Biomedical subjects

Andreas Meyer

Publications and source records attributed to Andreas Meyer.

23 records · Page 2Linked to original sources

PubMed2002

Inhaled iloprost for severe pulmonary hypertension.

BACKGROUND: Uncontrolled studies suggested that aerosolized iloprost, a stable analogue of prostacyclin, causes selective pulmonary vasodilatation and improves hemodynamics and exercise capacity in patients with pulmonary hypertension. METHODS: We compared repeated daily inhalations of 2.5 or 5.0 microg of iloprost (six or nine times per day; median inhaled dose, 30 microg per day) with inhalation of placebo. A total of 203 patients with selected forms of severe pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (New York Heart Association [NYHA] functional class III or IV) were included. The primary end point was met if, after week 12, the NYHA class and distance walked in six minutes were improved by at least one class and at least 10 percent, respectively, in the absence of clinical deterioration according to predefined criteria and death. RESULTS: The combined clinical end point was met by 16.8 percent of the patients receiving iloprost, as compared with 4.9 percent of the patients receiving placebo (P=0.007). There were increases in the distance walked in six minutes of 36.4 m in the iloprost group as a whole (P=0.004) and of 58.8 m in the subgroup of patients with primary pulmonary hypertension. Overall, 4.0 percent of patients in the iloprost group (including one who died) and 13.7 percent of those in the placebo group (including four who died) did not complete the study (P=0.024); the most common reason for withdrawal was clinical deterioration. As compared with base-line values, hemodynamic values were significantly improved at 12 weeks when measured after iloprost inhalation (P<0.001), were largely unchanged when measured before iloprost inhalation, and were significantly worse in the placebo group. Further significant beneficial effects of iloprost treatment included an improvement in the NYHA class (P=0.03), dyspnea (P=0.015), and quality of life (P=0.026). Syncope occurred with similar frequency in the two groups but was more frequently rated as serious in the iloprost group, although this adverse effect was not associated with clinical deterioration. CONCLUSIONS: Inhaled iloprost is an effective therapy for patients with severe pulmonary hypertension.

Administration, Inhalation↗

PubMed2002

Hydroxylation of indole by laboratory-evolved 2-hydroxybiphenyl 3-monooxygenase.

Directed enzyme evolution of 2-hydroxybiphenyl 3-monooxygenase (HbpA; EC ) from Pseudomonas azelaica HBP1 resulted in an enzyme variant (HbpA(ind)) that hydroxylates indole and indole derivatives such as hydroxyindoles and 5-bromoindole. The wild-type protein does not catalyze these reactions. HbpA(ind) contains amino acid substitutions D222V and V368A. The activity for indole hydroxylation was increased 18-fold in this variant. Concomitantly, the K(d) value for indole decreased from 1.5 mm to 78 microm. Investigation of the major reaction products of HbpA(ind) with indole revealed hydroxylation at the carbons of the pyrrole ring of the substrate. Subsequent enzyme-independent condensation and oxidation of the reaction products led to the formation of indigo and indirubin. The activity of the HbpA(ind) mutant monooxygenase for the natural substrate 2-hydroxybiphenyl was six times lower than that of the wild-type enzyme. In HbpA(ind), there was significantly increased uncoupling of NADH oxidation from 2-hydroxybiphenyl hydroxylation, which could be attributed to the substitution D222V. The position of Asp(222) in HbpA, the chemical properties of this residue, and the effects of its substitution indicate that Asp(222) is involved in substrate activation in HbpA.

Catalysis↗

PubMed2001

Changing the substrate reactivity of 2-hydroxybiphenyl 3-monooxygenase from Pseudomonas azelaica HBP1 by directed evolution.

The substrate reactivity of the flavoenzyme 2-hydroxybiphenyl 3-monooxygenase (EC, HbpA) was changed by directed evolution using error-prone PCR. In situ screening of mutant libraries resulted in the identification of proteins with increased activity towards 2-tert-butylphenol and guaiacol (2-methoxyphenol). One enzyme variant contained amino acid substitutions V368A/L417F, which were inserted by two rounds of mutagenesis. The double replacement improved the efficiency of substrate hydroxylation by reducing the uncoupled oxidation of NADH. With guaiacol as substrate, the two substitutions increased V(max) from 0.22 to 0.43 units mg(-1) protein and decreased the K'(m) from 588 to 143 microm, improving k'(cat)/K'(m) by a factor of 8.2. With 2-tert-butylphenol as the substrate, k'(cat) was increased more than 5-fold. Another selected enzyme variant contained amino acid substitution I244V and had a 30% higher specific activity with 2-sec-butylphenol, guaiacol, and the "natural" substrate 2-hydroxybiphenyl. The K'(m) for guaiacol decreased with this mutant, but the K'(m) for 2-hydroxybiphenyl increased. The primary structure of HbpA shares 20.1% sequence identity with phenol 2-monooxygenase from Trichosporon cutaneum. Structure homology modeling with this three-domain enzyme suggests that Ile(244) of HbpA is located in the substrate binding pocket and is involved in accommodating the phenyl substituent of the phenol. In contrast, Val(368) and Leu(417) are not close to the active site and would not have been obvious candidates for modification by rational design.

Amino Acid Sequence↗

PubMedDate not supplied

Long-term survival over 28 years of a patient with metastatic adrenal cortical carcinoma--case report.

Adrenal cortical carcinoma (ACC) is a rare and highly malignant tumour with up to 70% of the patients diagnosed at an advanced clinical stage, up to 40% presenting with metastases. Even after complete surgical excision, up to 80% of the patients show locoregional recurrence or metastases. We report a case of a 62-year-old woman with a non-functional ACC of the left adrenal gland (T2N0M0 classified as stage II). After the initial resection, 3 operations for metastasis of the contralateral adrenal gland and 4 operations for metastasis of the lungs were carried out, allowing survival for more than 28 years with a good quality of life. This case report emphasises the need for careful clinical and radiographic follow-up. A repeat surgical approach should be adopted whenever possible providing long-term survival over decades.

Adrenal Cortex Neoplasms↗

PubMedDate not supplied

Partial resection of the sternum for osseous metastasis of differentiated thyroid cancer: case report.

BACKGROUND: Due to their resistance to radio-iodine therapy, skeletal metastases from differentiated thyroid cancer (DTC) are difficult to treat. Surgical resection of solitary skeletal metastasis may offer cure with prolonged survival. CASE REPORT: A patient with the simultaneous appearance of local recurrence of DTC and skeletal metastasis of the cranial sternum is reported. After radical excision of the tumour recurrence and the lymph nodes, a partial sternal resection was carried out, and the defect in the chest wall was reconstructed with polypropylene mesh. Radio-iodine ablation therapy was carried out 4 times after the operation for locally recurrent disease. At the follow-up, 4 1/2 years after the resection of the sternal metastasis, the patient is free of disease. CONCLUSION: Sternal resection for solitary osseous metastasis of DTC should be performed on selected, individual patients. Reconstruction of the sternum with polypropylene mesh, as a simple and effective method, produces satisfactory functional and cosmetic results and allows a more effective radio-iodine treatment.

Bone Neoplasms↗