PubMed HealthSearch

Biomedical subjects

L R Miller

Publications and source records attributed to L R Miller.

At least 19 recordsLinked to original sources

An immunohistochemical study of perianal Paget's disease. Possible origins and clinical implications.

The histogenesis of perianal Paget's disease is controversial. A clinical and pathologic study was done of a patient with a history of adenocarcinoma of the rectum for whom a subsequent diagnosis of perianal Paget's disease was the sole manifestation of recurrent rectal cancer. Immunohistochemical techniques were used to compare and contrast the original rectal adenocarcinoma with the subsequent perianal skin recurrence confined to the epidermis. Both the rectal adenocarcinoma and the Paget's cells were positive for cytokeratin, epithelial membrane antigen, B72.3, and carcinoembryonic antigen and negative for gross cystic disease fluid protein-15, Leu-M1, CA 125, and S-100 protein. These findings, their relevance to the histogenesis of perianal Paget's disease, and the possible clinical implications are discussed.

Adenocarcinoma

Effect of desmopressin on vein graft patency in a microvascular model.

Desmopressin acetate decreases blood loss after cardiac surgery by activating platelets. We studied whether this effect was detrimental to small-caliber vein grafts in rats. Thirty minutes before femoral artery grafting with 0.75-mm-diameter reverse autogenous saphenous vein grafts, 20 rats received desmopressin acetate intravenously at 1.0 micrograms/kg over 10 minutes, and 20 control rats received normal saline intravenously over 10 minutes. In each group, 10 rats received a 6-mm-long graft and 10 an 18-mm-long graft. Graft patency was evaluated at 20 minutes, 24 hours, and 30 days. Intimal thickening was assessed by light and scanning electron microscopy. At 30 days, 9 short grafts and 8 long grafts in the desmopressin-treated group were patent, whereas only 8 short control grafts and only 6 long control grafts were patent. Intimal thickening and platelet deposition were the same in both groups. These data show no detrimental effects of desmopressin acetate on saphenous vein graft patency.

Animals

Improved lung preservation with cold air storage.

Conventional topical slush cooling limits lung transport to 4 to 6 hours. For this canine study of an alternate air cooling system, 37 canine lungs were removed: 24 were placed in plastic bags, and inserted in a Transplanthermm container at core air temperatures (n = 6 lungs each) of (A) 4 degrees C, (B) 8 degrees C, (C) 12 degrees C, and (D) 20 degrees C; 6 were stored conventionally in ice slush (E); and 7 were transplanted immediately (F). After 8 hours, the stored lungs were transplanted and the contralateral pulmonary artery was ligated. Survival, arterial oxygen tension, and extravascular lung water were monitored at 15 minutes and every hour for 4 hours. Four-hour survival was 100% in groups A, B, and F; 83% in group C, 50% in group D, and 17% in group E. The mean arterial oxygen tension at 1 hour was lower in group E (6.4 +/- 2.4 kPa) than in group A (39.8 +/- 13.2 kPa) (p = 0.0002) or in group F (42.0 +/- 16.2 kPa) (p = 0.0035). Extravascular lung water in group E was higher at 15 minutes (15.44 +/- 5.63 mL/kg) than in group A (3.76 +/- 0.63 mL/kg) (p = 0.0001) and group F (4.69 +/- 1.65 mL/kg) (p = 0.003). Cold air storage appears to provide better lung preservation than hypothermic immersion in ice slush.

Air

In vivo clearance of low density lipoprotein in pigeons occurs by a receptor-like mechanism that is not down-regulated by cholesterol feeding.

The contribution of receptor-dependent and receptor-independent mechanisms for low density lipoprotein (LDL) clearance in vivo was determined in White Carneau and Show Racer pigeons fed either cholesterol free or cholesterol containing diets. The methylation of pigeon LDL resulted in the inhibition of recognition by the LDL receptor which allowed its use as a tracer of receptor-independent clearance. The fractional catabolic rate (FCR) of radiolabeled LDL in 20 control pigeons (means +/- S.E., 0.277 +/- 0.013 pools/h) was approximately seven times faster than for methylated LDL indicating that 86% of the total LDL clearance occurred by a receptor-mediated process. Total LDL clearance was reduced by 27% (FCR = 0.202 +/- 0.012 pools/h) in 14 cholesterol-fed pigeons, but receptor-mediated mechanisms were still responsible for 80% of the total LDL clearance. LDL uptake by individual tissues was measured using the residualizing label 125I-tyramine cellobiose. The liver was the primary site of LDL clearance in both control and cholesterol-fed birds. LDL receptors were active in every tissue examined and accounted for over 85% of the LDL clearance in the liver and over 90% in the adrenal gland. Consistent with the whole body LDL clearance findings, cholesterol-feeding did not significantly reduce receptor-mediated clearance of 125I-tyramine cellobiose-LDL by the liver or any of the other tissues. Hepatic sterol synthesis, however, was reduced by greater than 90% in cholesterol-fed animals. These data are consistent with the conclusion that LDL clearance in vivo in pigeons is mediated primarily by an LDL receptor-like mechanism that shows little down-regulation with hypercholesterolemia even though cholesterol synthesis is efficiently down-regulated.

Adrenal Glands

Acquired renal cystic disease in end-stage renal disease: an autopsy study of 155 cases.

Autopsy reports on 155 successive end-stage renal disease (ESRD) patients and 147 control patients without ESRD, matched for age, race and gender, were collected. Cystic transformation of the kidneys was noted in 58% of the ESRD patients and 13.6% of the control patients. There were 25 ESRD patients with renal adenoma and 3 with renal cell carcinoma. The single best predictor of cystic transformation or tumorous degeneration was patient's age. A statistically significant association between cystic transformation and gender, as well as the cause of ESRD, was also found. In contrast to previous reports we were unable to document a strong association between the incidence of either cystic transformation or tumorous degeneration with the duration of dialysis, nor did these two parameters correlate with mode of dialysis. We suggest that cystic transformation of the kidneys in ESRD is related to age and renal failure per se, is not strongly associated with duration of dialysis and is independent of mode of dialysis. Concomitant tumorous degeneration was frequent, but this was usually an incidental autopsy finding. Renal malignancy was uncommon and metastases were absent.

Adenoma

Inhibitors of sterol synthesis. Effects of dietary 5 alpha-cholest-8(14)-en-3 beta-ol-15-one on early enzymes in hepatic cholesterol biosynthesis.

The effects of dietary administration (0.1% in diet for 8 days) of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one on the levels of activity of cytosolic acetoacetyl coenzyme A thiolase, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase, and microsomal HMG-CoA reductase in liver have been studied in male Sprague-Dawley rats. Significant increases in the levels of activity of acetoacetyl-CoA thiolase and of HMG-CoA synthase were observed. The levels of microsomal HMG-CoA reductase activity were increased, relative to pair-fed control animals, in three experiments and increased, relative to ad libitum control animals, in one of three experiments. When compared with other agents for which the primary mode of action is an inhibition of the intestinal absorption of cholesterol, the magnitude of the increases in the levels of hepatic microsomal HMG-CoA reductase activity in the 15-ketosterol-fed rats was considerably smaller. In view of the previously described marked activity of the 15-ketosterol in the inhibition of the intestinal absorption of cholesterol, as well as its known effects in lowering HMG-CoA reductase activity in mammalian cells in culture, it is proposed that the 15-ketosterol may suppress the elevated levels of hepatic microsomal HMG-CoA reductase activity induced by the reduced delivery of cholesterol to liver as a consequence of the inhibition of the intestinal absorption of cholesterol.

Acetyl-CoA C-Acetyltransferase

Inhibitors of sterol synthesis. Studies of the metabolism of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one in Chinese hamster ovary cells and its effects on activities of early enzymes in cholesterol biosynthesis.

The metabolism of [2,4-3H]5 alpha-cholest-8(14)-en-3 beta-ol-15-one (I) has been studied in Chinese hamster ovary (CHO-K1) cells which were maintained in a lipid-deficient medium. The incorporation of I into the cells was linear with respect to sterol concentration in the medium over the ranges of concentrations studied and was more than 3.5 times that of the uptake of cholesterol. The results of detailed chromatographic analyses of the lipids recovered from the cells after 6 h of incubation with [2,4-3H]I (0.5 microM or 6.0 microM) indicated that most of the 3H was associated with free I. Considerably lesser amounts of the 3H was associated with esters of I. No formation of [3H]cholesterol or [3H]cholesteryl esters (or other C27 monohydroxysterols) from labeled I was observed. The labeled material with the chromatographic behavior of the esters of I gave, after mild alkaline hydrolysis, the free 15-ketosterol which was characterized by the results of chromatographic and cocrystallization studies. Upon transfer of the CHO-K1 cells from a culture medium containing 8% newborn calf serum to the same medium containing 8% lipid-deficient newborn calf serum, increases in the levels of activity of cytosolic acetoacetyl-CoA thiolase and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase and of HMG-CoA reductase were observed. These increases were blocked by the addition of I at a concentration of 1.0 microM. I (1.0 microM) also caused a decrease in the levels of activity of the three enzymes in cells previously grown in medium containing lipid-deficient serum. These results demonstrate that I not only affects the enzymatic reduction of HMG-CoA but also the enzymatic formation of this key intermediate in cholesterol biosynthesis.

Acetyl-CoA C-Acetyltransferase

5 alpha-cholest-8(14)-en-3 beta-ol-15-one. A competitive substrate for acyl coenzyme A:cholesterol acyl transferase.

5 alpha-Cholest-8(14)-en-3 beta-ol-15-one, a potent inhibitor of cholesterol biosynthesis with hypocholesterolemic activity, has been found to serve as an efficient substrate for acyl CoA:cholesterol acyl transferase of rat hepatic and jejunal microsomes and to inhibit the esterification of cholesterol. Concentrations required to give 50% inhibition of cholesterol ester formation in liver and jejunal microsomes were approximately 10 microM and approximately 3 microM, respectively.

Animals

Evidence for the existence of a lateral cervical nucleus in mice, guinea pigs, and rabbits.

The lateral cervical nucleus of carnivores is large and is thought to play a prominent role in somatosensory processing. In contrast, early studies indicated that rats, mice, guinea pigs, and rabbits did not have a lateral cervical nucleus. However, we reported the existence of a lateral cervical nucleus in rats as a result of studies using retrograde transport techniques. In the present study, similar techniques were used to examine the possibility that early studies also overlooked the lateral cervical nucleus in mice, guinea pigs, and rabbits. In each of these species, a retrograde tracer was injected into the thalamus. These injections labeled a small number of neurons contralaterally in the dorsal part of the lateral funiculi of rostral cervical segments. Mice had the greatest number of neurons projecting from the lateral cervical nucleus to the thalamus, and rabbits had the fewest.

Animals

Lupus lung.

The morphologic findings from 18 autopsy lungs of systemic lupus erythematosus were studied. Each case revealed varying degrees of pleuropulmonary disease. A universal feature was visceral pleural thickening, while findings present in more than one half of the cases included pulmonary congestion (17/18) and edema (15/18), pleural adhesions (11/18) and pleural effusions (10/18) and intraalveolar hemorrhage (10/18). Also seen were bronchopneumonia (9/18), interstitial fibrosis (6/18), cytomegalovirus infection (3/18), interstitial pneumonitis (2/18), hyaline membranes (2/18), and acute vasculitis (1/18) and pleuritis (1/18). These results, together with those of previously reported studies of lupus lung, establish that although certain characteristic pleuropulmonary disease processes are frequently found at autopsy, none is a highly specific marker for the disease.

Adolescent

Lactic acidosis as a result of iron deficiency.

Iron-deficient rats have an impaired work performance, even when their anemia is corrected by exchange transfusion. Muscle activity is associated with a higher blood lactate concentration than is observed in iron-replete animals. The accumulation of lactate is a result of excessive production as lactate clearance from the blood was shown to be unaffected. By adjusting the work load to a lower level, it was possible to divide iron-deficient animals into two groups, one capable of continued treadmill running and another in which animals stopped before 20 min. In the former, blood lactate concentration reached a plateau at moderate levels, whereas it continued to increase in the latter until the animal stopped running. Levels of alpha-glycerophosphate oxidase in skeletal muscle mitochondria were found to be much lower in the second group (P < 0.001). Lactate infusion into normal animals was shown to interfere with work performance, and maintenance of a normal pH in iron-deficient and iron-replete animals did not prevent the impairment in work associated with high blood lactate concentrations. Additional evidence was obtained that energy substrate (blood glucose and free fatty acids, muscle glycogen) was adequate in irondeficient animals. Oxygen tension in their vena caval blood was higher than in controls. Furthermore, the in situ behavior of electrically stimulated gastroenemius and soleus muscles appeared similar to that of control animals. Because the stimulation of the single muscle in the iron-deficient animal did not result in appreciable elevation of blood lactate and did not show impaired contractility further supported the hypothesis that the elevation of blood lactate caused the decreased work performance. It is concluded that iron deficiency by a depletion in the iron-containing mitochondrial enzyme, alpha-glycerophosphate oxidase, impairs glycolysis, resulting in excess lactate formation, which at high levels leads to cessation of physical activity.

Acidosis

Iron deficiency in the rat: effects on phenylalanine metabolism.

Concentrations of phenylalanine in the plasma were markedly elevated in iron-deficient rats and appeared to vary directly with the degree of iron deficiency. Plasma concentrations of phenylalanine returned to control levels within one week after treatment of the iron-deficient rats with iron dextran. The elevated levels of plasma phenylalanine were probably not produced by a deficiency in liver phenylalanine hydroxylase because levels of activity of the enzyme were found to be normal in the livers of the iron-deficient animals.

Animals

Iron deficiency in the rat: biochemical studies of brain metabolism.

Studies were performed to determine the effects of iron deficiency on brain metabolism in rats. Concentrations of cytochrome pigments, oxidative phosphorylation, and catalase and monoamine oxidase activities in brain tissue were unaffected by iron deficiency. However, activities of aldehyde oxidase, a key enzyme in the pathway of serotonin degradation, were significantly reduced, and concentrations of serotonin and total 5-hydroxyindole compounds were elevated in brain tissue of iron-deficient animals. Aldehyde oxidase activities and concentrations of 5-hydroxyindole compounds in brain tissues returned to approximately normal values one week after treatment of iron deficient animals with iron dextran.

Aldehyde Oxidoreductases

A comparison of operant and sensory integrative methods on developmental parameters in profoundly retarded adults.

The expertise of speech pathologists and occupational therapists was combined to compare the relative effectiveness of an operant approach, a modified sensory integrative approach, and a combination of both methods in eliciting vocalization on other developmental skills on a sample of 27 profoundly retarded, minimally vocal, institutionalized adults. The combined results indicated that the therapy programs promoted significant gains in frequency of eye contact, frequency of vocalization, and quality of postural adaptation. There were no differences in the effects of the respective therapies. The fact that the more controversial sensory integrative procedures elicited comparable gains when compared with the more widely recognized operant method lends credence to the viability of sensory integrative methods.

Adult

Tissue culture propagation of tropical foliage plants.

Procedures were established for clonal multiplication in vitro of Cordyline terminalis Kunth, Dracaena godseffiana Hort., Scindapsus aureus Engler, and Syngonium podophyllum Schott. Shoot tips of actively growing terminals were selected as explants for Cordyline and Dracaena, and lateral buds were employed for Scindapsus and Syngonium. The basal nutrient medium contained Murashige and Skoog salts, 3% sucrose, 100 mg per 1 i-inositol, and 0.4 mg per 1 thiamine-HCl. The optima with respect to auxin, cytokinin, adenine sulfate-2H2O, and NaH2PO4-H2O addenda were determined. Also assessed were the influences of certain physical qualities of the nutrient medium and of the light intensity of the culture environment. The multiplication of each of the four plants was achieved by repeatedly subculturing the shoots that arose in vitro. Rates of plant increase per year per explant were calculated conservatively to be as follows: Syngonium, 5,000:Scindapsus, 100,000; Dracena, 300,000; and Cordyline, 500,000.

Adenine