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Biomedical subjects

I Petersen

Publications and source records attributed to I Petersen.

At least 37 records · Page 2Linked to original sources
PubMed2000

Chromosomal instability and cytoskeletal defects in oral cancer cells.

Oral squamous cell carcinomas are characterized by complex, often near-triploid karyotypes with structural and numerical variations superimposed on the initial clonal chromosomal alterations. We used immunohistochemistry combined with classical cytogenetic analysis and spectral karyotyping to investigate the chromosomal segregation defects in cultured oral squamous cell carcinoma cells. During division, these cells frequently exhibit lagging chromosomes at both metaphase and anaphase, suggesting defects in the mitotic apparatus or kinetochore. Dicentric anaphase chromatin bridges and structurally altered chromosomes with consistent long arms and variable short arms, as well as the presence of gene amplification, suggested the occurrence of breakage-fusion-bridge cycles. Some anaphase bridges were observed to persist into telophase, resulting in chromosomal exclusion from the reforming nucleus and micronucleus formation. Multipolar spindles were found to various degrees in the oral squamous cell carcinoma lines. In the multipolar spindles, the poles demonstrated different levels of chromosomal capture and alignment, indicating functional differences between the poles. Some spindle poles showed premature splitting of centrosomal material, a precursor to full separation of the microtubule organizing centers. These results indicate that some of the chromosomal instability observed within these cancer cells might be the result of cytoskeletal defects and breakage-fusion-bridge cycles.

Antigens, Nuclear↗
PubMed2000

Telepathology by the Internet.

A new concept for telemicroscopy has recently been introduced using the Internet and conventional web browser, with Java support for microscope remote control as well as image transfer and discussion (http://amba.charite.de/telemic/). The system has two major components: the telemicroscopy server, which is a computer with Internet access connected to the automatic microscope, and the telemicroscopy client, who remotely operates the microscope. This simplified telemicroscopy system allows any Internet user to become a consultant for telepathology without the acquisition of specialized hardware or software. For the inquirer seeking advice, however, this solution is still very expensive, since it requires a fully automated microscope. The present study describes a system that can be used for conventional microscopes. A video camera mounted on a microscope with a photo tube is connected to the frame grabber of a PC. Java-based telemicroscopy software transforms the computer into an Internet server, which automatically distributes new microscope images, after manual operations, to all connected clients. Any Internet user can access the web page of the server to become a telemicroscopy client. A Chat function allows for the online exchange of written text and a Discuss function enables the mouse button to display an arrow to all connected clients, which highlights distinct structures of the images. The system was optimized for simplicity, while presenting all features that are necessary to show and discuss difficult cases with any expert in the field who has Internet access. It offers new perspectives for telepathology and it is envisaged that many pathologists and scientists will use this facility to connect their personal microscopes to the Internet, forming a network for teleconsultation. To foster this development, the software described in this paper is being made freely available. Hopefully, this development will promote communication between pathologists and may thus increase the quality of diagnosis. Information on inquiry and installation of the software is available at the website mentioned above. Telemicroscopy sessions using the Telemic version for conventional microscopes can be scheduled by contacting the authors by e-mail (iver. petersen@charite.de).

Communication↗
PubMed2000

[Improved prognostic assessment of head-neck carcinomas by new genetic markers].

In individual patients with head and neck squamous cell carcinomas (HNSCC), established prognostic factors do not satisfactorily predict clinical outcome. For the first time we investigated a total of 100 HNSCC by Comparative Genomic Hybridization (CGH) to define chromosomal alterations that are associated with the patients prognosis. Patients were followed for at latest 4 but at least 2 years after surgery or until death. During this observation period twenty-nine of them died because of cancer disease. The Kaplan-Meier method was used plotting survival curves for every single chromosomal alteration as well as every clinico-pathological parameter. The curves were tested for significance by the log rank as well as the Breslow test. Significance of particular prognostic parameters was then evaluated by the Cox regression model. The overall survival time as well as the recurrence free survival time were significantly lower in patients who's tumors showed amplifications of the chromosomal region 11q13 (p = 0.0008 for LR and p = 0.0024 for B). The survival time of the patients was also lower if the carcinomas carried over-representations of chromosome 3q (p = 0.0299 for LR and p = 0.0546 for B). Multivariate analysis (Cox's proportional hazards model) revealed both alterations as most important independent prognostic factors in HNSCC. None of the conventional clinicopathological parameters (pT-, pN-status, UICC stage, grading) achieved statistical significance in the multivariate model. These results suggest that in HNSCC the occurrence of 11q13 amplification and 3q overrepresentation are highly significant independent prognostic markers and of better value than the established TNM and grading criteria.

Biomarkers, Tumor↗
PubMed2000

Genetic imbalances with impact on survival in head and neck cancer patients.

Chromosomal imbalances in 113 primary head and neck squamous cell carcinomas (HNSCCs) determined by comparative genomic hybridization were correlated with patients survival using custom-made computer software which enabled the assessment of individual chromosomal loci. The Kaplan-Meier analysis revealed that overrepresentations of 2q12, 3q21-29, 6p21.1, 11q13, 14q23, 14q24, 14q31, 14q32, 15q24, 16q22, and deletions of 8p21-22 and 18q11.2 were significantly associated with both shorter disease-free interval and disease-specific survival in this tumor collective. Multivariate Cox proportional hazards regression models consistently identified the gains of 3q21-29, 11q13, and the loss of 8p21-22 as independent prognostic markers carrying a higher significance than the nodal status as the only clinicopathological parameter with statistical importance. In addition, these three markers allowed a molecular dissection of the patients with low clinical risk (pN0 and pT2 tumors). Thus, the genomic data being derived from the evaluation of primary HNSCC enabled a stratification of the patients into subgroups with different survival highlighting the necessity of a genetically based tumor classification for refining diagnosis and treatment of HNSCC patients.

Chromosome Aberrations↗
PubMed2000

Comprehensive integrated primary mental health care for South Africa. Pipedream or possibility?

While the vision for restructuring health care in South Africa is based on a comprehensive primary health care system, care at the primary level remains largely biomedical in orientation. Given this, I argue that whilst adding mental health care to primary level care may increase accessibility of psychiatric care. it will not, however, provide for comprehensive integrated primary mental health care as planned. This would require a paradigm shift towards a comprehensive discourse of care which includes mental health care. While efforts towards reorienting health care personnel in South Africa towards the primary health care approach have been initiated, an examination of the primary health care system in one sub-district in South Africa, reveals that the delivery of biomedical care is sustained by a number of factors within the primary health care system as well as within the macro-context. A shift in the paradigm of care provided would therefore require the transformation of the system on many fronts. Of central importance would be the restructuring of the primary health care system to be supportive of emotional labour, health promotion, empowerment of service users and of care which takes the subjectivity of the illness experience for the patient into account.

Culture↗
PubMed2000

Human papilloma virus status and chromosomal imbalances in primary cervical carcinomas and tumour cell lines.

Human papilloma virus (HPV) infection is the crucial step in the initiation of cervical carcinomas. In addition, HPV18 has been implicated in tumour progression and adverse clinical outcome. We determined the HPV types in 12 primary cervical carcinomas and 12 cell lines and compared the findings with the comparative genetic hybridisation (CGH) pattern of chromosomal alterations. The most frequent alteration was the deletion at 3p14 followed by the loss of 2q34-q36 along with 3q gain. High risk HPV types were detected in all samples except one primary tumour. In contrast to the normal distribution, HPV18 was present in 75% of cases including all cell lines. The cell lines carried a higher number of genetic alterations and a different CGH pattern for several chromosomes than the primary tumours, despite microdissection. Purely HPV18 positive cases indicated a high incidence of imbalances at specific loci with peaks of the histogram coinciding with known HPV integration sites. The study suggests that HPV infection is associated with a recurrent pattern of chromosomal changes in cervical carcinomas and that the development and progression of these alterations is triggered by integration into the host genome.

Carcinoma, Squamous Cell↗
PubMed2000

Analysis of chromosomal alterations in non-small cell lung cancer by multiplex-FISH, comparative genomic hybridization, and multicolor bar coding.

Lung cancer has a considerable impact on morbidity and mortality throughout the world. Despite extensive effort, no lung cancer-specific cytogenetic changes, such as lineage-specific translocations or inversions, have been described to date. In this study we used multiplex fluorescence in situ hybridization (M-FISH), comparative genomic hybridization, and multicolor bar coding to analyze eight cell lines derived from non-small cell lung cancers. M-FISH did not identify any balanced translocations, which are the dominating feature in leukemias and lymphomas. Instead, M-FISH unraveled an enormous number of numerical and structural aberrations, with each tumor having its own "private" pattern of chromosomal changes. In contrast, comparative genomic hybridization demonstrated similarities between tumors, because each cell line shared some chromosomal segments that were commonly gained or lost. One of these involved chromosome 12. Chromosome 12 specific bar code probe sets were constructed and used to demonstrate that breaks on chromosome 12 occur preferentially within specific bands. With the progressive use of higher resolution approaches, more information can be gained about the chromosomal alterations in cancer.

Carcinoma, Non-Small-Cell Lung↗
PubMed2000

Chromosomal alterations in the clonal evolution to the metastatic stage of squamous cell carcinomas of the lung.

Comparative genomic hybridization (CGH) was applied to squamous cell carcinomas (SCC) of the lung to define chromosomal imbalances that are associated with the metastatic phenotype. In total, 64 lung SCC from 50 patients were investigated, 25 each with or without evidence of metastasis formation. The chromosomal imbalances summarized by a CGH histogram of the 50 cases revealed deletions most frequently on chromosomes 1p21-p31, 2q34-q36, 3p, 4p, 4q, 5q, 6q14-q24, 8p, 9p, 10q, 11p12-p14, 13q13-qter, 18q12-qter and 21q21. DNA over-representations were most pronounced for chromosomes 1q11-q25, 1q32-q41, 3q, 5p, 8q22-qter, 11q13, 12p, 17q21-q22, 17q24-q25, 19, 20q and 22q. In ten cases, paired samples of primaries and at least one metastasis were analysed. The comparison revealed a considerable chromosomal instability and genetic heterogeneity; however, the CGH pattern indicated a clonal relationship in each case. The difference in histograms from the metastatic and non-metastatic tumour groups was most useful in pinpointing chromosomal imbalances associated with the metastatic phenotype, indicating that the deletions at 3p12-p14, 3p21, 4p15-p16, 6q24-qter, 8p22-p23, 10q21-qter and 21q22, as well as the over-representations at 1q21-q25, 8q, 9q34, 14q12 and 15q12-q15, occurred significantly more often in the metastatic tumour group. The comparison of the paired samples confirmed these findings in individual cases and suggested distinct genetic changes, in particular the extension of small interstitial deletions, during tumour progression. Importantly, metastasis-associated lesions were frequently detectable in the primary tumour providing a method of identifying patients at risk for tumour dissemination. Individual profiles and histograms are accessible at our web site http://amba.charite.de/cgh.

Carcinoma, Squamous Cell↗
PubMed2000

[Deletion of chromosome 10q--a marker for metastasis of head-neck carcinomas?].

BACKGROUND: Comparative genomic hybridization (CGH) was applied to squamous cell carcinomas of the head and neck to define genetic alterations that are associated with the metastatic phenotype. METHODS: CGH is a molecular cytogenetic method allowing the comprehensive analysis of a tumor genome for chromosomal imbalances. In total, 23 primary squamous cell carcinomas without evidence of metastasis formation and 20 lymph node metastases were investigated. RESULTS: Prevalent changes observed in more than 50% of the primary tumors included deletions on chromosomes 3p, 4p/q, 5q, 6q, 9p, 11q, 13q, and 18q, and DNA overrepresentations on chromosomes 1p, 3q, 5p, 8q, 9q, 11q13, 16p, 17q, 19p, 20q, and 22q. To evaluate the differences between both groups we used a histogram representation, calculation of a difference histogram, and statistical analysis. The analysis revealed that the lymph node metastases were frequently characterized by deletions on chromosomes 10, 11, and 14. In particular, DNA loss of the chromosomal bands 5p12, 10p11.2-12, 10q21, 10q22-23, 10q24-26, 11p13-14, 11q24-25, and 14q22-24 were significantly associated with metastases formation. The statistical analysis indicated that particularly the deletions on chromosome 10q were highly significant markers for the incidence of lymph node metastases. CONCLUSION: Our data indicate that tumor phenotypes are determined by patterns of chromosomal alterations, and that 10q deletions may predict the metastatic phenotype in head and neck squamous cell carcinomas.

Biomarkers, Tumor↗
PubMed2000

Detection of microsatellite alterations in the DNA isolated from tumor cells and from plasma DNA of patients with lung cancer.

In this paper, we show that the same panel of three microsatellite markers is useful for the detection of alterations in the DNA of tumor cells and plasma from patients diagnosed with SCLC and NSCLC. In 31% of the SCLC patients, we detected a microsatellite alteration(s) or LOH in at least one locus. In the group of patients diagnosed with NSCLC, a microsatellite alteration or LOH was detected in at least one locus in 33% of the patients. In all but 2 patients, the identical alteration observed in the DNA from tumor cells was also detected in the DNA isolated from blood plasma. This work confirms the results described by other groups and it extends the diagnostic possibilities of finding tumor cell-specific DNA alterations also in the DNA freely circulating in plasma and serum of patients with cancer.

Adult↗
PubMed2000

Chromosomal imbalances in brain metastases of solid tumors.

Metastases account for approximately 50% of the malignant tumors in the brain. In order to identify structural alterations that are associated with tumor dissemination into the central nervous system we used Comparative Genomic Hybridization (CGH) to investigate 42 brain metastases and 3 primary tumors of 40 patients. The metastases originated from lung cancer (14 cases), melanomas (7), carcinomas of breast (5), colon (5), kidney (5), adrenal gland (1) and thyroid (1). In addition, tumors of initially unknown primaries were assessed in 3 cases. The highest incidence of DNA gains were observed for the chromosomal regions 1q23, 8q24, 17q24-q25, 20q13 (>80% of cases) followed by the gain on 7p12 (77%). DNA losses were slightly less frequent with 4q22, 4q26, 5q21, 9p21 being affected in at least 70% of the cases followed by deletions at 17p12, 4q32q34, 10q21, 10q23-q24 and 18q21-q22 in 67.5% of cases. Two unusual narrow regional peaks were observed for the gain on 17q24-q25 and loss on 17p12. The incidence at individual loci can be viewed at our CGH online tumor database at http:// amba.charite.de/cgh/. The metastases of each tumor type showed a recurrent pattern of changes. In those cases with primary tumor and metastases available, the CGH pattern exhibited a high degree of conformity. In conclusion, our data suggests that specific genetic lesions are associated with tumor dissemination into the nervous system and that CGH analysis may be a useful supplementary tool for classification of metastases with unknown origin.

Brain Neoplasms↗
PubMed2000

From policy to praxis--a framework for the delivery of district mental health care in KwaZulu-Natal.

This article provides a schema for the provision of mental health care at district level. A framework for service delivery was derived from research conducted by the Community Mental Health Programme (CMHP) into the development of aspects of a district mental health care system in a semi-rural community area in KwaZulu-Natal. Furthermore, information was drawn from interviews with key stakeholders, national and provincial policy documents as well as international experience in the implementation of community-based systems of mental health care.

Community Mental Health Services↗
PubMed1999

Training for transformation: reorientating primary health care nurses for the provision of mental health care in South Africa.

Using programme research, this paper reports on the evaluation of a programme designed to orientate primary health care nurses towards the provision of a comprehensive approach to care. In addition to training in psychiatric care, this was deemed necessary in order to facilitate comprehensive integrated primary mental health care in South Africa. Nurse-patient consultations were evaluated on indicators of comprehensive care before and after the programme. Interviews were also conducted with the participants individually and in a group. The results indicate that there are several factors which mediate the provision of comprehensive care by primary health care nurses. These include individual factors as well as contextual factors, inter alia, the structure and organization of the health care system, which historically has been organized to promote biomedical care. Furthermore, biomedicine has dominated training models in South Africa, instilling in nurses a biomedical approach to patient care.

Culture↗
PubMed1999

[Rudolf-Virchow Prize 1999. Genetics of respiratory tract carcinomas: correlation of genotype and phenotype].

In contrast to carcinomas of the upper respiratory tract lung cancer shows a considerable variety of histological differentiations and is particularly known for its morphological heterogeneity. Of clinical relevance, however, is only the distinction between small cell carcinomas (SCLC) and non-small cell lung cancer (NSCLC). We meanwhile investigated a tumor collective of several hundred respiratory tract carcinomas by Comparative Genomic Hybridization (CGH) and developed computer software for the statistical comparison of tumor groups. The analysis revealed recurrent patterns of chromosomal imbalances which are associated with morphological histotypes and biological phenotypes, e.g. there are chromosomal imbalances predominantly found in SCLC compared to NSCLC but also a considerable overlap between both entities. Specifically, the pattern of metastasizing lung squamous cell carcinomas (SCC) approaches that of SCLC. In addition, the analysis of a metastasizing combined SCLC after microdissection showed a clonal relationship between the SCC component of the primary tumor and the SCLC metastasis. These findings have direct consequences for the pathogenesis and classification of lung cancer. First, SCLC should be differentiated into primary and secondary carcinomas. Whereas primary SCLC as the predominant tumor type evolve directly from a precursor cell of probably epithelial origin, secondary SCLC develop via a NSCLC intermediate. Second, neuroendocrine differentiation in lung carcinomas should be used as a marker for dedifferentiation, worse prognosis and rapid tumor progression rather than an indicator of a putative tumor stem cell. The primary data is available at our online tumor database at http://amba.charite.de/cgh/.

Awards and Prizes↗
PubMed1998

Distinct regions of allelic imbalance on chromosome 10q22-q26 in squamous cell carcinomas of the lung.

The genetic mechanisms underlying the progression to the metastatic phenotype of lung cancer are poorly understood. We recently showed that small cell lung cancer (SCLC) and metastasizing squamous cell carcinomas are characterized by an increased incidence of allelic loss on chromosome 10q. In the present study we performed a deletion mapping using 24 polymorphic markers on chromosome 10q22-q26 in 39 squamous cell carcinomas (SCC) of the lung identifying 14 metastatic carcinomas (74%) and three non-metastatic SCC (15%) with allelic imbalance. The allelotype analysis indicated three regions of allelic loss that were clustered at the loci Afm086/D10S541, D10S185 and D10S1782/D10S169. A localized microsatellite instability was observed in two carcinomas for the markers D10S1686 and D10S1782. In addition the PTEN/MMAC1 gene was analysed by direct DNA sequencing and Southern blot analysis in 25 and 28 carcinomas, respectively, without detecting any genomic alterations. Similarly, no altered transcript was detected in 15 tumor cell lines and 20 primary tumors by Northern blot analysis or RT-PCR. In summary, three distinct regions of allelic imbalance were identified suggesting that multiple tumor suppressor genes on chromosome 10q contribute to tumor progression and metastases formation of lung cancer.

Alleles↗
PubMed1998

Genomic alterations associated with malignancy in head and neck cancer.

BACKGROUND: Comparative genomic hybridization (CGH) was performed on 50 primary head and neck squamous cell carcinomas (HNSCC) to discover molecular genetic alterations underlying the progression of these tumors. METHODS: In CGH, equal amounts of differently labeled tumor deoxyribonucleic acid (DNA) and normal reference DNA were hybridized simultaneously to normal metaphase chromosomes. They were visualized by different fluorochromes, and the signal intensities were quantitated separately as gray levels along the single chromosomes. The over- and underrepresented DNA segments were determined by computation of ratio images and average ratio profiles. RESULTS: Prevalent changes observed in more than 50% of the HNSCC included deletions of chromosomes 1p, 4, 5q, 6q, 8p, 9p, 11, 13q, 18q, and 21q and DNA overrepresentations of 11q13 as well as 3q, 8q, 16p, 17q, 19, 20q, and 22q. The calculation of ratio profiles of tumor subgroups revealed that well differentiated carcinomas (G1) were defined by the deletions of chromosomes 3p, 5q, and 9p together with the overrepresentation of 3q, suggesting the association with early tumor development. Accordingly, the undifferentiated tumors (G3) were characterized by additional deletions of chromosomes 4q, 8p, 11q, 13q, 18q, 21q, and overrepresentations of 1p, 11q13, 19, and 22q. CONCLUSION: Our data indicate that the CGH patterns of chromosomal imbalances may help to define the malignant potential of head and neck squamous cell carcinomas.

Carcinoma, Squamous Cell↗