Search PubMed⌕ Search

Biomedical subjects

M Goodman

Publications and source records attributed to M Goodman.

At least 37 records · Page 2Linked to original sources
PubMed1991

Cyclic retro-inverso dipeptides with two aromatic side chains. II. Conformational analysis.

The conformations of cis and trans cyclic retro-inverso dipeptides--2-[(4-hydroxy)benzyl]-5-benzyl-4,6(1H,2H,3H,5H)-pyrimidinedi one (c[mTyr-gPhe]), and 2-benzyl-5-amino-5-[(4-hydroxy)benzyl]-4,6(1H,2H,3H,5H)-pyrimidinedione (c[mTyr-gPhe]), and 2-benzyl-5-amino-5-[(4-hydroxy)benzyl]-4,6(1H,2H,3H,5H)-pyrimidinedione (c[(alpha-amino)mTyr-gPhe])--and the parent cyclic dipeptides--c[tyrosyl-phenylalanine] (cis-c[L-Tyr-L-Phe]) and c[tyrosyl-D-phenylalanine] (trans-c[L-Tyr-D-Phe])--were studied by using 1H-nmr spectroscopy and semiempirical energy calculations. In the cis compounds of all the cyclic retro-inverso and parent dipeptides, the most stable conformer has both aromatic side chains sharing the space over the backbone ring in a "face-to-face" fashion. All the trans compounds predominantly assume a "sandwich" conformation in which the two aromatic rings are folded back over the backbone ring on opposite sides. However, different conformational preferences were observed for the backbones between the retro-inverso and parent cyclic dipeptides. The parent cyclic dipeptide trans-c[L-Tyr-D-Phe] adopts two types of boat structures with different side-chain orientations in almost equal amounts: one with the Tyr side chain in a pseudoaxial position and the Phe side chain in a pseudoequatorial position, the other with the Tyr side chain in a pseudoequatorial position and the Phe side chain in a pseudoaxial position. On the other hand, the cyclic retro-inverso dipeptides trans-c[mPhe-gTyr] and trans c[mTyr-gPhe] assume only one type of boat structure in which the malonyl side chain is in a pseudoequatorial and the gem-diamino side chain is in a pseudoaxial position. In addition to the preferred conformations, the conformational energies of the C alpha--C beta bonds in the malonyl and gem-diamino residues were estimated from the temperature variation of vicinal 1H--1H coupling constants for the H--C alpha--C beta--H groupings observed for the trans isomers of cyclic retro-inverso dipeptides. The energies were evaluated to be 1.1 and 1.8 kcal mol-1 for the malonyl and gem-diamino residues, respectively. Applying these energies to the parent cyclic dipeptide trans-c[L-Tyr-D-Phe], the observed fractions of three side-chain conformations are reasonably reproduced. The conformational energies as well as conformational properties of the molecules estimated in this investigation may be useful to refine force constants for both parent and retro-inverso peptides with aromatic side chains.

Amino Acid Sequence↗
PubMed1991

Absolute configuration for peptidomimetic residues in bioactive peptides.

A modern method is reported for the assignment of absolute configuration for peptidomimetics in bioactive peptides by use of 1H-NMR parameters in solution. Four peptide systems incorporating either retro-inverso modifications or 2-aminocyclopentanecarboxylic acid (2-Ac5c) as a peptidomimetic for proline are discussed. (1) Two 14-membered cyclic dermorphin analogs Tyr-c[D-A2bu-Phe-gPhe-(S and R)-mLeu] with a reverse amide bond between gPhe and mLeu residues where gPhe denotes a gem-diamino analog of Phe and mLeu refers to a malonyl analog of Leu. (2) Two cyclic hexapeptides related to somatostatin, c[gSar6-(S and R)-mPhe7-D-Trp8-Lys9-Thr10-Phe11], with a reverse amide bond between the gSar and mPhe residues where the gSar and mPhe denote the gemdiamino and malonyl analogs of the Sar and Phe residues, respectively. The superscript numbers refer to positions in native somatostatin. (3) Cyclic hexapeptide somatostatin analogs containing 2-Ac5c [trans-(1S,2S)-2-Ac5c, trans-(1R,2R)-2-Ac5c,cis-(1R,2S)-2-Ac5c, and cis-(1S,2R)-2-Ac5c] in place of proline c[(2-Ac5c)6-Phe7-D-Trp8-Lys9-Thr10-Phe11]. (4) Morphiceptin related analogs incorporating a cis-2-Ac5c residue as shown in Tyr-cis-2-Ac5c-Phe-Val-NH2. The methodology described in this investigation could be applied to a wide variety of peptide systems.

Magnetic Resonance Spectroscopy↗
PubMed1991

Social policy on the use of aversive interventions: empirical, ethical, and legal considerations.

In an effort to address the controversy regarding the use of aversive interventions in the treatment of individuals with developmental disabilities, this paper presents a review of the literature on the efficacy of such interventions, along with brief reviews of the ethical and legal issues involved. In general, there appears to be empirical, ethical, and legal support for the continued availability of aversive interventions as treatment options, but only if sufficient safeguards are in place.

Autistic Disorder↗
PubMed1991

The utility of 2-hydroxypropyl-beta-cyclodextrin as a vehicle for the intracerebral and intrathecal administration of drugs.

The substituted glucopyranose ring structure 2-hydroxypropyl-beta-cyclodextrin (CDEX) increases the solubility of molecules by inclusion of the agent in the lipophilic interior of the ring. This property is of particular use for the administration of molecules by the intracerebral (ICV) or intrathecal (IT) routes. In concentrations up to 40% w/v (isotonic), this agent (10 microliters) effect upon nociceptive or motor function after IT injection or on EEG and general behavior after ICV injection in rats. Using 20% CDEX, there is no change in the ED50 as compared to saline on the hot plate (HP) after IT injection of morphine, D-Ala2-D-Leu5 enkephalin or Tyr-Aib-Gly-gPhe-mAib-NH2, (Aib: alpha-aminoisobutyric acid) although there is an increase in their respective durations of effect. Cyclic peptide opioids: Tyr-c[D-A2bu-Gly-D-beta Nal(1)-D-Leu] (A2bu: alpha, gamma-diaminobutyric acid; beta-Nal(1): beta-naphthylalanine(1)) or Tyr-c[DA2bu-Gly-beta Nal(1)-D-Leu] are insoluble in saline but are readily dissolved in CDEX, and display a naloxone-sensitive antinociception following spinal administration. In other studies, saline insoluble capsaicin is administered in 25% dimethylsulfoxide (DMSO) or 20% CDEX (15 microliters; 5 mg/ml) which result in a significant reduction in the spinal levels of substance P and calcitonin gene related peptide and an increase in the HP latency. DMSO alone, but not CDEX alone, reduces the levels of the two peptides. These data emphasize the utility of complexation with CDEX for intracerebral drug delivery and compatibility with brain and spinal tissue.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed1991

Photon irradiation of unresectable carcinomas of salivary glands.

This paper presents our experience and the local control rates of a group of patients with inoperable and unresectable lesions treated by photon irradiation from 1980 through 1989. The patient material consists of a total of 24 patients, 9 with carcinoma arising from the parotid gland and 15 with lesions in the minor salivary glands, mainly the oral cavity and oropharynx. The pathologic slides were reviewed and malignancy of various cell types confirmed. The 5-year actuarial local control of parotid gland lesions after photon irradiation was 100% and the survival rate was 65%. For the minor salivary gland lesions, the 5-year actuarial local control was 78% and the survival rate with or without disease was 93%. All lesions were irradiated by accelerated hyperfractionated photons (bid) with 1.6 Gy per fraction, intermixed with various boost techniques including electron beam, intraoral cone, interstitial implant, and/or submental photons for a total of 65-70 Gy. Most treatment failures of parotid cancer were due to distant metastases. The present series showed excellent local control and satisfactory survival of inoperable and unresectable salivary gland carcinomas after state-of-the-art photon irradiation, comparable to that achieved by neutron irradiation. The late complications were minimal. A controlled randomized trial may be indicated.

Adenocarcinoma↗
PubMed1991

Adjuvant systemic therapy of stage I and II breast cancer.

The value of adjuvant systemic therapy has been clearly demonstrated in both node-positive and node-negative patients. However, there are many women with favorable prognoses whose breast cancer recurs. It has been possible only recently to identify subsets of patients who are at definite risk for recurrence. Advances both in selection and treatment of patients with early-stage breast cancer are being made as critical research questions are delineated and examined in prospective randomized trials.

Breast Neoplasms↗
PubMed1991

Phylogenetic scanning: a computer-assisted algorithm for mapping gene conversions and other recombinational events.

An algorithm, 'phylogenetic scanning', is described for mapping gene conversion events where comparative DNA sequence data are available from different species. In this algorithm, sets of hypothetical phylogenetic trees are constructed that describe possible sequence relationships due to gene conversions in different species lineages; these trees are then evaluated by the principle of parsimony at intervals in the sequence alignment. When used to map gene conversion events that occurred between the pair of gamma-globin genes of higher primates, the algorithm gives results nearly identical to those obtained using a tedious manual approach. Suggestions are also provided for adaptation of this procedure to the analysis of other recombination events.

Algorithms↗
PubMed1991

Key relationships of never married, childless older women: a cultural analysis.

The key relationships of never married, childless older women, that is, those relationships described as central, compelling, enduring, or significant throughout their lifetimes, were explored in this study. Analysis of qualitative, ethnographically based interviews with 31 women indicated that the key relationships they describe fall into three classes: ties through blood, friendships, and those we label "constructed" ties (kin-like nonkin relations). We report on types of key interpersonal relationships of these women and also examine limits to these key relations, describing some strategies these women have adopted for gaining kin-like relations and the problems inherent in them for the expectation of care in later life. Theoretical work by anthropologist David Schneider concerning American kinship as a cultural system is used to explore dimensions of these relationships.

Achievement↗
PubMed1991

Cultural differences among elderly women in coping with the death of an adult child.

This article describes differences between elderly Jewish and non-Jewish women in dealing with the death of an adult child. Dimensions of difference include the meaning of the death to the mother, her expression of grief, and her conceptualization of the future in the face of the loss. Results are based on data from 12 Jewish and 17 non-Jewish women taking part in a larger study examining generativity as a predictor of well-being in women over 60. Data collection included in-depth life histories and quantitative evaluations of well-being, affect, generativity, and personality variables associated with mothering. Qualitatively, Jewish women were depressed and fixed in grief, with the loss remaining central to their lives. Non-Jewish women articulated philosophies of acceptance, putting the death in a perspective that enabled them to move beyond their loss. Well-being, affect, generativity, and personality measures statistically supported the qualitative differences found between the groups.

Adaptation, Psychological↗
PubMed1991

Molecular evolution of the psi eta-globin gene locus: gibbon phylogeny and the hominoid slowdown.

An 8.4-kb genomic region spanning both the psi eta-globin gene locus and flanking DNA was sequenced from the common gibbon (Hylobates lar). In addition, sequencing of the entire orthologous region from galago (Galago crassicaudatus) was completed. The gibbon and galago sequences, along with published orthologous sequences from 10 other species, were aligned. These noncoding nucleotide sequences represented four human alleles, four apes (chimpanzee, gorilla, organgutan, and gibbon), an Old World monkey (rhesus monkey), two New World monkeys (spider and owl monkeys), tarsier, two strepsirhines (galago and lemur), and goat. Divergence and maximum parsimony analyses of the psi eta genomic region first groups humans and chimpanzees and then, at progressively more ancient branch points, successively joins gorillas, orangutans, gibbons, Old World monkeys, New World monkeys, tarsiers, and strepsirhines (the lemuriform-lorisiform branch of primates). This cladistic pattern supports the taxonomic grouping of all extant hominoids into family Hominidae, the division of Hominidae into subfamilies Hylobatinae (gibbons) and Homininae, the division of Homininae into tribes Pongini (orangutans) and Hominini, and the division of Hominini into subtribes Gorillina (gorillas) and Hominina (chimpanzees and humans). The additional gibbon and galago sequence data provide further support for the occurrence of a graded evolutionary-rate slowdown in the descent of simian primates, with the slowing rate being more pronounced in the great-ape and human lineages than in the gibbon or monkey lineages. A comparison of global versus local molecular clocks reveals that local clock predictions, when focused on a specific number of species within a narrow time frame, provide a more accurate estimate of divergence dates than do those of global clocks.

Animals↗
PubMed1991

Biological and conformational studies of [Val4]morphiceptin and [D-Val4]morphiceptin analogs incorporating cis-2-aminocyclopentane carboxylic acid as a peptidomimetic for proline.

We report the synthesis, biological activity, and conformational analysis of tetrapeptide analogs related to [Val4]morphiceptin and [D-Val4]morphiceptin in which the proline at the second position has been replaced with cis-2-aminocyclopentane carboxylic acid (cis-2-Ac5c). Since the cis-2-Ac5c residue contains a normal amide, only the trans form has been observed about the amide bond between the first and second residues. The cis-2-Ac5c is a beta amino acid with two chiral centers resulting in two possible configurational isomers, namely (1S, 2R) and 1R, 2S) forms. The analogs containing the (1S, 2R)-Ac5c residue show activity at the mu-receptor but are inactive at the delta-receptor, resulting in a high selectivity for the mu-receptor. The (1R,2S)-Ac5c containing analogs are completely inactive at both the mu- and delta-receptors. The conformational analysis indicates that the separation of the aromatic rings of the tyrosine and phenylalanine residues, as expressed by the center-to-center distance, is 10.1-12.7 A for the preferred conformations of the bioactive analogs containing the (1S,2R)-Ac5c residue while a range of 4.8-7.0 A is observed for the preferred conformations of the inactive analogs with the (IR,2S)-Ac5c residue. A comparison of the findings from the conformational analysis and biological assays establishes the fact that a relatively large separation of the two aromatic side chains is required for the mu-opioid receptor activity of these molecules. Since the tetrapeptide amides studied in this investigation show similar biological profiles to those of the morphiceptin-related analogs, we have compared the preferred conformations estimated for the cis-2-Ac5c containing analogs with those of morphiceptin. One of the low energy conformations calculated for morphiceptin with the cis form about the tyrosine and proline residues has considerable topological similarity with the bioactive analogs containing the (1S,2R)-Ac5c residue, indicating that the cis from about these two residues is required for the biological activity of the morphiceptin-related analogs containing the proline at the second position.

Amino Acid Sequence↗
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↗