X-ray microanalysis of ocular melanin in pigs maintained on normal and low zinc diets.

Retinal-choroidal tissues were collected from older sows that were fed either control (100% Zn), intermediate zinc (59% Zn) or low zinc (21% Zn) diets for a 6-month period. The tissues were prepared for elemental energy dispersive X-ray analysis and examined by scanning transmission electron microscopy. Melanosomes of the retinal pigment epithelium and choroidal melanocytes were specifically analysed. The elemental spectra of a specific type of melanosome within a sample region were consistently similar. The elemental spectra of choroidal melanosomes differed slightly from that of RPE melanosomes, having greater levels of calcium, iron and zinc. Changes of the elemental content of both types of melanosomes were observed in the animals that were maintained on low zinc nutrition. Iron and zinc decreased in level, while copper increased. Calcium decreased in the RPE melanosomes of intermediate and low zinc diet animals. However, calcium only decreased in choroidal melanosomes of the low zinc-fed sows, having increased substantially in the intermediate zinc-fed group. Abnormal melanosomes were concomitantly seen in the melanocytes of both the intermediate and low zinc groups.

DNA polymorphism analysis of hereditary multiple exostoses in horses.

Genomic DNA polymorphisms obtained by restriction fragment-length polymorphism from healthy horses and horses with hereditary multiple exostoses were analyzed. These DNA were digested by 12 restriction enzymes and were hybridized against 6 isotopically labeled oncogene probes. Hybridization was not detected with the viral oncogene, v-ras, which indicated this oncogene was absent in the equine genome. Oncogenes (c-raf-1, c-fes, c-myb, c-myc, and c-sis) were present and had similar hybridization patterns and signal intensities in DNA from healthy horses and horses with hereditary multiple exostoses. Unique and distinct restriction fragment-length polymorphisms were detected with the c-raf-1 probe only in BamHI- and PstI-digested equine DNA.

Oral zinc in macular degeneration.

Macular degeneration associated with age and drusen, an important cause of severe visual loss in older persons, is of unknown cause. The sensory retina and retinal pigment epithelium, which are cell layers in zinc, appear to be prominently involved in the disease process. Because zinc plays a role in the metabolic function of several important enzymes in the chorioretinal complex, we undertook a prospective, randomized, double-masked, placebo-controlled investigation of the effects of oral zinc administration on the visual acuity outcome in 151 subjects with drusen or macular degeneration. Although some eyes in the zinc-treated group lost vision, this group had significantly less visual loss than the placebo group after a follow-up of 12 to 24 months. This is the first controlled oral intervention study to show a positive, if limited, treatment effect in macular degeneration, a major public health problem. Because of the pilot nature of the study and the possible toxic effects and complications of oral zinc administration, widespread use of zinc in macular degeneration is not now warranted.

Hereditary multiple exostosis. A comparative human-equine-epidemiologic study.

Hereditary multiple exostosis (HME), a bone tumor first described by Virchow, has been studied over a period of 15 years on a comparative basis. The horse, an excellent biomedical model for this physically deforming multiple bone tumor in man, has been utilized in this study. The etiology, hereditary pattern, potential for malignancy and other aspects of this strange affliction need additional clarification. This in-depth study of 261 individuals from 144 families was compared with that of 55 horses bearing the HME trait, selectively bred and studied over the same period. Important information has been collected and evaluated about this condition that is suspect of being frequently missed diagnostically, with a higher incidence in humans that recognized. Continuing development studies of offspring of the original study participants; sarcomatous transformation monitoring; and recently developed genetic techniques should add to our understanding of this puzzling hereditary condition.

Macular degeneration and elevated serum ceruloplasmin.

Macular degeneration associated with age and drusen, an important cause of visual loss, is associated clinically with alterations in the retinal pigmented epithelium. Because the pigmented epithelium is a copper-rich tissue with antioxidant properties, the copper economy in patients and controls were studied by measuring ceruloplasmin. Ceruloplasmin, a multifunctional, copper-binding alpha-globulin, was significantly elevated in non-related patients as compared with controls (691 +/- 153 mg/L vs 312 +/- 64; P less than .001), both by the p-phenylenediamine oxidation technique and radial immunodiffusion assay. When 53 members of a large family were divided clinically into persons with and without macular degeneration, the ceruloplasmin concentrations were not significantly different from each other, but were elevated as compared with non-related controls (P less than .001). These differences were not due to an intragroup age mismatch. A group of patients with retinitis pigmentosa had normal serum ceruloplasmin concentrations. This study suggests a relationship between serum ceruloplasmin, trace metals, and the tissue alterations associated with macular degeneration that deserves further investigation.

Effect of excessive exposure to sodium fluoride on composition and crystallinity of equine bone tumors.

Sodium fluoride (5 mg/kg of body weight) was fed for 20 months to horses with hereditary multiple exostoses (HME), a skeletal disorder that primarily affects endochondral bones during skeletal development. Rib biopsies were performed on both HME horses not fed fluoride (control) and HME horses that were fed fluoride to obtain comparable specimens for chemical analyses and x-ray diffraction. Fluoride content of the rib from a horse fed fluoride for 20 months was approximately 20 to 30 times higher than that from a control horse. Fluoride content of the bone tumors was higher than those of normal bones in both control and fluoride-fed horses. The effect of fluoride uptake on the Ca/P ratio was slight. The Ca/P ratios did not differ significantly between tumorous and normal ribs. X-ray diffraction studies showed that the crystallinity (ie, crystal size/perfection) of the mineral apatite in tumor of the rib from the control horse was lower than that of normal bone from the same rib. Fluoride, however, induced a marked change in the crystallinity at both the tumorous and the normal bone sites. The crystallinity of the tumor apatite in the fluoride-fed horse exceeded that of normal bone in the control horse. Otherwise, there were not demonstrable fluoride-induced gross or radiographic changes in the bone tumors.

Hereditary multiple exostoses: clinicopathologic features of a comparative study in horses and man.

Investigation of hereditary multiple exostoses in horses under controlled research conditions for 10 years and epidemiologic studies that have spanned up to five generations of human families contain notable similarities. The present study demonstrated that a single dominant autosomal gene is responsible for hereditary multiple exostoses in horses and man. Affected individuals transmit this trait to approximately 50% of their progeny, whereas nonaffected individuals do not transmit the condition to their offspring. The tumors in affected horses are most often present at birth. They tend to be bilaterally symmetrical and vary in size, shape, and texture. Those on the legs generally do not appear to enlarge as the animal matures, but others, notably those on the ribs and scapulae, enlarge until skeletal maturity, Histologically, the tumors appear as typical ostosteochondromas in both horse and man. Sarcomatous transformations have not yet been detected after 10 years in horses, although such changes are occasionally reported in the similar disease condition in man. The remarkable similarities of hereditary multiple exostoses in the horse to that in man provide an opportunity for comparative biomedical study.

Hereditary multiple exostosis. A comparative genetic evaluation in man and horses.

Comparative studies are being conducted on hereditary multiple exostosis in man and the horse. In both, there is an unquestionable inheritance pattern of a typical single, dominant, autosomal gene. Those who carry the gene have a one-half chance of transmitting it to each offspring, whereas, those who do not carry the gene do not transmit this abnormality to their progeny. The lesions are clinically and histologically similar; no persistent chromosomal irregularities have been associated with the abnormality in either man or the horse and no single evidence of malignancy in either man or animal has been detected in this study to date.