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K Holzmann

Publications and source records attributed to K Holzmann.

At least 37 records · Page 2Linked to original sources
PubMed1998

Hypermethylation of the CDKN2/p16 promoter during neoplastic progression in Barrett's esophagus.

BACKGROUND & AIMS: Inactivation of the CDKN2/p16(INK4A) tumor-suppressor gene is one of the most frequent genetic alterations in human malignancies. In esophageal adenocarcinomas, mutations of the p16 gene or homozygous deletions of the gene locus 9p21 are rare. This study investigated whether p16 promoter hypermethylation is an alternative mechanism for p16 gene inactivation during neoplastic progression in Barrett's esophagus. METHODS: A methylation-specific polymerase chain reaction protocol was applied. A total of 95 specimens from 14 patients with Barrett's esophagus were analyzed longitudinally. The p16 promoter status was compared with histomorphological findings. RESULTS: p16 promoter hypermethylation was detected in 9 of the 10 patients who had displayed dysplasia at some time during surveillance, whereas none of the patients who had not displayed dysplasia during surveillance had p16 promoter hypermethylation. p16 promoter hypermethylation was detected in 3% (2 of 67) of the samples without dysplasia, 60% (3 of 5) of the samples with lesions indefinite for dysplasia, 55.6% (10 of 18) of the specimens with low-grade dysplasia, and 75% (3 of 4) of the specimens with high-grade dysplasia. CONCLUSIONS: These data suggest that p16 promoter hypermethylation is a common mechanism of p16 gene inactivation during neoplastic progression in Barrett's esophagus.

Barrett Esophagus↗
PubMed1998

Cloning, subcellular localization and functional expression of human RNase HII.

Recently we showed that the major mammalian RNase H, RNase HI, is evolutionarily related to prokaryotic RNase HII (Frank et al., FEBS-Lett. 421, 23-26, 1998), an enzyme described to be a minor activity in E. coli. As a consequence we addressed the question of whether a human RNase H exists, sharing homology with the main E. coli enzyme, RNase HI. Employing sequence analysis of expressed sequence tags, followed by specific PCR amplification of human cDNA, we cloned, sequenced and expressed a human open reading frame, coding for a 32 kDa protein. Purification of the recombinant His(6)-tagged protein from E. coli extracts using Ni(2+)-chelating chromatography and subsequent renaturation gel assay proved that it is an active RNase H. The properties of this enzyme suggest that it is identical with the human RNase HII, previously purified by one of us (Frank et al., Nucleic Acids Res. 22, 5247-5254, 1994). Studies using a green fluorescent protein-fusion construct reveal that this protein is located in the nucleus.

Amino Acid Sequence↗
PubMed1997

Identification of human common nuclear-matrix proteins as heterogeneous nuclear ribonucleoproteins H and H' by sequencing and mass spectrometry.

Nuclear-matrix proteins were prepared from different rat and human cells and separated by two-dimensional gel electrophoresis. By computer-assisted analysis of the images, two of the proteins were identified as ubiquitously occurring (common) nuclear-matrix proteins, which appeared in tissue-dependent concentrations. The two proteins that originated from human blood mononuclear cells were analyzed further. Tryptic digests of the blotted proteins were analyzed by partial peptide sequencing and matrix-assisted laser-desorption ionization-time-of-flight mass spectrometry. The two human common nuclear-matrix proteins were identified as heterogeneous nuclear ribonucleoproteins (hnRNP) H and H' or their variants. Furthermore, mass analysis revealed details on the N terminus of hnRNP H.

Amino Acid Sequence↗
PubMed1997

Distribution of cell populations with DNA aneuploidy and p53 protein expression in ulcerative colitis.

OBJECTIVE: Patients with ulcerative colitis are at an increased risk for developing colorectal neoplasms. p53 mutations and the occurrence of DNA aneuploidies are common events in the development of sporadic colorectal neoplasias. This study tried to determine the frequency of these events during the development of colitis-associated colorectal neoplasms. DESIGN/METHODS: Four colectomy specimens with a total of 124 biopsies were investigated. DNA content was measured by flow cytometry and p53 protein expression was detected by immunohistochemistry. These results were correlated with histological findings. RESULTS: DNA aneuploidies were found in 58 (46.8%), and p53 protein expression in 30 samples (24.2%). The presence of DNA aneuploidy as well as of p53 protein expression correlated with the histological characteristics of neoplastic transformation. In areas without dysplasias or with indefinite dysplasias, 31.5% of the samples showed DNA aneuploidies and in about 9% of the samples p53 protein expression could be detected; 33.7% of samples without or with indefinite dysplasias showed p53 protein expression and/or DNA aneuploidies. CONCLUSION: These results show that the occurrence of DNA aneuploidies and nuclear p53 protein expression is a common event in the development of colitis-associated colorectal neoplasias. p53 protein expression seems to be an early event in this process. DNA aneuploidies occur even earlier and more frequently in the absence of p53 protein expression. Therefore, other genetic alterations besides p53 gene mutations might be involved in colitis-associated tumour development.

Adult↗
PubMed1996

Cloning and characterization of the gene for the thermostable xylanase XynA from Thermomyces lanuginosus.

A thermostable xylanase from the filamentous fungus Thermomyces lanuginosus (DSM 5826) was purified. This enzyme has an apparent molecular weight of 24-26 kDa as determined by SDS polyacrylamide gel electrophoresis. cDNA and genomic DNA fragments coding for this enzyme were cloned and sequenced. The cDNA contains an open reading frame encoding a polypeptide of 225 amino acids and was functionally expressed in E. coli as a LacZ fusion protein. Comparison of the cDNA sequence with the genomic DNA sequence showed that the xylanase was encoded by two exons interrupted by an intron of 106 bp. Comparison of the deduced amino acid sequence to other published xylanases revealed high homology to xylanases of the family G glycanases.

Amino Acid Sequence↗
PubMed1996

Distribution and linkage of repetitive clusters from the heterochromatic region of human chromosome 22.

The pericentric regions of eukaryotic chromosomes consist of several types of repetitive DNA families. In human chromosome 22, the organization of such families was studied in more detail. In addition to the known families of alpha and beta repeats, an additional repeat with a 48-bp motif was previously assigned to 22pter-q11. Here, we report in more detail the distribution of these repeat families, applying pulsed-field gel electrophoresis, fluorescence in situ hybridization and physical linkage on cosmid recombinants. At least two clusters of 48-bp repeats are localized on chromosome 22, one on the distal p-arm and one in the region 22cen-q11. Cosmids from a chromosome 22 library, containing both 48-bp and beta-repeats, link both arrays on 22p and define their maximum distances to less than 44 kb. Loss of 48-bp repeat sequences in a Dl-George cell line carrying a deletion in 22q11 suggests the presence of a second cluster in 22q11, a distribution supported by (fluorescene in situ hybridization)-FISH signal analysis. As additional members of the 48-bp repeat family can be found on all acrocentric chromosomes. It remains to be determined whether the distribution seen on chromosome 22 is also common in other human acrocentric chromosomes.

Centromere↗
PubMed1993

Telomeric associations and loss of telomeric DNA repeats in renal tumors.

In a series of cytogenetically analyzed renal tumors of different histological types (chromophobe carcinoma, clear-cell carcinoma, chromophilic carcinoma, and oncocytoma) and normal renal tissue, the length of the telomeric DNA repeats was assessed using a (TTAGGG)3 oligonucleotide probe. A strong correlation was noted between pronounced telomere shortening and the appearance of telomeric associations of chromosomes. These data suggest an etiologic role of the loss of telomeric DNA repeats in the formation of telomeric associations and a possible involvement of this mechanism in the pathogenesis of chromosome aberrations in human tumors.

Adenocarcinoma↗
PubMed1992

A non-alphoid repetitive DNA sequence from human chromosome 21.

A non-alphoid repetitive DNA from human chromosome 22, consisting of a 48-bp motif, shows homology to both G-group chromosomes in the gorilla, thus indicating the presence of additional repeat family members on further human chromosomes. Therefore, we screened a chromosome-21-specific cosmid library using this repetitive sequence from chromosome 22 (D22Z3). Some 40-50 cosmid clones were positive in tests for hybridization. One of the clones giving the strongest signals was digested with EcoRI/PstI, which we knew to cut frequently within the repeats; this resulted in fragments containing repeat units only. The fragments were subcloned into plasmid vector pTZ 19. Sequence-analysis of a 500-bp insert showed ten copies of a 48-bp repeat similar to D22Z3, with about 15% sequence deviation from the chromosome 22 consensus sequence. In situ hybridization of the newly isolated recombinant established its chromosome 21 specificity at high stringency. Physical mapping by pulsed field gel electrophoresis placed this new repeat in close vicinity to the chromosome 21 alphoid repeat. No cross-hybridization with other mammalian genomes except for those of apes was observed. The locus has been designated D21Z2 by the Genome Data Base. A gel mobility shift assay indicated that this repetitive motif has protein-binding properties.

Animals↗
PubMed1991

Molecular characterization and functional analysis in Aspergillus nidulans of the 5'-region of the Penicillium chrysogenum isopenicillin N synthetase gene.

The isopenicillin N synthetase gene (pcbC) was isolated from a genomic library of Penicillium chrysogenum BC39813, a penicillin production strain. The nucleotide sequence, including 555 bp upstream of the translation start site was determined. Various deletions within the pcbC 5'-region were constructed and linked to the Escherichia coli lacZ gene. An Aspergillus nidulans argB strain was transformed with DNA of these constructions. The region essential for promoter function could be localized between positions -307 and -89 by analyzing beta-galactosidase expression of transformants containing a single copy of the corresponding plasmid integrated at the homologous argB locus. A region responsible for regulatory effects concerning nitrogen metabolism was identified by determining beta-galactosidase activities in cell-lysates of transformants cultivated under varying growth conditions. Two major transcription start sites at positions -131 and -132, as well as a further upstream located site at position -397 +/- 1 could be located by primer extension studies employing RNA isolated from P. chrysogenum BC39813.

Amino Acid Sequence↗
PubMed1989

[Data from the Bavarian perinatal survey on the problem of the incidence of cesarean section].

Data are presented on caesarean section rates during the first five-year period of the Bavarian Perinatal Study (BPE 1982-1986), comprising 450,000 births. In order to identify long-term trends, statistical studies from the Munich Perinatal Study (MPS) dating back to 1975 were continued in the same Munich hospitals through to 1982-1984. The results may be broken down as follows: 1. The overall rate of caesarean sections has been increasing, steadily, reaching 15% in the 1986 BPE. No clear levelling-off is evident yet. 2. The highest rates of caesarean sections and vaginal operative deliveries were found in university hospitals. Spontaneous deliveries occurred least often in university hospitals (about 70%), and most frequently in the larger country and private hospitals (77-79%). Smaller externally staffed private hospitals had about the same rate of vaginal-operative deliveries as university hospitals. 3. Following caesarean section, postoperative complications prompted a three- to sixfold higher rate of maternal transfer to other hospitals over that following spontaneous delivery. 4. As maternal age increases, so does the rate of caesarean section for primiparae. Nevertheless, recent years have witnessed a levelling-off for women over 34 years of age. No trend toward further increase is evident for this age group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1984

Sequential methotrexate and 5-fluorouracil: improved response rate in metastatic colorectal cancer.

The efficacy of chemotherapy with sequential methotrexate (MTX) and 5-fluorouracil (5-FU) in metastatic colorectal cancer was studied in a multicenter phase II trial using a seven-hour time interval. Forty-two patients were evaluable for response and 16 achieved objective tumor regression (greater than 50%). Median survival of all patients was 12.5 months. The result of this study indicates that MTX and 5-FU are synergistic in human colorectal cancer if given sequentially with a seven-hour time interval. This is supported by a review of the literature that reveals a significantly higher response rate in patients treated with a four-hour or more MTX/5-FU interval as compared to a one-hour interval.

Adult↗
PubMed1983

[Hysterectomy for septicemia following caesarean section].

From 1971 to 1980 20 patients at the first department of women of the university of Munich required a puerperal hysterectomy because of septicemia following caesarean section. During the same time a total of 2,726 caesarean sections were performed. 14 of the 20 women requiring hysterectomy had the caesarean section in the first department for women. Six women were referred with septicemia following caesarean section in another hospital. The causative relationship between caesarean section and septicemia was reviewed leading to the indication for hysterectomy. The indications for the caesarean section, risk factors for increased puerperal infection, the postoperative course, the indication for hysterectomy, the findings at operation the findings in the operative specimen and the course following hysterectomy were reviewed. Risk factors promoting an ascending infection postpartum were the type of labor, frequent vaginal examinations, previous attempts at vaginal delivery, and internal fetal monitoring by a scalp electrode. The recognition of incipient septicemia include severe pain in the abdomen and a subjective feeling of severe illness in the patient. The white blood count is increased, the body temperature is high and beginning respiratory insufficiency points to the severity of the illness. In these cases a repeat laparotomy with hysterectomy to eliminate the focus of infection is the treatment of choice for the septicemia. 19 of the patients who required hysterectomy for septicemia following caesarean section were discharged home after a mean hospital stay of 36 days. One of the patients died 41 days following caesarean section and 20 days following hysterectomy because of septicemia resistant to treatment.

Adnexa Uteri↗
PubMed1982

[Sequential methotrexate and fluorouracil in metastasizing colorectal carcinomas. Results of a phase II pilot study (author's transl)].

A sequential combination of methotrexate and 5-fluorouracil was used for treatment of 20 patients with metastasizing colorectal carcinomas. Pretreatment with 5-fluorouracil had been given to five patients. While the chemotherapeutically pretreated patients showed two partial remissions, two minimal remissions and one progression, the remaining patients showed one full remission, six partial remissions, five minimal remissions and three progressions. The average partial remission time of these patients was 7,9 months. The average survival time will probably be more than one year. The toxicity of treatment was slight.

Adult↗
PubMed1980

[Teratomas in the cervical region].

Teratomas in the cervical region have rarely been observed in infants. There are only a small number of reports in the literature of teratomas in this region. The complication rate after sugical removal of such a tumour is relatively high. A case report is presented of a newborn with a cervical teratoma which was removed without serious sequelae and with acceptable cosmetic and functional results.

Head and Neck Neoplasms↗