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Biomedical subjects

R L Guerrant

Publications and source records attributed to R L Guerrant.

At least 145 records · Page 8Linked to original sources
PubMed1986

Production of type II heat-labile enterotoxin by Escherichia coli isolated from food and human feces.

Escherichia coli strains isolated in Sao Paulo, Brazil, from feces of patients with diarrhea and from food samples produced toxin(s) that was shown to be related both immunologically and genetically to the recently characterized type II heat-labile enterotoxin of E. coli. The new isolates of type II heat-labile enterotoxin-producing E. coli belonged to five different serotypes and did not represent a single clone.

Bacterial Toxins↗
PubMed1985

Evaluation and diagnosis of acute infectious diarrhea.

The appropriate approach to the diagnosis and management of acute infectious diarrhea is determined by the frequency and setting of the illness, the recognizable causes or syndromes, the cost and yield of available diagnostic tests, and the treatability of the disease. Acute diarrhea affects everyone throughout the world from one to more than six times each year, depending on age, location, and living conditions. The range of identifiable viral, bacterial, and parasitic etiologies is great, and the cost of indiscriminate use of etiologic studies for diagnosis is prohibitive. Because of its insensitivity for many organisms and poor selection of cases for testing, routine stool culture has been one of the most costly and ineffective microbiologic tests; the cost per positive result has traditionally exceeded $900 to $1,000. The appropriate treatment for the vast majority of cases (independent of their cause) is simple and effective: oral glucose- and electrolyte-containing rehydration solution. On the basis of an appropriate history and understanding of pathogenesis, fecal specimens can be selectively obtained and promptly examined for leukocytes and parasites, and the common noninflammatory diarrheas can be separated from the inflammatory infections in order to focus further studies on the latter group. The bacteria for which specific antimicrobial therapy should be considered usually cause inflammatory diarrhea in the United States. Therefore, only when the history or fecal leukocyte findings indicates an inflammatory process is it appropriate to culture for the routine invasive bacterial pathogens. In sporadic inflammatory diarrhea, culture methods should include those for Campylobacter jejuni as well as Salmonella and Shigella. Several special circumstances may prompt a consideration of parasites (including Giardia, Entamoeba, Strongyloides, Cryptosporidium), Vibrio, Yersinia, Clostridium difficile, enterotoxigenic Escherichia coli, food-borne agents, or sexually transmitted pathogens. The practical value of specific identification of rotaviruses (by enzyme-linked immunosorbent assay, Rotazyme, or electron microscopy) is primarily epidemiologic, particularly in hospitalized infants or young children. Using such a selective approach to fecal culture will greatly increase its yield and can reduce the cost per positive result from $1,000 to less than $150.

Acute Disease↗
PubMed1985

Microbial toxins and diarrhoeal diseases: introduction and overview.

Without question, diarrhoeal diseases constitute one of the greatest causes of morbidity and death on a global scale. To an increasingly recognized extent, they are caused by an expanding array of microbial products or "toxins'. The symposium focuses on microbial products that alter normal bowel function either by augmenting secretory pathways or by selectively destroying mucosal cells or pathways, thus leading to an imbalance in the concert of normal absorptive function that results in diarrhoea. An understanding of normal intestinal physiology is thus the key to unraveling the specific actions of microbial toxins. In many instances, the microbial toxins are themselves providing unique pharmacological tools with which to dissect normal intestinal function. Specifically, families of enterotoxins are reviewed that appear to cause secretion through the recognized second messengers of cyclic AMP and cyclic GMP as well as cyclic nucleotide-independent and calcium-dependent pathways. Potential "third messengers' such as the protein kinases, through which one or more of the second messengers may act, are also considered. We examine cytotoxins that alter the orchestrated function of specialized regions of intact intestinal mucosa by selectively impeding or killing certain cells, so leading to small intestinal or colonic pathology and contributing to diarrhoea. We also consider a wide range of recognized bacterial and parasitic agents and their enterotoxic products. In some instances, these toxins may strikingly resemble our own endogenous humoral regulators or hormones. At this point, the possible roles of viruses or other transmissible genome products in this area await further clarification. Finally, we examine pharmacological and immunological approaches to attacking the toxins themselves or the deranged physiology they cause, in order to approach the control of the potentially devastating diseases of diarrhoea.

Acute Disease↗
PubMed1985

STb enterotoxin of Escherichia coli: cyclic nucleotide-independent secretion.

Escherichia coli may produce a heat-labile enterotoxin (LT) or two heat-stable enterotoxins (STa, STb). Experimentally, STb is consistently active only in 5 h-weaned pig intestinal loops (WPIL), an effect that is largely removable by rinsing. At least three mechanisms initiate small intestinal secretion: cyclic AMP (LT), cyclic GMP (STa) and calcium (A23187). All three increase short-circuit current (SCC) in Ussing chambers by stimulating net Cl- secretion. STb significantly increases SCC within 2-5 minutes in Ussing chambers and is independent of cyclic AMP and cyclic GMP. When compared to crude culture filtrates of a non-toxigenic strain of E. coli, crude culture filtrates of STb did not alter Na+ or Cl- undirectional or net fluxes. However, the calculated residual ion flux (JRnet) increased significantly in STb-treated tissues and appeared to largely account for the STb-induced increase in SCC. Furosemide applied serosally (10(-3) M), the removal of extracellular calcium, and lanthanum chloride (10(-3) M) did not inhibit the effect of STb on SCC. Chlorpromazine (0.4 mM) completely inhibited STb-induced secretion in porcine loops. This inhibition was a non-specific reversal of the STb effect because in Ussing chambers, chlorpromazine simply induced an equal and opposite effect on SCC. These results indicate that STb initiates intestinal secretion in porcine jejunum in vitro by stimulating primarily non-chloride anion secretion in the absence of extracellular calcium. We postulate that STb causes bicarbonate secretion by a mechanism distinct from those of previously studied enterotoxins.

Animals↗
PubMed1985

Entamoeba histolytica: impedance measurements and cytotoxicity in the presence of bepridil, verapamil, and cytochalasin D.

Entamoeba histolytica, and invasive enteric protozoa, kills mammalian target cells by sequential adherence and cytolytic events. Using platinum plate electrodes with an alternating current source placed in a Wheatstone bridge circuit, the impedance (resistance to ion flow) of a cell suspension of axenic amebae (strain HM1-IMSS) was measured. The impedance of the amebic cell suspension, expressed as resistivity (in ohm-cm), was significantly greater than the test solution and increased with decreasing temperature or greater cell packing (P less than 0.01), indicating that the resistivity measurements reflected the impedance of the amebic surface membrane. Cytochalasin D (10 micrograms/ml), a microfilament inhibitor which inhibited amebic in vitro adherence and cytolysis of target Chinese hamster ovary (CHO) cells (P less than 0.001), also increased resistivity of the amebic suspension (P less than 0.01). Exposure of amebae to bepridil (10(5) M), a slow-channel blocker, inhibited amebic killing of target cells (P less than 0.01) and also increased the resistivity of the amebic suspension (P less than 0.01), but both to a lesser degree than cytochalasin D (P less than 0.001). In contrast, exposure of amebae to verapamil followed by washing had no effect on amebic killing of target cells or resistivity of the amebic suspension. The increased resistivity measured in cytochalasin D or following exposure to bepridil was not due to a change in cell density of the amebic suspension. These studies indicate that changes in impedance of the amebic surface membrane are produced by bepridil and cytochalasin D. The effect of these agents on membrane impedance may contribute directly to the concurrent observed alteration in amebic cytopathogenic capacity or may serve as a parallel marker for the cell membrane alterations induced by such pharmacologic agents which inhibit amebic microfilament function or calcium flux.

Adhesiveness↗
PubMed1985

Feasibility and efficacy of in-home water chlorination in rural North-eastern Brazil.

The purpose of this study was to assess the feasibility, acceptability and effect of an in-home water chlorination programme in a rural village. Previous studies at this site showed high levels of faecal coliforms in household water, high diarrhoea rates in children, and enterotoxigenic Escherichia coli and rotaviruses were the most common pathogens isolated from patients. Household water came from a pond and was stored in clay pots. No homes had sanitary facilities. A blind, cross-over trial of treatment of household water with inexpensive hypochlorite by a community health worker was carried out over 18 weeks among 20 families. Water in the clay pots was sampled serially, and symptom surveillance was done by medical students. The programme was generally acceptable to the villagers and no change in water use patterns were apparent. The mean faecal coliform level in the chlorinated water was significantly less than in the placebo treated samples (70 vs 16000 organisms/dl, P less than 0.001). People living in houses receiving placebo treatment had a mean of 11.2 days of diarrhoea per year, and the highest rate of 36.7 was among children less than 2 years old. Diarrhoea rates were not significantly different among the participants while exposed to water treated with hypochlorite. We conclude that a low-cost programme of this type, which utilizes community resources, is logistically feasible, appears to be culturally acceptable in this setting, and can result in a marked reduction in water contamination. The lack of effect on diarrhoea rates suggests that improvement in water quality may affect morbidity only when other variables relating to faecal-oral agent transmission are ameliorated at the same time.

Adult↗
PubMed1985

N-Acetyl-D-galactosamine-inhibitable adherence lectin of Entamoeba histolytica. I. Partial purification and relation to amoebic virulence in vitro.

Adherence of axenic Entamoeba histolytica, strain HM1-IMSS, to Chinese hamster ovary (CHO) cells is mediated by an amoebic adhesin that is inhibited by N-acetyl-D-galactosamine (GalNAc). The in vitro virulence for CHO cells and human neutrophils (PMNs) of four strains of axenic amoebae was strain HM1-IMSS greater than H303-NIH = 200-NIH greater than nonvirulent Laredo (P less than .001). The HM1 strain had the greatest sensitivity to GalNAc-mediated inhibition of adherence (P less than .001). GalNAc (1.0 g/100 ml) inhibited the killing of CHO cells and PMNs by HM1 amoebae (P less than .001) and allowed PMNs to kill the amoebae (P less than .0047). Gel filtration chromatography of a soluble fraction of amoebic sonicate demonstrated a GalNAc-inhibitable amoebic lectin of 43,000-67,000 daltons that agglutinated CHO cells, erythrocytes, and PMNs. Strain HM1 contained greater specific lectin activity than did strains 303, 200, and Laredo amoebae (P less than .0016). The in vitro virulence of E. histolytica is associated with a GalNAc-inhibitable amoebic adhesin; this report is the first of a soluble GalNAc-inhibitable amoebic lectin.

Acetylgalactosamine↗
PubMed1985

Effect of antagonists of calcium and phospholipase A on the cytopathogenicity of Entamoeba histolytica.

The in vitro mechanisms by which Entamoeba histolytica trophozoites lyse target Chinese hamster ovary (CHO) cells were examined. Calcium chelators ethylenediaminetetraacetate and ethyleneglycol bis (beta-aminoethyl ether)-N,N'-tetraacetate (10 mM) inhibited amebic cytolysis of target CHO cells (P less than .01). A putative antagonist of intracellular calcium flux, 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8; greater than or equal to 250 microM), inhibited amebic adherence and cytolysis (P less than .001). Quinacrine, Rosenthal's inhibitor (dimethyl-dl-2,3-distearoyloxypropyl-2'-hydroxyethyl ammonium acetate), phosphatidylcholine, and hydrocortisone (greater than or equal to 10(-4) M), all pharmacological antagonists of eukaryotic phospholipase A enzymes, inhibited amebic killing of target CHO cells (P less than .001). At 37 C quinacrine and hydrocortisone reduced amebic adherence to CHO cells, whereas Rosenthal's inhibitor and phosphatidylcholine did not. Phosphatidylcholine and TMB-8 demonstrated a synergistic inhibitory effect on amebic killing of target CHO cells (P less than .001). These studies indicate that extracellular calcium ions, amebic intracellular calcium flux, and amebic phospholipase A activity are required for cytolysis of target cells by E. histolytica.

Adhesiveness↗
PubMed1985

Adherence of Entamoeba histolytica trophozoites to rat and human colonic mucosa.

We studied the adherence of [3H]thymidine-labeled axenic Entamoeba histolytica (strain HM1-IMSS) to in vitro preparations of rat and human colonic mucosa. Studies were performed with fixed or unfixed rat colonic mucosa, unfixed rat mucosa exposed to trypsin, unfixed rat submucosa, and fixed human colonic mucosa. Twenty percent of the amebae adhered to fixed rat colonic mucosa; adherence was specifically inhibited by N-acetyl-D-galactosamine (GalNAc), galactose, and asialofetuin. The adherence of amebae to fixed human colonic mucosa was also GalNAc inhibitable. Greater adherence was found with unfixed rat colonic mucosa (40.9%) and was not GalNAc inhibitable unless the tissue was first exposed to trypsin. However, GalNAc did inhibit the adherence of amebae to unfixed rat submucosa. Glutaraldehyde fixation of amebae inactivates known amebic adhesion proteins; there was a markedly decreased adherence of fixed amebae to trypsin-exposed mucosa or fixed rat colonic mucosa. However, fixed or viable amebae had equal levels of adherence to unfixed rat colonic mucosa, suggesting the presence of a host adhesion protein that binds to receptors on amebae. Human (10%) and rabbit (5%) immune sera reduced the adherence of viable amebae to fixed rat colonic mucosa. We concluded that the GalNAc-inhibitable adhesion protein on the surface of E. histolytica trophozoites mediated adherence to fixed rat mucosa, fixed human colonic mucosa, trypsin-exposed unfixed rat mucosa, and unfixed rat submucosa. The surface of unfixed rat colonic mucosa contained a glutaraldehyde- and trypsin-sensitive host adhesion protein, perhaps in the overlying mucus blanket, which bound viable or fixed E. histolytica trophozoites.

Acetylgalactosamine↗
PubMed1985

Stimulation of porcine jejunal ion secretion in vivo by protein kinase-C activators.

Microbial toxins act through cyclic nucleotide dependent (cAMP or cGMP) or cyclic nucleotide independent pathways to cause intestinal ion secretion. To explore the calcium dependent, cyclic nucleotide independent pathway that is postulated to involve protein kinase C activation, we measured protein kinase C activity and phorbol ester binding in isolated intestinal epithelial cells and examined the effects of the C-kinase activators, phorbol myristate acetate, phorbol dibutyrate, and 4-beta-phorbol-12,13-didecanoate, in weaned pig jejunum in vivo. We demonstrated both protein kinase C activity and specific phorbol ester binding in porcine jejunal epithelial cells. Phorbol myristate acetate, phorbol dibutyrate, and 4-beta-phorbol-12,13-didecanoate (10(-5) M) each caused striking secretory responses at 5 h with accumulation of Na+, K+, Cl-, and HCO3- intraluminally. In contrast, 4-alpha-phorbol and 4-alpha-phorbol-12,13-didecanoate, which do not affect protein kinase C, allowed normal net absorption of all electrolytes from the intestinal lumen equivalent to controls with only Ringer's lactate. Time course studies revealed significant secretion within 30 min after exposure to the C-kinase activators. These data suggest an important role for protein kinase C activation in intestinal ion secretion.

Animals↗
PubMed1985

Assessment of an implantable ileostomy sphincter.

A totally implanted, intermittently inflatable, silicone rubber cuff, reservoir, and control mechanism were evaluated for use as an artificial sphincter in 18 female beagle dogs that had undergone ileostomy. The dogs were divided into daily 8-hour occlusion, test, and always open, control, groups. Animals were evaluated daily for continence and peristomal irritation. Quantitative aerobic and anaerobic cultures, measurements of ileal accommodation, net fluxes of H2O, Na, K, and taurocholate, fecal fat loss, and urinary excretion of oral 58Co X B12 plus mucosal suction biopsies were done at 4, 12, 24, and 36 weeks. Eight hours of daily occlusion caused dependable continence without causing damage to the underlying or upstream mucosa and significantly reduced the incidence of peristomal erosion (6.8 +/- 0.8 days/dog-days X 100 versus 50.7 +/- 7 days/dog-days X 100 [+/- SEM] [p less than 0.001]). Occlusion also promoted anaerobic bacterial growth (9.00 +/- 0.41 logs versus 6.70 +/- 0.58 logs [p less than 0.001]). Test animals showed significant capacitance accommodation of the terminal ileum without incurring defects in ileal absorptive or secretory function. Gangrenous herniation of small bowel through an aperture formed by an intestinal loop adhering to the capsule surrounding the cuff, device failure, and fibrotic obstruction occurred sporadically as late as 29 weeks after implantation. The artifical sphincter was effective and was physiologically well tolerated, but its specific liabilities require further address.

Animals↗
PubMed1984

A controlled study of endemic sporadic diarrhoea among adult residents of southern Brazil.

The aetiology of sporadic summer diarrhoea and enterotoxin (LT) antibody titres was studied among 43 adult patients in southern Brazil who had an acute, untreated diarrhoeal illness and 43 age- and sex-matched controls from the same area. A potential pathogen was identified in 33 of 34 patients and in 17 of 43 controls (p less than 0.01). 10 Shigella, one invasive Escherichia coli, one Salmonella and one Entamoeba histolytica were identified in 17 patients with inflammatory diarrhoea (faecal polymorphonuclear neutrophil leucocytes (PMN) present). In the other four only enterotoxigenic strains of E. coli were identified. Among 26 patients with non-inflammatory (no faecal PMN) diarrhoea, heat-stable (ST) toxin-producing coliforms were the most common pathogens isolated (27%). Heat-labile (LT) toxin-producing coliforms or serological rises to LT were seen in five patients, Strongyloides larvae in five, Giardia lamblia trophozoites in four and an LT-producing Salmonella in one. No pathogen was found in 10 patients with non-inflammatory diarrhoea. Among 43 controls, 11 LT coliforms, two Shigella and two Strongyloides larvae were found. 40 of 41 controls had detectable serum anti-LT antibody. A single ST-producing E. coli was found in one other control. No pathogen was identified in 26 controls. No rotaviruses or Norwalk-like viral agents were seen by direct or immune electron microscopy of stool filtrates. While LT-producing E. coli are frequently associated with endemic summer childhood diarrhoea in southern Brazil and are recognized causes of travellers' diarrhoea, this study shows that they are often carried asymptomatically by adults living in this region.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗