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Biomedical subjects

D M Smith

Publications and source records attributed to D M Smith.

At least 307 records · Page 17Linked to original sources

An alternative method of draining the pelvis after excision of the rectum and anterior resections.

An alternative method of draining the extraperitoneal pelvis using a constant suction and irrigation drain in the retrorectal space was used in 16 patients undergoing excisional or restorative rectal operation for either inflammatory intestine disease or carcinoma. A transient fecal fluid leak from the drain site developed in one patient. The other patients showed no clinical evidence of anastomotic leakage or infective operative complication. We believe that continuous low pressure suction drainage and irrigation of the retrorectal space is important in the healing of excision and restorative operations of the rectum.

Drainage↗

Effects of pressure overload and insulin on protein turnover in the perfused rat heart. Prostaglandins are not involved although their synthesis is stimulated by insulin.

A modified anterogradely perfused rat heart preparation is described in which all the cardiac output passes through the coronary circulation. Such a preparation develops hypertensive aortic pressures. Hypertensive aortic pressures or insulin stimulate the rate of cardiac protein synthesis and inhibit the rate of protein degradation. Aortic pressure and insulin may be important in the regulation of cardiac nitrogen balance in vivo. By abolishing cardiac prostaglandin synthesis with 4-biphenylacetate, we were able to investigate the possible involvement of prostaglandins in the modulation of protein turnover by pressure overload or insulin. There was no evidence of any involvement. However, insulin stimulated and cycloheximide inhibited cardiac prostaglandin synthesis. These findings are consonant with an enzyme involved in prostaglandin synthesis being short-lived and prostaglandin synthesis being rapidly influenced by activators and inhibitors of protein synthesis and degradation.

Animals↗

Silica-induced alveolar cell tumors in rats.

Min-U-Sil5, a form of alpha quartz, has been shown to induce peripheral lung tumors in rats exposed to the dust by inhalation. The animals were exposed to a nominal particle concentration of 12.4 mg/m3 for 8 hr/day, 4 days/week, for 2 years. The induced tumors were large and peripheral, and, when examined by electron microscopy, were found to be composed predominantly of alveolar type II cells. These cells were found in papillary, acinar, and solid forms of the tumors and were characterized by lamellar inclusion bodies. This is in contrast to the mouse, in which the papillary form was associated with Clara cells and the acinar form was linked with the type II cell. In this study, the Clara cell was a minor component of the tumor mass. No clear risk is established in man linking silica exposure to increased lung tumor rates.

Animals↗

Distribution and modulation of the cellular receptor for transforming growth factor-beta.

Scatchard analyses of the binding of transforming growth factor-beta (TGF-beta) to a wide variety of different cell types in culture revealed the universal presence of high affinity (Kd = 1-60 pM) receptors for TGF-beta on every cell type assayed, indicating a wide potential target range for TGF-beta action. There was a strong (r = +0.85) inverse relationship between the receptor affinity and the number of receptors expressed per cell, such that at low TGF-beta concentrations, essentially all cells bound a similar number of TGF-beta molecules per cell. The binding of TGF-beta to various cell types was not altered by many agents that affect the cellular response to TGF-beta, suggesting that modulation of TGF-beta binding to its receptor may not be a primary control mechanism in TGF-beta action. Similarly, in vitro transformation resulted in only relatively small changes in the cellular binding of TGF-beta, and for those cell types that exhibited ligand-induced down-regulation of the receptor, down-regulation was not extensive. Thus the strong conservation of binding observed between cell types is also seen within a given cell type under a variety of conditions, and receptor expression appears to be essentially constitutive. Finally, the biologically inactive form of TGF-beta, which constitutes greater than 98% of autocrine TGF-beta secreted by all of the twelve different cell types assayed, was shown to be unable to bind to the receptor without prior activation in vitro. It is proposed that this may prevent premature interaction of autocrine ligand and receptor in the Golgi apparatus.

Animals↗

Comparison of arachidonic acid metabolism in nasal polyps and eosinophils.

Nasal polyp tissue is characterized by its frequent infiltration by large numbers of eosinophils. We have studied the metabolism of 14C-labeled arachidonic acid by both nasal polyp tissue and by eosinophils. The major metabolite produced by both is 15-hydroxyeicosatetraenoic acid (HETE) with lesser amounts of 12-HETE. No cyclooxygenase pathway products were found. The 15-lipoxygenase activity of nasal polyps averages 30 times that of normal nasal mucosa or chronically inflamed sinus mucosa. Nasal polyps which contained significant numbers of eosinophils averaged 7 times the 15-lipoxygenase activity of nasal polyps without eosinophilia. Thus, eosinophils appear to be a major source of 15-lipoxygenase activity in nasal polyps.

Arachidonic Acid↗

Counseling medical and dental patients about cigarette smoking: the impact of nicotine gum and chart reminders.

To investigate methods for improving and expanding the counseling of smokers by physicians and dentists, we assigned 112 physicians and 50 dentists (in separate studies) to one of the following conditions: the control or advice-only group received a one-hour lecture on the consequences and management of smoking and a booklet detailing a four-step protocol for counseling patients about smoking; three other groups received, in addition, either, protocol reminder stickers placed on their patients' charts; nicotine gum made freely available to their patients; or both chart reminders and nicotine gum. Exit interviews of 1,091 medical and 647 dental patients indicated that the presence of chart reminders and/or the availability of nicotine gum increased the time spent counseling and altered the nature of the smoking cessation counseling provided by both physicians and dentists.

Adolescent↗

Modified extraction 2-thiobarbituric acid method for measuring lipid oxidation in poultry.

A simple and accurate objective test for monitoring lipid oxidation in poultry products is needed. Thiobarbituric acid (TBA) values of cooked poultry meat were determined by a distillation method and by a modified extraction method. Perchloric acid was used in the extraction method to release TBA reactive substances from the meat. The maximum absorption wavelength of the TBA-malonaldehyde complex was 531 nm. The TBA values for cooked chicken and turkey were highly correlated (r = .91) for both the extraction and distillation methods. Sensory scores of warmed-over flavor in precooked poultry were highly correlated with TBA values in both the distillation (r = .83) and extraction (r = .85) methods. Results indicate that the extraction method is faster, easier to perform, and as accurate as the distillation method for monitoring lipid oxidation in poultry.

Animals↗

Stereologic analysis of the in vivo alveolar type II cell response to isoproterenol or saline administration.

Previous studies have demonstrated enhanced secretion of pulmonary surfactant from type II alveolar epithelial cells following beta-adrenergic stimulation. The present study was undertaken in order to provide quantitative morphologic data supporting this effect in vivo. Adult male Sprague-Dawley rats were injected subcutaneously with 150 mg/kg L-isoproterenol, a wide-range beta-adrenergic agonist, and killed at times 0.25-12 hours post-injection. Other rats were similarly injected with saline, and killed at times 0.25-6 hours post-injection. A third group of animals was not injected, nor handled, prior to the time of death, and served as baseline controls. Stereologic analysis of the intracellular organelles of the type II cells in the animals treated with L-isoproterenol revealed a significant decrease in lamellar body volume density, indicating increased secretion of surfactant, at 0.5-4 hours. The rough endoplasmic reticulum volume density increased significantly at 2-6 hours, indicating increased synthetic activity. In contrast, the type II cells of saline-injected animals showed no significant evidence of increased secretion, but did demonstrate a large increase in synthetic activity, resulting in many large lamellar bodies at 2 and 4 hours post-injection. The results of this study provide quantitative morphological evidence of beta-adrenergic stimulation of the secretion and synthesis of pulmonary surfactant secretion by type II cells of the adult rat lung in vivo. In addition, they suggest an enhancement of surfactant synthesis following saline injection, which is perhaps based on endogenous catecholamine release.

Animals↗

Acute renal failure associated with autologous bone marrow transplantation.

A review of 33 consecutive autologous bone marrow transplant (BMT) cases revealed three cases of acute renal failure which developed immediately following reinfusion of cryopreserved bone marrow, and which could not be explained on the basis of hypotension or nephrotoxic drugs. Gross hemoglobinuria was noted in all 33 autologous BMT patients, and may have contributed to the acute renal failure seen in the three patients. Histologic examination of the kidneys of one patient who died 3 days after BMT showed markedly dilated renal tubules filled with hemoglobin casts. The kidneys of the other two patients, who died 8 and 20 days after BMT, showed renal tubular necrosis and regeneration with numerous hemoglobin casts. All three patients had systemic candidiasis at autopsy, and there is evidence to suggest that the infection was also present at the time of BMT. Fungal sepsis may have predisposed these patients to the development of acute renal failure. We recommend the use of procedures that minimize the hemolysate content of cryopreserved bone marrow.

Acute Kidney Injury↗

Preparation of viable single cell suspensions of tracheal epithelial cells.

This paper reports a procedure used for isolating the entire epithelial lining of the rat trachea. Isolated trachea was initially filled with 0.2% hyaluronidase and incubated at 37 degrees C for 30 min. Tracheas were flushed with medium and then reinflated with 0.5 microgram/ml cytochalasin B and re-incubated for 60 min. The tracheal lumens were again flushed and reinstilled with 24 iu/ml pronase and incubated for a further 30 min. The tracheas were flushed again and the cells removed enumerated and viability assessed by trypan blue dye exclusion. Cell yields (X 10(6)) from 30 consecutive Fischer 344 rats were 5.06 +/- 0.16 (s.e.m.) and the mean percentage of viable cells was 83.13 +/- 1.10 (s.e.m.). This cell yield was close to the estimated tracheal cell population (5.3 X 10(6)). The suspensions were predominantly single cells which apparently retained a normal ultrastructural appearance.

Animals↗

Contrasting response of protein degradation to starvation and insulin as measured by release of N tau-methylhistidine or phenylalanine from the perfused rat heart.

An isotope-dilution method is described for the measurement of N tau-methylhistidine release from the perfused rat heart. We argue that release of N tau-methylhistidine is indicative of cardiac actin degradation. N tau-Methylhistidine release is compared with phenylalanine release in the presence of cycloheximide (phenylalanine release being a measure of degradation of mixed proteins). In hearts perfused with glucose plus acetate, the rate of actin degradation was increased by starvation and was not inhibited by insulin. In contrast, the rate of mixed-protein degradation was decreased by starvation and was inhibited by insulin. The fractional rate of degradation of mixed proteins in hearts from fed or starved rats was greater than that for actin. It is suggested that there are at least two pools of intracellular protein, the degradation rates of which differ in terms of their response to insulin and starvation.

Actins↗

The effects of lactate, acetate, glucose, insulin, starvation and alloxan-diabetes on protein synthesis in perfused rat hearts.

Compared with glucose, lactate + acetate stimulated ventricular protein synthesis in anterogradely perfused hearts from fed or 72 h-starved rats. Stimulation was greater on a percentage basis in starved rats. Atrial protein synthesis was not detectably stimulated by lactate + acetate. Insulin stimulated protein synthesis in atria and ventricles. The stimulation of protein synthesis by lactate + acetate and insulin was not additive, the percentage stimulation by insulin being less in the ventricles of lactate + acetate-perfused hearts than in glucose-perfused hearts. Perfusion of hearts from 72 h-starved or alloxan-diabetic rats with glucose + lactate + acetate + insulin did not increase protein-synthesis rates or efficiencies (protein synthesis expressed relative to total RNA) to values for fed rats, implying there is a decrease in translational activity in these hearts. In the perfused heart, inhibition of protein synthesis by starvation and its reversal by re-feeding followed a relatively prolonged time course. Synthesis was still decreasing after 3 days of starvation and did not return to normal until after 2 days of re-feeding.

Acetates↗

A comparison of rates of protein turnover in rat diaphragm in vivo and in vitro.

Protein synthesis and degradation rates in diaphragms from fed or starved rats were compared in vivo and in vitro. For fed rats, synthesis rates in vivo were approximately twice those in vitro, but for starved rats rates were similar. Degradation rates were less in vivo than in vitro in diaphragms from either fed or starved rats.

Animals↗

Phospholipid metabolism in human neutrophil subfractions.

We describe a procedure for isolating human neutrophil subfractions by sucrose density centrifugation following nitrogen cavitation. Using this procedure we were able to isolate and characterize a cytosolic fraction, two separate plasma membrane-enriched fractions, and specific and azurophilic granule fractions. We used this procedure to examine the subcellular localization of the enzymes and substrates involved in the release of arachidonic acid from cellular phospholipids in response to whole cell stimulation. Whole cells were prelabeled for 2 h with [3H]arachidonic acid and [14C] stearic acid. When prelabeled cells were challenged with calcium ionophore A23187 (2 microM) for 5 min at 37 degrees C, each membrane-associated fraction, including both plasma membrane fractions and specific and azurophilic granule fractions, exhibited deacylation of phosphatidylinositol (PI) and phosphatidylcholine (PC). The specific granule fraction exhibited the greatest proportion of deacylation from PI while the more dense plasma membrane fraction was deacylated to a much lower extent than the other fractions. In terms of mass, the azurophilic granules deacylated the greatest amount of radiolabeled arachidonic acid. Although all membrane fractions may be sources of arachidonic acid to some extent, the azurophilic granule fraction may contain the largest pool of radiolabeled arachidonic acid that is released upon cell stimulation.

Arachidonic Acid↗

Effects of heavy metal ions on phospholipid metabolism in human neutrophils: relationship to ionophore-mediated cytotoxicity.

This study examined the effects of 0.1mM heavy metal ions (Au3+, Zn2+, Cr3+, Mn2+, and Cu2+) on ionophore-treated human neutrophils. Treatment of human neutrophils with 5-10 microM ionophore A23187 resulted in phospholipid deacylation and eicosanoid release within 5 min. After approximately 20 min, viability decreased significantly with near total cell death by 50 min. Heavy metal ions altered phospholipid metabolism, eicosanoid synthesis, and cytotoxicity in parallel fashion. Radioimmunoassays for 5-HETE and LTB4 demonstrated that Au3+ and Zn2+ stimulated, Cr3+ had little effect on, and Mn2+ and Cu2+ inhibited eicosanoid release from ionophore-treated neutrophils. Cells prelabelled with [3H]arachidonic acid exhibited similar metal-mediated effects on lipid metabolism. Strong negative correlations between metal effects on viability and the metabolism of arachidonic acid suggest that eicosanoids participate in ionophore-induced cytotoxicity.

Arachidonic Acids↗

Angiosarcoma of the prostate: report of 2 cases and review of the literature.

We report 2 cases of angiosarcoma of the prostate gland. The patients were 42 and 60 years old, which is in sharp contrast to the presentation of rhabdomyosarcoma, which occurs primarily in children. Immunoperoxidase staining for factor VIII associated antigen was positive in both cases, and was particularly useful in confirming the diagnosis in 1 case that was otherwise poorly differentiated. One patient is alive without evidence of recurrence 2 years after surgical excision, while the other presented with unresectable tumor and died 6 months after presentation. Angiosarcoma represents less than 2 per cent of sarcomas of the prostate but it should be considered in the differential diagnosis of poorly differentiated sarcomas, particularly those occurring in adults.

Adult↗