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Biomedical subjects

R E Moore

Publications and source records attributed to R E Moore.

At least 37 records · Page 2Linked to original sources

Sexual attitudes and associated psychiatric features among youths in a community sample.

OBJECTIVE: Using an epidemiological sample of adolescents, this study examined associations between the acceptability of potential sex partners and psychiatric status. METHOD: Subjects aged 14 to 17 years (N = 161) from the Columbia site of the National Institute of Mental Health (NIMH) Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) Study were grouped according to their responses about the acceptability of youths their age having sex with partners of (1) the opposite sex, (2) neither sex, and (3) either sex. Youths endorsing either sex were compared with youths endorsing the other two types of partners according to psychiatric indicators obtained from the Diagnostic Interview Schedule for Children Version 2.3. RESULTS: Higher-than-expected proportions of male and female youths endorsed sex partners of either sex as potentially acceptable for peers. Youths who did so abused substances and used mental health services more than peers but did not differ in rates of suicidal ideation or attempts. Males endorsing either sex also had higher rates of mood disorders and, compared with males endorsing only the opposite sex, a higher intelligence level. CONCLUSIONS: Attitudes about the potential acceptability of sex partners for peers are associated with psychiatric morbidity and mental health service use in the respondent as well as with intelligence level in males. Youths who endorsed potential sex partners of either sex, especially males, appear to be at higher risk for multiple psychiatric problems.

Adolescent↗

Quantitative determination of cholesterol in lipoprotein fractions by electrophoresis.

The Helena REP cholesterol profile system (Helena Laboratories, Beaumont, TX) separates VLDL, LDL, HDL and Lp(a) by agarose gel electrophoresis, and quantitates cholesterol by enzymatic staining and densitometry. We compared results by electrophoresis to combined ultracentrifugation/precipitation (beta-quantification, BQ) for VLDL, LDL, and HDL cholesterol and to immunonephelometry for Lp(a) mass (Behring Diagnostics, Westwood, MA) in serum from 64 patients with a variety of lipid disorders. There was good agreement between methods, with a mean bias of -0.19 (-7.3), 0.09 (3.5), and 0.09 (3.4) mmol/l (mg/dl) for VLDL, HDL, and LDL cholesterol for electrophoresis vs. BQ. These differences were significant for HDL and VLDL cholesterol (P < 0.001), but not for LDL cholesterol measurement (P > 0.05). There was also good correlation between methods with coefficients of 0.83, 0.92, 0.91, and 0.97 for VLDL, HDL, Lp(a), and LDL, respectively. Our data indicate that this method can accurately and precisely measure LDL cholesterol directly in fresh serum from patients with a wide range of triglyceride values. However, HDL cholesterol measurement did not meet NCEP guidelines for precision and accuracy. Also, the poor resolution of VLDL and LDL in some specimens is a concern.

Chemical Precipitation↗

Tumonoic acids, novel metabolites from a cyanobacterial assemblage of Lyngbya majuscula and Schizothrix calcicola.

Five new metabolites have been isolated from a lyngbyastatin 1- and dolastatin 12-producing assemblage of Lyngbya majuscula and Schizothrix calcicola collected at Tumon Bay, Guam. Structure elucidation employed 2D NMR techniques and chemical derivatization. These compounds have been assigned the trivial names tumonoic acids A (2), B (1), and C (5); methyl tumonoate A (3), and methyl tumonoate B (4). Compounds 1 and 4 were also found in a lyngbyastatin 1-producing strain of L. majuscula from Guam.

Cyanobacteria↗

Symplostatin 2: a dolastatin 13 analogue from the marine cyanobacterium Symploca hydnoides.

An analogue of dolastatin 13 (2) has been isolated from a marine cyanobacterium, Symploca hydnoides, collected near Guam. This new cyclic depsipeptide contains a L-methionine sulfoxide residue; however, the sulfoxide exists as both R- and S-forms, resulting in the doubling of several signals in the 1H and 13C NMR spectra. Structure elucidation required extensive application of 2-D NMR techniques such as COSY, HMQC, HMBC, and ROESY. The trivial name symplostatin 2 (1) has been assigned to the new metabolite and its isolation from S. hydnoides further supports the proposal that many compounds originally isolated from the sea hare Dolabella auricularia are most probably of cyanobacterial origin.

Amino Acids↗

Lyngbyastatin 2 and norlyngbyastatin 2, analogues of dolastatin G and nordolastatin G from the marine cyanobacterium Lyngbya majuscula.

Lyngbyastatin 2 (1) and norlyngbyastatin 2 (2), new cytotoxic analogues of dolastatin G (3) and nordolastatin G (4), respectively, have been isolated as constituents from a Guamanian variety of the marine cyanobacterium Lyngbya majuscula. Structure elucidation of these cyclic depsipeptides relied on extensive application of 2D NMR techniques. The finding of these new metabolites further supports the proposal that many compounds originally isolated from the sea hare Dolabella auricularia are most likely of cyanobacterial origin.

Animals↗

Depressive and disruptive disorders and mental health service utilization in children and adolescents.

OBJECTIVE: To examine the relationship of depressive and disruptive disorders with patterns of mental health services utilization in a community sample of children and adolescents. METHOD: Data were from the NIMH Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) Study. The sample consisted of 1,285 child (ages 9-17 years) and parent/guardian pairs. Data included child psychopathology (assessed by the Diagnostic Interview Schedule for Children), impairment, child need and use of mental health services, and family socioeconomic status. RESULTS: After adjusting for potential confounding factors, disruptive disorder was significantly associated with children's use of mental health services, but depressive disorder was not. For school-based services, no difference was found between the 2 types of disorders. Parents perceived greater need for mental health services for children with disruptive disorders than for those with depression. Conversely, depression was more related to children's perception of mental health service need than was disruptive disorder. CONCLUSIONS: The findings highlight the need for more effective ways to identify and refer depressed children to mental health professionals, the importance of improving school-based services to meet children's needs, and the necessity to better educate parents and teachers regarding the identification of psychiatric disorders, especially depression.

Adolescent↗

A microscale electrospray interface incorporating a monolithic, poly(styrene-divinylbenzene) support for on-line liquid chromatography/tandem mass spectrometry analysis of peptides and proteins.

A methodology is described for creating a monolithic chromatography support within a pulled fused-silica electrospray needle. The monolith was formed from a mixture of styrene, divinylbenzene, 1-dodecanol, and toluene using 2,2'-azobis(isobutyronitrile) as the catalyst. The mixture was loaded into 150-micron-i.d. fused-silica capillary tubing with a pulled 5-10-micron needle tip at one end. Polymerization at 65 degrees C followed by removal of the porogen material yielded a stable, porous, monolithic support which had excellent properties for the separation and on-line, electrospray, mass spectrometry analysis of peptides and proteins. The performance of the monolith-filled electrospray needles was compared with similar needles filled with commercial C18 silica and polymeric particulate supports. Separation efficiencies for both protein and peptide mixtures were generally equal to or better than the particulate supports at comparable pressures and flow rates. The ion chromatograms derived from the on-line MS analysis were remarkably free from chemical background signals that often complicate the LC/MS analysis of femtomole amounts of sample. Good sequence coverage was obtained by LC/MS/MS analysis of the peptide mixture obtained from a protein isolated by silver-stained gel electrophoresis. The capability of the monolith to do peak parking experiments was demonstrated by the characterization of an immunoreactive HPLC fraction. The simple fabrication method, chromatographic performance, and robust nature of these microscale integrated column electrospray sources make them ideally suited for high-sensitivity tandem LC/MS analyses.

Amino Acid Sequence↗

Isolation, structure determination, and biological activity of dolastatin 12 and lyngbyastatin 1 from Lyngbya majuscula/Schizothrix calcicola cyanobacterial assemblages.

Lyngbyastatin 1 (1a), a new cytotoxic analogue of dolastatins 12 (2a) and 11 (4), was isolated as an inseparable mixture with its C-15 epimer (1b) from extracts of a Lyngbya majuscula/Schizothrix calcicola assemblage and a L. majuscula strain collected near Guam. Dolastatin 12 (2a) was also encountered as an inseparable mixture with its C-15 epimer (2b) in L. majuscula/S. calcicola assemblages. At least one of the compounds in each mixture appeared to exist in solution as a mixture of slowly interconverting conformers resulting in broadened signals in 1H NMR spectra. Structure elucidation therefore relied principally on mass spectroscopy and chemical degradation studies. Both 1ab and 2ab proved toxic with only marginal or no antitumor activity when tested against colon adenocarcinoma #38 or mammary adenocarcinoma #16/C. Both 1ab and 2ab were shown to be potent disrupters of cellular microfilament networks.

Actin Cytoskeleton↗

Symplostatin 1: A dolastatin 10 analogue from the marine cyanobacterium Symploca hydnoides.

A new solid tumor selective cytotoxic analogue of dolastatin 10 (1) has been isolated from the marine cyanobacterium Symploca hydnoides, collected near Guam. This metabolite has been assigned the trivial name symplostatin 1 (2). This discovery supports the proposal that many compounds isolated from the seahare Dolabella auricularia, the original source of the dolastatins, are of dietary origin.

Antineoplastic Agents↗

Use of long RT-PCR to characterize splice variant mRNAs.

Recent advances in long reverse transcription (RT)-PCR technology allow the copying of full-length coding regions of large mRNAs in one step. Using long RT-PCR, one can be certain that a given cDNA is derived from a single mRNA. In what to our knowledge is a novel application, we can isolate and characterize splice variants for any given mRNA in a systematic manner. We optimized long RT-PCR to copy the full-length coding region of human multidrug resistance (MDR1) mRNA or the major vault protein (MVP) mRNA in one step, so that only one full-length PCR product was synthesized in each case. Such stringent conditions are necessary to ensure that smaller than full-length products derived from total cell RNA are true splice variants. Twenty MDR1 double-stranded (ds) cDNAs, isolated from either the full-length or one prominent splice-variant DNA band, visualized on agarose gels, were cloned and sequenced. Two were full-length, wild-type in sequence as expected, and the rest were splice-variant mRNAs. Fourteen of the clones were identical and encoded a prominent splice-variant mRNA that can be detected in two tumor cell lines. This approach is shown to be generally applicable to the systematic analysis of splice-variant mRNAs derived from any gene.

Alternative Splicing↗

Mechanism of action of the unusually potent microtubule inhibitor cryptophycin 1.

Cryptophycin 1 is a remarkably potent antiproliferative compound that shows excellent antitumor activity against mammary, colon, and pancreatic adenocarcinomas in mouse xenographs. At picomolar concentrations, cryptophycin 1 blocks cells in the G2/M phase of the cell cycle by an apparent action on microtubules. The compound binds to tubulin, inhibits microtubule polymerization, and depolymerizes preformed microtubules in vitro. Its exceptionally powerful antitumor activity (many-fold greater than paclitaxel or the vinca alkaloids) raises important questions about its mechanism of action. By quantitative video microscopy, we examined the effects of cryptophycin 1 on the dynamics of individual microtubules assembled to steady state from bovine brain tubulin. At low nanomolar concentrations, in the absence of net microtubule depolymerization, cryptophycin 1 potently stabilized microtubule dynamics. It reduced the rate and extent of microtubule shortening and growing and increased the frequency of rescue. The results suggest that cryptophycin 1 exerts its antiproliferative and antimitotic activity by binding reversibly and with high affinity to the ends of microtubules, perhaps in the form of a tubulin-cryptophycin 1 complex, resulting in the most potent suppression of microtubule dynamics yet described.

Animals↗

Running hard and falling behind: a welfare analysis of two-earner families.

"This paper investigates the commonly asserted proposition that long term economic changes have put the family in a financial bind. Structural parameters of a family utility model are obtained by estimating simultaneous labor supply functions for a two-earner household. We find evidence indicating that the average 1990s two-earner family would prefer to receive the 1980s real wage package (were it available) instead of the real wage package it actually faces. The degree to which the 1990s family is worse off (in terms of the changes in the real wage package) is roughly equivalent to an hour of leisure per week." The data are from the 1993 Current Population Survey and concern the United States.

Americas↗

Correlates of unmet need for mental health services by children and adolescents.

BACKGROUND: Little is known about the extent and correlates of unmet need for mental health services in community samples of children and adolescents. METHODS: Data were obtained from the 1285 parent/youth pairs interviewed at four sites in the USA and Puerto Rico in the Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) Study. Unmet need was defined to exist if psychopathology and associated functional impairment were present but no mental health services had been received in the previous 6 months. RESULTS: Of the total sample, 17.1% had unmet need. Adjusting for demographic variables, logistic regression analyses revealed that unmet need was significantly associated with: indicators of economic disadvantage, such as being on public assistance and not being covered by health insurance; opinions of the parents and children or adolescents that the latter had poor mental health; parental psychopathology; poor school grades; and parent-reported access barriers such as concern that the child would want to solve the problem unassisted, would refuse to attend mental health services, or would be hospitalized or taken away against the parent's will. No youth-reported access barriers were significantly associated with unmet need. CONCLUSIONS: The economic correlates of unmet need may attain increased importance in the light of current reform in health care financing in the USA. Access may be facilitated by increasing parental knowledge of mental health services and enabling children and adolescents to initiate contact with services independently of their families.

Adolescent↗

Three new cryptophycins from Nostoc sp. GSV 224.

Cryptophycin 46 (2), -175 (3), and -176(4) have been identified as three new trace constituents of Nostoc sp. GSV 224. Cryptophycin-46 is an epimer of cryptophycin-3 (5) and to date is the only naturally occurring analogue having the S configuration at C-10 (C-2 in Unit B). Cryptophycins-175 and -176 also differ in unit B where 3 is the O-methyl analogue of cryptophycin-45 (6) and 4 is the O-desmethyl analogue of cryptophycin-21 (8). The relative and absolute stereochemistries of the three new analogues have been related to known cryptophycins by synthesis.

Chromatography, High Pressure Liquid↗

Psychosocial characteristics of physically abused children and adolescents.

OBJECTIVE: To examine the association between physical abuse and selected psychosocial measures in a community-based probability sample of children and adolescents. METHOD: A sample of 9- through 17-year-olds (N = 665) and their caretakers in New York State and Puerto Rico were interviewed in the Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) Study. Assessments included the Columbia Impairment Scale, the Instrumental and Social Competence Scale, the Diagnostic Interview Schedule for Children, the Peabody Picture Vocabulary Test, and questions regarding physical abuse. Regression analyses were conducted controlling for family income, family psychiatric history, perinatal problems, physical health, and sexual abuse. RESULTS: A history of physical abuse was reported in 172 (25.9%) of the sample. It was significantly associated with global impairment, poor social competence, major depression, conduct disorder, oppositional defiant disorder, agoraphobia, overanxious disorder, and generalized anxiety disorder but not with suicidality, school grades, or receptive language ability. CONCLUSION: A community probability sample of children and adolescents demonstrated significant associations between physical abuse and psychopathology, after controlling for potential confounders. This supports comprehensive screening for psychopathology among physically abused children and for physical abuse among those with psychopathology. Interventions aimed at improving social competence may be indicated.

Adolescent↗

Cyclic peptides and depsipeptides from cyanobacteria: a review.

An elaborate array of structurally-novel and biologically-active cyclic peptides and depsipeptides are found in blue-green algae (cyanobacteria). Several of these compounds possess structures that are similar to those of natural products from marine invertebrates. Most of these cyclic peptides and depsipeptides, such as the microcystins and the lyngbyatoxins, will probably only be useful as biochemical research tools. A few, however, have the potential for development into useful commercial products. For example, cryptophycin-1, a novel inhibitor of microtubule assembly from Nostoc sp GSV 224, shows impressive activity against a broad spectrum of solid tumors implanted in mice, including multidrug-resistant ones, and majusculamide C, a microfilament-depolymerizing agent from Lyngbya majuscula, shows potent fungicidal activity and may have use in the treatment of resistant fungal-induced diseases of domestic plants and agricultural crops.

Amino Acid Sequence↗