Biomedical subjects

Andreas Meyer

Publications and source records attributed to Andreas Meyer.

At least 19 recordsLinked to original sources

PubMed2006

AtGAT1, a high affinity transporter for gamma-aminobutyric acid in Arabidopsis thaliana.

Functional characterization of Arabidopsis thaliana GAT1 in heterologous expression systems, i.e. Saccharomyces cerevisiae and Xenopus laevis oocytes, revealed that AtGAT1 (At1g08230) codes for an H(+)-driven, high affinity gamma-aminobutyric acid (GABA) transporter. In addition to GABA, other omega-aminofatty acids and butylamine are recognized. In contrast to the most closely related proteins of the proline transporter family, proline and glycine betaine are not transported by AtGAT1. AtGAT1 does not share sequence similarity with any of the non-plant GABA transporters described so far, and analyses of substrate selectivity and kinetic properties showed that AtGAT1-mediated transport is similar but distinct from that of mammalian, bacterial, and S. cerevisiae GABA transporters. Consistent with a role in GABA uptake into cells, transient expression of AtGAT1/green fluorescent protein fusion proteins in tobacco protoplasts revealed localization at the plasma membrane. In planta, AtGAT1 expression was highest in flowers and under conditions of elevated GABA concentrations such as wounding or senescence.

Animals↗

PubMed2006

Long-term results of interstitial brachytherapy (LDR-Brachytherapy) in the treatment of patients with prostate cancer.

Permanent interstitial brachytherapy represents the most conformal form of radiation therapy of the prostate and the number of patients with prostate cancers treated with permanent radioactive implants is increasing world wide. In the meanwhile long-term data on tumor control and treatment morbidity become available. Biochemical and clinical tumor control appears to be as effective as after radical prostatectomy or external beam radiation therapy in early prostate cancer. The risk of postreatment urinary incontinence and bowel dysfunction is low and erectile function can be preserved in the majority of patients. However, prostate brachytherapy requires a careful selection of patients as pretreatment factors predict for long-term outcome. The need for combined modality approaches in intermediate and high-risk patients remains controversely discussed. The continous refinement of intraoperative planning techniques and the elucidation of the etiology of urinary, sexual, and bowel dysfunction should result in further improvements in biochemical outcomes and decreased morbidity. Improved and standardized postimplantation evaluation will make outcome data more reliable and comparable.

Brachytherapy↗

PubMed2006

Chemoradiotherapy in patients with anal cancer: impact of length of unplanned treatment interruption on outcome.

The aim of this retrospective analysis was to evaluate feasibility and effectiveness of definitive chemoradiotherapy without split-course technique in anal cancer patients. From 1993 to 2003, 81 patients were treated; 13 were excluded due to various chemotherapeutic regimes, thus 68 patients were analysed. In case of acute grade 3 toxicities, treatment was halted until improvement or resolution independent of dose. Short interruption was defined as completing treatment without exceeding eight cumulative treatment days beyond scheduled plan, other patients were considered to have had prolonged interruption. Median follow-up was 46 months. Median overall treatment time was 53 days corresponding to an interruption of eight cumulative treatment days. Thirty-five patients (51%) had treatment interruption of <or=8 days. No acute grade 4 toxicities were observed; one fatality occurred during treatment due to ileus-like symptoms according to acute grade 5 toxicity. Comparing patients with short vs. prolonged interruption 5-year actuarial rates for local control were 85% vs. 81% (p = 0.605) and for colostomy-free survival 85% vs. 87% (p = 0.762), respectively. Chemoradiotherapy with short individualised treatment interruptions seems to be feasible with acceptable acute or late toxicities. Treatment is highly effective in terms of local control and colostomy-free survival.

Adult↗

PubMed2005

[Mental disorders in puberty].

Puberty is characterized by a complexity of different developmental tasks. During this period of sometimes dramatic changes, the adolescent must find a new balance between personal experiences and the demands made by the environment. In this period of development, some 18% of all adolescents experience a mental crisis, and 5% need specialist treatment. Such mental disorders in puberty as anorexia nervosa, depression or suicidality can be classified on the basis of their development and course. They must be taken seriously and treated as early as possible.

Adolescent↗

PubMed2005

Long-term follow-up after adrenalectomy for primary aldosteronism.

The objective of this study was to assess the long-term effects of adrenalectomy on the blood pressure and antihypertensive medication in patients with primary aldosteronism (PA). Twenty-four patients (15 female and 9 male) with a mean age of 48.3 +/- 10.8 years underwent surgery for PA in our institution between 1988 and 2001. All subjects were re-examined with a complete clinical work-up after a mean follow-up period of 86 +/- 48 months, including blood pressure readings (<140/90 mmHg defined as normal), endocrine adrenal function, and specific medication. All patients suffered from hypertension (onset 8.5 +/- 5.5 years prior to surgery). In 92% of the patients, hypokalemia was present (onset 2.0 +/- 2.6 years prior to surgery). The histopathologic examinations revealed unilateral adenomas in 23 patients and a bilateral hyperplasia in one patient. At follow-up, 33% (8) of the patients were completely cured (normal blood pressure and no antihypertensive treatment), with seven of these eight patients being under 50 years of age at the time of surgery. One patient revealed a contralateral aldosterone-secreting adrenal adenoma during the subsequent endocrine and imaging examination 44 months after the first operation. Despite normalized plasma-aldosterone concentration (PAC), plasma-renin-activity (PRA) and serum potassium levels, a long-lasting insufficiently treated hypertension due to the delayed diagnosis in patients with PA may explain the persistent blood pressure elevation, indicating the necessity of a life-long, regular control of the blood pressure and antihypertensive medication.

Adenoma↗

PubMed2005

Adjuvant radiotherapy in stage I seminoma: is there a role for further reduction of treatment volume?

An analysis was performed to determine whether a cranial reduction of the portals to the T11/T12 junction instead of the common T10/T11 junction would alter the outcome of patients with stage I seminoma. Of 163 consecutive patients with newly diagnosed testicular seminoma referred to the authors' institution between April 1992 and April 1999, 80 patients with stage I seminoma were treated with cranially reduced para-aortic treatment fields reaching from the top of T12 to the bottom of L4. Median total dose was 20.0 Gy (range, 19.8-27.2 Gy). Patients were followed-up by the use of CT in regular intervals. After a median follow-up of 7.1 years (range, 4.1-11.1 years), four patients (5%) had relapsed resulting in an actuarial 5-year relapse-free survival of 95%. No patients relapsed within the cranially reduced treatment volume above the top of T12. The cranial reduction of the para-aortic treatment fields resulted in a median reduction of treatment volume of 16% (range, 13-21%). The achieved median reduction in treatment volume of 16% appears to be relevant and is not associated with an increased relapse rate. This approach is recommended in analogy to the surgical approach in NSGCT to further minimize the risk of radiation-related late effects.

Adult↗

PubMed2005

Characterization of the Xanthomonas campestris pv. campestris lipopolysaccharide substructures essential for elicitation of an oxidative burst in tobacco cells.

The lipopolysaccharides (LPS) of gram-negative bacteria are essential for perception of pathogens by animals and plants. To identify the LPS substructure or substructures recognized by plants, we isolated water-phase (w)LPS from different Xanthomonas campestris pv. campestris mutants and analyzed their sugar content and ability to elicit an oxidative burst in tobacco cell cultures. The different wLPS species are characterized by lacking repetitive subunits of the O-antigen, the complete O-antigen, or even most of the core region. Because loss of lipid A would be lethal to bacteria, pure lipid A was obtained from X. campestris pv. campestris wild-type wLPS by chemical hydrolysis. The elicitation experiments with tobacco cell cultures revealed that LPS detection is dependent on the bioavailability of the amphiphilic wLPS, which can form micelles in an aqueous environment. By adding deoxycholate to prevent micelle formation, all of the tested wLPS species showed elicitation capability, whereas the lipid A alone was not able to trigger an oxidative burst or calcium transients in tobacco cell cultures. These results suggest that the LPS substructure recognized by tobacco cells is localized in the inner core region of the LPS, consisting of glucose, galacturonic acid, and 3-deoxy-d-manno-oct-2-ulosonic acids. Although lipid A alone seems to be insufficient to induce an oxidative burst in tobacco cell cultures, it cannot be ruled out that lipid A or the glucosamine backbone may be important in combination with the inner core structures.

Aequorin↗

PubMed2005

Presentation and therapy of myelolipoma.

BACKGROUND: Adrenal myelolipoma is a rare and benign, hormonally inactive tumor frequently discovered incidentally. Because of the increasing rate of detection of adrenal myelolipoma, use of the correct diagnostic examination and treatment, with respect to surgical excision or regular controls, is continually gaining importance. We report herein on the largest series of surgically treated patients with adrenal myelolipoma from a single institute. METHODS: The clinical charts of 12 patients who underwent adrenal surgery for myelolipoma were reviewed. Follow up was carried out by means of re-examination or by personal contact with the primary physician. It was possible to perform a re-examination on eight of the 12 patients 6.9 years after the operation: one patient had died 5.2 years after surgery. RESULTS: Diagnosis of adrenal myelolipoma was made incidentally in seven patients, and during examination for reasons of unspecific abdominal or flank pain in five patients. A transabdominal approach was taken in five patients, a subcostal approach was taken in three patients and a translumbal approach was taken in four patients. At the follow up, all formerly symptomatic patients were free of symptoms. No recurrence could be seen; however, in one patient a contralateral adrenal myelolipoma had developed. CONCLUSIONS: Symptomatic tumors, growing tumors or tumors larger than 10 cm should be excised surgically by means of an endoscopic or conventional approach, depending on the size. Surgical indication should not be liberalized by the introduction of more gentle operative techniques such as the translumbal or the endoscopic approach. A close follow up should be maintained in the case of patients free of symptoms, and for those with a definite diagnosis from imaging procedures.

Adrenal Gland Neoplasms↗

PubMed2005

Topiramate: a prospective study on the relationship between concentration, dosage and adverse events in epileptic patients on combination therapy.

RATIONALE: The relationship between topiramate (TPM) concentration, dosage and adverse events in patients with epilepsy is still controversial. We therefore performed a prospective study in patients with poorly controlled epilepsy treated with TPM, predominantly in combination with other antiepileptic drugs. The goal of the study was to investigate the relationship between the occurrence of adverse events due to TPM and its serum concentration or dosage, respectively. METHODS: The relationship between the occurrence of adverse events and TPM serum concentration or dosage, respectively, was examined in a group of 42 young adult and adult patients with poorly controlled epilepsy. Within 22 months, all patients treated with TPM had been included in the study. The 8 adverse events occurring most frequently (difference > or = 10%) in TPM-treated patients in 5, double-blind, placebo-controlled, parallel group studies, were checked regularly. This side effect profile has been presented by Reife et al. (1995a). Other possible or probable adverse events were also documented. RESULTS: The difference in TPM serum concentrations and TPM dosages (mg/kg) for patients without an adverse event, and patients with a given adverse event was statistically significant for "abnormal thinking, impaired concentration, weight loss, dizziness, speech problems, somnolence, ataxia, increased seizure frequency and paresthesia". To avoid adverse events, we recommend an initial "maintenance serum concentration" of below 4 microg/mL. As regards the TPM dosage, our results suggest initial maintenance dosages of 100 TPM or lower, 1.5 mg/kg or lower, respectively. These conclusions are limited by the relatively small number of patients.

Adolescent↗

PubMed2004

The AtProT family. Compatible solute transporters with similar substrate specificity but differential expression patterns.

Proline transporters (ProTs) mediate transport of the compatible solutes Pro, glycine betaine, and the stress-induced compound gamma-aminobutyric acid. A new member of this gene family, AtProT3, was isolated from Arabidopsis (Arabidopsis thaliana), and its properties were compared to AtProT1 and AtProT2. Transient expression of fusions of AtProT and the green fluorescent protein in tobacco (Nicotiana tabacum) protoplasts revealed that all three AtProTs were localized at the plasma membrane. Expression in a yeast (Saccharomyces cerevisiae) mutant demonstrated that the affinity of all three AtProTs was highest for glycine betaine (K(m) = 0.1-0.3 mM), lower for Pro (K(m) = 0.4-1 mM), and lowest for gamma-aminobutyric acid (K(m) = 4-5 mM). Relative quantification of the mRNA level using real-time PCR and analyses of transgenic plants expressing the beta-glucuronidase (uidA) gene under control of individual AtProT promoters showed that the expression pattern of AtProTs are complementary. AtProT1 expression was found in the phloem or phloem parenchyma cells throughout the whole plant, indicative of a role in long-distance transport of compatible solutes. beta-Glucuronidase activity under the control of the AtProT2 promoter was restricted to the epidermis and the cortex cells in roots, whereas in leaves, staining could be demonstrated only after wounding. In contrast, AtProT3 expression was restricted to the above-ground parts of the plant and could be localized to the epidermal cells in leaves. These results showed that, although intracellular localization, substrate specificity, and affinity are very similar, the transporters fulfill different roles in planta.

Arabidopsis↗

PubMed2004

Cushing's syndrome: adrenalectomy and long-term results.

BACKGROUND: The objective of this study was to assess the preoperative symptoms, intra- and postoperative complications and follow-up in patients after uni- or bilateral adrenalectomy due to Cushing's syndrome (CS), independent of etiology. METHODS: Clinical charts of 42 patients (5 with ACTH-dependent, 37 with ACTH-independent CS) were reviewed, and follow-up data were obtained from re-examination of the patients. RESULTS: The symptoms most frequently seen were hypertension, changes of the skin and obesity. Eight bilateral and 36 unilateral adrenalectomies were carried out without any intraoperative complications. Postoperative complications occurred in 5 patients, 1 patient died on the fourth postoperative day. After a mean duration of 4.6 years 28 of 41 patients could be re-examined, 5 patients had died. One patient showed recurrence 4.3 years after unilateral adrenalectomy due to nodular hyperplasia, contralateral adrenalectomy again revealed nodular hyperplasia. CONCLUSION: Early diagnosis is essential in order to decrease the rate of pre-, intra- and postoperative complications. Endoscopic approach should be taken in a specialized center due to poor patient's condition. Recurrent disease on the contralateral side may represent bilateral adrenal hyperplasia with sequential tumor formation, demonstrating the importance of extensive preoperative biochemical and imaging testing and close follow-up.

Adenoma↗

PubMed2004

Decreased interleukin-18 expression in BAL cells and peripheral blood mononuclear cells in adult cystic fibrosis patients.

Lymphocytes from cystic fibrosis (CF) patients secrete less interferon-gamma (IFN-gamma) upon stimulation compared to controls. Expression of interleukin (IL)-18 as an IFN-gamma inducing factor and of IL-10 as an IL-18 inhibiting factor were determined in bronchoalveolar lavage (BAL) cells from CF patients (n=5) and from normal control subjects (n=9) as well as in peripheral blood mononuclear cells (PBMC) from patients (n=12) and from control subjects (n=9) with RT-PCR. IL-18 and IL-10 serum protein levels were measured using ELISA. BAL cells and PBMC of CF patients expressed significantly less IL-18 compared to controls (p<0.05). There was no significant difference for IL-10 in BAL cells. However, PBMC from patients expressed significantly more IL-10 mRNA (p<0.05). IL-18 serum protein levels were decreased in the patient group, whereas IL-10 serum concentrations were elevated. Stimulation with rhIL-10 reduced IL-18 expression in PBMC from CF patients. Decreased IL-18 expression in CF patients may contribute to decreased IFN-gamma production. IL-10 may contribute to inhibit IL-18 expression in PBMC in CF.

Adult↗

PubMed2004

Breast cancer in female carriers of ATM gene alterations: outcome of adjuvant radiotherapy.

BACKGROUND AND PURPOSE: We analyzed the clinical outcome of breast cancer patients carrying sequence variants in the ATM gene who received postoperative radiotherapy after breast conservative surgery to test whether an increased cellular radiosensitivity may translate into enhanced tumor cell killing and thereby result in an improvement of the therapeutic ratio. PATIENTS AND METHODS: We investigated a cohort of 138 breast cancer patients who received adjuvant radiotherapy following breast conservative surgery for T1 and T2 tumors. Genomic DNA samples of these patients had previously been scanned for mutations in the ATM gene. Follow-up data were available in 135 patients, with a median follow-up of 87 months. Local relapse-free, metastasis-free and overall survival were compared between carriers and non-carriers of a sequence variant in the ATM gene. RESULTS: Twenty patients were found to carry a sequence variant in the ATM gene (truncating, 7; missense, 13). The actuarial 7-year local relapse-free survival of carriers vs. non-carriers were 88 vs. 94% (P=0.34). Actuarial metastasis-free and overall survival after 7 years were 63 vs. 85% (P=0.01) and 73 vs. 89% (P=0.055), respectively. However, the presence of a variant in the ATM gene did not remain a significant discriminator for metastasis-free survival in a multivariate Cox regression analysis (P=0.068). CONCLUSIONS: Our results do not support the hypothesis that breast cancer patients carrying a sequence variant in the ATM gene differentially benefit from postoperative radiotherapy. These findings have to be verified using larger number of cases to clarify the clinical consequences of sequence variants in the ATM gene.

Adult↗

PubMed2004

Percutaneous tracheostomy is safe in patients with severe thrombocytopenia.

STUDY OBJECTIVES: Severe thrombocytopenia has been described as a contraindication for percutaneous tracheostomy (PT). The objective of this study was to assess the safety of PT in mechanically ventilated patients with severe thrombocytopenia (defined by a platelet count of < 50 x 10(9) cells/L). DESIGN: Retrospective, single-center cohort study. SETTING: Medical ICU of the University Hospital Hamburg-Eppendorf, Germany. PATIENTS: Forty-two medical patients with acute respiratory failure and severe thrombocytopenia. INTERVENTIONS: Bedside PT under bronchoscopic guidance using the Griggs guidewire forceps technique. MEASUREMENTS AND MAIN RESULTS: The mean (+/- SD) intubation time prior to undergoing PT was 6.7 +/- 3.9 days (range, 1 to 20 days). The mean platelet count was 26.4 +/- 11.6 x 10(9) cells/L (range, 1 x 10(9) to 47 x 10(9) cells/L). The median transfusion of platelets before the procedure in 40 of the 42 patients was 6 +/- 2.5 U (range, 3 to 12 U). Twenty-two patients (52%) had an additional coagulopathy (activated partial thromboplastin time [APTT], > 40 s; international normalized ratio, > 1.5). PT was safely performed in all 42 patients. Only two (5%) patients developed major postprocedural bleeding complications that required suturing. Both of these patients had an elevated APTT due to heparin therapy. CONCLUSIONS: When performed by experienced personnel, PT with bronchoscopic guidance has a low complication rate in patients with severe thrombocytopenia, provided that platelets are administered beforehand. However, in order to minimize bleeding complications heparin infusions should be temporarily interrupted during the procedure.

Cohort Studies↗

PubMed2003

Diffusion in a metallic melt at the critical temperature of mode coupling theory.

According to mode coupling theory, liquidlike motion becomes frozen at a critical temperature T(c) well above the caloric glass transition temperature T(g). Here, for the first time, we report on radiotracer diffusion in a supercooled Pd43Cu27Ni10P20 alloy from T(g) to the equilibrium melt. Liquidlike motion is seen to set in exactly above T(c) as evidenced by a gradual drop of the effective activation energy. This strongly supports the mode coupling scenario. Isotope effect measurements, which have never been carried out near T(c) in any material, show atomic transport up to the equilibrium melt to be far away from the hydrodynamic regime of uncorrelated binary collisions.

Journal Article↗

PubMed2003

Crystallization and preliminary X-ray analysis of native and selenomethionine 2-hydroxybiphenyl 3-monooxygenase.

2-hydroxybiphenyl 3-monooxygenase (HbpA; EC 1.14.13.44) from Pseudomonas azelaica HBP1 was produced in Escherichia coli both as native and SeMet-labelled protein. The two enzymes were purified to homogeneity and crystallized by the hanging-drop vapour-diffusion method. The crystals belong to the monoclinic space group C2, with unit-cell parameters a = 108.6, b = 196.8, c = 79.3 A, beta = 97.7 degrees for the native protein and a = 108.3, b = 196.8, c = 79.0 A, beta = 97.8 degrees for SeMet HbpA. Crystal-packing considerations led to the assumption of two HbpA subunits per asymmetric unit, which corresponds to a V(M) value of 3.3 A(3) Da(-1) and a solvent content of 62%. The crystals were radiation-sensitive and only had a lifespan of about 120 s when exposed to synchrotron radiation on an undulator beamline. To obtain complete data sets, data were collected from 23 native and 26 derivative crystals. The high-resolution limit was 2.0 A for native and 2.25 A for SeMet HbpA.

Crystallization↗

PubMed2003

Synthesis of 3-tert-butylcatechol by an engineered monooxygenase.

Recombinant Escherichia coli JM101 was used for the in vivo biocatalytic synthesis of 3-tert-butyl- catechol. The bacterial strain synthesized the laboratory-evolved variant HbpA(T2) of 2-hydroxybiphenyl 3-monooxygenase (HbpA, EC 1.14.13.44) from Pseudomonas azelaica HBP1. The mutant enzyme HbpA(T2) is able to hydroxylate 2-tert-butylphenol to the corresponding catechol, a reaction that is not catalyzed by the wild-type enzyme. The biotransformation was performed in a 3-L bioreactor for 24 h. To mitigate the toxicity of the 2-tert-butylphenol starting material, we applied a limited substrate feed. Continuous in situ product removal with the hydrophobic resin Amberlite XAD-4 was used to separate the product from culture broth. In addition, binding to the resin stabilized the product, which was important because 3-tert-butylcatechol is very labile in aqueous solution. The productivity of the process was 63 mg L(-1) h(-1) so that after 24 h, 3.0 g of 3-tert-butylcatechol were isolated. Down-stream processing consisted of two steps. First, bound 2-tert-butylphenol and 3-tert-butylcatechol were eluted from Amberlite XAD-4 with methanol. Second, the two compounds were separated over neutral aluminum oxide, which selectively binds the produced catechol but not the phenol substrate. The final purity of 3-tert-butylcatechol was greater than 98%.

Bioreactors↗

PubMed2003

Increased expression of Interleukin-13 but not Interleukin-4 in cystic fibrosis patients.

BACKGROUND: Many patients with cystic fibrosis (CF) suffer from allergic disease, which can complicate treatment of CF lung disease. Interleukin (IL)-4 and IL-13 have been shown to be important mediators in allergic disease. OBJECTIVE: To investigate the role of IL-4 and IL-13 in allergic and non-allergic CF patients. METHODS: Expression of IL-4 and IL-13 mRNA was investigated in peripheral blood mononuclear cells (PBM) of seven CF patients with allergy, of six patients without allergy and of nine healthy subjects as well as in BAL cells of four patients and of all controls. PBM from six patients were incubated with recombinant human IL-13 or human antiIL-13 antibody without and with LPS stimulation and TNFalpha levels were measured by ELISA. RESULTS: IL-13 mRNA expression was increased in allergic and non-allergic patients compared to controls. No significant difference in IL-4 expression could be found between patients and controls. Addition of IL-13 decreased TNFalpha in PBM culture supernatants. CONCLUSION: Our data suggest that IL-13 rather than IL-4 might play an important role in both allergic and non-allergic CF patients. IL-13 might also compromise host defence by decreasing TNFalpha production.

Adolescent↗