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Biomedical subjects

A Lewis

Publications and source records attributed to A Lewis.

At least 127 records · Page 7Linked to original sources
PubMed1994

Active site lysine backbone undergoes conformational changes in the bacteriorhodopsin photocycle.

Results are presented demonstrating that the backbone of the active site lysine of bacteriorhodopsin undergoes light-induced structural alterations during bacteriorhodopsin-mediated light-induced proton pumping. This conclusion is based on difference Fourier transform infrared spectroscopy of isotopically labeled bacteriorhodopsin. The data demonstrate that the backbone carbonyl of lysine achieves an extremely low vibrational frequency during M412 intermediate formation. This is preceded by a structural transition in the lysine backbone that leads to an active site lysine carbonyl with the observed low vibrational frequency, probably due to a high degree of solvation.

Amides↗
PubMed1994

A covalent link between the chromophore and the protein backbone of bacteriorhodopsin is not required for forming a photochemically active pigment analogous to the wild type.

Bacteriorhodopsin pigments lacking the retinal-Lys-216 covalent bond were prepared by reconstituting the K216G mutant protein with retinal alkylamine Schiff bases. The procedure follows the approach of Zhukovsky et al. [Zhukovsky, E., Robinson, P., & Oprian, D. (1991) Science 251, 558-560] in the case of visual (rhodopsin) pigments. Reconstitution leads to a mixture of three pigments. One of them, bR(K216G)/566a, absorbs (pH = 6.9) at 566 nm. Its absorption is pH-dependent, exhibiting a purple to blue transition. The pigment's laser-induced photocycle patterns are similar to those of wild-type all-trans-bR. A second component, bR(K216G)/566b, exhibits an independent photocycle reminiscent of that of wild-type 13-cis-bR. A third pigment component, bR(K216G)/630, absorbs around 630 nm. Experiments in the presence of a pH dye indicator show that illumination of bR(K216G)/566 produces a detectable proton gradient. It is concluded that a covalent bond between the retinal chromophore and the protein backbone is not a prerequisite for the basic structure and photochemical features of bR or for its proton pump activity.

Bacteriorhodopsins↗
PubMed1994

A comparison of the second harmonic generation from light-adapted, dark-adapted, blue, and acid purple membrane.

The second order nonlinear polarizability and dipole moment changes upon light excitation of light-adapted bacteriorhodopsin (BR), dark-adapted BR, blue membrane, and acid purple membrane have been measured by second harmonic generation. Our results indicate that the dipole moment changes of the retinal chromophore, delta mu, are very sensitive to both the chromophore structure and protein/chromophore interactions. Delta mu of light-adapted BR is larger than that of dark-adapted BR. The acid-induced formation of the blue membrane results in an increase in the delta mu value, and formation of acid purple membrane, resulting from further reduction of pH to 0, returns the delta mu to that of light-adapted BR. The implications of these findings are discussed.

Adaptation, Physiological↗
PubMed1994

Topical tretinoin improves the appearance of photo damaged skin.

A multicentre clinical trial has been conducted to assess the efficacy and safety of tretinoin 0.05% cream (Retin-A) in the treatment of photo-damaged Australian skin. Subjects with cutaneous facial photodamage were randomised to treatment with tretinoin (62) or vehicle (63) cream. After an initial two week run-in, all subjects applied the cream to the face, neck and left forearm/hand, once nightly for 24 weeks. Changes in clinical signs of photodamage and parameters of cutaneous irritation were assessed by investigators using a 7 point scale, whilst changes in signs of photodamage were rated by subjects using a 5 point scale. Changes in skin biopsies and silicone skin surface replicas were also assessed. Significant improvements in skin wrinkles, mottled hyperpigmentation, laxity, lentigines and roughness of tretinoin treated subjects were noted by investigators. Subjects receiving tretinoin noted significant improvements in skin wrinkles, tightness, colour and pores. Improvement in overall severity of photodamage was significantly greater for tretinoin treated subjects and was progressive over the study period. Histological findings included a significant increase in mean epidermal thickness. Significant topographical changes were not detected in skin surface replica sets. Cutaneous irritation, the most common side effect, was usually mild and transient. We conclude that tretinoin 0.05% cream significantly improved the appearance of photo-damaged skin.

Administration, Cutaneous↗
PubMed1994

X-ray induced visible luminescence of porphyrins.

A concept has been presented whereby X-ray irradiation can be used to induce visible luminescence of chromophores such as porphyrins. The essential aspects of the idea have been demonstrated in a supramolecular assembly consisting of a water-dispersed polystyrene latex with an embedded scintillating compound, 2,5-diphenyloxazole, and an externally attached hematoporphyrin. X-ray excitation of the assembly yields an emission spectra typical for hematoporphyrin with fluorescent yields of up to 3% with respect to 2,5-diphenyloxazole emission. Significant quenching in the presence of dioxygen indicates that singlet oxygen is formed at atmospheric conditions.

Humans↗
PubMed1994

ArF excimer laser-induced bubble formation during irradiation of NaCl solutions.

During application of the 193 nm excimer laser to vitreoretinal surgery, very deep cutting of the retina of about 100 microm/pulse was detected at the energy fluence in the range of 0.25-0.35 J/cm2/pulse. At the surface of the ablating tip insoluble bubbles were observed during the irradiation. In this paper we study production of these bubbles in aqueous solutions of sodium chloride. The yield of gaseous photoproducts was measured as a function of NaCl concentration and energy fluence. At concentrations of 100 g/L powerful water vapor bubbles and shock waves were observed. A mechanism of soft tissue cutting by the 193 nm laser in highly absorbing liquid media is suggested that explains the features of vitreoretinal ablation with this system: (1) the high cutting depth when the tip touches the tissue and (2) the absence of cutting when the tip is not in contact with tissue. The advantages of the ArF laser for microsurgery of internal organs are discussed.

Lasers↗
PubMed1994

Multiple non-melanoma skin cancer: evidence that different MHC genes are associated with different cancers.

HLA DR frequencies of patients with multiple non-melanoma skin cancers were analysed. There were significant differences in the frequencies of HLA DR1, DR4 and DR7 between patients who only had basal cell carcinomas and patients who had both basal and squamous cell carcinomas. There were significant differences in the frequency of HLA DR53 between the two groups. This antigen is in linkage disequilibrium with HLA DR4 and DR7, and it is not possible to distinguish the primary susceptibility locus.

Adult↗
PubMed1994

Appeals: the last word.

Appeals of denied precertifications have not received much attention from the managed care industry, in part because of ERISA's favorable liability climate. However, recent court cases, new accreditation standards, and increased incentives to physicians to economize on resource use may compound the risk inherent in commonly used appeals practices for both standard and investigational protocols. This article will review some common but high-risk appeals practices and suggest low-cost protocols that can virtually eliminate risk while increasing enrollee satisfaction.

Accreditation↗
PubMed1994

Cyclopropamitosenes: novel bioreductive anticancer agents--mechanism of action and enzymic reduction.

The mechanism of action of cyclopropamitosenes, novel bioreductive anticancer agents, has been investigated using a unique combination of chemical and biochemical techniques. The compounds 4 function as reductively activated alkylating agents under chemical reducing conditions, and the biochemical experiments establish that the methoxy- and aziridinyl-derivatives 4a and 4b behave differently upon bioreduction.

Alkylating Agents↗
PubMed1994

Vitreoretinal ablation with the 193-nm excimer laser in fluid media.

PURPOSE: To ablate retina and vitreous membranes using the 193-nm argon fluoride excimer laser in a fluid medium. METHODS: A special delivery system for the 193-nm excimer laser was developed that enabled the delivery of the laser into high-absorption liquid environments. The system was tested on the retina in an in vitro cup preparation of cow's eyes, and also in vivo on retina and vitreous membranes of rabbit eyes. The depth of cut as a function of laser energy was determined for an ablating needle with a 0.25-mm exit diameter. RESULTS: Gentle cutting of retinal tissue and of vitreous membranes was obtained in an energy range of 0.075 to 0.25 mJ/pulse. At the energy level of 0.075 mJ/pulse, four pulses were required for full-depth cut formation in rabbit retina, whereas at energy levels greater than 0.17 mJ/pulse, one pulse was sufficient for full-depth cut formation. The maximal rate of cutting achieved for the bovine retina was 2 mm/sec at a 20-Hz repetition rate of the laser. Ablation occurred only when the tip was held in contact with the tissue. CONCLUSIONS: The technology described herein appears to be advantageous and applicable to a variety of vitreoretinal surgical procedures.

Animals↗
PubMed1994

Fulminant ulcerative colitis in pregnancy.

Most pregnant women with a history of ulcerative colitis will have a normal pregnancy and deliver a healthy child. Medical therapy can usually control the disease in those patients who experience an exacerbation, and only a minority of women progress to severe colitis necessitating surgery in pregnancy. We describe a woman who developed colitis in the first weeks of pregnancy that initially responded to steroid enemas. She then relapsed and progressed to severe colitis requiring a sub-total colectomy in the 26th wk of pregnancy. This was complicated by intra-abdominal sepsis and an abscess that required drainage. She successfully completed pregnancy, to be delivered of a healthy daughter in the 32nd wk of pregnancy.

Adult↗
PubMed1993

Identification of regions in interleukin-1 alpha important for activity.

Saturation mutagenesis of the mature human interleukin-1 alpha (IL-1 alpha) gene has been performed. Following expression in Escherichia coli, the biological and receptor binding activities of the mutant proteins were examined. Most of the molecule could be altered with little effect on either function. More than 3,500 mutants were examined, and only 23 unique amino acid sequences were identified which resulted in an altered ratio of biological to binding activity when compared with wild-type IL-1 alpha. These proteins possessed mutations at 38 of the 159 amino acid residues in IL-1 alpha. Random mutagenesis at several of these positions identified further substitutions that affected activity. Examination of a model for IL-1 alpha localized most of the residues which altered activity along one face of the molecule. This region appears to be distinct from areas of IL-1 which have been postulated to make contact with IL-1 receptor.

Amino Acid Sequence↗
PubMed1993

Microsecond-resolved XAFS of the triplet excited state of Pt2(P2O5H2)4(4-)

Little is known about the excited-state structures of most inorganic compounds. Time-resolved resonance Raman and time-resolved infrared spectroscopies can provide only indirect structural information for short-lived excited species in solution at room temperature. Time-resolved X-ray diffraction has the potential to give more direct information, but no excited-state structures have yet been reported; picosecond gas-phase electron diffraction has been proposed recently, but not yet demonstrated. Here we report a technique that combines the X-ray absorption fine-structure (XAFS) method with rapid-flow laser spectroscopy to measure structural changes in a solution-phase excited-state transition-metal complex with microsecond resolution. We find that the triplet excited state of Pt2(P2O5H2)4(4-), with a lifetime of about 4 microseconds, undergoes a contraction in the Pt-Pt distance of 0.52 +/- 0.13 A relative to the ground state. We anticipate that time-resolved XAFS will have broad applications in chemistry and biology.

Absorptiometry, Photon↗
PubMed1993

The effect of the ArF excimer laser on Candida albicans in vitro.

Candida albicans colonies in Sabouraud agar plates were irradiated with the excimer laser as follows: (a) at 10 Hz, power densities of 115-300 mJ/cm2 and 200-3000 pulses, and (b) power density of 115 mJ/cm2 and 200 pulses at 10-50 Hz. Additional colonies were irradiated with a power density of 200 mJ/cm2 at 10 Hz and 500 pulses. Each colony was cultured and the visible colony forming units were counted after 24 h. The cultures remained sterile at: 115 mJ/cm2, 1500 or 3000 pulses; 200 mJ/cm2, 400 or 500 pulses; and 300 mJ/cm2, 300 or 400 pulses. They decreased significantly in other groups. Photoablation with a power density of 115 mJ/cm2 and 200 pulses significantly decreased the number of yeast colonies in the culture plates at 30 Hz (p < 0.029) and 50 Hz (p < 0.02). Photoablation did not affect the counts in colonies located 1 or 2 mm from the treated colonies. Various energies of the excimer laser may significantly reduce or eliminate yeast in vitro.

Candida albicans↗
PubMed1993

Probing membrane potential with nonlinear optics.

The nonlinear optical phenomenon of second harmonic generation is shown to have intrinsic sensitivity to the voltage across a biological membrane. Our results demonstrate that this second order nonlinear optical process can be used to monitor membrane voltage with excellent signal to noise and other crucial advantages. These advantages suggest extensive use of this novel approach as an important new tool in elucidating membrane potential changes in biological systems. For this first demonstration of the effect we use a chiral styryl dye which exhibits gigantic second harmonic signals. Possible mechanisms of the voltage dependence of the second harmonic signal are discussed.

Fluorescent Dyes↗