Biomedical subjects

P Hausner

Publications and source records attributed to P Hausner.

At least 19 recordsLinked to original sources

PubMed2006

Current treatment options and biology of peritoneal mesothelioma: meeting summary of the first NIH peritoneal mesothelioma conference.

Peritoneal mesothelioma is a rare cancer of the peritoneum with about 250 new cases diagnosed each year in the United States. It is the second most common site for mesothelioma development and accounts for 10-20% of all mesotheliomas diagnosed in the United States. A meeting sponsored by the NIH Office of Rare Diseases was held in Bethesda, Maryland on September 13 and 14, 2004. The objective of this meeting was to review the epidemiology, biology and current surgical and medical management of peritoneal mesothelioma. In addition, the meeting also discussed clinical and pre-clinical evaluation of novel treatments for mesothelioma as well as ongoing laboratory research to better understand this disease. This report summarizes the proceedings of the meeting as well as directions for future clinical and basic research.

Clinical Trials as Topic↗

PubMed2003

[Effects of hip arthroplasty followed by by inpatient rehabilitation on physical function and quality of life].

The aim of the present study was to investigate the effects of hip arthroplasty followed by an inpatient rehabilitation. Moreover, the relationships among functional status, quality of life and satisfaction with life or health status were examined. Patients were assessed before hip arthroplasty, at the start and at the end of the inpatient rehabilitation. Functional status was measured by using the WOMAC questionnaire and quality of life with the Medical Outcome Survey Short Form 36 (SF-36). Satisfaction was determined with a specific questionnaire (FLZ). Hip arthroplasty followed by an inpatient rehabilitation resulted in significant and clinically highly important improvements of functional status, quality of life and satisfaction with health and life.

Adult↗

PubMed1999

The "comparative growth assay": examining the interplay of anti-cancer agents with cells carrying single gene alterations.

We have developed a "comparative growth assay" that complements current assays of drug effects based on cytotoxicity. A co-culture of two cell lines, one of which is fluorescently labeled, is exposed to a cytotoxic agent and the proportion of fluorescent cells is compared with that of a baseline unexposed co-culture. For demonstration purposes, two HCT116 cell lines (an hMLH1 homozygous and an hMLH1 heterozygous mutant), altered by insertion of vector alone or the same vector carrying an insert for the expression of enhanced green fluorescent protein (EGFP), were exposed to numerous "anti-cancer" agents. The assay was further validated in a system of two cell lines differing only in the expression of the breast cancer resistance protein (BRCP). The assay allowed the estimation of the duration of action of a particular agent. Assessment of the agent's differential activity over a given time in culture could be expressed as a selection rate, which we chose to describe on an "average selection per day" basis. We conclude that this assay: 1) provides insight into the differential dynamic effects of chemotherapeutic agents or radiation; and 2) allows, through the use of matched cell lines, the investigation of critical physiologic features that govern cell sensitivity.

ATP Binding Cassette Transporter, Subfamily G, Mem↗

PubMed1998

Disseminated growth of murine plasmacytoma: similarities to multiple myeloma.

Murine plasma cell tumors share a number of common features with human multiple myeloma, suggesting their possible use as a model for this disease. However, one major difference between the two is the peritoneal localization of murine tumors as opposed to bone marrow residence of malignant plasma cells in early stages of multiple myeloma. We have thus examined the ability of murine plasmacytoma to produce disseminated growth similar to that seen in myeloma or other lymphoid neoplasias. Of four murine cell lines evaluated, all were demonstrated to effect highly metastatic disease involving multiple organs, although variation was observed between lines. A temporal analysis was accordingly performed with the S107 line to assess the pattern of cellular localization. Both light microscopy and PCR analysis revealed that engraftment of plasma cells occurs first in the bone marrow, followed by dissemination to other sites including the spleen, lung, and liver. Cells passaged in vivo through the bone marrow display an entirely different metastatic pattern with no homing preference to bone marrow or any other organ, suggesting the occurrence of a phenotypic change. Microscopic osteolytic lesions were observed adjacent to plasma cell tumor masses in the bone marrow, indicating early stages of bone disease. These findings demonstrate previously unrecognized similarities between the murine and human diseases and suggest the use of this in vivo model for experimental approaches to the treatment of human disease.

Animals↗

PubMed1997

Mutations in beta-catenin are uncommon in colorectal cancer occurring in occasional replication error-positive tumors.

Beta-catenin has been identified as an oncogene in colon cancer and melanoma. Phosphorylation of sites in exon 3 of beta-catenin leads to degradation of this protein. These sites are primary targets for activating mutations. The frequency with which oncogenic mutations at these sites are found in colorectal cancer is unknown, as is the frequency of their occurrence in other malignancies. We analyzed 92 colorectal cancers (CRCs) and 57 cancer cell lines (representing a diversity of tumor types) to determine the frequency of activating mutations in this gene. Mutations in exon 3 of beta-catenin were found in 2 of 92 CRCs and in the colorectal cancer cell line HCT 116. Both tumors with beta-catenin mutations exhibited widespread microsatellite instability, which is indicative of a replication error phenotype, a phenotype known to be present in HCT 116. This suggests that mutations in beta-catenin are infrequent in CRC and miscellaneous cancer cell lines and may occur in association with a replication error phenotype.

Adult↗

PubMed1997

Characterization of C57BL/6 plasmacytomas lacking a c-myc translocation.

BALB/c peritoneal plasmacytomas induced by a variety of agents are invariably associated with a c-myc translocation. In contrast, naturally arising bone marrow plasma cell tumors in C57BL/KaLwRij mice lack this translocation. This difference has led to the suggestion that these are 2 fundamentally different plasma cell diseases. Herein, we have analyzed 2 rare C57BL/6 peritoneal plasmacytomas in terms of characteristics associated with the bone marrow-derived lines. Like the bone marrow lines, these peritoneal plasmacytomas do not exhibit c-myc translocations, indicating that c-myc translocation is not an obligatory event in the development of all murine extramedullary plasmacytomas. However, myc is dysregulated at the mRNA level, indicating that myc overexpression may be fundamental to most plasma cell diseases but that dysregulation can occur by alternative mechanisms possibly reflecting different genetic backgrounds.

Animals↗

PubMed1992

[Use of flow cytometry in the diagnosis of acute leukemias in childhood].

The authors examined, using the method of flow cytometry, 56 children with acute lymphoblastic leukaemia. Leukaemic cells of the bone marrow aspirate and peripheral blood were examined on a FACS 440 apparatus for establishment of the diagnosis before treatment was initiated. Individual immunological subtypes were differentiated by means of a panel of monoclonal antibodies. 80.5% of acute lymphoblastic leukaemias originated from different developmental stages of B cells, 12.5% were formed by leukaemias from T cells and 7% were non-differentiated leukaemias. The mean follow-up period in the group was 33 months. According to the therapeutic results children with leukaemia ensuing from precursors of B cells had a more favourable prognosis than children with T leukaemia and children with non-differentiated leukaemia. Quantitative examination of nuclear DNA of leukaemic cells revealed in 55% of the patients of the group aneuploidy with clear predominance of hyperdiploidy, 45% of the patients suffered from diploidy. The least number of relapses was recorded in the investigation period in children with hyperploid acute lymphoblastic leukaemia. The proliferating activity of leukaemic blasts was expressed by the number of cells in the S + G2M stage of the cellular cycle and was higher in the bone marrow than in peripheral blood but did not differ in individual immunological subtypes or in diploid leukaemias. The authors were not able to prove its prognostic importance. Flow cytometry is a rapid and sensitive diagnostic method which makes it possible to characterize more satisfactorily the heterogeneous group of acute lymphoblastic leukaemias.

Cell Separation↗

PubMed1992

[DNA flow cytometry: perspective prognostic parameters in carcinoma of the uterine cervix].

We studied the relation between the 5-year disease free interval and the flow cytometric DNA content in a group of 55 patients treated by radiation for squamous cell carcinoma of the uterine cervix, stages Ib-IIIb (FIGO). The diploid DNA content was associated with a better prognosis, while prognostically unfavourable tumours tended to be aneuploid. The relation was statistically significant in the whole group (p = 0.016), in stage II disease (p = 0.003) and in the subgroup formed by the combination of stages I and II (p = 0.000). In stage III we did not prove the relation. Analysis of the survival function revealed also a better prognosis of diploid tumours (p = 0.041) in the whole group. The division into clearly diploid and non-diploid tumours seems to be more suitable for evaluation (p = 0.012). The difference between the prognostically favourable and unfavourable groups is expressed more clearly. We consider the flow cytometric DNA content a perspective prognostic parameter in squamous cell carcinoma of the uterine cervix. Its significance is apparent especially in patients treated by radiotherapy, because the size of the tumour cannot be assessed reliably in these cases.

Carcinoma, Squamous Cell↗

PubMed1991

[T-lymphocyte subpopulations in chronic active hepatitis].

In 33 patients with chronic active hepatitis quantitative changes were found in the ratio of different sub-populations of T lymphocytes in the peripheral blood stream which were either associated with treatment or with the presence of HbsAg in serum. A reduction of CD 3 positive lymphocytes was found in patients not treated by immunosuppression. In HbsAg positive patients an increase of CD 4 positive lymphocytes was found, as compared with HBsAg negative patients. Signs of activity of the hepatic process correlated with the presence of sign CD 8.

Adult↗

PubMed1991

[Cervico-acetabular impingement after femoral neck fracture].

Six cases of femoral neck-acetabular impingement following fracture of the femoral neck are reported. To our knowledge, this complication has not previously been described in the literature. A bony prominence at the level of the former fracture site following primary or secondary valgus position of the femoral head showed a conflict with the acetabular rim causing pain and limited motion. In four patients this impingement was posterior, between the femoral neck and the acetabulum in extension with external rotation, and in two patients it was anterior in flexion with internal rotation. A detailed description of the symptoms, diagnostic procedures and treatment options is presented.

Acetabulum↗

PubMed1990

Common variable immunodeficiency and malignancy: a report of two cases and possible explanation for the association.

Two patients with common variable immunodeficiency (CVID) and malignant tumours are reported. The first patient developed myelogenous leukaemia soon after the myelodysplastic syndrome has been diagnosed. The undifferentiated gastric lymphoma found in the second patient suggests that an increased risk of gastrointestinal malignancies in CVID could partly be due to lymphomas. We hypothesize that the tissue- or site-specific risk of lymphomas and gastrointestinal cancer can be explained by an increased chromosomal or genomic instability with a higher mutation rate and genomic disorganization, and that this instability could be related to viral carcinogenesis. The primary immunodeficiency per se may not be responsible for the cancer susceptibility in CVID patients.

Adult↗

PubMed1990

[Factors affecting the prognosis of acute lymphoblastic leukemia in childhood].

The authors tried to test the value of some clinical and laboratory characteristics for the prognosis of acute lymphoblastic leukaemia (ALL) in a group of 69 children treated according to three different protocols. The results were evaluated by methods of one-dimensional and multidimensional analysis. The absolute number of blasts in the peripheral blood stream and initial leucocytosis during establishment of the diagnosis proved to be the most important risk factors influencing the prognosis of the patients. Other adverse signs for the prognosis of ALL in the group were a mediastinal tumour, L2 type of leukaemic blasts according to the morphological FAB classification and age above 10 years when the diagnosis was established. The patient's sex, immunophenotype of the leukaemic blasts, chromosomal abnormality of the karyotype in the leukaemic cells, marked hepatosplenomegaly, thrombocytopenia, haemoglobin values and PAS reaction in the blasts, did not affect the therapeutic results in the author's group of patients.

Adolescent↗

PubMed1990

[Advances in the treatment of acute lymphoblastic leukemia in childhood: experience with intensive protocol treatments].

The authors analyzed a group of 64 children with acute lymphoblastic leukaemia (ALL) treated according to three protocols of different intensity. The best therapeutic results were obtained in children treated according to the most intensive protocol of the West German Multicentre Investigation BFM 83 which is graded as to its intensity with regard to the degree of risk of an adverse course. Successful remission in the entire group of patients was 93%, one third of the children developed during the investigation period a relapse of the basic disease. 12% of the children died during remission from complications of treatment. The surprising agreement of therapeutic results of different protocols after three years' complete remission is apparent from the fact that early relapses during the first two years of treatment, implying resistance to administered therapy, are at present the greatest problem of effective treatment which is not resolved even by the ever increasing intensity of treatment. In the conclusion the authors define the group of patients with a high risk of early relapse for whom new therapeutic procedures must be sought.

Adolescent↗

PubMed1990

[Immunologic profile in patients with acute anterior uveitis].

The authors investigated 52 patients (22 men and 30 women) with acute anterior uveitis where they ruled out systemic autoimmune disease, metabolic disease and focal or chronic infection. At the time of the infection the patients had not been treated for several months by any immunosuppressive treatment. The authors investigated in these patients serum concentrations of immunoglobulins G, A and M, the concentration of the C3 component of complement and the concentration of circulating immune complexes. Before the onset of therapy they investigated the response to antigens of the Immunoskin test. They assessed also the ratio of transplantation antigens class I by the microlymphocytotoxic test. They compared furthermore immunological indicators in subjects with a first attack and relapse of the disease and in groups, classified by the severity of the inflammatory symptoms. The authors detected significantly more frequently (p = 0.0005) the incidence of HLA-B27 antigen. Those where it was present were more frequently affected with a severe inflammation, as compared with subjects who did not have this phenotype (p less than 0.04). The relapse of the disease was more frequent in women (p = 0.1). The immunological laboratory findings did not differ in the first attacks and relapses of the disease, differences were, however, found in groups which differed as to the severity of inflammatory symptoms. In these groups the response rate to tests of skin sensitivity differed also. Based on these findings the authors assume that the ratio of immune processes in the development of acute idiopathic anterior uveitis cannot be ruled out.

Acute Disease↗

PubMed1990

Amplification of N-myc oncogene in human melanoma cells.

Tissue specimens from two melanoma patients and two patients with laryngeal carcinoma were studied for the expression of c-myc, N-myc and v-src oncogenes. Out of three different probes, only the N-myc probe one signalled amplification. While the two patients with laryngeal carcinoma showed only single copy of the N-myc gene in tumor cells, amplification of this gene was found in both two melanoma patients. The patients with 1 extra copy of the N-myc gene and its protein product had an early recurrence but is still alive, while the other melanoma patient with 4 extra copies of the gene, relapsed very early and died of melanoma within 7 months after diagnosis. Thus a higher amplification (4 extra copies) seems to correlate with very poor outcome of the disease.

Adult↗

PubMed1990

The importance of blast cell DNA content for prognosis of childhood acute lymphoblastic leukemia.

The prognostic value of cellular DNA content measured by static cytophotometry was evaluated in 69 children with acute lymphoblastic leukemia (ALL) using the pretreatment distribution of the DNA content in blast cells of bone marrow and peripheral blood. The median follow-up of the whole group of patients was 45 months. Aneuploidy was detected in 71% of children, most of them showing a hyperdiploid content (DNA index greater than 1.05). The duration of complete remission was significantly longer in patients with distinct hyperdiploid DNA content (DNA index greater than 1.16) than in those with less hyperdiploid and diploid DNA content (DNA index less than 1.16). The results achieved by static cytophotometry were compared with flow cytometry analysis and with cytogenetic investigations of chromosomal abnormalities in leukemic cells. Higher correlation was found between flow cytometry and cytogenetics. Flow cytometry proved to be a more convenient method for detection of the DNA content in leukemic cells than static cytophotometry.

Adolescent↗

PubMed1989

The Thy-1 glycoprotein is expressed in mouse embryonal carcinoma cells P19.

Thy-1 is a well characterized glycoprotein known to be variably expressed on the surface of different cell types. Serological analysis of a limited number of teratocarcinoma-derived cell lines suggested that mouse embryonal carcinoma cells do not express Thy-1 and that its expression is associated with the appearance of differentiated cells. In this report we show that monoclonal antibody 1aG4, recognizing Thy-1.2 epitope, binds specifically to P19 embryonal carcinoma cells and their undifferentiated subclones. A number of control experiments confirmed that 1aG4 antibody binds to the Thy-1.2 glycoprotein expressed on the surface of P19 embryonal carcinoma cells and not to the antigen expressed on differentiated derivatives of these cells or to a cross-reactive epitope. Transcriptional activity of the Thy-1 gene in undifferentiated P19 cells was shown by transfection experiments in which transfer of the Thy-1.1 gene into P19 cells resulted in stable expression of the Thy-1.1 antigen on the surface of recipient cells. Direct evidence for the presence of Thy 1 mRNA in P19 cells was obtained by Northern blot analysis with a Thy-1-specific cDNA probe. Treatment of P19 cells with retinoic acid resulted in a decrease in the expression of Thy-1 antigen which preceded changes in morphology of the cells. These data indicate that Thy-1 is a developmentally regulated surface marker of P19 embryonal carcinoma cells which is amenable to direct genetic analysis.

Animals↗

PubMed1989

Alpha-2b interferon in the treatment of advanced chronic lymphocytic leukemia.

In four patients treated for progressive B-CLL, stage C, with alpha-2b interferon a detailed analysis of the distribution of surface molecules characterizing both the leukemic and the residual populations of peripheral blood lymphocytes as evaluated by flow cytometry did not reveal any significant changes during and after the interferon therapy. With the dosage of 3 x 10(6) IU of interferon injected subcutaneously three times per week, no effect on progression of the disease was detected. The treatment was well tolerated, thrombocytopenia was the only side-effect observed.

Aged↗