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PubMedDate not supplied

On the respective roles of nitric oxide and carbon monoxide in long-term potentiation in the hippocampus.

Perfusion of hippocampal slices with an inhibitor nitric oxide (NO) synthase blocked induction of long-term potentiation (LTP) produced by a one-train tetanus and significantly reduced LTP by a two-train tetanus, but only slightly reduced LTP by a four-train tetanus. Inhibitors of heme oxygenase, the synthetic enzyme for carbon monoxide (CO), significantly reduced LTP by either a two-train or four-train tetanus. These results suggest that NO and CO are both involved in LTP but may play somewhat different roles. One possibility is that NO serves a phasic, signaling role, whereas CO provides tonic, background stimulation. Another possibility is that NO and CO are phasically activated under somewhat different circumstances, perhaps involving different receptors and second messengers. Because NO is known to be activated by stimulation of NMDA receptors during tetanus, we investigated the possibility that CO might be activated by stimulation of metabotropic glutamate receptors (mGluRs). Consistent with this idea, long-lasting potentiation by the mGluR agonist tACPD was blocked by inhibitors of heme oxygenase but not NO synthase. Potentiation by tACPD was also blocked by inhibitors of soluble guanylyl cyclase (a target of both NO and CO) or cGMP-dependent protein kinase, and guanylyl cyclase was activated by tACPD in hippocampal slices. However, biochemical assays indicate that whereas heme oxygenase is constitutively active in hippocampus, it does not appear to be stimulated by either tetanus or tACPD. These results are most consistent with the possibility that constitutive (tonic) rather than stimulated (phasic) heme oxygenase activity is necessary for potentiation by tetanus or tACPD, and suggest that mGluR activation stimulates guanylyl cyclase phasically through some other pathway.

Animals↗
PubMed1999

Use of complementary and alternative medicine in Hawaii cancer patients.

This research investigated complementary and alternative medicine (CAM) use by Hawaii cancer patients. Thirty-six percent of patients used CAM, most commonly religious/spiritual therapy and herbal treatments. CAM use was linked with younger age, female gender, Catholic religion, and more education. More research is needed to inform decision-making.

Aged↗
PubMed2001

Smoothened mutants reveal redundant roles for Shh and Ihh signaling including regulation of L/R symmetry by the mouse node.

Genetic analyses in Drosophila have demonstrated that the multipass membrane protein Smoothened (Smo) is essential for all Hedgehog signaling. We show that Smo acts epistatic to Ptc1 to mediate Shh and Ihh signaling in the early mouse embryo. Smo and Shh/Ihh compound mutants have identical phenotypes: embryos fail to turn, arresting at somite stages with a small, linear heart tube, an open gut and cyclopia. The absence of visible left/right (L/R) asymmetry led us to examine the pathways controlling L/R situs. We present evidence consistent with a model in which Hedgehog signaling within the node is required for activation of Gdf1, and induction of left-side determinants. Further, we demonstrate an absolute requirement for Hedgehog signaling in sclerotomal development and a role in cardiac morphogenesis.

Animals↗
PubMed2004

Suppression of cytokine-inducible nitric oxide synthesis during intraperitoneal Meth A tumor growth.

Nitric oxide (NO*) synthesis is induced within many tumors. The time course of NO* synthesis was evaluated during intra-peritoneal Meth A fibrosarcoma progression. While increasing macrophage recruitment into ascites was noted, inducible nitric oxide synthase (iNOS) antigen and function peaked between days 3-6 after tumor implantation. The capacity of cells to respond to LPS and IFNgamma stimulation was markedly depressed on day 9 and 11. Cellular proliferation correlated in an inverse fashion with levels of NO* synthesis. Electron paramagnetic resonance spectroscopy and nitrotyrosine immunostaining failed to show accumulation of characteristic target cell lesions induced by NO*. These findings lead us to conclude that NO* production was increasingly suppressed during Meth A tumor progression. Depression of NO* production did not correlate with levels of the inhibitory cytokines TGFbeta and IL-10, but could be partially overcome by addition of sepiapterin (a tetrahydrobiopterin prodrug). Thus, depletion of essential co-factors necessary for iNOS function may contribute to depressed NO* responses during cancer progression.

Animals↗
PubMed1991

Molecular mechanisms for mammalian melanogenesis. Comparison with insect cuticular sclerotization.

Melanogenesis is an important biochemical process for the production of skin pigments which protect many animals from the damage of solar radiation. The abnormalities in melanogenesis are associated with albinism, vitiligo, as well as malignant melanoma in humans. In the lower forms of animals viz., insects, the exoskeleton is hardened to protect their soft bodies by a process called sclerotization, which is often accompanied by melanization. Recent advances in the biochemistry of sclerotization and melanization reveal remarkable similarity between these two processes. The seven stages of sclerotization are: (a) enzymatic oxidation of N-acyldopamine, (b) Michael-1,4-addition reactions of N-acyldopamine quinone, (c) tautomerization of quinone to quinone methide, (d) Michael-1,6-addition of quinone methides, (e) tautomerization of N-acyldopamine quinone methide to 1,2-dehydro-N-acyldopamine, (f) enzymatic oxidation of 1,2-dehydro-N-acyldopamine, and (g) the reactions of resultant quinonoid compounds. Amazingly, striking similarities in the reaction sequences are found in the melanization process starting from dopa. These comparisons predict a central role for quinone methides as reactive intermediates during melanization. Accordingly, recent studies provide increasing evidence in favor of this proposition.

Animals↗
PubMed2002

Antagonism of activin by inhibin and inhibin receptors: a functional role for betaglycan.

Activin and inhibin research has provided important insight into reproductive physiology as well as many areas involving regulation of cell growth, differentiation and function. Progress in understanding the roles of these hormones in various cell and tissue types has been complimented by novel discoveries at the molecular level that have shed light on ligand/receptor interactions, signaling mechanisms and regulation. While the receptors and signaling pathway for activin are now well characterized, the molecular basis for inhibin action has remained relatively unclear. Here we summarize recent advances in understanding inhibin's mode of action focusing on our recent identification of betaglycan as an inhibin co-receptor capable of mediating inhibin action.

Activins↗
PubMed1988

Involvement of a cryptic ATPase activity of UvrB and its proteolysis product, UvrB* in DNA repair.

The incision of damaged DNA by the Escherichia coli UvrABC endonuclease requires ATP hydrolysis. Although the deduced sequence of the UvrB protein suggests a putative ATP binding site, no nucleoside triphosphatase activity is demonstrable with the purified UvrB protein. The UvrB protein is specifically proteolyzed in E. coli cell extracts to yield a 70 kD fragment, referred to as UvrB*, which has been purified and is shown to possess a single-strand DNA dependent ATPase activity. Substrate specificity and kinetic analyses of UvrB* catalyzed nucleotide hydrolysis indicate that the stimulation in DNA dependent ATPase activity following formation of the UvrAB complex results from the activation of the normally sequestered UvrB associated ATPase. Using nucleotide analogues, it can be shown that this activity is essential to the DNA incision reaction carried out by the UvrABC complex.

Adenosine Triphosphatases↗
PubMed1992

The core protein of epican, a heparan sulfate proteoglycan on keratinocytes, is an alternative form of CD44.

Epican, a heparan sulfate proteoglycan, was recently identified on the surface of keratinocytes with the aid of a monoclonal antibody to its core protein. Using that antibody to screen a human keratinocyte cDNA library, a clone encoding the entire epican core protein was selected and sequenced. The core protein of epican is a form of CD44. The deduced protein sequence of 699 amino acids has a novel 339 amino acid domain inserted into the proximal extracellular domain of the standard, leukocyte form of CD44. The additional domain adds a number of potential N- and O-linked glycosylation sites and two proteolysis sites to this form of CD44.

Amino Acid Sequence↗
PubMed2001

Mass transfer effects on microbial uptake of naphthalene from complex NAPLs.

The bioavailability of naphthalene present as a component of a complex nonaqueous phase liquid(NAPL) comprised by nine aromatic compounds was investigated. Specifically, the effects of naphthalene mass transfer from the NAPL to the aqueous phase on rates of its microbial degradation were examined. The investigations were conducted using a pure culture, ATCC 17484, and a mixed culture of naphthalene-degrading bacteria, the former having been implicated previously in the direct uptake of sorbed naphthalene. The studies were conducted in mass-transfer-limited, segregated-phase reactors(SPRs) in which both the NAPL and aqueous phases were internally well-mixed. A 30-day active biodegradation period was preceded and followed by a 5-7-day period devoid of bioactivity, during which time the rates and extents of mass transfer of components from the NAPL to the aqueous phase were quantified. The NAPL-phase naphthalene mass depletion profiles during biodegradation were compared to those predicted by assuming maximum mass depletion under mass-transfer-limited conditions using both pre- and post-biodegradation dissolution rate and equilibrium parameters. The observed mass depletion rates were high during the initial stages of biodegradation but decreased significantly in later stages. Throughout biodegradation, even in the initial rapid stage, mass depletion rates never exceeded maximum predicted rates based on pre-biodegradation mass transfer parameters. Reduced depletion rates in the later stages appear to relate to mass transfer hindrance caused by formation of biofilms at the NAPL-water interface.

Bacteria↗
PubMed1996

Membrane regulation of the chromosomal replication activity of E. coli DnaA requires a discrete site on the protein.

The capacity of DnaA protein to initiate DNA synthesis at the chromosomal origin is influenced profoundly by the tightly bound nucleotides ATP and ADP. Acidic phospholipids can catalyze the conversion of inactive ADP-DnaA protein into the active ATP form. Proteolytic fragments of the nucleotide form of DnaA protein were examined to determine regions of the protein critical for functional interaction with membranes. A 35 kDa chymotryptic and 29 kDa tryptic fragment retained the tightly bound nucleotide. The fragments, whose amino-termini are within three residues of each other, but differ at their carboxyl ends, showed strikingly different behavior when treated with acidic phospholipids. The larger chymotryptic fragment released the bound nucleotide in the presence of acidic, but not neutral phospholipids. In contrast, the smaller tryptic fragment was inert to both forms of phospholipids. Acidic membranes, but not those composed of neutral phospholipids, protect from tryptic digestion a small portion of the segment that constitutes the difference between the 29 and 35 kDa fragments. The resulting 30 kDa tryptic fragment, which possesses this protected region, interacts functionally with acidic membranes to release the bound effector nucleotide. Inasmuch as the anionic ganglioside GM1, a compound structurally dissimilar to acidic glycerophospholipids, efficiently releases the nucleotide from DnaA protein, an acidic surface associated with a hydrophobic environment is the characteristic of the membrane that appears crucial for regulatory interaction with DnaA protein.

Adenosine Triphosphate↗
PubMed2000

A comparison of alternative assessments of depressive symptom severity: a pilot study.

This study compared the performance of an itemized symptom self-report (Inventory of Depressive Symptomatology - Self-Report; IDS-SR), patient global ratings, and clinician global ratings with an itemized clinician-rated symptom severity measure (Inventory of Depressive Symptomatology - Clinician-Rated; IDS-C) in detecting treatment effects in patients with major depressive disorder (MDD). A total of 28 inpatients (30.8% psychotic) and 34 outpatients (17.9% psychotic) with MDD began treatment that followed the Texas medication algorithm. The clinicians completed the IDS-C and a Physician Global Rating Scale (PhGRS) at each assessment visit, while the patients completed the IDS-SR and a Patient Global Rating Scale (PtGRS). Change scores from the baseline to subsequent weeks were computed for all subjects, utilizing all four measures. The IDS-SR was a significant independent predictor of the response to treatment as compared to the two global ratings. The IDS-SR was as sensitive to change as the IDS-C. While the clinician-rated itemized symptom severity rating scale remains the standard to assess the symptomatic outcome of the treatment of MDD, a self-report of identical symptomatology may be a reasonable alternative for many patients.

Adult↗
PubMed2006

Identifying critical beliefs about sleep in primary insomnia.

SUBJECT OBJECTIVE: Maladaptive beliefs about sleep are associated with insomnia and are assessed with the Dysfunctional Beliefs and Attitudes about Sleep scale (DBAS). Three studies explored which DBAS items (1) maximally differentiated people with insomnia from good sleepers, (2) declined with cognitive behavior therapy (CBT), and (3) were related to other clinical improvement indexes. DESIGN: Data from previous studies were analyzed to evaluate the above 3 hypotheses. PARTICIPANTS: The total sample (N = 332) was comprised of experimental and treatment-seeking people with insomnia and good sleepers ranging from 20 to 79 years of age (mean +/- SD 51.3 +/- 14.7). RESULTS: The analyses of variance of the 30 items of the DBAS in Study 1 suggested that 16 items differentiated insomnia sufferers from good sleepers. In Study 2, 8 items showed significantly greater changes in response to CBT than alternate therapies. However, only 2 of these items were among the 16 items that discriminated insomnia sufferers from good sleepers in Study 1. In Study 3, declining scores on 15 of 30 DBAS items in response to CBT were related to 1 or more indexes of clinical improvement. CONCLUSION: The 16 beliefs of the DBAS-30 that best discriminated insomnia sufferers from good sleepers related to helplessness and hopelessness in the insomnia group. CBT addressed some of these beliefs, although some beliefs relating to helplessness remained relatively elevated. These residual beliefs should be investigated further, as they may confer cognitive risk for future insomnia and imply ways to improve current CBT strategies.

Adult↗
PubMed1995

Glycine-induced CA1 excitotoxicity in the rat hippocampal slice.

We evaluated the effects of glycine exposure upon CA1 evoked response in the rat hippocampal slice. Exposure to 10 mM glycine for 16 min, produced rapid neuronal firing and increased orthodromic population spike (PS), followed by loss of CA1 neural transmission. Upon recovery, CA1 orthodromic and antidromic PS regained a mean of only 12 +/- 6% and 8 +/- 5% of initial amplitude. The electrophysiological pattern of glycine injury was similar to the excitotoxic damage produced by 8 min exposure to sodium glutamate 9 mM. L-Histidine, an inhibitor of glycine transport, exacerbated glycine-induced injury, just as dihydrokainic acid, a glutamate transport inhibitor, exacerbated glutamate-induced injury. The anticonvulsant felbamate (1.3 mM), as well as 100 microM zinc chloride, provided excellent protection from glycine-induced injury. 7-Chlorokynurenic acid appeared to be toxic. Blockers of the NMDA-associated ionic channel and methyl arginine, prevented loss of neural transmission, but did not prevent accompanying hyperexcitability. Only 10 mM magnesium sulfate provided full protection against 9 mM glutamate exposure. Perfusion with low calcium ACSF protected against both glycine and glutamate-induced injury. Thus, exposure to glycine resembled the excitotoxic effects of glutamate, but showed a different profile of protection. These results suggest that glycine elevations as occur under physiologic and pathologic conditions may modulate neuronal activity.

Animals↗
PubMed2003

[Choanal atresia: therapeutic management and results in a series of 58 children].

INTRODUCTION: An error of table being slipped during the publication of this article in number 1 (2003), the Review republishes it in entirety for a better comprehension. The preceding reference must be replaced by this one: Rev Laryngol Otol Rhinol 2003;124,3:139-143. OBJECTIVES: To assess and compare long term results after surgical correction (transnasal or transpalatine approaches) of unilateral or bilateral choanal atresia, in children with or without associated anomalies. PATIENTS: During a 13-year period, 58 children were included in this retrospective study. Seventy-five choanas were operated on (41 unilateral and 17 bilateral). The transpalatine approach was performed in 41 children (56 choanas) while the transnasal approach was performed in 17 patients (19 choanas). Associated anomalies were reported in 28 children and corresponded to CHARGE association in 13 cases. RESULTS: With a mean follow-up of 7 years, perfect choanal permeability was reported in 90% of children operated on through a transpalatine approach and in 76% of children with a transnasal approach. A complementary therapeutic procedure was required in 54% of transpalatine approaches and 46% of transnasal approaches to yield these results. Postoperative choanal permeability was obtained in 93% of children without an associated anomaly and in 77% of those with associated anomalies, such as in 88% of unilateral atresias and 80% of bilateral ones. CONCLUSION: Initial success rate after surgery is similar for all surgical procedure insofar as nearly half choanas required a complementary therapeutic procedure. The endonasal procedure using the microdebrider appears hopeful and the KTP laser is interesting in fibrous residual stenosis. Associated anomalies are factors which lower general prognosis while inducing a higher surgical failure rate.

Abnormalities, Multiple↗
PubMed1988

Potential role of proteolysis in the control of UvrABC incision.

UvrB is specifically proteolyzed in Escherichia coli cell extracts to UvrB*. UvrB* is capable of interacting with UvrA in an apparently similar manner to the UvrB, however UvrB* is defective in the DNA strand displacement activity normally displayed by UvrAB. Whereas the binding of UvrC to a UvrAB-DNA complex leads to DNA incision and persistence of a stable post-incision protein-DNA complex, the binding of UvrC to UvrAB* leads to dissociation of the protein complex and no DNA incision is seen. The factor which stimulates this proteolysis has been partially purified and its substrate specificity has been examined. The protease factor is induced by "stress" and is under control of the htpR gene. The potential role of this proteolysis in the regulation of levels of active repair enzymes in the cell is discussed.

DNA Damage↗
PubMed1992

Attenuation of luteinizing hormone secretory burst amplitude as a proximate basis for the hypoandrogenism of healthy aging in men.

To evaluate the impact of healthy aging on specific features of endogeneous LH secretion and clearance, we applied deconvolution analysis to 24-h serum immunoradiometric LH concentration series obtained in normal men whose ages ranged from 21-73 yr. Deconvolution analysis was employed to quantitate the number, amplitude, duration, and mass of individual LH secretory bursts underlying the serum LH concentration profiles, and simultaneously estimate the half-life of LH in individual men. Plasma total and free testosterone and estradiol concentrations and body mass index (a measure of relative adiposity) were studied as possible significant covariates of age and LH secretion. We found that age was a negative determinant of LH secretory burst amplitude (r = -0.519, P = 0.013), and a positive predictor of LH secretory burst frequency (r = +0.435, P = 0.043) and basal LH secretory rates (r = +0.486, P = 0.029). Increasing age also correlated positively with LH secretory burst half-duration (duration of the secretory event at half-maximal amplitude, r = +0.656, P less than 0.001). In contrast, age did not relate to daily pulsatile LH production rate, the mass of LH secreted per burst, or the mean (24-h) serum concentration of immunoradiometric LH. Age correlated negatively with serum free testosterone (r = -0.622, P = 0.0034) but not estradiol concentrations. The serum free testosterone concentration also declined significantly with increasing body mass index (r = -0.519, P = 0.023). Although there were strong combined effects of age, body mass index, and LH secretory burst amplitude on serum free testosterone concentrations (P = 0.0006, multi-r value 0.820), LH secretory burst amplitude was the most prominent single determinant of blood androgen concentrations.

Adult↗