The role of transferrin in the in vivo uptake of gallium-67 in a canine tumor.
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Biomedical subjects
Publications and source records attributed to H Wong.
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1 The responses of the guinea-pig taenia coli, urinary bladder, and the rabbit portal vein to ultraviolet (u.v.) light were compared to those elicited by purinergic nerve stimulation and exogenous adenosine triphosphate (ATP).2 In the presence of sodium nitrite, u.v. light between 340-380 nm produced a maximum relaxation of the taenia coli. The relaxation was reversible and fast in onset. It was unaffected by atropine, guanethidine or low concentrations of phentolamine or propranolol. When the tone was low, the relaxation was usually followed by a ;rebound contraction' upon cessation of stimulation. Thus, the response to u.v. light closely resembles the responses to both purinergic nerve stimulation and exogenously applied ATP.3 U.v. light did not initiate impulses in purinergic nerves since its action was unaffected by tetrodotoxin; nor did it release ATP from nerve terminals (in contrast to its release during purinergic nerve stimulation). The adenosine-uptake inhibitor, dipyridamole, which potentiates the responses to purinergic nerve stimulation and ATP, did not affect the response to u.v. light.4 Agents known to alter postjunctional responses to purinergic nerve stimulation and ATP also altered the response to u.v. light. High concentrations of the 2-substituted imidazoline compounds, antazoline and phentolamine, which antagonize the responses to purinergic nerve stimulation and ATP, reduced the responses to u.v. irradiation. The prostaglandin synthesis inhibitor, indomethacin, which abolishes the ;rebound contraction' following stimulation of purinergic nerves, also blocks the ;rebound ;contraction' following u.v. irradiation. Increases in the K(+) concentration produced parallel changes in the inhibitory responses to u.v. light and purinergic nerve stimulation.5 U.v. light produced relaxation and inhibition of spontaneous activity of the rabbit portal vein (relaxed by ATP), but had no effect on the guinea-pig urinary bladder (contracted by ATP) and ureter (unaffected by ATP).6 It is suggested that u.v. light is acting on some part of the purinergic receptor complex which is involved in the mediation of inhibitory responses to ATP and purinergic nerve stimulation, and may therefore provide a way of investigating the chemistry of inhibitory purinergic receptors.
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Cellular aging is accompanied by a reduction in proliferative activity and changes in gene expression. To further elucidate the mRNA phenotype of aging fibroblasts we have monitored the expression of an array of genes implicated in regulating cell-cycle progression. Fourteen genes, including 3 cyclin-dependent kinase (CDK) inhibitors (p16INK4, p21SDI/CIP/WAF and p27KIP), 5 cyclins, 4 CDKs, Cdi-1, and PCNA were tested in four primary fibroblast strains. Relative mRNA expression levels were assessed using a rapid and sensitive Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) assay called the "Primer-dropping" method. p16INK4, a specific inhibitor of the cyclin D-associated kinases CDK4 and CDK6, was, in addition to p21 and cyclin D1, overexpressed in higher passage cells, while the abundance of the D-type kinase mRNAs remained relatively constant. Levels of cyclin H, a component of the CDK-activating kinase (CAK) were markedly reduced in all strains examined, suggesting that the activity of target cyclin/CDK complexes may not be activated in aging cells. These results corroborate and extend previous observations demonstrating elevated expression of specific cell cycle genes in higher passage cells and suggest that overexpression of the CDK-inhibitors p16INK4 and p21SDI/CIP/WAF, but not p27KIP, may contribute to lower proliferative activity of senescing primary fibroblasts.
The Bayesian evidence framework has become a standard of good practice for neural network estimation of class conditional probabilities. In this approach the conditional probability is marginalised over the distribution of network weights, which is usually approximated by an analytical expression that moderates the network output towards the midrange. In this paper, it is shown that the network calibration is considerably improved by marginalising to the prior distribution. Moreover, marginalisation to the midrange can seriously bias the estimates of the conditional probabilities calculated from the evidence framework. This is especially the case in the modelling of censored data.
The involvement of somatostatin in urethane-anesthesia-evoked suppression of gastric acid secretion has been described. The present study has examined the role of endogenous somatostatin in diminished pancreatic enzyme secretion during anesthesia, while monitoring acid secretion concurrently. Rats were anesthetized with either urethane or sodium pentobarbital. An indwelling catheter was placed into the right jugular vein. The esophagus and the pylorus were ligated, and the stomach was perfused with saline. The common bile duct was ligated at the hepatic hilum, and cannulated at the duodenal end of the duct for collecting pure pancreatic juice. Purified somatostatin monoclonal antibody (CURE.S6) or control antibody (keyhole limpet hemacyanin, KLH) was injected iv in increasing doses (0.05; 0.15; 0.5; and 1.5 mg) every 30 min (n = 6). Gastric acid and pancreatic amylase secretions were measured. The effect of the antibodies on CCK-8-stimulated (0.25-2.50 nmol/kg/h) pancreatic amylase secretion was also tested. During urethane anesthesia somatostatin antibody induced a dose-dependent increase in acid output, while control antibody did not change it. Basal pancreatic amylase secretion was not affected by either somatostatin or by control antibody. Pancreatic secretory responses to high but not to low doses CCK-8 were found to be significantly increased following immunoneutralization of somatostatin. In sodium pentobarbital-anesthetized rats somatostatin antibody stimulated basal acid secretion but did not affect basal pancreatic amylase secretion. Our data indicate that in anesthetized rats endogenous somatostatin mediates suppression of basal gastric acid secretion but not that of basal pancreatic amylase secretion, and this action does not depend on the type of anesthesia. Furthermore, endogenous somatostatin may play a physiological role in modulating stimulated pancreatic enzyme secretion in this species.
4-Pentenoate (4P) is a short-chain fatty acid which causes a complete renal Fanconi syndrome. We have examined the mechanism of 4P toxicity along the nephron after a prolonged (30 min) exposition of isolated renal tubular segments to this agent. In proximal tubules, 4P inhibited the activity of alpha-ketoglutarate dehydrogenase, pyruvate dehydrogenase, and beta-oxidation, but not in thick ascending limb or inner medullary collecting duct tubules in suspension. These proximal effects were accompanied by a marked oxidation of the proximal redox state, with a fall in the tissue respiration and a low content of ATP. The acetyl-CoA content of proximal tubules was simultaneously reduced. Butyrate, acetate, hexanoate or octanoate did not exert these effects. In proximal tubules the metabolism of 4P led to the tissue accumulation of 3-keto-4-pentenoyl-CoA, a known unspecific inhibitor of metabolic oxidation. This metabolite was not detectable in thick ascending limbs which metabolized 4P rapidly. No metabolism of 4P was noted in collecting ducts. We conclude that beta-oxidation probably differs in proximal and thick ascending limb tubules, allowing 4P metabolism to exert a specific toxicity in proximal tubules. A selective proximal defect in energy metabolism probably explains the Fanconi syndrome observed with exposition to 4P.
The prevalence of degenerated cells in the thickened intima of cholesterol-fed animals suggested that necrotic regions might become a focus for lesion development by attracting histiocytes or monocytes. We propose that cholesterol-rich necrotic products scavenged by macrophages incite the accumulation of cholesteryl ester and the formation of cholesteryl ester droplets. The feasibility of this hypothesis was tested with readily available materials, namely, lung macrophages and plasma membrane vesicles (PMV) released from dying cholesterol-rich and normal hepatocytes. PMV from cholesterol-rich hepatocytes contained 30-fold more cholesteryl ester than PMV from normal hepatocytes. Degradation of 125I-PMV to trichloroacetic acid-soluble products by macrophages was fourfold higher than that of 125I-acetylated low density lipoprotein (acetyl-LDL) at 100 micrograms/ml of ligand in the incubation medium. Within this concentration range, degradation of PMV increased almost linearly with increasing concentrations of PMV, while the degradation of acetyl-LDL followed a saturation curve. Cholesterol-rich PMV increased the cholesteryl ester content of macrophages fourfold and augmented the incorporation of oleate threefold relative to normal PMV. These studies were extended to aortic smooth muscle cells. As with hepatocyte-PMV, smooth muscle cell-PMV was internalized and degraded by macrophages. The results suggested that cholesterol-rich necrotic materials could play a significant role in atherogenesis.
Health care professionals assume that tube feeding is an unpleasant, distressing experience for patients, which is only partially substantiated by experience. Thirty patients were interviewed via a tube feeding and hospital experience checklist (a 47-item interview schedule). Common experiences were operationally defined as those felt by at least 50%; subjectively distressful experiences were those identified by patients as causing distress. The most common and most distressful experiences of nasogastric tube feeding were: sensory irritations and sensory deprivation. The psychosensory irritation experiences were: thirst, sore nose or throat, dry mouth, runny nose, a tube in the nose, taking food through a tube, breathing through the mouth, breathing with a tube in the nose, taking food in a treatment type container, and taking food with a different texture and smell than usual. The psychosensory deprivation experiences were: an unsatisfied appetite for certain foods, deprivation of tasting, chewing, swallowing food, and drinking liquids, limited mobility, and deprivation of regular food. Except for burping, gastrointestinal symptoms were not common though they were usually distressful. This information has been used to develop teaching programs which are being tested for effectiveness in reducing distress associated with nasogastric tube feeding.
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The metabolism and elimination of 3H-butorphanol (levo-3, 14-dihydroxy-N-(cyclobutylmethyl)[15-3H]morhinan) tartrate were determined in man after therapeutic im (2 mg) and iv (1 mg) doses. As judged from urinary excretion of radioactivity, the im dose was completely absorbed. Butorphanol was rapidly distributed to tissues, had a plasma half-life of about 3 hr, and was extensively metabolized prior to elimination. The major route of elimination was renal, with fecal excretion being a minor route. Hydroxybutorphanol [3, 14-dihydroxy-N-(trans-3'-hydroxycyclobutylmethyl)morphinan] was isolated and identified as a major urinary metabolite and was also present in the plasma. The disposition of butorphanol is compared and contrasted to the disposition of morphine and pentazocine.