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Biomedical subjects

M Goodman

Publications and source records attributed to M Goodman.

At least 253 records · Page 14Linked to original sources

Effect of serial casting for the prevention of equinus in patients with acute head injury.

Ten adults with traumatic head injury received serial casts within 14 days of injury for the prevention or correction of equinus. Eighteen limbs (16 bilateral) with spasticity were involved. An average of five casts for a total duration of four to 64 days were used for each limb. Comparisons of passive dorsiflexion measures before and after casting showed a mean gain of 21 degrees (paired t-test, P less than .05). Of the 18 limbs, 13 reached a passive dorsiflexion of 0 degrees or more (ie, no equinus) which could be maintained without force for at least one hour. The procedures appeared safe and the results of the trial were clinically judged to be favorable. There is a need to further assess the efficacy of serial casting through randomized controlled trials and long-term followups.

Adult↗

An adaptation of the Miller patient classification system for the postanesthesia care unit at Children's Hospital of Eastern Ontario.

Using the Miller Patient Classification framework, a descriptive three-phase study was carried out in order to develop a classification system specifically for the PACU of the Children's Hospital of Eastern Ontario. This study contributes further understanding of the complexities of developing a reliable classification system for the pediatric PACU.

Hospitals, Pediatric↗

In vivo administration of interleukin-1 inhibits glucose-stimulated insulin release.

Recombinant interleukin-1 beta (IL-1 beta) was administered intraperitoneally for 3 days to normal C57BL/6ByJ (B6) mice. The islets from IL-1-treated and control animals were isolated and glucose-stimulated insulin secretion studied in the perifusion system. The total islet insulin content and the ultrastructure of the islets isolated from the animals treated with IL-1 did not differ from those seen in control animals. However, glucose-stimulated insulin release was significantly impaired after 3 days of in vivo administration of IL-1, either 3 micrograms/animal/day or 0.3 micrograms/animal/day. The administration of IL-1 inhibited an acute phase of glucose-induced insulin release, whereas neither basal insulin secretion nor insulin release from 10-30 min of perifusion with glucose was impaired. There was an only partial (27%) and non-significant restoration of the insulin secretory response to glucose stimulation 4 days after discontinuation of IL-1 treatment. We conclude that IL-1 administered in vivo is capable of adversely affecting pancreatic islet response to glucose stimulation. After 3 days of administration, these changes are confined to the process of insulin release, with the islet cell morphology and total insulin content being unaffected.

Animals↗

Tarsius delta- and beta-globin genes: conversions, evolution, and systematic implications.

Comparisons between duplicated genes have shown that gene conversions play an important role in the evolution of multigene families. Previous comparisons have documented in the recently duplicated gamma-fetal globin genes of catarrhine primates, over 15 separate conversions affecting extensive stretches of coding and noncoding sequences. In the present study, delta- and beta- globin genes from a lower primate Tarsius syrichta, and the delta-globin gene of the Asian great ape, Pongo pygmaeus, have been isolated and sequenced. Comparisons of these sequences with other primate delta and beta sequences confirmed a previously reported conversion in an anthropoid ancestor and revealed additional conversions in basal primate, stem haplorhine, tarsier, and early lemur lineages. Conversions found between primate delta- and beta-globin genes contrast with those found in the gamma-genes in that delta-beta conversions appear much less frequently and are more restricted to regions conserved by selection (i.e. coding and 5'-regulatory sequences). These differences indicate that soon after a duplication occurs, conversions can be quite frequent and encompass extensive portions of the duplicated region. With time, sequence differences accumulate, particularly in noncoding regions, and limit both the frequency and size of the conversions. Sequences conserved by selection accumulate differences more slowly and are therefore subject to gene conversions for a longer period of time. Both unconverted and converted sequences were consistent in supporting the placement of tarsier with anthropoids.

Animals↗

Clinical and radiographic improvement of bone of the second lumbar vertebra in Paget's disease following therapy with etidronate disodium: a case report.

Paget's disease of bone is most commonly seen in the spine; it may either be asymptomatic or may cause pain and neurologic impairment. We describe a patient with back pain due to Paget's disease of the second lumbar vertebra and spinal stenosis. The patient had a dramatic clinical and radiographic response to 2 courses of etidronate disodium, which was evidenced by resolution of the back pain and improvement in bony spinal stenosis. Etidronate may be effective in reversing bony spinal stenosis due to Paget's disease.

Etidronic Acid↗

Interactive NMR and computer simulation studies of lanthionine-ring structures.

We report progress in elucidating the structure of nisin, a naturally occurring peptide antibiotic. Nisin contains five rings constrained by lanthionine or methyllanthionine bridges, as well as alpha, beta-unsaturated amino acids. We have determined conformations for two model compounds of ring A and a derivative of ring B through interactive nmr and computer simulation studies. High-resolution nmr techniques provides structural information, which was further refined through molecular dynamics simulations. These methods are being applied to the remaining constrained fragments of the molecule. This conformational information will be employed in an aufbau approach to determining the structure of the entire molecule.

Alanine↗

A morphometric study of the vascularity of oral squamous cell carcinomas and its relation to outcome of radiation therapy.

In 26 patients the vascular morphology of pretreatment biopsies from oral squamous cell carcinomas (scc) was studied. Patients had been treated by radiation alone and followed up for 25-73 months. Vascular endothelial cells were identified using antifactor VIII staining. The distances from 700 randomly selected tumor cells to the closet blood vessel were measured in each tumor. Stepwise logistic regression analysis revealed that tumors with fewer than 21% of the morphologically intact tumour cells located within 48 microns of the closest blood vessel had a better control rate than tumors with a higher proportion of tumor cells within this distance. Using the analysis as a predictive assay, local tumor control was predicted from a single histological section with a sensitivity of 81% and a specificity of 60%. In correctly predicted cases of local control, the average median distance between tumor cells and blood vessels was 105 microns. These tumors formed well differentiated avascular tumor cell nests that were surrounded by stroma and blood vessels. Mitotic figures were observed only in the outer rim of cell nests while the center was often keratinizing or necrotic. In cases of correctly predicted treatment failures the average median distance from intact tumour cells to capillaries was 76 microns. These tumors showed varying degrees of organization and capillaries penetrating tumor cell areas. Clinical outcome of radiation therapy of oral scc appears to be correlated with different patterns of tumor architecture and blood supply.

Carcinoma, Squamous Cell↗

Managing the side effects of chemotherapy.

More chemotherapy is being administered today than ever before. Megadoses of these drugs are becoming commonplace. Better methods of drug delivery, patient monitoring, and sophisticated support services such as infectious disease specialists, transfusion therapy, intensive care facilities, oncology clinical nurse specialists, and others, enable the physician to treat the patient in a variety of settings, including ambulatory care centers and the home. Just as the nurse needs advanced skills and the knowledge to know the subtle differences between an expected side effect and a toxic reaction, the patient needs to learn preventive health care and which symptoms to report at a time when management strategies can be most effective. Research by Dodd indicates that patients who received information on side-effect management techniques performed more self-care behaviors, and many acted promptly before side effects became persistent or severe. In addition, Stromberg advocates teaching self care to encourage persons with cancer to increase their sense of self-control and lessen feelings of helplessness that often accompany cancer and its treatment. The nurse is further challenged to teach patients to actively participate in their care rather than remaining dependent on the health-care professional. Using skill as a patient educator, the nurse enlists the patient and family members in a partnership to promote self-care. This requires the nurse to use great creativity and flexibility to individualize the approach to patient management problems.

Antineoplastic Combined Chemotherapy Protocols↗

A statistical test that supports a human/chimpanzee clade based on noncoding DNA sequence data.

Using the aligned DNA sequence data of Miyamoto et al. and Maeda et al., all noncoding genetic material, and a simple statistical test, we show that a Homo/Pan clade is supported at approximately the 3% level of significance. The method accommodates polymorphism and different evolutionary rates for different sites. All assumptions on which the statistical study is based are made explicit. (See the Note added in proof, which--adding recently published data--improves the significance level to about 1%.

Animals↗

A molecular view of primate phylogeny and important systematic and evolutionary questions.

Phylogenetic analysis of extensive nucleotide sequence data from primate beta-globin gene clusters elucidates the systematics and evolution of the order Primates and reveals that rates of accumulation of mutations vary by as much as a factor of seven among different primate lineages. The picture of primate phylogeny from DNA sequences clarifies many ambiguities of the morphological picture. In the molecular picture, dwarf and brown lemurs group together into superfamily Lemuroidea, Lemuroidea and Lorisoidea into suborder Strepsirhini, and Tarsius and Anthropoidea into suborder Haplorhini. The molecular picture also provides both significant evidence for a human-chimpanzee clade that narrowly excludes gorilla and overwhelming evidence for the gorilla-chimpanzee-human clade within Hominoidea. Rates of DNA sequence evolution appear to have been fastest in the early primates ancestral to Anthropoidea and next fastest on the lorisoid branch. Rates were slowest over the past 25 Myr of hominoid descent, suggesting that mechanisms lowering the mutation rate evolved in correlation with lengthened life spans.

Animals↗

Sebaceous carcinoma. Diuretic use, lacrimal system spread, and surgical margins.

Twenty cases of adnexal sebaceous carcinoma managed by contemporary methods, including monitoring of surgical margins, were reviewed. Eight of 20 patients were taking diuretic medications. The initial clinical diagnosis was incorrect in all cases, and 50% of cases were misdiagnosed by the pathologist interpreting the initial biopsy. The canaliculus was identified in 7 cases, and was involved by tumor in 3 cases. Tumor was identified in the lacrimal sac and inferior turbinate in an additional case. Thus, tumor spread into the lacrimal excretory system was documented by histologic findings in 4 cases.

Adenocarcinoma↗

Neuropeptide Y and neuropeptide Y18-36. Structural and biological characterization.

Neuropeptide Y (NPY), a 36-residue peptide amide, has been shown by numerous studies to be a potent vasoconstrictor. In order to gain an appreciation of the structural requirements for this action, we have previously synthesized a number of fragments of NPY. It had been shown that sequential deletions from the N-terminus resulted in peptides with decreasing hypertensive activity. In the present study we present data supporting the unexpected finding of two fragments, NPY17-36 and NPT18-36 with substantial hypotensive action in vivo. This action was dose dependent (data not shown) and was also observed to a lesser extent with NPY19-36 but not NPY16-36 or NPY20-36. It was, however, slower in onset and of longer duration than the hypertensive action of NPY. These differing kinetics of action may suggest that NPY and NPY18-36 act through different mechanisms. Structural studies using circular dichroism were performed. While NPY was found to assume an ordered helical structure in both aqueous buffer and trifluoroethanol (TFE), 30% TFE in aqueous buffer was required to induce substantial helicity for NPY18-36. This structural investigation suggests that both NPY and NPY18-36 assume an ordered conformation upon reaching the lipid rich receptor environment.

Animals↗

Molecular phylogeny of the family of apes and humans.

The morphological picture of primate phylogeny has not unambiguously identified the nearest outgroup of Anthropoidea and has not resolved the branching pattern within Hominoidea. The molecular picture provides more resolution and clarifies the systematics of Hominoidea. Protein and DNA evidence divides Hominoidea into Hylobatidae (gibbons) and Hominidae, family Hominidae into Ponginae (orangutan) and Homininae, and subfamily Homininae into two tribes, one for Gorilla, and the other for Pan (chimpanzee) and Homo. Parsimony and maximum likelihood analyses, carried out on orthologous noncoding nucleotide sequences from primate beta-globin gene clusters, provide significant evidence for the human-chimpanzee tribe and overwhelming evidence for the human-chimpanzee-gorilla clade. These analyses also indicate that the rate of molecular evolution became slower in hominoids than in other primates and mammals.

Animals↗

In vitro pharmacological properties of a series of isoprenaline derivatives.

The p-trifluoromethylanilide congener of isoprenaline, tert-butyl N-[(S)[( 4-[(R)-6-[2-(3,4-dihydroxyphenyl-2- hydroxyethyl]amino]heptanamido]phenyl]methyl][(N-methylcarbamoy l) methyl]carbamoyl]methyl]carbamate (1S,4R)-4,7,7-trimethyl-3-oxo-2- oxabicyclo[2.2.1]heptane-1-carboxylate (1:1) (Ro 17-2218) was investigated for its effects in various pharmacological tests in vitro and compared to the parent compound. As Ro 17-2218 represented a mixture of four diastereomers, the pure isomers were synthesized. They had a purity of 97-98%. By pharmacological testing of the diastereomers the highest potency was found in the 6R,2'R-isomer Ro 17-8648, while the potency of the 6S,2'S-isomer, Ro 17-9651 was lower by three orders of magnitude. The amorphous hydrochloride Ro 17-8648/001 had 1/10 the potency of the respective crystalline camphanate Ro 17-8648/003. (R)-6-[(R)-[2-(3,4-Dihydroxyphenyl)-2-hydroxyethyl]amino]-N-[4- (trifluoromethyl) phenyl]heptan amide (Ro 17-8648/003) was found to have potent beta-agonist properties with clear beta 1-selectivity in radioligand binding studies. It exerted an extremely tight binding to membrane receptors. As a full beta-agonist it elicited positive inotropic effects in isolated cardiac tissues, with a potency 10-360 times that of isoprenaline and an extremely long duration of action. Electrophysiological studies in isolated guinea-pig papillary muscles confirmed the beta 1-receptor-mediated effects of the compound.

Animals↗

Embryonic epsilon and gamma globin genes of a prosimian primate (Galago crassicaudatus). Nucleotide and amino acid sequences, developmental regulation and phylogenetic footprints.

Sequence analysis of epsilon and gamma genes and encoded globins and high-pressure liquid chromatography analysis of globin compositions in blood hemolysates obtained from embryos, fetuses and adults show that the prosimian primate Galago crassicaudatus expresses its epsilon and gamma genes only embryonically. Since rabbit, mouse and galago all have embryonic gamma genes but simian primates have fetal gamma genes, we conclude that gamma E evolved into gamma F in stem-simians. An elevated non-synonymous substitution rate characterizes this transition. The alignment of epsilon and gamma nucleotide sequences and the parsimoniously reconstructed evolutionary history of these sequences identify several anciently conserved cis-regulatory elements (phylogenetic footprints) important for gamma expression in primates and also cis-mutations which may have been involved in the recruitment of the gamma gene to a fetal program in simian primates.

Amino Acid Sequence↗

Rhesus fetal globin genes. Concerted gene evolution in the descent of higher primates.

The comparison of the nucleotide sequences of closely linked duplicated genes of higher eukaryotes has been important in the identification of molecular events that shape the evolution of mammalian genes, most notably recombinational events such as unequal crossovers and gene conversions. Toward this goal we have been comparing the nucleotide sequences of the paired gamma 1- and gamma 2-fetal globin genes from species of catarrhine primates. Previous comparisons document that, within each great ape species as in humans, the paired gamma-genes have been involved in gene conversion events. We now extend our analysis to the catarrhine superfamily Cercopithecoidea by obtaining the nucleotide sequence of the paired gamma 1- and gamma 2-genes of rhesus monkey (Macaca mulatta). The rhesus gamma 1- and gamma 2-genes diverge less from each other than from human, chimpanzee, gorilla, and orangutan gamma 1- or gamma 2-genes. This finding indicates that a species-specific gene conversion occurred between rhesus gamma 1- and gamma 2-genes. This gamma-gene conversion (labeled C14 in our series) involved at least 1898 base pairs, extending across the complete transcriptional region of the rhesus gamma-genes. C14 could have resulted from a single large conversion or several short conversion events which may have involved the (TG)n repetitive sequence element. Parsimony analysis of the enlarged body of gamma-gene sequence data also strengthens the evidence for the 14 previously suggested gamma-gene conversion events: labeled C2, C3, and C4 in Homo; C5, C6, and C7 in Pan; C8, C9, and C10 in Gorilla; C11, C12, C13 in Pongo; C1 in the stem to Homininae (the subfamily of Homo, Pan, and Gorilla) and CO in the stem of Hominidae (the family of Pongo and Homininae).

Amino Acid Sequence↗

An evolutionary tree for invertebrate globin sequences.

A phylogenetic tree was constructed from 245 globin amino acid sequences. Of the six plant globins, five represented the Leguminosae and one the Ulmaceae. Among the invertebrate sequences, 7 represented the phylum Annelida, 13 represented Insecta and Crustacea of the phylum Arthropoda, and 6 represented the phylum Mollusca. Of the vertebrate globins, 4 represented the Agnatha and 209 represented the Gnathostomata. A common alignment was achieved for the 245 sequences using the parsimony principle, and a matrix of minimum mutational distances was constructed. The most parsimonious phylogenetic tree, i.e., the one having the lowest number of nucleotide substitutions that cause amino acid replacements, was obtained employing clustering and branch-swapping algorithms. Based on the available fossil record, the earliest split in the ancestral metazoan lineage was placed at 680 million years before present (Myr BP), the origin of vertebrates was placed at 510 Myr BP, and the separation of the Chondrichthyes and the Osteichthyes was placed at 425 Myr BP. Local "molecular clock" calculations were used to date the branch points on the descending branches of the various lineages within the plant and invertebrate portions of the tree. The tree divided the 245 sequences into five distinct clades that corresponded exactly to the five groups plants, annelids, arthropods, molluscs, and vertebrates. Furthermore, the maximum parsimony tree, in contrast to the unweighted pair group and distance Wagner trees, was consistent with the available fossil record and supported the hypotheses that the primitive hemoglobin of metazoans was monomeric and that the multisubunit extracellular hemoglobins found among the Annelida and the Arthropoda represent independently derived states.

Amino Acid Sequence↗