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K A Mason

Publications and source records attributed to K A Mason.

At least 73 records · Page 4Linked to original sources
PubMed1988

Primary and secondary structural determinants in the receptor binding sequence beta-(38-57) from human luteinizing hormone.

The intercysteine "loop" sequence 38-57 in the beta subunit has been shown to be a determinant for expression of biological activity in human lutropin (hLH) and choriogonadotropin (hCG) [Keutmann, H. T., Charlesworth, M. C., Mason, K. A., Ostrea, T., Johnson, L., & Ryan, R. J. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 2038]. Together with other sequences, the 38-57 region may contribute to a multicomponent receptor binding domain in hLH/hCG. Because the structural features influencing activity in this important region are not easy to evaluate in the full-length subunit, we have used analogues of hLH beta-(38-57) prepared by solid-phase synthesis. The peptides were tested for inhibition of 125I-labeled hCG binding to rat ovarian membrane receptors. Secondary structure was analyzed by circular dichroism (CD) and by reactivity with antibodies to the native 38-57 peptide. An analogue lacking the 38-57 disulfide linkage retained 20% receptor binding and full immunoreactivity. "Far"-ultraviolet CD profiles were essentially identical with those of the disulfide-intact peptide; a transition from 10% to 30% alpha-helix in 90% trifluoroethanol was characteristic of both. The peptide thus appears not to require the disulfide bridge to retain a looped conformation with amphipathic secondary structure. An essential positive charge at position 43 was shown by complete loss of activity upon substitution of Asp or Ala for the Arg found in all known species of LH. Other analogues showed a requirement for a neutral residue at position 47, also highly conserved.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1987

Palliative radiotherapy of a mouse mammary carcinoma.

A mouse mammary carcinoma was exposed to one of three palliative treatment schemes: rapid, split, and extended. Tumors were treated at either 4 mm diameter or 8 mm diameter to compare the responses of small and large tumors to the three treatment schemes. In addition, acute skin reaction and late skin contracture were assessed. The results were: (1) The rapid treatment resulted in the greatest tumor response for 4 and 8 mm tumors but it also caused the most severe normal tissue reaction. (2) Lengthening the overall treatment time to 5 weeks (extended treatment) resulted in the poorest response for both large and small tumors. (3) The split course technique was almost as effective as the rapid course in treating small tumors, but its effectiveness was reduced if treatment was delayed until the tumor reached 8 mm in diameter. (4) The survival of mice with 4 mm tumors clearly depended upon the type of radiation schedule used, with the rapid treatment being superior. (5) If treatment was delayed until the tumors were large (8 mm diameter), there was no survival advantage between the three treatment schedules. (6) Palliation and survival were better when the tumor was treated when it was small, suggesting that palliation may be better if treatment is given early or electively.

Animals↗
PubMed1987

A receptor-binding region in human choriogonadotropin/lutropin beta subunit.

Synthetic fragments have not been widely used thus far to evaluate structure-activity relations in the glycoprotein hormones. We prepared a series of peptides representing the intercysteine "loop" sequence (residues 38-57) in human choriogonadotropin (hCG) and lutropin (hLH) beta subunits, anticipating that it might be oriented toward the surface and accessible to receptors. The peptides were characterized chemically and tested for bioactivity by binding to rat ovarian membrane receptor and stimulation of Leydig cell testosterone production. The hCG beta-(38-57) and hLH beta-(38-57) peptides inhibited binding of 125I-labeled hCG half-maximally at 1.51 X 10(-4) and 2.03 X 10(-5) M, respectively, while other peptide hormones and fragments from elsewhere in the beta subunit were inactive. Both peptides stimulated testosterone production, with half-maximal responses at 3.55 X 10(-5) M (hCG) and 2.18 X 10(-5) M (hLH). By radioimmunoassay with an antibody to thyroglobulin-conjugated hCG beta-(38-57) peptide, native hCG and beta subunit were highly reactive, as were the reduced and carboxymethylated subunit and peptide. Helical-wheel projection predicted an amphipathic region in the N-terminal portion of the 38-57 sequence, and circular dichroic measurements showed an increase in ordered structure, especially alpha-helix, when the 38-57 peptides were transferred from an aqueous to a more lipophilic (90% trifluoroethanol) environment. These results indicate that the 38-57 region of beta subunit is exposed on the surface and constitutes a component in the receptor-binding domain for hCG and hLH. A region of amphipathic-helical structure in the 38-57 sequence may promote hormone-receptor interactions in a manner proposed for several other peptide hormones.

Amino Acid Sequence↗
PubMed1986

Late radiation response of kidney assayed by tubule-cell survival.

An assay for the survival of renal tubule cells was developed using mice. It is analogous to other in-situ clonogenic cell survival assays. One kidney was irradiated using a 137Cs irradiator and removed 60-68 weeks later for histological examination. In unirradiated animals there were about 370 tubules in contact with the capsule in a coronal cross section at the middle of the kidney. After irradiation, extensive tubular damage was the dominant lesion. The number of epithelialized tubules in contact with the capsule showed a dose-dependent logarithmic decline. The dose-survival relationship for the clonogenic cells responsible for the regeneration of tubule epithelium was described by a D0 value of 1.5 Gy over the dose range 11-16 Gy. This radiosensitivity resembles that of stem cells in acutely responding tissues. The lack of histological evidence of damage to the arterial vasculature at the time the tubules are initially denuded of epithelium, and the similarity of renal tubule cell radiosensitivity to that of other mammalian cells, support the hypothesis that "late" radiation injury results primarily from depletion of parenchymal cells, not indirectly from injury to blood vessels, as has been the prevailing belief.

Animals↗
PubMed1985

MR effect on murine spermatogenesis.

The cytotoxic effects of magnetic resonance (MR) on spermatogenesis in mice were studied. Mice were exposed to a strong static magnetic field from a 0.3-T MR imaging device. The effect of this treatment on different classes of spermatogenic cells was investigated by counting sperm heads at various times after exposure. Sixty-six hours of continuous exposure did not produce any significant cytotoxicity to these cells. This period of continuous exposure is far longer than any anticipated occupational exposure to humans. Thus, acute and subacute exposure to static magnetic fields associated with diagnostic use of MR imaging devices is unlikely to have any significant adverse effect on spermatogenesis.

Animals↗
PubMed1985

Acute effects of a perfluorochemical oxygen carrier on normal tissues of the mouse.

A single iv dose of 15 ml/kg fluosol DA (20%), a perfluorochemical oxygen carrier, caused hepatomegaly and splenomegaly which persisted for at least 3 weeks after drug injection. The peak increase in weight was at 3 days in the spleen (1.7x) and at 14 days in the liver (1.5x). Lung and kidney weights were not altered 1-21 days after administration of fluosol DA. The slopes of the single-dose radiation survival curves for intestinal epithelial cells and spermatogenic stem cells in mice breathing air or oxygen were not significantly altered by the administration of fluosol DA 10 min before irradiation, and the doses to achieve an isoeffect were altered by 1.03 or less. When mice were challenged with iv injected FSa tumor cells 24 h after treatment with fluosol DA, no increase in the number of artificial pulmonary metastases was observed.

Animals↗
PubMed1983

A dose-surviving fraction curve for mouse colonic mucosa.

A dose-surviving fraction curve representing the response of the mouse colonic mucosa to single doses of 137Cs gamma radiation was obtained from the results of a multifraction in vivo colony assay. Construction of the curve required an estimate of the average number of clonogens initially present per colonic crypt. The estimated clonogen count (88) was determined by a statistical method based on the use of doses per fraction common to different fractionation protocols. Parameters for the LQ and TC models of cell survival were obtained by weighted least-squares fits to the data. A comparison of the survival characteristics of cells from the mouse colonic and jejunal crypts suggested that the epithelium of the colon is less radiosensitive than that of the jejunum.

Animals↗
PubMed1981

Effects of hyperthermia and radiation on mouse testis stem cells.

The response of mouse testis stem cells to hyperthermia and combined hyperthermia-radiation treatments was assayed by spermatogenic colony regrowth, sperm head counts, testis weight loss, and fertility. With the use of spermatogenic colony assay, thermal enhancement ratios at an isosurvival level of 0.1 were 1.27 at 41 degrees, 1.80 at 42 degrees, and 3.97 at 43 degrees for testes exposed to heat for 30 min prior to irradiation. Sperm head counts were reduced by heat alone from a surviving fraction of 0.58 at 41 degrees to 0.003 at 42.5-43.5 degrees. Curves for sperm head survival measured 56 days after the testes had been heated for 30 min prior to irradiation were biphasic and showed a progressive downward displacement to lower survival with increasing temperature. The 41, 42, and 43 degrees curves were displaced downward by factors of 2, 58, and 175, respectively. The proportion of animals remaining sterile after 30 min of heat (41-43 degrees) and the median sterility period in days increased with increasing temperature. The minimum sperm count necessary to regain fertility was 13% of the normal mouse level.

Animals↗
PubMed1979

The critical influence of timing of combined modality cytoreductive regimens.

When sequential high dose drug-radiation cytoreductive regimens are employed, the interval between chemotherapy and total body irradiation (TBI) can markedly influence both toxicity in rapid cell renewal systems and the probability of successfully ablating normal and malignant hemopoietic stem cells. This is primarily due to the intense regenerative responses manifested by cells of these tissues that survive the first cytoreductive insult. Since the total doses of chemotherapy and radiation used are limited by toxicity to slowly or non-proliferating tissues, the best therapeutic effect should be obtained when the interval between chemotherapy and TBI is the shortest consistent with acceptable toxicity to rapid cell renewal systems, provided adequate time for drug metabolism and excretion is allowed to minimize the risk of interactive toxicity. In mice treated with piperazinedione 50 mg/m2 and fractionated TBI, the optimal interval between drug administration and irradiation is 3-4 days.

Animals↗
PubMed1977

Pitfalls in the use of the lung colony assay to assess T-cell function in irradiated mice.

Mice depleted of T lymphocytes by thymectomy, whole-body irradiation and bone-marrow reconstitution showed a marked increase in susceptibility to the development of lung colonies after i.v. injection of cells of an immunogenic fibrosarcoma. However, a similar increase was observed in unthymectomized, irradiated and reconstituted mice that had recovered their T-cell function, as evidenced by rejection of allogeneic skin grafts. In both thymectomized and unthymectomized mice subjected to whole-body irradiation, the lung-colony-forming efficiency was high 1 day after irradiation, declined to a minimum at 7 days, and thereafter increased again, unless the animals were held in a pathogen-free environment. Reconstitution of T-cell-depleted mice with thymocytes and/or a thymic lobe graft tended to increase further, rather than reduce, lung-colony-forming efficiency. Induction of profound lymphopenia, by irradiation of the whole body except the thorax, did not significantly increase lung colony yields. These studies show that the lung colony assay is not a reliable method of assessing T-cell function in irradiated mice.

Animals↗
PubMed1977

RBE of neutrons generated by 50 MeV deuterons on beryllium for control of artificial pulmonary metastases of a mouse fibrosarcoma.

Artificial pulmonary metastases of a mouse fibrosarcoma were produced by the intravenous injection of 10(4) cells admixed with 2 X 10(6) plastic microspheres into mice preconditioned with 600 rad whole-body irradiation 24 hours earlier. Four days after injection of tumour cells, mice were irradiated with neutrons generated by 50 MeV deuterons on Be at the Texas A & M Variable Energy Cyclotron or with 137Cs gamma rays. One, three or six fractions of radiation were delivered on a three-hour fractionation schedule. Surviving lung metastases were scored macroscopically 16 days after irradiation. The data indicate that: (1) the RBE (n/gamma) was in the range 1.6-2.6 depending on the size of dose per fraction; (2) the slopes of the gamma-ray curves decreased with increasing fraction number (i.e. decreasing fraction size); (3) the slopes of the neutron curves decreased only slightly with increasing fraction number (and decreasing fraction size); (4) no additional sparing was achieved by further fractionating doses of neutrons of 300 rad or less.

Animals↗