Prognostic value of mitotic metaphase rate in oesophageal cancer.

OBJECTIVE: To assess the prognostic value of the mitotic metaphase rate in patients with oesophageal cancer. DESIGN: Retrospective study. SETTING: University hospital, Japan. SUBJECTS: 41 patients with oesophageal cancer. INTERVENTIONS: We calculated the ratio of mitotic metaphase to anaphase cells among tumour cells in sections stained with haematoxylin and eosin, a ratio that shows the status of mitotic metaphase-anaphase transition. The DNA ploidy pattern was examined by flow cytometry. MAIN OUTCOME MEASURE: Correlation between survival and mitotic metaphase rate. RESULTS: A high mitotic metaphase rate was correlated with vascular invasion and is expected to be a useful prognostic factor. DNA diploidy combined with a low rate was an independent favorable prognostic factor. CONCLUSION: Mitotic metaphase rate is a useful index of malignant potential, independent of DNA ploidy. It can distinguish high malignant potential from low in a diploid tumour, which has a poor prognosis that is equal to that of the aneuploidy tumour.     

Microtubule associated protein (tau) gene variability in patients with frontotemporal dementia

Frontotemporal dementia represents up to 10% of all dementias and is, next to Alzheimer's disease and Lewy body disease, the third most common cause of degenerative dementia. The term "frontotemporal dementia" covers a range of conditions, including Pick's disease, frontal lobe degeneration and dementia associated with motor neurone disease. Neuropathologically FTD is characterised by atrophy of the frontal and temporal lobes of the cerebral cortex, often with additional subcortical changes. Both familial and more frequently sporadic forms of FTD can be recognised. Recently, mutations in the microtubule-associated protein (tau) gene have been found in families with frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). The identification of mutations in the tau gene indicates that the protein plays a central role in the process of neurodegeneration. Epidemiology of frontotemporal dementias in Poland remains still unknown. A prevalence of tau mutations among Polish patients has not been established yet. Here, we report results of a mutational analysis of the tau gene among Polish FTD patients. No pathogenic mutation was found in the analysed sample. The study confirmed that the frequency of tau mutations is very low and depends strongly on the clinical criteria used to select patients. Mutations in the tau gene account only for a small number of FTD cases with a clear autosomal dominant pattern of disease inheritance. Therefore there should exist additionalgenetic and non-genetic factors contributing to the pathogenesis of both familial (linked and non-linked to chromosome 17) and sporadic forms of FTD.     

Autonomic regulation of experimental autoimmune encephalomyelitis in IL-4 knockout mice

The effect of chemical sympathectomy induced with 6-hydroxydopamine (OHDA) on experimental autoimmune encephalomyelitis (EAE) was studied in wild type and IL-4^−/− C57BL/6 (B6) mice. When actively sensitized with myelin oligodendrocyte glycoprotein (MOG)_35–55 peptide, control B6 mice developed a mild form of EAE with full recovery. The sympathectomized mice developed paralysis with higher maximum disease score and did not recover completely, indicating that the sympathetic nervous system (SNS) down-modulates the process of EAE. Unexpectedly, however, sympathectomy resulted in suppression of EAE in IL-4^−/− mice, implying that control of actively induced EAE by the SNS depends on the genetic background of mice. We also induced EAE by passive transfer of MOG_35–55-reactive lymph node cells, and this disease was augmented by sympathectomy in both wild type and knockout animals. Further experiments showed that changes in T cell populations and the activity of antigen presenting cells might be responsible for the altered immune response and clinical course after sympathetic ablation. Our studies indicate that the absence of a single cytokine can severely alter nervous–immune system interactions.     

3H-thymidine autoradiography of CSF cells in primary reticulum cell sarcoma of the brain

Summary CSF cells in a case of primary reticulum cell sarcoma of the brain with diffuse subarachnoid spreading were examined by ³H-thymidine autoradiography. Immediately after lumbar puncture, the CSF withdrawn was incubated at 37°C for 1 hr with an admixture of ³H-thymidine at a rate of 1 Ci/ml CSF. The cells were collected by centrifugation and the microautoradiographic procedure was performed. The labeling index (L.I.) of the total CSF cells was 10.5%, and when non-neoplastic cells, i.e. polymorphonuclear leukocytes, small lymphocytes, monocytes etc., were excluded, the real L.I. of the tumor cells in the CSF was supposed to be more than 14.4%. Referring to the results of various brain tumors reported in the literature, this belongs at least to the highest labeling group. The high L. I. of the tumor cells in this case was well consistent with the extremely rapid clinical course. It should be stressed that the examination of CSF cells by ³H-thymidine autoradiography in cases of brain tumors could be one of the valuable methods indicating the DNA synthesis of the tumor cells, which is an important parameter of malignancy.

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Zusammenfassung Liquorzellen in einem Fall von primärem Reticulumzellsarkom des Gehirns mit diffuser subarachnoidealer Ausbreitung wurden mit ³H-Thymidin-Autoradiographie untersucht. Sofort nach der Lumbalpunktion wurde der entnommene Liquor bei 37°C für 1 Std mit ³H-Thymidin inkubiert. Die Zellen wurden durch Zentrifugation gesammelt, und ein mikroautoradiographisches Verfahren wurde ausgeführt. Der Markierungsindex der gesamten Liquorzellen wurde mit 10.5% errechnet. Wenn nichtneoplastische Zellen, d. h. Granulocyten, Monocyten, Lymphocyten usw., ausgeschlossen wurden, dann betrug der echte Markierungsindex der Tumorzellen im Liquor mehr als 14.4%. Der Index entspricht somit den höchsten von den in der Literatur berichteten Markierungen bösartiger Gehirntumoren des Menschen. Der hohe Markierungsindex dieses Tumors entsprach dem außerordentlich rasch progredienten klinischen Bild. Es wird hier betont, daß die Untersuchung der Liquorzellen bei Gehirntumoren mit ³H-Thymidin-Autoradiographie für eine Beurteilung der Fähigkeit der DNS-Synthese der Tumorzellen verwendet werden kann, und damit einen Hinweis auf die Malignität gibt.

     

Familial amyotrophic lateral sclerosis and parkinsonism-dementia complex--tauopathy without mutations in the tau gene?

We present the clinical and genetic characteristics of a Japanese patient with neuropathologically confirmed familial amyotrophic lateral sclerosis/parkinsonism dementia complex (ALS/PDC). The 68-year-old proband with an 8-year history of parkinsonism and neurogenic amyotrophy and her three siblings suffering from parkinsonism associated with dementia originated from the Kii Peninsula of Japan. The proband's brain exhibited mild frontal lobe atrophy, moderate atrophy of the pes hippocampi, decoloration of the substantia nigra and locus coerules, and atrophy of the anterior root of the spinal cord. Microscopic examinations revealed degeneration of the CA1 portion of the hippocampus to the parahippocampus gyrus, substantia nigra, locus coerules and the spinal anterior horn with Bunina bodies. Neurofibrillary tangles (NFTs) were observed in widespread regions of the central nervous system through the cerebral cortex to the spinal cord. The predominant distribution of NFTs in the the third layer of the cerebral cortex was compatible with the characteristic feature of ALS/PDC in Guam. No tau mutation was found in the proband. The lack of mutations in the tau gene not only in this patient but also in earlier reported cases of ALS in the Western Pacific seems to suggest that other genetic factors may be contributing to ALS/PDC.     

A clinical and pathological study of a Japanese case of Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex with family history

This report concerns a Japanese family with neuropathological findings consistent with amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) in the Island of Guam. The proband was a 68-year-old woman with an 8-year history of parkinsonism which was followed by psychiatric symptoms and neurogenic amyotrophy 5 years after the onset. She had a family history of parkinsonism associated with dementia in all of her three siblings. They grew up in the Hobara village, a focus of amyotrophic lateral sclerosis in the Kii Peninsula of Japan in their childhood. Their parents were not consanguineous nor natives of the Kii Peninsula. The brain weight was 1040 g and there were mild frontal lobe atrophy, moderate atrophy of pes hippocampi, decoloration of the substantia nigra and locus coeruleus, and atrophy of the anterior root of the spinal cord. The microscopic examinations revealed degeneration of CA1 portion of the hippocampus to the parahippocampus gyrus, substantia nigra, locus coeruleus and spinal anterior horn with Bunina bodies. The spinal pyramidal tracts also mildly degenerated. Neurofibrillary tangles (NFT) were observed in the cerebral cortex, especially in the cortices from hippocampus to lateral occipitotemporal gyri, basal nucleus of Mynert, basal ganglia, thalamus, substantia nigra and widespread regions of the central nervous system through the brainstem to spinal cord including the nucleus of Onufrowitcz. In spite of a small amount of the senile plaques in the cerebral cortex and Lewy bodies in the substantia nigra and locus coeruleus, abundant NFT were distributed mainly in the third layer of the cerebral cortex, which is the characteristic feature of ALS/PDC. Thus, this was likely to be an ALS/PDC case outside the Guam Island. A tau mutation was not found on DNA analysis.     

Cerebral cortical amyloid protein precursor mRNA expression is similar in Alzheimer's disease and other neurodegenerative diseases.

The expression of 3 beta-amyloid protein precursor (APP) mRNAs (695, 751, and 770) in the cerebral cortex in Alzheimer's disease and other neurodegenerative diseases was analyzed by the S1 nuclease protection assay. We found no significant Alzheimer's disease-specific alteration of APP mRNA expression when compared to the other neurological diseases as controls. Since the expression of this mRNA was not correlated with amyloid deposition, it is possible that gliosis/neuronal loss may secondarily alter APP mRNA expression. However, the current study revealed no significant correlation between them.