2 ) for >6 mo. Analysis was by intention to treat. A single patient (3.1%) in the ACE-I group and five (14.7%) in the placebo group showed a worsening of CrCl >30%. The composite end point of >30% decrease of CrCl or worsening of proteinuria until nephrotic range was reached by one (3.1%) of 32 patients in the ACE-I group, and nine (26.5%) of 34 in the placebo group; the difference was significant (log-rank P ‫؍‬ 0.035). A stable, partial remission of proteinuria was observed in 13 (40.6%) of 32 patients in the ACE-I group versus three (8.8%) of 34 in the placebo group (log-rank P ‫؍‬ 0.033), with total remission in 12.5% of ACE-I-treated patients and in none in the placebo group (log-rank P ‫؍‬ 0.029). The multivariate Cox analysis showed that treatment with ACE-I was the independent predictor of prognosis; no influence on the composite end point was found for gender, age, baseline CrCl, systolic or diastolic BP, mean arterial pressure, or proteinuria.

No abstract

An increasing number of scrapie cases with atypical characteristics, designated Nor98, have recently been recognized. Here, the proteinase K (PK)-resistant prion protein (PrP) fragments from two Swedish cases of Nor98 atypical scrapie have been characterized. The prominent, fast-migrating band in the distinct Nor98 Western immunoblot electrophoretic profile was determined to be of 7 kDa in size and was accordingly designated Nor98-PrP7. The antigenic composition of Nor98-PrP7, as assayed by a panel of anti-PrP antibodies, revealed that this fragment comprised a mid-region of PrP from around aa 85 to 148. N-and C-terminally truncated fragments spanning the mid-region of PrP have only been observed in the genetic prion disorder Gerstmann-Strä ussler-Scheinker disease. It is shown here that the long-term PK resistance of Nor98-PrP7 is reduced compared with that of PrP res in classical scrapie. Enzymic deglycosylation did not change the distinct electrophoretic profile of Nor98-PrP7. A previously unidentified, PK-resistant, C-terminal PrP fragment of around 24 kDa was detected and its PK resistance was investigated. After deglycosylation, this fragment migrated as a 14 kDa polypeptide and was designated PrP-CTF14. Antigenic determination and the size of 14 kDa suggested a fragment spanning approximately aa 120-233. The existence of two PK-resistant PrP fragments, Nor98-PrP7 and PrP-CTF14, that share an overlapping region suggests that at least two distinct PrP conformers with different PK-resistant cores are present in brain extracts from Nor98-affected sheep. The structural gene of PrP in three Nor98-affected sheep was analysed, but no mutations were found that could be correlated to the aberrant PK-resistant profile observed.

A prospective study to determine the value of cerebrospinal fluid analysis in the differential diagnosis of meningitis was performed in 710 consecutively observed patients, both children and adults, who underwent lumbar puncture due to suspected central nervous system infection. Diagnoses included acute or presumed bacterial meningitis (n = 79), acute or presumed viral meningoencephalitis (n = 218), acute unclassified meningitis (n = 6), other infections of the central nervous system (n = 37), non-infectious neurological diseases (n = 76) and control patients (n = 294). The sensitivity, specificity and predictive values were determined for cerebrospinal fluid white blood cell count, total protein, lactate, glucose and C-reactive protein levels as well as the blood/cerebrospinal fluid glucose ratio. Determination of cerebrospinal fluid levels of lactate (greater than or equal to 3.5 mmol/l) was found to be superior to the other tests. The C-reactive protein level gave no additional diagnostic information when the lactate level was determined. The white blood cell count, and total protein and glucose levels were often unreliable tools for differential diagnosis, largely due to low sensitivity at realistic discriminatory limits. The study confirms that no cerebrospinal fluid test is fully reliable in distinguishing bacterial meningitis from other forms of meningitis.

The virus‐coded 72000‐Mr DNA‐binding protein from adenovirus‐type‐2‐infected cells has been purified to homogeneity by DEAE‐cellulose chromatography, selective precipitation and gel filtration. The 72000‐Mr DNA‐binding protein is phosphorylated and the phosphate is covalently linked predominantly to serine. Analysis of tryptic digests of the 32P‐labeled 72000‐Mr protein showed that the phosphate residue(s) is present in only one peptide. The DNA‐binding fraction contains an additional non‐phosphorylated protein with an approximate molecular weight of 45000. Tryptic peptide maps of [35S]methionine‐labeled 72000‐Mr and 45000‐Mr polypeptides are indistinguishable. The amino acid compositions of the 72000‐Mr and 45000‐Mr polypeptides show closely related distributions. An antiserum produced against the purified 72000‐Mr DNA‐binding protein precipitates both the 72000‐Mr and the 45000‐Mr protein from extracts of adenovirus‐infected cells. Immunofluorescence studies revealed DNA‐binding protein to be accumulated in characteristic structures in nuclei of the infected cells.

The prion protein (PrP) sequence of European moose, reindeer, roe deer and fallow deer in Scandinavia has high homology to the PrP sequence of North American cervids. Variants in the European moose PrP sequence were found at amino acid position 109 as K or Q. The 109Q variant is unique in the PrP sequence of vertebrates. During the 1980s a wasting syndrome in Swedish moose, Moose Wasting Syndrome (MWS), was described. SNP analysis demonstrated a difference in the observed genotype proportions of the heterozygous Q/K and homozygous Q/Q variants in the MWS animals compared with the healthy animals. In MWS moose the allele frequencies for 109K and 109Q were 0.73 and 0.27, respectively, and for healthy animals 0.69 and 0.31. Both alleles were seen as heterozygotes and homozygotes. In reindeer, PrP sequence variation was demonstrated at codon 176 as D or N and codon 225 as S or Y. The PrP sequences in roe deer and fallow deer were identical with published GenBank sequences.

The adenovirus type 2 DNA‐binding protein is phosphorylated. Alkaline phosphatase treatment removes phosphate groups resulting in a decrease in molecular weight from 72000 to 70000. The dephosphorylated protein binds to single‐stranded and double‐stranded DNA as well as the phosphorylated protein does. Controlled chymotrypsin treatment cleaves the DNA‐binding protein into two subspecies of Mr about 45000 and 25000. The 45000‐Mr polypeptide contains most of the methionine residues but no phosphate and binds to DNA. The 25000‐Mr polypeptide contains all the phosphate groups and shows no binding to DNA. Isoelectric focusing gels show heterogeneity of the DNA‐binding protein and 15 subspecies with different charges can be observed after partial dephosphorylation by alkaline phosphatase. After extensive dephosphorylation two or three basic species with a molecular weight around 70000 are observed. Quantitative immunoprecipitation from cells labeled to equilibrium with inorganic 32PO4 gives a molar ratio of phosphate to protein of 4–7 and direct chemical determination of the phosphate residues yields 4 mol Pi/mol protein. These results suggest that there exist subspecies of the protein moiety of the adenovirus DNA‐binding protein. The DNA‐binding protein isolated from infected cells after a short ‘pulse’ of [35S]methionine has a molecular weight which corresponds to that of the dephosphorylated protein. After a ‘chase’ period the molecular weight increases to 72000, but alkaline phosphatase treatment converts it to a species with the same molecular weight as the newly synthesized DNA‐binding protein, indicating that the modification of the protein is due to phosphorylation.

The relationship between urine interleukin-6 (IL-6) and interleukin-8 (IL-8)/creatinine quotients and 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy, performed within 10 days of acute first-time pyelonephritis and after 1 year, was studied in 41 children. The urine IL-6 and IL-8/creatinine quotients were also related to the urine N-acetyl-beta-D-glucosaminidase (NAG) and albumin/creatinine quotients. Presence of DMSA uptake defects, reflecting local inflammation, in children in the acute phase of pyelonephritis, were associated with elevated urine IL-6/creatinine quotients (median 27 pg/mumol); in children without DMSA changes there was no increase in quotients (median non-detectable) (P < 0.05). Persistent DMSA changes at the 1-year follow-up, probably reflecting renal scarring, were only seen in children with increased urine IL-6/creatinine quotients in the acute phase (P < 0.01). No correlation was found between urine IL-8 and DMSA uptake defects. Vesicoureteral reflux (VUR) at 6-8 weeks did not correlate with the urine cytokine levels in the acute phase. The urine excretion of NAG and albumin, reflecting renal dysfunction, was associated with values of both urine IL-6 and IL-8/creatinine quotients, but not with DMSA defects or VUR. Thus, the initial urine IL-6/creatinine quotients might be used as an indicator of risk for persistent renal damage in acute pyelonephritis.