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Biomedical subjects

R L Guerrant

Publications and source records attributed to R L Guerrant.

At least 181 records · Page 10Linked to original sources
PubMed1981

Interaction between Entamoeba histolytica and human polymorphonuclear neutrophils.

The interaction of human polymorphonuclear neutrophils (PMNs) with two strains of Entamoeba histolytica that exhibit different degrees of "virulence" was examined in animal and tissue culture systems. PMNs actively migrated toward both strains of amoebae. Less virulent amoebae (strain 303) were surrounded by PMNs (greater than or equal to 300/amoeba), fragmented and ingested by PMNs by means that appeared to be independent of oxygen. In contrast, contact with virulent amoebae (HM1) caused loss of PMN motility, PMN degranulation, death, and occasional phagocytosis by the amoebae, which survived concentrations of greater than 1,000 PMNs/amoeba. PMNs that did not directly contact virulent amoebae remained alive and active. At least two separate components of cytopathogenicity by virulent amoebae were observed: first, extracellular, contact-dependent, serum-independent cytolysis that was dependent on intact microfilament function; and second, amoeba phagocytosis of human PMNs. This contact-dependent ability of virulent amoebae to kill and phagocytize host neutrophils may be important in their pathogenic capacity.

Blood↗
PubMed1981

Resistance among fecal flora of patients taking sulfamethoxazole-trimethoprim or trimethoprim alone.

Because of the widespread occurrence of resistance to sulfonamides among Enterobacteriaceae, some researchers have suggested using trimethoprim (TMP) alone instead of the combination sulfamethoxazole-trimethoprim (SMX-TMP) in treating infections with TMP-susceptible organisms. To answer whether SMX-TMP suppresses the emergence of resistant organisms compared with TMP alone, quantitative fecal cultures were made for total and TMP-resistant organisms before, during, and after SMX-TMP (800/160 mg twice a day) or TMP (200 or 100 mg twice a day) was given to 48 patients for 4 weeks in a prospective, randomized study. All three regimens left anaerobes intact and reduced the total aerobic coliform fecal flora by approximately 4 logs throughout the 4-week treatment period. In 11 of 19 (58%) patients taking TMP 200 mg twice daily, TMP-resistant organisms emerged or increased during therapy (P less than 0.01, compared with none of the 12 controls), whereas in only 4 of 18 (22%) patients on SMX-TMP did TMP-resistant organisms increase. These TMP-resistant organisms increased by less than 1 log and were predominantly Pseudomonas and Acinetobacter species. In only one instance did an SMX-TMP-resistant Escherichia coli strain emerge after 4 weeks of SMX-TMP therapy. The slight increase in Pseudomonas and Acinetobacter species seen with TMP alone in this study raises a potential risk of giving TMP alone in settings where these organisms may cause serious infections, as in immunosuppressed patients.

Adult↗
PubMed1981

Diminished neutrophil oxidative metabolism after phagocytosis of virulent Salmonella typhi.

The interactions of human polymorphonuclear neutrophils (PMNs) with virulent and avirulent strains of Salmonella typhi were examined. Ingestion of the S. typhi strains by PMNs was evaluated with three techniques: visual examination of PMN monolayers (phagocytic index); uptake of radiolabeled S. typhi by PMNs; and removal of S. typhi from the supernatant of suspensions of PMNs and bacteria. All three techniques indicated equivalent phagocytosis of the strains. Postphagocytic PMN oxidative metabolism was quantitated with measurements of oxygen consumption, protein iodination, and chemiluminescence. We found that although PMNs ingested equal numbers of virulent and avirulent S. typhi, those PMNs ingesting the virulent organisms exhibited a significantly smaller increase in postphagocytic oxidative metabolism than PMNs ingesting avirulent S. typhi. Despite this muted oxidative burst the virulent bacteria were killed as well as the avirulent strains. Virulent S. typhi either fail to stimulate receptors that trigger PMN oxidative metabolism or inhibit PMN oxidative metabolism. Our data support the former hypothesis.

Blood Bactericidal Activity↗
PubMed1981

Attachment factors amont enterotoxigenic Escherichia coli from patients with acute diarrhea from diverse geographic areas.

To cause diarrhea, enterotoxigenic Escherichia coli (ETEC) must initially colonize the small bowel. Different surface structures have been implicated in this initial attachment. Recognized attachment factors include colonization factor antigens I and II (CFA/I and CFA/II) and type I pili. Several methods of detection for each of these factors have been reported. In this study, we screened for the presence of these attachment factors among enterotoxigenic E. coli isolated from 40 patients with acute diarrhea and 40 asymptomatic control individuals and examined their ability to attach to ATCC 407 human intestinal cells in vitro. Of 40 patients with diarrhea, 16 (40%) had enterotoxigenic E. coli isolates which exhibited an attachment trait. Fourteen (35%) of these isolates demonstrated the ability to attach to ATCC 407 cells, whereas only four isolates from asymptomatic controls attached (P < 0.02). A total of 20% of the patient isolates and 7.5% of the control isolates possessed CFA/I. Only one patient isolate demonstrated CFA/II. Evidence for type I pili was found on 10% of the patient isolates and 12.5% of the control isolates. Attachment to ATCC 407 cells allowed the detection of 87.5% (14 of 16) of enterotoxigenic E. coli isolates with any type of attachment trait. Of the 14 cases demonstrating attachment ability to ATCC 407 cells, 7 did not attach in the presence of mannose. Three of these showed evidence for both CFA/I and type I pili, one showed only CFA/I, and one showed only type I pili. Two of those mannose-sensitive attaching isolates showed no other demonstrable trait. Seven patient isolates showed mannose-resistant attachment. Of these, two were classified as possessing CFA/I, and one was classified as possessing CFA/II. The four remaining isolates could not be classified into any recognized attachment factor category, suggesting that other attachment factors remain to be identified.

Antigens, Bacterial↗
PubMed1981

Role of adherence in cytopathogenic mechanisms of Entamoeba histolytica. Study with mammalian tissue culture cells and human erythrocytes.

The enteric pathogen, Entamoeba histolytica, appears to cause disease by adhering to and then destroying mucosal barriers. Using an in vitro method of studying the interaction of E. histolytica with target cells (Chinese hamster ovary [CHO] and human erythrocytes [RBC]), we examined the mechanism of amebic adherence and its role in lysis of target cells. Killing and phagocytosis of target cells by amebas ceases at 4 degrees C, allowing observation of adherence. Amebas adhere to CHO cells at 4 degrees C, 78.9% formed rosettes (amebas with >/=3 adherent CHO cells each) at 2 h. At 37 degrees C, cytochalasins B and D inhibit adherence of amebas to CHO cells (P < 0.0005). Amebas adhere to and kill CHO cells in media with <0.1 muM calcium and magnesium plus 10 mM EDTA, indicating that divalent cations are not required in the medium. Adherence of amebas to human RBC was not ABO blood group specific and showed greater adherence to human than bovine or sheep RBC (P < 0.005). Neither Fc nor complement receptors were found on amebas by standard rosette studies. The amebic adherence receptor is not trypsin (0.125%) sensitive nor inhibited by trypan blue (1 mM). N-acetyl-d-galactosamine (GALNAc) inhibited the adherence of amebas to CHO cells and human RBC (0.1 g/100 ml or 4.5 mM GALNAc, P < 0.005) by binding to a receptor on the amebic surface. GALNAc abolishes amebic cytolysis of target CHO cells (determined by (111)Indium oxine release from CHO cells, P < 0.001) but not amebic phagocytosis of CHO cells. By suspending ameba-CHO cells rosettes in dextran, we found that GALNAc (1%) reversibly inhibits amebic adherence (P < 0.0005) and that cytochalasins decrease amebic killing of adherent CHO cells (P < 0.025). These findings indicate that the adherence of E. histolytica to target cells requires microfilament function, is via a specific amebic receptor that has affinity for GALNAc, and is required to lyse cells. Inhibition of the adherence of E. histolytica may alter the pathogenicity of this organism.

Acetylgalactosamine↗
PubMed1980

Cytopathogenic mechanisms of Entamoeba histolytica.

Cinemicrography of Entamoeba histolytica destruction of Chinese hamster ovary (CHO) cells shows that ameba cytopathogenicity consists of separate components: a contact-dependent cytolethal effect, and phagocytosis. Cells not in contact with amebae remain intact. Quantitation of ameba destruction of CHO cells by applying the one-hit hypothesis confirms that the cytoethal effect of amebae is contact dependent. Studies with 111Indium oxine-labeled cells provide further evidence of extracellular killing by E. histolytica and indicate that > 94% of the target cells are killed before phagocytosis. When we examined for a cytotoxin release by E. histolytica, we found no effect on CHO cells with filtrates of amebae, and a nonspecific effect of cell rounding and release with sonicates of amebae. The ameba sonicate effect was time-dose dependent, was not cytolethal, was reversible, and was inhibited by alpha II macroglobulin. Cytochalasin B altered ameba motility and morphology, and monolayer experiments confirmed that cytochalasins A, B, or D inhibited CHO cell destruction by E. histolytica. Cytochalasin D also inhibited extracellular killing of CHO cells by amebae in pellets, apparently independent of effects on ameba motility or phagocytosis. Colchicine and vinblastine, alone or in combination with cytochalasin D, did not inhibit E. histolytica cytopathogenicity, which indicates that microtubule function is not required for target cell killing by amebae.

Amebiasis↗
PubMed1980

Activation of intestinal guanylate cyclase by heat-stable enterotoxin of Escherichia coli: studies of tissue specificity, potential receptors, and intermediates.

Heat-stable enterotoxin (ST) of Escherichia coli increased guanylate cyclase activity in homogenates of rat and rabbit intestinal mucosa and stimulated intestinal fluid secretion in suckling mice. The ST effect on guanylate cyclase was dose-dependent, occurred without a time lag, and was confined to the particulate fraction. ST activation of guanylate cyclase was tissue-specific; ST did not alter activity of soluble or particulate rat liver, lung, heart, kidney, or cerebral cortex enzyme. The ST activity on guanylate cyclase and secretion was methanol-soluble and alkali-labile, and its effects were not altered by phentolamine, propranolol, or atropine. Monosialoganglioside did not reduce ST-induced secretion. However, indomethacin and butylated hydroxyanisole decreased the ST effect on both guanylate cyclase and secretion. Fluid secretion with ST sppears to result from specific activation of particulate intestinal guanylate cyclase. While adrenergic and cholinergic events are probably not involved in this process, the effects of ST may be mediated through prostaglandin synthesis or oxidative mechnanisms.

Alkalies↗
PubMed1980

Sulfamethoxazole- trimethoprim versus ampicillin in treatment of acute invasive diarrhea in adults.

Twenty-seven Navajo adults with moderate to severe acute inflammatory diarrhea were hospitalized and randomly given ampicillin or sulfamethoxazole-trimethoprim. All patients had invasive diarrhea as defined by sheets of fecal leukocytes, seen on methylene blue wet-slide preparations, and significant clinical symptoms, including postural hypotension from dehydration or fever (temperature greater than 100 degrees F [or 37.8 degrees C]). Patients were followed daily for 5 days in the hospital. Responses of symptoms in all 13 patients who were given sulfamethoxazole-trimethoprim were comparable to or better than those 14 patients randomly assigned to receive ampicillin. Nineteen (73%) of the 27 patients had culture-proven shigellosis, 6 of whom had ampicillin-resistant Shigella isolates. All isolates were susceptible to sulfamethoxazole-trimethoprim in vitro. The eight patients with culture-proven shigellosis treated with sulfamethoxazole-trimethoprim responded as well as the eight patients with ampicillin-susceptible infections treated with ampicillin. Three of the eight patients successfully treated with sulfamethoxazole-trimethoprim had ampicillin-resistant organisms. The three patients with ampicillin-resistant organisms who were treated with ampicillin appeared to do less well; one was a clinical and bacteriological failure at 72 h and subsequently improved after sulfamethoxazole-trimethoprim therapy. As predicted by in vitro susceptibility studies and by studies in children, sulfamethoxazole-trimethoprim was highly effective in treating adult patients with shigellosis and appears to be the treatment of choice in areas where ampicillin resistance among Shigella is common.

Acute Disease↗
PubMed1980

Inhibition of Escherichia coli heat-stable enterotoxin by indomethacin and chlorpromazine.

Purified heat-stable enterotoxin (ST) from a procine strain of enterotoxigenic Escherichia coli activates quanylate cyclase in particulate fractions of rat intestinal tissue and induces fluid accumulation in suckling mice. These effects of ST were examined in the presence of either indomethacin or chlorpromazine. We also examined the effects of these two drugs on fluid accumulation in suckling mice induced by the 8-bromo analog of cyclic guanosine monophosphate. Either indomethacin or chlorpromazine reduced ST activation of guanylate cyclase. Both drugs also reduced intestinal fluid accumulation in suckling mice that resulted from submaximal doses of ST (both P < 0.001). However, there was no reduction in fluid secretion by either drug when a maximally effective dose of ST was used, suggesting that inhibition of fluid secretion by both drugs can be overcome by increasing the ST dose and that a threshold level of guanylate cyclase activity results in maximal secretory response. Both drugs also reduced basal guanylate cylase activity in rat intestinal tissue and fluid secreton in suckling mice. Chlorpromazine also reduced intestinal secretion mediated by 8-bromo cyclic guanosine monophosphate (P < 0.001). These findings indicate that chlorpromazine interferes with the effects of ST both before and after its activation of guanylate cyclase, whereas indomethacin interfers with ST only before its activation of guanylate cyclase.

Animals↗
PubMed1980

Etiology of summer diarrhea among the Navajo.

The etiology of diarrhea in children and adults on the Navajo Indian Reservation was investigated in August 1975. Fifty-six ill individuals and 37 controls were included in the study. Shigella was most commonly associated with diarrhea, and was isolated from 32% of ill children and adults. Fifty percent of Shigella isolates tested were resistant to ampicillin. Heat-stable enterotoxin-(ST)-producing organisms were associated with noninflammatory diarrhea in adults (27% of these cases had ST-producing strains) but not in children. Heat-labile enterotoxin-producing organisms were found among controls as well as individuals with diarrhea. No children had evidence of rotavirus infection. These findings suggest that ST-producing organisms are important causes of sporadic cases of noninflammatory summer diarrhea among Navajo adults and confirm the importance of Shigella in inflammatory diarrhea among adults and children in this setting.

Arizona↗
PubMed1980

Studies on the cytopathogenicity of Entamoeba histolytica.

We have explored the interaction of virulent and avirulent E. histolytica (HM1 and 303 respectively) with human polymorphonuclear leukocytes (PMNs) and Chinese hamster ovary (CHO) cells. PMNs exhibit chemotaxis to both HMl and 303. On contact with HMl, PMNs degranulate and die (trypan blue uptake); incubation at a ratio of 100 PMNs per ameba for 40 minutes revealed 70 per cent PMN death with 84 per cent HMl viability. 303s are often ingested by PMNs on contact; after incubation as above, only 1 per cent of 303 were intact with PMN mortality equaling that of control. HMl leukotoxicity occurred under anaerobic conditions, in immune serum, and was not mediated by complement. CHO cells are disrupted by HMls, less than 50 per cent of CHO monolayer remains after < 3 hours with 10(4) HMl/ml. Sonicated HMls (.5 x 10(5)/ml) washed in phosphate buffered saline caused cell release without cell death versus control (by trypan blue uptake). When 5 microgram/ml of Cytochalasin B was added to PMNs and CHO cells, cytopathogenicity by HMls decreased 62 per cent (p < .01) and nearly to control values (p < .01) respectively. Colchicine 0.25 mM had no significant effect on PMN cytopathogenicity. Washed HMl and 303 (1 x 10(5)/ml) were agglutinated by 10 microgram/ml and 100 microgram/ml of the lectin concanavalin A. Cytopathogenicity was associated with intact microfilament function and ameba motility. Surface membrane receptors may be important mediators of virulence. Further studies of potential membrane receptors and inhibitors are underway.

Animals↗
PubMed1979

Comparison of assay of coliform enterotoxins by conventional techniques versus in vivo intestinal perfusion.

Thirty-six strains of coliform bacteria were tested for enterotoxigenicity both by conventional assays, including the Y-1 adrenal and Chinese hamster ovary cell assays for heat-labile toxin and the suckling mouse assay for heat-stable toxin, and by determining the ability of graded concentrations of ultrafiltrate high- or low-molecular-weight toxin preparations to induce water secretion during in vivo perfusion in the rat jejunum. The ultrafiltrates of all 18 strains isolated from persons with infectious diarrheal disease, including seven of Escherichia coli, seven of Klebsiella pneumoniae, and four of Enterobacter cloacae, contained one (nine strains) or two (nine strains) potent toxin fractions (resembling either heat-labile or heat-stable toxin in terms of apparent molecular weight and heat lability characteristics) that induced water secretion at perfusion concentrations of 10 ng/ml or less. Unconcentrated broth filtrates of five of the E. coli strains and two of Klebsiella reacted positively in one or more of the conventional assay systems. Concentrated ultrafiltrates from two strains that were negative in the in vitro assays for heat-labile toxin were tested and also proved to be inactive in these test systems. None of 18 strains isolated from control sources produced, in the ultrafiltrates, enterotoxins capable of inducing water secretion at low concentrations, and none reacted positively in the conventional assays. These results indicate that some strains of coliform bacteria elaborate potent toxin materials that are capable of inducing water secretion and can be detected by perfusion of concentrated ultrafiltrates but not by conventional assay systems for enterotoxigenicity. Whether this represents quantitative or qualitative differences between the toxin materials that stimulate these different test systems remains to be established.

Animals↗