The diagnosis of sporadic Creutzfeldt-Jakob disease (CJD) is based on typical clinical findings and is supported by a positive 14-3-3 Western blot of cerebrospinal fluid. However, it is not clear whether 14-3-3 indicates general neuronal damage or is of pathophysiological relevance in CJD. The fact that the 14-3-3 isoform spectrum in cerebrospinal fluid does not correspond to that found in the brain points to a regulated process. To investigate a possible role of 14-3-3 proteins in transmissible spongiform diseases, we generated a 14-3-3gamma-deficient mutant mouse line by using a classical knockout strategy. The anatomy and cage behavior of the mutant mice were normal. Western blot analyses of brain homogenates revealed no changes in the protein expression of other 14-3-3 isoforms (epsilon, beta, zeta, and eta). Proteomic analyses of mouse brains by two-dimensional differential gel electrophoresis showed that several proteins, including growth hormone, 1-Cys peroxiredoxin, CCT-zeta, glucose-6-phosphate isomerase, GRP170 precursor, and alpha-SNAP, were differentially expressed. Mutant and wild-type mice were inoculated either intracerebrally or intraperitoneally with the Rocky Mountain Laboratory strain of scrapie, but no differences were detected in the postinoculation survival rates. These results indicate that 14-3-3gamma is unlikely to play a causal role in CJD and related diseases.

Biochemical markers of brain damage, e.g. ischemic stroke, should reflect the volume of irreversibly damaged brain parenchyma and the clinical outcome in a single patient in order to allow estimation of prognosis at an early stage. Tau protein, which derives predominantly from neurons and axons, is elevated in the cerebrospinal fluid of patients with neurodegenerative disease. This makes tau protein a potential marker of neuronal/axonal injury. In order to test this hypothesis, the current study aimed at showing that tau protein is measurable in the blood after acute ischemic stroke and that it correlates with clinical disability and stroke volume. In a longitudinal prospective study we measured tau protein serum levels with an ELISA in 30 patients longitudinally after ischemic stroke. Tau protein was detectable within 5 days after ischemia in the sera of 7/20 patients with MRI-proven infarction and in 2/10 patients with transitory ischemic attack; both of them had a small infarction visible on the MRI scan. Tau protein was measurable within 6 h after symptom onset, peaked after 3-5 days and correlated with infarct volume and disability after 3 months. In conclusion, serum tau protein is a candidate marker of axonal injury. In stroke, its clinical use is limited, because it is detectable only in a proportion of patients.

14-3-3 proteins are involved in signalling processes in neuronal cells. Using isoform-specific antibodies we have examined the variation in 14-3-3 isoform neurolocation in normal and scrapie-infected murine brain and show that in defined areas of the brain there are significant changes associated with the pathology of the disease process. The appearance of 14-3-3 proteins in the cerebrospinal fluid (CSF) is a consequence of neuronal disease and the detection of specific isoforms of the 14-3-3 proteins in the CSF is characteristic of some neurodegenerative diseases. In this study, monitoring specifically for the gamma 14-3-3 isoform in the CSF by both Western-blot analysis and ELISA we can show a level of correlation between the assays.

Permanent neurological dysfunction is the primary medical concern of boxing. Recently it was reported that patients presenting elevated levels of the glial protein S-100B in serum after minor head injuries are more prone to develop neuropsychological deficits than patients with lower levels of S-100B protein. We assessed this protein before and after amateur boxing competitions (n =10)and sparring bouts (n = 15). In several control groups, we investigated S-100B levels of participants before and after a 25 km race (n=11), jogging (10 km, n=12), shortterm running (n = 12), and heading footballs (n =12). There was an increase in S-100B protein after boxing and the running disciplines but not after ergometer cycling or soft heading of footballs. The increase in S-100B protein concentrations due to competitive boxing and after the 25 km race was significantly higher than that after performing other disciplines (p<0.001). There was no significant difference between the increases caused by sparring and the running disciplines (p = 0.21). The number and severity of the strikes to the head correlated significantly with the increase in the S-100B protein levels. Levels of S-100B protein known to be associated with neuropsychological deficits were not reached in our study. In professional boxing, much higher levels are to be expected and would be worthy of investigation.

Following recent reports of elevated serum S100 beta protein (S100 beta) levels in patients with genetic and sporadic Creutzfeldt-Jakob disease and in rodents parenterally infected with scrapie, the suitability of serum S100 beta as a preclinical marker for transmissible spongiform encephalopathies was assessed in time-course studies. Syrian hamsters were orally and intraperitoneally challenged with scrapie and assayed for serum S100 beta levels at various times after infection. Although elevated serum S100 beta levels were consistently observed in terminally ill animals for both routes of infection, the experiments failed to detect significantly increased S100 beta serum concentrations prior to the manifestation of clinical symptoms. Thus, in this animal model, serum S100 beta does not appear to be an appropriate marker for the preclinical detection of scrapie, but it may provide a convenient laboratory aid for the diagnosis of transmissible spongiform encephalopathy in naturally or accidentally infected animals and humans.

A Drosophila melanogaster mutant, fs(1)pyr Su(b) , carrying a mutation that maps to the tip of the X chromosome, has been isolated. The mutation, when present alone, does not confer a detectable phenotype. However, this mutation causes female sterility and reduces embryonic viability when combined with mutations which deregulate the pyrimidine and β-alanine pools. Embryos that are homozygous for the mutations fs(1)pyr Su(b) , r Su(b) [previously designated as Su(b) ] and b , and originate from a female parent homozygous for the three mutations show severely reduced viability. Newly laid eggs begin development normally, but the majority of the embryos die just before the eggs are due to hatch.

Two-dimensional polyacrylamide gel electrophoresis of CSF has been used in the diagnosis of Creutzfeldt-Jakob disease (CJD). One of the two diagnostic protein spots was identified as isoform(s) of the 14-3-3 family of abundant brain proteins. This has led to the development of one-dimensional 14-3-3 sodium dodecyl sulfate polyacrylamide gel electrophoresis immunoblot, which is currently used to support the diagnosis of CJD. In the present study employing western blot analysis, we have identified the panel of 14-3-3 isoforms that appear in the CSF of 10 patients with CJD compared with 10 patients with other dementias. The results clearly show that the 14-3-3 isoforms beta, gamma, epsilon, and eta are present in the CSF of patients with CJD and can be used to differentiate other dementias. 14-3-3eta also gave a baseline signal in all patients with other dementias, including six patients with Alzheimer's disease. The presence of 14-3-3eta in the CSF of a patient with herpes simplex encephalitis was particularly noteworthy. This study has determined that isoform-specific 14-3-3 antibodies against beta, gamma, and epsilon should be considered for the neurochemical differentiation of CJD from other neurodegenerative diseases.

Neuropsychiatric symptoms due to any type of dysfunction and/or portal-systemic shunting are summarized as hepatic encephalopathy (HE). HE in the presence of liver cirrhosis and/or portal-systemic shunting has been termed portal-systemic encephalopathy (PSE). PSE is most frequent among the HE syndromes and is almost exclusively seen in patients with advanced cirrhosis and portal hypertension. Portal-systemic shunting either spontaneous due to portal hypertension, following surgical portocaval anastomosis, or subsequent to transjugular intrahepatic portosystemic stent-shunt (TIPSS) is regarded as the primary causative condition for PSE, not hepatic dysfunction per se. PSE may be considered as a disorder of multiple neurotransmitter systems among which derangements of the serotonergic system have been documented most consistently. Incipient PSE is frequently paralleled by the occurrence of sleep disorders, however, their relation to PSE remains unclear. We observed a transient increase of sleep disorders post-TIPSS, which were only in part correlated to other symptoms of PSE. Among the biochemical parameters studied only an association between arterial ammonia levels and sleep disorders became apparent, whereas no significant relation was observed for peripheral tryptophan.

Recently, immunoluminometric analysis revealed elevated levels of serum SlOO beta protein in sporadic and genetic cases of Creutzfeldt-Jakob disease (CJD) as compared to demented and non-demented control patients (Otto et al, 1998). SlOO beta protein is a well established marker for the activation of astrocytes and also shows enhanced histochemical presentation in Alzheimer's disease (Sheng et al, 1997). Thus, it will be necessary to precisely assess the specificity of the new test for human transmissible spongiform encephalopathies (TSE) in larger study populations.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of unknown origin characterized by loss of upper and lower motor neurons and concomitant astrogliosis. We have investigated the S100 beta protein levels in serum as a marker for astroglia of patients with ALS (n = 41) in comparison to a control group (n = 32). Additionally we have investigated 12 patients at different follow-up time points (minimum 6 months). We could not observe a significant difference of S100 beta protein in patients with ALS in comparison to our control group (P = 0.11) but we could clearly see a decrease of S100 beta levels in the further course of the disease. As S100 beta is also seen as a protein with nerve growth factor activity we assume that the fall of serum levels may reflect the loss of nerve growth stimulation in patients with ALS and suppose that repetitive measurements of S100 beta in serum can be used as an objective marker for disease progression.

Pyrimidine nucleotides play a central role in cellular metabolism and regulation. In most organisms two pathways provide pyrimidines: the de novo biosynthetic pathway and the salvage pathway. Drosophila melanogaster, the fruit fly, is an ideal organism for study of the genetic basis and regulatory mechanisms of various metabolic pathways. De novo pyrimidine biosynthesis in the fruit fly is a six-step pathway, which is catalyzed by enzymes encoded by three separate genes (Freund and Jarry, 1987; Rawls et al., 1993; Eisenberg et al., 1993). The gene rudimentary (r) is Drosophila’s equivalent of the mammalian gene for CAD (Freund and Jarry, 1987). De novo pyrimidine biosynthesis is important for the proper development of flies. However, the salvage pathway can suffice when the external supply of pyrimidines is very high (Falk and Nash, 1974).

HereditasVolume 99, Issue 2 p. 309-310 Open Access Suppression of the semidominant Suppressor of black by rudimentary mutants in Drosophila melanogaster E. BAHN, E. BAHN Institute of Genetics, University of Copenhagen, DenmarkSearch for more papers by this authorL. SØNDERGAARD, Corresponding Author L. SØNDERGAARD Institute of Genetics, University of Copenhagen, Denmark*Institute of Genetics, 0ster Fari-magsgade 2 A, DK-1353 Copenhagen K, DenmarkSearch for more papers by this author E. BAHN, E. BAHN Institute of Genetics, University of Copenhagen, DenmarkSearch for more papers by this authorL. SØNDERGAARD, Corresponding Author L. SØNDERGAARD Institute of Genetics, University of Copenhagen, Denmark*Institute of Genetics, 0ster Fari-magsgade 2 A, DK-1353 Copenhagen K, DenmarkSearch for more papers by this author First published: December 1983 https://doi.org/10.1111/j.1601-5223.1983.tb00904.xAboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. Literature cited Bahn, E. 1973. A suppressor locus for the pyrimidine requiring mutant rudimentary. – Drosophila Inf. Serv. 49: 98. Barr, C. and Pedersen, M. B. 1982. Photometric measurement of the reflectance from Drosophila cuticles. – Carlsberg Res. Commun. 47: 401– 403. Carlson, P. S. 1971. A genetic analysis of the rudimentary locus of Drosophila melanogaster. – Genet. Res. 17: 53– 81. Green, M. M. 1963. Interallelic complementaion and recombination at the rudimentary wing locus in Drosophila melano-gaster. – Genetica 34: 242– 253. Hodgetts, R. B. and Choi, A. 1974. β-alanine and cuticle maturation in Drosophila. – Nature 252: 710– 711. Holaday, B. J. and Fristrom, J. W. 1977. Phosphonacetyl-L-aspartate: an aspartate transcarbamylase inhibitor causing larval death and rudimentary wing phenocopies in Drosophila melanogaster. – Experientia 33: 428– 430. Jarry, B. and Falk, D. 1974. Functional diversity within the rudimentary locus of Drosophila melanogaster. – Mol. Gen. Genet. 135: 113– 122. Lewis, E. B. and Bacher, F. 1968. Method of feeding ethyl-methane sulfonate (EMS) to Drosophila males. – Drosophila Inf. Serv. 43: 193. Nørby, S. 1970. A specific nutritional requirement for pyrimi-dines in rudimentary mutants of Drosophila melanogaster. – Hereditas 66: 205– 214. Nørby, S. 1973. The biochemical genetics of rudimentary mutants of Drosophila melanogaster. 1. Aspartate carbamoyl-transferase levels in complementing and non-complementing strains. – Hereditas 73: 11– 16. Pedersen, M. B. 1982. Characterization of an X-linked semi-dominant suppressor of black Su(b) (1-55.5) in Drosophila melanogaster. – Carlsberg Res. Commun. 47: 391– 400. Rawls, J. M. 1980. Identification of a small genetic region that encodes orotate phosphoribosyltransferase and orotate decarboxylase in Drosophila melanogaster. – Mol. Gen. Genet. 178: 43– 49. Rawls, J. M. 1981. A small genetic region that controls dihydroorotate dehydrogenase in Drosophila melanogaster. – Biochem. Genet. 19: 115– 127. Rawls, J. M. and Fristrom, J. 1975. A complex genetic locus that controls the three first steps of pyrimidine biosynthesis in Drosophila. – Nature 255: 738– 740. Sherald, A. F. 1981. Intergenic suppression of the black mutation of Drosophila melanogaster. – Mol. Gen. Genet. 183: 102– 106. Volume99, Issue2December 1983Pages 309-310 ReferencesRelatedInformation

HereditasVolume 58, Issue 1-2 p. 1-12 Open Access CROSSING OVER IN THE CHROMOSOMAL REGION DETERMINING AMYLASE ISOZYMES IN DROSOPHILA MELANOGASTER ERIK BAHN, ERIK BAHN INSTITUTE OF GENETICS, UNIVERSITY OF COPENHAGEN, DENMARKSearch for more papers by this author ERIK BAHN, ERIK BAHN INSTITUTE OF GENETICS, UNIVERSITY OF COPENHAGEN, DENMARKSearch for more papers by this author First published: December 1967 https://doi.org/10.1111/j.1601-5223.1967.tb02138.xCitations: 9AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume58, Issue1-2December 1967Pages 1-12 ReferencesRelatedInformation