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M Goodman

Publications and source records attributed to M Goodman.

At least 55 records · Page 3Linked to original sources

Molecular evolution of cytochrome c oxidase subunit I in primates: is there coevolution between mitochondrial and nuclear genomes?

Phylogenetic analyses carried out on cytochrome c oxidase (COX) subunit I mitochondrial genes from 14 primates representing the major branches of the order and four outgroup nonprimate eutherians revealed that transversions and amino acid replacements (i.e., the more slowly occurring sequence changes) contained lower levels of homoplasy and thus provided more accurate information on cladistic relationships than transitions (i.e., the more rapidly occurring sequence changes). Several amino acids, each with a high likelihood of functionality involving the binding of cytochrome c or interaction with COX VIII, have changed in Anthropoidea, the primate suborder grouping New World monkey, Old World monkey, ape, and human lineages. They are conserved in other mammalian lineages and in nonanthropoid primates. Maximum-likelihood ancestral COX I nucleotide sequences were determined utilizing a near most parsimonious branching arrangement for the primate sequences that was consistent with previously hypothesized primate cladistic relationships based on larger and more diverse data sets. Relative rate tests of COX I mitochondrial sequences showed an elevated nonsynonymous (N) substitution rate for anthropoid-nonanthropoid comparisons. This finding for the largest mitochondrial (mt) DNA-encoded subunit is consistent with previous observations of elevated nonsynonymous substitution/synonymous substitution (S) rates in primates for mt-encoded COX II and for the nuclear-encoded COX IV and COX VIIa-H. Other COX-related proteins, including cytochrome c and cytochrome b, also show elevated amino acid replacement rates or N/S during similar time frames, suggesting that this group of interacting genes is likely to have coevolved during primate evolution.

Amino Acid Sequence↗

Impulsive aggression in borderline personality disorder.

Impulsive aggressive behaviors that include physical aggression directed towards others, self-mutilation, suicide attempts, domestic violence, substance abuse, and property destruction account for a substantial portion of the morbidity and mortality associated with personality disorders, in particular borderline personality disorder (BPD). Recent genetic, neurobiologic, and diagnostic studies suggest a dimensional approach to BPD symptomatology with impulsive aggression as one of the core dimensions for the disorder. The underlying biologic basis for impulsive aggression is centered on the serotonin hypothesis; that central 5-HT function is inversely related to aggression and suicidality. More recent research refines the theory to include associated brain regions, receptor types and neuromodulators potentially involved in the etiology of aggressivity. Treatment utilizes this information with substantial progress in well-designed placebo-controlled studies of selective serotonin reuptake inhibitors such as fluoxetine, and open-label series of atypical neuroleptics, mood stabilizers, and opioid antagonists

Aggression↗

Predictors of operative outcome in patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome.

BACKGROUND: Plasma viral load has recently been associated with clinical outcome in patients with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). We hypothetized that, in addition to CD4 lymphocytes, plasma HIV-1 RNA counts are predictive of postoperative outcome. METHODS: HIV-infected and AIDS patients admitted to a major teaching hospital requiring invasive or surgical procedures were retrospectively analyzed for postoperative outcome. Preoperative and postoperative immune cell counts including plasma HIV-1 RNA counts were recorded. Chi-square analysis, Fisher's exact test, and multivariate regression were performed with statistical significance P </=0.05. RESULTS: Fifty-five consecutive patients between 14 and 62 years of age were admitted in a 1-year period and underwent 64 diagnostic and therapeutic procedures. Fourteen (22%) postoperative infections and 18 (28%) complications other than infection, with an overall mortality of 11%, were documented. Total preoperative white blood cell count ([WBC] P <0.01), preoperative percent lymphocyte count (P <0.01), absolute postoperative CD4 lymphocyte count (P <0.01), and postoperative plasma viral load (P <0.0001) are associated with mortality. Multivariate regression indicated that postoperative percent CD4 lymphocyte count is an independent predictor of both postoperative infection and other complications (P <0.05, R = 0.848, power = 0.9911), while the decrement in percent CD4 lymphocyte count is an independent predictor of postoperative complications other than infection (P <0.05, R = 0.596, power = 0.7838). CONCLUSIONS: In accordance with the medical literature for clinical outcome in HIV-infected and AIDS patients, both immune cell counts and HIV-1 RNA counts were found to associate with postoperative mortality. However, the postoperative and decrement in percent CD4 lymphocyte proved to be the independent predictors of postoperative complications.

Acquired Immunodeficiency Syndrome↗

c-myc gene sequences and the phylogeny of bats and other eutherian mammals.

The complete protein-coding sequences of the c-myc proto-oncogene were determined for five species of four new orders of eutherian (placental) mammals. These newly obtained sequences were aligned to each other and to other available orthologs for the phylogenetic estimation of eutherian interordinal relationships. Several measures of sequence difference and base composition were first calculated to assess the major evolutionary properties of the three codon positions and two protein-coding exons of the gene. On the basis of these calculations, different parsimony, distance, and maximum likelihood approaches were adopted, with the most sophisticated involving the separate, then combined, likelihood analyses of the third codon positions of exon 2 versus all other sites. These phylogenetic approaches provided clear support for the grouping of Chiroptera (bats) with Artiodactyla (ruminants, camels, and pigs) and Carnivora (cats, dogs, and their allies), an interordinal arrangement that receives strong corroboration from other lines of evidence including complete mitochondrial DNA sequences. In contrast, these analyses failed to provide strong to reasonable support for any other interordinal group. This study concludes with specific recommendations about sampling and other strategies for maximizing the phylogenetic contributions of the c-myc gene to the continued resolution of the eutherian ordinal tree.

Animals↗

Comparison of blood collected in acid-citrate-dextrose and EDTA for use in human immunodeficiency virus peripheral blood mononuclear cell cultures.

Paired blood samples collected in acid-citrate-dextrose and EDTA were compared for human immunodeficiency virus (HIV) infectivity on the day of collection or after 1 day of storage at room temperature. No significant differences between the anticoagulants were observed. Culture positivity was significantly associated with HIV RNA viral loads for both anticoagulants.

Anticoagulants↗

The sin of Onan.

Explore the source record for details and available documents.

Bible↗

Pentostatin (Nipent) and high-dose cyclophosphamide for the treatment of refractory autoimmune disorders.

Autoimmune rheumatologic disease has a wide range of clinical expression that occasionally can be disabling. Patients with visceral organ involvement are exposed to significant morbidity and mortality if effective therapy is not forthcoming. The mainstay of therapy has been immunosuppression. However, some patients fail to respond to conventional doses of corticosteroids, methotrexate, or cyclophosphamide, and new approaches are needed for these patients. One new approach involves the use of intensified immunosuppression by combining cyclophosphamide with purine nucleoside analogs, including the adenosine deaminase inhibitor pentostatin (Nipent; SuperGen, San Ramon, CA).

Adenosine Deaminase Inhibitors↗

Solid-phase synthesis of pyridones and pyridopyrazines as peptidomimetic scaffolds.

[formula: see text] We report the syntheses of peptidomimetic opioids containing the core structure N-alkyl-2-alkyl-2,3-dihydro-4-pyridone. By employing imines bound on a solid support and the Danishefsky diene, this [4 + 2] cyclocondensation reaction facilitates the synthesis of novel complex heterocycles. The central reaction is carried out under mild conditions and employs readily available building blocks. In this study we demonstrate the suitability of N-alkyl-2-alkyl-2,3-dihydro-4-pyridones as a central scaffold for peptidomimetics and establish the scope of this [4 + 2] cyclocondensation reaction with imino acids on a solid phase. We also combine the synthesis of diketopiperazines with the [4 + 2] cyclocondensation reaction to form a 9,9a-dihydro-2H-pyrido-[1,2a]- pyrazine-3,8(1,4-dialkyl)dione, a bicyclic molecule containing a pyridopyrazine core structure.

Molecular Mimicry↗

Comparison of five methods for finding conserved sequences in multiple alignments of gene regulatory regions.

Conserved segments in DNA or protein sequences are strong candidates for functional elements and thus appropriate methods for computing them need to be developed and compared. We describe five methods and computer programs for finding highly conserved blocks within previously computed multiple alignments, primarily for DNA sequences. Two of the methods are already in common use; these are based on good column agreement and high information content. Three additional methods find blocks with minimal evolutionary change, blocks that differ in at most k positions per row from a known center sequence and blocks that differ in at most k positions per row from a center sequence that is unknown a priori. The center sequence in the latter two methods is a way to model potential binding sites for known or unknown proteins in DNA sequences. The efficacy of each method was evaluated by analysis of three extensively analyzed regulatory regions in mammalian beta-globin gene clusters and the control region of bacterial arabinose operons. Although all five methods have quite different theoretical underpinnings, they produce rather similar results on these data sets when their parameters are adjusted to best approximate the experimental data. The optimal parameters for the method based on information content varied little for different regulatory regions of the beta-globin gene cluster and hence may be extrapolated to many other regulatory regions. The programs based on maximum allowed mismatches per row have simple parameters whose values can be chosen a priori and thus they may be more useful than the other methods when calibration against known functional sites is not available.

Animals↗

3-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-one (DEPBT): a new coupling reagent with remarkable resistance to racemization.

[formula: see text] The new crystalline phosphate reagent 3-(diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-one (DEPBT) mediates amide bond formation with a remarkable resistance to racemization. Comparative racemization studies were carried out and DEPBT proved to be superior to typical phosphonium and uronium coupling reagents. DEPBT is easily prepared and is exceedingly stable with a shelf life of months at room temperature. The advantageous properties of DEPBT render it a useful and unique addition to the arsenal of coupling reagents.

Amides↗

Structural and compositional determinants of cortistatin activity.

Cortistatin-14 (CST-14) is a putative novel neuropeptide that shares 11 of its 14 residues with somatostatin-14 (SRIF-14), yet its effects on sleep physiology, locomotor behavior and hippocampal function are different from those of somatostatin. We studied the structural basis for cortistatin's distinct biological activities. As with SRIF-14, CST-14 does not show any preferred conformation in solution, as determined by circular dichroism and nuclear magnetic resonance. Synthetic cortistatin analogs were designed and synthesized based on the cyclic structure of octreotide. Biological assays were carried out to determine their binding affinities to five somatostatin receptors (sstl-5) and their ability to produce changes in locomotor activity and to modulate hippocampal physiology and sleep. The results show that the compound with N-terminal proline and C-terminal lysine amide exhibits cortistatin-like biological activities, including reduction of population spike amplitudes in the hippocampal CA1 region, decrease in locomotor activity and enhancement of slow-wave sleep 2. These findings suggest that both proline and lysine are necessary for cortistatin binding to its specific receptor.

Amino Acid Sequence↗

Analysis of linked human epsilon and gamma transgenes: effect of locus control region hypersensitive sites 2 and 3 or a distal YY1 mutation on stage-specific expression patterns.

Stage-specific expression of the human beta-like globin genes is controlled by interactions between regulatory elements near the individual genes and additional elements located upstream in the Locus Control Region (LCR). Elucidation of the mechanisms that govern these interactions could suggest strategies to reactivate fetal (gamma) or embryonic (epsilon) genes in individuals with severe hemoglobinopathies. This study extends an earlier analysis of a transgenic construct, HS3epsilon gamma, testing: (A) the effect of substitution of HS2 for HS3 on stage-specific expression of the epsilon and gamma genes and, (B) the role of an evolutionarily conserved YY1 binding site in transcriptional regulation of the gamma gene. The data show that both HS3epsilon gamma and HS2epsilon gamma can individually support embryonic expression of epsilon and fetal expression of Agamma. Thus, the cis regulators of distinct expression patterns for epsilon and gamma are likely to reside near the genes, rather than in specific hypersensitive sites of the LCR. Alterations in Agamma expression patterns observed in transgenic lines carrying a construct with a mutation in a conserved YY1 binding site at -1086 indicate that this site might function to facilitate active transcription of the gamma gene in fetal life.

Animals↗

Model for the fetal recruitment of simian gamma-globin genes based on findings from two New World monkeys Cebus apella and Callithrix jacchus (Platyrrhini, Primates).

The originally embryonic gamma-globin locus duplicated and acquired a novel (fetal) pattern of expression in a defined time period (55-40 million years ago) during primate phylogeny. The objective of this study was to determine some of the factors that led to first the emergence of fetal gamma specificity and then the maintenance of different fetal gamma expression patterns in extant simian primates (e.g., human, capuchin monkey). Analyses focused on two platyrrhine (New World monkey) species: the common marmoset (Callithrix jacchus) and the brown capuchin monkey (Cebus apella), each of which has paired, non-allelic gamma loci (5'-gamma 1-gamma 2-3'). Quantitation of beta-type globin mRNAs expressed in a 4.5 week old embryo of Callithrix jacchus revealed that in addition to its primary epsilon-globin message, considerable amounts of gamma 1 message and just trace levels of gamma 2 message are present. In contrast, analyses of gamma-globin messenger RNAs expressed in a Cebus apella fetal liver indicated that gamma 2 expression is at least 120 times greater than gamma 1 expression. Using a luciferase reporter and a transient assay system, the strengths of gamma 1 and gamma 2 promoter fragments of Cebus apella were compared in erythroid (K562) and non-erythroid (HeLa) cell lines. Due to the lack of chromatin repression in a transient expression system, the results do not fully recapitulate globin expression. However, the results suggest that sequences contained within the Cebus gamma 1 and gamma 2 proximal promoter regions (-200 to +1 bp) can direct gamma transcription in both cell lines. In K562 and, to a lesser extent, in HeLa cells Cebus gamma 2 promoter fragments were significantly stronger (P < 0.01) than gamma 1 promoter fragments. This is consistent with the fact that the Cebus gamma 1 promoter contains several mutations, including a proximal CCAAT box mutation (CCAAT-->CCAAc). The epsilon-gamma 1 intergenic distances in these platyrrhines (5.4 kb in Cebus apella and 6.9 kb in Callithrix jacchus) are short, supporting the inference that it was also short in the stem simian primates. The results suggest that immediately following the gamma duplication, the gamma 1 gene of the stem simians was still embryonic and the downstream gamma 2 gene was largely silent. A further inference is that once gamma 2 accumulated regulatory mutations that disrupted binding of fetal repressors, gamma 2 was expressed fetally and, through gene conversion, passed these characteristics to the gamma 1 gene. The fetal expression of gamma 1 is most evident in catarrhines (Old World monkeys and hominoids), which preferentially express the gamma 1 locus during fetal life.

Animals↗

Patient Impairment Lexicon: a validation study.

Growth of managed behavioral health organizations (MBHOs) has increased the need for a standardized diagnostic language. The Patient Impairment Lexicon (PIL; Goodman, Brown, & Deitz, 1992, 1996) is intended to address this need. Augmenting previous psychometric assessment (Klewicki, Bjorck, Leucht, & Goodman, 1998), the current study evaluated the PIL's construct validity. Sixteen raters completed impairment inventories; diagnoses based on the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised (DSM-III-R; American Psychiatric Association, 1987); and independent measures of psychiatric functioning for patients in 20 vignettes. Overall rater accuracy was significantly higher for PIL impairments than for diagnoses. As predicted, there were positive correlations between PIL impairments and psychiatric functioning for all 20 vignettes, 11 of which were significant. Results remained significant after controlling variance due to: (a) raters' past experience with similar patients and (b) vignette imaginability. Findings are discussed in terms of MBHO applications and future PIL research.

Adolescent↗

Sequences from the 5' flanking region of the epsilon-globin gene support the relationship of Callicebus with the pitheciins.

The purpose of this study was to determine nucleotide sequences from the 5' flanking region of the epsilon-globin gene of selected platyrrhine primates and to analyze the data for phylogenetic information and estimated times of divergence. We report new sequence data for two species of New World monkeys, Callicebus torquatus and Pithecia irrorata. We analyzed these data in conjunction with homologous sequences from other primate species. The data support the hypothesis that the titi monkeys (Callicebus) and seed predators (Tribe Pitheciini) form a clade (Subfamily Pitheciinae), and also provide limited support for that subfamily being allied with the atelines. We also present estimated dates of divergence for the Callicebus and pitheciin lineages.

Animals↗

Synthesis and binding properties of cyclohexapeptide somatostatin analogs containing naphthylalanine and arylalkyl peptoid residues.

We report the synthesis, binding affinities to the recombinant human somatostatin receptors, and structure-activity relationship studies of compounds related to the cyclic hexapeptide, c-[Pro6-Phe7-D-Trp8Lys9-Thr10-Phe11], L-363,301 (the numbering in the sequence refers to the position of the residues in native somatostatin). The Pro residue in this compound is replaced with the arylalkyl peptoid residues Nphe (N-benzylglycine), (S)betaMeNphe [(S)-N-[alpha(-methyl)benzyl]glycine] or (R)betaMeNphe [(R)-N-[(alpha-methyl)benzyl]glycine] and L-1-naphthylalanine is incorporated into either position 7 or 11 of the parent compound. The synthesis and binding data of the Nnal6 ([N-naphthylmethyl]glycine) analog of L-363,301 is also reported. The incorporation of the Nnal residue into position 6 of L-363,301 resulted in an analog with weaker binding affinities to all hsst receptors but enhanced selectivity towards the hsst2 receptor compared with the parent compound. The other compounds bind effectively to the hsst2 receptor but show some variations in the binding to the hsst3 and hsst5 receptors resulting in different ratios of binding affinities to the hsst5 and hsst2 or hsst3 and hsst2, respectively. The incorporation of the Nphe residue into position 6 and the Nal residue into position 7 of L-363,301 led to a compound which binds potently to the hsst2 and has increased selectivity towards this receptor (weaker binding to hsst3 and hsst5 receptors) compared with the parent compound. The analogs with beta-methyl chiral substitutions in the aromatic peptoid side chain and Nal in position 7 or 11 bind effectively to the hsst2 and hsst5 receptors. They exhibit similar ratios of binding affinities to the hsst5 and hsst2 receptors as observed for L-363,301. There are however minor differences in binding to the hsst3 receptor among these analogs. These studies allow us to investigate the influence of additional hydrophobic groups on the binding activity to the isolated human somatostatin receptors and the results are important for the design of other somatostatin analogs.

Alanine↗

Conformational analyses of cyclic hexapeptide analogs of somatostatin containing arylalkyl peptoid and naphthylalanine residues.

We report the conformational analysis by 1H-NMR in DMSO and computer simulations involving distance geometry and molecular dynamics simulations of peptoid analogs of the cyclic hexapeptide c-[Phe11-Pro6-Phe7-D-Trp8-Lys9-Thr10] L-363,301 (the numbering refers to the positions in native somatostatin). The compounds c-[Phe11-Nphe6-Nal7-D-Trp8-Lys9-Thr10] (Nphe6-Nal7 analog 1), c-[Nal11-Nphe6-Phe7-D-Trp8-Lys9-Thr10] (Nal11-Nphe6 analog 2) and c-[Phe11-Nnal6-Phe7-D-Trp8-Lys9-Thr10] (Nnal6 analog 3), where Nphe denotes N-benzylglycine and Nnal denotes N-(1-naphthylmethyl)glycine, are subjected to SAR studies in order to investigate the influence of the bulky naphthyl aromatic ring on the conformation. The Nal11-Nphe6 and Nphe6-Nal7 analogs exhibit potent binding to the hsst2, hsst3 and hsst5 receptors, whereas the Nnal6 analog has decreased binding affinity to all receptors but is more selective towards the hsst2 than the other two analogs and L-363,301. The conformational search employing distance geometry, energy minimization and molecular dynamic simulations gives insight into the conformational flexibility of these analogs. The molecules adopt both cis and trans orientations of the peptide bond between residues 11 and 6. The cis isomers of these analogs adopt type II' beta-turns with D-Trp in the i + 1 position and type VIalpha beta-turns with the cis peptide bond between residues 6 and 11. The results of free and distance restrained molecular dynamics simulations at 300 K indicate that the Nphe6-Nal7 and Nal11-Nphe6 compounds adopt a preferred backbone conformation which can be described as 'folded' about residues 7 and 10. The Nnal6 analog, which binds less effectively to the hsst receptors, has a more flexible backbone structure than the Nal11-Nphe6 and Nphe6-Nal7 analogs and prefers a 'flat' structure with regard to the orientations about Phe7 and Thr10 during molecular dynamics simulations.

Alanine↗