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Biomedical subjects

M Goodman

Publications and source records attributed to M Goodman.

At least 145 records · Page 8Linked to original sources

Reduction of two functional gamma-globin genes to one: an evolutionary trend in New World monkeys (infraorder Platyrrhini).

Nucleotide sequences were determined for the gamma1- and gamma2-globin loci from representatives of the seven anciently separated clades in the three extant platyrrhine families (Atelidae, Pitheciidae, and Cebidae). These sequences revealed an evolutionary trend in New World monkeys either to inactivate the gamma1 gene or to fuse it with the gamma2 gene, i.e. to have only one functional fetally expressed gamma gene. This trend is clearly evident in six of the seven clades: (i) it occurred in atelids by deletion of most of the gamma1 gene in the basal ancestor of this clade; (ii-iv) in pitheciid titi, saki, and cebid capuchin monkeys by potentially debilitating nucleotide substitutions in the proximal CCAAT box of the gamma1 promoters and (v and vi) in cebid owl and squirrel monkeys by crossovers that fused 5' sequence from gamma1 with 3' sequence from gamma2. In the five clades with gamma1 and gamma2 loci separated by intergenic sequences (the fifth clade being the cebid marmosets), the gamma2 genes retained an unaltered proximal CCAAT motif and their gamma2 promoters accumulated fewer nucleotide substitutions than did the gamma1 promoters. Thus, phylogenetic considerations indicate that the stem platyrrhines, ancestral to all New World monkeys, had gamma2 as the primary fetally expressed gamma gene. A further inference is that when the earlier stem anthropoid gamma gene duplicated, gamma2 (at its greater downstream distance from epsilon) could evade embryonic activation by the locus control region but could be fetally activated once released by regulatory mutations from fetal repressors.

Animals↗

Fetal globin expression in New World monkeys.

Reverse phase chromatography of the globin chains of adult, newborn, and fetal erythrocytes from three species of New World monkeys (Cebus apella, Aotus azarae, and Callithrix jacchus) representing three of the seven platyrrhine clades showed that gamma-globin expression was fetal in these animals. The globins were identified by a combination of chemical sequencing and mass spectrometric analysis. Since gamma-globin expression is fetal in the other major simian branch, the catarrhines, but embryonic in prosimian primates and nonprimate placental mammals, the evolution of fetal recruitment can now be assigned to the period between the simian-prosimian divergence (55 million years ago) and the platyrrhine-catarrhine divergence (35 million years ago). The gamma-globin gene underwent tandem duplication during the same evolutionary epoch, in accord with a model that suggests that the downstream duplicated gamma-gene (gamma2) was free to acquire the mutations necessary for fetal recruitment. Mass spectrometric analysis of tryptic digests of the gamma-globins verified the amino acid sequences deduced from genomic sequencing. Detailed analysis of high performance liquid chromatography and matrix-assisted laser desorption/ionization mass spectrometry data showed that gamma2-globin in Cebus was expressed to a far greater extent than gamma1-globin, supporting inferences drawn from a study of the promoter sequences. A "pre-gamma"-globin was observed in C. apella and shown to be primarily the glutathionyl adduct. The other species, A. azarae and C. jacchus, also express only one gamma-globin polypeptide. This work provides biochemical evidence of an evolutionary trend in the platyrrhines to alter the duplicated gamma-globin gene locus so that only one gamma-globin polypeptide is expressed.

Abortion, Veterinary↗

Reconstitution of repair-gap UV mutagenesis with purified proteins from Escherichia coli: a role for DNA polymerases III and II.

Using a cell-free system for UV mutagenesis, we have previously demonstrated the existence of a mutagenic pathway associated with nucleotide-excision repair gaps. Here, we report that this pathway can be reconstituted by using six purified proteins: UvrA, UvrB, UvrC, DNA helicase II, DNA polymerase III core, and DNA ligase. This establishes the minimal requirements for repair-gap UV mutagenesis. DNA polymerase II could replace DNA polymerase III, although less effectively, whereas DNA polymerase I, the major repair polymerase, could not. DNA sequence analysis of mutations generated in the in vitro reaction revealed a spectrum typical of mutations targeted to UV lesions. These observations suggest that repair-gap UV mutagenesis is performed by DNA polymerase III, and to a lesser extent by DNA polymerase II, by filling-in of a rare class of excision gaps that contain UV lesions.

Adenosine Triphosphatases↗

Molecular phylogeny of the New World monkeys (Platyrrhini, primates) based on two unlinked nuclear genes: IRBP intron 1 and epsilon-globin sequences.

Nuclear sequences of the 1.8 kilobase (kb) long intron 1 of the interstitial retinol-binding protein gene (IRBP), previously determined for 11 of the 16 extant genera of New World monkeys (superfamily Ceboidea, infraorder Platyrrhini), have now been determined for the remaining 5 genera. The maximum parsimony trees found, first with IRBP sequences alone and then with tandemly combined IRBP and epsilon-globin gene sequences from the same species, supported a provisional cladistic classification with the following clusters. Subtribes Callitrichina (Callithrix, Cebuella), Callimiconina (Callimico), Leontopithecina (Leontopithecus) and Saguina (Saguinus) constitute subfamily Callitrichinae, and subfamilies Callitrichinae, Aotinae (Aotus), and Cebinae (Cebus, Saimiri) constitute family Cebidae. Subtribes Chiropotina (Chiropotes, Cacajao) and Pitheciina (Pithecia) constitute tribe Pitheciini; and tribes Pitheciini and Callicebini (Callicebus) constitute subfamily Pitheciinae. Subtribes Brachytelina (Brachyteles, Lagothrix) and Atelina (Ateles) constitute tribe Atelini, and tribes Atelini and Alouattini (Alouatta) constitute subfamily Atelinae. The parsimony results were equivocal as to whether Pitheciinae should be grouped with Atelinae in family Atelidae or have its own family Pitheciidae. The cladistic groupings of extant ceboids were also examined by different stochastic evolutionary models that employed the same stochastic process of nucleotide substitutions but alternative putative phylogenetic trees on which the nucleotide substitutions occurred. Each model, i.e., each different tree, predicted a different multinomial distribution of nucleotide character patterns for the contemporary sequences. The predicted distributions that were closest to the actual observed distributions identified the best fitting trees. The cladistic relationships depicted in these best fitting trees agreed in almost all cases with those depicted in the maximum parsimony trees.

Animals↗

Urethane-protected alpha-amino acid N-carboxyanhydrides and peptide synthesis.

The preparation, physical properties and analytical data are reported for seventy urethane-protected (Boc, Cbz, FMOC) amino acid N-carboxyanhydrides (UNCAs). Most of the UNCAs are crystalline and the X-ray diffraction patterns for several of these are described. UNCAs are stable to routine laboratory manipulations and can be stored for extended periods of time (1-2 years at below 0 degrees C). Most are completely stable to the conditions commonly employed for peptide synthesis. The correct choice of base is key for the successful introduction of urethane protecting groups into NCAs. N-Methylmorpholine is used for the introduction of FMOC, Cbz or Boc from the chloroformates, and pyridine is used for the introduction of the Boc group from Boc anhydride. UNCAs represent a unique class of preactivated, isolable and stable amino acid derivatives that generate no side products or co-products, other than CO2, during condensation reactions. The application of UNCAs in peptide synthesis in both solid phase and in solution is reviewed in detail.

Amino Acid Sequence↗

Collagen-based structures containing the peptoid residue N-isobutylglycine (Nleu): synthesis and biophysical studies of Gly-Pro-Nleu sequences by circular dichroism, ultraviolet absorbance, and optical rotation.

A peptoid residue N-isobutylglycine (Nleu) was introduced as a proline surrogate in collagen-like triple helical structures. A series of single chain and template-assembled collagen-based peptide-peptoid structures composed of Gly-Pro-Nleu sequences were prepared by solid-phase segment condensation methods. Both a synthetic route in solution and a solid phase method were employed to couple the KTA (cis,cis-1,3,5-trimethylcyclohexane-1,3,5-tricarboxylic acid, also known as the Kemp triacid) based template, KTA-(Gly-OH)3, to peptide-peptoid chains. Biophysical studies using CD, uv absorbance, and optical rotation measurements demonstrated that these compounds form triple-helical structures when the chains are longer than critical lengths. Results from melting curve measurements indicated that the Gly-Pro-Nleu sequence is comparable to the Gly-Pro-Pro sequence in stabilizing a triple-helical conformation. The KTA-based template stabilized triple-helical structures as can be seen by the increased melting temperatures as compared to equivalent single chain molecules. In addition, the template reduced the minimum chain length necessary to form a triple helix from six to only three trimer repeats.

Biophysical Phenomena↗

Evolutionary strategies for the elucidation of cis and trans factors that regulate the developmental switching programs of the beta-like globin genes.

We describe three strategies for the identification of specific cis and trans factors that regulate globin gene expression, all three of which are based on the evolution of the globin genes and their expression patterns. The first approach, phylogenetic footprinting, relies on a search for sequence similarities and is designed to elucidate the factors that control those expression patterns which are shared by orthologous globin genes of all eutherian mammals (e.g., the expression of the epsilon globin genes in the embryonic yolk sac and its repression in fetal and adult hematopoietic tissues). The second approach, differential phylogenetic footprinting, relies on a search for sequence differences. This approach may be of value in identifying the mechanisms underlying the generation of novel expression patterns in specific lineages (e.g., the expression of gamma as a fetal gene in the simian primates in contrast with the embryonic expression of gamma in all other mammals). Finally, motif-based phylogenetic analysis takes into consideration the fact that many transcription factors are quite flexible in the recognition of their cognate sites. The approach allows the detection of functionally conserved binding sites despite their sequence variation.

Adult↗

Evidence on mammalian phylogeny from sequences of exon 28 of the von Willebrand factor gene.

Phylogenetic relationships among 27 extant mammalian species (representing 15 placental orders) were studied using sequences of exon 28 of the gene encoding von Willebrand Factor (vWF), a glycoprotein which functions in blood clotting. Analysis of sequences coding for vWF revealed evidence for several subordinal and superordinal groupings, but the earliest branching sequence of placental mammals was left largely unresolved. Strong support was found for a monophyletic clade consisting of elephants, sea cows, hyraxes, aardvarks, and elephant shrews. This systematic placement of the elephant shrews agrees strongly with two other molecular data sets (interphotoreceptor retinoid binding protein and alpha-lens crystallins) and is consistent with analysis of fossil elephant shrews recently discovered in north Africa. Evidence from vWF sequences agrees with a number of previous molecular and morphological studies in providing strong support for the monophyly of both bats and rodents. The orders Primates, Proboscidea, Carnivora, Perissodactyla, and Artiodactyla were represented by more than one species which joined in each case to form a monophyletic order.

Animals↗

How many sphygmomanometric cuff inflations are necessary to obtain a hemodynamic baseline?

The purpose of this study was to determine the minimum number of consecutive blood pressure cuff inflations required to obtain seated stable resting baseline measurements of heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP). Sixty male college students aged 18 to 31 years volunteered as study subjects. Thirteen observations of HR, SBP, DBP, and MAP were recorded at 90-second intervals for each subject using a Critikon-Dinamap monitor. Stable readings for SBP and MAP were obtained in 6.5 minutes or 3 to 5 cuff inflations in the population tested. Using this procedure, additional age- and gender-specific norms could be established for normal and hypertensive subjects. Knowing the approximate quantity and frequency of blood pressure cuff inflations needed to generate baseline minimum measurements of HR, SBP, DBP, and MAP will be helpful in studies of cardiovascular reactivity, as well as for clinical and psychophysiologic treatment of hypertension.

Adult↗

Mammalian evolution and the interphotoreceptor retinoid binding protein (IRBP) gene: convincing evidence for several superordinal clades.

Phylogenetic relationships of 25 mammalian species representing 17 of the 18 eutherian orders were examined using DNA sequences from a 1.2-kb region of the 5' end of exon 1 of the single-copy nuclear gene known as interphotoreceptor retinoid binding protein (IRBP). A wide variety of methods of analysis of the DNA sequence, and of the translated products, all supported a five-order clade consisting of elephant shrew (Macroscelidea)/aardvark (Tubulidentata)/and the paenungulates (hyracoids, sirenians, and elephants), with bootstrap support in all cases of 100%. The Paenungulata was also strongly supported by these IRBP data. In the majority of analyses this monophyletic five-order grouping was the first branch off the tree after the Edentata. These results are highly congruent with two other recent sources of molecular data. Another superordinal grouping, with similar 100% bootstrap support in all of the same wide-ranging types of analyses, was Artiodactyla/Cetacea. Other superordinal affinities, suggested by the analyses, but with less convincing support, included a Perissodactyla/Artiodactyla/Cetacea clade, an Insectivora/Chiroptera clade, and Glires (an association of rodents and lagomorphs).

Animals↗

Hostility predicts restenosis after percutaneous transluminal coronary angioplasty.

OBJECTIVE: To investigate the "toxic" total (potential for) hostility component of the type A behavior pattern (assessed by means of the structured interview) as it relates to prediction of restenosis after percutaneous transluminal coronary angioplasty (PTCA). DESIGN: Patients with single vessel or multivessel coronary artery disease in whom PTCA had been scheduled or done were administered the structured interview by one trained interviewer prospectively or retrospectively (blinded to angiographic endpoints). MATERIAL AND METHODS: A total of 41 patients underwent 53 initial balloon dilations on native arteries by 1 of 5 participating cardiologists. Inclusion criteria for this study were a successful initial PTCA and post-PTCA recatheterization if a patient complained of ischemic symptoms possibly related to restenosis. RESULTS: Of the 41 patients, 15 (36.6%) had restenoses at a total of 18 previous angioplasty sites. Patients with high total (potential for) hostility ratings were almost 2.5 times more likely to have restenosis than those with low total (potential for) hostility scores (95% confidence interval = 1.03 to 5.32). Logistic regression revealed that total (potential for) hostility scores predicted post-PTCA restenosis overall as well as when adjusted for gender and race. Total (potential for) hostility scores were also positively associated with the number of arteries restenosed (P = 0.01). CONCLUSION: This is the first report of type A total (potential for) hostility behavior conferring an increased risk for restenosis after PTCA. Its modification may be effective in reducing recurrent cardiac events. A coronary-prone behavior modification program for patients with persistent, same-site restenosis after PTCA has been initiated.

Aged↗

Group treatment for adult women who experienced childhood sexual trauma: is telling the story enough?

Long-term process-oriented psychotherapy groups for adult survivors of childhood sexual abuse allow an in-depth exploration of both the individual meaning of traumatic experiences and the subsequent effects on current adult life functioning. It may not be curative just to tell the traumatic story. Therapists must also pay careful attention to unconscious reenactments by examining the process of interpersonal relating between and among group members and their therapists. Rather than avoidances, these reenactments are better viewed as a necessary form of remembering and can contribute to the understanding of the past trauma and recognition of current, previously unconscious manifestations in maladaptive behaviour. Such therapeutic benefit began to be evident in some members within 6 months in the group; for others, more time was necessary, often a year or more. Additional study and understanding of the role of reenactments in trauma treatment may lead to more effective intervention strategies that can further elucidate the complexity of this form of memory.

Adult↗

Globins in nonvertebrate species: dispersal by horizontal gene transfer and evolution of the structure-function relationships.

Using a new template based on an alignment of 145 nonvertebrate globins we examined several recently determined sequences of putative globins and globin-like hemeproteins. We propose that all globins have evolved from a family of ancestral, approx. 17-kDa hemeproteins, which displayed the globin fold and functioned as redox proteins. Once atmospheric O2 became available the acquisition of oxygen-binding properties was initiated, culminating in the various highly specialized functions known as present. During this evolutionary process, we suggest that (1) high oxygen affinity may have been acquired repeatedly and (2) the formation of chimeric proteins containing both a globin and a flavin binding domain was an additional and distinct evolutionary trend. Furthermore, globin-like hemeproteins encompass hemeproteins produced through convergent evolution from nonglobin ancestral proteins to carry out O2-binding functions as well as hemeproteins whose sequences exhibit the loss of some or all of the structural determinants of the globin fold. We also propose that there occurred two cases of horizontal globin gene transfer, one from an ancestor common to the ciliates Paramecium and Tetrahymena and the green alga Chlamydomonas to a cyanobacterium ancestor and the other, from a eukaryote ancestor of the yeasts Saccharomyces and Candida to a bacterial ancestor of the proteobacterial genera Escherichia, Alcaligenes, and Vitreoscilla.

Amino Acid Sequence↗

Hyalinizing clear cell carcinoma: report of a case.

Hyalinizing clear cell carcinoma (HCCC) is a recently described low-grade malignant neoplasm of minor salivary glands. Of the thirteen reported patients with this neoplasm, the majority have occurred in the oral cavity of elderly women. We report another case and add further supporting evidence that hyalinizing clear cell carcinoma is a distinct pathological entity.

Adenocarcinoma, Clear Cell↗

Training hospitalized patients with schizophrenia in community reintegration skills.

OBJECTIVE: The study examined the effectiveness of the Community Re-Entry Program, a brief, time-limited skills training module designed to help acutely ill inpatients become engaged in community-based treatment programs. METHODS: Of 84 consecutive admissions to a chronic psychotic disorders unit, 44 completed assessments and attended the Community Re-Entry Program. The program consists of 16 daily small-group therapy sessions that engage the patient in efforts to define discharge readiness, identify symptoms and medication effects, and assist with discharge planning. Skill levels and positive and negative symptoms were assessed on admission and on completion of training, and a subsample of patients received two-week postdischarge follow-up assessments. RESULTS: From admission to discharge, positive symptoms diminished substantially, negative symptoms diminished to a lesser but statistically significant degree, and skill levels increased significantly. Posttraining skill level was predicted by pretraining skill level and level of participation in the skills training module. Patients' symptom levels did not predict participation in the program or skill acquisition. Skill level at discharge was also more predictive of two-week postdischarge community adjustment than were symptom levels. CONCLUSIONS: Although further controlled studies are required to fully establish the efficacy of the Community Re-Entry Program, these data suggest that brief, focused skills training may play an important role in augmenting optimal pharmacotherapy for hospitalized patients with chronic psychotic disorders.

Activities of Daily Living↗