Search PubMed⌕ Search

Biomedical subjects

M Goodman

Publications and source records attributed to M Goodman.

At least 73 records · Page 4Linked to original sources
PubMed1999

Conformations and pharmacophores of cyclic RGD containing peptides which selectively bind integrin alpha(v)beta3.

This paper reports a detailed conformational characterization in solution by 1H-NMR in H2O and DMSO-d6 and molecular modeling simulations of cyclic peptides containing the RGDDV pharmacophore and the RGDY(Me)R pharmacophore. These two pentapeptide sequences when properly constrained in cyclic peptides are low to sub-nanomolar inhibitors of integrin alpha(v)beta3. The peptides containing the RGDDY(Me)R sequence bind potently to integrin alphaIIb3 as well. The conformations found in H2O and in DMSO-d6 solutions are valuable for the design of peptidomimetics of these two pharmacophores. The structure-activity relationships of the RGDDV and RGDY(Me)R pharmacophores within cyclic peptides are discussed. Specifically, the orientation of surface-accessible chemical features on the ligand, such as hydrophobic, positive and negative ionizable groups, which are considered to be responsible for the desired biological activity, is focused on.

Magnetic Resonance Spectroscopy↗
PubMed1999

Molecular phylogeny of ateline new world monkeys (Platyrrhini, atelinae) based on gamma-globin gene sequences: evidence that brachyteles is the sister group of lagothrix.

Nucleotide sequences, each spanning approximately 7 kb of the contiguous gamma1 and gamma2 globin genomic loci, were determined for seven species representing all extant genera (Ateles, Lagothrix, Brachyteles, and Alouatta) of the New World monkey subfamily Atelinae. After aligning these seven ateline sequences with outgroup sequences from several other primate (non-ateline) genera, they were analyzed by maximum parsimony, maximum likelihood, and neighbor-joining algorithms. All three analyzes estimated the same phylogenetic relationships: [Alouatta [Ateles (Brachyteles, Lagothrix)]]. Brachyteles and Lagothrix are sister-groups supported by 100% of bootstrap replications in the parsimony analyses. Ateles joins this clade, followed by the basal genus Alouatta; these joinings were strongly supported, again with 100% bootstrap values. This cladistic pattern for the four ateline genera is congruent with that obtained in previous studies utilizing epsilon-globin, IRBP, and G6PD nuclear genomic sequences as well as mitochondrial COII sequences. Because the number of aligned nucleotide positions is much larger in the present datasetoff than in any of these other datasets, much stronger support was obtained for the cladistic classification that divides subfamily Atelinae into tribes Alouattini (Alouatta) and Atelini, while the latter divides into subtribes Atelina (Ateles) and Brachytelina (Brachyteles and Lagothrix).

Animals↗
PubMed1999

The Tarsius gamma-globin gene: pseudogene or active gene?

We sequenced the approximately 5-kb long gamma-globin gene locus from Tarsius bancanus and compared it to the published gamma-globin gene sequence from the related species Tarsius syrichta. The T. syrichta gene's promoter lacks the distal CCAAT box and has a point mutation in the functionally important proximal CCAAT box (CCgAT). This previous finding had suggested that in tarsiers the gamma-globin gene might be a nonexpressed pseudogene. The two tarsier species show the same point mutation at the third nucleotide of the proximal CCAAT element and absence of the distal CCAAT element. Nevertheless, our results indicate that in tarsiers the gamma-globin gene is active, since all three coding regions show only synonymous substitutions and a much lower level of divergence than the noncoding regions. This is significantly different from what would be expected for a silent gene evading stabilizing selection. Thus, we hypothesize that the tarsier's gamma-globin gene locus is expressed even with the mutation in the proximal CCAAT box.

Animals↗
PubMed1999

Molecular phylogeny of Old World monkeys (Cercopithecidae) as inferred from gamma-globin DNA sequences.

DNA sequence data of the nuclear-encoded gamma1-gamma2-globin duplication region were used to examine the phylogenetic relationships of 16 cercopithecid (Old World monkey) species representing 12 extant genera. Morphology- and molecular-based hypotheses of Old World monkey branching patterns are generally congruent, except for generic relationships within the subtribe Papionina. The cercopithecids divide into colobines (leaf-eating monkeys) and cercopithecines (cheek-pouched monkeys). The colobines examined by the DNA data divide into an Asian clade (Nasalis, proboscis monkeys; Trachypithecus, langurs) and an African clade (Colobus, colobus monkeys). The cercopithecines divide into tribes Cercopithecini (Erythrocebus, patas monkey; Chlorocebus, green monkeys; Cercopithecus, guenons) and Papionini. Papionins divide into subtribes Macacina (Macaca, macaques) and Papionina (Papio, hamadryas baboons; Mandrillus, drills and mandrills; Theropithecus, gelada baboons; Lophocebus, arboreal mangabeys; Cercocebus, terrestrial mangabeys). In a morphologically based classification, Mandrillus is a subgenus of Papio, whereas Lophocebus is a subgenus of Cercocebus. In contrast, the molecular evidence treats Mandrillus as a subgenus of Cercocebus, and treats both Theropithecus and Lophocebus as subgenera of Papio. Local molecular clock divergence time estimates were used as a yardstick in a "rank equals age" system to propose a reduction in taxonomic rank for most clades within Cercopithecidae.

Animals↗
PubMed1999

The place of Callimico goeldii in the Callitrichine phylogenetic tree: evidence from von Willebrand factor gene intron II sequences.

Sequences of a 0.9-kb DNA segment spanning intron 11 of the von Willebrand Factor gene (vWF) were determined for 21 individuals of 19 primate species. The results of maximum parsimony and maximum likelihood analyses of these vWF sequences are congruent with previous molecular findings from other nonlinked nuclear genomic loci which divide the platyrrhine superfamily Ceboidea into three monophyletic families: Cebidae, Atelidae, and Pitheciidae. The vWF results strongly support the taxon Callitrichinae as a monophyletic subfamily within Cebidae. The four extant callitrichine genera constitute tribe Callitrichini, and the basal branchings within this tribe first separate out Saguinus (tamarins), next Leontopithecus (lion tamarins), and last the sister genera Callimico (Goeldi's monkeys) and Callithrix (marmosets). Callithrix divides into three subclades, with pygmy marmosets (C. pygmaea) as sister of the C. argentata species group and with the C. jacchus species group as their sister. Fossil and DNA evidence place the emergence of the callitrichine clade in the basal cebid radiation at about 20 Ma (million years ago) and the three basal branchings in the callitrichin radiation at about 13 to 11 Ma. In turn, the branchings separating the three subclades of Callithrix are placed at about 5 to 4 Ma.

Animals↗
PubMed1999

Triple helical stabilities of guest-host collagen mimetic structures.

The peptoid Nleu (N-isobutylglycine) has been successfully incorporated into a series of collagen mimetics composed of Gly-Pro-Nleu and Gly-Nleu-Pro sequences and has been able to maintain triple helices in appropriate structures. The achiral trimeric sequence Gly-Nleu-Nleu as a guest sequence in structures such as Ac-(Gly-Pro-Hyp)3-(Gly-Nleu-Nleu)3-(Gly-Pro-Hyp)3-NH2 retains triple helicity. As an extension of this study, we report, in this paper, on a series of guest-host collagen mimetic structures in which Gly-Nleu-Pro sequences are employed as the host. The guest sequences for these guest-host structures include Gly-Nleu-Nleu and Gly-Nx-Pro sequences where Nx is composed of a variety of alkyl and aralkyl peptoid residues. From these guest-host collagen mimetic structures, we are able to elucidate the contributions of hydrophobic and steric effects on triple helix formation. The Gly-Nleu-Pro sequences have been shown to be effective in inducing triple helicity. Conformational characterization of the guest-host collagen mimetic structures was established by techniques such as temperature-dependent optical rotation measurements and circular dichroism (CD) spectroscopy.

Amino Acid Sequence↗
PubMed1999

Cancer in asbestos-exposed occupational cohorts: a meta-analysis.

OBJECTIVE: To examine existing asbestos-exposed occupational cohorts and apply a meta-analytic technique to determine the magnitude of association between exposure and lung cancer and to investigate other cancer sites that may be related to such an exposure. METHODS: We summarized the data from 69 asbestos-exposed occupational cohorts reporting on cancer morbidity and mortality. Data were extracted regarding numbers of deaths for each cancer, numbers of mesotheliomas, occupations and latency for respiratory, gastrointestinal, urinary and lymphohematopoietic cancers. For each cancer, we calculated a meta-SMR and examined heterogeneity of results using a chi-square test and by calculating a Z-statistic for each study. To examine the dose-response effect, we divided the studies into tertiles according to the percentage of mesothelioma deaths that served as a proxy estimation of asbestos exposure. RESULTS: Lung cancer data demonstrated meta-SMRs of 163 and 148 with and without latency, respectively, with significant heterogeneity of results even after stratification according to occupational groups. Stratification of lung cancer studies according to percentage of mesothelioma deaths showed a dose-response effect. Z-scores ranged from -12.21 to + 29.49. Analysis for laryngeal cancer yielded meta-SMRs of 157 and 133 with and without latency, respectively, demonstrating homogeneous results across studies but accompanied by no evidence of a dose-response effect. Data for gastrointestinal cancers showed no evidence of a significant association and no dose-response effect. Kidney cancer demonstrated statistically non-significant meta-SMRs of 120 (95% CI 88-160) and 111 (95% CI 94-131) with and without latency respectively. CONCLUSIONS: This meta-analysis demonstrates a wide variability of the association between occupational asbestos and lung cancer. There was a suggestion of an association between asbestos and laryngeal carcinoma and no clear association with other cancers.

Adult↗
PubMed1999

Synthesis and binding potencies of cyclic hexapeptide analogs of somatostatin incorporating acidic and basic peptoid residues.

The synthesis, binding affinity, and structure-activity relationships of compounds related to the cyclic hexapeptide, c[Pro6-Phe7-D-Trp8-Lys9-Thr10-Phe11], L-363,301 (the numbering in the sequence refers to the position of the residue in native somatostatin) is reported. The Pro residue in this compound is replaced with the peptoid residues Nasp [N-(2-carboxyethyl) glycine], Ndab [N-(2-aminoethyl) glycine] and Nlys [N-(4-aminobutyl) glycine]. This series of compounds enables us to draw conclusions about the influence of positively or negatively charged residues in the bridging region on the binding affinity towards the isolated human somatostatin receptors. A loss of binding to the recombinant human somatostatin (hsst) receptors in the Nasp analog compared with L-363,301 and compared with the Ndab and Nlys analogs clearly demonstrates that the presence of an acidic residue in the bridging region is unfavorable for binding to the hsst receptors. Comparison between the Ndab analog and the Nlys analog suggests that the presence of a basic residue in the bridging region might be advantageous for binding to the hsst5 receptor provided that the residue bearing the basic group extends far enough to allow for interaction with the receptor, while the length of the basic peptoid residue does not influence binding to the hsst2 receptor. These results are useful for the design of hsst5 selective somatostatin analogs.

Chromatography, High Pressure Liquid↗
PubMed1999

Conformational analyses by 1H NMR and computer simulations of cyclic hexapeptides related to somatostatin containing acidic and basic peptoid residues.

We report the conformational analysis by 1H NMR in DMSO and computer simulations involving distance geometry and molecular dynamics simulations at 300K of peptoid analogs of the cyclic hexapeptide c-[Phe11-Pro6-Phe7-D-Trp8-Lys9-Thr10]. The analogs c-[Phe11-Nasp6-Phe7-D-Trp8-Lys9-Thr10](1), c-[Phe11-Ndab6Phe7-D-Trp8-Lys9-Thr10] (2) and c-[Phen11-Nlys6-Phe7-D-Trp8-Lys9-Thr10](3) where Nasp denotes N-(2-carboxyethyl) glycine, Ndab N-(2-aminoethyl) glycine and Nlys N-(4-aminobutyl) glycine are subject to conformational studies. The results of free and restrained molecular dynamics simulations at 300K are reported and give insight into the conformational behaviour of these analogs. The compounds show two sets of nuclear magnetic resonance signals corresponding to the cis and trans orientations of the peptide bond between residues 11 and 6. The backbone conformation of the cis isomers that we believe are the bioactive isomers of the three compounds are very similar to each other while there are larger variations amongst the trans isomers. The binding data to the isolated receptors show that the introduction of the Nlys residue in analog 3 leads to an enhancement of binding potency to the hsst5 receptor compared with analog 2 while maintaining identical binding potency to the hsst2 receptor. The Nasp6 analog 1 binds weakly to the hsst2 and is essentially inactive towards the other receptors. Comparison of the conformations and binding activities of these three analogs indicates that the Nlys residue extends sufficiently far to allow binding to a negatively charged binding domain on the hsst5 receptor. According to this model, the Ndab analog 2 cannot extend far enough to allow for binding to the receptor pocket. The loss of activity observed for the Nasp6 compound 1 indicates that the presence of a negatively charged residue in position 6 is unfavorable for binding to the hsst receptors.

Amino Acid Sequence↗
PubMed1999

Endoscopic thoracic sympathectomy for primary palmar hyperhidrosis: intermediate term results.

BACKGROUND: The authors' experience of the efficacy and safety of endoscopic thoracic sympathectomy in the treatment of primary palmer hyperhidrosis was examined. METHODS: A retrospective study of 71 patients (126 sympathectomies) was undertaken. Data were retrieved by hospital records and telephone interview. RESULTS: Follow-up was possible for 92 sympathectomies in 53 patients. Overall, satisfactory results were achieved in 93% of patients and complications were uncommon. Compensatory hyperhidrosis was the most common complication, which occurred in 64% of patients; the trunk and feet were the most common sites. Horner's syndrome occurred in five patients, although in two it was a permanent complication. No patient expressed dissatisfaction with the procedure as a consequence of this complication. Pneumothorax occurred in 17.5% of cases, although the vast majority were incidental findings on a postoperative chest X-ray, and none required drainage. With the newer techniques of access, patient dissatisfaction with the cosmetic appearance has fallen from 27.3 to 6.4%. Overall 90% of patients said they would have the operation again, which represents a high level of patient satisfaction. CONCLUSIONS: Endoscopic thoracic sympathectomy is a safe and effective technique for primary palmer hyperhidrosis. Evolution of the technique has resulted in improvement in patient satisfaction.

Adolescent↗
PubMed1999

Molecular evolution of the COX7A gene family in primates.

COX VIIa is one of 10 nuclear-encoded subunits of the COX holoenzyme, and one of three that have isoforms with tissue-specific differences in expression. Analysis of nucleotide substitution rates revealed an accelerated rate of nonsynonymous substitutions relative to that of synonymous substitutions for the heart isoform gene (COX7AH) in six primate lineages. Rate accelerations have been noted for four other COX-related genes in this time period, suggesting that the COX holoenzyme has experienced an episode of adaptive evolution. A third member of the gene family, COX7AR, has recently been described. Although its function is currently unknown, low nonsynonymous substitution/synonymous substitution (N/S) ratios in mammalian evolution suggest that COX7AR is of functional importance. When the COX7A isoforms were divided into domains, examination of nucleotide substitution rates suggested that mitochondrial targeting residues experienced an accelerated nonsynonymous substitution rate in the period following gene duplication. In contrast, paralogous comparisons of the targeting residues of each isoform show they have been relatively conserved in mammalian evolution. This pattern is consistent with the evolution of tissue-specific function.

Amino Acid Sequence↗
PubMed1999

The relative influences of symptoms, insight, and neurocognition on social adjustment in schizophrenia and schizoaffective disorder.

Impaired insight and neurocognitive deficits are commonly seen in schizophrenia. No study to date, however, has documented the relative influences of insight deficits, neurocognitive functioning, and psychotic symptoms on overall social adjustment in this population. This was done in a cohort of individuals recovering from acute exacerbations. Forty-six individuals with schizophrenia or schizoaffective disorder were recruited upon discharge from an inpatient unit. Symptom levels, neurocognitive functioning (information processing, memory, and executive functioning), and symptom awareness were documented, and social adjustment was assessed in three domains: treatment compliance, social behavior, and subjective quality of life. Cross-sectional data from initial assessments are reported. Sequential linear regression analyses identified differential associations between illness characteristics and outcome domains. Treatment compliance was most influenced by insight; social behavior deficits were associated with thought disorder and neurocognitive (working memory and visuo-spatial) impairments; and quality of life was associated with mood disturbances. Outcome is multidimensional in schizophrenia, and there are differential patterns of associations between illness characteristics and domains of social adjustment. Studies such as this can guide clinicians in determining the most appropriate treatments for specific individuals and should also guide researchers in efforts to clarify the processes that underlie treatment response and recovery in schizophrenia.

Adult↗
PubMed1999

Health-related quality-of-life assessment of patients with life-threatening ventricular arrhythmias.

The purpose of this study was to determine whether treatments for life-threatening ventricular arrhythmias are associated with quality-of-life (QOL) and psychological distress. Multidimensional measures of QOL and psychological distress were used to cross-sectionally compare patients with ICDs to patients treated with antiarrhythmic drugs and patients without serious cardiac conditions. The sample consisted of 157 patients: 35 patients treated with antiarrhythmic medication only, 24 patients treated with ICD only, 25 patients treated with ICD and antiarrhythmic medication, and 73 controls. Patients completed the Medical Outcomes Study SF-36 health survey, the Brief Symptom Inventory, and background questionnaires. There were no significant differences in self-reported QOL and psychological distress between patients with or without ICD, and the occurrence of defibrillator shocks was unrelated to QOL and psychological distress. However, patients treated with antiarrhythmic drugs reported greater QOL impairment in physical functioning, vitality, emotional role limitations, and sleep, as well as greater psychological distress than patients not treated with antiarrhythmics. These limitations may be attributed to adverse effects arising from antiarrhythmic pharmacotherapy. Results of the present investigation suggest that QOL and psychological distress are maintained among ICD patients, whereas treatment with antiarrhythmic drugs are associated with a diminished QOL and greater psychological distress. These findings may assist cardiologists to select the optimal treatment for life-threatening ventricular arrhythmias that minimizes disturbances in health-related QOL and psychological distress and increases patient compliance.

Activities of Daily Living↗
PubMed1999

Characterization of V3 sequence heterogeneity in subtype C human immunodeficiency virus type 1 isolates from Malawi: underrepresentation of X4 variants.

We have examined the nature of V3 sequence variability among subtype C human immunodeficiency virus type 1 (HIV-1) sequences from plasma-derived viral RNA present in infected men from Malawi. Sequence variability was assessed by direct sequence analysis of the V3 reverse transcription-PCR products, examination of virus populations by a subtype C V3-specific heteroduplex tracking assay (V3-HTA), and selected sequence analysis of molecular clones derived from the PCR products. Sequence variability in V3 among the subtype C viruses was not associated with the presence of basic amino acid substitutions. This observation is in contrast to that for subtype B HIV-1, where sequence variability is associated with such substitutions, and these substitutions are determinants of altered coreceptor usage. Evolutionary variants in subtype C V3 sequences, as defined by the V3-HTA, were not correlated with the CD4 level in the infected person, while such a correlation was found with subtype B V3 sequences. Viruses were isolated from a subset of the subjects; all isolates used CCR5 and not CXCR4 as a coreceptor, and none was able to grow in MT-2 cells, a hallmark of the syncytium-inducing phenotype that is correlated with CXCR4 usage. The overall sequence variability of the subtype C V3 region was no greater than that of the conserved regions of gp120. This limited sequence variability was also a feature of subtype B V3 sequences that do not carry the basic amino acid substitutions associated with altered coreceptor usage. Our results indicate that altered coreceptor usage is rare in subtype C HIV-1 isolates in sub-Saharan Africa and that sequence variability is not a feature of the V3 region of env in the absence of altered coreceptor usage.

Base Sequence↗
PubMed1999

Jamaica's measles elimination experience.

OBJECTIVES: This article describes the effort to eliminate measles from Jamaica and its impact on measles incidence. METHODS: In addition to routine measles vaccination, the Jamaican Ministry of Health implemented a strategy of a 1-time-only catch-up vaccination campaign, conducted in 1991, and periodic follow-up campaigns, the first of which occurred in 1995. RESULTS: Since 1991, despite careful surveillance, no serologically confirmed indigenous cases of measles have occurred in Jamaica. CONCLUSIONS: Measles virus circulation has been interrupted in Jamaica. The Jamaican experience provides further evidence that global measles eradication is achievable.

Adolescent↗
PubMed1999

The health and economic benefits of influenza vaccination for healthy and at-risk persons aged 65 to 74 years.

OBJECTIVE: The objective of this study was to assess the health and economic benefits of influenza vaccination in both healthy and at-risk seniors aged 65 to 74 years. DESIGN AND SETTING: We used administrative claims data from 6 consecutive serial cohorts spanning the years 1990 to 1991 through 1995 to 1996. All members of a Twin-Cities managed care organisation who were > or = 65 years of age for the respective study year were included in each cohort. Other information obtained included demographic characteristics, baseline comorbidities, prior resource utilisation, and influenza vaccination status. Study outcomes included hospitalisations for pneumonia and influenza and for all respiratory conditions and death. Economic analyses assumed the societal perspective and included both direct and indirect costs. MAIN OUTCOME MEASURES AND RESULTS: During the 6 study seasons, there were 100 195 person-periods of observation for persons aged 65 to 74 years. Of these, two-thirds were healthy and one-third had at least one major baseline comorbidity. Influenza vaccination was associated with reductions in hospitalisations for pneumonia and influenza and for all respiratory conditions in both healthy and at-risk groups, although the results did not reach statistical significance among the healthy individuals. Vaccination was also associated with significant reductions in the risk of death for both groups. The economic analysis demonstrated that vaccination against influenza in the base case was associated with direct and total cost savings for both healthy and at-risk seniors aged 65 to 74 years. CONCLUSION: Influenza vaccination of healthy and at-risk seniors aged 65 to 74 years is associated with substantial health benefits and is cost saving. These findings support age-based vaccination strategies for all persons > or = 65 years of age.

Aged↗