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S Carstens

Publications and source records attributed to S Carstens.

7 recordsLinked to original sources
PubMed2006

Differential DNA methylation patterns of small B-cell lymphoma subclasses with different clinical behavior.

Non-Hodgkin's lymphoma (NHL) is a group of malignancies of the immune system with variable clinical behaviors and diverse molecular features. Despite the progress made in classification of NHLs based on classical methods, molecular classifications are a work in progress. Toward this goal, we used an array-based technique called differential methylation hybridization (DMH) to study small B-cell lymphoma (SBCL) subtypes. A total of 43 genomic DMH experiments were performed. From these results, several statistical methods were used to generate a set of differentially methylated genes for further validation. Methylation of LHX2, POU3F3, HOXC10, NRP2, PRKCE, RAMP, MLLT2, NKX6.1, LRP1B and ARF4 was validated in cell lines and patient samples and demonstrated subtype-related preferential methylation patterns. For LHX2 and LRP1B, bisulfite sequencing, real-time reverse transcriptase-polymerase chain reaction and induction of gene expression following treatment with the demethylating agent, 5'-aza-2'-deoxycytidine, were confirmed. This new epigenetic information is helping to define molecular portraits of distinct subtypes of SBCL that are not recognized by current classification systems and provides valuable potential insights into the biology of these tumors.

Adult↗
PubMed1996

Ion transport mechanisms in native rabbit nasal airway epithelium.

Net ion transports in rabbit nasal airway epithelium (RNAE) were estimated from unidirectional fluxes of 22Na+, 36Cl-, and 86Rb+ (K+ tracer), short-circuit current (Isc), and epithelial conductance (Gt) under short-circuit conditions in excised parallel RNAE from the two sides of the nasal septum mounted in Ussing chambers at 37 degrees C. Net Na+ absorption (JNa; 76 nmol.min-1.cm-2) was nearly equal to the net charge flux (Jnet), equivalent to the control Isc of 137 microA/cm2 (Jnet = Isc/zF = 85 neq.min-1.cm-2). Secretions of Cl- (9 nmol.min-1.cm-2) and K+ (Rb+) (1.2 nmol.min-1.cm-2) were small. Intra-animal variations between right- and left-side Isc values were small compared with large interanimal variations, suggesting long-term regulation of JNa. Serosal ouabain (10(-4) M) abolished Isc. Mucosal amiloride (10(-4) M) maximally inhibited Isc by 68% and JNa by 78%, abolished K+ (Rb+) secretion, increased Cl- secretion slightly (to 16 nmol.min-1.cm-2), and decreased control Gt (13.4 mS/cm2) by 26%. Amiloride-insensitive JNa was inhibited approximately 50% by mucosal hydrochlorothiazide (10(-4) M) but not by mucosal bumetanide, phloridzine, or ethoxzolamide. The Cl- secretion was abolished by serosal bumetanide (10(-4) M) and also by mucosal diphenylamine-2-carboxylate (2.5.10(-4) M) or bumetanide (10(-4) M). Serosal Ba2+ (2 mM) inhibited JNa and increased K+ (Rb+) secretion. The latter was blocked by mucosal Ba2+. Passive Cl- (but not Na+) fluxes varied proportionally with Gt and were approximately four times higher than passive Na+ fluxes, suggesting 1) significant anion selectivity of a low-resistance paracellular pathway and 2) separate routes for paracellular Cl- and Na+ fluxes. We conclude that RNAE is a suitable model organ for studies of regulation of JNa in native human airway epithelia.

Amiloride↗
PubMed1996

Effects of a short-chain phospholipid on ion transport pathways in rabbit nasal airway epithelium.

We investigated the mechanism of interference of mucosal application of the short-chain phospholipid didecanoyl-L-alpha-phosphatidylcholine (DDPC; 0.1-0.5%) with ion transport pathways in isolated rabbit nasal airway epithelium (RNAE). Transports of Na+ and Cl- were evaluated from tracer ion fluxes, short-circuit current (Isc), and epithelial conductance (Gt) under short-circuit conditions in Ussing chambers. DDPC rapidly and reversibly abolished net Na+ absorption, reduced control Isc (approximately 110 microA/cm2) by approximately 80%, and induced a small Cl secretion. Intracellular Ca2+ concentration ([Ca2+]i) increased dose dependently and transiently (measured by fura 2 in cultured rabbit airway epithelium), but ionomycin failed to mimic the decrease in Isc. The rise in [Ca2+]i may explain a Ba(2+)-sensitive transient activation of a basolateral K+ conductance. Indomethacin-sensitive prostaglandin E2 production in RNAE increased severalfold, but cyclooxygenase and lipoxygenase inhibitors did not prevent DDPC-induced changes in Isc. DDPC initially decreased control Gt (approximately 13 mS/cm2) by approximately 25% due to inhibition of amiloride-sensitive Na+ channels, and then reversibly increased Gt to approximately 45% above control values. Passive Na+ fluxes increased more than Cl fluxes, suggesting that the increase in Gt is due to formation of a paracellular shunt conductance in parallel with unaffected, anion-selective tight junction channels. The results suggest that DDPC inhibits apical membrane Na+ channels and causes structural changes in tight junctions after incorporation in apical cell membranes.

Animals↗
PubMed1994

[Intranasal glucagon in the treatment of hypoglycemia. A therapeutic possibility in the future].

Nearly 10% of IDDM patients receiving conventional insulin treatment and about three times as many in intensive insulin therapy yearly experience severe hypoglycaemia (requiring external assistance) The conventional treatment of severe hypoglycaemia is glucagon given intramuscularly by a relative or glucose administered intravenously by a physician. These are however not optimal treatments. Obtaining intravenous access requires a medical doctor and glucagon injection is not always properly done by family members. Glucagon administered intranasally has been proven to raise blood glucose levels in volunteers. The effect of intranasal glucagon on blood glucose is similar to that seen after intramuscular administration for the first 15 minutes following administration. However, intranasal glucagon seems more physiological in that is stabilizes blood glucose concentrations at nearfasting levels, whereas glucagon given intramuscularly tends to give hyperglycaemia. Intranasal glucagon is easy to administer, and can thus prevent serious hypoglycaemic crises and thereby make diabetics and their families more secure.

Administration, Intranasal↗
PubMed1993

Transport of insulin across rabbit nasal mucosa in vitro induced by didecanoyl-L-alpha-phosphatidylcholine.

To investigate the short-term effects of didecanoyl-L-alpha-phosphatidylcholine on the nasal mucosa and the mechanism by which didecanoyl-L-alpha-phosphatidylcholine enhances the nasal absorption of insulin, an in vitro model was developed. The mucosa from the posterior part of the rabbit nasal septum was mounted in an Ussing chamber and incubated in bicarbonate Ringer solution at 37 degrees C. Potential difference, transmucosal conductance, and unidirectional tracer fluxes were measured across an exposed tissue area of 0.44 cm2. Morphological and physiological examinations revealed a typical respiratory epithelium containing amiloride-sensitive Na+ channels and diphenylamine-2-carboxylate-sensitive Cl- channels. Spontaneous potential difference (10.8 +/- 0.4 mV [n = 50]; serosa positive) and transmucosal conductance (10.5 +/- 0.4 mS/cm2 [n = 50]) were stable for several hours. Mucosal addition of 0.1-0.5% didecanoyl-L-alpha-phosphatidylcholine increased transmucosal conductance (by 43-53%) and decreased potential difference (to 0-2 mV) to new steady-state values within 10-15 min. Control unidirectional rate constants for permeation of sucrose, polyethylene glycol 4000, and insulin were low and varied according to the molecular size. After addition of didecanoyl-L-alpha-phosphatidylcholine, unidirectional rate constants for the three compounds all increased 3- to 5.5-fold. The didecanoyl-L-alpha-phosphatidylcholine effects on potential difference and transmucosal conductance were reversible after a recovery period of at least 40 min when didecanoyl-L-alpha-phosphatidylcholine had been applied to the mucosal side for 15 min. The results suggest that didecanoyl-L-alpha-phosphatidylcholine may increase the transepithelial absorption of insulin by facilitating a paracellular passage through a reversible opening of tight junctions.

Amiloride↗
PubMedDate not supplied

Prehospital treatment of severe hypoglycaemia: a comparison of intramuscular glucagon and intravenous glucose.

INTRODUCTION: By introducing an intensified insulin treatment regime to patients with insulin-dependent diabetes mellitus (IDDM), the frequency of long-term complications that the patient will experience has been shown to decrease. The price is an increase in the frequency of severe and mild hypoglycaemic events. Therefore, constant monitoring of these patients is necessary. HYPOTHESIS: This study compares the time until full recovery of IDDM patients with severe hypoglycaemia after treatment with either intravenous glucose or intramuscular glucagon. METHODS: 14 patients with IDDM with severe hypoglycaemia requiring treatment by the medical staff was randomised to treatment either with 50 ml of 50% glucose intravenously or intramuscular 1 mg glucagon. The time to recovery was recorded. Plasma glucose was measured at fixed intervals to achieve a glycaemia profile. Demographic data were acquired through patient interviews following recovery. RESULTS: Recovery time between the two groups was significantly different statistically. Recovery time ranged for 1 to 3 minutes for those receiving glucose intravenously and 8 to 21 minutes for those receiving intramuscular glucagon. Characteristic glycaemia profiles were identified and differences were present between the two groups with a greater fluctuating pattern for the glucose group compared to the steadily increasing pattern seen after glucagon treatment. Alcohol was believed to be involved in 8 out of the 14 cases, and thereby, is the major confounding factor in this study. CONCLUSION: Intramuscularly administered glucagon is a safe and reliable alternative to intravenous glucose infusion. The fluctuating glycemia pattern seen after glucose treatment indicates a low risk for secondary hypoglycaemia. However, further studies are necessary to support this assertion.

Adult↗