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S Barnes

Publications and source records attributed to S Barnes.

At least 91 records · Page 5Linked to original sources
PubMed1997

The effect of treatment variables on mood and social adjustment in adult patients with pituitary disease.

OBJECTIVE: Studies of mood in hypopituitary adults have yielded inconsistent results. This investigation was carried out to investigate whether treatment characteristics may be responsible for the inconsistent results. DESIGN AND MEASUREMENTS: We compared three groups of patients with a group of matched healthy controls on self-report measures of mood and social adjustment (Beck depression inventory, State-trait anxiety inventory, Social adjustment scale (modified)) and a measure of quality of life (Nottingham health profile, NHP). PATIENTS: The patient groups were those treated with transfrontal surgery (n = 23), transsphenoidal surgery (n = 23) or medication only (n = 23). In addition, a close informant of each subject was asked to complete a social adjustment measure about the subject's level of adjustment. RESULTS: On the self-report mood and social adjustment measures and the emotion sub-scale of the NHP, the transsphenoidal and medication patient groups rated themselves as being more depressed, anxious and having poorer social adjustment than the transfrontal or control groups. The close informants, however, rated all three patient groups as having poorer social adjustment than the controls. Patients treated with surgery and without radiotherapy reported fewer symptoms of depression than those treated with radiotherapy. Realistic self-appraisal of social adjustment in surgical patients was found only in those treated with transsphenoidal surgery without radiotherapy. CONCLUSIONS: Patients treated for pituitary tumour, excepting those treated with transfrontal surgery and to a lesser extent those treated with radiotherapy, suffer from mild mood disturbance and self-perceived decreased social adjustment. All patient groups are seen by others as having decreased social adjustment, raising the possibility that the transfrontal patients and possibly those who have had radiotherapy, lack insight. This may explain some of the discrepancies in the previous literature and needs to be taken into account when using self-report measures with these patients.

Adenoma↗
PubMed1997

Superoxide dismutase catalyzes nitration of tyrosines by peroxynitrite in the rod and head domains of neurofilament-L.

Superoxide dismutase (SOD) catalyzes the nitration of specific tyrosine residues in proteins by peroxynitrite (ONOO-), which may be the damaging gain-of-function resulting from mutations to SOD associated with familial amyotrophic lateral sclerosis (ALS). We found that disassembled neurofilament-L (light subunit) was more susceptible to tyrosine nitration catalyzed by SOD in vitro. Neurofilament-L was selectively nitrated compared with the majority of other proteins present in brain homogenates. Assembled neurofilament-L was more resistant to nitration, suggesting that the susceptible tyrosine residues were protected by intersubunit contacts in assembled neurofilaments. Electrospray mass spectrometry of trypsin-digested neurofilament-L showed that tyrosine 17 in the head region and tyrosines 138, 177, and 265 in alpha-helical coil regions of the rod domain of neurofilament-L were particularly susceptible to SOD-catalyzed nitration. Nitrated neurofilament-L inhibited the assembly of unmodified neurofilament subunits, suggesting that the affected tyrosines are located in regions important for intersubunit contacts. Neurofilaments are major structural proteins expressed in motor neurons and known to be important for their survival in vivo. We suggest that SOD-catalyzed nitration of neurofilament-L may have a significant role in the pathogenesis of ALS.

Amino Acid Sequence↗
PubMed1997

Intestinal uptake and biliary excretion of the isoflavone genistein in rats.

The intestinal absorption, biliary excretion and metabolism of genistein, a potent and specific protein tyrosine kinase inhibitor that occurs naturally in soy foods, was examined in anesthetized, adult female rats fitted with indwelling biliary cannulas. 4-14C-Genistein, when infused into the duodenum, was rapidly absorbed from the intestine, taken up by the liver and excreted into the bile as its 7-O-beta-glucuronide conjugate. Cumulative recovery of 14C-radioactivity in the bile over a 4-h period was 70-75% of the dose. When genistein was infused into the portal vein, it was also taken up efficiently by the liver, conjugated with glucuronic acid and transported into bile. However, portal blood collected after duodenal infusions of genistein contained mostly genistein 7-O-beta-glucuronide, suggesting that in vivo glucuronidation occurred in the intestinal wall rather than the liver. This was confirmed using everted intestinal sac preparations. Reinfusion of genistein 7-O-beta-glucuronide into the duodenum or into the mid small intestine resulted in its reappearance in the bile, albeit more slowly than when genistein was infused. Over a 4-h collection period, the cumulative recovery of 14C-radioactivity in bile was 27 and 70-75% of the administered dose for duodenal and ileal infusions, respectively. These data indicate that genistein is highly bioavailable in rats and because of its enterohepatic circulation may accumulate within the gastrointestinal tract.

Animals↗
PubMed1997

Regulation of M-like K+ current, IKx, by Ca(2+)-dependent phosphorylation in rod photoreceptors.

An M-like K+ current (IKx) helps set the rod photoreceptor resting potential and accelerates the response to dim light. Recorded with ruptured-patch whole cell techniques, the amplitude of IKx diminished, and activation occurred at increasingly negative potentials as a function of time. In contrast, IKx was stable during nystatin perforated-patch recording. Stability during ruptured-patch recording could be induced by raising the intracellular Ca2+ concentration ([Ca2+]i) or by including caffeine or D-myo-inositol 1,4,5-trisphosphate in the pipette. This Ca(2+)-induced stability of IKx was blocked by inhibitors of Ca2+/calmodulin-dependent protein kinases, such as W-7, KN-62, chelerythrine, or H-7. Okadaic acid, an inhibitor of protein phosphatases, maintained IKx stability even at low [Ca2+]i. The requirement for phosphorylation was demonstrated by depleting MgATP or by providing 5'-adenylylimidophosphate, a nonhydrolyzable analog of ATP, either of which blocked the Ca(2+)-induced stability of IKx. These observations show that phosphorylation regulates IKx and that a stimulus controlling this action is [Ca2+]i. Should [Ca2+]i change during light adaptation, changes in IKx might alter the resting potential and temporal response properties of rod photoreceptors.

Ambystoma↗
PubMed1997

Ionic currents of isolated retinal pacemaker neurons: projected daily phase differences and selective enhancement by a phase-shifting neurotransmitter.

The eye of Aplysia expresses a robust circadian rhythm of neuronal activity. We dissociated the retinal cells in primary culture and studied isolated pacemaker neurons to identify ionic currents that may have roles in the circadian clock mechanism. Individual neurons were studied with perforated-patch whole cell recording techniques in current- and voltage-clamp modes. Pacemaker neurons had resting potentials near -40 mV and, if neurites had grown out, produced spontaneous action potentials in darkness at <1 Hz. Depolarizing current injections increased the rate of action potential firing. Hyperpolarizing current injections were followed by slowly decaying (1-3 s) afterhyperpolarizations. Four ionic currents were characterized under voltage-clamp, including a Ca current (I(Ca)), a voltage-gated potassium current (I(KV)), an A current (I(A)), and a hyperpolarization-activated Cl current (I(Cl)). I(Cl) was only seen using Cl(-)-filled electrodes when high concentrations of Cl- diffused from the electrode and is therefore unlikely to be important under physiological conditions. The magnitude of I(KV) was significantly larger during the projected zeitgeber predawn phase than during the postdawn phase, whereas the magnitude of I(A) was constant at these circadian phases, suggesting that only I(KV) is controlled by the circadian clock. Serotonin increased I(KV) by 29%, consistent with reports that serotonin suppresses optic nerve activity and phase shifts the circadian rhythm recorded from the intact eye. The enhancement of I(KV) likely contributes to membrane hyperpolarization, and it may be required for phase shifting. The phase-dependent changes in I(KV) provide evidence that each retinal pacemaker neuron contains a circadian clock, but confirmation must await further recordings made from individual pacemaker neurons that are isolated completely from all other cells in primary culture. From the present experiments, it appears that I(KV) is controlled by the circadian clock, in part, and it may be a required element in the pathway that is activated during serotonin-induced phase shifts.

Animals↗
PubMed1997

Urinary phytoestrogen levels in young women from a multiethnic population.

Phytoestrogens include several classes of chemical compounds (i.e., isoflavones, coumestans, and lignans) which are structurally similar to endogenous estrogens. In biological systems, they have both estrogenic and antiestrogenic effects and may reduce the risk of developing certain types of hormonally related diseases. However, little information is available on population differences in exposure to phytoestrogens. To examine racial/ethnic differences in urinary phytoestrogen levels, 50 young women (ages 20-40 years) were randomly selected from participants in a previous epidemiological study in which 24-h urine specimens and a dietary assessment were obtained. Subjects were members of the Kaiser Permanente Medical Care Program of northern California. Selection was stratified on race/ethnicity. Urinary levels of seven phytoestrogens were measured using high-performance liquid chromatography-mass spectrometry. Substantial variation in phytoestrogen levels was observed and racial/ethnic differences are described. The highest levels of coumestrol and the lignans were observed in white women and the lowest levels in Latina and African American women. Genistein levels, however, were highest in Latina women; other isoflavone levels did not differ significantly by race/ethnicity.

Adult↗
PubMed1997

Cloning, expression, and chromosomal localization of mouse liver bile acid CoA:amino acid N-acyltransferase.

A mouse liver lambda Zap XR cDNA library was screened using the coding region of human bile acid CoA:amino acid N-acyltransferase (BAT) cDNA as a probe. Ten positive clones were isolated and purified, two of which apparently possessed complete open reading frames for BAT based on sequence analysis of the ends of the cDNAs. One clone (mBAT#9) was selected for sequence analysis and characterization. mBAT#9 is 1869 basepairs in length and the full-length cDNA possesses a 189 basepair 5'-nontranslated region, an open-reading frame of 1260 basepairs, and a 404 basepair 3'-nontranslated region followed by a poly(A) tail. The open-reading frame codes for a 420 amino acid protein with a calculated molecular mass of 46,525 daltons. The structural gene for mBAT was mapped to mouse Chromosome 4. The amino acid sequence of mBAT is 69% identical and 84% similar to that of hBAT, and 86% identical and 95% similar to that of kan-1, a putative rat liver BAT. Enzymatically active mBAT was expressed in E. coli using the bacterial expression vector pKK233-2. Immunoblot analysis of expressed mBAT with rabbit anti-human BAT polyclonal antibodies detected a single protein with a molecular mass of approximately 45,000 daltons. Cytosol from cells transformed with mBAT#9/pKK233-2 possessed significant amounts of BAT-catalyzed conjugating activity with taurine as substrate but the expressed enzyme did not use glycine or fluoro-beta-alanine as substrates. The K(m) value for taurine was 1.9 mM +/- 0.1 mM in reactions with cholyl CoA as a cosubstrate. The specificity of mBAT for taurine as a substrate was confirmed by the demonstration, using HPLC-electrospray ionization mass spectrometry, that mouse gallbladder bile contained only taurine conjugates of bile acids. The identification of the types of amino acid conjugates of bile acids present in mouse bile had not been previously reported. These results indicate that a taurine-specific form of BAT has been cloned and expressed from mouse liver.

Acyltransferases↗
PubMed1997

Intravenous immunoglobulin in symptomatic and asymptomatic children with perinatal HIV infection.

One hundred thirty-five children born to human immunodeficiency virus (HIV)-infected mothers were selected randomly to receive immunoglobulin (Gamimune-N, Miles Pharmaceutical Co) 200 mg/kg monthly for 1 year. All patients were seropositive by ELISA and Western blot at birth. At the time of the study, 15 symptomatic (P2) and 57 asymptomatic (P1) patients with evidence of viral infection (positive HIV culture or P24 antigen) received the immunoglobulin. Sixty-three indeterminate (PO) patients with no evidence of infection served as the control. Mean age for infants in group P2 was 32 months, 26 months for group P1, and 11 months for group PO. Significant reduction in the frequency of bacterial infections (ie, otitis media, upper respiratory tract infections, urinary tract infections, and acute gastroenteritis) was seen in the symptomatic group compared with both the asymptomatic and the control groups. Growth as measured by weight and height > 50th percentile was also markedly better in the symptomatic group than either asymptomatic or control patients. There was no significant difference in head circumference in all three groups. These results indicate that monthly intravenous immunoglobulin infusion (IVIG) appears to be beneficial to both symptomatic and asymptomatic HIV patients in reducing the frequency of bacterial infection and also enhancement of the immune response. However, symptomatic patients responded much better than the asymptomatic patients.

CD4 Lymphocyte Count↗
PubMed1996

Riluzole.

Explore the source record for details and available documents.

Aged↗
PubMed1996

Variable effects of tyrosine kinase inhibitors on avian osteoclastic activity and reduction of bone loss in ovariectomized rats.

We compared the effects of the tyrosine kinase inhibitor genistein, a naturally occurring isoflavone, to those of tyrphostin A25, tyrphostin A47, and herbimycin on avian osteoclasts in vitro. Inactive analogs daidzein and tyrphostin A1 were used to control for nonspecific effects. None of the tyrosine kinase inhibitors inhibited bone attachment. However, bone resorption was inhibited by genistein and herbimycin with ID50s of 3 microM and 0.1 microM, respectively; tyrphostins and daidzein were inactive at concentrations below 30 microM, where nonspecific effects were noted. Genistein and herbimycin thus inhibit osteoclastic activity via a mechanism independent of cellular attachment, and at doses approximating those inhibiting tyrosine kinase autophosphorylation in vitro; the tyrphostins were inactive at meaningful doses. Because tyrosine kinase inhibitors vary widely in activity spectrum, effects of genistein on cellular metabolic processes were compared to herbimycin. Unlike previously reported osteoclast metabolic inhibitors which achieve a measure of selectivity by concentrating on bone, neither genistein nor herbimycin bound significantly to bone. Osteoclastic protein synthesis, measured as incorporation of 3H-leucine, was significantly inhibited at 10 microM genistein, a concentration greater than that inhibiting bone degradation, while herbimycin reduced protein synthesis at 10 nM. These data suggested that genistein may reduce osteoclastic activity at pharmacologically attainable levels, and that toxic potential was lower than that of herbimycin. To test this hypothesis in a mammalian system, bone mass was measured in 200 g ovariectomized rats treated with 44 mumol/day genistein, relative to untreated controls. During 30 d of treatment, weights of treated and control group animals were indistinguishable, indicating no toxicity, but femoral weight in the treated group was 12% greater than controls (P < 0.05). Our data indicate that the isoflavone inhibitor genistein suppresses osteoclastic activity in vitro and in vivo at concentrations consistent with its ID50s on tyrosine kinases, with a low potential for toxicity.

Animals↗
PubMed1996

Analysis of plasma isoflavones by reversed-phase HPLC-multiple reaction ion monitoring-mass spectrometry.

A HPLC-MS procedure for the rapid, sensitive and specific measurement of the isoflavones, daidzein, dihydrodaidzein, O-desmethylangolensin and genistein, in human plasma has been developed. Synthetic radiolabeled genistein conjugates were used for evaluation of optimum conditions for solid phase extraction. Biochanin A was added to plasma as a recovery marker for isoflavones and phenolphthalein glucuronide and 4-methylumbelliferone sulfate were added to ensure completeness of hydrolysis with beta-glucuronidase/sulfatase. Isoflavones in plasma extracts were separated using an isocratic HPLC method and analyzed by negative ion multiple reaction ion monitoring-mass spectrometry using a heated nebulizer-atmospheric pressure chemical ionization interface. Using plasma samples from four subjects consuming two servings a day of an isolated soy protein beverage for 14 days, the mean plasma genistein and daidzein concentrations were 556 and 345 nM, respectively. Within assay and between assay coefficients of variation for measurement of daidzein and genistein in five aliquots of the same plasma sample were 8.51% and 7.76%, and 5.98% and 6.12%, respectively.

Beverages↗
PubMed1996

Low-calcium-induced enhancement of chemical synaptic transmission from photoreceptors to horizontal cells in the vertebrate retina.

According to the classical calcium hypothesis of synaptic transmission, the release of neurotransmitter from presynaptic terminals occurs through an exocytotic process triggered by depolarization-induced presynaptic calcium influx. However, evidence has been accumulating in the last two decades indicating that, in many preparations, synaptic transmitter release can persist or even increase when calcium is omitted from the perfusing saline, leading to the notion of a "calcium-independent release" mechanism. Our study shows that the enhancement of synaptic transmission between photoreceptors and horizontal cells of the vertebrate retina induced by low-calcium media is caused by an increase of calcium influx into presynaptic terminals. This paradoxical effect is accounted for by modifications of surface potential on the photoreceptor membrane. Since lowering extracellular calcium concentration may likewise enhance calcium influx into other nerve cells, other experimental observations of "calcium-independent" release may be reaccommodated within the framework of the classical calcium hypothesis without invoking unconventional processes.

Ambystoma↗
PubMed1996

Selective detection and site-analysis of O-GlcNAc-modified glycopeptides by beta-elimination and tandem electrospray mass spectrometry.

Over the past decade, a number of nuclear and cytoplasmic proteins have been identified that are modified by single N-acetylglucosamine residues attached to the hydroxyl side chain of serines or threonines (O-GlcNAc). O-GlcNAc is a dynamic modification and therefore may act in a regulatory capacity analogous to phosphorylation. To undertake site-directed mutagenesis studies of O-GlcNAc's function, it is necessary to identify the sites of glycosylation on various proteins. The current method of site mapping, which involves galactosyltransferase labeling, generation of glycopeptides by proteolysis, purification by several rounds of HPLC, and gas-phase and manual Edman sequencing, is very tedious and requires about 10 pmol of pure, labeled glycopeptide. In this report, synthetic glycopeptides were generated and used to demonstrate that O-GlcNAc-modified peptides can be rapidly identified in complex mixtures by HPLC-coupled electrospray mass spectrometry due to the partial loss of the O-linked glycan (204 amu) at a modest orifice potential. Furthermore, the exact site of glycosylation was directly identified in the low picomole range by collision-induced dissociation (CID) of the glycopeptide after removal of the O-GlcNAc by alkaline beta-elimination. The conversion of glycosylserine to 2-aminopropenoic acid (2-ap) by beta-elimination both decreased the mass of the glycopeptide by 222 amu and resulted in a CID fragment ion representing the loss of 69 amu (2-ap) instead of 87 amu (Ser) at the position of the glycosylserine. Finally, we tested this method on an identical synthetic, alpha-linked O-GalNAc-modified peptide. Like O-GlcNAc, the O-GalNAc moiety was selectively removed at a modest orifice potential; however, the beta-elimination conditions that efficiently removed the O-GlcNAc only liberated about 20% of the O-GalNAc. We conclude that the selectivity and the sensitivity of this method will make it a powerful tool for determining the sites of O-GlcNAc modification on proteins of low abundance such as transcription factors and oncogenes.

Acetylglucosamine↗
PubMed1996

Acute lymphoblastic leukemia, hypercalcemia, and pseudohyperkalemia in a dog.

A 5-month-old sexually intact male Chesapeake Bay Retriever was evaluated for lameness of 2 weeks' duration and lymphocytosis. Acute lymphoblastic leukemia was diagnosed on the basis of results of cytologic and cytochemical evaluation of a bone marrow aspirate. Serum biochemical abnormalities included hypercalcemia and hyperkalemia. Hypercalcemia was likely paraneoplastic; hyperkalemia was believed to be a result of release of potassium from large numbers of lymphocytes in vitro (pseudohyperkalemia). The dog was euthanatized, and necropsy revealed infiltration of the hepatic vasculature and sinusoids, renal parenchyma, mesenteric and peripheral lymph nodes, bone marrow, and iridial tissue with neoplastic cells. Unique features of this case include the young age of the dog and the hypercalcemia and hyperkalemia associated with acute lymphoblastic anemia.

Animals↗
PubMed1996

Rhythmic activities of isolated and clustered pacemaker neurons and photoreceptors of Aplysia retina in culture.

Each eye of Aplysia contains a circadian clock that produces a robust rhythm of optic nerve impulse activity. To isolate the pacemaker neurons and photoreceptors of the eye and determine their participation in the circadian clock and its generation of rhythmic autoactivity, the retina was dissociated and its cells were placed in primary cell culture. The isolated neurons and photoreceptors survived and vigorously extended neurites tipped with growth cones. Many of the photoreceptors previously described from histological sections of the intact retina were identified in culture, including the large R-type photoreceptor, which gave robust photoresponses, and the smaller tufted, whorled, and flared photoreceptors. The pacemaker neurons responsible for the rhythmic impulse activity generated by the eye were identified by their distinctive monopolar morphology and recordings were made of their activity. Isolated pacemaker neurons produced spontaneous action potentials in darkness, and pacemaker neurons attached to fragments of retina or in an isolated cluster interacted to produce robust spontaneous activity. This study establishes that isolated retinal pacemaker neurons retain their innate autoactivity and ability to produce action potentials in culture and that clusters of coupled pacemaker neurons are capable of generating robust autoactivity comparable to pacemaker neuron rhythmic activity recorded in the intact retina, which was previously shown to correspond to 1:1 with the optic nerve compound action potential activity.

Action Potentials↗
PubMed1996

Soy isoflavonoids and cancer prevention. Underlying biochemical and pharmacological issues.

The isoflavonoids in soy, genistein and daidzein, have been proposed to contribute an important part of the anti-cancer effect of soy. Although there have been many interesting studies on the effects of isoflavones on biochemical targets in tissue culture experiments, in most cases the concentrations used by investigators have exceeded 10 microM. However, based on simple pharmacokinetic calculations involving daily intake of isoflavones, absorption from the gut, distribution to peripheral tissues, and excretion, it is unlikely that blood isoflavone concentrations even in high soy consumers could be greater than 1-5 microM. Experiments designed to evaluate these pharmacological principles were carried out in anesthetized rats with indwelling biliary catheters and in human volunteers consuming soy beverages. The data from these experiments indicate that genistein is efficiently absorbed from the gut, taken up by the liver and excreted in the bile as its 7-O-beta-glucuronide. Re-infused genistein 7-O-beta-glucuronide was also well absorbed from the gut, although this occurred in the distal small intestine. In human subjects fed a soy beverage for a period of two weeks, plasma levels of genistein and daidzein, determined by HPLC-mass spectrometry, ranged from 0.55-0.86 microM, mostly as glucuronide and sulfate conjugates. In summary, genistein is well absorbed from the small intestine and undergoes an enterohepatic circulation. Although the plasma genistein levels achievable with soy food feeding are unlikely to be sufficient to inhibit the growth of mature, established breast cancer cells by chemotherapeutic-like mechanisms, these levels are sufficient to regulate the proliferation of epithelial cells in the breast and thereby may cause a chemopreventive effect.

Animals↗