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Biomedical subjects

W R Hanson

Publications and source records attributed to W R Hanson.

At least 37 records · Page 2Linked to original sources
PubMed1989

Hyperfractionation decreases the deleterious effects of conventional radiation fractionation on vertebral growth in animals.

Craniospinal axis irradiation in the treatment of pediatric tumors is associated with serious long-term sequelae including decreased bone growth (short sitting stature). In this study, an animal model was used to determine the effects of smaller incremental doses of radiation on bone growth. Sprague-Dawley weanling rats were given 25 Gy to the spine in 8 to 9 days, with fraction sizes ranging from 1.0 to 1.8 Gy. The animals receiving smaller doses per fraction (1.0 or 1.25 Gy) showed significantly more growth of the vertebral bodies in the treated fields than animals given larger incremental doses (1.5 or 1.8 Gy). These findings indicate a protective effect on bone growth for hyperfractionated irradiation of vertebral bodies.

Abdomen↗
PubMed1989

Cerebral glucose metabolism in Wernicke's, Broca's, and conduction aphasia.

Cerebral glucose metabolism was evaluated in patients with either Wernicke's (N = 7), Broca's (N = 11), or conduction (N = 10) aphasia using 18F-2-fluoro-2-deoxy-D-glucose with positron emission tomography. The three aphasic syndromes differed in the degree of left-to-right frontal metabolic asymmetry, with Broca's aphasia showing severe asymmetry and Wernicke's aphasia mild-to-moderate metabolic asymmetry, while patients with conduction aphasia were metabolically symmetric. On the other hand, the three syndromes showed the same degree of metabolic decline in the left temporal region. The parietal region appeared to separate conduction aphasia from both Broca's and Wernicke's aphasias. Common aphasic features in the three syndromes appear to be due to common changes in the temporal region, while unique features were associated with frontal and parietal metabolic differences.

Aphasia↗
PubMed1989

Tissue responses to low protracted doses of high LET radiations or photons: early and late damage relevant to radio-protective countermeasures.

Early and late murine tissue responses to single or fractionated low doses of heavy charged particles, fission-spectrum neutrons or gamma rays are considered. Damage to the hematopoietic system is emphasized, but results on acute lethality, host response to challenge with transplanted leukemia cells and life-shortening are presented. Low dose rates per fraction were used in some neutron experiments. Split-dose lethality studies (LD 50/30) with fission neutrons indicated greater accumulation of injury during a 9 fraction course (over 17 days) than was the case for gamma-radiation. When total doses of 96 or 247 cGy of neutrons or gamma rays were given as a single dose or in 9 fractions, a significant sparing effect on femur CFU-S depression was observed for both radiation qualities during the first 11 days, but there was not an earlier return to normal with dose fractionation. During the 9 fraction sequence, a significant sparing effect of low dose rate on CFU-S depression was observed in both neutron and gamma-irradiated mice. CFU-S content at the end of the fractionation sequence did not correlate with measured LD 50/30. Sustained depression of femur and spleen CFU-S and a significant thrombocytopenia were observed when a total neutron dose of 240 cGy was given in 72 fractions over 24 weeks at low dose rates. The temporal aspects of CFU-S repopulation were different after a single versus fractionated neutron doses. The sustained reduction in the size of the CFU-S population was accompanied by an increase in the fraction in DNA synthesis. The proliferation characteristics and effects of age were different for radial CFU-S population closely associated with bone, compared with the axial population that can be readily aspirated from the femur. In aged irradiated animals, the CFU-S proliferation/redistribution response to typhoid vaccine showed both an age and radiation effect. After high single doses of neutrons or gamma rays, a significant age- and radiation-related deficiency in host defense mechanisms was detected by a shorter mean survival time following challenge with transplantable leukemia cells. Comparison of dose-response curves for life shortening after irradiation with fission-spectrum neutrons or high energy silicon particles indicated high initial slopes for both radiation qualities at low doses, but for higher doses of silicon, the effect per Gy decreased to a value similar to that for gamma rays. The two component life-shortening curve for silicon particles has implications for the potential efficacy of radioprotectants. Recent studies on protection against early and late effects by aminothiols, prostaglandins, and other compounds are discussed.

Aging↗
PubMed1988

Disconnection and cerebral metabolism. The case of conduction aphasia.

Ten patients with conduction aphasia were studied with computed tomography and 18-F-fluorodeoxyglucose positron emission tomography to examine glucose metabolism. Computed tomographic results identified a postrolandic structural locus for conduction aphasia. All patients demonstrated resting glucose hypometabolism throughout the parietal and temporal regions, and half of the patients also demonstrated reduced metabolic rates in the posterior, inferior, frontal (Broca's) regions. These data suggest that disconnection between posterior and anterior language areas may not be the best anatomical explanation for conduction aphasia.

Adult↗
PubMed1988

Subcortical structures in aphasia. An analysis based on (F-18)-fluorodeoxyglucose, positron emission tomography, and computed tomography.

Subcortical structural damage that includes the anterior and posterior internal capsule, caudate, thalamus, lenticular nuclei, and insula has been shown to cause aphasias. A critical question that has not been resolved is whether the role of these structures on behavior is a direct one or whether it is indirect through the cortex. We have used pathway analysis to evaluate computed tomography, glucose metabolic, and language data from 47 aphasic patients to answer this question. For fluency (from the Western Aphasia Battery), subcortical structural damage had direct and indirect (through frontal lobe) effects on the behavior. For a comprehension task (sequential commands), subcortical damage had no direct effect and only a slight indirect effect through the temporal lobe. Thus, both direct and indirect effects of subcortical damage can be demonstrated for specific behavioral measures.

Adult↗
PubMed1988

Language production in Parkinson's disease: acoustic and linguistic considerations.

The hypokinetic dysarthria of Parkinson's disease (PD) has been described extensively. In contrast, patterns of hesitation and the language structure in spontaneous speech of the PD patient have not been investigated, although several studies have shown language-related abnormalities in word naming, word generation, and verbal recall. In the present study, 10 male Parkinson's patients and 10 normal male speakers were compared in a reading and spontaneous speaking paradigm for acoustic and linguistic features. Among acoustic measures, fundamental frequency and relative intensity differentiated PD from control subjects, consistent with reported features of hypokinetic dysarthria. The striking observations among linguistic measures differentiating PD from control subjects were an increase in the number of (a) silent hesitations per minute, (b) abnormally long silent hesitations, (c) words per silent hesitation, (d) open class phrases, and (e) optional open phrases per speech sample, and a decrease in the number of modalizations and interjections. An increase in the number of filled hesitations occurring per minute, as well as a decrease in syntactic complexity separated moderate from mild Parkinson's patients. Our interpretation of the data favors the hypothesis that changes in the structure of spontaneous language production with increasing severity of dysarthria reflect PD patients' adaptation to their disease.

Dysarthria↗
PubMed1988

Apparent shift in visual field preference after unilateral stroke.

Patients with either a left- or a right-hemisphere stroke lesion scored higher in tasks of word-picture matching and of nonverbal shape matching when information was presented tachistoscopically (120 msec) to the visual field (VF) projecting to their undamaged hemisphere. Left-hemisphere stroke patients (n = 13) were dissociated from right-hemisphere stroke patients (n = 15) by low word recognition from memory and by low right VF but nearly normal left VF accuracy in word-picture matching or shape matching; the former appeared to rely upon processing of word meaning by the right hemisphere. In contrast, right-stroke patients had higher right than left VF scores in both tasks, and their discrimination of nonverbal shapes via the right VF was not different from that of controls (n = 15). Preferred processing by the VF projecting to the undamaged hemisphere appeared as a shift in perceptual asymmetry but may indicate, in support of a "direct access" model, that each hemisphere responds more or less efficiently to word and to nonverbal shape discriminations.

Aged↗
PubMed1988

Radiation protection of the murine intestine by misoprostol, a prostaglandin E1 analogue, given alone or with WR-2721, is stereospecific.

Misoprostol, a prostaglandin (PG) E1 analogue, is one of the most effective radiation protectors of the PGs investigated to date. Misoprostol-induced protection is also additive to protection by the widely studied thiol compound, WR-2721. The mechanism of PG-induced radiation protection and its interaction with WR-2721 is unknown. One important step in the investigation of the mechanism is to determine if PG-induced protection and its interaction with WR-2721 is mediated through PG receptor sites. A direct determination of receptor sites on murine intestinal clonogenic cells could not be made; however an indirect approach was possible. Misoprostol is composed of four stereoisomers of about equal proportions of which only one is gastric antisecretory and cytoprotective. Studies reported here compared radiation protection by this active isomer with that of one of the three inactive isomers. Furthermore, the additional protection of the two isomers when administered with WR-2721 was investigated. Results showed that only the active isomer was protective from radiation injury and this isomer was the only one which afforded additional protection with WR-2721. These data show that PG-induced radiation protection is receptor site dependent and stereospecific.

Alprostadil↗
PubMed1988

Ionizing radiation induces early, sustained increases in collagen biosynthesis: a 48-week study in mouse skin and skin fibroblast cultures.

Groups of 10 CF1 female mice, irradiated to the thorax with a dual-head 137Cs gamma-RAY source, received single doses of 0, 5, 10, 15, or 25 Gy. One to forty-eight weeks later collagen synthesis was measured in minced skin specimens incubated in medium containing [3H]proline and then assayed for radioactive hydroxyproline. A progressive, generally dose-dependent increase in collagen biosynthesis, up to 50% above control sites, was found 1, 4, and 12 weeks after radiation exposure. These changes showed further small fluctuations at 12-36 weeks, increasing again at the 48-week interval. At the same times throughout the study fibroblasts were cultured from skin explants. Following the second subculture, these cells were also incubated in medium containing [3H]proline, and collagen synthesis was again determined by [3H]hydroxyproline assay. At all radiation dose levels studied, collagen production increased threefold by 12 weeks postradiation and remained elevated for the 48-week duration of the study. In vitro radiation dose response differences were not observed.

Animals↗
PubMed1987

Comparison of in vivo murine intestinal radiation protection by E-prostaglandins.

The gastrointestinal cell renewal system is sensitive to injury by ionizing radiation. Natural prostaglandins (PGs) and their analogs have been shown to protect intestinal clonogenic cells (stem cells) in vivo from radiation injury. To further investigate structure and activity relationship in PGs as radiation protectors, studies were done with four E-series PGs: E1, E2, 16,16-dimethyl (dm) PGE2, and 15-deoxy, 16-methyl, 16-hydroxy PGE1 (misoprostol). No protection was seen with PGE1 at doses ranging from 1-100 ug/mouse given from 15 min to 3 hrs before 15.0 Gy137Cs. In contrast, the other three E-series PGs increased intestinal clonogenic cell survival when given 15 min before irradiation. The optimum pre-irradiation time of PG administration was 1 hr for PGE2 and 16,16-dm PGE2 and 2 hrs for misoprostol. The degree of maximum radiation protection was markedly different among the four PGs. PGE2 increased survival to 200% of control values and 16,16-dm PGE2 increased survival to about 400% of controls. The greatest radioprotection was seen with misoprostol, which increased survival to 600% of control. These results suggest that molecular alterations in the side chains of PGs change the efficiency of PG-induced radiation protection. The highest protection to date has been observed with misoprostol. This important finding warrants clinical investigation in patients subjected to radiotherapy.

Animals↗
PubMed1987

Radiation-induced DNA single-strand breaks in the intestinal mucosal cells of mice treated with the radioprotectors WR-2721 or 16-16 dimethyl prostaglandin E2.

Both S-2-(3-aminopropylamino) ethylphosphorothioic acid (WR-2721) and 16-16 dimethyl prostaglandin E2 (dm PGE2) protected the intestinal clonogenic cells to some degree from the effects of 137Cs gamma-irradiation. The D0 was increased from 1.1 +/- 0.12 Gy in controls to 1.55 +/- 0.48 Gy in 16-16 dm PGE2 treated and 2.12 +/- 0.20 Gy in WR-2721 treated mice. Both agents also increased the shoulder of the clonogenic-cell survival curve. Studies were done to measure the effects of these two different radioprotectors on radiation-induction of DNA single-strand breaks in cells comprising the murine intestinal mucosa. The number of DNA single-strand breaks increased with increasing doses of gamma-rays in animals killed immediately following exposure. WR-2721 reduced the number of initial radiation-induced DNA single-strand breaks when given one-half hour before exposure; the time of maximum protection. In contrast, 16-16 dm PGE2 given 1 hour before irradiation (the time required to afford maximum protection from radiation cytotoxicity) did not reduce the number of initial DNA breaks. Both agents impeded the rate of rejoining of DNA breaks with increasing time after irradiation. However, the relationship between these effects on the rate of strand rejoining and cell survival is unknown. These results suggest that either both agents are similarly distributed within the cells but the mechanisms of radioprotection are different, or the mechanisms by which these agents protect are similar, but the two agents affect different subcellular targets, the protection of which contributes to increased cell survival.

Amifostine↗
PubMed1987

Cerebellar glucose metabolism in chronic aphasia.

(18F)-Fluorodeoxyglucose PET was used to compare left/right cerebellar hemispheric glucose metabolism in 37 aphasic patients with left hemisphere lesions and 22 age-matched controls. Sixteen aphasic subjects showed cerebellar symmetry. Twenty-one aphasic subjects were found to have cerebellar metabolic asymmetry, which (1) resulted from an absolute reduction in local cerebral metabolic rates of glucose in the right cerebellar hemisphere; (2) was associated with left less than right glucose metabolic asymmetry in the frontal, parietal, caudate, and thalamic regions; (3) was associated with Broca's region and deep hemisphere structural damage to the internal capsule and basal ganglia; (4) related to reduced functional motor performance, spontaneous speech, naming, reading, and writing; and (5) included all Broca's aphasia subjects.

Aphasia↗
PubMed1987

Radiation protection of murine intestine by WR-2721, 16,16-dimethyl prostaglandin E2, and the combination of both agents.

The survival of murine intestinal clonogenic cells (ICC) and the survival of mice after whole-body exposure to 137Cs irradiation were used to measure radiation protection by ethiophos (WR-2721), 16,16-dimethyl prostaglandin E2, and the combination of the two. Doses from 2 to 12.5 mg/mouse of WR-2721 increased cell survival linearly from 3.2 +/- 0.3 in controls given 15.0 Gy to 93.1 +/- 5.2 per jejunal circumference. In contrast, 16,16-dm PGE2 increased ICC survival at 15.0 Gy rapidly from 1 to 10 micrograms/mouse, followed by a plateau up to 100 micrograms/mouse. Animal survival at 6 days (LD50/6) increased from 16.3 +/- 0.4 Gy (95% confidence limits) in controls to 20.3 +/- 0.6 Gy in the PG-treated animals. WR-2721 increased the LD50/6 to 26.1 +/- 1.4 Gy. The dose modification factors were 1.25 and 1.60, respectively. The combination of agents increased ICC survival above that seen with each agent alone up to 8 mg WR-2721, above which no additional protection was seen. Animals given 10 micrograms PG plus 10 mg WR-2721 survived longer than with either agent given alone. The LD50/6 was 36.3 +/- 1.8 Gy for a dose modification factor (DMF) of 2.23. In addition, the slope of the probit curve was reduced from those of each agent alone. PG-induced changes in villus epithelial cell morphology and survival may account, in part, for these observations. The results suggest that either the mechanisms for these two types of radiation protectors are different or they act on separate subcellular targets which are critical to survival from radiation injury.

16,16-Dimethylprostaglandin E2↗
PubMed1987

Comparison of intestine and bone marrow radiosensitivity of the BALB/c and the C57BL/6 mouse strains and their B6CF1 offspring.

The radiosensitivity as measured by LD50/6 or LD50/30 of the F1 hybrid B6CF1 (C57BL/6 X BALB/c) is similar to that of C57BL/6 mice but markedly different from BALB/c. The LD50/6 for BALB/c mice was about 8.8 Gy compared to 16.4 Gy for the B6CF1. The difference in LD50/6 between the parent strains or between BALB/c and the F1 hybrid could not be explained by any differences in crypt cell number, cell cycle time, or transit time. Likewise, the observed differences in the LD50/6 do not appear to result from marked differences in the radiosensitivity of marrow stem cells (CFU-S) since the D0's for the three genotypes of mice were similar. Also, there were no apparent differences in the red blood cell contents of several enzymes associated with antioxidant defenses. The microcolony assay was used to determine the D0 for the crypt clonogenic cells and the D0 values for 60Co gamma rays were about 0.8 Gy for BALB/c mice and 1.4 Gy for B6CF1 mice. However, the D0 values for JANUS fission neutrons were similar; 0.6 Gy for the BALB/c mice and 0.5 for the B6CF1 mice. A comparison of clonogenic cell kinetics, using prolonged colcemid block to distinguish between slowly and rapidly cycling cells suggest that, normally, the stem cells are slowly cycling in both the BALB/c and the B6CF1 hybrid. However, the stem cells of the B6CF1 appear to go into rapid cell cycle more rapidly than those of the BALB/c following irradiation or prolonged colcemid treatment. The more rapid recovery in intestinal epihelial cell production in the B6CF1 hybrid after irradiation may provide an increased mucosal barrier and may, in part, explain the difference in the response to radiation compared to that in the BALB/c.

Animals↗
PubMed1986

Clinical and acoustical variability in hypokinetic dysarthria.

Ten male patients with parkinsonism secondary to Parkinson's disease or progressive supranuclear palsy had clinical neurological, speech, and acoustical speech evaluations. In addition, seven of the patients were evaluated by x-ray computed tomography (CT) and (F-18)-fluorodeoxyglucose (FDG) positron emission tomography (PET). Extensive variability of speech features, both clinical and acoustical, were found and seemed to be independent of the severity of any parkinsonian sign, CT, or FDG PET. In addition, little relationship existed between the variability across each measured speech feature. What appeared to be important for the appearance of abnormal acoustic measures was the degree of overall severity of the dysarthria. These observations suggest that a better understanding of hypokinetic dysarthria may result from more extensive examination of the variability between patients. Emphasizing a specific feature such as rapid speaking rate in characterizing hypokinetic dysarthria focuses on a single and inconstant finding in a complex speech pattern.

Aged↗
PubMed1986

Left hemisphere intracerebral hemorrhages studied by ( (F-18)-fluorodeoxyglucose PET.

We used PET to study patients with intracerebral hemorrhages in the left hemisphere. Three anatomic and physiologic patterns were observed. Patients 1 and 2 had midputamen hemorrhages with diffuse left less than right hemispheric metabolic asymmetry most prominent in temporal and parietal regions. Patients 3 and 4 had posterior putamen-insula-temporal hemorrhages with left less than right metabolic asymmetry in temporoparietal cortex and thalamus. Patients 5, 6, and 7 had smaller posterior hemorrhages. Left cortical metabolism was little affected in these three cases. Persistent aphasia was associated with severe metabolic left less than right asymmetry in posterior middle temporal regions.

Adult↗