Transforming growth factor-alpha expression of renal proximal tubules in Wistar rats treated with ferric and aluminum nitrilotriacetate

A high incidence of renal adenocarcinoma has been observed in rats treated with ferric nitrilotriacetate (Fe-NTA) but not in rats treated with aluminum nitrilotriacetate (Al-NTA). Transforming growth factor (TGF)-alpha is one of the several cytokines that is known to be expressed in human and rat renal adenocarcinomas. However, its role in neoplastic transformation is still questionable. Therefore, we investigated the effect of repeated Fe-NTA and Al-NTA administration on renal TGF-alpha expression. Male Wistar rats were given Fe-NTA (n = 16, 5-10 mg Fe/kg) and Al-NTA (n = 19, 1-2 mg Al/kg) i.p., three times a week for 3 or 12 weeks. Another group of rats (n = 4) was given Fe-NTA (5-10 mg Fe/kg) three times a week for 12 weeks and then left untreated for one year. Immunoreactivity for TGF-alpha was positive in the collecting ducts and on the apical surface of proximal tubules in the outer stripe of the outer medulla in all the animals including NTA-injected control animals. However, TGF-alpha immunoreactivity in the regenerative proximal tubular epithelium was observed only in the animals treated with Fe-NTA for 12 weeks. Northern blot analysis also showed expression of TGF-alpha mRNA only in animals treated with Fe-NTA for 12 weeks. The expression of TGF-alpha mRNA in the kidney was stronger than that in the liver or brain. TGF-alpha was also positive in renal cell carcinoma found in animals treated with Fe-NTA for 12 weeks and left untreated for one year. These results suggest that TGF-alpha expression may play an important role in renal carcinogenesis and that it may be a sensitive marker during the induction stage of renal cell carcinoma.     

Diversity of calcium signaling by metabotropic glutamate receptors

During prolonged application of glutamate (20 min), patterns of increase in intracellular Ca2+ concentration ([Ca2+]i) were studied in HEK-293 cells expressing metabotropic glutamate receptor, mGluR1alpha or mGluR5a. Stimulation of mGluR1alpha induced an increase in [Ca2+]i that consisted of an initial transient peak with a subsequent steady plateau or an oscillatory increase in [Ca2+]i. The transient phase was largely attributed to Ca2+ mobilization from the intracellular Ca2+ stores, but the sustained phase was solely due to Ca2+ influx through the mGluR1alpha receptor-operated Ca2+ channel. Prolonged stimulation of mGluR5a continuously induced [Ca2+]i oscillations through mobilization of Ca2+ from the intracellular Ca2+ stores. Studies on mutant receptors of mGluR1alpha and mGluR5a revealed that the coupling mechanism in the sustained phase of Ca2+ response is determined by oscillatory/non-oscillatory patterns of the initial Ca2+ response but not by the receptor identity. In mGluR1alpha-expressing cells, activation of protein kinase C selectively desensitized the pathway for intracellular Ca2+ mobilization, but the mGluR1alpha-operated Ca2+ channel remained active. In mGluR5a-expressing cells, phosphorylation of mGluR5a by protein kinase C, which accounts for the mechanism of mGluR5a-controlled [Ca2+]i oscillations, might prevent desensitization and result in constant oscillatory mobilization of Ca2+ from intracellular Ca2+ stores. Our results provide a novel concept in which oscillatory/non-oscillatory mobilizations of Ca2+ induce different coupling mechanisms during prolonged stimulation of mGluRs.     

Directional stability radius: a stability analysis tool for uncertain polynomial systems

Coefficients of characteristic polynomials for stable parametrically uncertain systems are allowed to perturb to some extent for stability. Stability radius is a useful tool to assess the allowance of the stability for the systems. To enhance its usefulness, we modify stability radius so that it takes into account of given restricted perturbations, which we call directional stability radius. For an application, we show shifted-Hurwitz stability conditions and a stability analysis method for interval polynomial systems using the directional stability radii.     

New diagnostic finding to assess para-Hisian pacing observed in a patient with a permanent form of junctional reciprocating tachycardia

Para-Hisian pacing, a useful method to differentiate conduction over an accessory pathway from conduction over the AV node, is assessed essentially by comparing the timing of local atrial electrograms between His-bundle captured beats and His-bundle noncaptured beats. We describe the case of a patient with a permanent form of junctional reciprocating tachycardia, in whom an atrial double potential was recorded only during the tachycardia at the right posterior septum. During para-Hisian pacing, a morphologic change in the atrial electrogram at the posterior septum was also identified, as well as a change in the retrograde atrial sequence. Since the morphologic change of atrial electrograms during para-Hisian pacing cannot be demonstrated in a patient without an accessory pathway, this new finding could be considered a new additional diagnostic criterion suggesting the presence of an accessory pathway.     

Purification of a novel muscle cell growth factor S-myotrophin from porcine skeletal muscle

A comparison of muscle weight between denerved and control rabbit hind legs revealed that a water-soluble 12 kDa substance was reduced in atrophied muscles after denervation. We hypothesised that a water-soluble growth factor exists which mediates a signal from motor nerves to muscles. To isolate this factor we modified the purification procedures of Sen et al. [S. Sen, G. Kundu, N. Mekhail, J. Castel, K. Misono, B. Healy, Myotrophin: purification of a novel peptide from spontaneously hypertensive rat heart that influences myocardial growth, J. Biol. Chem. 265 (1990) 16635-16643.], who originally purified a water-soluble growth factor from cardiac muscles. Four additional purification steps were added to the method. Using this technique, a novel muscle cell growth factor, named s-myotrophin, was purified from porcine skeletal muscle (M. longissimus thoracis). Purified s-myotrophin appeared as a single band (12 kDa) on SDS-PAGE and had a strong growth promoting activity (increase of protein synthesis) of cultured primary skeletal muscle cells. Almost no loss of growth promoting activity was observed after trypsin and chymotrypsin digestion. No fragmentation of s-myotrophin was observed after exposure to lysylendopeptidase, thermolysin, trypsin and chymotrypsin. Crude preparation of this molecule could be detected by periodic acid/Schiff (PAS) staining. Deglycosylation of s-myotrophin produced a smaller molecule having an approximately 7 kDa mass. These data indicate a novel 12 kDa protein has been isolated which has growth promoting properties on skeletal muscle cells.     

An automated method for the simultaneous determination of pravastatin and its main metabolite in human plasma by high-performance liquid chromatography/atmospheric pressure chemical ionization mass spectrometry

An unexpected t(1;19) translocation is described in a fetus. Inherited from the mother, this translocation was found during the course of a normal prenatal diagnosis made for maternal age. The very short length of chromosomal translocated segments and their labelling pattern made high-resolution cytogenetic methods and fluorescence in situ hybridization techniques necessary for the correct identification of this karyotype rearrangement, both in mother and fetus. Different modes of meiotic segregation, leading to potential erroneous prenatal diagnoses, are discussed.     

A 75-ch SQUID Biomagnetometer System for Human Cervical Spinal Cord Evoked Field

A 75-ch SQUID biomagnetometer system for the measurement of the cervical spinal cord evoked magnetic field (SCEF) was developed for the purpose of the noninvasive functional diagnosis of the spinal cord. The sensor array has 25 SQUID vector sensors arranged along the cylindrical surface to fit to the shape of the subject's neck. The magnetic fields, not only in the direction radial to the subject's body surface but also in the tangential direction, are observed in the area of 80 mm times 90 mm at one time. The dewar has a unique shape with a cylindrical main body and a protrusion from its side surface. The sensor array is installed in the protruded part. This design is optimized to detect magnetic signals at the back of the neck of the subject sitting in a reclining position. We applied the developed SQUID system to the cervical SCEF measurement of normal subjects who were given electric pulse stimulation to their median nerves at the wrists. The evoked magnetic signals were successfully detected at the cervixes of all subjects. A characteristic pattern of transition of the SCEF distribution was observed as a reproducible result and the signal components propagating along the spinal cord were found in the time varying SCEF distribution. We expect that the investigation of the propagating signal components would help to establish a noninvasive functional diagnosis of the spinal cord.     

Right atrial pressure and forearm blood flow during prolonged exercise in a hot environment

Right atrial pressure (RAP) at rest is known to be reduced by an increase in skin blood flow (SkBF) in a hot environment. However, there is no clear evidence that this is so during exercise. To clarify the effect of the increase in SkBF on RAP during exercise, we measured forearm blood flow (FBF) (as an index of SkBF) and RAP continuously using a Swan-Ganz catheter in five male volunteers exercising on a cycle ergometer at 60% of peak aerobic power for 50 min in a hot environment (30 degrees C, relative humidity 20%). Cardiac output increased from 5.5 +/- 0.2 l/min at rest to 17.9 +/- 1.2 l/min (mean +/- SE, P < 0.01) in the first 10 min of exercise and then remained steady until the end of exercise. FBF did not change significantly during the first 5 min, but then increased from 2.7 +/- 0.5 ml/100 ml per min at rest to 10.8 +/- 1.7 ml/100 ml per min (P < 0.001) by 25 min as pulmonary arterial blood temperature (Tb) rose from 37.0 +/- 0.1 degrees C to 38.1 +/- 0.1 degrees C (P < 0.001). FBF then reached a plateau, despite a continuing increase in Tb. RAP increased significantly from 4.3 +/- 0.8 to 7.6 +/- 1.2 mm Hg (P < 0.001) during the first 5 min of exercise and then gradually declined to 6.1 +/- 1.0 mm Hg by 25 min (P < 0.001 vs. 5 min) and further to 5.7 +/- 1.0 mm Hg by 50 min, a value not significantly higher than at rest.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sucrose permeability as a means of detecting diseases of the upper digestive tract

This study evaluated the in vivo deployment and the healing characteristics of a self-expanding endoluminal graft [Wallgraft (WG) Endoprosthesis] in a canine (n = 22) aorta. The WG consisted of a 10 or 12 mm x 7.5 cm Wallstents (Schneider, Inc.) covered with polyethylene terephthalate (Dacron) graft material. Twenty-two WGs were deployed using fluoroscopic guidance. Devices were oversized approximately 10 per cent. Intravascular ultrasound (IVUS) was repeated, and balloon expansion along the length of the WG was performed to assure maximum expansion. WGs were evaluated with IVUS, angiography, and histology at 14 (n = 4), 30 (n = 4), 90 (n = 4), 180 (n = 5), and 365 (n = 5) days. Predeployment aortic diameters were 9.9 +/- 1 mm. Mid-WG diameters were 9.0 +/- 0.8 mm before balloon dilation and 9.2 +/- 0.5 mm after dilation with 8- (n = 1), 10- (n = 16), and 12- (n = 5) mm balloons. Twenty-two of 23 devices were deployed accurately with good apposition and aortic flow after deployment. On explant, all of the covered grafts were widely patent on IVUS and angiogram. Four explants demonstrated gaps (due to WG taper) between the proximal or distal ends of the graft on IVUS. The device length (9.1 + 0.5 cm) did not change significantly after deployment. Histologically at 6 months and 1 year the lumens were cell-lined. Scanning electron micrography demonstrated endothelial-like cells. This study demonstrates the ability of a WG to be accurately deployed and maintain excellent patency. Balloon expansion after deployment did not significantly increase the diameter. Clinical evaluation of this device is in progress.