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Biomedical subjects

M L Katz

Publications and source records attributed to M L Katz.

At least 91 records · Page 5Linked to original sources
PubMed1987

Age-related alterations in vitamin A metabolism in the rat retina.

Vitamin A plays a central role in visual transduction and in maintaining the structural integrity of the retina. It is possible that age-related alterations in vitamin A metabolism in the eye could contribute to the impairment of visual function that occurs during senescence. Therefore, investigations were conducted to determine whether the metabolism of this vitamin in the rat retina was altered during aging. Pigmented rats aged 12-, 22-, and 32 months were dark-adapted, and one eye from each animal was enucleated under dim red light. The neural retinas were separated from the retinal pigment epithelium (RPE)-choroid-scleral complexes, and the amounts and forms of vitamin A in both tissues were determined. The animals were then fully light-adapted, and the same measurements were performed on the tissues from the remaining eye of each rat. A number of age-related alterations in the vitamin A composition and content of the retina and RPE were observed. The most pronounced of these changes were significant increases in the ratios of retinyl palmitate to retinyl stearate with advancing age in both the neural retina and RPE. The total vitamin A ester contents of the RPEs increased during senescence in the dark-adapted state, but not in the light-adapted state. Retinyl ester levels in the neural retinas, on the other hand, did not differ significantly between 12- and 32-month-old animals in either the light-adapted or dark-adapted states. The amounts of all-trans retinol in the neural retinas decreased during aging, mainly in the dark-adapted state, whereas aging had no influence on RPE all-trans retinol content. The age-related alterations in metabolism of vitamin A that these observations reflect may be related to certain changes in visual function that occur during senescence.

Adaptation, Ocular↗
PubMed1986

Evidence of cell loss from the rat retina during senescence.

In order to determine whether neuronal cell death in the retina accompanies senescence, retinas from pigmented ACI rats of various ages were analysed for changes in dimensions, cell densities, DNA content, and rhodopsin levels. Between the ages of 4 and 30 months, there were significant declines in the densities of nuclei in all three nuclear layers of the retina. Over this age span, nuclear density in the outer nuclear layer (ONL) declined by 32-41%, depending on the region of the retina examined, while inner nuclear layer (INL) nuclear density decreased by 25-34%. Over the same age range, the nuclear density in the ganglion cell layer (GCL) declined by 25-28%. The eye increased in size over the 4-30 month age span, particularly between 4 and 12 months. The retinal stretching that resulted from this growth could only partially account for the age-related decline in retinal cell densities. Depending on the region of the retina examined, decreases in nuclear density of 17-26% for the ONL, 9-17% for the INL, and 16-20% for the GCL were apparently due to cell death. Measurements of retinal DNA content support the conclusion that significant cell loss from the retina occurs during senescence; between 4 and 30 months of age retinal DNA content decreased by about 13%. Age-related changes in retinal rhodopsin content did not parallel apparent changes in photoreceptor number. Between 4 and 11 months of age, rhodopsin levels rose by about 10%, and then remained constant up to 26 months. Over this same age span, there was an apparent decrease in photoreceptor number of about 15%.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1986

Relationship between dietary retinol and lipofuscin in the retinal pigment epithelium.

A variety of evidence suggests that autoxidation of cellular components probably plays a significant role in the age-related accumulation of lipofuscin, or age-pigment, in the mammalian retinal pigment epithelium (RPE). Among the likely candidates for conversion into RPE lipofuscin fluorophores via autoxidative mechanisms are vitamin A compounds, which are present in the retina and RPE in high concentrations. Vitamin E, an important lipid antioxidant, is likely to inhibit vitamin A autoxidation. Experiments were conducted to evaluate the significance of vitamin A autoxidation in the deposition of lipofuscin in the RPE. Albino rats were fed diets either supplemented with or lacking vitamin E. Each of these two groups of animals was further subdivided into three groups which were fed different levels of vitamin A palmitate: none, 14.0 mumol/kg diet, and 80.5 mumol/kg diet. After 26 weeks, the animals were killed and the RPE lipofuscin contents were determined by both fluorescence measurements and quantitative ultrastructural morphometry. Vitamin A palmitate deficiency led to significant reductions in RPE lipofuscin deposition, relative to the amounts of this pigment present in the groups receiving vitamin A palmitate in their diets. The relative magnitude of the vitamin A effect was greater in the vitamin E-supplemented groups than in the groups fed the diets deficient in vitamin E. This finding suggests that vitamin E interacts with vitamin A ester metabolites in vivo in a more complex manner than simply acting as an antioxidant protectant. Rats fed the diets containing the higher level of vitamin A palmitate failed to display elevated RPE lipofuscin contents relative to those in the rats fed 14.0 mumol of vitamin A palmitate/kg diet. Failure of high vitamin A intake to enhance RPE lipofuscin deposition may have been due to the fact that intake of vitamin A above normal levels did not lead to an elevation in vitamin A content of the retinal tissue. Establishing an effect of vitamin A deficiency on RPE lipofuscin deposition and characterization of the interactions between vitamins E and A are important steps toward defining precisely the molecular and cellular mechanisms underlying age-pigment accumulation in the RPE.

Animals↗
PubMed1986

Influence of early photoreceptor degeneration on lipofuscin in the retinal pigment epithelium.

Experiments were conducted to evaluate the role played by photoreceptor cells in the accumulation of age pigment, or lipofuscin, in the retinal pigment epithelium (RPE). The age-related accumulation of RPE lipofuscin was compared between rats with hereditary photoreceptor degeneration (RDY) and congenic rats with normal retinas. In the RDY animals, the age-related increase in RPE lipofuscin content was substantially less than in normal controls. This suggests that the photoreceptor cells play a significant role in RPE lipofuscin deposition, although they may not be the sole contributors to RPE lipofuscin formation. Evidence that outer-segment components may be converted into lipofuscin fluorophores was provided by the discovery that in young RDY rats, fragments of outer segments from degenerating photoreceptor cells had fluorescence properties similar to those of RPE lipofuscin. Chloroform-methanol extraction of retina-RPE tissue from young normal and dystrophic rats, and analysis of the chloroform fractions by thin-layer chromatography, revealed three distinct fluorescent components associated with the lipofuscin-like fluorescence of the outer-segment fragments in the RDY rats.

Aging↗
PubMed1986

Age-related thickening of retinal capillary basement membranes.

Capillary basement membrane thickness is known to increase in a variety of tissues during aging and as a consequence of certain systemic disease states. In order to determine whether capillary basement membrane thickness increases during senescence in the outer plexiform (OPL) and ganglion cell (GCL) layers of the retina, eyes of pigmented ACI rats aged 4, 11, 17, and 32 mo were examined. Basement membrane thickness in the OPL and GCL were determined at each of these ages using computer-assisted ultrastructural morphometry. Capillary basement membranes in both the OPL and GCL showed a linear increase in thickness over the 4 to 32 mo age span. The increase in thickness averaged 54% for the OPL and 65% for the GCL over this age range. At all ages examined, the GCL basement membranes were 80 to 90% thicker than those in the OPL. Age-related changes in the substructure of the capillary basement membranes differed between the OPL and GCL. It is possible that the observed age-related changes in retinal capillary basement membranes may play a role in the development of senile retinopathies.

Aging↗
PubMed1985

Diagnostic methods for deep vein thrombosis: venous Doppler examination, phleborheography, iodine-125 fibrinogen uptake, and phlebography.

Since clinical diagnosis of DVT is often inaccurate, it has become accepted that an objective means of diagnosing clot in the deep venous system becomes critically important in the management of these patients. Important to understanding the diagnostic capabilities of any test are the anatomic and physiologic characteristics of the deep venous system. The venous Doppler examination monitors the velocity of blood flowing through a particular vein. Doppler probes in the 5 to 10 mHz range are routinely used. Respiratory variation is a normal finding due to a diminished flow signal during inspiration, followed by a progressive increase in flow signal during expiration. Characteristics of the spontaneous flow signals are the most important part of interpreting the venous Doppler examination. In addition, the response to distal or proximal compression (augmentation) adds important information to the interpretation; however, the response during any augmentation maneuver depends on the rapidity of compression, the force of compression, the quantity of blood in the veins at the time of compression, and the distance between the Doppler probe and the compression point. The literature reports a wide range of sensitivity and specificity for the Doppler examination, but there is uniform agreement and an observable trend that physicians with a large experience and a dedicated interest will obtain much better results than physicians with less experience and less interest. Phleborheography is a six-channel volumetric plethysmographic technique that monitors volume changes in the lower extremities associated with respiration and foot and calf compression. The volumetric tracings obtained are similar to the velocity profiles obtained on the venous Doppler examination. The criteria used in interpreting phleborheographic tracings are respiratory waves and baseline elevation (major criteria), and prominent arterial pulse waves and foot emptying (minor criteria). Previously reported overall sensitivities for detecting DVT are 83 to 93 percent, with sensitivities of detecting proximal vein thrombosis of 92 to 96 percent. Specificities have been reported to be 87 to 97 percent. In a prospective analysis of 126 extremities with phleborheography and phlebography carried out within the same 24 hour period at Temple University Hospital, we found an overall sensitivity of 79 percent (51 of 65 patients); however, the sensitivity for proximal vein thrombosis was 91 percent (49 of 54 patients).(ABSTRACT TRUNCATED AT 400 WORDS)

Fibrinogen↗
PubMed1985

Senescence and the retinal pigment epithelium: alterations in basal plasma membrane morphology.

Marked age-related changes in the morphology of retinal pigment epithelial (RPE) cell basal infoldings were found in pigmented rats. Quantitative morphometric analysis revealed that during senescence the amount of basal plasma membrane per unit RPE length increased substantially, the regional distribution of the basal infoldings along the RPE became more irregular, and the average depth of penetration of the basal infoldings into the RPE increased dramatically. The crucial role of the RPE in maintaining retinal integrity suggests that the observed changes in RPE morphology may be involved in the development of senile retinopathies which occur in a variety of species, including man.

Aging↗
PubMed1985

Localization of lipofuscin in the duodenums of vitamin E-deficient rats.

In human malabsorption syndromes, lipofuscin accumulation has been reported to occur exclusively within the muscle layers of the intestine. It has been widely speculated that this lipofuscin deposition is related to vitamin E deficiency. To determine whether vitamin E deficiency leads to the same pattern of intestinal lipofuscin accumulation as that seen in many human malabsorption syndromes, the duodenums of rats that had been fed a vitamin E-deficient diet for 17 or 34 wk were examined for the presence of lipofuscin. Lipofuscin did not appear in the muscle layers of the duodenum until 34 wk, at which time occasional fibers containing large amounts of lipofuscin were present. An earlier and more pronounced deposition of lipofuscin occurred within connective tissue cells of the intestinal villi. After 17 wk, many fibroblastlike cells in the lamina propria of the villi contained large amounts of lipofuscin. By 34 wk, the numbers of these lipofuscin-containing cells in the lamina propria had increased substantially, and scattered cells containing lipofuscin were also seen in the submucosa. The difference in intestinal lipofuscin distribution between vitamin E-deficient rats and humans with malabsorption syndromes suggests that other factors, in addition to vitamin E, probably play important roles in regulating lipofuscin accumulation in the intestine.

Animals↗
PubMed1984

Age-related changes in the retinal pigment epithelium of pigmented rats.

A number of significant age-related changes were found to occur in the retinal pigment epithelium (RPE) of normal pigmented ACI rats. Age-related morphological changes in the RPE included: changes in RPE cell height, an increase in lipofuscin content, alterations in the apical microvilli and basal infoldings, and an apparent thickening of the RPE basal lamina. Unusual banded structures were often seen within the basal infoldings of the RPE in senescent but not in young adult rats. Lipid droplets were relatively common in the RPE of senescent rats, but were quite rare in 4- and 11-month-old animals. In addition, contact between the RPE apical microvilli and the photoreceptor outer segments appeared to become less intimate with age. Phagocytosis of rod outer segment discs appeared to be reduced between 4 and 32 months of age. This reduction was greater than could be accounted for solely by a concomitant age-related decrease in the number of photoreceptors per unit retinal length. RPE-choroid acid phosphatase activity (a lysosomal marker), on the other hand, did not appear to change with age. The molar ratio of vitamin A-palmitate to vitamin A-stearate in the PRE-choroid rose significantly with age, from about 1.85 at both 4 and 11 months, to over 2.5 at 28 months. At each age, the palmitate- to stearate-ester ratio was the same in the dark-adapted and light-adapted eyes.

Acid Phosphatase↗
PubMed1984

Real-time B-mode carotid imaging. A three-year multicenter experience.

This report attempts to establish the place of real-time B-mode carotid imaging in the diagnosis of carotid artery disease through an analysis of the results of 3 years of experience in three major noninvasive vascular laboratories. Over 7000 patients were studied noninvasively with real-time B-mode carotid imaging and oculoplethysmography (OPG). Angiographic comparisons of 1723 vessels form the basis of this study. All tests were interpreted by physicians who had no knowledge of the angiograms. Images and x-ray films were classified by diameter of stenosis: grade I (0% to 39%), grade II (40% to 69%), grade III (70% to 99%), and grade IV (total occlusion). The effect of the imaging experience was determined by dividing the study into two periods. The results of image quality vs. accuracy and of combining the anatomic study (scan) and physiologic study (OPG) were also evaluated. The overall data show a specificity of 87% (985 of 1139), a sensitivity for grade II disease of 72% (193 of 267), a sensitivity for grade III of 66% (133 of 201), and a sensitivity for grade IV of 64% (74 of 116). With experience each center showed improvement of the imaging technique in diagnosing grade III (p greater than 0.1: not significant) and grade IV disease (p less than 0.0002: highly significant), although there was no improvement in the specificity and sensitivity of grade II disease. All scan errors were analyzed. Most errors were interpretation errors (27%: 90 of 338), scan/arteriogram mismatches (23%: 79 of 338), or poor-quality scans secondary to existing disease (22%: 75 of 338). There was a direct correlation of scan quality and accuracy, with a 97% specificity for grade I scans of good to excellent quality. When the scan and OPG agreed, there were uniform predictive values for all grades (88% to 93%). Sixteen of 79 scan/arteriogram mismatch vessels were operated on, and the scan proved more reliable in 86%. Real-time B-mode carotid imaging is a reliable technique for defining the normal carotid artery and is becoming increasingly sensitive in identifying existing disease. Despite its limitations, its strong points make it a valuable clinical tool.

Carotid Artery Diseases↗
PubMed1983

Lipofuscin response to the "aging-reversal" drug centrophenoxine in rat retinal pigment epithelium and frontal cortex.

The effects of centrophenoxine on the lipofuscin contents of the retinal pigment epithelium (RPE) and frontal cortex of the brain were examined in senescent female Fischer rats. Rats (106 weeks old) were injected daily for 11 weeks with centrophenoxine (80 to 120 mg/kg body weight) or saline, and then sacrificed along with untreated 28- and 46-week-old controls. The number of lipofuscin granules seen in the RPE by light microscopy increased by 70% between 28 and 117 weeks of age in control animals. There was a concomitant age-related increase in lipofuscin specific fluorescence in the RPE. Centrophenoxine treatment neither reduced the amount of lipofuscin, nor altered the ultrastructural appearance of lipofuscin granules in the RPE. Between 28 and 117 weeks of age, there was an almost nine-fold increase in the lipofuscin content of the frontal cortex of control animals; centrophenoxine treatment failed to reverse this pigment accumulation.

Aging↗
PubMed1978

Fluorescent pigment accumulation in retinal pigment epithelium of antioxidant-deficient rats.

A yellow autofluorescent pigment, generally thought to be indicative of membrane autoxidation, was found to accumulate in the retinal pigment epithelium (RPE) of rats maintained for 32 weeks on diets producing physiological antioxidant deficiency. The largest build-up of fluorescent pigment occurred in rats fed a diet high in polyunsaturated fatty acids (PUFAs) and deficient in alpha-tocopherol (vitamin E), selenium, sulfur-containing amino acids, and chromium. These latter four nutrients have all been implicated in maintaining the antioxidant status of tissues, whereas PUFAs are pro-oxidants. Dietary supplementation with methionine and chromium significantly reduced the amount of fluorescent pigment accumulated in the RPE. Supplementation with all four nutrients further reduced the amount of fluorescent pigment to a very low level. Rats maintained on a normal laboratory diet, relatively low in PUFAs and presumably adequate in other nutrients, accumulated relatively small amounts of fluorescent pigment in the RPE. Of all tissues in the retina and choroid, the autofluorescent pigment was found to be almost entirely restricted to the RPE. The autofluorescence produced in the RPE by antioxidant deficiency was more concentrated than that produced in the testes, kidney, intestine, and heart. This suggests that the RPE is particularly sensitive to physiological antioxidant deficiencies. The increased fluorescent pigment build-up in the RPE of antioxidant-deficient rats appears to correlate with a decreased RPE melanin content. Similar changes in pigmentation have been reported to occur in human RPE with age and in dominantly inherited retinitis pigmentosa. Thus, with respect to its effect on RPE pigmentation, antioxidant deficiency appears to mimic aging and possibly some aspects of one type of retinitis pigmentosa.

Amino Acids, Sulfur↗
PubMed1977

Chromosomal effects of carcinogens and non-carcinogens on WI-38 after short term exposures with and without metabolic activation.

The human diploid fibroblast culture, WI-38 was analyzed for chromosomal damage after 24 h exposures to benzo(a)pyrene (BP), 3-methylcholanthrene (MCA), n-methyl-n'-nitrosoguanidine (MNNG), 4-nitroquinoline-1-oxide (4NQO), pyrene and caffeine. A low concentration of 4NQO (0.15 micron) and MNNG (1.9 micron) produced breakage and exchange figures. A relatively high concentration of caffeine (1300 micron) caused breakage. The other compounds (BP, MCA and pyrene) caused little or no increase in damage above the control levels. A 1-h pulse exposure of WI-38 cells to BP (40 micron) in the presence of a rat liver homogenate supernate (S-9) resulted in damage significantly greater than the untreated cells or cells treated with BP alone. 4NQO (0.25 micron) produced exchange figures after a similar 1-h exposure, but this effect was eliminated by the S-9. A much higher concentration of caffeine (10,300 micron) was required to cause breakage greater than control levels after a one hour exposure. The results indicate a possible short term in vitro human cell system for distinguishing carcinogens, procarcinogens, and noncarcinogens.

4-Nitroquinoline-1-oxide↗
PubMed1975

The effect of methylxanthines on chromosomes of human lyphocytes in culture.

The effect of caffeine (I,3,7-trimethylxanthine), theophylline (I,3-dimethylxanthine), theobromine (3,7-dimethylxanthine), paraxanthine (I,7-dimethylxanthine) I-methylxanthine, 3-methylxanthine, and 7-methylxanthine added at the 48th h on the chromosomes of human lymphocytes in 72-h cultures has been investigated. Caffeine and the dimethylxanthines cause breakage at 750 mug/ml, with caffeine the most, and paraxanthine the least clastogenic. I-Methylxanthine and dimethylxanthines with a methyl group in the I-position are the most effective in depressing mitotic indices. No chromosome damage was exhibited by the monomethylxanthines.

Caffeine↗