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Biomedical subjects

C Jönsson

Publications and source records attributed to C Jönsson.

9 recordsLinked to original sources

Patterned self-assembled beads in silicon channels.

A novel technique enabling selective bead trapping in microfluidic devices without the use of physical barriers is presented in this paper. It is a fast, convenient and simple method, involving microcontact printing and self-assembly, that can be applied to silicon, quartz or plastic substrates. In the first step, channels are etched in the substrate. The surface chemistry of the internal walls of the channels is then modified by microcontact printing. The chip is submerged in a bead slurry where beads self-assemble based on surface chemistry and immobilize on the internal walls of the channels. Silicon channels (100 microm wide and 50 microm deep) have been covered with monolayers of streptavidin-, amino- and hydroxy-functionalized microspheres and resulted in good surface coverage of beads on the channel walls. A high-resolution pattern of lines of self-assembled streptavidin beads, as narrow as 5 microm, has also been generated on the bottom of a 500 microm wide and 50 microm deep channel. Flow tests were performed in sealed channels with the different immobilized beads to confirm that the immobilized beads could withstand the forces generated by water flowing in the channels. The presented results indicate that single beads can be precisely positioned within microfluidic devices based on self-assembly which is useful as screening and analysis tools within the field of biochemistry and organic chemistry.

Animals↗

Arsenic trioxide inhibits neuroblastoma growth in vivo and promotes apoptotic cell death in vitro.

Recent clinical studies have shown that inorganic arsenic trioxide (As(2)O(3)) at low concentrations induces complete remission with minimal toxicity in patients with refractory acute promyelocytic leukemia (APL). Preclinical studies suggest that As(2)O(3) induces apoptosis and possibly differentiation in APL cells. Like APL cells, neuroblastoma (NB) cells are thought to be arrested at an early stage of differentiation, and cells of highly malignant tumors fail to undergo spontaneous maturation. Both APL and NB cells can respond with differentiation to retinoic acid (RA) treatment in vitro and probably also in vivo. For that reason we investigated the effect of As(2)O(3) alone and in combination with RA on NB cell lines. In vitro, the number of viable NB cells was reduced at As(2)O(3) concentrations around 1 microM after 72 h exposure. The IC50 in six different cell lines treated for 3 days was in the 1.5 to 5 microM concentration interval, the most sensitive being SK-N-BE(2) cells derived from a chemotherapy resistant tumor. The combined treatment with RA (1 and 3 microM) showed no consistent additional effect with regard to induced cell death. The effect of As(2)O(3) on NB cell number involved As(2)O(3)-induced apoptotic pathways (decreased expression of Bcl-2 and stimulation of caspase-3 activity) with no clear evidence of induced differentiation. The in vivo effect of As(2)O(3) on NB growth was also investigated in nude mice bearing tumors of xenografted NB cells. Although tumor growth was reduced by As(2)O(3) treatment, complete remission was not achieved at the concentrations tested. We suggest that As(2)O(3), in combination with existing treatment modalities, might be a treatment approach for high risk NB patients.

Antigens, Differentiation↗

Is the esophageal squamous epithelial barrier function impaired in patients with gastroesophageal reflux disease?

BACKGROUND: A disturbed epithelial barrier function has been promoted as one factor in the pathogenesis of gastroesophageal reflux disease (GERD). We therefore studied the effect of acid perfusion on the transmural potential difference (PD) of the distal esophagus in relation to onset of reflux symptoms. METHODS: PD was assessed during perfusion with saline and with 0.1 M HCl in healthy controls (n = 17) and in GERD patients without (n = 15) or with esophagitis (n = 6) and in remission after a fundoplication (n = 10). Heartburn and other upper GI symptoms were recorded concomitantly. Endoscopy-negative patients were studied before and after omeprazole treatment. RESULTS: HCl perfusion induced more lumennegative peak PD values in patients with active GERD, regardless of the presence or absence of esophagitis, than in healthy controls. After successful therapy, the PD response to acid perfusion equalled that of healthy subjects. Acid perfusion was associated with the onset of heartburn in most patients with active GERD but in none of the healthy subjects, and less frequently after medical and surgical therapy. CONCLUSIONS: The epithelial permeability to hydrogen ions differs between healthy subjects and patients with active GERD. Effective treatment, such as omeprazole or fundoplication, might improve the barrier function.

Adolescent↗

Identification of regions of HIV-1 p24 reactive with sera which give "indeterminate" results in electrophoretic immunoblots with the help of long synthetic peptides.

We analyzed nine sera from persons unlikely to be HIV infected which had an IgG reactivity directed against HIV-1 p24, and in two cases also to its precursor p55, but to no other HIV proteins, nor to proteins of the H9 host cell, in electrophoretic immunoblots (EIB). These sera are also referred to as having an indeterminate HIV EIB pattern or as HIV antibody false positive sera. Seven of nine sera reacted with longer (61-77 amino acids) and none with shorter (17-25 amino acids) p24-derived peptides in enzyme immunoassays (EIAs). This is compatible with a conformational (discontinuous) nature of the epitopes involved in many false positive HIV-1 p24 antibody reactions. Four sera reacted with an N-terminal, one with an internal, and two with a C-terminal fragment. Each of the seven sera thus only reacted with one of the long p24 peptides. The specificity and singularity of the reaction was further demonstrated by competition and/or absorption experiments with synthetic peptides. In contrast, 18 of 20 confirmed HIV-1+ sera with p24 reactivity in EIB reacted with at least one and often several of the longer peptides, most frequently the C-terminal one. Thus, the distribution of peptide reactivity of true HIV-1 antibody-positive sera was different from that of the falsely reactive sera. According to two of several explanations, these antibodies may have arisen because of (1) molecular mimicry by chance or by functional selection, (2) immunization by activation, noninfectious exposure, or infection involving non-HIV endogenous or exogenous retroviral antigens. The latter gains some support from our finding of antibody reactions with capsid proteins of the simian viruses, simian sarcoma-associated virus (SSAV), and Mason-Pfizer monkey retrovirus in some of the p24 +/- p55 reactive sera.

Adult↗

Studies of cholera toxin-induced changes of alkaline secretion and transepithelial potential difference in the rat intestine in vivo.

A pH-stat technique was used to investigate the effects of cholera toxin (CT) on alkaline secretion from denervated intestines (jejunum, ileum, colon) in anaesthetized rats. Transepithelial potential difference (PD) was also followed in some experiments. CT, given intraluminally, caused a marked increase in jejunal alkaline secretion, whereas only a small effect was observed in the ileum and no apparent effect was noted in the proximal colon. The pronounced increase in jejunal alkaline secretion was found to be inhibited by 10-25% by hexamethonium (10 mg kg-1 body wt i.v.) and similarly by serosal application of lidocaine, whereas atropine (0.25 mg kg-1 body wt i.v.) had no effect. Thus the cholera toxin-induced alkaline secretion in the jejunum is attributed mainly to a non-nervous mechanism. The small effect of CT on ileal alkaline secretion observed in this study contrasts with the high ileal bicarbonate concentration reported in cholera by authors who estimated the concentration from the total carbon dioxide/bicarbonate contents. This discrepancy may be explained by a CT-evoked increased transport of the coupled Na+/H+ and Cl-/HCO3- exchangers, which cannot be measured with the pH-stat technique used in this study.

Animals↗

Effects of histamine H2-receptor blockade on the cardiovascular reflex response to lower-body negative pressure in man.

The role of histamine H2-receptors in cardiovascular control is unknown. In seven healthy volunteers, we studied how histamine H2-receptor blockade affected the reflex response to hypovolaemia induced by lower-body negative pressure (LBNP). In placebo-treated individuals, LBNP down to -40 mmHg did not change systolic pressure but increased diastolic pressure, heart rate, forearm vascular resistance, plasma noradrenaline concentration and plasma renin activity. After pretreatment with ranitidine, a specific histamine H2-receptor antagonist, the diastolic pressure rise no longer sufficed to maintain a constant systolic pressure during LBNP. Ranitidine pretreatment also attenuated the heart rate response and the rise in plasma renin activity induced by LBNP, but did not significantly change the reflex forearm vasoconstriction or the forearm plasma noradrenaline response. The results suggest that histamine H2-receptor blockade attenuates the reflex vasoconstrictor response to lower-body negative pressure. The mechanism behind this effect remains unknown, but the data do not support the idea that the effect is exerted in the skeletal muscle vascular bed.

Adult↗

Calculation and measurements of absorbed dose in total body irradiation.

A method which is simple, reliable, and rapid to use in clinical routine for basic dose calculation in total body irradiation (TBI) has been tested with 8 MV x-rays. The dosimetry follows, as far as possible, national and international recommendations for conventional radiotherapy. The dose rate at different locations and depths is calculated from the absorbed dose rate at dose maximum for a phantom size of 30 x 30 x 30 cm in the TBI field (Dc), an inverse square law factor (SAD2/SPD2), the tissue-maximum ratio (TMR), an equivalent phantom and patient size correction factor (A), a factor for lack of back-scattering material (B), an off-axis output correction factor (O), and a factor that corrects for off-axis variations in effective photon beam energy and for oblique beam penetration of the patient (R). The collimator opening is constant for all patient sizes. It is shown that TMR, A, B and R can be measured in conventional geometry in ordinary phantoms but at an extended distance, while Dc, O and SAD2/SPD2 must be measured in TBI geometry. Tests in Humanoid phantoms showed an agreement in measured and planned AP/2 doses of 2% or better. If the calculation method is used for lower photon energies or in other TBI geometries it may be necessary to correct for the elliptical shape of the patient and for back-scattered radiation from the walls or floor.

Radiation Dosage↗