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Biomedical subjects

D Jones

Publications and source records attributed to D Jones.

At least 631 records · Page 35Linked to original sources

Inactive renin in peritoneal fluid of the cat: responses to acute stimuli which alter plasma renin.

Active and inactive renin in plasma and peritoneal dialysate were studied in pentobarbitone anesthetized cats during 8 hours of peritoneal dialysis. In control cats, despite a significant rise in plasma active renin from 1.3 +/- 0.22 to 4.4 +/- 0.76 pmoles AI/ml/hr over 8 hours, plasma inactive renin was unchanged. Four-fold rises in plasma active renin after hemorrhage (15 ml/kg) and captopril (1 mg/Kg I.V.) were unaccompanied by significant change in inactive renin. Bilateral nephrectomy resulted in undetectable plasma active renin after 3 hours but plasma inactive renin was 25-30% of initial levels 6 hours post-nephrectomy. In peritoneal dialysate, active renin remained low in control cats but there was a ten-fold rise of inactive renin from 0.06 +/- 0.02 to 0.60 +/- 0.07 pmoles AI/ml/hr. After hemorrhage there was a slight rise of active renin after 3 and 4 hours. Inactive renin was lower than control 6 hours after nephrectomy and captopril, but higher than control 1 and 2 hours after hemorrhage. Dialysate inactive renin accumulation slopes were not different among treatments. Acute changes in plasma active renin have little effect on peritoneal dialysate renin.

Animals↗

Induction of nephrotoxicity by high doses of gentamicin in diabetic rats.

Rats with streptozotocin-induced diabetes mellitus (DM) are resistant to aminoglycoside (AG) nephrotoxicity presumably because of defective transport and accumulation of drug by proximal tubular cells. To test this hypothesis we injected DM rats with saline or with gentamicin, 100, 200, and 400 mg/kg per day for 6 days, to determine if the renal cortical concentration of gentamicin could be raised to toxic levels. Nephrotoxicity was assessed by monitoring for evidence of accelerated lipid peroxidation in the renal cortex, for elevation of the serum creatinine concentration, and for evidence of proximal tubular cell injury and necrosis by light and electron microscopy. At 100 mg/kg per day renal cortical gentamicin was 454 +/- 85 micrograms/g. Except for an increase in renal cortical phospholipids these rats manifested no evidence of accelerated lipid peroxidation or elevation of serum creatinine. At 200 mg/kg per day renal cortical gentamicin rose to 636 +/- 20 micrograms/g. These rats manifested mild functional and morphological evidence of toxicity. At 400 mg/kg renal cortical gentamicin rose to 741 +/- 43 micrograms/g. These rats developed severe nephrotoxic injury as manifested by a marked increase of lipid peroxidation evident by an increase of malondialdehyde from a control level of 0.48 +/- 0.02 to 1.72 +/- 0.12 nmole/mg protein, a shift from unsaturated to saturated fatty acids esterified in renal cortical phospholipids, depression of superoxide dismutase and catalase, and a shift from reduced to oxidized glutathione. The serum creatinine rose from a baseline level of 0.24 +/- 0.01 to 0.46 +/- 0.05 mg/dl. Light and electron microscopy revealed enlarged lysosomes distended with typical myeloid bodies and extensive proximal tubular cell necrosis. These observations provide compelling evidence in support of the view that the resistance of DM rats to AG nephrotoxicity is causally linked to the low rate of drug uptake by renal proximal tubular cells. When the renal cortical concentration reaches a critical level, it elicits a pattern of toxic injury indistinguishable from that of nondiabetic rats. Thus, there is nothing inherent to the diabetic state that prevents AGs from causing their usual adverse effects on the metabolism of renal proximal tubular cells once they gain access in sufficient quantity into these cells.

Animals↗

A prospective evaluation of magnetic resonance imaging, computed tomography, and mediastinoscopy in the preoperative assessment of mediastinal node status in bronchogenic carcinoma.

Computed tomography, magnetic resonance imaging, chest roentgenography, and mediastinoscopy were compared prospectively as staging modalities to assess mediastinal node status in 84 patients with presumed operable bronchogenic carcinoma. Computed tomography was associated with a sensitivity of 71.0%, a specificity of 87.7% and an overall accuracy of 82.1%. Magnetic resonance imaging did not provide any advantage over computed tomography in the assessment of mediastinal node status. The accuracy of computed tomography was not dependent on cell type of the primary tumor. Although chest roentgenography had a sensitivity of 80.7%, the overall accuracy of 57.1% was unacceptably low. The sensitivity (87.1%), specificity (100%), positive (100%) and negative (93.0%) predictive values, and accuracy (95.2%) of mediastinoscopy exceeded those observed with all other modalities. We continue to recommend mediastinoscopy as the most accurate staging investigation in the routine management of patients with bronchogenic carcinoma.

Carcinoma, Bronchogenic↗

Therapeutic application of radiolabeled monoclonal antibody UJ13A in children with disseminated neuroblastoma.

Dosimetric data from UJ13A scanning studies using 131I are presented for children with stage IV neuroblastoma and primary brain tumor. The data demonstrate a large variation among patients in dose delivery to vulnerable organs and tumors. Against this background, a phase I toxicity study is under way with escalating amounts of conjugate administered to patients who have stage IV neuroblastoma. Major toxicity has been confined to bone marrow aplasia and necessitates bone marrow harvest prior to therapy. Specific problems encountered include altered kinetics during therapy following tracer studies and adequate dose delivery in large tumor masses.

Antibodies, Monoclonal↗

Tryptophan photolysis is responsible for gramicidin-channel inactivation by ultraviolet light.

The decay of gramicidin fluorescence resulting from ultraviolet exposure was compared to the decay of conductance from gramicidin-containing planar bilayer membranes under the same conditions of illumination. The decay rate was the same for both processes. The fluorescence decay was identical whether gramicidin was dissolved in methanol or incorporated into lipid vesicles, indicating that the peptide conformation does not affect the sensitivity of gramicidin to photolysis. The correlation of fluorescence decay and conductance decay imply that conductance loss from gramicidin-doped membranes illuminated with ultraviolet light is due to photochemical modifications of the channel tryptophans rather than simply to disturbance of the conformation of gramicidin channels.

Gramicidin↗

Structure, expression, and evolution of a heat shock gene locus in Caenorhabditis elegans that is flanked by repetitive elements.

A locus containing two hsp16 genes in Caenorhabditis elegans has been characterized by DNA sequencing. Each gene encodes a 16-kDa polypeptide which is expressed following heat induction. The two genes, designated hsp16-2 and hsp16-41, are arranged in divergent orientations, and each contains a single intron of 46 and 58 base pairs, respectively. Although both gene transcripts are spliced efficiently in vivo, hsp16-41 corresponds to a previously isolated cDNA which contains an unspliced intron sequence. The 5'-noncoding regions of both genes contain TATA boxes preceded 18 or 19 nucleotides upstream by a heat shock regulatory sequence. The 3'-noncoding regions contain polyadenylation signals (AATAAA) either downstream (hsp16-2) or immediately adjacent (hsp16-41) to a sequence capable of forming a hairpin. This pair of hsp16 genes is flanked by three copies of an approximately 200-bp dispersed repetitive element (two copies on one side and a single one on the other side of the locus) which occurs in at least 70 copies throughout the C. elegans genome, and has been designated CeRep-16. Together with data described previously (Russnak, R. H., and Candido, E. P. M. (1985) Mol. Cell. Biol. 5, 1268-1278), the results presented here define a family of four distinct, related small heat shock protein genes. These are arranged in divergently transcribed pairs at two loci. The hsp16-48/41 genes code for one class of HSP16, 143-amino acid residues long, while the hsp16-1/2 genes encode the other class, which is 2 amino acid residues longer. Thus each locus codes for the two major types of HSP16. The two loci differ in a number of respects, including the presence of a tandem inverted duplication of two heat shock protein genes at one locus, and of repetitive elements at the other. Sequence comparisons allow us to propose a scheme for the evolution of the four genes and reveal conserved features of noncoding regions which may be involved in the regulation of their transcription, RNA processing, or translation. Using locus-specific hybridization probes, we have found that the genes at locus hsp16-2/41 are expressed at levels approximately 20-40-fold higher than those at locus hsp16-1/48.

Animals↗

High resolution isoelectric focusing of juvenile hormone esterase activity from the hemolymph of Trichoplusia ni (Hübner).

Juvenile hormone esterase (JHE) activity from the hemolymph of larval Trichoplusia ni was analyzed by two different isoelectric focusing (IEF) methodologies. Use of techniques capable of progressively higher resolution split ultimately what appeared at lower resolution to be a single peak into two discrete peaks of JHE activity (pI 5.5 and 5.3). Neither peak was a degradation artifact of the other caused by conditions of IEF.

Animals↗

De-functioning stomas: a prospective controlled trial comparing loop ileostomy with loop transverse colostomy.

Patients undergoing colorectal surgery who required a defunctioning stoma were randomly allocated to receive either a loop ileostomy (n = 23) or transverse loop colostomy (n = 24). Assessment was made during construction, immediately postoperatively, during the period of outpatient supervision and before and after stoma closure. The ileostomy was associated with significantly less odour than the colostomy (P less than 0.01) and required significantly less appliance changes (P less than 0.05). Furthermore eleven patients (58 per cent) with a colostomy experienced three or more problems with stoma management compared with only three patients (18 per cent) with an ileostomy (P less than 0.05). Wound infection was also significantly more common after closure of the colostomy compared with the ileostomy. Both types of stoma were demonstrated objectively to defunction the distal bowel almost completely. These results indicate that a loop ileostomy is the procedure of first choice when a stoma is needed to defunction the distal colorectum.

Adult↗

Chelonus sp.: suppression of host ecdysteroids and developmentally stationary pseudoparasitized prepupae.

When eggs of the caterpillar Trichoplusia ni are stung by Chelonus sp. (near C. curvimaculatus) (Braconidae), the developing host larvae precociously spin a cocoon but then remain developmentally stationary in the prepupal stage. The latter event happens even in hosts which were stung and precociously spin cocoons but which, upon dissection, contain no obvious parasite. Injection of radiolabeled ecdysone into either pseudoparasitized or allatectomized larvae demonstrates suppressed rates of conversion of ecdysone to 20-hydroxyecdysone when compared with controls. The data indicate that the occurrence of developmentally stationary pseudoparasitized prepupae is due to less production of ecdysteroid and less conversion of ecdysone to 20-hydroxyecdysone, both probably as a result of suppressed juvenile hormone titer.

Animals↗

The biologic and toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in chickens.

The administration of 2,3,7,8-TCDD to 2-week-old White Leghorn cockerels produced a dose-dependent induction of hepatic microsomal ethoxyresorufin O-deethylase (EROD) and benzo[alpha]pyrene (B[alpha]P) hydroxylase activities with induction EC50 values of 778 and 302 ng/kg, respectively. In addition, 2,3,7,8-TCDD also induced 4-dimethylaminoantipyrine (DMAP) N-demethylase (EC50 = 561 ng/kg), this result contrasting with studies reported for other animal species in which 2,3,7,8-TCDD either does not induce or inhibits this cytochrome P-450 dependent monooxygenase enzyme activity. However, the reduced cytochrome P-450:CO binding difference spectral absorption maxima for the 2,3,7,8-TCDD induced microsomes was observed at 448 nm which was similar to that reported for most animals which have been investigated. Electrophoresis of control and 2,3,7,8-TCDD induced microsomal proteins using SDS polyacrylamide slab gels showed intensification of 3 protein staining bands at Mr 53 000, 56 000 and 58 000. Incubation of the 2,3,7,8-TCDD-induced microsomes with SKF-525A and alpha-naphthoflavone showed that both compounds inhibited DMAP N-demethylase, EROD and AHH and that alpha-naphthoflavone was the more potent inhibitor of all 3 microsomal monooxygenases. 2,3,7,8-TCDD treatment caused significant involution of the Bursa of Fabricius when administered at a dose level of 10 micrograms/kg for 3 days and this result confirmed the extreme sensitivity of the immature White Leghorn cockerel to the biologic and toxic effects elicited by 2,3,7,8-TCDD. However, in contrast to other sensitive species, no high affinity cytosolic receptor protein for [3H]2,3,7,8-TCDD could be detected in the liver of chick embryos or 2-week-old birds.

Animals↗

Multiple forms of juvenile hormone esterase active sites in the hemolymph of larvae of Trichoplusia ni.

Kinetic analysis was performed on the juvenile hormone (JH) esterase activity in the hemolymph of feeding, last instar larvae of Trichoplusia ni (Lepidoptera: Noctuidae). When the results were analyzed by several different graphical and regression procedures, all approaches yielded the same conclusion that at least two forms of JH esterase active sites exist in the hemolymph. The apparent Km for one site for JH I, II and III was 8.5 X 10(-8) M, and 6.6 X 10(-8) M, respectively. The Km for the other site for JH I, II and III was 6.6 X 10(-7) M, 7.6 X 10(-7) M, 40 X 10(-7) M, respectively. When hemolymph JHE activity was subjected to high resolution isoelectric focusing (IEF), two distinct large peaks of JHE activity were observed, with pIs of 5.3 and 5.5, as well as a small peak at pI 5.1. Separate kinetic analysis of the JHE activity in each peak showed that only the higher Km active site for each substrate was present (in the 10(-7) M range). These data necessitate a change in the current model for JHE in T. ni, and some other insects, which states that a single active site is responsible for most or all of the JH esterase activity in vivo. The data also explain the different estimates of the Km of JHE in T. ni obtained by different laboratories. Studies on the purification of, and the development of inhibitors for, JHE esterase must consider the role of both JHE forms and sites in regulation of T. ni metamorphosis.

Animals↗

Precocious expression of the final larval instar developmental pattern in larvae of Trichoplusia ni pseudoparasitized by Chelonus spp.

The present study has used a number of electrophoretic approaches to analyze the proteins in normal Trichoplusia ni larvae and those pseudoparasitized by Chelonus spp. A number of feeding-stage, hemolymph proteins appear or increase dramatically only during the final larval stadium. Other proteins highly abundant only during the penultimate stadium disappear or decrease dramatically during the final stadium. The comparative protein profiles of penultimate instar, pseudoparasitized larvae are very similar to those of last instar larvae. These changes in hemolymph proteins are seen on gels resulting from electrophoresis, isoelectric focusing (wide range and narrow range Ampholine and very narrow range Immobiline gels) and SDS-disc electrophoresis. It is concluded that the entire last instar developmental pattern of protein gene products is occurring precociously in pseudoparasitized larvae.

Animals↗

Radiotherapy treatment planning using lymphoscintigraphy.

A method for the three dimensional location of lymph nodes with respect to the skin surface is described. The technique is based on the reconstruction of surface shape using isocentric radiographs taken with metal chains draped on the patient. Registration of the radiographic study to the lymphoscintigraphic study is accomplished automatically by matching the location of four radiopaque and radioisotope markers. This method allows nodes to be located in a beam's eye view with any set up of an isocentric radiotherapy machine. An accurate determination of the depth of lymph nodes is obtained, which is of value in electron beam therapy.

Breast Neoplasms↗

Comparisons of preoperative and postoperative MMPI data in chronic back patients.

The purpose of this study was to analyze 42 patients disabled with low-back pain in order to assess Minnesota Multiphasic Personality Index (MMPI) changes before and after surgery, the predictive value of MMPI, the results of anterior lumbar fusion in one group of severely disabled lumbar low-back pain patients. Statistical analyses were performed to compare and contrast MMPI, pain assessment, functional and occupational levels, and disability index before and after surgery. The degree of morbidity of the patients preoperatively was severe. After surgery, the majority of the patients showed improvement in their overall status. The available evidence suggests the following: Improvement in physical condition can produce improvement in psychological test scores; The preoperative MMPI is not a reliable indicator of surgical success.

Back Pain↗