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Biomedical subjects

R S Baker

Publications and source records attributed to R S Baker.

At least 109 records · Page 6Linked to original sources

Mutagenicity of metal ions in bacteria.

The mutagenicity of 24 metal salts was investigated in plate incorporation and fluctuation assays with Salmonella TA strains or Escherichia coli WP2 uvrA pKm 101. Chromate(VI) and selenate(VI) ions were found to be mutagenic in plate incorporation assays employing conventional media. On the other hand, cadmium(II), beryllium(II), chromate(VI), and metavanadate(V) ions were detected in conventional fluctuation assays, indicating the importance of this technique in detection of metal mutagens. Modified culture media, with trimetaphosphate ions in place of orthophosphate as the sole phosphate source for bacterial growth, were also used in this study. The media modifications prevented precipitation of metals such as nickel and cadmium as their insoluble phosphates, and allowed detection of the mutagenicity of metavanadate ions in plate incorporation assays. However, the fluctuation technique using standard media was shown to detect a wider range of mutagenic metal ions than tests with modified media. It is notable that metaarsenite(III), arsenate(V), and nickel(II) ions were not found to be mutagenic in any of the assays although they are known to be carcinogenic and are mutagenic in other test systems. Their lack of mutagenicity in the modified media indicates that precipitation of these ions as orthophosphates is not the reason for their lack of activity in standard bacterial assays.

Beryllium↗

Effect of induction by DDT on metabolism and mutagenicity of benzo[a]pyrene.

Liver microsomal enzymes are essential for the detection of benzo[a]pyrene (B[a]P)-mediated mutagenesis in the Salmonella/mammalian microsome mutagenicity test and, furthermore, this mutagenicity is considerably enhanced by induction of hepatic enzymes involved with drug metabolism. Although Aroclor 1254 is most commonly used for induction of S9 enzymes, DDT is also capable of this induction. This paper reports a comparison of liver S9 fraction induced by the two agents: there is a marked difference in their concentration optima for metabolism of B[a]P; greater numbers of revertant colonies are seen with Aroclor-induced S9, which is optimal at a concentration of 10% (v/v), whereas DDT-induced S9 is optimal at 2.5% (v/v); Aroclor induces aryl hydrocarbon hydroxylase (AHH), cytochrome P-450 and epoxide hydrase while DDT induces only AHH, to about half the level detected in the Aroclor-induced S9 fraction. A comparison of metabolite distribution for Aroclor- and DDT-induced hepatic microsomes reveals quantitative differences only. DDT-induced microsomes yield a greater proportion of B[a]P-4,5-oxide and its metabolic product B[a]P-4,5-dihydrodiol than do Aroclor-induced microsomes. Time course studies on the mutagen half-life measured on the agar plate provides good evidence that metabolites responsible for mutagenicity were different for each inducer.

Animals↗

Allergens in the white and yolk of hen's egg. A study of IgE binding by egg proteins.

The radioallergosorbent test (RAST) was used to compare the IgE binding of egg white and yolk, and allergenic proteins were detected by immunoelectrotransfer ('Western blotting'). The main allergens were found in egg white, but for a large proportion of the egg-sensitive patients, yolk contained specific IgE-binding constituents. For blood sera from 36 patients, there was a positive correlation between the results of RAST for egg white and for yolk. Lysozyme was found to be an allergen for some patients. The effect of heating on the allergenicity of egg white was examined and the allergenicity of hen egg white was compared with that of a duck egg. The allergens in yolk were associated with each of the three yolk fractions, and several of the proteins in the low-density lipoprotein fraction bound IgE.

Adolescent↗

Early menopausal changes in bone mass and sex steroids.

Eighty-four healthy perimenopausal and early postmenopausal women were divided into four groups: group A, those with slightly irregular menstrual periods and plasma FSH below 40 mIU/ml; group B, those with irregular periods and FSH above 40 mIU/ml; group C, those whose last menstrual period was within 1 yr of study; and, group D, those whose last menstrual period was between 12 and 55 months before the study. Plasma concentrations of estrone and estradiol progressively decreased in groups B, C and D compared to those in A in parallel with a decrease in the production rates, and FSH and LH were significantly increased. There was little change in the concentration of androstenedione or testosterone. Vertebral bone mass was significantly decreased in groups B, C, and D compared to that in A, and radial bone mass was decreased in group D. There was a significantly positive correlation between plasma estrone and estradiol and bone mass at both the radius and vertebra. Increased bone remodeling was suggested by increases in serum calcium and bone gla protein. These data suggest that bone loss, at least from the spine, may begin before menses cease and is correlated with decreases in estrogen production and increases in bone remodeling.

Adult↗

Metabolism of the carcinogen 7-methylbenz[c]-acridine in the rat.

The biliary excretion of radioactivity by adult Wistar rats given i.v. 7-methyl-[7-14C]benz[c]acridine(14C-7-MBAC) and [methyl-3H]-7-methylbenz[c]acridine (3H-7-MBAC) (2 mg/kg) was 61% and 48%, respectively, in males in six hours. Females excreted 33% of a 2 mg/kg dose of 3H-7-MBAC in the same time-period. For male rats, the urinary and faecal excretions were about 10% and 61% of the dose of 14C-7-MBAC, respectively, in seven days. No enterohepatic circulation could be demonstrated in control male rats. The biliary excretion of radioactivity by phenobarbital- and 3-methylcholanthrene-induced male rats given 14C-7-MBAC was similar to or greater than that of control male rats. The organo-soluble biliary metabolites after beta-glucuronidase/arylsulphatase hydrolysis were separated by h.p.l.c., and quantitative metabolite distributions were obtained for induced and control rats by comparison with metabolite standards. The mutagenicity of bile from carcinogen-dosed control rats was greater than that of equivalent bile from carcinogen-dosed 3-methylcholanthrene-pretreated animals.

Acridines↗

Vertical ocular motility disturbance in pseudotumor cerebri.

Three patients with pseudotumor cerebri developed transient vertical ocular motor abnormalities. All had associated sixth nerve palsies and two had significant abnormalities of visual acuity and fields. Effective treatment of elevated intracranial pressure (ICP) resulted in resolution of the motility disturbance in all cases. This unusual oculomotor feature of elevated ICP may be due to skew deviation or fourth nerve palsy, but in either instance it is not a localizing sign.

Abducens Nerve↗

Sudden visual loss in pseudotumor cerebri due to central retinal artery occlusion.

A patient with a 16-month history of papilledema from pseudotumor cerebri had sudden loss of vision in one eye because of a central retinal artery occlusion (CRAO). The CRAO was transient and visual acuity improved from light perception to 6/7.5 OS in long-term follow-up. A visual field abnormality and color-vision deficit have persisted. Both eyes demonstrated peripapillary neovascular membranes. The eye with CRAO had extensive chorioretinal folds extending from the disc through the macula. Thorough investigations failed to demonstrate a coagulation abnormality, hyperviscosity, or source of emboli. Although the mechanism remains unclear, we postulate that CRAO may have been caused by a local pathologic condition in the optic nerve.

Adolescent↗

Autoreactivity to collagen in a murine lupus model.

MRL/l mice exhibit many characteristics of human systemic lupus erythematosus including antinuclear antibodies, circulating immune complexes, glomerulonephritis, and death secondary to renal failure. In addition, these mice have elevated levels of rheumatoid factor and spontaneously develop arthritis that has many similarities to human rheumatoid arthritis. Our present studies indicate that, with age, they also develop reactivity to types I and II collagen. The levels of antibodies against native or denatured types I and II collagen in the sera of 4-5-month-old MRL/l mice are significantly higher than those in the sera of age-matched Balb/c or MRL/n mice. The specificity of these antibodies for collagen was demonstrated by a competitive binding assay. The T cells from 1- or 2-month-old MRL/l mice exhibited a significant proliferative response in the presence of type I collagen and a mild or no response to type II collagen. Both antigenic and mitogenic responses decreased with age. The results suggest that the development of autoimmunity to collagen may play an important role in the perpetuation of arthritis, vasculitis, and glomerulonephritis in MRL/l mice.

Animals↗

Androgen and estrogen dynamics in women with vertebral crush fractures.

Using constant infusions of [3H]androgen/[14C]estrogen we measured metabolic clearance and production rates and aromatization of androgens to estrogens in post-menopausal women with vertebral crush fractures and compared these results to similar measurements in a similar population of post-menopausal women who did not have vertebral crush fractures. The mean +/- SEM values for the metabolic clearance rates of testosterone and estrone, 220 +/- 10 and 880 +/- 50 1/day per m2, were significantly less in the crush fracture group than the respective mean values in the control group, 280 +/- 15 and 1110 +/- 70 1/day per m2. The mean concentration of estradiol was higher in the crush fracture group, 18 +/- 2 pg/ml, compared to that in the control group, 13 +/- 1 pg/ml. However, for the crush fracture group the mean blood production rates of both androstenedione, 0.7 +/- 0.1 mg/day, and testosterone, 56 +/- 9 micrograms/day, were significantly less than the respective values in the control group, 1.2 +/- 0.2 mg/day and 115 +/- 15 micrograms/day. The production rates for estrone and estradiol were not different for the two groups. In addition the mean value for the fraction of adrostenedione converted to testosterone ( [rho]A, T BB) was lower in the crush fracture, 0.030 +/- 0.002 compared to the control group, 0.041 +/- 0.004. Thus the amount of biologically available androgen is less in the vertebral crush fracture group than in the control group. However, since these measurements represent an isolated point temporally removed from major changes in bone morphology, their exact relationship to the crush fracture and osteoporotic process remains uncertain.

Androgens↗

Ultraviolet carcinogenesis in the hairless mouse skin. Influence of the sunscreen 2-ethylhexyl-p-methoxycinnamate.

The mutagenicity of some samples of a commonly used sunscreen, 2-ethylhexyl-p-methoxycinnamate (2-EHMC), led to these studies of its potential carcinogenicity in the HRA/Skh hairless mouse. In a daily treatment regime, repeated for 9 weeks, groups of mice were painted on the dorsum with 2-EHMC, and were then exposed to low doses of one of two artificial ultraviolet (UV) light sources. Mice were also treated with UV alone and with 2-EHMC alone. The accumulated UV exposure alone produced tumours in 40-100% of mice. However, 2-EHMC-treated mice were protected. Subsequent treatment of the 2-EHMC-protected mice, and mice previously treated with 2-EHMC alone, with the tumour promoter, croton oil, produced tumours on a significant number of animals. We conclude that 2-EHMC protects from UV tumorigenesis in the absence of a tumour promoter. However, although tumours appeared on only 4 out of 160 2-EHMC-treated mice exposed to UV, the carcinogenic process had been initiated in others, as application of the tumour promoter, croton oil, produced tumours. Statistical analysis of the incidence of promoted tumours inferred that prior irradiation with UV may not have been implicated. Therefore, 2-EHMC itself may initiate tumours in this strain of hairless mouse.

Animals↗

Hypertension screening in the eye clinic.

We studied the suitability of the eye clinic as a site for hypertension detection with attention to the ophthalmologist's role in the broad context of hypertension control. Sixty of 300 consecutive eye clinic patients were referred to their primary care physician for re-evaluation of an elevated blood pressure recording. Only seven of these were started on therapy or had a change made in their existing regimen by the primary physician. When the benefit to this small percentage is weighed against the potential effects of such a high "false positive" referral rate we cannot support the proposal that the ophthalmologist does more good than harm by measuring the blood pressure of every patient.

Adult↗

Palisade endings in human extraocular muscles.

The presence of nerve terminals in the tendinous insertions of human eye muscles was investigated histologically in adult human eye muscles obtained from donor eyes and in muscle pieces resected from juvenile patients undergoing surgical correction for strabismus. Lateral and medial recti, superior and inferior oblique muscles from adults, were stained "en bloc" using a silver impregnation method. Numbers of nerve terminals were isolated that resembled "palisade endings" previously described in other species. A single palisade ending usually appeared as an interwoven network of fine neural filaments that cupped the inserting tip of a single extrafusal fiber. A collection of palisade endings on several neighboring muscle fibers were supplied by a single myelinated axon that branched from a nerve bundle in the muscle mass. The presence of nerve terminals at the distal musculotendinous interface of juvenile muscle also was observed when some resected specimens of lateral and medial recti were sectioned and stained using Holmes' silver method with a picrofuschin counterstain. No conventional Golgi tendon organs were seen.

Aged↗

Sensitivity of two Chinese hamster cell lines to SCE induction by a variety of chemical mutagens.

SCE induction in Chinese hamster Don (lung) cells was compared with that in CHO (ovary) cells exposed under identical conditions to 14 known mutagens. Test protocols used for comparison were selected following a study of Don and CHO cell responses to aflatoxin B1 and benzo[a]pyrene. In the absence of added metabolizing enzymes 9-aminoacridine, 4-nitroquinoline 1-oxide, N-methyl-N-nitrosourea, dimethylcarbamoyl chloride, beta-propiolactone, daunomycin, aflatoxin B1 and 2-aminoanthracene were directly active in both cell lines; every substance positive in CHO cells was also positive in Don cells. However, the latter detected cyclophosphamide, hydrazine sulphate, benz[c]acridine, 3-methylcholanthrene and benzo[a]pyrene without addition of S9. CHO cells did not respond equivalently to these mutagens, either in the presence or absence of S9. Other differences between the cell lines depended on chemical exposure time, S9 pre-incubation or co-incubation conditions. For example, the ability of CHO cells to detect SCEs due to 2-aminoanthracene was acutely dependent on exposure time. In addition, Don cells exhibited lower background SCE values which were less variable than those of CHO cells under the same culture conditions. Although incapable of detecting 4-dimethylaminoazobenzene (butter yellow) and not as sensitive to cyclophosphamide as certain cell lines of liver origin, the pseudodiploid Don cell line possesses other desirable characteristics required for in vitro SCE assays, particularly with regard to intrinsic metabolic activation of polycyclic aromatic hydrocarbons and related substances.

Aflatoxin B1↗

Mutagenic activity of heated potato/oil systems.

Mutagens detected with Salmonella typhimurium strain TA 98 in the presence of liver S9 mix were extracted from potato slices, but not pure potato starch, after frying in oil. No mutagenic activity was detected using strain TA 100, in the presence or absence of S9 mix with either fried potato slices or potato starch. Mutagenic activity was detected at frying temperatures of 140 degrees C and above. The mutagenic activity was limited to the outer portion of the fried potato slices and increased with frying time and temperature. Mutagenic activity ratios for extraction with both (NH4)2SO4/NH4OH and Na2SO4/NaOH were similar.

Food Contamination↗

Is pulsed ultrasound mutagenic?

The possibility that microsecond pulses of 3 MHz ultrasound may interact at the cellular level, with genetic consequences, was investigated using two different endpoints. The Ames mammalian microsome test was employed to assess mutagenicity and viability in Salmonella typhimurium bacteria, while the sister chromatid exchange frequency provided an indicator of ultrasound induced effects at the chromosome level in Chinese hamster ovary cells.

Animals↗

Sister chromatid exchange induction in two cell lines.

Sister chromatid exchange (SCE) induction by the procarcinogen benzo (a)-pyrene (BP) was studied using two established cell lines. Chinese hamster ovary (CHO) and Chinese hamster lung (Don) cells were exposed to varying concentrations of BP in the presence and absence of a rat liver metabolizing system. Results showed a significant difference in the abilities of the two cell lines to induce SCE in the absence of liver homogenate. These experiments demonstrate that Don cells are capable of generating active metabolites from biologically inactive procarcinogens presumably due to an inherent metabolizing system which is deficient or absent in CHO cells.

Animals↗