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H F Otto

Publications and source records attributed to H F Otto.

At least 55 records · Page 3Linked to original sources
PubMed1999

Comparison of losses of heterozygosity and replication errors in primary colorectal carcinomas and corresponding liver metastases.

In order to investigate genetic alterations specific to liver metastases of colorectal carcinomas, losses of heterozygosity and replication errors have been compared in 15 cases of primary colorectal carcinoma and in the corresponding metastatic liver tumours. Fifteen microsatellite markers located on 13 different chromosomal arms were used in the study. The LOH patterns of the primary and the metastatic tumours were identical in eight cases and showed differences in seven cases. Areas of deletion predominantly or completely common to the colorectal and the metastatic tumour were detected on chromosomes 5q, 8p, 17p, 18q, and 22q. Preferential loss in metastatic tumours was observed on chromosomal arm 3p. Replication errors were found in four primary tumours and in three of the corresponding secondaries. A replication error phenotype specific to a metastasis was not observed.

Adult↗
PubMed1999

Intracardiac yolk sac tumor in an infant girl.

We report about a two and a half year old girl with a primary yolk sac tumor (YST) of the heart, located in the interventricular septum. The girl was admitted to the hospital with a systolic cardiac murmur. Echocardiography revealed a smoothly surfaced tumor which based on the interventricular septum below the aortic valve and filled out more than half of the left ventricular cavity. Diagnosis of a yolk sac tumor was established on a frozen section of a biopsy taken at surgery and confirmed by the examination of the resected material. Excessively elevated serum alpha-fetoprotein (AFP) levels contributed to this diagnosis. Follow up examinations of the patient including computed tomography (CT) of head, thorax and abdomen, did not indicate an extracardiac tumor manifestation. We found no previous report of a primary intracardial yolk sac tumor in the literature.

Child, Preschool↗
PubMed1999

Expression of the membrane protein tyrosine phosphatase CD148 in human tissues.

CD148, a receptor-like protein tyrosine phosphatase also known as HPTP-eta/DEP-1, is involved in signal transduction in leucocytes and is thought to contribute to mechanisms of cellular differentiation. We have investigated the in situ expression of CD148 in various fresh-frozen tissues by immunohistology and analyzed its expression on subpopulations of activated peripheral blood leucocytes by flow cytometry. In lymphoid organs, CD148 was found to be widely expressed on B and T cells, granulocytes, macrophages, certain dendritic cells as well as mature thymocytes. The cellular level of CD148 was increased after in vitro activation of peripheral blood leucocytes. Comparative analysis of tissue samples from normal gut and from patients with active Crohn's disease showed that leucocytes expressing CD148 are significantly upregulated in inflamed tissues and that a subset of these cells co-express the activation marker CD25. In non-lymphoid tissues, CD148 was found to be present on many epithelial cell types with glandular and/or endocrine differentiation as well as on fibrocytes, melanocytes and Schwann cells. CD148 expression was maintained also in malignant counterparts of such tissues. However, a marked loss of CD148 immunoreactivity was apparent in some of the investigated high-grade carcinomas. In summary, our results confirm a role of CD148 as a leucocyte activation marker. Among non-hematopoietic cells, CD148 is expressed by characteristic types of epithelial and non-epithelial cells. Downregulation of CD148 might promote dedifferentiation and autonomous growth of such cells in malignant tumors.

Adenocarcinoma↗
PubMed1999

Extraneural metastasizing ependymoma of the spinal cord.

This paper reports a case of the rare entity of an extraneural metastasizing ependymoma of the spinal cord. The tumor which arose in the conus medullaris and in the cauda equina was first diagnosed in 1956 when a thoracolumbar myeloresection was performed. At autopsy, 40 years after the primary diagnosis, a massive local tumor recurrence with extraneural metastases in the lungs, the pleura, the liver, and the thoracal and abdominal lymph nodes were found. Immunohistochemical stains of the extraneural metastases showed a strong cytoplasmatic expression of glial fibrillary acidic protein (GFAP). Neither the primary tumor nor its metastases showed any of the conventional morphological criteria of malignancy. Reviewing the literature we discuss the possible mechanism of extraneural tumor spread and the incidence of metastases with regard to the tumor type.

Adolescent↗
PubMed1999

Pericardial involvement by thymomas. Entirely intrapericardial thymoma and a pericardial metastasis of thymoma with glomeruloid vascular proliferations.

Thymomas are usually found in the anterior mediastinum, the normal location of the thymus. Involvement of the pericardium by thymic tumors is seen in invasive or metastasized thymoma. Very rarely, thymomas arise primarily in the pericardium. These tumors are believed to derive from thymic tissue which was misplaced in the pericardium during embryologic development. In contrast to patients with orthotopic thymoma who commonly suffer from paraneoplastic diseases, especially myasthenia gravis, patients with intrapericardial thymoma manifestations mainly have symptoms of congestive heart failure which are caused by local complications of tumor growth. In this study, we present two cases of thymoma involving the pericardium. Both tumors were polygonal-oval cell thymomas. In one of the cases diagnosis of an entirely intrapericardial thymoma was established by autopsy. In the other case, explorative thoracotomy revealed massive pericardial and pleural tumor manifestations. The latter tumor showed a peculiar histological pattern with multiple glomeruloid bodies, a finding reported only once for thymomas.

Adult↗
PubMed1999

Refractory congenital ascites as a manifestation of neonatal sialidosis: clinical, biochemical and morphological studies in a newborn Syrian male infant.

A Syrian newborn with coarse facies, hepato-splenomegaly, and refractory ascites is reported. Examination of the ascitic fluid showed vacuolated lymphocytes and thin-layer chromatography of urinary oligosaccharides revealed an abnormal pattern indicative of sialidosis. Despite intensive care, the baby died of respiratory insufficiency 28 days after birth. In cultured skin fibroblasts an increase of the incorporation of [14C]methylamine pointed to excessive lysosomal storage and the demonstration of an isolated deficiency of alpha-N-acetylneuraminidase (sialidase) led to the diagnosis of a sialidosis. At postmortem examination, foam cells were found mostly in bone marrow, liver, and brain. To date very few cases of neonatal sialidosis have been reported, and, to the best of our knowledge, this is the first child with neonatal sialidosis from Syria and the first case of neonatal sialidosis studied by the [14C]methylamine incorporation assay.

Ascites↗
PubMed1999

Low-dose budesonide treatment for prevention of postoperative recurrence of Crohn's disease: a multicentre randomized placebo-controlled trial. German Budesonide Study Group.

OBJECTIVE: Endoscopic recurrence of Crohn's disease frequently occurs within weeks after 'curative' operation. Treatment with 3 x 1 mg oral pH-modified release budesonide was tried to prevent postoperative recurrence. DESIGN: A multicentre randomized double-blind placebo-controlled trial of 1 year duration was performed. SETTING: Departments of surgery, endoscopy and pathology of three university hospitals participated in the trial. PATIENTS: Patients with Crohn's disease who underwent ileal and/or colonic resection and whose anastomosis was accessible to colonoscopy were admitted to the study. Of the 88 randomized patients, 83 patients were included in the efficacy analysis (budesonide n = 43, placebo n = 40). Treatment was started within 2 weeks after surgery. INTERVENTIONS: Colonoscopy was performed 3 and 12 months postoperatively. The anastomosis and the adjacent bowel were evaluated by endoscopy and histology. For follow-up of the clinical course of the disease the Crohn's disease activity index (CDAI) was used. MAIN OUTCOME MEASURES: The primary outcome variable was recurrence of Crohn's disease based on endoscopic findings. Secondary efficacy variables were histology scores, CDAI, time-to-failure and global judgement of well-being of the patient. RESULTS: The recurrence rate after 1 year (endoscopic and/or clinical) was 57% (20/35) in the budesonide group and 70% (19/27) in the placebo group (n.s.). Mean time-to-failure was 196 days under budesonide and 154 days under placebo (n.s.). Median CDAI (relapse 19% vs. 28%) and global patients' judgement at the end of treatment (bad 5% vs. 15%) was slightly in favour of budesonide. One patient in each group discontinued the trial because of adverse events. Potentially steroid-related side effects were reported more frequently in the placebo than in the budesonide group (32% vs. 17%) (n.s.). SUMMARY AND CONCLUSION: Although the effect of budesonide was altogether positive in almost all variables studied in this trial (e.g. endoscopic and histopathological score, time-to-failure, CDAI, patients' global judgement and rate of side effects), this increase in efficacy was small and the power for detecting differences versus placebo was too low to be statistically significant. According to these results, low-dose oral budesonide cannot be recommended to be used for the prevention of postoperative relapse in Crohn's disease.

Administration, Oral↗
PubMed1999

Analysis of chromosomal imbalances in sporadic and NF1-associated peripheral nerve sheath tumors by comparative genomic hybridization.

Peripheral nerve sheath tumors arise either sporadically or in association with neurofibromatosis type 1 (von Recklinghausen's neurofibromatosis, NF1) or type 2. In this study, comprehensive screening for relative chromosome copy number changes was performed on 10 benign and 19 malignant peripheral nerve sheath tumors (MPNSTs) by applying comparative genomic hybridization (CGH). In benign tumors, no chromosomal imbalances were found by CGH, whereas in MPNSTs chromosomal gains and losses were frequently detected. No differences regarding the frequency and distribution of chromosomal imbalances were observed between the 13 sporadic and 6 NF1-associated MPNSTs analyzed. In both, the number of gains was significantly higher than the number of losses, suggesting a predominant role of proto-oncogene activation during MPNST progression. Candidate regions with potentially relevant proto-oncogenes included chromosomal bands 17q24-q25, 7p11-p13, 5p15, 8q22-q24, and 12q21-q24; those with putative tumor suppressor genes were 9p21-p24, 13q14-q22, and 1p. High-level amplifications were restricted to sporadic tumors and affected eight different chromosomal subregions. In three of these MPNSTs, identical subregions on chromosomal arms 5p and 12q were coamplified. This study revealed a number of new characteristic chromosomal imbalances and provides a basis for molecular identification of oncogenes and tumor suppressor genes of pathogenetic relevance in both sporadic and NF1-associated MPNSTs. Genes Chromosomes Cancer 25:362-369, 1999.

Adolescent↗
PubMed1999

Beta-catenin accumulation and mutation of the CTNNB1 gene in hepatoblastoma.

Hepatoblastoma is a rare malignant tumor of the liver that occurs in children at an average age of 2 to 3 years. Epidemiologic studies have shown an increased frequency of this tumor type in families affected by adenomatous polyposis coli. In addition to the epidemiologic data, molecular genetic studies suggest that inactivation of the APC tumor suppressor may be involved in hepatoblastoma tumorigenesis. A major function of APC is the downregulation of beta-catenin, a transcription-activating protein with oncogenic potential. In an ongoing immunohistochemical study of beta-catenin expression in sporadic cases of tumor types that are associated with adenomatous polyposis coli, we observed increased beta-catenin levels in the cytoplasm and in the nuclei of three investigated hepatoblastomas. Sequencing of exon 3 of the beta-catenin gene (CTNNB1) revealed an activating mutation in one of the tumor samples. Our data indicate for the first time that beta-catenin accumulation may play a role in the development of hepatoblastoma and that activating mutations of the beta-catenin gene may substitute biallelic APC inactivation in this tumor type. Genes Chromosomes Cancer 25:399-402, 1999.

Cadherins↗
PubMed1999

CATCH 22 syndrome: report of 7 infants with follow-up data and review of the recent advancements in the genetic knowledge of the locus 22q11.

CATCH 22 is a medical acronym for Cardiac defects, Abnormal facies, Thymic hypoplasia, Cleft palate, and Hypocalcemia, and a variable deletion on chromosome 22. The deletion within the chromosome region of 22q11 may occur in patients with three well-described dysmorphologic+ cardiological syndromes: DiGeorge syndrome (DGS), velocardiofacial syndrome (VCFS), and conotruncal anomaly face syndrome (CTAFS). We report in detail seven infants with a deletion of the locus 22q11 showing overlapping clinical features of DGS and CTAFS with complex congenital heart defects (double outlet right ventricle, atresia or stenosis of the pulmonary valve, atrial and ventricular septal defects, patent ductus arteriosus, tetralogy of Fallot, major aortopulmonary collateral arteries, arcus aortae dexter, and persistence of the left superior vena cava). A homograft was implanted between the right ventricle and the main stem of the pulmonary artery in 2 patients, while a balloon valvuloplastic of the pulmonary valve was performed in one patient only. Pulmonary hemorrhage, acute hypoxia, and Aspergillus pneumonia were the complications. Death occurred in three out of seven patients. Recent advancements in the genetic knowledge of the locus 22q11 are described. Since the locus 22q11 is highly heterogeneous, the CATCH 22 acronym should be used and temporarily the old eponyms should be abandoned waiting for the identification of the different genes.

Abnormalities, Multiple↗
PubMed1998

Short-rib-polydactyly syndrome type Verma-Naumoff-Le Marec in a fetus with histological hallmarks of type Saldino-Noonan but lacking internal organ abnormalities.

Up to seven short-rib-polydactyly (SRP) syndromes have been identified so far with marked clinical and pathological overlap. We describe a 32-week-old, nonhydropic male fetus with thoracic "dysplasia," short limbs, and unilateral postaxial polydactyly. All internal organs were normally developed, including the central nervous system. The external genitalia were unambiguously male, in accordance with a 46,XY karyotype. Radiological signs most closely resembled those of SRP, type Le Marec, though histology of the femoral physeal growth zone was consistent with the Saldino-Noonan type. The remarkable lack of visceral anomalies in conjunction with the radiological and histological findings further adds to the phenotypic spectrum of the SRP syndromes. The histological analysis in this case supports a close relationship between types Saldino-Noonan and Verma-Naumoff-Le Marec.

Fetal Diseases↗
PubMed1998

Carcinoid tumor of the middle ear in a 28-year-old patient.

Carcinoid tumor of the middle ear is an extremely rare condition. The origin of the tumor cells is still speculative and the closeness of relationship to adenomas of the middle ear has been a matter of discussion since the first description of this tumor entity in 1980. In this study we report a case of a 28-year-old male patient with a carcinoid tumor of the middle ear. We present the results of histomorphological, immunohistochemical and electron microscopic examinations and compare our findings to those of previously published cases.

Adult↗
PubMed1998

In situ expression of interleukin-10 in noninflamed human gut and in inflammatory bowel disease.

A dysregulated secretion of contra-inflammatory cytokines such as interleukin-10 (IL-10) could play a role in the pathogenesis of inflammatory bowel disease (IBD). We have investigated the expression of IL-10 in gut tissues from patients with Crohn's disease (CD), ulcerative colitis (UC) and controls by mRNA in situ hybridization and immunohistochemistry. Intestinal epithelial cells were found to express IL-10 mRNA and IL-10 protein in all of the tissues investigated without any major differences in the expression patterns. However, compared with noninflamed gut, significantly increased numbers of mononuclear cells (MNCs) producing IL-10 were present in inflamed gut, both in CD and UC. This cytokine was expressed most prominently by inflammatory infiltrates enriched in macrophages, although T cells seem to contribute to its production as well. Elevated IL-10 expression in IBD was mainly detected in the submucosa, whereas IL-10 production by lamina propria cells remained comparably low. In contrast, the expression of IL-1beta mRNA was preferentially increased in the lamina propria. Our data argue against a general deficiency in IL-10 production in IBD. The results suggest rather that the local production of IL-10 by mucosal MNCs in IBD is insufficient to down-regulate pro-inflammatory cytokines such as IL-1beta in the lamina propria compartment.

Adult↗
PubMed1998

The distribution of HBV, HCV and HGV among livers with fulminant hepatic failure of different aetiology.

BACKGROUND/AIMS: The aim of the study was to assess the impact factor of HCV and HGV in fulminant hepatic failure. METHODS: The 5'-untranslated regions of HCV RNA and HGV RNA and a segment of the core antigen sequence of HBV were amplified after extracting the nucleic acids from snap-frozen tissue aliquots from explanted livers of 26 consecutive patients undergoing orthotopic liver transplantation for fulminant hepatic failure preoperatively diagnosed as either autoimmune (n=2), HAV/HBV (n=8), toxic (n=4) or aetiologically unknown (n=12). RESULTS: HCV RNA was detected in five of 26 (19.2%) livers with fulminant hepatic failure. All five HCV RNA-positive livers belonged to the group of non-toxic, non-autoimmune liver failure (n=20), three of them were found in the group of liver failure with unknown aetiology (n=12) and two in the group of HBV-associated liver failure (n=7), making an HCV incidence of 25%, 25% and 28.6%, in the different groups, respectively. HGV RNA was detected in 10 of 17 (58.8%) explants and in all four groups of fulminant hepatic failure as defined preoperatively. HBV DNA was identified in six livers of 26 patients (23.1%) with fulminant hepatic failure. Neither HCV RNA nor HBV DNA was detected in the livers of patients with toxic or autoimmune fulminant hepatic failure. CONCLUSIONS: These results indicate that HBV and HCV, but not HGV, play an aetiologic role in fulminant hepatic failure. HCV-positive cases were concentrated either in the group of otherwise unexplained fulminant hepatic failure or in the group of HBV fulminant hepatic failure. HGV-positive cases, on the other hand, were found within all four preoperatively defined groups, indicating a role as cofactor rather than as single aetiologic agent.

Adolescent↗
PubMed1998

Extensive and predominant in situ component in breast carcinoma: their influence on treatment results after breast-conserving therapy.

Intramammary tumour recurrence is one of the most important problems in breast-conserving therapy. We reviewed a series of 957 patients treated with breast-conserving therapy for primary invasive breast carcinomas between 1 January 1985 and 31 December 1992 at the University of Heidelberg. All histological slides were re-evaluated for risk factors with special emphasis on the extent and subclassification of the in situ tumour and the margin status. Six parameters were identified as significant risk factors for intramammary recurrence in the univariate analysis, including extensive or predominant in situ component (EIC, with at least twice the greatest dimension of the invasive tumour component), histological grade, angioinvasion, lobular tumour type, involved resection margin and lymph node status. The presence of an EIC was statistically correlated with low tumour grade, tumour at the resection margins and in re-excision specimens and with multifocal tumour invasion. Multivariate logistic regression analysis revealed that EIC (relative risk (RR) = 1.9), tumour grade (RR = 1.76), angioinvasion (RR = 1.34), lobular tumour type (RR = 1.65) and young age (< or = 40 years, RR = 1.39) were independent predictors of local recurrence. When combining these factors in a linear model, the simultaneous presence of at least two of the five risk factors predicted a 5-year risk of intramammary recurrence of 20.9% compared with a risk of only 1-5% when none or one of these risk factors were identifiable. We conclude that the risk of subsequent intramammary recurrence after breast-conserving therapy can be estimated from a scoring system that includes four histological risk factors and the patient's age.

Adenocarcinoma, Mucinous↗
PubMed1998

In situ upregulation of IL-10 reflects the activity of human glomerulonephritides.

A reciprocal regulation between the expression of tumor necrosis factor (TNF)-alpha and interleukin (IL)-10, demonstrated in monocytes and mesangial cells, provides a rationale for new therapeutic approaches in glomerulonephritis (GN). Administration of IL-10 to mice with antibody-mediated GN attenuated the severity of glomerular lesions. Recently, however, it has been shown that the genetically determined predominance of Th1 or Th2 cytokines results in different glomerular responses to the same planted antigen, but in an equally severe impairment of renal function. We looked for the expression of IL-10 and TNF-alpha in 111 renal biopsy specimens with proliferative and nonproliferative forms of GN and in 10 control kidneys, by means of immunocytochemistry, in situ hybridization, or reverse-transcriptase polymerase chain reaction (RT-PCR). Six patients had acute endocapillary GN (AGN), 10 patients had pauci-immune GN due to microscopic polyangiitis (MP), 48 patients had immunoglobulin-A (IgA)-GN, 18 patients had idiopathic membranous GN (IMGN), 12 patients had minimal change disease (MCD), and 13 patients had focal segmental glomerulosclerosis (FSGS) and four other forms of GN. Antibodies against monocytes (CD14) and macrophages (CD68) were applied to attribute the expression of TNF-alpha and IL-10 to resident renal or infiltrating cells. We show that mRNAs for TNF-alpha and IL-10 are detected by RT-PCR and in situ hybridization in the normal kidney. A constitutive expression of TNF-alpha protein is observed in mesangial cells, smooth muscle cells in renal arteries, and in the interstitium. A trace immunoreactivity for IL-10 is restricted to arterial smooth muscle cells, distal tubular epithelial cells, and some interstitial cells. Upregulation of both cytokines is found in glomerular diseases. The expression of TNF-alpha increases in mesangial areas in MCD, IMGN stages I/II, and IgA-GN with minor glomerular abnormalities, that is, under conditions with a generally well-preserved glomerular structure. Conversely, marked glomerular proliferation in IgA-GN and, particularly, acute vascular lesions in MP, are accompanied by a significant upregulation of IL-10 (at the mRNA and protein level). Patients with nephrotic-range proteinuria show a significant increase in tubulointerstitial expression of IL-10, whereas the immunoreactivity for TNF-alpha reflects the extent of interstitial fibrosis. Thus, our results confirm previous suggestions that proinflammatory and antiinflammatory cytokines are produced in situ by resident renal cells and contribute to the natural course of human GN.

Adult↗
PubMed1998

Meconium aspiration syndrome complicated by massive intravascular thrombosis.

Fetal aspiration of meconium in amniotic fluid during fetal distress by newborn infants can induce the meconium aspiration syndrome (MAS), a form of neonatal respiratory distress. Should this event occur, admission to a Neonatal Intensive Care Unit and vigorous airway management and monitoring are required. We present a term gestation resulting in MAS complicated by a massive intravascular thrombosis. Despite airway management considered appropriate, the infant developed respiratory distress a few hours after birth and died 5 days later. Postmortem examination showed a diffuse alveolar damage of the lungs with alveoli filled with meconium and amniotic epithelial cells as well as disseminated thrombi in the pulmonary vascular tree, portal system, suprahepatic veins, and peripheral arterial vascular tree.

Diagnosis, Differential↗