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Biomedical subjects

J Mullen

Publications and source records attributed to J Mullen.

17 recordsLinked to original sources
PubMed1995

Lipoxygenase inhibitors block PDGF-induced mitogenesis: a MAPK-independent mechanism that blocks fos and egr.

Hepatic Ito cells proliferate during liver injury and fibrogenesis. Platelet-derived growth factor (PDGF)-induced [3H]thymidine incorporation was studied as Ito cells express the PDGF receptor after injury and activation. Pretreatment with either the nonspecific lipoxygenase inhibitor (nordihydroguaiaretic acid) or specific inhibitors of 5-lipoxygenase (SC-41661 and ICI-230487) inhibited PDGF-induced mitogenesis. Ito cells predominantly produce the leukotriene (LT) C4 >> LTB4. The PDGF-induced signal transduction cascade was studied to determine the potential mechanism of action of the lipoxygenase inhibitors. It was found that PDGF receptor abundance and receptor activation were not altered by lipoxygenase inhibition, suggesting that a postreceptor mechanism was involved. The two-key cytoplasmic serine-threonine kinases Raf and MAPK (mitogen-activated protein kinase), which are induced by PDGF and transmit the signal to the nucleus, were also not altered. Because Raf and MAPK can independently induce nuclear signaling, this suggests that the mechanism of action lies parallel or distal to these secondary messengers. Lipoxygenase inhibition did result in the suppression of PDGF-induced fos and egr expression. Collectively, this work suggests that lipoxygenase inhibition leads to the suppression of mitogenesis in part by disrupting the nuclear signaling that is required for protooncogene transcription at a step distal or parallel to MAPK activation.

Animals↗
PubMed1995

An investigation of the role of Fusarium moniliforme in duodenitis/proximal jejunitis of horses.

Duodenitis/proximal jejunitis syndrome (DPJ) is a small intestinal disease of horses that is associated with depression and copious gastric reflux. Since an infectious cause for DPJ remains unsubstantiated, these studies were designed to investigate the possible role of Fusarium moniliforme toxins in this disease. Fusarium moniliforme was isolated by culturing 2 samples of feed that had been fed to horses with clinical signs of DPJ. These isolates (AU 2/3) were subsequently grown concurrently on autoclaved corn and their toxicity evaluated in a feeding trial utilizing horses. Isolates of F moniliforme known to be low and high producers (RRC 415 and MRC 826, respectively) of fumonisin B1 (FB1) were cultured individually on corn and each fed separately to other groups of horses. Control horses were fed autoclaved corn that was not inoculated with fungus. Production of FB1 by isolates RRC 415, MRC 826 and AU 2/3 were 19, 4360 and 1455 ppm, respectively. Each group contained 2 horses and the test diets were prepared by diluting culture material with sweet feed and clean corn. The test diets consisted of control corn that contained < 1 ppm FB1, RRC 415 diluted to < 1 ppm FB1, MRC 826 diluted to 200 ppm FB1, and AU 2/3 culture material diluted to contain 65 ppm FB1 on days 1-10 and 130 ppm on days 11-27. Horses fed either MRC 826 or AU 2/3 had elevated serum gamma-glutamyltransferase after 7 to 21 d exposure and elevated serum L-iditol dehydrogenase activity after 7 to 19 d exposure to test diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗
PubMed1994

Medical considerations and practice guidelines for the neonatal occupational therapist.

Provision of safe and effective occupational therapy in neonatal intensive care units requires an understanding of neonatal medical conditions and treatment modalities. This article explains basic medical concepts and technology with terminology frequently encountered in neonatal intensive care. Discussions of neonatal thermoregulation, respiratory care, hemodynamic monitoring, and metabolic support are presented as general areas of focus. Equipment usage and precautions are included. Several case studies illustrate the incorporation of medical knowledge into neonatal occupational therapy practice.

Abnormalities, Multiple↗
PubMed1985

The ilvB locus of Escherichia coli K-12 is an operon encoding both subunits of acetohydroxyacid synthase I.

The ilvB locus of Escherichia coli K-12 encloses two open reading frames defining polypeptides of 60,000 and 11,200 molecular weight. The entire locus, about 2.3 kb, is co-transcribed as an operon. The molecular weights and amino acid compositions of the presumptive operon polypeptides agree with those of the large and small subunit polypeptides of acetohydroxyacid synthase (AHAS) I, for which ilvB is the structural locus. We reserve the designation ilvB for the promoter proximal (longer) cistron and designate the promoter distal cistron ilvN. The molecular weight and amino acid sequence of the ilvB polypeptide are strikingly similar to those of the I1vI (larger subunit of AHAS III) and I1vG (larger subunit of AHAS II) polypeptides. There is less size uniformity among the I1vN, I1vH (smaller subunit of AHAS III), and I1vM (smaller subunit of AHAS II) polypeptides. Nevertheless, there is significant amino acid sequence homology among the three small subunit polypeptides. Thus, all three AHAS isozymes of E. coli K-12 probably have a common evolutionary origin.

Acetolactate Synthase↗
PubMed1985

The effects of glucose and amino acids on tumor and host DNA synthesis.

Tumor-bearing animals provided with intravenous glucose and amino acids (TPN) exhibit enhanced response to S-phase-specific chemotherapeutic agents (H. M. Reynolds, J. M. Daly, B. Rowlands, S. J. Dudrick, and E. M. Copeland. Cancer 45: 3069, 1980; M. H. Torosian, J. L. Mullen, E. E. Miller, et al. J. Parenter. Enteral Nutr. 7: 337, 1983). To determine the mechanism of this response, DNA synthesis rate during starvation or a 48-hr infusion of glucose/amino acids (Glu/AA) was evaluated in tumor, liver, and terminal ileal cells of 68 rats. Tumor cells exhibited a rapid increase in DNA synthesis following the initiation of an infusion of Glu/AA. This increase was most marked after 2 hr of infusion and returned to control levels within 24 hr. Liver DNA synthesis rate increased in both starved and Glu/AA animals over 48 hr with a larger increase in animals receiving Glu/AA. Ileal DNA synthesis decreased equally in both groups. Short pulse Glu/AA produced transient increases in tumor DNA synthesis. Changes in host tissues occurred but followed a different temporal sequence. This may indicate the existence of a period of time following initiation of metabolic manipulation when tumor susceptibility to phase-specific chemotherapeutic agents will be enhanced while host tissues will be spared from increased toxicity.

Adenocarcinoma↗
PubMed1985

Effects of reduced left ventricular mass on chamber architecture, load, and function: a study of anorexia nervosa.

We investigated the effects of reduction in left ventricular mass on cavity geometry, afterload, pump function, and exercise performance in 17 patients with anorexia nervosa and in 10 age-and sex-matched normal subjects. Left ventricular mass index determined by two-dimensional echo-cardiography was significantly lower than that in normal subjects (53 +/- 15 vs 79 +/- 18 g/m2; p less than .005). Left ventricular end-diastolic and end-systolic volume indexes were also reduced in patients with anorexia nervosa compared with normal subjects (49 +/- 11 vs 65 +/- 17 ml/m2, p less than .005; 14 +/- 5 vs 19 +/- 4 ml/m2, p less than .025). In spite of the reductions in left ventricular mass and volume indexes, left ventricular chamber architecture described as h/R ratio, mass to volume ratio, and short/long left ventricular axis ratio were normal. Left ventricular afterload assessed as end-systolic meridional and circumferential wall stress was normal (59 +/- 18 vs 79 +/- 19 dyne/cm2 X 10(3) and 170 +/- 26 vs 167 +/- 23 dyne/cm2 X 10(3)). Ejection fraction, percent fractional shortening, and the relationship between end-systolic wall stress and ejection fraction were all within normal limits. In seven patients restudied after a 15% to 20% weight gain, left ventricular mass and volume indexes increased significantly but end-systolic wall stress and ejection fraction did not change. Ten patients with anorexia nervosa and resting heart rates and systolic blood pressures significantly lower than control values underwent treadmill testing. Exercise duration, peak heart rate, peak systolic blood pressure, and peak oxygen consumption in these patients were all significantly lower than normal. The hypotensive effect of fasting resulted in an initial decrease in afterload, which was the stimulus for reduction in left ventricular mass. The left ventricular remodeling associated with the mass reduction occurred in such a way that (1) orthogonal, meridional, and circumferential wall stresses were normalized, (2) normal chamber shape and architecture were maintained, and (3) chamber function and stress-shortening relationships were preserved. Thus down-regulation of left ventricular mass per se, like up-regulation of left ventricular mass, is not associated with abnormal left ventricular function.

Adolescent↗