Biomedical subjects

A Kopp

Publications and source records attributed to A Kopp.

28 records · Page 2Linked to original sources

PubMed1994

[MRT diagnosis of recurrence of gynecologic tumors].

Because of the differences in the signals from recurrent tumours and fibrosis during MRT, this method is highly suitable for differentiating between recurrent gynaecological tumours and scar formation. The value of MRT in investigating suspected recurrences was studied in 27 patients aged between 34 and 83 years. It was possible to distinguish between recurrent tumour with its high intensity signal from low signal fibrosis, using T2-weighted spin echo sequences in all cases. By means of multiplanar reconstruction and because of its high soft tissue contrast it was possible to determine the extent of tumour growth and differentiate it from surrounding tissues. With a sensitivity of 90%, specificity of 100% and accuracy of 92%, MRT is superior to all other imaging methods, including CT, in the diagnosis of tumour recurrence.

Adult↗

PubMed1994

Proteolytic cleavage of bovine herpesvirus 1 (BHV-1) glycoprotein gB is not necessary for its function in BHV-1 or pseudorabies virus.

Glycoprotein B homologs represent the most highly conserved group of herpesvirus glycoproteins. They exist in oligomeric forms based on a dimeric structure. Despite the high degree of sequence and structural conservation, differences in posttranslational processing are observed. Whereas gB of herpes simplex virus is not proteolytically processed after oligomerization, most other gB homologs are cleaved by a cellular protease into subunits that remain linked via disulfide bonds. Proteolytic cleavage is common for activation of viral fusion proteins, and it has been shown that herpesvirus gB homologs are essential for membrane fusion events during infection, e.g., virus penetration and direct viral cell-to-cell spread. To analyze the importance of proteolytic cleavage for the function of gB homologs, we isolated a mutant bovine herpesvirus 1 (BHV-1) expressing a BHV-1 gB that is no longer proteolytically processed because of a deletion of the proteolytic cleavage site and analyzed its phenotype in cell culture. We showed previously that BHV-1 gB can functionally substitute for the homologous glycoprotein in pseudorabies virus (PrV), based on the isolation of a PrV gB-negative PrV recombinant that expresses BHV-1 gB (A. Kopp and T. C. Mettenleiter, J. Virol, 66:2754-2762, 1992). Therefore, we also isolated a mutant PrV lacking PrV gB but expressing a noncleavable BHV-1 gB. Our results show that cleavage of BHV-1 gB is not essential for its function in either a BHV-1 or a PrV background. Compared with the PrV recombinant expressing cleavable BHV-1 gB, deletion of the cleavage site in the recombinant PrV did not detectably alter the viral phenotype, as analyzed by plaque assays, one-step growth kinetics, and penetration kinetics. In the BHV-1 mutant, the uncleaved BHV-1 gB was functionally equivalent to the wild-type protein with regard to penetration and showed only slightly delayed one-step growth kinetics compared with parental wild-type BHV-1. However, the resulting plaques were significantly smaller, indicating a role for proteolytic cleavage of BHV-1 gB in cell-to-cell spread of BHV-1.

Amino Acid Sequence↗

PubMed1993

[Immunohistochemical detection of EGF-receptors in breast cancers].

We examined the possibility of a quick and easy-to-perform way to determine the EGF receptor status in primary breast cancer cells by immunohistochemical staining. For this, we used two different monoclonal antibodies on corresponding tissue slides (Gullick, London; Mendelsohn, New York). The staining was interpreted by a semiquantitative histoscore. With both antibodies, we were able to detect EGF-R in breast tumours. We examined 80 tumours. 15 respectively 21% were EGF-R rich. 25% of the tumours were classified EGF-R poor. In 64 (54%) we were not able to detect EGF-R. The judgement of the EGF-R status by the different antibodies was identical in 80%. The results were also compared with the oestrogen receptor status (ER). We did not find a significant accumulation of EGF-R positive tissues in the group of ER-negative tumours (11/28 respectively 16/32). Nevertheless most ER-positive tumours showed a negative EGF-R receptor score (32/52; 27/48). These results are comparable to the studies of the Sainsbury group. In addition we compared the EGF-R of our tumours also with other parameters for the prognosis of breast cancer such as lymph node status, histological grading and menopausal status. We found, that nearly two thirds of the EGF-R negative tumours were lymph node negative. Only 18% of the lymph node negative tumours had a positive EGF-R status in both techniques. The results of immunohistochemical staining were also compared with a radio-receptor assay. The results were identical in 85% of the cases.

Adult↗

PubMed1992

Stable rescue of a glycoprotein gII deletion mutant of pseudorabies virus by glycoprotein gI of bovine herpesvirus 1.

Glycoproteins homologous to glycoprotein B (gB) of herpes simplex virus constitute the most highly conserved group of herpesvirus glycoproteins. This strong conservation of amino acid sequences might be indicative of a common functional role. Indeed, gB homologs have been implicated in the processes of viral entry and virus-mediated cell-cell fusion. Recently, we showed that pseudorabies virus (PrV) lacking the essential gB-homologous glycoprotein gII could be propagated on a cell line expressing the gB homolog of bovine herpesvirus 1, gI(BHV-1), leading to a phenotypic complementation of the gII defect (I. Rauh, F. Weiland, F. Fehler, G. Keil, and T.C. Mettenleiter, J. Virol. 65:621-631, 1991). However, this pseudotypic virus could still replicate only on complementing cell lines, thereby limiting experimental approaches to analyze the effects of the gB exchange in detail. We describe here the construction and isolation of a PrV recombinant, 9112C2, that lacks gII(PrV) but instead stably carries and expresses the gene encoding gI(BHV-1). The recombinant is able to replicate on noncomplementing cells with growth kinetics and final titers similar to those of its gII-positive wild-type PrV parent. Neutralization tests and immunoprecipitation analyses demonstrated incorporation of gI(BHV-1) into 9112C2 virions with concomitant absence of gII(PrV). Analysis of in vitro host ranges of wild-type PrV, BHV-1, and recombinant 9112C2 showed that in cells of pig, rabbit, canine, monkey, or human origin, the plating efficiency of 9112C2 was similar to that of its PrV parent. Exchange of gII(PrV) for gI(BHV-1) in recombinant 9112C2 or by phenotypic complementation of gII- PrV propagated on gI(BHV-1)-expressing cell lines resulted in penetration kinetics intermediate between those of wild-type PrV and BHV-1. In conclusion, we report the first isolation of a viral recombinant in which a lethal glycoprotein mutation has been rescued by a homologous glycoprotein of a different herpesvirus. Our data show that in gII- PrV, gI(BHV-1) in vitro fully complements the lethal defect associated with lack of gII(PrV). These results conclusively demonstrate that gI(BHV-1) in a PrV background can execute all essential functions normally provided by gII(PrV). They also indicate that the origin of gB-homologous glycoproteins influences the penetration kinetics of herpesviruses.

Animals↗

PubMed1991

[Managing a high risk pregnancy after liver transplantation from the obstetrician's point of view. A case report].

We report about a pregnancy and obstetrical management of a patient who had undergone a liver transplantation. Following a normal pregnancy, the newborn was born spontaneously in the 39th week of pregnancy. During the pregnancy the CSA blood levels were controlled frequently as well as the fetal development. An amniocentesis for chromosomal analysis, measurement of AFP blood levels, virus diagnostic and a phase III ultrasound diagnostic were performed. Immediately after delivery the baby was examined carefully by a pediatrician. Management of such a risk pregnancy, after organ transplantation, is possible if there is a close interdisciplinary cooperation between obstetricians, pediatricians, transplant surgeons and internal medicine specialist.

Adult↗

PubMed1990

[Pregnancy following organ transplantation].

In 17 of 74 patients, in the 20-40 years of age group, who had undergone an organ transplantation (kidney or liver), the course and outcome of pregnancy were evaluated. In three cases, the pregnancies ended in premature miscarriage and in five cases they were terminated for medical reasons. Nine infants were born alive between the 32nd to the 40th week of gestation, six of them spontaneously, three of them by abdominal Caesarean section. One of these infants born in the 32nd week of gestation with a birth weight of 800 grams died on the second day after birth. One infant born in the 33rd week of gestation showed incidence of a persistent ductus arteriosis Botalli. Four of the nine newborns suffered from intrauterine dystrophy. The birth weight of four further infants corresponded to the 10th to 25th percentile. Neither the incidence of a maternal varicella zoster infection in the early stages of pregnancy nor the reactivation of a herpes simplex (HSV) and cytomegalia virus infection during the pregnancy resulted in any perceptible damage to the infant or transplant. During pregnancy, three of the mothers were treated with immunosuppressants, either with a combination of azathioprine and prednisone (conventional) or cyclosporine (CSA) and prednisone, or with a combination of all three drugs (triple therapy). As opposed to the newborn of those mothers, who had been treated conventionally, the newborn of those treated with CSA showed post partum a tendency towards hypocalcaemia. Two of the mothers gave birth to their infants outside the Federal Republic of Germany.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗

PubMed1990

Biologically based models for risk assessment.

The modelling problems associated with the estimation of risks from long-term chemical exposures at low dose levels represent a statistical and mathematical challenge with special relevance to environmental research. Determining an adequate model for estimating the relationship between dose and response is critical to reducing potential bias in the risk estimation process. This paper discusses the various assumptions and models used in carcinogenic risk assessment. The emphasis is on our ability to accurately determine the magnitude of the carcinogenic risk, the shape of the dose-response relationship and the overall variability of the risk estimates.

Animals↗

PubMed1989

A note on approximating the cumulative distribution function of the time to tumor onset in multistage models.

The general multistage theory of carcinogenesis is a very special type of interconnected birth and death process in which the final state is absorbing and all states except the first one are empty at time zero. An approximation proposed by Whittemore and Keller (1978, SIAM Review 20, 1-30) is assessed. It is shown that the adequacy of this approximation depends on the number of malignant cells resulting from a single normal cell. If more than one malignant cell is likely to occur, the approximation will fail.

Animals↗

PubMedDate not supplied

A randomized study comparing fluconazole with amphotericin B/5-flucytosine for the treatment of systemic Candida infections in intensive care patients.

In this prospective, randomized study fluconazole and amphotericin B/5-flucytosine were compared in the treatment of systemic candidiasis. Seventy-two non-neutropenic intensive care patients with systemic Candida infections were enrolled. Thirty-six patients were randomly assigned to receive fluconazole (400 mg on the first day then 200 mg) and 36 were randomized to amphotericin B/5-flucytosine (1.0-1.5 mg/kg body weight every other day and 3 x 2.5 g flucytosine/day) for 14 days following the diagnosis. There was no statistically significant difference in clinical outcome in regard to the treatment of pneumonia and sepsis: 18/28 of the patients were treated successfully with fluconazole and 17/27 with amphotericin B/5-flucytosine. For the treatment of peritonitis, however, amphotericin B/5-flucytosine was more effective than fluconazole (55% vs. 25%). Furthermore, amphotericin B/5-flucytosine was found to be superior to fluconazole with regard to pathogen eradication (86% vs. 50%). Fluconazole was associated with less toxicity than amphotericin B/5-flucytosine.

Adult↗

PubMedDate not supplied

Comparison of 18FDG-PET with CT scans in the evaluation of patients with residual and recurrent Hodgkin's lymphoma.

The reliable assessment of residual masses after treatment as well as of new lesions suspected for relapse remains a diagnostic problem in patients with Hodgkin's disease (HD). The current study compares the results obtained by CT scan to FDG-PET imaging in a blind analysis with respect to the viability of residual masses and in case of suspected relapse. Between 1/94 and 10/99, 47 comparisons of PET and corresponding CT scans - 26 comparisons in 24 patients with residual tumors and 21 comparisons in 20 patients with suspected relapse of HD - were evaluated by independent reviewers blinded to he results of each other. Patients with primary diagnosis had been treated within trials of the German HD Trial study group. Relapsed patients received intensified salvage chemotherapy regimens. PET was assessed visually and by quantifying glucose uptake (SUV). Changes in size of tumor lesions as well as contrast medium enhancement served as criteria for assessment by CT scans. Results were validated either by histologic examination of a resected mass or biopsy (n=17) or by a clinical follow-up over 6 months following treatment (n=30). In 26 cases with residual lesions FDG-PET showed an increased tracer uptake in 8, 7 of which were true positive (TP) and 1 false positive (FP). Eighteen cases were classified as being negative (no viable HD), 17 true negative (TN) and 1 FN. In the blinded reading of the corresponding CT scans, 10 cases with residual lesions were considered to contain vital lymphoma (2 TP, 8 FP). Sixteen CT scans were classified as negative (10 TP, 6 FN). The resulting sensitivity and specificity of PET were 87.5% and 94.4% in contrast to only 25% and 56% for CT scans. The positive and negative predictive values of PET and CT scans were 87.5% and 94.4% and 20% and 62.5%, respectively. In patients with suspected relapse, sensitivity and positive predictive value for the diagnosis of the relapse were 100% and 86%, respectively, yielding the same results for both methods. FDG-PET performed in HD patients with residual masses appears to offer important additional information regarding the presence of viable HD in these residual lesions. In patients with suspected relapse of HD, FDG-PET seems not to offer any information over CT scans. Using SUVs is not superior to visual assessment of PET alone.

Adult↗