Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 59-year-old demented Japanese man who was proven to have high titer of serum alpha-fetoprotein (AFP) and carcino-embryonic antigen (CEA) was admitted to our hospital. Neurological examinations revealed moderate dementia with deterioration and loss of memory, and decreased deep tendon reflexes in all extremities. Sensory disturbances were not obvious. There were no significant changes in the usual laboratory findings including CSF, except for elevated serum AFP and CEA. Three months after admission, he died of gastric cancer and its metastases in liver and lymph nodes. Post-mortem examination in the central nervous system (CNS) revealed many senile plaques and neurofibrillary tangles throughout the cerebral cortex and hippocampus. There was marked loss of neurons in the hippocampus. All the neuropathological findings in the CNS were consistent with those in Alzheimer disease. In the peripheral nervous system, necrotizing arteritis was found throughout the length of sciatic nerve. Large myelinated fibers seemed to be preferentially degenerated with proximo-distal gradient. Teased fiber preparation revealed de/remyelination and axonal degeneration more frequently at the distal portion. Immunohistologically, the serum IgG of this patient specifically reacted to the endothelial cells of all vessels in control organs, which strongly suggested the autoimmune mechanism for the necrotizing arteritis in this patient. The pathogenetic role of this antibody for necrotizing arteritis, found selectively in the peripheral nervous system, still remained unclear. However, paraneoplastic neuropathy due to necrotizing arteritis is a distinct entity in addition to common form of paraneoplastic subacute sensory neuropathy.
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PMID:[A case of paraneoplastic neuropathy with necrotizing arteritis localized in the peripheral nervous system]. 165 26

Thirty-two care-givers of persons with Alzheimer's disease and 30 care-givers of persons with recurrent metastatic cancer were interviewed three times over a 2-year period. Both groups showed a decline in anxiety and negative mood while dementia care-givers also experienced a decline in anger. A multiple regression analysis revealed that care-giver neuroticism, self-reported low strength of religious beliefs and anger explained 54% of the variance of the negative affect balance score at 2-year follow-up while higher number of social contacts at index interview and strong self-reported religious faith explained 43% of the variance of positive affect balance.
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PMID:Emotional adaptation over time in care-givers for chronically ill elderly people. 236 79

An 80-year-old retired teacher developed impairment of memory and suffered from delusions of theft. Four years later, she became disoriented as to person, time and situation, restless, began mutter to herself, and displayed night delirium and insomnia. She was subsequently diagnosed as having senile dementia of the Alzheimer type (SDAT). She died of bronchopneumonia and multiple metastases from breast cancer at the age of 85 years. Family history was non-contributory. The brain weighed 1,020 g and showed diffuse atrophy. Histologically, there was moderate loss of neurons in the cerebral cortex, which was accentuated in the frontal and temporal lobes. In addition, numerous senile plaques were observed in the neocortex and hippocampus. Several senile plaques were also found in the amygdala, innominate substance, neostriatum, claustrum, thalamus, hypothalamus and tegmentum of the mesencephalon. Neurofibrillary tangles (NFTs) were mostly restricted to the hippocampus and parahippocampal gyrus, their number being compatible with the patient's age. No obvious neuronal loss was noted in the nucleus basalis of Meynert, neostriatum, substantia nigra or locus ceruleus, which are well known to be involved in Alzheimer's disease and SDAT. Recently, Terry et al proposed a new disease concept, "SDAT without neocortical NFTs". The histopathology of the cerebral cortex in our patient was very similar, if not identical, to those observed in their patients. However, the above authors did not mention any subcortical changes, leaving the detailed neuropathological picture unclear. Tentatively, we classified the present case as senile dementia with numerous neocortical senile plaques and preserved subcortical nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[An autopsy case of senile dementia with numerous neocortical senile plaques and preserved subcortical nuclei]. 259 44

In most cell types intermediate or 10-mm filaments (IF) are a major cytoskeletal organization and, thus, directly or indirectly influence the structural appearance of the cytoplasm. In line with the cell type-specific expression patterns of different IF proteins in normal animal and human tissue, IF typing distinguishes the major tumor groups, as documented by results with several hundred human tumors classified by conventional histologic methods. Carcinomas are characterized by cytokeratins, sarcomas of muscle cells by desmin, nonmuscle sarcomas by vimentin, and gliomas by glial fibrillary acidic protein. Furthermore, certain tumors originating from the sympathetic nervous system, e.g., ganglioneuroblastoma, pheochromocytoma, and at least some neuroblastomas, are characterized by the presence of neurofilaments. Carcinomas can often be further subdivided with regard to their possible derivation by examining their cytokeratin profiles. The IF type characteristic of the cell of origin seems to be kept not only in the primary tumor but usually also in solid metastases. In general, tumors do not acquire additional IF types. Therefore, IF typing can provide an unambiguous and rapid characterization in certain cases, that are difficult to diagnose by conventional techniques. Some useful examples are the small cell tumors of childhood and the discrimination between undifferentiated carcinoma and lymphoma. IF typing of a few tumors has already led to a revision or reconsideration of the original light microscopic diagnosis. The combined results indicate that at least certain carcinomas, as well as certain other tumor types, seem to arise by the selective multiplication of a particular and identifiable cell type present in the normal tissue. The procedure is not restricted to tumor material. IF typing of Mallory bodies, Alzheimer's disease tangles, certain myopathies, and the cells of the amniotic fluid offers further interesting applications. Thus, IF typing should become a valuable new tool both in histology and surgical pathology.
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PMID:Tumor diagnosis by intermediate filament typing: a novel tool for surgical pathology. 618 96

Programmed cell death (PCD) via apoptosis is characterized by nuclear pyknosis and fragmentation, and biochemically by oligonucleosomal cleavage of DNA. Apoptosis occurs in the developing nervous system, whereas its role in neurodegenerative diseases is still debated. Recognition of apoptotic cells has recently been facilitated by in situ end-labeling (ISEL) techniques which identify DNA strand breaks through incorporation of labeled nucleotides. We have applied two ISEL assays to physiological and pathological conditions affecting the nervous system in which PCD is likely to occur. Terminal transferase assay was more sensitive than DNA polymerase assay and allowed the recognition of a larger number of cells than conventional histology. Apoptotic cells were readily found in the developing spinal cord and dorsal root ganglia. Medulloblastomas, gliomas, brain lymphomas and metastases showed abundant apoptotic cells either isolated or grouped in small foci. Labeling was also found in cells without a clearcut apoptotic morphology. Apoptotic cells were not found in Alzheimer's disease, amyotrophic lateral sclerosis and human and mouse prionic encephalopathies. Our results show that ISEL is a useful technique for demonstrating apoptotic cells in nervous tissue during development and in brain tumors. Lack of staining in neurodegenerative diseases suggests that other types of PCD might be involved.
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PMID:A study of apoptosis in normal and pathologic nervous tissue after in situ end-labeling of DNA strand breaks. 752 80

We have come to understand apoptosis as not merely a single form of cell death, but as a fundamental theme in cell biology that has far-reaching implications in the fields of physiology and pathology. At the present time, however, the mechanism of apoptosis is not clearly understood, as research into apoptosis is still at the initial stages. Nevertheless, the links between apoptosis and a variety of pathological conditions are gradually becoming clearer. In this article, we will provide a simple explanation of apoptosis and its mechanism as a novel concept of cell death and discuss the way in which apoptosis has been linked to a variety of pathological conditions. WHAT IS APOPTOSIS?: In normal tissue, cells that are no longer needed are rapidly eliminated without affecting the overall function of the tissue. In this process cells undergo an active and spontaneous suicide called programmed cell death. In fact, the majority of physiological cell deaths take the form of apoptosis. The word apoptosis is used, in contrast to necrosis, to describe the situation in which a cell actively pursues a course toward death upon receiving certain stimuli [1]. The morphological changes of apoptosis found in most cell types first involve contraction in cell volume and condensation of the nucleus. When this happens the intracellular organelles such as the mitochondria retain their normal morphology. As apoptosis proceeds, blebbing of the plasma membrane occurs, and the nucleus becomes fragmented. Finally, the cell itself fragments to form apoptotic bodies that are engulfed by nearby phagocytes. With respect to biochemical changes, it is known that the chromosomes become fragmented into nucleosome units, and DNA forms characteristic ladder patterns when subjected to agarose gel electrophoresis. MECHANISM OF APOPTOSIS: It has been reported that apoptosis is induced in various cells by many kinds of irritations, but the precise mechanism is still unclear. Cell injuries that induce apoptosis include those that cause DNA damage such as radiation and anticancer drugs, those that are mediated by the TNF receptor and Fas receptor (the so-called "death signal receptors"), and the deprivation of cytokines that supply survival signals such as IL-3 and erythropoietin. The tumor suppressor gene p53 plays a very important role in apoptosis induced by damage to DNA. This has been demonstrated by studying resistance to apoptosis of cells derived from p53 knockout mice [2]. Other than the irritations that induce apoptosis, molecules that have been strongly implicated as major players in the drama of apoptosis include the Bcl-2 family proteins and the IL-1 converting enzyme (ICE) and its homolog proteases (caspase family). Both groups of proteins show homology with proteins that affect cell death in nematodes. It is believed that molecules that contribute to cell death have been well conserved in multicellular organisms all the way from the relatively primitive nematodes to mammals including humans. It was discovered that Bcl-2 suppressed apoptosis induced in IL-3 dependent cells by deprivation of IL-3 [3]. It has since become the gene around which apoptosis research revolves. Recently, it has become clear that cell death involving the Bcl-2 protein is under the control of similar proteins from the same family [4]. It is interesting that the phenomenon of cell death may be regulated by the balance of the molecules involved in it. APOPTOSIS ABNORMALITIES AND DISEASE: Physiological cell death plays a major role in the growth and permanent maintenance of the human body [5]. In the process of forming the nervous system, neurons that do not form proper connections die. Physiological cell death also accompanies the removal of virus-infected cells by cytotoxic T cells, the elimination of autoreactive immune cells, the formation of the gut, the reconstitution of cartilage and bone, etc. When physiological cell death that normally should occur is inhibited, inappropriate physiological cell death may occur that is harmful to the body and forms the basis of disease. For example, in patients with neural degenerative disorders such as Alzheimer's disease and Parkinson's disease, we can find premature cell death in a particular subset of neurons. The death of T cells in AIDS patients is also a form of physiological cell death. Inhibition of cell death in the immune system enables the survival of autoreactive B cells and T cells, and is therefore a cause of autoimmune disorders. Apoptosis has been particularly linked to cancer. Normal cells are programmed for death if they are subjected to many types of non-physiological stress such as anticancer drugs or radiation, if they become isolated from surrounding cells and are unable to receive their tissue-specific survival signals [6], or if oncogenes are expressed haphazardly [7]. On the other hand, it is believed that the ability to survive is enhanced in transformed cancer cells because they are more resistant to apoptosis, they exhibit resistance to anticancer drugs, they are no longer dependent on survival signals, and they can metastasize. Therefore, the cancer progresses as the cancer cells maintain the proliferative superiority they acquire from their oncogenes. In other words, when cancer cells become resistant to apoptosis, they become resistant to treatment, metastasize, and proliferate destructively. The concept that the malignancy of cancer is due to its resistance to apoptosis is a relatively new one and is worthy of further study.
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PMID:Physician Education: Apoptosis. 1038 21

While limiting and forgoing therapy at the end of life is now accepted on medical, ethical, moral and legal grounds, many Americans continue to die with heroic measures being taken to prevent their death. Recent studies have demonstrated that physicians frequently attend to their patients without knowledge of their preferences with regards to end-of-life issues. It is postulated that a physician's personal preferences with regard to the limitation and withdrawal of life support and active euthanasia would effect the discussion they had with their patients. The purpose of this study was to analyze end-of-life preferences of a diverse group of practicing physicians. The participants were active attending physicians at a community hospital, a rural referral center, a large tertiary care referral academic complex, and a specialized tertiary care referral center all within the United States. A questionnaire was developed which was mailed to attending physicians at the four participating medical centers. The respondents provided basic demographic data, do-not-resuscitate (DNR) preferences under various clinical circumstances as well as responses to a number of case vignettes. Six hundred and forty physicians responded to the survey. The mean age of the respondents was 46 years; 72% were male. In the event of a cardiac arrest less than 20% of respondents would want to undergo cardiopulmonary resuscitation in the setting of chronic end stage organ failure; the positive response rate was 5% for metastatic cancer and 2% for Alzheimer's disease. If death was imminent, 87% of physicians indicated they would want treatment withdrawn. Similarly, 95% of respondents indicated that they would want treatment withdrawn should they be in a persistent vegetative state. Only 1% of respondents believed that health care providers should never remove or withhold life-sustaining therapy. Should they have advanced motor neuron disease, 38% of physicians indicated they would request that their life be ended. The majority of physicians surveyed volunteered that they would want life-sustaining measures to be limited at the end of their life. A significant number were in favor of active euthanasia. This study suggests that it is unlikely that physicians' personal beliefs in regards to end-of-life care result in the failure to discuss these issues with their patients.
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PMID:Physicians' own preferences to the limitation and withdrawal of life-sustaining therapy. 1062 60

PET and SPECT are molecular imaging techniques that use radiolabeled molecules to image molecular interactions of biological processes in vivo. PET imaging technologies have been developed to provide a pathway to the patient from the experimental paradigms of biological and pharmaceutical sciences in genetically engineered and tissue transplanted mouse models of disease. PET provides a novel way for molecular therapies and molecular diagnostics to come together in the discovery of molecules that can be used in low mass amounts to image the function of a target and, by elevating the mass, to pharmacologically modify the function of the target. In both cases, the molecules are the same or analogs of each other. PET can be used to titrate drugs to their sites of action within organ systems in vivo and to assay biological outcomes of the processes being modified in the mouse and the patient. The goal is to provide a novel way to improve the rates of discovery and approval of radiopharmaceuticals and pharmaceuticals. Extending this relationship into clinical practice can improve drug use by providing molecular diagnostics in concert with molecular therapeutics. Diseases are biological processes, and molecular imaging with PET is sensitive and informative to these processes. This sensitivity is exemplified by the detection of disease with PET without evidence of anatomic changes on CT and MRI. These biological changes are seen early in the course of disease, even in asymptomatic stages, as illustrated by the metabolic abnormalities detected with PET and FDG in Huntington's and familial Alzheimer's diseases 7 and 5 y, respectively, before symptoms appear. Differentiation of viable from nonviable tissue is fundamentally a metabolic question, as shown by the use of PET to differentiate patients with coronary artery disease who will benefit from revascularization from those who will not. Although beginning within a specific organ, cancer is a systemic disease the most devastating consequences of which result from metastases. Whole-body PET imaging with FDG enables inspection of glucose metabolism in all organ systems in a single examination to improve the detection and staging of cancer, selection of therapy, and assessment of therapeutic response. In lung and colorectal cancers, melanoma, and lymphoma, PET FDG improves the accuracy of detection and staging from 8% to 43% over conventional work-ups and results in treatment changes in 20%-40% of the patients, depending on the clinical question. Approximately 65% are upstaged because unsuspected metastases are detected, and 35% are downstaged because a structural diagnosis of lesions is changed from malignant to benign. Similar results are now being shown for other cancers. The main difference between CT, sonography, MRI, and PET or SPECT is not technologic but, rather, a difference between detecting and characterizing a disease by its anatomic features as opposed to its biology. The importance and success of developing new molecular imaging probes is increasing as PET becomes integral to the study of the integrative mammalian biology of disease and as molecular therapies targeting the biological processes of disease are developed.
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PMID:PET: the merging of biology and imaging into molecular imaging. 1076 68

The receptor for advanced glycation end products (RAGE), a multi-ligand member of the immunoglobulin superfamily of cell surface molecules, interacts with distinct molecules implicated in homeostasis, development and inflammation, and certain diseases such as diabetes and Alzheimer's disease. Engagement of RAGE by a ligand triggers activation of key cell signalling pathways, such as p21ras, MAP kinases, NF-kappaB and cdc42/rac, thereby reprogramming cellular properties. RAGE is a central cell surface receptor for amphoterin, a polypeptide linked to outgrowth of cultured cortical neurons derived from developing brain. Indeed, the co-localization of RAGE and amphoterin at the leading edge of advancing neurites indicated their potential contribution to cellular migration, and in pathologies such as tumour invasion. Here we demonstrate that blockade of RAGE-amphoterin decreased growth and metastases of both implanted tumours and tumours developing spontaneously in susceptible mice. Inhibition of the RAGE-amphoterin interaction suppressed activation of p44/p42, p38 and SAP/JNK MAP kinases; molecular effector mechanisms importantly linked to tumour proliferation, invasion and expression of matrix metalloproteinases.
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PMID:Blockade of RAGE-amphoterin signalling suppresses tumour growth and metastases. 1083 Sep 43

Although head imaging studies are frequently used in the work-up of dementia, published criteria for the clinical diagnosis of Alzheimer's disease (AD) do not require them. Since our brain bank contains cases in which physicians had specifically diagnosed AD without using a head imaging study, we thought it of interest to investigate the accuracy of their clinical diagnoses. We retrospectively reviewed 911 consecutive dementia cases for those clinically diagnosed as either AD or senile dementia (SD). Twenty-one were identified in which head imaging studies had not been used, each diagnosed as AD or SD by a different physician. In only three had the physician reported a reason why a study was not done. In all 21 cases the primary neuropathological cause of the dementia was AD. Neuropathology in addition to AD was also noted, including cortical Lewy bodies in three, infarcts on gross examination in three, multiple microscopic infarcts in four, and multiple cerebral metastases in one. Acknowledging a number of study limitations, it is remarkable that the judgment of the physicians was correct regarding AD in all 21 cases. It is questionable if a head CT or MRI scan at time of diagnosis would have benefited any of the patients.
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PMID:The clinical diagnosis of Alzheimer's disease without the use of head imaging studies. A cliniconeuropathological study. 1475 36


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