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Biomedical subjects

J Dillon

Publications and source records attributed to J Dillon.

At least 55 records · Page 3Linked to original sources
PubMed1996

Experimental model of light focusing of the peripheral cornea.

PURPOSE: Epidemiologic studies have shown that the onset of cortical cataract occurs primarily in the inferonasal human lens and that the incidence of cortical cataract is correlated with ultraviolet light. Ray tracing analysis has suggested that the peripheral cornea concentrates light on the opposite peripheral lens and that the nose and orbit block peripheral light, except temporally, resulting in a relative concentration of light on the inferonasal lens. Studies were performed to test these theories. METHODS: A model cornea and anterior chamber, set on a disc of light-sensitive paper, was placed in the orbit of a human skull coated with wax to simulate soft tissue. The "eye" was exposed to summer sunlight at various times of day, with and without sunglasses. Discs from the different experimental groups were scanned, and the digitized images were analyzed densitometrically using image analysis software. RESULTS: With the head upright, the inferonasal section of the disc exhibited the most intense exposure under all lighting conditions. Sunglasses decreased the intensity of overall light exposure but did not eliminate the inferonasal bias. Only blocking the temple eliminated this effect. CONCLUSIONS: This model supports the idea that the peripheral cornea focuses light on the inferonasal portion of the human lens. These results may explain the correlation between light and the location of cortical cataract.

Cataract↗
PubMed1995

Photophysical studies on human retinal lipofuscin.

Fluorescent material generated in the human retina accumulates within lipofuscin granules of the retinal pigment epithelium (RPE) during aging. Its presence has been suggested to contributed to various diseases including age-related macular degeneration. Because this material absorbs light at wave lengths as long as 550 nm, photophysical studies were performed to determine whether lipofuscin could contribute to light damage and to determine if its composition is similar to a synthetically prepared lipofuscin. Time-resolved experiments were performed to monitor (1) fluorescence decay, (2) the UV-visible absorption of longer-lived excited states and (3) the formation and decay of singlet oxygen at 1270 nm. Steady-state and time-resolved fluorescence studies indicate that human and synthetic lipofuscin have fluorophores in common. Time-resolved absorption experiments on human retinal lipofuscin and synthetic lipofuscin showed the presence of at least two transient species, one absorbing at 430 nm (lifetime ca 7 microseconds) and a second absorbing at 580 nm, which decays via second order kinetics. In addition, there is a third absorbing species stable to several hundred milliseconds. The transient species at 430 nm is quenched by oxygen, suggesting that it is a triplet state. Subsequent studies showed the formation of singlet oxygen, which was monitored by its phosphorescence decay at 1270 nm. These studies demonstrate that lipofuscin can act as a sensitizer for the generation of reactive oxygen species that may contribute to the age-related decline of RPE function and blue light damage.

Adult↗
PubMed1995

The photochemistry of human retinal lipofuscin as studied by EPR.

Fluorescent material generated in the human retina accumulates within lipofuscin (HLF) granules of the retinal pigment epithelium (RPE) during aging. We have been investigating the possible light-induced contribution of these fluorophores to various diseases including age-related macular degeneration. Our studies have shown that some of the fluorescent components of HLF are products of the reaction of retinaldehyde with ethanolamine and that synthetic mixtures of this reaction can serve as a useful model for photophysical studies. Previous research by us has demonstrated that irradiation of either natural or synthetic lipofuscin resulted in the formation of a triplet state and possibly a free radical. Here EPR studies were performed to verify the formation of that radical. The UV irradiation of either synthetic or natural human retinal lipofuscin extracts in oxygen-free methanol led to the formation of a 5,5-dimethylpyrroline-N-oxide (DMPO) spin-trapped carbon-centered radical resulting from either hydrogen atom or electron abstraction from solvent molecules. In the presence of oxygen superoxide was formed, which was observed as a DMPO adduct. It is concluded that certain components of the chloroform-soluble fluorophores of human RPE lipofuscin granules and the fluorescent reaction products of retinaldehyde and ethanolamine are photophysically similar but not the same. Electron or hydrogen abstraction from a substrate by these fluorophores in vivo and the resulting radical products may contribute to the age-related decline of RPE function and blue light damage in the retina.

Adult↗
PubMed1995

Age-related changes in the human lens as monitored by detection of porphyrin excited states.

Previous studies have shown that the triplet state lifetimes of various porphyrins are increased by several orders of magnitude when they are bound to lens protein. Flash photolysis studies of mesotetra (p-sulfonatophenyl)porphyrin (TPPS) on intact bovine lenses indicated a biexponential decay of the triplet state with lifetimes of 160 microsecond and 1.6 ms. Here we extend those measurements to TPPS associated with intact human lenses. Steady-state fluorescence measurements indicate that TPPS binds to both young and old human lenses. In an intact young human lens, the TPPS triplet state is observed to decay biexponentially with lifetimes of 50 and 680 microsecond. As the age of the lens increases, the lifetime of the shorter-lived component lengthens while that of the longer-lived component decreases slightly. In order human lenses, the two lifetimes coalesce and the triplet decay exhibits purely monoexponential behavior. These photophysical characteristics apparently are due to age-related modification(s) of the protein in the human lens resulting in an increasingly more homogeneous environment around the porphyrin.

Aging↗
PubMed1995

Photoreactivity of biologically active compounds. VIII. Photosensitized polymerization of lens proteins by antimalarial drugs in vitro.

The drugs commonly used in the treatment of malaria are photochemically unstable. Several of these compounds cause dermal and ocular toxic reactions that may be light induced. The in vitro photopolymerization of calf lens proteins in the presence of antimalarial drugs was studied as part of a screening of the photochemical properties and phototoxic capabilities of these compounds. The pseudo-first-order rate constant for the reaction was calculated, and related to the amount of light absorbed by the compounds in order to determine the relative photosensitizing effect of each drug. The reaction mechanisms were evaluated by adding a variety of quenchers to the reaction medium during irradiation. Based on the results obtained in this study and previous knowledge about the pharmacokinetic behavior of these compounds, several of the drugs investigated have to be considered as potential photosensitizers in the human lens, the retina and the skin.

Animals↗
PubMed1994

Photolysis of intact young human, baboon and rhesus monkey lenses.

Intact young human, baboon and rhesus monkey lenses were subjected to near-UV irradiation under identical conditions and fluorophore buildup was continuously monitored for several hours. The compositional changes occurring in the lenses were monitored by analyzing the ethanol extracts of the irradiated and control lenses using high-performance liquid chromatography and thin-layer chromatography (TLC). The chromatograms of the supernatant detected at 365 nm as well as the TLC scans showed the presence of 3-hydroxykynurenine glucoside (3-HKG) and two other kynurenine-type compounds. The 3-HKG and one of the compounds were found in all three species, while the remaining one was structurally different in the lower primates. A loss of 3-HKG as a result of irradiation was apparent in all the lenses and correlated with the buildup of the blue fluorophore, suggesting that the latter may be a photoproduct(s) of 3-HKG. The kinetic analysis of baboon and human lenses showed a slowdown in the fluorophore buildup as irradiation times increased. This was probably due to the competitive absorptions of 3-HKG and other chromophores present. Rhesus monkey lenses did not exhibit this slowdown.

Animals↗
PubMed1994

Model studies on the photochemical production of lenticular fluorophores.

With aging, human lens proteins accumulate fluorophores having blue and green emissions. Model studies were undertaken to determine the role of 3-hydroxykynurenine (3-HK) and its glucoside (3-HKG) in the photochemical production of those fluorophores. Experiments were carried out using 10(-3) M 3-HK solutions in the presence or absence of glycine (1 M), which was used to mimic the environment of the lens. The solutions were photolyzed (transmission above 295 nm) for various periods of time while the loss of starting material and the formation of fluorescent photoproducts (blue emission at 470 nm, and green emission at 520 nm) were monitored using fluorescence and UV-visible spectroscopy and thin-layer and high-pressure liquid chromatography analysis. Several parameters were varied such as oxygen tension and the addition of the free radical scavenger, penicillamine. The photolytic loss of 3-HK in the absence of glycine occurred approximately 5-10 times faster than in its presence. Conversely, blue and green fluorophores formed in irradiated solutions containing glycine but not with the photolysis of 3-HK alone. The blue fluorophore was formed first and appeared then to be photochemically converted to the green one, with the rate of formation of the latter increasing with an increase in UV dosage or oxidizing conditions. The addition of penicillamine drastically reduced the photochemical formation of both fluorophores. Both the blue and green fluorophores appear to result from the photochemically induced covalent attachment of 3-HK to glycine.(ABSTRACT TRUNCATED AT 250 WORDS)

Fluorescent Dyes↗
PubMed1994

Risk stratification for restenosis after coronary angioplasty by means of exercise echocardiography.

To assess the prognostic contribution of exercise two-dimensional echocardiography in patients undergoing elective coronary angioplasty, 60 patients (44 males, 16 females, mean age 61 years) were enrolled in this study. The series included 31 patients with single-vessel disease, 23 with two vessel, and 5 with three vessel disease. After successful PTCA, they underwent stress echocardiographic testing either by treadmill (n = 23) or bicycle ergometry (n = 37), performed with digital continuous loop technique. A wall motion index (WMI) was calculated at rest and at peak stress. According to WMI values, the study population was divided into three groups: patients with normal WMI both at rest and stress (Group 1); patients with abnormal baseline WMI without change at stress (Group 2) and abnormal WMI diagnostic of stress-induced ischemia (Group 3). During the follow-up period, minimum of 1 year, 21 patients complaining of recurrent angina or chest discomfort, had repeat angiography: in 13 of these, typical restenosis of a previously dilated artery was found; 2 patients had progression of atherosclerotic plaque and in 6 the angiogram showed a good result of PTCA. Thirteen patients with restenosis or progressive disease underwent repeat PTCA. In this group, only 2 belonged to Group 1, 4 to Group 2, and 7 to Group 3. Thus, a linear correlation between the WMI value post-angioplasty and the clinical course could be documented (p = 0.001). Stress echocardiography was superior to stress ECG in both negative predictive value (88 and 77% respectively) and positive predictive value (73 versus 50%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

A pulse radiolysis study of the reactions of 3-hydroxykynurenine and kynurenine with oxidizing and reducing radicals.

Pulse radiolysis has been used to study the reactions of 3-hydroxykynurenine and kynurenine with solvated electrons, superoxide radicals, hydroxyl radicals and azide radicals. Both 3-hydroxykynurenine and kynurenine react with solvated electrons with diffusion controlled rate constants (k = 2.5 x 10(10) M-1 s-1 and 2.3 x 10(10) M-1s-1, respectively). Neither compound was observed to react with superoxide radicals under our experimental conditions, an upper limit of 1.2 x 10(5) M-1s-1 for the rate constant of this reaction was estimated for both compounds. However, we do observe that a stable product of autooxidation of 3-hydroxy-kynurenine reacts with superoxide radicals and we calculate a lower limit for the rate of this reaction of 5.8 x 10(6) M-1s-1. Reactions of 3-hydroxykynurenine and kynurenine with hydroxyl radicals proceed with diffusion controlled rate constants (1.2 x 10(10) M-1 s-1 and 1.3 x 10(10) M-1 s-1, respectively). The measured values for the rate constants for reaction of 3-hydroxykynurenine and kynurenine with azide radicals are 2.1 x 10(10) M-1s-1 and 4.8 x 10(9) M-1 s-1, respectively. The differences in these rate constants are attributed to differences in the measured oxidation potentials for 3-hydroxykynurenine (+1.0 V vs. NHE) and kynurenine (+1.15 V vs. NHE).

Electrons↗
PubMed1993

Molecular changes during the photooxidation of alpha-crystallin in the presence of uroporphyrin.

Singlet oxygen reacts preferentially with three amino acids in proteins, His, Trp and Met. In order to study the specific molecular events that result from such oxidations, calf alpha-crystallin was photooxidized in the presence of uroporphyrin and the reactions were investigated by high performance liquid chromatography peptide mapping using a photodiode array detector followed by fast atom bombardment mass spectrometry (FAB-MS). From these studies, the following conclusions can be inferred: (1) Upon photooxidation residue Met-68 of the B chain is oxidized to Met sulfoxide, whereas residue Trp-60 remains intact. (2) Two of the 16 His residues in alpha-crystallin are photooxidized with an apparent pKa of ca 7.0 (3) FAB-MS analysis suggests that residue Lys-166 close to the C-terminal end of the A chain forms a cross-link with the His-7 residue close to the N-terminal end of the A chain. This may be either an inter- or intramolecular cross-link.

Amino Acid Sequence↗
PubMed1992

The potential ocular phototoxicity of antidepressant drugs.

Light Therapy is a new treatment for patients with Seasonal Affective Disorder (SAD), a depressive state occurring during the winter as a result of decreased sunlight. The treatment involves placing the patient in front of a light box (2-10,000 lux) for approximately 30 min to 1 hour per day during the winter months. Although there have been no reports of damage to the eye from this treatment with light alone there is increased risk in light damage to the lens and retina if these depressed patients are being treated with antidepressant/neuroleptic drugs concurrently with their light therapy. As we have been previously reported certain drugs, having absorptions longer than 295 nm can act as photosensitizers resulting in enhanced light damage to the eye. Using a screening method developed by Roberts, we examined the potential phototoxicity of a variety of antidepressant and neuroleptic drugs.

Animals↗
PubMed1992

Committal procedures in Ireland.

The study aims to describe current committal practice in an Irish public psychiatric service and to establish the role of 'dangerousness' in determining practice. A six month retrospective review was undertaken using casenotes and original temporary forms of all patients committed to St Brendan's Hospital, Dublin within a six month period in 1990. A total of 136 cases were examined. In 65% of cases the application for detention was initiated by a spouse or relative. The recommending physician was identified as a General Practitioner in 80% of cases, although most were locum GP's. The number of male and female patients were almost equal. There was a wide age range with the largest group (42%) in the range 26-40 years. Previous contact with the psychiatric service was found in 89% of cases. There was a wide range of diagnoses with the largest category (56%) suffering from schizophrenia. Of those not admitted with alcohol or drug related illness 66% showed evidence of acute psychotic symptoms. Length of admission was relatively short with 84% of patients being discharged within three months. A total of 43% showed evidence of being a danger to themselves or others. Significant differences were found between these patients and the non-dangerous group, the latter being more likely to be older and to suffer from a major psychotic illness. These findings indicate that a committal law based purely on 'dangerousness' criteria would be likely to significantly affect committal practice in Ireland. These findings are discussed in relation to proposed changes in mental health legislation in Ireland.

Adolescent↗
PubMed1991

A peptide mimetic of calcium.

Proteins of the troponin superfamily use homologous amino acid sequences as binding sites for Ca2+ and seem to have evolved from an ancestral Ca2+ binding site. We have utilized this ancestral sequence to construct a peptide (Ca(2+)-like peptide) with inverted hydropathy to the calcium-coordinating region of this protein. This synthetic peptide acted like Ca2+ in that (i) it increased the calmodulin-dependent hydrolysis of cAMP by phosphodiesterase, (ii) it interacted with EDTA, and (iii) it enhanced contraction of urinary bladder smooth muscle in vitro. Unlike Ca2+, the peptide's effects were destroyed by acid hydrolysis. These findings demonstrate the synthesis of a peptide that can substitute for Ca2+ and may have considerable utility for the study of Ca(2+)-regulated pathways and possible therapeutic value as a pharmacologic agent.

Amino Acid Sequence↗
PubMed1991

Photooxidation of specific residues in alpha-crystallin polypeptides.

Singlet oxygen is a biologically important, photochemically generated species that preferentially oxidizes His, Trp, and Met residues of protein molecules. Calf alpha-crystallin was photooxidized with use of meso-tetra(p-sulfonatophenyl)porphyrin (TPPS) and uroporphyrin (UP) as singlet oxygen generators. The effects of photooxidation were monitored by analyzing the changes in alpha-crystallin peptide maps obtained by reversed-phase HPLC using a photodiode array absorbance detector. The reaction led to the loss of six specific peptides, five of which contained photooxidizable residues. Peptides containing His-97 and His-154 from the A chain and Met-68 from the B chain are preferentially photooxidized, suggesting that those residues have access to singlet oxygen. Trp residues in the N-terminal region are converted to NFK, whereas Trp-60 in the B chain is not photooxidized strongly suggesting that the former are close to the surface of alpha-crystallin while the latter Trp residue is buried. Only one peptide that is lost from the peptide maps does not contain a photooxidizable group; however, this peptide does contain an apparently undigested Lys residue. It is suggested that it forms a cross-link with a photooxidized His residue.

Amino Acid Sequence↗
PubMed1991

The photophysics and photobiology of the eye.

The eye consists of three major segments: the cornea, lens and retina. The main function of the anterior ocular tissue, the cornea and the lens is to transmit and focus light on the retina without distortion. They also filter out UV light (less than 400 nm) and prevent it from reaching the retina. Much of the light reaching the retina is used for sight. However, light can have numerous other effects on the constituents of the eye, both beneficial and deleterious. This article reviews the interaction of light with the eye, various protective mechanisms, the possible role of light in aging and disease states and the role of light in biological processes other than sight such as mood, hormonal secretions and the cyclic growth and phagocytosis of the rods and cones.

Animals↗
PubMed1991

The use of iohexol in patients with previous reactions to ionic contrast material. A multicenter clinical trial.

Patients who have had prior reactions to iodinated contrast material have increased risk for repeat reactions. Nonionic contrast agents have been reported to reduce the risk of contrast reactions. A multicenter study was undertaken to determine the repeat reaction rate using iohexol. Two hundred ninety-one repeat reactors were included in the study, of whom one-third received premedication. Sixteen patients (5.5%) experienced repeat reactions; none was severe, and only one was more serious than the prior reaction. This is in contrast to the reported 16% to 44% repeated reaction rate for ionic agents. We conclude that iohexol is effective in reducing the occurrence of repeat reactions from the level observed with ionic agents without premedication. Iohexol appears to be as effective as ionic agents plus premedication in this high-risk group of patients.

Adult↗
PubMed1991

Light damage in the rat retina: effect of a radioprotective agent (WR-77913) on acute rod outer segment disk disruptions.

Primary events in the course of light induced retinal lesions are still not fully elucidated. Under chronic conditions, lipid peroxidation in the retina and death of photoreceptor cells are observed. The radioprotective agent WR-77913 scavenges singlet oxygen, hydrated electrons and free radicals. WR-77913 was used to protect against acute light induced photoreceptor outer segment membrane disruptions in the rat retina. There was a partial but not complete protection at higher illuminance levels (800 lx for 30 min), whereas threshold lesions (400 lx for 30 min) were almost completely prevented. These observations indicate an involvement of photodynamic reactions in causing acute photoreceptor lesions.

Amifostine↗