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Biomedical subjects

C Perry

Publications and source records attributed to C Perry.

At least 19 recordsLinked to original sources

Role of Tyr and Trp in membrane responses of Pyrularia thionin determined by optical and NMR spectra following Tyr iodination and Trp modification.

Pyrularia thionin is a strongly basic and bioactive 47 amino acid peptide which contains two Tyr residues at positions 13 and 45 and one Trp at position 8. Limited iodination does not have a significant effect, but prolonged iodination of the peptide leads to progressive inactivation for all known cellular responses (Evans, J. et al. (1989) Proc. natn. Acad. Sci. U.S.A. 86, 5849-5853). 1H NMR spectra of the native Pyrularia thionin show four Tyr bands, two arising from each Tyr residue. One resonance band for the epsilon hydrogens of Tyr 45 disappears early during limited iodination and the band from the delta hydrogens shifts to low field. The two bands corresponding to Tyr 13 remain during limited iodination, but both decrease in intensity during prolonged iodination, with the epsilon hydrogen band decreasing somewhat more. The resonance bands arising from Trp disappear during prolonged iodination. This sequence of reactions is verified by the optical absorbance properties of two small peptide fragments obtained by Staphylococcal V8 protease hydrolysis of thionin which had been iodinated to varying degrees. Limited iodination did not significantly inhibit the thionin's biological activity, yet the fragment from the -COOH terminus showed the conversion of Tyr 45 to diiodoTyr. This treatment did not significantly modify the Tyr 13 or Trp 8 located in the -NH2 terminal fragment. More extensive iodination resulted in a disappearance of Trp 8 absorbance with an accompanying conversion of Tyr 13 to the monoiodo form. Extensive iodination yielded two atoms of iodine in the Tyr 45-containing fragment, and only one atom in the Tyr 13 fragment. The data indicate that Tyr 45 of the native thionin is more readily iodinated, proceeding to the diiodo form without significant loss of activity. Prolonged iodination does not lead to the formation of any diiodoTyr 13, but does lead to modification of Trp 8 and probably formation of monoiodoTyr 13. Modification of Trp 8 with N-bromosuccinimide inhibits the hemolytic activity of the thionin, showing that Trp 8 is necessary for Pyrularia thionin activity. It is most likely Trp 8 modification during prolonged iodination which results in the loss of biological activity.

Antimicrobial Cationic Peptides

Theorizing about hypnosis in either/or terms.

The present paper addresses 3 issues raised by Coe (1992). First, it maintains that the "altered state" issue of the 1960s remains buried in current dichotomous classifications of hypnosis theories as involving either "special processes" or the social-psychological position. Given the current diversity of the field, it appears imprudent to classify theorizing in either/or terms; additionally, despite a history of using the term "altered state" in a circular way, it is not an inherently circular formulation. It can be used descriptively simply to point to the observation that some individuals in hypnosis report subjective alterations. A second issue broached concerns the metaphorical status of the term "hypnosis"; it is accepted as a misleading metaphor inherited from 19th century investigators such as Braid, Faria, Puységur, and Liébeault. Provided that is is recognized that this metaphor refers to a "domain" (E.R. Hilgard, 1973) of characteristically elicited behaviors, no problem ensues in retaining this metaphor derived from nocturnal sleep. A subsequent discussion of current conceptualizations of hypnosis indicates considerable agreement among investigators; there is much consensus that hypnosis is an individual differences phenomenon, in which imagination may, in some individuals, become so intense and so vivid, as to take on "reality value," to the extent that a hypnotized person may have difficulty in distinguishing fantasy from reality. The S abilities of imagery/imagination, absorption, dissociation, and automaticity (which may be proved to be an index of dissociation) are proposed as being the main ingredients of the hypnotic experience. Finally, a synergistic approach is proposed as a means of progressing beyond the current impasse of either/or theorizing.

Awareness

A novel dipyridodiazepinone inhibitor of HIV-1 reverse transcriptase acts through a nonsubstrate binding site.

A novel dipyridodiazepinone, 6,11-dihydro-11-cyclopropyl-4-methyldipyrido[2,3-b:2',3'-e]- [1,4]diazepin-6-one (BI-RG-587), is a selective noncompetitive inhibitor of HIV-1 reverse transcriptase (RT-1). An azido photoaffinity analogue of BI-RG-587 was synthesized and found to irreversibly inhibit the enzyme upon UV irradiation. BI-RG-587 and close structural analogues competitively protected RT-1 from inactivation by the photoaffinity label. A thiobenzimidazolone (TIBO) derivative, a nonnucleoside inhibitor of RT-1, also protected the enzyme from photoinactivation, which suggests a common binding site for these compounds. Substrates dGTP, template-primer, and tRNA afforded no protection from enzyme inactivation. A tritiated photoaffinity probe was found to stoichiometrically and selectively label p66 such that 1 mol of probe inactivates 1 mol of RT-1.

Affinity Labels

The antimicrobial activity of mupirocin--an update on resistance.

Mupirocin (pseudomonic acid A) has a novel chemical structure that is unrelated to any other known class of antibiotic, and possesses a unique mode of action. As a consequence, mupirocin lacks cross-resistance with other antibacterial agents and exhibits activity against strains of bacteria that are multiresistant. The selection in vitro of resistant variants of Staphylococcus aureus is slow, which is reflected in the low incidence of mupirocin resistance encountered in clinical practice. Pulse field gel electrophoresis studies on S. aureus highly resistant to mupirocin, have confirmed the presence of a large plasmid in the majority, but not all, of the isolates. Restriction endonuclease digests of the large plasmid DNA, and DNA hybridization studies with a non-radiolabelled probe constructed from total plasmid DNA, have shown that there were marked differences in plasmid types between isolates from different locations, but general similarities between plasmid types isolated from the same location.

DNA, Bacterial

Treatment of acutely infected arthroplasty with local antibiotics.

The authors have identified 22 patients with acutely infected total joint arthroplasties, 9 hips, and 13 knees. Following organism identification and assessment of the patients' general medical condition, the patients were treated with an implantable antibiotic pump. This allowed the delivery of a high concentration of antibiotic solution to a localized area. Systemic levels of antibiotic were kept to a minimum, thereby eliminating potential serious side effects of antibiotic treatment. Local concentrations were extremely high, exceeding the minimal inhibitory concentration (MIC) in all cases by 8-10-fold. Twenty patients have been followed for 30 months, and of these, 17 patients are considered to be infection free. There were three failures. The organisms that have been treated have been gram negatives, gram positives, and some mixed infections. Results are encouraging with this form of treatment, and additional patients are continually being added to the study.

Amikacin

An integrated, hospital information system based obstetrical medical record and database.

Described in this paper is the implementation and integration of an obstetrical medical record and database into an existing hospital information system. A unique feature of this system was the integration of existing data captured by the established hospital information systems with the newly implemented obstetrical database to form a complete patient data profile. This complete database integrated data from hospital functions such as demographic data obtained at patient registration, outpatient visits and tests, inpatient admission historical data, tests and procedures, newborn data and miscellaneous data required for birth registration. An important second feature was the utilization of physicians and nurses to enter the obstetrical data. This permitted immediate access to patient data from any hospital information system terminal, immediate retrieval for generating reports, and subsequently, ad hoc queries, statistical analysis and the electronic transfer of birth registration data to the State Vital Statistics Registry.

Academic Medical Centers

Hypnotizability, preference for an imagic cognitive style, and memory creation in hypnosis.

We sought to extend the finding (Laurence & Perry, 1983) that it is possible through hypnosis to create a pseudomemory of a specific event. Subjects were compared on their responses to a hypnotic suggestion. We also examined the relation between nonhypnotic measures (Preference for an Imagic Cognitive Style [PICS] test and the Tellegen Absorption Scale [TAS]) and response to the suggestion. Highly (45.45%) and moderately-highly (46.15%) susceptible subjects believed that the pseudomemory was veridical, but none of the low susceptible subjects did so. Together, hypnotic susceptibility, the PICS, and their interaction more strongly predicted pseudomemory creation than any of these main effects alone. Performance on the TAS was also related to the occurrence of pseudomemory, but this relation was redundant with performance on the other measures. These results point to the complexity of the variables involved in pseudomemory creation during hypnosis.

Adolescent

Hypnosis with a criminal defendant and a crime witness: two recent related cases.

2 legal cases involving hypnosis have recently been adjudicated by American courts. In Rock v. Arkansas (1987), the United States Supreme Court ruled that the hypnotically elicited testimony of a criminal defendant was admissible in court. This decision was grounded upon the constitutional right of a defendant both to testify, and to call witnesses, on his or her own behalf. Shortly afterwards, citing Rock as a precedent, a Texas Court of Appeals admitted the hypnotically elicited testimony of an eyewitness in Zani v. State (1988), on the grounds that it would be unfair to admit the hypnotically elicited testimony of defendants, and proscribe it for victims and witnesses. It is not clear what effect this doctrine of equity will have upon other North American court cases that involve hypnosis.

Criminal Law

Children's suits for suffering life.

In some recent court cases, parents have sued physicians and testing institutions for negligence resulting in injury not only to themselves but also to their newly born, defective children. The suits on behalf of the children have not endeavored to demonstrate that the responsible medical sector caused the child's affliction, but rather that the child would not have suffered his abnormality 'but for' the remiss behavior of those responsible parties. That such harm due to negligence should be compensated is the aim of wrongful life suits. Although such suits are often argued to be untenable because of the alleged impossibility of comparing the harm of existence in the defective state with the harm of nonexistence, this essay suggests that such comparisons are indeed possible and that wrongful life suits cannot be so easily dismissed.

Child

Interactions of Escherichia coli SO-187 tRNA(IVal) with Bacillus stearothermophilus valine-tRNA synthetase studied by 13C-NMR.

Uracil isotopically labelled with 13C at C4 and C5 has been incorporated into nucleic acids of the Escherichia coli uracil auxotroph, SO-187. [4,5-13C]uracil-labeled tRNA(IVal) was isolated and purified. 13C longitudinal relaxation times measured at 67.8 MHz demonstrated that the C5 dipole caused a 20-50% increase in the C4 relaxation. Interactions of this tRNA with valine-tRNA synthetase (VTS) purified from Bacillus stearothermophilus were established by 13C-NMR. Specific spectral changes were seen at 4-thiouridine, ribothymidine and pseudouridine of the 'bend' in the three-dimensional structure, and particularly at the uridine-5-oxyacetic acid in the wobble position of the anticodon. Thus, the protein seems to be in contact along the entire tRNA molecule, including the anticodon loop.

Amino Acyl-tRNA Synthetases

In vivo [31P]NMR studies on the influence of age on rat brain hypoxia.

In this paper the response of cerebral phosphate metabolism to mild hypoxia in young, medium and old rats has been studied via in-vivo [31P]nuclear magnetic resonance (NMR). It was found that the young adults (5-6 months) were more sensitive to this mild stress than either the mature adult (11-12 months) or senescent (23-24 months) rats even though the depth of hypoxia (paO2 = 45-55 mm Hg) was equal for all age groups. They displayed an earlier onset of acidosis, a greater fall in PCr and larger rise in Pi. This response is presumably an attempt to maintain adequate adenosine triphosphate (ATP) levels via anaerobic glycolysis. In contrast, mature adults and senescent adults appear to be able to maintain ATP levels by increasing mitochondrial rates. Acidosis is less severe as are drops in PCr and rises in Pi. Recovery is less complete for the young rats: Pi levels remain high while PCr and pHi levels stay low after normoxia has been reinstigated. All metabolite levels in the mature and senescent adults return to within 10% of control levels. All the data were analyzed and differences were found to be statistically significant. This study reveals that, contrary to popular belief, mature and old rats respond more favorably to reduced O2 than younger individuals. This is due to a more severe anaerobic acidosis in the latter age group. Speculations to explain this disparity are based on the fact that previous in-vitro studies involve systems that are totally or partially disconnected from the organism will not account for important feedback control present in an in-vivo system as studied here.

Aging

Total glossectomy.

Total glossectomy is a procedure based on sound oncologic principles, and its usefulness may not be fully appreciated. Given the dimensions of the tongue and the need to obtain a wide margin of resection, this procedure may be indicated in selected T3 lesions and recurrences after irradiation. The procedure offers excellent palliation of pain, and form and function may be preserved by rim mandibulectomy when indicated. New reconstructive techniques allow for speedier recovery. Aspiration need not be a complication of total glossectomy if care is taken to preserve the superior laryngeal nerve. Speech rehabilitation plays an important role in returning these patients to their normal environment. Overall 1 and 3 year disease-free survival rates have been encouraging.

Adolescent