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Biomedical subjects

M Goodman

Publications and source records attributed to M Goodman.

At least 397 records · Page 22Linked to original sources

Evolution of cytochrome C investigated by the maximum parsimony method.

Rates of evolution for cytochrome c over the past one billion years were calculated from a maximum parsimony dendrogram which approximates the phylogeny of 87 lineages. Two periods of evolutionary acceleration and deceleration apparently occurred for the cytochrome c molecule. The tempo of evolutionary change indicated by this analysis was compared to the patterns of acceleration and deceleration in the ancestry of several other proteins. The synchrony of these tempos of molecular change supports the notion that rapid genetic evolution accompanied periods of major adaptive radiations. Rates of change at different time in several structural-functional areas of cytochrome c were also investigated in order to test the Darwinian hypothesis that during periods of rapid evolution, functional sites accumulate proportionately more substitutions than areas with no known functions. Rates of change in four proposed functional groupings of sites were therefore compared to rates in areas of unknown function for several different time periods. This analysis revealed a significant increase in the rate of evolution for sites associated with the regions of cytochrome c oxidase and reductase interaction during the period between the emergence of the eutherian ancestor to the emergence of the anthropoid ancestor.

Animals↗

An exceptional amino acid replacement on the distal side of the iron atom in proboscidean myoglobin.

Amino acid sequence determination of elephant myoglobin revealed the presence of the unusual substitution E7 His leads to Gln. Stereochemical analyses suggest that the most suitable residue which can functionally substitute for His at this position in vertebrate globins is Gln. Physiochemical studies imply that the slower rate of autooxidation of elephant myoglobin is the result of this substitution which may confer some selective advantage on the species. Comparative sequence data of paenungulate myoglobins suggest that the His leads to Gln mutation probably occurred in an ancestor of Elephantinae.

Amino Acid Sequence↗

Topochemically related hormone structures. Synthesis of partial retro-inverso analogs of LH-RH.

The syntheses of five partial retro-inverso luteinizing hormone-releasing hormone (LH-RH) analogs [g-Tyr5, m-Gly6]LH-RH, [g-Tyr5-r-Gly6, R,S-m-Leu7] LH-RH, [g-p-Glu1, m-His2]LH-RH, [g-p-Glu1-r-D-His-R,S-m-Trp3]LH-RH, and [g-Pro9-propionyl-des-Gly10]LH-RH, have been accomplished by solution methods. The choice of sequence to be reversed was based on suggested biodegradation mechanisms of LH-RH. A (gem)-diamino alkylidene residue, which was produced via Curtius rearrangement of a peptide segment, and a 2-substituted malonyl residue mark the initiating and terminating site, respectively, of the reversed sequence.

Amino Acid Sequence↗

Quantitation of carcinoembryonic antigen in the lung lining fluid of normal smokers and nonsmokers.

Bronchoalveolar lavage was performed in 47 volunteers: 19 nonsmokers and 28 smokers. Total protein, albumin, immunoglobulins G and A, and carcinoembryonic antigen (CEA) were measured in the concentrated lavage effluent. Although a significant increase (p < 0.001) in the ratio of CEA to total protein recovered from the group of smokers was found, this increase primarily reflected the greater increase that occurred in a subgroup of 7 smokers. However, the increases in lavage CEA correlated weakly (p = 0.096) with smoking history in pack-years, and not at all with plasma CEA concentrations. Results regarding the number of cells recovered and immunoglobulin-to-albumin concentration ratios in these subjects were similar to those reported by others. Thus, CEA was increased in the lavage fluid of a subgroup of otherwise normal young smokers. It is possible that CEA might serve as a useful indicator of future airway disease in certain young smokers.

Adult↗

Inactivation of purified human alpha 2-antiplasmin and purified human C1 inhibitor by synthetic fibrinolytic agents.

3-Hydroxypropyl flufenamide (Flu-HPA) is one of a series of flufenamic acid derivatives that enhances blood clot lysis in vitro. Studies of possible mechanisms of action of Flu-HPA were undertaken. The profibrinolytic activity of Flu-HPA in clot lysis assays was found to be dependent on plasminogen. The influence of Flu-HPA on the ability of purified alpha 2-antiplasmin to inhibit purified plasmin was studied. Plasmin activity was determined using 125I-fibrin plates or the spectrophotometric tripeptide substrate, Val-Leu-Lys-paranitroanilide. At Flu-HPA concentrations greater than 1 mM, the inhibitory activity of alpha 2-antiplasmin was abolished in a time-dependent and concentration-dependent manner. The influence of Flu-HPA on the ability of purified Cl inhibitor to inhibit purified plasma kallikrein and beta-Factor XIIa was also studied. Cl inhibitor activity was abolished by Flu-HPA at concentrations greater than 2 mM. Notably, Flu-HPA up to 60 mM did not affect the amidolytic activities of plasmin, kallikrein, or beta-Factor XIIa. Flu-HPA did not release enzyme activity from preformed complexes of either alpha 2-antiplasmin and plasmin of Cl inhibitor and kallikrein. A water-soluble derivative of flufenamic acid, N-flufenamyl-glutamic acid, also inactivated alpha 2-antiplasm and Cl inhibitor. This inactivation was shown to be reversible. These results indicate that synthetic fibrinolytic compounds such as flufenamic acid derivatives may promote fibrinolysis by directly inactivating alpha 2-antiplasmin and Cl inhibitor.

Blood Coagulation↗

Cartilaginous tumors of the larynx.

Laryngeal cartilaginous tumors are well-defined masses that arise within the endolaryngeal structures, predominantly the cricoid cartilage. Twelve cases with long-term followup are reviewed. The importance of early and complete radiological evaluation and the potential for recurrence is emphasized. Since metastases or extralaryngeal extension is rare, conservative surgery, preserving laryngeal function as long as possible, is the treatment of choice. The histological distinction of chondroma versus chondrosarcoma is not essential for the clinical management of these lesions, and we suggest they be designated as cartilaginous tumors of the larynx.

Adolescent↗

The amino acid sequence of alligator (Alligator mississippiensis) myoglobin. Phylogenetic implications.

The amino acid sequence of myoglobin from cardiac muscle of the American alligator (Alligator mississippiensis) was established by alignment of overlapping peptides and dansyl-Edman degradation. The chain initiating methonine seems to be retained. Thus, this molecule has 154 amino acid residues rather than 153 as in other tetrapod myoglobins. Maximum parsimony analysis indicated that alligator myoglobin diverges more from both bird and mammal myoglobins than these latter do from each other. The phylogenetic implications are discussed with respect to a possible diphyletic origin for diapsid reptiles.

Alligators and Crocodiles↗

The amino acid sequence of elephant (Elephas maximus) myoglobin and the phylogeny of Proboscidea.

The complete amino acid sequence of skeletal myoglobin from the Asian elephant (Elephas maximus) is reported. The functional significance of variations seen when this sequence is compared with that of sperm whale myoglobin is explored in the light of the crystallographic model available for the latter molecule. The phylogenetic implications of the elephant myoglobin amino acid sequence are evaluated by using the maximum parsimony technique. A similar analysis is also presented which incorporates all of the proteins sequenced from the elephant. These results are discussed with respect to current views on proboscidean phylogeny.

Amino Acid Sequence↗

Early surgical correction in the cerebral palsied hand.

The 5 year follow-up of 20 children suffering from cerebral palsy who had undergone early surgical release procedures for deformities of the hand has indicated certain positive advantages for this method of treatment. In all cases there was an improved cosmetic appearance of the hand and improved function to a greater or lesser degree, as compared with the preoperative state. Night splints have been retained, as it was found that deformities tend to recur if splintage is discarded completely. None of the patients has developed fixed contractures, and to date improvement in function has been sufficient to obviate the need for further surgical procedures.

Cerebral Palsy↗

Peptide sweeteners. 3. Effect of modifying the peptide bond on the sweet taste of L-aspartyl-L-phenylalanine methyl ester and its analogues.

A series of analogues designed to assess the importance of the amide bond in the dipeptide sweetener L-aspartyl-L-phenylalanine methyl ester has been synthesized and tested. The peptide bond was methylated, replaced by an ester bond, or reversed. all of these modifications produced compounds that did not have a sweet taste. We conclude that the steric, electronic, and directional characteristics of the amide bond are essential for biological activity in the dipeptide sweeteners.

Aspartame↗

Peptide sweeteners. 4. Hydroxy and methoxy substitution of the aromatic ring in L-aspartyl-L-phenylalanine methyl ester. Structure-taste relationships.

A series of analogues of the dipeptide sweetener L-aspartyl-L-phenylalanine methyl ester having hydroxy and/or methoxy substitution on the aromatic ring was synthesized and tasted. The introduction of a methoxy group in the para position of the aromatic ring of the peptide sweetener is crucial to the reduction or destruction of the sweet taste. The effects of substituents in the ortho or meta position are not as pronounced. In the case of o-methoxy substitution, the resulting analogue is only slightly less sweet than the parent dipeptide sweetener.

Humans↗

Radiological aspects of inverted papilloma.

Of 115 proved cases of inverted papilloma, 81 were studied radiographically. The tumor was seen in both early and late stages. Many cases presented as recurrent tumor after multiple surgical procedures. A common radiologic presentation was a unilateral mass in the nasal fossa with opacification of the contiguous maxillary sinus in a moderately advanced tumor stage. However, other radiologic patterns were encountered and it was therefore impossible to categorize any of these findings as specific for inverted papilloma.

Adolescent↗

Partially modified retro-inverso-enkephalinamides: topochemical long-acting analogs in vitro and in vivo.

The synthesis of four enkephalinamide analogs is described in which the peptide bond between residues 4 and 5 is reversed with or without simultaneous reversal of the carboxyl-terminal amide bond. These so-called partially modified retro-inverso-isomers are new, potent, topochemical analogs of the enkephalins. Tests, both in vitro and in vivo, have shown that these analogs are considerably longer acting than any previously studied enkephalins. Thus, partial reversal of the peptide bonds of the backbone can result in peptides with enhanced activity compared to a parent compound, provide that the structural complementarity of both the side chains and end groups are conserved.

Animals↗

The radioisotope spleen scan in the assessment of patients with suspected spleen trauma.

The radioisotope spleen scan was reviewed in 29 patients with suspected trauma of the spleen who had been admitted for observation to a surgical ward. At the time of the study, all patients had stable pulse rates and blood pressures. The scans of six patients showed space defects and, of these, splenic injury was subsequently proven operatively in five patients. As a detector of splenic trauma, the radionuclide scan proved to be reliable. Although the findings of radioisotope scanning are not specific for trauma, the interpretation of the scan in conjunction with other observations increases the accuracy of diagnosis.

Adolescent↗