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Saphenofemoral junction ligation supplemented by postoperative sclerotherapy: a review of long-term clinical and hemodynamic results.

This review article summarizes information found in the literature concerning long-term results following high ligation supplemented in the postoperative period by sclerotherapy. Subjective complaints, recurrent reflux, and recurrent varicose vein rates as well as changes in venous hemodynamics are reviewed and compared with results after high ligation and stripping. The fate of the greater saphenous vein trunk after high ligation, the question whether it could actually be used as a graft in arterial and coronary artery reconstructions, and the relevance of saphenous vein saving surgery are discussed. The trunk of the greater saphenous vein, when incompetent preoperatively, continues to be patent and incompetent after surgery in most cases. It is not diffusely degenerated and could be used as an arterial substitute. However, ligation of the saphenofemoral junction alone provokes a higher recurrence rate in comparison with high ligation and stripping. The excellent hemodynamic improvement achieved immediately after high ligation deteriorates progressively during the follow-up owing to recurrent reflux. Sclerotherapy can compensate this undesirable feature, because it is itself capable of reducing or even abolishing reflux and improving venous hemodynamics, although only transitorily, but repeated sclerosing injections can restore improvement at any time, if necessary, during the follow-up period. The improvement of venous hemodynamics and subjective symptoms achieved with the combined procedure (high ligation plus sclerotherapy) is comparable with that after high ligation and stripping.

Femoral Vein↗

Outcome following patent ductus arteriosus ligation in premature infants: a retrospective cohort analysis.

BACKGROUND: The patent ductus arteriosus (PDA) is an important problem in premature infants. Surgical PDA ligation is usually only be considered when medical treatment has either failed or was contraindicated. The aims of our study were to determine the mortality and morbidity following patent ductus arteriosus ligation in premature infants, and whether prostaglandin synthetase inhibitor (PSI) use prior to ligation affects outcome. METHODS: A retrospective case note review study to determine the outcome of premature infants undergoing patent ductus arteriosus ligation in one tertiary neonatal intensive care unit and two paediatric cardiothoracic centres. RESULTS: We had follow-up data on 87 infants. Cumulative mortality rates at 7 days, 30 days and at hospital discharge were 2%, 8% and 20% respectively. The incidence of chronic lung disease, intraventricular haemorrhage, necrotising enterocolitis and retinopathy of prematurity were 77%, 39%, 26% and 28% respectively. There was no difference in mortality, incidence of chronic lung disease or duration of oxygen dependence between those who had and those who had not received a PSI prior to surgical ligation. In those who had received 2 or more courses of PSI prior to surgical ligation, there was a trend to increase in the duration of oxygen therapy and chronic lung disease, but no difference in mortality. CONCLUSION: This study shows that patent ductus arteriosus ligation is a relatively safe procedure (30 day survival 92%) but there is substantial late mortality and a high incidence of morbidity in the survivors. 2 or more courses of PSI prior to surgical ligation trends to increased oxygen dependence and chronic lung disease. This high risk population requires careful follow-up. A definitive prospective cohort study is lacking.

Cardiovascular Surgical Procedures↗

Treatment outcomes of uterine artery embolization and laparoscopic uterine artery ligation for uterine myoma.

In treating women with leiomyoma and who wish to preserve their uterus, laparoscopic uterine artery ligation or uterine artery embolization should be considered as possible options. This study was performed to evaluate the efficacy of laparoscopic uterine artery ligation and uterine artery embolization in treating uterine myoma. The treatment outcomes of 23 patients who underwent uterine artery embolization and 17 laparoscopic uterine artery ligation were evaluated. The uterine volume reduced 3 months after uterine artery embolization, but thereafter no significant changes were observed. On the other hand, the uterine volumes were only slightly reduced 3 months after laparoscopic uterine artery ligation, and slightly more reduced 6 months later. The average reduction in the case of laparoscopic uterine artery ligation was about 58.5%. After laparoscopic uterine artery ligation, 20% of the patients complained of vaginal spotting. Furthermore, the mechanism of volume reduction was evaluated using specimens obtained from a biopsy taken after each procedure. The results suggested that laparoscopic uterine artery ligation results mainly in physiologic cell death, that is apoptosis, whereas, the corresponding result is cell necrosis for uterine artery embolization. Uterine artery embolization and laparoscopic uterine artery ligation are both effective in relieving the symptoms caused by uterine myoma, and therefore both procedures can be used in place of hysterectomy or myomectomy.

Adult↗

Effect of ZVAD-fmk on hepatocyte apoptosis after bile duct ligation in rat.

AIM: Retention and accumulation of toxic hydrophobic bile salts within hepatocyte may cause hepatocyte toxicity by inducing apoptosis. Apoptosis is a pathway of cell death orchestrated by a family of proteases called caspases. Z-Val-Ala-Asp (OMe)-fluoromethyl ketone (ZVAD-fmk) is a cell-permeable irreversible inhibitor of caspase. The purpose of this study was to evaluate the possible effect of ZVAD-fmk on hepatocyte apoptosis after bile duct ligation in the rat. METHODS: Male Sprague-Dawley rats, weighing 250-300 g, were randomized to five groups of five rats each. Group 1 underwent common bile duct ligation and simultaneous treatment with ZVAD-fmk (dissolved in dimethylsulfoxide (DMSO)). Group 2 underwent common bile duct ligation and simultaneous treatment with Z-Phe-Ala-fluoromethyl ketone ( ZFA-fmk, dissolved in DMSO). Group 3 underwent sham operation and simultaneous treatment with the same amount of DMSO. Group 4 underwent sham operation and simultaneous treatment with the same amount of normal saline. Group 5 underwent common bile duct ligation without other manipulation. After three days, liver tissue was harv-ested for histopathologic analysis and measurements of apoptosis. RESULTS: When compared with sham operation, common bile duct ligation significantly increased hepatocyte apoptosis (P = 0.008) and ductular proliferation (P = 0.007). ZVAD-fmk significantly diminished the increased hepatocyte apoptosis and ductular proliferation after common bile duct ligation (P = 0.008 and P = 0.007, respectively). ZFA did not show the same effects. CONCLUSION: Hepatocyte apoptosis and ductular proliferation significantly increased after common bile duct ligation. ZVAD-fmk effectively diminished the increased hepatocyte apoptosis and ductular proliferation after common bile duct ligation, whereas ZFA-fmk did not.

Amino Acid Chloromethyl Ketones↗

Effects of nuclear factor-kappaB on rat hepatocyte regeneration and apoptosis after 70% portal branch ligation.

AIM: To detect the DNA binding activity of nuclear factor-kappaB (NF-kappaB) in rat hepatocyte and to investigate the effects of NF-kappaB on rat hepatocyte regeneration and apoptosis after 70% portal branch ligation. METHODS: Sixty Wistar rats were randomly divided into control group and portal branch ligation group. The animals were killed 12 h, 1, 2, 3, 7, and 14 d after surgery to determine the contents of plasma ALT. Hepatocytes were isolated and nuclear protein was extracted. DNA binding activity of NF-kappaB was measured by EMSA. Hepatocyte regeneration and apoptosis were observed under microscope by TUNEL staining. The ultrastructural changes of liver were observed under electron microscope. RESULTS: Seventy percent portal branch ligation produced atrophy of the ligated lobes and the perfused lobes underwent compensatory regeneration, the total liver weight and plasma ALT levels were maintained at the level of sham-operated animals throughout the experiment. After 2 d of portal branch ligation, DNA binding activity of NF-kappaB in hepatocyte increased and reached its peak, the number of apoptotic hepatocyte in the ligated lobes and the number of mitotic hepatocyte in the perfused lobes also reached their peak. Typical apoptotic changes and evident fibrotic changes in the ligated lobes were observed under electron microscope. CONCLUSION: After 70% portal branch ligation, DNA binding activity of NF-kappaB in hepatocyte is significantly increased and NF-kappaB plays an important role in hepatocyte regeneration and apoptosis.

Animals↗

Endoscopic ligation compared with sclerotherapy for the treatment of bleeding esophageal varices.

OBJECTIVE: Comparison of the safety and efficacy of endoscopic sclerotherapy and ligation for the treatment of bleeding esophageal varices. DESIGN: Randomized, controlled trial. SETTING: An urban county hospital. PATIENTS: Patients with clinically severe bleeding from esophageal varices. INTERVENTION: A total of 77 patients were randomly assigned to receive sclerotherapy or ligation at the initial endoscopic examination. Treatment was repeated weekly until variceal obliteration was achieved. After eradication, patients had endoscopic examinations every 3 months or for any episode of rebleeding. Recurrent varices were treated with the originally assigned form of endoscopic therapy. MEASUREMENTS: Patients were assessed for further bleeding, for transfusion requirements, for time in hospital, for variceal eradication, for number of treatment sessions required, for complications, for treatment failure, and for risk of death. RESULTS: Rebleeding tended to be less frequent with ligation than with sclerotherapy: 10 of 38 (26%) compared with 17 of 39 (44%) (difference, 17% [95 CI, -4% to 38%]), but results in the two groups were comparable for blood transfusions, for length of hospital stay, and for risk of death. Comparison of Kaplan-Meier estimates of time to rebleeding and death showed no statistical differences between treatments. Complications were less common in the ligation group: fewer patients in the ligation group had esophageal strictures (0 of 38 compared with 13 of 39 [33%]; P < 0.001) and had complicated esophageal ulcers (1 of 38 [2.6%] compared with 6 of 39 [15%]; P = 0.11). In addition, fewer ligation treatments were required to achieve variceal eradication (4.1 +/- 0.3 compared with 6.2 +/- 0.4; P < 0.001). CONCLUSION: Endoscopic ligation causes statistically fewer local complications than sclerotherapy and achieves variceal eradication more rapidly. Ligation is a viable alternative to sclerotherapy and may have some advantages as a treatment for bleeding esophageal varices.

Adult↗

[Prevention of acute hepatic failure after "90%" hepatectomy by portal branch ligation in rats].

In this study, ligation of portal branches feeding 90% liver mass was performed in rats. After the ligation, 10% liver mass with portal blood perfusion underwent a progressive hypertrophy. It gained weight against the control by about 5-fold at the 14th day. The measurement of incorporation rate of H3-thymidine showed that the DNA synthesis increased rapidly in the liver tissue keeping portal blood supply. It reached a peak at 24 hours and retumed to normal at 7 days after the ligation. The ligated liver lobes under-went an atrophy gradually. With the pretreatment of such portal branch ligation 2 weeks before, 80% rats survived from the resection of ligated liver lobes which composed of 90% preceding liver mass. In the control group of sham portal branch ligation, all rats died within a short period of time after 90% hepatectomy. This study demonstrated that a secondary extended hepatectomy following the ligation of portal branches feeding 90% liver mass could prevent acute hepatic failure induced by primary 90% hepatectomy in rats.

Animals↗

Endoscopic injection sclerotherapy with ligation versus endoscopic injection sclerotherapy alone in the management of esophageal varices: a prospective randomized trial.

BACKGROUND/AIMS: Endoscopic injection sclerotherapy with ligation is a technique by which endoscopic injection sclerotherapy is first carried out for a target esophageal varix using an endoscope equipped with a device for endoscopic variceal ligation, and subsequently, endoscopic variceal ligation is performed for the varix together with the injection site of the sclerosing agent. The aim of this prospective, randomized trial was to compare endoscopic injection sclerotherapy with ligation with endoscopic injection sclerotherapy techniques in utility for patients with esophageal varices. METHODOLOGY: Twenty-four patients with esophageal varices who were to undergo either an elective treatment of bleeding esophageal varices or a prophylactic treatment of non-bleeding esophageal varices underwent endoscopic injection sclerotherapy with ligation (n = 12) or without ligation (n = 12). The patients were followed for a mean of 19.9 +/- 8.1 months in the endoscopic injection sclerotherapy with ligation (EISL) group and 19.5 +/- 5.4 months in the Endoscopic injection sclerotherapy (EIS) group. RESULTS: The red color sign disappeared in 10 patients in the EISL group and 3 in the EIS group (P = 0.004) after initial treatment. The length of time required for initial treatment was 16.3 +/- 4.7 min for the EISL group and 27.2 +/- 6.2 min for the EIS group (P = 0.0003). For treatment-related complications, no significant difference was noted between the 2 groups and no serious complication were noted in the 2 groups. The total quantity of ethanolamine oleate used to attain the endpoint was 17.3 +/- 7.9 mL for the EISL group and 25.2 +/- 9.7 mL for the EIS group (P < 0.05). The cumulative non-relapse rate for 2 years following attainment of the endpoint [F1, RC(-)] was 81.5% for the EISL group and 47.5% for the EIS group, producing no significant difference between the 2 groups. The cumulative non-bleeding and survival rates were 100% in the 2 groups. CONCLUSIONS: Endoscopic injection sclerotherapy with ligation is more useful for esophageal varices than endoscopic injection sclerotherapy alone.

Aged↗

Comparative study between multiple and single rubber band ligation in one session for bleeding internal, hemorrhoids: a prospective study.

OBJECTIVE: The aim of this study was to compare the cessation of bleeding and the complications between multiple and single ligation using high ligation technique. MATERIAL AND METHOD: All first-visit patients with bleeding internal hemorrhoids were studied and randomly divided into multiple and single ligation groups. High ligation technique was used. Patients visited the clinic in the second week and were invited to visit the clinic or completed questionnaires after one year. RESULTS: 109 patients were included in the study. 61 patients had multiple ligation and 48 patients had single ligation. The cessation of bleeding in one week occurred in 96.7 per cent of patients in the multiple group and 79 per cent of patients in the single group (p = 0.004). There were no differences between the multiple group and single group concerning postligation pain and tenesmus (6.5% vs 2%, p = 0.532), urinary hesitancy and frequency (6.5% vs 4%, p = 0.904), and rebleeding in one year (27.9% vs 34%, p = 0.710). No major complications such as massive bleeding and pelvic sepsis were noted. CONCLUSIONS: Multiple ligation of bleeding internal hemorrhoids in one session can stop bleeding better than single ligation with no more complications.

Adult↗

[Vascular ligation for severe obstetrical hemorrhage: review of the literature].

OBJECTIVE: Assess the contribution of vascular ligation in the treatment of severe obstetrical hemorrhage. Method. We reviewed the anatomic and pathophysiological basis of vascular ligation analyzing the technique, results, and indications for this conservative procedure for the severe post-partum hemorrhage. New developments in suture techniques for uterine bleeding are under study. RESULTS: Outcome after uterine artery ligation is good. A stepwise procedure with progressive ligation of the uterine and ovarian arteries is a good solution (100% success). Bilateral ligation of the hypogastrics can provide success in 66% of cases. Vascular ligation can be an alternative between embolization and hysterectomy. CONCLUSION: Ligation of the bleeding vessels preserves the patient's life and uterus. More than fifty pregnancies have been reported after vascular ligation.

Arteries↗

Long-term follow-up of patients with liver cirrhosis after endoscopic esophageal varices ligation therapy: comparison with ethanol injection therapy.

BACKGROUND/AIMS: Esophageal variceal hemorrhage is the most dreaded complication of liver disease. Prevention or emergency therapy of bleeding is important. METHODOLOGY: A group of 217 patients underwent endoscopic esophageal variceal therapy including endoscopic ethanol injection, endoscopic esophageal variceal ligation, or a combination of the two. RESULTS: Esophageal varices were eradicated by endoscopic esophageal variceal ligation with the least sessions required, and associated complications with endoscopic esophageal variceal ligation therapy were lower than with the other two approaches. However, the cumulative recurrence-free period of esophageal varices was significantly higher after endoscopic ethanol injection than after endoscopic esophageal variceal ligation and in some cases F3 varices were observed post-endoscopic esophageal variceal ligation hemorrhage. A combined endoscopic esophageal variceal ligation and endoscopic ethanol injection therapy had no advantage with respect to cumulative recurrence-free rate, session number, or complication frequency, relative to either therapy alone. CONCLUSIONS: While the combined observations indicate that endoscopic esophageal variceal ligation is safe and simple, we should consider additional therapy to achieve complete mucosal fibrosis of the esophagus after endoscopic esophageal variceal ligation.

Adult↗

Esophageal variceal ligation for acute variceal bleeding: results of three years' follow-up.

BACKGROUND/AIMS: Endoscopic variceal ligation is widely accepted as the optimum endoscopic treatment for esophageal variceal hemorrhage. However, the rebleeding course and long-term outcome of patients with esophageal variceal hemorrhage after ligation have been poorly defined. Therefore, we conducted a long-term follow-up study to delineate the outcome of ligation. METHODS: Twenty-one liver cirrhotic patients with endoscopically proven esophageal variceal hemorrhage were treated by endoscopic variceal ligation. These patients received regular follow-up and detailed clinical assessment of at least 24 months. RESULTS: Twenty-one eligible patients were followed up for a mean of 44.45 months (range 33.5-64 months). The mean number of sessions required to obtain eradication was 3.57+/-1.99 (range 1-8). Esophageal varices could be obliterated within 11.57+/-6.8 weeks (range 3-30). The percentage of variceal recurrence during follow-up was 57.14% (12/21) after endoscopic variceal ligation. Recurrence were observed in a mean of 34 months (median 29 months). Rebleeding from esophageal varices appeared in four patients (19.04%). The appearance rates of portal hypertensive gastropathy and fundal gastric varices after varice obliteration were found to be 45.45% (5/11) and 25% (3/12), respectively. CONCLUSIONS: Based on the results of long-term follow-up of endoscopic variceal ligation, although the percentage of variceal recurrence was high, endoscopic ligation achieved variceal obliteration faster and in fewer treatment sessions. Furthermore, endoscopic variceal ligation had a lower rate of rebleeding and of development of fundal gastric varices, but high portal hypertensive gastropathy.

Adult↗

Thrombomodulin plays an important role in arterial remodeling and neointima formation in mouse carotid ligation model.

Thrombomodulin (TM) is a cell membrane-bound glycoprotein that functions as a thrombin cofactor in the activation of protein C. Its protein structure includes a N-terminal lectin-like domain (D1), 6 epidermal growth factor repeats (D2), a serine-threonine-rich region (D3), a transmembrane domain (D4) and a short cytoplasmic tail (D5). Recent studies have demonstrated the direct effect of TM on cellular proliferation, adhesion and inflammation. In the study, we investigated the role of TM in vascular remodeling and neointima formation in a mouse carotid ligation model. TM expressions on the endothelium, neointima and media were examined in the ligated carotid artery by immunohistochemistry and quantitative real-time reverse transcription PCR. Endothelial TM expression decreased after ligation and appeared later in the media and neointima, which is quite similar to the appearance of TM in the human atherosclerotic process. Recombinant TMD123 was prepared. It was effective for thrombin-dependent protein C activation and the inhibition of leukocyte adhesion to the vessel wall after carotid ligation. Recombinant TMD123 and saline was administered immediately before and after carotid ligation. The TM-treated arteries demonstrated significantly less arterial dilatation (30279 +/- 12605 vs 73789 +/- 15073 microm(2), p < 0.05) in response to less neointima formation (14179 +/- 6538 vs 42227 +/- 8754 microm(2), p < 0.05) at 4 weeks after ligation. Our data indicated that there was a compensatory increase in TM expression in the media and neointima in relation to the reduced endothelial TM after carotid ligation. Early recombinant TM treatment in mice undergoing carotid ligation altered vascular remodeling and decreased the severity of neointima formation.

Animals↗

[Evaluating prophylactic ligation of thoracic duct during radical resection of esophageal carcinoma].

BACKGROUND & OBJECTIVE: Prophylactic ligation of thoracic duct during the radical resection of esophageal carcinoma is usually used to prevent and treat chylothorax, but there is dispute about the effect. Its correlation to other complications and prognosis of esophageal carcinoma patients after operation has seldom been reported. The study was to evaluate its preventive effect on chylothorax and its influences on other complications and prognosis of esophageal carcinoma patients. METHODS: Clinical data from 389 patients who underwent radical transthoracic esophagectomy from Jun. 1991 to Jun. 1996 in Cancer Center of Sun Yat-sen University were retrospectively analyzed. Of the 389 patients, 171 received thoracic duct ligation (ligation group), and 218 had thoracic duct preserved (preservation group). The occurrence rates of chylothorax and other complications, and the survival rates were compared between the 2 groups. RESULTS: The occurrence rates of chylothorax were 1.17% in ligation group and 0.46% in preservation group (P<0.001). The occurrence rates of complication were 18.2% in ligation group and 11.5% in preservation group (P=0.063). Perioperative mortalities were 1.75% in ligation group and 0.92% in preservation group (P=0.658). The 1-, 2-, 3-, and 5-year survival rates were 74.3%, 52.1%, 42.1%, and 29.2% in ligation group, and 74.3%, 53.2%, 43.1%, and 29.8% in preservation group (P=0.992, 0.819, 0.841, 0.902). CONCLUSION: Prophylactic ligation of thoracic duct during esophagectomy for patients with esophageal carcinoma could not prevent chylothorax effectively, and has no obvious influence on the occurrence of other complications and survival of the patients after operation.

Chylothorax↗

CD40 ligation of rheumatoid synovial fibroblasts regulates RANKL-mediated osteoclastogenesis: evidence of NF-kappaB-dependent, CD40-mediated bone destruction in rheumatoid arthritis.

OBJECTIVE: To determine whether CD40 ligation of rheumatoid arthritis synovial fibroblasts (RASFs) is able to induce RANKL expression and osteoclastogenesis in RASFs, and to identify its mechanism of action in patients with RA. METHODS: CD40 of RASFs was ligated with CD40 ligand (CD40L)-transfected L cells or activated T cells. The formation of osteoclasts in cocultures of CD40-ligated RASFs and T lymphocyte-depleted peripheral blood mononuclear cells was evaluated by tartrate-resistant acid phosphatase staining, detection of calcitonin receptor, and resorption pit formation assay. The expression of NF-kappaB, IkappaB alpha, ERK-1/2, phospho-ERK-1/2, p38, phospho-p38, and RANKL was examined by immunoblotting and/or semiquantitative reverse transcription-polymerase chain reaction. RESULTS: CD40 ligation of RASFs by CD40L-transfected L cells or activated T cells induced RANKL expression and enhanced osteoclastogenesis. CD40 ligation of RASFs also induced activation of ERK-1/2, p38 MAPK, and NF-kappaB and up-regulation of CD40 ligation-induced RANKL expression, whereas osteoclastogenesis was reduced in RASFs transfected with a dominant-negative mutant of IkappaB alpha or by an NF-kappaB inhibitor. However, specific inhibitors of MAPK/ERK-1/2 and p38 MAPK partially blocked the induction of RANKL expression and osteoclastogenesis. Monoclonal antibodies against interleukin-1 and tumor necrosis factor alpha partially inhibited CD40 ligation-mediated osteoclastogenesis. CONCLUSION: These results indicate that CD40 ligation of RASFs induces RANKL expression mainly via NF-kappaB activation and also results in enhanced osteoclast formation, both of which might play important roles in bone and cartilage destruction in RA. Inhibition of the CD40-CD40L interaction is a potential strategy for the prevention of bone damage in RA.

Arthritis, Rheumatoid↗

Peach latent mosaic viroid is locked by a 2',5'-phosphodiester bond produced by in vitro self-ligation.

Although some viroid-like satellite RNAs possess self-cleavage and self-ligation activities, we show that the peach latent mosaic viroid (PLMVd) is unique among all known viroids since it also has such activities. These catalytic activities should have important roles in the rolling circle replication of PLMVd. According to this proposed mechanism, self-cleavage of the multimeric strands occurs via hammerhead structures producing monomers possessing 2',3'-cyclic phosphate and 5'-hydroxyl termini. In the most stable predicted secondary structure for PLMVd these two extremities are juxtaposed, in order for self-ligation to occur. To establish the nature of the phosphodiester bond produced by self-ligation, we followed the classical procedure of complete enzymatic RNA hydrolysis coupled with thin layer chromatography fractionation. Using this procedure, we report that the self-ligation of PLMVd transcripts produces almost exclusively the 2',5' isomer (>96%). Primer extension assays also revealed that reverse transcriptase can read througth this 2', 5' linkage, suggesting that it does not prevent further replication of the viroid. Moreover, we have observed that this 2',5' linkage is resistant to the debranching activity contained in nuclear extracts, as well as being capable of preventing further viroid self-cleavage. Thus, if viroids do indeed self-ligate in vivo, the resulting 2', 5'-phosphodiester bond could contribute to the stability of these RNA species. Finally, an analysis of both the sequence and the structural requirements for hammerhead self-cleavage and self-ligation suggests that these two RNA processes may be interrelated. We hypothesize that the intramolecular self-ligation which produces circular conformers may contribute to the circularization step of the rolling circle replication, while the intermolecular non-enzymatic ligation is a potential mechanism for the sequence reassortment of viroids and viroid-like species.

Endoribonucleases↗

Intra- and intermolecular nonenzymatic ligations occur within transcripts derived from the peach latent mosaic viroid.

We report here the nonenzymatic self-ligation of transcripts corresponding to the peach latent mosaic viroid (PLMVd). This is the first description of this process with viroid sequences, although it has been reported to occur with human hepatitis delta virus RNA. Self-ligation occurs when the 5'-hydroxyl and the 2',3'-cyclic phosphate termini produced by the hammerhead self-cleavage of the viroid RNA are juxtaposed by the viroid rod-like structure, and a phosphodiester bond is formed between the two following hydrolysis of the cyclic phosphate. Unit-length transcripts undergo intramolecular folding, and their subsequent self-ligation produces circular molecules. The self-ligation observed in vitro may contribute to PLMVd circularization during rolling circle replication; however, this does not exclude the possibility that a host RNA ligase catalyzes the ligation steps in vivo. Like self-cleavage, self-ligation is probably an ancestral reaction, and the enzyme-catalyzed ligation most likely evolved from this primitive mechanism. Furthermore, the intermolecular self-ligation of annealed transcripts derived from PLMVd is demonstrated, suggesting a possible mechanism for sequence reassortment in viroids.

Base Sequence↗

Ureteral ligation induces Fos expression in the dorsal horn.

To describe a sympathetic afferent circuit, the left ureter was ligated in anesthetized rats for 1.5-2 h followed by immunocytochemical processing to localize expression of either the immediate early gene (IEG) c-fos or Krox-24 in the spinal cord or dorsal root ganglia (DRG). No IEG expression was detected in DRG. Both Fos and Krox-24 expression was found in the dorsal horn. More Fos immunocytochemically stained cells were found in the dorsal horn both ipsi- and and contralateral to the ligated ureter at spinal segments T10-T13 after ureteral than after either sham ligation or anesthesia control procedures. More Fos stained cells were in the dorsal horn ipsilateral to the ligated ureter than on the contralateral side. The Fos staining patterns in the dorsal horn of ligated and sham-ligated animals were similar with most labeled cells in dorsomedial portions of laminae I and II. In contrast, the Fos staining pattern in the dorsal horn in anesthetized animals (unoperated controls) was noticeably different from operated animals with the most Fos cells in the ventrolateral part of laminae I-II. These results indicate that (1) Fos Immunocytochemistry may be useful for tracing sympathetic afferent pathways, (2) the sensory pathway activated by ureteral ligation enters the spinal cord at lower thoracic levels, where renal and upper ureteral afferents are terminating, and (3) some of this sympathetic afferent pathway is located contralateral to the stimulated kidney. Neurons activated by ureteral ligation in the contralateral dorsal horn may mediate reno-renal reflexes.

Afferent Pathways↗