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Biomedical subjects

J Dillon

Publications and source records attributed to J Dillon.

At least 73 records · Page 4Linked to original sources
PubMed1991

Detection of porphyrin excited states in the intact bovine lens.

Previous steady state and time resolved spectroscopic studies on porphyrins have shown that the triplet lifetimes of those sensitizers that bind to lens proteins are lengthened by several orders of magnitude. Presented here is an extension of this experiment to measure these transients in an intact bovine lens. As demonstrated by steady state fluorescence spectroscopy and flash photolysis, mesotetra (p-sulfonatophenyl)porphyrin (TPPS) binds to lens proteins. In air-saturated aqueous solution, TPPS has a triplet lifetime of 2 microseconds. In an intact bovine lens the triplet state decayed via biexponential kinetics with lifetimes of 0.16 and 1.6 microseconds. In addition to a lengthening of the lifetime there was a red shift in the triplet transient spectra of 10-20 nm of the porphyrin in the intact lenses.

Animals↗
PubMed1991

In vivo and photophysical studies on photooxidative damage to lens proteins and their protection by radioprotectors.

Photooxidation, whether initiated by an endogenous or exogenous sensitizer, is an important mechanism in light induced damage to the lens. One of the substrates for this damage is lens protein. A porphyrin sensitizer which binds to lens proteins [mesotetra(p-sulfonatophenyl) porphyrin (TPPS)] was found to photooxidize Skh-2 pigmented mice lens protein in vivo. Uroporphyrin, a model for a non-binding photosensitizer, did not induce photooxidative damage to the mouse lens. The radioprotector 3-amino-2-hydroxypropyl phosphorothioate (WR-77913) was investigated as an agent to retard or negate in vivo photooxidative damage to the lens. Intraperitoneal injections of WR-77913 prior to irradiation reduced the TPPS induced photodestruction of lens protein in Skh-2 pigmented mice. The mechanism of protection was also investigated. Thiols were found to quench both the triplet state of porphyrins and the reactive intermediate singlet oxygen on the order of 10(5) and 10(6) M-1 s-1 respectively. These are probably not fast enough to explain most of the protection afforded by thiols. An additional mechanism may be the accelerated photobleaching of porphyrins by thiols which protects tissue by reducing the absorptions due to the porphyrins.

Amifostine↗
PubMed1991

Enhanced tumour selectivity of photodynamic therapy in the rat colon using a radioprotective agent.

Radioprotective agents have been found to protect normal tissues during photodynamic therapy (PDT). We have investigated a phosphorylated thiol protectant WR-77913 (W7) with the photosensitizer aluminium sulphonated phthalocyanine (AISPc). We compared the effects of PDT on normal and tumour tissue in the rat colon, with and without this protectant. In normal colon no necrosis was seen in sites treated after administration of the W7. Necrosis of mean diameter 4.2 mm was seen in those given the protectant after light exposure. At tumour sites the area of necrosis was similar after light exposure before and after the administration of the protective agent. These results suggest a possible role for W7 in enhancement of selectivity of PDT action. Several mechanisms of protection against porphyrin phototoxicity by these drugs have been proposed, including acceleration of photobleaching. We used fluorescence to detect AISPc in strips of rat colon before and after laser treatment, with and without W7. However, a primary role for the photobleaching of AISPc as the mechanism for the protection shown is not supported by these observations.

Aluminum↗
PubMed1990

Brachial approach to emergency cardiac catheterization during thrombolytic therapy for acute myocardial infarction. TAMI Study Group.

The use of the brachial approach to acute coronary intervention has not been previously studied. In the course of the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) trials, we used the transbrachial approach to cardiac catheterization with or without angioplasty in 202 of 704 (28.6%) patients. The baseline characteristics of age, sex, risk factors, medical history, time from symptom onset to therapy, and left ventricular function were similar for the 2 different approaches. Time from therapy to coronary angiography was not delayed by the brachial approach compared with the femoral approach: 97.1 +/- 26 min vs. 99.9 +/- 133.8 min, respectively. Chemical patency was established in 78 vs. 73% of patients and technical success with acute PTCA with the brachial approach was 89% vs. 78% with the femoral approach. Clinical outcomes were quite similar with respect to death (6 vs. 6%), reocclusion (10 vs. 14%), and emergency coronary bypass surgery (5 vs. 6%). Baseline hematocrit was 43.9 +/- 4.4 and 43.5 +/- 4.8, respectively with a nadir of 32.9 +/- 5.6 vs. 33.0 +/- 5.4. The need for vascular repair occurred in 1% vs. 3% of patients and retroperitoneal hemorrhage was documented in 1% vs. 1% of patients. This study indicates that in the hands of experienced operators the transbrachial approach to acute coronary intervention in the acute phase of treatment with thrombolytic therapy can be used with equal risks and efficacy as the femoral approach.

Aged↗
PubMed1990

Mechanisms of photochemically produced turbidity in lens protein solutions.

Calf alpha- and gamma-crystallin were photolyzed in 1-2 mg ml-1 aqueous solutions, using both laser and conventional UV radiation in the 297-320 nm wavelength region. Gamma-crystallin solutions became highly turbid upon UV irradiation, while alpha-crystallin developed no turbidity when irradiated under identical conditions. The photolyzed solutions were analyzed by SDS-PAGE. These gels revealed loss of normal 20 kDa polypeptide, and formation of higher molecular weight peptides, in both alpha- and gamma-crystallin, presumably as a result of photocross-linking reactions and/or protein insolubilization. Thus, although both crystallins underwent photocross-linking, significant turbidity production only occurred in gamma-crystallin. Some possible explanations for these differences are proposed, with one possibility being that most photocross-links in alpha-crystallin occur between subunits of the 1000-kDa oligomer, while in gamma-crystallin the cross-links occur between 20-kDa monomer units. Hence, cross-linking in alpha-crystallin does not affect the average size of particles in solution (or the turbidity), while cross-linking in gamma-crystallin results in a significant increase in average particle size with concomitant increase in turbidity. Another possible explanation is that UV-irradiated gamma-crystallin becomes insoluble (due to charge changes resulting in non-covalent aggregation) while alpha-crystallin does not. Other differences in the photochemical behavior of alpha- vs. gamma-crystallin were noted--gamma-crystallin photolysis rate was about 50% greater than alpha-crystallin. Alpha-crystallin photolysis yielded strong NFK-like fluorescence, while gamma-crystallin did not. One similarity was that photolyzed alpha- and gamma-crystallin lost amino acids His and Trp at about the same rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1990

Mycobacterium kansasii infection in the wrist and hand.

Mycobacterium kansasii infection of the deep structures of the wrist and hand can cause progressive damage which may eventually lead to permanent loss of hand function. This report describes three cases followed by a review of the literature. The important principles of management in this unusual infection are discussed.

Adult↗
PubMed1990

Time resolved spectroscopic studies on the intact human lens.

The human lens is continually under photooxidative stress from ambient radiation. In the young lens the major absorbing (between 300-400 nm) species is the glucoside of 3-hydroxy kynurenine. Using time resolved fluorescence spectroscopy on both the isolated compound and the intact human lens, the first excited singlet state of this compound is shown to have fast (ps) decay processes. This would tend to minimize damage to lens constituents because there would be little time for energy transfer into more harmful channels. Thus, this compound appears to act as a protection for the retina. With aging, human lens proteins become yellow with absorption out to 450 nm. Time resolved diffuse reflectance spectroscopic studies on intact older human lenses showed that excitation (355 nm) resulted in the formation of long lived (microseconds) transient species with an absorption maximum at ca 490 nm. Similar spectra were obtained from two model systems used to explain age related changes in human lens proteins.

Aging↗
PubMed1990

Photophysical studies on the binding of tetrasulfonatophenylporphyrin to lens proteins.

Previous studies have shown that mesotetra(p-sulfonatophenyl)porphine (TPPS) binds to lens proteins. This characteristic should increase the residence time of the sensitizer in the lens and therefore enhance the probability of inducing photooxidative damage to that tissue in vivo. Subsequent in vivo studies have verified that contention. The present studies were performed to determine the effect of such binding on the spectroscopy and photophysics of the porphyrins. It was found that the binding of TPPS (1) quenches the fluorescence of lens proteins, (2) causes a shift in the ground state absorption spectra, fluorescence excitation spectra and the triplet excited state spectrum of TPPS to longer wavelengths and (3) results in an increase in the triplet state lifetime of TPPS. In the presence of the isolated crystallins the average triplet lifetime increases in the following order: gamma less than beta less than alpha.

Animals↗
PubMed1990

Photochemical and photophysical studies on human lens constituents.

The young human lens contains species (3-hydroxy kynurenine; 3-HK and its glucoside; 3-HKG) which absorb most light between 300 and 400 nm. Photochemical studies have indicated that these compounds are relatively inefficient sensitizers of lens proteins. An investigation of the fluorescent properties of 3-HKG indicate that it contains a fast deactivation pathway (ps) which would be expected to have minimal photochemical effect on the integrity of the lens. Further phot physical studies on 3-HK indicates that it has an even faster fluorescent lifetime (less than 10 ps) with a much lower quantum yield of fluorescence (0.001 vs 0.03 for 3-HKG). With aging, the human lens proteins undergo numerous changes including a generalized yellowing. These chromophores exhibit a higher quantum yield of fluorescence, an increase in the fluorescent lifetime by 2 orders of magnitude and the formation of two long lived transient species (microsecond). These species might be expected to drastically increase the susceptibility of the human lens to ambient radiation. Based upon quantitative experimental comparisons with 3-HK this does not seem to be the case. Further time resolved studies on old lens proteins indicate that the two transient species are interconnected in that the first transient species is the precursor to the second. The implications of this mechanism on the integrity of the lens and origin of those chromophores is discussed.

Aging↗
PubMed1990

Diazoluminomelanin: a synthetic luminescent biopolymer.

The purpose of this work was to synthesize a water-soluble derivative of 5-amino-2, 3-dihydro-1, 4-phthalazinedione (luminol) that generated sustained high level luminescence under physiologic conditions without the necessity of a catalyst. The derivative was made by a diazotization reaction with luminol and 3-amino-L-tyrosine. The resulting orange-brown anionic polymer has been given the trivial name of diazoluminomelanin (DALM). It was water soluble above and insoluble at or below pH 5.0. DALM luminesced when treated with hydrogen peroxide without the presence of a catalyst at pHs ranging from 6.5 to 12.0. Microgram quantities produced high levels of chemiluminescence for longer than 52 hr. Dried polymer generated a long-term stable electron spin resonance spectrum. The long-term chemiluminescence of DALM at pH 6.8-7.4 makes it a potentially useful reagent for detecting free radicals and peroxides in cellular and biochemical preparations.

Chemical Phenomena↗
PubMed1990

Screening for potential in vivo phototoxicity in the lens/retina.

The eye is particularly vulnerable to damage from the phototoxic side effects of drugs since it is constantly subjected to ambient light. Presented here are several screens that can be used to determine the potential of drugs to cause light damage to the eye. These include a simple screen that takes into account the optical properties of the eye and the absorption spectra of the various drugs. This can be used to omit various drugs as potential photooxidants in the eye. In addition a second, more detailed screen is presented. This can be used to determine a) the quantitative potential for a drug to cause photooxidative damage in the eye, b) the mechanism by which it occurs and c) the in vivo verification of phototoxicity.

Animals↗
PubMed1990

Balloon valvuloplasty.

Percutaneous balloon valvuloplasty has been used for several years for the treatment of stenosis of all four cardiac valves. It has been particularly effective in pulmonary stenosis in children and in rheumatic mitral stenosis, especially in the younger age groups without severe calcification. After initial enthusiasm, results have not been as good in severe calcific aortic stenosis, although there is a place for aortic valvuloplasty in patients who are truly inoperable for reasons of age or coexisting disease. The procedure also may be applicable to occasional cases of tricuspid stenosis. The techniques used and results obtained with these procedures at Indiana University are described.

Adolescent↗
PubMed1989

UV laser photodamage to whole lenses.

Lenses from rat or calf were exposed in vitro to UV radiation from a nitrogen laser operated at 337.1 nm or from an excimer laser operated at 3.8 nm. Visible light transmission was monitored during calf lens irradiations at 308 nm and found to decrease. Proteins were extracted from the irradiated rat or calf lenses, separated into water soluble and insoluble fractions, and analysed using SDS-PAGE. Comparison of these gels with dark controls showed that, following photolysis, there was loss of polypeptide material in the 20-30 kDa region and concomitant formation of polymers at 40 and 60 kDa, and at greater than 100 kDa in calf lens (308 nm irradiation) and rat lenses (337.1 nm irradiation) in vitro. In addition, there was evidence for formation of lower molecular weight polypeptides at 10 kDa in the protein from irradiated rat lenses. The rat SDS-PAGE gels were challenged against anti-calf gamma crystallin serum. There was clear evidence that the polymeric material, in the water insoluble protein fraction from the 337.1 nm photolyzed rat lenses was derived in part from gamma crystallin. The macromolecular changes detected in these photolyzed rat and calf lens proteins were similar to those previously reported to accompany aging in the human lens. Biochemical changes of the type observed in UV irradiated rat and calf lenses may be responsible for the loss of visible light transmission seen in calf lenses.

Animals↗
PubMed1989

Failure to detect complement-mediated antibody-dependent cytotoxicity against human orbital tissue cells in the serum of patients with thyroid-associated ophthalmopathy.

Antibodies which are cytotoxic to human eye muscle cells and orbital fibroblasts in antibody dependent cell-mediated cytotoxicity (ADCC) are routinely detected in the serum of patients with thyroid-associated ophthalmopathy (TAO). In the present study sera from patients with TAO, most of which were shown to be positive in ADCC against eye muscle cell targets, were tested for complement-mediated antibody-dependent cytotoxicity (CMAC) against human and pig eye muscle cells, human (abdominal) skeletal muscle cells and human orbital fibroblasts, in 51Cr release assays. Several different assay protocols and complement sources were used and patient and age, sex matched normal sera compared. In preliminary studies tests were always negative when eye muscle cells, other skeletal muscle cells, or orbital fibroblasts were used as targets, regardless of the complement source, or concentration, or assay conditions used. When larger numbers of patients and normals were tested in a single assay mean (+/- SE) % specific lysis for patients with TAO was not significantly different from that for normals for either eye muscle cells or other skeletal muscle cells and taking the upper limit of normal as mean + 2 SD for the normals, tests were positive in no patient with either target. On the other hand ADCC tests were positive in 57% of the same sera tested with the same eye muscle cell targets. When human thyroid cells were used as targets, tests were positive in 10 of the 14 patients tested and monoclonal antibodies, in enzyme-linked immunosorbent assay, reactive with eye muscle antigens gave positive lysis of eye muscle cells.2+ t

Adult↗
PubMed1989

Comparison of endogenous and exogenous photosensitization in the lens using in vitro and photophysical studies.

Age related, photochemically induced damage to the lens can eventually lead to light-scattering areas which would be evidenced as an opacification of the lens. These modifications may occur at ambient radiation over an extended period, resulting from the initial absorption of radiation by relatively inefficient endogenous sensitizers (eg. tryptophan and/or 3 hydroxy kynurenine glucoside). However, the introduction of an efficient exogenous photosensitizer into the lens can markedly increase the rate by which these changes occur. Photophysical studies of various excited states of these endogenous and exogenous photosensitizers of the lens help explain these differing rates of photolytically induced damage in the lens.

Crystallins↗
PubMed1989

Neonatal intensive care admissions: changing profile in Georgia, 1974 to 1982.

Birthweight-specific admission rates were reviewed from 1974 to 1982 for Georgia's five regional perinatal centers. Analysis of birthweight-specific neonatal intensive care unit (NICU) admissions as a proportion of total live births revealed an upward trend for infants weighing 1,000 to 1,499 gm and a downward trend for those weighing 2,000 gm or more. This method revealed no significant trends for infants of weight groups less than 500 gm or 500 to 999 gm. Analysis of birthweight-specific admissions as a proportion of total NICU admissions revealed significant increases for all birthweight groups of less than 2,000 gm, with decreases in admissions for infants weighing more than 2,000 gm. Analysis of mortality data revealed improved survival for infants weighing less than 1,500 gm, but some centers showed increases in neonatal mortality, postneonatal mortality, or infant mortality among infants weighing 2,500 gm or more. During this study, low birthweight infants comprised an increasingly larger proportion of neonatal intensive care admissions. This trend evolved gradually through the process of regionalization and can be directly linked to the cost requirements of regional neonatal intensive care units.

Georgia↗