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Biomedical subjects

M A Nelson

Publications and source records attributed to M A Nelson.

At least 73 records · Page 4Linked to original sources
PubMed1988

Induction of strand breaks in DNA by trichloroethylene and metabolites in rat and mouse liver in vivo.

The ability of trichloroethylene (TCE) and selected metabolites to induce single-strand breaks in hepatic DNA of male B6C3F1 mice and Sprague-Dawley rats in vivo was evaluated using an alkaline unwinding assay. Doses of TCE of 22-30 mmol/kg were required to produce strand breaks in DNA in rats, whereas a dose of 11.4 mmol/kg was sufficient to increase the rate of alkaline unwinding in mice. To assess the importance of TCE metabolism to this response, rats were subjected to pretreatments of ethanol, phenobarbital, TCE, or the appropriate vehicle for 4 days prior to challenge doses of TCE. Phenobarbital and TCE, but not ethanol pretreatments, reduced the dose of TCE required to produce significant increases in single-strand breaks. In another series of experiments, mice and rats were treated with metabolites of TCE. Trichloroacetate, dichloroacetate, and chloral hydrate induced strand breaks in hepatic DNA in a dose-dependent manner in both species. Strand breaks in DNA were observed at doses that produced no observable hepatotoxic effects as measured by serum aspartate aminotransferase and alanine aminotransferase levels. The slopes of the dose-response curves and the order of potency of these metabolites differed significantly between rats and mice, suggesting that different mechanisms of single-strand break induction may be involved in the two species. These data provide a potential explanation for the different sensitivity of mice and rats to the hepatocarcinogenic effects of TCE.

Alanine Transaminase↗
PubMed1988

Diastolic measurements from alternate R-wave gating of radionuclide angiograms.

Left ventricular diastolic filling measurements were determined by means of standard consecutive R-wave gating, list mode acquisition, and alternate R-wave gating. Time-activity curves obtained by the latter two methods were equally accurate in quantifying rapid, slow, and atrial left ventricular filling, whereas curves obtained by means of standard gating were inadequate for this purpose.

Cardiomegaly↗
PubMed1988

Active specific immunotherapy with an autologous tumor cell vaccine in patients with resected non-small cell lung cancer.

Eighteen postoperative patients with non-small cell lung cancer were actively immunized with a vaccine that included autologous cryopreserved irradiated tumor cells admixed with bacillus Calmette-Guerin. Patients received three weekly intradermal immunizations beginning 1-3 months after surgery (15 patients) or after completion of postoperative radiotherapy (3 patients). There was marked heterogeneity in the relative proportion of tumor cells versus host infiltrating cells within individual vaccines (range of percent tumor cells 7-75%). Five patients exhibited positive delayed cutaneous skin test reactivity (DCR) to autologous irradiated tumor cells prior to immunization, whereas 8 of 13 converted from skin test negative to positive. There were no correlations between DCR reactivity and in vitro lymphoproliferative responses to autologous tumor cells or to clinical outcomes, i.e., freedom from relapse. Possible explanations for the heterogeneity of the lung cancer vaccine and approaches for improving its immunogenicity are discussed.

BCG Vaccine↗
PubMed1988

Prophylactic knee braces and injury to the lower extremity.

Five hundred and eighty high-school football players were studied over a period of two seasons to determine the effect of so-called prophylactic knee braces on the lower extremity. Two hundred and forty-seven athletes who wore single-hinged braces and eighty-three who wore double-hinged braces were paired for the same season of play with 250 athletes who were similar in height, weight, and playing position but who did not wear braces. The fifty-three injuries of the knee that occurred were significantly more frequent (p less than 0.001) in the group that wore single-hinged braces than in the matched, non-braced group. While there were more injuries of the knee in the participants who were double-hinged braces than in the matched controls, who did not wear braces, the increase in the number of injuries was not significant. There was also a dramatic increase (p less than 0.01) in the number of injuries of the ankle and foot in the athletes who wore braces. Our results question the efficacy of the braces that were studied and call attention to the potentially adverse effect of the braces on adjacent joints in the ipsilateral limb.

Adolescent↗
PubMed1987

Structure and expression of the overlapping ND4L and ND5 genes of Neurospora crassa mitochondria.

Genes homologous to the mammalian mitochondrial NADH dehydrogenase subunit genes ND4L and ND5 were identified in the mitochondrial genome of the filamentous fungus Neurospora crassa, and the structure and expression of these genes was examined. The ND4L gene (interrupted by one intervening sequence) potentially encodes an 89 residue long hydrophobic protein that shares about 26% homology (or 41% homology if conservative amino acid substitutions are allowed) with the analogous human mitochondrial protein. The ND5 gene (which contains two introns) encodes a 715 residue polypeptide that shares 23% homology with the human analogue; a 300 amino acid long region is highly conserved (50% homology) in the two ND5 proteins. The stop codon of the ND4L gene overlaps the initiation codon of the downstream ND5 gene, and the two genes are cotranscribed and probably cotranslated. A presumed mature dicistronic (ND4L plus ND5) RNA was detected. The postulated mRNA (about 3.2 kb) contains 5' and 3' non-coding regions of about 86 and 730 nucleotides, respectively; this species is generated from very large precursor RNAs by a complex processing pathway. The ND4L and ND5 introns are all stable after their excision from the precursor species.

Amino Acid Sequence↗
PubMed1987

Three class I introns in the ND4L/ND5 transcriptional unit of Neurospora crassa mitochondria.

The overlapping ND4L and ND5 genes of Neurospora crassa mitochondria are interrupted by one and two intervening sequences, respectively, of about 1,490, 1,408 and 1,135 bp in length. All three intervening sequences are class I introns and as such have the potential to fold into the conserved secondary structure that has been proposed for the majority of fungal mitochondrial introns. They contain long open reading frames (ORFs; from 306 to 425 codons long) that are continuous and in frame with the upstream exon sequences. These ORFs contain the conserved decapeptide-encoding sequences that are characteristic of the ORFs present in most class I introns. Extensive homology exists among the ORFs encoded by the ND4L intron, ND5 intron 1, and the second intron of the N. crassa oli2 gene. Also, internal repeats of about 130 amino acid residues are present twice in each of these three ORFs, suggesting that a duplication event may have occurred in the formation of these ORFs. The ND4L intron shares extensive homology (at the levels of both primary and proposed secondary structures) with the self-splicing intervening sequence present in the Tetrahymena nuclear rRNA gene. This homology includes but is not limited to the core secondary structure, as peripheral structural elements are also conserved in the two introns.

Amino Acid Sequence↗
PubMed1987

Zinc (II) and the single-stranded DNA binding protein of bacteriophage T4.

The DNA binding domain of the gene 32 protein of the bacteriophage T4 contains a single "zinc-finger" sequence. The gene 32 protein is an extensively studied member of a class of proteins that bind relatively nonspecifically to single-stranded DNA. We have sequenced and characterized mutations in gene 32 whose defective proteins are activated by increasing the Zn(II) concentration in the growth medium. Our results identify a role for the gene 32 protein in activation of T4 late transcription. Several eukaryotic proteins with zinc fingers participate in activation of transcription, and the gene 32 protein of T4 should provide a simple, well-characterized system in which genetics can be utilized to study the role of a zinc finger in nucleic acid binding and gene expression.

DNA Mutational Analysis↗
PubMed1987

The haemodynamic effects of cyclosporin A in sheep.

1. Cyclosporin A (CyA; 12 mg/kg/day) was infused into six conscious sheep over 5 days to examine the haemodynamic effects of the drug in normal animals. 2. Mean arterial pressure was increased from 73(1) mmHg to 90(4) mmHg (P less than 0.001). There was no change in cardiac output but calculated total peripheral resistance was elevated from 16(1) to 21(2) mmHg min/1 (P less than 0.001) on day 4. 3. There was no change in plasma [Na], but a fall in plasma [K]. Urinary Na excretion decreased. Glomerular filtration rate, filtration fraction, renal blood flow, renal vascular resistance, body weight, plasma renin and blood aldosterone concentration were unchanged. 4. CyA produces an increase in blood pressure in sheep associated with an increase in total peripheral resistance on days 1, 3, and 4, in the absence of changes in renal function. This suggests that CyA hypertension is not simply a consequence of nephrotoxicity.

Animals↗
PubMed1987

Role of the autonomic nervous system, renin-angiotensin system, and arginine vasopressin during the onset and maintenance of ACTH hypertension in sheep.

The roles of the autonomic nervous system, renin-angiotensin system, and arginine vasopressin (AVP) during the onset of ACTH-induced hypertension were investigated in conscious sheep. Autonomic ganglion blockade or combined adrenergic and cholinergic receptor blockade demonstrated that an intact sympathetic nervous system was not essential for the development or maintenance of the hypertension. Autonomic blockade augmented the pressor response to ACTH, indicating that baroreceptor-mediated reflexes normally operate to suppress the degree of hypertension produced by ACTH. Evidence was obtained suggesting that the renin-angiotensin system and AVP may partially contribute to the maintenance of ACTH hypertension in the presence of autonomic blockade. However, the precise mechanism by which ACTH raises arterial pressure remains to be elucidated.

Adrenocorticotropic Hormone↗
PubMed1987

Structure-activity relationships for blood pressure effects of prednisolone in sheep.

This study investigated the effect of 5 day infusions of 6 alpha and 9 alpha-fluoro and 16 alpha, 17 alpha-acetal analogues of prednisolone on blood pressure in conscious sheep. In vivo mineralocorticoid (MC) and glucocorticoid (GC) activities of these steroids were also measured. Prednisolone (100 mg/d) produced a small increase in mean arterial pressure associated with increased fasting plasma [glucose] and polyuria, but had no MC activity. 9 alpha-fluoro substitution greatly enhanced both the pressor and MC activity of prednisolone. The effect of 9 alpha-fluoro substitution on pressor activity was not affected by beta-methylation at C-16 (betamethasone), but was attenuated by either alpha-hydroxylation or alpha-methylation at C-16 (triamcinolone and dexamethasone, respectively). The effect of 9 alpha-fluoro substitution on MC activity as determined by urinary Na excretion was not altered by a methyl group at C-16 in either alpha or beta configuration but the MC activity was attenuated by an alpha-hydroxyl group at C-16. In contrast, 6 alpha-fluoro substitution had little influence on pressor, MC and GC activities. 16 alpha, 17 alpha-acetonide and 16 alpha, 17 alpha-butylidenedioxy substitution increased the pressor activity of parent compounds, but had no influence on either GC or MC activity. This study demonstrates a dissociation between the pressor effects and the MC and GC activities associated with steroid administration and provides further evidence to support the concept of 'hypertensinogenic' class of steroid activity which can be distinguished from their MC and GC activity.

Animals↗
PubMed1985

RNA processing in Neurospora crassa mitochondria: transfer RNAs punctuate a large precursor transcript.

The pattern of transcripts arising from a large contiguous portion of the Neurospora crassa mitochondrial genome and the processing of these transcripts have been investigated. Evidence is presented for the transcription of a single, at least 12.5 kb, precursor RNA that contains sequences corresponding to the apocytochrome b (cob), tRNACys, cytochrome oxidase subunit 1 (CO I), tRNAArg and unidentified reading frame (URF) 1 genes. The two tRNA sequences serve as punctuation signals for the cleavage of this large transcript. Processing at the tRNACys and tRNAArg sequences directly generates the proposed CO I mRNA, as well as the mature 3' end of the cob transcripts. Moreover, three other sites have been identified that are specifically involved in further 5' end processing events. One of the two 5' end processing sites of the cob transcript shares homology with the 5' end processing sites of the mitochondrial 19S and 25S rRNA precursors. PstI palindromes do not act as processing signals because six of these palindromic sequences are present in the cob and CO I mRNAs.

Base Sequence↗
PubMed1985

Serotonergic mechanisms and blood pressure in sheep.

This study examined the effects of the serotonergic (5-HT2) antagonist ketanserin in sheep on haemodynamic responses to infused serotonin (5-HT), development of adrenocorticotrophin (ACTH)-induced hypertension, and the effect of ACTH on in vivo pressor responsiveness to 5-HT. Serotonin produced a dose-related increase in mean arterial pressure and heart rate. These increases in mean arterial pressure were attenuated or abolished by ketanserin, but increases in heart rate were enhanced. Ketanserin modified the pressure response to the alpha-adrenergic agonist phenylephrine, and did not further lower mean arterial pressure in sheep pretreated with the alpha-antagonist prazosin. Thus, ketanserin exhibits alpha-adrenergic antagonism in sheep. Ketanserin infusion lowered mean arterial pressure in normal sheep but did not affect the pressor response to ACTH infusion. There was no difference in pressor responsiveness to 5-HT (0.1-30 micrograms/kg) before and after ACTH treatment. Thus, 5-HT raises mean arterial pressure in sheep in a dose-related fashion, but there is no evidence of a role for 5-HT in ACTH-induced hypertension.

Adrenergic alpha-Antagonists↗
PubMed1985

Costo-iliac impingement syndrome.

A syndrome of back and loin pain produced by impingement of the lowest rib against the iliac crest is described in six patients. All had noticed a significant loss of height and five had osteoporosis of the vertebral column. It is suggested that mechanical irritation of the lowest rib against the iliac crest was the cause of the pain and that subperiosteal resection of the outer two-thirds of the rib would stop this irritation and relieve the symptoms. The six patients who underwent resection of the twelfth rib all obtained relief of symptoms; in one patient the eleventh rib also was resected. At latest review 5 to 34 months postoperatively there has been no recurrence of symptoms.

Adult↗
PubMed1984

Steroid antagonism of the 'hypertensinogenic' activity of 9 alpha-fluoroprednisolone.

We have previously reported that adrenocortical steroids raise blood pressure by a 'hypertensinogenic' mechanism of action which is not simply related to their classical 'mineralocorticoid' or 'glucocorticoid' actions. This study presents evidence for specific antagonism of this 'hypertensinogenic' activity. The effects of separate IV infusions of prednisolone (P) 100 mg/d and 9 alpha-fluoro-prednisolone (9 alpha F-P) 0.6 mg/d on mean arterial pressure (MAP), plasma [K], plasma [glucose] and urinary Na excretion (UNaV) after 2 days were studied in sheep. In the same group of sheep which received P alone for 2 days, 9 alpha F-P was given for a further 2 days while continuing the P infusion (P + 9 alpha F-P). P alone had no effect on MAP or plasma [K] or UNaV but increased plasma [glucose], effects which are characteristic of 'glucocorticoid' activity. 9 alpha F-P alone increased MAP by 14 mmHg (P less than 0.001) and reduced plasma [K] and UNaV but had no effect on plasma [glucose]. Thus 9 alpha F-P exhibited both 'hypertensionogenic' and 'mineralocorticoid' activity. In the sheep which received the combined P + 9 alpha F-P infusion, the increase in MAP normally produced by 9 alpha F-P was blocked. Although pretreatment with P blocked the pressor effect of 9 alpha F-P, it did not alter the 'mineralocorticoid' effects, namely hypokalaemia and urinary Na retention, produced when 9 alpha F-P was infused alone. These results provide further evidence for our concept of a 'hypertensinogenic' class of steroid activity and are the first demonstration of specific antagonism of steroid induced hypertension.

Adrenal Cortex Hormones↗
PubMed1984

EEG spectra in 9-13-year-old boys are stable over 1-3 years.

Good reliability was found in EEG spectra recorded during resting conditions in two studies 1-3 years apart in groups of adolescent dyslexic and control boys who were well screened for neurological, sensory and emotional disabilities. The studies used different equipment and analysis (FFT in study 1 vs. iterative digital bandpass filters in study 2). The central leads (C3 and C4) referenced to vertex were recorded in both studies. Pearson correlation coefficients were computed as reliability estimates for each spectral band separately for each group, for absolute and relative power and for eyes open and eyes closed recording conditions. For both groups and for all conditions, the absolute power reliabilities were above 0.71 for all bands except delta for which they were above 0.54. Reliabilities were more variable for relative power measures.

Adolescent↗