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Biomedical subjects

H F Otto

Publications and source records attributed to H F Otto.

At least 73 records · Page 4Linked to original sources

[Analysis of chromosome copy number changes in leiomyosarcoma through molecular cytogenetic methods].

Leiomyosarcoma (LMS) is a rare type of malignant soft tissue tumor occurring predominantly in adults. Up to now only few zytogenetic data resulting from chromosomal banding analyses were obtained from this tumor type. In general, highly complex karyotypes were observed, but no recurrent chromosomal aberrations could be identified. The aim of the present study was to analyze chromosomal imbalances in 14 cases of LMS using comparative genomic hybridization (CGH). Imbalances were detected in all cases analyzed, with chromosomal gains occurring more frequently than losses (9.9 gains/case vs. 6.9 losses/case, respectively). Chromosome arms predominantly overrepresented included Xp (9/14 cases), 5p and 8q (8/14 each), as well as 17p and 17q (6/14 each). Nineteen distinct high level amplifications, indicative for the location of relevant proto-oncogenes in LMS, were identified in nine different tumors. Interestingly, in three cases chromosomal arm 17p was involved. Interphase analysis with probes derived from the commonly amplified region 17p11-p12 revealed, that the tre oncogene is co-amplified and therefore could play a relevant role in LMS development. With regard to losses chromosome 13q was affected in 12/14, 10q in 8/14, and 2p as well as 2q in 7/14 tumors, respectively. The frequent deletions of chromosome 13 with a minimal affected region 13q14-q15 strongly support preliminary molecular evidence, that loss of the RB1 tumor suppressor gene is a critical step in LMS tumorigenesis.

Adult↗

[Demonstration of SYT-SSX11/2 fusion transcripts in synovial sarcomas using RT-PCR].

Various mesenchymal malignancies with a spindle cell morphology may mimic monophasic synovial sarcomas. We analysed, whether detection of SYT-SSX1/2 fusion transcripts, present as a consequence of a specific translocation [t(X;18)(p11.2;q11.2)] found in synovial sarcomas, are useful to confirm the diagnosis of synovial sarcoma. A nested RT-PCR protocol was established for the detection of SYT-SSX1/2 fusion transcripts. After RNA extraction of snap frozen tissue reverse transcription was carried out. In a nested PCR, the resulting cDNA samples were amplified and visualized on agarose gels. DNA sequencing of PCR products enabled the assignment of fusion transcripts to either the SYT-SSX1 or the SYT-SSX2 variant. We detected SYT-SSX1/2 fusion transcripts in seven monophasic and three biphasic synovial sarcomas. 20 out of 21 control tumour including leiomyosarcomas, malignant peripheral nerve sheath tumours, gastrointestinal stromal sarcomas and fibrosarcomas were negative in RT-PCR analysis. One case of recurrent spindle cell sarcoma originally classified as a fibrosarcoma revealed a SYT-SSX2 fusion transcript. These data provide further evidence that the RT-PCR amplification of SYT-SSX1/2 fusion transcripts permits the specific identification of synovial sarcomas. This diagnostic approach may be especially useful in cases with equivocal histomorphology.

Chromosome Mapping↗

Wolf-Hirschhorn syndrome: case report and review of the chromosomal aberrations associated with diaphragmatic defects.

A female fetus showing severe growth retardation was delivered at 31 weeks of gestation because of fetal distress. At birth, the infant showed bradycardia and no spontaneous breathing. Although high frequency oscillatory ventilation was started, severe asphyxia persisted and the infant died of respiratory insufficiency. At the autopsy, the propositus showed microcephaly, prominent glabella, broad bridge of the nose, ocular hypertelorism, poorly differentiated and low-set ears, bilateral palatoschisis, and micrognathia. Midline closure defects of the cervical spine bodies, lower jaw, and skull base were seen at postmortem radiography. An extreme hypoplasia of both lungs, a large defect of the left diaphragm with upward displacement of viscera, and multiple cortical cysts in both kidneys were seen at postmortem examination. Karyotyping revealed a chromosomal imbalance with 46, XX, del(4) (pter-->13), characterizing the Wolf-Hirschhorn syndrome. Because diaphragmatic defects can occur in association with specific recognizable patterns of human malformation careful pathologic and genetic workup of all affected infants in crucial for accurate genetic counseling.

Abnormalities, Multiple↗

[DNA cytometry in breast carcinoma. Review of method and value in assessing prognosis].

DNA flow cytometry (FCM) has become a routine method in breast cancer diagnosis for evaluation of ploidy and proliferation kinetics (cell cycle analysis). Image cytometry is less practicable and provides less information than flow cytometry. An optimized technique with a low coefficient of variation is required for optimal results in flow cytometry. The S-phase fraction and the proliferation index (sum of S-phase fraction and G2M fraction) provide prognostic and therapeutically relevant information. A profound knowledge of the technique and its limitations is indispensable for the interpretation of FCM results. It remains to be established whether immunohistological evaluation of cell proliferation has the same prognostic value. Future developments are to be expected from multiparametric analysis and the improvement of mathematical analysis of FCM measurements.

Breast↗

[Subtyping and prognostic assessment of invasive lobular breast carcinoma].

Invasive lobular carcinoma (ILC) is recognized in its classical form and as variants with tubulo-lobular, solid, pleomorphic, alveolar or signet ring cell differentiation. The most common classical form differs from invasive ductal carcinoma (IDC) by its slower tumor proliferation and less common axillary metastases. When compared stage by stage, long term prognosis is similar to IDC, however. Prognostic subtyping of ILC can be achieved by the recognition of variant forms and mitotic counting. The combination of these factors may be used for tumor grading (5-year survival 100% with grade 1 vs. 82% with grade 2, and 57% with grade 3, n = 241). The detailed histopathologic diagnosis therefore permits prognostic assessment also in ILC.

Adult↗

A 19-week-old fetus with craniosynostosis, renal agenesis and gastroschisis: case report and differential diagnosis.

A case of a fetus affected with craniosynostosis, unilateral renal agenesis and gastroschisis is reported. The propositus was delivered on the 19th week of gestation for premature rupture of the membranes. Macroscopy showed turricephaly, shallow orbits, exophthalmos, hypertelorism, hypoplastic maxilla with relative mandibular prognathism and gastroschisis. Additional autopsy findings included a premature bilateral closure of the lambdoid suture and a unilateral renal agenesis. The nosological aspects of this fetus and the differential diagnosis of well-described craniosynostosis syndromes with characteristic craniofacial growth patterns (Crouzon syndrome, Jackson-Weiss syndrome, Apert syndrome, Saethre-Chotzen syndrome, Pfeiffer syndrome) are discussed.

Abdominal Muscles↗

Podocytes are the major source of IL-1 alpha and IL-1 beta in human glomerulonephritides.

To address the question of in situ production of IL-1 alpha and IL-1 beta in proliferative and non-proliferative forms of human glomerulonephritis (GN), we performed immunocytochemical and in situ hybridization studies on renal biopsies from patients with mesangial IgA-GN (N = 38), idiopathic membranous GN (MGN; N = 12), minimal change disease (MCD; N = 9), focal segmental glomerulosclerosis (FSGS; N = 5) and acute endocapillary GN (AGN; N = 3). Normal kidneys (N = 10) served as controls. Concomitantly, the expression of IL-1 receptor type I (IL-1 RI), IL-1 receptor type II (IL-1 RII) and of IL-1 receptor antagonist (IL-1 RA) was analyzed. Antibodies against antigens expressed on podocytes (PP-44), endothelial cells (CD31) and monocytes/macrophages (CD11b, CD14, CD68) were applied to attribute the expression of IL-1/IL-1 related peptides to intrinsic glomerular and/or blood-derived infiltrating cells. Our results demonstrate that IL-1 RII is constitutively expressed on endothelial cells, and its expression can be induced in proximal tubular cells and in the interstitium. In diseased glomeruli podocytes are capable of producing IL-1 alpha/beta. In MGN and MCD/FSGS, the expression of both IL-1 forms is particularly noted in early stages of the disease and is not only accompanied by a marked reactivity for IL-1 RI, but also for IL-1 RA. In segmental sclerosing lesions in FSGS and in IgA-GN with marked glomerular proliferation and/or sclerosis, a reduced expression of the PP-44 antigen and a diminished ability of podocytes to produce IL-1/IL-1 related peptides are noted. These results suggest that intrinsic glomerular production of IL-1 may be of relevance for the protection of glomeruli from continuing injury.

Acute Disease↗

Epidemiology of Whipple's disease in Germany. Analysis of 110 patients diagnosed in 1965-95.

BACKGROUND: The epidemiology of Whipple's disease (WD) is obscure. To obtain basic data, we performed an evaluation of WD patients in Germany. METHODS: Information was collected from 110 WD patients diagnosed during 1965-95 at 5 institutions in different regions of Germany. Four items were evaluated: 1) year in which the diagnosis was made; 2) residence and 3) age at the time of diagnosis; and 4) sex. RESULTS: WD patients originated from all parts of Germany. The incidence of new cases was relatively stable, with a mean of one to two cases per year per collecting centre. In 1995, a maximum of 13 new WD patients was diagnosed. There was a significant increase in the mean age of patients (1965-75, 48.7 years; confidence interval, +/- 3.98 years; 1976-85, 50.7 years, +/- 3.69 years; 1986-95, 57.0 years, +/- 2.80 years; P < 0.01) and an increasing proportion of women (1965-85, 4%; 1986-1995, 22%). CONCLUSIONS: Whipple's disease is not quite as rare as commonly assumed. There is no obvious geographic predominance. During the past three decades, the demography of WD patients has changed.

Adult↗

Transferral of extrathoracic donor neoplasm by the cardiac allograft.

The transference of neoplasm from the donor to the recipient is a rare but recognized complication of organ transplantation. It has been reported after kidney transplantation from cadaver donors. We report a case in which an extrathoracic tumor was transmitted by the donor heart. The donor heart was harvested from a 46-year-old local donor and immediately transplanted to a 62-year-old female recipient. While implantation was performed, a hypernephroma was detected in the multiorgan donor. The ongoing heart transplantation could not be stopped. Four weeks after operation, the patient was discharged from the hospital. During the first year after transplantation, the clinical course was uneventful. One year after operation, the patient was admitted to the hospital with symptoms of weakness and fever. A right facial hemiparesis occurred, and a soft tumor was palpable subcutaneously in the right supraorbital region. Histologic examination revealed a malignant tumor with characteristics identical to the donor hypernephroma. In spite of chemotherapy and radiation therapy, dramatic tumor progression occurred with multiorgan metastases, which led to the death of the patient 2 months after admission.

Brain Neoplasms↗

Aspergillus endocarditis, myocarditis and pericarditis complicating necrotizing fasciitis. Case report and subject review.

A patient with Aspergillus endocarditis, myocarditis and pericarditis is described. A 55-year-old man developed necrotizing fasciitis of the lower abdominal wall, pelvis and right thigh. Despite aggressive surgical débridement and antibiotic coverage, the patient died of multisystem organ failure. Autopsy revealed Aspergillus thromboulcerative endocarditis, myocarditis and pericarditis, acute necrotizing fungal bronchopneumonia and mycotic dissemination to brain, kidney and thyroid gland. A review of the literature showed that in the absence of open-heart surgery Aspergillus endocarditis and myocarditis are very uncommon.

Aspergillosis↗

Histology of intestinal Whipple's disease revisited. A study of 48 patients.

Whipple's disease is an infectious disorder with intestinal and extra-intestinal manifestations. We reinvestigated the intestinal histology in a series of 48 patients (10 females, 38 males; mean age 56.5 years, standard deviation of the mean +/- 11.2 years). A total of 126 biopsy samples, obtained prior to, during, and after therapy, were evaluated by light microscopy. In 43 patients (90%), histology was consistent with common descriptions, while it was uncommon in 3 patients (6%), and non-diagnostic in 2 patients (4%). During treatment, several alterations occurred. Apart from a continuous decrease in PAS-positive macrophages, the pattern of mucosal infiltration changed from diffuse to patchy. Moreover, the cytological aspects of PAS-positive macrophages changed substantially, and this change was used to propose four different subtypes. Initially, subtype 1 macrophages predominated (74%), but showed a gradual decrease within a few months of therapy. After 15 months, subtype 3 and subtype 4 macrophages predominated (< 80%). In 7 of 9 patients followed over long periods some subtype 3 or subtype 4 macrophages persisted. It is concluded that at diagnosis and during treatment the intestinal histology of Whipple's disease is heterogeneous. A few PAS-positive macrophages commonly persist at long-term follow-up. This and other features suggest the presence of a persistent immune defect.

Animals↗

A rapid and highly specific technique to detect hepatitis C RNA in frozen sections of liver.

AIMS: To develop a polymerase chain reaction (PCR) based technique that would permit the rapid and highly specific detection of hepatitis C virus (HCV) RNA extracted from frozen liver tissue. METHODS: Samples of liver tissue from 18 patients undergoing orthotopic liver transplantation were studied. Nine patients were HCV positive. Total RNA was extracted from between one and 10 sections, 10 microns thick, from each tissue sample. HCV RNA was amplified by (1) conventional, multistep reverse transcription PCR (RT-PCR) and by (2) combined, single step RT-PCR using coupled oligonucleotide primers based on the sequence of the 5' untranslated region of the viral genome. Positive results were confirmed by dot blot analysis using a digoxigenin labelled oligoprobe (Alx 89). RESULTS: HCV RNA was detected in the nine HCV positive patients by both conventional and combined RT-PCR. HCV RNA was not detected in the HCV negative patients. As little as 500 ng total RNA was needed as the template to yield detectable amounts of amplified cDNA. The digoxigenin labelled oligoprobe hybridised with HCV RNA positive specimens only. CONCLUSIONS: The combined, single step RT-PCR is a rapid and sensitive technique for detecting HCV RNA in frozen liver tissue.

Base Sequence↗

Melanotic paraganglioma of the posterior mediastinum.

A melanotic paraganglioma occurred in a 57-year-old woman, located in the left paravertebral space of the upper mediastinum. It was totally resected. During a 5 year follow up period neither tumour recurrence nor metastasis were observed. Histological examination of the tumour revealed a paraganglioma with monomorphous chief cell like elements which were arranged in a "zellballen" pattern. Immunohistochemical results also were in accordance with the diagnosis since neuron-specific enolase, chromogranin and synaptophysin were found in tumour cells whereas keratin was not. Additionally, neurosecretory granules were found in tumour cells during electron microscopy. A peculiar feature of the tumour was its strong pigmentation due to melanin located within the tumour cells and tumour associated melanophages. The simultaneous expression of functional properties of two different neural crest derived cells in one tumour stresses the close relationship between all neural crest elements and is in accordance with the observation of other melanotic, non-melanomatous tumours.

Cytoplasmic Granules↗