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  • 1
    Electronic Resource
    Electronic Resource
    A specific member of the Cab multigene family can be efficiently targeted and disrupted in the moss Physcomitrella patens (1999)
    Springer
    Molecular genetics and genomics 261 (1999), S. 92-99 
    Details
    ISSN: 1617-4623
    Keywords: Key words Gene disruption ; Gene targeting ; Homologous recombination ; Plant transformation ; Physcomitrella patens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The analysis of phenotypic change resulting from gene disruption following homologous recombination provides a powerful technique for the study of gene function. This technique has so far been difficult to apply to plants because the frequency of gene disruption following transformation with constructs containing DNA homologous to genomic sequences is low (0.01 to 0.1%). It has recently been shown that high rates of gene disruption (up to 90%) can be achieved in the moss Physcomitrella patens using genomic sequences of unknown function. We have used this system to examine the specificity of gene disruption in Physcomitrella using a member of the Cab multigene family. We have employed the previously characterised Cab gene ZLAB1 and have isolated segments of 13 other closely related members of the Cab gene family. In the 199-bp stretch sequenced, the 13 new members of the Cab family show an average of 8.5% divergence from the DNA sequence of ZLAB1. We observed 304 silent substitutions and 16 substitutions that lead to a change in the amino acid sequence of the protein. We cloned 1029 bp of the coding region of ZLAB1 (including 177 of the 199 bp with high homology to the 13 new Cab genes) into a vector containing a selectable hygromycin resistance marker, and used this construct to transform P. patens. In three of nine stable transformants tested, the construct had inserted in, and disrupted, the ZLAB1 gene. There was no discernible phenotype associated with the disruption. We have therefore shown that gene disruption is reproducible in P. patens and that the requirement for sequence homology appears to be stringent, therefore allowing the role of individual members of a gene family to be analysed in land plants for the first time.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004380050945
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  • 2
    Electronic Resource
    Electronic Resource
    bli-4, a gene that is rapidly induced by blue light, encodes a novel mitochondrial, short-chain alcohol dehydrogenase-like protein inNeurospora crassa (1996)
    Springer
    Molecular genetics and genomics 252 (1996), S. 223-229 
    Details
    ISSN: 1617-4623
    Keywords: Neurospora crassa ; Blue light ; Mitochondria ; Short-chain alcohol dehydrogenase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Blue light plays an important role in developmental control throughout nature. Thebli-4 gene ofNeurospora crassa, together withbli-3, al-1 andal-2, is rapidly inducible by blue light. Induction leads to a ninety-fold increase in transcription rate over the dark control level, and the gene therefore appears to be of prime importance in the blue-light induction pathway ofN. crassa. We describe the sequencing and analysis ofbli-4 and the 38 kDa protein it encodes. We show that the protein is very rapidly imported into the mitochondria and exhibits high homology with the family of short-chain alcohol dehydrogenases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02173767
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    bli-4, a gene that is rapidly induced by blue light, encodes a novel mitochondrial, short-chain alcohol dehydrogenase-like protein in Neurospora crassa (1996)
    Springer
    Molecular genetics and genomics 252 (1996), S. 223-229 
    Details
    ISSN: 1617-4623
    Keywords: Key words Neurospora crassa ; Blue light ; Mitochondria ; Short-chain alcohol dehydrogenase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  Blue light plays an important role in developmental control throughout nature. The bli-4 gene of Neurospora crassa, together with bli-3, al-1 and al-2, is rapidly inducible by blue light. Induction leads to a ninety-fold increase in transcription rate over the dark control level, and the gene therefore appears to be of prime importance in the blue-light induction pathway of N. crassa. We describe the sequencing and analysis of bli-4 and the 38 kDa protein it encodes. We show that the protein is very rapidly imported into the mitochondria and exhibits high homology with the family of short-chain alcohol dehydrogenases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02173767
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    5-Fluorouracil plus interferon α-2a compared to 5-fluorouracil alone in the treatment of advanced colon carcinoma: A multicentric randomized study (1998)
    Springer
    Journal of cancer research and clinical oncology 124 (1998), S. 191-198 
    Details
    ISSN: 1432-1335
    Keywords: Key words Advanced colon cancer  ;  Biochemical modulation  ;  5-Fluorouracil  ;  Immunotherapy  ;   Interferon α-2a
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Biochemical modulation is one of the most interesting fields in cancer chemotherapy. Interferon-α (IFNα) is a cytokine that is able to influence the pharmacodynamics of 5-fluorouracil (5FU) through a number of mechanisms. With the aim of confirming some data emerging from the literature, we initiated a multicentric randomized study comparing the combination of 5FU and IFNα-2a with 5FU alone in the treatment of advanced or metastatic colon cancer. A group of 205 colon cancer patients (104 in the 5FU arm and 101 in the 5FU+IFNα-2a arm) were included in the final intention-to-treat analysis. Rectal cancers were not considered eligible. All patients had measurable disease, were aged 75 years or less, had a Karnofsky index of at least 60 and had good bone marrow, renal, liver and cardiac functions. No previous chemo-immunotherapy was allowed. The treatment was 750 mg/m2 5FU (4 h i.v. infusion) on days 1–5 and then i.v. bolus weekly, starting from day 12, with or without IFNα-2a given s.c. three times weekly (starting dose 3 × 106 IU rising to 9 × 106 IU, if tolerated). Patients were treated until progression or, if responsive, for a maximum of 48 weeks and then observed for a period of 2 years. The primary end-point of the study was objective clinical response (OR); secondary parameters were time to progression, overall survival, and time to death after progression. WHO criteria were used for both clinical response and toxicity measurements. Dose reduction was planned a priori in the event of significant toxicity due to 5FU, IFNα-2a or both. Association between primary and secondary end-points and treatment was studied by univariate and multivariate analysis. Altogether, 47 patients achieved a documented response. A 25% OR was observed in the combination arm while a 21% OR was seen in the 5FU arm; this difference is not statistically significant (P=0.6). Patients with a small tumour burden (below 5 cm2) showed a higher probability of response in both arms. Patients in the experimental arm had a higher but not statistically significant cumulative progression-free probability. Median survival was 47.1 weeks overall, while it was 43.7 and 48.5 weeks in the control and experimental arms, respectively. The combination was clearly more toxic than 5FU alone, leukopenia being the most frequent side-effect in the experimental arm and nausea and vomiting in the control arm. In conclusion these results are quite disappointing and 5FU + IFNα-2a can not be considered a standard treatment for advanced colon cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004320050154
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  • 5
    Electronic Resource
    Electronic Resource
    Circulating endothelin-1 levels in type 2 diabetic patients with ischaemic heart disease (1996)
    Springer
    Acta diabetologica 33 (1996), S. 246-248 
    Details
    ISSN: 1432-5233
    Keywords: Endothelin-1 (Et-1) ; Type 2 diabetes mellitus ; Coronary artery disease (CAD)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To investigate whether circulating endothelin-1 (Et-1) may be related to the increased incidence and severity of ischaemic heart disease in type 2 diabetes mellitus, we compared the concentrations in type 2 diabetic patients and in non-diabetic patients with coronary artery disease (CAD) angiographically documented. Plasma levels of Et-1 were determined in 34 type 2 diabetic patients with CAD (16 with stable angina, 6 with unstable angina, 12 with previous myocardial infarction) and in 19 non-diabetic patients with CAD (4 with stable angina, 5 with unstable angina, 10 with previous myocardial infarction). Fifteen diabetic patients without CAD and 9 healthy volunteers served as control subjects. In the type 2 diabetic patients, the mean Et-1 levels were 3.19±1.61 pmol/l in those with stable angina, 3.58±1.92 pmol/l in those with unstable angina, 4.24±2.53 pmol/l in those with myocardial infarction. These values were not significantly different one another, nor from the values obtained from type 2 diabetic controls (3.64±2.13 pmol/l). In the non-diabetic patients, the mean Et-1 levels were 3.92±0.73 pmol/l in those with stable angina, 4.35±1.67 pmol/l in those with unstable angina, 4.33±1.66 pmol/l in those with myocardial infarction. These values were not significantly different one another, but significantly higher than those obtained from healthy controls (2.07±0.67 pmol/l;P〈0.001). No significant differences were found in Et-1 levels between diabetic and non-diabetic patients with stable, unstable angina and previous myocardial infarction. In contrast, a statistically significant difference was found in Et-1 levels between diabetic and non-diabetic control subjects (P〈0.05). In conclusion, similar raised concentrations of Et-1 in diabetic and non-diabetic patients with stable, unstable angina and previous myocardial infarction do not support the hypothesis that higher levels of Et-1 in diabetic patients are responsible for the increased incidence of CAD in diabetes mellitus. However, the raised Et-1 levels found in diabetic patients in the absence of CAD strongly suggest that a generalised endothelial dysfunction, documented in our study by increased levels of Et-1, most probably precedes subsequent cardiovascular diseases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02048552
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  • 6
    Electronic Resource
    Electronic Resource
    Circulating endothelin-1 levels in type 2 diabetic patients with ischaemic heart disease (1996)
    Springer
    Acta diabetologica 33 (1996), S. 246-248 
    Details
    ISSN: 1432-5233
    Keywords: Key words Endothelin-1 (Et-1) ; Type 2 diabetes mellitus ; Coronary artery disease (CAD)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To investigate whether circulating endothelin-1 (Et-1) may be related to the increased incidence and severity of ischaemic heart disease in type 2 diabetes mellitus, we compared the concentrations in type 2 diabetic patients and in non-diabetic patients with coronary artery disease (CAD) angiographically documented. Plasma levels of Et-1 were determined in 34 type 2 diabetic patients with CAD (16 with stable angina, 6 with unstable angina, 12 with previous myocardial infarction) and in 19 non-diabetic patients with CAD (4 with stable angina, 5 with unstable angina, 10 with previous myocardial infarction). Fifteen diabetic patients without CAD and 9 healthy volunteers served as control subjects. In the type 2 diabetic patients, the mean Et-1 levels were 3.19±1.61 pmol/l in those with stable angina, 3.58±1.92 pmol/l in those with unstable angina, 4.24±2.53 pmol/l in those with myocardial infarction. These values were not significantly different one another, nor from the values obtained from type 2 diabetic controls (3.64±2.13 pmol/l). In the non-diabetic patients, the mean Et-1 levels were 3.92±0.73 pmol/l in those with stable angina, 4.35±1.67 pmol/l in those with unstable angina, 4.33±1.66 pmol/l in those with myocardial infarction. These values were not significantly different one another, but significantly higher than those obtained from healthy controls (2.07±0.67 pmol/l; P〈0.001). No significant differences were found in Et-1 levels between diabetic and non-diabetic patients with stable, unstable angina and previous myocardial infarction. In contrast, a statistically significant difference was found in Et-1 levels between diabetic and non-diabetic control subjects (P〈0.05). In conclusion, similar raised concentrations of Et-1 in diabetic and non-diabetic patients with stable, unstable angina and previous myocardial infarction do not support the hypothesis that higher levels of Et-1 in diabetic patients are responsible for the increased incidence of CAD in diabetes mellitus. However, the raised Et-1 levels found in diabetic patients in the absence of CAD strongly suggest that a generalised endothelial dysfunction, documented in our study by increased levels of Et-1, most probably precedes subsequent cardiovascular diseases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02048552
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    Paper (German National Licenses)
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  • 7
    Electronic Resource
    Electronic Resource
    A family of rapidly evolving genes from the sex reversal critical region in Xp21 (1995)
    Springer
    Mammalian genome 6 (1995), S. 571-580 
    Details
    ISSN: 1432-1777
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Patients with an intact SRY gene and duplications of portions of Xp21 develop as phenotypic females. We have recently mapped this sex reversal locus, DSS, to a 160-kb region of Xp21 that includes the adrenal hypoplasia congenita locus. To clone the gene(s) underlying DSS and AHC, we isolated expressed sequences quences from the region. Here we describe the characterization of two related genes. DAM10 and DAM6, expressed in adult testis and lung tumors. The predicted DAM10 and DAM6 proteins are 66% identical and are both highly similar to the MAGE family of tumor-associated antigens and to mouse necdin. Genes belonging to the MAGE superfamily, DAMs, MAGEs, and necdin, are likely to have originated from a common ancestor and to be subject to an unusually rapid evolution. The tumor-restricted expression of DAM proteins and their structural similarity to MAGE genes suggest that DAM peptides may be targets for active immunotherapy in lung cancer patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00352360
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    Paper (German National Licenses)
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