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Biomedical subjects

D Wolf

Publications and source records attributed to D Wolf.

At least 55 records · Page 3Linked to original sources
PubMed1999

Induction of Fas ligand expression by HIV involves the interaction of Nef with the T cell receptor zeta chain.

During HIV/SIV infection, there is widespread programmed cell death in infected and, perhaps more importantly, uninfected cells. Much of this apoptosis is mediated by Fas-Fas ligand (FasL) interactions. Previously we demonstrated in macaques that induction of FasL expression and apoptotic cell death of both CD4(+) and CD8(+) T cells by SIV is dependent on a functional nef gene. However, the molecular mechanism whereby HIV-1 induces the expression of FasL remained poorly understood. Here we report a direct association of HIV-1 Nef with the zeta chain of the T cell receptor (TCR) complex and the requirement of both proteins for HIV-mediated upregulation of FasL. Expression of FasL through Nef depended upon the integrity of the immunoreceptor tyrosine-based activation motifs (ITAMs) of the TCR zeta chain. Conformation for the importance of zeta for Nef-mediated signaling in T cells came from an independent finding. A single ITAM motif of zeta but not CD3epsilon was both required and sufficient to promote activation and binding of the Nef-associated kinase (NAK/p62). Our data imply that Nef can form a signaling complex with the TCR, which bypasses the requirement of antigen to initiate T cell activation and subsequently upregulation of FasL expression. Thus, our study may provide critical insights into the molecular mechanism whereby the HIV-1 accessory protein Nef contributes to the pathogenesis of HIV.

Fas Ligand Protein↗
PubMed1999

Enteroaggregative and enterotoxigenic Escherichia coli among isolates from patients with diarrhea in Austria.

In a 3-month prospective study among 203 Austrian outpatients with diarrhea, the role of pathogenic Escherichia coli and the use of the polymerase chain reaction in screening Escherichia coli isolates from clinical stool specimens were evaluated. Enteroaggregative Escherichia coli and enterotoxigenic Escherichia coli combined were identified as the second most frequent cause of diarrhea. Of a total of 85 bacterial pathogens isolated from 80 patients, 15 were pathogenic Escherichia coli, 13 enteroaggregative Escherichia coli and two enterotoxigenic Escherichia coli. Enteropathogenic, enteroinvasive, and enterohemorrhagic Escherichia coli isolates were not detected.

Adolescent↗
PubMed1999

Preprocessing of control portal images for patient setup verification during the treatments in external radiotherapy.

The main problem in processing the control portal images is their poor quality. We have developed a way of improving the image quality to allow a segmentation stage. Three items were studied for this purpose the background gradient of intensity correction, the noise reduction, and the image restoration. The background was corrected by subtracting a smoothed version of the image from the original. We tested 15 noise reduction methods. The most appropriate for control portal images was found to be the truncated average. Finally, four restoration techniques were compared. The maximum a posteriori (MAP) algorithm was the most efficient. The algorithms were tested over a wide range of conditions (image quality). They produced a great improvement in anatomic detail for all the imaging systems, energies, and anatomical zones tested. For example, the signal-to-noise ratio of a SRI-100 pelvis image, acquired with 4 monitor units (MU) at 10 MV (very low quality image), increased from 0.97 to 42.84 after preprocessing. We found that the improvement in image quality facilitated or even enabled segmentation of the control portal images. The percentage of segments belonging to a structure increased from 30% to 65% in the example cited. The preprocessing of control portal images is the first step in checking the patient setup.

Algorithms↗
PubMed1999

Control portal images enhancement.

The general aim of our study is the patient setup verification using control portal images during the treatments. The main problem of the control portal images processing is their poor quality. We investigated a way of improving the image quality in order to allow a segmentation stage. Four items were studied for this purpose: the presence of distortion, the background gradient of intensity correction, the noise reduction, and the image restoration. The absence of significant distortion was checked with a grid pattern phantom. The background correction was performed by the subtraction from the original image of a smoothed version of this image. We tested 14 noise reduction methods. The most appropriate for our images is the truncated average. Four restoration techniques were compared. The Maximum a Posteriori algorithm is the most efficient. For all the imaging systems, the energies, and the anatomical zones tested an important improvement in anatomic detail was apparent. For example, the SNR of a SRI-100 pelvis image (4 monitor units at 10 MV), went up from 0.97 to 20.06 after enhancement. The image quality improvement will facilitate or enable the segmentation of the control portal images. It is the first step in the patient setup verification.

Humans↗
PubMed1998

New diterpene isonitriles from the sponge Phakellia pulcherrima.

Seven new diterpene isonitriles and isothiocyanates were isolated from the sponge Phakellia pulcherrima along with eight known ones. Six of the new compounds, 9-14, and the eight known ones, 1-8, belong to the kalihinol family of diterpenes. Structures were determined from spectroscopic data. This is the first report of diterpenes from sponges of this genus. All of the other kalihinol diterpenoids have been isolated from the sponge Acanthella cavernosa collected in diverse locations.

Animals↗
PubMed1998

Single-dose antibiotic prophylaxis in transurethral resection of the prostate: a prospective randomized trial.

OBJECTIVE: To evaluate the efficacy of single-dose antibiotic prophylaxis in transurethral resection of the prostate (TURP). PATIENTS AND METHODS: A total of 139 patients were entered into a prospective randomized trial comparing single-dose antibiotic prophylaxis with no antibiotic before surgery. Twelve patients were excluded because they had significant bacteriuria before surgery (defined as > or = 10(5) bacteria/mL). Of the remaining 127 patients, 62 were allocated to the single-dose group (A) and 65 to the no-antibiotic group (B). All 62 patients in group A received 1 g of ceftriaxone intravenously 1-2 h before surgery with the anaesthetic premedication, the 65 in group B receiving none. Urine cultures were collected post-operatively as the catheter was removed and again 4 weeks after hospitalization. RESULTS: The incidence of post-operative bacteriuria was statistically significantly different, occurring in five patients (9%) in group A and 16 patients (26%) in group B (Fisher's exact test, one-tail P = 0.009). There was no significant difference between the groups 4 weeks after hospitalization. The overall incidence of bacteriuria post-operatively and 4 weeks after hospitalization was 11 patients (18%) in group A and 22 patients (34%) in group B (P = 0.03). CONCLUSION: Single-dose antibiotic prophylaxis with 1 g of ceftriaxone intravenously is effective in patients undergoing TURP and is recommended for such surgery.

Antibiotic Prophylaxis↗
PubMed1998

Vitamin E: the radical protector.

Since its discovery and isolation the importance of vitamin E in maintaining normal physiologic processes and its value in treating various disease states have been the subject of much controversy. It was our intention to review and highlight some of the arguments and problems regarding the usefulness of vitamin E and to try to put them into proper perspective. The major area of interest concerning vitamin E lies essentially in its role in preventing damage caused by free radicals. The latter are now known to play an important role in radiation induced carcinogenesis, photoaging and photosensitization. The chemistry of vitamin E, its physiological function as a major antioxidant and its interaction with other antioxidants are described by the sum of animal studies, in vitro research and epidemiological investigations. In preparing the current data, it appeared that despite the controversy and conflicting results the body of literature as a whole judges vitamin E to be useful as an antioxidant. Although, in principle, the use of vitamin E can be quite advantageous, the manner of its administration, especially regarding topical application, remains unclear.

Animals↗
PubMed1997

Combined lesions of perirhinal and entorhinal cortex impair rats' performance in two versions of the spatially guided radial-arm maze.

The present study examined the effects of combined lesions of the entorhinal and perirhinal cortex (PRER) on performance of two versions of the spatially guided eigh-tarm radial maze. In the first version, all arms were baited and in each session the rats were allowed to explore the maze freely until they retrieved all of the reinforcers. PRER subjects were profoundly impaired in performance of this task, making fewer correct choices and more total errors than control subjects. In the second task, a delayed nonmatching to sample version of the radial-arm maze, each daily session was separated into two phases. In the first, predelay phase, four arms were open and the remaining four arms were blocked with clear Plexiglas barriers; subjects were permitted to visit each of the four arms and retrieve the reinforcers. In the second, postdelay phase, the subject was placed on the maze with free access to all eight of the arms, but only those arms that were blocked in the predelay phase contained reinforcers. Delays of either 10 min or 30 s separated the pre- and postdelay phases. PRER subjects were significantly impaired in their performance of this task at both delays, making fewer correct choices and more errors than controls; the magnitude of this deficit was not dependent on length of delay. These data suggest that, along with the hippocampal formation, the entorhinal and perirhinal cortices actively participate in the acquisition and performance of appetitively motivated spatial memory tasks.

Analysis of Variance↗
PubMed1997

Characterization of the muscarinic receptor subtype(s) mediating contraction of the guinea-pig lung strip and inhibition of acetylcholine release in the guinea-pig trachea with the selective muscarinic receptor antagonist tripitramine.

1. The muscarinic receptor subtypes mediating contraction of the guinea-pig lung strip and inhibition of the release of acetylcholine from cholinergic vagus nerve endings in the guinea-pig trachea in vitro have previously been characterized as M2-like, i.e. having antagonist affinity profiles that are qualitatively similar but quantitatively dissimilar compared to cardiac M2 receptors. The present study sought to establish definitely the identity of these receptor subtypes by using the selective muscarinic receptor antagonist, tripitramine. Guinea-pig atria and guinea-pig trachea (postjunctional contractile response) were included for reference. 2. It was found that tripitramine antagonized methacholine-induced contractions of the guinea-pig lung strip with pKB value of 8.76 +/- 0.05. Both the parallel shifts of the concentration-response curves and the slope of the Schild plot begin not significantly different from unity (when antagonist preincubation was for 2 h) indicated the involvement of a single population of receptors in the contractile response. From the pKB values obtained with tripitramine and a range of other selective muscarinic receptor antagonists (cf. Roffel et al., 1993), this single population of receptors can only be classified as M2-like. 3. Tripitramine antagonized methacholine-induced chronotropic and inotropic responses in guinea-pig right and left atria with apparent pKB values of 9.4-9.6. However, such values were only obtained when antagonist preincubation was relatively long and/or antagonist concentration relatively high (e.g with 1 h at 100 or 300 nM but 3 h at 30 nM). It thus appears that low concentrations of tripitramine do not readily equilibrate with M2 receptors in guinea-pig atria nor with M2-like receptors in the guinea-pig lung strip. 4. Tripitramine increased electrical field stimulation-induced cholinergic twitch contractions in guinea-pig trachea in concentrations of 0.3-100 nM, by blocking prejunctional muscarinic inhibitory autoreceptors; with higher concentrations, twitch contractions were progressively diminished, as a result of blocking postjunctional M3 receptors (apparent pKB value 6.07 +/- 0.15). The pEC20 value (-log concentration that increases twitch by 20% maximum) was 8.29 +/- 0.08, which would suggest that M4 receptors are involved in this response. 5. Oxotremorine-induced inhibition of the release of prelabelled [3H]-acetylcholine from guinea-pig trachea, under conditions where there is no auto-feedback, was blocked by tripitramine (2 h preincubation) with a pKB value of 8.56 +/- 0.06. The slope of the corresponding Schild plot was not significantly different from unity, which together with the parallel shifts of the concentration-response curves indicated the involvement of a single muscarinic receptor subtype. 6. Since the pKB value for tripitramine at prejunctional receptors in guinea-pig trachea is in between the affinities towards M2 and M4 receptors, correlation plots were constructed to compare the pKB values obtained with tripitramine and a range of other selective muscarinic receptor antagonists (cf. Kilbinger et al., 1995) to reported affinities at M1-M4 receptors. This showed rather similar distribution patterns of the data points around the line of equality in the case of M2 and M4 receptor subtypes. However, the correlation coefficient was markedly better for M2 (0.9667) than for M4 (0.5976). Since recent evidence suggests that M4 receptors are not expressed in cholinergic nerves from guinea-pig trachea, it is concluded that prejunctional muscarinic autoinhibitory receptors in this tissue exhibit an atypical M2 type character, with a pharmacological profile distinct from cardiac M2 receptors.

Acetylcholine↗
PubMed1997

Antiviral therapy for recurrent herpes simplex reconsidered.

The purpose of this paper is to present our long-time concern about the safety of using antiherpetic drugs over extended periods of time as a preventive therapy for recurrent herpetic attacks. It has been shown that when herpes simplex virus (HSV) is inactivated and has thus lost its cytolytic activity by exposure to certain chemicals or ultraviolet irradiation, it can cause neoplastic changes in mammalian cells. Therefore, substances that inhibit (but not absolutely eliminate) HSV replication for prolonged periods of time might be of potential danger for the development of cancer. It becomes incumbent upon us to ask ourselves whether the prolonged inhibitory effect of prophylactic antiviral drugs might not carry with it the same risks as has been proposed for other substances known to inhibit viral replication.

Animals↗
PubMed1997

The long-term tolerability of enalapril in hypertensive patients with renal impairment.

There has been some concern raised regarding the safe use of ACE-inhibitors in patients with severe renal insufficiency, including the development of hyperkalaemia in these patients. Therefore, the objective of the current analysis was to evaluate the long-term safety of enalapril in patients with severe renal sufficiency and hypertension. Three protocols with similar randomized, double blind, placebo-controlled designs were selected for analysis. A total of 153 patients, enrolled at six sites, were treated for up to 3 years with enalapril; 164 patients served as controls. One protocol used a fixed dose (5 mg/day) of enalapril, while the other two protocols allowed open titration up to 40 mg/day. The primary comparison was between the enalapril and control populations. For the analysis, patients, by treatment, were grouped according to the degree of renal insufficiency (serum creatinine > or < 3 mg/dl) at baseline. The incidence of the most common, as well as important, clinical and laboratory adverse events for this patient population were summarized. In addition, trends in important laboratory adverse events and the incidence of first-dose events, cough and angioedema were evaluated. The incidence of clinical adverse events was similar for both treatment groups, regardless of the severity of renal insufficiency. Seven patients died, four in the control group and three in the enalapril treatment group; none was considered related to treatment. Enalapril appeared to be well-tolerated in this group of patients with severe renal impairment.

Adult↗