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Biomedical subjects

M E Johnson

Publications and source records attributed to M E Johnson.

At least 127 records · Page 7Linked to original sources
PubMed1992

Design, synthesis and conformational analysis of gamma-turn peptide mimetics of bradykinin.

Gamma-turns are regular secondary structure elements, found with some frequency in small peptides, that have been implicated in the biologically active conformations of several systems. This report describes the design, synthesis and conformational analysis of a non-peptide gamma-turn mimetic. Low energy conformations of the mimetic system exhibit good conformational agreement with an experimentally observed peptide gamma-turn. The mimetics were incorporated into the nonapeptide bradykinin, for which a gamma-turn, formed by residues Ser 6 to Phe 8, has been hypothesized to be a bioactive conformation. The results indicate that a bioactive conformation of bradykinin may include a reverse turn at this position.

Amino Acid Sequence↗
PubMed1992

Design and synthesis of a CD4 beta-turn mimetic that inhibits human immunodeficiency virus envelope glycoprotein gp120 binding and infection of human lymphocytes.

Poor bioavailability, rapid degradation, antigenicity, and high cost often limit the use of proteinaceous pharmaceuticals. One goal of structural biochemistry is the reduction of complex molecules to small functional units that are amenable to high-resolution structural analysis and rapid modification. The dissection of complex proteins into small synthetic conformationally restricted components is an important step in the design of low molecular weight nonpeptides that mimic the activity of the native protein. We have developed a reverse-turn mimetic system to explore peptide and protein structure-function relationships. We now report the design and synthesis of a small molecule (M(r) 810, as its trifluoroacetate salt), water soluble, proteolytically stable mimetic of residues Gln40-Thr45 of the complementarity-determining 2-like region of CD4. This mimetic has a low micromolar Kd for human T-lymphotropic virus type IIIB gp120 and reduces syncytium formation.

Binding, Competitive↗
PubMed1992

Peptide mimetics of the thrombin-bound structure of fibrinopeptide A.

Recent work has suggested that the thrombin-bound conformation of fibrinopeptide A exhibits a strand-turn-strand motif, with a beta-turn centered at residues Glu-11 and Gly-12. Our molecular modeling analysis indicates that the published fibrinopeptide conformation cannot bind reasonably to thrombin but that reorientation of two residues by alignment with bovine pancreatic trypsin inhibitor provides a good fit within the deep thrombin cleft and satisfies all of the experimental nuclear Overhauser effect data. Based on this analysis, we have successfully designed and synthesized hybrid peptide mimetic substrates and inhibitors that mimic the proposed beta-turn structure. The results indicate that the turn conformation is an important aspect of thrombin specificity and that our turn mimetic design successfully mimics the thrombin-bound conformation of fibrinopeptide.

Amino Acid Sequence↗
PubMed1992

Location of potential binding sites on deoxy hemoglobin for the design of antigelling agents.

The binding sites of indole-based gelation inhibitors with sickle cell hemoglobin were investigated by two parallel theoretical approaches. A geometric approach originated by Kuntz and co-workers uses a spatial buildup scheme to locate potential binding regions, while a hybrid grid/geometric search method searches for specific indole ring binding pockets over the hemoglobin surface. The binding sites derived from these calculations were tested for their ability to accommodate indole rings by means of accessibility calculations with probes of various radii. These sites were further scanned for van der Waals' overlap and electrostatic interactions. A full 5BrTrp residue was built in each indole ring binding site, and its conformational energy of association with sickle hemoglobin was calculated at that site. Our theoretical results predict a total of 14 potential binding regions, including all of the sites observed from X-ray crystallography, and sites that are consistent with solution nuclear magnetic resonance studies.

Antisickling Agents↗
PubMed1992

Diagnostic use of emergency department echocardiogram in massive pulmonary emboli.

Massive pulmonary embolism represents a small percentage of patients presenting to the emergency department with clinical symptoms suggestive of embolic phenomenon. Definitive therapy with thrombolytics or embolectomy is usually delayed until angiographic verification of the clinical suspicion can be obtained. A case is described in which embolectomy was based on clinical diagnosis and confirmatory echocardiogram obtained in the ED. The rapid diagnostic role of echocardiographic data in a subset of patients presenting with clinical symptoms suggestive of massive pulmonary emboli deserves further evaluation.

Acute Disease↗
PubMed1992

Survival of Listeria monocytogenes during the manufacture and ripening of Swiss cheese.

Rindless Swiss cheese was made from a mixture of pasteurized whole and skim milk that was inoculated to contain 10(4) to 10(5) cfu of Listeria monocytogenes (strain Ohio, California, or V7)/ml. During clotting of milk, numbers of L. monocytogenes remained nearly unchanged. When the curd was heated gradually to attain the cooking temperature (50 degrees C), numbers of L. monocytogenes increased by approximately 40 to 45% over those in inoculated milk. Cooking curd at 50 degrees C (122 degrees F) for 30 to 40 min resulted in resilient curd having a pH of 6.40 to 6.45 and decreased L. monocytogenes by 48% compared with numbers of the pathogen in inoculated milk. After curd was pressed under whey, numbers of L. monocytogenes increased by approximately 52% over those in inoculated milk and reached their maxima at the end of this stage. A sharp decrease in numbers of L. monocytogenes occurred during brining of cheese blocks (7 degrees C for 30 h). The population of L. monocytogenes continued to decrease during cheese ripening. Average D values for strains California, Ohio, and V7 were 29.2, 24, and 22.5 d, respectively. Listeria was not detected (direct plating, and cold enrichment) after 80, 77, and 66 d of ripening of Swiss cheese made from milk inoculated with strains California, Ohio, and V7, respectively. Thus, Swiss cheese made in this study did not permit extended survival of L. monocytogenes.

Animals↗
PubMed1992

The oocyte nucleus isolated in oil retains in vivo structure and functions.

We describe a technique for isolating the nucleus of the giant amphibian oocyte under paraffin oil. The method precludes the losses of small solutes and proteins that accompany isolation of nuclei into aqueous media. An individual oocyte is blotted, placed under oil, punctured near the animal pole and then squeezed to gently extrude the nucleus into the oil, thereby avoiding exposure to any aqueous environment. Light and electron microscopy of the oil-isolated nucleus demonstrate that its in vivo morphology is preserved. We also describe techniques that facilitate the study of nuclear functions under oil. Oil-isolated oocyte nuclei retain many in vivo functions for several hours, including size-selective envelope permeability, RNA synthesis and the ability to break down in response to cdc2/cyclin meiotic maturation promoting factor.

Animals↗
PubMed1991

Fullerenes C60 and C70 in flames.

The fullerenes C60 and C70 were first identified in carbon vapour produced by laser irradiation of graphite, and have recently been produced in macroscopic quantities by vaporization of graphite with resistive heating. It has also been suggested that fullerenes might be formed in sooting flames, and indeed all-carbon ions with mass/charge ratios suggestive of fullerenes have been detected in flames. These species were assumed to have the cage structures of fullerenes, but the mass spectroscopic evidence could not establish this conclusively. We have now collected samples of condensible compounds and soot from hydrocarbon combustion under a range of conditions, and analysed these using conventional techniques in an effort to detect fullerenes. Spectroscopic studies reveal the presence of C60 and C70 in yields and ratios that depend on temperature, pressure, carbon/oxygen ratio and residence time in the flame. Control of these conditions allows optimal yields of 3 g of fullerenes per kilogram of fuel carbon burned, and variation of the C70/C60 ratio over the range 0.26-5.7.

Carbon↗
PubMed1991

Design and synthesis of nonpeptide mimetics of jaspamide.

Jaspamide is a novel metabolite of mixed peptide/polyketide biosynthesis that was isolated from sponges of the genus Jaspis, and that has been reported to exhibit both insecticidal and antifungal activity. We have evaluated three nonpeptide mimetic designs, and have synthesized a nonpeptide mimic of the proposed bioactive region to investigate the structure activity relationship. Structural investigations of potential mimetics, utilizing molecular modeling in conjunction with spectroscopic and crystallographic data, indicate that positioning of the critical functional groups in two mimetics corresponds closely to that observed in jaspamide, and that the flexibility of mimetic 4 approximates that of jaspamide. Initial biological evaluation suggests that lactam mimetic 4 exhibits a biological profile similar to jaspamide.

Antifungal Agents↗
PubMed1991

Subtle-obvious scales of the MMPI: indicators of profile validity in a psychiatric population.

This study explored the usefulness of the Minnesota Multiphasic Personality Inventory (MMPI) Subtle-Obvious scales as profile validity indicators with a inpatient psychiatric population. Some 292 MMPI profiles were utilized and divided into overreporters, underreporters, and standard reporters, based on their Subtle-Obvious scale scores. Reporting style was shown to be unrelated to actual patient pathology because of the lack of relationship between reporting style and diagnostic categorization according to the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev. [DSM-III-R]; American Psychiatric Association, 1987) Axis I and II. Comparisons of MMPI profiles of the three groups revealed that overreporters endorsed more pathology on the MMPI clinical scales than did either underreporters or standard reporters. The same pattern of response style was demonstrated by subjects on another objective measure, the Beck Depression Inventory, whereas on a projective measure, the Rorschach Inkblot Test, there were no differences between groups. These findings suggest that clinicians may want to utilize the Subtle-Obvious scales to gain information about MMPI profile validity. Specifically, profiles of patients identified as overreporters should be interpreted with caution so as to not overstate their level of pathology.

Adjustment Disorders↗
PubMed1991

Shoulder strength analysis using the Cybex II isokinetic dynamometer.

The purpose of this study was to establish a data base of normal shoulder strength of young adults using the Cybex II dynamometer and specially designed fixation devices. Fifty healthy subjects aged 21 to 40 years old (26 men, 24 women) were tested. The mean peak torque values of their shoulders were measured at speeds of 0 degree, 60 degrees, 180 degrees, and 300 degrees per second. Mean peak torque values generally decreased as speed increased. Men were significantly stronger than women for all motions and speeds tested. Shoulder extension torque was greatest followed by adduction, flexion, internal rotation, abduction, and external rotation. Torque production tended to be greater on the dominant side.

Adult↗
PubMed1991

Reconstructions after resections of tumors involving the proximal femur.

Advances in prosthesis design, the use of allografts, and a systematic approach to the staging and surgical treatment of musculoskeletal tumors have made limb salvage possible in the proximal femoral region. With the use of effective adjuvant therapy, limb salvage is now an option for the majority of patients presenting with locally invasive neoplasms in this area. The increase in functional outcome is sufficient to warrant serious consideration of limb salvage over the corresponding amputation. Preoperative planning is discussed along with surgical techniques.

Arthrodesis↗
PubMed1990

Further exploration of the Egocentricity Index in an inpatient psychiatric population.

Using the Rorschach protocols from 129 adult psychiatric inpatients, the Egocentricity Index as calculated in the Exner Comprehensive System was investigated relative to MMPI standard and special scales, Beck Depression Inventory, and other Rorschach variables. Results indicate that rather than being a measure of self-focus and self-centeredness, the Index might be related to introversion and introspection. Additionally, the Index may have differential implications about mental health for males vs. females.

Adolescent↗
PubMed1990

Development of specific nucleic acid probes for the differentiation of porcine rotavirus serotypes.

A dot blot hybridization assay is described for the detection and differentiation of porcine rotavirus serotypes. Recombinant complementary DNA (cDNA) representing gene 9 (the gene encoding the neutralization antigens in VP7 glycoprotein) from OSU (porcine rotavirus serotype 1) and Gottfried (porcine rotavirus serotype 2) strains were used to determine the optimal hybridization conditions which allow specific detection of group A porcine rotaviruses. Probes were prepared by excision of the inserts from the recombinant plasmids and radiolabeling of cDNA with 32P by the random primer extension method. Probes were hybridized at various stringencies with viral RNA from different rotavirus serotypes bound to nylon membranes. Hybridization at low stringency (26% base pair mismatch for stable hybrid formation) had high sensitivity but low specificity. Hybridization at high stringency (16% base pair mismatch for stable hybrid formation) produced high specificity but decreased the sensitivity observed at low stringency. Probes were specific for rotavirus at both stringencies and did not hybridize with nucleic acids from other porcine viruses. Subgenomic gene 9 fragments were then tested to provide more specific probes. A 322 bp fragment from OSU gene 9 between nucleotides 382 and 704 and a 266 bp fragment from Gottfried gene 9 between nucleotides 230 and 496 were found to be specific as hybridization probes. These studies demonstrated the feasibility of the dot blot hybridization assay using subgenomic fragments of gene 9 to detect and differentiate serotypes of porcine rotavirus. Additional studies are warranted to further evaluate the sensitivity and the capability of these probes to detect porcine field isolates of the same serotype.

Animals↗
PubMed1990

Hemoglobin S antigelation agents based on 5-bromotryptophan with potential for sickle cell anemia.

5-Bromotryptophan (5-BrTrp) is the most potent amino acid derivative reported in the literature to inhibit the gelation of hemoglobin S (from sickle cell anemia patients). Trp-Trp is also more potent than Trp as an antigelation agent. Therefore, we have prepared a series of dipeptides containing 5-BrTrp and evaluated the antigelation activity. 5-BrTrp-5-BrTrp is the most potent, i.e., 5.9 times the activity of Trp, followed by 5-BrTrp-Trp and then Trp-5-BrTrp. This improved antigelation potency for 5-BrTrp-5-BrTrp and 5-BrTrp-Trp is very significant and will be pursued further as lead compounds with potential for sickle cell anemia.

Anemia, Sickle Cell↗