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H Wolf

Publications and source records attributed to H Wolf.

At least 235 records · Page 13Linked to original sources
PubMed1996

Somatostatin receptor scintigraphy in the differential diagnosis of meningioma.

The aim of this study was to evaluate somatostatin receptor scintigraphy (SRS) in patients with meningioma proven or suspected on magnetic resonance imaging (MRI). Prior to surgery, 47 patients were investigated up to 24 h following the injection of 200 MBq 111In-octreotide. Tracer uptake was compared with the histological presence of meningioma. Histology revealed 43 meningiomas, 3 neurinomas and 1 ependymoma. A true-positive SRS result was obtained in 36 patients, in 13 of whom a tumour volume of < 10 ml was noted. A false-negative SRS result was obtained in seven patients, all of whom had a tumour volume of < 10 ml. Whereas MRI alone was decisive in 38 of 47 patients, it could only provide a differential diagnosis in the remaining 9 patients. A positive SRS result confirmed meningioma in five of these patients, and a negative SRS result excluded meningioma in the other four. Therefore, cases of SRS-negative meningioma do exist. Nevertheless, significant clinical benefit can be obtained from functional imaging with 111In-octreotide in patients with an inconclusive MRI result, as large meningiomas can be excluded by scintigraphy alone, whereas meningiomas of any size may be confirmed in combination with specific MRI results.

Adult↗
PubMed1996

The value of bone scanning in pre-operative decision-making in patients with progressive facial asymmetry.

Hemimandibular elongation is characterized by persistent unilateral growth, resulting in unilateral overgrowth of the mandible. The surgical treatment strategy depends on condylar growth activity, which cannot be assessed by conventional radiological procedures. Therefore, this study was undertaken to evaluate the usefulness of bone scanning in hemimandibular elongation. Twenty-seven patients underwent bone scanning prior to surgery. Growth activity was quantified by calculating the L/R ratio. In the case of more pronounced right-sided growth producing a L/R ratio of less than 1, inverse values were used. Corrective osteotomy was performed in the patients with a L/R < 1.10, whereas patients with a L/R > 1.10 underwent condylectomy. Twenty-three patients had a L/R ratio < 1.10 and were followed up for 3 years. In 16 patients, a corrective osteotomy was performed without any relapse post-operatively. Four patients showed marked unilateral increased uptake. In one patient, a pre-operative bone scan was not considered, and corrective osteotomy was performed with subsequent recurrence of unilateral overgrowth of the mandible. The final patient underwent condylectomy without relapse. In two patients, it was decided to repeat the bone scan after a follow-up period of 12 months. In conclusion, bone scanning has significant clinical value in pre-operative decision-making in hemimandibular elongation by guiding surgical strategy with respect to condylar growth activity.

Adolescent↗
PubMed1996

Quantitative salivary gland scintigraphy in the diagnosis of parenchymal damage after treatment with radioiodine.

This study was undertaken to quantify salivary gland parenchymal damage after radioiodine treatment with a standard protective regimen of ascorbic acid. Altogether, 106 patients underwent quantitative salivary gland scintigraphy with 99Tcm-pertechnetate prior to and 3 months after radioiodine therapy. Parenchymal function was quantified by calculating 99Tcm-pertechnetate uptake 13 min post-injection. Patients received 131I doses ranging from 400 MBq to 24 GBq (cumulative). Among the patients who received large doses of 131I, severe parenchymal destruction could be visually analysed as well as quantitatively evaluated. In contrast, after low-dose radioiodine treatment, mild parenchymal impairment was demonstrated by quantitative evaluation only. In conclusion, standardized quantitative salivary gland scintigraphy is essential for the reliable detection of mild parenchymal malfunction. Despite the standard protection regimen using ascorbic acid as a sialogogue, radioiodine therapy induces loss of salivary gland parenchymal function even with low doses of 131I.

Adult↗
PubMed1996

Glutathione S-transferase mu as a risk factor in bladder tumours.

Glutathione transferases are involved in the detoxification of many zenobiotica involved in the etiology of cancer. To investigate the role of the glutathione S-transferase M1 deletion (GSTM1*0/0) in bladder carcinogenesis, the polymerase chain reaction was used to determine the GSTM1 genotypes of cancer patients (n = 234) and hospital controls (n = 202). Overall, the proportion of GSTM1*0/0 in the case group was 57%, compared to 50% in the control group giving an odds ratio (OR) of 1.33, (0.91-1.94; 95% confidence interval (CI)). Dividing the bladder cancer group into incident (n = 87) and surviving case groups (n = 147), a modest association between the GSTM1*0/0 genotype and bladder cancer was found in the surviving group, whereas, in the incident group no association was found. Logistic regression analysis of the incident cases, adjusting for age, gender, and cigarette smoking, revealed ORs of 1.12 (0.61-2.08) and 0.74 (0.33-1.73) for the malignant and benign tumours, respectively. The corresponding adjusted ORs for the surviving cases were 1.81 (1.04-3.13) for benign and 1.43 (0.80-2.56) for malignant tumours. Thus, in this study, the GSTM1 deletion is not a risk factor for the development of bladder cancer, but may be related to the survival of the bladder cancer patients. This finding is very important for the design of case-control studies in general, and for the interpretation of existing data.

Aged↗
PubMed1996

Sequence variability among different parvovirus B19 isolates.

Parvovirus B19 is the causative agent of a variety of clinical manifestations, ranging from asymptomatic to severe infection. The basis for this complex pattern of B19-associated diseases is as yet poorly understood. In general there are two different possibilities: firstly, the infected individuals may have a genetic or acquired predisposition, which renders them susceptible for a certain course of infection; secondly, differences in the B19 genome may result in different outcomes of infection. In order to investigate this second possibility we have partially sequenced the genomes of 20 different B19 isolates derived from serum samples from patients with various B19-associated diseases. Four distinct regions, which cover nearly half of the genome and include parts of the coding regions of all three major B19 proteins-NS1, VP1 and VP2, were selected for sequencing. Comparisons between the different extracted virus isolates at the DNA and protein levels revealed that isolates from patients with persistent parvovirus B19 infection show a tendency towards higher genome variability with respect to isolates derived from persons with acute infection.

Base Sequence↗
PubMed1996

Lymphoproliferative responses after infection with human parvovirus B19.

Immunity after infection with the parvovirus B19 is assumed to be conferred by a humoral immune response with development of neutralizing antibody. In contrast, little is known about the nature of T-cell-mediated responses to parvovirus B19 infection in humans. We used recombinant proteins VP1, VP2, and NS1, as well as a recombinant VP1-specific amino-terminal sequence, to test the proliferative responses of peripheral blood mononuclear cells after infection of otherwise healthy individuals with parvovirus B19. These proteins were used as antigens for the stimulation of freshly isolated cells. The results show that a B19 virus-specific cellular immunity develops that is directed against the capsid proteins VP1 and VP2. We also demonstrate that viral determinants are presented to CD4+ T cells by HLA class II molecules.

Antigens, Viral↗
PubMed1996

Defined amino acids in the gag proteins of human immunodeficiency virus type 1 are functionally active during virus assembly.

A structurally highly ordered arrangement of the polyprotein precursor, Pr55gag is a necessary prerequisite for assembly, budding and maturation of the human immunodeficiency virus type 1 (HIV-1). In particular, distinct regions of the matrix protein (p17) and the capsid protein (p24) contained within Pr55gag are functionally active during these processes. In order to determine such regions we exchanged amino acid triplets within p17 (amino acids 46-61) and p24 (amino acids 341-352) for alanine residues and deleted the whole regions. Synthetic peptides derived from these regions had been shown previously to inhibit the production of infectious virus. The effect of the mutations on the release of viral particles was investigated by using recombinant baculoviruses for the expression of mutated Pr55gag as virus-like particles and by use of the respective HI proviruses for monitoring the production of infectious particles.

Amino Acids↗
PubMed1996

Safety and immunogenicity of recombinant human immunodeficiency virus-like particles in rodents and rhesus macaques.

Data from long-term non-progressing human immunodeficiency virus (HIV)-infected individuals and populations at high risk suggest that an early cytolytic T cell response rather than the humoral immune response might be involved in controlling disease progression. These observations may be used as a guide to the type of response that a vaccine should induce. To clarify the role of different arms of the immune system in conferring protection, the candidate vaccine should allow a regulated, selective induction of different immune responses. Based on a better understanding of the molecular mechanisms regulating the morphogenesis of HIV, we developed an autologous, non-replicating and safe antigen delivery system. This system takes advantage of molecular characteristics of the HIV group-specific antigens (gag) to self-assemble to highly immunogenic virus-like particles (VLP). The immunogenicity of the gag-derived VLP was expanded either by replacing defined domains by selected HIV-1 cytotoxic T lymphocyte (CTL) epitopes (type 1 VLP) or by stable anchoring derivatives of the HIV-1 envelope protein on the surface of the VLP (type 2 VLP). In complete absence of adjuvants, type 1 and type 2 VLP stimulated CD8+ CTL in BALB/c mice, which specifically recognised HIV sequences. In contrast to type 1 VLP, generating an HIV-specific CTL response in the absence of env-specific antibodies, type 2 VLP induced both arms of the immune system including reasonable levels of neutralising antibodies. Initial studies performed in rhesus macaques confirmed these results. Thus, depending on the type and formulation of the VLP, the proposed antigen delivery system allows either the induction of a CTL response (1) in the absence and (2) the presence of an envelope-specific antibody response. A comparison of these approaches in appropriate animal models might contribute to further define the correlates of protection.

Animals↗
PubMed1996

Gain changes in sensorimotor pathways of the locust leg

Feedback systems that control the leg joints of animals must be highly flexible in adapting to different behavioural tasks. One manifestation of such flexibility is changes in the gain of joint control networks. The femur&shy;tibia (FT) control network of the locust leg is one of the feedback systems most thoroughly studied with regard to its neural circuitry. Despite excellent information concerning network topology, however, actual gain changes and their underlying mechanisms have not yet been examined because of the marked spontaneous variations in the action of the control network for this joint. We describe a behavioural situation and a preparation in which the locust (Locusta migratoria L.) FT control network exhibits reproducible changes in gain, allowing investigation of the neuronal basis of gain control. After ('fictive') flight motor activity, the gain of resistance reflexes in the FT joint of the locust middle leg is significantly decreased, with the flexor tibiae muscles being affected more strongly than the extensor muscles. Immediately after flight motor activity, the gain may be as low as 30 % of pre-flight levels. It returns to pre-flight values in under 150 s. The decrease in gain following flight motor activity is due to a decrease in motoneurone recruitment in the resistance reflex elicited by stimulation of the appropriate mechanoreceptor, the femoral chordotonal organ. Motoneurone recruitment is changed as a result of a drastic decline in the stimulus-related synaptic input to the motoneurones, which appears to be produced exclusively at the level of the pre-motor network. Two factors led to this conclusion: first, we found no indication of changes in membrane potential or membrane conductance of the tibia flexor and extensor motoneurones; second, recording from identified pre-motor nonspiking interneurones demonstrated that these may be involved in the observed gain changes. The putative behavioural relevance is discussed.

Journal Article↗
PubMed1996

Bladder squamous cell carcinomas express psoriasin and externalize it to the urine.

PURPOSE: To report a single biomarker, psoriasin (Mr 11.0 kd, pI 6.2), a calcium binding protein which is expressed largely by stratified squamous epithelia and is externalized to the urine of bladder squamous cell carcinoma (SCC) bearing patients. MATERIALS AND METHODS: Protein expression profiles of SCCs obtained immediately after surgery were analyzed by two-dimensional gel electrophoresis and Coomassie blue staining. Protein identity was determined by microsequencing and immunoblotting. Protein expression in cryosections was studied by immunofluorescence. RESULTS: Four patients with SCC were identified from 100 samples of patients with suspected transitional cell carcinoma (TCC). The protein profiles of the 4 SCCs (56-1, grade III, T4; 181-1, grade I, T3; 219-1, grade III, T3 and 239-1, grade not determined, T2-4) resembled that of keratinocytes, suggesting that these cells express an early developmental pattern of gene expression. Besides expressing markers characteristic of keratinizing stratified squamous epithelia, the SCCs exhibited psoriasin, a protein externalized to the medium by keratinocytes. Immunohistochemistry of 3 of the SCCs with psoriasin antibodies showed that the positive cells were confined chiefly to the "squamous pearls." The presence of psoriasin in the urine of the 4 SCC patients was demonstrated by two-dimensional gel immunoblotting. Similar analysis of 43 urines from patients with bladder tumors other than SCC revealed 7 positives, some of which may reflect squamous differentiation. Analysis of the urine of 13 control individuals (12 males matched by age and a 42-year-old female) revealed 2 positives. Immunoblotting of the SCC patients' serum proteins with psoriasin antibodies failed to reveal the protein. CONCLUSION: The results point towards psoriasin, alone or as part of a biomarker profile, as a potential marker for the noninvasive follow-up of patients with SCC.

Adult↗
PubMed1996

Towards a comprehensive database of proteins from the urine of patients with bladder cancer.

PURPOSE: To establish a comprehensive two-dimensional database of proteins from the urine of patients with bladder cancer. MATERIALS AND METHODS: Urines dialized against distilled H2O were freeze-dried and subjected to isoelectrofocusing two-dimensional gel electrophoresis. Coomassie brilliant blue stained dry gels were scanned and analyzed with the PDQUEST software. Proteins were identified by one or more of the following techniques: microsequencing (44 proteins), mass spectrometry, comigration and immunoblotting. RESULTS: The urine protein database, which includes all the polypeptides detected in the urines of 50 patients, lists 339 proteins (including variants) of which 124 have been identified. Of these, psoriasin, the psoriasis-associated fatty acid binding protein 5, the gelsolin fragments and prostaglandin D2 synthetase have not been previously described. CONCLUSIONS: The database provides a solid basis for further studies aiming at identifying tumor markers in the urine that may serve as prognostic factors in bladder cancer.

Amino Acid Sequence↗
PubMed1996

Finasteride in the treatment of benign prostatic hyperplasia.

Finasteride is an enzyme inhibitor which blocks the conversion of testosterone by 5 alpha-reductase to dihydrotestosterone, the active androgenic metabolite in the prostate. In a double-blind, placebo-controlled study, 707 patients with moderately symptomatic BPH were treated for 2 years. The study confirmed that treatment significantly improved symptoms, reduced prostate size and increased urine flow rate. Side effects were usually mild. The authors find that finasteride can reverse the natural progression of BPH.

Aged↗
PubMed1996

A fixed-dose combination of low molecular weight heparin with dihydroergotamine versus adjusted-dose unfractionated heparin in the prevention of deep-vein thrombosis after total hip replacement.

The low dose heparin regimen (LDH) is not appropriate for prevention of intra- and postoperative thromboembolic complications in high risk patients, especially those undergoing elective hip replacement. Despite LDH prophylaxis, the incidence of deep-vein thrombosis (DVT) remains in a range of 20 to 35%. Adjusted-dose unfractionated heparin prophylaxis is thought to be one of the most effective regimens for thrombosis prophylaxis in this indication, but it requires two or three daily injections as well as precise monitoring of the activated partial thromboplastin time (aPTT). As an attractive alternative, we investigated the efficacy and safety of the low molecular weight heparin (LMWH) certoparin combined with dihydroergotamine (DHE) given once daily. In a randomised, open clinical trial, a total number of 305 patients undergoing total elective hip replacement were enrolled and divided into two groups, either receiving a fixed-dose combination of LMWH (3,000 IU) and DHE (0.5 mg) subcutaneously once daily, or adjusted-dose unfractionated heparin (UFH) subcutaneously every 8 h. The UFH dosage was adjusted daily to keep an aPTT of about 50 s. The aPTT was determined 3 h after the morning injection. During the study, the starting dose (15,000 IU/day) was increased to a plateau value of 28,800 +/- 7,150 IU/day (mean +/- SD) to maintain the aPTT in the prescribed range. The plateau value was achieved after 8 postoperative days. For analysis of efficacy 289 patients were evaluable. The occurrence of deep vein thrombosis was determined by bilateral ascending venography, which was performed on the same day in patients with clinical signs suggesting DVT; and in all remaining patients at the end of the prophylaxis period. Deep vein thrombosis was diagnosed in 17 of 142 patients (12.0%) treated with LMWH/DHE and in 13 of 147 patients (8.8%) treated with adjusted-dose UFH. Combined distalproximal thrombosis was more frequently in patients receiving UFH (n = 5; 3.4%) compared to the LMWH/DHE group (n = 2; 1.4%). These differences are statistically not significant. In the UFH group one case of non-fatal pulmonary embolism occurred. Both prophylaxis regimens were well tolerated; wound bleeding was observed in 8 (5.3%) patients in the LMWH group and in 6 (4.0%) patients in the UFH group. Intraoperative blood-loss volume (mean +/- SD) was 751 +/- 339 mL (LMWH/DHE) and 736 +/- 380 mL (UFH), whereas postoperative drain-loss volume (mean +/- SD) was found to be 523 +/- 333 mL (LMWH/DHE) and 581 +/- 404 mL (UFH). Whole blood transfusion volumes (mean +/- SD) were 570 +/- 202 mL (LMWH/DHE) and 748 +/- 455 mL (UFH). Additionally, red cell replacement volumes (mean +/- SD) were 804 +/- 435 mL (LMWH/DHE) and 720 +/- 328 mL (UHF). Revision of wound or additional drainage were necessary in 3 LMWH/DHE and 7 UFH patients. One patient needed reoperation due to bleeding, 3 (2.0%) had petechia and 1 exhibited an allergic exanthema, all of them in the UFH group. A slight erythema at the injection site was observed in 6 (3.9%) patients receiving LMWH/DHE. During the course of prophylaxis, injection hematomas were documented in 57.9% (LMWH/DHE) and in 61.4% (UFH) of the patients. All differences were statistically not significant. Single daily subcutaneous injections of LMWH/DHE appeared to be safe and efficacious compared to adjusted-dose UFH for prophylaxis of DVT in high-risk patients.

Aged↗
PubMed1996

[Stimulation of synthesis of secretory immunoglobulin A in the lung by oral immunization: an approach with therapeutic relevance?].

Due to its strategic position on mucosal surfaces secretory immunoglobulin A (sIgA) is one of the first protective factors of the specific immune system against invading pathogens. As a factor of acquired immunity, the synthesis of sIgA can be modulated by various immunization strategies. Our experiments aimed at the enhancement of the sIgA pool in the lungs by oral immunization. As reported previously, commercially available LW 50020, an immunomodulator consisting of lysates of seven common pneumotropic pathogens, is effective in inducing significant IgA antibody responses in the lungs following oral immunization [1]. In the present study we developed new strategies to enhance this effect by encapsulating LW 50020 into microspheres and liposomes. Microspheres and liposomes with entrapped immunomodulator each enhanced the effect of soluble LW 50020 by about 45% and 90%, respectively. In addition, microsphere based immunization induced a significantly increased immunoglobulin G (IgG) response in the lungs. In further experiments we demonstrated that a similar effect could be achieved by administration of a high molecular weight conjugate of lipopolysaccharide from Klebsiella pneumoniae (LPS) and lipoteichoic acid from Streptococcus pyogenes (LTA). This conjugate enhanced the synthesis of IgA in the lungs by 45% and, furthermore, induced a significantly enhanced IgG response in the lungs, without any obvious toxic or pyrogenic side effects. This new conjugate possibly offers an opportunity to replace the complex immunomodulator LW 50020 by a less complex vaccine.

Adjuvants, Immunologic↗
PubMed1995

A monoclonal antibody-cobra venom factor conjugate increases the tumor-specific uptake of a 99mTc-labeled anti-carcinoembryonic antigen antibody by a two-step approach.

Monoclonal antibodies (mabs) have considerable potential for specific cancer treatment. However, due to the antigen heterogeneity and especially the low uptake in solid tumors, mabs have not been used successfully in most clinical trials to date. This study investigates the effects of a mab-cobra venom factor (CVF) conjugate in vitro and in vivo in an orthotopic pancreatic cancer model using nude rats. CVF, a nontoxic glycoprotein from cobra venom, permanently activates the alternative pathway of complement. Coupled to a mab with tumor-binding properties, the complement activation can be targeted to the tumor tissue. We studied the activity of a mab CA19-9-CVF conjugate with the human pancreatic cancer cells PancTu I. PancTu I cells express the complement resistance factors CD46, CD55, and CD59, as we demonstrated by immunostaining, an observation that may explain the lack of cytotoxicity of the CA19-9-CVF conjugate. However, using ELISA, Western blot, and immunostaining, we showed that CA19-9-CVF activates the complement cascade, including the release of the anaphylatoxin C3a, a mediator of an inflammatory reaction. The in vivo studies of CA19-9-CVF-treated nude rats showed an increased tumor infiltration by natural killer cells and macrophages. The tumor uptake of 99Tc-labeled anti-carcinoembryonic antigen antibody was increased approximately 2-fold in rats pretreated with 70 micrograms of CA19-9-CVF, compared to animals that received an equimolar mixture of noncoupled mab and CVF. This study indicates the value of mab-CVF conjugates in adjuvant immunotherapy. mab-CVF conjugates might be useful in pretargeting approaches by increasing the uptake of a therapeutic mab.

Animals↗
PubMed1995

Loss of ABH antigen expression in bladder cancer is not caused by loss of heterozygosity of the ABO locus.

The significance of loss of heterozygosity (LOH) of chromosome 9 as an early event in human bladder tumors has been demonstrated by several studies. We have studied LOH of the ABO gene locus at 9q34.2 by means of polymerase chain reaction (PCR) genotyping of tumor preparations and leukocytes. Twenty-two tumors, all of which were immunohistochemically negative for ABH antigens, were examined. Eleven tumors were from blood-group O individuals, and were examined by denaturing gradient gel electrophoresis (DGGE). They showed normal band patterns with no sign of single base mutations or LOH. All II A and B tumors were sorted on a fluorescence-activated cell sorter (FACS) according to DNA content, thereby making it possible to study differences in genotype between subpopulations of cells in the same tumor. In 2 genotypically AO cases, we found 2 aneuploid subpopulations. In both cases, the most abnormal, with the highest DNA content, showed complete loss of the O allele, leaving the A allele intact. As all tumors were ABH antigen-negative, this study demonstrates that LOH of the ABO locus on chromosome 9q34 is not the cause of loss of blood-group ABH expression in human bladder cancer.

ABO Blood-Group System↗
PubMed1995

Prognostic significance of DNA content in bladder cancer based on flow cytometric analysis of 249 transitional cell carcinomas.

The prognostic significance of DNA index (DI), S-phase fraction, and heterogeneity determined by flow cytometric DNA analysis was assessed in a prospective study of 249 newly diagnosed transitional cell carcinomas of the bladder. The median observation time was 4.8 years. A total of 456 subpopulations were detected. The S-phases could be estimated in 299 subpopulations. A DI > 1.25 or an S-phase above 9.7% were strongly correlated to invasiveness. One hundred and ten patients were treated with transurethral resection (TUR). Relapse-free survival could not be predicted by the DNA-derived parameters. Univariate analysis of survival showed prognostic significance of diploidy (0.98 < DI < or = 1.02, P = 0.02), hypotetraploidy (1.50 < DI < or = 1.96, P = 0.002), and S-phase size (P = 0.008). Multivariate analysis pointed to the T-classification (RR = 1.64) and hypotetraploidy (RR = 1.57) as prognostic parameters for survival of TUR-treated patients. One hundred and thirty-nine patients received radiotherapy (RT). A significantly better response was found for tumors with a subpopulation with a hypertetraploid DNA content (DI > 2.04, P = 0.05), and a significantly worse response for subpopulations with a maximum S-phase > 24.5% (P = 0.04). T-classification and histological grade had no predictive value. A logistic regression analysis indicated an estimated probability of response to RT of 77% for tumors with a DI > 2.04 and an S-phase < 24.5%, whereas tumors with a DI < 2.04 and an S-phase > 24.5% had only a 28% probability of response. The poor response to RT, predicted by an S-phase > 24.5%, translated into a poor survival, whereas the better treatment response found for patients with a DI > 2.04 did not result in a longer survival. Multivariate analysis pointed to S-phase (RR = 1.70), T-classification (RR = 1.60), and grade (RR = 0.65) as independent prognostic parameters for survival of RT-treated patients.

Adult↗