Ca2+ signaling induced by sphingosylphosphorylcholine and sphingosine 1-phosphate via distinct mechanisms in rat glomerular mesangial cells

BACKGROUND: To elucidate the molecular mechanism underlying sphingosine 1-phosphate (S1P) and sphingosylphosphorylcholine (SPC) mediated signaling, we compared their effects with those of adenosine triphosphate (ATP) and angiotensin II (Ang II) on the cytosolic free Ca2+ concentration ([Ca2+]i), inositol 1,4, 5-trisphosphate (IP3) generation and arachidonic acid release in rat glomerular mesangial cells. METHODS: The fluorescent Ca2+ indicator, Fura-2, was used to measure the [Ca2+]i changes in cultured rat glomerular mesangial cells either in suspension or attached to the coverslips. RESULTS: SPC 5 microM, S1P 5 microM, ATP 100 microM and Ang II 90 nM all induced increases in the [Ca2+]i, and the effect showed marked homologous desensitization, while heterologous desensitization was less. After the initial exposure of the cells to SPC, the increase in [Ca2+]i induced by subsequent addition of ATP or Ang II was only reduced by about 14.3% and 4.8%, respectively. After the initial exposure to S1P, a greater reduction was seen (42. 1% and 47.7%, respectively). Both arachidonic acid release and IP3 generation were activated by all four agonists with an identical rank order of effectiveness of SPC > S1P > ATP = Ang II; both were pertussis toxin-sensitive and cholera toxin-resistant. The arachidonic acid release induced by all four agonists showed identical susceptibility to removal of extracellular Ca2+, whereas IP3 generation displayed differential extracellular Ca2+ dependence. Only SPC-induced IP3 generation was highly sensitive to extracellular Ca2+ level, and this Ca2+ dependence was abolished after pretreatment of cells with arachidonyl trifluoromethyl ketone (AACOCF3), a phospholipase A2 inhibitor. Furthermore, the Mn2+ influx was markedly greater in SPC-stimulated cells than in either control or other agonist-stimulated cells, and was decreased by prior exposure of cells to AACOCF3. After phospholipase A2 was inhibited or in the absence of extracellular Ca2+, SPC displayed identical effectiveness as S1P on desensitizing the action of ATP or Ang II on the increase in [Ca2+]i. Conclusions. Our results indicate that all four agents primarily activate phospholipase C through their receptor occupancies, but that SPC alone also induces further significant Mn2+ influx and IP3 generation attributable to its primary stimulatory effect on arachidonic acid release. Thus, the heterologous desensitization to ATP or Ang II induced by SPC was less profound than that induced by S1P, since SPC induced a Ca2+ influx.     

The Canadian National Breast Screening Study: a Canadian critique

The Canadian National Breast Screening Study (CNBSS) was the first study designed to determine the efficacy of screening for breast carcinoma in women 40-49 years old. Women were randomized to undergo either annual mammography and physical examination or usual care after an initial physical examination [1]. Women 50-59 years old were randomized to undergo either annual mammography and physical examination or annual physical examination only [2]. This study, published by epidemiologists on the efficacy of a radiologic examination, therefore, invites evaluation by radiologists.     

Strength and functional recovery following repair of flexor digitorum superficialis in zone 2

Since 1989 we have performed 21 endoscopic hernia repairs in 19 female patients. One recurrent hernia occurred 3 months after laparoscopic preperitoneal patch repair using a single layer of resorbable mesh. Hernioscopy was developed as the transcutaneous endoscopic CO2-gas dissection and subsequent inspection of the preperitoneal hernial sac. Hernioscopic stuffing of the preperitoneal hernial sac using resorbable patch material was performed in seven direct inguinal hernias and in one femoral hernia. Postoperative pain was minimal and convalescence was short. No recurrent hernia occurred during a 1-9-month follow-up.     

Long-term effects of nutrition with fat-reduced foods on energy consumption and body weight

In a 3-month intervention study 70 women (40 < age < 60; 24 < BMI < 29), randomized into two groups, were supplied ad libitum and free of charge with 1) customary fat-reduced foods (D group) or 2) products with normal fat content (K group). After 6 months without any contact to the volunteers food intake and body weight were controlled. Results: During the intervention period fat intake (by 22 g/d) and total energy intake (by 266 kcal/d) of the volunteers in the D group were significantly lower than in the K group. Fat reduction was not accompanied by a compensative increase in the intake of other nutrients. The weight loss was significant in the D group (1.5 kg) and not significant in the K group (0.7 kg). Between the two groups the difference in weight reduction was not significant. In the follow-up a lowered fat and energy intake had been voluntarily retained in the D group and adopted by most of the individuals in the K group. Conclusion: The consumption of low-fat products lowers the energy and fat intake and may be useful for a long-term weight control and health support.     

Intra-assay performance characteristics of five assays for quantification of human immunodeficiency virus type 1 RNA in plasma

Three kits (Roche AMPLICOR human immunodeficiency virus type 1 [HIV-1] Monitor, Chiron enhanced-sensitivity bDNA, and Organon Teknika NASBA HIV-1 QT) and two in-house assays (from National Genetics Institute and Baylor College of Medicine) were compared with a blinded panel. The results were evaluated as to intra-assay sensitivity, precision, and ability to detect differences in a dilution series.     

Unresolved issues in the pathogenesis of Bartter's syndrome and its variants

Recent physiologic information concerning the renal response to potassium deprivation has been used to reevaluate potassium wasting in Bartter's syndrome. Experimental patient data support the notion that failure of potassium conservation is due to an imbalance between tubular secretory and reabsorptive processes. Suggestions are presented for the further evaluation of potassium reabsorptive pathways in the distal tubule.     

Management of a short femur discovered via ultrasound in utero. Prenatal diagnosis of Stuve-Wiedemann syndrome

BACKGROUND: Malignant mesothelioma reportedly shows different epidemiology and pathology in females, and a proportion are believed to arise spontaneously. METHODS: One hundred and seventy seven cases of malignant mesothelioma in females were reviewed, examined by histochemistry and immunohistochemistry, assessed for asbestosis and lung fibre burden by transmission electron microscopy with energy dispersive x ray analysis, and compared with 31 female controls. RESULTS: Two of one hundred and three cases tested for carcinoembryonic antigen were positive and were excluded from further analysis. Tumour cases showed increased amphibole burdens; in those in whom exposure information was known, 74 (80%) of 93 patients had a history of exposure to asbestos. Seventy two (47%) of 152 patients had lung fibrosis. Tumour site and histological type were little different from those reported in adult males. Mixed type histological pattern, lung fibrosis, and peritoneal site were associated with heavier lung asbestos burdens, but not exclusively. Thirty five (30%) of 117 patients had amphibole burdens of less than 2 x 10(6) fibres/g; the sites affected and the histological pattern of tumours in this group were similar to those in cases with amphibole fibre counts of > or = 2 x 10(6)/g lung. A higher lung amphibole burden than the mean burden in control females was found in 115 (98%) of 117 patients tested. CONCLUSIONS: The pathology of malignant mesothelioma appears to be similar in women and in men, and in cases associated and unassociated with asbestos.     

Bronchoscopy versus empirical therapy in HIV-infected patients with presumptive Pneumocystis carinii pneumonia. A decision analysis

The outcomes of alternative strategies for the management of pulmonary complications in patients infected with the human immunodeficiency virus (HIV) and with suspected Pneumocystis carinii pneumonia were compared using a decision analysis model. A decision tree was constructed using baseline probabilities derived from published data and expert opinion. The case scenario analyzed was that of a patient not currently receiving anti-Pneumocystis prophylaxis who presents with moderate pulmonary symptoms and fulfills the Centers for Disease Control (CDC) criteria for presumptive P. carinii pneumonia. Two strategies were compared: (1) early bronchoscopy with appropriate therapy based on the results, and (2) empiric treatment for P. carinii (trimethoprim/sulfamethoxazole or pentamidine, and steroids) with delayed bronchoscopy in those not responding to 5 days of empiric therapy. The expected 1-month survival rate (with and without quality of life adjustment) was found to be essentially the same for the two strategies using the baseline probabilities, and the decision remained a toss-up within the clinically relevant range of published probabilities for P. carinii pneumonia in patients fulfilling the CDC criteria. Because early bronchoscopy does not offer any additional survival benefits and is associated with greater costs and disutility, empiric therapy would appear to be the superior management strategy in this scenario.