Staphylococcal enterotoxin A-induced fever is associated with increased circulating levels of cytokines in rabbits

Rabbits were injected intravenously with 10 to 100 ng of staphylococcal enterotoxin A (SEA) per kg, and colonic temperatures were monitored. The febrile responses were compared with circulating levels of interferon (IFN), tumor necrosis factor (TNF), interleukin-1 (IL-1), IL-2, and IL-6 just before the injection of SEA. Both colonic temperatures and circulating levels of IFN, TNF, and IL-2 started to rise at 1 to 2 h and reached their peak levels at 3 to 5 h after SEA injection. Both the fever and the increased circulating levels of IFN, TNF, and IL-2 produced by SEA were decreased by pretreatment with indomethacin (a cyclo-oxygenase inhibitor) (15 mg/kg, intraperitoneally), anisomycin (a protein synthesis inhibitor) (15 mg/kg, subcutaneously), or dexamethasone (an effective anti-inflammatory and immunosuppressive agent) (4 mg/kg, intravenously) in rabbits. Rabbits were injected intravenously with 30 ng of SEA per kg on four consecutive days, and colonic temperatures were monitored. Compared to rabbits that received the single injection of SEA, rabbits that received four consecutive injections of SEA showed a lesser increase in circulating levels of IFN, TNF, and IL-2 as well as colonic temperatures in response to an intravenous dose of SEA (30 ng/kg). The data suggest that the prevention of the febrile response elicited by SEA by indomethacin, anisomycin, or dexamethasone is due to prevention by these compounds of the increase in the circulating levels of IFN, TNF, and IL-2. The pyrogenic hyporesponsiveness to repeated injection of SEA is associated with decreased production of these circulating cytokines.     

Multi-domain architecture for policy management inumts ip multimedia subsystem

The Universal Mobile Telecommunications System (UMTS) offers IP-based multimedia applications and services with end-to-end Quality of Service (QoS) guarantee. The key component providing these services is the IP Multimedia Subsystem (IMS) that uses Service-Based Local Policy (SBLP) management for QoS control. To support end-to-end QoS, the UMTS IMS network should be scalable, reliable and flexible in policy deployment and enforcement, characteristics that are not found in single-domain policy architecture. A hybrid policy architecture is proposed, in which a hierarchical architecture is applied to the multi-domain environment in a single operator UMTS IMS network, while a peering architecture is employed in a multi-operator UMTS IMS network. The proposed multi-domain policy architecture potentially minimizes the session setup delay and policy exchange traffic while maximizing network scalability.     

Crystallization and stone formation inside the nephron

A model is presented visualizing the events leading to calcium-salt, crystal- and stone-formation inside the nephron. For each nephron segment, handling of urine components relevant to stone formation is considered and urine composition determined. This information was applied to nucleation experiments simulating passage of urine through a nephron. The model and in vitro experiments suggest that within normal transit times for the respective nephron segments, particles of a hydroxyapatite-like material first form near the bend in the Loop of Henle of juxtamedullary nephrons. From there on, calcium oxalate particles start to appear: first dihydrate, then monohydrate. In the collecting duct system, particle size increases primarily due to crystal agglomeration. Several conclusions with clinical and experimental relevance can be drawn. An increase in urinary volume does not decrease the chance of crystal formation in the Loop of Henle, but does decrease passage time through the collecting ducts, and thus, the time allowed for large particle formation. A calcium load does not increase the risk for nucleation up to the distal tubule, but does increase the risk of large particle formation in the collecting ducts. An oxalate load increases the chance for nucleation throughout the nephron. For experiments simulating crystallization processes occurring inside the nephron, diluted urines should be used. They should be diluted 16 to 50 times for testing nucleation, 2 to 30 times for testing crystal growth, and 2 to 20 times for testing crystal agglomeration. Undiluted urines may be used to mimic conditions in the pelvis and the bladder.     

Frameless stereotactic lesion contour-guided surgery using a computer-navigated microscope

BACKGROUND: The Zeiss MKM System is a recently developed computerized operating microscope for image-guided neurosurgery. The clinical advantages, reliability, accuracy, and limitations of this technique were investigated. METHODS: Since February 1995, 78 consecutive frameless stereotactic image-guided procedures were performed in 73 patients (30 males, 43 females; mean age, 46.9 years; range, 16-77 years) for tumor surgery (50/64.1%), cavernoma removal (16/20.5%), and functional procedures (12/15.4%). Skin markers (74 cases) or bone markers (4 cases) and a standard imaging protocol (2-mm cranial computed tomography (CCT) in 59 cases/1.5-mm magnetic resonance imaging (MRI) in 19 cases) were used. RESULTS: The main advantages were pre-operative skin incision, craniotomy and corticotomy planning, and determination of lesion boundaries. Useful registration and system reliability were noted in 97% (76/78) of the procedures. A significant improvement in registration accuracy was observed over the test period from a mean of 4.8 mm (SD = 3.36; Cases 1-25) to a mean of 2.2 mm (SD = 0.86; Cases 26-78). This resulted in an improvement in application accuracy from <5 mm in 71% (Cases 1-25) to <2 mm in 95% (Cases 26-78) of cases, and the accuracy led to successful localization of the lesion in every case. Accuracy was reliable at the beginning of every procedure, but degraded to values >5 mm by the end of the procedure in 29% (22/78) of cases. MRI cases achieved higher application accuracy values (2.1 mm mean) than CT cases (3.7 mm mean). CONCLUSIONS: The system offers a reliable alternative to frame-assisted stereotactic craniotomies in lesion targeting, but would need an intraoperative image update for resection guidance.     

Inhibition of hemopoiesis in vitro by neuroblastoma-derived gangliosides

Hemopoiesis is disturbed in bone marrow-involving cancers like leukemia and neuroblastoma. Shedding of gangliosides by tumor cells may contribute to this tumor-induced bone marrow suppression. We studied in vitro the inhibitory effects of murine neuroblastoma cells (Neuro-2a and C1300) and their gangliosides on hemopoiesis using normal murine hemopoietic progenitor colony-forming assays. Transwell cultured neuroblastoma cells showed a dose-dependent inhibition on hemopoiesis, indicating that a soluble factor was responsible for this effect. Furthermore, the supernatant of Neuro-2a cultured cells inhibited hemopoietic proliferation and differentiation. To determine whether the inhibitory effect was indeed due to shed gangliosides and not, for instance, caused by cytokines, the effect of DL-threo-1 -phenyl-2-decanoylamino-3-morpholino-1-propanol (DL-PDMP) on Neuro-2a cells was studied. DL-PDMP is a potent inhibitor of glucosylceramide synthase, resulting in inhibition of the synthesis and shedding of gangliosides. The initially observed inhibitory effect of supernatant of Neuro-2a cells was abrogated by culturing these cells for 3 days in the presence of 10 microM DL-PDMP. Moreover, gangliosides isolated from Neuro-2a cell membranes inhibited hemopoietic growth. To determine whether the described phenomena in vitro are a reflection of bone marrow suppression occurring in vivo, gangliosides isolated from plasma of neuroblastoma patients were tested for their effects on human hemopoietic progenitor colony-forming assays. These human neuroblastoma-derived gangliosides inhibited normal erythropoiesis (colony-forming unit-erythroid/burst-forming unit-erythroid) and myelopoiesis (colony-forming unit-granulocyte/macrophage) to a higher extent compared with gangliosides isolated from control plasma. Altogether these results suggest that gangliosides shed by neuroblastoma cells inhibit hemopoiesis and may contribute to the observed bone marrow depression in neuroblastoma patients.     

Analysis of assembly systems for interdeparture time variability and throughput

This paper studies the effect of the number of component stations (parallelism), work transfer, processing time distributions, buffers and buffer allocation schemes on throughput and interdeparture time variability of assembly systems. As an alternative to work transfer, variability transfer is introduced and its effectiveness is assessed. Previous research has indicated that the optimal throughput displays an anomaly at certain processing time distributions and, this phenomenon is now thoroughly analyzed and the underlying details are uncovered. This study also yields several new findings that convey important practical implications.     

Biphasic cellular repair and implications for multiple field radiotherapy treatments

Data describing the response of several normal tissues to fractionated irradiation, in terms of a biphasic repair of sub-lethal damage, have now been published. Typical results of such analyses have been taken and applied to a conventional radiotherapy protocol of 60 Gy in 30 daily fractions. The effect of using a four field treatment plan is shown to reduce the biological effect of the radiation schedule by increments dependent upon the time interval between each field in a treatment fraction, with a 10% reduction in the extrapolated dose response (ERD) resulting from a 5 min interfield interval. When applied to tissues having the same repair characteristics as pig skin this reduction in ERD is predicted to result in an approximately 25% reduction in the probability of acute morbidity from a protocol of 60 Gy in 30 fractions. These results imply that the basic LQ model, which is unable to correct for interfield intervals, overestimates the effect on normal tissues of radical clinical protocols, most of which use more than a single field. Increasing the interfield interval could be used to reduce the normal tissue side effects from radical radiotherapy when multiple fields are used.     

Muscle Rad expression and human metabolism: potential role of the novel Ras-related GTPase in energy expenditure and body composition

Ras associated with diabetes (Rad), a new ras-related GTPase, was recently identified by subtractive cloning as an mRNA in skeletal muscle that is overexpressed in NIDDM. To better understand its metabolic significance, we measured skeletal muscle Rad expression in well-characterized insulin sensitive (IS) and insulin resistant (IR) subjects with normal glucose tolerance and in untreated NIDDM patients. We found no differences in expression of Rad mRNA levels among IS, IR, and NIDDM groups using a ribonuclease protection assay (0.22 +/- 0.06, 0.13 +/- 0.01, and 0.16 +/- 0.02 relative units, respectively; NS) and no differences in Rad protein expression using a specific anti-peptide Rad antibody (1.05 +/- 0.18, 1.14 +/- 0.08, and 1.08 +/- 0.21 units/mg protein, respectively; NS). However, Rad protein levels were positively correlated with BMI (r = 0.43, P = 0.03) and percentage body fat (r = 0.55, P < 0.005), two independent measures of obesity, and negatively correlated with resting metabolic rate (r = 0.49, P = 0.01). In multiple regression analyses, percentage body fat and resting metabolic rate independently accounted for 30 and 10% of individual variability in muscle Rad protein expression. In conclusion, Rad expression in skeletal muscle is not altered as a function of insulin resistance or NIDDM in humans. However, these data, for the first time, implicate a role for Rad in regulating body composition and energy expenditure and provide a framework for studies designed to elucidate Rad's cellular functions.