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At least 973 records · Page 54Linked to original sources
PubMed2001

A new beta-1,2-N-acetylglucosaminyltransferase that may play a role in the biosynthesis of mammalian O-mannosyl glycans.

Recent studies have shown that O-mannosyl glycans are present in several mammalian glycoproteins. Although knowledge on the functional roles of these glycans is accumulating, their biosynthetic pathways are poorly understood. Here we report the identification and initial characterization of a novel enzyme capable of forming GlcNAc beta 1-2Man linkage, namely UDP-N-acetylglucosamine: O-linked mannose beta-1,2-N-acetylglucosaminyltransferase in the microsome fraction of newborn rat brains. The enzyme transfers GlcNAc to beta-linked mannose residues, and the formed linkage was confirmed to be beta 1-2 on the basis of diplococcal beta-N-acetylhexosaminidase susceptibility and by high-pH anion-exchange chromatography. Its activity is linearly dependent on time, protein concentration, and substrate concentration and is enhanced in the presence of manganese ion. Its activity is not due to UDP-N-acetylglucosamine: alpha-3-D-mannoside beta-1,2-N-acetylglucosaminyltransferase I (GnT-I) or UDP-N-acetylglucosamine: alpha-6-D-mannoside beta-1,2-D-acetylglucosaminyltransferase II (GnT-II), which acts on the early steps of N-glycan biosynthesis, because GnT-I or GnT-II expressed in yeast cells did not show any GlcNAc transfer activity against a synthetic mannosyl peptide. Taken together, the results suggest that the GlcNAc transferase activity described here is relevant to the O-mannosyl glycan pathway in mammals.

Animals↗
PubMed1997

Time course of pronuclear deoxyribonucleic acid synthesis in parthenogenetically activated bovine oocytes.

The progress of pronuclear DNA synthesis was monitored by the radioactive precursor 3H-thymidine during the first cell cycle of parthenogenetically activated bovine oocytes. Bovine oocytes were exposed to Ca2+ ionophore A23187 at 24, 30, or 36 h after the onset of in vitro maturation. Young 24-h oocytes were subsequently cultured for 6 h in the protein synthesis inhibitor, cycloheximide (CHX), to ensure similar rates of activation (96-100%) and pronuclear formation (93-97%) among all groups of oocytes. Subsequent autoradiographic experiments revealed a slightly, but not significantly, accelerated start of DNA synthesis in aged (36 h) oocytes. Maximum levels of DNA labeling were reached within 4 h regardless of oocyte maturation age and persisted for 4 h in 30-h oocytes compared to 2 h in 36-h and 24-h oocytes. The period of DNA synthesis lasted for a total of 12-14 h in all groups of oocytes, and the duration of S-phase was less than 6 h. Since rates of pronuclear formation (58%) and labeling (58%) corresponded to each other, it is argued that only a fully developed pronucleus can synthesize DNA. Oocyte labeling performed in the presence of CHX revealed the capability of CHX to inhibit DNA synthesis up to 8 h postactivation. Removal of CHX by washing when the majority (94%) of oocytes had formed a fully developed pronucleus (at 8 h postactivation) led to the synchronous start of DNA synthesis within 1.5-2 h post-CHX culture. This concomitantly defined the time required for synthesis of vital proteins needed for the entry into S-phase and/or DNA replication. The prolonged exposure of activated oocytes to CHX (10-12 h) negatively affected the pattern of DNA synthesis. The start of DNA synthesis was postponed and reduced pronuclear labeling was observed. In addition, CHX-treated oocytes often exhibited a characteristic punctate pattern of pronuclear labeling in which silver grains were accumulated into clusters. In conclusion, the present results provide knowledge about timing and a possible synchronization of DNA synthesis in parthenogenetically activated bovine oocytes.

Animals↗
PubMed2003

Parainfluenza viruses.

Human parainfluenza viruses (HPIV) were first discovered in the late 1950s. Over the last decade, considerable knowledge about their molecular structure and function has been accumulated. This has led to significant changes in both the nomenclature and taxonomic relationships of these viruses. HPIV is genetically and antigenically divided into types 1 to 4. Further major subtypes of HPIV-4 (A and B) and subgroups/genotypes of HPIV-1 and HPIV-3 have been described. HPIV-1 to HPIV-3 are major causes of lower respiratory infections in infants, young children, the immunocompromised, the chronically ill, and the elderly. Each subtype can cause somewhat unique clinical diseases in different hosts. HPIV are enveloped and of medium size (150 to 250 nm), and their RNA genome is in the negative sense. These viruses belong to the Paramyxoviridae family, one of the largest and most rapidly growing groups of viruses causing significant human and veterinary disease. HPIV are closely related to recently discovered megamyxoviruses (Hendra and Nipah viruses) and metapneumovirus.

Animals↗
PubMed2002

Selective parasympathetic innervation of subcutaneous and intra-abdominal fat--functional implications.

The wealth of clinical epidemiological data on the association between intra-abdominal fat accumulation and morbidity sharply contrasts with the paucity of knowledge about the determinants of fat distribution, which cannot be explained merely in terms of humoral factors. If it comes to neuronal control, until now, adipose tissue was reported to be innervated by the sympathetic nervous system only, known for its catabolic effect. We hypothesized the presence of a parasympathetic input stimulating anabolic processes in adipose tissue. Intra-abdominal fat pads in rats were first sympathetically denervated and then injected with the retrograde transneuronal tracer pseudorabies virus (PRV). The resulting labeling of PRV in the vagal motor nuclei of the brain stem reveals that adipose tissue receives vagal input. Next, we assessed the physiological impact of these findings by combining a fat pad-specific vagotomy with a hyperinsulinemic euglycemic clamp and RT-PCR analysis. Insulin-mediated glucose and FFA uptake were reduced by 33% and 36%, respectively, whereas the activity of the catabolic enzyme hormone-sensitive lipase increased by 51%. Moreover, expression of resistin and leptin mRNA decreased, whereas adiponectin mRNA did not change. All these data indicate an anabolic role for the vagal input to adipose tissue. Finally, we demonstrate somatotopy within the central part of the autonomic nervous system, as intra-abdominal and subcutaneous fat pads appeared to be innervated by separate sympathetic and parasympathetic motor neurons. In conclusion, parasympathetic input to adipose tissue clearly modulates its insulin sensitivity and glucose and FFA metabolism in an anabolic way. The implications of these findings for the (patho)physiology of fat distribution are discussed.

Adipose Tissue↗
PubMed2002

Molecular epidemiology of tuberculosis.

Despite the almost 50 yrs since the introduction of curative antituberculosis drugs, Mycobacterium tuberculosis continues to exert an enormous toll on world health, and tuberculosis remains the world's leading cause of death due to a single infectious agent. This has stimulated research efforts into finding new tools to tackle the continuing tuberculosis pandemic. One of the few successes to date has been the development of a new discipline, molecular epidemiology. This has added a further dimension to the classical epidemiology of tuberculosis and enhanced understanding of how M. tuberculosis continues to be successfully transmitted within populations. In the process, inadequacies in tuberculosis control programmes have been identified, helping accumulate resources for their improvement. Other technologies, based on knowledge of the complete genome sequence of M. tuberculosis, which will provide newer tools for probing the epidemiology of tuberculosis, are now emerging. In spite of these advances, tuberculosis continues to remain a devastating infectious disease, disproportionately impacting on the world's poorest countries. The future challenge for molecular epidemiology is to provide better understanding of the transmission dynamics of tuberculosis in these settings and to stimulate the implementation of control measures on a more global scale.

Genetic Markers↗
PubMed1991

Kinetic evaluation for measurement of in vivo receptor occupancy by psychotropic drug in brain: implication for human studies.

In vivo receptor occupancy of psychotropic drugs in brain can be estimated by measuring the tissue radioactivity of the tracer, which binds specifically to the receptor unoccupied by the drugs (back titration method). In this study, the validity of this method was evaluated by computer simulation, using various values for the plasma elimination rate, rate of transport across the blood-brain barrier, rate of receptor association and dissociation for both drug and tracer, and the sampling time. The differential equations based on a nonlinear three-compartment model including a plasma pool, precursor pool, and specific binding pool were solved numerically by the Runge-Kutta-Gill method. The receptor occupancy calculated by this method was close to the true value when the plasma concentration and specific binding fraction of the drug did not change greatly during circulation of the tracer. Although the error in calculated occupancy at 5 min after the tracer administration was smaller than that at 20 min, tracer may not greatly accumulate in brain tissue during the initial 5 min in some situations. Our analysis shows that it is necessary to adequately control the elimination rate of drug from plasma and to allow sufficient time for radioactivity to accumulate in the tissue. Therefore, this method requires previous knowledge of the pharmacokinetic behavior of both the drug and the tracer in plasma and tissue. The operation scheme that we suggest for the accurate measurement of the receptor occupancy in vivo can be used in human studies with positron emission tomography and may be useful for therapeutic drug monitoring.

Brain↗
PubMedDate not supplied

Distribution of hydrolysable tannins in the foliage of Finnish birch species.

On the basis of qualitative and quantitative analysis with liquid chromatography--electrospray ionisation mass spectrometry, the foliage of dwarf birch (Betula nana L.), silver birch (B. pendula Roth) and mountain birch (B. pubescens ssp. czerepanovii (Orlova) Hämet-Ahti) were found, for the first time, to contain the same individual HTs that were described earlier for white birch (B. pubescens Ehrh.). In addition, one previously unidentified ellagitannin was preliminarily identified from the leaves of white and mountain birches, being totally absent from the foliage of the other two species. There were large variations in the contents of HTs between species. Seasonal variation affected significantly the contents of some individual HTs within species, and these changes were mainly in accordance with the biosynthetic pathway of HTs. All species converted galloylglucoses (GGs) into ellagitannins (ETs), dwarf birch being the only one that's efficient ET synthesis resulted in seasonally increased contents of ETs and thereof total HTs as well. The presence of insoluble ETs as well as the absence of insoluble GGs was confirmed in all four birch species for the first time. Furthermore, the amounts of insoluble ETs per one birch leaf were found to accumulate during the growing season. These findings complemented our knowledge of the biosynthetic pathway of birch leaf HTs: from soluble GGs via soluble ETs into insoluble ETs. The possible role of HTs in the herbivore defence of these species is discussed.

Chromatography, High Pressure Liquid↗
PubMed2006

Examining substrate uptake patterns of Rhodocyclus-related PAO in full-scale EBPR plants by using the MAR-FISH technique.

While recognised as the important population responsible for enhanced biological phosphorus removal (EBPR), detailed knowledge on the physiology of Rhodocyclus-related polyphosphate accumulating organisms (PAO) has yet to be grasped. The objective of this study was to examine the in situ substrate uptake patterns of Rhodocyclus-related PAO present in full-scale EBPR plants by the combined technique of microautoradiography-fluorescent in situ hybridization (MAR-FISH). The presence of these PAO in the four investigated plants was confirmed by FISH and they constituted 17%, 9%, 8%, and 7% of the sludge community. By using MAR-FISH technique, Rhodocyclus-related PAO in all the plants demonstrated similar anaerobic substrate uptake patterns. They were capable of assimilating acetate, aspartate and glutamate under anaerobic condition but they showed negative uptake with palmitate. A significant fraction of the MAR-positive cells assimilated acetate, aspartate or glutamate was found to be Rhodocyclus-related PAO. Dual staining with DAPI and FISH showed that these PAO also accumulated polyphosphate aerobically with aspartate and glutamate as carbon source. The ability of assimilating amino acids besides acetate strongly indicates the versatile physiology of Rhodocyclus-related PAO, which could benefit them to achieve predominance in EBPR activated sludge.

Environmental Restoration and Remediation↗
PubMed2001

Loss of skeletal muscle in cancer: biochemical mechanisms.

Patients with cancer often undergo a specific loss of skeletal muscle mass, while the visceral protein reserves are preserved. This condition known as cachexia reduces the quality of life and eventually results in death through erosion of the respiratory muscles. Nutritional supplementation or appetite stimulants are unable to restore the loss of lean body mass, since protein catabolism is increased mainly as a result of the activation of the ATP-ubiquitin-dependent proteolytic pathway. Several mediators have been proposed. An enhanced protein degradation is seen in skeletal muscle of mice administered tumour necrosis factor (TNF), which appears to be mediated by oxidative stress. There is some evidence that this may be a direct effect and is associated with an increase in total cellular-ubiquitin-conjugated muscle proteins. Another cytokine, interleukin-6 (IL-6), may play a role in muscle wasting in certain animal tumours, possibly through both lysosomal (cathepsin) and non-lysosomal (proteasome) pathways. A tumour product, proteolysis-inducing factor (PIF) is produced by cachexia-inducing murine and human tumours and initiates muscle protein degradation directly through activation of the proteasome pathway. The action of PIF is blocked by eicosapentaenoic acid (EPA), which has been shown to attenuate the development of cachexia in pancreatic cancer patients. When combined with nutritional supplementation EPA leads to accumulation of lean body mass and prolongs survival. Further knowledge on the biochemical mechanisms of muscle protein catabolism will aid the development of effective therapy for cachexia.

Animals↗
PubMed1993

The biology of interleukin-5 and its receptor.

IL-5 is primarily a T-cell-derived cytokine that has multiple regulatory functions on eosinophils and (in the mouse) on antibody-secreting B cells. A complex network of cytokines appear to control transcription of the gene for IL-5 and its production. Abnormally high levels of this cytokine are associated with infections with tissue-dwelling parasites and a diverse group of hypereosinophilic conditions of no known etiology. Our understanding of the biological role of IL-5 in the regulation of Ig production and the development of immunity to parasites is far from complete, but basic knowledge of its action at the cellular level is accumulating and will be critical for the intelligent application of immunotherapy with IL-5 or antibodies to IL-5 in infectious, neoplastic, and possibly other diseases.

Animals↗
PubMed2004

[Advance and perspective of clinical nutrition].

Although nutritional support using nutrient enemas was recorded almost 3,500 years ago, the modern era of clinical dietetics commenced with the development of intravenous hyperalimentation by Dudrick et al. and the development of the chemically defined diet by Greenstein et al. Thereafter, clinical nutritional support became widely accepted as one of the basic tools of patient care, and knowledge of the metabolism of nutrients has been extended. In particular, the significance of micronutrients in systemic function, importance of gut function on the systemic metabolism and immune system, and involvement of amino acids and fat elements in the development and amelioration of specific disease status such as renal and hepatic failure have been recognized, and specific nutritional support has been created as a treatment strategy. In addition to knowledge of renal and hepatic failure or metabolic disorders, accumulated information on tumor metabolism and pathophysiology in cancer cachexia has also enabled cancer treatment using a nutritional approach. An enteral diet containing certain amino acids such as arginine or glutamate, omega-3 unsaturated fatty acids, and nucleic acids has been developed, and its clinical application under the new concept of "immunonutrition" has demonstrated reduction of the incidence of infection and shortening of hospital stay. Many questions on Immunonutrition remain to be answered such as its mechanism or optimal composition, although it is a promising field for future evolution. Currently, the assessment of nutritional status and gut function is required through lifelong education of medical doctors as well as the popularization of nutritional support teams. In the near future, tailor-made nutritional support will be required based on gene polymorphisms.

Adjuvants, Immunologic↗
PubMed2004

[Molecular pathogenesis of chronic lymphocytic leukemia with emphasis on cell cycle regulation and apoptosis].

In spite of the fact that many papers dealing with the chronic lymphocytic leukemia include a sentence in Introduction, that the molecular pathology of the disease "is still largely unknown", the amount of accumulated information is impressive and enables to create the first models of the overall genesis of this "most frequent leukemia in the Western world". Since many studies have confirmed that B-CLL lymphocytes in peripheral blood are anchored in G0/G1-phase of the cell cycle, the recent general opinion is, that CLL is primarily caused by defects in apoptosis--lymphocytes are slowly accumulating, being not able to "die properly". However, it becomes evident, that in the microenvironment appropriate for the cell growth, i.e. in the bone marrow and lymph nodes, B-CLL lymphocytes proliferate and they are subsequently accumulated in peripheral blood. This review summarizes namely the knowledge about status and expression of key genes regulating apoptosis and cell cycle in B-CLL lymphocytes, including p53, ATM, MDM2, Bcl-2/Bax, caspase-3, CDK-inhibitor p27, cyclins D2 and D3. Relationship between some of these genes and the standard therapy is discussed and prospective therapeutic alternatives resulting from the new molecular-genetic findings are presented.

Apoptosis↗
PubMed2004

Using mandatory data collection on multiresistant bacteria for internal surveillance in a hospital.

OBJECTIVES: Multiresistant pathogens cause major clinical problems and considerably increase treatment costs. Since 2001 the Protection Against Infection Act (PIA) obligates hospitals in Germany to the documentation of multiresistant bacteria. We analyzed the use of these data for routine internal surveillance. METHODS: We used standard data collected for the mandatory documentation and studied consecutive diagnoses of Methicillin-resistant Staphylococcus aureus (MRSA) in a 893-bed tertiary level hospital in North Rhine-Westphalia in Germany. Based on the Poisson distribution for the cumulative yearly incidence of MRSA, we defined a threshold level for an outbreak. RESULTS: During a 12-month time period 80 patients were diagnosed with MRSA. The time structure and spatial distribution of different MRSA phenotypes (defined through specific antibiotic resistance patterns) were consistent with the within-hospital transmission. In the two preceding time periods of 12 months each, 15 respectively 8 patients with MRSA were found. The defined alert threshold level for cumulative yearly incidence was crossed in the beginnings of the outbreak. CONCLUSION: Monitoring the mandatory data collected on multiresistant bacteria allows the early detection of accumulations suspect for the within-hospital transmission. This knowledge can be used for a fast reaction and breaking off the transmission chains.

Data Collection↗
PubMed1990

[Human immunodeficiency virus (HIV): a review].

Since its discovery in 1983, a lot of knowledge about the human immunodeficiency virus (HIV) has been accumulated. Our paper gives a brief survey on what is known at present about the structure, molecular biology, and the cell tropism of this virus. We discuss its relationship to other lentiviruses as well as its possible origin; in addition, we refer to the immune response to HIV and its interactions with the infected host. We also briefly summarize the difficulties encountered in the attempts to produce a vaccine against HIV and highlight some promising approaches in the development of such a vaccine.

DNA Replication↗
PubMed1986

Cellular interactions of L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT)-specific suppressor factors. I. Inhibition of the activity of GAT-specific helper T cell clones by monoclonal GAT-specific suppressor T cell factors.

Considerable information concerning the serology and biochemistry of antigen-specific, T cell-derived suppressor factors has been obtained with the use of T cell hybridomas as a source of homogeneous material. Similarly, knowledge of helper T cell products and receptors is accumulating from studies of helper T cell clones and hybridomas. Our strategy for studying the mechanisms by which suppressor factors inhibit responses was to determine whether monoclonal suppressor factors could inhibit antibody responses specific for L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) in cultures containing unprimed splenic B cells, macrophages, and GAT-specific T cell clones as a source of helper activity. The MHC-restricted, two chain suppressor factors, GAT-TsF2, inhibited these responses if the helper T cell clones and suppressor factor were derived from H-2-compatible mice. Furthermore, responses were inhibited by briefly pulsing T cell clones with GAT-TsF2 in the presence of GAT, indicating that suppressor factors need not be present continuously. In addition, helper T cell clones adsorbed syngeneic, but not allogeneic, GAT-TsF2 in the presence of GAT. Adsorption also requires a shared antigenic specificity between the H-2b-derived helper T cells and TsF2 factor. Thus, helper T cells can serve as the cellular target of antigen-specific, MHC-restricted GAT-TsF2, and cloned helper T cells can be used as a homogeneous target population for analysis of the molecular mechanisms of T cell suppression.

Adsorption↗
PubMed1986

The mechanism and structure of thymidylate synthetase.

We have been involved in studies of the mechanism, inhibition and structure of the enzyme thymidylate synthetase. Knowledge of fundamental catalytic features of thymidylate synthetase has accumulated over the past decade, and will be described. Recently, we have been involved in studies of the x-ray crystallography of thymidylate synthetase, the first phase of which has been completed.

Kinetics↗
PubMedDate not supplied

Spontaneous intracranial hypotension: spinal MR findings.

We report three patients with spontaneous intracranial hypotension in whom spinal MR imaging revealed ventral extradural fluid collections that were centered at the cervicothoracic junction in two patients and extended throughout the entire spine in the third patient. These spinal fluid collections most likely resulted from the accumulation of CSF at the site of dural leakage. Knowledge of this association can be helpful in the selection of imaging studies to facilitate diagnosis and treatment.

Adult↗
PubMed1998

[New pharmacologic aspects in the neurologic profile of propentofylline (Karsivan ad us. vet.)].

Propentofylline (Karsivan, Hoechst Roussel Vet) is a selective inhibitor of adenosine transport and phosphodiesterase. For several years it has been well established in the geriatric therapy of the dog improving hemodynamics in cerebral and peripheral compartments. In human medicine clinical development of this pharmaceutical has already entered an advanced stage for the long-term therapy of patients with Alzheimer's disease and vascular dementia. In the brains of senile dogs and in human patients suffering from Alzheimer's disease comparable neuropathological findings can be made. In senile dogs a distinctive correlation exists between the quantity of beta-amyloid accumulation and the degree of dementia. The extension of knowledge by clinical studies in humans and by experimental studies in animals may contribute to a deeper understanding of therapeutical approaches of cognitive dysfunction in the old dog. The xanthine derivative propentofylline [1-(5'-oxohexyl)-3-methyl-7-propylxanthine] directly interfers with the neurodegenerative process and reduces the extent of damage to brain structures. In experimental models of vascular dementia and/or Alzheimer's disease it improves cognitive functions, inhibits inflammatory processes as well as excessive activation of microglia, formation of free radicals, cytocines and abnormal amyloid precursor proteins (APP). It stimulates synthesis and liberation of nerve growth factor (NGF) and reduces ischemic damage to the brain. In clinical studies in humans it improved cognitive functions as well as global functions and the ability to cope with tasks of routine daily life in patients suffering from Alzheimer's disease and vascular dementia.

Adenosine↗