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Mechanism and prevention of enlargement or new development of aneurysm following treatment by clipping or coiling.

The mechanisms of cerebral aneurysm recurrence and enlargement were investigated in 11 patients: two with dissecting aneurysms, six with fully grown aneurysms after neck clipping, one with enlarged aneurysm after dome clipping, and two with enlarged aneurysm due to recanalization after GDC coil embolization. We concluded that it is fundamentally important to ensure complete attachment of the internal elastic lamina around the aneurysm neck by precise neck clipping and effective embolization, with accurate positioning of remaining internal elastic lamina.

Endothelium, Vascular↗

Thoracoscopic T2-sympathetic block by clipping--a better and reversible operation for treatment of hyperhidrosis palmaris: experience with 326 cases.

Although thoracoscopic sympathectomy or sympathicotomy is the best treatment for hyperhidrosis palmaris, a new approach of clipping only without transection of T2-sympathetic trunk is just as effective. Aside from the guaranteed cure of hyperhidrosis, this new method has fewer complications and has the advantage of recovery of the sympathetic tone in the hands if the procedure is reversed by the removal of the clips. Between March 18 and September 30 of 1996, 326 patients (190 female and 136 male with a mean age of 20.5 years) underwent thoracoscopic T2-sympathetic block by clipping to treat hyperhidrosis. Good results and few complications were noted during follow up six months to one year postoperatively. Five of the 326 patients, all female, had the operation reversed because of intolerable compensatory sweating. Three recovered from the compensatory sweating within two months and had less palmar sweating than before their sympathetic block; the fourth achieved relief of compensatory sweating after nine months, and the fifth reported no improvement.

Adolescent↗

Clipping versus coiling: neuropsychological follow up after aneurysmal subarachnoid haemorrhage (SAH).

Patients treated with microsurgical clipping of ruptured intracranial aneurysms often suffer from neuropsychological deficits in spite of a good neurological outcome. The purpose of this study was to explore if the deficits are related to the type of therapy. Two groups of 16 patients each suffering from aneurysmal SAH, matched for sex, age, aneurysm-site and Hunt and Hess score, and 16 control subjects were examined with a battery of neuropsychological tests including memory, attention, and executive function. Depression, mood, and quality of life were also assessed. One patient group had been treated with surgical clipping, the other with endovascular coiling. Both patient groups showed deficits in verbal and visual memory. Clipped patients were slightly more impaired than coiled patients, especially on measures of affect and on a self-assessment measure of executive function. The pattern of results suggests that the neuropsychological outcome after aneurysmal SAH is affected by both the severity of the bleeding and the type of therapy.

Affect↗

Alf1p, a CLIP-170 domain-containing protein, is functionally and physically associated with alpha-tubulin.

Tubulin is a heterodimer of alpha- and beta-tubulin polypeptides. Assembly of the tubulin heterodimer in vitro requires the CCT chaperonin complex, and a set of five proteins referred to as the tubulin cofactors (Tian, F., Y. Huang, H. Rommelaere, J. Vandekerckhove, C. Ampe, and N.J. Cowan. 1996. Cell. 86:287-296; Tian, G., S.A. Lewis, B. Feierbach, T. Stearns, H. Rommelaere, C. Ampe, and N.J. Cowan. 1997. J. Cell Biol. 138:821-832). We report the characterization of Alf1p, the yeast ortholog of mammalian cofactor B. Alf1p interacts with alpha-tubulin in both two-hybrid and immunoprecipitation assays. Alf1p and cofactor B contain a single CLIP-170 domain, which is found in several microtubule-associated proteins. Mutation of the CLIP-170 domain in Alf1p disrupts the interaction with alpha-tubulin. Mutations in alpha-tubulin that disrupt the interaction with Alf1p map to a domain on the cytoplasmic face of alpha-tubulin; this domain is distinct from the region of interaction between alpha-tubulin and beta-tubulin. Alf1p-green fluorescent protein (GFP) is able to associate with microtubules in vivo, and this localization is abolished either by mutation of the CLIP-170 domain in Alf1p, or by mutation of the Alf1p-binding domain in alpha-tubulin. Analysis of double mutants constructed between null alleles of ALF1 and PAC2, which encodes the other yeast alpha-tubulin cofactor, suggests that Alf1p and Pac2p act in the same pathway leading to functional alpha-tubulin. The phenotype of overexpression of ALF1 suggests that Alf1p can act to sequester alpha-tubulin from interaction with beta-tubulin, raising the possibility that it plays a regulatory role in the formation of the tubulin heterodimer.

Amino Acid Sequence↗

Role of dynein, dynactin, and CLIP-170 interactions in LIS1 kinetochore function.

Mutations in the human LIS1 gene cause type I lissencephaly, a severe brain developmental disease involving gross disorganization of cortical neurons. In lower eukaryotes, LIS1 participates in cytoplasmic dynein-mediated nuclear migration. We previously reported that mammalian LIS1 functions in cell division and coimmunoprecipitates with cytoplasmic dynein and dynactin. We also localized LIS1 to the cell cortex and kinetochores of mitotic cells, known sites of dynein action. We now find that the COOH-terminal WD repeat region of LIS1 is sufficient for kinetochore targeting. Overexpression of this domain or full-length LIS1 displaces CLIP-170 from this site without affecting dynein and other kinetochore markers. The NH2-terminal self-association domain of LIS1 displaces endogenous LIS1 from the kinetochore, with no effect on CLIP-170, dynein, and dynactin. Displacement of the latter proteins by dynamitin overexpression, however, removes LIS1, suggesting that LIS1 binds to the kinetochore through the motor protein complexes and may interact with them directly. We find that of 12 distinct dynein and dynactin subunits, the dynein heavy and intermediate chains, as well as dynamitin, interact with the WD repeat region of LIS1 in coexpression/coimmunoprecipitation and two-hybrid assays. Within the heavy chain, interactions are with the first AAA repeat, a site strongly implicated in motor function, and the NH2-terminal cargo-binding region. Together, our data suggest a novel role for LIS1 in mediating CLIP-170-dynein interactions and in coordinating dynein cargo-binding and motor activities.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Three-stranded clip of the oligonucleotide 5'-(dT)10pO(CH2CH2O)3p(dT)10pO(CH2CH2O)3p(dA)10-3'.

Temperature dependence of UV and CD spectra of the oligonucleotide 5'-(dT)10-L-(dT)10-L-(dA)10-3' [tripl(ATT)] [L = -pO(CH2CH2O)3p-] in phosphate buffer, pH 7, at various NaCl concentrations and in the presence or absence of 0.01 M MgCl2 has been studied. At low oligonucleotide concentrations (2.2 x 10(-5) M nucleotide concentration) all structural transitions proceed intramolecularly. Tripl(ATT) exists in three forms: as a three-stranded clip (at low temperatures), a double-stranded hairpin (at intermediate temperatures), and as an open strand (at high temperatures). Thermodynamic parameters of the triplex formation depending on the NaCl concentration were calculated. The CD spectra were assigned to the single-, double-, and three-stranded forms. Ethidium bromide (EtBr) binding to the three-stranded clip was studied. Ethidium bromide molecules were shown to intercalate into the triple helix with the stable complex formation (association constant is 10(6)). One molecule of three-stranded clip binds not more than three EtBr molecules. The proposed synthetic model (oligonucleotide blocks coupled by hydroxyalkyl chains) has been shown to be convenient for studies of the physical and chemical properties of the triplex and other multistranded complexes of DNA.

Base Composition↗

Ureteral pseudodiverticulum associated with absorbable suture clips after laparoscopic pyeloplasty: case report.

A 48 year-old woman with pyelonephritis was found to have bilateral ureteropelvic junction (UPJ) obstruction and a nonfunctioning right kidney. She initially underwent a laparoscopic left nondismembered pyeloplasty using absorbable polydioxanone Lapra-Ty suture clips (Ethicon Endosurgery, Cincinnati, OH) to secure the anastomosis. An antegrade endopyelotomy was later necessitated. Both procedures were complicated by postoperative bacteruria and funguria. She then underwent a laparoscopic dismembered pyeloplasty, again utilizing Lapra-Ty suture clips to secure the anastomosis. Postoperatively, her course was complicated by anastomotic extravasation, bacteriuria, and funguria. Subsequently, an antegrade nephrostogram revealed a 2.5-cm diverticulum just distal to the UPJ, which contained numerous 2- to 4-mm filling defects. Nephroscopic exploration of the pseudodiverticulum revealed numerous Lapra-Ty clips, which were basket extracted. The pseudodiverticulum was fulgurated with a holmium laser. She eventually had restricturing with recurrence of the pseudodiverticulum and was treated successfully by open ureterocalicostomy.

Anastomosis, Surgical↗

An altered invariant chain protein with an antigenic peptide in place of CLIP forms SDS-stable complexes with class II alphabeta dimers and facilitates highly efficient peptide loading.

We report an experimental system for abundant expression of specific peptide-class II complexes in vivo and in vitro. We have constructed a cassette which allows for the replacement of the CLIP region of invariant chain (Ii) with an antigenic peptide. In fibroblasts expressing an altered Ii protein, in which CLIP has been replaced with peptide 52-68 from the class II I-E alpha chain (pEalpha), pEalpha-I-Ab complexes are formed with high efficiency. This peptide loading occurs in the endoplasmic reticulum (ER) when the Ii:pEalpha fusion protein associates with the I-Ab alpha and beta chains. The trimeric complexes of Ii:pEalpha and I-Ab molecules are stable in SDS and can be detected by the pEalpha-I-Ab-specific mAb, YAe, indicating that pEalpha is bound in the class II groove in the context of full-length Ii. These data strongly suggest that the CLIP region of intact Ii prevents peptide loading in the ER by binding in the peptide binding groove of newly synthesized class II alphabeta dimers.

Amino Acid Sequence↗

Mechanisms of DNA cleavage by copper complexes of 3-clip-phen and of its conjugate with a distamycin analogue.

Mechanisms of DNA oxidation by copper complexes of 3-Clip-Phen and its conjugate with a distamycin analogue, in the presence of a reductant and air, were studied. Characterisation of the production of 5-methylenefuranone (5-MF) and furfural, associated with the release of nucleobases, indicated that these copper complexes oxidised the C1' and C5' positions of 2-deoxyribose, respectively, which are accessible from the DNA minor groove. Oxidation at C1' was the major degradation route. Digestion of DNA oxidation products by P1 nuclease and bacterial alkaline phosphatase allowed characterisation of glycolic acid residues, indicating that these copper complexes also induced C4' oxidation. However, this pathway was not associated with base propenal release. The ability of the copper complex of the 3-Clip-Phen conjugate with the distamycin analogue to produce sequence-selective DNA cleavage allowed confirmation of these mechanisms of DNA oxidation by PAGE. Comparison of DNA cleavage activity showed that conjugation of 3-Clip-Phen with a DNA minor groove binder, like the distamycin analogue, decreased both its ability to perform C1' oxidation as well as the initial rate of the reaction, but this conjugate is still active after 5 h at 37 degrees C, making it an efficient DNA cleaver.

Animals↗

Leukocyte infiltration and ICAM-1 expression in two-kidney one-clip hypertension.

How an increase in blood pressure, in and of itself, induces hypertensive nephrosclerosis is unclear. In an earlier study we found that leukocyte infiltration, proximal tubular cell proliferation, matrix deposition and interstitial fibrosis occur in the unclipped kidney of 2 K 1 C Goldblatt hypertensive rats. In this study we tested the hypothesis that the cell surface adhesion molecule ICAM-1 is expressed on the vascular endothelium and tubular epithelium of unclipped kidneys at 4 weeks. As a positive control, we examined the clipped kidney as well. We found that systolic blood pressure was significantly elevated in renovascular hypertensive rats compared to sham-operated controls after 4 weeks (198 +/- 5 mmHg vs 121 +/- 2 mmHg, P < 0.001). Furthermore, quantitative (densitometry) measurements showed that ICAM-1 expression on vascular endothelium and on tubular cells was significantly increased in unclipped kidneys compared to controls (P < 0.05). The same was true for monocyte and granulocyte infiltration (P < 0.05). These same variables were even more prominent in the clipped kidneys, compared to unclipped and control kidneys (P < 0.05). Our data show that ICAM-1 is expressed in unclipped kidneys exposed to hypertension as well as in clipped kidneys exposed to ischemia. We suggest that mechanical injury induced by increased blood pressure is responsible for an inflammatory adhesion molecule-mediated response and concomitant renal injury.

Animals↗

Introduction of patient video clips into computer-based testing: effects on item statistics and reliability estimates.

PURPOSE: Using patient video clips to evaluate examinees' skills in interpreting physical examination findings is possible with computer-based testing, but the psychometric properties of video-based questions are unknown. METHOD: We developed parallel test questions incorporating video clips or text descriptions of abnormal neurologic findings and administered them to 106 fourth-year medical students finishing their Neurology Clerkship. RESULTS: Overall, video-based questions had comparable difficulty and discrimination compared to analogous text-based questions. Preliminary studies indicated similar reliability with text- and video-based questions. CONCLUSIONS: The inclusion of patient video clips in computer-based testing is feasible from technical, practical, and psychometric perspectives. Further study is needed to gather validity evidence for this novel question format.

Clinical Clerkship↗

Hypopituitarism after surgical clipping of a ruptured cerebral aneurysm.

OBJECTIVE: The causes of hypopituitarism in adult life are most frequently cerebral tumors, pituitary infarction, head trauma, pituitary surgery, or irradiation. We report a case of hypopituitarism after surgical clipping of a ruptured cerebral aneurysm. Two previous cases after the rupture of a cerebral aneurysm have been reported. DESIGN: Case report. PATIENTS: One 42-yr-old man. MEASUREMENTS AND MAIN RESULTS: A 42-yr-old man was admitted as an emergency for unconsciousness. The computed tomography showed a massive subarachnoid hemorrhage, and specific angiography showed an aneurysm in the internal carotid. The aneurysm was successfully clipped through craniotomy. The patient's hospital course was marked by a few episodes of pulmonary infection, and a tracheotomy was performed. The patient was transferred to the rehabilitation unit; he received a rating of 9 on the Glasgow Coma Scale. Seven months after rupture of the aneurysm, the patient was readmitted to the intensive care unit for septic shock, with pulmonary infection associated with vomiting and diarrhea. Despite standard therapy and inotropic support, there was no improvement of his clinical condition. Adrenal failure was then suspected. Treatment was started immediately with hydrocortisone (50 mg) four times a day. Within hours, his clinical condition improved. The following month, the patient was weaned off his tracheotomy and had nearly recovered. Endocrine tests confirmed the cortisol insufficiency but also hypothyroidism and hypogonadotropic hypogonadism secondary to hypopituitarism. CONCLUSION: Our case is the first one reported of hypopituitarism after surgical clipping of a ruptured cerebral aneurysm.

Adult↗

Central and peripheral catecholamine synthesizing enzymes during the development of two-kidney, one clip hypertension in rats.

The activities of the catecholamine synthesizing enzymes have been determined in discrete brain areas and in peripheral tissues of rats, at different times after clipping the left renal artery (two-kidney Goldblatt hypertension, 2KGH) and in sham operated animals. Three days after clipping the only enzymatic change was a slight decrease in plasma dopamine-beta-hydroxylase (DBH) activity. Ten days after clipping no change in enzymatic activity was found at the central level. However, the DBH and the phenylethanolamine-N-methyltransferase (PNMT) activities were increased in the adrenal medulla (+49.0%, P less than 0.001 and +36.6%, P less than 0.001, respectively) and DBH activity was also increased in the superior cervical ganglia (+22.8%, P less than 0.01). These data suggest that sympathetic hyperactivity is present in 2KGH rats when hypertension is established. In addition, as this type of hypertension does not alter the PNMT activity in brainstem areas, it seems that the alterations in PNMT activity reported for genetically hypertensive rats are unlikely to be secondary to the elevated blood pressure.

Adrenal Medulla↗

Unclipping of two-kidney, one clip hypertensive rats produces endothelium-dependent inhibition of sympathetic vasoconstriction.

Removal of the renal artery-constricting clip in two-kidney, one clip (2-K,1C) Goldblatt-hypertensive rats produces a rapid fall in blood pressure which has been attributed to the release of vasodepressor lipids from the renal medulla. The aim of this study was to demonstrate the effect of unclipping 2-K,1C hypertensive rats, and of any hormone thereby released, on vasoconstrictor responses to sympathetic stimulation in the ex vivo blood-perfused tail artery, as well as the role of the vascular endothelium in mediating this effect. Blood was withdrawn at a rate of 2 ml/min from the carotid artery of an anaesthetized 2-K,1C rat and used to perfuse, via an extracorporeal circuit, a cannulated segment of tail artery which had been taken from a killed, normal rat and mounted in an organ bath. The blood was returned to the 2-K,1C rat via the jugular vein. Vasoconstriction and increases in perfusion pressure were produced by periarterial electrical stimulation of the tail artery. The tail artery was either intact or had had its endothelium removed. Sham operations which did not remove the renal artery clip did not change blood pressure or vasoconstrictor responses. Unclipping lowered blood pressure and reduced vasoconstrictor responses in ex vivo blood-perfused tail arteries in which the endothelium was intact, but did not decrease responses in tail arteries from which the endothelium had been removed. It is concluded that unclipping releases a hormone which lowers blood pressure and inhibits sympathetic vasoconstrictor responses via an endothelium-dependent mechanism.

Animals↗

Changes in gene expression of the renin-angiotensin system in two-kidney, one clip hypertensive rats.

To investigate the molecular mechanism of sustained hypertension in two-kidney, one clip (2K1C) hypertensive rats, possible changes in renin gene expression in the kidney and angiotensinogen in the liver were studied. In 2K1C rats 4 weeks after clipping, the plasma renin and angiotensin II levels were significantly higher than those in sham-operated rats, but the plasma angiotensinogen levels were similar in the two groups. At this time, expression of the renin gene in the ischaemic kidney of 2K1C rats was 2.6-times that in sham-operated rats (P less than 0.05), but expressions of the angiotensinogen gene were similar in the two groups. Sixteen weeks after clipping, the plasma renin and angiotensin II levels in 2K1C rats were not significantly higher than those in sham-operated controls, but expression of the renin gene in the kidney was still 2.2-times higher in 2K1C rats than in controls (P less than 0.05). The plasma angiotensinogen level was significantly higher in 2K1C rats than in controls (P less than 0.05), and expression of the angiotensinogen gene in the liver was 2.9-times higher in 2K1C rats than in controls (P less than 0.01). These results indicate that the roles of the renin-angiotensin system in maintenance of hypertension in 2K1C rats differ in the acute and chronic phases: in the acute phase, over-expression of the renal renin gene coupled to increased renin secretion plays the major role in elevating the blood pressure; in the chronic phase, a counter-regulatory mechanism may affect the post-transcriptional fate of renin.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensinogen↗

A comparison of the actions of cilazapril in normal, dietary sodium-depleted and two-kidney, one clip Goldblatt hypertensive anaesthetised rats.

OBJECTIVE: This study aimed to examine the role of the renin-angiotensin system in the regulation of kidney haemodynamic and excretory function when angiotensin II levels were modestly and markedly raised. DESIGN: Three groups of male Sprague-Dawley rats were used: control rats fed a sodium-replete diet; rats fed a sodium-deficient diet for 2 weeks; and two-kidney, one clip (2K1C) Goldblatt hypertensive rats, 4-5 weeks postclipping. METHODS: The rats were acutely anaesthetized with sodium pentobarbitone and prepared for renal function measurements. The converting enzyme inhibitor, cilazapril, was then infused at increasing dose levels to progressively block the renin-angiotensin system. RESULTS: Cilazapril did not affect blood pressure in sodium-replete animals; it raised RBF and increased water and sodium excretion. In dietary sodium-depleted rats, cilazapril decreased blood pressure and increased RBF, water and sodium excretion at the lower doses of the drug; however, at vasodepressor doses, water and sodium excretion fell towards baseline values. In 2K1C Goldblatt hypertensive rats, cilazapril maximally decreased blood pressure whilst the non-clipped kidney blood flow, filtration rate and fluid excretion rates were similar to dietary sodium-depleted rats; in contrast, the clipped kidney filtration rate was well maintained and fluid excretion was raised in a dose-related fashion. CONCLUSION: These results show that during gradual cilazapril administration, renal function is well preserved in 2K1C Goldblatt hypertensive rats when pressure is progressively reduced.

Angiotensin-Converting Enzyme Inhibitors↗

Endothelial nitric oxide synthase protein is reduced in the renal medulla of two-kidney, one-clip hypertensive rats.

OBJECTIVE: We studied endothelial nitric oxide synthase (eNOS) expression in the kidneys of two-kidney, one-clip renal hypertensive rats (2K1C) before and after removal of the clip (unclipping, UC). We hypothesised that the haemodynamic changes induced by 2K1C and UC would change eNOS expression in the two kidneys. METHODS: Six weeks after inducing 2K1C, mean arterial pressure (MAP) was measured in conscious rats and hypertension reversed by UC. Left and right kidney eNOS protein in cortex and outer medulla was semi-quantified using immunoblotting. Groups were; normotensive (n = 10), 2K1C (n = 10), 3 h (n = 10), 48 h (n = 7) and 4 weeks (n = 7) after UC. The effect of 7 days of aldosterone or angiotensin II (Ang II) infusion on medullary eNOS protein was tested as well as the effect of L-NAME (nitric oxide (NO) synthase inhibitor) on medullary blood flow (MBF) in anaesthetized 2K1C. RESULTS: UC reduced MAP from 178 +/- 5 to 134 +/- 3 mmHg after 3 h and normalized MAP at 48 h and 4 weeks. The medulla from 2K1C kidneys contained about 33% less eNOS protein compared with normotensive kidneys (P < 0.05). This difference was still evident at 3 h (P < 0.05), but completely reversed at 48 h and 4 weeks after UC. Similar levels of eNOS expression were seen in the left and right kidney at all time points. Cortical eNOS was increased in kidneys from 2K1C. Neither Ang II nor aldosterone affected eNOS expression in the medulla. MBF was under similar influence of NO in 2K1C compared with normotensive kidneys. CONCLUSIONS: 2K1C is associated with reduced levels of eNOS protein in the renal medulla of both clipped and contralateral kidney. eNOS expression in right and left kidney was not changed despite expected large changes in haemodynamics of the two kidneys. The reduced level of eNOS may be associated with a reduction in MBF and thus be of patho-physiological importance in renovascular hypertension.

Aldosterone↗

New aneurysm clip appliers for "key-hole" neurosurgery.

A new set of aneurysm clip appliers has been developed to overcome many of the obstacles to safe clipping of complex intracranial aneurysms. The applier set consists of six units, each one delivering clips at a different specified angle to the applier shaft. These appliers have been independently tested on over 250 aneurysm operations and found to be of great utility.

Equipment Design↗