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C J Hardy

Publications and source records attributed to C J Hardy.

68 records · Page 4Linked to original sources
PubMed1983

Adiabatic compressibility of globular proteins.

The adiabatic compressibility of several globular proteins has been measured by using an ultrasonic technique in the frequency range 0.5 to 10 MHz. The contributions to the measured compressibility from the protein matrix and from surface processes involving ionization of side chains and solvation effects are discussed. The internal protein compressibility is very low, indicating the existence of "dynamic domains" which are tentatively assigned to secondary structure elements.

Animals↗
PubMed1983

Manage or be managed.

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Health Facility Administrators↗
PubMed1975

Methacholine: a 7-day inhalation toxicity study with primates.

The acute and sub-acute inhalation toxicity of methacholine to cynomolgus monkeys was assessed by exposure of animals to an aerosol of a 2% solution of the material in sterile saline. The acute response was characterized by a decrease in tidal volume, increase in respiratory rate, a fall in dynamic compliance and an increased pulmonary resistance. Onset of the acute response was rapid, reached a peak after 2-3 min of exposure and recovery appeared to be complete after 30 min following termination of an exposure. The sub-acute inhalation toxicity of methacholine was assessed by single daily aerosol exposure of primates to graded doses of the compound for 7 days. Pre- and post-exposure measurements of haematology and blood biochemistry, urinalysis, blood gas analysis and ECG showed no changes which could be attributed to exposure to methacholine. Nor were treatment-related histopathological changes observed in exposed animals. Distinct changes were seen in the mechanical characteristics of the lungs of exposed animals. Pulmonary resistances, measured on the day following final exposure, were increased in all animals exposed to the methacholine aerosol. During 9 weeks following the last of the daily exposures, increased pulmonary resistance values persisted in the animals retained for this period, although there was some indication of a gradual return to pre-exposure resistance values.

Aerosols↗
PubMedDate not supplied

Inhalation toxicity and genotoxicity of hydrochlorofluorocarbon (HCFC)-225ca and HCFC-225cb.

The acute, subchronic and genetic toxicity of the hydrochlorofluorocarbons HCFC-225ca and HCFC-225cb were evaluated to assist in establishing proper handling guides. In acute inhalation studies, rats were exposed for 4 h to various concentrations of each isomer. Based on the mortality incidence, the LC50 value for HCFC-225cb for males and females (combined) was 36800 ppm. For HCFC-225ca, the LC50 for males and females (combined) was 37300 ppm. Narcotic-like effects, e.g. prostration, incoordination and reduced motor activity, were observed during exposure to either isomer, but these signs were not evident 15 min after termination of exposure. Histopathological examination of the liver revealed an increase in mitotic figures with vacuolation of hepatocytes and fluid-filled, congested hepatic sinusoids. In cardiac sensitization studies, HCFC-225cb induced a cardiac sensitization response at 20000 ppm, with one fatal response, whereas a blend of the two isomers (45% HCFC-225ca/55% HCFC-225cb) produced a cardiac sensitization response at 15000 ppm. In 4-week subchronic inhalation studies, male and female rats were whole-body exposed to HCFC-225cb at concentrations of 0, 1000, 5000 or 15000 ppm for 6 h a day, 5 days per week. Similarly, male and female rats were whole-body exposed to HCFC-225ca concentrations of 0, 50, 500 or 5000 ppm for 6 h a day, 5 days per week. During exposure, narcotic-like and irritant effects were observed. A dose-related decrease in cholesterol and triglycerides was observed in the treated rats, with males being affected more than females. Increases in liver weight were observed in most male and female rats exposed to either isomer. The increase in liver weight was consistent in male rats with microscopic evidence of hepatocyte hypertrophy. Although liver weight was increased in female rats, no hepatocyte enlargement was observed in treated female rats. Increases in cytochrome P-450 and beta-oxidation activities were also observed in male and female rats exposed to either isomer. Neither of the HCFC-225 isomers was mutagenic in the Ames reverse mutation assay, or clastogenic in the chromosomal aberration assay with Chinese hamster lung cells. Also, neither isomer induced unscheduled DNA synthesis in liver cells. However, both isomers were clastogenic in the chromosomal aberration assay with human lymphocytes in the absence of S-9. No increases in aberrant cells were observed in activated cells exposed to either isomer.

Administration, Inhalation↗
PubMedDate not supplied

Chronic toxicity/oncogenicity study of styrene in CD-1 mice by inhalation exposure for 104 weeks.

Groups of 70 male and 70 female Charles River CD-1 mice were exposed whole body to styrene vapor at 0, 20, 40, 80 or 160 ppm 6 h per day 5 days per week for 98 weeks (females) or 104 weeks (males). The mice were observed daily; body weights, food and water consumption were measured periodically, a battery of hematological and clinical pathology examinations were conducted at weeks 13, 26, 52, 78 and 98 (females)/104 (males). Ten mice of each gender per group were pre-selected for necropsy after 52 and 78 weeks of exposure and the survivors of the remaining 50 of each gender per group were necropsied after 98 or 104 weeks. An extensive set of organs from the control and high-exposure mice were examined histopathologically, whereas target organs, gross lesions and all masses were examined in all other groups. Styrene had no effect on survival in males. Two high-dose females died (acute liver toxicity) during the first 2 weeks; the remaining exposed females had a slightly higher survival than control mice. Levels of styrene and styrene oxide (SO) in the blood at the end of a 6 h exposure during week 74 were proportional to exposure concentration, except that at 20 ppm the SO level was below the limit of detection. There were no changes of toxicological significance in hematology, clinical chemistry, urinalysis or organ weights. Mice exposed to 80 or 160 ppm gained slightly less weight than the controls. Styrene-related non-neoplastic histopathological changes were found only in the nasal passages and lungs. In the nasal passages of males and females at all exposure concentrations, the changes included respiratory metaplasia of the olfactory epithelium with changes in the underlying Bowman's gland; the severity increased with styrene concentration and duration of exposure. Loss of olfactory nerve fibers was seen in mice exposed to 40, 80 or 160 ppm. In the lungs, there was decreased eosinophilia of Clara cells in the terminal bronchioles and bronchiolar epithelial hyperplasia extending into alveolar ducts. Increased tumor incidence occurred only in the lung. The incidence of bronchioloalveolar adenomas was significantly increased in males exposed to 40, 80 or 160 ppm and in females exposed to 20, 40 and 160 ppm. The increase was seen only after 24 months. In females exposed to 160 ppm, the incidence of bronchiolo-alveolar carcinomas after 24 months was significantly greater than in the controls. No difference in lung tumors between control and styrene-exposed mice was seen in the intensity or degree of immunostaining, the location of tumors relative to bronchioles or histological type (papillary, solid or mixed). It appears that styrene induces an increase in the number of lung tumors seen spontaneously in CD-1 mice.

Administration, Inhalation↗
PubMedDate not supplied

Accuracy of arterial pulse-wave velocity measurement using MR.

The performance of a one-dimensional MR technique for the estimation of pulse-wave velocity in the aorta was evaluated. An expression for the error in this estimate was formulated and verified both by simulation and by experiment. On the basis of this formulation, guidelines for increasing the efficiency of the acquisition were established. The technique was further validated by comparison with pulse-wave velocity measurements made with a pressure catheter. All data were acquired from a latex tube driven by a pulsatile flow system. MR measurements of pulse-wave velocity in the tube were found to be very reproducible in the presence of white noise. Measurements by other techniques were in good agreement, falling within 2 SD of the mean. Because of its sensitivity and spatial resolution, this technique shows promise for making spatially resolved estimates of vessel distensibility. This would allow assessment of diseases, such as atherosclerosis, that cause local changes in the material properties of the vasculature.

Aorta↗
PubMedDate not supplied

Effects in the rat of inhaling PVC dust at the nuisance dust level (10 mg/m3).

Rats inhaled a paste polymer polyvinyl chloride dust at an aerosol concentration of 10 mg/m3 for 6 hr/day, 5 days/wk for a 15-wk period. A small number of randomly scattered lung lesions were detected at 15 wk; these lesions were also present 15 wk after exposure to polyvinyl chloride had ceased. Few if any biochemical changes were detected at the alveolar surface in lung tissues or other organs of polyvinyl chloride-exposed rats. It is therefore concluded that at "nuisance" dust level this form of polyvinyl chloride polymer exhibits a weak biological reactivity.

Aerosols↗
PubMedDate not supplied

Rapid NMR cardiography with a half-echo M-mode method.

A real-time NMR cardiac profiling pulse sequence has been developed that incorporates two-dimensional (2D) selective excitation and a half-echo readout. The time resolution has been improved by a factor of two relative to the previous flow-compensated, full-echo version. The technique produces a 2D plot of "beam"-axis position versus time, analogous to M-mode echocardiography. In human subjects, details of valve leaflet motion, intracardiac flow, wall motion, and wall thickening may be observed along optimal lines of sight selected interactively. The pulse sequence uses a low-tip-angle 2D selective-excitation pulse derived from a spiral k-space trajectory to excite a narrow cylinder of magnetization, followed by a half-echo readout gradient oriented along the axis of the cylinder. One-dimensional Fourier transformation of the acquired signal results in a magnetization profile along the length of the cylinder, or beam. The pulse sequence is effectively flow compensated without any additional gradient lobes, because the rapid oscillation in the gradient wave forms of the 2D excitation pulse produces relatively small net gradient moments, and the shortened readout gradient has minimal first-order moment relative to center echo. The signal from moving blood can alternatively be velocity encoded by the addition of bipolar gradients along any of the three axes, producing Doppler-like traces of intracardiac blood flow.

Echocardiography↗
PubMedDate not supplied

One-dimensional NMR thermal mapping of focused ultrasound surgery.

OBJECTIVE: The aim of this study was to evaluate a technique for real-time monitoring of tissue temperature and tracking of the heat source during minimally invasive thermal interventions such as focused ultrasound surgery. MATERIALS AND METHODS: A temperature-sensitive NMR line scan pulse sequence was directed interactively from a workstation during the application of focused ultrasound to samples of excised bovine skeletal muscle. The NMR signal along a sensitive line was monitored during and after heating by means of a scrolling display on the workstation. RESULTS: The temperature sensitivity was found to be approximately 2 degrees C with a time resolution of 300 ms along a line intersecting the ultrasonic focal point. Experimental temperature rises determined from the NMR signal showed close agreement with theoretical temperature behavior derived from the heat equation. Temperature quantitation capabilities were lost upon onset of thermal denaturation and coagulation. CONCLUSION: This technique could serve as a noninvasive guide in tracking the heat source and in monitoring thermal dose during focused ultrasound surgery and other minimally invasive thermal interventions.

Animals↗
PubMedDate not supplied

A review of 1H nuclear magnetic resonance relaxation in pathology: are T1 and T2 diagnostic?

The longitudinal (T1) and transverse (T2) proton (1H) nuclear magnetic resonance (NMR) relaxation times of pathological human and animal tissues in the frequency range 1-100 MHz are archived, reviewed, and analyzed as a function of tissue of origin, NMR frequency, temperature, species, and in vivo versus in vitro status. T1 data from specific disease states of the bone, brain, breast, kidney, liver, muscle, pancreas, and spleen can be characterized by simple dispersions of the form T1 = AvB in the range 1-100 MHz with A and B empirically determined pathology-dependent constants. Pathological tissue T2 values are essentially independent of NMR frequency. Raw relaxation data, best-fit T1 parameters A and B, and the mean T2 values, are tabulated along with standard deviations and sample size to establish the normal range of pathological tissue relaxation times applicable to NMR imaging or in vitro NMR examination. Statistical analysis of relaxation data, assumed independent, reveals that most tumor and edematous tissue T1 values and some breast, liver, and muscle tumor T2 values are significantly elevated (p greater than or equal to 0.95) relative to normal, but do not differ significantly from other tumors and pathologies. Statistically significant abnormalities in the T1 values of some brain, breast, and lung tumors, and most pathological tissue T2 values could not, however, be demonstrated in the presence of large statistical errors. Both T1 and T2 in uninvolved tissue from tumor-bearing animals or organs do not demonstrate statistically significant differences from normal when considered as a group, suggesting no appreciable systemic effects associated with the presence of tumors compared to the statistical uncertainty. Statistical prediction analysis for both T1 and T2 indicates that of all the tissues studied, only liver hepatoma can be reliably distinguished from normal liver based on a single T1 measurement (p greater than or equal to 0.95) given the scatter in the current published data. Indeed, data scatter, not easily attributable to temperature, species, in vivo versus in vitro status, the inclusion of implanted or chemical induced tumors, or the possible existence of multiple component relaxation, is recognized as the major factor inhibiting the diagnostic utility of quantitative NMR relaxation measurements. Malignancy indexes that combine T1 and T2 data as a diagnostic indicator suffer similar problems of uncertainty. The literature review reveals a dearth of information on the temperature and frequency dependence of pathological tissue relaxation and the possible existence of multiple relaxation components.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗