Biomedical subjects

R E Moore

Publications and source records attributed to R E Moore.

At least 19 recordsLinked to original sources

PubMed2004

Minimally invasive incisional herniorrhaphy: a review of 208 cases.

BACKGROUND: Minimally invasive incisional herniorrhaphy has become an accepted approach for incisional hernia. However, the ideal technique for this procedure is not known. The authors present their technique and personal experience with minimally invasive incisional herniorrhaphy. METHODS: A retrospective review investigated 208 consecutive patients who underwent minimally invasive incisional hernia repair under the supervision of a single surgeon between 1995 and 2002. RESULTS: An intraperitoneal mesh repair was performed in all cases. There were no conversions. The mean operative time was 2.1 h (range, 0.8-4.5 h). The mean length of hospital stay was 2.5 days (range, 0-13 days). There were six complications, including two bowel perforations, and zero mortality. There were three recurrences during the follow-up period, which ranged from 6 to 72 months (median, 24 months). CONCLUSIONS: Minimally invasive incisional herniorrhaphy yielded an acceptable morbidity and recurrence rate during the follow-up period. The outcome compares favorably with that for open incisional hernia repair. Although long-term follow-up evaluation is desirable, the data support the contention that the minimally invasive approach is an appropriate option for incisional hernia.

Adult↗

PubMed2001

In vitro bioassays for anticancer drug screening: effects of cell concentration and other assay parameters on growth inhibitory activity.

In vitro growth inhibition assays were performed using human cancer cell lines at various concentrations with experimental anticancer drugs such as the cryptophycins and other cytotoxins. The effect of variations in assay parameters on the observed growth inhibition of these anticancer therapeutic agents was determined. The results demonstrated that the observed inhibitory activity of these compounds varied inversely with the cell concentrations used. The observed differences in activity between different cytotoxins were not necessarily proportionate. Thus, the relative activities of two toxins also varied with cell concentration. Furthermore, the sensitivity of these cell lines to the cytostatic purine analog, 6-mercaptopurine (used as a control), varied with cell concentration as well. The activity of this compound was dependent on the medium used for cell growth, yielding good activity in Eagle's minimum essential medium, but not in Ham's F-12 (Kaigin) medium. Moreover, growth inhibition by cryptophycin as well as 6-mercaptopurine was also dependent on the serum concentration in the medium. Finally, the sensitivity of the cancer cell lines to various organic solvents commonly used as drug vehicles for in vitro testing, such as ethanol, dimethylformamide, and dimethylsulfoxide, was likewise found to vary inversely with cell concentration.

Antineoplastic Agents↗

PubMed2001

Total structure determination of apratoxin A, a potent novel cytotoxin from the marine cyanobacterium Lyngbya majuscula.

Apratoxin A (1), a potent cytotoxin with a novel skeleton, has been isolated from the marine cyanobacterium Lyngbya majuscula Harvey ex Gomont. This cyclodepsipeptide of mixed peptide-polyketide biogenesis bears a thiazoline ring flanked by polyketide portions, one of which possesses an unusual methylation pattern. Its gross structure has been elucidated by spectral analysis, including various 2D NMR techniques. The absolute configurations of the amino acid-derived units were determined by chiral HPLC analysis of hydrolysis products. The relative stereochemistry of the new dihydroxylated fatty acid unit, 3,7-dihydroxy-2,5,8,8-tetramethylnonanoic acid, was elucidated by successful application of the J-based configuration analysis originally developed for acyclic organic compounds using carbon-proton spin-coupling constants ((2,3)J(C,H)) and proton-proton spin-coupling constants ((3)J(H,H)); its absolute stereochemistry was established by Mosher analysis. The conformation of 1 in solution was mimicked by molecular modeling, employing a combination of distance geometry and restrained molecular dynamics. Apratoxin A (1) possesses IC(50) values for in vitro cytotoxicity against human tumor cell lines ranging from 0.36 to 0.52 nM; however, it was only marginally active in vivo against a colon tumor and ineffective against a mammary tumor.

Adenocarcinoma↗

PubMed2001

Osteoclasts secrete the chemotactic cytokine mim-1.

Osteoclasts are terminally differentiated, multinucleated cells of monocytic origin. In this study, we report that osteoclasts secrete a 35 kD protein and that phorbol myristate acetate treatment stimulates secretion dramatically. Peptide digests of the protein were analyzed by mass spectroscopy. The protein was identified as myb induced myeloid protein-1 precursor (mim-1 protein). Mim-1 is expressed specifically by hematopoietic cells and has no known function. It is homologous with the neutrophil chemokine, chondromodulin II, which stimulates proliferation of osteoblasts and chondrocytes. Western analysis showed that osteoclasts secrete mim-1 into culture media. Immunofluorescence studies demonstrated a cytoplasmic and perinuclear distribution of mim-1 in both avian osteoclasts and human osteoclast-like cells. Expression and secretion of a chemokine-like protein by osteoclasts suggests a novel signaling pathway in the bone microenvironment that may be involved in coordinating bone remodeling.

Acetyltransferases↗

PubMed2001

Isolation and structure determination of nostocyclopeptides A1 and A2 from the terrestrial cyanobacterium Nostoc sp. ATCC53789.

The isolation and total structure determination of nostocyclopeptides A1 (1) and A2 (2) are described. These cyclic heptapeptides, which possess a unique imino linkage in the macrocyclic ring, are characteristic constituents of the cryptophycin-producing cyanobacterium Nostoc sp. ATCC53789. 1D TOCSY experiments proved to be very useful in identifying the seven amino acid residues in each compound, and HMBC and NOESY correlations made it possible to sequence the seven units into a total gross structure. The absolute stereochemistry was determined by directly comparing the amino acids in the acid hydrolyzate of each natural product and its peroxide oxidation and borohydride reduction products with authentic standards. Studies were carried out on the biosynthesis and initiated on the biological activity of these cyclic peptides.

Antibiotics, Antineoplastic↗

PubMed2001

Pitipeptolides A and B, new cyclodepsipeptides from the marine cyanobacterium Lyngbya majuscula.

Two new cyclodepsipeptides have been isolated from a population of the marine cyanobacterium Lyngbya majuscula collected at Piti Bomb Holes, Guam. They appear to be unique to this particular Guamanian collection and have been named pitipeptolides A (1) and B (2). Their structures have been elucidated by spectroscopic techniques and by characterization of degradation products. Distinctive features include the presence of a 2,2-dimethyl-3-hydroxy-7-octynoic acid residue in 1 and a 2,2-dimethyl-3-hydroxy-7-octenoic acid residue in 2, previously shown to be biosynthetic signatures of cyanobacterial metabolites. Pitipeptolides A (1) and B (2) exhibit weak cytotoxicity against LoVo cancer cells, but possess moderate antimycobacterial activity and stimulate elastase activity.

Cyanobacteria↗

PubMed2001

Isolation of dolastatin 10 from the marine cyanobacterium Symploca species VP642 and total stereochemistry and biological evaluation of its analogue symplostatin 1.

The potent antitumor agent dolastatin 10 (1) was originally isolated from the sea hare Dolabella auricularia, and we now report its isolation from the marine cyanobacterium Symploca sp. VP642 from Palau. The chemically related analogue symplostatin 1 (2) has been reisolated from Guamanian and Hawaiian varieties of S. hydnoides and its total stereochemistry completed by determining the N,N-dimethylisoleucine unit to be L. Symplostatin 1 (2), like dolastatin 10 (1), is a potent microtubule inhibitor. The antitumor activity of 2 was assessed in vivo against several murine tumors. Symplostatin 1 (2) was effective against a drug-insensitive mammary tumor and a drug-insensitive colon tumor; however, it was only slightly effective against two MDR tumors.

Animals↗

PubMed2001

Factors associated with use of mental health services for depression by children and adolescents.

OBJECTIVE: This study examined patterns of mental health service use among depressed children and adolescents and factors associated with help seeking and treatment modalities. METHODS: The sample consisted of 206 children and adolescents aged 9 to 17 years who were assessed as part of a larger survey of mental health service use in five service systems and in the community and who met DSM-III-R criteria for depressive disorders (major depression or dysthymia). RESULTS: Among the 206 children, 75 (36 percent) never received professional help for depressive symptoms. Among the 131 children who received professional help for depression, antidepressants were prescribed for 40 (31 percent) in the year before the interview. The findings indicate possible undertreatment of depression among children and adolescents, especially among African Americans. Socioeconomic factors, such as the mother's education and the child's health insurance, were not associated with receiving professional help for depressive symptoms but were associated with receiving antidepressants. Parental perception of a child's mental health service need was associated with receiving professional help but not with receiving antidepressants. Also, depressed children were more likely to receive antidepressants when they had life-threatening or severe symptoms, such as a suicide attempt or drug abuse. CONCLUSIONS: Whether a depressed child receives mental health services and the types of treatment received are influenced by different individual and family factors and by the type of symptoms exhibited. Better understanding of these factors will help in meeting the service needs of depressed children and adolescents.

Adolescent↗

PubMed2001

Biochemical and genetic analyses of the U5, U6, and U4/U6 x U5 small nuclear ribonucleoproteins from Saccharomyces cerevisiae.

We have purified the yeast U5 and U6 pre-mRNA splicing small nuclear ribonucleoproteins (snRNPs) by affinity chromatography and analyzed the associated polypeptides by mass spectrometry. The yeast U5 snRNP is composed of the two variants of U5 snRNA, six U5-specific proteins and the 7 proteins of the canonical Sm core. The U6 snRNP is composed of the U6 snRNA, Prp24, and the 7 Sm-Like (LSM) proteins. Surprisingly, the yeast DEAD-box helicase-like protein Prp28 is stably associated with the U5 snRNP, yet is absent from the purified U4/U6 x U5 snRNP. A novel yeast U5 and four novel yeast U4/U6 x U5 snRNP polypeptides were characterized by genetic and biochemical means to demonstrate their involvement in the pre-mRNA splicing reaction. We also show that, unlike the human tri-snRNP, the yeast tri-snRNP dissociated upon addition of ATP or dATP.

Adenosine Triphosphate↗

PubMed2000

The role of the FRE family of plasma membrane reductases in the uptake of siderophore-iron in Saccharomyces cerevisiae.

Saccharomyces cerevisiae takes up siderophore-bound iron through two distinct systems, one that requires siderophore transporters of the ARN family and one that requires the high affinity ferrous iron transporter on the plasma membrane. Uptake through the plasma membrane ferrous iron transporter requires that the iron first must dissociate from the siderophore and undergo reduction to the ferrous form. FRE1 and FRE2 encode cell surface metalloreductases that are required for reduction and uptake of free ferric iron. The yeast genome contains five additional FRE1 and FRE2 homologues, four of which are regulated by iron and the major iron-dependent transcription factor, Aft1p, but whose function remains unknown. Fre3p was required for the reduction and uptake of ferrioxamine B-iron and for growth on ferrioxamine B, ferrichrome, triacetylfusarinine C, and rhodotorulic acid in the absence of Fre1p and Fre2p. By indirect immunofluorescence, Fre3p was expressed on the plasma membrane in a pattern similar to that of Fet3p, a component of the high affinity ferrous transporter. Enterobactin, a catecholate siderophore, was not a substrate for Fre3p, and reductive uptake required either Fre1p or Fre2p. Fre4p could facilitate utilization of rhodotorulic acid-iron when the siderophore was present in higher concentrations. We propose that Fre3p and Fre4p are siderophore-iron reductases and that the apparent redundancy of the FRE genes confers the capacity to utilize iron from a variety of siderophore sources.

Carrier Proteins↗

PubMed2000

Siderophore-iron uptake in saccharomyces cerevisiae. Identification of ferrichrome and fusarinine transporters.

A family of four putative transporters (Arn1p-4p) in Saccharomyces cerevisiae is expressed under conditions of iron deprivation and is regulated by Aft1p, the major iron-dependent transcription factor in yeast. One of these, Arn3p/Sit1p, facilitates the uptake of ferrioxamine B, a siderophore of the hydroxamate class. Here we report that ARN family members facilitated the uptake of iron from the trihydroxamate siderophores ferrichrome, ferrichrome A, and triacetylfusarinine C. Uptake of siderophore-bound iron was dependent on either the high-affinity ferrous iron transport system or the ARN family of transporters. The specificity of each siderophore for individual transporters was determined. Uptake of ferrichrome and ferrichrome A was facilitated by both Arn1p and Arn3p. Uptake of triacetylfusarinine C was facilitated by Arn2p, although small amounts of uptake also occurred through Arn1p and Arn3p. In contrast to the trihydroxamates, uptake of iron from the dihydroxamate rhodotorulic acid occurred only via the high-affinity ferrous iron system. Epitope-tagged Arn1p was expressed in intracellular vesicles in a pattern that was indistinguishable from that of Arn3p, whereas Ftr1p, a component of the high-affinity ferrous system, was expressed on the plasma membrane. These data indicate that S. cerevisiae maintains two systems of siderophore uptake, only one of which is located on the plasma membrane.

Biological Transport↗

PubMed2000

Synthesis of cryptophycin 52 using the sharpless asymmetric dihydroxylation: diol to epoxide transformation optimized for a base-sensitive substrate.

A synthesis of cryptophycin 52 (2) is reported using a Sharpless asymmetric dihydroxylation (AD) strategy to install the epoxide moiety. The high stereoselectivity of the AD reaction that allows for an efficient means of preparing the epoxide is in contrast to the standard direct epoxidation of cryptophycin substrates, which proceeds with poor diastereoselectivity. Methodology for conversion of the diol AD product to the requisite epoxide is disclosed. The transformation has been optimized to proceed in high yield in the presence of base sensitive functionality.

Antineoplastic Agents↗

PubMed2000

Seasonal variations in internalizing, externalizing, and substance use disorders in youth.

Seasonal variations were assessed in symptoms of internalizing (anxiety and mood), externalizing (attention-deficit/hyperactivity and oppositional defiant disorders), and substance use disorders in youth. This study is based on secondary data analysis of two NIMH-funded epidemiologic-services studies: (a) Alternative Service Use Patterns by Youth with Serious Emotional Disturbance (N=936, ages 9-17); and (b) Methods for the Epidemiology of Child and Adolescent Mental Disorders (N=1285, ages 9-17). Child psychiatric diagnoses were measured by the Diagnostic Interview Schedule for Children. Variables that indicate site of the interview and service system, as well as age, gender, and ethnicity, were used as covariates. Significant annual variations were found in symptom counts of overanxious disorder, obsessive-compulsive disorder, separation anxiety disorder, social phobia, and major depressive disorder, with the estimated nadir in August-October. There may be weak seasonal variations in attention-deficit/hyperactivity disorder with estimated nadir in August, oppositional defiant disorder with estimated nadir in August-September, and marijuana use with estimated zenith in August-September. Significant seasonality in alcohol, other substance use, agoraphobia, and panic disorder was not found. There may be an instrument-specific bias in estimated nadir. Real nadirs may be up to 3 months prior to the estimated nadirs specified above. Findings suggest that seasonality in symptoms should be considered when assessment instruments of childhood psychiatric disorders are developed, as well as when epidemiological and clinical data are collected and analyzed.

Adolescent↗

PubMed2000

Biosynthesis of cylindrospermopsin.

Studies on the biosynthesis of cylindrospermopsin (1), a potent hepatotoxin associated with the cyanobacterium Cylindrospermopsis raciborskii, indicate that 1 is an acetogenin with guanidinoacetic acid serving as the starter unit of the polyketide chain. Feeding experiments show that C14 and C15 of 1 are derived from C1 and C2 of glycine, respectively, and C4 through C13 arise from five contiguous acetate units attached head to tail. The methyl carbon on C13 originates from the C(1) pool. The starter unit, established by the incorporation of [guanidino-(13)C,alpha-(15)N]-guanidinoacetic acid into N16 and C17 of 1, does not appear to be formed from glycine by known amidination pathways. The origin of the NH-CO-NH segment in the uracil ring is also unknown.

Alkaloids↗

PubMed2000

Method for screening peptide fragment ion mass spectra prior to database searching.

A methodology is described for screening fragment ion spectra of peptides prior to database searching for protein identification. A software routine written in the Perl programming language was used to analyze data from previous Sequest database searches and develop a set of statistical descriptors that could be used to identify spectra not likely to yield useful results in a database search. A second Perl program used an evolutionary algorithm to optimize the criteria for each statistical descriptor and generate a formula for determining spectral quality. This formula was used by a third Perl program to screen data sets from four independent liquid chromatography tandem mass spectrometry runs. On the average, use of the screening program reduced the time required for a database search by 1/2 with little loss of useful information from the database search results.

Algorithms↗

PubMed2000

Apramides A-G, novel lipopeptides from the marine cyanobacterium Lyngbya majuscula.

Six new metabolites have been isolated from a lyngbyastatin 2-producing strain of the marine cyanobacterium Lyngbya majuscula collected at Apra Harbor, Guam, and their structures elucidated. These linear lipopeptides have been assigned the trivial names apramides A-F (1-6). From a more recent collection of this cyanobacterium, a structurally related compound, apramide G (7), has been found instead of apramides A-F (1-6). Structure elucidation of the lipopeptides 1-7 is based on spectroscopic techniques and chiral chromatography of hydrolysis products. The apramides appear as NMR-spectroscopically distinguishable conformers in solution, and this has been ascribed to the presence of a thiazole-containing modified amino acid unit.

Chromatography, Gel↗

PubMed2000

Isolation and structure of the cytotoxin lyngbyabellin B and absolute configuration of lyngbyapeptin A from the marine cyanobacterium Lyngbya majuscula.

An analogue of the potent microfilament-disrupter lyngbyabellin A (1) has been isolated as a minor metabolite from the marine cyanobacterium Lyngbya majuscula collected at Apra Harbor, Guam. It possesses slightly weaker cytotoxicity than 1 and has been named lyngbyabellin B (2). Primarily NMR spectroscopy was used to determine its structure. The absolute configuration of 2 has been ascertained by chiral HPLC analysis of degradation products and by comparison with lyngbyabellin A (1). The known modified tetrapeptide lyngbyapeptin A (3) has also been found in the same extract, and its absolute stereochemistry could be determined for the first time.

Bacterial Toxins↗

PubMed2000

Isolation, structure determination, and biological activity of Lyngbyabellin A from the marine cyanobacterium lyngbya majuscula.

Lyngbyabellin A (1), a significantly cytotoxic compound with unusual structural features, was isolated from a Guamanian strain of the marine cyanobacterium Lyngbya majuscula. This novel peptolide is structurally related to dolabellin (2) in that both depsipeptides bear a dichlorinated beta-hydroxy acid and two functionalized thiazole carboxylic acid units. Its gross structure has been elucidated by spectral analysis, including 2D NMR techniques. The absolute stereochemistry of 1 was determined by chiral HPLC analysis of hydrolysis products and by characterization of the degradation products methyl 7,7-dichloro-3-hydroxy-2,2-dimethyloctanoate (3) and the corresponding acid 4. The total structure was further supported by molecular modeling studies. The isolation of 1 from L. majuscula once more supports the proposal that many compounds originally isolated from the sea hare Dolabella auricularia are of cyanobacterial origin. Lyngbyabellin A (1) was shown to be a potent disrupter of the cellular microfilament network.

Antineoplastic Agents↗