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Biomedical subjects

E Lederer

Publications and source records attributed to E Lederer.

At least 37 records · Page 2Linked to original sources

Urinary sediment changes in severe preeclampsia.

We analyzed the urinary sediment of 30 patients with severe preeclampsia every 4 hours during early labor, delivery, and the postpartum period. Fifteen normal control patients were also followed in a similar fashion. No casts were noticed in the urine samples of the control group. However, the urinary sediment of preeclamptic patients revealed the same uniform pattern regardless of the state of coagulation, or the presence or absence of oliguria or eclamptic seizures. Numerous granular and hyaline casts, red-cell, and tubular cell casts were identified during microscopic evaluation. These data reflect both glomerular and tubular damage in preeclampsia. We conclude that urinary sediment analysis in severe preeclampsia uniformly reflects renal parenchymal damage and does not correlate with or predict the clinical course of the disease.

Adult↗

Electron microscopic study of an unusual posttransplant glomerular lesion.

Glomerular lesions are frequently seen in renal allografts and are usually classified into transplant glomerulopathy and posttransplant glomerulonephritis. The latter is subdivided into donor-related, de novo, and recurrent glomerulonephritis. We report a distinctive posttransplant glomerular lesion that does not fit into any diagnostic category mentioned above. This lesion was characterized by the presence of global, diffuse, subepithelial, electron-lucent deposits, in addition to the usual features of transplant glomerulopathy. This unusual usual lesion, to the best of our knowledge, has been reported only once and, indeed, was recognized in only one of 297 renal allograft biopsy specimens in our file. Although the classification, pathogenesis, and origin of this rare lesion remain to be elucidated, it can be associated with nephrotic syndrome, deterioration of renal function, and eventual graft loss.

Adult↗

Effect of sinefungin on macromolecular biosynthesis and cell cycle of Plasmodium falciparum.

The growth of the malarial parasite P. falciparum was arrested by the adenine containing nucleoside sinefungin at the trophozoite stage. The synthesis of DNA, of polyamines and the specific proteins of the schizont stage were completely blocked by the drug. The inhibition of DNA synthesis was not due to a decrease in the amount of DNA polymerase, but to the depletion of polyamines which are required for DNA synthesis.

Adenosine↗

Management of acute hydronephrosis of pregnancy by ureteral stenting: risk of stone formation.

Acute hydronephrosis of pregnancy has long been managed with ureteral stenting. Although many articles have been published recently concerning stent incrustation none has addressed the etiology. We report a case of accelerated incrustation due to the hypercalciuric state of pregnancy. We propose conservative management with hydration, calcium restriction and close monitoring for infections and stone debris. Antibiotic suppression and stent changes should not be used routinely but rather they should be individualized.

Adult↗

Membranoproliferative glomerulonephritis in Takayasu's arteritis.

The occurrence of glomerulonephritis (GN) in patients with Takayasu's arteritis (TA) is rare. We describe a 28-year-old man with TA who presented with mesangial proliferative GN and subsequently developed membranoproliferative GN with nephrotic syndrome and deterioration of the renal function. The former is the most common type of GN complicating TA, while the latter has not been adequately reported in association with this disease. Although the mechanisms for the initiation and progression of these glomerular injuries are not clear, the present case suggests that a wider spectrum of GN can be seen in patients with TA and that cases of TA with urinary abnormalities should be followed carefully.

Adult↗

Antitoxoplasmosis properties of sinefungin in mice.

Sinefungin, an antifungal and antiviral antibiotic, which also has interesting antiparasitic properties, was examined for antitoxoplasma activity. Mice infected with a lethal dose of Toxoplasma gondii trophozoites, when injected daily for 6 days with the antibiotic, starting 2 days after infection, showed significantly increased survival times especially with the highest dose tested (2.5 mg/kg). No overt clinical signs of toxicity due to Sinefungin were observed.

Adenosine↗

Curative properties of muramyl dipeptide in experimental Naegleria meningoencephalitis.

Naegleria fowleri is a free-living amoeba which causes a fatal meningoencephalitis in man. Mice injected with the immunostimulant MDP or an attenuated 11RX strain of Salmonella enteritidis showed some resistance to an intranasal challenge with N. fowleri. In addition it was observed that some of the mice infected with N. fowleri and showing symptoms of naegleria meningoencephalitis, given a single injection of MDP were cured of this disease. Our findings suggest that the use of immunostimulants could be a new approach in the quest for therapeutic agents for this disease.

Acetylmuramyl-Alanyl-Isoglutamine↗

New developments in the field of synthetic muramyl peptides, especially as adjuvants for synthetic vaccines.

MDP (N-acetylmuramyl-L-alanyl-D-isoglutamine), the first synthetic peptidoglycan derivative capable of replacing whole mycobacteria in Freund's complete adjuvant, is highly active in stimulating antibody production. It also produces delayed hypersensitivity and stimulates non-specific resistance. MDP itself is pyrogenic but murabutide (N-acetyl-muramyl-L-alanyl-D-glutamine-n-butyl ester) is not pyrogenic and is undergoing clinical trials. MDP and its derivatives will prove useful as adjuvants, especially for the "new generation" of synthetic vaccines, which will be discussed in detail. They are also interesting for increasing host resistance against various bacterial and parasitic infections and in experimental tumour immunotherapy. MDP and its derivatives, such as murabutide, will also prove useful in combination with chemotherapy, especially for immunodepressed and elderly patients. Some muramyl peptides are also active in prolonging slow wave sleep in rabbits, cats and monkeys. Muramyl peptides are typical bacterial metabolites, which are apparently essential for establishing a normal immune status and slow wave sleep; they thus represent a new category of vitamins.

Acetylmuramyl-Alanyl-Isoglutamine↗

Vaccination of rabbits against Entamoeba histolytica with aqueous suspensions of trehalose-dimycolate as the adjuvant.

Rabbits were immunized with soluble Entamoeba histolytica antigen with an aqueous suspension of trehalose-6,6'-dimycolate used as the adjuvant. Induction of protective immunity in the immunized animals was demonstrated by enhanced humoral and cell-mediated immune responses and 100% survival after challenge. Administration of soluble antigen only failed to induce a similar degree of protective immunity. Trehalose-6,6'-dimycolate alone produced only a slight increase in nonspecific resistance.

Adjuvants, Immunologic↗

Activation of macrophage cytostatic and cytotoxic activity in vitro by liposomes containing a new lipophilic muramyl peptide derivative, MDP-L-alanyl-cholesterol (MTP-CHOL).

The ability of liposomes containing a new lipophilic muramyl peptide derivative, MDP-L-alanyl-cholesterol (MTP-CHOL), to induce peritoneal macrophage cytostatic activity and alveolar macrophage cytotoxic activity toward tumor cell targets in vitro was determined. MTP-CHOL was shown to be efficiently incorporated and subsequently retained in distearoylphosphatidylcholine/phosphatidylserine liposomes (DSPC/PS; 7:3 molar ratio), whereas hydrosoluble muramyl dipeptide (MDP) was rapidly lost due to leakage. Liposomes containing MTP-CHOL were able to stimulate mouse peritoneal macrophage cytostatic activity under conditions where free MDP was without effect. MTP-CHOL incorporated into liposomes was approximately eightfold more effective than liposomes containing entrapped MDP and 7,400-fold more effective than free MDP in inducing rat alveolar macrophage cytotoxic activity. These results provide evidence that the coupling of MDP to a lipophilic molecule, cholesterol, results in the formation of a viable liposome formulation that is a potent inducer of macrophage-mediated antitumor activity.

Acetylmuramyl-Alanyl-Isoglutamine↗

Muramyl peptides. Variation of somnogenic activity with structure.

Sleep-promoting activities of muramyl dipeptide (MDP) (NAc-Mur-L-ala-D-isogln) and the naturally occurring muramyl peptide(s), factor S, have recently been demonstrated. We now have amplified our understanding of structural requirements for somnogenic activity. The effects of several analogs of MDP on rabbit slow-wave sleep are presented and these results are compared to the dose-response relationship for MDP. Some tentative conclusions as to structural requirements for somnogenic activity are presented; most notably, amidation of the free gamma-carboxyl of MDP and several of its analogs resulted in the loss of somnogenic activity. MDP also can induce febrile and immunostimulatory responses. In the present paper, we show that some analogs possess immunostimulatory and pyrogenic activity but not somnogenic activity, thus suggesting that these biological activities of muramyl peptides may, in part, be mediated by separate mechanisms.

Acetylmuramyl-Alanyl-Isoglutamine↗

Amoebicidal activity of the antifungal antibiotic sinefungin against Entamoeba histolytica.

The antifungal antibiotic sinefungin, a potent inhibitor of methyl transferases and a potential inhibitor of polyamine biosynthesis, exhibited marked cytolytic activity against Entamoeba histolytica in vitro with respect to all the amoeba strains tested. Strains of high and low virulence displayed equal sensitivity to the antibiotic. Minimal Amoebicidal Concentration was 5 to 10 micrograms/ml.

Adenosine↗

Comparison of immunomodulatory activities in mice and guinea pigs of a synthetic desmuramyl peptidolipid triglymyc.

A nonpyrogenic desmuramyl peptidolipid, 1-O-(L-alanyl-D-isoglutaminyl-L-alanyl-glycerol-mycolate), had previously been shown to be inactive as adjuvant in guinea pigs, but to be very active in stimulating nonspecific resistance. We now show that 1-O-(L-alanyl-D-isoglutaminyl-L-alanyl-glycerol-mycolate) is capable of enhancing or suppressing the immune responses in mice when injected with or before an antigen. In vivo suppression of the immune response to sheep erythrocytes was also observed with high doses of murabutide, a nonpyrogenic adjuvant-active N-acetylmuramyl-L-alanyl-D-isoglutamine analog. Chemiluminescence measurements with mouse spleen cells show a very strong activity of 1-O-(L-alanyl-D-isoglutaminyl-L-alanyl-glycerol-mycolate) by far superior to the effect obtained with the corresponding muramyl peptide, N-acetylmuramyl-L-alanyl-D-isoglutaminyl-L-alanyl-glycerol-myco late.

Acetylmuramyl-Alanyl-Isoglutamine↗

Antitrypanosomal activity of sinefungin.

Sinefungin, a naturally occurring antifungal antibiotic nucleoside containing an ornithine residue, linked by a C-C bond to C-5' of adenosine, cures mice infected with Trypanosoma brucei brucei, T. congolense, or T. vivax; the effect of the drug is more pronounced towards T. congolense. Anti-trypanosomal activity of sinefungin could be the result of the inhibition of transmethylation reactions or of polyamine biosynthesis--or both--in parasites.

Adenosine↗