Biomedical subjects
Publications and source records attributed to B Güvenç.
Multiple myeloma (MM) is a plasma cell dyscrasia seen in the elderly that constitutes 10% of all haematopoietic neoplasias. It is a systemic disorder affecting various organs, in particular the kidneys and bones. Skin involvement is not a common finding. This report presents a case of MM with skin involvement.
An increase in the activity of membrane-associated protein phosphatase type 1 (mb-PP1) is associated with stimulation of erythrocyte K-Cl cotransport (KCC). We have recently proposed that membrane-associated protein phosphatase type 2A (mb-PP2A) is also involved in KCC regulation by cell swelling (Bize et al., 1999. Am. J. Physiol. 277:C899-C912). We used two protein phosphatase inhibitors, okadaic acid (OA) and calyculin A (CalA), and two KCC activating treatments, n-ethylmaleimide (NEM) and Mg(i)++-depletion, and determined KCC transport activity and mb-PP1 and mb-PP2A activities. OA, an inhibitor of erythrocyte mb-PP2A, partially prevents stimulation of KCC activity by NEM but not by Mg(i)++-depletion. CalA, an inhibitor of both mb-PP1 and mb-PP2A prevents stimulation of KCC activity by both treatments. NEM and Mg(i)++-depletion inhibit mb-PP1 activity, suggesting that activation of KCC can take place in the absence of mb-PP1 activation. Mb-PP2A activity is stimulated in NEM-treated cells but not in Mg(i)++-depleted cells. In NEM-treated cells, Mg(i)++-depletion inhibits both KCC and mb-PP2A. In Mg(i)++-depleted cells, NEM does not stimulate KCC or mb-PP2A. The strong correlation between KCC stimulation and mb-PP2A stimulation provides further support to the idea that mb-PP2A plays an important role in KCC regulation. Our results are consistent with the hypothesis that KCC regulation involves at least two distinguishable phosphorylation sites.
Activation of K-Cl cotransport is associated with activation of membrane-bound serine/threonine protein phosphatases (S/T-PPases). We characterize red blood cell S/T-PPases and K-Cl cotransport activity regarding protein phosphatase inhibitors and response to changes in ionic strength and cell size. Protein phosphatase type 1 (PP1) activity is highly sensitive to calyculin A (CalA) but not to okadaic acid (OA). PP2A activity is highly sensitive to CalA and OA. CalA completely inhibits K-Cl cotransport activity, whereas OA partially inhibits K-Cl cotransport. Membrane PP1 and membrane PP2A activities are elevated in cells suspended in hypotonic solutions, where K-Cl cotransport is elevated. Increases in membrane PP1 activity (62 +/- 10% per 100 meq/l) result from decreases in intracellular ionic strength and correlate with increases in K-Cl cotransport activity (54 +/- 10% per 100 meq/l). Increases in membrane PP2A activity (270 +/- 77% per 100 mosM) result from volume increases and also correlate with increases in K-Cl cotransport activity (420 +/- 47% per 100 mosM). The characteristics of membrane-associated PP1 and PP2A are consistent with a role for both phosphatases in K-Cl cotransport activation in human erythrocytes.
A vasodilating Ca2+ channel blocker, bencyclane, was used in 18 patients with homozygous sickle cell anaemia (SCD) to test the possible anti-sickling effect. With bencyclane intervention the Na(+)-K+ ATPase activity increased from 256 +/- 29 to 331 +/- 37 nmol Pi/mg protein/h (P < 0.0001) and the Ca(2+)-Mg2+ ATPase level increased from 172 +/- 12 to 222 +/- 44 nmol Pi/mg protein/h (P < 0.0001). The intracytoplasmic Ca2+ concentration reduced from 3.5 +/- 0.6 to 2.7 +/- 0.25 mumol/l (P < 0.0001). The patient's blood contained fewer irreversibly sickled cells (ISCs) (a reduction from 21.4% to 14.4%) (P < 0.05). At the same time MCHC of the erythrocytes decreased from 34.5 to 33.0 g/dl (P < 0.05). Bencyclane appears to be a promising anti-sickling agent that can be used orally in SCD.
The major complications in sickle cell disease (SCD) are microcirculation lesions and impairment of renal function. The aim of this study was the evaluation of renal vascular resistance by means of spectral pulsed Doppler sonography and its relationships with haematological and clinical features in patients with SCD. 40 patients with SCD (mean age 22.4 +/- 7.0) and 14 age and sex matched healthy subjects (mean age 25.7 +/- 9.5) were included into the study. Spectral Doppler sonography of main renal, segmental and interlobar arteries were performed on both kidneys in all patients and controls. Peak systolic, end diastolic and mean velocities through the entire cardiac cycle were obtained, with calculation of the resistive (RI) and pulsatility (PI) indices. All the patients were investigated in stable state conditions and had not been transfused within a month before investigation. Patients were followed for up to 6 months. Patients with SCD had higher values of RIs and PIs than control subjects (p < 0.0001, p < 0.0001, respectively). Patients with high value of RIs (RI > 0.70) had more pronounced disturbances of blood parameters (all p < 0.05), than patients with normal RIs (RI < 0.70). Significant positive correlation existed between RIs and ISC number, MCHC level (r = 0.52, p < 0.001 and r = 0.42, p < 0.01), while RBC count and Hb level correlated inversely with RIs (r = -0.39, p < 0.01 and r = -0.42, p < 0.01). During follow-up, nine patients (33.3%) with high RIs and only one patient (5.5%) with normal RI developed painful crises. In conclusion, renal vascular resistance, assessed by Doppler sonography was raised in SCD patients as compared with age matched apparently healthy persons. These changes were more pronounced in those with more severe manifestations of disease and correlated with haematological and clinical features of sickle cell disease.