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Biomedical subjects

M Hahn

Publications and source records attributed to M Hahn.

At least 37 records · Page 2Linked to original sources
PubMed2000

Preparation and in vitro evaluation of self-microemulsifying drug delivery systems containing idebenone.

A new self-microemulsifying drug delivery system (SMEDDS) was developed to increase the dissolution rate, solubility, and, ultimately, bioavailability of a poorly water soluble drug, idebenone. Pseudoternary phase diagrams were used to evaluate the self-microemulsification existence area, and the release rate of idebenone was investigated. The mixtures consisting of Labrafac hydro or Labrafil 2609 (HLB values > 4) with the surfactant (Labrasol containing 80% Transcutol) and cosurfactant (Plurol oleique WL 1173) were found to be optimum formulations. Using the SMEDDS formulations of 5% to 20% of Labrafac hydro or Labrafil 2609 in combination with the surfactant/cosurfactant mixing ratio of 3, the microemulsion existence field was wider compared to the other SMEDDS formulations due to high affinity for the continuous phase. The in vitro dissolution rate of idebenone from SMEDDS was more than twofold faster compared with that of tablets. The developed SMEDDS formulation can be used as a possible alternative to traditional oral formulations of idebenone to improve its bioavailability.

Antioxidants↗
PubMed2000

High level activation of vitamin B1 biosynthesis genes in haustoria of the rust fungus Uromyces fabae.

In the rust fungus Uromyces fabae, the transition from the early stages of host plant invasion toward parasitic growth is accompanied by the activation of many genes (PIGs = in planta induced genes). Two of them, PIG1 (= THI1) and PIG4 (= THI2), were found to be highly transcribed in haustoria, and are homologous to genes involved in thiamine (vitamin B1) biosynthesis in yeast. Their functional identity was confirmed by complementation of Schizosaccharomyces pombe thiamine auxotrophic thi3 (nmt1) and thi2 (nmt2) mutants, respectively. In contrast to thiamine biosynthesis genes of other fungi that are completely suppressed by thiamine, THI1 and THI2 expression was not affected by the addition of thiamine to rust hyphae grown either in vitro or in planta. Immunoblot analysis revealed decreasing amounts of THI1p in extracts from spores, germlings, and in vitro-grown infection structures with increasing time after inoculation. Immunofluorescence microscopy of rust-infected leaves detected high concentrations of THI1p in haustoria, and only low amounts in intercellular hyphae. In the sporulating mycelium, THI1p was found in the basal hyphae of the uredia, but not in the pedicels and only at very low levels in uredospores. These data indicate that the haustorium is an essential structure of the biotrophic rust mycelium not only for nutrient uptake but also for the biosynthesis of metabolites such as thiamine.

Amino Acid Sequence↗
PubMed2000

Glutathione S-transferase genetic polymorphisms and individual sensitivity to the ototoxic effect of cisplatin.

One of the side effects of cisplatin therapy in malignant neoplasms is ototoxicity. This effect shows a wide inter-individual range which is more variable than the pharmacokinetic parameters. Oxidative stress has been implicated in cisplatin ototoxicity. The glutathione S-transferase (GST) supergene family encodes isoenzymes that appear to be critical in protection against oxidative stress. Certain GST loci are polymorphic, demonstrating alleles that are null (GSTM1 and GSTT1), encode low-activity variants (GSTP1) or are associated with variable inducibility (GSTM3). The aim of our study was to investigate genetic risk factors involved in the ototoxicity of cisplatin and to determine whether the polymorphisms in five GST genes affect the individual risk of ototoxicity by cisplatin. Two groups of patients were analyzed in this study: group H, 20 patients early and highly sensitive to the ototoxicity of cisplatin; and group N, 19 patients with no hearing impairment under comparable doses of the drug. We found a protective effect for the GSTM3*B allele with a frequency of 0.18 in the group with normal hearing after therapy versus 0.025 in the group with hearing impairment. (chi2=5.37; p=0.02).

Adolescent↗
PubMed2000

Prevention of positional brachial plexopathy during surgical correction of scoliosis.

Continuous intraoperative monitoring of spinal cord function using somatosensory evoked potentials (SSEP) has gained nearly universal acceptance as a reliable and sensitive method for detecting and possibly preventing neurologic injury during surgical correction of spinal deformities. In several reports, spinal cord injury was identified successfully based on changes in SSEP response characteristics, specifically amplitude and latency. Less well documented and used, however, is monitoring of peripheral nerve function with SSEPs to identify and prevent the neurologic sequelae of prolonged prone positioning on a spinal frame. The authors describe a patient who underwent surgical removal of spinal instrumentation but was not monitored. A brachial plexopathy developed in this patient from pressure on the axilla exerted by a Relton-Hall positioning frame during spinal surgery. In addition, data are presented from 15 of 500 consecutive pediatric patients who underwent surgical correction of scoliosis between 1993 and 1997 with whom intermittent monitoring of ulnar nerve SSEPs was used successfully to identify impending brachial plexopathy, a complication of prone positioning. A statistically significant reduction in ulnar nerve SSEP amplitude was observed in 18 limbs of the 500 patients (3.6%) reviewed. Repositioning the arm(s) or shoulders resulted in nearly immediate improvement of SSEP amplitude, and all awoke without signs of brachial plexopathy. This complication can be avoided by monitoring SSEPs to ulnar nerve stimulation for patients placed in the prone position during spinal surgery.

Adult↗
PubMed2000

Atomic resolution structure of native porcine pancreatic elastase at 1.1 A.

A data set from the serine protease porcine pancreatic elastase was collected at atomic resolution (1.1 A) with synchrotron radiation. The improved resolution allows the determination of atom positions with high accuracy, as well as the localization of H atoms. Three residues could be modelled in alternative positions. The catalytic triad of elastase consists of His57, Asp102 and Ser195. The His57 N(delta1) H atom was located at a distance of 0.82 A from the N(delta1) atom. The distance between His57 N(delta1) and Asp102 O(delta2) is 2.70 +/- 0.04 A, thus indicating normal hydrogen-bonding geometry. Additional H atoms at His57 N(varepsilon2) and Ser195 O(gamma) could not be identified in the F(o) - F(c) density maps.

Animals↗
PubMed2000

Structure of jack bean chitinase.

The structure of jack bean chitinase was solved at 1.8 A resolution by molecular replacement. It is an alpha-helical protein with three disulfide bridges. The active site is related in structure to animal and viral lysozymes. However, unlike in lysozyme, the architecture of the active site suggests a single-step cleavage. According to this mechanism, Glu68 is the proton donor and Glu90 assists in the reaction by moving towards the substrate and recruiting a water molecule that acts as the nucleophile. In this model, a water molecule was found in contact with Glu90 O(epsilon1) and Thr119 O(gamma) at a distance of 3.0 and 2.8 A, respectively. The model is in accordance with the observed inversion mechanism.

Amino Acid Sequence↗
PubMed2000

Does the application of constraint-induced movement therapy during acute rehabilitation reduce arm impairment after ischemic stroke?

BACKGROUND AND PURPOSE: Motor dysfunction after unilateral deafferentation in primates can be overcome by restraining the unaffected limb. We asked whether a constraint-induced movement (CIM) program could be implemented within 2 weeks after stroke and whether CIM is more effective than traditional upper-extremity (UE) therapies during this period. METHODS: Twenty-three persons were enrolled in a pilot randomized, controlled trial that compared CIM with traditional therapies. A blinded observer rated the primary end point, the Action Research Arm Test (ARA). Inclusion criteria were the following: ischemic stroke within 14 days, persistent hemiparesis, evidence of preserved cognitive function, and presence of a protective motor response. Differences between the groups were compared by using Student's t tests, ANCOVA, and Mann-Whitney U: tests. RESULTS: Twenty subjects completed the 14-day treatment. Two adverse outcomes, a recurrent stroke and a death, occurred in the traditional group; 1 CIM subject met rehabilitation goals and was discharged before completing 14 inpatient days. The CIM treatment group had significantly higher scores on total ARA and pinch subscale scores (P:<0.05). Differences in the mean ARA grip, grasp, and gross movement subscale scores did not reach statistical significance. UE activities of daily living performance was not significantly different between groups, and no subject withdrew because of pain or frustration. CONCLUSIONS: A clinical trial of CIM therapy during acute rehabilitation is feasible. CIM was associated with less arm impairment at the end of treatment. Long-term studies are needed to determine whether CIM early after stroke is superior to traditional therapies.

Aged↗
PubMed2000

Extracellular matrix effects on a neuroblastoma cell line.

Cells of various lines assume similar shapes when grown attached to substrates like coverslips. In contrast, cells cultured in a collagen and/or laminin matrix often assume a relatively normal morphology in comparison with their in situ counterparts. During investigations of neuroblastoma SH-SY5Y cells, an attempt was made to identify culture conditions which would cause the cells to assume a more regular shape. SH-SY5Y cells cultured on bare coverslips, on coverslips coated with rat-tail collagen, and in approximately 1 mm thick gels containing extracellular matrix components were compared. Striking differences were apparent when comparing the gel-cultured cells with cells cultured on coverslips. Cells grown in the gel formed ganglia-like clusters which generated bundles of neurites which targeted other 'ganglia'. The same cells grown on coverslips, whether or not they were collagen-coated, appeared unaware of the presence of other cells, and did not cluster, nor did they generate neurites.

Axons↗
PubMed2000

Influence of DNA target melting behavior on real-time PCR quantification.

BACKGROUND: Quantitative real-time PCR is increasingly used to quantify copy numbers of nucleic acids for clinical applications. We observed that the measurements of allele imbalances of the tumor suppressor gene p16 and the oncogene ErbB-2 yielded results with variable precision under certain experimental conditions. METHODS: We used the LightCycler(TM) real-time PCR system to quantify different genomic target sequences using hybridization probes or SYBR Green for detection. RESULTS: With two primer/template systems (p16 and ErbB-2), we observed sinusoidal scattering of the threshold cycle values depending on the capillary position in the thermostated reaction chamber. This scattering depended on the denaturation temperature only when complete genomic DNA was used as template and did not occur when PCR product or restricted or boiled genomic DNA was used or the denaturation temperature in the first cycles was increased (and other targets, such as p53, HBB, IGF-1, GAPDH, and PBGD, did not show this behavior). CONCLUSIONS: Before a primer system is used for precise quantitative real-time PCR, the dependence of the quantification results on the positions of reaction tubes in the thermocycler should be tested. Our data indicate that amplification efficiencies, especially in the first cycles, depend not only on the priming efficiencies of the primers and the melting temperature of the amplicon, but also on the melting behavior of the amplicon's genomic vicinity. Complete denaturation of genomic DNA is necessary to maximize precision of quantitative PCR. Higher denaturation temperatures in the initial cycles or boiling of DNA before the PCR can improve the accuracy of quantification in some cases.

Cyclin-Dependent Kinase Inhibitor p16↗
PubMed2000

Microcirculatory dysfunction in chronic venous insufficiency (CVI).

The elevated ambulatory pressure in the peripheral venous system of chronic venous insufficiency (CVI) patients manifests itself not only in the form of disturbed macrocirculation but also and particularly in microangiopathic changes. For this reason, it is closely correlated with trophic disorders of the skin and can ultimately lead to ulceration. Using microcirculation research techniques, we are able to provide clear evidence of a typical microangiopathy in chronic venous insufficiency. Fifty CVI in Widmer stages I, II, and III were examined with fluorescence video microscopy, intravital video capillaroscopy, transcutaneous oxygen partial pressure measurement, TcpO2 and laser Doppler flowmetry. The effects of compression therapy with individually fitted compression stockings on capillary morphology were studied over a period of 4 weeks in 20 CVI patients in Widmer stages I and II. The capillary pressure was measured during simulated muscle contraction using a servo-null micropressure system. We periodically drew blood from the dorsalis pedis vein and a brachial vein of 11 healthy test persons and 8 patients with stage III CVI during experimental venous hypertension in order to evaluate the expression pattern of leukocyte adhesion molecules involved in inflammation: LFA-1 (CD11a), Mac-1 (CD11b), p150,95 (CD11c), CD18, VLA-4 (CD49d), and L-selectin (CD62L). In the same patients, we used immunohistochemical methods to examine clinically unaffected skin and the skin near an ulcer, focusing on the adhesion molecules ICAM-1, VCAM-1, and E-selectin. The microangiopathic changes observed with worsening clinical symptoms include a decrease in the number of capillaries, glomerulus-like changes in capillary morphology, a drop in the oxygen content (tcpO2) of the skin, increased permeability of the capillaries to low-molecular-weight substances, increased laser Doppler flux reflecting elevated subcutaneous flow, and diminished vascular reserve. These microangiopathic changes worsen in linear proportion to the clinical severity of chronic venous insufficiency. In patients with venous ulcerations, the baseline expression of LFA-1 and VLA-4 on lymphocytes, Mac-1 expression on the myeloid cell line, and L-selectin expression on all three cell lines was not significantly different form that in healthy controls. During orthostatic stress, there was a significant reduction in the expression of L-selectin in blood cells collected at foot level in the controls (p=0.002), but not in the patients. Clinical improvement by compression therapy was accompanied by an increase in the number of nutritive capillaries, while the diameter of the capillaries and the dermal papillae was reduced. When ulcers healed in a short period (<6 weeks), we observed a concomitant increase in the number of capillaries (p<0.05). Microangiopathy appears before tropic disorders of the skin develop. Even trophically normal skin areas may have dilated nutritive capillaries, an early sign of disturbed skin perfusion. These changes represent a plausible explanation for the development and to recurrency tendency of venous ulcers. The reduced expression of lymphocytic L-selectin in healthy controls during the orthostatic stress test may be an indication that the cells are activated by venous stasis. Clinically effective therapeutic measures improve the impaired microcirculation of the skin in the ankle area.

Bandages↗
PubMed1999

Hearing screening in healthy newborns: feasibility of different methods with regard to test time.

Clicked-evoked otoacoustic emissions and automated auditory brainstem response are both considered appropriate hearing screening tools. The aim of this study was to compare their practicability with respect to test duration. In the first part of the study, clicked-evoked otoacoustic emissions were recorded in 388 healthy infants on the newborn ward in the first days of life. To reduce false positive rates of screening, clicked-evoked otoacoustic emissions combined with automated auditory brainstem response measurement (A-ABR, Algo 1E and Algo 2) were used in a second investigation. Fifty-five newborns screened by this two-stage method recorded an increased pass rate. The new digital technique of automated auditory brainstem response measurement (Algo 1E and Algo 2) employed in the second part of the study has a test time even shorter than that of clicked-evoked otoacoustic emissions and is no longer a time-consuming test due to improved technology of the second generation of automated auditory brainstem response equipment. Screening including preparation and follow-up time took 9.43 min (Algo 1E) and 8.26 min (Algo 2) respectively and was thus less time-consuming than reported in former studies.

Audiometry, Evoked Response↗
PubMed1999

Local cold exposure test with a new arterial photoplethysmographic sensor in healthy controls and patients with secondary Raynaud's phenomenon.

Local cold exposure tests are used to diagnose cold-induced vasospastic disorders and to evaluate therapeutic success. We investigated the pulsatile signal detected with a newly developed arterial photoplethysmography (APPG) method and the signal change induced by local cold exposure using a temperature-controlled finger holder, comparing it with laser Doppler flux (red and green laser, rLDF and gLDF) and red blood cell velocity measured in nailfold capillaries (CBV). Ten healthy volunteers and 10 age- and sex-matched patients suffering from Raynaud's phenomenon due to systemic sclerosis were investigated using a moderate cooling temperature of 16 degrees C for 5 min. All signals were recorded simultaneously. The results show a significant reduction of CBV (P < 0.0001), rLDF (P < 0.0003), and gLDF (P = 0.0214) during cooling and characteristic changes in the APPG signal (for instance a decrease in pulse wave amplitude; P < 0.0001). Significant differences in the APPG amplitude could be detected under resting conditions; at cooling temperatures there were also significant differences in CBV and APPG. The temperature-controlled finger holder with its built-in APPG probe appears to be a useful tool for evaluating the effect of local cooling on finger skin perfusion and differentiating between healthy controls and patients with secondary Raynaud's phenomenon due to systemic sclerosis. The gLDF signal was rather weak, limiting its value in cold stress tests. The differences between controls and patients in CBV were somewhat smaller than in previous studies, suggesting the advantage of lower local cooling temperatures, e.g., 12 degrees C.

Adult↗
PubMed1999

[Preventive surgery of inherited colorectal cancer identified through molecular diagnosis].

Numerous inherited genetic changes predisposing to cancer have already been identified and the number is increasing. Accurate prediction of individual risk by means of molecular diagnosis implies clinical consequences in the treatment of cancer-predisposing syndromes. Using familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC) as an example, we present here the underlying genetic changes that contribute to tumor development. These genetic alterations can be efficiently identified through molecular diagnostic techniques. Identification of the familial germline mutation permits one to distinguish mutation carriers from non-mutation carriers within affected families and results in individually tailored surveillance and prevention. Therefore, molecular diagnosis is making a contribution to the advances in preventive surgical therapy. The indications are discussed.

Colorectal Neoplasms↗
PubMed1999

Hereditary colorectal cancer: clinical consequences of predictive molecular testing.

The continuing increase in knowledge about the genetic basis of carcinogenesis has led to diverse efforts to exploit this knowledge clinically, primarily in the form of predictive genetic testing. In conjunction with family history, gene tests are intended to improve individual cancer risk assessment. The objectives of predictive molecular testing are to identify the disease-causing germline mutation in an index person who has already developed the disease and to distinguish asymptomatic mutation carriers from non-mutation carriers within a given cancer-prone family. At present, genetic testing for colorectal cancer risk, primarily in form of DNA sequencing, is applied in familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC). In these inherited colorectal tumor syndromes determining the genetic status may result in an individually tailored surveillance program and prophylactic treatment. The implications of genetic testing for the clinical management of disease, both of mutation and non-mutation carriers, in familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer families are discussed.

Adenomatous Polyposis Coli↗
PubMed1999

Collagen type I metabolism after bone surgery.

This study follows the postoperative course of serum collagen type I metabolites in patients after uncomplicated implantation of a cemented total hip endoprothesis (TEP; n = 12, mean age: 69.3 years), a cemented hemiendoprothesis (HEP; n = 13, mean age 79.7 years), a dynamic condylar or hip screw (DCS/DHS; n = 12, mean age 75.1 years) and osteosynthetic treatment of a Weber B or C fracture (OS; n = 17, mean age 54.3 years). The course of the propeptide of human type I procollagen (PICP) as an anabolic marker as well as of I-carboxyterminal telopeptide (ICTP) as a catabolic marker of bone metabolism was characterized. Measurements were done preoperatively and weekly for 3 weeks after surgery. The concentrations of both markers increased and reached a maximum in the 2nd or 3rd week after surgery. However, the PICP values differed, depending on the kind of surgical intervention and the type of bone healing. Secondary fracture healing with formation of callus occurred in the DCS/DHS group, which developed the highest median PICP concentrations (initial 83 microg/l, second week 337 microg/l; P < 0.001). In contrast, the primary bone healing in the OS group showed increasing ICTP but unchanged PICP concentrations. Patients in the cemented TEP and HEP groups as a kind of artificial bone healing had comparable concentrations. To consider the effective metabolism of collagen type I, the PICP/ICTP ratio was calculated. Although the median PICP and ICTP concentrations of the studied groups differed, the PICP/ICTP ratios were similar. In comparison to 54 young and healthy volunteers (median PICP/ICTP ratio: 37), the ratios of the studied groups were still normal but low (median ratios: < 20). This could be an effect of decreasing collagen type I metabolism with age. Although the results are in agreement with animal studies and histomorphometric investigations, the clinical use of PICP and ICTP determination as a tool for the detection of complicated bone healing is limited by the marked interindividual variability and the uncertain bone specificity.

Aged↗
PubMed1999

[Pt(dien)]2+ migrates intramolecularly from methionine S to imidazole Nepsilon2 in the peptides H-His-Gly-Met-OH and Ac-His-Ala-Ala-Ala-Met-NHPh.

The pH- and time-dependent reaction of [Pt(dien)(H2O)]2+ with the methionine- and histidine-containing peptides H-His-Gly-Met-OH and Ac-His-Ala-Ala-Ala-Met-NHPh at 313 K has been investigated by HPLC and NMR spectroscopy. For both peptides, initial relatively rapid formation of the kinetically favoured methionine S-bound complex is followed by slow intramolecular migration of the [Pt(dien)]2+ fragment to imidazole Nepsilon2 (or, in the case of H-His-Gly-Met-OH, to a much lesser extent to the competing imidazole Ndelta1) of the histidine side chain over a period of 500 h. Time-dependent studies for the pentapeptide at pH 8.0 demonstrate that this isomerization can take place by either direct S-->Nepsilon2 migration or by a two-step mechanism involving initial Nepsilon2 coordination of a second [Pt(dien)]2+ fragment and subsequent cleavage of the orginal Pt-S bond in the resulting dinuclear complex. The rate of kappaS/kappaNepsilon2 isomerization is markedly reduced on lowering the pH to 5.1.

Amino Acid Sequence↗