Chronic renal failure associated with bilateral nephroliths and ureteroliths in a two-year-old Thoroughbred colt.
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Animals↗
Biomedical subjects
J H Wilson
Publications and source records attributed to J H Wilson.
Comparison of filler DNA at immune, nonimmune, and oncogenic rearrangements suggests multiple mechanisms of formation.
Extra nucleotides (termed filler DNA) are commonly found at the junctions of genetic rearrangements in mammalian cells. The filler DNA at immune system rearrangements, which are called N regions, are generated at VDJ joints primarily by terminal deoxynucleotidyl transferase. However, the origin of filler DNA at genetic rearrangements in nonlymphoid cells is uncertain. In an analysis of more than 200 junctions that arose by circularization of transfected linear DNA (D. B. Roth and J. H. Wilson, Mol. Cell. Biol. 6:4295-4304, 1986), we found 18 junctions with extra nucleotides exactly at the point of circularization. Analysis of these 18 junctions indicated that nonlymphoid cells could add extra nucleotides to the ends of duplex DNA. The characteristics of the extra nucleotides at these junctions and at 31 other rearrangement junctions from nonlymphoid cells were quite similar, suggesting that many genetic rearrangements may pass through a stage with free DNA ends. A comparison of the filler DNA at these 49 nonimmune system rearrangements with 97 N regions derived from immune system rearrangements suggested that lymphoid and nonlymphoid cells use different mechanisms for insertion of filler DNA, as expected from the absence of detectable terminal deoxynucleotidyl transferase in cells from nonlymphoid tissues. The filler DNAs at a smaller group of 22 translocations associated with cancer had features in common with both immune and nonimmune system rearrangements and therefore may represent a mixture of these two processes. Mechanisms that might account for the presence of filler DNA in nonlymphoid cells are discussed.
Animals↗
Significance of prostaglandin E2 in acute necrotising pancreatitis in rats.
Acute necrotising pancreatitis in rats was induced by injecting 5% sodium taurocholate into the pancreatic duct. Prostaglandin E2 (100 micrograms/kg subcutaneously twice) decreased the mortality rate from 100% to 60% (NS). When treatment with prostaglandin E2 was combined with simultaneous administration of either dazmegrel (UK 38,485, 50 mg/kg bodyweight) or Sibelium (Flunarizine R 14,950, 0.2 mg/kg body weight) a significant decrease in the mortality rate (p less than 0.05) was recorded. Dazmegrel is a selective thromboxane A2 synthetase inhibitor and prevents the formation of thromboxane A2. Flunarizine (a calcium entry blocker) decreases thromboxane A2 formation and also inhibits the effects of raised thromboxane A2 concentrations. As plasma thromboxane B2 (the stable metabolite of thromboxane A2) concentrations increase and the plasma prostaglandin E2 concentrations decrease in acute necrotising pancreatitis in rats, the results of the present study indicate that these prostaglandins play a role in the pathophysiology of the disease. It is suggested that restoration of the balance in prostanoid concentrations will have a beneficial effect on the course of acute necrotising pancreatitis.
Acute Disease↗
Recurrent calcium emboli in a patient with aortic stenosis.
We report a patient with moderate aortic stenosis who had two episodes of calcium embolus to the left popliteal artery within ten months. This case suggests that calcium emboli can be recurrent and that major calcium emboli should warrant consideration of valve replacement, even in patients with mild aortic stenosis.
Adult↗
In-vitro versus in-vivo activities of new 5-lipoxygenase inhibitors with antiinflammatory activity.
The possible relationship between in-vitro inhibition of lipoxygenase (LO)/cyclooxygenase (CO) and in-vivo antiinflammatory effects of compounds such as isoflavanes (Zy 16369, Zy 16372, Zy 16681) was investigated. The latter were all shown to be potent 5-LO inhibitors when tested in vitro on human peritoneal macrophages (IC50 = 1-7 mumol/l). Zy 16372 and Zy 16681 also inhibited the 12- and 15-LO and, to a minor extent, the CO. In order to evaluate the antiinflammatory and antiproliferative effects of these compounds in vivo they were applied topically to mice. No definite correlation could be made between the inhibition of the ear oedema induced by arachidonic acid (AA), the inhibition of the epidermal ornithine-decarboxylase (ODC) activity induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), and the in-vitro activities of the compounds. Zy 16372 appeared to inhibit the oedema dose-dependently (ED50 = 5 mumol/ear) and seemed to be the most potent among the 3 compounds tested and slightly more potent than the reference compound nordihydroguaiaretic acid. As inhibitors of TPA-induced ODC, all 3 compounds exhibited comparable activity. These results suggest that the in-vivo effects of the compounds might be mediated by components other than AA metabolites, and/or be related to their specific kinetic patterns.
Animals↗
The effect of very low energy diets on the fatty acid composition of serum lipids.
The fatty acid composition of serum phospholipids, cholesteryl esters and triglycerides was measured in 11 obese individuals before and after 2 and 4 weeks treatment with a liquid diet providing about 600 kcal and 70 g protein per day. The patients received 20g of lipid, which was either maize oil and safflower oil (6 patients) or maize oil and evening primrose oil (5 patients). During treatment serum phospholipid linoleic acid (C18:2n-6) concentration remained constant, the dihomo-gamma-linolenic acid (C20:3n-6) concentration decreased by 44 percent in the safflower oil group and by 37 percent in the evening primrose oil group and the arachidonic acid (C20:4n-6) increased by 26 percent in the safflower oil group and by 20 percent in the evening primrose oil group. The increase in phospholipid arachidonate showed a significant positive correlation with total weight loss during the treatment period. These results suggest that during weight reduction there is a increased mobilization of arachidonic acid from tissues and a decreased rate of linoleic acid desaturation and elongation, which was not significantly influenced by providing gamma-linolenic acid in the diet.
Adult↗
Hemoperitoneum caused by rupture of a juvenile granulosa cell tumor in an equine neonate.
A neonatal foal was examined because of apparent abdominal pain and distention, anemia, and hemoperitoneum. Exploratory laparotomy was performed, and a large spherical mass, which had ruptured, was found in the area of the left ovary. Left salpingo-oophorectomy was performed. The mass was determined to be a juvenile granulosa cell tumor.
Animals↗
[Reye syndrome in The Netherlands: report of a survey in 1981-1984].
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Biopsy↗
Serum procollagen III N-terminal peptide and laminin P1 fragment concentrations in alcoholic liver disease and primary biliary cirrhosis.
Procollagen type III N-peptide (PIII NP) and laminin P1 fragment (LP1) have both been proposed as markers of liver fibrosis. In this study we evaluated the diagnostic application of both peptides in alcoholic liver disease and primary biliary cirrhosis. Serum concentrations of the peptides were measured by radioimmunoassay. PIII NP and LP1 levels appeared to be significantly raised in patients with alcoholic and primary biliary cirrhosis. Patients with alcohol abuse without cirrhosis had normal or slightly elevated PIII NP levels, but significantly raised LP1 levels. There was a strong correlation between PIII NP and LP1 concentrations.
Humans↗
Genetic analysis of structure and function in phage T4 tRNASer.
We have determined the nucleotide sequences of 55 spontaneous mutations that inactivate a suppressor gene of phage T4 tRNASer. Most of the mutations caused substitutions or deletions of single nucleotides at 18 different positions in the tRNA. Two of three mutations that allowed the synthesis of mature tRNA had nucleotide substitutions at the junction of the dihydrouridine and anticodon stems, suggesting that this region of tRNASer is important for aminoacylation. The third mutation that synthesized tRNA had a nucleotide deletion in the anticodon loop, which presumably affected the translational capacity of the tRNA. We also sequenced 58 spontaneous reversion mutations derived from strains with the inactive suppressor genes. Some of these regenerated the initial tRNA sequence, while other generated a second-site mutation in the tRNA. These second-site mutations restored helical base-pairings to the tRNA that had been eliminated by the initial mutations. The new base-pairings involved G.C and A.U, and the A.C wobble pair at certain positions in the tRNA. This finding establishes the existence of A.C wobble pair in tRNA helices.
Base Sequence↗
Heteroduplex-induced mutagenesis in mammalian cells.
We have shown previously that heteroduplexes containing single-stranded loops are repaired efficiently in monkey cells, but not always correctly: 2% of the repair products acquired mutations within a 350 base-pair target (Weiss, U. and Wilson, J.H., Proc. Natl. Acad. Sci. USA 87:1123-1126, 1987). The structures of the mutant genomes, which are described here, are consistent with an error-prone repair system. The spectrum of mutations includes about 25% point mutations and 75% rearrangements, which consist of deletions, duplications, and substitutions. The mutations are clustered in the vicinity of single-stranded loops in the original heteroduplex. The high frequency of mutation, their clustering, and the positions of rearrangement endpoints suggest that the mutations were generated during repair of the heteroduplexes.
Animals↗
Nisoldipine: kinetics and effects on blood pressure and heart rate in patients with liver cirrhosis after intravenous and oral administration.
The pharmacokinetics and effects on blood pressure and heart rate of nisoldipine were studied in 8 patients with cirrhosis and in 8 age-matched healthy controls. On separate occasions each subject received nisoldipine by i.v. infusion (0.37 mg in 40 min) and as a tablet (5 mg for patients and 20 mg for control subjects). After i.v. nisoldipine, the elimination half-life was 9.7 h in control subjects and 16.6 h in the cirrhotics. The volume of distribution was 4.1 l/kg and 6.4 l/kg and the total systemic clearance was 847 ml/min and 494 ml/min, respectively. On oral nisoldipine, systemic availability was fourfold higher in patients with cirrhosis: 14.7% versus 3.7%. After i.v. administration of nisoldipine there was a brief decrease in systolic and diastolic blood pressure in both groups, whereas the heart rate increased. After 4 h a second effect peak appeared in the control subjects. After oral nisoldipine similar effect-time profiles were found, but effects lasted longer than after i.v. administration. Comparison of the maximal total plasma concentration of nisoldipine and the maximal effect in the two groups revealed that sensitivity to nisoldipine was not different in patients with cirrhosis. A reduction in the dose of nisoldipine is recommended when cirrhotics require oral nisoldipine in therapeutic practice.
Administration, Oral↗
Blood exchange and transfusion therapy for acute cholestasis in protoporphyria.
Acute cholestasis is a rare complication of EPP with a high mortality rate despite extensive treatment with corticosteroids, cholestyramine, and antioxidants. A single survivor, reported in the literature, was treated with blood exchange transfusions. We treated two EPP patients with blood exchange and additional blood transfusions which resulted in full clinical and biochemical recovery from the cholestasis and accompanying hepatitis. Recurrences of the cholestasis and hepatitis could repeatedly be corrected by additional blood transfusions.
Acute Disease↗
ERCP diagnosis of tumors in the region of the head of the pancreas. Analysis of criteria and computer-aided diagnosis.
During the period 1974-1983, 320 patients with pancreas carcinoma, papilla of Vater carcinoma, bile duct bifurcation carcinoma, or duodenal carcinoma were examined by ERCP. Using 30 ERCP criteria, a radiological diagnosis was made. A valid pathological diagnosis was available in 200 patients (62.5%). In 183 of the 200 patients (91.5%), the ERCP diagnosis and the pathological diagnosis were identical. We then performed an analysis using 52 ERCP criteria. In 192 of the 200 patients (96.0%), the ERCP diagnosis based on this reanalysis and the pathological diagnosis were identical. By discriminant analysis, 13 ERCP criteria with a maximal discriminatory value were selected in patients in whom all diagnostic structures (bile ducts, pancreatic duct, and duodenum) were visible. Using these 13 criteria selected by discriminant analysis, the diagnostic score was 98.9%. A computer program based on these 13 ERCP criteria was designed for use in practice. The diagnostic accuracy of this computer program was 98.4%. Finally we tested this computer program on 171 new patients who were seen in the period 1983-1986. In 143 of the 171 patients, a valid pathological diagnosis was available (83.6%). Comparing the ERCP diagnosis in all patients (even if not all structures were visible) with a valid pathological diagnosis, the prospective score of the computer program was 91.6%. Using this program it was possible to evaluate examinations in which not all structures were visible. When the ERCP diagnosis was uncertain, the doubt could be quantified.
Ampulla of Vater↗
Comparison of the production of eicosanoids by human and rat peritoneal macrophages and rat Kupffer cells.
Human and rat peritoneal macrophages and rat Kupffer cells were labelled with [1-14C] arachidonic acid and stimulated with the calcium ionophore A23187. The metabolites formed were separated by high pressure liquid chromatography (HPLC). Human peritoneal macrophages formed especially leukotriene B4, 5-hydroxy-6,8,11,14 eicosatetraenoic acid and small amounts of leukotriene C4 and thromboxane B2, 12-hydroxy-5,8,10 heptadecatrienoic acid and 6-keto-prostaglandin F1 alpha, whereas rat peritoneal macrophages mainly produced cyclooxygenase products and in particular thromboxane B2 and 12-hydroxy-5,8,10 heptadecatrienoic acid. Rat Kupffer cells synthesized mainly cyclooxygenase products such as prostaglandin F2 alpha, prostaglandin D2 and prostaglandin E2. These results indicate that the profile of eicosanoids production by macrophages is dependent both on the species and on the tissue from which the macrophage is derived.
Animals↗
Breast milk tocainide levels.
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Anti-Arrhythmia Agents↗
Apparent undersensing due to oversensing of low amplitude pulses in a thoracic impedance-sensing, rate-responsive pacemaker.
A case in which apparent undersensing was caused by detection of low amplitude impedance-measuring pulses emitted by a thoracic impedance-sensing rate-modulated pacemaker is described. The detection of these high frequency pulses was interpreted as "noise" by the pacemaker and led to asynchronous pacing in the interference reversion mode. Increasing the sensitivity failed to correct the problem. Decreasing the sensitivity eliminated oversensing of the low amplitude pulses and the apparent undersensing. Recognition of this phenomenon is important to prevent a misdiagnosis of undersensing.
Cardiography, Impedance↗
The effects of human growth hormone administration in elderly adults with recent weight loss.
The effects of human GH administration in elderly adults with recent weight loss were investigated in a metabolic ward study. Four patients were studied for 20 days. In addition to a constant caloric and nitrogen-sufficient diet, consisting of the recommended amounts of protein and energy plus 20%, the patients received GH in dosages of 25 and 50 micrograms/kg.day for two 4-day periods (days 5-8 and 13-16, respectively). Significant increases in nitrogen retention of 1.6 (114.2) and 1.4 g/day (100 mmol/day), respectively, occurred compared with that in the control periods. No difference was found between the two GH dosages, but the nitrogen-retaining effect of the higher dose appeared to last for several days after its administration was stopped. Plasma insulin-like growth factor I levels rose during both treatment periods. No important disturbances in carbohydrate metabolism occurred. Body weight increased 2.3 kg during each treatment period, probably due to water retention. We conclude that even during more than adequate nutritional intake, low GH doses cause considerable nitrogen retention in underweight adults.
Aged↗