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Results for “knowledge accumulation”

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At least 1,711 records · Page 95Linked to original sources

PubMed2005

Mast cells in allergic airway disease and chronic rhinosinusitis.

Conventional knowledge tells us that mast cells are only important in the acute IgE-mediated reactions as seen in anaphylaxis, asthma and rhinitis. Yet, in recent years, much evidence has accumulated on the versatile role of mast cells in allergic inflammation. Here, we describe the novel and potential roles of mast cells in the late phase allergic reaction as well as in chronic allergic inflammation. Mast cells in patients with allergic rhinitis and asthma produce Th2 type cytokines, induce IgE synthesis in B cells and can autoactivate itself via the mast cell-IgE-FcepsilonRI cascade. In addition, mast cells upregulate the production of a variety of cytokines/chemokines in epithelial cells and fibroblasts and induce the recruitment of basophils, T cells and eosinophils into sites of allergic inflammation as well as their own intraepithelial accumulation. Furthermore, mast cells express MMPs and interact with extracellular matrix proteins and ASM and may play a role in nasal and bronchial hyperresponsiveness as well as tissue remodelling. In chronic rhinosinusitis with nasal polyps, the potential role of mast cells not only in orchestrating eosinophilic inflammation but also in the genesis and perpetuation of nasal polyp formation via FcepsilonRI and TLR mediated activation is also of growing interest.

Asthma↗

PubMed1991

Peroxisomal fatty acid beta-oxidation in relation to adrenoleukodystrophy.

X-linked adrenoleukodystrophy is a neurological disease characterized by progressive demyelination with destruction of the white matter, and adrenal insufficiency. Biochemically there is accumulation of very-long-chain fatty acids resulting from an impairment in the peroxisomal oxidation of these fatty acids. In this paper we describe the present state of our knowledge with regard to the organization of the peroxisomal fatty acid oxidation system, with particular emphasis on X-linked adrenoleukodystrophy.

Adrenoleukodystrophy↗

PubMed2004

Endometrium implantation and ectopic pregnancy.

Embryo in uterine implantation is a complex and multifactor-related process and is a downstream and ideal point for woman fertility control. Understanding the cellular and molecular mechanism of implantation is a prerequisite for development of anti-implantation contraceptives. In spite of considerable accumulation of information from the laboratory animals that has been achieved, it is difficult to generate such information in human due to ethical restriction and experimental limitation, and the present knowledge for understanding the definitive mechanisms which control these events remains elusive. Embryo implantation can also occur outside uterus. Some women with abdominal pregnancies could successfully complete the processes of gestation and bear normal babies, implying that implantation itself may be not an endometrium-specific process. Reproductive biologists should cooperate with gynecologists to further comparatively study the molecular and cellular mechanisms of implantation normally occurring in endometrium and abnormally appearing outside uterine cavity. Such collaborative studies may generate new important information for developing anti-implantation contraceptive and for techniques of accurate diagnosis of ectopic pregnancy. A specially designed GnRH-2 analog and a combination use of low dose RU486 and gossypol as anti-implantation contraceptives have been suggested.

Animals↗

PubMed1993

Population growth and economic development revisited with reference to Asia.

"This article takes another look at the old issue of population growth and economic development in the context of recent developments and with the benefit of the increasing stock of knowledge on the subject. It first presents a demographic perspective; then it analyzes the implications of population growth with respect to such integral aspects of economic development as human capital accumulation, income distribution and poverty, the environment, and sustainable economic growth. The approach in each case is to review the theoretical considerations, survey the empirical evidence, and then draw policy implications. An overall conclusion with implications for policy caps the paper." The geographical focus is on Asia.

Asia↗

PubMed2005

The cell recognition molecule L1 and cognition.

Cell adhesion molecules were classically known to be key players in a whole array of biological functions during development through cell-cell and cell-substratum adhesion. Accumulating evidence suggests, however, that the functional significance of adhesion molecules may extend well beyond embryonic development into adult stage. The aim of this article is to review our current knowledge on the implications of adhesion molecules in various cognitive processes. Particular emphasis was placed on the immunoglobulin superfamily of adhesion molecules, which are found to be involved in activity-dependent plasticity of the nervous system, and hence promising candidates in modulating cognitive functions.

Animals↗

PubMed1986

[Human cancers and viruses].

There is an increased amount of evidence to suggest that viruses play important roles in the development of certain types of human tumors. These include the hepatitis B virus in hepatocellular carcinoma, human papillomaviruses in cervical cancer, Epstein-Barr virus in Burkitt's lymphoma and nasopharyngeal carcinoma, and human T-lymphotrophic virus in adult T cell leukemia and hairy cell leukemia. These pieces of evidence have accumulated from both clinical and basic studies which have shown that these viruses are involved in some stage of the carcinogenic process. Because of the rapid development of techniques and knowledge of molecular biology, most of the gene structures of these viruses and their products have been identified. These results make it possible to understand more clearly the route of infection and have facilitated the production of vaccines, using DNA-recombinant techniques. A significant decrease in the incidence of these types of cancers is expected through prevention programs conducted throughout the general population against these viruses within 10 to 20 years. These virus-related human cancers also provide us with a good opportunity to understand the basic mechanisms involved in the development of human cancers in general. In the present paper, these points are stressed in addition to describing the recent progress made in the study on virus-related human cancers.

Carcinoma, Hepatocellular↗

PubMed1986

Scintigraphic study of the evolution of cortical homografts in the treatment of fractures.

Twelve patients who had undergone osteosynthesis with a metal plate combined with a frozen homoplastic bone graft for the treatment of fractures or pseudarthrosis were subjected to bone scintigraphy with 99 Tc MDP. This investigation showed the graft to be a site of early and specific accumulation of the tracer. This finding supports early colonization of the graft by vascular structures and osteoblastic cells. In view of the small number of cases studied and our incomplete knowledge of the metabolic processes involved these considerations must remain hypotheses but given the excellent clinical results obtained, the relationships between homoplastic bone and host bone merit further investigation.

Adult↗

PubMed1976

Lithium carbonate versus E.C.T. in the treatment of the manic state of identical twins with bipolar affective disease.

Scientific evidence accumulated to date of the efficacy of lithium in the treatment and prophylaxis of bipolar affective states rests primarily on quantitative vector analysis and some double blind studies. To our knowledge, no clinical studies similar to this one exist in literature wherein indentical twins were subjected to the variables of electroconvulsive therapy and phenothiazines versus lithium carbonate and phenothiazines. The only other variable in the study was the hospital settings involved. The twins' course of treatment over a period of 12 years prior to their presentation wherein they received phenothiazines in various hospital settings is presented in detail. The current study would seem to suggest that E.C.T. and phenothiazines are superior to phenothiazines alone in shortening hospital course and perhaps in improving post-hospital adjustment. Further, prior to the advent of lithium, it may be evident that psychiatrists were not attuned to the diagnosis of affective states. Finally, lithium carbonate and phenothiazines, while requiring a significantly longer period of hospitalization than E.C.T. and phenothiazines, appear to be associated with preventing re-hospitalization for manic states, but a slightly decreased level of occupational adjustment. The author discusses the potential value of these patients in determining the clinical efficacy of future drugs in bipolar affective states, as well as the necessity to obtain future studies of the creatinine phosphokinase level.

Bipolar Disorder↗

PubMedDate not supplied

[An expert system based on the principle of brain functional asymmetry].

The generalized concept is proposed for automation of secondary data processing. Initial information is stored in the knowledge base. During processing the verbal description is generated for each object. All further operations are reduced to the transformation of the textual data. This approach makes it possible to accumulate information of diverse types and efficiently analyze it according to the universal scheme.

Brain↗

PubMed1993

A brief history of Indian alchemy covering pre-Vedic to Vedic and Ayurvedic period (circa 400 B.C.-800 A.D.).

History of Indian alchemy can be traced to pre-Vedic period. The archaeological excavations at Mohenjodaro and Harappa in the Indus valley have brought to light that, the people in ancient India were possessing chemical knowledge as early as in the pre-historic period. In Vedic period single herbs were prescribed. Minerals and animal substances were also prescribed but no compound preparations were in use. Alchemy in India, was started for the preparation of an elixir of life for imparting immortality and later for the transmutation process for converting base metals into gold. Indian alchemy derived its colour and flavour to a large extent from the Tantric cult. Then, during the iatro-chemical period all the previous accumulated alchemical ideas were put into something more practical and tangible. a number of preparations of mercury and other metals were evolved as helpful accessories in medicine. Here a bried history of this Indian alchemy is presented which will give an idea about the development of chemical knowledge in India in its multiple aspects.

Alchemy↗

PubMed1992

Reduced drug accumulation in a newly established human lung squamous-carcinoma cell line resistant to cis-diamminedichloroplatinum(II).

A human lung squamous-carcinoma cell line resistant to cis-diamminedichloroplatinum(II) (CDDP), designated PC10-B3, has been established from the original cell line PC10 by a stepwise increment of the CDDP concentration. This is the first report, to our knowledge, to establish a CDDP-resistant lung squamous-carcinoma cell line. PC10-B3 has continued to proliferate in the presence of 0.5 micrograms/mL CDDP, whereas PC10 could not survive. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay revealed that PC10-B3 was 11.4-fold more resistant to CDDP than PC10 and cross-resistant to diammine(1,1-cyclobutanecarboxylate)platinum(II) (CBDCA) and 254-S, but not to doxorubicin or etoposide. PC10-B3 was characterized by a smaller DNA index and a larger cell size compared to PC10. The level of intracellular platinum accumulation was reduced by about 5- to 8-fold in PC10-B3 when compared with PC10, suggesting that reduced drug accumulation may be one of the important factors in contributing to CDDP resistance in PC10-B3.

Carcinoma, Squamous Cell↗

PubMed2005

Identification of novel targets of cephaloridine in rabbit renal proximal tubules synthesizing glutamine from alanine.

Cephaloridine, which accumulates in the renal proximal tubule, is a model compound used for studying the toxicity of antibiotics towards this nephron segment. Several studies have demonstrated that cephaloridine alters renal intermediary and energy metabolism, but the mechanism by which this compound interferes with renal metabolic pathways remains incompletely understood. In an attempt to improve our knowledge in this field, we have studied the influence of cephaloridine on the synthesis of glutamine, which represents a key metabolic process involving several important enzymatic steps in the rabbit kidney. For this, suspensions of rabbit renal proximal tubules were incubated for 90 and 180 min in the presence of 5 mM alanine, an important glutamine precursor, both in the absence and the presence of 10 mM cephaloridine. Glutamate accumulation and glutamine synthesis were found to be inhibited by cephaloridine after 90 and 180 min of incubation, and cephaloridine accumulation in the renal proximal cells occurred in a time-dependent manner. The renal proximal tubule activities of alanine aminotransferase and glutamate dehydrogenase, which initiates alanine removal and releases the ammonia needed for glutamine synthesis, respectively, were inhibited to a significant degree and in a concentration-dependent manner by cephaloridine concentrations in the range found to accumulate in the renal proximal cells. Citrate synthase and glutamine synthetase activities were also inhibited by cephaloridine, but to a much lesser extent. The above enzymatic activities were not found to be inhibited when they were measured after successive dilutions of renal proximal tubules incubated for 180 min in the presence of 5 mM alanine and 10 mM cephaloridine. When microdissected segments (S1-S3) of rabbit renal proximal tubules were incubated for 180 min with 5 mM alanine with and without 5 and 10 mM cephaloridine, glutamate accumulation and glutamine synthesis were also inhibited in the three renal proximal segments studied; the latter cephaloridine-induced inhibitions observed were concentration-dependent except for glutamine in the S3 segment. These results are consistent with the view that cephaloridine accumulates and is toxic along the entire rabbit renal proximal tubule. They also demonstrate that cephaloridine interferes in a concentration-dependent and reversible manner mainly with alanine aminotransferase and glutamate dehydrogenase, which are therefore newly-identified targets of the toxic effects of cephaloridine in the rabbit renal proximal tubule.

Alanine↗

PubMed2000

Epidermal growth factor receptor tyrosine kinase as a target for anticancer therapy.

Increasing knowledge of the structure and function of the epidermal growth factor receptor (EGFR) subfamily of tyrosine kinases and of their role in the initiation and progression of various cancers has, in recent years, provided the impetus for a substantial research effort aimed at developing new anticancer therapies that target specific components of the EGFR signal transduction pathway. Selective compounds have been developed that target either the extracellular ligand-binding region of the EGFR or the intracellular tyrosine kinase region, resulting in interference with the signalling pathways that modulate mitogenic and other cancer-promoting responses (e.g. cell motility, cell adhesion, invasion and angiogenesis). Potential new anticancer agents that target the extracellular ligand-binding region of the receptor include a number of monoclonal antibodies, immunotoxins and ligand-binding cytotoxic agents. Agents that target the intracellular tyrosine kinase region include small molecule tyrosine kinase inhibitors (TKIs), which act by interfering with ATP binding to the receptor, and various other compounds that act at substrate-binding regions or downstream components of the signalling pathway. Currently, the most advanced of the newer therapies undergoing clinical development are antireceptor monoclonal antibodies (e.g. trastuzumab and cetuximab) and a number of small molecule EGFR-TKIs principally of the quinazoline and pyrazolo-pyrrolo-pyridopyrimidine inhibitor structural classes. The latter group of compounds offers several advantages in cancer chemotherapy, including the possibility of inhibiting specific deregulated pathways in cancer cells while having minimal effects on normal cell function. They also have favourable pharmacokinetic and pharmacodynamic properties and low toxicity, and some TKIs such as the reversible inhibitor ZD1839 ('Iressa') are now undergoing phase II to III clinical trials. In addition, the accumulation of evidence from laboratory studies strongly suggests that EGFR-selective TKIs will have synergistic effects with other antitumour agents or therapy such as cytostatic agents, conventional cytotoxic drugs and radiotherapy. As our knowledge of signal transduction pathways in cancer increases, it is hoped that further advances in this area will allow the therapeutic potential of these compounds as anticancer agents to be realised.

Antineoplastic Agents↗

PubMedDate not supplied

Weapons of penile smooth muscle destruction: androgen deficiency promotes accumulation of adipocytes in the corpus cavernosum.

In men with erectile dysfunction, venous leakage is a common condition among non-responders to medical management and is attributed to penile smooth muscle atrophy. Androgens play a role in regulating trabecular smooth muscle growth and function. Further, androgens stimulate differentiation of progenitor cells into smooth muscle cells and inhibit their differentiation into adipocytes. We postulate that androgens exert a direct effect on penile tissue to maintain erectile function, and that androgen deficiency produces metabolic and structural imbalances in the corpus cavernosum, resulting in venous leakage and erectile dysfunction. To date, research efforts on the mechanisms by which androgens regulate penile erectile physiology have mainly focused on investigating the role of the NO/cGMP pathway. However, androgen-dependent mechanisms that regulate tissue remodeling have been poorly defined. Characterization of the molecular and cellular mechanisms by which androgens regulate corpus cavernosum structural and functional integrity would provide significant gains in knowledge and understanding of an important pathogenic process. In this review, we discuss the potential role of androgen in maintaining differentiation of progenitor cells into smooth muscle lineage and inhibition of differentiation into adipocytes. Androgen deficiency promotes differentiation into adipogenic lineage, and accumulation of adipocytes in the corpus cavernosum may contribute to erectile dysfunction.

Adipocytes↗

PubMed1997

Drug administration in patients with renal insufficiency. Minimising renal and extrarenal toxicity.

Renal insufficiency has been associated with an increased risk of adverse effects with many classes of medications. The risk of some, but not all, adverse effects has been linked to the patient's degree of residual renal function. This may be the result of inappropriate individualisation of those agents that are primarily eliminated by the kidney, or an alteration in the pharmacodynamic response as a result of renal insufficiency. The pathophysiological mechanism responsible for alterations in drug disposition, especially metabolism and renal excretion, is the accumulation of uraemic toxins that may modulate cytochrome P450 enzyme activity and decrease glomerular filtration as well as tubular secretion. The general principles to enhance the safety of drug therapy in patients with renal insufficiency include knowledge of the potential toxicities and interactions of the therapeutic agent, consideration of possible alternatives therapies and individualisation of drug therapy based on patient level of renal function. Although optimisation of the desired therapeutic outcomes are of paramount importance, additional pharmacotherapeutic issues for patients with reduced renal function are the prevention or minimisation of future acute or chronic nephrotoxic insults, as well as the severity and occurrence of adverse effects on other organ systems. Risk factors for the development of nephrotoxicity for selected high-risk therapies (e.g. aminoglycosides, nonsteroidal anti-inflammatory drugs, ACE inhibitors and radiographic contrast media) are quite similar and include pre-existing renal insufficiency, concomitant administration of other nephrotoxins, volume depletion and concomitant hepatic disease or congestive heart failure. Investigations of prophylactic approaches to enhance the safety of these agents in patients with renal insufficiency have yielded inconsistent outcomes. Hydration with saline prior to drug exposure has given the most consistent benefit, while sodium loading and use of pharmacological interventions [e.g. furosemide (frusemide) dopomine/dobutamine, calcium antagonists and mannitol] have resulted in limited success. The mechanisms responsible for altered dynamic responses of some agents (benzodiazepines, theophylline, digoxin and loop diuretics) in renally compromised patients include enhanced receptor sensitivity secondary to the accumulation of endogenous uraemic toxins and competition for secretion to the renal tubular site of action. Application of the pharmacotherapeutic principles discussed into clinical practice will hopefully enhance the safety of these agents and optimise patient outcomes.

Humans↗

PubMed2005

PIGA (N,N-Di-n-butyl-5-chloro-2-(4-chlorophenyl)indol-3-ylglyoxylamide), a new mitochondrial benzodiazepine-receptor ligand, induces apoptosis in C6 glioma cells.

Mitochondrial benzodiazepine-receptor (mBzR) ligands constitute a heterogeneous class of compounds that show a pleiotropic spectrum of effects within the cells, including the modulation of apoptosis. In this paper, a novel synthetic 2-phenylindol-3-ylglyoxylamide derivative, N,N-di-n-butyl-5-chloro-2-(4-chlorophenyl)indol-3-ylglyoxylamide (PIGA), which shows high affinity and selectivity for the mBzR, is demonstrated to induce apoptosis in rat C6 glioma cells. PIGA was able to dissipate mitochondrial transmembrane potential (DeltaPsim) and to cause a significant cytosolic accumulation of cytochrome c. Moreover, typical features of apoptotic cell death, such as caspase-3 activation and DNA fragmentation, were also detected in PIGA-treated cells. Our data expand the knowledge on mBzR ligand-mediated apoptosis and suggest PIGA as a novel proapoptotic compound with therapeutic potential against glial tumours, in which apoptosis resistance has been reported to be involved in carcinogenesis.

Animals↗

PubMedDate not supplied

Towards Alzheimer's beta-amyloid vaccination.

Beta-amyloid pathology, the main hallmark of Alzheimer's disease (AD), has been linked to its conformational status and aggregation. We recently showed that site-directed monoclonal antibodies (mAbs) towards the N-terminal region of the human beta-amyloid peptide bind to preformed beta-amyloid fibrils (Abeta), leading to disaggregation and inhibition of their neurotoxic effect. Here we report the development of a novel immunization procedure to raise effective anti-aggregating amyloid beta-protein (AbetaP) antibodies, using as antigen filamentous phages displaying the only EFRH peptide found to be the epitope of these antibodies. Due to the high antigenicity of the phage no adjuvant is required to obtain high affinity anti-aggregating IgG antibodies in animals model, that exhibit identity to human AbetaP. Such antibodies are able to sequester peripheral AbetaP, thus avoiding passage through the blood brain barrier (BBB) and, as recently shown in a transgenic mouse model, to cross the BBB and dissolve already formed beta-amyloid plaques. To our knowledge, this is the first attempt to use as a vaccine a self-anti-aggregating epitope displayed on a phage, and this may pave the way to treat abnormal accumulation-peptide diseases, such as Alzheimer's disease or other amyloidogenic diseases.

Alzheimer Disease↗

PubMed1999

Bacterial magnetosomes: microbiology, biomineralization and biotechnological applications.

Magnetotactic bacteria orient and migrate along geomagnetic field lines. This ability is based on intracellular magnetic structures, the magnetosomes, which comprise nanometer-sized, membrane-bound crystals of the magnetic iron minerals magnetite (Fe3O4) or greigite (Fe3S4). Magnetosome formation is achieved by a mineralization process with biological control over the accumulation of iron and the deposition of the mineral particle with specific size and orientation within a membrane vesicle at specific locations in the cell. This review focuses on the current knowledge about magnetotactic bacteria and will outline aspects of the physiology and molecular biology of the biomineralization process. Potential biotechnological applications of magnetotactic bacteria and their magnetosomes as well as perspectives for further research are discussed.

Aerobiosis↗