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Biomedical subjects

M Schulte

Publications and source records attributed to M Schulte.

At least 19 recordsLinked to original sources
PubMed2006

Polybrene improves transfection efficacy of recombinant replication-deficient adenovirus in cutaneous cells and burned skin.

BACKGROUND: The hostile environment found in acute and chronic wounds decreases the physiological half-life of purified synthetic or recombinant peptides dramatically. Gene therapy, on the other hand, may be a viable option since it relies on the cellular machinery of the host to locally manufacture the proteins of interest. The aim of this study was to evaluate and optimize the local administration of transient cutaneous adenoviral gene delivery in wounds. METHODS: Primary human keratinocytes (HKC) and HaCaT cells were transfected with replication-deficient adenovirus (Ad5) containing the reporter gene for beta-galactosidase (LacZ). The vector was used alone or precoated with either (1) Lipofectamine 2000, (2) FuGENE 6, or (3) Polybrene. For in vivo testing a rat burn model was used. Animals were randomized into three groups: (1) Ad5-LacZ alone; (2) Ad5-LacZ precoated with Polybrene, or (3) carrier control (phosphate-buffered saline (PBS)). Samples were harvested from burned and unburned tissue sections after either 48 h or 7 days. Transgene expression was quantified by bioluminometric assay and localized using immunohistochemistry. A BrdU assay was performed to determine the influence of the used transfection reagents on cell proliferation. RESULTS: Transfection efficacy was significantly improved in vitro (p < 0.001) as well as in partial thickness burned (p = 0.015) and unburned skin (p > 0.001) after precoating Ad5 with Polybrene compared to Ad5 alone. Transgene expression was 10-fold higher in burned skin (9305 pg/mg protein) compared to unburned skin (859 pg/mg protein). CONCLUSIONS: It is feasible to improve transfection efficacy in vitro and in vivo by precoating the adenovirus with Polybrene.

Adenoviridae↗
PubMed2005

Electron spin resonance on a two-dimensional electron gas in a single AlAs quantum well.

Direct electron spin resonance (ESR) on a high mobility two-dimensional electron gas in a single AlAs quantum well reveals an electronic g factor of 1.991 at 9.35 GHz and 1.989 at 34 GHz with a minimum linewidth of 7 G. The ESR amplitude and its temperature dependence suggest that the signal originates from the effective magnetic field caused by the spin-orbit interaction and a modulation of the electron wave vector caused by the microwave electric field. This contrasts markedly with conventional ESR that detects through the microwave magnetic field.

Journal Article↗
PubMed2005

Optimum peripheral drug deposition in patients with cystic fibrosis.

In order to identify the optimum particle size and breathing pattern for high peripheral deposition of inhaled drugs in patients with cystic fibrosis, regional deposition in these patients was studied systematically as a function of particle size, inhalation volume and flow rate. Regional deposition was assessed using the single-breath regional deposition technique in which the concentration profile of inhaled and exhaled non-radioactive, monodisperse test particles is analyzed. Using this technique particle deposition within the functional dead space volume and peripherally can be assessed. Regional deposition was measured in 12 patients with cystic fibrosis using 2, 3, 4, and 5.5 microm particles, inhalation volumes of 500, 1000, 1500, and 2000 cm(3), and inhalation flow rates of 100, 250, 500, and 750 cm(3)/sec. Peripheral deposition was highest when 2-3-microm particles were inhaled with air-flow rates of 250-500 cm(3)/sec. With these parameters peripheral deposition increased with increasing inhalation volume and reached values of about 60% of the total drug inhaled. It has been shown that high peripheral drug deposition can be achieved in patients with CF when inhalations are performed using an optimized combination of particle size and breathing pattern.

Administration, Inhalation↗
PubMed2004

[Hematogenous osteomyelitis in adults].

Hematogenous osteomyelitis (HOM) in adults is a very rare event in industrialised countries. However, in tropical regions the morbidity of HOM is more important, primarily due to the impact of sickle cell disease, thalassemia, HIV-infection and tuberculosis. HOM is most commonly caused by pyogenic bacteria and mycobacteria, but infections by fungi, viruses and parasites must also be considered. In spite of modern diagnostic procedures such as nuclear and magnetic resonance imaging, the histopathologic and microbiologic examination of bone remains the gold standard for diagnosing OM. Other diagnoses should also be considered. Nonbacterial osteomyelitic lesions (plasmacellular OM, sclerosing OM, SAPHO syndrome) as well as acute leukemia, malignant bone tumors (i.e., Ewing's sarcoma, osteosarcoma) are conditions with similar presentations. Acute HOM is best managed by appropriate antibiotic therapy. In case of failure and in chronic HOM, surgical debridement is mandatory.

AIDS-Related Opportunistic Infections↗
PubMed2004

Prevalence of antiretroviral drug resistance in the HIV-1-infected urban indigent population in San Francisco: a representative study.

We determined the prevalence of antiretroviral (ARV) resistance in HIV-1 infected indigent persons in San Francisco, California. Three hundred and twenty-seven subjects (159 (49%) ARV naïve, and 168 (51%) ARV-experienced), were recruited during 1996-97 and 1999-2000. Plasma HIV-1 viral load quantification and genotypic resistance testing were performed. Twice as many subjects received nucleoside reverse transcriptase inhibitors (NRTIs) as non-nucleoside reverse transcriptase inhibitors (NNRTIs) or protease inhibitors (PIs); resistance mutation prevalences were 30%, 14% and 16% respectively. Risk of any resistance mutations was strongly and independently associated with prior ARV exposure (OR = 1.3 per year of exposure, P < 0.0001) and with ARV exposure prior to HAART (OR = 2.5, P = 0.015). Prevalences of primary ARV resistance mutations among both treatment-naive and treatment-experienced subjects in this indigent urban population are low compared to other observational cohorts, are directly related to length and type of prior ARV exposure, and did not increase significantly between recruitment periods.

Adolescent↗
PubMed2002

[Multiple enchondromatosis: Ollier's disease].

In contrast to solitary enchondroma,patients with multiple enchondromatosis of bone (Ollier's disease) get affected in childhood by bone swelling and growth retardation. In adults, the main problem is the risk of malign transformation up to 40%.Pain, increasing local tumor and thinning of the corticalis are the typical clinical and radiological signs of transformation to a low grade chondrosarcoma. There is no need for a regular radiological screening. If a malign transformation occurs,marginal or wide resection of the lesion should be performed.

Adolescent↗
PubMed2001

Monolithic silica sorbents for the separation of diastereomers by means of simulated moving bed chromatography.

Monolithic silica sorbents with a dual pore system can be used in preparative chromatography for the separation of diastereomers. They exhibit some special features, which allows them to be operated at high linear velocities due to their reduced pressure drop and fast diffusion kinetics. Especially in the continuous set-up of simulated moving bed chromatography monolithic sorbents show high productivities, which make them well suited in pharmaceutical drug development for the production of pure isomers.

Absorption↗
PubMed2001

[cyclo-CH2[Sn(CI2)CH2Si(Me2)]2O]: synthesis and complexation behaviour of a novel, cyclic, bidentate Lewis acid and its conversion into a tin-containing fluorosilane with intermolecular Si-F...Sn bridges.

Acid-catalysed hydrolysis of [CH2[(Sn(Ph2)CH2Si(OiPr)Me2]2] followed by subsequent reaction with mercuric chloride in acetone afforded the novel silicon- and tin-containing eight-membered ring [cyclo-CH2[Sn(Cl2)CH2Si(Me2)]2O] in good yield, the crystal structure of which is reported. 119Sn NMR and X-ray studies indicate that [cyclo-CH2[Sn(Cl2)CH2Si(Me2)]2O] acts as a bidentate Lewis acid towards chloride ions exclusively forming the 1:1 complex [(Ph3P)2N]+[cyclo-CH2[Sn(Cl2)CH2Si(Me2)]2OCl]- upon addition of [(Ph3P)2N]+Cl- . Also reported are the synthesis and structure of [K(dibenzo[18]crown-6)]+[cyclo-CH2(Sn(Cl2)CH2Si(Me2)]2OF]-, the first completely characterised organostannate with a C2SnCl2F- substituent pattern. No ring-opening polymerisation could be achieved for [cyclo-CH2[Sn(Cl2)CH2Si(Me2)]2O] or for its perphenylated derivative [cyclo-CH2[Sn(Ph2)CH2Si(Me2)]2O]. The reaction of [cyclo-CH2[Sn(Cl2)CH2Si(Me2)]2O] with Me3O+BF4- gave the tin-containing fluorosilane [CH2[Sn(Cl2)CH2Si(F)Me2]2], in which the Si-F bond is activated by intermolecular Si-F...Sn interactions in the solid state.

Journal Article↗
PubMed2001

Preparative enantioseparation by simulated moving bed chromatography.

Simulated moving bed (SMB) chromatography was invented in the 1960s in the petrochemical industry and has since then been widely used to produce petrochemicals and sugars at the multi-ton scale. In the early 1990s its principle could be successfully adapted to chromatographic enantioseparation, due to developments in system design, chiral stationary phase synthesis and improvements in modelling and simulation of non-linear chromatographic behaviour. Since then a lot of separation systems have been brought into production, which are reviewed. In addition new developments are outlined in the field of system design and stationary phase development.

Chromatography, Liquid↗
PubMed2001

Genome-wide analysis of sixteen chordomas by comparative genomic hybridization and cytogenetics of the first human chordoma cell line, U-CH1.

Cytogenetic information on chordomas is rudimentary and restricted to GTG-banding analysis of 26 cases worldwide. In this study, we present the chromosomal imbalances detected in a series of 16 chordomas (10 sacrococcyeal, five sphenooccipital, and one spinal) from 13 patients using comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH). On average, 3.2 losses and 4.2 gains were detected per tumor. The most common DNA copy number alterations were losses on chromosomal arms 3p (50%) and 1p (44%). Losses of 3p were detected in five of seven primary chordomas. Therefore, the loss of 3p might be an early event in chordoma genesis. The most common gains involved 7q (69%), 20 (50%), 5q (38%), and 12q (38%). Additionally, we raised the first human chordoma cell line, U-CH1, from a recurrence of a sacral chordoma. U-CH1 and its parent tumor had almost the same CGH profile. According to GTG-banding and multicolor FISH, U-CH1 has the following clonal chromosomal abnormalities: der(1)t(1;22), del(4), +del(5), +del(6), +7, del(9), del(10), +der(20)t(10;20), +21. Thus, the novel permanent human chordoma cell line U-CH1 has chordoma-typical cytogenetic aberrations. Our data suggest that tumor suppressor genes or mismatch repair genes (located at 1p31 and 3p14) and oncogenes (located in 7q36) might be involved in chordoma genesis.

Adult↗
PubMed2001

[Clinical value of positron emission tomography (PET) in the diagnosis of bone and soft tissue tumors. 3rd Interdisciplinary Consensus Conference "PET in Oncology": results of the Bone and Soft Tissue Study Group].

PURPOSE: In the framework of the 3rd Consensus Conference "PET in Oncology" the bone and soft-tissue tumors study group evaluated the present position of PET for these tumor entities on the basis of international publications. METHODS: After a systematic review of the literature, publications were evaluated according to previously defined quality criteria. For various indications the clinical usefulness of PET was assessed using a classification system. RESULTS: Most studies had been performed with a small number of patients (n < 35). Therefore, only 8 of 46 publications were judged relevant. On the basis of these literature data, use of FDG-PET for grading was classified 1b (literature results predominantly show clinical usefulness). As before (1995/97), all other indications were categorized with 3 (assessment not yet possible, literature data inadequate). OUTLOOK: According to the opinion of experts, the detection of osseous metastases of Ewing's sarcoma, therapy monitoring and the diagnosis of recurrences are potentially useful clinical indications for FDG-PET. Therefore, prospective studies with large patient groups are essential to further evaluate the benefit of FDG-PET in these indications.

Age Factors↗
PubMed2001

Surgical treatment of pelvic sarcomas: oncologic and functional outcome.

The experiences in treating 93 consecutive patients (56 males, 37 females; mean age, 38.5 years; range, 4-69 years), including 76 patients with primary malignant bone tumors and 17 patients with soft tissue sarcomas involving the innominate bone, are reported. Oncologic and functional results were investigated in relation to the tumor stage, to the achieved surgical margin, and to the surgical procedure (hemipelvectomy, internal hemipelvectomy and endoprosthetic replacement, and continuity resection). The mean followup was 48 months (range, 8-222 months). The 5-year survival was 86% in patients with low-grade malignant bone tumors, 42% in patients with high-grade malignant bone tumors, and 25% in patients with high-grade soft tissue sarcomas. Survival was influenced by the grade of malignancy, the tumor stage, and the achieved surgical margins. Forty-six patients who survived were examined an average of 36 months after primary surgery. Excellent and good functional results were seen in 82% of patients who underwent continuity resection and in 55.5% of patients who underwent partial or total internal hemipelvectomy. All patients who survived hemipelvectomy had poor functional results. Surgical treatment of pelvic sarcomas is an extensive procedure with a considerable incidence of complications. It requires the knowledge of different techniques of resection and reconstruction of bone, joints, soft tissue, and intrapelvic organs.

Adolescent↗
PubMed2001

Glucagon-like peptide 1 increases secretory burst mass of pulsatile insulin secretion in patients with type 2 diabetes and impaired glucose tolerance.

The insulinotropic gut hormone glucagon-like peptide (GLP)-1 increases secretory burst mass and the amplitude of pulsatile insulin secretion in healthy volunteers without affecting burst frequency. Effects of GLP-1 on secretory mechanisms in type 2 diabetic patients and subjects with impaired glucose tolerance (IGT) known to have impaired pulsatile release of insulin have not yet been studied. Eight type 2 diabetic patients (64+/-9 years, BMI 28.9+/-7.2 kg/m2, HbA1c 7.7+/-1.3%) and eight subjects with IGT (63+/-10 years, BMI 31.7+/-6.4 kg/m2, HbA1c 5.7+/-0.4) were studied on separate occasions in the fasting state during the continued administration of exogenous GLP-1 (1.2 pmol x kg(-1) x min(-1), started at 10:00 P.M. the evening before) or placebo. For comparison, eight healthy volunteers (62+/-7 years, BMI 27.7+/-4.8 kg/m2, HbA1c 5.4+/-0.5) were studied only with placebo. Blood was sampled continuously over 60 min (roller-pump) in 1-min fractions for the measurement of plasma glucose and insulin. Pulsatile insulin secretion was characterized by deconvolution, autocorrelation, and spectral analysis and by estimating the degree of randomness (approximate entropy). In type 2 diabetic patients, exogenous GLP-1 at approximately 90 pmol/l improved plasma glucose concentrations (6.4+/-2.1 mmol/l vs. placebo 9.8+/-4.1 mmol/l, P = 0.0005) and significantly increased mean insulin burst mass (by 68%, P = 0.007) and amplitude (by 59%, P = 0.006; deconvolution analysis). In IGT subjects, burst mass was increased by 45% (P = 0.019) and amplitude by 38% (P = 0.02). By deconvolution analysis, insulin secretory burst frequency was not affected by GLP-1 in either type 2 diabetic patients (P = 0.15) or IGT subjects (P = 0.76). However, by both autocorrelation and spectral analysis, GLP-1 prolonged the period (lag time) between subsequent maxima of insulin concentrations significantly from approximately 9 to approximately 13 min in both type 2 diabetic patients and IGT subjects. Under placebo conditions, parameters of pulsatile insulin secretion were similar in normal subjects, type 2 diabetic patients, and IGT subjects based on all methodological approaches (P > 0.05). In conclusion, intravenous GLP-1 reduces plasma glucose in type 2 diabetic patients and improves the oscillatory secretion pattern by amplifying insulin secretory burst mass, whereas the oscillatory period determined by autocorrelation and spectral analysis is significantly prolonged. This was not the case for the interpulse interval determined by deconvolution. Together, these results suggest a normalization of the pulsatile pattern of insulin secretion by GLP-1, which supports the future therapeutic use of GLP-1-derived agents.

Aged↗
PubMed2000

Assessment of developmental toxicity of antiretroviral drugs using a rat whole embryo culture system.

BACKGROUND: Previous guidelines for HIV-infected pregnant women have recommended zidovudine (ZDV) monotherapy during the second and third trimesters of pregnancy to prevent fetal HIV infection. New guidelines suggest that women should continue or be offered combination antiretroviral therapy (including protease inhibitors) during pregnancy. Nevertheless, little animal or human toxicity data underlie these recommendations. METHODS: We used an in vitro rat whole embryo culture system to assess the embryo toxicity of various nucleoside analogues, namely, ZDV, dideoxyinosine (ddI), and 2', 3'-dideoxycytidine (ddC), and the HIV-1 protease inhibitor, indinavir, both alone and in combination. RESULTS: Although human fetal concentrations of these compounds are unknown, no gross abnormalities were detected after incubation with these agents, either alone or in combination at concentrations that would be expected to be achievable in human maternal serum (1-50 microM). ZDV in combination with ddC at >100 microM, resulted in severe growth retardation and morphologic abnormalities not seen with either agent singly. CONCLUSIONS: We conclude that the combination of ZDV/ddC results in severe concentration-dependent embryo toxicity. No growth retardation or gross morphologic abnormalities were found for any of the agents, either singly or in combination, at clinically relevant concentrations.

Abnormalities, Drug-Induced↗