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H Michael

Publications and source records attributed to H Michael.

At least 19 recordsLinked to original sources
PubMed2005

CYGD: the Comprehensive Yeast Genome Database.

The Comprehensive Yeast Genome Database (CYGD) compiles a comprehensive data resource for information on the cellular functions of the yeast Saccharomyces cerevisiae and related species, chosen as the best understood model organism for eukaryotes. The database serves as a common resource generated by a European consortium, going beyond the provision of sequence information and functional annotations on individual genes and proteins. In addition, it provides information on the physical and functional interactions among proteins as well as other genetic elements. These cellular networks include metabolic and regulatory pathways, signal transduction and transport processes as well as co-regulated gene clusters. As more yeast genomes are published, their annotation becomes greatly facilitated using S.cerevisiae as a reference. CYGD provides a way of exploring related genomes with the aid of the S.cerevisiae genome as a backbone and SIMAP, the Similarity Matrix of Proteins. The comprehensive resource is available under http://mips.gsf.de/genre/proj/yeast/.

Binding Sites↗
PubMed2004

The Helmholtz Network for Bioinformatics: an integrative web portal for bioinformatics resources.

SUMMARY: The Helmholtz Network for Bioinformatics (HNB) is a joint venture of eleven German bioinformatics research groups that offers convenient access to numerous bioinformatics resources through a single web portal. The 'Guided Solution Finder' which is available through the HNB portal helps users to locate the appropriate resources to answer their queries by employing a detailed, tree-like questionnaire. Furthermore, automated complex tool cascades ('tasks'), involving resources located on different servers, have been implemented, allowing users to perform comprehensive data analyses without the requirement of further manual intervention for data transfer and re-formatting. Currently, automated cascades for the analysis of regulatory DNA segments as well as for the prediction of protein functional properties are provided. AVAILABILITY: The HNB portal is available at http://www.hnbioinfo.de

Algorithms↗
PubMed2003

TRANSFAC: transcriptional regulation, from patterns to profiles.

The TRANSFAC database on eukaryotic transcriptional regulation, comprising data on transcription factors, their target genes and regulatory binding sites, has been extended and further developed, both in number of entries and in the scope and structure of the collected data. Structured fields for expression patterns have been introduced for transcription factors from human and mouse, using the CYTOMER database on anatomical structures and developmental stages. The functionality of Match, a tool for matrix-based search of transcription factor binding sites, has been enhanced. For instance, the program now comes along with a number of tissue-(or state-)specific profiles and new profiles can be created and modified with Match Profiler. The GENE table was extended and gained in importance, containing amongst others links to LocusLink, RefSeq and OMIM now. Further, (direct) links between factor and target gene on one hand and between gene and encoded factor on the other hand were introduced. The TRANSFAC public release is available at http://www.gene-regulation.com. For yeast an additional release including the latest data was made available separately as TRANSFAC Saccharomyces Module (TSM) at http://transfac.gbf.de. For CYTOMER free download versions are available at http://www.biobase.de:8080/index.html.

Animals↗
PubMed2002

The effect of abduction differences between cup and contralateral acetabular angle on polyethylene component wear.

One hundred forty-two patients who underwent cemented or uncemented hip replacement were studied radiographically to determine acetabular component wear. Mean duration of follow-up was 58 months (range: 35-92 months). Average linear wear was 0.78 mm (range: 0-1.9 mm), and average wear rate was 0.16 mm/year (range: 0-0.45 mm/year). An increased wear rate per year correlated with a discrepancy >18.3 degrees between contralateral acetabular angle and acetabular cup inclination (P<.005). Statistical analysis revealed no significant correlation between cup inclination and polyethylene wear, which was studied without considering the contralateral hip (P>.3). There was no relationship between polyethylene wear and cup design, weight, and initial polyethylene thickness.

Aged↗
PubMed2001

Molecular evidence for the independent origin of extra-ovarian papillary serous tumors of low malignant potential.

BACKGROUND: Molecular data suggest that peritoneal tumors in women with advanced-stage ovarian papillary serous adenocarcinoma are monoclonal in origin. Whether the same is true for ovarian tumors of low malignant potential is not known. We compared peritoneal and ovarian tumors from women with advanced-stage ovarian papillary serous tumors of low malignant potential to determine whether the peritoneal tumors arose from the same clone as the ovarian tumors. METHODS: We studied the clonality of 73 peritoneal and ovarian tumors from 18 women with advanced-stage ovarian papillary serous tumors of low malignant potential. Formalin-fixed, paraffin-embedded tumors and representative normal tissues were sectioned and stained with hematoxylin-eosin, representative sections from separate tumors were manually microdissected, genomic DNA was extracted from the microdissected tumors, and the polymerase chain reaction was used to amplify a CAG polymorphic site in the human androgen receptor locus on the X chromosome to determine the inactivation pattern of the X chromosome and the clonality of the tumors. RESULTS: The pattern of X-chromosome inactivation could be determined from the tumors of 13 of 18 patients. Of the 13 patients, seven (54%) had nonrandom inactivation of the X chromosome, and six of the seven had different inactivation patterns in the peritoneal and ovarian tumors. Three of these patients also had different patterns of nonrandom X-chromosome inactivation in tumors from each ovary. The remaining six patients had random patterns of X-chromosome inactivation in the peritoneal and ovarian tumors. CONCLUSIONS: Our data suggest that peritoneal and ovarian tumors of low malignant potential arise independently.

Adenocarcinoma, Papillary↗
PubMed2001

The TRANSFAC system on gene expression regulation.

The TRANSFAC database on transcription factors and their DNA-binding sites and profiles (http://www.gene-regulation.de/) has been quantitatively extended and supplemented by a number of modules. These modules give information about pathologically relevant mutations in regulatory regions and transcription factor genes (PathoDB), scaffold/matrix attached regions (S/MARt DB), signal transduction (TRANSPATH) and gene expression sources (CYTOMER). Altogether, these distinct database modules constitute the TRANSFAC system. They are accompanied by a number of program routines for identifying potential transcription factor binding sites or for localizing individual components in the regulatory network of a cell.

Binding Sites↗
PubMed2001

Multiple antibiotic changes during the first 72 hours of hospitalization.

BACKGROUND: Increasing concern about inappropriate antibiotic use prompted us to examine whether our patients were receiving frequent and perhaps unwarranted changes of antibiotic therapy. METHODS: We evaluated antibiotic prescribing by the physicians in the Emergency Department and by those on the inpatient medical service during the first 72 hours of hospitalization in 119 patients admitted with suspected serious infections to an acute care, university-affiliated, municipal teaching hospital. The appropriateness of antibiotic prescriptions was assessed independently and retrospectively by 2 infectious disease specialists (each based at a different hospital) using a 4-grade scale (from 1 = wrong choice to 4 = appropriate). Of their evaluations of the 427 antibiotic regimens given to the 119 patients during 4 defined intervals during their first 72 hours of hospitalization, 90% agreed with each other within 1 grade. Their evaluations were then compared with the selections that had been made at each interval by the prescribing physicians. RESULTS: Successive prescribing physicians changed the antibiotic regimens in 77% of cases during the first 24 hours and in 56% during the next 48, often without apparent clinical or microbiologic indications. By 72 hours, the 119 patients had received a mean of 3.1 +/- 1.3 (+/-SD) different antibiotics, and 40 received between 4 and 7. Only 7% of the patients had no change in the regimen prescribed originally. CONCLUSIONS: Many patients had multiple changes of antibiotics, often unnecessarily, resulting in exposure to too many agents.

Anti-Bacterial Agents↗
PubMed2001

Germ cell tumor associated primitive neuroectodermal tumors.

PURPOSE: This retrospective review was done to assess the prognosis and response in patients presenting with primitive neuroectodermal tumor admixed with germ cell tumor. MATERIALS AND METHODS: Of the 40 patients treated at our institution from 1984 to 1999, 15 had initial stage I and 25 had initial metastatic disease. Median followup after the diagnosis was 25 months (range 4 to 142). RESULTS: Of the 40 patients 15 presented with clinical stage I disease, including 9 treated with retroperitoneal lymph node dissection and 6 who elected surveillance. Seven of the 9 patients had normal lymph nodes and all continuously had no evidence of disease. Two of the 9 patients had lymph nodes involved with teratoma with or without primitive neuroectodermal tumor. Retroperitoneal relapse in 5 of the 6 patients on surveillance was treated with cisplatin based chemotherapy followed by post-chemotherapy retroperitoneal lymph node dissection. Residual primitive neuroectodermal tumor was noted in 4 of the 5 patients and only 3 of 6 are currently without disease at a median followup of 17 months (range 15 to 69). A total of 25 patients presented with metastatic disease, of whom 23 underwent cisplatin based chemotherapy. Only 3 patients achieved complete remission with chemotherapy alone and 2 of the 3 subsequently relapsed. Of the remaining 20 patients 16 underwent post-chemotherapy retroperitoneal lymph node dissection, including 11 with primitive neuroectodermal tumor in the resected specimen. Two of these 11 patients have continuously had no evidence of disease, while an additional 3 currently have no evidence of disease after further therapy. Teratoma was present in the resected specimen in 5 of 16 patients, of whom 2 have continuously had no evidence of disease, while an additional 2 currently have no evidence of disease after further surgical resection. Therefore, 11 of 25 patients who presented with metastatic disease currently have no evidence of disease at a median followup of 19 months (range 2 to 111). CONCLUSIONS: Primitive neuroectodermal tumor in the orchiectomy specimen has adverse prognostic significance. This condition in the retroperitoneum is potentially curable by retroperitoneal lymph node dissection but rarely eradicated by chemotherapy. Therefore, we recommend retroperitoneal lymph node dissection for all clinical stage I cases with primitive neuroectodermal tumor in the orchiectomy specimen. Patients who present with metastatic primitive neuroectodermal tumor should be treated aggressively with surgical resection as an integral part of the therapeutic strategy.

Adolescent↗
PubMed2000

The pathology of late recurrence of testicular germ cell tumors.

A total of 91 men had histologically documented late recurrences of testicular germ cell tumors characterized by a complete response to treatment with a subsequent disease-free interval of at least 2 years and no evidence of a second primary lesion. Ninety percent of the patients for whom information was available received chemotherapy shortly after their initial diagnosis of testicular germ cell tumors; most of the other patients were known to have stage I disease initially. Overall, 60% of patients had teratoma in their late recurrences, including 20 patients (22%) in whom teratoma was the only element. Thus, teratoma was the most common type of neoplasm in late recurrences. Excluding teratoma coexisting with other types of neoplasms, yolk sac tumor was the most frequent type of tumor in patients with late recurrence. It occurred in 47% of patients, either alone or with teratoma, another nonteratomatous germ cell tumor type, or a "nongerm cell malignant tumor." Unusual types of yolk sac tumor, including glandular, parietal, clear cell, and pleomorphic patterns, were seen frequently in late recurrences and often raised differential diagnostic problems with "nongerm cell" carcinomas. A smaller number of late recurrences consisted of other types of neoplasms. Twenty percent of patients with late recurrence had a nonteratomatous germ cell tumor other than yolk sac tumor, either alone, with yolk sac tumor, or with a "nongerm cell malignant tumor." Most of these nonteratomatous germ cell tumors other than yolk sac tumor were embryonal carcinoma, although rarely seminoma and choriocarcinoma were encountered. "Nongerm cell malignant tumors," including both sarcomas and carcinomas of various types, occurred in 23% of late-recurrence patients, either alone or with a nonteratomatous germ cell tumor. Late recurrences were seen in many different sites in these patients, including the retroperitoneum, abdomen, pelvis, liver, mediastinum, lung, bone (femur, vertebra, and rib), lymph nodes outside the retroperitoneum and mediastinum (supraclavicular, neck, and axillary regions), scrotum and inguinal regions, adrenal gland, chest wall, and buttocks. Follow-up data were available for 79 of the 91 patients studied. Duration of follow-up ranged from 2 months to 13 years after the patient's first late recurrences; the mean length of follow-up was 4.8 years. Patients whose late recurrences consisted of teratoma only had the most favorable outcomes, with 79% having no evidence of disease at last follow-up. Patients whose late recurrences consisted of pure "nongerm cell malignant tumor" or pure germ cell tumor (yolk sac tumor or other types) had a much worse prognosis: Only 36% to 37% were alive with no evidence of disease. Patients with two different types of nonteratomatous malignancies in their late recurrences had a dismal clinical course: Only 17% with both yolk sac tumor and other nonteratomatous germ cell tumor had no evidence of disease, whereas no patient with both nonteratomatous germ cell tumor and "nongerm cell malignant tumor" was disease free. Late recurrences consisting of teratoma alone often have a favorable outcome, but the prognosis in all other patients is poor. Furthermore, late recurrence is not likely to respond to chemotherapy and is best treated by surgical excision when possible.

Adolescent↗
PubMed2000

Primary yolk sac tumor of the rectum.

Extragonadal germ cell tumors are well recognized in men but have rarely been reported in women. Reports have primarily focused on the pediatric population and have suggested a poor prognosis for extragonadal yolk sac tumors. A 23-year-old woman with a yolk sac tumor arising in the rectum is described. A review of the English-language literature (MEDLINE 1966-1998) regarding extragonadal germ cell tumors in females is provided. Treatment with four courses of cisplatin, etoposide, and bleomycin was followed by surgical resection of the involved area. No residual tumor was identified. She remains disease free 3.5 years later. Previous reports are limited by the small number of patients, focus on the pediatric population, and treatment before the availability of cisplatin. Extragonadal germ cell tumors in women are extremely rare but can be successfully treated with aggressive chemotherapy and surgery similar to testis cancer.

Adult↗
PubMed2000

Alterations in the expression of the DNA repair/redox enzyme APE/ref-1 in epithelial ovarian cancers.

The DNA base excision repair pathway is responsible for the repair of alkylation and oxidative DNA damage. A crucial step in the base excision repair pathway involves the cleavage of an apurinic/apyrimidinic (AP) site in DNA by an AP endonuclease (APE). The major AP endonuclease in mammalian cells is APE/ref-1, a multifunctional enzyme that acts not only as an AP endonuclease but as a redox-modifying factor for a variety of transcription factors. The purpose of this study was to determine the expression of APE/redox factor-1 (ref-1) in ovarian tissues, particularly ovarian cancers. Formalin-fixed, paraffin-embedded specimens of ovarian tissues (normal, various benign conditions, and epithelial cancers) were studied using both polyclonal and monoclonal antibodies to APE/ref-1. The relationship between APE/ref-1 protein levels and DNA repair activity was studied in ovarian Hey and Hey-C2 cell lines using Western blot and a specific AP-site oligonucleotide cleavage assay. Hey and Hey-C2 cells were fractionated, and the nuclear and cytoplasmic extracts were quantitated for protein levels and assessed for APE/ref-1 with Western blot. Normal ovarian tissues consistently demonstrated strong nuclear staining of the surface epithelium, epithelial inclusions, corpora lutea and albicantia, and stroma. Cytoplasmic staining was absent. A similar pattern was seen for benign conditions including endometriosis. Low malignant potential ovarian cancers stained in a pattern similar to normal ovarian and nonneoplastic tissues; however, two specimens also had areas of cytoplasmic staining. Epithelial ovarian cancers were remarkably different from all other ovarian tissues studied. Both nuclear and cytoplasmic staining of the malignant epithelium were seen and ranged from strong to weak, often with considerable staining heterogeneity within the same tumor. The AP-site oligonucleotide cleavage assay indicated that APE/ref-1 protein levels correlate well with DNA repair activity. The increased levels of APE/ref-1 in the Hey-C2 cells was mainly attributable to increased cytoplasmic enzyme. APE/ref-1 immunoreactivity is altered in malignant ovarian tumors. Further studies will determine whether the altered expression and subcellular location reflect changes in redox regulatory functions.

Adenocarcinoma↗
PubMed1998

Nephroblastoma-like tumors in patients with testicular germ cell tumors.

Nephroblastoma-like tumors (NLTs) developed in metastatic sites in nine men with testicular germ cell tumors (GCTs). These tumors had a characteristic "triphasic" admixture of primitive tubular structures, sometimes with a glomeruloid pattern, blastema and stroma. Skeletal muscle differentiation was apparent in two cases. Specific neuroendocrine markers (synaptophysin and chromogranin A) were negative. All patients were treated by surgical excision. Six patients were alive with no evidence of disease from 4 to 12 years after diagnosis of GCT and NLT. One patient was alive with disease 6 years after diagnosis of GCT and 3 years after diagnosis of NLT. One man who also had metastatic primitive neuroectodermal tumor (PNET) had short survival, and one patient died of postoperative infection. We conclude that patients with testicular GCTs in whom NLTs develop in metastatic sites often experience prolonged survival. Surgical excision appears to be adequate treatment for NLT arising in metastatic testicular GCT in most patients. It is important to distinguish NLTs from PNETs in metastatic GCTs because of the more aggressive course and the frequently fatal outcome of the latter.

Abdominal Neoplasms↗
PubMed1998

Unclassified sex cord-stromal tumors of the ovary: a report of eight cases.

OBJECTIVE: To evaluate the histologic features and biologic behavior of unclassified sex cord-stromal tumors. PATIENTS: The eight patients' ages at presentation ranged from 14 to 83 years. Presenting symptoms and physical findings included abdominal pain, abnormal uterine bleeding, ascites, and abdominal and pelvic masses. One patient also had bilateral sex cord tumors with annual tubules and probable Peutz-Jeghers syndrome. RESULTS: The tumors ranged from 4 to 27 cm in diameter and were described as partially encapsulated, solid, and cystic. Histologically, the tumors were composed of diffuse proliferations of sex cord cells, with cords, tubules, and follicle-like structures. The stromal cells were spindle-shaped, with scanty cytoplasm. The neoplasms were vimentin-positive and, sometimes, cytokeratin CAM 5.2- and AE1/3-positive and epithelial membrane antigen-negative. Six patients were disease-free from 2 months to 6 years after operation. One patient was lost to follow-up. The patient with probable Peutz-Jeghers syndrome had a tumor with unusual morphology and died of the neoplasm 4 years after the diagnosis. Three of 32 other cases with clinical follow-up mentioned in the pathology literature have been associated with a malignant behavior. CONCLUSION: The biologic behavior of unclassified sex cord-stromal tumors resembles that of Sertoli-Leydig cell tumors of intermediate differentiation rather than poorly differentiated tumors, which might have been expected in view of the lack of specific differentiation. This finding is important with regard to postoperative management.

Adolescent↗
PubMed1997

Primitive neuroectodermal tumors arising in testicular germ cell neoplasms.

Twenty-nine young men (mean age 29 years) had primitive neuroectodermal tumors (PNETs) arising in germ cell tumors (GCTs). Nine patients had PNETs confined to the testis, eight patients had PNETs in the testis and at metastatic sites, and 12 patients had PNETs identified only at extratesticular sites. Immunohistochemistry was of use in the further classification of these PNETs as neuroblastoma, medulloepithelioma, peripheral neuroepithelioma, or ependymoblastoma. The histologic pattern of PNETs in the testis (neuroblastoma or medulloepithelioma) did not predict which tumors metastasized. PNETs localized to the testis did not affect prognosis. Eight patients with no PNETs outside the testis were free of disease 1 month to 10 years after diagnosis. PNETs in extratesticular sites were an adverse prognostic factor. Nineteen patients with extratesticular PNETs had adequate clinical follow-up. Thirteen are dead of disease from 4 months to 5 1/2 years (mean 26 months) after diagnosis, four are alive with disease 6 months to 2 years after diagnosis, and two have no evidence of disease with short follow-up (6 and 17 months). Mean survival was longer (34 months) for patients whose extratesticular PNET was neuroblastoma than for those with other types of PNETs (13 months). Chemotherapy directed against GCTs was not effective in patients who developed metastatic PNETs of GCT origin. We conclude that extratesticular PNETs in patients with testicular GCTs are usually fatal, but patients with neuroblastomatous metastases may have a more prolonged course.

Adolescent↗
PubMed1996

DNA ploidy, cell cycle kinetics, and low versus high grade atypia in endometrial hyperplasia.

There have been few studies of DNA ploidy and cell cycle kinetics in endometrial hyperplasia. The authors studied archival cases of proliferative endometrium, simple, complex and atypical endometrial hyperplasia and well, moderately, and poorly differentiated endometrial adenocarcinoma by flow cytometry and also evaluated the significance of the degree of cytologic atypia (low versus high) in endometrial hyperplasia relative to the occurrence of carcinoma. All proliferative endometria, all types of hyperplasia and well and moderately differentiated carcinomas were diploid. Two-thirds of poorly differentiated adenocarcinomas were aneuploid. Neither S-phase fractions or proliferative fractions (S+G2M) could distinguish among the different types of hyperplasia or predict which hyperplasias were associated with carcinomas. The degree of cytologic atypia in atypical hyperplasia was not predictive of the occurrence of carcinoma. Poorly differentiated carcinomas showed significant differences in DNA ploidy, S-phase, and proliferative fractions from endometrial hyperplasia and lower grade carcinoma. These results support the concept that there are two fundamentally different types of endometrial carcinoma.

Adenocarcinoma↗
PubMed1995

Hyperspeckled mutants of Schizosaccharomyces pombe: frequent mating-type switching without detectable double-strand breaks.

Mating-type (MT) switching in homothallic (h90) strains of Schizosaccharomyces pombe is initiated by a DNA double-strand break (DSB) at the distal end of the expression cassette mat1. The cis-acting smt-s1 mutation C13-P11 reduces the frequency of MT switching. It is a small deletion mapping approximately 50 bp distal to the site of the DSB. From the h90 smt-s1 strain we isolated 13 mutants with a hyperspeckled iodine reaction. In these mutants the frequency of MT switching is increased. The mutations define nine different hsp genes, none of which maps in or close to the MT region. We tested one mutant of each gene for the presence of DSBs at mat1. Curiously, in none of the h90 smt-s1 hsp strains could DSBs be detected, although some sporulate nearly as efficiently as the h90 smt-n wild type. The hsp mutations show no effect in smt-0 strains; the smt-0 deletion abolishes MT switching completely. Furthermore, we tested the interaction of hsp1-1 with swi1, swi2 and swi7 mutations. hsp1-1 has no effect in swi2 strains, whereas it increases MT switching in swi7 and, to a lesser degree, in swi1 mutants.

Autoradiography↗
PubMed1995

Retroperitoneal leiomyosarcoma: eight cases and a literature review.

Leiomyosarcoma, a rare malignancy of smooth muscle, may arise from the retroperitoneum and present with the same vague symptoms as a malignancy of the pelvic organs. The purpose of this paper is to review eight cases of retroperitoneal leiomyosarcoma and to illustrate the presenting symptoms, prognostic indicators, and outcomes of patients seen at Indiana University Medical Center between 1989 and 1994. Patients in this study were white females who presented between the ages of 46 and 73 (mean age of 61.4) with nonspecific presenting symptoms of weight loss and back pain (37.5% for each). Tumor size (mean diameter of 14.6 cm in the range 4 to 35 cm), tumor extension, and the presence of distant metastases were of greater prognostic significance than tumor grade (7/8 were grade II, 1/8 was grade I). Surgical resection improved long-term prognosis; three of five patients undergoing resection are alive with no evidence of disease compared to zero of three treated nonsurgically. Due to location and vague presenting symptoms, this tumor continues to have a bleak prognosis and further evaluation and innovative treatment are required before a reasonable cure rate may be expected.

Aged↗