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M Goodman

Publications and source records attributed to M Goodman.

At least 235 records · Page 13Linked to original sources
PubMed1991

Solid phase synthesis of human growth hormone-releasing factor analogs containing a bicyclic beta-turn dipeptide.

Three analogs derived from the N-terminal 29-residue fragment of human growth hormone-releasing factor (hGRF) which contained a bicyclic beta-turn dipeptide (BTD) at 7-8, 8-9, and 9-10 positions were synthesized by solid phase methodology to ascertain if the beta-turns are important for the biological activity of hGRF and also to show the applicability of the BTD unit to solid phase synthesis. All three analogs were obtained in good yield and purity indicating that the BTD unit can be used in the usual condition of solid phase synthesis. The capacity of these analogs to release growth hormone (GH) was tested in an in vitro bioassay using rat anterior pituitary cells. All three BTD-containing analogs showed the same maximal GH secretion with parallel dose-response curves to that of hGRF(1-29)NH2, except their relative potencies were very low.

Amino Acid Sequence↗
PubMed1991

Leiomyosarcoma of the trachea. Case report.

Leiomyosarcoma of the trachea is a rare primary tumor of the upper airway. Twelve cases have been reported in the English-language literature. Our experience with a patient with leiomyosarcoma of the cervical trachea is presented. The classic symptoms, diagnosis, and surgical management of this case are contrasted with those of the previously reported cases. The surgical technique used for our patient, primary tumor resection with skin grafting and placement of a Montgomery Laryngeal Stent, is a unique and effective treatment.

Adult↗
PubMed1991

Six-year follow-up of early physiotherapy intervention in very low birth weight infants.

Eighty very low birth weight infants assigned to neurologically normal or at-risk groups on the basis of a neurodevelopmental score were previously described. Infants were assigned to physiotherapy or control groups, and the effect of physiotherapy was assessed at 1 year. At-risk infants had a significantly lower developmental quotient than the normal group and no beneficial effect of physiotherapy was shown. Of the original 80 subjects, 49 were reassessed at a mean age of 74.7 months. As observed previously, physiotherapy until 1 year did not influence subsequent outcome in either normal or at-risk children. At-risk and normal children had similar mean developmental quotients at 6 years, but the locomotor score of at-risk children was significantly below that of normal children. Cerebral palsy occurred in 6 of 24 at-risk vs 0 of 25 normal subjects (P less than .01) and remedial therapy was recommended in 17 of 24 at-risk subjects vs 6 of 25 normal subjects (P less than .001). These results confirm that the neurodevelopmental score predicts a risk for either cerebral palsy or soft neurological problems, and early physiotherapy is of questionable benefit in preventing such problems.

Central Nervous System↗
PubMed1990

The -175T----C mutation increases promoter strength in erythroid cells: correlation with evolutionary conservation of binding sites for two trans-acting factors.

A point mutation at position -175 has been detected in Agamma as well as Ggamma globin genes in individuals with hereditary persistence of fetal hemoglobin (HPFH). To prove that this single point mutation results in increased promoter strength, we transfected erythroid and nonerythroid cell lines with constructs containing normal and mutant promoters linked to the bacterial chloramphenicol acetyl transferase (CAT) gene. Differences in transfection efficiency were controlled by cotransfection of pRSVgpt. In K562 erythroleukemia cells, the -175 HPFH promoter directed three- to fourfold more CAT activity than its wild type counterpart. However, in HeLa cells the two promoters were similar in strength. The -195 to -165 region of the gamma-globin promoter contains binding sites for two proteins: a ubiquitously distributed octamer binding protein, OBP, and the erythroid-specific protein, GF-1. We find that while the GF-1 binding site is highly conserved among related primate gamma-globin genes, the octamer binding site is not. The evolutionary conservation of GF-1 as well as its erythroid-specific distribution suggest that this protein is important in gamma-globin gene expression. A role for OBP in the regulation of gamma-globin, if any, must have arisen recently in primate evolution.

Animals↗
PubMed1990

Molecular history of gene conversions in the primate fetal gamma-globin genes. Nucleotide sequences from the common gibbon, Hylobates lar.

Comparative and phylogenetic analyses of homologous sequences from closely related species reveal genetic events which have happened in the past and thus provide considerable insight into molecular genetic processes. One such process which has been especially important in the evolution of multigene families is gene conversion. The fetal gamma 1 and gamma 2-globin genes of catarrhine primates (humans, apes, and Old World monkeys) underwent numerous gene conversion events after they arose from a gene duplication event 25-35 million years ago. By including the gamma 1- and gamma 2-globin gene sequences from the common gibbon, Hylobates lar, the present work expands the gamma-globin data set to represent all major groups of hominoid primates. A computer-assisted algorithm is introduced which reveals converted DNA segments and provides results very similar to those obtained by site-by-site evolutionary reconstruction. Both methods provide strong evidence for at least 14 different converted stretches in catarrhine primates as well as five conversions in ancestral lineages. Features of gene conversions generalized from this molecular history are 1) conversions are restricted to regions maintaining high degrees of sequence similarity, 2) one gene may dominate in converting another gene, 3) sequences involved in conversions may accumulate changes more rapidly than expected, and 4) certain elements, such as polypurine/polypyrimidine [Y)n) and (TG)n elements, appear to be hotspots for initiating or terminating conversion events.

Amino Acid Sequence↗
PubMed1990

Enkephalin analogues containing beta-naphthylalanine at the fourth position.

To examine the importance of the aromatic side chains of enkephalin on opiate activity, we report the synthesis and conformational analysis of a series of analogues related to enkephalin with beta-naphthylalanine in place of phenylalanine at the fourth position. Three linear analogues (Tyr-D-Ala-Gly-(L and D)-beta Nal(1)-Leu-NH2 and Tyr-D-Ala-Gly-beta Nal(2)-Leu-NH2) were initially synthesized to examine the effect of the substitution on biological activity. The increased activity of these peptides at the mu-opiate receptor, compared to native Leu-enkephalin, prompted us to examine the more conformational constrained analogues, Tyr-c[D-A2bu-Gly-(L and D)-beta Nal(1)-Leu], incorporating a alpha, gamma-diaminobutyric acid at the second position and cyclization to the carboxylic end of the leucine. These two cyclic analogues provide insight into the necessity for the L chirality of the aromatic residue at position 4. The Tyr-c[D-A2bu-Gly-L-beta Nal(1)-Leu] analogue is highly potent and displays a slight preference for the mu receptor. The conformational analysis indicates that despite the high flexibility of the tyrosine side chain, the aromatic rings of the tyrosine and naphthylalanine are relatively distant from each other. The presence of two intramolecular hydrogen bonds help maintain the conformation of the 14-membered backbone ring that keeps the side chains directed away from each other. These findings are in agreement with our model of an extended structure required for mu selectivity and a folded form with close aromatic ring placement for delta selectivity.

Alanine↗
PubMed1990

Primate evolution at the DNA level and a classification of hominoids.

The genetic distances among primate lineages estimated from orthologous noncoding nucleotide sequences of beta-type globin loci and their flanking and intergenic DNA agree closely with the distances (delta T50H values) estimated by cross hybridization of total genomic single-copy DNAs. These DNA distances and the maximum parsimony tree constructed for the nucleotide sequence orthologues depict a branching pattern of primate lineages that is essentially congruent with the picture from phylogenetic analyses of morphological characters. The molecular evidence, however, resolves ambiguities in the morphological picture and provides an objective view of the cladistic position of humans among the primates. The molecular data group humans with chimpanzees in subtribe Hominina, with gorillas in tribe Hominini, orangutans in subfamily Homininae, gibbons in family Hominidae, Old World monkeys in infraorder Catarrhini, New World monkeys in semisuborder Anthropoidea, tarsiers in suborder Haplorhini, and strepsirhines (lemuriforms and lorisiforms) in order Primates. A seeming incongruency between organismal and molecular levels of evolution, namely that morphological evolution appears to have speeded up in higher primates, especially in the lineage to humans, while molecular evolution has slowed down, may have the trivial explanation that relatively small genetic changes may sometimes result in marked phenotypic changes.

Animals↗
PubMed1990

Evolution of EF-hand calcium-modulated proteins. I. Relationships based on amino acid sequences.

The relationships among 153 EF-hand (calcium-modulated) proteins of known amino acid sequence were determined using the method of maximum parsimony. These proteins can be ordered into 12 distinct subfamilies--calmodulin, troponin C, essential light chain of myosin, regulatory light chain, sarcoplasmic calcium binding protein, calpain, aequorin, Stronglyocentrotus purpuratus ectodermal protein, calbindin 28 kd, parvalbumin, alpha-actinin, and S100/intestinal calcium-binding protein. Eight individual proteins--calcineurin B from Bos, troponin C from Astacus, calcium vector protein from Branchiostoma, caltractin from Chlamydomonas, cell-division-cycle 31 gene product from Saccharomyces, 10-kd calcium-binding protein from Tetrahymena, LPS1 eight-domain protein from Lytechinus, and calcium-binding protein from Streptomyces--are tentatively identified as unique; that is, each may be the sole representative of another subfamily. We present dendrograms showing the relationships among the subfamilies and uniques as well as dendrograms showing relationships within each subfamily. The EF-hand proteins have been characterized from a broad range of organismal sources, and they have an enormous range of function. This is reflected in the complexity of the dendrograms. At this time we urge caution in assigning a simple scheme of gene duplications to account for the evolution of the 600 EF-hand domains of known sequence.

Amino Acid Sequence↗
PubMed1990

Synthesis and beta-adrenergic antagonist activity of stereoisomeric practolol and propranolol derivatives.

A series of stereoisomeric practolol and propranolol derivatives has been synthesized in which the N-isopropyl group of the drug was replaced by an asymmetric heptanoic acid terminated by a substituted p-toluidide or p-(trifluoromethyl)anilide. The asymmetric epoxide, 3-(p-acetamidophenoxy)-1,2-epoxypropane, was allowed to react with a preformed enantiomeric 6-aminoheptanoic acid amide to yield the stereoisomeric practolol congener derivatives. An asymmetric drug precursor epoxide was prepared from p-acetamidophenol and enantiomeric 3-(tosyloxy)-1,2-epoxypropane 6-aminoheptanoic acid amides were allowed to react with one of the enantiomers of 3-(1-naphthyloxy)-1,2-epoxypropane. This drug precursor epoxide was prepared either by combining 1-naphthol with enantiomeric 3-(tosyloxy)-1,2-epoxypropane (the Sharpless epoxide) or by combining 1-naphthol with enantiomeric 3-(tosyloxy)-1,2-propanediol followed by epoxidation. Pharmacological studies carried out for the practolol derivatives demonstrated a significant dependence of enhanced potency and tissue/subreceptor specificity on both the configuration of the drug asymmetric carbon and the configuration of the spacer asymmetric carbon. The compounds containing the S configuration at the drug asymmetric center and the R configuration at the spacer asymmetric carbon exhibited an increase in potency over the other stereoisomeric congener derivatives and the progenitor drug. For the propranolol congener derivatives, a large decrease in potency was observed for all of the stereoisomers over the progenitor drug. The propranolol stereoisomers containing the S configuration at the drug asymmetric center were more active than those containing the R configuration at that center.

Adipose Tissue↗
PubMed1990

Morphiceptin analogs containing 2-aminocyclopentane carboxylic acid as a peptidomimetic for proline.

As part of a program to study the structure-activity relationship of peptide opioids we report the synthesis, conformational characterization and biological activity of four analogs related to morphiceptin in which the proline at position two has been substituted with 2-aminocyclopentane carboxylic acid (beta Ae5c). The beta Ac5c residue is a beta amino acid with two chiral centers resulting in four possible configurations; two configurational cis (R,S and S,R) and two configurational trans (R,R and S,S) forms. Utilizing high resolution n.m.r. at 500 MHz and computer simulations with NOE restraints the chirality of the beta Ac5c residues are assigned. The analog containing the R,S-beta Ac5c is active at both the mu and delta-opioid receptors, with a slight preference for the mu-receptor. The (S,R), (S,S), and (R,R) analogs show minimal activity at the mu-receptor and are inactive at the delta-receptor. A comparison of the findings from the conformational analysis and biological assays lends insight into the structure-activity relationship of this important peptide opiate.

Amino Acid Sequence↗
PubMed1990

Cyclic hexapeptides related to somatostatin. Synthesis and biological testing.

As a continuation of our program to study the structure-function relationship of the peptide hormone somatostatin, we report the synthesis and biological potencies of a series of cyclic hexapeptide analogs related to somatostatin. The parent peptide of this series was designed by Veber and coworkers, c[-Pro6-Phe7-D-Trp8-Lys9-Thr10-Phe11-], and has been reported to be superactive in the inhibition of the release of growth hormone. (The superscript numbers refer to the positions of residues in native somatostatin). The series of analogs has been designed to examine the role of the so-called bridging region, Phe11-Pro6, which has been postulated to be important in maintaining the proper conformation of the biologically active tetrapeptide, Phe-D-Trp-Lys-Thr. We have incorporated peptidomimetics and the retro-inverso modification into the bridging region of the molecule, with the aim of affecting the conformational preferences found in the parent peptide. Results from the biological assay--in vitro inhibition of growth hormone--and the conformational analysis (adjoining paper) of our analogs will provide insight into the relationship between structure and biological activity of somatostatin.

Amino Acid Sequence↗
PubMed1990

Cyclic hexapeptides related to somatostatin. Conformational analysis employing 1H-NMR and molecular dynamics.

We report the conformational analysis of a series of cyclic hexapeptides related to the hormone somatostatin utilizing 1H NMR spectroscopy and NOE restrained molecular dynamics. The conformational preferences and results from biological analysis of these analogs (previous paper) allow for refinement of the current understanding of the structure-activity relationship of somatostatin. For most of the molecules examined, a beta II' turn about the D-tryptophan-lysine residues, postulated to be required for biological activity, was present. From the NOE restrained molecular dynamics, it can be seen that the turn structure is important for the maintenance of the proper orientation of the side chains of the adjacent phenylalanine, tryptophan and lysine. The biologically active analogs have the side chains of lysine and D-tryptophan extended away from the 18-membered ring in close proximity to each other for a significant portion of the dynamic simulations. Although other conformations are accessible and monitored during the simulations, we believe this is important for biological recognition. The absence of the beta II' turn at the D-tryptophan-lysine disrupts this side chain array producing inactive molecules. The role of the bridging region, the Phe-Pro dipeptide, is to stabilize the beta II' turn and help maintain the proper orientation of the biologically important side chains.

Amino Acid Sequence↗
PubMed1990

Characterization of chromosomes and localization of the rDNA locus in the aye-aye (Daubentonia madagascariensis).

The karyotype of a prosimian primate, the aye-aye (Daubentonia madagascariensis), is described. Results from a variety of staining methods (Q-, R-, G-, and C-banding, distamycin A/DAPI and methyl-green/DAPI) are reported. Sites of methylation were visualized using antibodies against 5-methylcytosine. Digestion of aye-aye fixed metaphase chromosomes with the restriction endonuclease HaeIII produced G-banding. No other restriction enzymes tested produced clear G- or C-banding patterns. Ag-staining of the nucleolar organizer regions (NORs) revealed the location of rDNA sites on the short arms of the smallest pairs of acrocentric chromosomes, 13p and 14p.

5-Methylcytosine↗