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Biomedical subjects

S J Hunter

Publications and source records attributed to S J Hunter.

48 records · Page 3Linked to original sources

Gastric mucosal lesions induced by hemorrhagic shock in baboons. Role of oxygen-derived free radicals.

In this study we sought to define the role of oxygen-derived free radicals during ischemia and reperfusion in the production of acute damage to the gastric mucosa of baboons. The protective effect of the xanthine oxidase inhibitor, allopurinol, the superoxide scavenger, superoxide dismutase (SOD), and a long-acting SOD-albumin was determined. Mucosal damage was evaluated using light and scanning electron microscopy. Evidence for oxidative insult to the gastric mucosa was sought by measuring tissue concentrations of reduced (GSH) and oxidized (GSSG) glutathione. Gastric mucosal blood flow was estimated using the microsphere technique. A similar pattern of tissue damage was found at the end of ischemia in all three groups. Thirty minutes after reperfusion, severe mucosal damage (grade 3) increased only in the untreated control. In the two treated groups, grade 3 damage remained unchanged during reperfusion and a decrease in the percentage of moderate damage (grade 2) was seen. Both GSH and GSSG tissue concentrations were lower in the untreated controls as compared to the scavenger-treated groups, making it questionable whether GSH/GSSG tissue levels adequately reflect oxidative stress. We conclude that in our ischemia-reperfusion model the generation of oxygen-derived free radicals produces mucosal damage and prevents the restitution of moderate mucosal damage during reperfusion. In ischemia, factors other than free radicals seem to be responsible for mucosal damage. The protective effect of allopurinol and SOD was not mediated by changes in gastric mucosal blood flow.

Allopurinol↗

Propofol for inpatient dental anaesthesia. A comparison of propofol as sole anaesthetic agent with thiopentone and halothane for inpatient dental anaesthesia.

The induction, maintenance and recovery characteristics of propofol anaesthesia were compared with thiopentone induction and halothane maintenance in 51 spontaneously breathing, intubated patients who underwent dental surgery. Induction with thiopentone produced fewer side effects than propofol, notably pain on injection. Control of the depth of anaesthesia was better in patients who breathed halothane than in those who received intermittent bolus doses of propofol. Recovery characteristics of the two groups were similar.

Adult↗

Prevention of gastric mucosal lesions following aortic cross-clamping.

Stress ulceration is frequently encountered after cardiovascular surgery. In this study of 32 male baboons, severe gastric ischaemia was used to produce gastric stress lesions. The occurrence of these lesions was reduced by allopurinol (P = 0.03) and completely prevented by the combination of allopurinol with superoxide dismutase (P = 0.004). A shorter ischaemic period also reduced the number of lesions (P = 0.02). Concurrent with the stress lesion formation, there was a fall in mucosal glutathione and oxidized glutathione levels (P less than 0.05).

Allopurinol↗

Cross-clamping of the thoracic aorta. Influence of aortic shunts, laminectomy, papaverine, calcium channel blocker, allopurinol, and superoxide dismutase on spinal cord blood flow and paraplegia in baboons.

There is a high incidence of paraplegia associated with thoracic aortic cross-clamping, even when cardiopulmonary bypass or shunts are used. In 56 adult baboons, spinal cord blood flow (SCBF), vascular anatomy, and paraplegia rates were evaluated. Tissue blood flow was measured by radioactive microspheres. Various procedures were used to increase SCBF and to prevent ischemia-reperfusion injury. It was found that the rate of paraplegia was inversely correlated with neural tissue ischemia (SCBF) and directly correlated with reperfusion hyperemia. Two methods completely prevented paraplegia. These two methods were a thoracic shunt with occlusion of the infrarenal aorta or cerebrospinal fluid drainage plus intrathecal papaverine injection, both of which were associated with an increased SCBF. Furthermore, papaverine dilated the anterior spinal artery (ASA) (p = 0.007) and increased the blood flow through the lower ASA. Whereas procedures utilizing a calcium channel blocker (flunarizine), allopurinol, superoxide dismutase (SOD), laminectomy alone, and a thoracoabdominal shunt not perfusing the arteria radicularis magna (ARM) all failed to prevent paraplegia, allopurinol (p = 0.026) and SOD (p = 0.004) did prevent gastric stress lesions, indicating that their failure to prevent paraplegia was not due to a lack of activity. Of great clinical interest is that, if a shunt is used and the ARM is perfused, infrarenal aortic cross-clamping increases SCBF, thus preventing paraplegia. Intrathecal application of papaverine proved to be even more effective in increasing SCBF and also completely prevented paraplegia. As this is a safer procedure than the insertion of shunts, this is the method of choice for the prevention of paraplegia associated with thoracic aortic cross-clamping. The preliminary trial using intrathecal papaverine in human beings has thus far shown no adverse side effects from the drug, and no paraplegia has occurred.

Allopurinol↗

Nucleoside incorporation as a function of hormone levels during the early phases of estrogen-induced genesis of medullary bone in the Japanese quail, Coturnix coturnix.

The sequence of changes in RNA synthesis during the early phases of genesis of medullary bone induced in male Japanese quail by estrogen treatment was studied by 3H-uridine uptake. Analyses of plasma estrogen and testosterone were done by radioimmunoassay at 12, 24, 38 and 61 h. A dose of 5 mg kg-1 estradiol-17 beta was found to stimulate the same 3H-uridine uptake 15 h after hormone treatment as a dose of 20 mg kg-1 of estradiol valerate. The uptake of 3H-uridine rose as the dose of estradiol-17 beta increased. Plasma estrogen levels, which were highest 12 h after injection, declined sharply during the next 12 h, returning to control levels between 38 and 61 h. Testosterone levels declined after estrogen administration and remained below control values at all time points. Following estrogen administration, 3H-uridine uptake declined from control values for the first 8 h. Twelve hours after hormone administration control levels were again reached, with maximum 3H-uridine uptake occurring 16 h after hormone treatment. The 16-h maximum was followed by a steady decline to below control levels at 20, 24 and 28 h, the time at which the experiment was discontinued. Maximum 3H-uridine uptake following estrogen stimulation is similar to that observed for the stimulated immature rat uterus.

Animals↗

In vitro synthesis of proteoglycans associated with medullary bone in Japanese quail.

A short-term incubation system was used to study proteoglycan synthesis during the early stages of medullary bone formation in estrogen-treated male Japanese quail. The proteoglycans were separated by chromatography on a DEAE Bio-Gel A column eluted with a 400-ml 0-1 M NaCl gradient. The profile from uninjected control birds showed a single peak, whereas profiles from estrogen-treated birds showed development of another peak. Incorporation of [35S]sulfate into the estrogen-induced proteoglycan increased most dramatically between 25 and 37 h after hormone treatment. The estrogen-induced proteoglycan has a Kav = 0.65 on Sepharose CL-4B, an average buoyant density of 1.50 g/ml, and contains keratan sulfate as its constituent glycosaminoglycan. The second proteoglycan has a Kav = 0.52 on Sepharose CL-4B, an average buoyant density of greater than or equal to 1.7 g/ml, and has chondroitin sulfate as it major glycosaminoglycan. It may also contain some heparin or heparan sulfate. The results support the usefulness of the incubation system for studying the dynamics of bone matrix production.

Animals↗

Characterization of an established cell line (SH-3) derived from pleural effusion of patient with breast cancer.

Spontaneous emergence of fast-growing cells in prolonged culture of pleural effusion cells obtained from a patient with breast cancer has led to the establishment of a cell line designated as SH-3. By morphological criteria, as revealed by light and electron microscopy, SH-3 cells are epithelial and resumble the poorly differentiated cells of a series of established human tumor cell lines. Their karyotype is hypotetraploid and different from that of HeLa cells. Isoenzyme analysis has shown the presence in the cells of a bone-type alkaline phosphatase and of the fast (A) band of G6PD. The line is free of mycoplasma.

Alkaline Phosphatase↗

Establishment of a cell line (SH-4) from pleural effusion of a patient with melanoma.

A continuous tissue culture line (SH-4) derived from pleural effusion cells of a patient with metastatic melanoma is described. The cells became established after five passages lasting a period of 5 months of slow growth. Doubling time of the continuous culture was 20 hr in passage 51. The cell line is now in passage 60. The cells of all passages examined appear spindle-shaped or oligodendritic as seen by light microscopy. Pigment deposition in the cells is light and incomplete, but more marked than in cells of the original pleural effusion as shown by electron microscopy. Chromosome complement shows a single peak with a modal number of 51.

Cell Division↗