The antiproteinuric action of angiotensin-converting enzyme inhibitors in chronic glomerulonephritis and diabetic nephropathy

Antiproteinuria effects of angiotensin-converting enzyme (ACE) inhibitors was studied in 23 patients with chronic nephritis (CN) and 32 patients with diabetic nephropathy (DN). CN patients received Capoten, DN patients were given enalapril. The drugs were also examined for the action on systemic arterial pressure, renal function and intrarenal hemodynamics. Significantly decreased urinary excretion of protein occurred in DN patients on the treatment month 1, in CN subjects on month 3. In both groups ACE inhibitors produced marked hypotensive effect, did not affect renal function, noticeably improved intraglomerular hemodynamics. Hypotensive and antiproteinuria activity of the drugs were unrelated. The mechanism of antiproteinuria action of ACE inhibitors works via normalization of intrarenal hemodynamics. Systemic arterial hypertension seems to be an additional factor aggravating disturbances of intrarenal circulation and provoking proteinuria.     

Immunization of BALB/c mice with Helicobacter urease B induces a T helper 2 response absent in Helicobacter infection

BACKGROUND & AIMS: Infection with Helicobacter induces a T helper type 1 response in mice and humans. Mice can be cured or protected from infection with Helicobacter by mucosal immunization with recombinant H. pylori urease B subunit (rUreB). This study characterizes the immune response of infected mice immunized with rUreB. METHODS: BALB/c mice were infected with H. felis. Two weeks later, they were orally immunized four times with rUreB and cholera toxin (CT) at weekly intervals. Controls were only infected or sham-immunized with CT. Animals were killed at various times after immunization. Splenic CD4(+) cells were obtained and cultured in vitro with rUreB to evaluate antigen-specific proliferation and induction of interferon gamma and interleukin 4 secretion. RESULTS: All rUreB-immunized mice (n = 8) were cured from infection 3 weeks after the fourth immunization. Immunization induced a proliferative response of splenic CD4(+) cells, a progressive decrease in interferon gamma secretion, and a concomitant increase in interleukin 4 secretion after each immunization. A simultaneous increase in rUreB specific serum immunoglobulin G1 levels was observed in infected/immunized mice. CONCLUSIONS: In BALB/c mice, therapeutic mucosal immunization with rUreB induces progressively a Th2 CD4(+) T cell response resulting in the elimination of the pathogen.     

A novel phosphorylation-dependent RNase activity of GAP-SH3 binding protein: a potential link between signal transduction and RNA stability

A potential p120 GTPase-activating protein (RasGAP) effector, G3BP (RasGAP Src homology 3 [SH3] binding protein), was previously identified based on its ability to bind the SH3 domain of RasGAP. Here we show that G3BP colocalizes and physically interacts with RasGAP at the plasma membrane of serum-stimulated but not quiescent Chinese hamster lung fibroblasts. In quiescent cells, G3BP was hyperphosphorylated on serine residues, and this modification was essential for its activity. Indeed, G3BP harbors a phosphorylation-dependent RNase activity which specifically cleaves the 3'-untranslated region of human c-myc mRNA. The endoribonuclease activity of G3BP can initiate mRNA degradation and therefore represents a link between a RasGAP-mediated signaling pathway and RNA turnover.     

Aging and the scope of visual attention

OBJECTIVE: To discover whether some cognitive deficits associated with aging could be related to a restricted scope of visual attention. DESIGN: Cross-sectional study, with subjects in each age group receiving the same four conditions. Subjects: 24 elderly (mean age 65.2 years, 12 men and 12 women) and 24 young (mean age 21.8 years, 12 men and 12 women) matched for handedness, gender, and education level. METHODS: Subjects viewed a display that contained four light-gray squares arranged as if on the tips of a plus sign, then black X marks appeared and the subjects indicated whether one or two Xs appeared in the squares as quickly and accurately as possible. The time to respond and accuracy level were recorded. Two types of displays were used; one with squares spread out over a large area and one with squares condensed into a small area. In two thirds of the trials the size remained the same (with half being large, and half small), and in one third it changed (with half of these trials changing from large-to-small and half from small-to-large). RESULTS: In the trials that had a consistent display size, the elderly subjects performed the task better with the smaller display, whereas the young subjects performed equally well with both sized displays. In addition, the elderly found it easier to shift from large to small scope than to maintain attention at the large scope; in contrast, the younger subjects found it easiest to maintain attention on a static display size. CONCLUSIONS: The elderly prefer to focus attention on a smaller region of space than do younger people.     

MRI of hyperpolarized 3He gas in human paranasal sinuses

Relapsed or refractory adult acute lymphoblastic leukemia (ALL) carries a grave prognosis. The most promising strategy for curing these patients is through re-induction chemotherapy followed by successful allogeneic transplant. We studied a new high-dose induction regimen in order to improve the outcome for these patients. Eighteen adult patients with relapsed/refractory ALL were treated on a phase I study of high-dose cytarabine combined with a single escalating dose of idarubicin. Five patients had primary refractory disease and 13 were treated in refractory relapse. Nine patients (50%) had Ph+ ALL. The induction regimen was cytarabine 3 g/m2/day intravenously days 1-5 and idarubicin as a single intravenous dose on day 3. G-CSF 5 microg/kg subcutaneously every 12 h was started on day 7. The initial idarubicin dose was 20 mg/m2 with dose escalations of 10 mg m2. Cohorts of three patients were treated at each idarubicin dose level. Unacceptable toxicity was encountered at 50 mg/m2 with one death from infection and one death from cardiotoxicity in a patient with significant prior anthracycline exposure. There were no instances of grade 4 non-hematologic toxicity encountered at idarubicin doses of 20 mg/m2, 30 mg/m2, or 40 mg/m2. The data suggest a dose-response relationship for increasing doses of idarubicin with 0/3 complete responses (CR) at 20 mg/m2, 1/3 CR at 30 mg/m2, and 7/12 (58%) CR at idarubicin doses > or = 40 mg/m2. We conclude that concomitant administration of cytarabine 3 g/m2/day x 5 and high-dose idarubicin at 40 mg/m2 as a single dose on day 3 can be administered safely to patients with refractory and relapsed ALL.     

New developments in the role of cytokines and chemokines in inflammatory myopathies

Humans are readily able to distinguish expected and unexpected sensory events. Whether a single mechanism underlies this ability is unknown. The most common type of expected sensory events are those generated as a consequence of self-generated actions. Using H2 15O PET, we studied brain responses to such predictable sensory events (tones) and to similar unpredictable events and especially how the processing of predictable sensory events is modified by the context of a causative self-generated action. Increases in activity when the tones were unpredictable were seen in the inferior and superior temporal lobe bilaterally, the right parahippocampal gyrus and right parietal cortex. Self-generated actions produced activity in a number of motor and premotor areas, including dorsolateral prefrontal cortex. We observed an interaction between the predictability of stimuli and self-generated actions in several areas, including the medial posterior cingulate cortex, left insula, dorsomedial thalamus, superior colliculus and right inferior temporal cortex. This modulation of activity associated with stimulus predictability in the context of self-generated actions implies that these areas may be involved in self-monitoring processes. Detection of expected stimuli and the detection of the sensory consequences of self-generated actions appear to be functionally distinct processes, and are carried out in different cortical areas. These observations support theoretical approaches to cognition that postulate the existence of a self-monitoring system.     

Diverse molecular provocation of programmed cell death

The experimental study and manipulation of programmed cell death has been greatly assisted by the identification of genetic and pharmacological tools that can either induce or block cell lethality. This review discusses new insights into the molecular sensing of perturbations induced by such tools, as well as the possible consequences of this detection in determining cell survival.     

Early confirmation of stress fractures in joggers

Four joggers had early confirmation of clinically suspected stress fractures by radionuclide bone scans. The radioactive bone scan was abnormal as early as six weeks prior to the appearance of conventional roentgenographic changes. The stress fractures involved the bones of the lower extremities and included the femur, tibia, and calcaneus. Radioactive bone scanning also correctly identified stress fractures with bilateral involvement and referred pain. In joggers, when a stress fracture is clinically suspected and the conventional radiographs are negative, a radioactive bone scan is indicated for early confirmation and institution of appropriate treatment.