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Biomedical subjects

H Wolf

Publications and source records attributed to H Wolf.

At least 487 records · Page 27Linked to original sources
PubMed1987

Polymorphic proteins encoded within BZLF1 of defective and standard Epstein-Barr viruses disrupt latency.

These experiments identify an Epstein-Barr virus-encoded gene product, called ZEBRA (BamHI fragment Z Epstein-Barr replication activator) protein, which activates a switch between the latent and replicative life cycle of the virus. Our previous work had shown that the 2.7-kilobase-pair WZhet piece of rearranged Epstein-Barr virus DNA from a defective virus activated replication when introduced into cells with a latent genome, but it was not clear whether a protein product was required for the phenomenon. We now use deletional, site-directed, and chimeric mutagenesis, together with gene transfer, to show that a 43-kilodalton protein, encoded in the BZLF1 open reading frame of het DNA, is responsible for this process. The rearrangement in defective DNA does not contribute to the structural gene for the protein. Similar proteins with variable electrophoretic mobility (37 to 39 kilodaltons) were encoded by BamHI Z fragments from standard, nondefective Epstein-Barr virus genomes. Plasmids expressing the ZEBRA proteins from B95-8 and HR-1 viruses were less efficient at activating replication in D98/HR-1 cells than those which contained the ZEBRA gene from the defective virus. It is not yet known whether these functional differences are due to variations in expression of the plasmids or to intrinsic differences in the activity of these polymorphic polypeptides.

Cell Line↗
PubMed1987

Computer-assisted analysis of envelope protein sequences of seven human immunodeficiency virus isolates: prediction of antigenic epitopes in conserved and variable regions.

Independent isolates of human immunodeficiency virus (HIV) exhibit a striking genomic diversity, most of which is located in the viral envelope gene. Since this property of the HIV group of viruses may play an important role in the pathobiology of the virus, we analyzed the predicted amino acid sequences of the envelope proteins of seven different HIV strains, three of which represent sequential isolates from a single patient. By using a computer program that predicts the secondary protein structure and superimposes values for hydrophilicity, surface probability, and flexibility, we identified several potential antigenic epitopes in the envelope proteins of the seven different viruses. Interestingly, the majority of the predicted epitopes in the exterior envelope protein (gp120) were found in regions of high sequence variability which are interspersed with highly conserved regions among the independent viral isolates. A comparison of the sequential viral isolates revealed that changes concerning the secondary structure of the protein occurred only in regions which were predicted to be antigenic, predominantly in highly variable regions. The membrane-associated protein gp41 contains no highly variable regions; about 80% of the amino acids were found to be conserved, and only one hydrophilic area was identified as likely to be accessible to antibody recognition. These findings give insight into the secondary and possible tertiary structure of variant HIV envelope proteins and should facilitate experimental approaches directed toward the identification and fine mapping of HIV envelope proteins.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Effects of pro-urokinase and urokinase on the fibrinolytic system in man.

The fibrinolytic and fibrinogenolytic properties of kidney cell pro-urokinase (PUK) were compared with those of natural urinary urokinase in human volunteers. Comparable degrees of fibrinolysis were obtained at a concentration of 500,000 U UK and a concentration of 500,000 IU natural urokinase. Natural urokinase showed a strong activation of the fibrinolytic system in plasma, evidenced by plasminogen activation, alpha 2-antiplasmin consumption, and the rise in fibrinogen-fibrin degradation products. In contrast to UK, there was no fall in plasminogen, no consumption of alpha 2-antiplasmin, and only a slight amount of fibrinogen-fibrin degradation products produced with PUK. These findings with PUK reveal a high affinity for fibrin and may result in better clot selectivity.

Adult↗
PubMed1987

Urothelial atypia concomitant with primary bladder tumour. Incidence in a consecutive series of 500 unselected patients.

A consecutive series of 500 primary bladder tumours from a single clinic is presented, with distribution of the tumours according to T category and histologic type and grade. Mucosal biopsies were obtained from pre-selected sites at initial cystoscopy or initial transurethral resection of the tumour in 396 cases. In 54% of the patients with grade III tumour there was concomitant urothelial atypia, either carcinoma in situ (urothelial atypia grade III, 30%) or urothelial atypia grade II (24%). In 30% of the patients with invasive grade II bladder tumour and in 14% of those with noninvasive grade II tumour there was concomitant urothelial atypia, mostly grade II. Since concomitant urothelial atypia predicts new tumour growth after successful transurethral surgery or radiotherapy, mucosal biopsies should be performed at preselected sites during initial cystoscopy or transurethral tumour resection in order to identify high-risk patients.

Adenocarcinoma↗
PubMed1987

[Prognosis of non-Hodgkin's lymphomas in the Dresden district with special reference to combined radio-/chemotherapy].

The total population affected with non-Hodgkin's lymphoma and treated by means of radiotherapy or combined radio-chemotherapy between 1960 and 1985 at the Medical Academy Dresden was analysed as to prognosis. 247 patients were classified according to the previous German scheme, 79 were subdivided on the basis of the recommendations laid down in the Kiel classification. The remission rates and survival curves achieved will stand out the comparison with international literature (remission rates of the low malignancy group amounted to 85.3 p.c. and those of the high malignancy group to 80.0 p.c.; the 5-years survival rates of the low malignancy group amounted to 61.9 p.c. and those of the high malignancy group to 41.7 p.c.). The influence of histology, clinical stage and involvement of organs is discussed on the basis of our results and informations obtained in literature. Our analysis confirms the high importance which must be attached to a common radiologic-internal outpatient-department for co-ordinating the diagnostic and therapeutical programme.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Effect of heparin and dihydroergotamine on platelet adenosine-3',5'-cyclic monophosphate.

Human platelet adenosine-3',5'-cyclic monophosphate (cAMP) levels were determined in platelet rich plasma (PRP) and in washed platelets by a modification of the protein binding assay; the validation of the method is described. Dihydroergotamine (DHE) inhibited epinephrine induced platelet aggregation (ID50 = 2.5 X 10(-7) mol/l), and increased cAMP levels in platelets by an alpha-adrenergic receptor blocking effect, since phentolamine but not propranolol, behaved similarly. The DHE induced cAMP accumulation was correlated to the inhibitory effect on aggregation and showed a characteristic alpha-adrenergic receptor pattern in the presence of alprostadil (PGE1) and epinephrine but not collagen or adenosine diphosphate (ADP). Thrombin induced aggregation was similarly affected by DHE but with 100 times higher concentration. Heparin was found to increase slightly ADP and epinephrine induced aggregation and to decrease cAMP. Also, heparin was found to inhibit thrombin induced platelet aggregation. In washed platelets, the inhibitory effect of thrombin on PGE1 induced cAMP accumulation was counteracted by heparin. This indicates that the binding site of thrombin on platelets is important in the control of adenyl cyclase. Evidence is presented that some of the beneficial synergistic effect of DHE and heparin may consist in the ability of those compounds to produce opposite effects on cAMP system in platelets.

Alprostadil↗
PubMed1987

Prophylaxis of deep vein thrombosis in high risk patients undergoing total hip replacement with low molecular weight heparin plus dihydroergotamine.

In 160 high risk patients with total hip replacement the antithrombotic efficacy and tolerance of a single daily injection of 1500 aPTT-U (aPTT = activated partial thromboplastin time) low molecular weight heparin plus 0.5 mg dihydroergotamine (HNMD; Embolex NM) was compared with a twice daily application of 5000 IU of the heparin-dihydroergotamine combination Heparin-Dihydergot in a double-blind study. Deep vein thrombosis measured by means of the radiofibrinogen uptake test occurred in 20.5% of patients in both groups. In addition, intra- and postoperative blood loss and the development of hematoma were similar in both groups. Thus, on account of the "once-daily" application HNMD offers some substantial advantages: The stress of the patient in the postoperative convalescence phase can be appreciably lowered and thereby the nursing staff are spared a great deal of work.

Adult↗
PubMed1987

Effect of low molecular weight heparin on coagulation parameters and bleeding time in healthy volunteers.

In a randomized intraindividual cross-over study 8 healthy volunteers received subcutaneously 1500 IU, 2000 IU and 25,00 IU, respectively, of low molecular weight heparin (LMWH) in 24-h intervals, as well as 12-hourly 3 applications of 5000 IU of unfractionated heparin. The wash-out phases between the different medications lasted 7 days each. The course of the activated partial thromboplastin time showed no difference between the medications given, whereas the inhibition of factor Xa was significantly stronger after application of all dosages of LMWH than after unfractionated heparin injections. Bleeding time was prolonged only under 1500 IU of LMWH as compared to heparin. Neither LMWH nor unfractionated heparin caused an influence on the antithrombin III levels.

Antithrombin III↗
PubMed1987

The role of acute and latent virus infections in the pathogenesis of inner ear disturbances.

The possible role of herpesviral infections of the inner ear in suddenly appearing inner ear disturbances was investigated. Experimental pseudorabies virus (PRV, Herpes sui 1) infection of mice and swine was used as a model system. Infected mice represented the productive cycle of PRV infection (acute phase), whereas the latent phase of infection could be tested in swine. From the acutely infected mice the virus could be reisolated from perilymphatic fluid and various parts of the brain. Massive histopathologic alterations and signs of total cell damage to the organ of Corti and the vestibular organ were found. Accordingly, in all of the cells of the inner ear multiple copies of the PRV genome could be demonstrated. We therefore suggest that the disturbances of the inner ear were induced by the acute virus infection. In two latently infected swine (sixty weeks after infection), PRV could not be recovered either from the perilymphatic fluid or from a variety of different neural and extraneural tissues. However, histopathologic changes similar to those found in the acutely infected mice were observed. The presence of viral DNA could be demonstrated by in situ cytohybridization in both sensory and supportive cells of the inner ear and vestibular organ, but not in the corresponding nerve fibers, which is in contrast to the acutely infected mice. The distribution of the viral genome was further analyzed in adjacent areas of the central nervous system. An involvement of acute and latent herpes virus infection in inner ear dysfunction including sudden deafness and vestibular neuronitis in man, might be suggested from the results described. The presented animal model system, PRV-infected swine, should permit further studies on a possible role of herpetic recurrences, particularly with regard to inner ear disturbances.

Acute Disease↗
PubMed1987

[Detection of low molecular weight trypsin inhibitors in small samples of cartilage, cartilage extracts and synovial fluid by gel diffusion].

The radial diffusion assay is a very useful method for detection of low amounts of proteinase inhibitors in biological materials. The determination of low molecular weight (LMW) inhibitors in the presence of high molecular weight inhibitors is possible by the combination of radial diffusion and ultrafiltration. Using this method LMW trypsin inhibitors could be demonstrated in human articular cartilage, but not in human synovial fluid. In cow, pig and sheep a LMW trypsin inhibitor could be found in both the articular cartilage and in the synovial fluid. On the other hand, a LMW trypsin inhibitor could not be found neither in the canine cartilage nor in the canine synovial fluid. The method allows also the direct determination of LMW trypsin inhibitors in cartilage extracts in the presence of 4 M guanidinium hydrochloride or 6 M urea. Therefore, the method is recommended for direct determination of LMW inhibitors by column chromatographic separations of inhibitors.

Animals↗
PubMed1987

Transurethral surgery in the treatment of invasive bladder cancer (T1 and T2).

Ninety-nine primary transitional cell bladder tumours of categories T1 or T2 were treated by transurethral resection. 25% of these patients experienced a true recurrence indicating that surgery failed to control the tumour locally. These patients had a 5-year survival of 20%. We suspect that many of them did not have local disease when treated. Twenty-five % of the total patient population did not within five years get a new tumour. They were cured by the first transurethral resection. 30% of the patients experienced new non-invasive tumour growth that could be managed by repeated resections. These two groups of patients did extremely well, since the 5-year survival was equivalent to the 5-year survival of an age and sex matched control population. Thus, more than 50% of the patients benefitted from transurethral surgery. Less than 20% experienced a new invasive tumour growth. They are patients at risk of getting a progressive bladder cancer disease. 5-year survival of these patients was about 50%. We conclude that transitional cell bladder tumours of category T1 and some of category T2 are well treated by transurethral resection.

Aged↗
PubMed1987

Initial experience with percutaneous nephrolithotomy: results, problems and complications.

Initial experience from 132 cases of percutaneous lithotripsy performed at three departments in Arhus County in 1984-85 is reviewed. Twenty patients were not offered a percutaneous operation during this period. In 12 cases the stone had to be removed by open operation. Another 12 cases were also regarded as failures due to important residual stones or fragments. Stone free kidneys were obtained in 86 cases (64%), whereas 22 (17%) had minor residual stones or fragments considered unimportant in relation to the present indications for operation. Stones 20 mm in diameter, and especially staghorn stones frequently gave failures. Minor complications were recorded in 29 patients and resulted in 7 open operations, mostly from the early part of the series. Five severe complications were seen. An old weak man died from late complications after bleeding. The four others were operated for pulmonary embolism (1 pt), late bleeding (traumatic aneurysm, 2 pt) and colonic perforation (1 pt). They all recovered.

Adult↗
PubMed1987

[Transmissibility of HIV infections via allogeneic transplants].

HIV-infections can be transferred by blood and blood products, semen or organ transplants. For this reason, the WHO recommended a screening of all donors of blood, semen, tissues and organs. Those who belong to high-risk groups should be excluded from donations. If this recommendation should be also applied to cialit preserved auditory aussicles, this would probably mean the end of allogeneic transplantations of middle-ear surgery which are being performed daily. Therefore, we carried out experimental examinations with HIV-infected auditory aussicles in cialit. According to our results, it can be assumed that a virus-destruction takes place via a cialit-treatment. The same applies to solvent-dried fascia as to auditory aussicles which have been preserved in the same way. Consequently, there is no objection to further application of these allogeneic transplants in respect to HIV-infections.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Identification and characterization of conserved and variable regions in the envelope gene of HTLV-III/LAV, the retrovirus of AIDS.

To determine the extent and nature of genetic variation present in independent isolates of HTLV-III/LAV, the nucleotide sequences of the entire envelope gene and parts of gag and pol were determined for two AIDS viruses. The results indicated that variation throughout the viral genome is extensive and that the envelope gene in particular is most highly variable. Within the envelope, changes were most prevalent within the extracellular region where clustered nucleotide substitutions and deletions/insertions were evident. Based on predicted secondary protein structure and hydrophilicity, these hypervariable regions represent potential antigenic sites. In contrast to the hypervariable regions, other sequences in the extracellular envelope and the overall envelope structure (including 18 of 18 cysteine residues), as well as most of the transmembrane region, were highly conserved.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Detection of IgG and IgA antibodies to Epstein-Barr virus membrane antigen in sera from patients with nasopharyngeal carcinoma and from normal individuals.

IgG and IgA antibodies to Epstein-Barr virus (EBV) membrane antigen (MA) were detected in sera from 96 NPC patients and normal individuals by the indirect immunofluorescence test. For MA/IgG antibody, 100% of NPC patients were positive with a GMT of 1:439.7 and 97.9% of normal individuals were positive with a GMT of 1:94.7. In contrast, for MA/IgA antibody, 58.3% of NPC patients were positive with a GMT of 1:7.3 and none of the normal individuals were positive. There was no difference in the detection of antibodies to EBV MA when other P3HR-1 or B95-8 cell lines, differing in their major membrane antigen, were used.

Antibodies, Viral↗
PubMed1986

Thyrotropin-releasing hormone precursor: characterization in rat brain.

To characterize the precursor of mammalian thyrotropin-releasing hormone (TRH), a rat hypothalamic lambda gt11 library was screened with an antiserum directed against a synthetic peptide representing a portion of the rat TRH prohormone. The nucleotide sequence of the immunopositive complementary DNA encoded a protein with a molecular weight of 29,247. This protein contained five copies of the sequence Gln-His-Pro-Gly flanked by paired basic amino acids and could therefore generate five TRH molecules. In addition, potential cleavage sites in the TRH precursor could produce other non-TRH peptides, which may be secreted. In situ hybridization to rat brain sections demonstrated that the pre-proTRH complementary DNA detected neurons concentrated in the parvocellular division of the paraventricular nucleus, the same location as cells detected by immunohistochemistry. These findings indicate that mammalian TRH arises by posttranslational processing of a larger precursor protein. The ability of the TRH prohormone to generate multiple copies of the bioactive peptide may be an important mechanism in the amplification of hormone production.

Amino Acid Sequence↗