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PubMed2005

The CLIP-170 homologue Bik1p promotes the phosphorylation and asymmetric localization of Kar9p.

Accurate positioning of the mitotic spindle in Saccharomyces cerevisiae is coordinated with the asymmetry of the two poles and requires the microtubule-to-actin linker Kar9p. The asymmetric localization of Kar9p to one spindle pole body (SPB) and microtubule (MT) plus ends requires Cdc28p. Here, we show that the CLIP-170 homologue Bik1p binds directly to Kar9p. In the absence of Bik1p, Kar9p localization is not restricted to the daughter-bound SPB, but it is instead found on both SPBs. Kar9p is hypophosphorylated in bik1delta mutants, and Bik1p binds to both phosphorylated and unphosphorylated isoforms of Kar9p. Furthermore, the two-hybrid interaction between full-length KAR9 and the cyclin CLB5 requires BIK1. The binding site of Clb5p on Kar9p maps to a short region within the basic domain of Kar9p that contains a conserved phosphorylation site, serine 496. Consistent with this, Kar9p is found on both SPBs in clb5delta mutants at a frequency comparable with that seen in kar9-S496A strains. Together, these data suggest that Bik1p promotes the phosphorylation of Kar9p on serine 496, which affects its asymmetric localization to one SPB and associated cytoplasmic MTs. These findings provide further insight into a mechanism for directing centrosomal inheritance.

Cell Proliferation↗
PubMed1989

Hypotensive effects of the lipoxygenase inhibitor phenidone in two-kidney, one clip Goldblatt hypertension.

This study examined the role of the lipoxygenase (LO) pathway in the maintenance of hypertension in rats with two-kidney, one clip (2K,1C) Goldblatt hypertension. A single dose of the lipoxygenase blocker phenidone was injected intraperitoneally to 2K,1C rats during the early phase (14 days) of the development of hypertension (mean intraarterial blood pressure 137 +/- 3.9 mm Hg). Phenidone (60 mg/kg) markedly decreased arterial pressure to nadir levels of 58.9% of resting blood pressure. The maximal changes were observed 15 min after injection and the hypotensive response was sustained for at least 2 h. Plasma renin concentration (PRC) increased from 74.3 +/- 18.9 to 281.0 +/- 6.5 ng/mL/h after injection (P less than .05). Thus, the hypotensive effect of phenidone was not due to suppression of renin secretion but presumably due to inhibition of its effects. It is suggested that arachidonate metabolites of the LO pathway at the vascular bed may be involved in maintenance of high arterial pressure in 2K,1C renovascular hypertension in rat.

Animals↗
PubMed1991

Renal function in one-kidney, one-clip hypertension and low renin essential hypertension.

One-kidney, one-clip hypertension (1-K, 1-C HT) is initiated by increased preglomerular resistance which decreases nephron perfusion and causes several intrarenal changes that lead to increased mean arterial pressure (MAP). Elevated MAP serves to return nephron perfusion and sodium excretion to normal, so that fluid intake and output are balanced. Increased MAP usually occurs through volume homeostasis mechanisms that initially raise cardiac output and later elevate total peripheral vascular resistance via autoregulatory adjustments. However, if adequate volume is unavailable because of sodium restriction, sustained activation of the renin-angiotensin system increases blood pressure sufficiently to restore nephron perfusion. Thus, depending upon the availability of volume, renal perfusion and sodium balance can be restored either by volume retention or by increased angiotensin II (ANGII) formation and peripheral vasoconstriction. Similarities exist between 1-K, 1-C HT and low-renin essential hypertension (LRHT). In both cases, renal-pressure natriuresis is shifted to higher levels and there are marked increases in preglomerular resistance that necessitate increased MAP to maintain sodium balance. However, in 1-K, 1-C HT, there is a parallel shift of pressure natriuresis with little or no change in the slope of this curve, similar to that found in the normal-renin essential hypertension. In LRHT the slope of pressure natriuresis is decreased, indicating that blood pressure is much more salt sensitive than normal. Another difference is that PRA is low compared to normal PRA in 1-K, 1-C HT after compensatory increases in MAP. There is also no indication of glomerular membrane damage in 1-K, 1-C HT, whereas LRHT may have significant glomerulopathy, especially as hypertension progresses. These differences suggest that there may be additional factors besides preglomerular vasoconstriction involved in the etiology of LRHT. One possible factor is a reduction in nephron number in LRHT. Decreased functional nephrons would lead to glomerular hyperfiltration and increased distal tubular flow rate in the remaining nephrons, causing decreased PRA and eventually glomerular damage. Increased fractional sodium reabsorption, particularly in distal tubular segments, could also contribute to decreased PRA and cause blood pressure to be salt sensitive. These abnormalities, along with preglomerular vasoconstriction, may explain many of the characteristics of LRHT.

Animals↗
PubMed1991

On the role of renin in one-kidney, one-clip hypertension.

It is known that the renin angiotension system as it is usually understood is not the mediator of experimental one-kidney, one-clip (1K,1C) hypertension in animals. There is also ample evidence that the blood pressure of dogs and rabbits with this form of hypertension can be lowered by immunization with hog renin, which implies that renin is the mediator. In an effort to resolve this contradiction, we searched for a second hypertensive substance which we thought may have been present in the crude hog kidney extracts that had been used to immunize the hypertensive animals. Instead, we ultimately discovered that the blood pressure of hypertensive rabbits could be lowered by immunization with pure hog renin. This remarkable finding could be explained if renin were transformed in vivo, exhibiting new antigenic sites and eliciting a second antihypertensive antibody. We found such an antibody. When free of antirenin, it lowered the blood pressure of 1K,1C hypertensive rabbits. The same antibody stained the cytoplasm of vascular smooth muscle cells and certain other cells in the tissues of normal and hypertensive rabbits. The presence of this transformed renin in the tissues of the rabbit was confirmed by chronic infusion of 125I-labeled renin into hypertensive rabbits. A significant portion of the radioactivity was found to be incorporated into a very high molecular weight, insoluble form. Its function in this location is unknown but must directly or indirectly involve vasoconstriction since its neutralization by specific antibody lowers the blood pressure of 1K,1C hypertensive rabbits.

Animals↗
PubMed1991

Parathyroid hypertensive factor is present in DOCA-salt but not two-kidney-one-clip hypertensive rats.

In order to determine whether the expression of parathyroid hypertensive factor (PHF) is secondary to hypertension or whether it is specifically related to low-renin hypertension, PHF levels were measured in DOCA-salt and two-kidney-one-clip (2K-1C) hypertensive rats. Despite equivalent elevations of blood pressure, PHF was detected in the DOCA-salt rats, but not in the 2K-1C rats (17.5 +/- 3.1 mm Hg, P less than .0001 v 0.9 +/- 2.8 mm Hg, P = NS, respectively). Moreover, PHF levels correlated with mean arterial pressure in the DOCA-salt group (r = 0.91, P less than .0001). We conclude that PHF expression is not a secondary phenomenon caused by hypertension, but rather may be causally related to the development of low-renin forms of hypertension.

Animals↗
PubMed2003

GSCope: a clipped fisheye viewer effective for highly complicated biomolecular network graphs.

UNLABELLED: A graphical tool to visualize highly complicated biomolecular network graphs is described. It helps us to understand the graphs from macroscopic and microscopic viewpoints by incorporating continuous transition from global to clipped hyperbolic projection. GSCope also helps us to find a molecule in the graphs by offering several searching functions. It is useful to publish biomolecular network graphs on the internet. AVAILABILITY: GSCope is available at http://gscope.gsc.riken.go.jp.

Computer Graphics↗
PubMed1990

Anaesthesia for simultaneous caesarean section and clipping of intracerebral aneurysm.

A 38-yr-old woman who was 35 weeks pregnant presented with a subarachnoid haemorrhage, secondary to a ruptured anterior communicating artery aneurysm. Following initial recovery, she subsequently underwent simultaneous elective Caesarean section and clipping of the aneurysm. The anaesthetic management of the case is described and discussed.

Adult↗
PubMed2006

Development of torsade de pointes caused by exacerbation of QT prolongation during clipping of cerebral artery aneurysm in a patient with subarachnoid haemorrhage.

We report the case of a 79-yr-old woman with subarachnoid haemorrhage (SAH) in whom torsade de pointes (TdP) caused by worsening the QT prolongation occurred during clipping of cerebral artery aneurysm. This patient shows a potential risk of occurrence of life-threatening tachyarrhythmia, TdP by prolonging the QT interval during surgery in patients with SAH even with no additional factors that predispose to TdP. Therefore, a proper monitoring of the QT interval is necessary as a predictor of TdP. When ventricular tachyarrhythmia occurs, recognition of TdP is important because antiarrhythmic drug therapy for TdP is different from that for ventricular tachyarrhythmias that is not TdP.

Aged↗
PubMed1980

A rare-male advantage in the housefly induced by wing clipping and some general considerations for Drosophila.

Multiple-choice crosses among five geographic strains of the housefly, Musca domestica L., were carried out in equal (10:10) and low-frequency (4:16) ratios. Initially, a low-frequency-male mating advantage was apparent, but further analyses related this minority advantage to a reduction of male mating success during marking by wing clipping. When there are fluctuating differences in the level of sexual vigor between competing male types over replicate trials of a cross, a mating advantage will accrue to the minority type. Even if males from the two competing strains are equally vigorous, such fluctuating differences will occur during sampling of flies. Harming the flies during marking will serve to enhance this effect and make significant departures toward greater mating success of rare males highly likely. This statistical bias in favor of minority males was substantiated in simulations of the KENCE-BRYANT model of mating success and compared with our results of a minority advantage in the housefly and with published results of a minority advantage in Drosophila. Our evidence, though circumstantial, that an advantage to minority males could have been induced by such an experimental bias suggests that a re-examination of existing data, as well as new experimentation, is necessary to discern whether or not a real rare-male advantage exists.

Animals↗
PubMed2006

Nitric oxide mediates the blood-pressure lowering effect of garlic in the rat two-kidney, one-clip model of hypertension.

Garlic reduces blood pressure (BP) in two-kidney, one-clip (2K-1C) rats, and enhances nitric oxide (NO) synthesis in in vivo and in vitro experiments. NO is an important modulator of BP in the 2K-1C model. This study investigated the role of NO in the BP-lowering effect of garlic in the 2K-1C model. BP readings (mm Hg) were obtained from 2K-1C rats in 4 groups treated intraperitoneally for 2 wk with either normal saline (NS), garlic, L-nitroarginine-methylester (L-NAME), or L-NAME+garlic (n=4x5). BP was determined using the tail-cuff method and compared with data of 4 similarly treated groups of normal (unclipped) rats (NRs). The BP readings of NR groups were 120+/-3 mm Hg for the NS-treated group, 120+/-2 mm Hg for the garlic-treated group, 167+/-3 mm Hg for the L-NAME treated group (higher than NS or garlic, P<0.001) and 128+/-5 mm Hg for the garlic+L-NAME-treated group (lower than L-NAME, P<0.001). The BP readings of 2K-1C rat groups were: for the NS group, 169+/-6 mm Hg (higher than NRs, P<0.001); for the garlic group, 116+/-7 mm Hg (lower than NS, P<0.001); for the L-NAME group: 184+/-8 mm Hg (higher than garlic, P<0.001), and for the L-NAME+garlic group: 130+/-6 mm Hg (lower than garlic or NS, P<0.001). The data show that L-NAME increases the BP of both NRs and 2K-1C rats, with the rise more evident in the NRs (39 vs. 9%, respectively). Garlic counteracts the hypertensive effect of L-NAME in NRs as well as 2K-1C rats. We conclude that the BP-lowering effect of garlic in the rat 2K-1C model may be partly mediated through the NO pathway.

Analysis of Variance↗
PubMedDate not supplied

Use of vascular clips to approximate skin grafts.

During excisions of acute burn wounds, attention to aesthetic detail often is secondary to the goal of rapid gross coverage. Expeditious approximation of adjacent skin grafts has long presented a problem to surgeons. Some surgeons simply place the grafts next to each other, relying on the intervening areas to "scar in". Others use staples to hold grafts together. These staples, however, can become buried under healed grafts and can cause "foreign body" reactions in the months and years ahead. In addition, staples cause bleeding beneath the newly placed grafts, contributing to hematoma formation. Still other surgeons suture or tape adjacent pieces of skin graft together, a tedious exercise. The cosmetic result of these techniques is often less than optimal resulting in the unfortunately familiar "patchwork quilt" appearance of grafts interweaved among scars. Vascular clips have proven to be useful for holding adjacent pieces of skin graft together.

Burns↗
PubMed1983

Effects of captopril on vascular noradrenergic transmission during the development of two-kidney, one clip Goldblatt hypertension in rats.

Vascular noradrenergic transmission and the effect of captopril on this transmission were examined in the blood perfused rat mesenteric vasculature in situ during the development of two-kidney, one clip Goldblatt hypertension. Three groups of rats including sham operated, 6-8 day hypertensive and 4-6 week hypertensive were studied. Mean blood pressures during anaesthesia were 90.0 +/- 2.0, 119.7 +/- 4.7 and 131.8 +/- 6.8 mmHg in the three groups, respectively. Mesenteric vasoconstrictor responses to norepinephrine were significantly potentiated in both of the hypertensive groups relative to the sham group. Mesenteric vasoconstrictor responses to nerve stimulation were similar in the sham and 6-8 day hypertensive groups. However, responses to nerve stimulation were significantly potentiated in the 4-6 week hypertensive group relative to the sham group. Captopril (1 mg/kg, i.v.) lowered mean blood pressure in all groups, equalizing blood pressure in the 6-8 day hypertensive and sham groups. However, the blood pressure in the 4-6 week hypertensive rats remained significantly elevated after 1 mg/kg captopril. An additional dose of captopril did not lower blood pressure further in this group. Mesenteric vasoconstrictor responses to nerve stimulation and norepinephrine in the three groups were minimally affected by captopril, with significant differences between control and captopril-treated responses occurring randomly at a point or two in a dose-response or frequency-response curve for a given group. The differences in vascular responsiveness to nerve stimulation and norepinephrine between the hypertensive and sham groups continued to be evident after captopril.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1986

Sympathomedullary activity in one-kidney, one clip hypertensive rats.

In order to evaluate more directly the implications of the sympatho-adrenal system in one-kidney, one clip hypertension (1K1C), we studied adrenal catecholamine synthesis after a bolus injection of 3H-tyrosine, tissue norepinephrine and dopamine concentrations, as well as the urinary excretions of norepinephrine, epinephrine, dopamine and those of the major dopamine metabolites, dihydroxphenylacetic acid (DOPAC) and homovanillic acid (HVA) in 1K1C and control uninephrectomized rats. When compared with controls, the hypertensive rats had a markedly enhanced formation of adrenal 3H-norepinephrine and 3H-epinephrine, higher urinary norepinephrine and epinephrine excretions but lower heart and kidney content of norepinephrine and dopamine as well as decreased urinary excretions of the main dopamine metabolites, DOPAC and HVA. These data suggest an increased norepinephrine and epinephrine synthesis in 1K1C hypertensive rats associated with dopamine synthesis, which is normal but probably disproportionally low relative to the synthesis of norepinephrine and epinephrine. This abnormality may be an important pathogenetic factor in this model of experimental hypertension.

Adrenal Glands↗
PubMed1987

Elevated vascular angiotensin converting enzyme in chronic two-kidney, one clip hypertension in the dog.

The possible role of the vascular angiotensin converting enzyme (ACE) in the development of two-kidney, one clip (2-K, 1C) hypertensive dogs was studied in different blood vessels. Vascular ACE activity per mg protein differed in a variety of blood vessels; the activity appeared to vary inversely with the outer diameter of arteries. The systemic blood pressure in mongrel dogs increased after partial occlusion of the left renal artery, and the hypertension lasted for 8 months. Plasma renin activity (PRA) was raised only for the first 4 weeks after the operation and then returned to the original level in the chronic stage of hypertension. Plasma ACE activity did not alter during the experimental period. In contrast, ACE activities in the jejunal, pulmonary and renal arteries, aorta, lung and cerebral cortex, significantly increased in the chronic hypertensive stage (8 months after occlusion). The production of angiotensin II (ANG II) from ANG I was significantly greater in isolated arteries from 8-month hypertensive dogs than in those from normotensive dogs when assessed by the contractile responses to ANG I and ANG II. These results indicate that acceleration by increased vascular ACE activity of the production of ANG II in the vascular wall may contribute to the maintenance of hypertension in the chronic stage of 2-K, 1C hypertensive dogs having normal PRA and plasma ACE activity.

3-Mercaptopropionic Acid↗
PubMed1990

Arterial disease of the iris predicts visceral arterial necrosis in rabbits with acute one-kidney, one clip hypertension: comparisons with acute one-kidney, one wrapped hypertension.

Tortuosity, dilations, aneurysms and satellite hemorrhages consistently develop in the circular arteries of the iris of rabbits with acute one-kidney, one clip (1K1C) malignant hypertension. These lesions are easily visualized, quantitated and monitored during life. Graded iridoarteriopathy correlates directly with visceral arterial necrosis (r15 = 0.843; P less than 0.001), final indirect blood pressure (r15 = 0.591; P less than 0.02) and cardiac hypertrophy (r15 = 0.565; P less than 0.02). Arterial necrosis in the irises and other viscera in acute 1K1C hypertension in rabbits is qualitatively similar to that occurring in rabbits with acute one-kidney, one wrapped (1K1W) hypertension with regard to both the histological features and organ distribution. However, over three times as many arterial lesions occur in rabbits with acute 1K1W hypertension as occur in those with acute 1K1C hypertension (P less than 0.001). Since blood pressure elevation does not correlate with graded iridoarteriopathy or with visceral arterial necrosis in 1K1W rabbits, factors other than blood pressure elevation appear to be especially important in the pathogenesis of arterial necrosis in the 1K1W model. On the other hand, the present study indicates that high grade iridoarteriopathy appears to be indicative of a high risk of cerebral hemorrhage in 1K1C rabbits, as earlier studies have shown for 1K1W rabbits.

Animals↗
PubMed1993

Heterogeneous regulation of renal atrial natriuretic factor receptor subtypes in one-kidney, one clip hypertensive rats.

OBJECTIVES: To investigate the regulation of papillary atrial natriuretic factor (ANF) receptors and the differential regulation of glomerular ANF receptor subtypes in one-kidney, one clip (1-K,1C) hypertension. METHODS: Plasma immunoreactive ANF levels and atrial and ventricular ANF content were measured in 1-K,1C rats and their normotensive uninephrectomized controls. Glomerular and papillary ANF receptor subtypes were characterized by competitive radioligand binding assay. Stimulation of cyclic GMP (cGMP) production, by increasing ANF doses, was examined in isolated glomeruli. RESULTS: Plasma amino-terminal ANF levels were higher in 1-K,1C than in control rats. ANF concentrations in the left atrium were lower and ventricular ANF concentrations were higher in the 1-K,1C group. Competition binding curves for glomerular membranes revealed the presence of two binding sites (ANF-R1 and ANF-R2) in both groups. Total glomerular ANF receptor density was lower in 1-K,1C rats than in their normotensive controls. Both receptor subtypes were downregulated in 1-K,1C rats and their relative proportion was similar to that in glomerular preparations from the controls. ANF-stimulated cGMP production by isolated glomeruli was lower in 1-K,1C than in normotensive rats. In papillary membranes, ANF was bound to a homogeneous population of high-affinity binding sites in both groups. A modest augmentation in the density of papillary ANF receptors was observed in 1-K,1C rats. CONCLUSION: Glomerular and papillary ANF receptors may be regulated differently in the presence of elevated plasma ANF levels. The present results indicate that the downregulation of glomerular ANF-R1 and the reduced cGMP response may lead to altered sodium and water handling by the kidney of 1-K,1C hypertensive rats.

Animals↗
PubMed1993

The role of activated vascular angiotensin II generation in vascular hypertrophy in one-kidney, one clip hypertensive rats.

OBJECTIVE: To investigate the role of vascular angiotensin II (Ang II) in the vascular thickening of one-kidney, one clip (1-K, 1C) hypertensive rats, which show normal plasma renin activity. METHODS: The type 1 Ang II receptor antagonist TCV-116 (1 mg/kg per day), the angiotensin converting enzyme (ACE) inhibitor delapril (20 mg/kg per day), hydralazine (20 mg/kg per day) or vehicle were administered to four groups of 1-K, 1C rats aged 6-10 weeks. Vehicle was also given to uninephrectomized rats. RESULTS: The aortae of 1-K, 1C rats contained significantly higher levels of Ang II than those of uninephrectomized rats and showed hypertrophy, but not hyperplasia of their medial smooth muscle cells. Hypertrophy was estimated by immunohistochemical staining of alpha-actin. Hyperplasia was estimated by DNA content and incorporation of 5-bromo-2'-deoxyuridine. The blood pressure of the 1-K, 1C rats was not affected by either TCV-116 or delapril, even at doses sufficient to induce depressor effects in spontaneously hypertensive rats. However, subdepressor doses of TCV-116 and delapril both significantly reduced the alpha-actin-stained area to 78 and 73%, respectively, of that in the 1-K, 1C rats, whereas a depressor dose of hydralazine did not affect the alpha-actin-stained area. The level of Ang II in the aorta, but not in plasma, was suppressed by delapril but not by hydralazine. CONCLUSIONS: These results suggest strongly that vascular Ang II plays a major role in the development of vascular hypertrophy, independently of plasma Ang II, bradykinin and ACE-independent pathways of Ang II generation, and in the regulation of blood pressure in this normoreninaemic hypertensive model.

Actins↗