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C Graf

Publications and source records attributed to C Graf.

At least 19 recordsLinked to original sources
PubMed2006

No evidence of association between genetic variants of the PDCD1 ligands and SLE.

PDCD1, an immunoreceptor involved in peripheral tolerance has previously been shown to be genetically associated with systemic lupus erythematosus (SLE). PDCD1 has two ligands whose genes are located in close proximity on chromosome 9p24. Our attention was drawn to these ligands after finding suggestive linkage to a marker (gata62f03, Z=2.27) located close to their genes in a genome scan of Icelandic families multiplex for SLE. Here, we analyse Swedish trios (N=149) for 23 single nucleotide polymorphisms (SNPs) within the genes of the PDCD1 ligands. Initially, indication of association to eight SNPs was observed, and these SNPs were therefore also analysed in Mexican trios (N=90), as well as independent sets of patients and controls from Sweden (152 patients, 448 controls) and Argentina (288 patients, 288 controls). We do not find support for genetic association to SLE. This is the first genetic study of SLE and the PDCD1 ligands and the lack of association in several cohorts implies that these genes are not major risk factors for SLE.

Antigens, CD↗
PubMed2006

[Integrated Health Care in cardiology].

Integrated Health Care forces rethinking of all partners. Health care providers need to cooperate and have to face an emerging competition among themselves. Health insurance companies are no longer the common enemy, but a business partner on an individual basis. Rethinking has already commenced. The Barmer insurance company has initiated a considerable number of similar contracts with respect to Integrated Health Care in cardiology. One of the first contracts was agreed upon at Recklinghausen (it is reported later in this volume) and a couple of them have been concluded in the Berlin/Brandenburg region (which are also reported in this volume).A special feature is the support for the general disease management programs that have been initiated in light of the new laws beginning in 2000. The Barmer company will enroll some 500,000 patients with coronary artery disease in these programs.

Adolescent↗
PubMed2006

Melanoma cultures show different susceptibility towards E1A-, E1B-19 kDa- and fiber-modified replication-competent adenoviruses.

Replicating adenovirus (Ad) vectors with tumour tissue specificity hold great promise for treatment of cancer. We have recently constructed a conditionally replicating Ad5 AdDeltaEP-TETP inducing tumour regression in a xenograft mouse model. For further improvement of this vector, we introduced four genetic modifications and analysed the viral cytotoxicity in a large panel of melanoma cell lines and patient-derived melanoma cells. (1) The antiapoptotic gene E1B-19 kDa (Delta19 mutant) was deleted increasing the cytolytic activity in 18 of 21 melanoma cells. (2) Introduction of the E1A 122-129 deletion (Delta24 mutant), suggested to attenuate viral replication in cell cycle-arrested cells, did not abrogate this activity and increased the cytolytic activity in two of 21 melanoma cells. (3) We inserted an RGD sequence into the fiber to extend viral tropism to alphav integrin-expressing cells, and (4) swapped the fiber with the Ad35 fiber (F35) enhancing the tropism to malignant melanoma cells expressing CD46. The RGD-fiber modification strongly increased cytolysis in all of the 11 CAR-low melanoma cells. The F35 fiber-chimeric vector boosted the cytotoxicity in nine of 11 cells. Our results show that rational engineering additively enhances the cytolytic potential of Ad vectors, a prerequisite for the development of patient-customized viral therapies.

Adenoviridae↗
PubMed2005

Endothelial function in the forearm circulation of patients with the metabolic syndrome--effect of different lipid-lowering regimens.

We compared the effect of statin therapy (either alone or combined with ezetimibe) on the inhibition of cholesterol resorption and endothelial function by measuring forearm blood flow in male patients with the metabolic syndrome. Compared to 40 mg atorvastatin alone, combination therapy with 10 mg ezetimibe and 10 mg atorvastatin for 8 weeks resulted in significantly decreased total serum cholesterol and triglycerides levels (n = 14). Endothelium-dependent, acetylcholine-mediated vasodilation was significantly better with combination therapy (p < 0.05). In contrast, endothelium-independent forearm blood flow response to sodium nitroprusside was comparable in both groups. Our data suggest a more effective restoration of endothelial function with the statin/ezetimibe combination compared to statin monotherapy in patients with the metabolic syndrome.

Acetylcholine↗
PubMed2004

Correlation between BMI, leisure habits and motor abilities in childhood (CHILT-project).

INTRODUCTION: The prevalence of childhood obesity is increasing with its negative medical and psychosocial consequences. This paper examines the association between body mass index (BMI), motor abilities and leisure habits of 668 children within the CHILT (Children's Health InterventionaL Trial) project. METHOD: A total of 668 children (51.0% boys; 49.0% girls) and their parents were questioned on sport and leisure behaviour of the children. The anthropometric data were measured. Motor abilities were determined by a body gross motor development test for children (Köperkoordinationstest für Kinder; KTK) and a 6-min run. RESULTS: The children were 6.70 +/- 0.42 y old, 122.72 +/- 5.36 cm tall and weighed 24.47 +/- 4.59 kg, the average BMI was 16.17 +/- 2.27 kg/m2. KTK showed an average motor quotient (MQ) of 93.49 +/- 15.01, the 6-min run an average of 835.24 +/- 110.87 m. Both tests were inversely correlated with BMI (KTK and BMI r=-0.164 (P<0.001); 6-min run and BMI r=-0.201 (P<0.001)); the group of overweight/obese children showed poorer results than the normal/underweight ones, even after adjustment for gender and age (in each case P<0.001). Children with the greatest extent of exercise achieve the highest MQ (P=0.035). SUMMARY: Overweight/obesity is associated with a poorer body gross motor development and endurance performance. On the other hand, an active lifestyle is positively correlated with a better gross motor development in first-grade children. Therefore, to prevent the negative consequences of physical inactivity and overweight/obesity early intervention to support exercise and movement is recommended.

Analysis of Variance↗
PubMed2004

[Ultrasound follow-up of palpable solid, probably benign breast lesions (BI-RADS category III)].

PURPOSE: To determine whether palpable non-calcified solid breast masses with benign morphology on ultrasound can be classified as probably benign and whether these lesions fulfill the criteria required for BI-RADS (TM) category III. MATERIALS AND METHODS: This analysis includes 78 patients with 80 palpable non-calcified solid masses that were classified as probably benign at initial sonography. Of 78 patients, 66 had periodic imaging surveillance (2 - 8 years, mean 4.6 years). The remaining 12 patients had a biopsy after initial imaging. RESULTS: In the 64 patients under surveillance, palpable lesions remained stable at follow-up. In 2 patients lesions increased in size during follow-up and no malignancy was diagnosed at subsequent open biopsy. In 19 of the 66 patients, 29 additional nonpalpable lesions of similar morphology were detected on ultrasound. No malignancy was diagnosed in the 12 patients, who had a biopsy after initial imaging. CONCLUSION: Our data suggest that palpable non-calcified solid breast masses with benign morphology on ultrasound can be classified as probably benign (BI-RADS (TM) category III). Biopsy can be averted when lesions remain stable at follow-up.

Adolescent↗
PubMed2003

A novel attenuated replication-competent adenovirus for melanoma therapy.

To generate a replication-competent adenovirus (Ad) with specificity for melanoma, we constructed a tissue-specific promoter restricting E1A expression to melanoma cells. The combination of four copies of a mouse tyrosinase enhancer element (TE) fused to the human tyrosinase promoter (TP) yielded up to 2000-fold higher luciferase reporter activity in tyrosinase-expressing melanoma cells than in nonmelanoma cells. Insertion of the composite TETP construct upstream of the E1A gene was combined with deleting as far as possible the intertwined endogenous Ad enhancer/promoter (EP). The resulting AdDeltaEP-TETP vector, also deleted for the E3 region, was found to replicate in tyrosinase-positive melanoma cells, such as SK-Mel23 as efficiently as wild-type Ad5, but at a more than 50-fold reduced level in nonmelanoma tumour cells and primary human cells. Injection of AdDeltaEP-TETP into xenotransplanted melanomas, but not into HeLa-derived tumours led to long-lasting tumour regression in nude mice. This AdDeltaEP-TETP virus might be useful for the treatment of accessible lesions in advanced melanoma patients.

Adenoviridae↗
PubMed2002

Remitting seronegative symmetrical synovitis with pitting oedema: a study of 12 cases.

Twelve patients with remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) were analysed. Eight of them had typical RS3PE without underlying disease, and four presented associated neoplasia. The first patients experienced an excellent response to low doses of prednisone, and they all achieved complete and permanent remission. The mean treatment duration was 18 months and the mean follow-up was 4.4 years. During the follow-up, none of these patients relapsed, had fever or general health deterioration, and hand and foot radiographs did not show erosion. One of them developed a panarteritis nodosa 6 years later. Four RS3PE patients had associated neoplasia. Two were with solid malignancies, and the other two presented haematological malignancies. In one of them RS3PE preceded the diagnosis of malignancy. The diagnosis of RS3PE in the other patients was subsequent to cancer. The first patients presented clinical characteristics suggestive of paraneoplastic RS3PE, and they had a poor response to corticosteroid therapy. Two patients died, and the rest of them had a complete response to surgical resection of the tumour or to chemotherapy. In general, idiopathic RS3PE patients do not show either general health deterioration or fever and they do respond to low doses of steroids (10 mg/day). We observed strong contrasts with the results obtained when treating RS3PE patients with associated neoplasia. In patients with RS3PE the presence of systemic symptoms along with resistance to low doses of corticosteroid therapy should alert the physician to the possible presence of malignancy.

Adenocarcinoma↗
PubMed2001

[Changes in penile blood flow during cycling--how does one prevent a decreased perfusion?].

BACKGROUND AND OBJECTIVES: An increased incidence of erectile dysfunction has been observed in cycling enthusiasts. Compression of the perineal region during cycling seems to cause decreased penile perfusion. The resulting hypoxaemia in the corpus cavernosum is associated with penile fibrosis, which leads in the long run to erectile dysfunction. This study set out to determine if cycling can cause changes in penile perfusion and, if so, what precautions can be taken to avoid any associated health hazards, including whether various saddle forms and designs might influence penile blood flow. COHORTS AND METHODS: In 100 healthy athletic men (aged 36 +/- 6.2 years) transcutaneous penile oxygen pressure (tpO (2)) at the glans penis was measured during cycling in different positions and with different types of saddle, using a modified Clark oxygen electrode. RESULTS: The penile blood supply decreased significantly during cycling in a seated position. Cycling in a standing or reclining position (on a reclining bicycle) did not lead to any decrease in penile blood flow. Saddle width was the most important factor for ensuring adequate penile perfusion while cycling in a seated position. CONCLUSION: This study demonstrates that changing from a seated to a standing position during cycling leads to a significant increase in penile perfusion. Therefore we suggest frequent changes from a seated to a standing position during cycling. Additionally we suggest taking sufficient breaks during prolonged and vigorous bike tours, in order to avoid any possible health hazards. Another, not yet widespread, alternative for avoiding a reduction in penile blood flow is cycling on a reclining bicycle.

Adult↗
PubMed2001

[Preventing coronary heart disease by physical activity. How much exercise is necessary?].

The value of general measures, in particular physical exercise, for the prevention of cardiac disease has been unequivocally demonstrated. Meta-analyses done to investigate the preventive character of exercise have shown that the coronary risk of physically active persons is lower by a factor of 2 to 3. This reduction in risk is independent of the presence of other risk factors, and is not due to the better health awareness of those who are physically active. However, the amount or intensity of such training actually required remains uncertain. A number of studies report a protective effect only for intensive physical effort, while others claim a risk reduction independent of training intensity. In the last resort, however, any form of exercise is better than none at all, when it comes to lowering the coronary risk. Not only endurance sports, but also other types of sport, such as tennis, or daily activities, can be recommended.

Adult↗
PubMed2001

Integrated effects of the vasodilating beta-blocker nebivolol on exercise performance, energy metabolism, cardiovascular and neurohormonal parameters in physically active patients with arterial hypertension.

OBJECTIVE: The present study was designed to investigate the integrated effects of the beta-1-selective blocker with vasodilator properties, nebivolol, on systemic haemodynamics, neurohormones and energy metabolism as well as oxygen uptake and exercise performance in physically active patients with moderate essential hypertension (EH). DESIGN AND METHODS: Eighteen physically active patients with moderate EH were included: age: 46.9 +/- 2.38 years, weight: 83.9 +/- 2.81 kg, blood pressure (BP): 155.8 +/- 3.90/102.5 +/- 1.86 mm Hg, heart rate: 73.6 +/- 2.98 min(-1). After a 14-day wash-out period a bicycle spiroergometry until exhaustion (WHO) was performed followed by a 45-min submaximal exercise test on the 2.5 mmol/l lactate-level 48 h later. Before, during and directly after exercise testing blood samples were taken. An identical protocol was repeated after a 6-week treatment period with 5 mg nebivolol/day. RESULTS: Nebivolol treatment resulted in a significant (P < 0.01) decrease in systolic and diastolic BP and heart rate at rest and during maximal and submaximal exercise. Maximal physical work performance, blood lactate and rel. oxygen uptake (rel. VO(2)) before and after nebivolol treatment at rest and during maximal and submaximal exercise remained unaltered. Free fatty acid, free glycerol, plasma catecholamines, beta-endorphines and atrial natriuretic peptide (ANP) increased before and after treatment during maximal and submaximal exercise but remained unaltered by nebivolol treatment. In contrast, plasma ANP levels at rest were significantly higher in the presence of nebivolol, endothelin-1 levels were unchanged. CONCLUSIONS: Nebivolol was effective in the control of BP at rest and during exercise in patients with EH. Furthermore, nebivolol did not negatively affect lipid and carbohydrate metabolism and substrate flow. The explanation for the effects on ANP at rest remain elusive. This pharmacodynamic profile of nebivolol is potentially suitable in physically active patients with EH.

Adrenergic beta-Antagonists↗