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M H Nathanson

Publications and source records attributed to M H Nathanson.

At least 55 records · Page 3Linked to original sources
PubMed1995

Differences in laser-induced autofluorescence between adenomatous and hyperplastic polyps and normal colonic mucosa by confocal microscopy.

Laser-induced autofluorescence has been used to discriminate normal from adenomatous colonic mucosa. However, few studies to date have studied the origin of colonic autofluorescence. Using confocal microscopy (excitation wavelength 488 nm), we have shown that autofluorescence at this wavelength is present predominantly in the lamina propria of normal mucosa but in the epithelium in adenomatous and hyperplastic polyps. The intensity ratio of epithelial cell to lamina propria fluorescence was significantly lower (P < 0.0001) in normal mucosa (0.52 +/- 0.01) compared with either adenomatous (1.6 +/- 0.2) or hyperplastic polyps (1.7 +/- 0.15). However, the ratios were not significantly different between hyperplastic and adenomatous polyps. Thus, confocal microscopy enables the detection of the sites of autofluorescence within colonic mucosa and the quantitation of differences in fluorescence between different tissue types.

Adenomatous Polyps↗
PubMed1995

Effects of Hg2+ on cytosolic Ca2+ in isolated skate hepatocytes.

Hg2+ is an environmental pollutant that adversely affects a range of cellular functions, including those that regulate free cytosolic Ca2+ (Ca(i)2+). To investigate the mechanism of Hg(2+)-induced Ca(i)2+ signaling, we examined the effects of Hg2+ on Ca(i)2+ in isolated skate hepatocytes, and developed a method to assess cytosolic Hg2+ (Hgi2+) in these cells as well. At lower concentrations (1-5 microM), Hg2+ induced little detectable change in Ca(i)2+. At higher concentrations (10 microM-1 mM), Hg2+ induced a dose-dependent, progressive increase in Ca(i)2+, which occurred even in Ca(2+)-free medium. Pretreatment of hepatocytes with the membrane-impermeant Hg2+ chelator glutathione (GSH) blocked the Hg(2+)-induced Ca(i)2+ increase, whereas addition of GSH after exposure to Hg2+ slowed but did not prevent further increases in Ca(i)2+. Pretreatment with the membrane-permeant Hg2+ chelator dithiothreitol (DTT) also blocked Hg(2+)-induced increases in Ca(i)2+. Unlike GSH, however, addition of DTT after Hg2+ significantly decreased Ca(i)2+, returning it to near-baseline levels. Thapsigargin induced a sustained increase in Ca(i)2+, but subsequent addition of Hg2+ resulted in a further, progressive Ca(i)2+ increase. We also describe the use of the fluorescent dye BTC-5N to measure Hgi2+, and with it found that Hgi2+ reaches nanomolar levels within minutes of extracellular application, but that these measurable levels of Hgi2+ do not precede elevations in Ca(i)2+. Hg2+ did not irreversibly damage the hepatocytes over this time period (< 5 min), as determined both by propidium iodide permeability and light microscopic appearance. Together, these findings suggest: (i) Hg2+ increases Ca(i)2+ in skate hepatocytes; (ii) Hg2+ must enter the hepatocytes for this Ca(i)2+ increase to occur; (iii) this increase is mediated by release of Ca2+ from endogenous stores that are distinct from the thapsigargin-sensitive Ca2+ stores; and (iv) this increase occurs in association with measureable levels of Hg2+ in the cytosol. Adverse cellular effects of Hg2+ may be mediated by changes in Ca(i)2+ that result from intracellular accumulation of this toxic metal.

Animals↗
PubMed1995

Sevoflurane for outpatient anesthesia: a comparison with propofol.

Three different anesthetic techniques were compared in 146 healthy outpatients undergoing ambulatory surgery. In Groups I and II, anesthesia was induced with propofol (1.5-2.0 mg/kg, intravenously [iv]) and maintained with nitrous oxide (N2O) 60% in oxygen and either a propofol infusion, 75-160 micrograms.kg-1.min-1 IV, or sevoflurane, 1%-2% end-tidal, respectively. In Group III, anesthesia was induced and maintained with sevoflurane, 1%-4% end-tidal and N2O 60% in oxygen. In addition to 60% N2O in oxygen at a total gas flow of 3 L/min, all patients received fentanyl, 2-3 micrograms/kg IV, and vecuronium, 0.1 mg/kg IV. IV induction of anesthesia with propofol (90 +/- 53 s and 94 +/- 48 s in Groups I and II, respectively) was significantly faster than inhalation induction with sevoflurane (153 +/- 100 s). There were no significant differences in the incidence of coughing, airway irritation, or laryngospasm during induction of anesthesia. Although the mean arterial blood pressure values were similar in all three groups, the use of sevoflurane was associated with consistently lower heart rate values during the early maintenance period. Early and intermediate recovery times were the same in all three treatment groups. The use of sevoflurane for induction and/or maintenance of anesthesia was associated with a higher incidence of postoperative emetic sequelae compared with propofol. Finally, the times at which patients were considered "fit for discharge" and the actual discharge times were similar in all three groups. Sevoflurane is an acceptable alternative to propofol for induction and maintenance of outpatient anesthesia.

Adult↗
PubMed1995

Sevoflurane versus desflurane for outpatient anesthesia: a comparison of maintenance and recovery profiles.

The recovery characteristics of desflurane and sevoflurane were compared when used for maintenance of ambulatory anesthesia. After obtaining informed consent, 42 healthy, unpremedicated women undergoing laparoscopic sterilization procedures were studied. Anesthesia was induced with propofol, 1.5-2.0 mg/kg, and maintained with either desflurane 3%-6% (n = 21) or sevoflurane 1%-2% (n = 21) with 60% nitrous oxide in oxygen. Intraoperative analgesia and neuromuscular block was achieved using fentanyl and vecuronium, respectively. The inhaled anesthetics were titrated to achieve an adequate clinical "depth of anesthesia" and to maintain mean arterial pressure (MAP) within 20% of the preinduction baseline values. Visual analog scales (VAS) and the digit-symbol substitution test (DSST) were performed preoperatively and at 30-min intervals during the recovery period. There were no differences between the two groups in the total doses of propofol, fentanyl, or vecuronium. Heart rate (HR) values were lower in the sevoflurane group during the induction-to-incision period. However, HR and MAP were otherwise similar during the maintenance and recovery periods. Use of desflurane led to a more rapid emergence (4.8 +/- 2.4 vs 7.8 +/- 3.8 min) and shorter time to extubation (5.1 +/- 2.2 vs 8.2 +/- 4.2 min) compared to sevoflurane (mean values +/- SD). Intermediate recovery times, postoperative VAS and DSST scores, and side effects were similar in the two treatment groups. Although sevoflurane was associated with a slower emergence from anesthesia than desflurane after laparoscopic surgery, recovery of cognitive function and discharge times were similar in the two anesthetic groups. Thus, it would appear that sevoflurane is an acceptable alternative to desflurane for maintenance of outpatient anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

The role of sevoflurane in outpatient anesthesia.

Sevoflurane appears to have several properties that make it an attractive alternative to the currently available anesthetics for outpatient anesthesia. The relative low solubility of sevoflurane, as well as an impressive lack of airway irritation, makes it a very useful anesthetic for inhalation induction of anesthesia. This feature is likely to make sevoflurane a population choice for pediatric outpatient anesthesia. For adult outpatients, the relatively low solubility of sevoflurane permits rapid alterations in alveolar concentration during the maintenance period (even when administered at relatively low flow rates of 2-3 L/min), thereby improving control of the depth of anesthesia. Low solubility should also allow for a more predictable emergence from anesthesia (versus isoflurane), thereby facilitating patient turnover in a busy ambulatory surgery center. The commercial development of sevoflurane has been slow because of concerns regarding the potential toxicity of its metabolites and breakdown products (24). However, the large body of clinical experience from Japan and the worldwide Phase II and III clinical development programs suggests that these concerns may be unfounded. The short duration of exposure in the outpatient setting should further decrease the risk of nephrotoxicity. The relatively low solubility of sevoflurane will facilitate its use with total gas flow rates of 2-3 L/min. In the final analysis, clinicians will have to balance the cost of sevoflurane (versus halothane, enflurane, isoflurane, and desflurane) against its potential advantages in the ambulatory surgery population. Although the search for anesthetics that are more ideally suited for use in the outpatient setting will continue, sevoflurane clearly represents a step in the right direction (3).

Adult↗
PubMed1995

Altered expression and function of hepatocyte gap junctions after common bile duct ligation in the rat.

Gap junction channels allow intercellular exchange of ions and small molecules between adjacent cells. Such communication coordinates cellular and organ function in tissues, although it is unclear if altered gap junction expression and communication contribute to organ dysfunction in pathological states. We examined the immunofluorescent (IF) localization and mRNA and protein levels of the two hepatocyte gap junction proteins connexin 32 and connexin 26, after hepatic injury induced by common bile duct ligation (CBDL) in the rat. Intercellular communication was measured by comparing gap junction-mediated coordination of hormone-induced Ca2+ signals in isolated rat hepatocyte couplets from control and CBDL animals. Connexin 32 plasma membrane IF, protein, and mRNA levels decreased markedly early after CBDL and remained low at 14 days. Connexin 26 plasma membrane IF and protein levels also decreased markedly after CBDL, but mRNA levels rose, and a partial return in membrane IF and protein levels was noted at 9 and 14 days. Coordination of vasopressin-induced Ca2+ signals between cells in isolated rat hepatocyte couplets 1 day after CBDL was significantly impaired compared with controls. These results demonstrate that hepatocyte gap junction communication is impaired early after CBDL because of decreased connexin protein levels. Disruption of gap junctions after CBDL may contribute to loss of hepatic functions that depend on gap junction communication.

Animals↗
PubMed1995

Ca2+ waves are organized among hepatocytes in the intact organ.

Hormone-induced increases in cytosolic Ca2+ (Cai2+) begin as Cai2+ waves in cells isolated from most types of tissue (1, 11), but whether such waves actually occur in vivo is unknown. To investigate this, we examined vasopressin-induced Cai2+ signals in hepatocytes within the perfused rat liver. Using confocal fluorescence video microscopy, we found that increases in Cai2+ began as waves that usually originated in hepatocytes near central venules, then spread opposite to the direction of blood flow, to hepatocytes near portal venules. We used immunochemistry to determine that the liver vasopressin V1a receptor is most concentrated among hepatocytes in the pericentral region, providing the mechanism by which Cai2+ waves originate there. Pericentral-to-periportal Cai2+ waves may direct peristaltic flow of bile, since Cai2+ induces contraction of the apical pole of hepatocytes and since peristaltic contractions in liver also occur in a pericentral-to-periportal direction. The organization of Cai2+ waves among cells in intact tissue may be a means by which an integrative, organ-level response is provided in response to hormonal stimuli.

Animals↗
PubMed1995

NO modulates the apicolateral cytoskeleton of isolated hepatocytes by a PKC-dependent, cGMP-independent mechanism.

Nitric oxide (NO) induces smooth muscle relaxation. We examined whether NO or its mediator of this action, guanosine 3',5'-cyclic monophosphate (cGMP), similarly induces relaxation of the apicolateral cytoskeleton in hepatocytes. Apical (canalicular) contractions were observed in isolated rat hepatocyte couplets by videomicroscopy, tight junction permeability was determined in the couplets by paracellular penetration of Texas red-dextran, and cytosolic Ca2+ (Ca2+i) was measured in isolated hepatocytes by fluorescence imaging. Unexpectedly, the NO donor sodium nitroprusside potentiated rather than inhibited apical contraction, in a cGMP-independent manner. This action of nitroprusside was blocked by hemoglobin or by inhibition of protein kinase C (PKC). Nitroprusside and 3-morpholinosydnonimine, another NO donor, each increased the permeability of hepatocyte tight junctions, a known effect of PKC in this cell type, and induced translocation of that kinase to the plasma membrane, as determined by immunocytochemistry. Neither nitroprusside nor dibutyryl cGMP changed the amplitude or frequency of Ca2+i signals in hepatocytes. Exogenous NO thus modulates the apicolateral cytoskeleton of hepatocytes via PKC activation rather than via cGMP or Ca2+i. These observations suggest a new role for NO: to activate PKC.

Animals↗
PubMed1995

Nitric oxide and liver disease.

Nitric oxide is a highly reactive, diffusible gas that is produced by many tissues, and it exerts a range of physiological and pathophysiological effects. The liver is one organ clearly influenced by nitric oxide, and acute versus chronic exposure to this substance has been associated with distinct patterns of liver disease. Bacterial infections, including the sepsis syndrome, acutely increase nitric oxide systemically and may lead to acute hepatic dysfunction. We review etiology, diagnosis, and treatment of cholestasis associated with these infections, because this condition in particular has been linked to nitric oxide. Chronic increases in nitric oxide may cause the hyperdynamic circulation seen in cirrhosis and portal hypertension. Therefore, we also review etiology, diagnosis, and treatment of the hepatorenal and hepatopulmonary syndromes, because both these syndromes occur in end-stage liver disease, and they may be linked to nitric oxide as well. An appreciation of nitric oxide and its evolving role in hepatology may be important to understand the pathogenesis of and treatment strategies for these different types of liver disease.

Humans↗
PubMed1994

Histamine augments cytokine-stimulated IL-11 production by human lung fibroblasts.

Histamine mediates its effects via histamine receptors and by participating in a multicellular cytokine cascade. IL-11 is a stromal cell-derived cytokine with biologic activities that overlap with IL-6. To further understand the biology of histamine and IL-11, we determined whether histamine regulates the production of IL-11 by human lung fibroblasts. Histamine was a weak stimulator of IL-11 production. Importantly, it also interacted in a synergistic fashion with TGF-beta 1 to further augment IL-11 protein production and mRNA accumulation. This synergistic interaction was not altered by the H2 receptor antagonist cimetidine and could not be reproduced with the H2 receptor agonist 4-methylhistamine. In addition, it was not abrogated by the cyclic nucleotide-dependent protein kinase inhibitor N-(2-1-guanidinoethyl)-5 isoquinolinesulfonamide hydrochloride), and histamine and TGF-beta 1 did not stimulate intracellular cAMP. In contrast, the synergy was abrogated by the H1 histamine receptor antagonists diphenhydramine and pyrilamine, could be reproduced when histamine was replaced with the H1 agonist 2-methylhistamine, and was abrogated by the calmodulin antagonists N-(6-aminohexyl)-1-napthalenesulfonamide), N-(6-aminohexyl)-5-chloro-1-napthalenesulfonamide), and trifluoperazine dichloride and by the intracellular calcium chelator 1,2-bis-(2-amino-5-bromo-phenoxy)ethane-N,N,N',N'-tetraacetic acid, tetra(acetoxymethyl)-ester. In addition, although TGF-beta 1 did not alter cytosolic Ca2+, histamine caused a biphasic increase in cytosolic Ca2+, and the majority of cells incubated with TGF-beta 1 plus histamine exhibited sustained Ca2+ oscillations. These studies demonstrate that histamine is an important regulator of fibroblast IL-11 production, that histamine interacts with TGF-beta 1 in the induction of this cytokine, and that this interaction is mediated, to a great extent, by a pretranslational mechanism that is dependent on H1 receptors and a calcium/calmodulin-dependent activation pathway.

Calcium↗
PubMed1994

Role in host cell invasion of Trypanosoma cruzi-induced cytosolic-free Ca2+ transients.

Trypanosoma cruzi enters cells by a unique mechanism, distinct from phagocytosis. Invasion is facilitated by disruption of host cell actin microfilaments, and involves recruitment and fusion of host lysosomes at the site of parasite entry. These findings implied the existence of transmembrane signaling mechanisms triggered by the parasites in the host cells before invasion. Here we show that infective trypomastigotes or their isolated membranes, but not the noninfective epimastigotes, induce repetitive cytosolic-free Ca2+ transients in individual normal rat kidney fibroblasts, in a pertussis toxin-sensitive manner. Parasite entry is inhibited by buffering or depleting host cell cytosolic-free Ca2+, or by pretreatment with Ca2+ channel blockers or pertussis toxin. In contrast, invasion is enhanced by brief exposure of the host cells to cytochalasin D. These results indicate that a trypomastigote membrane factor triggers cytosolic-free Ca2+ transients in host cells through a G-protein-coupled pathway. This signaling event may promote invasion through modulation of the host cell actin cytoskeleton.

Animals↗
PubMed1994

Localization of the type 3 inositol 1,4,5-trisphosphate receptor in the Ca2+ wave trigger zone of pancreatic acinar cells.

Agonist-induced cytosolic Ca2+ (Ca2+i) signals begin as apical-to-basal Ca2+i waves in pancreatic acinar cells and in other polarized epithelia. However, the basis of this polarized Ca2+i signaling pattern is unknown. Here we use immunocytochemistry to demonstrate that the type 3 inositol trisphosphate receptor is localized to the extreme apex of pancreatic acinar cells, the region which corresponds to the trigger zone from which Ca2+i signals originate in this cell type (Kasai, H., Li, Y.X., and Miyashita, Y. (1993) Cell 74, 669-677). We also show that inositol trisphosphate-mediated Ca2+ release induces amylase release from permeabilized pancreatic acini. Since Ca2+i signals begin by inositol trisphosphate-mediated Ca2+ release, these findings suggest that localization of the type 3 inositol trisphosphate receptor to the trigger zone is responsible for the generation of apical-to-basal Ca2+i waves, and that this organization may be important for regulating apical exocytosis in pancreatic acinar cells.

Amylases↗
PubMed1994

Effects of protein kinase C and cytosolic Ca2+ on exocytosis in the isolated perfused rat liver.

Both protein kinase C and cytosolic Ca2+ are involved in the regulation of exocytosis in a number of cell types. However, the relative importance of each of these for apical exocytosis in the hepatocyte is unknown. To investigate this, we studied the effects of protein kinase C and Ca2+ agonists on horseradish peroxidase excretion in the isolated perfused rat liver. Vasopressin increased both horseradish peroxidase concentration and net horseradish peroxidase excretion in bile, and these effects were abolished by the protein kinase C inhibitor H-7. The protein kinase C activator phorbol dibutyrate also increased both net excretion and the concentration of biliary horseradish peroxidase. In contrast, the Ca2+ ionophore A23187 and the Ca2+ mobilizing agent 2,5'-di(tertbutyl)-1,4-benzohydroquinone both had minimal effects on horseradish peroxidase concentration and inhibited the rate of horseradish peroxidase excretion. These results suggest that protein kinase C stimulates apical exocytosis in the hepatocyte, whereas increased Cai2+ per se does not influence exocytosis and inhibits excretion only transiently by reducing bile flow.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1994

Cellular and subcellular calcium signaling in gastrointestinal epithelium.

Ca2+ is a critical second messenger in virtually all cell types, including the various epithelial cell types within the digestive system. When measured in cell populations, Ca2+ signals usually appear as a single transient or prolonged elevation. In individual epithelial cells, signaling patterns often vary from cell to cell and may contain more complex features such as Ca2+ oscillations. Subcellular Ca2+ signals show a further level of complexity, such as Ca2+ waves, and may relate to the polarized structure and function of epithelial cells. The approaches to detect cytosolic Ca2+ signals, the patterns and mechanisms of Ca2+ signaling, and the role of such signals in regulating the function of polarized epithelium within the gastrointestinal tract, pancreas, and liver are reviewed in this report.

Calcium↗
PubMed1994

Tracheal intubation in a manikin: comparison of supine and left lateral positions.

Tracheal intubation in the left lateral position may be necessary in some circumstances. Using a manikin we demonstrated that anaesthetic trainees found tracheal intubation in the left lateral position was more difficult and took longer than in the supine position. However, the time to successful tracheal intubation decreased with practice, indicating the presence of a learning curve. We suggest that tracheal intubation in the left lateral position should become part of training in the management of the difficult airway.

Anesthesiology↗