PubMed Health⌕ Search

Biomedical subjects

H R Withers

Publications and source records attributed to H R Withers.

At least 145 records · Page 8Linked to original sources
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↗
PubMed1980

Malignant properties and DNA content of daughter clones from a mouse fibrosarcoma: differentiation between malignant properties.

Freshly isolated cones of high cloning efficiency from a mouse fibrosarcoma were examined for DNA content, cell size, protein content, and malignant characteristics such as artificial lung-colony-forming ability, s.c. tumour take, host survival, and spontaneous metastatic ability. These malignant characteristics and other cell properties were heterogeneous among these clones; the malignant characteristics could vary and were not "all or none" in their nature. The higher the DNA content or the larger the cell volume, the higher the malignancy in terms of artificial lung-colony forming, efficiency, s.c. tumour take, and host survival. Despite variability of each parameter, the ratio of DNA content to cell size or protein content remained constant through these variations: the increased DNA paralleled increased protein and increased cell volume. The increased DNA was correlated with the more malignant characteristics of local growth and lung-colony-forming efficiency. Spontaneous metastasis to the lung was totally different from the local growth abilities; the small-cell clone produced more metastases. The graded nature of malignant properties and the differentiation between local growth and metastatic potential among the daughter clones indicate that malignancy reflects a complex moiety of cell properties.

Animals↗
PubMed1980

Test of equal effect per fraction and estimation of initial clonogen number in microcolony assays of survival after fractionated irradiation.

In the use of multifraction microcolony assays to infer the low-dose response of in situ renewal systems such as intestinal crypts, the assumption of equal effect per dose fraction is required. Moreover, the construction of a cell-survival curve requires knowledge of the initial count of cells capable of repopulating each renewal structure. We describe a method of designing fractionation protocols which provides a regression estimate of the initial number of clonogens per renewal structure and a test of the hypothesis of equal effect per fraction. The essential factor in the experimental design is the use of common dose fractions (use of the same dose per fraction in series with different numbers of fractions). Applications of the method to data for which the assumption of equal effect per fraction holds (four-hour fractionation interval testis study) and does not hold (one-hour fractionation interval jejunal crypt study) are presented.

Animals↗
PubMed1979

Radiobiological considerations in the use of total-body irradiation for bone-marrow transplantation.

On radiobiological grounds, a therapeutic advantage should result when total body irradiation (TBI) in preparation for bone-marrow engraftment is given as a fractionated course, rather than as a single exposure at logistically reasonable dose rates. This is because cells of hemopoietic origin in general show less capacity for repair of sublethal radiation injury than do cells of other organs. Dose-limiting lung tolerance, in the context of fractionated TBI, is estimated to be at least 12 Gy (without correction) in increments of 2 Gy regardless of dose rate. A practical method for delivering TBI using a high-energy linear accelerator is described.

Animals↗
PubMed1979

The opossum as an animal model for studying radiation esophagitis.

Six opossums were evaluated as a possible animal model of radiation esophagitis. In a single exposure to the esophagus, four animals received 60Co radiation of various doses; two served as controls. Pre- and postirradiation evaluations using fiberoptic endoscopy, mucosal biopsy, barium esophagography, and manometry were performed. Esophagitis developed at one week in irradiated animals. Opossums receiving 17.5, 20, and 22.5 Gy (1,750; 2,000; and 2,250 rad) became anorexic one week postirradiation, and abnormal motility subsequently developed. The controls and the animal receiving 15 Gy (1,500 rad) remained normal. Histological changes in the irradiated opossum esophagus resembled those found in humans.

Animals↗
PubMed1978

Radiotherapy combined with curative surgery. Its use as therapy for carcinoma of the sigmoid colon and rectum.

Local recurrence rates for colorectal carcinoma occur in the range from 20% to 35%. For this reason, postoperative radiotherapy was evaluated as a measure to achieve local disease control in the pelvis. Patients with tumors penetrating the entire bowel wall or with regionally involved lymph nodes received approximately 5,000 rads over a six-week period that commenced three to six weeks after surgery. Sixty-two patients treated by this method are compared with 168 patients treated without adjunctive radiotherapy. Five local recurrences occurred in the group receiving radiotherapy; a reduced incidence compared to the group managed by surgery alone. Complications attributable to radiotherapy included radiation enteritis and bowel obstruction. Measures to minimize complications with this combined approach have been identified. Surgery followed by adjuvant radiotherapy may be performed with an acceptable complication rate and this appears promising in reducing local recurrence of carcinomas of the sigmoid colon and rectum.

Adenocarcinoma↗
PubMed1978

Isolation from a murine fibrosarcoma of cell lines with enhanced plating efficiency in vitro.

The technique for the isolation of mutants was applied to establish highly clonogenic cells from a fibrosarcoma (FSA) that had an extremely poor growth capacity in vitro (10(-6)--10(-7) of surviving fraction of cells). After consecutive clonings, the surviving fraction of cells increased to 1--5 X 10(-1), whereas that of the ordinarily maintained culture remained at a low level. Selected clones were analyzed in vitro and/or in vivo. The results indicated that the FSA was composed of heterogeneous cells or cells having a potential variability in cloning ability in vitro, metastatic ability in vivo [lung colony-forming efficiency (LCFE)], and DNA content. The relatively high DNA content of one of the clones, FSA 1233, continued after growth in vivo or in vitro, indicating its hereditary nature. FSA 1233 was also demonstrated to have a lower LCFE when the cell suspension was made from a tumor rather than from a culture in vitro. The difference of surviving fractions between the cells in the two conditions was not enough to explain the difference in LCFE's between them. These cells could grow under either in vitro or in vivo conditions and could be made readily into single-cell suspensions. The cells are, therefore, available as a system for analysis of the response of cells in vitro after in vivo treatment with various agents.

Animals↗
PubMed1978

Dibutryl cyclic adenosine monophosphate: effect on radiosensitivity of tumors and normal tissues in mice.

The effect of dibutryl cyclic adenosine monophosphate (db-cAMP, 30 mg/kg), injected into mice before irradiation, on the radiation sensitivity of various tissues was investigated. Survival of proliferating hair follicles, small gut stem cells, fibrosarcoma (FSa) micrometastases in the lungs, and two different mammary carcinomas, as assayed by the TCD50 method, were studied. Intraperitoneal injection of db-cAMP before irradiation resulted in higher survival of hair follicles irradiated on the third day after plucking. Stem cells in the small gut showed increased survival if irradiated 4 hours after injection. There was no effect on the survival of FSa micrometastases by preinjection and the TCD50/120 days of the mammary carcinomas was not altered.

Animals↗