CARBOHYDRATE-DEFICIENT TRANSFERRIN AS A SCREENING MARKER FOR DRINKING IN A GENERAL HOSPITAL POPULATION

We investigated the usefulness of the laboratory marker of alcoholconsumption carbohydrate-deficient transferrin (CDT) in 101consecutively admitted patients in a surgical and internal medicalward of a hospital in a rural wine-growing area. Four majoraspects were considered: the influence of liver disease, themethod of expression of CDT values (relative % vs absolute units/1),level and pattern of alcohol consumption and comparison with     

Phenytoin modulates the pharmacokinetics of prednisolone and the pharmacodynamics of prednisolone as assessed by the inhibition of the mixed lymphocyte reaction in humans

Following induction of the microsomal liver enzymes, lower total prednisolone concentrations in plasma and an altered pattern of the prednisolone metabolites generated were observed. The purpose of the present study was to establish whether--as a consequence of an enhanced clearance--lower unbound concentrations of prednisolone in plasma are detectable after enzyme induction and to determine if the altered prednisolone metabolism modulates the biological effect. Before and during phenytoin dosage in ten volunteers, the mean (+/-SD) total body clearance (ml min-1 kg-1) of both total and unbound prednisolone increased from 2.74 +/- 0.47 to 3.94 +/- 0.66 (P less than 0.001) and from 10.76 +/- 2.68 to 16.00 +/- 3.17 (P less than 0.001), respectively. These increments were due to increased non-renal clearances. The immunosuppressive activity as a function of time in plasma determined as the percent inhibition of the mixed lymphocyte reaction decreased by one third after phenytoin dosing, while the EC50 values of unbound prednisolone were unaffected. Thus enzyme induction decreases both the unbound prednisolone concentration and the steroid efficacy.     

PRIMARY STRUCTURE OF LOBSTER-MUSCLE ARGININE KINASE: Amino and Carboxyl-terminal Structure of the Enzyme and Complete Alignment of the Cyanogen-Bromide Peptides

The acetylation state of the blocked NH₂-terminal end of arginine kinase was characterized by the occurrence of 1 mol acetyl group/mol protein; a 5-residue segment corresponding to the amino-terminal portion was isolated from a pronase digest of the enzyme and its amino acid sequence determined as N-acetyl Ala-Asx-Ala-Ala-Thr. Arginine kinase is terminated at the carboxyl end by the sequence Lys-Glu-MetOH; this particular 3-residue sequence is repeated three times in the overall structure of the protein and is present in three CNBr fragments. One of these, a peptide of 14 amino acid residues, was identified in the course of this study and its amino acid sequence determined. Its location at the COHO-terminal end of the enzyme was recognized on the basis of investigations carried out with des-MetOH-Glu-arginine kinase, a specific proteolytic derivative. The alignment of the eight CNBr-fragments which constitute the arginine kinase molecule was established according to the sequential and compositional properties of seven unique tryptic methionyl peptides isolated from the whole protein. The alignment was confirmed by using BNPS-skatole fragments of the enzyme as another protein source.     

Project Megapoles: Promoting better health for socially disadvantaged groups across Europe

A new public health network is looking at ways of achievingbetter health and reducing differences in health between Europe'scapital cities. A report from the Socially Disadvantaged Groupssub-network of Megapoles.     

ALCOHOL DEPENDENCE: IS CARBOHYDRATE-DEFICIENT TRANSFERRIN A MARKER FOR ALCOHOL INTAKE?

We investigated %CDT (carbohydrate-deficient transferrin) in92 ethanol-intoxicated alcohol-dependent patients after consecutiveadmission to hospital and followed them for 28 days under controlledconditions. At admission, 63% (58 patients) showed elevatedCDT (>2.5%) and 34 patients (37%) had normal CDT levels (<2.5%).No correlation of the %CDT values to alcohol-related disabilities,severity of the withdrawal syndrome, alcohol-drinking patternbefore admission, or several other factors was found. The sensitivityof GGT (     

Case Report: Secondary biliary cirrhosis possibly related to congenital hepatic fibrosis. Evidence for decreased number of portal branch veins and hypertrophic peribiliary vascular plexus

A 30-year-old man with presinusoidal portal hypertension was transplanted for cryptogenic cirrhosis. On the explanted liver, few intrahepatic stones, biliary cirrhosis, chronic cholangitis of the large bile ducts and a peculiar proliferation of small dilated bile ducts at the periphery of the portal tracts led to the diagnosis of secondary biliary cirrhosis and cholangitis, possibly linked to ductal plate malformation, including congenital hepatic fibrosis associated with a minor form of Caroli's disease. Ex vivo portogram and histology showed the paucity of portal vein branches and the hypertrophy of the peribiliary vascular plexus. This hypertrophy, which has been reported in livers with presinusoidal hypertension, is another indirect argument to suggest the diagnosis of congenital hepatic fibrosis.     

Different cortical activation patterns in blind and sighted humans during encoding and transformation of haptic images

In this study, we investigated whether the occipital cortex of blind humans is activated during haptic perception and/or transformation of a haptic image. Slow event-related brain potentials were monitored from 18 electrodes in 12 sighted and 15 congenitally blind participants while they were engaged in a haptic mental rotation task. In both groups, slow negative shifts appeared over (a) the frontal cortex at the beginning of each processing episode, (b) the left-central to parietal cortex during encoding and maintaining of a haptic image, and (c) the central to parietal cortex during image transformation. A pronounced slow negative potential over the occipital cortex emerged only in the blind individuals and was time-locked to the processing epochs. Its amplitude increased with the amount of processing load. The slow wave effects observed in the blind individuals could indicate that occipital areas participate in specific, nonvisual functions or they could reflect a coactivation of these areas whenever the activation level of task-specific processing modules located elsewhere in the cortex is raised by nonspecific thalamocortical input.     

Trypanosoma brucei infection in nude mice: B lymphocyte function is suppressed in the absence of T lymphocytes

B lymphocyte function was assessed in outbred nude mice and nu/+controls infected with Trypanosoma brucei brucei. On day 10 of the infection in outbred nu/nu mice in which the initial wave of parasites was strongly controlled, B cell function was unaltered on enhanced compared with uninfected animals or infected nu/+. In other nu/nu mice unable to control the initial parasitaemia, thymidine incorporation and Ig secretion by spleen cells were increased on day 10 and their response to lipopolysaccharide in vitro negated. By day 15 however, even the spleen cells of infected nu/nu which controlled the initial wave of parasites were proliferating and secreting Ig on removal from the mice and they were unable to respond to LPS in vitro. These experiments confirm results of a previous study of B cell function in T cell-depleted mice (Askonas et al. 1979). T. b. brucei infection of mice causes both enhanced Ig production and suppression of the ability of B cells to respond to mitogen even in the absence of T cells, but the presence of T cells may accelerate the changes which occur in B lymphocytes following this infection.     

Cerebral vasculitis in severe Kawasaki disease: early detection by magnetic resonance imaging and good outcome after intensive treatment

Kawasaki disease is an acute vasculitis, that has a classic complication of acquired coronary artery aneurysm. Severe forms with multi‐organ involvement or neurological dysfunction are rare. Cerebral vascular involvement has been related to large‐vessel injury or cardioembolism, leading to focal brain infarction. A 4‐year‐old female presented with unusual, rapidly catastrophic Kawasaki disease with refractory shock, acute renal failure, and coma, requiring intensive haemodynamic management. The observation of diffuse micro‐haemorrhages (T2*‐weighted sequence) associated with white matter injury on brain magnetic resonance imaging (MRI) pointed towards lesions of the medium/small blood vessels. Cerebral vasculitis was suspected and the immunosuppressive treatment was increased Subsequently, the patient’s recovery was rapid. On follow‐up severe, bilateral vitritis was evident and surgery improved visual outcome. Early recognition of severe or unusual forms of Kawasaki disease could lead to more favourable outcome using appropriate treatment strategies. Diffuse cerebral micro‐haemorrhages on T2* brain MRI sequences might be a key sign for the diagnosis of medium or small cerebral vessel involvement.     

Synthesis of a metal binding protein designed on the α/β scaffold of charybdotoxin*

The α/β scaffold of the scorpion toxin charybdotoxin has been used for the engineering of a metal binding site. Nine substitutions, including three histidines as metal ligands, have been introduced into the original toxin sequence. The newly designed sequence, 37 amino acids long, has been assembled by solid-phase synthesis and HBTU (2-(1H-benzotriazol-l-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate) coupling of Fmoc-protected amino acids. Formation of the three disulfide bonds occurred efficiently and rapidly in the presence of glutathione, and this post-synthesis modification has facilitated the purification task enormously. The process of synthesis and purification was performed in less than a week with an overall 10.2°, yield. Circular dichroism analysis showed that the newly designed protein is folded in a α/β structure, similarly to the parent toxin. Electronic absorption spectroscopy, circular dichroism and gel filtration experiments have been used to show that Cu²⁺ and Zn²⁺ ions bind with high affinity to the newly engineered protein. These results demonstrate that the α/β fold, common to all scorpion toxins, is a very versatile basic structure, tolerant for substitutions and able to present new sequences in a predetermined conformation. The chemical approach is shown to be effective, rapid and practical for the production of novel designed small proteins. © Munksgaard 1995.