No association between the Pro197Leu polymorphism in the glutathione peroxidase (GPX1) gene and schizophrenia

OBJECTIVE: Oxidative stress such as free radical-mediated neuronal dysfunction may be involved in the pathophysiology of schizophrenia. The human glutathione peroxidase (GPX1) is a selenium-dependent enzyme, which plays an important role in the detoxification of free radicals. We therefore hypothesized that the GPX1 gene, which is located on chromosome 3p21.3, may be involved in the pathophysiology of schizophrenia. The aim of this study is to examine whether a potentially functional polymorphism, a proline (Pro) to leucine (Leu) substitution at codon 197 (Pro197Leu) of the human GPX1 gene, is associated with susceptibility to schizophrenia. METHODS: We genotyped the Pro197Leu polymorphism in a total of 113 nuclear families that had a proband with schizophrenia. Genetic association was tested using the transmission disequilibrium test (TDT), the sib transmission disequilibrium test (STDT), and the family-based association test (FBAT). RESULTS: The minor allele (Leu) frequency was calculated to be 0.282. We could not find significant transmission disequilibrium of the alleles for the Pro197Leu polymorphism in the GPX1 gene in association with the presence of schizophrenia in our family sample (TDT, chi2=0.03, degrees of freedom=1, P=0.86; combined TDT-STDT, Z'=-0.052, P=0.47; FBAT, Z=0.000, P=1.000). CONCLUSION: The results of this study suggest that the GPX1 polymorphism is unlikely to be associated with susceptibility to schizophrenia.     

The origin of human chromosome 2 analyzed by comparative chromosome mapping with a DNA microlibrary

Fluorescencein situ hybridization (FISH) of microlibraries established from distinct chromosome subregions can test the evolutionary conservation of chromosome bands as well as chromosomal rearrangements that occurred during primate evolution and will help to clarify phylogenetic relationships. We used a DNA library established by microdissection and microcloning from the entire long arm of human chromosome 2 for fluorescencein situ hybridization and comparative mapping of the chromosomes of human, great apes (Pan troglodytes, Pan paniscus, Gorilla gorilla, Pongo pygmaeus) and Old World monkeys (Macaca fuscata andCercopithecus aethiops). Inversions were found in the pericentric region of the primate chromosome 2p homologs in great apes, and the hybridization pattern demonstrates the known phylogenetically derived telomere fusion in the line that leads to human chromosome 2. The hybridization of the 2q microlibrary to chromosomes of Old World monkeys gave a different pattern from that in the gorilla and the orang-utan, but a pattern similar to that of chimpanzees. This suggests convergence of chromosomal rearrangements in different phylogenetic lines.     

Does feeding regime affect physiologic and thermal responses during exposure to 8, 20, and 27° C?

Summary When the loss of body heat is accelerated by exposure to low environmental temperatures, additional substrates must be oxidized to provide energy to sustain temperature homeostasis. Therefore, the present investigation examined the relation between feeding regime [pre-experimental carbohydrate feeding (FED) vs a fast (FAST)], during 120 min of exposure to 8, 20, and 27° C in well-nourished men. The following were examined: tissue insulation (I; °C · m² · W^–1), rectal temperature (T _re; °C), and oxygen consumption ( O₂; ml · kg^–1 · min^–1). O₂, T _re, and I revealed no significant differences between treatments (FED vs FAST) at any temperature. At 27° C, I was less (P < 0.05) than at 20 and 8° C, and decreased (P < 0.05) as exposure time increased. At 8° C, O₂was higher (P < 0.5) than at 20 or 27°C, and O₂increased as time increased (P < 0.05). T _re decreased (P < 0.05) as time increased for all conditions. Respiratory exchange ratio (R) differed (P < 0.05) between treatments (FED vs FAST), temperature (8 vs 20° C), and across time. Values for R suggests that carbohydrate accounted for 56% and 33% of caloric utilization during the FED vs FAST conditions, respectively. At 8 vs 20° C, R represented 54% vs 30% of cabohydrate utilization. Across time, R demonstrated that in both conditions (FED vs FAST) there was a decreased reliance on carbohydrate utilization for energy provision. From these data it appears that while substrate utilization differed between dietary treatment and across time this did not differentially affect O₂or T _re during protracted exposure to 8, 20, and 27° C. The higher R in the 8° C condition for both dietary treatments demonstrates that carbohydrate utilization is increased in shivering cold-exposed humans. However, the reduction in R across time suggests that fat oxidation is also involved in metabolic heat production and core temperature maintenance during shivering in the cold.     

Biological and clinical significance of cytogenetic abnormalities in low-risk and high-risk gastrointestinal stromal tumors

We report cytogenetic findings in 19 c-Kit-positive gastrointestinal stromal tumors (GISTs) that represent a heterogenous group of mesenchymal neoplasms with respect to site, histology, and biologic behavior. All of the GISTs (5 low-risk, 11 high-risk, 3 recurrences) displayed clonal chromosomal aberrations; 15 were hypo- to near-diploid, and 4 were near-triploid and hypotetraploid. The most common abnormalities were loss of chromosomes 14 and/or 22, demonstrated in 14 GISTs irrespective of site or predominant phenotype. Ten cases (2 low-risk, 5 high-risk, 3 recurrences) were characterized by loss of both chromosomes 14 and 22, 2 cases (1 low-risk, 1 high- risk), by loss of chromosome 14; and 2 high-risk cases, by loss of chromosome 22. Additional chromosomal aberrations occurred preferentially in high-risk and recurrent GISTs, including loss of 9p and 1p in 8 cases each, loss of 15 in 6 cases, loss of 3p in 5 cases, loss of 13q and 10q in 4 cases each, loss of 19 in 3 cases, and complete or partial gains of chromosomes 5 and 4 in 2 cases each. More significantly, 5 of 6 patients with clinically aggressive GISTs, including 2 recurrences and 3 metastasing GISTs, were additionally characterized by loss of 9p; four of these had additional loss of chromosomes 1p and 15. The presented results herein indicate that loss of chromosome 14 and/or 22 is an early change in GIST tumorigenesis irrespective of site or differentiation, whereas malignant transformation and progression of GISTs appear to be associated with an increasing incidence of additional secondary aberrations.     

HnRNP CBP35-CBP67 interaction during stress response and ageing

Previous studies have demonstrated the existence of nuclear carbohydrate binding proteins in a variety of mammalian cells with molecular masses of 35 000, 67 000, and 70 000 (CBP35, CBP67, and CBP70), which are associated with nuclear ribonucleoprotein (RNP) complexes. CBP35 consists of two domains, an aminoterminal portion that is homologous to certain regions of proteins of the heterogeneous nuclear RNP complex, and a carboxyl-terminal portion homologous to β-galactoside-specific lectins. CBP35 it has been proposed, like the glucose-specific lectin, CBP67, to guide RNP complexes through the nuclear pore. Here we show that the exposure of mature rats to stress induces an increase in nuclear CBP35 bound to CBP67 and retained on immobilized glucose. Nuclear extracts from the livers of old rats displayed no detectable stress response. This CBP35·CBP67 association detected in rat liver is considered with respect to the CBP35·CBP70 association recently observed in HL60 cell nuclear extracts.     

Licht- und elektronenmikroskopische Untersuchungen zur Histopathogenität vonMacracanthorhynchus hirudinaceus (Archiacanthocephala) in experimentell infizierten Hausschweinen

Zusammenfassung Die vonMacracanthorhynchus hirudinaceus verursachten Läsionen im Dünndarm von experimentell infizierten Hausschweinen (7 Tage p.i. und 84 Tage p.i.) wurden licht- und elektronenmikroskopisch untersucht. Die Würmer der 84 Tage alten Infektion waren tiefer in die Darmwand eingedrungen als die 7 Tage alten Würmer. Ihr Präsoma wurde von Entzündungsbzw. Bindegewebe umhüllt, das zahlreiche Plasmazellen enthielt. Bei 7 Tage alten Infektionen wurde noch keine Fibrose nachgewiesen. Eosinophilen-ähnliche Granulozyten, die an den Proboscishaken akkumulierten, herrschten in der Läsion vor. Eine osmiophile Gleitflüssigkeit, die offenbar an der Basis der Proboscishaken ausgeschieden wurde, schien eine stark antigene Wirkung auf die Leukozyten des Schweins auszuüben. In keinem Fall wurden Würmer angetroffen, die die gesamte Darmwand perforiert hatten, wie es in China bei Menschen beschrieben wurde.

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Light and electron microscopical investigation of the histopathogenicity ofMacracanthorhynchus hirudinaceus in experimentally infected swine

One and 12 weeks after infection the lesions in the small intestine of two domestic pigs caused byMacracanthorhynchus hirudinaceus were studied by means of light and electron microscopy. Worms of 7 d.p.i. were found to have penetrated with their presoma into the tunica propria and partly into the tunica muscularis where they had caused local mechanic destructions and heavy eosinophilic-like and hemorrhagic reactions. Most eosinophilic-like granulocytes were attracted to the proboscis hooks, at the base of which an osmiophilic substance apparently was excreted. Worms of 84 d.p.i. had penetrated with their proboscis deeply into the tunica muscularis. The presoma had become encapsulated by a solid capsule of necrotic/inflammatory tissue in its inner part and by filamentous connective tissue in its outer part. The predominant leucocytes in the inflammatory tissue now were plasma cells indicating a progressive immune reaction. No worms were found to have perforated the entire intestinal wall as was described from human patients in China.

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Unterstützt durch ein Stipendium der VR China für Herrn Bin Zhao     

Recurrent Bacteremia Caused by a “Flexispira”-Like Organism in a Patient with X-Linked (Bruton’s) Agammaglobulinemia

Helicobacter spp., except for Helicobacter cinaedi, have only rarely been reported in cases of septicemia. A patient with X-linked (Bruton's) agammaglobulinemia was found to have persistent sepsis with a Helicobacter-like organism despite multiple courses of antibiotics. His periods of sepsis were associated with leg swelling thought to be consistent with cellulitis. The organism was fastidious and required a microaerophilic environment containing H(2) for growth. Optimal growth was observed at 35 to 37 degrees C on sheep blood, CDC anaerobe, and Bordet-Gengou agars. Serial subcultures every 4 to 5 days were required to maintain viability. The organism was strongly urease positive and showed highest relatedness to Helicobacter-like organisms with the vernacular name "Flexispira rappini" by 16S rRNA gene sequence analysis. Genomic DNA hybridization studies, however, found 24 to 37% relatedness to "F. rappini" and even less to other Helicobacter spp. Although the organism phenotypically resembles "Flexispira" and Helicobacter, it is thought to represent a new taxon. The patient's infection was eventually cleared with a prolonged (5-month) course of intravenous imipenem and gentamicin.     

Endoreduplication in conjunction with tumor progression in an aneuploid laryngeal squamous cell carcinoma

We report the case of a 58-year-old man who presented with a squamous cell carcinoma pT1a G2 of the left vocal cord. Six months after histologically verified complete resection, the patient experienced an endolaryngeal and extralaryngeal local recurrence pT4 pN2b G2. We applied DNA flow cytometry (FCM) and comparative genomic hybridization (CGH) on both primary and recurrent tumor. The primary tumor and the endolaryngeal compartment of the relapse was an aneuploid cell clone with a FCM DNA index of 1.42 and 1.44, respectively. The extralaryngeal compartment showed a shift featuring a DNA index of 2.78. In the primary tumor and in both compartments of the recurrence there was an identical pattern of complex chromosomal imbalances as detected in CGH (CGH karyotype: rev ish enh [8q24.2-q24.3, 10q26.1-q26.3, 11q24-q25, 12q24.2-q23.33,X], dim [4q, 13q14.3-q31], amp[1p36.1-p36.2]). Hence, the recurrence was not associated with further gains and losses of chromosomal material. However, in the anterior part of the recurrence, the aneuploid tumor cell genome had completely doubled, obviously due to endoreduplication. Immunohistochemical analysis of several cell-cycle regulators revealed altered expression of checkpoint proteins, pointing to a complex disturbance in cell-cycle regulation.     

Alternating copolymerization of butadiene and propene with the catalyst VO(ONeo)2 Cl/Al(i-C4H9)3, 1

The influence of basic reaction parameters—the ratio of catalyst components, the composition of the monomer mixture and the temperature—on the progress of the copolymerization, the molecular weight and the molecular weight distribution as well as on the composition of the copolymers obtained is reported. Conversion data for the variation of the mole ratio of comonomers show a maximum for an [Al]/[V] mole ratio of approximately 7, whereas the molecular weight of copolymers is not significantly influenced. An increase in the molecular weight of the copolymers can be obtained by an increase of butadiene content in the monomer mixture. However, there is also an increasing incorporation of butadiene into the copolymer. Raising the temperature from ?60°C to 0°C results in a significant decrease in molecular weight, whereas the composition of the copolymers is not significantly changed.