Synergistic effect of elastase and 60 percent oxygen on pulmonary airspace enlargement.
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Animals↗
Biomedical subjects
S Keller
Publications and source records attributed to S Keller.
Polar surface distribution of type II insulin-like growth factor receptor in rat hepatocytes.
We describe the distribution of type II insulin-like growth factor receptors among canalicular (cLPM) and basolateral (bLPM) subfractions of rat liver plasma membranes (LPM). BLPM bound 3 times more 125I-IGF II than cLPM. The number of receptors was (1.3 +/- 0.15) X 10(-12) mol/mg in bLPM, and (0.4 +/- 0.17) X 10(-12) mol/mg in cLPM. Insulin-like growth factor II (IGF II) was 10 times more potent than insulin-like growth factor I (IGF I) in displacing 125I-IGF II from both basolateral and canalicular binding sites. Insulin did not interfere with binding of 125I-IGF II in either LPM preparations. Our findings point to an asymmetrical hepatocellular distribution of type II IGF receptors, thus extending the concept of surface polarization of hepatocytes to growth promoting hormone receptors.
Animals↗
The effect of 60% oxygen on air-space enlargement and cross-linked elastin synthesis in hamsters with elastase-induced emphysema.
Hyperoxia is routinely administered to patients with severe emphysema. To gain insight into the possibly adverse effects of such treatment, hamsters were exposed to 60% oxygen for 5 days, beginning 48 h after induction of pulmonary emphysema by intratracheal instillment of pancreatic elastase. Control groups consisted of (1) animals instilled with elastase and exposed to room air, (2) animals instilled with saline and exposed to 60% oxygen, and (3) animals instilled with saline and exposed to room air. Cross-linked elastin content and synthesis in the lung were measured immediately following termination of hyperoxia, and the mean linear intercept was determined 4 wk later. Cytologic examination of bronchoalveolar lavage fluids was also performed. Statistical significance was determined by a two-way analysis of variance. Results indicate that exposure to 60% oxygen significantly affected (p less than 0.05) air-space size, causing a 51% increase among elastase-treated hamsters (124 versus 82 microns) but only a 4% increment among saline-treated animals (52 versus 50 microns). When compared to other groups, animals treated with both elastase and hyperoxia had a significantly greater (p less than 0.01) percentage of neutrophils (28%) in their lung lavage fluids immediately following exposure to 60% oxygen. Although total lung elastin content was not altered by hyperoxia at this time, labelling of elastin cross-links was significantly increased (p less than 0.05). These studies demonstrate that exposure to 60% oxygen enhances elastase-induced lung injury. They also raise the possibility that oxygen therapy may, under certain circumstances, accelerate the progression of human emphysema.
Animals↗
Effect of insulin on glucose transporter distribution in white fat cells from hypophysectomized rats.
Glucose transport in white fat cells from hypophysectomized rats is increased and unresponsive to insulin. The goal of this study was to explain this observation. The number of glucose transporters, as determined by D-glucose-inhibitible cytochalasin B binding, in the plasma membranes from fat cells of hypophysectomized rats is: (1) elevated, (2) not increased by insulin, and (3) the same as in plasma membranes from insulin-stimulated fat cells of control rats. In microsomal membranes from fat cells of hypophysectomized rats the number of glucose transporters is: (1) smaller than in basal and insulin-stimulated fat cells from control rats, and (2) not changed by insulin.
Adipose Tissue↗
Growth of aneurysms can be understood as passive yield to blood pressure. An experimental study.
The strength of aneurysm walls obtained intraoperatively or at autopsy immediately after death was evaluated by measurements of the force response to one-directional stretch and compared to the walls of intracranial arteries. The maximum stress that aneurysm tissue could tolerate was found slightly lower than in arteries, which is most probably due to the amount of immature forms of collagen. The stress resistance of aneurysms and arterial tissue decayed over a period of several hours. The relaxation curve could be approximated by the sum of 2 exponential terms. The half decay times of these terms were found identical in aneurysms and arteries, they appear to be collagen characteristics. The strength measured in vitro was compared to the stress in vivo, which was calculated on the basis of blood pressure and aneurysm radius. The stress tolerated by aneurysm walls over a period of 24 hours was found to be in the range of the stress that is imposed in vivo by the mean blood pressure. Arteries resisted stresses corresponding to pressures 10 to 20 times higher than physiological values. The thickness of the aneurysm walls correlated with the aneurysm radius in a linear fashion. It is suggested that aneurysm growth can be understood as passive yield to blood pressure, and reactive healing and thickening of the wall with increasing aneurysm diameter.
Biomechanical Phenomena↗
Strength, elasticity and viscoelastic properties of cerebral aneurysms.
Tissue strength and stiffness of cerebral aneurysm walls obtained intraoperatively or at autopsy were evaluated by uniaxial strain/stress measurements. For comparison, corresponding measurements were also made on autopsy specimens of intracranial arteries. The maximum stress that the aneurysm tissue could tolerate, the yield stress, was found to be slightly lower than in arteries, which is likely due to the content of immature forms of collagen. The material stiffness, as determined by division of the yield stress by the corresponding strain, was also smaller in aneurysms than in arteries. The stress resistance of aneurysms and arterial tissue decreased over a period of several hours. The relaxation curves were found to be identical in aneurysms and arteries. The stress tolerated by aneurysm walls was found to be in the range of the stress that is imposed in vivo by the blood pressure. Arteries resisted stresses corresponding to pressures 5-10 times higher than physiological values. It is suggested that the balance of tissue strength and the stress imposed by the blood pressure is causally related to aneurysm growth.
Adult↗
Significance of extramucosal residual tumor at the bronchial resection margin.
Extramucosal microscopic residual disease (MRD) at the bronchial resection margin was identified in 45 (1.6%) of 2,890 patients who underwent resection of primary non-small cell lung cancer between 1975 and 1985. In 9 of these patients, residual tumor was confined to submucosal lymphatics, whereas in the other 36, MRD was found in peribronchial soft tissue. All patients underwent complete mediastinal lymphadenectomy. Three patients had stage I disease, 3 had stage II, 33 had stage IIIa, 4 had stage IIIb, and 2 had stage IV. Recurrent disease developed in 34 (81%) of the evaluable patients; the recurrence was local in 11 (32%). Median time from operation to diagnosis of local recurrence was 8 months. Sixty percent of the recurrences in the N0 group were local, and only 23% of those in the N2 group were local. Extramucosal MRD is most frequently associated with advanced-stage disease. Postoperative therapy had no effect on the development of recurrent disease. We found no difference in survival between patients whose initial site of recurrence was local as opposed to distant. Median survival after the identification of either local or distant recurrence was 5 months. The finding of extramucosal MRD identifies a subset of patients with a poorer prognosis compared with those with clear resection margins.
Adult↗
Inhibition of insulin degradation by insulin-like growth factors I and II in human hepatoma (HepG2) cells.
IGF-I infused at pharmacological doses in healthy men markedly decreases C-peptide levels, whereas insulin levels remain within the normal range. One possible explanation is decreased insulin removal. As the liver is the major site of insulin degradation, we studied insulin degradation by HepG2 cells in the presence of IGF. We found that IGF-I at a concentration of 130 nmol/l inhibits insulin degradation by HepG2 cells when the initial insulin concentration is 0.34 nmol/l. The effect of IGF-I on insulin degradation is dose-dependent and the rate of insulin degradation is dependent on the insulin concentration. IGF-II is 6 to 10 times more potent than IGF-I in inhibiting 125I-insulin binding to HepG2 cells and in protecting insulin from being degraded. Thus, IGF-I and IGF-II inhibit insulin degradation most likely by competing for binding at insulin binding sites of liver cells.
Carcinoma, Hepatocellular↗
Revisited: is subclinical protein deficiency a significant public health concern?
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Adult↗
Heparin-neutralizing activity in the plasma of women with gynecologic malignancy: the effect of tumor stage on heparin concentration and fibrin generation after low-dose heparin.
The relationship between tumor stage and the concentration of circulating heparin achieved after subcutaneous administration and its effect on fibrin generation were studied in 24 women with gynecologic malignancy. A single subcutaneous injection of 5000, 7500, and 10,000/U of sodium heparin was given in random order on different days. Plasma specimens for antithrombin III, fibrinopeptide A, and heparin were obtained serially over an 11-hour interval. Women with a Stage III or IV malignancy had significantly lower circulating heparin after the 5000 and 10,000/U doses. There was a significant decline in fibrinopeptide A as the concentration of circulating heparin increased. Thirty-three percent of women with a Stage III or IV malignancy had no detectable circulating heparin at any point examined over the 11 hours after 5000/U of heparin. Likewise, 16.7% and 8.4% had no detectable circulating heparin after 7500 and 10,000/U, respectively. A similar percentage was noted in a smaller group of women with Stage II malignancy. Next, a known quantity of heparin was added to the plasma from these patients and the concentration of heparin was determined. A significant amount of heparin-neutralizing activity was documented. We conclude that a large percentage of women with an advanced gynecologic malignancy are able to neutralize heparin administered for the prevention of thromboembolic disease. This heparin-neutralizing activity may account for the failure of low-dose heparin to prevent thromboembolic complications in this patient population.
Antithrombin III↗
Decreased elastic fibers and desmosine content in incompetent cervix.
Incompetence of the uterine cervix is a syndrome of painless, progressive dilatation and effacement occurring between the sixteenth and twenty-fourth weeks of gestation that represents abnormal functioning. It may serve as a model to elucidate normal function. Because the incompetent cervix results in painless opening of this organ without uterine contraction before term gestation, it is considered one of the causes of midtrimester spontaneous abortion, habitual spontaneous abortion, and early preterm labor. Untreated, it leads to rapid expulsion and often death of the fetus. We used light microscopy to compare decreased elastic fibers in incompetent cervices with those of normal nonpregnant and pregnant cervices. Morphologic analysis of this difference was extended to biochemical quantification of elastin content in one patient with cervical incompetence. The decrease in elastin suggests that one function of cervical elastin may be to maintain a closed and undilated cervix throughout gestation. There may be a relationship between changes in cross-linked elastin and the incompetent cervix; further studies are therefore indicated.
Amino Acids↗
Increased synthesis of elastin in amiodarone-induced pulmonary fibrosis.
Both synthesis and total content of lung elastin were measured after induction of interstitial pulmonary fibrosis in hamsters by a single intratracheal insufflation of amiodarone. Elastin synthesis, as measured by 14C-lysine incorporation into desmosine and isodesmosine, was significantly elevated (P less than 0.05) above control values for a 3-week interval after induction of lung injury. Total lung elastin content in the amiodarone-treated animals was 32% greater than in controls (P less than 0.05) 2 weeks after insufflation of the agent. Furthermore, the time course of elastin synthesis in this experimental model was similar to that observed in bleomycin-induced pulmonary fibrosis in hamsters. Increases in elastin may therefore be a common feature of interstitial pulmonary fibrosis and may contribute to the altered lung mechanics seen in this disease.
Amiodarone↗
Naloxone and experimental spinal cord injury: Part 1. High dose administration in a static load compression model.
Previous studies by other investigators using a dynamic weight drop injury model in cats or rats have demonstrated a beneficial effect of naloxone in promoting motor recovery after experimental spinal cord injury. The effective doses ranged from 0.8 mg (total dose) in rats to a high dose of 10 mg/kg in cats. We report here an evaluation of high dose naloxone (10 mg/kg) in a model of cord injury in rats using a static load compression technique. After induction of injury at T-12, naloxone (10 mg/kg) was administered by the intraperitoneal route, followed by five additional bolus injections over the course of the next 2 days. Animals were randomly assigned to this treatment regimen (n = 10) or to a saline control group (n = 10). The animals were observed for 4 weeks, with testing of recovery of hind limb motor function (Tarlov score and on an inclined plane). Although there were slight differences in recovery, the overall evaluation showed no statistically significant difference between the naloxone-treated and control groups. The spinal cords of the sacrificed animals were studied morphometrically; there was no statistically significant difference between the residual gray and white matter at the site of cord injury between the treated and control groups. Naloxone did not seem to promote recovery of motor function in this model of spinal cord injury.
Animals↗
Naloxone and experimental spinal cord injury: Part 2. Megadose treatment in a dynamic load injury model.
We previously reported that high dose naloxone (10 mg/kg) failed to promote recovery of motor function after a static load injury of the spinal cord in rats. In the present experiments, using the more traditional dynamic weight drop model, we tested megadose naloxone administered by the intraperitoneal route in 23 rats, including saline controls (Experiment 1). Thirty minutes after a cord injury at T-12, naloxone was given i.p. in a bolus of 100 mg/kg, followed by a continuous i.p. infusion of 50 mg/kg/hour for 23 hours. Again, no benefit was observed; this raised a question regarding naloxone and its absorption and serum levels. In another study, reported separately, we found that naloxone administered by the subcutaneous route affords higher and more sustained serum levels than by i.p. administration. Consequently, in 20 rats (Experiment 2), we repeated the protocol, using subcutaneous naloxone in a bolus dose of 150 mg/kg, followed by continuous infusion of 75 mg/kg/hour for 23 hours; the result was again negative. Morphometric determination of the residual (normal) cross sectional areas of gray and white matter at the epicenter of the cord lesion showed no statistically significant difference between treated and control animals in either Experiment 1 or Experiment 2. In view of the negative findings at high dose (10 mg/kg) and megadose naloxone, it seems that a reasonable next step would be an evaluation of lower doses using a factorial research design, incorporating a range of doses of naloxone in relation to a variety of intensities of cord injury. This question will be addressed in future experiments.
Animals↗
Synthesis of crosslinked elastin by a mesothelial cell culture.
Synthesis of crosslinked elastin was measured in cultures of pleural mesothelial cells. Results indicate that mesothelial cells are a rich source of crosslinked elastin and may therefore be useful for in vitro studies of this connective tissue component.
Autoradiography↗
Preeclampsia is not associated with excess fetal clotting.
Paired maternal and umbilical vein blood samples were obtained from 15 women and the plasma antithrombin III activity and fibrinopeptide A concentration measured. Women with preeclampsia had significantly lower antithrombin III activities and higher fibrinopeptide A concentrations (P less than .05) than normals. However, there were no significant differences between the two groups of fetuses. Thus, thrombin generation was not increased in the fetuses delivered from preeclamptic women.
Antithrombin III↗
Collagenous membrane from the surface of human visceral pleura.
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Adult↗
Psychological intervention for adults with cystic fibrosis.
This study assessed the effects of a stress management and life-style modification program on the physical and psychological well-being of young adults with cystic fibrosis. Four fibrocystic patients recently transferred to an adult rehabilitation centre completed this 6-week program. Instruction in stress management consisted of both behavioural (e.g. relaxation training) and cognitive techniques. Discussion on life-style included the topics of drug and alcohol abuse, leisure, and nutrition. Individual assessments were conducted before and after a 6-week non-intervention control period and after a 6-week training program. Assessments included a battery of psychometric inventories as well as electromyographic testing of trapezius muscle tension. At the end of the program, participants reported that they experienced fewer physical and psychological symptoms of stress. Electromyographic measures provided some suggestion of a trend toward greater stability at posttest.
Adult↗