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D Jonas

Publications and source records attributed to D Jonas.

At least 91 records · Page 5Linked to original sources

Comparison of ras activation during epidermal carcinogenesis in vitro and in vivo.

Mouse epidermal cells have frequently been used to study the role of ras oncogenes in transformation in vivo and in vitro. After initiation with dimethylbenzanthracene (DMBA) in vivo, greater than 90% of the papillomas arising show the same A:T----T:A transversion at codon 61 of the H-ras gene, presumed to be the initiating event. On the other hand, initiation of epidermal cells in culture with carcinogens, followed by selection of initiated cells by resistance to calcium-induced differentiation, does not in general lead to the isolation of clones carrying mutant ras genes. Some other aspects of tumour progression in vivo can be reproduced using epidermal cells in culture: a rare DMBA transformant carrying the codon 61 mutation and expressing a 2:1 ratio of normal to mutant ras alleles gave rise upon transplantation to a more aggressive line in which the ratio of normal to mutant H-ras genes (and p21 products) was reversed. Similar alterations in ras gene dosage have been seen during progression of papillomas to carcinomas in vivo. We conclude that the mechanisms of initiation in vitro may differ substantially from in vivo, and depend on the particular culture conditions used. Moreover, the effects of mutant H-ras expression in mouse epidermal cells are variable depending on the genetic background of the cell.

9,10-Dimethyl-1,2-benzanthracene↗

Animal models for the biological effects of continuous high cytokine levels.

Transgenic animals or animals engrafted with retrovirus-derived expression vectors provide models for studying the in vivo effects of high and continuous serum levels of cytokines. Studies employing these models in order to analyze the biological effects for granulocytes-macrophages colony-stimulating factors (CSFs), granulocytes of interleukin (IL-)2, IL-3, IL-6 and erythropoietin are reviewed. In all of these models, overexpression of the different cytokines achieved by use of these approaches resulted in syndromes that were related to nonneoplastic hyperplasia of the respective target cell population. In some but not all models, these syndromes were lethal, mostly due to hypercellularity. These models allow conclusions about the biological effects of very high and continuous levels of these substances as well as about their regulation in different tissues.

Animals↗

Interferon alfa-2c in chronic myelogenous leukemia (CML): hematologic, cytogenetic and molecular-genetic response of patients with chronic phase CML previously resistant to therapy with interferon gamma.

Alpha- and gamma-interferons have been shown to actively suppress hematopoiesis in patients in the chronic phase of chronic myelogenous leukemia in vitro and in vivo. Since both interferons act through different receptors on their hematopoietic target cells, they are expected to be capable of independently inhibiting abnormal blood cell development in patients with chronic myelogenous leukemia. We have utilized recombinant human interferon alfa-2c to treat 11 patients with Philadelphia chromosome positive chronic myelogenous leukemia in chronic phase, who were resistant to previous interferon gamma therapy. Ten of the patients were evaluable for hematologic, cytogenetic and molecular-genetic response following interferon alfa-2c therapy for 6 to 30 months. In 5 patients, IFN alfa-2c treatment failed due to lack of hematologic response. A complete hematologic or partial hematologic response was achieved in the remaining 5 patients. Three of these experienced cytogenetic improvement with reappearence of 100% diploid hematopoietic cells and disappearence of c-abl/bcr rearrangement in one patient. In two patients interferon alfa-2c did not prevent transformation of the disease into an accelerated state or blast crisis, respectively. We conclude that recombinant human interferon alfa-2c may also control hematopoiesis in interferon-gamma resistant chronic myelogenous leukemia patients, although the long-term response will need to be elucidated in further studies.

Adult↗

Histological and scanning electron microscopic alterations in ileal conduit depending on the time factor.

Five ileal conduit biopsies, taken after 1-7 years, were examined by light microscopy and scanning electron microscopy. The total height of the lamina mucosa decreased from 700 to 275 microns. The height of the villi diminished from 550 to 50 microns; the depth of the crypts increased from 130 to 244 microns and the villus-crypt index changed from 4.2 to 0.2. Signs of chronic inflammation could be observed. Scanning electron microscopy shows that the number of microvilli per cell was markedly reduced. There was a varied picture of different stages of atrophy. After 3 years microvilli could no longer be observed. In view of the prolonged urinary contamination time, it appears to be imperative to check neobladders with regard to possible carcinoma induction.

Cell Transformation, Neoplastic↗

Retrospective analysis of ras gene activation in myeloid leukemic cells.

Ras genes are activated by point mutations at critical sites of their coding regions. Activated N-ras genes with transforming ability have been detected in patients with myelodysplastic syndromes (MDS), acute myelogenous leukemia (AML) and in human myeloid cell lines. We used polymerase chain reaction (PCR), differential oligonucleotide hybridization and direct DNA sequencing to retrospectively analyze the N-ras gene of blast cells from the same patient (a) at time of diagnosis of MDS, (b) after the patient had developed AML. Two types of archival tissue samples served as a source of cells. Different passages of the KG-1 myeloid cell line which had been established from leukemic blasts of this patient were also analyzed. We found that native blast cells isolated at either of the two disease stages did not carry an N-ras mutation, and neither did early passage KG-1 cells. However, direct DNA sequencing of PCR-amplified DNA from nude mice transformants induced by DNA from late passage of the KG-1 cell line revealed two linked mutations involving both the second nucleotide of codon 12 and the third nucleotide of codon 15 of N-ras. The nucleotide substitution at codon 15 did not result in an amino acid substitution (silent mutation). The mutations probably occurred during prolonged passaging of the KG-1 cells and might have been overlooked by oligonucleotide hybridization assay.

Animals↗

Tumour imaging of bladder carcinomas and their metastases with 111indium-labelled monoclonal anti-CEA antibody BW 431/26.

Fifty-one patients with muscle-infiltrating bladder carcinoma (T2-T4, N0-3, M0-1) were studied with a new imaging technique using murine monoclonal antibody directed against the carcinoembryonic antigen (CEA). A total number of 67 investigations were performed. The intact 111indium-labelled antibody (BW 431/26, Behringwerke Marburg) detected 86% of primary tumours, 93% of local and 75% of distant metastases whether there was an elevated CEA level in serum or not. Immunohistologically (avidin-biotin-peroxidase method) positive frozen tissue sections from tumour biopsies stained with the same monoclonal anti-CEA antibody, thus confirming the presence of the CEA antigen in vitro. The method was of much higher sensitivity in detecting even very small metastases than X-ray computed tomography (86% versus less than 30%). The specificity was in the region of 90%. The response to chemotherapy (MVEC regimen) was shown by repeated studies demonstrating reduced uptake (partial remission) or no accumulation (complete remission) in the second immunoscan. We suggest immunoscintigraphy of bladder tumours and their metastases as an additional method in preoperative staging and postoperative care.

Antibodies, Monoclonal↗

Actin as a component of cytoskeleton in the collecting tubule system of the mouse kidney.

Actin as a component of the cytoskeleton is familiar as a protein which possibly mediates contraction in nonmuscular cells. In 20 mouse kidneys, the distribution of intracellular actin in the collecting tubule system was investigated by means of the anti-actin PAP method. It could be shown that the positive PAP reaction increases from the proximal to distal up to the collecting tubules in the region of papilla. Stiffening, stabilization and contraction functions are discussed with regard to the biology of the collecting tubule actin.

Actins↗

Adrenal myelolipoma: clinical, radiologic, and histologic features.

The adrenal myelolipoma is a benign, endocrinologically inactive tumor whose histologic structure consists of mature adipose tissue with foci of hematopoietic cells. A case is presented of a seventy-one-year-old woman in whom the diagnosis was established preoperatively by means of sonography, computerized tomography, and magnetic resonance tomography. In a review of the literature, the radiologic profile is discussed, and based on the analysis of 59 surgically treated cases a therapy recommendation is given.

Adrenal Gland Neoplasms↗

Inheritance and testicular cancer. Arguments based on a report of 3 cases and a review of the literature.

Cryptorchidism and antecedent contralateral testicular tumor formation are risk factors for the formation of testicular germ cell neoplasms. The question arises if familial occurrence of testicular cancer constitutes another risk factor. In a series of 184 patients, treated for testicular tumors, three pairs of non-twin brothers were recorded. The analysis of 82 cases reported in the literature to date as well as the clinical features of early age of onset, high incidence of bilateral testicular tumors in familial cases, ethnic differences in occurrence of testicular cancer, HLA studies and the detection of oncogenes give relevance to the concept of the participation of genetic factors in the etiology of testicular germ cell cancer.

Adolescent↗

Bilateral testicular germ cell tumors. Report of nine cases and review of the literature.

In a series of 181 patients with testicular germ cell tumors, the phenomenon of bilateral involvement of the testicles was observed nine times (5%). Two patients evidenced a simultaneous bilateral tumor, and, in seven others, a second tumor occurred after an interval ranging between 8 months and 6 years and 11 months. The incidence, histologic findings, therapy, and prognosis of bilateral testicular tumors are discussed on the basis of a survey of the literature. Emphasis is placed on the significance of a long-term follow-up period as well as on the important role of sonography in the early detection of a contralateral tumor.

Adolescent↗

Polarization optic investigations on the anatomy of the bladder neck and the vesical fundus in women.

On the basis of an investigation technique, not so far applied in the urinary bladder, whole-organ preparations were rendered transparent and examined at supramicroscopic magnifications. The results available so far with regard to the fiber structure of the neck of the bladder and the vesical fundus were checked in 12 female urinary bladders. The following results were obtained: (1) the structure of the posterior longitudinal muscle is confirmed, as already described previously; (2) an anterior longitudinal muscle almost symmetrical to the posterior longitudinal muscle is demonstrated, and (3) the fiber course of the base plate has so far been described as running in the form of a horseshoe around the urethra. We see that in their main portions the fibers cross under the margins of the deep trigonum, then change their direction and turn laterodorsally, thus acting subtrigonally in the median line. The construction of the investigation instrument and the investigation technique are described in detail. The investigation results are discussed in the context of anatomical and physiological knowledge.

Adolescent↗

[Differential postmortem diagnosis of rabies in cats].

300 cats, sent in for rabies diagnosis, which were obviously not infected, have been further examined with regard to their causes of disease and death. Traumata, uremia and panleucopenia have been observed most frequently. As expected, affections of the central nervous system often have been stated. The results of our investigations have been compared with autopsy statistics on rabies-unsuspected cats, published in literature. Furthermore the preliminary reports have been examined and compared with the anamnesis of 214 rabies-positive cats. The information of preliminary reports on rabies-negative cats and their pathological diagnosis has been discussed in the context of differential diagnosis.

Animals↗

The value of morphological prognostic criteria in the assessment of renal cell carcinoma.

In this study, we examined some of the morphological values from the large number of prognostic parameters indicated in the literature by establishing survival statistics. Primary distant metastasis formation was confirmed to be a prognostically unfavorable factor. Regional metastasis formation takes an intermediate position between the primarily distantly metastasized and the primary non-metastasized renal cell carcinoma. In the primarily non-metastasized renal cell carcinoma, tumor invasion into the renal vein is associated with prognostic deterioration, obviously due to a linkage to other unfavorable tumor characteristics. The histological degree of malignancy as a single prognostic parameter seems to be of little informational value if no other tumor data are taken into consideration. The classification of renal tumors according to Robson proves to be of great clinical relevance, especially when it is combined with the histological degree of malignancy. The prognostic scheme by Hermanek 'combined staging and grading' must be recommended as the prognostic scheme of choice. Apart from special histological types of the renal cell carcinoma, such as the papillary or sarcomatous variant, and with reservation as to the tendency to unpredictable secondary metastasis formation that is peculiar to the renal cell carcinoma, a prediction of the prognosis according to the morphological criteria mentioned above is possible to a satisfactory degree within certain limits.

Adult↗