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Biomedical subjects

J C Miller

Publications and source records attributed to J C Miller.

At least 19 recordsLinked to original sources
PubMed1991

Leiomyosarcoma arising in atypical fibromuscular hyperplasia (phyllodes tumor) of the prostate with distant metastasis.

An extremely rare neoplasm of the prostate, commonly known as phyllodes type of atypical prostatic hyperplasia, is described in a 57-year-old man. Over a 2-year period, the atypical smooth muscle component has transformed into leiomyosarcoma, and eventually metastasized to the bones and the lungs. Such an evolution has never been documented for this tumor.

Cell Transformation, Neoplastic↗
PubMed1991

Noradrenergic activation of immediate early genes in rat cerebral cortex.

Previous studies have shown that stimulation of adrenergic receptors in the brain increases the expression of the immediate early gene (IEG), c-fos, in vivo (Mol. Brain Res., 6(1989) 39-45). The present study was undertaken to determine whether this also holds for other IEGs which have been shown to be activated in brain cell culture by adrenergic agonists. Both yohimbine injection and stressful stimulation, two treatments causing brain norepinephrine (NE) release, were found to cause a parallel, transient activation of at least 5 IEGs (c-fos, nur77, tis-7, zif-268 and tis-21) in the rat cortex. Genes that are not immediate early (beta-actin, NGF and HSP70) were found not to be affected in the interval used (6 h). The responses were mediated predominantly by beta-adrenoceptors with some contribution from alpha 1 receptors. The parallel activation of multiple genes by noradrenergic receptors may enable the coding of different biochemical responses to the activation of different receptors.

Animals↗
PubMed1991

Receptor reserve for D2 dopaminergic inhibition of prolactin release in vivo and in vitro.

The full dopamine agonist R-(-)-N-n-propylnorapomorphine (NPA) completely suppressed (ED50 0.12 micrograms/kg) serum prolactin (PRL) levels elevated by pretreatment with gamma-butyrolactone (750 mg/kg). Pretreatment with the receptor-inactivating agent N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (1 and 2 x 6 mg/kg) progressively shifted the dose-response curve for NPA to the right, but PRL secretion was still maximally inhibited. Receptor inactivation elicited smaller (2-fold) dextral shifts in the ED50 for the partial agonists (+)- and (-)-3-(3-hydroxyphenyl)-N-n-propylpiperidine. These results are consistent with the presence of a sizable receptor reserve at the D2 receptor regulating PRL release in the anterior pituitary. Analogous results were obtained in vitro utilizing primary cultures of anterior pituitary cells. NPA potently inhibited basal PRL release in culture (ED50 0.06 nM, maximal inhibition 83%). Receptor alkylation with phenoxybenzamine (1 microM, 1 hr) did not affect basal PRL release but right-shifted the ED50 for NPA more than 6-fold and attenuated maximal inhibition (to 68%); both effects were significant (P less than .01). The extracellular accumulation of cyclic AMP (cAMP) stimulated by a combination of forskolin (1 microM) and 3-isobutyl-1-methyl xanthine (100 microM) required higher concentrations of NPA (ED50 0.36 nM), and the maximal effect was much smaller (46%). Phenoxybenzamine treatment did not alter either basal or forskolin-stimulated cAMP accumulation, but it reduced the maximal inhibitory response to NPA (to 13%) without shifting the ED50. Plots of receptor occupancy vs. response demonstrated a 60% receptor reserve for NPA inhibition of PRL release, but none for inhibition of cAMP production.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1990

Identification by sequence analysis of a second rat brain cDNA encoding the dopamine (D2) receptor.

A rat brain cDNA library constructed in lambda ZAP II was screened with three oligonucleotide probes based on the reported coding region of the D2 receptor gene, RGB-2. A complete cDNA clone, D2(8)-1, showing positive signals with the three probes was subsequently identified by restriction analysis and dideoxy sequence analysis to be a variant of the RGB-2 gene. Comparison of the two genes revealed almost complete homology except that D2(8)-1 contains an 87 bp insert within the protein coding region and 265 additional nucleotides 5' upstream from the 5' end reported for RGB-2. It is suggested that at least two mRNA species encoding for D2 receptors exist in rat brain, possibly resulting from alternative splicing of RNA.

Amino Acid Sequence↗
PubMed1990

Effects of prolonged mental work on functional brain topography.

Topographic patterns of event-related covariance between electrodes were measured from subjects performing a difficult memory and fine-motor control task for 10-14 h. Striking changes occurred in the patterns after subjects performed the task for an average of 7-9 h, but before performance deteriorated. Pattern strength was reduced in a fraction-of-a-second-long response preparation interval over midline precentral areas and over the entire left hemisphere. By contrast, pattern strength in a succeeding response inhibition interval was reduced over all areas. The pattern changed least in an intervening interval associated with visual-stimulus processing. This suggests that, in addition to the well-known global reduction in neuroelectric signal strength, functional neural networks are selectively affected by sustained mental work in specific fraction-of-a-second task intervals.

Analysis of Variance↗
PubMed1990

A simple method for estimating average number of nucleotide substitutions within and between populations from restriction data.

A simple method is proposed for estimating the average number of nucleotide substitutions per site within and between populations for the case where a large number of individuals are examined for many restriction enzymes. This method gives essentially the same results as those obtained by Nei and Li's method but saves a large amount of computer time. The variances of the quantities estimated can be obtained by the jackknife method, and these variances are very similar to those obtained by Nei and Jin's more sophisticated method. A similar method can also be applied to DNA sequence data.

Analysis of Variance↗
PubMed1990

Induction of c-fos mRNA expression in rat striatum by neuroleptic drugs.

The effect of selective dopamine D2 receptor-acting drugs on striatal c-fos mRNA expression in the rat has been investigated by Northern hybridization and autoradiography to determine a possible role for c-fos in the initiation of adaptive changes in D2 receptor number by neuroleptic drugs. The neuroleptic drug haloperidol, a D2 receptor antagonist, was found to produce a rapid and transient induction of c-fos mRNA expression as compared with the expression in animals treated with saline. This induction by haloperidol was found to be dose dependent and D2 receptor mediated, inasmuch as a D2 agonist completely reversed the induction and the inactive isomer of the neuroleptic butaclamol, which does not produce an increase in D2 receptors, had no effect on c-fos mRNA expression. From these data, it can be concluded that c-fos expression in striatum is under dopamine D2 receptor-mediated inhibitory control. It is suggested that c-fos may play a role in the initiation of the increase in D2 receptor number produced by chronic neuroleptic drug treatment.

Animals↗
PubMed1990

Effects of pyridostigmine bromide on in-flight aircrew performance.

The effects of a chemical defense pretreatment drug, pyridostigmine bromide (PB), on in-flight aircrew performance were assessed using the Total In-Flight Simulator (TIFS) aircraft. TIFS was used to supply appropriate control dynamics, handling characteristics, and cockpit instrumentation for a tactical transport airdrop simulation. Twenty-one C-130 pilots flew two familiarization and four data flights. During two data flights PB was given to both members of the aircrew using the dosage regimen of 30 mg/8 h prescribed by the U.S. Air Force surgeon general. The drug was administered using a double-blind technique. The results indicated that (1) aircrews successfully completed their assigned mission, (2) airdrop inaccuracies and navigation errors in time and distance were not specifically related to PB, (3) performance and crew coordination were not affected by PB, (4) PB and pilot/copilot not discriminate beyond chance between PB and placebo conditions.

Adult↗
PubMed1990

Effects of rapeseed silage variety and dietary level on digestion and growth performance of beef steers.

A digestion and ruminal fermentation trial involving five ruminally cannulated steers assigned to a 5 x 5 Latin square with a 2 x 2 + 1 arrangement of dietary treatments was conducted to evaluate the effects of variety of rapeseed silage (RS) containing either a high (HG) or a low (LG) glucosinolate concentration when fed at 100 or 50% of diet DM. A bromegrass hay-corn-soybean meal mixture, which was expected to be isocaloric and isonitrogenous with the RS, was used as the control (C) treatment and replaced RS in the 50% diets. In situ disappearance of substrate from both RS varieties was measured in ruminal environments created by each diet. No dietary treatment x RS substrate interactions were observed for any in situ variable. Total tract digestibility and extent of in situ disappearance of both DM and NDF were greater (P less than .01) for HG than for LG. In situ DM and NDF disappearance at 8, 16 and 24 h was greater (P less than .01) for RS than for the C diet. Similarly, total tract DM digestibility was greater (P less than .01) for RS (61.0%) vs C (56.0%) diets. Diets with 50% RS had greater (P less than .01) NDF digestibility (50.4%) than 100% RS (43.6%) diets. Variety of RS had no effect on particulate passage rate. In a 77-d growth trial with 60 beef steers, ADG was greater (P less than .01) for HG vs LG (.46 vs .36 kg), 50 vs 100% (.52 vs .31) and C vs RS (.64 vs .41) diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Efficacy of vaginal spaying and anabolic implants on growth and carcass characteristics in beef heifers.

Ninety crossbred beef heifers averaging 260 kg were blocked by weight and allotted randomly to 15 pens of six heifers each, with three replicates per treatment. The treatments were spayed heifers (S); intact heifers (I); S + Synovex-H7 (SH); I + Synovex-H (IH); and S + Synovex-S7 (SS). The heifers were spayed vaginally with a Willis instrument; intact heifers were rectally palpated for reproductive soundness. Heifers were fed a growing diet (55 d), re-implanted and subsequently fed a finishing ration (73 or 101 d). All heifers were observed for estrus daily at approximately 0600 and 2000 until d 69. A jugular vein blood sample was obtained from each heifer on d 48, 55, 62 and 69 for blood progesterone analysis. Results of blood progesterone analysis and reproductive tract examination indicated that two spayed heifers were incompletely spayed, a 96% success rate. The SH and SS heifers continued to exhibit estrous behavior despite being successfully spayed. Heifers implanted with Synovex-H had greater (P less than .01) ADG and were more efficient (P less than .03) than nonimplanted heifers. The SS heifers had greater ADG (P less than .05) during the finishing phase than SH heifers, but no advantage of SS over SH was apparent during the growing phase. The overall ADG response to implantation was fourfold greater (P less than .07) in the spayed heifers than in the intact heifers (32 vs 8%). Heifers implanted with Synovex-H had greater adjusted hot carcass weight (P less than .02) and ribeye area (P less than .002) than nonimplanted heifers. For adjusted live weight and ribeye area, the response to implantation was approximately threefold greater in the spayed heifer than the intact heifer. These results demonstrate that spaying and implanting heifers can increase rates and efficiency of gain even though behavioral estrus is not eliminated.

Animals↗
PubMed1990

Phase II study of daily oral etoposide in refractory germ cell tumors.

Etoposide was found to be schedule-dependent in both preclinical and clinical trials. A study was initiated in March 1988 at Indiana University (Indianapolis, IN), using daily oral etoposide in patients with refractory germ cell tumors. The dose was 50 mg/m2/d, administered daily until progression or toxicity not ameliorated by dose adjustment occurred. Twenty-two patients have been entered to date. Primary sites were testis (11 patients), retroperitoneum (five patients), and mediastinum (six patients). All 22 patients had had previous treatment with cisplatin/etoposide combination regimens, including six patients who were also previously treated with high-dose etoposide and carboplatin with autologous bone marrow transplantation. The median number of treatment regimens was 2.9 (range, 1 to 4). Five patients had progressive disease during treatment with etoposide. Median length of treatment was 11.5 weeks (range, 2 to 30), with six patients continuing on treatment. Median white blood cell nadir was 1.5 x 10(9)/L, median hemoglobin nadir 9.1 g/dL, and the median platelet nadir 184,000/microL. Granulocytopenia required temporary cessation of treatment in eight patients and dose reductions in four. Five patients developed granulocytopenic fevers, including pneumonia (two patients) and bacteremia (one patient). Additionally, two patients (who tested negative for human immunodeficiency virus) died from Pneumocystis pneumonia with granulocyte counts higher than 500/microL. Of 21 evaluable patients (there was one protocol violation), three responded with a greater than 90% decrease in markers and a greater than 50% decrease in measurable radiographic disease. One of these had previously progressed on cisplatin/etoposide combination therapy. Three other patients responded with a greater than 90% decrease in markers but with stable radiographic disease; two of them had previously resected teratoma. The remaining ten patients were nonresponders. In conclusion, daily oral etoposide has definite activity in refractory germ cell tumors. Further evaluation of this regimen is warranted.

Administration, Oral↗
PubMed1990

Effects of calcium loading and impaired energy production on metabolic and ultrastructural features of cell injury in cultured neonatal rat cardiac myocytes.

We evaluated the contributions of calcium loading and impaired energy production to metabolic and ultrastructural manifestations of cell injury in a cultured neonatal rat ventriculocyte model. Direct calcium loading was produced by incubation in K(+)-free medium to inhibit the Na+,K(+)-ATPase and promote Na(+)-Ca2+ exchange, and inhibition of energy metabolism was produced by incubation with 30 microM iodoacetic acid (IAA). Measurements were made of total cell calcium, [3H] arachidonic acid (AA) release (an index of membrane phospholipid degradation), ATP, and ultrastructural features of cell damage. Inhibition of the Na(+),K(+) pump resulted in the rapid onset of cellular calcium loading, increased [3H]AA release, and moderate ATP reduction. After return to control medium for 24 hours, myocytes previously exposed to K(+)-free medium for 1 hour showed recovery of ATP level and little additional [3H]AA release. However, after 2 to 3 hours of calcium loading, the ATP level remained moderately depressed, residual [3H]AA release was greater, and a mixed population of relatively normal and severely damaged myocytes was observed by electron microscopy. IAA treatment for 1 hour resulted in moderate ATP reduction without calcium accumulation or [3H]AA release, whereas IAA treatment for 3 hours resulted in marked ATP reduction associated with calcium accumulation and [3H]AA release. Reversal experiments showed substantial recovery of ATP level after 1 hour of IAA exposure, and marked ATP depression and [3H]AA release associated with widespread irreversible injury after 3 hours. Thus, the data indicate that increased calcium accumulation itself can initiate accelerated membrane phospholipid degradation, but that progression to irreversible injury is influenced by other factors, including the magnitude of ATP depression associated with calcium loading.

Adenosine Triphosphate↗
PubMed1989

Exogenous prostaglandin protects against acid-induced deep mucosal injury by stimulating alkaline secretion in rat duodenum.

In the anesthetized rat, exogenous acid (0.1-0.3 N HCl) perfused through the duodenum produced a dose-related increase in the severity of duodenal villous injury. Increasing the duration of perfusion of the 0.1 N HCl also increased the severity of the injury. The increase in the severity of the lesion score was due to an increase in the percentage of villi with damage extending to the lower half of the villus. 16,16-Dimethyl prostaglandin E2 (dm PGE2, 5 micrograms/kg) administered subcutaneously significantly increased duodenal mucosal alkaline secretion and significantly reduced the duodenal villous injury produced by 0.1 N HCl. The reduction in the severity of the lesion score was due to a decrease in the percentage of villi with the deeper type of damage. These data indicate: (1) perfusion of the rat duodenum with 0.1 N HCl at 0.1 ml/min for 30 min provides a valid model for assessing deep duodenal villous injury, (2) exogenous prostaglandin enhances the resistance of the duodenal mucosa against acid induced deep villous injury, and (3) the enhanced resistance may be mediated at least in part by stimulation of duodenal alkaline secretion. The results support the hypothesis that stimulated duodenal alkaline secretion may play a role in defense of the duodenal mucosa against acid-induced deep villous injury.

Animals↗
PubMed1989

Association between inhibition of arachidonic acid release and prevention of calcium loading during ATP depletion in cultured rat cardiac myocytes.

The development of irreversible myocardial ischemic injury is associated with progressive degradation of membrane phospholipids, accumulation of arachidonate and other free fatty acids, and electrolyte derangements, including calcium accumulation. To study the relationship between arachidonate release and calcium loading during adenosine triphosphate (ATP) depletion in cardiac myocytes, the effects of two purported phospholipase inhibitors, mepacrine and U26,384, were evaluated. Cultured neonatal rat ventricular myocytes were pretreated for 90 minutes with 5 to 10 microM U26,384 (a steroidal diamine) or 10 to 50 microM mepacrine (an alkyl acridine) and then treated for 3 hours with 30 microM of the metabolic inhibitor, iodoacetic acid (IAA), with or without an additional dose of drug. IAA treatment resulted in a marked reduction in ATP level and a several-fold increase in free fatty acid radioactivity released from myocytes prelabeled with tritiated arachidonic acid (3H-AA). U26,384 produced substantial inhibition of the increased 3H-AA release, and was effective when given as a single pretreatment dose before IAA exposure or as continuous treatment before and during IAA exposure (for example, with 5 microM U26,384, the percentage of 3H-AA release versus IAA alone was 8% +/- 2% [SEM] [N = 15] for pretreatment only and 13% +/- 4% [N = 10] for continuous treatment). Mepacrine also resulted in significant reduction in 3H-AA release, but was more effective when given as continuous treatment (for example, with 50 microM mepacrine, the percentage of 3H-AA release versus IAA alone was 43% +/- 9% [N = 6] for pretreatment only and 22% +/- 7% [N = 9] for continuous treatment). More detailed analysis showed that U26,384 and mepacrine blocked the IAA-induced redistribution of 3H-AA into free fatty acids from other lipid species. Electron probe x-ray microanalysis of freeze-dried cryosections revealed marked electrolyte derangements in myocytes exposed to IAA, including a 24-fold increase in cellular Ca, a four fold increase in cellular Na, and a seven fold decrease in cellular K, and associated changes in cytoplasm and mitochondria. U26,384 treatment markedly reduced these electrolyte abnormalities, and maintained normal Ca levels in some protocols. Mepacrine treatment was less effective, but did produce normal Ca levels in 50% of myocytes. Prevention of IAA-induced cellular hypercontraction and blebbing also was observed. These data support the hypothesis that reduction of free fatty acid accumulation by inhibition of accelerated phospholipid degradation is associated with protection of myocytes from calcium loading and morphologic damage during inhibition of ene

Adenosine Triphosphate↗
PubMed1988

Ethanolaminephosphotransferase in rat lung: selectivity for endogenous and exogenous diacylglycerol.

Ethanolaminephosphotransferase (EC 2.7.8.1) activity was determined in lung microsomes using diacylglycerols generated endogenously from [14C]glycerol 3-phosphate and different mixtures of fatty acids. Ethanolaminephosphotransferase used endogenously generated dipalmitoylglycerol better than dioleoylglycerol. The apparent Km and the reaction rates for four different endogenously generated mixtures were the same (16 nmol/mg microsomal proteins). The apparent Km values for CDP-ethanolamine were the same (0.26 mm) for endogenously generated dipalmitoylglycerol and dioleoylglycerol. The amount of diacylglycerol generated in microsomes was 2-3-times the apparent Km for diacylglycerol. Dipalmitoylglycerol, supplied exogenously as a Tween 20/phosphatidylglycerol emulsion, was nearly twice as active as dioleoylglycerol. Both dipalmitoylglycerol and dioleoylglycerol were more active as substrates when emulsions were made with phosphatidylglycerol/Tween 20 than with Tween 20 alone. The results suggest that ethanolaminephosphotransferase in lung is relatively nonselective for molecular species of diacylglycerol. In addition, the results suggest that the concentration of diacylglycerol and the physical state in which it is presented to the enzyme can affect the apparent selectivity of ethanolaminephosphotransferase for diacylglycerols.

Animals↗