Plutonium-induced proliferative lesions and pulmonary epithelial neoplasms in the rat: immunohistochemical and ultrastructural evidence for their origin from type II pneumocytes.

Immunohistochemistry and transmission electron microscopy were used to clarify the cellular origin for plutonium-239-induced pulmonary proliferative (preneoplastic) epithelial lesions and epithelial neoplasms in F344 rats. Examples of each histologic type of proliferative lesion and neoplasm were stained by the avidin-biotin complex immunoperoxidase method using antibodies to rat surfactant apoprotein and Clara cell antigen. Rat surfactant apoprotein immunostaining was detected in type II pneumocytes in sections of normal lung, in the cells of the proliferative lesions classified histologically as alveolar epithelial hyperplasia (51) and mixed foci (alveolar epithelial hyperplasia with fibrosis) (30), and in adenomas (2), adenocarcinomas (3), and adenosquamous carcinomas (2). With the exception of one adenosquamous carcinoma, Clara cell antigen immunostaining was not detected in any of the pulmonary lesions but was detected in nonciliated cuboidal epithelial (Clara) cells in normal bronchioles. The epithelial cells of the proliferative lesions and neoplasms had ultrastructural features consistent with type II pneumocytes, i.e., the presence of cytoplasmic lamellar and multivesicular bodies. The results of these studies indicate that the majority of plutonium-induced proliferative epithelial lesions and neoplasms in the rat originate from alveolar type II pneumocytes.

Animals↗
PubMed1993

Sequential analysis of the pathogenesis of plutonium-induced pulmonary neoplasms in the rat: morphology, morphometry, and cytokinetics.

Light microscopy, morphometry, and cytokinetic techniques were used to examine the dynamics of plutonium-induced pulmonary proliferative lesions and neoplasms in rats at several intervals to 450 days after inhalation exposure to aerosols of 239PuO2. Maximal increases in alveolar and bronchiolar epithelial cell labeling were seen at 30 days; decreasing subsequently, the levels remained elevated above control indices. Focal proliferative epithelial lesions developed in the lung by 180 days and before the onset of pulmonary neoplasms. Pulmonary neoplasms, predominantly adenocarcinomas and squamous cell carcinomas, were initially observed at 308 days. The proliferative lesions progressed through a succession of morphological changes leading to the development of neoplasms. The volume density (fraction) and epithelial surface area of foci of alveolar epithelial hyperplasia increased progressively between 180 and 450 days after exposure, in contrast to the other proliferative lesions. We conclude that plutonium-induced pulmonary neoplasms develop through a succession of focal proliferative lesions that represent developmental preneoplastic lesions. Progressive increases in volume and epithelial surface area of the alveolar epithelial hyperplasias suggest that they may be more at risk for neoplastic transformation than the other histological types of proliferative foci.

Adenocarcinoma↗
PubMed1992

A perspective on the biotechnological potential of extremophiles.

It is well recognized that many environments considered by man to be extreme are colonized by microorganisms which are specifically adapted to these ecological niches. A diverse range of bacteria, cyanobacteria, algae and yeasts have been isolated from such habitats and it is now widely accepted that these microorganisms provide a valuable resource not only for exploitation in novel biotechnological processes but also as models for investigating how biomolecules are stabilized when subjected to extreme conditions. This short review summarizes our current state of knowledge of this unique group of microorganisms and their enzymes, and attempts to identify their future biotechnological potential.

Bacteria↗
PubMed1991

The role of trehalose in the osmoadaptation of Escherichia coli NCIB 9484: interaction of trehalose, K+ and glutamate during osmoadaptation in continuous culture.

Natural abundance 13C nuclear magnetic resonance spectroscopy identified the disaccharide trehalose as the major organic osmolyte synthesized by Escherichia coli grown in continuous culture under nitrogen limitation in the presence of 0.5 M-NaCl. Trehalose accumulation was dependent on both the growth phase of the culture and the osmolality of the growth medium, but independent of the solute used to increase the osmolality as long as the solute was non-penetrant. The penetrant solute glycerol did not induce trehalose synthesis indicating that the loss of cell turgor rather than increasing medium osmolality per se was the mechanism stimulating trehalose synthesis. Under conditions of either carbon or nitrogen limitation osmoadaptation was distinctly biphasic. The initial response consisted of a rapid (within 30 min) accumulation of K+ and a concurrent synthesis of the amino acid glutamate; trehalose synthesis occurred during the second slower phase of osmoadaption. Chloramphenicol severely inhibited trehalose accumulation indicating that the enzyme(s) involved in trehalose synthesis were inducible.

Adaptation, Physiological↗
PubMed1982

Career paths of graduates of a degree-linked nursing course.

The aim of this study was to follow the career development of all 103 former students of the BSc (Hons) degree in human biology at the University of Surrey who also took the nursing option leading to qualification as SRN, at St George's School of Nursing, London. These individuals qualified between 1970 and 1980. A postal questionnaire was used and a 97% response was obtained. The employment of each respondent was recorded at various time intervals after qualification and categorized to facilitate analysis. Findings were generally in accordance with the preliminary findings of the Universities of Manchester and Edinburgh follow-up studies. The majority of respondents chose and followed careers in nursing. The most common categories of employment for the first 5 years after qualification were hospital and community nursing. Sixty-two percent had taken further training in various fields of nursing. A larger proportion of human biologist nurse graduates had selected careers in community nursing, nursing research and nursing education than had Edinburgh nurse graduates. There was support for the suggestion that nurse graduates choose to consolidate their experience before breaking their career on account of motherhood. Between 9 and 31% were in non-nursing employment during the first 5 years of employment. Most of these were studying or working in health related fields. This figure was higher than that found in Edinburgh and reflects the nature of the degree-linked human biology/nursing option course.

Career Choice↗
PubMed1980

Asparagine and glutamine metabolism in Rhodopseudomonas acidophila.

Rhodopseudomonas acidophila strain 7050 achieved balance growth when provided with either asparagine or glutamine as nitrogen source. Under these growth conditions R. acidophila synthesized a mixed amidase which exhibited similar activity (223--422 nmol/min . mg protein) against either nitrogen source. Determination of the free intracellular amino acid pools show that deamidation of asparagine and glutamine resulted in elevated levels of both aspartate and glutamate. Cell-free extracts of R. acidophila showed significant aminotransferase activity, particularly glutamine-oxaloacetate aminotransferase (89.7--209.3 nmol/min . mg protein), glycine oxaloacetate aminotransferase (135--227 nmol/min . mg protein), alanine glyoxylate aminotransferase (66.3--163.2 nmol/min . mg protein) and serine-glyoxylate aminotransferase (57.1--68.4 nmol/min . mg protein). Short term labelling experiments using 14C-glyoxylate show that glycine plays an important role in amino nitrogen transfer in R. acidophila and that the enzymes for the metabolism of glyoxylate via glycine, serine and hydroxypyruvate were present in cell-free extracts. These data confirm that R. acidophila can satisfy all its' nitrogen requirements by transamination.

Asparaginase↗