Biomedical subjects
Publications and source records attributed to S Lerman.
Psoralen photoproducts were identified in association with cataracts in a psoriatic patient several years after oral methoxsalen plus ultraviolet A light (PUVA) therapy. Patients should be required to wear adequate optical protection not only during PUVA therapy but 24 hours following ingestion of methoxsalen.
13C-enriched acrylamide was employed to further delineate the action of this compound in preventing the cold cataract phenomenon when it is incorporated (in vitro) into young human and rabbit lenses. The extent of acrylamide incorporation, in the dark and with concurrent UV exposure, was monitored by 13C NMR spectroscopy. These studies provide further evidence that UV exposure causes permanent acrylamide photobinding within the lens. In such lenses, the gamma crystallin fraction of the soluble lens proteins is affected to the greatest extent. It appears to become aggregated and/or combined with the alpha and beta fractions resulting in an apparent loss of most of the gamma monomers. There is also an age-related effect with respect to the amount of acrylamide that can be incorporated into the lens. The decrease in acrylamide incorporation with age directly parallels the age-related decline in gamma crystallin levels.
We excepted from the logs of the adult and children's emergency room at Soroka Hospital Medical Center the number and types of services requested by day for the year 1980. Both total visits and visits for respiratory conditions were examined in order to test whether rain, heat, or pollutants led to increased requests for emergency room care. The total visits for adults were 72,375, of which 1,727 (2.4%) were for selected respiratory conditions. The total visits for children were 19,232, and respiratory conditions were 3,980 (20.7%). There is marked seasonal excess for respiratory visits for children in winter, and a lesser excess for adult respiratory conditions. Non-respiratory conditions and overall visits are higher in summer months. Fewer visits occur on Saturday and on Friday, with the maximum on Sunday. Otitis and bronchitis among children show little day-of-week trends. "High event" days for admissions are determined by fitting a Poisson distribution to the numbers of admissions by day for various respiratory complaints, and we then examine the concordance between these high event days and days with rain, high pollution or temperature. Adult respiratory conditions were more likely to occur on days with high total particulates (TSP) and "respirable" particulates (RSP). When the mean values of RSP and TSP for high asthma and shortness of breath days were compared with a random day for the same month, significant differences were found for RSP for adults, but not for TSP. Natural dust is the more likely cause of this association. Emergency room monitoring should be useful in locations with high levels of man-made pollutants.
We examined 11 cataractous lenses (or aspirated lens matter from extracapsular extractions) from patients ranging in age from 55 to 84 years who used allopurinol on a long-term basis (more than two years). Phosphorescence analyses demonstrated the characteristic allopurinol triplet in these lenses. When we analyzed normal lenses from patients taking allopurinol in a similar manner we found no evidence of allopurinol photobinding. These data indicated that allopurinol has a cataractogenic action only in patients in whom the drug has become photobound within the lens. Long-term allopurinol therapy does not necessarily cause or enhance cataracts in all patients. There may be a relationship between ultraviolet radiation exposure and circulating allopurinol levels (and perhaps renal function) in the genesis of photosensitized allopurinol cataracts.
Exposure of four monkey and 26 rabbit eyes to neodymium-YAG laser irradiation to the posterior lens capsule or the mid-vitreous area clearly demonstrated significant vitreous changes (liquefaction) as measured by viscosity analyses and proton relaxation studies. We found marked molecular alterations in the vitreous of the exposed eye compared with the contralateral control (unirradiated) eye. These alterations, occurring immediately after laser treatment, were probably the result of acoustic transients accompanying the laser irradiation.
The chemical composition and morphology of the cornea and lens can provide significant information regarding what wavelengths of nonionizing radiation these two tissue should absorb and transmit. Such data, including a variety of parameters determined by biophysical techniques, can provide us with information regarding the molecular basis for corneal and lenticular transparency and the subtle changes occurring with aging and ambient radiation exposure during our lifetime. The biophysical approach (fluorescence and NMR spectroscopy) has already provided new clinical tools for studying and delineating the initial events responsible for eventual opacification in these two tissues, months to years before they become manifest by current conventional clinical methods of examination.
During the aging process, the lens is subjected to changes of its pertinent properties which condition the transmission of light of different wavelengths. Between the second and the third decade, for instance, wavelengths below 400 nm are almost completely absorbed. The increase in lens thickness, effected by the appositional growth during life, might be considered responsible for this phenomenon, if the newly developing lens fibers in the outer periphery would synthesize proteins which, with respect to light transmission, differ from those formed during the embryonic phase. For such a phenomenon, however, no indication was found either by clinical observations or biochemical research. -Microdensitometric analysis of Scheimpflug-photographs of the anterior eye segment allows measurements of lens transparency in the single lens which directly depend on the respective wavelengths used in the photographic procedure. Investigations performed with this method on a normal age-grouped population, show that the changes in light transmission are most evident in two of the lens segments. The lens nucleus shows a continuous increase in light scatter during aging. Also the anterior cortex - particularly in the deeper layers - shows changes in light transmission. With advancing age (beginning between 30 and 40 years of age), increased lens fluorescence is found in the region of the deeper anterior cortex, which can be excited by UV wavelengths of 330-380 nm. This phenomenon is not found in the lens nucleus. The localization of the changes within the lens clearly shows that they are due to age-related modifications of the protein properties earlier designated as posttranslational or postsynthetic molecular modifications.(ABSTRACT TRUNCATED AT 250 WORDS)
A 70-year-old female presented with a generalized allergic reaction to heterologous insulin. Subsequent epicutaneous testing to human insulin (Humulin) evoked a large wheal and flare reaction and generalized pruritus. The institution of human insulin therapy in patients allergic to heterologous insulin may cause further allergic reactions.
Young (less than 1 year) and old (greater than 15 years) Rhesus monkeys were utilized in this study in order to determine whether ultraviolet (UV) radiation at ambient levels induces psoralen photobinding in primate eyes (in particular the lens and retina). Unilateral aphakia or pseudophakia was induced surgically and the eyes were allowed to heal. The animals then were given a single intraperitoneal injection of 3H 8-methoxypsoralen (8-MOP) and immediately exposed to BLB lights (of measured radiation intensity at the corneal surface). The animals were killed at varying time periods (2-6 weeks), and the eyes were removed immediately. One-half of each cornea and lens was frozen for subsequent optical spectroscopy and the remaining ocular tissues were fixed for histopathologic studies and autoradiography. These data demonstrate that low level UV radiation (less than 0.4 mW/cm2) can cause 8-MOP photobinding to lens proteins and DNA and to aphakic, pseudophakic, and young phakic primate retinas. The older phakic primate lens serves as a protective UV filter and prevents psoralen photobinding within the retina. These data suggest that older aphakes and pseudophakes may require UV radiation protection to prevent direct as well as photosensitized retinal photodamage.
Optical spectroscopy (fluorescence, phosphorescence, and electron spin resonance) has demonstrated the presence of 8-methoxypsoralen (8-MOP) and its potential for photobinding (to DNA and proteins) in human and animal ocular lenses. Similar photobinding in other ocular tissues, particularly the retina, has also been shown to occur in the young eye (lens has not yet developed as an effective UVA filter) and in aphakic and pseudophakic eyes. Skin biopsies were performed on a series of patients before, during, and following psoralen photochemotherapy (PUVA). High-resolution phosphorescence spectroscopy of PUVA patients enabled us to monitor the presence of 8-MOP in the skin and blood samples. These data indicated that significantly higher levels of 8-MOP accumulate within the psoriatic skin compared with uninvolved areas and demonstrated the feasibility of monitoring 8-MOP metabolism by this method. A second series of patients who had been on chronic PUVA therapy for many years were also evaluated by this technique and all patients' eyes were monitored by UV slit-lamp densitography with respect to determining lenticular photodamage in "unprotected eyes" compared with protected and untreated controls. The latter data have delineated at least 3 cases of presumptive PUVA cataracts. Phosphorescence assays on lens matter derived from individuals with a clinical diagnosis of PUVA cataracts demonstrated a photoproduct identical with the previously reported triplet noted in the lenses from experimental PUVA-treated animals.
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Polypropylene discs and shavings were exposed to simulated ambient ultraviolet (UV) radiation (lambda 300-400 nm) for a period equivalent to at least two years of wear within the eye, assuming the eye to be exposed to ambient UV radiation for four hours per day at 1 mW/cm2. The polypropylene and the incubation media were measured by several forms of optical spectroscopy, and there was no photochemical change in either. Where polypropylene discs were exposed to a very high level of UV radiation (greater than 500 W/cm2), they became brittle and discolored within five to ten days. This level of exposure, however, was equivalent to a total of over 20 million joules/cm2, which is at least one million times levels for expected ambient UV exposure to polypropylene within the eye.
The normal human lens is a precisely formed structure containing about 65% water and 35% organic matter, the latter being mainly (greater than 90%) structural proteins. The lens becomes encapsulated at the 13 mm embryonic stage and is consequently divorced from a direct blood supply for life. It provides the investigator with an organ that exists in an environment analogous to a single-cell type of tissue culture system and can be reproduced in vitro. Since the cornea and lens are transparent one can directly monitor morphologic and biochemical aging changes in vivo. Recent developments now permit us to monitor certain molecular changes as well. Thus this organ can serve as a unique model for studying in vivo aging parameters. In vivo UV slit lamp densitography to monitor lens fluorescence provides us with a useful diagnostic and prognostic screening method to identify lens photodamage due to excess UV exposure (occupational or accidental), photosensitizers (e.g. psoralens) as well as the normal age related increase in lenticular fluorescence. Cortical opacities are also a common finding in older individuals. In vitro NMR (human and animal lenses) and in vivo (animal experiments) currently in progress are rapidly elucidating the physicochemical basis for the development of light scattering areas in the aging lens cortex. This review demonstrates the feasibility of utilizing biophysical methods, in particular, optical spectroscopy and NMR analyses to delineate and monitor specific age related parameters in the ocular lens, in vivo as well as in vitro.
The tricyclic ring structure of several of the aldose reductase inhibitors indicates that they could be detected by optical spectroscopy in certain ocular tissues. Four of these compounds (Quercetin, Quercitrin, AY22-284, and Sorbinil) were investigated with respect to their UV absorption, fluorescence, and phosphorescence characteristics. All absorb in the UV wavelength and have measurable fluorescence (room temperature) and phosphorescence characteristics (77 K). The phosphorescence characteristics were utilized to monitor for the presence of Quercetin, Quercitrin, and AY22-284 in rat, rabbit, and human lenses incubated with each of the inhibitors. Following IP injection, rat and rabbit lenses were removed and subjected to phosphorescence spectroscopy for these three reagents. AY22-284 gave the sharpest and clearest phosphorescence spectra with emission wavelengths well removed from intrinsic lens phosphorescence. It can be detected in the extracted ocular lens within 30 minutes after in vivo IP administration, as well as in vitro lens incubations. The spectral data correlate well with aldose reductase inhibitor levels in such lenses as measured by a biochemical technique. Similar data were obtained with Quercitrin. Sorbinil was best monitored by fluorescence spectroscopy and could be detected in the lens following in vivo administration, as well as in vitro lens incubations.
Water proton relaxation studies were performed on total soluble protein (TSP) solutions and individual alpha-, beta-, and gamma-crystallin fractions derived from weanling rat lenses, 16 month, and 60- to 70-year-old normal human lenses. The effects of perturbants (temperature and acrylamide) were monitored in order to delineate further the mechanisms involved in the generation of the cold cataract phenomenon (in young lenses) and the role of acrylamide and age in preventing this phenomenon. The data demonstrate a relationship between the relative concentration of the alpha-, beta-, and gamma-crystallin fractions within the lens and the cold cataract phenomenon. It is possible that cross-linking between acrylamide and the gamma-crystallins within the lens alters one or more of the intracytoplasmic protein-water phases. The gamma-crystallin solution showed greater than 35% increase in T2 when 1% acrylamide was added; the young TSP solution T2 increased by approximately 20%. However none of the T2 values for the alpha, beta and old TSP solutions changed significantly when acrylamide was added. The unique response of gamma-crystallin in these experiments suggests a significant role for this protein fraction in the phenomenon associated with cold cataractogenesis. Our data indicate that most of the UVA radiation-induced acrylamide binding occurred with the gamma-crystallins within the lens. We have also noted that only the gamma-crystallin and the young lens TSP solutions become opaque at 4 C while the alpha, beta and "old" TSP solutions remain clear at this temperature. It is suggested that acrylamide exerts its role by cross-linking to one or more of the gamma-crystallins, thereby altering the normal protein water relationship and preventing cold opacification.
The effect of systemic 8-methoxypsoralen (8-MOP; 100 mg/kg daily) and subsequent long ultraviolet irradiation (UVA; 300 mJ/cm2; peak: 365 nm) on albino and pigmented rat eyes was studied in a 3-dimensional experimental set-up. While 8-MOP and UVA did not cause any ocular pathology when administered alone, a combined application of the two factors caused reversible corneal opacities, and irreversible iris devascularisation and cataracts. The irreversible changes were seen only in the albinos and accompanied by a significant decrease in lens wet weight. Phosphorescence and EPR spectroscopy demonstrated the formation of an 8-MOP-protein photoadduct in the animals treated with both 8-MOP and UVA. The results of this study emphasize the necessity of shielding the eyes of patients on photochemotherapy with protective spectacles.
Long-term ingestion of allopurinol, an antihyperuricemic agent used to treat gout, may be related to the development of lens opacities in relatively young patients (second to fifth decades of life). Cataracts obtained from three patients taking allopurinol were subjected to high-resolution phosphorescence spectroscopy. The characteristic allopurinol triplet was demonstrated in all three cataracts. Identical spectra were obtained for normal human lenses incubated in media containing 10(-3)M allopurinol and exposed to 1.2 mW/cm2 ultraviolet radiation for 16 hours; control lenses (irradiated without allopurinol) showed no allopurinol triplets. Similar data were obtained for lenses from rats given one dose of allopurinol and exposed to ultraviolet radiation overnight. These data provide evidence that allopurinol can be photobound in rat and human lenses and suggest its cataractogenic potential.