Search PubMed⌕ Search

Biomedical subjects

W R Hanson

Publications and source records attributed to W R Hanson.

At least 55 records · Page 3Linked to original sources
PubMed1986

A comparison of radioprotection from three neutron sources and 60Co by WR-2721 and WR-151327.

Two thiophosphoroate radiation protectors (WR-2721 and WR-151327) were assessed for their ability to modify the effects of neutron or gamma irradiation on the gastrointestinal tract. Three neutron sources (DOSAR, JANUS, and FERMILAB) were compared to the response obtained after 60Co irradiation. The end points studied were intestinal stem cell survival and LD50(6). DOSAR and JANUS, both fission-spectrum neutrons, showed somewhat different gut sensitivities [LD50(6)] of about 240 and 400 cGy respectively. The intestinal LD50 obtained with FERMILAB neutrons (25 meV) was closer (875 cGy) to that obtained after 60Co (1068 cGy) irradiation. WR-151327 protected against the lethal effects of fission neutron (DOSAR and JANUS) to a greater degree (DMF = 2.2) than with lower LET sources such as FERMILAB neutrons (DMF = 1.7) or 60Co (DMF = 1.7). The results did not correlate with the intestinal stem cell assays where WR-2721 when compared to WR-151327 showed either similar (DOSAR; fission spectrum neutrons) or somewhat better (60Co and FERMILAB neutrons) protection. Possible explanations for the differing results are discussed.

Amifostine↗
PubMed1985

Quantitative analysis of collagen, protein and DNA in fixed, paraffin-embedded and sectioned tissue.

Modifications and adaptations of chemical techniques have been used to quantitate hydroxyproline (collagen), total protein and DNA in fixed, paraffin-embedded and sectioned tissue. The assays are rapid and sensitive to between 0.1 and 1.0 micrograms of each of the three components. Values for the ratio of collagen to total protein or collagen per DNA obtained from sectioned material are the same as values derived from fresh or fixed starting material. Depending on the tissue and the sample size, as little as three to five 5 micron thick sections can be analysed for these three components. The ratios of collagen per total protein or collagen per DNA are given for several murine tissues. The assay of these components in tissue sections will allow a more precise correlation between histological appearance and the quantitative biochemical changes that may accompany many pathological disorders. The techniques are particularly useful in retrospective studies where the experimental material may be en bloc.

Animals↗
PubMed1985

16,16-Dimethyl prostaglandin E2 induces radioprotection in murine intestinal and hematopoietic stem cells.

Exogenous prostaglandins (PGs) have been shown to protect gastrointestinal mucosa, liver, and pancreas from several injurious agents, including the PG inhibitor, indomethacin. Previous studies from this laboratory showed exogenous administration of 16,16-dimethyl (dm) PGE2 also protected mouse intestinal stem cells from radiation injury. The present study extended that observation and demonstrated that PGs given to B6D2F1 mice 1 hr before irradiation increased the shoulder of the intestinal clonogenic cell survival curve. The D0 increased from 1.10 + 0.09 to 1.58 + 0.10 Gy. PGs increased the LD50/6 from 16.3 + 0.41 (95% confidence limits) in controls to 20.25 + 0.55 Gy. The 16,16-dm PGE2 increased the hematopoietic CFU-S survival in a qualitatively similar way; the extrapolation number (n) was increased from 1.03 (0.89-1.20) to 1.40 (1.27-1.54) and the D0 increased from 0.92 (0.87-0.98) to 1.14 (1.10-1.19) Gy. A large number of human tumors secrete a variety of PGs. Our results suggest that those tumors may be, in part, protected from radiation injury.

16,16-Dimethylprostaglandin E2↗
PubMed1984

The recruitability and cell-cycle state of intestinal stem cells.

Evidence is presented which suggests that the crypts of the small intestine contain at least two discrete but interdependent classes of stem cells, some with discrete cell kinetic properties and some with discrete radiation responses or radiosensitivities. Very low doses of X rays or gamma rays, or neutrons, kill a few cells in the stem cell regions of the crypt in a sensitive dose-dependent manner. Similar doses generate several different cell kinetic responses within either the clonogenic fraction or the cells at the stem cell position within the crypt. The cell kinetic responses range from apparent recruitment of G0 clonogenic cells into cycle, to a marked shortening of the average cell cycle of the cells at the stem cell position. It is suggested that the cell kinetic changes may be the consequence of the cell destruction.

Animals↗
PubMed1984

Correlations of glucose metabolism and structural damage to language function in aphasia.

Studies of aphasic patients using [18F]fluorodeoxyglucose positron computed tomographs have shown areas of metabolic depression in the left hemisphere larger than the area of infarction noted on CT. To evaluate these metabolic differences in relationship to language abnormalities, 11 patients had metabolic scans, CT, and were administered the Boston Diagnostic Aphasia Battery and the Porch Index of Communicative Ability. Correlation analyses were computed between metabolic, CT, and language data. CT demonstrated reliable correlations of speaking, oral reading, and repetition to Wernicke' area, consistent with current anatomic language models, while metabolic data from areas posterior, inferior, and superior to the traditional Wernicke's area and the head of the caudate nucleus also had reliable correlations with aphasic language function. The utilization of both structural and metabolic brain measures may improve our understanding of the anatomy of language as related to aphasia.

Adult↗
PubMed1984

Local cerebral metabolic rates of glucose in movement and language disorders from positron tomography.

Positron-computed tomography with [18F]fluorodeoxyglucose to measure glucose metabolism has shown changes in the brain distant to a focal area of infarction, demonstrating that what appears as a focal abnormality represents a more widespread functional process. Several approaches are presented to better understand quantitative metabolic data and focus on caudate and basal ganglia function. Area-to-area correlations in Parkinson's and Huntington's diseases showed decreases in the number of cortical relationships compared with control subjects, suggesting that the basal ganglia are involved with the ability of cortical regions to function together. In aphasia, caudate metabolism correlated with several language measures that suggested a role in some undefined basic process, seemingly related to Broca's area function. The studies presented suggest that the caudate may involve integrating the processing of language and cognition with the execution of the resulting response. Motor and cognitive function seem related to similar and overlapping brain systems. The disruption of such systems may result in loss of both cognitive and motor aspects of a function.

Aphasia↗
PubMed1984

Relative biological effectiveness measurements using murine lethality and survival of intestinal and hematopoietic stem cells after fermilab neutrons compared to JANUS reactor neutrons and 60Co gamma rays.

The relative biological effectiveness (RBE) of the 25-MeV (average energy) neutron beam at the Fermi National Accelerator Laboratory was measured using murine bone marrow (LD50/30) and gut (LD50/6) lethality and killing of hematopoietic colony forming units (CFU-S) or intestinal clonogenic cells (ICC). The reference radiation was 60Co gamma rays. The LD50/30 and LD50/6 for mice exposed to the Fermilab neutron beam were 6.6 and 8.7 Gy, respectively, intermediate between those of JANUS neutrons and 60Co gamma rays. The D0 values for CFU-S and ICC were 47 cGy and 1.05 Gy, respectively, also intermediate between the lowest values found for JANUS neutrons and the highest values found after 60Co gamma rays. The split-dose survival ratios for CFU-S at intervals of 1-6 hr between doses were essentially 1.0 for both neutron sources, while the corresponding split-dose survival ratio for 60Co gamma rays was consistantly above 1, reaching a maximum of 1.7 with a 1-hr interval between doses. The 3-hr split-dose survival ratios for ICC were 1.0 for JANUS neutrons, 1.85 for Fermilab neutrons, and 6.5 for 60Co gamma rays. The RBE estimates for LD50/30 were 1.5 and 2.3 for Fermilab and JANUS neutrons, respectively. Based on LD50/6, the RBEs were 1.9 (Fermilab) and 3.0 (JANUS). The RBEs for CFU-S D0 were 1.4 (Fermilab) and 1.9 (JANUS) and for jejunal microcolony D0 1.4 (Fermilab) and 2.8 (JANUS).

Animals↗
PubMed1983

The relationship between the compensatory response in the stomach and colon and the extent of small bowel resection in the rat.

The proximal and distal extent of the compensatory response in the gastrointestinal tract of the young adult rat to resection of 10-80 percent of the combined ileum and jejunum was investigated. Thirty days after intestinal resection and subsequent end-to-end anastomosis, rats were injected with tritiated thymidine and sacrificed one hour later. The incorporation of label into colonic crypts or stomach glands was used as an index of the compensatory proliferative response. Although no compensatory response was observed in stomach glands, a significant compensatory proliferative response was found in descending colon after resections involving removal of greater than 60% of the combined ileum and jejunum. These observations imply that the compensatory proliferative response to resection is caused, at least in part, by a humoral mechanism. However, this does not exclude a role for luminal factors, intestinal blood flow, and paracrine effector substances as secondary modifiers of the compensation. The observations that resection of the small bowel can have significant effects distally on cell proliferation in the colon may be important to the planning of combination therapies which involve bowel resection in both animal models and in man.

Adaptation, Physiological↗
PubMed1983

Comparison of metabolic rates, language, and memory in subcortical aphasias.

Four patients with subcortical lesions and either aphasia or amnesia were compared to four patients with cortical lesions and aphasia. Each patient had [18F] fluorodeoxyglucose positron-emission computed tomography, language, and memory evaluations. Marked metabolic depression was found in the thalamus and caudate in all patients. The subcortical patients had only mild left-cortical changes, while the cortical patients showed marked cortical metabolic changes in the left hemisphere. Language changes were mild in the subcortical patients, while moderate to severe in the cortical patients. All patients showed severe verbal memory dysfunction. The only common abnormalities in the two groups were metabolic changes in the thalamus and severity of verbal memory dysfunction. These findings suggest a relationship between verbal memory and thalamic function.

Adult↗
PubMed1983

Cytosar-U (Ara-C) induced changes in mouse jejunal crypt epithelial kinetics and radiosensitivity to gamma rays and fast neutrons.

Pretreatment with the S phase specific cytotoxic agent Cytosine Arabinoside (Ara-C) protects the intestinal stem cells from gamma radiation injury by nearly tenfold. Studies were undertaken to test whether an altered cell age distribution could account for the reported duration and degree of Ara-C induced protection and to measure the degree of protection from the high energy neutrons of the Fermilab Cancer Treatment Facility. Twelve hours after treatment with Ara-C, B6CF1/ANL mice were exposed to increasing single doses of either 137Cs gamma-rays or neutrons from the Fermilab accelerator, or a split dose of neutrons with intervals of 1, 2, and 3 hours. The number of regenerating microcolonies per jejunal circumference in Ara-C treated and irradiated animals was compared to irradiated controls. Another group of mice was given Ara-C but in the 12-hour interval between Ara-C and irradiation, colcemid was given every 3 hours to continuously block and kill cells in mitosis. The results suggest that Ara-C given 12 hours prior to neutron irradiation protects intestinal stem cells to nearly the same degree as it does from 137Cs gamma-ray damage. Furthermore, the control split-dose recovery ratio to neutron irradiation at 1, 2, or 3 hours was 1.8 and was unchanged 12 hours after Ara-C. Colcemid reduced the crypt cell population to less than half the normal 250 cells per crypt; however, the cell survival curve was unaltered from the survival curve 12 hours after Ara-C. These results suggest that Ara-C recruits intestinal clonogenic stem cells, but inhibits their normal passage through DNA synthesis. These cells, responsible for intestinal mucosal regeneration, appear to be held in a radioresistant portion of the cell cycle for a period of about 10-16 hours after Ara-C.

Animals↗
PubMed1983

16, 16-dimethyl prostaglandin E2 increases survival of murine intestinal stem cells when given before photon radiation.

A variety of prostaglandins (PG) protect the gastric and intestinal mucosa when given before damaging agents such as absolute ethanol, acidified taurocholate, boiling water, or nonsteroidal anti-inflammatory agents (NSAI). A synthetic prostaglandin, 16, 16-dimethyl PGE2, shown to be cytoprotective at physiologic levels to the above agents was given to mice 1 hr before or 15 min after 137Cs gamma (gamma) whole-body irradiation. The survival of intestinal stem cells measured by their ability to form in situ colonies of regenerating epithelium was increased when 16, 16-dimethyl PGE2 was given before but not after 137Cs gamma irradiation. The maximum degree of 16, 16-dimethyl PGE2-induced radioprotection was seen when the drug was given 1 hr before irradiation. No radioprotection was seen when the interval between drug and irradiation was 3 hr or longer. When the time between 16, 16-dimethyl PGE2 and irradiation was kept at 1 hr, the degree of radioprotection was dependent on the PG drug dose. There was a steep rise in the number of surviving cells at low doses of PG. These results imply that tumors which secrete PGE2 may in part be protected from the lethal effects of ionizing photon radiation.

16,16-Dimethylprostaglandin E2↗
PubMed1982

Decision speed and bias after unilateral stroke.

Nonverbal visual memory together with speed and bias in response decisions were evaluated in two experiments comparing patients with a left-hemisphere stroke lesion to those with a right-hemisphere stroke lesion. In the first experiment, the decision times of vocal recognition responses from aphasic (left stroke) patients did not correlate with their verbal scores on the Porch Index of Communicative Ability, taken as an estimate of severity of their language impairment. Thus, impairment of verbal processing was not reflected in speed of response. In the second experiment, 19 left and 19 right-stroke patients were compared with 19 volunteers on a recurrent recognition task of complex nonverbal art designs using measures of discriminability and decision bias derived from Theory of Signal Detection. Right stroke patients had lowest recognition scores but adopted normal decision criteria, whereas left stroke patients employed high negative decision bias (i.e., made few false as well as few correct recognitions). Both stroke groups responded significantly slower than controls; the right stroke patients, however, had markedly fewer long-latency decisions than left stroke patients. Compared with controls, only the speed and bias of decision making were deficient in left stroke patients independent of their verbal deficit; their recognition ability was relatively preserved.

Aphasia↗
PubMed1982

Proliferative and morphological adaptation of the intestine to experimental resection.

The proliferative and morphological adaptation of the residual intestine following resection is briefly reviewed. Within days after a partial intestinal resection, the number of crypt cells increases. There is a proportional increase in the number of proliferative cells, thus there is no change in the growth fraction. Villus height and morphological complexity increases, particularly in the ileum. The thickness of the muscularis mucosae increases, most likely through an increase in cellularity. The size of the adaptive response is dependent on the amount of tissue removed. The possibility of an adaptive change in the number and proliferative characteristics of rat intestinal stem cells was investigated using the microcolony assay (38). Regenerative foci of mucosal epithelium were quantitated as a function of 137Cs gamma ray irradiation in control or 30 days after a 60% resection of the combined jejunum and ileum. Hydroxyurea, (HU), an S phase cytotoxic agent was given to one group of control and one group of resected rats five minutes before a single dose of radiation. HU had little effect on control jejunum or ileum, however, HU reduced the clonogenic cell survival by over tenfold in resected animals which implies a post-resection change in the intestinal stem cell age distribution. The radiation dose-survival curve of clonogenic cells was shifted to the right after resection compared to control values. These results suggest that an increase in intestinal stem cell number and a shift in the proliferative characteristics (from slowly to rapidly cycling) occur as an adaptive response to intestinal resection.

Adaptation, Physiological↗
PubMed1981

FDG positron emission computed tomography in a study of aphasia.

Positron emission computed tomography (PECT) using 18F-2-fluoro-2-deoxy-D-glucose (FDG) was used to investigate the correlations between clinical status, anatomy (as described by CT), and metabolism in five patients with stable aphasia resulting from ischemic cerebral infarction. Local cerebral metabolic activity was diminished in an area larger than the area of infarction demonstrated by CT. In one patient, FDG PECT revealed a metabolic lesion that probably caused the aphasic syndrome and was not apparent by CT. The data suggest that reliance on CT in delineating the extent of the brain lesion in aphasia or other neuropsychological defects can be misleading; FDG PECT may provide important additional information. Two patients with similar metabolic lesions had very different clinical syndromes, showing that even when currently available methods are combined, major gaps remain in clinicoanatomical correlations in aphasia.

Aged↗