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Biomedical subjects

H Wolf

Publications and source records attributed to H Wolf.

At least 307 records · Page 17Linked to original sources
PubMed1994

29-week doxazosin treatment in patients with symptomatic benign prostatic hyperplasia. A double-blind placebo-controlled study.

In a placebo-controlled study, the safety and efficacy of the selective alpha 1-adrenoceptor-blocking agent doxazosin 4 mg once daily in the symptomatic treatment of benign prostatic hyperplasia (BPH) were evaluated. One hundred patients were primarily included in a 9-weeks study, and after this 75 patients accepted to continue in the present 20 weeks extension. Of the patients in the doxazosin-group (DG) 61% reported overall improvement against 53% in the placebo-group (PG)--(p = 0.56). In the DG, 49% of obstructive symptoms were improved compared to 27% in the PG (p < 0.01), and a reduction of 60% of irritative symptoms was found in the DG against 36% in the PG (p < 0.01). Daytime frequency was reduced by median 1.5 in the DG and remained unchanged in the PG (p < 0.01). Nocturia was reduced by median 1 and 0.5 respectively (p = 0.06). Maximum urinary flow rate (MFR) was improved by median 1.5 ml/s in the DG, while it deteriorated by median 0.5 ml/s in the PG (p < 0.05), Considering postvoid residual urine volume, cystometry variables (first sensation and bladder capacity), changes in sexual function and adverse events there was no difference between the two groups. In conclusion, doxazosin 4 mg once daily in long-term treatment of patients with BPH reduces both obstructive and irritative symptoms, daytime voiding frequency and although only slightly, significantly augments MFR without interference with sexual function and without other serious adverse effects.

Aged↗
PubMed1994

A comparison of the resolution provided by different imaging systems and display media in surgery.

In microsurgery and in endoscopy in particular, the resolution provided by different imaging systems and display media is often a subject of discussion. Starting with the concept of contrast transfer, the terms pixel, pixel availability, and pixel acceptance are then introduced here. These parameters are determined for the applications relevant in practice for endoscopes, surgical microscopes, and the associated display media (eye, 35 mm film, video camera, and monitor). A comparison between pixel availability and pixel acceptance also allows a comparison between the different display media and the determination of the limiting factor in the image reproduction chain.

Endoscopes↗
PubMed1994

Induction of a MHC class I-restricted, CD8 positive cytolytic T-cell response by chimeric HIV-1 virus-like particles in vivo: implications on HIV vaccine development.

New insights into HIV-pathogenesis suggest that the cell mediated immune response might play a crucial role in controlling HIV infection by suppressing HIV-replication in CD4-positive cells by a lymphokine-like soluble factor and by killing HIV-infected cells via classical CTL mediated lysis. This type of a cellular immune response rather than an antibody response seems to be most promising to protect if not from infection, so at least from disease. Therefore rationally designed candidate vaccines should be capable of inducing a cell mediated immunity in addition to a humoral immune response. In order to avoid adverse side effects upon immunization, carefully selected antigens and epitopes should be presented in a favourable manner to the immune system. In previous experiments, we could demonstrate that the gag-polyprotein precursor, known to include a series of T-helper and CTL epitopes, assembles to highly immunogenic, complete noninfectious HIV-1 virus-like particles (VLP). Based on these VLP we developed a novel antigen presentation system, which allows the presentation of selected epitopes derived from HIV reading frames other than gag to the immune system. Alternatively complete derivatives of the HIV-1 external glycoprotein can be presented by the VLP. Immunological analysis of different VLP preparations in a BALB/c mouse model revealed the induction of a strong CTL response. The significance of these observations for future vaccine strategies is discussed.

AIDS Vaccines↗
PubMed1994

[Enhanced antibody production by lung lymphocytes after oral immunization with Bordetella pertussis surface antigens].

The purpose of our study was to evaluate the effect of oral vaccination with Bordetella pertussis surface antigens on the immune response at the site of antigen application. We orally immunized female BALB/c mice on five consecutive days and repeated this procedure after a free interval of 10 days. Lymphocytes of the lung (LL), Peyer's patches (PPL) and lamina propria of the gut (LPL) were isolated and the immunoglobulin secretion rate was measured with time-resolved immunofluorescence. Oral immunization was found to enhance the IgA secretion rate by 69.9% in LL compared to unimmunized animals. The IgG synthesis in LL was increased by 28.1% and the IgM synthesis by 14.1%. In addition, an improvement of 47.8% was observed for the IgG secretion in LPL and PPL. Thus, our results demonstrate a strong local immune response after oral immunization with Bordetella pertussis.

Administration, Oral↗
PubMed1994

Natural history of carcinoma in situ of the urinary bladder.

Thirty-one patients with primary or secondary carcinoma in situ of the urinary bladder were followed in an intensive surveillance program to study the untreated natural history of carcinoma in situ. Few patients received any treatment for carcinoma in situ. The patients were followed for up to 14 years, to disease progression or decrease from other causes than untreated cancer. All patients except three experienced new tumour growths, of these 50% within the first year of follow-up. At 5 years of follow-up half of the patients had experienced progressing disease, i.e. muscle invasion, upper tract invasive cancer or metastases. Most patients would seem eventually to experience progressing disease. Short-term results of treatment with BCG should be viewed on background of such long-term follow-up of untreated carcinoma in situ.

Aged↗
PubMed1994

[Results of Shouldice femoral hernia repair. A prospective study of 94 operations].

At the Department of Surgery, RWTH Aachen, 89 patients with femoral hernia were operated upon between December 1, 1985 and November 30, 1993 and prospectively analyzed. Five patients had a bilateral hernia, 55 were located on the right and 29 on the left side. In 35.1% the operation was performed for incarceration and in 7 cases segments of small intestine had to be removed. Reparation was routinely done in a continuous double-layer technique. Local anaesthesia was mostly used in recent elective cases. Postoperatively, we saw 2 superficial wound infections an 5 subcutaneous fluid collections which had to be aspirated. There was no mortality. Average postoperative time in hospital was 5.5 days. Three recurrences were seen during follow-up. Routine ultrasound in cases of suspected femoral hernia helps to prevent delay of surgical therapy. The positive results justify the application of this technique even in the event of incarceration.

Adolescent↗
PubMed1993

The inhibitory motoneurons of crayfish thoracic limbs: identification, structures, and homology with insect common inhibitors.

The three inhibitory motoneurons supplying crayfish thoracic limbs were identified, stained, and compared structurally. The inhibitors to the walking leg muscles (in Orconectes) were identified anatomically by a combination of immunocytochemical staining for gamma-aminobutyric acid (GABA) or glutamate decarboxylase and differential backfill staining with nickel and cobalt ions. The cheliped inhibitors were identified intracellularly and injected with Lucifer Yellow (Pacifastacus) or cobalt (Procambarus). The common inhibitor (CI) in each thoracic segment has a medial or slightly contralateral soma near the ganglion's posterior boundary, a gently curving primary neurite, an extensive ipsilateral dendritic tree, and an axon emerging through the anterior root. The stretcher-closer inhibitor (SI) has a soma slightly anterior and ipsilteral to the CI's a sharply bent proximal neurite, a smaller dendritic tree, and an axon in the posterior root. The opener inhibitor (OI) lies more laterally and often posterior to the CI; its diagnoally directed neurite enters the posterior root. The inhibitors' structures were related to major neuroanatomical landmarks within the ganglion, to soma positions of excitatory motoneurons revealed by backfilling, and to soma locations of inhibitory interneurons revealed by GABA-like immunoreactivity. In their peripheral distributions to the leg muscles and in their central structures, these crayfish limb inhibitors show striking similarities with those of the locust. Crayfish and locust thoracic ganglia also show more general neuroanatomical similarities. These observations suggest that the crayfish CI, SI, and OI are, respectively, homologous with the locust CI1, CI2, and CI3. The implications of such a homology for arthropod phylogeny are discussed.

Animals↗
PubMed1993

Identification of a region in the Pr55gag-polyprotein essential for HIV-1 particle formation.

The pr55gag polyprotein of HIV-1 plays a critical role in the formation of immature virus particles in the cell and during the budding process. We investigated the influence of amino acid substitutions in the p24CA- region of the gag polyprotein on the viral assembly process. Deletion of the amino acids 341-352 in the carboxy terminal part of the p24CA resulted in a loss of the capacity of the gag polyprotein to form virus-like particles when expressed in eucaryotic cells by recombinant vaccinia virus. In further experiments it turned out that the amino acids 341-346 and 350-352 are important for the ability of the pr55gag to form virus-like particles. Because these stretches are conserved among HIV-1, HIV-2, SIV, and FIV, we conclude that these amino acids form a domain highly important for the assembly of these lentiviruses.

Amino Acid Sequence↗
PubMed1993

Iodine-123 labelling of atrial natriuretic peptide and its analogues: initial results.

Receptors for atrial natriuretic peptide (ANP) are known to be present in many organs, e.g. brain, liver and kidney. The aim of this study was to optimize the labelling method for ANP analogues with iodine-123 and to describe their pharmakokinetics. ANP 99-126, atriopeptin III, Tyr-atriopeptin II and urodilatin were labelled by the Iodogen method. Of the various labelling conditions tested, the Iodogen procedure with 10 micrograms Iodogen, 10 micrograms peptides in 100 microliters phosphate buffer (pH 7.2) and a reaction time of 60 min proved to be optimal. Separation was performed using a Sep-pak reversed-phase extraction cartridge. In all cases quality control by thin-layer chromatography resulted in a radiochemical purity higher than 98%. After intravenous administration of 15 MBq/kg kinetic profiles of various organs in rabbits were investigated by whole-body scintigraphy with a gamma camera. Organ kinetics showed accumulation and excretion via the kidney. No bowel accumulation was observed. Interestingly, increasing tracer uptake in the head region was registered with three of the four tested tracers. Liver accumulation decreased rapidly during the first 40 min. No tracer degradation was registered over the whole time period, as shown by the low thyroid accumulation with a maximum of only 1%. Thus, labelling of ANF and its analogues is possible. These compounds seem to be of interest for further experiments and perhaps clinical studies because of their potential for brain receptor imaging.

Animals↗
PubMed1993

The lytic transition of Epstein-Barr virus is imitated by recombinant B-cells.

Lytic transition of Epstein-Barr virus (EBV) is initiated by distinct immediate early regulators of the viral cycle, in synchronization to temporary, permissive conditions during host cell differentiation. We developed eukaryotic vectors suitable to imitate the processes involved in lytic transition in cell culture systems. Two stable B cell lines were established: R59Z activator cells were used to induce lytic EBV expression in a constitutive manner by the production of the BZLF 1 trans-activator (Zta). R7-57 reporter cells, on the other hand, signaled induced activity of the lytic origin of EBV replication (ori Lyt). Different modes, like chemical induction, lytic superinfection with EBV and single gene trans-activation converted the recombinant ori Lyt element in R7-57 reporter cells. BZLF 1, transiently expressed in R7-57 reporter cells, was the only EBV trans-activator found, sufficient in inducing the viral lytic cycle. Basing on these experiments, trans-cellular activation of EBV was tested by cocultivation of BZLF 1-expressing R59Z activator cells with the R7-57 reporter line. No lytic effect on the reporter cells could be measured, neither by cocultivation of activator cells nor by coincubation of BZLF 1-containing cell lysates. Latency breaking activity, however, was transferred from activator to reporter cells when active, exogenous virus was added. The cell system described in these experiments provides a tool for the detection of EBV reactivation and demonstrates the potential of the lytic regulatory gene BZLF 1.

Animals↗
PubMed1993

Serological diagnosis of infectious mononucleosis using three anti-Epstein-Barr virus recombinant ELISAs.

A new Epstein-Barr virus (EBV) ELISA system (Biotest Anti-EBV recombinant) was evaluated for usefulness for routine diagnosis of EBV primary infection. The assay system is composed of three different microtest plates coated with three highly purified recombinant EBV antigens. The early antigens p138 (BALF2, truncated) and p54 (BMRF1, whole sequence) are used as a mixture for testing IgM (assay 1) and IgG (assay 2) antibodies. In addition, the EBNA-1 antigen p72 (BKRF1, carboxy-half) is used for detecting IgG antibodies (assay 3). Three panels of sera were examined in direct comparison with standard immunofluorescence (IF): Specimens of (i) 120 infectious mononucleosis (IM) patients, (ii) 60 patients with acute CMV infection, toxoplasmosis or rheumatic disease, respectively, and (iii) 185 healthy blood donors as a control group. 119 IM patients were clearly recognized as having acute primary infection (sensitivity 99.2% compared to VCA-IgM by IF). Three apparently false-positive results were obtained with patients of other diseases and none within the control group (specificity 98.8%). The data suggest that the recombinant ELISA can be used advantageously for standardized rapid diagnosis of acute EBV primary infection.

Adolescent↗
PubMed1993

Determination of placental ferritin-positive peripheral lymphocytes in early stages of breast cancer.

"Ferritin-blocked lymphocytes" or placental ferritin (PLF) -positive T cells have repeatedly been described in the circulation of patients with female breast cancer. Since a monoclonal antibody directed against PLF became available, a study was performed to evaluate its usefulness in an easily reproducible system. One hundred patients with controversial or highly suspicious findings on mammography who subsequently underwent operation entered this trial. Sixty-one healthy blood donors served as controls. Patients with early (lymph-node negative) stages of breast cancer (in situ and T1N0 tumors) revealed significantly higher numbers of PLF-positive cells (9.00% +/- 4.5% and 6.21% +/- 3.4%) as compared with controls or patients with benign lumps (p < 0.001). Patients with negative lymph nodes differed significantly from node-positive patients (9.79% versus 2.55%; p < 0.001), whereas no difference as related to menopausal and estrogen-receptor status was observed. In order to define the sensitivity and specificity of this test, we analyzed four different cutoff levels (3%, 4%, 5%, and 6% of PLF-positive T cells). At a level of PLF-positive lymphocyte cells of 4%, 94% of cancer patients with stage T1N0 disease or ductal carcinoma in situ, 5% of patients with benign lumps, and 7% of healthy controls were identified. Furthermore, 88% of all lymph node-negative cancer patients had more than 4% positive cells, compared with only 25% in patients with axillary node involvement. The fact that more than 90% of all patients with in situ carcinomas and patients with stage T1N0 cancer had values above 4% offers promising aspects for this method to be used to complement mammography in the early detection of breast cancer.

Adult↗
PubMed1993

Regulation of cytochrome P450 gene expression in human colon and breast tumour xenografts.

It is extremely difficult to identify the factors which regulate the expression of drug-metabolising enzymes in man. To address this problem, we have developed a model involving the use of human tumours grown as xenografts in immune deficient mice. Mice bearing human colon or breast tumours as xenografts were challenged with a range of compounds, known from animal studies to be inducers of cytochrome P450s from a variety of gene families. Almost all of the compounds tested could induce human tumour P450 expression, measured either by Western blot or immunohistochemical analysis. Indeed, the levels of P450s from several distinct gene families or subfamilies including CYP2A, CYP2B, CYP2C, CYP3A and CYP4A were induced. Of particular interest was the profound induction of human P450s by 1,4 bis 2-(3,5dichloro-pyridyloxybenzene)(TCPOBOP), a compound which exhibits a marked species specificity in its ability to induce P450 expression in experimental animals. Induction of a human CYP2B protein by this compound was confirmed by Northern blot analysis and in situ hybridisation for mRNA, indicating that induction occurred at the level of transcription. These studies have a variety of implications: they provide a method for approaching the previously intractable problem of how environmental, hormonal and metabolic factors regulate human P450 genes and other genes involved in drug metabolism; they demonstrate that human tumours express P450s constitutively and that the levels of these proteins can be modulated by exogenous agents.

Animals↗
PubMed1993

Oral administration of a bacterial immunomodulator enhances murine intestinal lamina propria and Peyer's patch lymphocyte traffic to the lung: possible implications for infectious disease prophylaxis and therapy.

LW50020, a bacterial immunomodulator, is a preparation consisting of seven bacteria, commonly causing respiratory disease. When given orally, LW50020 has been shown to enhance the host defense of the respiratory tract. Intestinal lamina propria lymphocytes (LPL), Peyer's patch lymphocytes (PPL), and splenocytes from BALB/c mice gavaged either with LW50020 or carrier alone were isolated, labeled with either H33342, a supravital nuclear fluorochrome, or 51Cr, and injected i.v. into untreated, age-matched BALB/c mice. Two hours later, spleen, liver, lung, kidneys, Peyer's patch, and mesenteric lymph nodes of the recipients were harvested and screened for the presence of labeled cells. LPL from mice gavaged with carrier only (controls) migrated preferentially to the lung, PPL equally well to the lung, and the spleen and splenocytes were found mostly in the spleen. LPL and PPL from LW50020-treated mice were found in significantly larger numbers in the lungs of recipients than LPL and PPL from control animals. Both labeling techniques gave roughly the same results. Sixty-five per cent of LPL in the lung were Thy-1.2+ and 20% B cells. These findings should contribute to the understanding of parameters necessary for the assessment of the mode of action and efficacy of immunomodulation and vaccination via the mucosa-associated lymphoid tissue.

Adjuvants, Immunologic↗
PubMed1993

Induction of cytolytic T lymphocytes directed towards the V3 loop of the human immunodeficiency virus type 1 external glycoprotein gp120 by p55gag/V3 chimeric vaccinia viruses.

T cell-mediated cytotoxicity may play an important role in controlling infection by human immunodeficiency virus (HIV). In order to study the ability of rationally designed antigens to induce cytolytic T lymphocytes (CTLs) we replaced stretches of 30 to 50 amino acids at the p17-MA/p24-CA cleavage site, within the p24-CA moiety and within the p6-LI portion of the HIV type 1 p55gag precursor by the third variable domain (V3) of the external glycoprotein gp120. This site is known to be a target for CTL attack in mice and humans. The chimeric antigens were recombined into highly attenuated vaccinia viruses in order to investigate class I major histocompatibility complex (MHC)-restricted presentation of antigenic V3 peptides. Immunoprecipitation and Western blot analysis of the group-specific antigen (p55gag)/V3 chimeric proteins demonstrated significant differences in the accessibility of the V3 domain for a monoclonal antibody or polyclonal V3-specific antisera, depending on the position of the V3 loop within the p55gag carrier protein. Immunization of BALB/c mice with three variants of p55gag/V3 recombinant vaccinia virus, however, resulted in a comparable priming of CD4-CD8+ CTLs in vivo irrelevant of the position of the V3 loop within p55gag. Local conformational changes, including the V3 domain within the p55gag/V3 chimeras, did not demonstrate a significant effect on V3-specific lysis of the target cells when compared to the authentic gp120 envelope protein. Class I MHC-restricted CTLs induced by a V3 consensus sequence cross-reacted perfectly with the LAI strain-derived V3 loop sequence. These data indicate that the combination of selected epitopes (V3) with immunologically relevant complex carrier proteins (p55gag) can be accomplished without the loss of biological activity.

AIDS Vaccines↗