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Biomedical subjects

D S Reiner

Publications and source records attributed to D S Reiner.

46 records · Page 3Linked to original sources
PubMed1984

Inhibition of growth of Giardia lamblia by difluoromethylornithine, a specific inhibitor of polyamine biosynthesis.

Difluoromethylornithine (DFMO) is a specific and irreversible inhibitor of ornithine decarboxylase, an enzyme which catalyzes the first step in the biosynthetic pathway of the polyamines. We tested the effect of DFMO on the growth of Giardia lamblia, Entamoeba histolytica, and Trichomonas vaginalis. Growth of G. lamblia was inhibited by DFMO at concentrations of greater than or equal to 1.25 mM. Culture doubling time increased with increasing DFMO concentration. Growth inhibition was reversed if spermidine was added within 53 h of addition of DFMO; no growth was observed if spermidine was added later, indicating eventual parasite death. The growth of E. histolytica and T. vaginalis, two unrelated mucosal-dwelling parasites of humans, was not inhibited by 20 mM DFMO. These studies indicate that polyamine biosynthesis from ornithine is required for growth of G. lamblia.

Animals↗
PubMed1983

Human milk kills parasitic intestinal protozoa.

Giardia lamblia, a common pathogenic intestinal parasite of humans, was rapidly killed by exposure to normal human milk in vitro. The killing did not depend on secretory immunoglobulin A. Entamoeba histolytica, the dysentery amoeba, was also killed by normal human milk. Giardia-cidal activity cochromatographed with an unusual lipase that is present in the milk of humans but not of lower mammals. Human milk may play a protective role in infants exposed to this parasite.

Entamoeba histolytica↗
PubMed1983

Killing of Giardia lamblia trophozoites by normal human milk.

The clinical course of giardiasis is variable, and serum antibodies do not appear to be protective. We propose that natural factors either produced by intestinal tissue, transported into the intestine, or ingested (ie, by breast-fed babies) might promote resistance to this disease. Human milk is very rich in secretory IgA (S-IgA) antibodies, as well as nonspecific antibacterial factors (eg, lactoferrin, lysozyme). Previous studies showed that Giardia lamblia trophozoites were killed by nonimmune human milk (NHM) in a time- and concentration-dependent manner. Removal of greater than 99% of the S-IgA from NHM did not decrease its Giardia-cidal activity. Thus, the killing was not antibody dependent. This is the first demonstration of nonimmune antiparasitic defenses in human milk. The present studies show that in the presence of NHM, trophozoites lost motility, swelled, and lysed. The Giardia-cidal activity (GCA) may be specific to human milk, since unheated cow's and goat's milk were virtually devoid of activity. Much, but not all, of the GCA was lost when NHM was heated or reacted with diisopropylfluorophosphate (DIFP), a specific esterase inhibitor. Activity of the major human milk lipase (BSL, bile salt-stimulated lipase, a fatty acid esterase) was lost after heat or DIFP treatment and was absent from cow's or goat's milk. The parasites were also killed by pure BSL. These studies suggest that BSL may be a heat-labile Giardia-cidal component of NHM.

Animals↗
PubMed1982

Effects of oxygen tension and reducing agents on sensitivity of Giardia lamblia to metronidazole in vitro.

The effects of oxygen tension and reducing agents upon the sensitivity of Giardia lamblia to metronidazole in vitro were determined using two different assays. First, the parasites were exposed to drug under high or low oxygen tension in liquid medium with or without fresh cysteine and ascorbic acid. Survival was determined by colony assay. Second, the effect of thiol reducing agents was measured directly by colony assay in semi-solid media (low pO2 conditions). Trophozoites were strikingly (greater than 100-fold) less sensitive to metronidazole under the aerobic condition of the first assay. In contrast, the reducing agents had much lesser effects (2- to 5-fold) depending upon the assay. Finally, G. lamblia isolated from a patient treated with metronidazole unsuccessfully four times showed similar metronidazole sensitivity to a standard strain under both aerobic and reduced O2 tension conditions.

Animals↗
PubMed1982

Comparative evaluation of selective and nonselective peripheral portosystemic shunts for treatment of variceal hemorrhage.

There is currently available a variety of operative techniques that, by shunting of portal blood into the systemic circulation, decompress esophagogastric varices. Continued evaluation of when to employ a specific type of portosystemic shunt is indicated. This report compares experience with nonselective peripheral portosystemic shunts with selective distal splenorenal shunts. Twenty-nine patients were divided into two operative groups. All patients were operated on for variceal hemorrhage. The two patient groups were similar preoperatively in all parameters evaluated except that the patients having nonselective peripheral shunts had more ascites and four were operated on for acutely bleeding varices, whereas the selective shunt patients had minimal ascites and non were operated on for acute bleeding. Rebleeding rates, incidence of encephalopathy, and long-term survival were not significantly different between the two groups. Eight of 14 (57 percent) patients discharged from the hospital with selective distal splenorenal shunts were alive with a mean follow-up interval of 19 months. Eight of 11 (72 percent) patients discharged with nonselective peripheral shunts were alive with a mean follow-up interval of 34 months. These results suggest that if technical or clinical conditions preclude the performance of a selective distal splenorenal shunt, a nonselective peripheral shunt will produce comparable results and can be used with confidence.

Adult↗
PubMed1982

Bruceantin, a potent amoebicide from a plant, Brucea antidysenterica.

Bruceantin, purified from an Ethiopian plant used to treat dysentery, killed Entamoeba histolytica in vitro (IC50 [the concentration of drug which decreased the number of colonies to half that of controls] = 0.018 microgram/ml). Six related quassinoids of 17 tested were also amoebicidal. No relationship between quassinoid structure and amoebicidal activity was apparent.

Amebicides↗
PubMed1982

Attachment of the flagellate Giardia lamblia: role of reducing agents, serum, temperature, and ionic composition.

The flagellated protozoan Giardia lamblia has been grown only in highly complex media under reduced oxygen tension. Therefore, the organic and physiological requirements for in vitro attachment and short-term (12-h) survival of this organism were determined. In defined maintenance media, a thiol reducing agent (e.g., cysteine) was absolutely required for attachment and survival of this aerotolerant anaerobe. The crude bovine serum Cohn III fraction greatly stimulated attachment and survival. Attachment was decreased at a reduced temperature (24 degrees C as compared with 35.5 degrees C) and absent at 12 degrees C or below. Attachment and survival were strongly dependent upon pH and ionic strength, with optima at pH 6.85 to 7.0 and 200 to 300 mosmol/kg. Sodium chloride was better tolerated than KC1. Reduction of Ca2+ and Mg2+ to below 10(-8) M did not significantly affect attachment.

Animals↗
PubMedDate not supplied

A lipoprotein-cholesterol-albumin serum substitute stimulates Giardia lamblia encystation vesicle formation.

We found previously that the A6 clone of Giardia lamblia strain WB that did not encyst in vitro was blocked at an early stage in differentiation, as it did not form encystation secretory vesicles (ESV) efficiently or express cyst antigens, in comparison with the related clone C6. We now report that A6 formed ESV normally in the suckling mouse model. Therefore, we asked whether our serum-containing encystation media might lack a stimulus or component or contain an inhibitor of ESV formation to which A6 was especially sensitive. We found that replacing bovine serum with a lipoprotein-cholesterol solution and bovine serum albumin (LPC) in pre-encystation and encystation media increased ESV formation by both A6 and C6. The % of A6 cells with ESV increased from 8% in BS medium to 48% in LPC medium, compared with 64% and 98% for C6. Similarly, the average number of ESV/positive cell increased from 1.5 in BS medium to 7.7 in LPC medium for A6, and from 13.3 to 19.7 for C6. Moreover, in LPC encystation media, A6 expressed the cyst wall epitope recognized by monoclonal GCSA-1. Although formation of water-resistant cysts by A6 was increased > 60 fold in LPC media, the numbers of cysts remained only approximately 3-15% that of C6. This suggests that LPC may primarily affect early events in encystation and that A6 may require additional factors later in encystation.

Animals↗