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Biomedical subjects

G Hansen

Publications and source records attributed to G Hansen.

At least 55 records · Page 3Linked to original sources

Reversed phase-high performance liquid chromatographic (RP-HPLC) method to measure migration of semi-volatile compound, vanillin, in ipratropium bromide inhalation solution.

Ipratropium bromide, a bronchodilator, is used as an inhalation solution. Commercial ipratropium bromide solution products are packaged in low-density polyethylene (LDPE) vials, through which semivolatile compounds are reported to migrate. In this article, a specific reversed phase-high performance liquid chromatographic method to assay vanillin, a semivolatile compound, in ipratropium bromide solution is described. The method was validated for a concentration range for vanillin from 30 ng/mL to 1,600 ng/mL. Migration of vanillin was assessed in two commercial preparations, ATROVENT (ipratropium bromide) Inhalation Solution packaged in a secondary foil pouch and a generic ipratropium bromide inhalation solution packaged in a carton. Levels of vanillin detected in ATROVENT after 6 months of storage at 40 degrees C and 75% RH were below the limit of detection (11 ng/mL). Significant migration of vanillin was observed after 1 month in the generic product and reached 165 ng/mL to 999 ng/mL in three months under the same storage conditions. It is concluded that this method can be readily used to measure vanillin in commercial preparations of ipratropium bromide inhalation solution. The results strongly indicate that a protective secondary packaging material is critical in preventing migration of semivolatile compounds. This study result is in agreement with the FDA's recommendation to consider even the secondary packaging components as potential sources of contamination and the use of an overwrap (typically aluminum foil) to decrease the overall permeability.

Administration, Inhalation↗

[Nutritional status of Danish patients with rheumatoid arthritis and effects of a diet adjusted in energy intake, fish content and antioxidants].

This study deals with the nutritional status of Danish rheumatoid arthritis (RA) patients and addresses the question whether or not RA can be directly influenced by dietary manipulation. In a prospective, single-blinded study of six months' duration, 109 patients with active RA were randomly assigned to treatment with or without a specialized diet. The energy consumption was adjusted to normal standards for body-weight and the intake of fish and antioxidants was increased. A daily food diary was completed by the patients, and the total intake of 47 different food-elements was calculated. Nutritional status together with disease activity parameters were recorded. At baseline, the Danish RA-patients had neglected food habits with a significant reduction in intake of total energy, of D-vitamin and of E-vitamin. A very low intake of n-3 fatty acids was also found. During the study, 28 of the 109 patients dropped out, introducing a confounding effect on the overall result. In the remaining 81, those following the diet demonstrated a significant improvement in the duration of morning stiffness, the number of swollen joints, the pain status and reduced the cost of medicine, while doctors' global assessment, laboratory data, X-ray and the daily activities were unaltered. In conclusion, dietary analysis and appropriate, corrective advice should be offered to Danish RA patients.

Adult↗

T-strand integration in maize protoplasts after codelivery of a T-DNA substrate and virulence genes.

We describe a plant protoplast transformation method that provides transformants with a simple pattern of integration of a foreign gene. The approach is to deliver into plant protoplasts by direct gene transfer the Agrobacterium virulence genes virD1 and virD2 with or without virE2, together with a target plasmid containing a gene of interest flanked by Agrobacterium T-DNA border repeat sequences of 25 bp. We present evidence of T-DNA formation in maize protoplasts and its integration into the maize genome. The frequency of VirD1-VirD2-mediated integration events was about 20-35% of the total number of transformants. The addition of virE2 doubled the transformation efficiency. The method described here is of sufficient efficiency and simplicity to be useful for the production of transgenic plants with single-copy well-defined transgenic inserts.

Bacterial Proteins↗

Wound-inducible and organ-specific expression of ORF13 from Agrobacterium rhizogenes 8196 T-DNA in transgenic tobacco plants.

Tissue-specific expression of the ORF13 promoter from Agrobacterium rhizogenes 8196 was assessed throughout the development of transgenic tobacco plants using a GUS reporter gene. ORF13 exhibited high activity in roots but with different patterns of expression. The activity of the ORF13 promoter in vascular tissues increased from the base to the tip of the stem. The ORF13 promoter is wound inducible in a limited area adjacent to the wound site. The time course of wound induction of ORF13 in transgenic tobacco containing an ORF13 promoter-GUS translational fusion was similar to that previously described for genes involved in plant defense responses. A series of 5' deletions of the ORF13 promoter fused to the beta-glucuronidase gene was examined for expression in roots and leaves of transgenic plants. Cis-acting elements that modulate quantitative expression of the transgene after wounding were detected.

Base Sequence↗

"Agrolistic" transformation of plant cells: integration of T-strands generated in planta.

We describe a novel plant transformation technique, termed "agrolistic," that combines the advantages of the Agrobacterium transformation system with the high efficiency of biolistic DNA delivery. Agrolistic transformation allows integration of the gene of interest without undesired vector sequence. The virulence genes virD1 and virD2 from Agrobacterium tumefaciens that are required in bacteria for excision of T-strands from the tumor-inducing plasmid were placed under the control of the CaMV35S promoter and codelivered with a target plasmid containing border sequences flanking the gene of interest. Transient expression assays in tobacco and in maize cells indicated that vir gene products caused strand-specific nicking in planta at the right border sequence, similar to VirD1/VirD2-catalyzed T-strand excision observed in Agrobacterium. Agrolistically transformed tobacco calli were obtained after codelivery of virD1 and virD2 genes together with a selectable marker flanked by border sequences. Some inserts exhibited right junctions with plant DNA that corresponded precisely to the sequence expected for T-DNA (portion of the tumor-inducing plasmid that is transferred to plant cells) insertion events. We designate these as "agrolistic" inserts, as distinguished from "biolistic" inserts. Both types of inserts were found in some transformed lines. The frequency of agrolistic inserts was 20% that of biolistic inserts.

Agrobacterium tumefaciens↗

Near-infrared spectroscopy and spectral mapping of Jupiter and the Galilean satellites: results from Galileo's initial orbit.

The Near Infrared Mapping Spectrometer performed spectral studies of Jupiter and the Galilean satellites during the June 1996 perijove pass of the Galileo spacecraft. Spectra for a 5-micrometer hot spot on Jupiter are consistent with the absence of a significant water cloud above 8 bars and with a depletion of water compared to that predicted for solar composition, corroborating results from the Galileo probe. Great Red Spot (GRS) spectral images show that parts of this feature extend upward to 240 millibars, although considerable altitude-dependent structure is found within it. A ring of dense clouds surrounds the GRS and is lower than it by 3 to 7 kilometers. Spectra of Callisto and Ganymede reveal a feature at 4. 25 micrometers, attributed to the presence of hydrated minerals or possibly carbon dioxide on their surfaces. Spectra of Europa's high latitudes imply that fine-grained water frost overlies larger grains. Several active volcanic regions were found on Io, with temperatures of 420 to 620 kelvin and projected areas of 5 to 70 square kilometers.

Ammonia↗

[The value of preoperative thoracic CT. 19 patients with bronchial cancer surgically treated].

The incidence of bronchial carcinoma is increasing. The only curative treatment so far has been surgery. The correlation between preoperative CT thorax and peroperative/pathologic findings was evaluated in order to assess the value of preoperative CT thorax in patients with bronchial carcinoma. The thoracic CTs of 96 patients with bronchial carcinoma who were referred to our outpatient clinic from January 1992 to September 1994 were reviewed. Only 19 patients (20%) underwent surgery (seven pulmectomies, nine lobectomies, two wedge resections, one explorative thoracotomy). The remaining 77 patients received either irradiation, chemotherapy or other palliative treatment. The tumours were classified according to the TNM system (T = tumour, N = node, M = metastases) of UICC (Union Internationale Centre le Cancer). In 11 of the 19 patients who underwent surgery a correct TN classification was assessed at CT, while in four the T classification and in another four the N classification was changed after peroperative and pathologic assessment. CT showed a slight tendency to overestimate T classification. As for the N classification, overestimation and underestimation were equal. We conclude that CT thorax is valuable in the preoperative staging of bronchial carcinoma.

Adult↗

[211At]methylene blue for targeted radiotherapy of human melanoma xenografts: dose fractionation in the treatment of cutaneous tumours.

3,7-(dimethylamino) phenazathionium chloride [methylene blue (MTB)] labelled with alpha-particle emitter astatine-211 (211At) selectively accumulates in melanoma cells due to an exceptionally high affinity of MTB to melanin, and proves to be a very effective agent in targeting radiotherapy for pigmented human melanoma grown in mice. This study aimed at a selection of the most advantageous [211At]MTB dose fractionation leading to irreversible regression of the treated lesions. Nude mice bearing subcutaneous human melanoma xenografts of either highly pigmented HX118 or poorly pigmented HX34 human melanoma were treated with [211At]MTB administered intravenously. The treatment was performed using three different schedules of [211At]MTB fractionation: a single large dose, five fractions delivered sequentially every 48 h and two to five fractions given with a mean frequency of one per week. The effectiveness of [211At]MTB treatment was assessed by determination of the growth rate of cutaneous tumours and length of time between tumour implantation and killing of moribund mice. [211At]MTB applied with a mean frequency of one fraction per week appeared to be the most efficient treatment for highly pigmented HX118 melanomas. Its effectiveness was dependent on [211At]MTB activity used per fraction and the size of the cutaneous tumours at the beginning of the treatment. A total dose of [211At]MTB seemed of less importance. An irreversible regression of the lesions was achieved. Poorly pigmented cutaneous melanoma xenografts were affected most significantly by [211At]MTB applied as five fractions given every 48 h. The treatment caused a temporary inhibition of tumour growth after which the lesions regained the control growth rate. These and previous results suggest that [211At]MTB could successfully control the growth of already formed lesions of pigmented melanoma, as well as prevent metastatic spread of the tumour, provided an appropriate fractionation régime of the radiolabelled compound is employed.

Animals↗

Clinical impact of adrenal expansive lesions in bronchial carcinoma.

PURPOSE: To estimate the prevalence of adrenal expansive lesions in patients with bronchial carcinoma, and assess the relationships among adrenal masses, TNM classification, and histology of the bronchial carcinoma, and to reveal other signs of inoperability in these patients. MATERIAL AND METHODS: CT findings of the thorax and upper abdomen in 96 patients with bronchial carcinoma were reviewed. Brain- and upper abdominal metastases, together with TNM classification and histology of the bronchial carcinoma, was recorded. CT was performed with 10-mm slice thickness from the thorax aperture to the renal hilum under i.v. contrast medium injection. RESULTS: Eight adrenal expansive lesions (1.5-10 cm, mean 4.6 cm) were revealed in 6 of the 96 patients (6.3%). Two of these patients, classified as N0, had metastases in other organs; one had brain metastases and the other liver metastases. The bronchial carcinomas in the remaining 4 patients were classified as N3. Three of the patients had adenocarcinoma, one each of small-cell-, large-cell-, and unclassified bronchial carcinoma. Squamous cell carcinoma was most common in the total patient population, but no patient with adrenal masses showed this histologic type. CONCLUSION: The finding of adrenal expansive lesions in bronchial carcinoma has little clinical impact, because these patients usually show other signs of inoperability. Hence, the value of upper abdominal CT as a routine examination is questionable.

Adrenal Gland Neoplasms↗

Effects of native and oxidation-resistant secretory leukoprotease inhibitor on cystic fibrosis sputum: inhibition of neutrophil elastase activity and of sputum-induced secretion from porcine tracheal submucosal glands.

Because the antiprotease defense in cystic fibrosis (CF) airways is overwhelmed by neutrophil elastase (NE), substitution of antiproteases such as secretory leukoprotease inhibitor (SLPI) seems to be a reasonable therapeutic approach. Knowing, however, that native antiproteases may be liable to rapid inactivation by the locally abundant oxidants, we comparatively investigated the interactions of CF sputum with recombinant native SLPI (rSLPI) and its partially oxidation-resistant variant (rSLPI-242), respectively, to estimate their therapeutic potentials. NE activity in supernatants from diluted CF sputum samples was dose-dependently inhibited by both rSLPI and rSLPI-242, with comparable potency. Addition of the oxidant N-chlorosuccinimide resulted in significant superiority of rSLPI-242 over rSLPI. When fresh neutrophil-rich CF sputum was incubated with rSLPI and rSLPI-242, respectively, rSLPI-242 inhibited sputum NE activity significantly more potently than did rSLPI; addition of the antioxidant superoxide dismutase significantly improved the effect of rSLPI. Furthermore, secretion of radiolabeled macromolecules from porcine tracheal glands induced by purified NE or by CF sputum was inhibited dose-dependently by rSLPI and even better by rSLPI-242. We conclude that both rSLPI and rSLPI-242 effectively inhibit NE activity and NE-induced gland hypersecretion in vitro. In vivo effects of CF remain to be analyzed; an advantage of the partially oxidation-resistant rSLPI-242 can be expected.

Adolescent↗

[Schizophrenia or spiritual crisis? On "raising the kundalini" and its diagnostic classification].

Two patients are described who had been diagnosed as schizophrenic, but had actually instead been going through spiritual crises, which in Eastern spiritual tradition are called raising the kundalini. Perhaps this experience is not a disease, but many--especially if not understood by oneself, the nearest relations and the medical profession--cause mental illness. In WHO ICD-10 the experience could be classified as F48.8, disordines neurotici specificati alii. The process falls outside the categories of both normal and psychotic. When allowed to progress to completion this process culminates in deep psychological balance, strength, and maturity.

Adult↗

[Guidelines for understanding and treating chronic obstructive lung diseases. Institute for Pharmacotherapy].

A group of chest physicians, general practitioners, clinical pharmacologist and pharmacists appointed by the Institute of Pharmacotherapy, University of Oslo has evaluated the present knowledge about treatment of chronic obstructive lung disease. The group discusses today's medical treatment of this rather numerous group of patients. It is stated that, to a high degree, the treatment of these patients lacks proper documentation, and that treatment needs to be tested out on an individual basis. The group proposes a flow chart for this purpose.

Humans↗

Inactivation of cell surface receptors by pheophorbide a, a green pigment isolated from Psychotria acuminata.

The inhibition of cytokine and monoclonal antibody binding cell surfaces caused by an extract of Psychotria acuminata, a medicinal plant used in the traditional medicine of the people of Belize (Central Africa), was attributed to the presence of pheophorbide a and pyropheophorbide a. Since the binding of tumor necrosis factor-alpha, interleukin-8, complement factor 5a as well as epidermal growth factor to target cells was dramatically reduced, the inhibition was not receptor or cytokine specific. In addition, the respective binding of radiolabeled monoclonal antibodies CL203 and R15.7 to the cell surface antigens intracellular cell adhesion molecule-1 and lymphocyte function-associated antigen-1 beta-chain was decreased by pretreatment of cells with pheophorbide a as well. In all cases, the inhibition by pheophorbides was dependent on the simultaneous presence of light, indicating causative involvement of a photodynamic process. These observations are not unique to pheophorbides and can be extended to porphyrins as well as to other photodynamic agents. Cytotoxicity resulting from photodynamic therapy (PDT) has been documented by many studies. Our investigations suggest that the inactivation of cell surface receptors contributes not only to an antitumor effect of PDT but also to the systemic immunosuppression, a serious side effect of PDT.

Belize↗

Alpha 1-proteinase inhibitor abrogates proteolytic and secretagogue activity of cystic fibrosis sputum.

Airway disease in cystic fibrosis (CF) is characterized by neutrophil-dominated chronic inflammation with an excess of uninhibited neutrophil elastase (NE), which is regarded as an important factor in progressive lung destruction. Therefore, inhalation of alpha 1-proteinase inhibitor (alpha 1-PI) seems to be a reasonable therapeutic approach. To estimate its therapeutic potential, we quantitatively investigated the in vitro interactions of exogenous alpha 1-PI with CF sputum samples (n = 28). High NE and alpha 1-PI concentrations were detected in CF sputum (6.03 +/- 0.78 and 2.56 +/- 0.16 mumol/l, respectively). There was significant NE activity (2.6 +/- 0.4 U/l) due to both the surplus of NE and proteolytic degradation of alpha 1-PI. Addition of exogenous alpha 1-PI resulted in a dose-dependent inhibition of NE activity in CF sputum; > 90% inhibition was achieved at 10 micrograms/ml alpha 1-PI. Purified NE as well as CF sputum potently induced secretion from porcine tracheal glands. Corresponding to inhibition of NE activity, CF sputum-induced secretion was also inhibited by exogenous alpha 1-PI; > 90% inhibition was also achieved at 10 micrograms/ml alpha 1-PI. Incubation of exogenous alpha 1-PI with CF sputum for 24 h did not reduce the inhibitory effects. From our in vitro results we conclude that inhalation of alpha 1-PI might effectively inhibit both NE activity and airway gland hypersecretion in CF airways.

Adolescent↗

Constitutive expression of the virulence genes improves the efficiency of plant transformation by Agrobacterium.

Inducible virulence (vir) genes of the Agrobacterium tumefaciens tumor-inducing (Ti) plasmid are under control of a two-component regulatory system. In response to environmental factors (phenolic compounds, sugars, pH) VirA protein phosphorylates VirG, which in turn interacts with the promoters of other vir genes, causing induction. A mutation of virG, virGN54D (which codes for a Asn-54-->Asp amino acid change in the product), causes constitutive expression of other vir genes independent of virA. We have investigated whether providing Agrobacterium with a plasmid containing virGN54D augments the efficiency of transfer of the T-DNA (transferred DNA). For both tobacco and cotton, we observed an enhancement of transformation efficiency when the inciting Agrobacterium strain carries the virGN54D mutation. We also tested whether supplying Agrobacterium with a similar plasmid containing wild-type virG affects the efficiency of T-DNA transfer. An intermediate efficiency was observed when this plasmid was employed. Using a beta-glucuronidase (GUS) reporter gene to assess transient expression of T-DNA after transfer to tobacco and maize tissues, we observed a higher frequency of GUS-expressing foci after inoculation with Agrobacterium strains carrying virGN54D than with Agrobacterium carrying the wild-type virG. Gene-transfer efficiency to maize by an octopine strain was greatly improved upon introduction of virGN54D. Multiple copies of wild-type virG were equally effective in promoting transient expression efficiency in tobacco but were virtually ineffective in maize. We propose the use of virGN54D to improve the efficiency of Agrobacterium-mediated transformation, especially for recalcitrant plant species.

Agrobacterium tumefaciens↗