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Reported a case of liposarcoma of the left thigh with accumulation of 99mTc-PYP and Ga-citrate, which was remarkably decreased by transarterial embolization. To our knowledge, this is the first case that concentration of Tc-PYP and Ga-citrate was the useful indicator of the effect of transarterial embolization.
Angiotensin converting enzyme inhibitors (ACEI) are used widely in the treatment of both hypertension and congestive heart failure. Although usually well tolerated, these medications may produce side effects that may be encountered by the allergist, including cough, angioedema, and rhinitis symptoms. The severity of ACEI-induced cough may vary, and is associated with increased bronchial hyperreactivity in some (but not all) patients as judged by methacholine sensitivity. Angiotensin converting enzyme inhibitor-induced cough may have its onset from one day to 12 months after initiation of therapy, and is not dose dependent. Angioedema caused by ACEI is usually mild and clears with discontinuation of the drug, however cases requiring intubation and tracheostomy have been reported. The mechanism of ACEI-induced cough remains unclear, but could be in part due to accumulation of substances whose degradation may also be impeded by ACEI, such as substance P, bradykinins, and/or prostaglandins. Knowledge of the side effects produced by this class of medication may help patients avoid unnecessary, costly, and often invasive diagnostic evaluations.
The management of sleep difficulties which arise during air operations must be related, at least initially, to the cause, but the aeromedical specialist is frequently faced with the possible use of hypnotics. There are no simple guidelines, but an understanding of various issues will help toward the effective use of these drugs in those who have to cope with irregularity of rest and carry out skilled work. Some knowledge of the pharmacokinetics of the drugs concerned is useful as persistence of effect and the potential for accumulation with repeated ingestion are important factors, while efficacy in relation to sleep of different durations and at unusual times must also be considered.
Studies with heat-inactivated MS-2 serum have indicated that active immunization against hepatitis B infection can be achieved even though the virus has not been cultivated in tissue culture. The development of new biophysical, biochemical and immunological techniques has increased knowledge of the hepatitis B virus and its associated antigens. In the wake of these recent developments the accumulating evidence indicates that active immunization could be achieved by the use of purified hepatitis B surface antigen or by one of its polypeptides or glycolipids.
The methods of multidrug resistance (MDR) detection in human malignant tumors are numerous. The process of molecular biology (Slot Blot, Northern Blot, Reverse Transcription Polymerase Chain Reaction, PCR) and the process of in situ hybridization or immunohistochemistry are complementary. The process of molecular biology are quantitative and especially sensitive for PCR, by contrast they fail in specificity. This specificity is obtained by in situ hybridization and immunohistochemistry. However, none of these methods give knowledge of GP170 functional activity. The detection of functional GP170 can be identified by rhodamine or daunorubicin intracellular accumulation with flux cytometry or by scintigraphically imaging GP170 expression in vivo with Tc-Sestamibi. The multiplicity of methods for detecting multidrug resistance show that there is no consensus about the best process to employ commonly. In consequence, the alone MDR biological diagnosis should not be the rationale of choice for second line chemotherapy or for using MDR revertant agents. In other words, the MDR biological diagnosis, keeping in mind that other chemoresistant mechanisms (topoisomerases, glutathione system, etc) could be present simultaneously or successively during tumor spreading or during successive antineoplastic treatments.
We reported the scanning electron microscopic findings of an aneurysm embolized with interlocking detachable coils (IDC). A 78-year-old man was referred to our hospital because of left hemiparesis and dysphagia. CT scan showed multiple lacunar infarction in the bilateral corona radiata. Angiography demonstrated a small incidental aneurysm of the right internal carotid artery (IC-PC junction). The left hemiparesis gradually improved and 2 weeks after admission the aneurysm was treated with IDC. Three coils were placed in the aneurysm and post-operative angiography demonstrated complete embolization. Dysphagia caused by the pseudobulbar pulse did not improve and, 4 weeks after endovascular surgery, the patient died of aspiration pneumonia. An autopsy was performed and the scanning electron microscopical findings of the aneurysm showed development of endothelial cells on the coil surface. Many clinical reports supported the usefulness of Guglielmi detachable coils (GDC) and several experimental reports demonstrated the intimal proliferation in aneurysms embolized with coils. However, pathological changes of the aneurysms treated with coils have been reported in only four clinical cases. There was no evidence of endothelialization in any of these cases. To our knowledge, our case is the first report describing the endothelial proliferation over the coils. It is necessary to accumulate histopathological data and long-term follow-up in humans treated with coils.
BACKGROUND: It is thought that lipofuscin plays a central role in the pathogenesis of age-related macular degeneration (AMD). The lack of histopathological material has been a severe limitation in our knowledge on lipofuscin in this disease. A new technique has been developed that allows in vivo imaging of fundus autofluorescence derived from lipofuscin in the retinal pigment epithelium (RPE) using a confocal Laser Scanning Ophthalmoscope (LSO). We studied the dynamics of lipofuscin accumulation and degradation in patients with AMD. MATERIALS AND METHODS: Serial examinations of the spatial distribution of fundus autofluorescence were performed in 148 eyes of 74 patients with AMD using a LSO over a period of 1-3.5 years. RESULTS: Fundus autofluorescence changed over time in almost all eyes studied. Areas of increased autofluorescence occurred progressively during follow up in eyes with drusen and hyperpigmentation. The size of pathologic autofluorescence increased over time in almost all eyes with geographic atrophy, subretinal neovascularisations and disciform scars. Irregular autofluorescence was seen over most subretinal neovascularisations. Autofluorescence intensity decreased in old subretinal neovascularisations and disciform scars over time. CONCLUSIONS: Changes of the distribution of autofluorescence occur in eyes with AMD over time. Fundus autofluorescence imaging allows in vivo analysis of the dynamics of accumulation and degradation of lipofuscin in the RPE in eyes with AMD and documentation of metabolic activity of the RPE.
The use of free-living invertebrates as indicators of freshwater quality is long established and well documented. The basic approaches employed are 1) recognition of indicator species, 2) recognition of changes, usually reduction, in community diversity and 3) construction of biological indices, combining knowledge of 1) and/or 2) and taking into account changes in species abundance. These approaches employ invertebrates because of their immobility and longevity, and rely on a detailed body of ecological knowledge so that biotic changes can be related clearly to particular environmental changes. If we are to use parasites in the same way, we must show that pollution does affect parasites and then ask whether they can serve as indicator species, and whether changes in parasite communities can serve as indicators of specific changes in environmental conditions. We must also ask if parasites are better indicators than free living organisms. Parasites also pose additional difficulties: they are mobile because their fish hosts are, and the effects of pollution may be direct on the parasite or indirect on any of its hosts or act via host immune systems. No species has evolved and adapted to pollution, and presence or absence of a parasite species or changes in community may have many causes. Both presence and community structure vary considerably between localities and over time within localities and we cannot yet relate these changes to particular causes. We can record changes and differences, but with present lack of knowledge cannot relate them unequivocally to specific causal factors or environmental changes. Use of parasites as bio-accumulators shows promise, as does monitoring of a locality over time, but one-off surveys are of no use. Until we are prepared to stand up in a court of law and be cross-examined on our statement that these parasites clearly show a particular change in the environment, the answer to both questions above must be no.
Expression of viral CP genes in transgenic plants can lead to virus resistance by interference of either the transcript or the protein with virus infection. Dependence of resistance on CP accumulation can be most convincingly shown by comparison of plants that accumulate CP with plants that accumulate a nontranslatable CP transcript. Even in cases in which CP accumulation is required, the degree of resistance does not always correlate with CP levels in transgenic plants. In cases in which CPMR can be overcome by inoculation with viral RNA instead of virions, interference with virion disassembly is the likely cause of resistance. Classical crossprotection can also sometimes be overcome by RNA inoculation, and, in this case, appears to work by a similar mechanism. There is no evidence yet that CPMR is caused by a nonspecific plant defense response that might be triggered by the accumulating CP. Measurement of virus accumulation in protoplasts prepared from transgenic plants was used to show interference with early events of virus infection. There is no clear evidence yet for inhibition of local virus spread in transgenic plants. A reduced rate of virus accumulation in inoculated leaves can usually also be explained with reduced rate of replication. However, in the case of CPMR to CMV, it appears that early events, as well as systemic spread, are affected. Reduced vector transmission of virus infection from inoculated transgenic plants to nontransgenic plants has been observed. It is not known whether this is just a consequence of lower virus levels in the transgenic plants or whether direct interference with acquisition and transmission by the vector is also involved. In addition to virion formation, CP can function in different ways in plant virus infections. Replication, long-distance spread, and vector transmission can also depend on the presence of CP. Expression of genes encoding nonfunctional CPs in transgenic plants can be tried in order to interfere with normal CP function. Knowledge of CP function(s) in a particular plant-virus interaction will be useful to design gene constructs. Since CP accumulation levels in transgenic plants do not always correlate with resistance, newly generated transgenic plant lines are now frequently tested for virus resistance before further characterization. However, if the objective of a transformation experiment is also to study the mechanism of CPMR, it is necessary to determine transcript and protein levels in the transgenic plants. Gene constructs encoding nontranslatable and antisense CP transcripts should be included in the experiment. If possible, transgenic plants should be inoculated with virions and viral nucleic acid, and replication in isolated protoplasts should be determined.
Eating and appetite disorders are frequent complications of the uremic syndrome which contribute to malnutrition in dialysis patients. The data suggest that uremic anorexia may occur with or without abdominal and visceral fat accumulation despite a lower food intake. This form of obesity (i.e., with low food intake and malnutrition) is more common in dialysis patients than obesity with high food intake. This article reviews the current knowledge regarding mechanisms responsible for appetite regulation in normal conditions and in uremic patients. Anorexia in dialysis patients has been historically considered as a sign of uremic toxicity due to "inadequate" dialysis as judged by uncertain means ("middle molecule" accumulation, Kt/V, "peak-concentration hypothesis," and others). We propose the tryptophan-serotonin hypothesis, based on a uremia-induced disorder in patients' amino acid profile--low concentrations of large neutral and branched-chain amino acids with high tryptophan levels. A high rate of tryptophan transport across the blood-brain barrier increases the synthesis of serotonin, a major appetite inhibitor. Inflammation may also play a role in the genesis of anorexia and malnutrition. For example, silent infection with Helicobacter pylori may be a source of cytokines with cachectic action; its eradication improves appetite and nutrition. The evaluation of appetite should take into account cultural and social aspects. Uremic patients showed a universal trend to carbohydrate preference and red meat refusal compared to healthy people. In contrast, white meat was less problematic. Uremic patients also have a remarkable attraction for citrics and strong flavors in general. Eating preferences or refusals have been related to the predominance of some appetite peptide modulators. High levels of cholecystokinin (CCK) (a powerful anorexigen) are associated with early satiety for carbohydrates and neuropeptide Y (NPY) (an orexigen) with repeated food intake. Obesity and elevated body mass index often falsely suggest a good nutritional status. In uremic patients (a hyperinsulinemia state), disorders in the regulation of fat distribution (insulin, leptin, insulin-like growth factor [IGF]-1, fatty acids, and disorders in receptors for insulin, lipoprotein lipase, mitochondrial uncoupling protein-2, and beta 3 adrenoreceptors) may cause abdominal fat accumulation without an increase in appetite. Finally, appetite regulation in uremia is highly complex. Disorders in adipose tissue, gastrointestinal and neuropeptides, retained or hyperproduced inflammatory end products, and central nervous system changes may all play a role. Uremic anorexia may be explained by a hypothalamic hyperserotoninergic state derived from a high concentration of tryptophan and low branched-chain amino acids.
BACKGROUND AND OBJECTIVE: Isoflurane is a chiral, volatile anaesthetic with low metabolic rate (0.17%) that is routinely administered in its racemic form. Knowledge about the distribution of the enantiomers in human beings may give some important information about the understanding of the mechanisms of volatile anaesthetics. METHODS: Blood samples were drawn immediately after tracheal extubation and daily up to 8 days postoperatively from patients undergoing general anaesthesia with isoflurane racemate. The enantiomer enrichment of isoflurane was determined by headspace gas chromatography-mass spectrometry. RESULTS: At all time points, there was a statistically significant accumulation of the S(+) enantiomer in blood, especially at days 2 (52.01%) and 7 (52.1%). Separate analysis of obese patients or in a small group of patients with co-existing lung disease did not show any difference to the total population. In addition, duration of anaesthesia did not influence the enantiomer concentrations. CONCLUSIONS: We suggest that a slower association and dissociation rate is responsible for the S(+) enrichment.
Aberrant processing of the amyloid precursor protein (APP) and the subsequent accumulation of amyloid beta (Abeta) peptide has been widely established as a central event in Alzheimer's disease (AD) pathogenesis. The sequential cleavage steps required for the generation of Abeta are well outlined; however, there is a relative dearth of knowledge pertaining to signaling pathways and molecular mechanisms that can modulate this process. Here, we demonstrate a novel role for p25/cyclin-dependent kinase 5 (Cdk5) in regulating APP processing, Abeta peptide generation, and intraneuronal Abeta accumulation in inducible p25 transgenic and compound PD-APP transgenic mouse models that demonstrate deregulated Cdk5 activity and a neurodegenerative phenotype. Induction of p25 resulted in enhanced forebrain Abeta levels before any evidence of neuropathology in these mice. Intracellular Abeta accumulated in perinuclear regions and distended axons within the forebrains of these mice. Evidence for modulations in axonal transport or beta-site APP cleaving enzyme 1 protein levels and activity are presented as mechanisms that may account for the Abeta accumulation caused by p25/Cdk5 deregulation. Collectively, these findings delineate a novel pathological mechanism involving aberrant APP processing by p25/Cdk5 and have important implications in AD pathogenesis.
In a relatively short period of time covering the last 2 decades, regeneration of retinofugal axons has become one of most prominent experimental models in restorative neurobiology. There is now a significant knowledge both on the mechanisms governing retinal ganglion cell responses to transection of the optic nerve, and the subsequent cell-cell interactions accumulating in death of the neurons. In addition, retinofugal axons served as an excellent model to examine whether, and to conclude that these axons have remarkable abilities for re-growth. This last issue was of invaluable importance, because axons could regenerate in vivo, into peripheral nerve grafts, and last but not least within the white matter of the cut optic nerve. As it stands to date, the extremely complex aspects of axonal regeneration will probably be understood within the retinofugal pathway. Final elucidation of this delicate system will essentially lead to some revision of our knowledge concerning neurotraumatology and CNS-repair.
Mercury is unique among the heavy metals in that it can exist in several physical and chemical forms, including elemental mercury, which is a liquid at room temperature. All forms of mercury have toxic effects in a number of organs, especially in the kidneys. Within the kidney, the pars recta of the proximal tubule is the most vulnerable segment of the nephron to the toxic effects of mercury. The biological and toxicological activity of mercurous and mercuric ions in the kidney can be defined largely by the molecular interactions that occur at critical nucleophilic sites in and around target cells. Because of the high bonding affinity between mercury and sulfur, there is particular interest in the interactions that occur between mercuric ions and the thiol group(s) of proteins, peptides and amino acids. Molecular interactions with sulfhydryl groups in molecules of albumin, metallothionein, glutathione, and cysteine have been implicated in mechanisms involved in the proximal tubular uptake, accumulation, transport, and toxicity of mercuric ions. In addition, the susceptibility of target cells in the kidneys to the injurious effects of mercury is modified by a number of intracellular and extracellular factors relating to several thiol-containing molecules. These very factors are the theoretical basis for most of the currently employed therapeutic strategies. This review provides an update on the current body of knowledge regarding the molecular interactions that occur between mercury and various thiol-containing molecules with respect to the mechanisms involved in the renal cellular uptake, accumulation, elimination, and toxicity of mercury.
BACKGROUND: The integration of the rapidly expanding corpus of information about the genome, transcriptome, and proteome, engendered by powerful technological advances, such as microarrays, and the availability of genomic sequence from multiple species, challenges the grasp and comprehension of the scientific community. Despite the existence of text-mining methods that identify biological relationships based on the textual co-occurrence of gene/protein terms or similarities in abstract texts, knowledge of the underlying molecular connections on a large scale, which is prerequisite to understanding novel biological processes, lags far behind the accumulation of data. While computationally efficient, the co-occurrence-based approaches fail to characterize (e.g., inhibition or stimulation, directionality) biological interactions. Programs with natural language processing (NLP) capability have been created to address these limitations, however, they are in general not readily accessible to the public. RESULTS: We present a NLP-based text-mining approach, Chilibot, which constructs content-rich relationship networks among biological concepts, genes, proteins, or drugs. Amongst its features, suggestions for new hypotheses can be generated. Lastly, we provide evidence that the connectivity of molecular networks extracted from the biological literature follows the power-law distribution, indicating scale-free topologies consistent with the results of previous experimental analyses. CONCLUSIONS: Chilibot distills scientific relationships from knowledge available throughout a wide range of biological domains and presents these in a content-rich graphical format, thus integrating general biomedical knowledge with the specialized knowledge and interests of the user. Chilibot http://www.chilibot.net can be accessed free of charge to academic users.
We report on the case of a 86-year-old male patient with a rapidly growing nodule within the right lobe of the thyroid gland, which after hemithyroidectomy, turned out to be a mucosa-associated lymphoid tissue (MALT) lymphoma of the thyroid gland. In addition, Hashimoto's thyroiditis was reported in the thyroid tissue adjacent to the MALT lymphoma. During follow-up a second nodule emerged within the left lobe and, because of evidence of MALT lymphoma recurrence, F-18-FDG-PET was performed. F-18-FDG-PET imaged a clearly increased accumulation within the whole left lobe and isthmus. Thus, no differences in the degree of hypermetabolism could be imaged between the nodule and the adjacent thyroid tissue. To our knowledge, this is the first report about F-18-FDG-PET in a patient with MALT lymphoma of the thyroid. Literature search revealed only a few cases of MALT lymphomas in locations other than the thyroid gland that were studied with F-18-FDG-PET. In no case was F-18 FDG accumulation seen in the MALT lesions. However, clear F-18 FDG accumulation was reported in some patients with Hashimoto's thyroiditis. It is concluded that the intensive F-18-FDG accumulation within the whole left lobe and isthmus of the presented case was due to the coexisting Hashimoto's thyroiditis. Consequently, F-18-FDG-PET imaging does not seem to be indicated in a patient with MALT lymphoma and known Hashimoto's thyroiditis in order to evaluate the status of the MALT lymphoma.
RNA helicase, encoded by the Saccharomyces cerevisiae nuclear gene SUV3, is a subunit of the mitochondrial (mt) degradosome: an enzyme complex that takes part in turnover of mtRNAs. Deletion of the SUV3 gene leads to a variety of disturbances in mtRNA metabolism and results in respiratory incompetence of yeast cells. Here we show that the nuclear gene MSS116, which codes for a mitochondrial putative RNA helicase necessary for splicing of several mt introns, can suppress the lack of the SUV3 gene. Overexpression of the Mss116 putative helicase from a multicopy plasmid present in the SUV3-deleted strains partially restores respiratory competence, brings the steady-state levels of COB and ATP6/8 mRNA back almost to normal and lowers the accumulation of 21S rRNA and ATP6/8 RNA precursors to the wild-type levels. To the best of our knowledge, this is the first reported case of a substitution of one RNA helicase by another, belonging to a different class of RNA helicases.
Amyloid fibrils are a major pathological feature of Alzheimer's disease as well as other amyloidoses including the prion diseases. They are an unusual phenomenon, being made up of different, normally soluble proteins which undergo a profound conformational change and assemble to form very stable, insoluble fibrils which accumulate in the extracellular spaces. In Alzheimer's disease the amyloid fibrils are composed of the A beta protein. Knowledge of the structure of amyloid is essential for understanding the abnormal assembly and deposition of these fibrils and could lead to the rational design of therapeutic agents for their prevention or disaggregation. Here we reveal the core structure of an Alzheimer's amyloid fibril by direct visualisation using cryo-electron microscopy. Synthetic amyloid fibrils composed of A beta residues 11 to 25 and 1 to 42 were examined. The A beta (11-25) fibrils are clearly composed of beta-sheet structure that is observable as striations across the fibres. The beta-strands run perpendicular to the fibre axis and the projections show that the fibres are composed of beta-sheets with the strands in direct register. This observation has implications not only for the further understanding of amyloid, but also for the development of cryo-electron microscopy for direct visualisation of secondary structure.