Biomedical subjects

G E Arnold

Publications and source records attributed to G E Arnold.

At least 19 recordsLinked to original sources

PubMed1992

Tryptophan contributions to the unusual circular dichroism of fd bacteriophage.

The circular dichroism (CD) spectrum of fd bacteriophage has a deep minimum at 222 nm characteristic of highly alpha-helical protein, but there is a shoulder at 208 nm rather than a minimum, with a 222/208-nm amplitude ratio near 1.5 rather than near 1. Oxidation of fd phage with the tryptophan reagent N-bromosuccinimide (NBS) changes the ratio. In this report, the NBS titration of fd is followed by CD and three other spectroscopies, the results of which yield an explanation of the unusual CD spectrum. Absorbance, fluorescence, and Raman data show the oxidation to have two phases, the first of which involves the destruction of tryptophan and the second, tryptophan and tyrosine. Raman spectra reveal the invariance of an environmentally-sensitive tyrosine Fermi resonance doublet during the first oxidative phase. Raman spectra also show that little or no change of alpha-helicity occurs in the first or second oxidation phase, although very slight changes in the helix parameters might be occurring. Concurrent with the destruction of tryptophan during the first phase is the appearance in CD difference spectra ([theta]NBS-treated fd - [theta]native fd) of positive maxima at 208-210 nm and negative maxima at 224 nm, with crossovers at 217 nm. Enormous difference ellipticities, per oxidized subunit of 50 amino acids, of +490,000 +/- 80,000 deg cm2 dmol-1 at 208 nm and -520,000 +/- 110,000 deg cm2 dmol-1 at 224 nm have been derived from the data.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteriophages↗

PubMed1992

Use of conditional probabilities for determining relationships between amino acid sequence and protein secondary structure.

The conditional probability, P(sigma/x), is a statement of the probability that the value of sigma will be found given the prior information that a value of x has been observed. Here sigma represents any one of the secondary structure types, alpha, beta, tau, and rho for helix, sheet, turn, and random, respectively, and x represents a sequence attribute, including, but not limited to: (1) hydropathy; (2) hydrophobic moments assuming helix and sheet; (3) Richardson and Richardson helical N-cap and C-cap values; (4) Chou-Fasman conformational parameters for helix, P alpha, for sheet, P beta, and for turn, P tau; and (5) Garnier, Osguthorpe, and Robson (GOR) information values for helix, I alpha, for sheet, I beta, for turn, I tau, and for random structure, I rho. Plots of P(sigma/x) vs. x are demonstrated to provide information about the correlation between structure and attribute, sigma and x. The separations between different P(sigma/x) vs. x curves indicate the capacity of a given attribute to discriminate between different secondary structural types and permit comparison of different attributes. P(alpha/x), P(beta/x), P(tau/x) and P(rho/x) vs. x plots show that the most useful attributes for discriminating helix are, in order: hydrophobic moment assuming helix greater than P alpha much greater than N-cap greater than C-cap approximately I alpha approximately I tau. The information value for turns, I tau, was found to discriminate helix better than turns. Discrimination for sheet was found to be in the following order: I beta much greater than P beta approximately hydropathy greater than I rho approximately hydrophobic moment assuming sheet. Three attributes, at their low values, were found to give significant discrimination for the absence of helix: I alpha approximately P alpha approximately hydrophobic moment assuming helix. Also, three other attributes were found to indicate the absence of sheet: P beta much greater than I rho approximately hydropathy. Indications of the absence of sigma could be as useful for some applications as the indication of the presence of sigma.

Amino Acid Sequence↗

PubMed1992

A molecular dynamics simulation of bacteriophage T4 lysozyme.

An analysis of a 400 ps molecular dynamics simulation of the 164 amino acid enzyme T4 lysozyme is presented. The simulation was carried out with all hydrogen atoms modeled explicitly, the inclusion of all 152 crystallographic waters and at a temperature of 300 K. Temporal analysis of the trajectory versus energy, hydrogen bond stability, r.m.s. deviation from the starting crystal structure and radius of gyration, demonstrates that the simulation was both stable and representative of the average experimental structure. Average structural properties were calculated from the enzyme trajectory and compared with the crystal structure. The mean value of the C alpha displacements of the average simulated structure from the X-ray structure was 1.1 +/- 0.1 A; differences of the backbone phi and psi angles between the average simulated structure and the crystal structure were also examined. Thermal-B factors were calculated from the simulation for heavy and backbone atoms and both were in good agreement with experimental values. Relationships between protein secondary structure elements and internal motions were studied by examining the positional fluctuations of individual helix, sheet and turn structures. The structural integrity in the secondary structure units was preserved throughout the simulation; however, the A helix did show some unusually high atomic fluctuations. The largest backbone atom r.m.s. fluctuations were found in non-secondary structure regions; similar results were observed for r.m.s. fluctuations of non-secondary structure phi and psi angles. In general, the calculated values of r.m.s. fluctuations were quite small for the secondary structure elements. In contrast, surface loops and turns exhibited much larger values, being able to sample larger regions of conformational space. The C alpha difference distance matrix and super-positioning analyses comparing the X-ray structure with the average dynamics structure suggest that a 'hinge-bending' motion occurs between the N- and C-terminal domains.

Bacteriophage T4↗

PubMed1991

A model for fd phage penetration and assembly.

Below 15 degrees C, chloroform causes fd phage to contract to I-forms, which are compact structures about 1/3 as long as the original phage. Above 15 degrees C, chloroform causes I-forms to contract to even more compact spheroidal S-forms. Here we show that the coat protein structure in I-forms is the same as the protein structure in the phage and the protein structure in S-forms is the same as the protein structure in bilayers. The conversions from fd----I-forms----S-forms are therefore suggested to mimic steps in fd penetration. The same conversions, in reverse order, are suggested to mimic steps in fd assembly.

Bacteriophages↗

PubMed1991

Proposed molten globule intermediates in fd phage penetration and assembly.

The fd filamentous phage can be contracted to short rods called I-forms and to spheroidal particles called S-forms. The conversions from fd----I-forms----S-forms were previously suggested to mimic steps in fd penetration. The same conversions, in reverse order, were suggested to mimic steps in fd assembly. The I-forms and S-forms bind the hydrophobic probe, 1-anilino-napthalene-8-sulfonate (ANS); under the same conditions, fd binds this probe very poorly. Rigidly packed side chains in fd and nonrigidly packed side chains in I-forms and S-forms would explain the differences in ANS binding. A compilation of the properties of I-forms and S-forms indicate that: (i) they have compact structures; (ii) they have secondary structures of the same type as native phage; (iii) they have non-native morphologies; and (iv) they may have nonrigid side chain packing. These are the properties of molten globules.

Anilino Naphthalenesulfonates↗

PubMed1987

Limited nucleosome migration can completely randomize DNA repair patches in intact human cells.

Following irradiation of human cells with ultraviolet light, DNA repair patches are initially inserted near the 5' and 3' ends of nucleosome core DNA leaving a "gap" in repair synthesis (of approximately 50 bases) near the center of the core DNA. With time, however, these same repair patches become randomized, apparently by nucleosome migration. We have developed both an analytical expression and a computer algorithm (which simulates nucleosome migration along DNA) to determine the average distance nucleosomes must migrate to change the initial, non-uniform distribution of repair patches in nucleosomes to a random distribution. Both of these methods yielded the same result: nucleosomes must migrate an average of about 50 base-pairs in either direction to produce the randomization observed.

Cell Movement↗

PubMed1983

Relaxation practice after biofeedback therapy: a long-term follow-up study of utilization and effectiveness.

This follow-up study 1 to 5 years after biofeedback therapy, involving 58 patients in six diagnostic groups (migraine headache, tension headache, mixed headache, chronic pain, anxiety, and essential hypertension), revealed that 86% of the patients who continued to practice relaxation techniques improved, while only 50% of those who had stopped practice improved (p = .04). Among the patients who improved, 91% had continued to practice and only 9% had stopped practice, while among the patients who did not improve, 63% had continued to practice and 36% had stopped practice. Patients who were practicing only "occasionally," "as needed," or "when stressed" improved as much as or more than those who practiced regularly and frequently (i.e., at least weekly): 89% versus 77% improved, respectively (p = n.s). There was no difference in the occurrence or frequency of relaxation practice between patients who have been out of therapy 3 to 5 years and those who completed therapy more recently, or between those who were in brief versus longer-term therapy. Although continued relaxation practice is significantly related to the maintenance of long-term improvement, a few patients manage to improve without it, or continue to practice yet relapse. Furthermore, it appears that only occasional relaxation practice after therapy is sufficient to maintain long-term therapeutic gains.

Adult↗

PubMed1983

EMG biofeedback for functional bladder-sphincter dyssynergia: a case study.

The present study utilized EMG biofeedback in the treatment of functional bladder-sphincter dyssynergia, a learned incoordination of bladder and urethral sphincter activity during voiding. The condition is usually associated with a history of painful urination due to bladder infections, surgery, or harsh toilet training. The subject was an 8-year-old girl with chronic diurnal urinary frequency, urge incontinence, and nocturnal enuresis. Treatment consisted of intensive instruction in alternately tensing and relaxing her lower pelvic musculature, as well as relaxing during voiding. These exercises were accompanied by EMG biofeedback from perianal and perivaginal surface electrode sites. Home practice consisted of the tense-relax exercise, relaxation during voiding, and self-monitoring and record-keeping. There were 17 sessions over a period of 9 months. No medication was used. Marked reduction (to normal levels) in diurnal urgency and frequency occurred by the 3rd week of therapy, and complete recovery of normal function, including nocturnal continence without waking, occurred by the 13th therapy session, 5 months after therapy began. Follow-up 1 year after therapy revealed that these gains were being maintained. Pre- and posttherapy urodynamic studies corroborated the achievement of normal urinary function.

Biofeedback, Psychology↗

PubMed1979

Autogenous vaccine treatment of juvenile laryngeal papillomatosis.

Seventeen cases of juvenile laryngeal papillomatosis have been seen and treated with microlaryngoscopy, removal of papillomas, and administering of autogenous vaccine. Holinger's original findings could be confirmed. The operation frequency of 9 patients was significantly reduced, 5 were improved, and 3 unchanged. In no case was an undesirable reaction to the vaccine observed. Electron microscopy showed no virus-like particles in the papilloma but a section of a vulvar wart did show the virus.

Adolescent↗

PubMed1976

Larynx injected with polytef paste.

A patient with inoperable lung cancer developed left-sided laryngeal paralysis. Her dysphonia, difficulty with swallowing, aspiration of secretions, and diminished cough reflex were improved with intracordal polytef injection for the remainder of her life. The foreign body reaction to the implant showed giant cells, few lymphocytes, and no polymorphonuclear leukocytes. This reaction may be described as a bland, chronic type consistent with the age of the implant. No areas of florid, acute reaction were found. Extrusion of part of the polytef through the cricothyroid space was observed. There were no signs of unfavorable tissue reaction, intolerance, or carcinogenicity. In a second case, part of the polytef paste exuded over the thyroid gland and was misinterpreted as a thyroid nodule. Excised 11 months after injection, the foreign body reaction appeared to be of a more acute type.

Adenocarcinoma↗

PubMed1975