Gains of chromosomes 7, 17, 12, 16, and 20 and loss of Y occur early in the evolution of papillary renal cell neoplasia: a fluorescent in situ hybridization study.

It has been suggested that gains of chromosomes 7 and 17 and loss of Y occur in renal papillary adenoma and that progression to papillary renal cell carcinoma is marked by gains of additional chromosomes, most frequently 12, 16, and 20. Previous studies have included very few lesions of <5 mm in diameter, a requirement of the present definition of papillary adenoma. Ten papillary adenomas (ranging from 1 to 5 mm in diameter) from autopsy material and 10 surgically resected papillary renal cell carcinomas were studied with fluorescence in situ hybridization in paraffin sections using centromeric probes for chromosomes 7, 12, 16, 17, 20, and Y diluted 1:100 with tDenHyb1 buffer. The signals in 50 to 150 nuclei were counted in each tumor. Controls for all the probes were normal renal tissues from the same patients. Three or more signals per nucleus were frequently observed in papillary adenomas: chromosome 7 (range, 10 to 50%; > or = 30% in 9 of 10), 17 (range, 10 to 47%; > or = 30% in 7), 16 (range, 1 to 63%; > or = 10% in 5), 12 (range, 0 to 32%; > or =10% in 4), and 20 (range, 5 to 49%; > or = 10% in 5). Loss of the Y chromosome was observed in 80 to 90% of nuclei in 9 adenomas from males. Three or more signals were frequent in papillary renal cell carcinomas: chromosome 7 (range, 32 to 63%; > or =30% in 10 of 10), 17 (range, 28 to 61%; > or = 30% in 7), 16 (range, 0 to 45%; > or = 10% in 6), 12 (range, 1 to 37, > or = 10% in 5), 20 (range, 2 to 44%; > or = 10% in 4). No signal for Y was observed in 12 to 88% (> or = 81% in 6) of nuclei in 7 carcinomas from males. Statistical analysis showed no difference between adenomas and carcinomas. Gains of chromosomes 7, 17, 16, 12, and 20 and loss of the Y chromosome occur early in the evolution of papillary renal cell neoplasia in tumors that are only a few millimeters in diameter. Progressive gains of these chromosomes do not appear to correlate with the transition from adenoma to carcinoma.     

Changes in total sodium intake do not lead to proportionate changes in total sodium removal in CAPD patients.

BACKGROUND: Dietary salt and fluid restriction is important in controlling fluid balance in patients on continuous ambulatory peritoneal dialysis (CAPD). However, it is often difficult to monitor patients' dietary total sodium intake (TSI). Usually, total sodium removal (TSR), the sum of urinary sodium removal (USR) and dialysate sodium removal (DSR), is suggested to represent TSI. In the present study, we investigated the reliability of using TSR as a surrogate to TSI in CAPD patients. METHODS: 40 clinically stable CAPD patients were closely followed for 3 months. Their TSI, USR, DSR, and fluid status were measured twice: at baseline and at the end of this study respectively. Fluid status was evaluated by bioimpedance analysis. Patients with increased sodium intake (group ISI) or decreased sodium intake (group DSI) (both >0.5 g/day or >21.74 mmol/day elemental sodium) were included in this study. RESULTS: There were 15 patients in group ISI and 9 patients in group DSI. During the follow-up, although TSI increased in group ISI and decreased in group DSI (p < 0.05), there were no significant changes in USR, DSR, or TSR in either group. No relationship was found between TSI and TSR. Changes in weight, blood pressure, urine volume, ultra-filtration, and small solute removal (Kt/V and creatinine clearance) were not statistically significant between the two groups. Fluid status deteriorated in group ISI and improved in group DSI (p < 0.05). CONCLUSIONS: Our study suggests that changes in total sodium intake do not lead to proportionate changes in total sodium removal in CAPD patients. Therefore, TSR (the sum of USR and DSR) should be used cautiously to monitor TSI in this patient population.     

In vitro growth inhibition of neoplastically transformed cells by non-transformed cells: requirement for gap junctional intercellular communication

We examined whether the inhibition of neoplastically transformedcell growth by co-cultured non-transformed cells involved gapjunctional intercellular communication (GJIC). The growth ofpoorly communicating (     

LONG-TERM OUABAIN ADMINISTRATION DOES NOT ALTER BLOOD PRESSURE IN CONSCIOUS SPRAGUE-DAWLEY RATS

1. We tested the ability of ouabain to cause chronic hyper tension by continuously infusing ouabain for 28 days (mini-osmotic pump implantation; i.p.). The blood pressure and metabolic effects of sham (150 mmol/L NaCI; n= 12) or ouabain infusion (10 μg/kg per day; n= 14; 100 μg/kg per day; n = 14) were examined in conscious Sprague-Dawley rats. 2. Plasma ouabain concentrations measured after 28 days of ouabain infusion were as follows: sham, not detectable (n= 11); ouabain 10 μg/kg per day, 0.60 ± 0.07 nmol/L (n= 14); and ouabain 100 μg/kg per day, 7.17 ± 0.57 nmol/L (n= 14; P < 0.001). 3. Sham or ouabain infusion did not alter food intake, bodyweight, water intake or urine output in conscious rats. 4. Blood pressure was not altered by sham treatment. Ouabain at 10 μg/kg per day or 100 μg/kg per day did not produce consistent rises in blood pressure. Ouabain at 10 μg/kg per day increased blood pressure on treatment day 12 only (+ 6mmHg; P < 0.05), while at 100μg/kg per day blood pres sure increased on treatment days 16 (+ 9 mmHg; P < 0.05) and day 18 (+ 8mmHg; P < 0.05) only. There was no significant difference in blood pressure between sham and ouabain groups. 5. Renal blood flow was decreased in rats infused with ouabain at 10 μg/kg per day (2.0 ± 0.3 mL/min per 100 g body-weight; n= 5; P < 0.01) and 100 μg/kg per day (2.2 ± 0.4 mL/ min per 100 g bodyweight; n= 7; P < 0.05) compared with sham treatment (3.5 ± 0.2 mL/min per 100 g bodyweight; n= 6). Renal vascular resistance was increased in rats treated with ouabain at 10 μg/kg per day (65.5 ± 12.6 mmHg/mL per min per 100 g bodyweight; n= 5; P < 0.01) and 100 μg/kg per day (66.0 ± 15.6 mmHg/mL per min per 100 g bodyweight; n= 7; P < 0.05) compared with sham treatment (32.6 ± 2.5 mmHg/mL per min per 100 g bodyweight; n= 6). 6. High plasma concentrations of ouabain do not cause consistent increases in blood pressure in conscious Sprague-Dawley rats.     

Compartmentalization of anterogradely and retrogradely transported organelles in axons and growth cones from chick optic tectum

Previous work suggests that organelles contacting microtubules in axons are in fast transport. Here, we examine the distribution of organelles contacting microtubules in growing axons and growth cones from chick optic tectum. Five axon segments, each 10 microns long, and 4 entire growth cones were reconstructed from serial electron micrographs of quick-frozen, freeze-substituted chick optic tectum. Organelles contacting microtubules in axons are evenly distributed along all microtubules. Smaller organelles, presumably in anterograde transport, are enclosed in fascicles of microtubules, while larger organelles in retrograde transport lie outside the fascicles. In contrast, organelles contacting microtubules are prevalent only in the most proximal parts of the growth cone, before the microtubule fascicles splay out more distally. The distance between noncontacting organelles and microtubules also becomes progressively greater, reaching a maximum in the mid- and more distal region of the growth cone. Contacts with microtubules of both the smaller, presumably anterogradely transported organelles, as well as the larger, presumably retrogradely transported organelles, abruptly become less frequent in the proximal midregion of the growth cone. It is therefore of possible significance in stopping and starting microtubule-based organelle transport that microtubules change from a straight to an undulating configuration in the midregion of the growth cone. The decrease in organelle binding to microtubules at the demarcations between the straight and undulating microtubule segments may depend on proteins or other local factors as well as the splaying out of the microtubule bundles.