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Seit wenigen Jahren kristallisiert sich mit dem plexiformen angiomyxoiden myofibroblastischen Tumor eine neue Entitat der gastralen Bindegewebstumoren heraus. Durch seine inzwischen erfolgte gute licht- und immunhistologische Charakterisierung wird dieser Tumor in Zukunft vermutlich haufiger diagnostiziert. Diese Tumorentitat wurde bisher nicht in der deutschsprachigen Literatur vorgestellt. Da der plexiforme angiomyxoide myofibroblastische Tumor bereits an suffizientem Biopsiematerial sicher diagnostiziert werden kann, konnen die richtigen therapeutischen Masnahmen ohne Verzogerung eingeleitet werden.

Background The combination of aflibercept with FOLFIRI has been shown to significantly prolong overall survival in patients with metastatic colorectal cancer (mCRC) after progression on oxaliplatin-based therapy. This trial evaluated the addition of aflibercept to oxaliplatin-based first-line treatment of patients with mCRC. Patients and methods Patients with mCRC were randomized to receive first-line therapy with mFOLFOX6 plus aflibercept (4 mg/kg) or mFOLFOX6 alone. The primary end point of this phase II study was the progression-free survival (PFS) rate at 12 months in each arm. The analysis of efficacy between the arms was a pre-planned secondary analysis. Results Of 236 randomized patients, 227 and 235 patients were evaluable for the primary efficacy analysis and safety, respectively. The probabilities of being progression-free at 12 months were 25.8% [95% confidence interval (CI) 17.2–34.4] for the aflibercept/mFOLFOX6 arm and 21.2% (95% CI 12.2–30.3) for the mFOLFOX6 arm. The median PFS was 8.48 months (95% CI 7.89–9.92) for the aflibercept/mFOLFOX6 arm and 8.77 months (95% CI 7.62–9.27) for the mFOLFOX6 arm; the hazard ratio of aflibercept/mFOLFOX6 versus mFOLFOX6 was 1.00 (95% CI 0.74–1.36). The response rates were 49.1% (95% CI 39.7–58.6) and 45.9% (95% CI 36.4–55.7) for patients treated with and without aflibercept, respectively. The most frequent treatment-emergent grade 3/4 adverse events (AEs) excluding laboratory abnormalities reported for aflibercept/mFOLFOX6 versus mFOLFOX6 were neuropathy (16.8% versus 17.2%) and diarrhea (13.4% versus 5.2%). Neutropenia grade 3/4 occurred in 36.1% versus 29.3%. The most common vascular endothelial growth factor inhibition class-effect grade 3/4 AEs for aflibercept/mFOLFOX6 versus mFOLFOX6 were hypertension (35.3% versus 1.7%), proteinuria (9.2% versus 0%), deep vein thrombosis (5.9% versus 0.9%) and pulmonary embolism (5.9% versus 5.2%). Conclusion No difference in PFS rate was observed between treatment groups. Adding aflibercept to first-line mFOLFOX6 did not increase efficacy but was associated with higher toxicity. Clinical Trial Number NCT00851084, www.clinicaltrials.gov , EudraCT 2008-004178-41.

PURPOSE Analysis of the course of disease in patients with histologically proven HCC before and after orthotopic liver transplantation (LTx) who received transarterial chemoembolization (TACE). MATERIAL AND METHODS Thirty-five of a total collective of 363 patients with histologically proven HCC underwent LTx. Before LTx, all patients were treated with sequential TACE. According to treatment pattern, TACE should be performed every 6 weeks, using a suspension consisting of max. 10 mg Mitomycin C as well as 10 - 30 ml iodized oil (Lipiodol). Patients were classified according to the Milano criteria. Criteria were called exceeded if the tumor size was > 5 cm and/or > 3 tumors larger than 3 cm were found. Therapy success and liver function were examined by means of spiral CT and laboratory controls. Investigation parameters included the number of tumor knots as well as the maximum tumor size. Additionally, the Lipiodol accumulation, the patency of the portal vein and the occurrence of complications were checked. RESULTS Altogether, 184 TACE procedures were accomplished (5.3 +/- 3.3, range 1 - 14). The waiting period up to the transplantation amounted to 366 +/- 255 days (range 44 - 1137). The average number of tumor knots for each patient was 3.1 +/- 2.2 before and 2.9 +/- 2.2 after TACE (p = 0.887). The average tumor size was 4.2 +/- 2.5 before and 2.8 +/- 1.4 after TACE. The Milano criteria to LTx crossed 17/35 patients. Patients with exceeded Milan criteria showed a highly significant size reduction of the tumor after TACE (p = 0.001); in 9/17 cases the transplantation criteria were secondarily fulfilled through downstaging. A successful LTx was accomplished in 35/35 cases. Follow up after LTx was 769 +/- 509 days. The tumor recurrence in patients with exceeded vs. fulfilled transplantation criteria was 11.1 % vs. 11.8 % (p = 0.99). The recurrence free survival was 93.3 %, 82.5 % and 82.5 % at 1, 3 and 5 years, respectively. There were no relevant differences between patients with exceeded vs. fulfilled transplantation criteria (p = 0.99). CONCLUSION The sequential TACE is an effective method for the therapy of the HCC before LTx in selected patients. A relevant downsizing could be achieved by TACE in patients with advanced HCC. Patients with larger tumors showed a significantly stronger size reduction after TACE. The recurrence rate and the survival rate for patients with advanced or small tumors do not differ.

Background Integrins are involved in tumour progression and metastasis, and differentially expressed on colorectal cancer (CRC) cells. Abituzumab (EMD 525797), a humanised monoclonal antibody targeting integrin αν heterodimers, has demonstrated preclinical activity. This trial was designed to assess the tolerability of different doses of abituzumab in combination with cetuximab and irinotecan (phase I) and explore the efficacy and tolerability of the combination versus that of cetuximab and irinotecan in patients with metastatic CRC (mCRC) (phase II part). Methods Eligible patients had KRAS (exon 2) wild-type mCRC and had received prior oxaliplatin-containing therapy. The trial comprised an initial safety run-in using abituzumab doses up to 1000 mg combined with a standard of care (SoC: cetuximab plus irinotecan) and a phase II part in which patients were randomised 1 : 1 : 1 to receive abituzumab 500 mg (arm A) or 1000 mg (arm B) every 2 weeks combined with SoC, or SoC alone (arm C). The primary end point was investigator-assessed progression-free survival (PFS). Secondary end points included overall survival (OS), response rate (RR) and tolerability. Associations between tumour integrin expression and outcomes were also assessed. Results Phase I showed that abituzumab doses up to 1000 mg were well tolerated in combination with SoC. Seventy-three (arm A), 71 (arm B) and 72 (arm C) patients were randomised to the phase II part. Baseline characteristics were balanced. PFS was similar in the three arms: arm A versus SoC, hazard ratio (HR) 1.13 [95% confidence interval (CI) 0.78–1.64]; arm B versus SoC, HR 1.11 (95% CI 0.77–1.61). RRs were also similar. A trend toward improved OS was observed: arm A versus SoC, HR 0.83 (95% CI 0.54–1.28); arm B versus SoC, HR 0.80 (95% CI 0.52–1.25). Grade ≥3 treatment-emergent adverse events were observed in 72%, 78% and 67% of patients. High tumour integrin αvβ6 expression was associated with longer OS in arms A [HR 0.55 (0.30–1.00)] and B [HR 0.41 (0.21–0.81)] than in arm C. Conclusion The primary PFS end point was not met, although predefined exploratory biomarker analyses identified subgroups of patients in whom abituzumab may have benefit. The tolerability of abituzumab combined with cetuximab and irinotecan was acceptable. Further study is warranted. ClinicalTrials.gov identifier NCT01008475

More than 90% of patients with genetic hemochromatosis carry a characteristic mutation in the HFE-gene (C282Y). HFE modulates the iron uptake by the transferrin receptor. Duodenal crypt cells of HFE-knockout mice show low intracellular iron concentrations which lead to an upregulation of the divalent metal transporter and enhanced iron uptake by duodenal enterocytes. Heterozygosity for the C282Y mutation appears to alter the course of other liver diseases like porphyria cutanea tarda and nonalcoholic steatohepatitis.

Recently the so-called plexiform angiomyxoid myofibroblastic tumors (PAMT) have emerged as a new entity of gastric soft tissue tumors and the light microscopic and immunohistological characteristics have now been well described. Until now PAMTs have not yet been reported in the German speaking literature. Worthy of note is that PAMTs can be diagnosed safely in sufficient biopsy material which enables adequate therapeutic steps to be initiated without delay, because PMATs although considered to be benign, can cause serious complications.

Analysis of the course of disease in patients with histologically proven HCC before and after orthotopic liver transplantation (LTx) who received transarterial chemoembolization (TACE).Thirty-five of a total collective of 363 patients with histologically proven HCC underwent LTx. Before LTx, all patients were treated with sequential TACE. According to treatment pattern, TACE should be performed every 6 weeks, using a suspension consisting of max. 10 mg Mitomycin C as well as 10 - 30 ml iodized oil (Lipiodol). Patients were classified according to the Milano criteria. Criteria were called exceeded if the tumor size was5 cm and/or3 tumors larger than 3 cm were found. Therapy success and liver function were examined by means of spiral CT and laboratory controls. Investigation parameters included the number of tumor knots as well as the maximum tumor size. Additionally, the Lipiodol accumulation, the patency of the portal vein and the occurrence of complications were checked.Altogether, 184 TACE procedures were accomplished (5.3 +/- 3.3, range 1 - 14). The waiting period up to the transplantation amounted to 366 +/- 255 days (range 44 - 1137). The average number of tumor knots for each patient was 3.1 +/- 2.2 before and 2.9 +/- 2.2 after TACE (p = 0.887). The average tumor size was 4.2 +/- 2.5 before and 2.8 +/- 1.4 after TACE. The Milano criteria to LTx crossed 17/35 patients. Patients with exceeded Milan criteria showed a highly significant size reduction of the tumor after TACE (p = 0.001); in 9/17 cases the transplantation criteria were secondarily fulfilled through downstaging. A successful LTx was accomplished in 35/35 cases. Follow up after LTx was 769 +/- 509 days. The tumor recurrence in patients with exceeded vs. fulfilled transplantation criteria was 11.1 % vs. 11.8 % (p = 0.99). The recurrence free survival was 93.3 %, 82.5 % and 82.5 % at 1, 3 and 5 years, respectively. There were no relevant differences between patients with exceeded vs. fulfilled transplantation criteria (p = 0.99).The sequential TACE is an effective method for the therapy of the HCC before LTx in selected patients. A relevant downsizing could be achieved by TACE in patients with advanced HCC. Patients with larger tumors showed a significantly stronger size reduction after TACE. The recurrence rate and the survival rate for patients with advanced or small tumors do not differ.

We have evaluated whether the MHC-class-I-chain-related gene A (MICA), being closely located to HLA-B, predisposes for endocrine autoimmunity. It encodes a cell surface protein. The gene shows in its transmembrane segment a GCT repeat encoding 4, 5, 6, or 9 alanine residues (alleles A4, A5, A6, A9), and A5.1 has an additional 1-bp-insertion (GGCT, A5.1). We determined the polymorphism in 48 patients with Graves' disease (GD), 59 with Hashimoto's thyroiditis (HT) and 206 healthy unrelated controls. 43 patients had one endocrinopathy (monoglandular autoimmunity, MGA) and 64 at least two endocrinopathies (polyglandular autoimmunity, PGA). After extraction of genomic DNA from whole blood, the MICA microsatellites were amplified by PCR, and fragment sizes were determined with an automatic DNA sequencer (ABI PRISM 310). The exact test of Fisher and Odds ratios (OR) were applied for group comparisons. We identified the MICA alleles A4, A5, A5.1, A6, and A9 in either homozygous or heterozygous form in 21.5%, 25.2%, 70.1%, 21.5%, 22.4% of patients versus 24.8%, 27.2%, 62.1%, 36.9%, 23.8% of controls, respectively. Patients with GD (14.6%, 33.3%, 70.8%, 18.8%, 22.9%) and HT (27.1%, 18.6%, 69.5%, 23.7%, 22.0%) did not differ in their frequencies. Allele A6 was less frequent in patients (21.5%) than controls (36.9%; OR=0.468, 95%CI=0.273–0.805); this was more pronounced in patients with PGA (18.8%; OR=0.395, 0.198–0.786 vs. controls) than MGA (25.6%; OR=0.671, 0.265–1.700 vs. controls). Allele A5.1 was more frequent in patients with PGA (78.1%) than MGA (58%; OR=2.571, 1.102–6.001) or controls (62.1%; OR=2.176, 1.129–4.195). No significant relationships were observed between thyroid antibodies against TPO and TSH receptor and MICA frequencies. Allele A5.1 creates a frameshift resulting in a premature termination codon in the transmembrane region of the MICA protein, lacking for its cytoplasmatic domain. This truncated protein is regarded as a soluble, secreted form of MICA. These results indicate that the MICA gene influences susceptibility to endocrine autoimmunity.

Over the last years the therapeutic possibilities for advanced gastric cancer have significantly increased. Here we discuss the new chemotherapeutic options and the existing results in palliative therapy.

Aim: Abituzumab (EMD 525797, DI17E6) is a humanized monoclonal IgG2 antibody specifically targeting the an subunit of integrin receptors. POSEIDON is a Phase I/II open-label, randomized, controlled, multicenter trial (NCT01008475). Abituzumab ≤1000 mg combined with standard of care (SoC) revealed no dose-limiting toxicities in Phase I; here Phase II results are reported. Methods: Pts were randomized 1:1:1 to abituzumab 500 mg (Arm A) or 1000 mg (Arm B) i.v. every 2-week cycle, combined with SoC (cetuximab [400 mg/m2, day 1 cycle 1; then 250 mg/m2 weekly] plus irinotecan [180 mg/m2/cycle]), or SoC alone (Arm C). Primary endpoint was investigator-assessed progression-free survival (PFS). Other objectives included overall survival (OS), safety and tolerability, and biomarker analysis. Eligible pts had confirmed KRAS wild-type colorectal cancer with distant metastasis and failure after oxaliplatin/fluoropyrimidine-containing treatment. Results: In total, 216 pts were randomized: 73 to Arm A, 71 to Arm B, and 72 to Arm C; baseline characteristics were matched. Median PFS (investigator assessed) was 5.4 vs 5.6 mo for Arm A vs Arm C, respectively (HR, 1.13 [95% CI, 0.78, 1.64]) and 5.6 mo with Arm B (HR, 1.11 [95% CI, 0.77, 1.61]). A trend for longer median OS was observed in Arms A and B, vs Arm C (15.0 and 14.4, vs 11.6 mo, respectively); response rates (RRs) were 27.4%, 25.4%, and 26.4%, respectively. Grade ≥3 treatment-emergent adverse events (TEAEs) were observed in 72%, 78%, and 67% of pts in Arms A, B, and C, respectively, and 13%, 10%, and 8% of TEAEs resulted in death (none considered abituzumab related). High integrin avb6 expression in the tumor tissue (98/197 analyzed pts) was associated with longer OS (HR, 0.48 [95% CI, 0.28, 0.82]) and better RR (31% vs 16%) for abituzumab-treated pts vs SoC. Additional data on circulating plasma proteins as candidate biomarkers and pharmacokinetics will be presented. Conclusions: Although no difference in PFS was observed with the addition of abituzumab to SoC, abituzumab did prolong OS and doubled RR in pts with high tumor expression of avb6. The overall safety profile of abituzumab combined with SoC was acceptable. Disclosure: C. Bokemeyer: Advisory Board: Merck-Serono, Sanofi Aventis Corporate-sponsored research: Merck Serono, Roche Pharma;E. Van Cutsem: Corporate-sponsored research: Research funding paid to my institution by Merckserono; B. Melichar: Advisory board: Merck, Roche, Sanofi, Lilly Other substantive relationships: honoraria for speeches Merck, Roche, Sanofi, Lilly;F. Rivera: Advisory board: Merck Serono Corporate-sponsored research: Merck Serono;J. Straub: Other substantive relationships: Employee of the trial sponsor; R. Bruns: Other substantive relationships: Employee of Merck KgaA; S. Quaratino: Other substantive relationships: Employee of Merck KgaA; J. Tabernero: Advisory board: Amgen, Imclone, Lilly, Merck KGaA, Millennium, Novartis, Roche, Sanofi, Celgene, Chugai and Taiho Other substantive relationships: Honoraria for presentations: Amgen, Merck KGaA, Novartis, Roche and Sanofi.All other authors have declared no conflicts of interest.

Metals such as cobalt and nickel are common contact allergens. We studied the mechanisms underlying an allergic reaction with marked synovial inflammation in a patient with a cobalt alloy arthroplasty. After removing the joint prosthesis the adjacent synovial tissue was examined for cobalt-specific T lymphocytes. Synovial membrane mononuclear cells were expanded in interleukin 2 and cloned using a representative cloning protocol. T cell clones were tested for their proliferative response to cobalt and further characterized with regard to cytokine secretion, phenotype, and HLA restriction. Additionally, synovial fibroblasts were tested for their function as antigen presenting cells (APC). Almost 30% of the T cell clones reacted to cobalt, but not to the control nickel. All these T cell clones were CD4 positive. The cobalt induced proliferative response could be blocked by anticlass II antibodies. Also, synovial fibroblasts expressing class II molecules induced by interferon-gamma were able to serve as APC. However, when testing a panel of APC of HLA class II mismatched donors, no requirement for a certain HLA class II molecule could be defined. Further studies are necessary to determine mechanisms of presentation and recognition of cobalt by T lymphocytes, a prerequisite for improved prevention and treatment of metal induced allergic reactions.

More than 90% of patients with genetic hemochromatosis carry a characteristic mutation in the HFE-gene (C282Y). HFE modulates the iron uptake by the transferrin receptor. Duodenal crypt cells of HFE-knockout mice show low intracellular iron concentrations which lead to an upregulation of the divalent metal transporter and enhanced iron uptake by duodenal enterocytes. Heterozygosity for the C282Y mutation appears to alter the course of other liver diseases like porphyria cutanea tarda and nonalcoholic steatohepatitis.

In the spondyloarthropathies human leukocyte antigen (HLA) B27 confers a strong genetic predisposition to the development and to the chronicity of disease after extra-articular infection with certain gram-negative bacteria. The close relationships between infection, HLA-B27, other genetic factors, and the host immune system, however, still are unexplained. HLA-B27-positive arthritis continues to be an area of intensive investigation in basic and clinical research. New animal models with HLA-B27 transgenic mice and rats, as well as recent developments in understanding the processes involved in signal transduction, cytokine production, and human T-lymphocyte activation, contribute to the development of new pathogenic models of the spondyloarthropathies. This article summarizes the current concepts of the cause and pathogenesis of the spondyloarthropathies resulting from studies of clinical materials. The host-microbial interplay in human disease, namely in bacteria-induced reactive arthritis, may eludicate principle disease mechanisms in acute disease and in the development of chronic autoimmune arthritis or ankylosing spondylitis.

Acute infection with hepatitis C virus (HCV) develops into a chronic hepatitis in about 50-70% of patients. Treatment of these patients with interferon-alpha (IFN-alpha) results in a sustained long-term response in only 15-20% but causes numerous unwanted side-effects in a higher percentage of patients. The aim of our study was to define host or viral parameters that would allow identification of responders and non-responders to IFN-alpha prior to the onset of treatment. We studied a group of 87 patients suffering from chronic hepatitis C who were treated with IFN-alpha. After long-term follow-up, 18 patients (21%) showed a sustained response to IFN-alpha therapy (normalization of serum transaminases and loss of viral RNA from serum) for up to 7 years after therapy had ceased. By univariate and multivariate analyses, no host factors were found to be predictive of response to therapy. Neither the degree of inflammation or fibrosis in liver biopsy samples obtained before treatment nor immunogenetic factors (major histocompatibility complex II haplotype and tumour necrosis factor-alpha promoter polymorphism) were associated with response to therapy. In contrast, viral parameters showed a strong association with response to therapy. HCV genotype 3 was found significantly more frequently in responders (P = 0.034), and mean HCV RNA concentration was lower in responders (3.1 x 10(4)) than in non-responders (2.5 x 10(5)) (P = 0.01). By multivariate analysis, both HCV genotype and HCV RNA concentration were independent predictors of response to therapy. However, exact prediction of response to treatment for an individual patient was not possible on the basis of pretreatment viral RNA concentration or viral genotype. The best association with response to therapy was found to be clearance of HCV RNA from serum 3 months after the start of treatment (32 of 34 partial and sustained responders vs 0 of 53 non-responders; P = 0.001). In conclusion, determination of pretreatment viral factors, but not host factors, was significantly correlated with treatment response but did not give an accurate prediction for patients, whereas clearance of HCV RNA from serum after 3 months of therapy was predictive of response to therapy.

To investigate the potential association of tumor necrosis factor alpha (TNFalpha) promoter alleles with ankylosing spondylitis.DNA from 141 HLA-B27 positive Caucasian patients with ankylosing spondylitis and 46 B27-positive and 99 B27-negative healthy Caucasian controls was investigated by polymerase chain reaction amplification of the TNFalpha promoter region and subsequent dot-blot analysis with allele-specific oligonucleotides.There was a significant decrease in the promoter alleles TNF-238.2 and TNF-308.2 in the ankylosing spondylitis group (266 wild-type alleles, 16 variant alleles) compared with the B27-positive (75 wildtype promoter alleles, 17 variant alleles; P0.0004) and the B27-negative (159 wild-type promoter alleles, 39 variant alleles; P0.00001) control groups. Positivity for the variant promoter alleles conferred protection and a relative risk of 0.3 to B27-positive individuals.These data indicate that allelic variations in the TNFalpha promoter influence disease susceptibility in HLA-B27 positive individuals. This protective effect of variant promoter alleles could be related to differences in TNFalpha production or could reflect the association of different B27 haplotypes with ankylosing spondylitis.

To investigate the potential role of the HLA-linked LMP2 (low molecular weight protein) and LMP7 gene polymorphisms in conjunction with HLA class I and class II genes on the disease pattern in individuals with psoriatic arthritis (PsA).Sixty-three patients with PsA and 99 unrelated controls were typed for HLA-class I and II antigens. LMP2 and LMP7 polymorphisms were determined by PCR and subsequent single stranded conformation polymorphism (SSCP) analysis or restriction enzyme digestion.PsA was associated with B27 (p0.0004), B57 (p0.002) and Cw2 (p0.008). Spondylarthritis was strongly associated with HLA-B27 (p0.000001), Cw2 (p0.0003) and DR4 (p0.008). For the polyarthritic pattern the only association was with B57 (p0.007). There was no association between the LMP2 or LMP7 genotypes and any particular disease pattern.These findings do not support an involvement of the HLA linked LMP2 and LMP7 gene polymorphisms in disease expression in psoriatic arthritis in addition to the known HLA class I and II associations.

Cytotoxic T cell (CTL) responses may influence the course of a hepatitis C infection. CTL recognize viral peptides on HLA class I molecules. Antigenic peptides for class I presentation are generated by proteasomes and transported into the endoplasmic reticulum by the TAP proteins. It is unknown whether polymorphisms of the antigen-processing genes might influence the development of chronic hepatitis C.75 patients with chronic hepatitis C and 99 unrelated controls were typed for TAP and LMP2 polymorphisms. Typing was done by allele-specific PCR techniques and PCR with subsequent single-stranded confirmation polymorphism (SSCP) analysis.Apart from minor increases of the TAP2*0101 allele and LMP2 heterozygotes in the chronic hepatitis group there were no statistically significant differences between the two groups.These findings suggest, that disease association for chronic hepatitis C does not extend beyond the HLA-DQ locus. Although TAP and LMP play an important role in the processing of viral antigens, their limited polymorphisms do not show any association with the development of chronic hepatitis C.

Summary Differences in carbon metabolism between leaves of Amaranthus paniculatus plants grown for 40 days in atmospheres containing 4% or 21% oxygen are observed in kinetic 14C2-feeding experiments on attached leaves during steady-state photosynthesis. Water-soluble leaf constituents were extracted from a defined area and the radioactivity and amount of certain metabolites measured. The basic difference was twice as much incorporation of 14C-radioactivity into the pool of aspartic acid after 15 min of 14CO2-fixation in 4% O2. This 14C-accumulation in the pool of aspartic acid was observed even after 2 min. After growth at low oxygen partial pressure the amount of aspartic acid and glycerate-3-phosphate (3-PGA) increases twofold. As judged on the base of relative specific activities (per cent of the feeding gas specific activity in dpm μg− 1 carbon) reached after 15 min of 14CO2-feeding nearly the total pool of aspartic acid is actively metabolised at both oxygen concentrations, whereas the entire amount of 3-PGA seems to be subdivided in at least two compartments differing largely in the turnover rates. The possible modes of the pool size changes of the two important metabolites as well as an “in vivo” inhibition of phosphoenolpyruvate carboxylase activity are discussed.

Summary Sinapis alba (white mustard) plants were grown under conditions of strong (100 W · m -2 ) and weak (3 W · m -2 ) light and the effect of the light intensity during growth on the CO 2 -compensation point and the activities of glycolic acid oxidase and ribulose bisphosphate carboxylase were studied. The CO 2 -compensation concentration was determined according to two methods: firstly in a closed system with an infrared CO 2 -analyzer, and secondly according to the curve of net photosynthesis as a function of C0 2 -concentration over the range of 400 vpm CO 2 to the CO 2 -compensation point (Fig. 4). The intensity of light during growth was observed to exert an unmistakable effect on the CO 2 -compensation point. In stronglight leaves the CO 2 -compensation point was lower than in weak-light leaves. Plants grown in strong light had a compensation value of 54 ± 3 vpm (first method) or 59 ± 4 vpm (second method), whereas values of 63 ± 4 vpm or 79 ± 7 vpm, respectively, were obtained with plants grown in weak light. The differences obtained were statistically significant at the 99% confidence level according to both methods. The in vitro activities and Michaelis-Menten constants of ribulose bisphosphate carboxylase from leaves of Sinapis alba grown for 16 days in strong light and for 26 days in weak light are presented in Table 1. Based on fresh weight or leaf area, the measurements indicated a 3.3- or 7.4-fold higher activity of this enzyme in the strong-light plants. The glycolate oxidase activities were 2- or 4-fold higher in the strong-light plants than in the weak-light plants, when based on fresh weight or leaf area, respectively (Table 3). The pH-curve and the influences of the preparation time, the presence of flavine mononucleotide and the use of different buffer on the enzyme activities were also tested (Fig. 1). The higher activities of ribulose bisphosphate carboxylase and glycolate oxidase in the strong-light leaves indicated a higher activity of the glycolate pathway and, therefore, a greater production of CO 2 in these cells. The lower CO 2 -compensation point due to the influence of strong light thus appears to contradict the findings of the enzyme measurements. This discrepancy is explained in terms of a greater re-fixation of the CO 2 produced in the glycolate pathway. In strong-light leaves the re-fixation of CO 2 is increased by the low carboxylation resistance of the enzymatic carboxylation system, as well as by the leaf anatomy. The palisade layers of strong-light leaves have a 4-fold greater volume than do those of weak-light leaves. The longer path lenghts from the CO 2 -producing reaction sites to the stomata and the open air and the more comapct arrangement of these palisade cells also contribute to the increased re-fixation of CO 2 produced in light. The CO 2 -compensation point can therefore not be valued as an exact indicator of the activity of the glycolate pathway formation of CO 2 in the leaves.

The (12)CO2- and (14)CO2-exchange of illuminated corn leaf discs were measured at normal (21%) and low (1%) oxygen. After periods of exposure to (14)CO2 or to (14)CO2 followed by (12)CO2, the discs were killed and the specific activities of some metabolites were determined. At both O2 concentrations the specific activity of 3-PGA increased and decreased rapidly during the first 5 min of (14)CO2-feeding or (12)CO2-flushing but did not equilibrate with that of the CO2 in the assimilation chamber even after 15 min. The specific activity of aspartic acid also showed bimodal kinetics during both feeding and flushing. The specific activities of 3-phosphoglyceric acid (3-PGA), aspartic acid and alanine were higher at 1% O2 than at 21% O2, but glycine and serine were lower in specific activity at 1% O2. The results are in agreement with the proposed initial fixation of CO2 into C4-dicarboxylic acids and subsequent transfer of this carbon to 3-PGA. Indirect evidence supports the idea that at 21% O2, CO2 was produced by the corn leaf discs in the light and was refixed into C4-dicarboxylic acids. At 1% O2, the photorespiratory process could also have been active although the flux of carbon through the glycolate pathway was probably smaller than at 21% O2.

An open, multicenter clinical trial of 6-cyclohexyl-1-hydroxy-4-methyl-2(1H)-pyridone, 2-aminoethanol salt (ciclopiroxolamine, Cic, Hoe 296, Batrafen) was performed in 150 patients with 246 nails afflicted by mycotic infection. Dermatophytes were observed in 96% of the initial cultures. A combination of 1% Cic solution and cream was applied, and a very strict nail toilet was performed. The mean duration of study was 12.7 +/- 5.6 weeks, followed by a 6 week follow-up period on the average. The share of pathologically changed nails of 35 +/- 16% was reduced to 8 +/- 10% of nail plate. In a total of 96% of patients, some of whom had only been treated for a brief period, a measurable improvement was observed, and 57% of the patients were free from signs of infection. Signs of intolerance or definite relapses were not observed.