Serum acute phase protein concentrations in dogs with autoimmune hemolytic anemia.

BACKGROUND: Serial monitoring of acute phase protein (APP) concentrations in canine autoimmune hemolytic anemia (AIHA) has not been reported. HYPOTHESES: Acute canine AIHA is accompanied by an acute phase response (APR) characterized by increased C-reactive protein (CRP) and alpha1-acid glycoprotein (AAG) concentrations and decreased albumin concentrations. ANIMALS: Twenty-seven dogs with AIHA and 11 control dogs. METHODS: Prospective, cohort study. CRP, AAG, and albumin concentrations, white blood cell (WBC) count, and packed cell volume (PCV) were determined at admission (day 1), every 48 hours until death or discharge, and on days 30, 90, 180, and 365. RESULTS: Compared with controls, CRP and AAG concentrations were increased and albumin concentration was decreased in dogs with AIHA (days 1-7; P < .002) and normalized with disease stabilization (days 9-365; P > .05). APP concentrations on day 1 were not predictive of survival, duration of hospitalization, or number of blood transfusions (P= .153-.940). PCV correlated with APP concentrations over time (CRP r=-.600, AAG r=-.665, albumin r= .533; P < .0001) as did WBC count (CRP r= .253, AAG r= .486, albumin r=-.246; P < .006). Day 1 CRP concentration was lower for dogs that received corticosteroids before referral (115.3 microg/mL) compared with dogs that did not (191.2 microg/mL; P= .02). CONCLUSIONS: An APR occurs in canine AIHA. Initial APP concentrations are not predictive of acute survival, correlate with hematologic markers of remission, and normalize rapidly with disease stabilization.

Intrarenal renin-angiotensin system and counteracting protective mechanisms in angiotensin II-dependent hypertension.

It is now well accepted that alterations in kidney function, due either to primary renal disease or to inappropriate hormonal influences on the kidney, are a cardinal characteristic in all forms of hypertension, and lead to a reduced ability of the kidneys to excrete sodium and the consequent development of elevated arterial pressures. However, it is also apparent that many extrarenal factors are important contributors to altered kidney function and hypertension. Central to many hypertensinogenic processes is the inappropriate activation of the renin-angiotensin system (RAS) and its downstream consequences by various pathophysiologic mechanisms. There may also be derangements in arachidonic acid metabolites, endothelium derived factors such as nitric oxide and carbon monoxide, and various paracrine and neural systems that normally interact with or provide a counteracting balance to the actions of the RAS. Thus, when the capacity of the kidneys to maintain sodium balance and extracellular fluid volume within appropriate ranges is compromised, increases in arterial pressure become necessary to re-establish normal balance.

Ion channels from linear and branched bola-amphiphiles.

The synthesis and characterization of the ion channel activity of three new bola-amphiphiles is described. These compounds are conceptually derived from a previously reported bis-cyclophane bola-amphiphile through opening of the cyclophanes to acyclic structures and were found to readily form ion channels in planar bilayer membranes as assessed by bilayer clamp single-channel analysis. All three compounds behaved very similarly: the dominant channels formed by all three are Ohmic with specific conductance of 10 +/- 1 pS (NaCl electrolyte) and 39 +/- 1 pS (CsCl electrolyte). Single-ion permeability ratios, determined from dissymmetric electrolyte experiments, showed the selectivity P(Cs(+)) > P(Na(+)) > P(Cl(-)). Less frequently, lower conductance channels were also observed to act independently of the dominant channels. The lifetimes of the dominant channels range from 70 to 280 ms for the three compounds with some very long-lived openings (20-40 s) observed for two of the three. The lower conductance states have shorter lifetimes. This study demonstrates that bis-macrocyclic compounds are not essential for channel formation by bola-amphiphiles, and opens a new class of channel-forming compounds for structure-activity optimization.

Role of nNOS in regulation of renal function in hypertensive Ren-2 transgenic rats.

The present study was performed to evaluate the role of neuronal nitric oxide synthase (nNOS)-derived nitric oxide (NO) during the developmental phase of hypertension in transgenic rats harboring the mouse Ren-2 renin gene (TGR). The first aim of the present study was to examine nNOS mRNA expression in the renal cortex and to assess the renal functional responses to intrarenal nNOS inhibition by S-methyl-L-thiocitrulline (L-SMTC) in heterozygous TGR and in age-matched transgene-negative Hannover Sprague-Dawley rats (HanSD). The second aim was to evaluate the role of the renal sympathetic nerves in mediating the renal functional responses to intrarenal nNOS inhibition. Thus, we also evaluated the effects of intrarenal L-SMTC administration in acutely denervated TGR and HanSD. Expression of nNOS mRNA in the renal cortex was significantly increased in TGR compared with HanSD. Intrarenal administration of L-SMTC decreased the glomerular filtration rate (GFR), renal plasma flow (RPF) and sodium excretion and increased renal vascular resistance (RVR) in HanSD. In contrast, intrarenal inhibition of nNOS by L-SMTC did not alter GFR, RPF or RVR and elicited a marked increase in sodium excretion in TGR. This effect of intrarenal L-SMTC was not observed in acutely denervated TGR. These results suggest that during the developmental phase of hypertension TGR exhibit an impaired renal vascular responsiveness to nNOS derived NO or an impaired ability to release NO by nNOS despite enhanced expression of nNOS mRNA in the renal cortex. In addition, the data indicate that nNOS-derived NO increases tubular sodium reabsorption in TGR and that the renal nerves play an important modulatory role in this process.

Bait ingestion by free-ranging raccoons and nontarget species in an oral rabies vaccine field trial in Florida.

Oral rabies vaccine-laden baits, with a tetracycline biomarker, were distributed in Pinellas County (Florida, USA) by helicopter drop and from cars from January to April 1997. A total of 130,320 baits was distributed throughout the county, yielding an average bait density of 185 baits per km2. Bait ingestion was estimated by microscopic detection of tetracycline in tooth and bone samples from 244 raccoons (Procyon lotor), 33 opossums (Didelphis virginianus), 31 feral cats, and two gray foxes (Urocyon cinereoargenteus) that were trapped during February-April 1997. Active surveillance consisted of 17 trapping sites that were further categorized by six community descriptors. Passive surveillance consisted of animals that were collected as nuisance animals by Pinellas County Animal Services. The proportion of tetracycline positive raccoons was compared between collection techniques, among trapping sites, vegetation communities, and age and sex categories. Since there was no statistically significant difference in the frequency of tetracycline positive raccoons trapped during active surveillance (59%, 110/187) and passive surveillance (53%, 30/57), the data were pooled, resulting in a tetracycline positive frequency of 57% (140/244). The range in the positive tetracycline frequency established for raccoons from the 17 active surveillance sites was 9% (1/11) to 100% (3/3). The tetracycline positive frequency for raccoons ranged from 25% (3/12) at the dumpster sites to 78% (14/18) at the landfills. Juvenile male raccoons (71%, 34/48) were the most commonly marked age and sex class and adult females (42%, 21/50) were the least commonly marked age and sex class. Eighty-five percent (28/33) of the opossums, 3% (1/31) of the feral cats, and 50% (1/2) of the gray foxes were tetracycline positive.

Renal responses to AT1 receptor blockade.

Because of the importance of the renin-angiotensin system in the pathophysiology of hypertension and in mediating associated alterations in renal function, angiotensin II (Ang II) AT1 receptor blockers provide a direct means of protecting against influences of excessive Ang II levels. The kidney is an important site of action of Ang II AT1 receptor blockers because intrarenal Ang II not only vasoconstricts the renal vasculature but also reduces sodium excretion and suppresses the pressure natriuresis relationship. Even in normal conditions, intrarenal Ang II content is greater than can be explained on the basis of circulating Ang II and is compartmentalized with proximal tubule concentrations of Ang I and Ang II being several times higher than plasma concentrations. The localization of angiotensinogen in proximal tubule cells further supports the concept that the proximal tubule secretes Ang II or precursors of Ang II into the tubular fluid to activate luminal Ang II receptors. Recent immunohistochemical studies have demonstrated an abundance of AT1 receptors on the luminal surface of proximal and distal tubule cells as well as on vascular smooth muscle cells of afferent and efferent arterioles and on glomerular mesangial cells. Activation of luminal AT1 receptors stimulates the sodium hydrogen exchanger and increases reabsorption rate. The prominence of AT1 receptors in vascular and epithelial tissues in the kidney provides the basis for the powerful effects of AT1 receptor blockers on renal function especially in hypertensive conditions. In the two-kidney, one-clip (2K1C) Goldblatt hypertensive rat model, the nonclipped kidney is renin depleted but the intrarenal Ang II levels are not suppressed and Ang II concentrations in proximal tubular fluid remain high (10(-8) mol/L). AT1 receptor blockers such as candesartan have been shown to cause significant increases in glomerular filtration rate, renal blood flow and proportionately much greater increases in sodium excretion and fractional sodium excretion. Ang II blockade also markedly increases the slope of the pressure natriuresis relationship. The collective actions of Ang II blockers on tubular transport and renal hemodynamics provide long-term effects to regulate sodium balance, which contributes to the long-term control of hypertension.

Renal function in mice: effects of volume expansion and angiotensin II.

The present study was performed to validate a simple means for assessing renal function in anesthetized mice and to characterize the renal hemodynamic responses to acute volume expansion and how these responses are altered by concurrent angiotensin II (AngII) infusions. Inulin and para-aminohippurate clearances were used to assess GFR and renal plasma flow (RPF) in three groups of male C57Bl/6 mice anesthetized with inactin (100 mg/kg, intraperitoneally) and ketamine (10 mg/kg). To avoid the hypotension associated with repeated blood sampling, a single blood sample was taken after three timed urine collections. Renal function and mean arterial pressure (MAP) were measured under euvolemic conditions (2.5 microl/min, intravenously, n = 7) during isotonic saline volume expansion (12.5 microl/min, intravenously, n = 5) and during volume expansion with concurrent AngII infusion (5 ng/min x g, n = 5). MAP in the control group was 77 +/- 2 mmHg; volume expansion alone did not change MAP significantly (83 +/- 2 mmHg), but led to significantly greater values in both GFR and RPF (1.35 +/- 0.14 versus 1.01 +/- 0.1 ml/min x g and 11.26 +/- 1.39 versus 6.29 +/- 0.5 ml/min x g, respectively). Infusion of AngII during volume expansion led to significant elevations of MAP (100 +/- 3 mmHg, P < 0.05) and prevented the increases in GFR and RPF elicited by volume expansion (0.77 +/- 0.08 and 5.35 +/- 0.48 ml/min x g, respectively). Volume expansion also elicited marked increases in absolute and fractional sodium excretion (6.1 +/- 1.0 versus 0.62 +/- 0.2 microEq/min x g and 3.1 +/- 0.7 versus 0.4 +/- 0.1%, respectively). AngII infusion attenuated the absolute and fractional sodium excretion responses to volume expansion (3.4 +/- 1.2 microEq/min x g and 2.5 +/- 0.5%, respectively). The present findings demonstrate that anesthetized mice exhibit marked renal hemodynamic and excretory responses to isotonic saline volume expansion. Concomitant AngII infusion attenuates these responses in spite of greater increases in arterial pressure.

Renal function in the AT1A receptor knockout mouse during normal and volume-expanded conditions.

BACKGROUND: Genetically altered mice lacking the AT1A angiotensin II (Ang II) receptor were used to examine the role of AT1A receptors in regulating renal hemodynamics, sodium excretion, glomerulotubular balance, and Ang II levels in plasma and kidney during normal and volume-expanded conditions. METHODS: AT1A receptor-deficient mice and their wild-type controls were anesthetized with inactin and ketamine, and were prepared to allow intravenous infusions of solutions and measurements of aortic pressure and urine collections. Inulin and para-aminohippurate (PAH) solutions were infused intravenously for clearance determinations under conditions of euvolemia (2.5 microliter/min infusion of isotonic saline) or volume-expansion conditions (12.5 microliter/min). After three 30-minute urine collections, blood samples were collected, and kidneys were harvested. Plasma and kidney Ang II measurements were made by radioimmunoassay. RESULTS: In the euvolemic state, mean arterial pressures (MAPs) were significantly lower in the AT1A receptor-deficient mice (68 +/- 4 mm Hg) compared with wild-type controls (89 +/- 3 mm Hg). Despite the lower MAP, the glomerular filtration rate (GFR), renal plasma flow (RPF), absolute sodium excretion, and fractional sodium excretion were not significantly different between wild-type and AT1A-/- mice. Volume expansion did not alter MAP in wild-type mice, but significantly increased MAP in the AT1A-/- mice (68 +/- 4 to 83 +/- 5 mm Hg). Similar increases in GFR, RPF, absolute sodium excretion, and fractional sodium excretion in AT1A+/+ and AT1A-/- mice were observed. Glomerulotubular balance was not disrupted by the absence of AT1A receptors. During euvolemia, plasma Ang II concentrations were significantly higher in the AT1A-/- mice compared with wild-type mice (536 +/- 172 vs. 198 +/- 36 fmol/ml). Although volume expansion had no effect on plasma Ang II levels in the AT1A+/+ group, plasma Ang II concentrations were markedly suppressed in the AT1A-/- mice to levels that were not different from those in wild-type mice. In contrast, kidney tissue Ang II contents were reduced in the AT1A-/- mice and were not significantly altered during volume expansion in either the AT1A-/- or the AT1A+/+ mice. CONCLUSIONS: The absence of AT1A receptors does not impair chronic regulation of renal blood flow, GFR, or glomerulotubular balance. The prompt restoration of MAP following volume expansion suggests that low blood pressure in the AT1A receptor-deficient mice is primarily due to reduced effective plasma and extracellular fluid volume. Normalization of plasma Ang II levels with volume expansion demonstrates a dominant effect of extracellular fluid volume and blood pressure over AT1A receptor-mediated short-loop feedback in the regulation of plasma Ang II levels.

Intrarenal angiotensin II generation and renal effects of AT1 receptor blockade.

The intrarenal renin-angiotensin system plays a critical role in the paracrine regulation of renal function and the pathophysiology of hypertension. Angiotensin II (AngII) is formed intrarenally from systemically delivered angiotensin I (AngI) and intrarenally formed AngI. Intrarenal AngII content, which is greater than can be explained by the circulating AngII concentrations, is compartmentalized such that proximal tubule concentrations of AngI and AngII greatly exceed plasma concentrations. Proximal tubule cells are thought to secrete AngII or precursors of AngII into the tubular fluid to activate luminal AngII receptors. Recent immunohistochemical studies have demonstrated an abundance of AT1 receptors on the luminal surface of proximal and distal tubule cells and on afferent and efferent arteriolar vascular smooth muscle cells and mesangial cells of glomeruli. Activation of luminal AT1 receptors stimulates tubular sodium reabsorption rate. To evaluate the direct effects of AT1 receptor blockade on renal function in AngII-dependent hypertension, experiments were performed on two-kidney, one-clip (2K1C) Goldblatt hypertensive rats. Although the nonclipped kidney is renin-depleted, the intrarenal AngII levels are not suppressed, and AngII concentrations in proximal tubular fluid remain high (10(-8) M). Candesartan was administered into the renal artery of nonclipped kidneys to avoid the confounding consequences of decreases in arterial pressure. Blockade of intrarenal AT1 receptors elicited significant increases in GFR, renal blood flow, sodium excretion, and fractional sodium excretion, suggesting synergistic actions on tubular transport and vascular smooth muscle cells.

Proximal tubular angiotensin II levels and renal functional responses to AT1 receptor blockade in nonclipped kidneys of Goldblatt hypertensive rats.

-Previous studies have shown that whereas the nonclipped kidney in two-kidney, one clip (2K1C) rats undergoes marked depletion of renin content and renin mRNA, intrarenal angiotensin II (Ang II) levels are not suppressed; however, the distribution and functional consequences of intrarenal Ang II remain unclear. The present study was performed to assess the plasma, kidney, and proximal tubular fluid levels of Ang II and the renal responses to intrarenal Ang II blockade in the nonclipped kidneys of rats clipped for 3 weeks. The Ang II concentrations in proximal tubular fluid averaged 9.19+/-1.06 pmol/mL, whereas plasma Ang II levels averaged 483+/-55 fmol/mL and kidney Ang II content averaged 650+/-66 fmol/g. Thus, as found in kidneys from normal rats with normal renin levels, proximal tubular fluid concentrations of Ang II are in the nanomolar range. To avoid the confounding effects of decreases in mean arterial pressure (MAP), we administered the nonsurmountable AT1 receptor antagonist candesartan directly into the renal artery of nonclipped kidneys (n=10). The dose of candesartan (0.5 microg) did not significantly decrease MAP in 2K1C rats (152+/-3 versus 148+/-3 mm Hg), but effectively prevented the renal vasoconstriction elicited by an intra-arterial bolus of Ang II (2 ng). Candesartan elicited significant increases in glomerular filtration rate (GFR) (0.65+/-0. 06 to 0.83+/-0.11 mL. min-1. g-1) and renal blood flow (6.3+/-0.7 to 7.3+/-0.9 mL. min-1. g-1), and proportionately greater increases in absolute sodium excretion (0.23+/-0.07 to 1.13+/-0.34 micromol. min-1. g-1) and fractional sodium excretion (0.38+/-0.1% to 1.22+/-0. 35%) in 2K1C hypertensive rats. These results show that proximal tubular fluid concentrations of Ang II are in the nanomolar range and are much higher than can be explained on the basis of plasma levels. Further, the data show that the intratubular levels of Ang II in the nonclipped kidneys of 2K1C rats remain at levels found in kidneys with normal renin content and could be exerting effects to suppress renal hemodynamic and glomerular function and to enhance tubular reabsorption rate.

Enhanced renal vascular responsiveness to angiotensin II in hypertensive ren-2 transgenic rats.

The present study was performed to evaluate renal vascular responsiveness (RVR) to ANG II in hypertensive transgenic rats [TGR; strain TGR(mRen2)27] harboring the mouse ren-2 renin gene. Renal blood flow (RBF) responses to either intravenous or intrarenal arterial administration of ANG II were assessed in pentobarbital sodium-anesthetized female heterozygous TGR (9-12 wk old) and age-matched transgene-negative Hanover Sprague-Dawley rats (HanSD). Intravenous bolus injections of 15 and 30 ng ANG II elicited dose-dependent increases in mean arterial blood pressure (AP) and decreases in RBF in both TGR and HanSD. However, the magnitude of the increases in AP was greater in TGR than in HanSD (24 +/- 1 vs. 17 +/- 2 mmHg and 33 +/- 2 vs. 25 +/- 1 mmHg, respectively, P < 0.05 in both cases). Similarly, the magnitude of the decrease in RBF elicited by intravenous administration of 15 ng of ANG II was greater in TGR than HanSD (-62 +/- 3 vs. -52 +/- 5%, P < 0.05). Intrarenal arterial administration of 1.5 and 3 ng ANG II did not alter mean AP in either group but elicited larger decreases in RBF in TGR than in HanSD (-24 +/- 2 vs. -13 +/- 1% and -41 +/- 5 vs. -30 +/- 2%, respectively, P < 0.05 in both cases). In contrast, intrarenal arterial administration of norepinephrine (40 and 80 ng) elicited smaller decreases in RBF in TGR than in HanSD (-24 +/- 3 vs. -40 +/- 6% and -51 +/- 9 vs. -71 +/- 8%, respectively, P < 0.05 in both cases), indicating that TGR do not exhibit a generalized increase in RVR to endogenous vasoconstrictors. Furthermore, the enhanced RVR to ANG II does not appear to reflect an impaired RVR to endogenous vasodilator factors since intrarenal administration of bradykinin and acetylcholine elicited larger increases in RBF in TGR than in HanSD. The present findings indicate that hypertensive TGR exhibit exaggerated renal and peripheral vascular responses to ANG II, which likely contributes to an increased renal and peripheral vascular resistance and thereby to the hypertension in TGR.

Concentrations and actions of intraluminal angiotensin II.

Although the presence of angiotensin II (AngII) receptors on the luminal membranes of proximal tubule cells has been recognized for many years, recent immunohistochemical studies using polyclonal and monoclonal antibodies to the AngII type 1 (AT1) receptor have demonstrated an abundance of the AT1 receptor not only on the luminal surface of proximal tubule cells but also on the luminal surfaces of distal nephron segments. An important role for these receptors in the regulation of tubular transport mechanisms was indicated by the recent findings of remarkably high proximal intratubular concentrations of AngII (in the range of 10(-9) to 10(-8) M). The high intratubular concentrations of AngII, as well as angiotensin I and angiotensinogen, are much greater than can be explained on the basis of delivery via glomerular filtration. When coupled with the findings demonstrating the presence of angiotensinogen and angiotensinogen mRNA in proximal tubule cells, the data indicate that AngII or precursors of AngII are secreted directly into the proximal tubule lumen by the epithelial cells. Although the mechanisms responsible for the regulation of intratubular AngII concentrations remain to be determined, micropuncture studies have provided direct evidence that activation of intraluminal AT1 receptors by AngII exerts a substantial stimulatory influence on sodium and bicarbonate transport by both proximal and distal tubules. Collectively, these data provide support for the hypothesis that activation of luminal AT1 receptors by AngII present in the tubular fluid contributes importantly to regulation of the tubular reabsorption rate.

Heterogeneous activation mechanisms in the renal microvasculature.

Vascular smooth muscle cells in different renal microvascular segments utilize different activation mechanisms to respond to mechanical and vasoactive stimuli. L-type Ca2+ channel blockers vasodilate primarily the preglomerular vascular resistance component responsible for autoregulation. Local interstitial infiltration of Ca2+ channel blockers increases glomerular pressure and markedly reduces vascular responsiveness of the tubuloglomerular feedback mechanism. Ca2+ channel blockers selectively attenuate the afferent vasoconstrictor responses to increases in perfusion pressure. Although both afferent and efferent arterioles constrict in response to angiotensin II (Ang II), afferent but not efferent constriction requires Ca2+ influx through L-type Ca2+ channels. Sensitivity of the preglomerular arterioles to Ang II is also heterogeneous with the greatest sensitivity in glomerulus-near, terminal segments. Adenosine triphosphate (ATP) is a vasoconstrictor agonist that selectively activates Ca2+ entry pathways in afferent arterioles but has no effect on efferent arterioles. In isolated preglomerular smooth muscle cells, increasing extracellular [KCl] increases intracellular Ca2+ by stimulating voltage-dependent Ca2+ influx. Ang II, norepinephrine, and ATP also elicit similar increases in intracellular Ca2+. Mechanical and agonist-induced voltage-dependent Ca2+ influx is thus a primary pathway in the control of cytosolic Ca2+ in afferent arterioles. Efferent arterioles, however, rely primarily on intracellular Ca2+ mobilization and other Ca2+ influx pathways.

Three dimensional image alignment, registration and fusion.

Combined assessment of three dimensional anatomical and functional images (SPECT, PET, MRI, CT) is useful to determine the nature and extent of lesions in many parts of the body. Physicians principally rely on their spatial sense to mentally re-orient and overlap images obtained with different imaging modalities. Objective methods that enable easy and intuitive image registration can help the physician arrive at more optimal diagnoses and better treatment decisions. This review describes a simple, intuitive and robust image registration approach developed in our laboratory. It differs from most other registration techniques in that it allows the user to incorporate all of the available information within the images in the registration process. This method takes full advantage of the ability of knowledgeable operators to achieve image registration and fusion using an intuitive interactive visual approach. It can register images accurately and quickly without the use of elaborate mathematical modeling or optimization techniques. The method provides the operator with tools to manipulate images in three dimensions, including visual feedback techniques to assess the accuracy of registration (grids, overlays, masks, and fusion of images in different colors). Its application is not limited to brain imaging and can be applied to images from any region in the body. The overall effect is a registration algorithm that is easy to implement and can achieve accuracy on the order of one pixel.

Chloral hydrate alters the organization of the ciliary basal apparatus and cell organelles in sea urchin embryos.

The mitotic inhibitor, chloral hydrate, induces ciliary loss in the early embryo phase of Lytechinus pictus. It causes a breakdown of cilia at the junction of the cilium and the basal body known as the basal plate. This leaves the plasma membrane temporarily unsealed. The basal apparatus accessory structures, consisting of the basal body, basal foot, basal foot cap, striated side arm, and striated rootlet, are either misaligned or disintegrated by treatment with chloral hydrate. Furthermore, microtubules which are associated with the basal apparatus are disassembled. Mitochondria accumulate at the base of cilia - underneath the plasma membrane - and show alterations in their structural organization. The accumulation of mitochondria is observed in 40% of all electron micrograph sections while 60% show the areas mostly devoid of mitochondria. The microvilli surrounding a cilium and striated rootlet remain intact in the presence of chloral hydrate. These results suggest that deciliation in early sea urchin embryos by chloral hydrate is caused by combined effects on the ciliary membrane and on microtubules in the cilia. Furthermore, it is suggested that chloral hydrate can serve as a tool to explore the cytoskeletal mechanisms that are involved in cilia motility in the developing sea urchin embryo.

Proximal tubular fluid, kidney, and plasma levels of angiotensin II in hypertensive ren-2 transgenic rats.

The present study was performed to assess the plasma and kidney levels of angiotensin I (ANG I) and ANG II during prehypertensive (4- to 5-wk old), development (6- to 8-wk old), and maintenance (10- to 12-wk old) phases of hypertension in pentobarbital-anesthetized transgenic rats [TGR; strain name: TGR(mRen2)27] and age-matched transgene-negative Hannover Sprague-Dawley rats (HanSD). At 4-5 wk, mean arterial pressures of TGR were not different from those of HanSD (110 +/- 5 vs. 114 +/- 4 mmHg). However, mean arterial pressures of 6-8 wk and 10-12 wk TGR were higher than those of HanSD (179 +/- 3 vs. 110 +/- 6 and 173 +/- 5 vs. 116 +/- 3 mmHg, respectively; P < 0.01 in both cases). Plasma ANG II levels in 4-5 wk and 6-8 wk TGR were not different from those in HanSD (70 +/- 11 vs. 66 +/- 7 and 60 +/- 8 vs. 48 +/- 12 fmol/ml, respectively). However, plasma ANG II levels in 10-12 wk TGR were higher than those in HanSD (125 +/- 26 vs. 38 +/- 12 fmol/ml, P < 0.01). Kidney ANG II levels in 4-5 wk, 6-8 wk, and 10-12 wk TGR averaged 370 +/- 57, 247 +/- 16, and 562 +/- 86 fmol/g, respectively, values not different from those in HanSD. In additional studies performed on 6-8 wk TGR and HanSD, multiple free-flow proximal tubular fluid collections were obtained and pooled for each animal. In these experiments, mean arterial pressures of the 10 TGR and 7 HanSD studied averaged 178 +/- 9 and 129 +/- 3 mmHg (P < 0.01), respectively. The ANG II concentration in proximal tubular fluid obtained from TGR averaged 5.6 +/- 2.1 pmol/ml (n = 10), a value not different from that in proximal tubular fluid collected from HanSD (5.3 +/- 2.8 pmol/ml, n = 7). However, the ANG II contents of the micropunctured left kidney and the nonmicropunctured right kidney of TGR were lower than those in HanSD (690 +/- 95 vs. 1,374 +/- 210 and 659 +/- 119 vs. 1,303 +/- 196 fmol/g, respectively; P < 0.01 in both cases). The present findings indicate that proximal tubular fluid of hypertensive TGR contains nanomolar concentrations of ANG II and that proximal tubular fluid, plasma and kidney ANG II levels in anesthetized hypertensive TGR are not markedly suppressed compared with those in normotensive control rats.

Vesicoureteral reflux in children: incidence and severity in siblings.

PURPOSE: We attempted to determine the incidence of vesicoureteral reflux in asymptomatic siblings of children with reflux at different ages and assess the incidence of renal damage in asymptomatic siblings with reflux. MATERIALS AND METHODS: We reviewed radionuclide cystograms of 482 consecutively referred siblings of children with vesicoureteral reflux, including 295 girls and 187 boys 2 weeks to 12.8 years old (mean age 2.8 years). Ultrasonograms and renal cortical scintigrams of children with reflux were evaluated. All siblings were considered asymptomatic by the referring physicians. RESULTS: The overall incidence of vesicoureteral reflux was 36.5%, and the incidence in girls and boys was 39.3 and 32.1%, respectively. Children 24 months old or younger had the highest incidence (45.7%) and the highest risk of bilateral reflux. From ages 25 to 72 months the incidence of reflux was 33.1% and in siblings older than 72 months it was 7%. Reflux of urine to the level of the renal pelvis was detected in 28.6% of all referred siblings. Renal damage was observed on sonography or scintigraphy in 4.7% of the siblings with reflux. CONCLUSIONS: The high incidence of vesicoureteral reflux through age 72 months indicates that it is important to screen siblings of children with reflux at an early age to prevent renal damage, which can occur in the absence of symptomatic urinary tract infection.

[Distribution of viruses from the Californian encephalitis serogroup (Bunyaviridae, Bunyavirus) in the northern expanses of Russia]. / Rasprostranenie virusov serogruppy Kaliforniiskogo éntsefalita (Bunyaviridae, Bunyavirus) v severnykh shirotakh Rossii.

The study was carried out in 1983-1991 and covered a territory of about 10 x 10(6) km2 in various physico-geographic areas (East Fennoscandia, Northern Russian Plain, West Siberia, Central Siberia, North-Eastern Siberia, and Northern Pacific Region) in the Arctic, Subarctic, Northern-Central-Southern taiga, forest-steppe, and steppe in Northern Russia. A total of 251 strains were isolated from 1391,900 mosquitoes, identified as the California group snowshoe hare (83), Inkoo (44), and Tahyna (2) viruses; 122 strains were not completely identified. Some of the strains with uncommon antigenic composition can be natural reassortants. Fifty-two percent of strains were isolated from Aedes communis and the associate species of mosquitoes, other hosts were A. excrucians (8%), A. cantans (6.25%), A. flavescens (6.25%), A. ciprius (6.25%), A. punctor (4.5%), A. vexans (4.5%), A. cataphylla (3.6%), A. nigripes (3.6%), and A. hexodontus (2.6%). The infection rate of mosquitoes was 0.009% in the tundra, 0.012% in forest-tundra, 0.01% in Northern taiga, 0.02% in Central taiga, 0.017% in Southern taiga, 0.026% in forest-steppe, and 0.097% in steppe. The epidemic season is one month in the tundra (from the beginning of July till the beginning of August), two months in Northern taiga (July-August), and three months in Central taiga (from the second half of June till the beginning of September). The highest infection rate of mosquitoes was observed at the end of the epidemic season in all regions. SSH strains prevailed to the East from the Enisei river, whereas to the West and in the Subarctic regions INK virus predominated, SSH being rare; in the taiga the distribution was quite the opposite. TAH virus was virtually absent. Human morbidity was observed in all territories studied. The immune stratum of adult population is about 30% in the tundra and forest-tundra and about 50% in Northern and Central taiga.

Registration and alignment of three-dimensional images: an interactive visual approach.

A three-dimensional registration and alignment algorithm was developed to align single photon emission computed tomography examinations and magnetic resonance images. Operators manipulated images interactively with real-time visual feedback, with use of both internal and surface features to achieve accurate alignment. Operators aligned five brain phantom examinations (accuracy, 1.6 pixels; consistency, 0.7 pixels) and eight patient brain examinations (consistency, 0.5 pixels).

Paracrine regulation of the renal microcirculation.

There has been an explosive growth of interest in the multiple interacting paracrine systems that influence renal microvascular function. This review first discusses the membrane activation mechanisms for renal vascular control. Evidence is provided that there are differential activating mechanisms regulating pre- and postglomerular arteriolar vascular smooth muscle cells. The next section deals with the critical role of the endothelium in the control of renal vascular function and covers the recent findings related to the role of nitric oxide and other endothelial-derived factors. This section is followed by an analysis of the roles of vasoactive paracrine systems that have their origin from adjoining tubular structures. The interplay of signals between the epithelial cells and the vascular network to provide feedback regulation of renal hemodynamics is developed. Because of their well-recognized contributions to the regulation of renal microvascular function, three major paracrine systems are discussed in separate sections. Recent findings related to the role of intrarenally formed angiotensin II and the prominence of the AT1 receptors are described. The possible contribution of purinergic compounds is then discussed. Recognition of the emerging role of extracellular ATP operating via P2 receptors as well as the more recognized functions of the P1 receptors provides fertile ground for further studies. In the next section, the family of vasoactive arachidonic acid metabolites is described. Possibilities for a myriad of interacting functions operating both directly on vascular smooth muscle cells and indirectly via influences on endothelial and epithelial cells are discussed. Particular attention is given to the more recent developments related to hemodynamic actions of the cytochrome P-450 metabolites. The final section discusses unique mechanisms that may be responsible for differential regulation of medullary blood flow by locally formed paracrine agents. Several sections provide perspectives on the complex interactions among the multiple mechanisms responsible for paracrine regulation of the renal microcirculation. This plurality of regulatory interactions highlights the need for experimental strategies that include integrative approaches that allow manifestation of indirect as well as direct influences of these paracrine systems on renal microvascular function.