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Biomedical subjects

S Schaffer

Publications and source records attributed to S Schaffer.

At least 19 recordsLinked to original sources

Plant foods and brain aging: a critical appraisal.

In the 21st century, human aging will be one of the biggest challenges for most societies throughout the world. The decline in human fitness is a typical hallmark of the aging process. Aside from the cardiovascular system, the brain most often suffers significantly from the life-long impact of stressors, such as reactive oxygen and nitrogen species. Oxytosis, i.e. oxidative stress-induced cell death, has been identified to play a major role in the development and onset of chronic diseases. Foods, especially of plant origin, are rich in antioxidants and numerous in vivo data suggest that a diet rich in fruits and vegetables supports the maintenance of animal and human health. These beneficial effects also extend to the central nervous system, which, due to the presence of the blood-brain barrier, tightly controls the influx of metabolites and nutrients. In earlier studies the impact of antioxidant vitamins, such as alpha-tocopherol and ascorbic acid, on brain health has been of interest. Recently, the focus moved to assessing the potential of unsaturated fatty acids and secondary plant metabolites, particularly of polyphenols, to act as neuroprotectants. Considerable experimental evidence suggests that polyphenols and other plant-derived bioactivities affect animal and human brain function not only by directly lowering oxidative stress load but also by modulating various signal transduction pathways.

Aged↗

Flavonoids and the aging brain.

Like in all other organs, the functional capacity of the human brain deteriorates over time. Pathological events such as oxidative stress, due to the elevated release of free radicals and reactive oxygen or nitrogen species, the subsequently enhanced oxidative modification of lipids, protein, and nucleic acids, and the modulation of apoptotic signaling pathways contribute to loss of brain function. The identification of neuroprotective food components is one strategy to facilitate healthy brain aging. Flavonoids were shown to activate key enzymes in mitochondrial respiration and to protect neuronal cells by acting as antioxidants, thus breaking the vicious cycle of oxidative stress and tissue damage. Furthermore, recent data indicate a favorable effect of flavonoids on neuro-inflammatory events. Whereas most of these effects have been shown in vitro, limited data in vivo are available, suggesting a rather low penetration of flavonoids into the brain. Nevertheless, several reports support the concept that flavonoid intake inhibits certain biochemical processes of brain aging, and might thus prevent to some extent the decline of cognitive functions with aging as well as the development or the course of neurodegenerative diseases. However, more data are needed to assess the true impact of flavonoids on brain aging.

Aging↗

Antioxidant properties of Mediterranean food plant extracts: geographical differences.

Locally grown, wild food plants seasonally contribute a considerable portion of the daily diet in certain Mediterranean areas and it has been suggested that the beneficial effects of the Mediterranean diet on human health partly originate from the antioxidant effect of flavonoid-rich food plants. The nutrient content of most wild plants is higher than that of cultivated ones and may vary depending on the prevailing environmental conditions. Accordingly, three local Mediterranean plant foods (i.e. Cichorium intybus, Sonchus oleraceus, Papaver rhoeas) were collected in Greece (Crete), southern Italy, and southern Spain in order to assess possible differences in their in vitro antioxidant potential. The biological assays revealed diverse intra-plant specific antioxidant effects for the tested extracts ranging from no activity to almost complete protection. Furthermore, substantial differences in the polyphenol content were found for the nutritionally used part of the same plant originating from different locations. However, no clear correlations between the polyphenol content and the extracts' antioxidant activities were found. Taken together, the data suggest that certain local Mediterranean plant foods possess promising antioxidant activity and that the observed biological effects are possibly influenced by the geographically-dependent environmental conditions prevailing during plant growth.

Animals↗

Proteome analysis of Corynebacterium glutamicum.

By the use of different Corynebacterium glutamicum strains more than 1.4 million tons of amino acids, mainly L-glutamate and L-lysine, are produced per year. A project was started recently to elucidate the complete DNA sequence of this bacterium. In this communication we describe an approach to analyze the C. glutamicum proteome, based on this genetic information, by a combination of two-dimensional (2-D) gel electrophoresis and protein identification via microsequencing or mass spectrometry. We used these techniques to resolve proteins of C. glutamicum with the aim to establish 2-D protein maps as a tool for basic microbiology and for strain improvement. In order to analyze the C. glutamicum proteome, methods were established to fractionate the C. glutamicum proteins according to functional entities, i.e., cytoplasm, membranes, and cell wall. Protein spots of the cytoplasmic and membrane fraction were identified by N-terminal sequencing, immunodetection, matrix assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) and electrospray ionization-mass spectrometry (ESI-MS). Additionally, a protocol to analyze proteins secreted by C. glutamicum was established. Approximately 40 protein spots were observed on silver-stained 2-D gels, 12 of which were identified.

Amino Acid Sequence↗

A high-resolution reference map for cytoplasmic and membrane-associated proteins of Corynebacterium glutamicum.

We present a high-resolution reference map for soluble proteins obtained from Corynebacterium glutamicum cells grown in glucose minimal medium. The analysis window covers the pl range from 4-6 and the molecular mass range from 5-100 kDa. Using overlapping narrow immobilized pH gradients for isoelectric focusing, 970 protein spots were detected after second-dimensional separation on SDS-polyacrylamide gels and colloidal Coomassie-staining. By tryptic peptide mass fingerprinting 169 protein spots were identified, representing 152 different proteins including many enzymes involved in central metabolism (18), amino acid biosynthesis (24) and nucleotide biosynthesis (11). Thirty-five of the identified proteins have no known function. A comparison of the observed and the expected physicochemical properties of the identified proteins indicated that nine proteins were covalently modified, since variants with apparently identical molecular mass, but differing pl were detected. The N-termini of eight proteins were determined by post-source decay (PSD) analysis of selected peptides. In addition to the soluble proteins, a map of the membrane-bound proteins within the pl range 4-7 is presented, which contains 660 protein spots, 22 of which were identified, representing 13 different proteins.

Bacterial Proteins↗

Predictors of serum selenium in cigarette smokers and the lack of association with lung and prostate cancer risk.

Epidemiological studies have suggested that low levels of selenium are associated with a higher incidence of both lung and prostate cancer. We analyzed the selenium serum concentration in 356 Carotene and Retinol Efficacy Trial (CARET) participants who later developed lung cancer and 356 matched controls and in 235 prostate cancer cases and 456 matched controls. Serum samples were obtained a mean of 4.7 years before diagnosis for both tumor types. Controls were matched to cases by year of randomization, age, smoking status, treatment arm, exposure population (asbestos workers or cigarette smokers), and year of blood draw. In the control population (n = 820), significant predictors of low serum selenium concentration were current smoking status and East Coast locations of the study center. Overall, there was no significant difference in mean serum selenium in lung cancer cases versus controls (11.91 microg/dl versus 11.77 microg/dl) or prostate cancer cases versus controls (11.48 microg/dl versus 11.43 microg/dl). No statistically significant trend in odds ratio was seen across quartiles of serum selenium for lung cancer (P = 0.49) or prostate cancer (P = 0.69). In a subpopulation of 174 prostate cancer patients who had clinical and pathological staging material reviewed, there was no association between serum selenium and Gleason score or clinical or pathological stage. In the CARET population of current and former smokers consuming an ad libitum diet, the serum concentration of selenium was not a risk factor for either lung cancer or prostate cancer.

Age Distribution↗

Role of osmoregulation in the actions of taurine.

Taurine regulates an unusual number of biological phenomena, including heart rhythm, contractile function, blood pressure, platelet aggregation, neuronal excitability, body temperature, learning, motor behavior, food consumption, eye sight, sperm motility, cell proliferation and viability, energy metabolism and bile acid synthesis. Many of these actions are associated with alterations in either ion transport or protein phosphorylation. Although the effects on ion transport have been attributed to changes in membrane structure, they could be equally affected by a change in the activity of the affected transporters. Three common ways of altering transporter activity is enhanced expression, changes in the phosphorylation status of the protein and cytoskeletal changes. Interestingly, all three events are altered by osmotic stress. Since taurine is a key organic osmolyte in most cells, the possibility that the effects of taurine on ion transport could be related to its osmoregulatory activity was considered. This was accomplished by comparing the effects of taurine, cell swelling and cell shrinkage on the activities of key ion channels and ion transporters. The review also compares the phosphorylation cascades initiated by osmotic stress with some of the phosphorylation events triggered by taurine depletion or treatment. The data reveal that certain actions of taurine are probably caused by the activation of osmotic-linked signaling pathways. Nonetheless, some of the actions of taurine are unique and appear to be correlated with its membrane modulating and phosphorylation regulating activities.

Animals↗

Taurine improves angiotensin II-induced hypertrophy of cultured neonatal rat heart cells.

The effect of taurine on angiotensin II-induced hypertrophy of cultured neonatal rat heart cells (myocytes and nonmyocytes) was examined. Angiotensin II (1-100 nM) alone caused an increase in the rate of protein synthesis and the surface area of myocytes without altering the rate of DNA synthesis or cell number. It also mediated an increase in DNA synthesis and in cell number of nonmyocytes. Exposure of the cells to taurine (20 mM) in the absence of angiotensin II had no effect on either hyperplastic growth or hypertrophy of the two types of cultured cardiac cells. However, myocytes pretreated with 20 mM taurine exhibited reduced responsiveness to angiotensin II. Following a 24 hr pretreatment with 20 mM taurine, the stimulation in protein synthesis by angiotensin II (1 nM) was significantly suppressed. Similarly, taurine treatment of nonmyocytes reduced the degree of angiotensin II-induced promotion of hyperplastic growth (DNA synthesis and cell number). Finally, taurine partially prevented the rise in [Ca2+]i mediated by angiotensin II in cardiac cells. The present results indicate that taurine is an effective inhibitor of angiotensin II action. The possibility that the beneficial effects of taurine in the treatment of heart failure might be related to its suppression of angiotensin II-mediated cellular responses is discussed.

Angiotensin II↗

Electroporation of, plasmid isolation from and plasmid conservation in Clostridium acetobutylicum DSM 792.

Procedures have been developed allowing recombinant DNA work with Clostridium acetobutylicum DSM 792. Electroporation was used to introduce plasmid DNA into exponentially growing clostridial cells and 6 x 10(2) transformants/microgram DNA could be obtained at a time constant of 5.5 ms, 1.8 kV, 50 microF, and 600 omega. The method also allowed the taxonomic group IV strain NI-4082 to be transformed (10(1) transformants/microgram DNA). Plasmid preparation from recombinant clostridia was optimal when a modification of the alkaline lysis method was employed. It was also important to use cells from the mid-logarithmic growth phase. Recombinant strains could be easily preserved as spore suspensions; under all conditions tested plasmids were maintained.

Anaerobiosis↗

Childhood lead poisoning and managed care.

Childhood lead poisoning is a problem that disproportionately affects impoverished children. Many aspects of affected children's lives may be involved in the prevention and treatment of this disease. Changes in child health services are occurring in the context of fundamental changes of virtually all human services. Managed care changes may alter the sites where children get primary care services, the content of that care, and linkages of medical services to public health, nutrition support, housing, mental health, education, and social services. This article discusses the opportunities and the dangers that managed care changes may pose to the prevention and treatment of childhood lead poisoning.

Child Health Services↗

Adaptation of active proton pumping and plasmalemma ATPase activity of corn roots to low root medium pH

Corn (Zea mays L.) root adaptation to pH 3.5 in comparison with pH 6. 0 (control) was investigated in long-term nutrient solution experiments. When pH was gradually reduced, comparable root growth was observed irrespective of whether the pH was 3.5 or 6.0. After low-pH adaptation, H+ release of corn roots in vivo at pH 5.6 was about 3 times higher than that of control. Plasmalemma of corn roots was isolated for investigation in vitro. At optimum assay pH, in comparison with control, the following increases of the various parameters were caused by low-pH treatment: (a) hydrolytic ATPase activity, (b) maximum initial velocity and Michaelis constant (c) activation energy of H+-ATPase, (d) H+-pumping activity, (e) H+ permeability of plasmalemma, and (f) pH gradient across the membranes of plasmalemma vesicles. In addition, vanadate sensitivity remained unchanged. It is concluded that plasmalemma H+-ATPase contributes significantly to the adaptation of corn roots to low pH. A restricted net H+ release at low pH in vivo may be attributed to the steeper pH gradient and enhanced H+ permeability of plasmalemma but not to deactivation of H+-ATPase. Possible mechanisms responsible for adaptation of plasmalemma H+-ATPase to low solution pH during plant cultivation are discussed.

Journal Article↗

Multicenter, randomized, prospective trial of early tracheostomy.

OBJECTIVES: Determine the effect of early (days 3-5) or late (days 10-14) tracheostomy on intensive care unit length of stay (ICU LOS), frequency of pneumonia, and mortality, and evidence of short-term or long-term pharyngeal, laryngeal, or tracheal injury in head trauma, non-head trauma, and critically ill nontrauma patients. STUDY DESIGN: Randomized, prospective. SETTING: Five Level I trauma centers. METHODS: Data were obtained prospectively and included Acute Physiology and Chronic Health Evaluation III score (AIII), Glasgow Coma Scale score, Emergency Room Trauma Score, Injury Severity Score, Acute Injury Score, type of endotracheal tube or tracheostomy, level of positive end-expiratory pressure, and peak inspiratory pressure. Patients were to undergo laryngoscopy for detection of injury according to the Lindholm criteria at the time of endotracheal tube or tracheostomy removal and be reevaluated at 3 to 5 months after discharge. RESULTS: One hundred fifty-seven patients were entered, 127 to early randomization (3-5 days) and 28 to late randomization (10-14 days); however, only 112 patients with early and 14 with late randomization had completed data forms for the primary study goals. An additional 22 patients from the early entry groups were rerandomized late. Early randomization data: the AIII score was higher (p < 0.05) in the head trauma tracheostomy (65 +/- 4) than in the nontracheostomy group (51 +/- 4) and in the nontrauma tracheostomy (92 +/- 6) than in the nontracheostomy group (68 +/- 7), but was equivalent in the non-head trauma group. Glasgow Coma Scale score, Emergency Room Trauma Score, Injury Severity Score, Acute Injury Score, positive end-expiratory pressure, and peak inspiratory pressure were not significantly different in any of the groups. There were no significant differences in ICU LOS, frequency of pneumonia, or death in any of the groups after either early or late tracheostomy compared with continued endotracheal intubation. Only 83 patients underwent postextubation laryngoscopy. There were no significant differences between the groups; however, there were trends to more vocal cord ulceration and subglottic inflammation in the continued intubation group. No patient was seen in this study with late vocal cord or laryngeal stenosis; there were no tracheal-innominate artery fistulae. Seven of the patients with abnormal findings at extubation had normal 3- to 5-month postextubation laryngoscopy. CONCLUSION: Physician bias limited patient entry into the study. Although there were higher AIII scores in the head trauma early tracheostomy patients, there were no differences in the primary end points of ICU LOS, pneumonia, or death in any of the groups studied. Long-term endoscopic follow-up was poor, but no known late tracheal stenosis was seen.

APACHE↗

Preventing nursing student exposure incidents: the role of personal protective equipment and safety engineered devices.

This descriptive study used a self-selected sample of 580 newly licensed Virginia registered nurses to examine risk factors for percutaneous (needlestick) and mucocutaneous (splash) exposure incidents to blood or body fluids that occurred while they were nursing students. Fifty-one exposure incidents were reported by 42 respondents (7% of total). Twenty of 31 percutaneous exposure incidents were potentially preventable through the use of safety-engineered devices. Similarly, 4 of 10 mucocutaneous incidents occurring during routine procedures were potentially preventable through the use of personal protective equipment. Limited use of safety-engineered devices and personal protective equipment in the occurrence of nursing student exposure incidents suggests that active steps by schools of nursing to ensure student access to and use of personal protective equipment and safety-engineered devices may minimize exposure incident risk for students.

Chi-Square Distribution↗

Stimulation of the Na+/Ca2+ exchanger by phenylephrine, angiotensin II and endothelin 1.

The Na+/Ca2+ exchanger plays an important role in the maintenance of calcium homeostasis in the heart. Therefore, factors which regulate the exchanger have a significant impact on cardiac function. Previously, we showed that the non-hydrolysable GTP analog, 5'guanylyl imidodiphosphate [Gpp(NH)p], stimulates Na+/Ca2+ exchange activity, implying the involvement of a G protein in exchanger regulation. In this study, we examined the effect of G protein agonists on Na+/Ca2+ exchanger activity. Isoproterenol, a Gs agonist, had no effect on exchanger activity. Likewise, the Gi agonist, carbachol, did not influence Na+/Ca2+ exchanger activity. Since these G proteins couple to the adenylate cyclase system, it would appear that cAMP-linked events do not regulate the Na+/Ca2+ exchanger. We next examined the influence of Gq-linked agonists on exchanger activity. Phenylephrine, an alpha 1-adrenergic agonist, increased Na+/Ca2+ exchanger activity up to 111% with an EC50 of 21 microM. Moreover, the Na+/Ca2+ exchanger activity was enhanced by angiotensin II and endothelin 1, which caused maximal stimulation of exchanger activity up to 125% and 211%, respectively. The selective protein kinase C inhibitor chelerythrine significantly attenuated the ability of phenylephrine and angiotensin II to stimulate the Na+/Ca2+ exchanger. In addition, the protein kinase C activator, phorbol 12-myristate 13-acetate, stimulated exchanger activity by 32%, raising the possibility that all three Gq agonists mediate their actions in part through the promotion of phospholipase C activity and the subsequent activation of protein kinase C. The contribution of Na+/Ca2+ exchange to the actions of phenylephrine, angiotensin II, and endothelin 1 is discussed.

Alkaloids↗

Signal transduction mechanism for the stimulation of the sarcolemmal Na(+)-Ca2+ exchanger by insulin.

The signal transduction pathway for insulin-mediated activation of sarcolemmal Na(+)-Ca2+ exchange was examined. Insulin stimulated Na(+)-Ca2+ exchanger activity in a dose-dependent manner, with the EC50 being about 0.7 U/l. The insulin effect was blocked by the protein kinase inhibitor, staurosporine, indicating possible involvement of a protein kinase in insulin action. Also, the relationship between the insulin effect and activation of a G protein was examined by testing the effects of 5' guanylyl imidodiphosphate (Gpp(NH))p) on Na(+)-Ca2+ exchange in the presence and absence of insulin. When exchanger activity was assayed at a calcium concentration of 40 microM, insulin alone had no effect whereas ATP and Gpp(NH)p increased exchanger activity. However, insulin responsiveness was restored in vesicles preloaded with either ATP or Gpp(NH)p, suggesting that insulin may act through a combination of G protein coupling and protein phosphorylation to enhance Na(+)-Ca2+ exchanger activity. We conclude that calcium overload in the diabetic heart may involve a defect in acute activation of the exchanger by insulin.

Adenosine Triphosphate↗