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Biomedical subjects

W R Hanson

Publications and source records attributed to W R Hanson.

67 records · Page 4Linked to original sources

DAF as instrumental treatment for dysarthria in progressive supranuclear palsy: a case report.

In this case study, a 59-year-old male with progressive supranuclear palsy and hypokinetic dysarthria wore a small, solid state, battery operated, delayed auditory feedback device to reduce speech rate and to aid speech intelligibility. Time series measurements were made from tape recordings taken at the beginning of treatment and again after three months of daily wearing of the device. Measures of speech rate, intensity, and overall intelligibility indicate that when the instrument is worn, the subject's speech is slowed, vocal intensity increases, and intelligibility is markedly improved. The subject and his family report satisfaction with the instrument. The application of delayed auditory feedback to the treatment of communication disorders is discussed.

Cerebral Palsy↗

Cytotoxic effects of colcemid or high specific activity tritiated thymidine on clonogenic cell survival in B6CF1 mice.

High specific activity tritiated thymidine (HSA-[3H]TdR) and colcemid were given in cytotoxic doses and regimens to B6CF1/Anl mice. The number of cells per intestinal crypt was reduced by the S-phase-specific (HSA-[3H]TdR and the metaphase blocking and cytotoxic effect of multiple injections of colcemid. In 50-day-old mice, the cytotoxic effect of multiple injections of colcemid reduced both the number of cells per crypt and the clonogenic cell survival. However, the number of surviving intestinal clonogenic or stem cells, assayed by the microcolony technique, did not change in 110--130-day old mice. These data suggest that most of the cells at risk from these cytotoxic agents are not clonogenic in adult 110--130-day old mice but are the cells in amplification division. However, since the stem cells of young mice are more susceptible to colcemid, they are apparently in a more rapid cell cycle than those of older mice. The clonogenic cell survival measured in 110--130-day old mice after a single radiation dose of 14 Gy (1400 rad) responded in a non-linear way to increasing time of continuous colcemid cytotoxicity. These data suggest that the intestinal stem cells can respond to amplification compartment cell death by a shortening of their cell cycle and thus, over time, the number of stem cells at risk to colcemid cytotoxicity increases.

Animals↗

Mechanisms of reduction of antitumor drug toxicity by liposome encapsulation.

Actinomycin D, when encapsulated within liposomes, has been previously shown to be less toxic to mice than nonencapsulated actinomycin D, but to retain its tumoricidal activity. We have compared the toxic effects of Act D encapsulated either in the aqueous phase or in the lipid phase of liposomes (APL and LPL, respectively), and the nonencapsulated Act D on the blood forming system, on cell proliferation in the intestine, and on antibody production by spleen lymphocytes. At a single dose of 0.4 mg/kg, APL-encapsulated Act D wass less toxic to white blood cells and to the nucleated cells and colony-forming stem cells of the bone marrow. During toxicity in the proliferating intestinal cells, measured by 3H-thymidine incorporation, was reduced by about a factor of 4 with encapsulation in APL, particularly 24 hours after Act D administration. The toxiciaty of LPL-encapsulated Act D to both the blood-forming system and the intestinal proliferating cells was, however, not significantly different from that of the nonencapsulated Act D. Effects of Act D on the antibody production by spleen cells, determined by the "limited hemolysis in agar" assay, showed that immunosuppression was most markedly reduced by liposome encapsulation either in APL or in LPL, when the drug was given one day before the antigen. These findings are important for considerations of liposome application in cancer chemotherapy.

Animals↗

The effect of transposition to jejunum on epithelial cell kinetics in an ileal segment.

Epithelial cell kinetics were studied in an ileal segment after transposition to proximal jejunum. The number of cells per villus column in the transposed ileum increased after 4--7 days to reach values normal for jejunum after 14--30 days. This increase was accompanied by a simultaneous increase in the number of cells per crypt column up to 130% of values in jejunum and ileum in situ. The percentage of labelled crypt cells, after labelling with 3H-thymidine, and the relative size of the proliferative cell compartment in the crypt in the transposed ileum did not differ from values in the ileum in situ at any time interval after surgery. The total proliferative activity per crypt, which was determined by scintillation counting of isolated crypts after 3H-thymidine labelling, increased two-fold from 7 days after surgery. Cell migration studies showed that the increase in the number of villus cells was probably not caused by a change in the life span of the epithelial cells. It seems that the increase in the number of villus cells in ileal epithelium after transposition to proximal jejunum is brought about by an enlargement of the crypt, while the relative size of the proliferative cell compartment in the crypt remains unchanged.

Animals↗

Compensation by the residual intestine after intestinal resection in the rat. I. Influence of amount of tissue removed.

Thirty days after resection of 10 to 80% of the midportion of the small intestine, excluding the duodenum, several cell kinetic parameters were investigated in the residual intestine. The degree of intestinal response increased in a stepwise fashion as the amount of tissue removed was increased. The response involved marked increases in: DNA synthesis per crypt expressed as disintegrations per minute of tritium (3H) reflecting (3H)thymidine incorporation, cells per crypt column, 3H-labelled cells per crypt column, cells per villus column, and thickness of all intestinal wall components. These changes occureed throughout the small intestine even at lesser resections. ""Crypt profiles'' reflected changes in cell counts, but when the labeling frequency of proliferative cells was expressed as a percentage of the total crypt height, there was no change. The total number of crypts in the duodenum remained unchanged and the total number of cyrpts in the residual jejunum plus ileum decreased proportionally to the amount of tissue removed. Intestinal compensation occurred by increasing the size of the structures present in the residual intestine, not by increasing the number of structural units.

Adaptation, Physiological↗

Compensation by the residual intestine after intestinal resection in the rat. II. Influence of postoperative time interval.

The sequence of events which comprise the early response of the residual intestine to 70% resection of the combined jejunum and ileum was investigated. Animals were killed at 2,4,6,8, and 12 postoperative days. Marked increases in DNA synthesis expressed as disintegraions per minute per crypt, cells per cyrypt column, labeled cells per crypt column, thickness of intestinal wall components, and cells per villus column were apparent as early as 2 to 4 postoperative days. By 12 days, the values had reached the 30-day postoperative levels found in earlier experiments, indicating that a new steady state had already been reached. Jejunal and ileal crypts responded nearly the same during the first 12 days with their sizes increasing to about 150% of control values. However, although jejunal villus cell counts increased to 125% of controls, the ileal villus cell counts increased to 180% of controls, indicating that the sizes of the two crypt and villus epithelial cell populations are independently controlled.

Adaptation, Physiological↗

The effect of ischemic villus cell damage on crypt cell proliferation in the small intestine: evidence for a feedback control mechanism.

In recent years the hypothesis that the number of villus cells regulates crypt cell proliferation in the epithelium of the small intestine has been brought forward by a number of investigators. To test this hypothesis, the villus cell population was reduced by clamping the superior mesenteric artery and vein in rats for 1 hr and the effects on the intestinal epithelium were studied during the first 24 hr. It was shown that temporary interruption of the blood flow to the small intestine led to a marked decrease in the number of functional villus cells within 2 hr; preferentially, cells from the upper part of the villus were lost and the number of crypt cells was not affected. This reduction in the number of villus cells led to an increase in the percentage of labeled crypt cells after pulse labeling with [3H]thymidine, and an expansion of the proliferative cell compartment in the crypt. After a peak of proliferative activity at 16 hr, the investigated crypt cell kinetic parameters approached control values after 24 hr, as did the number of villus cells. The enzyme activities of nonspecific esterase and neutral alpha-glucosidase showed marked decreases in isolated crypt and villus cell compartments as crypt cell proliferation increased. These data support the view that the feedback control of crypt cell proliferation by the functional villus cells, and confirm earlier data on the influence of changing cell kinetics on crypt cell maturation. Additional data which were obtained after creating temporary ischemia in part of the small intestine support the hypothesis of a feedback control of crypt cell proliferation by the functional villus cells, and confirm earlier data on the influence of changing cell kinetics on crypt cell maturation. Additional data which were obtained after creating temporary ischemia in part of the small intestine support the view that the feedback control of proliferation by the villus cells is a local control mechanism.

Animals↗

Estimating the number of animals: a rapid method for unidentified individuals.

A proposed model yields the density of a mobile population from quick, cursory surveys in which the observer identifies none of the animals. When the spaces on which animals were seen are successively removed, the decline in the counts permits estimation of the average probability of seeing a given animal. The method showed promise in initial trials.

Animal Population Groups↗