Hereditary nonspherocytic hemolytic anemia and hexokinase deficiency

An 11-yr-old child with mild chronic hemolytic anemia was found to have decreased red cell hexokinase activity in spite of the reduced mean age of her red cell population. Similar decreases in red cell hexokinase activity were documented in the patient's parents and in one sib. The red cells were morphologically normal. Red cell 2,3-DPG levels were normal and ATP and glucose-6-phosphate levels were diminished. The kinetic properties, electrophoretic mobility, and thermal stability of the residual red cell hexokinase were normal or nearly so. Glucose consumption of the hexokinase-deficient cells was not appreciably decreased, probably because less of the potent inhibitor glucose-6- phosphate was present in the erythrocytes. It is likely, although not certain, that in this patient nonspherocytic hemolytic anemia resulted from hexokinase deficiency.     

Chemosensitization of myeloma plasma cells by an antisense-mediated downregulation of Bcl-2 protein.

An antisense oligodeoxynucleotide (ODN) complementary to the first six codons of the Bcl-2 mRNA, G3139 (oblimersen sodium; Genasense), has been shown to downregulate Bcl-2 and produce responses in a variety of malignancies including drug-resistant lymphoma. Incubation of ex vivo purified plasma cells from patients with multiple myeloma (MM) with carboxyfluorescein (FAM)-labeled antisense ODNs resulted in a time- and dose-dependent uptake in the cytoplasm and nucleus. No major differences in uptake of Bcl-2 antisense ODNs were observed among patients' samples. Incubation of purified myeloma plasma cells with G3139, but not solvent or reverse polarity control ODNs, resulted in a reduction (>75%) of Bcl-2 mRNA levels after 2 and 4 days, as measured by Real-Time PCR. Treatment with G3139 led to a sequence-specific reduction of Bcl-2 protein levels within 4 days of exposure in 10 out of 11 clinical samples from patients with chemosensitive and multidrug-resistant disease, without significant reduction of alpha-Actin, Bax, Bcl-XL, or Mcl-1 proteins. This resulted in a significantly enhanced sensitivity of the myeloma tumor cells to dexamethasone or doxorubicin-induced apoptosis. G3139 can consistently enter myeloma cells, downregulate the expression of Bcl-2, and enhance the efficacy of myeloma therapy. These data support further clinical evaluation of G3139 therapy in multiple myeloma.     

Role of transforming growth factor beta in peritoneal fibrosis

SUMMARY: Technique survival of peritoneal dialysis is seriously limited by the development of peritoneal fibrosis. the mesothelial cell layer lining the peritoneum is important in the pathogenesis of peritoneal fibrosis. Mesothelial cells are able to produce transforming growth factor beta (TGF-β), and respond to stimulation by this cytokine. In this review, we will detail the evidence available so far for the role of the complex interaction between TGF-β and mesothelial cells in the development of peritoneal fibrosis.     

Morphology and electrophysiology of ventral mesencephalon nerve cell cultures

Electrophysiological changes occurring during the development of a kindled focus in the CA₁ region of the rat hippocampus were studied in vivo. The most conspicuous changes of the field potentials (EPs) recorded from the stratum radiatum to stimulation of the Schaffer collaterals were the following: (1) a progressive decrease of the slope of the decaying phase of the EPs which was significantly different (P < 0.02) from controls from sessions 8–12 onwards; (2) in the EPs recorded from the stratum pyramidale/oriens a population spike emerged from sessions 7–10 onwards; the ratio amplitude of the population spike/slope of the local EP increased progressively from session 8 onwards until a saturation level was reached; and (3) a progressive attenuation of paired-pulse depression; this decreased linearly with kindling session from session 1 up to session 11 (r = 0.97, P < 0.01) and thereafter stabilized. These results are interpreted as due to a progressive imbalance between excitatory and inhibitory processes resulting in a decrease of inhibitory control in CA₁ accompanied by a decrease in threshold of pyramidal neurons.     

Leadership in the nursing unit: relationships with nurses' well-being

The head nurse occupies an important position in the nursing unit Concerning leadership style, a distinction is traditionally made between consideration and initiating structure Sometimes a third style is distinguished as well, namely 'production-orientated' leadership In a study of 561 nurses from 16 general hospitals in The Netherlands, the influence of two leadership styles upon the reactions of nurses (job satisfaction, experienced meaningfulness, health complaints and absenteeism) to their work situations was examined, namely the styles of social (i e consideration) and instrumental leadership (a combination of the styles initiating structure and production-onentated) The separate effects of the two styles were studied, as well as the connection between combinations of leadership styles and reactions The results indicate that social leadership contributes positively to nurses' reactions to their job Instrumental leadership, on the other hand, leads to health complaints From the analyses of combinations of leadership styles it appears that nurses are most satisfied if the head nurse pays much attention to both dimensions of leadership For health complaints, a tendency in this directions is also found Finally, it becomes clear that nurses with a great need for autonomy prefer a different type of leadership from nurses with little need for autonomy     

Platelet adhesion to collagen types I through VIII under conditions of stasis and flow is mediated by GPIa/IIa (alpha 2 beta 1-integrin)

Platelet adhesion to fibrillar collagens (types I, II, III, and V) and nonfibrillar collagens (types IV, VI, VII, and VIII) was investigated in the presence of physiologic concentrations of divalent cations under conditions of stasis and flow. Under static conditions, platelet adhesion was observed to collagen types I through VII but not to type VIII. Under flow conditions, platelet adhesion to collagen types I, II, III, and IV was almost independent of shear rates above 300/s. Collagen type V was nonadhesive. Platelet adhesion to collagen type VI was shear rate-dependent and optimal at a rate of 300/s. Collagen types VII and VIII showed minor reactivity and supported platelet adhesion only between shear rates 100 to 1,000/s. Monoclonal antibody (MoAb) 176D7, directed against platelet membrane glycoprotein Ia (GPIa; very late antigen [VLA]-alpha 2 subunit), completely inhibited platelet adhesion to all collagens tested, under conditions of both stasis and flow. Platelet adhesion to collagen type III at shear rate 1,600/s was only inhibited for 85%. The concentration of antibody required for complete inhibition of platelet adhesion was dependent on the shear rate and the reactivity of the collagen. An MoAb directed against GPIIa (VLA-beta subunit) partially inhibited platelet adhesion to collagen. These results show that GPIa-IIa is a major and universal platelet receptor for eight unique types of collagen.