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Biomedical subjects

H Mason

Publications and source records attributed to H Mason.

At least 55 records · Page 3Linked to original sources

Excitatory sulphur amino acid-evoked neurotransmitter release from rat brain synaptosome fractions.

The neuroactive sulphur-containing amino acids L-cysteate (CA), L-cysteine sulphinate (CSA), L-homocysteine sulphinate (HSA), S-sulpho-L-cysteine (SC) and L-homocysteate (HCA) evoked the release of previously accumulated D-[3H]aspartate from rat brain cerebrocortical and cerebellar synaptosome fractions in a manner that was wholly Ca2+-independent. However, analysis of endogenous release by hplc revealed the presence of both Ca2+-dependent and -independent component of L-glutamate release but only a Ca2+-independent component of L-aspartate release. CA, CSA, HSA and SC but not HCA evoked the release of previously accumulated [3H]GABA from synaptosome fractions by a mechanism shown to comprise both a Ca2+-dependent and -independent component. The specific antagonists of the N-methyl-D-aspartate (NMDA) receptor, 3-[(+/-)-2-carboxypiperazin-4-yl]propyl-l-phosphonic acid (CPP) and the relatively selective competitive quisqualate (QUIS)/kainate (KA) receptor antagonist, 6-cyano-7-dinitroquinoxalinedione (CNQX), were ineffective in blocking the excitatory sulphur amino acid-evoked release of either D-[3H]aspartate, [3H]GABA or of endogenous established transmitter amino acids.

Amino Acids↗

Distinctive transforming genes in x-ray-transformed mammalian cells.

DNAs from hamster embryo cells and mouse C3H/10T1/2 cells transformed in vitro by x-irradiation into malignant cells transmit the radiation transformation phenotype by producing transformed colonies (transfectants) in two mouse recipient lines, the NIH 3T3 and C3H/101/2 cells, and in a rat cell line, the Rat-2 cells. DNAs from unirradiated cells or irradiated and visibly untransformed cells do not produce transformed colonies. The transfectants grow in agar and form tumors in nude mice. Treatment of the DNAs with restriction endonucleases prior to transfection indicates that the same transforming gene (oncogene) is present in each of the transformed mouse cells and is the same in each of the transformed hamster cells. Southern blot analysis of 3T3 or Rat-2 transfectants carrying oncogenes from radiation-transformed C3H/10T1/2 or hamster cells indicates that the oncogenes responsible for the transformation of 3T3 cells are not the Ki-ras, Ha-ras, or N-ras genes, nor are they neu, trk, raf, abl, or fms, although quick blot analysis using 11 oncogene probes detected increased transcripts of c-abl and c-fms in the 3T3 transformants containing oncogenic sequences from the x-ray-transformed C3H/10T1/2 cells. The work demonstrates that DNAs from mammalian cells transformed into malignancy by direct exposure in vitro to radiation contain genetic sequences with detectable transforming activity in three recipient cell lines. The results provide evidence that DNA is the target of radiation carcinogenesis induced at a cellular level in vitro. The experiments indicate that malignant radiogenic transformation in vitro of hamster embryo and mouse C3H/10T1/2 cells involves the activation of unique non-ras transforming genes, which heretofore have not been described.

Animals↗

Quantitative levels of C-reactive protein in cerebrospinal fluid in patients with bacterial meningitis and other conditions.

We measured levels of C-reactive protein (CRP) in the cerebrospinal fluid in 145 children, using a solid-phase radioimmunoassay. The CRP levels in 49 patients with culture-proved bacterial meningitis ranged from 0 to 51,000 ng/ml (median 1460 ng/ml). In 33 patients with aseptic meningitis, values were much lower range 0 to 438 ng/ml; (median 17 ng/ml). In patients with CSF pleocytosis (greater than 10 WBC/microliter), CRP greater than 100 ng/ml was 95% accurate in identifying those with bacterial meningitis. However, a few patients with bacterial meningitis and little or no CSF pleocytosis had low levels of CRP at admission. Among the 63 patients with nonmeningitic conditions, those with bacterial infections frequently (10 of 13 had CRP greater than 100 ng/ml, whereas CRP elevations were infrequent (seven (18%) of 40) in patients with viral infections and other conditions. CRP diffuses into the CSF as readily as other proteins, but in bacterial meningitis the CSF/serum ratio of CRP was lower than that of albumin and IgG. The measurement of CRP in CSF is potentially a very useful diagnostic tool, but certain inherent limitations must be recognized, because some patients may fail to mount a prompt inflammatory response.

Adolescent↗

Selenium and vitamin E inhibit radiogenic and chemically induced transformation in vitro via different mechanisms.

Results from in vivo and in vitro studies showing that antioxidants may act as anticarcinogens support the role of active oxygen in carcinogenesis and provide impetus for exploring the functions of dietary antioxidants in cancer prevention by using in vitro models. We examined the single and combined effects of selenium, a component of glutathione peroxidase, and vitamin E, a known antioxidant, on cell transformation induced in C3H/10T-1/2 cells by x-rays, benzo[a]pyrene, or tryptophan pyrolysate and on the levels of cellular scavenging systems and peroxide destruction. Incubation of C3H/10T-1/2 cells with 2.5 microM Na2SeO3 (selenium) or with 7 microM alpha-tocopherol succinate (vitamin E) 24 hr prior to exposure to x-rays or the chemical carcinogens resulted in an inhibition of transformation by each of the antioxidants with an additive-inhibitory action when the two nutrients were combined. Cellular pretreatment with selenium resulted in increased levels of cellular glutathione peroxidase, catalase, and nonprotein thiols (glutathione) and in an enhanced destruction of peroxide. Cells pretreated with vitamin E did not show these biochemical effects, and the combined pretreatment with vitamin E and selenium did not augment the effect of selenium on these parameters. The results support our earlier studies showing that free radical-mediated events play a role in radiation and chemically induced transformation. They indicate that selenium and vitamin E act alone and in additive fashion as radioprotecting and chemopreventing agents. The results further suggest that selenium confers protection in part by inducing or activating cellular free-radical scavenging systems and by enhancing peroxide breakdown while vitamin E appears to confer its protection by an alternate complementary mechanism.

Animals↗

Ozone acts alone and synergistically with ionizing radiation to induce in vitro neoplastic transformation.

Ozone, a major chemical oxidant in the atmosphere, is an environmental air pollutant whose ability to act as a direct carcinogen is unclear Using in vitro transformation, a technique which permits the study of oncogenesis in the absence of host specific effects, we report for the first time that ozone (5 p.p.m. for 5 min) induces neoplastic transformation in vitro in both primary hamster embryo cells and mouse fibroblast cultures (C3H/10-1/2). Exposure of the hamster and mouse cells to ozone also results in enhanced levels of free radical-mediated lipid peroxidation products. We also report for the first time on the carcinogenic interaction between ozone and ionizing radiation. Exposure of the cells to 3 or 4 Gy of gamma-rays, 2 h prior to O3 treatment, results in markedly enhanced rates of transformation, statistically consistent with a synergistic interaction between the agents. The results demonstrate that O3 acts as a direct carcinogen and co-carcinogen on susceptible cells, therefore having important consequences for public health.

Cell Line↗

Sodium bisulfite protects against radiogenic and chemically induced transformation in hamster embryo and mouse C3H/10T-1/2 cells.

Pretreatment of hamster embryo cells or mouse C3H/10T-1/2 cells with sodium bisulfite (0.5, 2.5, 5.0 and 100 ppm) inhibits the oncogenic transformation of the cells following their exposure to x-rays or benzo(a)pyrene. The results suggest that low doses of bisulfite, a widely used food additive, can serve as a radioprotective and chemopreventive agent with anticarcinogenic potential.

Animals↗

Ovulatory disorders in women with polycystic ovary syndrome.

With the use of pelvic ultrasound imaging we have found that more than half of the women presenting to our clinic with ovulatory disturbances have polycystic ovaries. As a group hirsutism is common, the serum LH, the LH:FSH ratio and serum androgen levels are higher than in other groups of patients with anovulation, but many of the women we studied were non-hirsute and had normal levels of these hormones. The aetiology of PCOS remains obscure and there is probably more than one cause. Disturbance of hypothalamic/pituitary, ovarian or adrenal function could all result in the development of polycystic ovaries. Our own data, based on pelvic ultrasound and measurement of serum androgen levels, suggest that an ovarian abnormality, other than the obvious morphological one, may be identified in most women although this does not prove (except perhaps in those women with unilateral PCOS) that the ovary is the primary site of the disturbance. Management of ovulatory disturbances includes symptomatic treatment of dysfunctional uterine bleeding and induction of ovulation. Although the ovulation rate following clomiphene is quoted as about 75%, this is probably an overestimate; less than half the 'ovulators' become pregnant and in those who do there is a high risk of early pregnancy loss. Induction of ovulation in clomiphene non-responders remains a difficult problem. The results of ovarian wedge resection are variable and any beneficial effect is short-lived with the risk of long-term infertility due to pelvic adhesions. Laparoscopic electrocautery may be a useful alternative, but it is too early to assess this form of treatment. Of the medical methods of ovulation induction in clomiphene non-responders, two methods have emerged as being highly promising: the first is administration of HMG following suppression of the pituitary by an LH-RH analogue; so far only a very small number of patients have been treated. The second is low-dose FSH. Initial studies, including our own, have shown a high incidence of ovulation and a pregnancy rate of 50%.

Androgens↗

Diurnal variations in urinary mercury excretion.

A consistent diurnal variation of urinary mercury concentration (expressed as nmol of mercury/mmol of creatinine) has been demonstrated in 36 occupationally exposed workers, the concentration being highest in the morning and lowest in the late evening. This variation is partly intrinsic and partly an artifact because creatinine excretion also varies diurnally, but in the opposite direction. The implications of these findings in relation to the biological monitoring of mercury workers is discussed.

Circadian Rhythm↗

Renal dysfunction in cadmium smelters: relation to in-vivo liver and kidney cadmium concentrations.

Biochemical indicators of renal dysfunction have been compared with liver and kidney cadmium levels measured by neutron activation analysis in a group of 37 cadmium smelters. Higher than normal concentrations of cadmium in the liver reflect past exposure; they were associated with evidence of renal dysfunction in workers exposed to cadmium for more than 10 years. A small group of 6 workers exposed to cadmium for only a short time (mean = 4.6 years) had high hepatic cadmium concentrations but normal renal function. Longitudinal studies are required to establish the natural history of renal dysfunction following cadmium accumulation in industrial workers.

Cadmium↗

Modification of sister chromatid exchanges and radiation-induced transformation in rodent cells by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate and two retinoids.

Modification of sister chromatid exchanges and radiation-induced transformation in mouse C3H/10T 1/2 and Syrian hamster embryo cells by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate and two retinoids, the trimethylmethoxyphenyl analog of N-ethyl retinamide and beta-all-trans-retinoic acid, has been studied. 12-O-tetradecanoylphorbol-13-acetate alone enhances, and retinoids alone reduce radiation-induced transformation. When both compounds were present, the retinoids not only reduced the oncogenic effects of radiation but completely eliminated the promoting effects of 12-O-tetradecanoylphorbol-13-acetate. These results were not paralleled by changes in sister chromatid exchange frequencies, indicating that, while sister chromatid exchanges may be useful as indicators of primary carcinogen mutagens, they may have little utility when secondary agents after the response of cells to a primary initiator.

Animals↗