Relapsing polychondritis with crescentic glomerulonephritis.

Relapsing polychondritis is rare and its cause is unknown. The tissues affected are those with a high glycosaminoglycan content, such as cartilage, the aorta, the sclera and cornea, and parts of the ear. Symptoms can usually be controlled with oral steroids, but when there is coexistent progressive crescentic glomerulonephritis quadruple chemotherapy may be used. Three cases of the clinical syndrome of relapsing polychondritis were studied in which rapidly progressive cresentic glomerulonephritis developed. In two the patients appeared to respond to aggressive treatment with immunosuppressive agents and anticoagulants. The multisystemic nature of the disease, the renal lesions, and the response to treatment all suggested that the condition might be related to periarteritis nodosa.     

3'-Phosphatase activity in T4 polynucleotide kinase.

The purification of T4 polynucleotide kinase results in the copurification of an activity which will specifically remove the 3'-terminal phosphate from a variety of deoxyribonucleotides and ribonucleotides in the absence of ATP. This phosphatase activity requires magnesium, has a pH optiumum of 6.0, and is more active with deoxyribonucleotides than ribonucleotides. T4 polynucleotide kinase and the 3'-phosphatase activity copurify by gradient elution column chromatography on DEAE-cellulose, phosphocellulose, and hydroxylapatite. The two activities are included in and comigrate on Sephadex G-200. Polyacrylamide gel electrophoresis at PH 9.2 results in conigration of the two activities together with the major protein band. The two activities respond in parallel to heat inactivation at 35 degrees C and ATP, a substrate for the kinase only, protects both activities from heat inactivation. It is therefore suggested that the two activities are functions of the same protein molecule.     

Presentation,management, complications,and outcome of acute renal failure in childhood: five years' experience.

During 1971-5, 72 episodes of acute renal failure were treated in 70 children aged up to 16 years. The commonest causes were renal hypoperfusion (31 cases), haemolytic-uraemic syndrome (12), glomerulonephritis (9), septicaemia (5), and congenital abnormalities (6). Though referral from other hospitals was generally prompt, 10 out of 51 patients had been observed for up to seven days before transfer. Dailysis was used in 44 cases, the most common complications of which were peritonitis in those treated with peritoneal dialysis and acute changes in fluid balance in those treated with haemodialysis. Altogether 37 patients fully recovered, 10 were discharged with chronically impaired renal function, 17 died, and six entered the dialysis and transplantation programme. The mortality fell from 33% in 1972 to 20% in later years, which was due solely to maintenance dialysis being available. Though all patients with irrevocable kidney failure who were suitable entered the dialysis and transplantation programme, with current financial restrictions we doubt whether we shall be able to find places for all such patients in the future.     

Equimolar addition of oligoribonucleotides with T4 RNA ligase.

T4 induced RNA ligase will join equimolar concentrations of two oligoribonucleotides, (Ap)3C and p(Up) 5, to form a single product, (Ap)3Cp(Up) 5, in high yield. The presence of the 3' phosphate on p(Up)5 prevents the oligomer from adding to itself. The pH optimum of the reaction is about 7.5, but less of the undesirable adenylated intermediate, App(Up) 5, forms at pH 8.2. The reaction rate is a linear function of oligomer concentration from 3 micronM to 0.6 mM. The data suggest that T4 RNA ligase will be a useful enzyme for the synthesis of oligomers of defined sequence.     

Cortical thickness measurements and photon absorptiometry for determination of bone quantity.

Reproducibility of estimates of cortical bone quantity in the appendicular skeleton by two methods was studied in healthy individuals and patients undergoing long-term hemodialysis. Repeated measurements of cortical thickness (CT) at the midpoint of the second metacarpal were taken from single radiographs of both hands by two independent observers. Repeated measurements by the same observer were more reproducible and the degree of reproducibility was far greater in healthy subjects than in dialysis patients. Repeated measurements were made of bone mineral content (BMC) and bone width (W) of the distal radius by photon absorptiometry. Repeated BMC/W determinations were highly reproducible in both healthy subjects and dialysis patients. High correlation was found between BMC and cross-sectional cortical area and between both simple cortical thickness and cortical area/width. Thus the photon absorptiometric technique is superior for the serial monitoring of bone quantity, particularly in patients with uremic osteodystrophy, but results obtained by the two methods in group studies should be comparable.     

Method for the Detection of Injured Vibrio parahaemolyticus in Seafoods

The sensitivity of Vibrio parahaemolyticus cells to refrigeration and frozen storage and the development of a method for detecting injured and uninjured V. parahaemolyticus cells were studied. Cell suspensions in different kinds of seafood homogenates were either regrigerated (4°C) or frozen (−20°C), stored, and examined for cell survival during storage. V. parahaemolyticus cells were sensitive to both storage temperatures. Many cells died, and many survivors were sublethally injured. In general, refrigeration storage appeared to be more injurious than frozen storage. The initial recovery of the sublethally injured cells was highest in a nutritionally rich, nonselective liquid medium such as Trypticase soy broth, whereas maximum cell multiplication was observed in Trypticase soy broth containing 3% NaCl. The sublethally injured V. parahaemolyticus cells demonstrated sensitivity to the selective enrichment medium, glucose salt teepol broth. From these findings, a new method (designated as the “repair-detection” method) was developed for the isolation and enumeration of V. parahaemolyticus. Comparative studies between the recommended and the repair-detection methods showed that injured V. parahaemolyticus cells were present in commercial seafoods and that the repair-detection method was definitely more effective for the detection of total numbers of V. parahaemolyticus cells.     

Enzymatic synthesis of [U-14C] ribose-labeled inosine.

A very potent anticholinesterase compound, 7-(diethoxyphosphinyloxy)-N-methylquinolinium fluorosulfate, has been used to determine the normality of acetylcholinesterase solutions. The inhibitor reacts rapidly and completely with acetylcholinesterase. The bimolecular rate constant is 2.5 × 10⁸m^?1 min^?1 and the equilibrium constant is about 10⁶. The reaction produces an inactive diethylphosphoryl enzyme in which the active serine is phosphorylated. The reaction produces the highly fluorescent 1-methyl-7-hydroxyquinolinium dipolar ion as a leaving group. The inhibited enzyme is quite stable and hydrolyzes to produce active enzyme only at the rate of 0.04%/min. The inhibitor was used in two ways for measuring the normality of acetylcholinesterase solutions: (1) The very fast reaction of the inhibitor with cholinesterase makes it convenient to determine the normality of enzyme solutions by measuring the decrease in enzyme activity caused by the addition of an accurately known quantity of the inhibitor. (2) The highly fluorescent nature of the leaving group makes it possible to measure the low concentration that is produced by the reaction of excess inhibitor with the enzyme. The two methods yielded activities per site of 6.9 × 10⁵ min^?1 and 7.3 × 10⁵ min^?1 using enzyme normalities of 1–2 × 10^?8m and 1–5 × 10^?m, respectively, using a commercial 11 S enzyme preparation from electric eel and acetylthiocholine as the enzyme substrate.     

Transport of C4-dicarboxylic acids in salmonella typhimurium.

C₄-Dicarboxylic acids are transported into Salmonella typhimurium by stereospecific systems of both high and low affinity. Succinate and l-malate are accumulated in a tricarboxylic acid cycle mutant as was d(+)-malate in induced wild-type cells. Accumulated dicarboxylates are exchangeable with exogenous dicarboxylates. The trichloroacetic acid cycle dicarboxylates are the best inducers of their own transport. Specific mutants devoid of dicarboxylate transport activity (dct) were isolated and differed from tricarboxylate transport mutants (tct) with respect to growth and transport. A mutant devoid of α-ketoglutarate dehydrogenase was unable to transport dicarboxylic acids but citrate transport remained unaffected. Tricarboxylic acid cycle mutants were markedly dependent on an exogenous energy source for the transport of succinate, proline, or leucine. Dicarboxylate transport was largely inhibited by various metabolic inhibitors but could only be inhibited by N,N'-dicyclohexylcarbodiimide anaerobically. ATPase mutants were unimpaired in their ability to transport succinate or proline aerobically.     

Multiplicity of induction patterns of rat liver microsomal mono-oxygenases and other polypeptides produced by administration of various xenobiotics.

Induction of hepatic microsomal mono-oxygenase species after administration of various xenobiotics is a well-documented phenomenon. To examine the number and specific species of rat liver microsomal membrane polypeptides involved in such responses, we have used sodium dodecyl sulphate/polyacrylamide-gel electrophoresis to analyse microsomal fractions from animals treated with a number of important xenobiotics. The following are the principal points to have emerged from this study. 1. A minimum of twelve electrophoretically distinct patterns of induction of haemopolypeptides and other polypeptides could be distinguished after administration, either singly or in certain combinations, of phenobarbital, 3-methylcholanthrene, polychlorinated biphenyls, 2-acetylaminofluorene, safrole (or isosafrole), pregnenolone-16 alpha-carbonitrile and ethanol. The patterns consisted of various permutations of the amounts of eight polypeptides of 47000-56000 mol.wt., of which at least three were haemopolypeptides. The possible identities of these polypeptides, which included species of cytochrome P-450, cytochrome P-448 and epoxide hydratase, are discussed. 2. Agents (3-methylcholanthrene, benzo[a]-pyrene, polychlorinated biphenyls, 2,3,7,8-tetrachlorodibenzo-p-dioxin and beta-naphthoflavone) that result in the induction of cytochrome P-448 caused a marked increase in two polypeptides of 54000 and 56000 mol.wt., whereas safrole and isosafrole induced only the former polypeptide. 3. Administration of 2-acetylaminofluorene resulted in the induction of two polypeptides; evidence is presented that suggests that one of these is a species of epoxide hydratase [cf. Levin, Lu, Thomas, Ryan, Kizer & Griffin (1978) Proc. Natl. Acad. Sci. U.S.A. 75, 3240-3243] ANd that the other may be a novel haemopolypeptide. 4. The overall results emphasize the complexity of the responses exhibited by rat liver microsomal fractions to the administration of xenobiotics.