Ultrasonic diagnosis of meniscus lesions

Controversy exists about the value of ultrasonography of meniscal tears. We therefore examined 101 knee joints of 99 patients in a prospective study. Prior to the arthroscopy the menisci were scanned from an independent team by using 7.5 and 10.0 MHz ultrasound waves. 81 meniscal tears were seen at arthroscopy; 36% of these tears could not be detected with the scanner (? false negative results) while 20% of intact menisci showed positive echogenic structures, which were analysed as meniscal tears. It seems that ultrasonography of the menisci is still of experimental use without any clinical importance.     

beta-Hydroxybutyrate fuels synaptic function during development. Histological and physiological evidence in rat hippocampal slices.

To determine whether ketone bodies sustain neuronal function as energy substrates, we examined the effects of beta-hydroxybutyrate (betaHB) on synaptic transmission and morphological integrity during glucose deprivation in rat hippocampal slices. After the depression of excitatory postsynaptic potentials (EPSPs) by 60 min of glucose deprivation, administration of 0.5-10 mM D-betaHB restored EPSPs in slices from postnatal day (PND) 15 rats but not in slices from PND 30 or 120 rats. At PND 15, adding D-betaHB to the media allowed robust long-term potentiation of EPSPs triggered by high frequency stimulation, and prevented the EPSP-spike facilitation that suggests hyperexcitability of neurons. Even after PND 15,D-betaHB blocked morphological changes produced by either glucose deprivation or glycolytic inhibition. These results indicate that D-betaHB is not only able to substitute for glucose as an energy substrate but is also able to preserve neuronal integrity and stability, particularly during early development.     

Breast cancer: locoregional recurrence and subsequent disease course]

The survival of 409 patients with breast cancer treated by surgery +/- adjuvant therapy is controlled in a retrospective study. 65 (15.9%) patients subsequently suffered from loco-regional recurrences. 41 (63.1%) of these patients showed either simultaneously with the loco-regional recurrence or at the latest within 2 1/2 years after the diagnosis of the loco-regional recurrence distant metastasis. The incidence of the distant metastasis is the more probable the shorter the interval between the primary treatment and the occurrence of the loco-regional recurrence. More prognostic factors for the survival after the diagnosis of the loco-regional recurrence are discussed.     

Hämaturie und Proteinurie im Kindesalter

Zusammenfassung Hämaturie und Proteinurie sind häufige Befunde im Kindesalter. Die Aufgabe des Kinderarztes ist es, beim Auftreten dieser Symptome die Dringlichkeit weiterer Untersuchungen abzuschätzen und diese evtl. durchzuführen, um die zugrunde liegenden Erkrankungen aufzudecken. Algorithmen zu Hämaturie und Proteinurie, die in dieser Mitteilung vorgestellt und diskutiert werden, sollen eine gezielte Diagnostik ermöglichen und überflüssige Untersuchungen vermeiden.     

Functional substitution of the TibC protein of enterotoxigenic Escherichia coli strains for the autotransporter adhesin heptosyltransferase of the AIDA system

The plasmid-encoded AIDA (adhesin involved in diffuse adherence) autotransporter protein derived from diffuse-adhering clinical Escherichia coli isolate 2787 and the TibA (enterotoxigenic invasion locus B) protein encoded by the chromosomal tib locus of enterotoxigenic E. coli (ETEC) strain H10407 are posttranslationally modified by carbohydrate substituents. Analysis of the AIDA-I adhesin showed that the modification involved heptose residues. AIDA-I is modified by the heptosyltransferase activity of the product of the aah gene, which is located directly upstream of adhesin-encoding gene aidA. The carbohydrate modification of the TibA adhesin/invasin is mediated by the TibC protein but has not been elucidated. Based on the sequence similarities between TibC and AAH (autotransporter adhesin heptosyltransferase) and between the TibA and the AIDA proteins we hypothesized that the AIDA system and the Tib system encoded by the tib locus are structurally and functionally related. Here we show that (i) TibC proteins derived from different ETEC strains appear to be highly conserved, (ii) recombinant TibC proteins can substitute for the AAH heptosyltransferase in introducing the heptosyl modification to AIDA-I, (iii) this modification is functional in restoring the adhesive function of AIDA-I, (iv) a single amino acid substitution at position 358 completely abolishes this activity, and (v) antibodies directed at the functionally active AIDA-I recognize a protein resembling modified TibA in ETEC strains. In summary, we conclude that, like AAH, TibC represents an example of a novel class of heptosyltransferases specifically transferring heptose residues onto multiple sites of a protein backbone. A potential consensus sequence for the modification site is suggested.     

Pore formation by the Escherichia coli hemolysin: evidence for an association-dissociation equilibrium of the pore-forming aggregates.

Lipid bilayer experiments were performed in the presence of hemolysin of Escherichia coli. The toxin had a rather low activity in membranes formed of pure lipids, such as phosphatidylcholine or phosphatidylserine. In membranes from asolectin, a crude lipid mixture from soybean, hemolysin was able to increase the conductance by many orders of magnitude in a steep concentration-dependent fashion, which suggested that several hemolysin molecules could be involved in the conductive unit. Furthermore, the much higher toxin activity in asolectin membranes would be consistent with the assumption that this lipid contains a receptor needed for membrane activity of the toxin. The results of single-channel records showed that the membrane activity of hemolysin is due to the formation of ion-permeable channels with a single-channel conductance of about 500 pS in 0.15 M KCl. The hemolysin channel seemed to be formed by a toxin oligomer which showed an association-dissociation reaction and had a mean lifetime of about 2 s at small transmembrane voltages. The conductance of the hemolysin channels was only moderately dependent on the salt concentration in the aqueous phase. Zero-current membrane potential experiments showed that the hemolysin channel is cation selective. The mobility sequence of the cations in the channel was similar to their mobility sequence in the aqueous phase, which was consistent with the assumption that the hemolysin channel is wide and that the interior field strength is not very high. From the single-channel conductance, a lower limit of about 1.0 nm for the effective channel diameter could be estimated.     

Messenger RNA processing sites in Trypanosoma brucei

In Kinetoplastids, protein-coding genes are transcribed polycistronically by RNA polymerase II. Individual mature mRNAs are generated from polycistronic precursors by 5' trans splicing of a 39-nt capped leader RNA and 3' polyadenylation. It was previously known that trans splicing generally occurs at an AG dinucleotide downstream of a polypyrimidine tract, and that polyadenylation is coupled to downstream trans splicing. The few polyadenylation sites that had been examined were 100-400 nt upstream of the polypyrimidine tract which marked the adjacent trans splice site. We wished to define the sequence requirements for trypanosome mRNA processing more tightly and to generate a predictive algorithm. By scanning all available Trypanosoma brucei cDNAs for splicing and polyadenylation sites, we found that trans splicing generally occurs at the first AG following a polypyrimidine tract of 8-25 nt, giving rise to 5'-UTRs of a median length of 68 nt. We also found that in general, polyadenylation occurs at a position with one or more A residues located between 80 and 140 nt from the downstream polypyrimidine tract. These data were used to calibrate free parameters in a grammar model with distance constraints, enabling prediction of polyadenylation and trans splice sites for most protein-coding genes in the trypanosome genome. The data from the genome analysis and the program are available from: .     

Expression of NK-associated surface-antigens cd-56 and cd-16 on aml-cells

Monoclonal antibodies Leu 11a (CD16) and Leu 19 (CD56) were tested for reactivity with cells from 36 patients with acute myelogenous leukemia (AML) using two-colour flow cytometry. Blast cells were identified by a broad panel of monoclonal antibodies. In 33% (12/36) the monoclonal antibody Leu 19, which has been demonstrated to bind to the 140 kD isoform of the human neural cellular adhesion molecule N-CAM, found on peripheral natural killer (NK)-cells, neuroectodermal cells, activated T-cells, and myeloma cells, was shown to bind strongly to the leukemic cells. The monoclonal antibody Leu 11a, which recognizes a surface differentiation antigen associated with the low affinity FcRIII for IgG, expressed on NK-cells, granulocytes and macrophages were found to bind to leukemic cells of four of the 12 Leu-19 positive cases. 50% (6/12) of Leu-19 positive patients were classified as having M4 according to the French-American-British (FAB) morphology criteria. The potential diagnostic and clinical importance of CD 56 and/or CD 16 expression in acute myelogenous leukemia is presently under investigation.     

Effect of de novo purine synthesis inhibitors on 5-fluorouracil metabolism and cytotoxicity

Methotrexate pretreatment of L1210 cells had been shown previously by us to cause an enhancement of the intracellular accumulation of 5-fluorouracil and of the formation of 5-fluorouracil nucleotides which was correlated with synergistic cytotoxicity. This effect of methotrexate was associated with increases in 5-phosphoribosyl-1-pyrophosphate, the cofactor required for the conversion of 5-fluorouracil to 5-fluorouridine-5'-monophosphate (FUMP). Because these influences on 5-fluorouracil metabolism were most likely mediated by the activity of methotrexate as an inhibitor of purine synthesis, the effects of other agents that inhibit purine synthesis were examined. An inhibitor of amidophosphoribosyltransferase, 6-methylmercaptopurine ribonucleoside, the glutamine antagonists, azaserine and 6-diazo-5-oxo-L-norleucine (DON), and the L-aspartate analogue inhibitor of adenylsuccinate synthetase, L-alanosine, all reduced the incorporation of [1-14C]glycine into adenine and guanine bases isolated from nucleic acids. Each drug also resulted in intracellular elevations of 5-phosphoribosyl-1-pyrophosphate that were 15- to 25-fold greater than control levels. These alterations in de novo purine nucleotide synthesis were associated with enhanced intracellular 5-fluorouracil accumulation and synergistic cytotoxicity.     

Does glucagon stimulation predict oral glucose tolerance in patients after simultaneous pancreas-kidney transplantation?

BACKGROUNDS: Exogenous glucagon rapidly stimulates insulin secretion. This test has been used to estimate insulin secretory capacity, which may predict oral glucose tolerance in patients after pancreas transplantation. METHODS: In 32 pancreas-kidney transplant recipients, in 10 nondiabetic kidney transplant recipients, and in 9 healthy control subjects, a glucagon stimulation test (1 mg i.v.) and a 75-g oral glucose tolerance test were performed with determination of glucose, insulin, and C-peptide profiles. RESULTS: Of 16 pancreas transplant recipients with the lowest insulin responses after glucagon, 7 had an impaired oral glucose tolerance, in contrast to 1 of 16 with high insulin responses (P=0.037). A low insulin response after glucagon was associated with significantly lower 120-min glucose concentrations (P=0.043) and a lower integrated incremental insulin response after oral glucose (P=0.006). CONCLUSIONS: In pancreas-kidney transplant recipients, a low insulin response after intravenous glucagon predicts a reduced insulin response after oral glucose and an impaired oral glucose tolerance. This simple test may be helpful in the follow-up of pancreas transplant recipients.