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Biomedical subjects

L R Miller

Publications and source records attributed to L R Miller.

At least 19 recordsLinked to original sources
PubMed1998

RoBo-1, a novel member of the urokinase plasminogen activator receptor/CD59/Ly-6/snake toxin family selectively expressed in rat bone and growth plate cartilage.

Using differential display polymerase chain reaction, we cloned a novel cDNA named RoBo-1 from rat tibia. RoBo-1 is abundantly expressed in bone, including the hypertrophic chondrocytes of the growth plate where cartilage is remodeled into bone. RoBo-1 mRNA expression increased in response to two modulators of bone metabolism, estradiol and intermittent mechanical loading, suggesting a role in bone homeostasis. The 1.6-kilobase cDNA encodes a 240-amino acid protein with a cysteine spacing pattern, suggesting that RoBo-1 is a novel member of the urokinase plasminogen activator receptor/CD59/Ly-6/snake toxin family. Furthermore, the C-terminal contains a glycosyl-phosphatidylinositol attachment site, suggesting that it is a cell surface protein similar to other mammalian members of this family. The strongest homology of RoBo-1 is to the snake serum-derived phospholipase A2 inhibitors, which uniquely contain two of the cysteine domains but are secreted proteins. Interestingly, RoBo-1 is likely the first membrane-anchored member of this family containing two cysteine domains. Thus, the tissue specificity, responsiveness to bone protective mediators, along with its relationship to the multifunctional urokinase plasminogen activator receptor/CD59/Ly-6/snake toxin family suggests that RoBo-1 may play a novel role in the growth or remodeling of bone.

Amino Acid Sequence↗
PubMed1998

Influence of radical prostatectomy on serum hormone levels.

PURPOSE: The influence of radical prostatectomy on the hypothalamic pituitary axis has not been well studied. It is also unclear how alterations in serum androgen levels that result from surgical removal of the prostate might influence the recovery of libido and sexual function following radical prostatectomy. We determined the influence of radical prostatectomy on the hypothalamic pituitary testicular axis of 63 men with clinically localized prostate cancer treated only with radical prostatectomy. MATERIALS AND METHODS: A total of 63 healthy men 43 to 67 years old were enrolled in this prospective study. Phlebotomy was performed immediately before and 1 year following radical retropubic prostatectomy. Sera were stored frozen and analyzed as a group at the end of the study. We measured serum testosterone, percent free testosterone, dihydrotestosterone (DHT), estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone binding globulin and prolactin. RESULTS: Following radical prostatectomy there was a statistically significant increase in serum testosterone, free testosterone, estradiol, LH and FSH (p <0.0001), and statistically significant decrease in serum DHT (p <0.0001). No difference was noted in serum sex hormone binding globulin or prolactin levels. There was no statistically significant correlation between any serum hormone and sample storage time, patient age or prostate volume that could limit potential bias in study design. Serum hormone changes did not correlate with pathological stage or histological grade for this group of patients. CONCLUSIONS: Radical prostatectomy influences the hypothalamic pituitary axis by increasing serum testosterone, percent free testosterone, estradiol, LH and FSH while decreasing serum DHT levels. These findings suggest that the sexual dysfunction associated with radical prostatectomy cannot be explained by androgen deficiency alone. These data further suggest that the normal prostate and/or prostate neoplasm could secrete a substance or substances that give negative feedback control to pituitary gonadotropin secretion. Further investigation is warranted to identify this substance or substances.

Adult↗
PubMed1995

Cyclic AMP signaling pathways are important in IL-1 beta transcriptional regulation.

An intact cAMP response element (CRE) in the upstream regulatory sequence of IL-1 beta (-2755/-2762) has been shown to be essential for maintaining full IL-1 beta inducibility following treatment with LPS, PMA, or TNF-alpha. In the present study, using the recombinant plasmid pIL-1(4.0 kb)-chloramphenicol acetyltransferase, containing 4.0 kb of the IL-1 beta upstream regulatory sequence, we have demonstrated that dibutyryl cAMP treatment alone is capable of induction. Due to the critical nature of the CRE for the induction of IL-1 beta transcription, an effort was made to determine the importance of the cAMP signaling pathway(s) by determining whether CRE binding protein (CREB) and other CREB/activating transcription factor (ATF) family members that responded to cAMP were associated with the DNA-protein complex that forms at this site. Nuclear extracts prepared from LPS-treated THP-1 5A cells were fractionated by ammonium sulfate precipitation and heparin-Sepharose chromatography, and the resulting fractions were characterized in electrophoretic gel mobility shift assays. These purification steps resulted in an approximately 100-fold enrichment of the proteins binding to the CRE site. Western blot analysis of isolated fractions, using CREB- and ATF-1-specific Ab showed an increased level of these proteins in the enriched fractions. Tryptic digest and DNase I protection studies showed the presence of CREB protein in the complex at the CRE site. Supershift electrophoretic gel mobility shift assays and immunoprecipitation analysis provided further evidence that both CREB and ATF-1 are present in the complex. In addition, an increase in CREB phosphorylation was observed when THP-1 5A cells were treated with dibutyryl cAMP, LPS, or both. These studies confirm the importance of a cAMP signaling pathway(s) in the regulation of IL-1 beta at the transcriptional level.

Base Sequence↗
PubMed1994

Evaluation of immunoperoxidase techniques to detect Rickettsia rickettsii in fixed tissue sections.

Standard immunoperoxidase techniques were evaluated in the diagnosis of Rocky Mountain spotted fever (RMSF). Formalin-fixed, paraffin-embedded tissue was tested to detect Rickettsia rickettsii using the same antibody provided by the Centers for Disease Control and Prevention that is used for direct immunofluorescence (DIF). Tissues from 23 patients with suspected RMSF were divided: some were snap-frozen for DIF; the remainder were fixed in formalin, processed routinely, and embedded in paraffin for immunoperoxidase and hematoxylin and eosin staining. Ten patients were ultimately determined to have RMSF; in nine of these patients, both DIF and immunoperoxidase staining were positive for R rickettsii. There were no discrepancies, positive or negative, between the two methods. In the one case with a false-negative result by both methods, the patient had received antirickettsial antibiotics 72 hours before the biopsy was performed. These data demonstrate that the immunoperoxidase technique is effective in diagnosing RMSF and may be applied to cases retrospectively.

Adolescent↗
PubMed1994

MR imaging of breast implants.

Magnetic resonance (MR) images of 57 implants in 32 women were reviewed for possible complications. Spin-echo T2-weighted MR imaging of one or both breasts was performed with dedicated breast coils in axial, coronal, and sagittal planes. At surgery in 19 patients, MR evaluation for rupture correlated in 17 cases (two false-negative ruptures). Implant ruptures were seen at surgery in 15 of the 19 patients. Nine ruptures involved single-lumen implants: Six were ruptured within the fibrous capsule that normally forms around the foreign implant (intracapsular rupture [two were seen only at surgery]), and three were ruptured beyond this fibrous capsule into the soft tissues (extracapsular rupture). Five ruptures involved double-lumen implants, in which only the outer lumen had ruptured, and one involved a single-lumen saline implant that had completely collapsed. Additional complications of capsule formation and infection were suggested in two implants, and infection was suggested in one. The MR imaging appearances of the various types of implants as well as their complications are presented.

Adolescent↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1987

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↗