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Biomedical subjects

W Koch

Publications and source records attributed to W Koch.

At least 91 records · Page 5Linked to original sources
PubMed1995

Differences in the target specificity of the transactivating factors MHBs(t) and HBx of hepatitis B virus.

Transient transfections of tissue culture cells with plasmids encoding the transactivating factors MHBs(t) and HBx of hepatitis B virus result in transcriptional stimulation of multiple target genes. Our experiments show that the NF-kappaB-binding enhancer element of simian virus 40 (SV40) and the AP-1-binding enhancer element of the human metallothionein IIA gene mediate the transactivating function of MHBs(t) and HBx. In contrast, the elements GT(IIC + I) and Sph(II + I) of the SV40 enhancer, that, as a common feature, require binding of transcription factor TEF-1 for activity, efficiently mediate transactivation only by HBx but not by MHBs(t). This finding suggests that at least one regulatory pathway exists that can only be activated by HBx but not by MHBs(t).

Cell Line↗
PubMed1994

Infrequent inactivation of the retinoblastoma gene despite frequent loss of chromosome 13q in head and neck squamous cell carcinoma.

Our recent allelic analysis of head and neck squamous cell carcinomas identified a high incidence of chromosomal loss on 13q. To further define an area of minimal loss, we tested 60 primary head and neck squamous cell carcinomas in 59 patients for loss of heterozygosity (LOH) by using 10 polymorphic microsatellite markers spanning the long arm of chromosome 13. We examined the same primary tumors for inactivation of the retinoblastoma (Rb) gene by immunohistochemical analysis of paraffin-embedded specimens. Thirty-one of 60 (52%) tumors demonstrated LOH in at least one 13q marker. Twenty-nine of 31 (94%) lost a portion of 13q that included D13s133, which lies just telomeric to the Rb gene at 13q14.3. However, immunohistochemical staining revealed absence of Rb protein in only 6 of these 31 tumors (19.4%) with LOH. All but one tumor without LOH on 13q displayed normal Rb protein staining. Although Rb may be inactivated by an unusual mechanism in some head and neck squamous cell carcinomas, our data suggest that another tumor suppressor gene locus at 13q14 is likely to be involved in head and neck tumor progression.

Adult↗
PubMed1994

Allelotype of head and neck squamous cell carcinoma.

To gain a better understanding of the molecular changes in head and neck squamous cell carcinoma, we tested every autosomal arm of 29 primary head and neck tumors for allelic loss. Fifty-eight microsatellite markers were used with at least two-thirds of patients informative for each chromosomal arm tested. A high frequency of allelic loss was found on chromosome 9p where 21 of 29 (72%) tumors had loss of heterozygosity for at least one polymorphic marker on this arm. Chromosomes 3, 11q, 13q, and 17p exhibited loss in over 50% of all informative cases, while chromosomes 4, 6p, 8, 14q, and 19q displayed loss in greater than 35% of all cases tested. Additionally, several other chromosomal arms exhibited loss of heterozygosity in 20 to 30% of tumors tested. This high frequency of allelic loss in these advanced stage neoplasms suggests multiple genetic steps in the progression of head and neck cancer and identifies several putative tumor suppressor loci on affected chromosomes.

Alleles↗
PubMed1994

Frequent loss of chromosome 9p21-22 early in head and neck cancer progression.

In order to define more clearly the role of chromosome 9 loss in head and neck squamous cell carcinoma (HNSCC), 29 invasive carcinomas and 17 preinvasive lesions were analyzed for loss of heterozygosity (LOH) on chromosome 9. We found LOH in 21 of 29 (72%) HNSCC tumors using highly polymorphic microsatellite markers. In 17 of 21, LOH was found at all informative sites on the p arm with no LOH of the q arm. Further mapping in tumors, with partial LOH of the 9p arm, localized a common region of loss between markers D9S165 and D9S156. Deletion of this region on chromosome 9 has been found in several other tumor types implying the presence of a tumor suppressor gene at this locus. The inactivation of a tumor suppressor gene on chromosome 9p may represent the most commonly described genetic alteration in HNSCC. A similar incidence of allelic loss on chromosome 9p was identified in 12 of 17 (71%) preinvasive lesions. The identical frequency of loss in preinvasive and invasive lesions suggests that loss of 9p is an early event in HNSCC progression.

Adult↗
PubMed1994

[Hemophiliac arthropathy of the knee joint. Gd-DTPA-enhanced MRI; clinical and roentgenological correlation].

17 patients with hemophilic arthropathy of the knee joint were studied with static and dynamic MRT before and after i.v. bolus injection of Gadolinium-DTPA (0.1 mmol/kg body weight). After contrast enhancement, synovial proliferations exhibited an increase of signal intensity (SI) on FFE and SE images of 47.7% and 37.4% respectively, whereas muscle and fatty tissue, tendons, bone marrow and joint effusion revealed only minor increase in SI. The gradient of signal intensity (ratio SI/time) of pannus was 39.6%/min. Gd-DTPA enhanced MRI studies delineate and quantify the synovial proliferations in hemophilic arthropathy. Dynamic studies in hemophilic arthropathy do not provide qualitative assessment of the inflammatory process.

Adult↗
PubMed1994

[Somatostatin receptor scintigraphy in neuroendocrine tumors exemplified by a patient with hepatic metastases of gastrinoma].

In a 66-year old woman, who suffered from recurrent melena, diarrhea and hematemesis with multiple untreatable gastric and duodenal ulcers, a markedly increased basal and secretin-stimulated gastrin level, clinically a Zollinger-Ellison syndrome was assumed. The conventional diagnostic procedures (esophago-gastro-duodenoscopy, colonoscopy, endosonography, ERCP, abdominal CT and small bowel enema) had failed to reveal the localisation of any gastrinoma. The thereupon performed scintigraphy with In-111-pentetreotide showed four somatostatin receptor expressing liver lesions: two of them could be detected at first site in the consecutively performed MR scans, another retrospectively bearing in mind the scintigraphic images. Today, the somatostatin receptor imaging seems to be a highly sensitive procedure for detecting and localizing hormonally active gastroenteropancreatic tumors. At the same time it is a method for in vivo evaluation of the somatostatin receptor status of localized GEP tumors, thus delivering a decisive diagnostic step for the evaluation of the effectiveness of a therapy with somatostatin analogues before such an expensive therapy is started.

Aged↗
PubMed1993

The incidence of p53 mutations increases with progression of head and neck cancer.

To establish a genetic model of the progression of head and neck squamous carcinoma we have defined the incidence and timing of p53 mutations in this type of cancer. We sequenced the conserved regions of the p53 gene in 102 head and neck squamous carcinoma lesions. These included 65 primary invasive carcinomas and 37 noninvasive archival specimens consisting of 13 severe dysplasias and 24 carcinoma in situ lesions. The incidence of p53 mutations in noninvasive lesions was 19% (7/37) and increased to 43% (28/65) in invasive carcinomas. These data suggest that p53 mutations can precede invasion in primary head and neck cancer. Furthermore, the spectrum of codon hotspots is similar to that seen in squamous carcinoma of the lung and 64% of mutations are at G nucleotides, implicating carcinogens from tobacco smoke in the etiology of head and neck squamous carcinoma.

Adult↗
PubMed1993

Molecular screening. Prospects for a new approach.

Tumors arise through a series of genetic steps that involve alterations of various cellular genes. The recent revolution in molecular genetic techniques has allowed direct identification of genetic changes within tumors. Because these changes are intimately involved in tumor progression, they are specific markers for cancer. A novel assay based on the polymerase chain reaction allows detection of a rare cancer cell containing a specific point mutation among an excess background of normal cells. This technique has allowed identification of p53 gene mutations in pathologic tissue samples from primary head and neck cancer. A small population of cancer cells has been detected in a variety of histologically negative clinical specimens, including saliva, surgical margins, lymph nodes, and chyle. The precise detection of these rare cancer cells in various clinical samples has significant implications for otolaryngology-head and neck surgery. This approach holds promise for screening of head and neck cancer and may call for the reassessment of current histopathologic staging through utilization of new molecular genetic techniques.

Genes, p53↗
PubMed1993

Oncogene mutations as intermediate markers.

Tumors arise through a series of genetic changes which include activation of protoocogenes and inactivation of tumor suppressor genes. It is now possible to identify rare cells containing genetic mutations in an excess background of normal cells. Theoretically, the identification of a clonal population of cells sharing an early genetic marker for malignant transformation would lead to valuable intermediate endpoints and could diagnose premalignant lesions amenable to chemoprevention. Ideally, these genetic changes would be specific point mutations that occur early in the tumor cascade, prior to the development of a clinically significant tumor. To identify these markers, precise histopathologic and genetic tumor models must be described. Early candidate markers include p53 point mutations in squamous cell carcinoma of the aerodigestive tract.

Anticarcinogenic Agents↗
PubMed1993

[Rheumatoid arthritis of the wrist. Dynamic Gd-DTPA enhanced MRT].

21 patients with rheumatoid arthritis of the wrist diagnosed according to the criteria of the American Rheumatism Association were examined by dynamic MRT before and after the i.v. injection of Gd-DTPA (0.1 mmol/kg). The results were correlated with the clinical and radiological findings. The increased signal intensity of the pannus was 1.17 +/- 0.45%/sec and this differed significantly (p < 0.001) from bone marrow (0.16 +/- 0.11%/sec) and from muscle (0.25 +/- 0.16%/sec). Blood sedimentation rate correlated with the gradient of synovial proliferation (p < 0.05). There were no further statistically significant correlations between the clinical, radiological and MRT findings and the change in signal intensity from synovial proliferation as shown by dynamic MRT.

Adult↗
PubMed1992

[Spontaneous necrosis of the femoral condyle--new findings in T2-weighted spin-echo sequences and gradient-echo studies].

The spontaneous necrosis of the femur condyles might cause diagnostic problems because clinical symptoms precede the radiologic changes on conventional x-ray. MRI offers an early detection of the necrosis of the femur condyle like bone necrosis of other localisation. Nine patients were examined by T1- and T2-weighted spin echo- and by T2*-weighted gradient echo sequences. All patients had reduced signal intensity in the subchondral bone marrow on T1-w SE sequences. In three patients new findings were observed on T2-w SE and gradient echoes respectively. These findings allow better understanding in the underlying pathologic-anatomical changes.

Aged↗
PubMed1992

[Dynamic functional MRT of the cervical spine].

To obtain functional studies of the cervical spine, a device has been developed which allows MRI examinations to be carried out in five different degrees of flexion. T1 and T2* weighted FFE sequences were used. Dynamic functional MRI was performed on 5 normals and 31 patients (5 disc herniation, 4 whiplash injuries, 6 spinal canal stenoses, 14 laminectomies and spinal fusions, 2 rheumatoid arthritis). The relationship of the spinal cord to the bony and ligamentous components in different degrees of flexion was particularly well shown in whiplash injury, spinal stenosis and postoperative situations.

Cervical Vertebrae↗