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Biomedical subjects

G M Rosen

Publications and source records attributed to G M Rosen.

At least 19 recordsLinked to original sources
PubMed2001

Feasibility of using unattended polysomnography in children for research--report of the Tucson Children's Assessment of Sleep Apnea study (TuCASA).

STUDY OBJECTIVES: The Tucson Children's Assessment of Sleep Apnea study (TuCASA) is designed to investigate the prevalence and correlates of objectively measured sleep-disordered breathing in pre-adolescent children. This paper documents the methods and feasibility of attaining quality unattended polysomnograms in the first 162 TuCASA children recruited. DESIGN: A prospective cohort study projected to enroll 500 children between 5 and 12 years of age who will undergo unattended polysomnography, neurocognitive evaluation, and physiological and anatomical measurements thought to be associated with sleep-disordered breathing. SETTING: Children are recruited through the Tucson Unified School District. Polysomnograms and anthropometric measurements are completed in the child's home. PARTICIPANTS: Of the 157 children enrolled in TuCASA, there were 100 children (64%) between 5-8 years old and 57 children (36%) between the ages of 9 to 12. There were 74 (47%) Hispanic children, and 68 (43%) female participants. INTERVENTIONS: N/A. MEASUREMENTS & RESULTS: Technically acceptable studies were obtained in 157 children (97%). The initial pass rate was 91%, which improved to 97% when 9 children who failed on the first night of recording completed a second study which was acceptable. In 152 studies (97%), greater than 5 hours of interpretable respiratory, electroencephalographic, and oximetry signals were obtained. The poorest signal quality was obtained from the chin electromyogram and from the combination thermister/nasal cannula. Parents reported that 54% of children slept as well as, or better than usual, while 40% reported that their child slept somewhat worse than usual. Only 6% were observed to sleep much worse than usual. Night-to-night variability in key polysomnographic parameters (n=10) showed a high degree of reproducibility on 2 different nights of study using identical protocols in the same child. In 5 children, polysomnograms done in the home were comparable to those recorded in a sleep laboratory. CONCLUSIONS: The high quality of data collected in TuCASA demonstrates that multi-channel polysomnography data can be successfully obtained in children aged 5-12 years in an unattended setting under a research protocol.

Anthropometry↗
PubMed2001

Differential effect of buffer on the spin trapping of nitric oxide by iron chelates.

Nitric oxide synthase (NOS) generates nitric oxide (NO*) by the oxidation of l-arginine. Spin trapping in combination with electron paramagnetic resonance (EPR) spectroscopy using ferro-chelates is considered one of the best methods to detect NO* in real time and at its site of generation. The spin trapping of NO* from isolated NOS I oxidation of L-arginine by ferro-N-dithiocarboxysarcosine (Fe(DTCS)2) and ferro-N-methyl-d-glucamide dithiocarbamate (Fe(MGD)2) in different buffers was investigated. We detected NO-Fe(DTCS)2, a nitrosyl complex, resulting from the reaction of NO* and Fe(DTCS)2, in phosphate buffer. However, Hepes and Tris buffers did not allow formation of NO-Fe(DTCS)2. Instead, both of these buffers reacted with Fe2+, generating sparingly soluble complexes in the absence of molecular oxygen. Fe(DTCS)2 and Fe(MGD)2 were found to inhibit, to a small degree, NOS I activity with a greater effect observed with Fe(MGD)2. In contrast, Fe(MGD)2 was more efficient at spin trapping NO* from the lipopolysaccharide-activated macrophage cell line RAW264.7 than was Fe(DTCS)2. Data suggested that Fe(DTCS)2 and Fe(MGD)2 are efficient at spin trapping NO* but their maximal efficiency may be affected by experimental conditions.

Animals↗
PubMed2001

Involvement of the perferryl complex of nitric oxide synthase in the catalysis of secondary free radical formation.

Neuronal nitric oxide synthase (NOS I) has been shown to generate nitric oxide (NO*) and superoxide (O(2)* during enzymatic cycling, and the ratio of each free radical is dependent upon the concentration of L-arginine. Using spin trapping and electron paramagnetic resonance spectroscopy, we detected alpha-hydroxyethyl radical (CH(3)*CHOH), produced during the NOS I metabolism of ethanol (EtOH). The generation of CH(3)*CHOH by NOS I was found to be Ca(2+)/calmodulin dependent. Superoxide dismutase prevented CH(3)*CHOH formation in the absence of L-arginine. However, in the presence of L-arginine, the production of CH(3)*CHOH was independent of O(2)* but dependent upon the concentration of L-arginine. Formation of CH(3)*CHOH was inhibited by substituting D-arginine for L-arginine, or inclusion of the NOS inhibitors N(G)-nitro-L-arginine methyl ester, N(G)-monomethyl-L-arginine and the heme blocker, sodium cyanide. The addition of potassium hydrogen persulfate to NOS I, generating the perferryl complex (NOS-[Fe(5+)=O](3+)) in the absence of oxygen and Ca(2+)/calmodulin, and EtOH resulted in the formation of CH(3)*CHOH. NOS I was found to produce the corresponding alpha-hydroxyalkyl radical from 1-propanol and 2-propanol, but not from 2-methyl-2-propanol. Data demonstrated that the perferryl complex of NOS I in the presence of L-arginine was responsible for catalyses of these secondary reactions.

Arginine↗
PubMed2001

"Echo attributions" and other risks when publishing on novel therapies without peer review.

A special series on Thought Field Therapy in the Journal of Clinical Psychology provides an opportunity for psychologists to learn about techniques and theories outside the mainstream of our field. Unfortunately, by publishing this series of manuscripts without meeting the standards of peer review, the Journal also provides an avenue for the misuse of its good reputation and the improper promotion of untested methods. "Echo attributions" can be made whereby an author attributes the source of his own words to the professional journal in which the text appears. Historical examples illustrate that such misuse of scientific journals and institutions occurs. A formal statement of guidelines is needed to instruct authors on appropriate versus unethical representations of their publications.

Advertising↗
PubMed2001

Tissue slices revisited: evaluation and development of a short-term incubation for integrated drug metabolism.

This work details the development of a model for the rapid evaluation of drug metabolism in an integrated fashion using in situ architecture of the liver. A Krumdieck tissue slicer was used to generate slices from 10-mm cores of rat liver (approximately 250-microm thick). Initial unsuccessful efforts with 6-well plate-based incubation were overcome with the use of a dynamic (rotating) incubation in 23-ml liquid scintillation vials containing titanium mesh supports for the slice. Incubation of 1 slice/5 ml of a Krebs-Henseleit solution buffered with HEPES showed a <2% increase over the initial 25% release of lactate dehydrogenase over 2 h of incubation at 37 degrees C under ambient oxygen conditions. Coupled O-dealkylase and conjugative metabolism of alkoxycoumarin derivatives was shown to be linear for both 7-methoxy- and 7-ethoxycoumarin (100 microM) with a low amount of nonconjugated 7-hydroxycoumarin (7-HC) at all time points. Metabolic profiles for 7-methoxy- and 7-ethoxycoumarin were compared between slice and microsomal incubations generated from the same tissue. The use of 7-HC as a primary substrate not only provided an assessment of the capacity-based differences in oxidative versus conjugative metabolism but also capacity-based differences in glucuronidation and sulfation. These studies underscore the physiological fact that phase I metabolism has a lower capacity for substrate metabolism than phase II metabolism. Additionally, this technique provides a model for examination of pharmacodynamic and pharmacokinetic influences in the context of maintenance of the in situ architecture of the liver.

Animals↗
PubMed2000

Role of paraquat in the uncoupling of nitric oxide synthase.

Nitric oxide synthase (NOS) oxidizes L-arginine to NO(&z.ccirf;) and L-citrulline. Recent studies have shown that this enzyme can also generate O(2)(&z.ccirf;-) during its enzymatic cycling. Herein, we used spin trapping and electron paramagnetic resonance (EPR) spectroscopy to investigate the impact paraquat has on the transport of electrons through purified neuronal NOS (NOS I). In a concentration-dependent manner, ranging from 10-100 microM of paraquat, paraquat free radical was observed under anaerobic conditions. This demonstrates that NOS shunts electrons to paraquat, thereby uncoupling this enzyme. This resulted in enhanced production of O(2)(&z.ccirf;-) at the expense of NO(&z.ccirf;). Experiments demonstrated that the reductase domain is the site of paraquat-mediated uncoupling of NOS.

Electron Spin Resonance Spectroscopy↗
PubMed2000

Stable expression of varied levels of inducible nitric oxide synthase in primary cultures of endothelial cells.

Nitric oxide (NO*), generated by nitric oxide synthase (NOS II) from immunostimulated cells during infection, plays an important role in host immune defense against microbial invasion. The impact of different rates of NO* production on host cell function has not been defined. Herein, we describe the development of a method to express varied levels of murine NOS II in bovine pulmonary artery endothelial cells. A retroviral vector (pMFGSNOS) encoding NOS II was used to transduce primary cultures of endothelial cells. Bovine endothelial cells were susceptible to this transduction and up to 18% of the cells expressed immunodetectable murine NOS II. The NOS II-transduced endothelial cells were cultured on the three-dimensional matrix, Gelfoam, for 8-10 days. Stable expression of NOS II was assessed by measuring nitrite accumulation in media every 2 days. By day 10, endothelial cells on Gelfoam were found to secrete NO* at a rate exceeding 1.0 microM/h/10(6) cells, concomitant with an enhanced level of NOS II activity. Argininosuccinate synthetase, a key enzyme in the metabolism of l-citrulline to l-arginine, increased as well, perhaps in response to dimunition of the intracellular arginine pool corresponding to the observed high output of NO*. In spite of the continuous flux of NO*, endothelial cell viability was not effected. This system provides the opportunity to assess the impact of different levels of sustained NO* production on endothelial cell physiology.

Animals↗
PubMed2000

Science and pseudoscience in the development of eye movement desensitization and reprocessing: implications for clinical psychology.

The enormous popularity recently achieved by Eye Movement Desensitization and Reprocessing (EMDR) as a treatment for anxiety disorders appears to have greatly outstripped the evidence for its efficacy from controlled research studies. The disparity raises disturbing questions concerning EMDR's aggressive commercial promotion and its rapid acceptance among practitioners. In this article, we: (1) summarize the evidence concerning EMDR's efficacy; (2) describe the dissemination and promotion of EMDR; (3) delineate the features of pseudoscience and explicate their relevance to EMDR; (4) describe the pseudoscientific marketing practices used to promote EMDR; (5) analyze factors contributing to the acceptance of EMDR by professional psychologists; and (6) discuss practical considerations for professional psychologists regarding the adoption of EMDR into professional practice. We argue that EMDR provides an excellent vehicle for illustrating the differences between scientific and pseudoscientific therapeutic techniques. Such distinctions are of critical importance for clinical psychologists who intend to base their practice on the best available research.

Anxiety Disorders↗
PubMed1999

Spin trapping of nitric oxide by ferro-chelates: kinetic and in vivo pharmacokinetic studies.

Biologically generated nitric oxide appears to play a pivotal role in the control of a diverse series of physiologic functions. Iron-chelates and low-frequency EPR spectroscopy have been used to verify in vivo production of nitric oxide. The interpretation of in vivo identification of nitric oxide localized at the site of evolution in real time is complicated by the varied kinetics of secretion. The quantitative efficiency of the spectroscopic measurement, so important in understanding the physiology of nitric oxide, remains elusive. The development of a more stable iron-chelate will help better define nitric oxide physiology. In this report, we present data comparing the commonly used ferro-di(N-methyl-D-glucamine-dithiocarbamate) (Fe2+(MGD)2) and the novel chelate ferro-di(N-(dithiocarboxy)sarcosine) (Fe2+(DTCS)2) quantifying the in vitro and in vivo stability of the corresponding spin trapped adducts, NO-Fe(MGD)2 and NO-Fe(DTCS)2. Finally, very low frequency EPR spectroscopy has been used to evaluate the pharmacokinetics of NO-Fe(MGD)2 and NO-Fe(DTCS)2 in mice in real time.

Drug Stability↗
PubMed1999

Mechanism of superoxide generation by neuronal nitric-oxide synthase.

Neuronal nitric-oxide synthase (NOS I) in the absence of L-arginine has previously been shown to generate superoxide (O-2) (Pou, S., Pou, W. S., Bredt, D. S., Snyder, S. H., and Rosen, G. M. (1992) J. Biol. Chem. 267, 24173-24176). In the presence of L-arginine, NOS I produces nitric oxide (NO.). Yet the competition between O2 and L-arginine for electrons, and by implication formation of O-2, has until recently remained undefined. Herein, we investigated this relationship, observing O-2 generation even at saturating levels of L-arginine. Of interest was the finding that the frequently used NOS inhibitor NG-monomethyl L-arginine enhanced O-2 production in the presence of L-arginine because this antagonist attenuated NO. formation. Whereas diphenyliodonium chloride inhibited O-2, blockers of heme such as NaCN, 1-phenylimidazole, and imidazole likewise prevented the formation of O-2 at concentrations that inhibited NO. formation from L-arginine. Taken together these data demonstrate that NOS I generates O-2 and the formation of this free radical occurs at the heme domain.

Arginine↗
PubMed1998

Effect of trifluoromethyl ketone-based elastase inhibitors on neutrophil function in vitro.

Neutrophils release elastase, which is known secondarily to cause tissue damage. However, it is rapidly inactivated by the endogenous alpha1-proteinase inhibitor (alpha1Pi). Nevertheless, under pathological conditions, alpha1i is inactivated by oxidants released from neutrophils, resulting in an excess of elastase at the site of inflammation. This elastase/alpha1Pi imbalance has been implicated as a pathogenic factor in cystic fibrosis, acute respiratory distress syndrome, and emphysema. Elastase inhibitors, which do not interfere with the microbicidal activity of neutrophils and are resistant to neutrophil-released oxidants, would undoubtedly represent an important advance in the management of neutrophil-mediated tissue injury. We report that a new family of elastase inhibitors ICI200355 and ZD0892 was found to be resistant toward superoxide, hypochlorous acid, hydrogen peroxide, hydroxyl radical, and peroxynitrite mediated degradation as well as having no effect on the formation of these oxidants by activated neutrophils. More importantly, we found that these inhibitors did not interfere with the ability of human neutrophils to phagocytose and to kill Staphylococcus aureus. In conclusion, a new potent class of elastase inhibitors, while blocking the effects of neutrophil elastase, was found not to impede various physiological functions of human neutrophils, in particular the ability of these phagocytic cells to phagocytose and kill bacteria.

Cell Survival↗
PubMed1997

MRI contrast enhanced study of cartilage proteoglycan degradation in the rabbit knee.

Early degeneration of cartilage is accompanied by a loss of proteoglycans and consequent changes in the content of water. Conventional magnetic resonance imaging (MRI) cannot reliably detect this change, since the relaxation properties of the cartilage are dominated by its collagen content. The applicability of a positively charged nitroxide as an MRI contrast agent in detection of the content of the negatively charged proteoglycans within the cartilage was investigated. The results from both MRI and electron paramagnetic resonance (EPR) spectroscopy indicate that the accumulation of the contrast agent reflects the amount of proteoglycans within the cartilage, presumably due to the electrostatic interactions between the negatively charged proteoglycans and the positively charged nitroxide. Such a contrast agent could be useful in the detection and study of early stages of the degeneration of joints.

Animals↗
PubMed1997

Welch's comments on Shapiro's walk in the woods and the origin of eye movement desensitization and reprocessing.

Welch's (Journal of Behavior Therapy and Experimental Psychiatry, 27, 175-179, 1996) response to Rosen's (Journal of Behavior Therapy and Experimental Psychiatry, 26, 121-122, 1995) limited study on the origin of eye movement desensitization and reprocessing (EMDR) does not resolve how best to interpret what Shapiro experienced during her reported walk in the woods. References cited by Welch actually argue against the conclusions he advances.

Humans↗
PubMed1997

Are free radicals responsible for endothelial cell killing of Staphylococcus aureus?

We have recently demonstrated that endothelial cells cultured on Gelfoam blocks, but not monolayer matrices can phagocytose and kill Staphylococcus aureus. Experiments determined that penicillin G, included in the endothelial cell growth medium, induces these cells to exhibit the observed bactericidal activity. In this communication, we report on studies aimed at elucidating the mechanism by which penicillin G-induced endothelial cells, cultured on Gelfoam blocks, kill S. aureus. Despite the fact that there is a substantial literature that demonstrates neutrophilic killing of bacteria can be mediated through free radical-dependent and free radical-independent mechanisms, considerably less is known about pathways by which endothelial cells can catalyze similar microbicidal activities. Studies described herein point to the fact that superoxide and products derived from this free radical were not responsible for endothelial killing of S. aureus. Likewise, a possible role for nitric oxide in bacterial killing was explored. As part of this inquiry, we stably transduced a NOS-2 encoding retrovirus into endothelial cells cultured on Gelfoam blocks in the absence of penicillin G. Even though these cells secreted nitric oxide at a rate of 0.5 microM/h per 1 x 10(6) cells, similar to what has been reported for murine macrophages induced with gamma-interferon, in our model, nitric oxide was not found to kill S. aureus. Data presented demonstrate that the microbicidal activity of endothelial cells is mediated through free radical-independent pathways.

Animals↗