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Biomedical subjects

C Welter

Publications and source records attributed to C Welter.

At least 19 recordsLinked to original sources
PubMed2007

1[alpha],25-dihydroxyvitamin D(3) enhances annexin II dependent proliferation of osteoblasts.

Cells experience a variety of physiological and non-physiological stresses and consequently have appropriate mechanisms to deal with such deviations from homeostasis. Particularly subject to mechanical stress and shear forces are the cells that make up the bones. Osteoblastic cells can interpret this stress as a stimulus for proliferation; however, the molecular mechanisms underlying this phenomenon are poorly understood. We have identified annexin II as being specifically upregulated in mechanically stressed osteoblasts and found that increased levels of this protein are necessary for 1[alpha],25-dihydroxyvitamin D(3) mediated augmentation of the proliferative response of osteoblasts after mechanical stress. Our data demonstrate a novel interaction between 1[alpha],25-dihydroxyvitamin D(3) and annexin II in the proliferative response of osteoblasts as well as a novel function for annexin II in the stress response. These findings may offer new therapeutic opportunities for conditions that require regenerative osteoblastic activity such as osteoporosis.

Adult↗
PubMed2005

Expression of the nm23 homologues nm23-H4, nm23-H6, and nm23-H7 in human gastric and colon cancer.

Eight members of the nm23-gene family have been described. The involvement of nm23-H1 and nm23-H2 in tumour progression and metastasis, as well as in gene regulation and apoptosis, has been shown in numerous studies. Whether nm23-H4, -H6, and -H7 play a role in tumours is, however, largely unknown. This study describes data on the expression of these three nm23 homologues in human colon and gastric cancer by real-time RT-PCR and immunohistochemistry. Increased expression of these genes, most strikingly nm23-H4 and -H7, was observed in the majority of tumours analysed. No correlation with tumour stage according to the TNM classification was found. In contrast, by immunohistochemical analysis, nm23-H4 and -H6 overexpression correlated with the intestinal tumour type in gastric cancer tissues, whereas no increased immunoreactivity for the three nm23 proteins was noted in the diffuse type tumour specimens. These findings indicate that nm23-H6, and particularly nm23-H4 and -H7, may be involved in the development of colon and gastric carcinoma, the latter possibly in a type-specific manner. A contribution to tumour progression or metastasis could not, however, be proven. Elucidation of the specific mechanisms by which the nm23 homologues nm23-H4, -H6, and -H7 are involved in tumour development requires further studies.

Adenocarcinoma↗
PubMed2005

2D and 3D Ultrasound in the evaluation of normal and abnormal fetal anatomy in the second and third trimesters in a level III center.

Between July 2000 and December 2003, a total number of 3,472 fetuses was evaluated by two-dimensional (2D) and three-dimensional (3D) ultrasonography. All examinations were carried out as part of a detailed level III ultrasound examination for fetal anomalies. The gestational age was between 11 and 35 weeks. A 3D endovaginal probe (5 - 7 MHz) was used for examinations between 11 and 13 weeks, and an abdominal 3D probe (5 MHz) after 13 weeks. Four different 3D image display modes were employed in visualizing fetal malformations: triplanar orthogonal display; surface display; transparent display; and the combined transparent and color display (= glass body-rendering). In 906 of the 3,472 high-risk pregnancies, fetuses with one to five fetal defects were found (mean 1.17). The total number of detected defects was 1,012, exclusive of 48 fetal heart defects. Fetal heart defects were excluded from this study since a reliable demonstration of these defects was not possible by 3D ultrasound. Comparing the 2D and 3D techniques, 3D sonography proved advantageous in 60.8 % of the defects, with the benefit derived from the exact tomographic survey using the multiplanar view in 69.9 % of these cases, from a more precise demonstration of the defect in the surface view in 25.2 %, from a distinct demonstration in the transparent view in 3.9 %, and from a precise demonstration in the combined transparent and color view in 1.0 %. In 42 of the 1,012 malformations (4.2 %), a defect was accurately identified or verified with 3D ultrasound only. 3D ultrasound proves not only a useful tool in appreciating the severity of a fetal defect, but also provides more convincing evidence of a normal fetus than conventional two-dimensional sonograms in cases with increased risk of a recurrent surface malformation.

Congenital Abnormalities↗
PubMed2001

Simultaneous surgical revascularization and angiogenic gene therapy in diffuse coronary artery disease.

OBJECTIVE: The cytokine vascular endothelial growth factor (VEGF) is capable of triggering angiogenesis and at higher concentrations vasculogenesis. We report on a pilot study where VEGF-DNA as an additional therapy to coronary artery bypass grafting was injected into the myocardium in 24 patients (pts) with proximal coronary artery stenosis and diffuse peripheral disease. One region of the myocardium with proven ischemia remained unsupplied after surgery because the respective epicardial coronary artery was not graftable. METHODS AND RESULTS: Plasmid DNA encoding for the 165- and 167-amino acid isoform of the human VEGF genes was injected directly into the myocardium, not amenable to surgical revascularization at a dosage of 1000 microg each, using a standardized protocol. A (99m)Tc-sestamibi-SPECT at rest performed 7 days prior to the operation, had shown decreased marker activity in the region of interest. Controls were made 1 week and 80-100 days postoperatively. Transmural scarring was ruled out intraoperatively. Coronary and left ventricular angiographies were performed preoperatively and 3 months postsurgery, respectively. One or more of the following angiographic items were found in 16/24 patients postoperatively. (1) Improvement of regional left ventricular function at the VEGF treated myocardial sector (5/24 pts). (2) Newly visible vessels considered as collaterals (8/24 pts). (3) Earlier filling of parent vessels (6/24 pts). (4) An increase in diameter of preoperatively existing collateral vessels (7/24). An increased perfusion at rest in the region of gene application was detected in 3/24 patients by early postoperative (99m)Tc-sestamibi-SPECT investigation. In six additional cases, local perfusion increased markedly until the late examination. No perioperative myocardial infarctions and no signs of inflammation were observed. Newly developed abnormal vasculature was not detected in any patient. CONCLUSIONS: Direct intramyocardial administration of VEGF(165)-DNA and VEGF(167)-DNA may result occasionally in an enhancement of collateral vascularization in regions with diffuse peripheral coronary artery disease not surgically amenable. During midterm follow-up no adverse effects of VEGF-DNA application are observed so far. The very slight midterm improvements caused us to stop further VEGF-DNA application and, in our opinion, do not justify a prospective, and randomized study with a control group.

Aged↗
PubMed2001

DNA mismatch repair enzyme hMSH2 in malignant melanoma: increased immunoreactivity as compared to acquired melanocytic nevi and strong mRNA expression in melanoma cell lines.

Mutations in the mismatch DNA repair gene human MutS homologen 2 (hMSH2) are causative for microsatellite instability and carcinogenesis in various human tumours, including hereditary nonpolyposis colorectal cancer. Because microsatellite instability has been detected in malignant melanoma, we have investigated hMSH2 in melanocytic tumours. We found strong nuclear immunoreactivity for hMSH2 that was elevated in malignant melanoma and melanoma metastases as compared to acquired nevi. These findings suggest that increased genomic instability in malignant melanoma is associated with elevated protein levels of this DNA repair enzyme. hMSH2 is not exclusively regulated by proliferative activity in melanocytes, because there was no correlation between staining patterns of hMSH2 and the proliferation marker Ki-67. In contrast, immunoreactivity scores for hMSH2 and p53 were both upregulated in malignant melanocytic tumours. These findings support the concept that hMSH2 gene expression may be regulated in melanocytes by the p53 protein, as has been reported previously in other tissues. Using the reverse transcription-polymerase chain reaction, we detected strong hMSH2 mRNA expression in each of 8 melanoma cell lines analysed (highest amounts in SK-MEL-25 cells, lowest amounts in MML-I cells). In conclusion, our findings indicate that hMSH-2 may be of importance for genetic stability, tumorigenesis and progression of malignant melanoma.

Base Pair Mismatch↗
PubMed2001

Reference values of fetal aortic flow velocity waveforms and associated intra-observer reliability in normal pregnancies.

OBJECTIVES: It was the aim of the present study to calculate new Doppler reference ranges for blood flow velocities (Vmax, Vmean, Vmin) and resistance indices (PI, RI) for the fetal descending aorta by automatic waveform analysis. DESIGN: Cross-sectional prospective study. SUBJECTS: Nine hundred and twenty-six low-risk pregnancies at 18-41 weeks' gestation. METHODS: Aortic blood flow velocities were derived with pulsed-wave color Doppler. Measurements were carried out at the level of the diaphragm. Reference ranges for the individual measuring parameters were constructed based on a growth function from a four-parameter class of monotonic continuous functions according to the smallest square principle. Further investigated were intra-observer reliability and the influence exerted by different measuring sites (aortic arch, diaphragm, below the renal vessels) on the aortic Doppler flow spectrum. RESULTS: Although a significant increase in aortic blood flow velocity was observed at 18-41 weeks' gestation (Vmax = 48.2 cm/s to 110.3 cm/s (P < 0.001), Vmean = 20 cm/s to 47.5 cm/s (P < 0.001) and Vmin = 7.6 cm/s to 18.6 cm/s (P < 0.001)), there were no significant changes in the pulsatility or resistance indices. The resistance indices PI and RI as well as absolute blood flow velocities (Vmax, Vmin) were significantly lower with increasing distance from the heart. Initial decreases were measured between the aortic arch and the diaphragm: PI, 2.34 to 1.87 (P < 0.0001); RI, 0.87 to 0.79 (P < 0.0001); Vmin: 8.5 cm/s to 15.0 cm/s (P < 0.0001). Furthermore, systolic blood flow velocities (Vmax) were decreased below the renal vessels from 97 cm/s to 64 cm/s (P < 0.0007). No significant changes were recorded in intensity-weighted mean flow velocities (Vmean). The intra-observer reliability was low, but of no clinical relevance. CONCLUSIONS: At constant measuring conditions, the reference ranges for blood flow velocities and resistance indices in the fetal aorta calculated by the authors serve as the basis for Doppler ultrasound antenatal examinations in a normal patient population and enable the early diagnosis of fetal risk.

Aorta, Thoracic↗
PubMed2001

[Personal Digital Assistants assisting in clinical and administrative tasks].

Personal digital assistants (PDAs) are increasingly used by many professional and private users. They replace and combine common calendars, directories, to-do-lists and much more. Supplemented by useful additional software they can assist the clinician in his daily routine work. This concerns typical medical information as well as administrative work but gets more importance with regard to the planned introduction of diagnosis related groups in Germany however. Exact coding of medical performance is essential for this future invoice system. How PDAs can be used convenient in this respect will be shown with examples from our department.

Diagnosis-Related Groups↗
PubMed2000

p53 and c-Jun functionally synergize in the regulation of the DNA repair gene hMSH2 in response to UV.

The tumor suppresser protein p53 is critical for guarding the genome from incorporation of damaged DNA (Lane, D. P. (1992) Nature 358, 15-16). A relevant stress that activates p53 function is UV light (Noda, A., Toma-Aiba, Y., and Fujiwara, Y. (2000) Oncogene 19, 21-31). Another well known component of the mammalian UV response is the transcription factor c-Jun (Angel, P., and Karin, M. (1991) Biochim. Biophys. Acta 1072, 129-157). We show here that upon UV irradiation p53 activates transcription of the human mismatch repair gene MSH2. Interestingly, this up-regulation critically depends on functional interaction with c-Jun. Hence, the synergistic interaction of a proto-oncogene with a tumor suppresser gene is required for the regulation of the mammalian stress response through activation of expression of MSH2.

Base Sequence↗
PubMed2000

Immunohistochemical analysis of DNA mismatch repair enzyme hMSH-2 in normal human skin and basal cell carcinomas.

We have analysed the expression and distribution of the DNA mismatch repair enzyme hMSH-2 in normal skin and basal cell carcinomas. hMSH-2 protein was investigated immunohistochemically (normal human skin: n = 10; basal cell carcinomas: n = 16) on frozen sections using a highly sensitive streptavidin-peroxidase technique and a specific mouse monoclonal antibody (clone FE11). In normal human skin, we found nuclear immunoreactivity for hMSH-2 in epidermal keratinocytes of the basal and first 1-3 suprabasal cell layers. All basal cell carcinomas analysed revealed strong nuclear imunoreactivity that was pronounced in peripheral tumour cells and cells of the palisade. Expression of hMSH-2 protein was consistently and strongly upregulated in tumour cells of the carcinomas as compared to adjacent unaffected epidermis or epidermis of normal human skin. Twelve of the sixteen carcinomas analysed revealed no visual correlation in comparing the labelling patterns for hMSH-2 with the labelling pattern for the proliferation marker Ki-67. Our findings indicate that (a) hMSH-2 is expressed in human epidermal keratinocytes, predominantly in lower cell layers of the viable epidermis; (b) expression of hMSH-2 protein is strongly upregulated in basal cell carcinomas as compared to unaffected epidermis; (c) the level of hMSH-2 proteins in the carcinomas is not exclusively regulated by the proliferative activity of these tumour cells; (d) inactivating mutations of the hMSH-2 gene may in the carcinomas not be involved in the carcinogenesis or microsatellite instability secondary to replication errors; (e) expression of hMSH-2 may be of importance for the genetic stability of basal cell carcinomas in vivo.

Adenosine Triphosphatases↗
PubMed2000

Value of the electronic scalpel (cut mode) in the evaluation of the fetal face.

OBJECTIVES: To evaluate the improvement of image quality and diagnostic value of fetal face examinations using the electric scalpel. METHODS: A total of 232 cases were examined. The fetuses were separated into two groups: Group A, including normal fetuses (n = 152) and Group B, fetuses with facial pathology (n = 80). The fetuses were divided into eight subgroups according to gestational age (9-12 weeks, 13-16 weeks, 17-20 weeks, 21-24 weeks, 25-28 weeks, 29-32 weeks, 33-36 weeks and 37-40 weeks). RESULTS: The number of cutting steps for the improvement of image quality ranged from 1 to 9 (mean value 3) in the group of normal fetuses and from 1 to 10 (mean value 3) in the group of fetuses with facial pathology. In the group of normal fetuses, superior image quality improvement was achieved in 68.4% of cases, moderate improvement in 28.9% and poor improvement in 2.6%. In the group of fetuses with facial pathology, high image quality improvement was obtained in 72.5% of cases, moderate improvement in 25.0% and insufficient improvement in 2.5%. There were no differences among the eight subgroups in the number of steps required relating to gestational age. CONCLUSIONS: The use of the electronic scalpel was associated with diagnostic improvement in 71.1% of cases in the group of normal fetuses, and in 75.0% in the group of fetuses with facial pathology.

Face↗
PubMed2000

Reference values of ductus venosus flow velocities and calculated waveform indices.

In recent years, investigations of the venous vascular system have become increasingly important in the assessment of fetal myocardial function. The aim of the present Doppler ultrasound study was to establish both new reference ranges for blood flow velocity during the different phases of the cardiac cycle (S, SD, D, a) and various calculated indices ((S-a)/S, (S-a)/V(mean), (S-a)D, S/D, a/S, S/a) for the ductus venosus. Pulsed-wave colour Doppler was used in this prospective cross-sectional study to examine 696 women with low-risk pregnancies during the period from 14 to 41 weeks' gestation. Reference curves were constructed for the individual measuring parameters based on a growth function from a four-parameter class of monotonic continuous functions according to the smallest square principle. A significant increase in blood flow velocity from 48 cm/s to 65.8 cm/s was observed during ventricular systole (=S) from 14 to 41 week's gestation. Similarly, increases in blood flow velocity were recorded during the endsystolic phase (=SD) (35.5 cm/s to 50.7 cm/s during early ventricular diastole (=D) (41.7 cm/s to 58 cm/s, p=0.0001) and atrial contraction (=a) (11.2 cm/s to 35 cm/s, p=0.0001), as well as for intensity-weighted mean velocity (30 cm/s to 48.3 cm/s). The venous indices were associated with significant decreases in the individual parameters with increasing gestational age: (S-a)/S from 0.77 to 0.47, (S-a)/V(mean) from 1.21 to 0.67, (S-a)/D from 0.89 to 0.54, S/a from 4.5 to 1.99. A significant increase from 0.23 to 0.53 was observed only for the quotient a/S. There were no changes in the S/D quotient (from 1.15 to 1.13). Regarding intra-observer reliability, more favourable results were obtained for calculated indices than for measurements of absolute blood flow velocities. At constant measuring conditions, the reference ranges established by this study for blood flow velocities and calculated indices in the ductus venosus may serve as the basis for Doppler ultrasound follow-up in a normal patient population as well as for the diagnosis of fetal myocardial insufficiency of hypoxic and congestive origin.

Adolescent↗
PubMed2000

Model of chronic systolic and diastolic dysfunction after cryothermia-induced myocardial necrosis in rats.

BACKGROUND AND PURPOSE: Left ventricular dysfunction following myocardial infarction is the most important predictor of adverse prognosis. Novel treatment options in infarction require an appropriate experimental model with a standardized, hemodynamically relevant myocardial injury. We evaluated a cryoinjury model in rodents that allows quantitative analysis of systolic and diastolic dysfunction. METHODS: Anesthetized, orally intubated, and ventilated Lewis rats (n = 12) underwent sternotomy. Myocardial necrosis was induced by use of a standardized cryolesion to the obtuse margin of the left ventricle, freezing for 3 minutes to -160 degrees C. Left ventricular performance was analyzed at day 120 after cryoinjury. Sham-operated animals (n = 10) served as controls. RESULTS: Cryoinjured animals behaved normally and gained weight up to day 120. Average heart weight of cryoinjured animals significantly exceeded that of controls. Left ventricular systolic pressure and systolic, diastolic, and mean aortic pressures were lower 4 months after cryoinjury, whereas left ventricular end-diastolic pressure was significantly increased. Cryoinjured animals had reduced aortic blood flow, as well as impaired maximal left ventricular dP/dt during aortic occlusion and aortic occlusion-provoked peak systolic pressure. Analysis of maximal rates of isovolumic pressure decrease revealed significant reduction in peak negative dP/dt in cryoinjured animals. Finally, time constants of isovolumic pressure decline were significantly prolonged in cryoinjured animals. CONCLUSION: Standardized cryothermia induces a myocardial lesion that results in highly reproducible impairment of left ventricular performance 120 days after cryothermia. The model is ideally suited to test novel therapeutic strategies for myocardial dysfunction.

Animals↗
PubMed1999

CAPN 8: isolation of a new mouse calpain-isoenzyme.

Recent molecular biological approaches indicate that calpain, also named CANP for calcium-activated neutral protease and originally characterized as an intracellular cytoplasmatic nonlysosomal cysteine protease that requires calcium ions for activity, constitutes a large superfamily consisting of ubiquitous and tissue specific homologues, which are widely distributed in cells of various organisms from human to fungus. Due to the increasing number of substrates along with the involvement of calpain isoenzymes in mammalian diseases, especially in malignancies, members of the calpain superfamily seem to be important biomodulators in physiological as well as pathological cell function. Here we report the characterisation of a new calpain, named CAPN 8 with a different C-terminal domain, implicating a putative new regulatory mechanism. Northern blot analysis revealed an ubiquitous expression with different RNA levels in all tissues examined. Highest levels were found in brain, kidney, and digestive tract, suggesting a specific regulatory function of CAPN 8 in these tissues.

Amino Acid Sequence↗
PubMed1999

Expression of calpain I messenger RNA in human renal cell carcinoma: correlation with lymph node metastasis and histological type.

Calpain, also named CANP (for calcium-activated neutral protease), is an intracellular cytoplasmatic non-lysosomal cysteine endopeptidase that requires calcium ions for activity. Many substrates of the calpain isoenzymes, such as the transcription factors c-Fos and c-Jun, the tumor supressor protein p53, protein kinase C, pp60c-src and the adhesion molecule integrin, have been implicated in the pathogenesis of different human tumors, suggesting an important role of the calpains in malignant diseases. We now report differential expression of the calpain I gene (CL I) in a variety of tumors, extending our study to a larger series of renal cell carcinomas. Using Northern-blot analysis, we studied calpain I expression in 30 renal cell carcinomas as compared with matched healthy tissues. Tumor samples were classified according to their histological type: 21 clear cell carcinomas, 4 chromophobe carcinomas, 3 papillary carcinomas and 2 oncocytomas. In renal tumor samples, calpain I gene mRNA was expressed at highly variable levels, significantly depending on the different histological types. Moreover, there was a correlation of higher calpain I expression with increased malignancy: within the clear cell carcinoma subset, tumor samples with advanced nodal status (N1 and N2) showed a significantly higher calpain I expression than tumors without metastasis to regional lymph nodes. Our data suggest an important role of calpain isoenzymes in carcinogenesis and tumor progression.

Biomarkers, Tumor↗
PubMed1999

Angiogenesis and microvascularization after cryothermia-induced myocardial infarction: a quantitative fluorescence microscopic study in rats.

OBJECTIVE: Microvascularization of infarcted myocardial tissue may be a prerequisite for successful therapeutic interventions, including cardiomyoblast or satellite cell transplantation. Because little is known on microvascular restitution within infarcted tissue, we studied angiogenesis and microvascularization after cryothermia-induced myocardial infarction using intravital fluorescence microscopic techniques. METHODS: In anesthetized, orally intubated and ventilated Sprague-Dawley rats (n = 20), a sternotomy was performed and a standardized cryolesion was induced to the right ventricle by freezing for 5 min to -160 degrees C. Myocardial angiogenesis and microvascularization were analyzed quantitatively after rethoracotomy on days 7 (n = 6) or 28 (n = 8). Sham-operated animals (n = 6) served as controls. RESULTS: Seven days after cryothermia, the central tissue area of the injured myocardium (28.4 +/- 9.2 mm2) was characterized by complete lack of capillary perfusion, while the periphery of the cryolesion (27.6 +/- 5.7 mm2) revealed a heterogeneous capillary perfusion pattern with a density of 300.9 +/- 38.9 cm-1. Adjacent myocardial tissue showed intact capillary perfusion (density: 563.0 +/- 44.4 cm-1) comparable with that of sham-operated controls. After 28 d the area with lack of capillary perfusion was found significantly reduced to 7.3 +/- 3.7 mm2 (P < 0.05); however, it was still surrounded by a heterogeneously perfused area of myocardial tissue of 57.7 +/- 19.2 mm2 (density: 271.1 +/- 52.7 cm-1), indicating partial restitution of capillary perfusion. Although at day 7 within the central zone of the cryolesions, capillary perfusion was completely shut down, perfusion of microvessels larger than capillaries, i.e., arterioles and venules, were found maintained, however, with a density markedly lower (1.96 +/- 1.04 mm-1) when compared with that of sham-controls (4.28 +/- 1.52 mm-1). After 28 d the number of these larger-sized microvessels increased significantly with values of density even higher compared with those observed in controls (6.89 +/- 1.71 mm-1; P < 0.05), indicating new vessel formation. CONCLUSIONS: Our study indicates partial restitution and function of the microvascular network within infarcted myocardial tissue, which may serve as an appropriate prerequisite for successful application of novel therapeutic strategies to improve myocardial function.

Animals↗
PubMed1999

The yeast two-hybrid system reveals no interaction between p73 alpha and SV40 large T-antigen.

SV40 and/or DNA sequences indistinguishable from SV40 have been detected in several types of human tumours. The oncoprotein of Simian virus 40, SV40 large T-antigen (Tag), is known to bind and inactivate tumour suppressor proteins, such as members of the retinoblastoma family and p53, thereby promoting cell transformation. In this study, we used the yeast two-hybrid system to investigate whether the Simian virus 40 (SV40) large T-antigen is able to interact with p73, a noval discovered putative tumour suppressor, that is homologous both structurally and functionally to p53. The yeast two-hybrid system is a genetic method to detect protein-protein-interactions in vivo. Our results suggest that the SV40 large T-antigen is not able to bind p73 in yeast although both proteins are expressed in the transformed yeast strain as was shown by western blot analysis.

Animals↗
PubMed1998

Glyceraldehyde-3-phosphate dehydrogenase and Nm23-H1/nucleoside diphosphate kinase A. Two old enzymes combine for the novel Nm23 protein phosphotransferase function.

We have recently discovered an alternative function of the putative metastasis suppressor protein Nm23, which is identical to nucleoside diphosphate kinase, as a protein phosphotransferase in vitro. While purified native Nm23 protein did not phosphorylate other proteins, we could purify a Nm23-associated protein that activates the protein phosphotransferase function; it was identified as a glyceraldehyde-3-phosphate dehydrogenase (GAPDH) isoenzyme. Co-expression and purification of (His)6-tagged GAPDH in combination with either Nm23-H1 or Nm23-H2 in baculovirus-infected Sf9 cells showed that only Nm23-H1, but not Nm23-H2, forms a stable complex with GAPDH. Protein phosphotransferase activity was confirmed for the recombinant GAPDH.Nm23-H1 complex but not for either of the enzymes alone, nor was this activity observed after simple mixing of the purified proteins in vitro. The molecular mass of the highly purified recombinant GAPDH.Nm23-H1 complex suggests that a dimer of GAPDH interacts with a dimer of Nm23-H1. In contrast to the complex with GAPDH, co-expression of Nm23-H1 with antioxidant protein (MER-5) or creatine kinase did not activate the protein phosphotransferase function, indicating that this activation may specifically require GAPDH as a binding partner.

Creatine Kinase↗