Normal frequency of chromosome breakage in lymphocytes from patients with musculoskeletal sarcoma

Spontaneous chromosome aberrations were studied in lymphocytes from 23 untreated patients with musculoskeletal sarcoma and 27 controls. Among the sarcoma patients, the mean gap, break, and gap + break events per 100 metaphases were 0.9, 2.2, and 3.0, respectively. The corresponding values for the control group were 1.3, 1.6, and 2.8. The mean number of aberrant mitoses was 2.4% in the sarcoma group and 2.5% in the controls. None of the differences between patients and controls were statistically significant. Thus, we found no evidence of inherent chromosome instability in patients with malignant mesenchymal tumors.     

Isochromosomes i(8q) or i(9q) in three adenocarcinomas of the lung

We have cytogenetically analyzed three primary adenocarcinomas of the lung. All tumors had chromosome numbers in the triploid region. The multiple structural aberrations included rearrangements of 3p, in two cases affecting the segment 3p14-23, where deletions are characteristically found in small cell lung carcinomas. Isochromosomes for 8q were present in two tumors and i(9q) in one tumor. In the few previously reported cytogenetic analyses of pulmonary adenocarcinomas, all of which examined metastases or cell lines, i(8q) was found in one case and i(9q) in two cases. These isochromosomes, therefore, represent previously unrecognized nonrandom changes in adenocarcinomas of the lung, and might constitute primary aberrations in this tumor type.     

Human Cytomegalovirus Infection Leads to Elevated Levels of Transplant Arteriosclerosis in a Humanized Mouse Aortic Xenograft Model

Recent findings emphasized an important role of human cytomegalovirus (HCMV) infection in the development of transplant arteriosclerosis. Therefore, the aim of this study was to develop a human peripheral blood lymphocyte (hu‐PBL)/Rag‐2^–/–γc^–/– mouse‐xenograft‐model to investigate both immunological as well as viral effector mechanisms in the progression of transplant arteriosclerosis. For this, sidebranches from the internal mammary artery were recovered during coronary artery bypass graft surgery, tissue‐typed and infected with HCMV. Then, size‐matched sidebranches were implanted into the infrarenal aorta of Rag‐2^–/–γc^–/– mice. The animals were reconstituted with human peripheral blood mononuclear cells (PBMCs) 7 days after transplantation. HCMV‐infection was confirmed by Taqman‐PCR and immunofluorescence analyses. Arterial grafts were analyzed by histology on day 40 after transplantation. PBMC‐reconstituted Rag‐2^–/–γc^–/– animals showed splenic chimerism levels ranging from 1–16% human cells. After reconstitution, Rag‐2^–/–γc^–/– mice developed human leukocyte infiltrates in their grafts and vascular lesions that were significantly elevated after infection. Cellular infiltration revealed significantly increased ICAM‐1 and PDGF‐R‐β expression after HCMV‐infection of the graft. Arterial grafts from unreconstituted Rag‐2^–/–γc^–/– recipients showed no vascular lesions. These data demonstrate a causative relationship between HCMV‐infection as an isolated risk factor and the development of transplant‐arteriosclerosis in a humanized mouse arterial‐transplant‐model possibly by elevated ICAM‐1 and PDGF‐R‐β expression.     

Molecular mechanism of slow acetylation of drugs and carcinogens in humans.

The acetylation polymorphism is one of the most common genetic variations in the transformation of drugs and chemicals. More than 50% of individuals in Caucasian populations are homozygous for a recessive trait and are of the "slow acetylator" phenotype. They are less efficient than "rapid acetylators" in the metabolism of numerous drugs and environmental and industrial chemicals. The acetylation polymorphism is associated with an increased risk of drug toxicity and with an increased frequency of certain cancers. We report the identification of the primary mutations in two alleles of the gene for the N-acetyltransferase (NAT; acetyl-CoA:arylamine N-acetyltransferase, EC 2.3.1.5) isozyme NAT2 associated with slow acetylation. These alleles, M1 and M2, account for more than 90% of slow acetylator alleles in the European population we have studied. M1 and M2 were identified by restriction fragment length polymorphisms with Kpn I and Msp I and subsequently cloned and sequenced. M1 and M2 each are characterized by a combination of two different point mutations, one causing an amino acid substitution (Ile-113----Thr in M1, Arg-197----Gln in M2), the other being silent (C 481----T in M1, C 282----T in M2). Functional expression of M1 and M2 and of chimeric gene constructs between mutant and wild-type NAT2 in COS-1 cells suggests that M1 causes a decrease of NAT2 protein in the liver by defective translation, whereas M2 produces an unstable enzyme. On the basis of the mutations described here and a rare mutant allele (M3) reported recently, we have developed a simple DNA amplification assay that allows the predictive genotyping of more than 95% of slow and rapid acetylator alleles and the identification of individuals at risk.     

Non-traumatic lower limb older amputees: a database survey from a geriatric centre

Purpose: The purpose of this survey was to examine the characteristic of a geriatric population admitted for amputation of a lower limb and to explore some of the factors that may affect the course of their hospital stay. Method: The study took place in the geriatric division of a tertiary general hospital and included a close geriatric-orthopaedic liaison. Two-hundred and forty-one patients were included in the final analysis. Results: Many above knee amputations were performed, which correlated with advanced age. Rates of in hospital mortality and systemic complications were 16% and 19%, respectively. Thirty-three percent of the patients were discharged back home, and only 6% were supplied with an artificial limb. The general condition of most patients remained poor. Conclusion: We conclude that despite a team approach to the care of the geriatric amputee a poor functional result was obtained. By encouraging earlier referrals from the community it is postulated that a reduction in the costly provision of antibiotics would be beneficial and that perhaps lower levels of amputation could be performed thereby enhancing the possibilities for ambulation.     

Chromogenic in situ hybridization for Her‐2/neu‐oncogene in breast cancer: comparison of a new dual‐colour chromogenic in situ hybridization with immunohistochemistry and fluorescence in situ hybridization

Aims: Her‐2/neu testing is used as a marker for Herceptin^® therapy. The aim was to investigate new dual‐colour chromogenic in situ hybridization (CISH), in a large number of breast carcinomas (n = 205) with DNA‐specific dual‐colour probes (ZytoVision, Bremerhaven, Germany) and to compare the results with immunohistochemistry (n = 205) and fluorescence in situ hybridization (FISH) (n = 129). Methods and results: Paraffin‐embedded tissue of 205 patients was used. After immunohistochemistry with a focus on immunohistochemically uncertain cases, Her‐2/neu amplification using dual‐colour CISH (ZytoVision^®) was analysed. Validation by FISH was performed. The results were: immunohistochemistry, 27.8% with strong expression, 53.7% with uncertain overexpression and 18.5% with no expression; FISH, 25.6% amplified and 74.4% negative; CISH, 35.6% amplified, 62.9% negative and 1.5% not evaluable. Comparison of immunohistochemistry with CISH: CISH negative in 100% with immunohistochemistry 0/1+, amplified in 82.5% with immunohistochemistry 3+; 5.9% contradictory results: 4.4% immunohistochemistry 3+ and negative by CISH, 1.5% negative in immunohistochemistry but amplified by CISH; FISH (129 cases), 8.5% contradictory results to immunohistochemistry, 6.2% immunohistochemistry 3+ and negative by FISH, 2.3% negative by immunohistochemistry and amplified by FISH; comparison of CISH and FISH, 94.6% same results, 3.9% different ones, 1.6% CISH not analysable. Conclusions: CISH, using dual‐colour probes (ZytoVision^®) is as good as FISH for Her‐2/neu analysis. The few discrepant results are likely to be caused by polysomy or tumour heterogeneity.     

The correlation between low birth weight and learning traits in senior school pupils--a retrospective survey

The purpose of this study was to establish whether a correlation exists between childrens birth weight and their scholastic achievements in high school. This correlation has previously only been investigated only in primary school children and it was felt that it would be interesting to observe whether schooling changed the known status. The records of 718 children were reviewed and there appears to be a statistically significant disability for low birth weight children in the study of exact sciences and foreign languages whilst no significant differences were noted in the humanities and sport.     

Les idées fixes et la psychologie de l'action de Pierre Janet

Janet's conception of the psychic trauma and the formation of emotional complexes (fixed ideas) was discussed. This conception of the psychic trauma and of the fixed ideas is the basis for Janet's nosology of neurotic disorders. The neuroses are understood as ”functional” disorders because of their functional pathogenesis. A stratified hierarchy of functions is explicated by Janet's psychology of action and by a hierarchy of nine different psychic tendencies. The impact of ”psychic tension” and ”psychic force” for the formation of and for the effects of the psychic tendencies is shown. The effect of changes in the hierarchy of the psychic tendencies on the pathogenesis of mental disorders is explicated.     

Chromosomal aberrations in benign and malignant Bilharzia-associated bladder lesions analyzed by comparative genomic hybridization

Background

Bilharzia-associated bladder cancer (BAC) is a major health problem in countries where urinary schistosomiasis is endemic. Characterization of the genetic alterations in this cancer might enhance our understanding of the pathogenic mechanisms of the disease but, in contrast to nonbilharzia bladder cancer, BAC has rarely been the object of such scrutiny. In the present study, we aimed to characterize chromosomal imbalances in benign and malignant post-bilharzial lesions, and to determine whether their unique etiology yields a distinct cytogenetic profile as compared to chemically induced bladder tumors.

Methods

DNAs from 20 archival paraffin-embedded post-bilharzial bladder lesions (6 benign and 14 malignant) obtained from Sudanese patients (12 males and 8 females) with a history of urinary bilharziasis were investigated for chromosomal imbalances using comparative genomic hybridization (CGH). Subsequent FISH analysis with pericentromeric probes was performed on paraffin sections of the same cases to confirm the CGH results.

Results

Seven of the 20 lesions (6 carcinomas and one granuloma) showed chromosomal imbalances varying from 1 to 6 changes. The most common chromosomal imbalances detected were losses of 1p21-31, 8p21-pter, and 9p and gain of 19p material, seen in three cases each, including the benign lesion.

Conclusion

Most of the detected imbalances have been repeatedly reported in non-bilharzial bladder carcinomas, suggesting that the cytogenetic profiles of chemical- and bilharzia-induced carcinomas are largely similar. However, loss of 9p seems to be more ubiquitous in BAC than in bladder cancer in industrialized countries.

     

Partial loss of dopaminergic neurons in the substantia nigra,ventrotegmental area and the retrorubral area -- model of the early beginning of Parkinson's symptomatology?

Summary. To test substances which might have protective effects on the dopaminergic system it is necessary to use models with a pathological symptomatology of the early beginning, i.e. models in which the chance exists to arrest the otherwise progressive pathological processes (see Heim et al., 2001). 6-hydroxydopamine (6-OHDA) injected unilaterally into the ventrolateral striatum of rats (6 μg dissolved in 2 μl 0.2% ascorbic acid) leads to specific stereotyped movements after subcutaneous injection of apomor-phine both 3 and 13 weeks after surgery. Ten weeks after surgery decreased spontaneous motor activity could be observed. Twelve weeks after 6-hydroxydopamine injection, the animals had difficulties in performing a spatial navigation task when the submerged escape platform was moved to another position. The switching of motor programs was less pronounced. The application of tyrosine-hydroxylase-staining showed a loss of ipsilateral neurones of the substantia nigra compacta as well as of dendrites in the pars reticulata, neurones in the ventral tegmental area and in the retrorubral area ipsilaterally as well as a loss of dopaminergic fibres both ipsilaterally and contralaterally in the striatum which should belong to the contralateral acting substantia nigra afferents. The loss of the neurones and the afferents was induced by the retrograde denervation following the 6-OHDA injection within the ventrolateral striatum. The question arises whether the model used here with the partially loss of dopaminergic neurons and fibres reflects some of pathological symptoms of Parkinson's disease in the early states. Received December 21, 2001; accepted February 25, 2002