Renal oxygenation changes during acute unilateral ureteral obstruction: assessment with blood oxygen level-dependent mr imaging--initial experience

PURPOSE: To prospectively determine if changes in intrarenal oxygenation during acute unilateral ureteral obstruction can be depicted with blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging. MATERIALS AND METHODS: The study was approved by the local ethics committee, and written informed consent was obtained from all patients. BOLD MR imaging was performed in 10 male patients (mean age, 45 years +/- 17 [standard deviation]; range, 20-73 years) with a distal unilateral ureteral calculus and in 10 healthy age-matched male volunteers to estimate R2*, which is inversely related to tissue Po(2). R2* values were determined in the cortex and medulla of the obstructed and the contralateral nonobstructed kidneys. To reduce external effects on R2*, the R2* ratio between the medulla and cortex was also analyzed. Statistical analysis was performed with nonparametric rank tests. P < .05 was considered to indicate a significant difference. RESULTS: All patients had significantly lower medullary and cortical R2* values in the obstructed kidney (median R2* in medulla, 10.9 sec(-1) [range, 9.1-14.3 sec(-1)]; median R2* in cortex, 10.4 sec(-1) [range, 9.7-11.3 sec(-1)]) than in the nonobstructed kidney (median R2* in medulla, 17.2 sec(-1) [range, 14.6-23.2 sec(-1)], P = .005; median R2* in cortex, 11.7 sec(-1) [range, 11.0-14.0 sec(-1)], P = .005); values in the obstructed kidneys were also significantly lower than values in the kidneys of healthy control subjects (median R2* in medulla, 16.1 sec(-1) [range, 13.9-18.1 sec(-1)], P < .001; median R2* in cortex, 11.6 sec(-1) [range, 10.5-12.9 sec(-1)], P < .001). R2* ratios in the obstructed kidneys (median, 1.06; range, 0.85-1.27) were significantly lower than those in the nonobstructed kidneys (median, 1.49; range, 1.26-1.71; P = .005) and those in the kidneys of healthy control subjects (median, 1.38; range, 1.23-1.47; P < .001). In contrast, R2* ratios in the nonobstructed kidneys of patients were significantly higher than those in kidneys of healthy control subjects (P = .01). CONCLUSION: Increased oxygen content in the renal cortex and medulla occurs with acute unilateral ureteral obstruction, suggesting reduced function of the affected kidney.

Noninvasive assessment of acute ureteral obstruction with diffusion-weighted MR imaging: a prospective study

PURPOSE: To prospectively assess the potential of noninvasive diffusion-weighted magnetic resonance (MR) imaging to depict changes in microperfusion and diffusion in patients with acute unilateral ureteral obstruction. MATERIALS AND METHODS: The local ethics committee approved the study protocol. Informed consent was obtained. Diffusion-weighted MR imaging was performed in 21 patients (two women, 19 men; mean age, 43 years +/- 10 [standard deviation]) with acute unilateral ureteral obstruction due to a calculus diagnosed at unenhanced computed tomography. A control group (one woman, 15 men; mean age, 44 years +/- 12) underwent the same MR protocol. Standard processing yielded an apparent diffusion coefficient (ADC) ADCT; the separation of microperfusion and diffusion contributions yielded the perfusion fraction FP and the pure diffusion coefficient ADCD. ADCT, ADCD, and FP were compared between obstructed and contralateral unobstructed kidneys and with control values. For statistical analysis, nonparametric rank tests were used. A P value of less than .05 was considered significant. RESULTS: No significant differences were observed between the ADCT of the medulla or cortex of the obstructed and unobstructed kidneys. Compared with control kidneys, only medullary ADCT was slightly increased in the obstructed kidney (P < .04). However, the ADCD in the medulla of the obstructed and unobstructed kidneys was significantly higher than that in control subjects (201 x 10(-5) mm2/sec +/- 16 and 199 x 10(-5) mm2/sec +/- 20 vs 189 x 10(-5) mm2/sec +/- 12; P < .008 and P < .03, respectively). FP of the cortex of the obstructed kidney was significantly lower than that in the unobstructed kidney (20.2% +/- 4.8 vs 24.0% +/- 5.8; P < .002); FP of the medulla was slightly lower in the obstructed kidney than in the unobstructed kidney (18.3% +/- 5.9 vs 20.7% +/- 6.4; P = .05). CONCLUSION: Diffusion-weighted MR imaging allows noninvasive detection of changes in renal perfusion and diffusion during acute unilateral ureteral obstruction, as exemplified in patients with a ureteral calculus.

Extracorporeal shock wave lithotripsy for distal ureteral calculi: what a powerful machine can achieve

PURPOSE: We assessed the efficacy of extracorporeal shock wave lithotripsy (ESWL, Dornier Medical Systems, Inc., Marietta, Georgia) for distal ureteral calculi with the HM3 (Dornier Medical Systems, Inc.) lithotriptor. MATERIALS AND METHODS: A total of 585 consecutive patients with distal ureteral calculi were treated with ESWL using an unmodified HM3 lithotriptor. Of these patients 67 referred for treatment only for whom no followup was available were excluded from further analysis. The remaining 518 cases were followed until they were radiologically documented to be stone-free or considered treatment failures. Before ESWL additional procedures were performed in 144 patients, including stone push back, ureteral catheter or Double-J (Medical Engineering Corp., New York, New York) stent placement, percutaneous nephrostomy, ureteral endoscopic maneuvers or stone basket manipulation. A total of 374 patients needed no preliminary treatment before ESWL. RESULTS: Of the 518 patients 469 (91%) were successfully treated with 1 ESWL session, while 49 (9%) needed 2 or 3. Manipulation after ESWL was performed in 22 cases, including stent placement, percutaneous nephrostomy, ureteral endoscopic stone removal and a stone basket procedure. On day 1 after ESWL 327 patients (63%) were stone-free, 158 (30%) had less than 5 mm. fragments and 33 (7%) had more than 5 mm. fragments. At 3 months the stone-free rate increased to 97%. CONCLUSIONS: These data show that ESWL for distal ureteral calculi with the powerful unmodified HM3 lithotriptor has a high success rate with a low rate of minimally traumatic manipulations before and after intervention. Results in terms of the re-treatment and stone-free rates are superior to those of any other second or third generation lithotriptor and comparable to the results of the best ureteroscopic series.

Optimization of extracorporeal shock wave lithotripsy delivery rates achieves excellent outcomes in ureteral stones. Results of a prospective, randomized trial

PURPOSE Management of ureteral stones remains controversial. To determine whether optimizing extracorporeal shock wave lithotripsy (ESWL) delivery rates improves treatment of solitary ureteral stones, we compared outcomes of two SW delivery rates in a prospective, randomized trial. MATERIALS AND METHODS From July 2010 to October 2012, 254 consecutive patients were randomized to undergo ESWL at SW delivery rates of either 60 pulses (n=130) or 90 pulses (n=124) per min. The primary endpoint was stone-free rate at 3-month follow-up. Secondary endpoints included stone disintegration, treatment time, complications, and the rate of secondary treatments. Descriptive statistics were used to compare endpoints between the two groups. Adjusted odds ratios and 95% confidence intervals were calculated to assess predictors of success. RESULTS The stone-free rate at 3 months was significantly higher in patients who underwent ESWL at a SW delivery rate of 90 pulses per min than in those receiving 60 pulses (91% vs. 80%, p=0.01). Patients with proximal and mid-ureter stones, but not those with distal ureter stones, accounted for the observed difference (100% vs. 83%; p=0.005; 96% vs. 73%, p=0.03; and 81% vs. 80%, p=0.9, respectively). Treatment time, complications, and the rate of secondary treatments were comparable between the two groups. In multivariable analysis, SW delivery rate of 90 pulses per min, proximal stone location, stone density, stone size and the absence of an indwelling JJ stent were independent predictors of success. CONCLUSIONS Optimization of ESWL delivery rates can achieve excellent results for ureteral stones.

Novel Features of the Prenatal Horn Bud Development in Cattle (Bos taurus).

Whereas the genetic background of horn growth in cattle has been studied extensively, little is known about the morphological changes in the developing fetal horn bud. In this study we histologically analyzed the development of horn buds of bovine fetuses between ~70 and ~268 days of pregnancy and compared them with biopsies taken from the frontal skin of the same fetuses. In addition we compared the samples from the wild type (horned) fetuses with samples taken from the horn bud region of age-matched genetically hornless (polled) fetuses. In summary, the horn bud with multiple layers of vacuolated keratinocytes is histologically visible early in fetal life already at around day 70 of gestation and can be easily differentiated from the much thinner epidermis of the frontal skin. However, at the gestation day (gd) 212 the epidermis above the horn bud shows a similar morphology to the epidermis of the frontal skin and the outstanding layers of vacuolated keratinocytes have disappeared. Immature hair follicles are seen in the frontal skin at gd 115 whereas hair follicles below the horn bud are not present until gd 155. Interestingly, thick nerve bundles appear in the dermis below the horn bud at gd 115. These nerve fibers grow in size over time and are prominent shortly before birth. Prominent nerve bundles are not present in the frontal skin of wild type or in polled fetuses at any time, indicating that the horn bud is a very sensitive area. The samples from the horn bud region from polled fetuses are histologically equivalent to samples taken from the frontal skin in horned species. This is the first study that presents unique histological data on bovine prenatal horn bud differentiation at different developmental stages which creates knowledge for a better understanding of recent molecular findings.

Rho1p-Bni1p-Spa2p Interactions: Implication in Localization of Bni1p at the Bud Site and Regulation of the Actin Cytoskeleton in Saccharomyces cerevisiae

Rho1p is a yeast homolog of mammalian RhoA small GTP-binding protein. Rho1p is localized at the growth sites and required for bud formation. We have recently shown that Bni1p is a potential target of Rho1p and that Bni1p regulates reorganization of the actin cytoskeleton through interactions with profilin, an actin monomer-binding protein. Using the yeast two-hybrid screening system, we cloned a gene encoding a protein that interacted with Bni1p. This protein, Spa2p, was known to be localized at the bud tip and to be implicated in the establishment of cell polarity. The C-terminal 254 amino acid region of Spa2p, Spa2p(1213–1466), directly bound to a 162-amino acid region of Bni1p, Bni1p(826–987). Genetic analyses revealed that both the bni1 and spa2 mutations showed synthetic lethal interactions with mutations in the genes encoding components of the Pkc1p-mitogen-activated protein kinase pathway, in which Pkc1p is another target of Rho1p. Immunofluorescence microscopic analysis showed that Bni1p was localized at the bud tip in wild-type cells. However, in the spa2 mutant, Bni1p was not localized at the bud tip and instead localized diffusely in the cytoplasm. A mutant Bni1p, which lacked the Rho1p-binding region, also failed to be localized at the bud tip. These results indicate that both Rho1p and Spa2p are involved in the localization of Bni1p at the growth sites where Rho1p regulates reorganization of the actin cytoskeleton through Bni1p.

The ricinosomes of senescing plant tissue bud from the endoplasmic reticulum

The ricinosome (synonym, precursor protease vesicle) is a novel organelle, found so far exclusively in plant cells. Electron microscopic studies suggest that it buds off from the endoplasmic reticulum in senescing tissues. Biochemical support for this unusual origin now comes from the composition of the purified organelle, which contains large amounts of a 45-kDa cysteine endoprotease precursor with a C-terminal KDEL motif and the endoplasmic reticulum lumen residents BiP (binding protein) and protein disulfide isomerase. Western blot analysis, peptide sequencing, and mass spectrometry demonstrate retention of KDEL in the protease proform. Acidification of isolated ricinosomes causes castor bean cysteine endopeptidase activation, with cleavage of the N-terminal propeptide and the C-terminal KDEL motif. We propose that ricinosomes accumulate during senescence by programmed cell death and are activated by release of protons from acidic vacuoles.

Budūr al-ḍāwīyah fī al-taʻrīf bi-al-sādāt ahl al-Zāwiyah al-Dilāʼīyah : manuscript, undated

بسم الله الرحمن الرحيم وصلى الله على سيدنا ومولانا محمد وآله حدايق الازهار النددية في التعريف باهل الزاوية ... :Incipit

Ectopic Meis1 expression in the mouse limb bud alters P-D patterning in a Pbx1-independent manner

During limb development, expression of the TALE homeobox transcription factor Meis1 is activated by retinoic acid in the proximal-most limb bud regions, which give rise to the upper forelimb and hindlimb. Early subdivision of the limb bud into proximal Meis-positive and distal Meis-negative domains is necessary for correct proximo-distal (P-D) limb development in the chick, since ectopic Meis1 overexpression abolishes distal limb structures, produces a proximal shift of limb identities along the P-D axis, and proximalizes distal limb cell affinity properties. To determine whether Meis activity is also required for P-D limb specification in mammals, we generated transgenic mice ectopically expressing Meis1 in the distal limb mesenchyme under the control of the Msx2 promoter. Msx2:Meis1 transgenic mice display altered P-D patterning and shifted P-D Hox gene expression domains, similar to those previously described for the chicken. Meis proteins function in cooperation with PBX factors, another TALE homeodomain subfamily. Meis-Pbx interaction is required for nuclear localization of both proteins in cell culture, and is important for their DNA-binding and transactivation efficiency. During limb development, Pbx1 nuclear expression correlates with the Meis expression domain, and Pbx1 has been proposed as the main Meis partner in this context; however, we found that Pbx1 deficiency did not modify the limb phenotype of Msx2:Meis1 mice. Our results indicate a conserved role of Meis activity in P-D specification of the tetrapod limb and suggest that Pbx function in this context is either not required or is provided by partners other than Pbx1.