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Biomedical subjects

R S Koff

Publications and source records attributed to R S Koff.

At least 73 records · Page 4Linked to original sources

Clinical manifestations and diagnosis of hepatitis A virus infection.

Hepatitis A is an acute, necroinflammatory disease of the liver which results from infection by the hepatitis A virus (HAV). The mean incubation period is approximately 30 days. Although the disease is usually self-limited, the severity of illness is age-dependent. In children, hepatitis A is usually asymptomatic, while in adults, symptomatic infection is characteristic and jaundice is common. Fulminant hepatitis A is rare and is also age-dependent. The onset of hepatitis A is often abrupt and characteristic prodromal symptoms are followed, within a few days to a week, by dark urine and jaundice. Mild to moderate tenderness over an enlarged liver is usually detected. Serum alanine and aspartate aminotransferase levels usually both rise rapidly during the prodromal period, reach peak levels and then decrease by approximately 75% per week. Serum bilirubin concentrations reach peak levels later and decline less rapidly than serum aminotransferases. Nonetheless, the period of jaundice persists for < 2 weeks in approximately 85% of cases. Nearly all adult patients with clinically apparent disease experience complete clinical recovery with restoration of normal serum bilirubin and aminotransferase values by 6 months. Relapses and prolonged cholestasis are unusual manifestations of hepatitis A, and even in these circumstances, recovery is the rule and chronic hepatitis is not seen. The diagnosis of hepatitis A requires the detection of immunoglobulin M antibody to HAV in a patient who presents with, or has recently had, clinical features of hepatitis (icteric or anicteric disease) or in an individual with inapparent, asymptomatic infection in whom serum aminotransferase elevations may be detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Long-term hepatic memory for hypersensitivity to nitrofurantoin.

Nitrofurantoin-induced hepatic injury has been established unequivocally as an entity by rechallenge experiences. We reviewed 12 previously reported cases in which rechallenge was described. The longest reported interval between initial injury and rechallenge-provoked injury was 4 yr. We report a 56-yr-old woman who experienced severe hepatocellular injury with brief low-dose administration of nitrofurantoin 17 yr after an initial hepatitis-like illness associated with ingestion of the drug. Despite a temporal relationship to nitrofurantoin administration and histologic features compatible with drug-induced hepatitis, the initial bout of hepatitis had been termed "infectious." Our case appears remarkable for the long interval between initial injury and rechallenge-induced injury. The severity of the hepatic injury seen on rechallenge underscores the concept that the inadvertent rechallenge can be dangerous. Failure to identify the first bout of hepatitis as nitrofurantoin-related, and failure to inform the patient about the possible relationship to nitrofurantoin, raises important risk-management concerns, because hepatic memory of nitrofurantoin hypersensitivity appears to be of long duration.

Chemical and Drug Induced Liver Injury↗

Effect of differentiation and cell density on glycosphingolipid class and molecular species composition of mouse neuroblastoma NB2a cells.

The effects of cell density and retinoic acid-induced differentiation on the class and molecular species composition of mouse neuroblastoma NB2a cell glycosphingolipids were examined under conditions where the period of culture was controlled. The total amount of neutral glycosphingolipids per cell decreased both with differentiation and as the cells became confluent. The relative amount of the neutral glycosphingolipid classes was not affected by differentiation, whereas there were small but significant changes in the relative amount of the neutral glycosphingolipid classes as the cells became confluent. The total amount of the gangliosides was unaffected by either differentiation or cell density, but there were significant changes in the ganglioside class composition as a result of both cell density and differentiation, and the effects were additive. The molecular species of all the major neutral glycosphingolipid and ganglioside classes were essentially identical, and were altered only slightly by either differentiation or cell density.

Animals↗

Feedback EEG in the detection of subclinical hepatic encephalopathy: a preliminary report.

The detection, monitoring, and quantification of subclinical hepatic encephalopathy present difficult problems for the clinician caring for patients with liver disease. Traditionally, pencil and paper tests such as signature-writing have been used at the bed-side to measure early encephalopathy. More recently, the Trail-making test has been employed to detect and quantify encephalopathic changes. While the electroencephalogram has provided information about the extent of clinically-obvious encephalopathy, it has only recently proved useful in the detection of subclinical disease. In these cases, evoked potentials and spectral analysis methods have discriminated between 35 and 62% of patients with subclinical hepatic encephalopathy. The present study used the method of feedback electroencephalography to detect and quantify differences in cortical arousal in 5 cirrhotic patients and 5 normal age-matched controls. Subject were also compared with respect to baseline measures of cortical arousal. Finally, arousal during feedback EEG stimulation was correlated with Trail-making test performance. The data revealed that cirrhotic patients can be discriminated from normal controls by baseline (80% detection) and feedback stimulation conditions (100% detection). In addition, feedback EEG reactivity (cortical arousal) was inversely correlated with Trail-making test performance (-0.86, P less than 0.01). The results indicate that simple features of the conventional EEG can reliably discriminate cirrhotic patients from normals. Clinical application of the feedback method in other metabolic encephalopathies, as well as in hypoaroused states secondary to, for example, narcolepsy, is discussed.

Brain↗

Lactosylceramide molecular species specificity of rat liver CMP-N-acetylneuraminate:lactosylceramide sialyltransferase.

Six naturally occurring and three synthetic molecular species of lactosylceramide (LacCer) were used to examine the molecular species specificity of CMP-N-acetylneuraminate:lactosylceramide alpha 2,3-sialyltransferase in a Golgi-rich fraction of rat liver. The enzyme molecular species specificity was determined either in the presence of nonspecific lipid transfer protein or in the presence of detergents. Assays performed in the presence of transfer protein showed that for those lactosylceramide molecular species with either d18:1 or d18:0 long chain base the enzyme activity decreased linearly as the effective carbon number of the fatty acid increased. An increase in the carbon number of the long chain base decreased the activity of the enzyme twice as much as a corresponding increase in the carbon number of the fatty acid. On the other hand, when the enzyme activity was assayed in the presence of detergents, there was no significant difference in activity among the various molecular species of lactosylceramide based upon the carbon number of the fatty acid or on the presence of a double bond in the long chain base. However, the decrease in enzyme activity with an increase in the carbon number of the long chain base persisted. These results demonstrate that sialyltransferase has binding specificity with respect to the long chain base, but not the fatty acid. The apparent molecular species towards the fatty acid is related to the aqueous solubility of the various LacCer molecular species.

Animals↗

Separation of derivatized glycosphingolipids into individual molecular species by high performance liquid chromatography.

The high performance liquid chromatography separation of the perbenzoyl derivatives of the neutral glycosphingolipids (GlcCer, LacCer, GbOse3Cer, GbOse4Cer, and GgOse3Cer) and the p-bromophenacyl and 2,4-dinitrophenyl hydrazide derivatives of the gangliosides (GM4, GM3, GM2, GM1, GD1a) into individual molecular species on a C18 reversed-phase column is described. Peaks were identified by comparing their relative retention times to the relative retention time of the corresponding glycosphingolipid of known molecular species composition. As little as 5 to 10 pmol of each molecular species of neutral glycosphingolipids and 3 to 5 pmol of the gangliosides can be detected. The effects of changes in the proportion of acetonitrile, methanol, and water in the mobile phase and of column temperature on the molecular species separation are described. A procedure for the tentative identification of glycosphingolipid molecular species based on their relative retention times is presented.

Chromatography, High Pressure Liquid↗

Nonspecific lipid transfer protein in the assay of a membrane-bound enzyme CMP-N-acetyl-neuraminate:lactosylceramide sialyltransferase.

CMP-N-acetylneuraminate:lactosylceramide alpha-2,3-sialyltransferase is tightly associated with the luminal side of the Golgi membrane as is its lipid substrate, lactosylceramide. In order to understand the kinetics, properties, and regulation of this enzyme, it is necessary to alter the amount and type of substrate in the membrane while minimizing changes in the membrane environment or in the conformation of the enzyme. Therefore, nonspecific lipid transfer protein, which accelerates the transfer of phospholipids, cholesterol, and glycosphingolipids between membranes was used to study the properties and kinetics of rat liver CMP-N-acetylneuraminate:lactosylceramide sialyltransferase. These results are compared to those obtained in parallel experiments using detergent-solubilized substrate. Enzyme activity was increased four- to fivefold by transfer protein and was consistently higher than the activity measured in the presence of detergents. In contrast to the results obtained with detergents, the enzyme activity increased linearly with both Golgi protein and with incubation time for up to 60 min. The Km values for the water-soluble substrate, CMP-neuraminic acid, were virtually identical when determined in the presence of transfer protein (0.23 mM) or detergents (0.27 mM). On the other hand, the apparent Km values for the lipophilic substrate, lactosylceramide, were markedly different when determined in the presence of transfer protein (47.9 microM) or in the presence of detergents (1.2 microM). These observations suggest that transfer protein is a useful tool to study the properties and kinetics of membrane-bound enzymes when both the enzyme and substrate are components of the same membrane.

Animals↗