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Biomedical subjects

S Sauter

Publications and source records attributed to S Sauter.

At least 19 recordsLinked to original sources

Chromosomal changes during progression of transitional cell carcinoma of the bladder and delineation of the amplified interval on chromosome arm 8q.

The cascade of genetic alterations leading to malignant transformation has been described for adenocarcinoma of the colon but is not established for other common tumor entities. In the present study, different stages of transitional cell carcinoma (TCC) of the bladder are analyzed by comparative genomic hybridization. A dynamic pattern of the chromosomal changes during tumor progression is described. Deletion of chromosome arm 9q is the earliest genetic alteration in pTa tumors. In stage pT1 carcinomas, losses of 9q, 9p, and 11p and gain of 1q and 8q are the most common. In addition to the changes specific for earlier stages, gain of 5p and 20q becomes prominent in carcinomas stage > or =pT2. Association analysis reveals a remarkable cooccurrence of 9p deletion with gain of 5p and 20q in > or =pT2 tumors. In order to determine more precisely the size of the amplified segment and the degree of amplification on chromosome arm 8q in stage pT1 tumors, this region was analyzed by semiquantitative PCR using polymorphic microsatellite markers. These studies revealed an up to 13-fold amplification. The common region of amplification could be narrowed down to 8q22.3 and between GAAT1A4 and D8S1834 (about 7 cM).

Carcinoma, Transitional Cell↗

Increased gene transfer into human CD34+ progenitor cells using retroviral vectors produced by a canine packaging cell line.

Using retroviral supernatants derived from the amphotropic murine packaging cell line PA317 and the amphotropic canine packaging cell line (DA), cord blood and mobilized peripheral blood CD34+ cells were transduced with the vector LN (neomycin resistance) and the vector L-TR/TAT neo (neomycin resistance in conjunction with a double-hammerhead ribozyme conferring anti-HIV activity). Different multiplicities of infection (MOI) were applied in the setup according to vector titrations on NIH-3T3 cells. PA317-based supernatants were tested at MOI of 10 and 30. Purified concentrated DA-derived vector preparations were tested at MOI of 10, 30, 100, and 300. Immediately after transduction, CD34+ cells were plated into colony assays in the presence and absence of G418 to evaluate the amount of gene transfer and potential toxic effects of the vectors on colony growth. The remaining cells were subjected to G418 selection in liquid culture for 12 days and subsequently challenged with HIV-1JR-FL to test for efficacy of the anti-HIV gene in macrophages derived from transduced CD34+ cells. Transduction by the PA317-packaged vectors was maximal at the lowest MOI used and did not increase with increasing MOI. In contrast, transduction by the DA-packaged vectors could be progressively increased using increased MOI. The net transduction efficiency per unit of reverse transcriptase activity in the DA vector preparations was 8.7-fold higher than in the PA317 vector supernatants. HIV-1 challenge of the cells transduced by the ribozyme vector derived from the PA317 packaging cells resulted in a 1.5 log inhibition of p24 output compared with the control cells containing neomycin resistance only. A 2.5 log inhibition of p24 output could be observed in the cell population transduced with DA-packaged vector supernatants. Compared with retroviral supernatants from PA317 packaging cell lines, DA packaging line-derived vector preparations demonstrated higher transduction efficiency into CD34+ cells, particularly at higher MOI, and increased efficacy of the transferred anti-HIV gene when challenged with HIV-1JR-FL. The increase in transduction efficiency may be due to a higher ratio of intact vs. defective vector particles in the DA-derived vector preparations.

Animals↗

Characterization of CD8+ cytotoxic T-lymphocyte responses after genetic immunization with retrovirus vectors expressing different forms of the hepatitis B virus core and e antigens.

Cytotoxic T-lymphocyte (CTL) activity appears to play an important role in resolving hepatitis B virus (HBV) infection, and the ability to induce such responses remains an important goal for developing effective immunotherapeutics. A panel of recombinant retrovirus vectors expressing different forms of the HBV core antigen (HBcAg) or e antigen (eAg) were found to induce antigen-specific major histocompatibility complex-restricted CTL responses in both mice and macaques. In addition, a novel retrovirus vector expressing an HBcAg-neomycin phosphotransferase II (HBc-Neo) fusion protein [LHBc-NEO(6A3)], which allows the measurement of the anti-Neo antibody response as a means of directly tracking biological activity of the vector, was generated. Doses greater than 10(7) CFU were necessary to induce CTL responses in H-2(k) mice. Intramuscular injections with 10(8) CFU of the LHBc-NEO(6A3) retrovirus vector into rhesus monkeys induced HBc/eAg-specific antibody production and CD8+ CTLs. The CTL response from one of the two responder rhesus monkeys was directed against a 9-residue peptide, GELMTLATW, at positions 63 to 71 of the HBc/eAg sequence. The CTL response is long lived, being detectable as late as 16 weeks after immunization, and can be boosted upon reimmunization. The potent ability of recombinant retrovirus vectors to induce HBcAg- and eAg-specific CTL responses may prove beneficial as a therapeutic treatment for chronic hepatitis B infection.

Animals↗

Central venous catheter infection by Aspergillus fumigatus in a patient with B-type non-Hodgkin lymphoma.

Invasive Aspergillus infection is still a major problem in immunocompromised patients. A central venous catheter infection by Aspergillus fumigatus, however, has not yet been reported. We describe the case of a 10-year-old female patient with B-type non-Hodgkin lymphoma treated according to the German chemotherapy protocol NHL-BFM 90. Isolation of Aspergillus fumigatus from the blood was the first hint of invasive aspergillosis. A central venous catheter-associated infection was suggested, since Aspergillus was also isolated from the thrombotic tip of the removed catheter. Secondary pulmonary aspergillosis was documented radiologically. The patient was treated successfully by Ampho-thericin B and Itraconazol and explantation of the central venous catheter under conditions of complete hematopoietic regeneration of the bone marrow with omission of the final chemotherapeutic cycle.

Antineoplastic Combined Chemotherapy Protocols↗

Pleuro-pulmonary blastoma: a case report and review of the literature.

Pleuro-pulmonary blastoma is a rare malignant lung tumor in children and distinct from ordinary pulmonary blastoma of adulthood. Combination chemotherapy plays an important role in the treatment of this tumor, but so far no attempt of high dose chemotherapy with subsequent bone marrow or blood stem cell transplantation has been published. The case is reported of a 2-year-old boy with pleuro-pulmonary blastoma who achieved partial remission with conventional chemotherapy and surgery. Subsequent administration of high dose melphalan, etoposide, and carboplatin, followed by autologous blood stem cell transplantation resulted in a 3-month disease-free interval but did not prevent eventual local recurrence, leading to death within a few weeks. Clinical presentation, pathology, management, and prognosis are discussed and the literature reviewed.

Child, Preschool↗

Hemophagocytosis: a complication of acute Q fever in a child.

We describe an 11-year-old boy with acute Q fever complicated by hemophagocytosis. In addition to pancytopenia, the boy presented with hyponatremia, hypofibrinogenemia, and changes in lipid metabolism. Examination of a bone marrow aspirate revealed striking hemophagocytosis. All of the pathological changes were caused by an activated macrophage system. We also discuss the possible role that pathogenetic mechanisms play in these changes.

Acute Disease↗

Non-Hodgkin's lymphomas of childhood and adolescence: results of a treatment stratified for biologic subtypes and stage--a report of the Berlin-Frankfurt-Münster Group.

PURPOSE: To prove the efficacy of a treatment stratified according to histology for children with non-Hodgkin's lymphoma (NHL), including acute B-cell leukemia (B-ALL). PATIENTS AND METHODS: From October 1986 to March 1990, 302 assessable patients, 0.6 to 17.8 years of age, with newly diagnosed NHL were enrolled onto study ALL/NHL-BFM 86. Fifty percent of patients had Burkitt-type lymphomas, including B-ALL; 24% had lymphoblastic lymphoma; 18% had diffuse large-cell lymphoma; and 8% had an NHL not further classified. Therapy group B included Burkitt's-type lymphomas, B-ALL, and most large-cell lymphomas including Ki-1 anaplastic large-cell lymphoma. Patients with stage I and II disease resected received three, while all others received six, 5-day therapy courses (dexamethasone, methotrexate [MTX] 0.5 g/m2 [5 g/m2 for stage IV and B-ALL], and intrathecal [IT] therapy in each course, plus ifosfamide, cytarabine, and etoposide alternating with cyclophosphamide and doxorubicin). Therapy for group non-B patients (lymphoblastic lymphoma and pleomorphic T-cell lymphoma [PTCL]) consisted of a Berlin-Frankfurt-Münster (BFM) acute lymphoblastic leukemia protocol, including cranial irradiation for advanced stage. Local therapy was restricted to patients with incomplete tumor regression. RESULTS: The probabilities of event-free survival (pEFS) at 7 years were 80% +/- 2% for the whole group, 81% +/- 3% for group B (n = 225), and 78% +/- 5% for group non-B (n = 77) with a follow-up duration of 3.6 to 7 years (median 5 years). Treatment results were comparable between NHL subtypes, except for PTCL, in which three of four patients suffered from relapse. Local disease manifestations were the most frequent site of failure. CONCLUSION: This therapy strategy provided patients of all NHL subtypes with an equally high chance to survive event-free, except patients with PTCL. With reduced systemic failure, local tumor control may become more important.

Adolescent↗

Chemotherapy in 998 unselected childhood acute lymphoblastic leukemia patients. Results and conclusions of the multicenter trial ALL-BFM 86.

In trial ALL-BFM 86, the largest multicenter trial of the Berlin-Frankfurt-Münster (BFM) study group for childhood acute lymphoblastic leukemia (ALL), treatment response was used as an overriding stratification factor for the first time. In the previous trial ALL-BFM 83, the in vivo response to initial prednisone treatment was evaluated prospectively. A blast cell count of > or = 1,000/microL peripheral blood after a 7-day exposure to prednisone and one intrathecal dose of methotrexate (MTX) identified 10% of the patients as having a significantly worse prognosis. In trial ALL-BFM 86 patients with > or = 1,000/microL blood blasts on day 8 were included in an experimental branch EG. Patients with < 1,000/microL blood blasts on day 8 were stratified by their leukemic cell burden into two branches, Standard Risk Group (SRG) and Risk Group (RG). SRG patients received an eight-drug induction followed by consolidation protocol M (6-mercaptopurine, high-dose [HD] MTX 4 x 5 g/m2) and maintenance. RG patients were treated with an additional eight-drug reinduction element. For EG patients protocol M was replaced by protocol E (prednisone, HD-MTX, HD-cytarabine, ifosfamide, mitoxantrone). All patients received intrathecal MTX therapy; only those of branches RG and EG received cranial irradiation. In branch RG, patients were randomized to receive or not to receive late intensification (prednisone, vindesine, teniposide, ifosfamide, HD-cytarabine) in the 13th month. During the trial reinduction therapy was introduced in branch SRG, because in the follow-up of trial ALL-BFM 83 the randomized low-risk patients receiving reinduction did significantly better. Nine hundred ninety-eight evaluable patients were enrolled, 28.6% in SRG, 61.1% in RG, 10.3% in EG. At a median follow-up of 5.0 (range 3.4 to 6.9) years, the estimated 6-year event-free survival was 72% +/- 2% for the study population, 58% +/- 5% in branch SRG for the first 110 patients without reinduction therapy, 87% +/- 3% for the next 175 patients with reinduction therapy, 75% +/- 2% in branch RG, and 48% +/- 5% in branch EG. Late intensification did not significantly affect treatment outcome of RG patients; however, only 23% of the eligible patients were randomized. Prednisone poor response remained a negative prognostic parameter despite intensified therapy. The results confirmed the benefit of intensive reinduction therapy even for low-risk patients. The strategy of induction, consolidation, and intensive reinduction may offer roughly 75% of unselected childhood ALL patients the chance for an event-free survival.

Adolescent↗

Job task and psychosocial risk factors for work-related musculoskeletal disorders among newspaper employees.

OBJECTIVES: A cross-sectional study was conducted to assess the association of upper extremity musculoskeletal disorders and work-related factors among employees using video display terminals at a large metropolitan newspaper. METHODS: The study included 1050 randomly selected workers from four departments. The workers were asked to complete questionnaires on symptoms, job tasks, and psychosocial and work organization conditions. Musculoskeletal disorders of the upper extremities were defined by frequency, duration, and intensity of symptoms not attributable to acute injury. Data were analyzed with the use of logistic regression. RESULTS: A total of 973 workers completed the survey. The one-year period prevalence rate for any musculoskeletal disorder of the upper extremities was 41%. Neck symptoms (26%) were the most frequently reported, followed by hand or wrist (22%), shoulder (17%), and elbow (10%) symptoms. Greater time working at the video display station was associated with increased hand or wrist symptoms in a dose-response relationship. In addition, variables corresponding to increased work-load demands (eg, increased time working under deadline and increased job pressure) were associated with increased neck, shoulder, and hand or wrist disorders. Women were more likely to report symptoms in several areas, but this finding may reflect the concentration of women in jobs involving more risk factors. CONCLUSIONS: The results suggest a high prevalence of musculoskeletal disorders of the upper extremities among newspaper employees, and they provide additional evidence that increased work load, time pressure, and greater hours of computer use are related to the occurrence of work-related musculoskeletal disorders among these workers, particularly for disorders in the hand or wrist area.

Adult↗

Current echoes.

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Journal Article↗

Acute onset deafness in a 4-year-old girl after a single infusion of cis-platinum.

Dose-dependent reduction of auditory function mainly in the high frequency range has been described as a common adverse side effect of cis-platinum. Here we report on a 4-year-old girl with osteosarcoma of the right distal femur who developed acute bilateral deafness 3 days after a single infusion of high-dose cis-platinum (150 mg/m2) during preoperative chemotherapy. Sudden disabling ototoxicity should be considered when administering high-dose cis-platinum to young children.

Acute Disease↗

Synergistic neurotoxicity of carbon tetrachloride/carbon disulfide (80/20 fumigants) and other pesticides in grain storage workers.

Neurophysiologic, neurobehavioral, and neuropsychologic profiles in 17 grain storage workers, 1 grain inspector, and 4 malting laboratory workers are described. The effects of CS2 toxicity as seen in viscose rayon workers as well as in experimental animals is remarkably similar to the clinical profile of our grain storage workers. CS2 use explains the dysfunction of peripheral axons, auditory nerve, the optic nerve, and the extrapyramidal system, as well as altered behavior and cognition changes. The signs and symptoms in these workers seem to be dose-related and we note that workers separated out from the areas where fumigation took place reported improvement not seen by fellow workers who continued the fumigant treatment routine. Likewise, malting laboratory workers exposed only to the grain dust from 3 to 7 years showed only minimal symptoms. Though a number of mechanism have been suggested for the alteration of neuropsychological function, the chelating ability of DDC derived from CS2 and its ability to markedly increase copper and zinc within the central nervous system suggests a mechanism of toxicity analogous to copper intoxication as in Wilson's Disease and may explain the production of extrapyramidal symptoms in these patients. Chelation of copper might prove therapeutic in CS2 poisoning. It is obvious that both basic and clinical research will be necessary to sort out the questions raised. We applaud the EPA's decision to ban the use of 80/20 fumigants and also methyl bromide, and trust that similar toxic substances be carefully studied before their selection for replacing these previous toxic agents. We further decry the technique of re-introducing grain dust into the food chain rather than destroying it, since the dust contains very high residues of fumigant material. We speculate on the possible role of CS2 and other pesticides in the food chain and the incidence of Parkinsonian symptoms in these patients and the general public.

Adult↗

Deposition of beta 1H globulin in kidneys of patients with immune renal disease.

Renal biopsies from patients with a variety of immune type renal diseases were examined by immunofluorescence for the presence of C3 and its control protein, beta 1H globulin. Deposits of beta 1H were found in every instance (21 of 21 biopsies) in which C3 deposits were observed, irrespective of the underlying disease resulting in the C3 deposits, including lupus nephritis, acute poststreptococcal glomerulonephritis, idiopathic membranous glomerulonephritis, and Goodpasture's syndrome. In no instance was beta 1H found independently of C3. As previously shown in in vitro systems, beta 1H also binds to C3, presumably C3b, during activation of the complement system in immunologically induced renal disease.

Anti-Glomerular Basement Membrane Disease↗