Tumor colony formation by Friend virus-infected cells in immunosuppressed mice.

We have investigated the role of host immunological factors in the formation of "tumor colonies" in the spleens of unirradiated C57BL/6 X C3Hf/Bi FI mice 9 days after i.v. injection of spleen cells from Friend virus (FV)-infected C3Hf/Bi donors. Pretreatment of hosts with antilymphocyte serum (ATS) increased the number of tumor colonies. Pretreatment with formalinized FV-infected cells had the opposite effect, and ATS diminished the inhibitory effect of preimmunization. Cell suspensions from 11 individual FV-infected donors were examined. The suspensions differed with respect to their behavior on transplantation into untreated and ATS-pretreated F1 hybrid hosts. With several suspensions, the number of tumor colonies produced was approximately proportional to the number of cells injected; in all of these, ATS increased the slope of the line relating colony number to cell number. With most of the suspensions, tumor colony-forming efficiencies in untreated hosts strikingly decreased with increasing number of cells injected; ATS induced an increase in the number of tumor colonies and rendered the colony-forming response more nearly proportional to cell number. With two suspensions, few or no colonies developed; pretreatment with ATS had no significant effect. When the 11 cell suspensions were considered together, a proportional relation was found between the magnitude of the ATS effect (i.e., colony number in the presence of ATS minus colony number in the absence of ATS) and the colony-forming efficiency in ATS-treated mice. The ATS effect on the average was equivalent to a 2-fold increase in tumor colony-forming efficiency. We interpret these findings to indicate that two factors interact to determine the number of tumor colonies produced by spleen cells from FV-infected C3H donors in untreated F1 hybrid hosts. One is a property of the FV-infected cell population and includes its frequency of tumor colony-forming units; this factor varies widely among different cell suspensions. The other is a property of the tumor colony-forming units-host interrelationship and includes the vulnerability of tumor colony-forming units to the host immune response elicited by the injected cells; this factor appears to be constant with different cell suspensions. The present results show that the two factors can be dissociated in immunosuppressed hosts.     

Changes in expression of sodium cotransporters and aquaporin-2 during ischemia-reperfusion injury in rabbit kidney

Ischemic renal injury is associated with defects in transport functions of the proximal tubules and urinary concentration ability. To determine whether alterations in expression of various transporter genes contribute to an impairment in renal functions, the expression of various solute transport genes was analyzed in renal cortex and medulla of rabbits with ischemic acute renal failure. Rabbits were subjected to 60 min of renal pedicle clamping followed by 24, 48, or 72 h of reperfusion. Urine volume and glomerular filtration rate were markedly decreased, which were accompanied by an increase in serum creatinine level and fraction Na+ excretion. Glucosuria and phosphaturia were evident during reperfusion periods. These alterations in renal functions were persisted to 72 h after reperfusion. The Na+-dependent uptakes of glucose and phosphate by brush border membrane vesicles were inhibited by 24 h of reperfusion. mRNA levels for Na+-glucose, Na+-phosphate, and Na+-succinate cotransporter analyzed by RT-PCR were not changed by 60 min of ischemia alone, but were significantly reduced by 24 h of reperfusion. mRNA levels for apical Na+-K+-2Cl- cotransporter, NaCl cotransporter, and turea transporter in the medulla were not changed during reperfusion. Protein levels for AQP2 in the medulla, but not AQP1 in the cortex, analyzed by Western blot were significantly reduced at 24 h after reperfusion. These results suggest that reductions in expression of Na+-cotransporter genes in the proximal tubules may be important factors in the impairment in Na+-dependent reabsorption of solutes and that decrease in AQP2 protein may be involved in defect in urinary concentration ability in rabbits with ischemic acute renal failure.     

Mechanism of regulation of Na+ transport by angiotensin II in primary renal cells

BACKGROUND: Angiotensin II (Ang II) has a dose-dependent, biphasic effect on the activity of the Na+/H+ antiport system in the renal proximal tubule (RPT). The aim of the present study was to further delineate the signaling pathways involved in Ang II action. METHODS: To examine Ang II signaling, 22Na+ uptake studies were conducted with a primary rabbit RPT cell culture system. The activation of phospholipase A2 (PLA2) was assessed by measuring the release of [3H]-arachidonic acid (AA), and changes in intracellular calcium levels were determined by means of confocal microscopy. RESULTS: Low dosages of Ang II (<10-10 mol/L) stimulated Na+ uptake, whereas high dosages of Ang II (>10-10 mol/L) inhibited Na+ uptake. Ang II (>10-10 mol/L) also caused an increase in AA release associated with an increase in intracellular calcium. Not only did exogenous AA inhibit Na+ uptake, but two PLA2 inhibitors (mepacrine and AACOCF3) blocked the Ang II-mediated inhibition of Na+ uptake. However, the cytochrome P450-dependent epoxygenase inhibitor econazole also blocked the Ang II-induced inhibition of Na+ uptake. Inhibition of Na+ uptake was obtained by the metabolic product of the epoxygenase 5,6-EET. In turn, the inhibitory effect of 5,6-EET was blocked by indomethacin. CONCLUSIONS: The results indicate the involvement of a calcium-dependent PLA2 in mediating the inhibitory effect of Ang II on Na+ uptake. The AA, which is released following PLA2 activation, acts indirectly, through its own metabolism, via a cytochrome P450 epoxygenase pathway and ultimately cyclooxygenase itself.     

Branch retinal artery occlusion secondary to a Hollenhorst plaque

Retinal arterial circulation obstruction has serious implications. It may result in acute visual loss, but more significantly, it implies that the patient's systemic health needs further review and investigations in order to prevent severe and life-threatening consequences such as myocardial infarction and cerebrovascular accidents. We report a case of a patient with branch retinal artery occlusion with the presence of a Hollenhorst plaque.     

Dynamic contrast-enhanced MR imaging of bacterial abscess and VX2 carcinoma in rabbits: comparison of gadopentetate dimeglumine and a macromolecular contrast agent

OBJECTIVE: The objective of this study was to compare enhancement patterns of a blood-pool contrast agent, Gadomer-17, with those of gadopentetate dimeglumine in bacterial abscesses and VX2 carcinoma in rabbits. MATERIALS AND METHODS: Fourteen rabbits with experimentally induced bacterial abscesses and VX2 carcinoma in both thighs underwent dynamic contrast-enhanced MR imaging with Gadomer-17 and gadopentetate dimeglumine at a 24-hr interval. The enhancement ratios (postcontrast to precontrast signal intensities) of lesions in the same animal were assessed and correlated with microvessel density. RESULTS: For Gadomer-17, the enhancement ratio of the abscesses (1.66 +/- 0.39) peaked 15 min after the injection, while that of the carcinoma (2.05 +/- 0.16) peaked at 10 min. The enhancement ratios of the carcinoma were consistently higher than those of the abscesses up to 30 min. For gadopentetate dimeglumine, peak enhancement ratio of the abscesses (2.30 +/- 0.75) was seen 5 min after the injection, while that of the carcinoma (2.32 +/- 0.51) was seen at 3 min. The enhancement ratios of the carcinomas were significantly higher at 1 min, but significantly lower at 20-30 min, compared with those of the abscesses, as a result of rapid decrease of enhancement ratios in the carcinomas. The microvessel density was 9.8 +/- 5.2 vessels per field of view for the abscesses and 36.3 +/- 9.5 vessels per field of view for the carcinoma (p < 0.001). CONCLUSION: Delayed peak enhancement and slow decay were found in both bacterial abscess and VX2 carcinoma with Gadomer-17, whereas early peak enhancement and rapid decay were found especially in VX2 carcinoma with gadopentetate dimeglumine. Enhancement ratios on MR imaging with a blood-pool contrast agent correlated well with the microvessel density in bacterial abscess and VX2 carcinoma.