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PubMed1998

Intracellular signal transduction mediated by ligation of MHC class I molecules.

A great deal of knowledge has accumulated regarding signal transduction after ligation of MHC class I (MHC-I) molecules. In recent years focus has been given to delineation of the intracellular signal pathways activated after MHC-I ligation. Activation of tyrosine kinases leading to a rise in the intracellular free calcium concentration ([Ca2+]i) is the major initial event occurring after MHC-I ligation of T cells. Curiously, the MHC-I-induced signaling is not dependent upon the cytoplasmic tail of the MHC-I molecule, suggesting that the MHC-I molecule induces intracellular signaling through association with other membrane-embedded molecules. More distal signaling events after MHC-I ligation includes activation of the Jak/Stat pathway leading to Stat-3 activation, and activation of the PI3-kinase leading to JNK activation and apoptosis. This review will sum up what is currently known about signaling induced by ligation of MHC-I.

Animals↗
PubMed1988

Simple ligation vs stump inversion in appendectomy.

The records of 886 patients who had appendectomy performed by the same surgeons within a five-year period were used to contrast appendiceal stump inversion vs simple ligation. Our analysis contrasted inversion vs simple ligation techniques as related to postoperative complications, hospital stay, and pathologic diagnosis. Adhesions requiring repeated operation to relieve bowel obstruction occurred in five of 87 patients with acute gangrenous appendicitis treated by inversion. Of 106 patients with acute gangrenous appendicitis treated with simple ligation, postoperative obstruction developed in none. No other statistically significant differences existed between the two techniques. These data suggest that simple ligation is at least as good as and probably better than inversion of the appendiceal stump.

Acute Disease↗
PubMed1995

Comparison of blood flow and myoelectric measurements in two chronic models of mesenteric ligation.

OBJECTIVE: To determine whether the predictive accuracy of intestinal motility and blood flow measurements is altered by the magnitude of ischemic damage. DESIGN: Inception cohort study (dogs). Motility was measured using a probe that quantifies both the electromyographic (EMG) measurements and the magnitude of evoked contractile response (ECR). Intestinal blood flow was assessed using Doppler ultrasonography in the marginal artery and perfusion fluorometry, which quantifies fluorescein in the bowel wall in dye fluorescence units. SETTING: Vivarium animal research facilities at a medical school. INTERVENTIONS: The blood supply of a 40-cm length of ileum was ligated in 102 dogs: 52 in which the marginal artery was ligated at two points 8 cm apart (severe model), and 50 in which the marginal artery was ligated only once (moderate model). Twenty-four hours after ligation, the motility and blood flow parameters were measured in normal bowel and at 2-cm intervals within the 40-cm ischemic segment. Resection and anastomosis of ischemic bowel was then performed using either EMG, ECR, or fluorometry to determine the site of resection. OUTCOME MEASURE: Anastomotic leak from progressive ischemia. RESULTS: There were 26 fatal anastomotic leaks, all due to necrosis at the anastomosis. Perfusion fluorometry and ECR measurements did not correlate with survival in either model. An audible Doppler pulse in the marginal artery correlated with survival in the moderate (P < or = .02) but not the severe model (P = .59). The EMG measurements were significantly greater in survivors vs nonsurvivors in both models. CONCLUSIONS: The EMG measurements may be useful in bowel viability assessment. Correlation of Doppler ultrasonographic findings with survival in the moderate model suggests that blood flow measurements may be more reliable in predicting viability in less ischemic bowel.

Anastomosis, Surgical↗
PubMed1980

Ligation of the pancreatic duct in pancreatectomy.

This study was undertaken to determine the safety of duct ligation in pancreatic surgery. Duct ligation was performed in 43 patients after pancreaticoduodenectomy and in 108 patients after distal pancreatectomy; 33 patients had a pancreaticojejunostomy after a pancreaticoduodenectomy. All procedures were performed between 1965 and 1975; the analysis was retrospective. The mortality and morbidity for the duct ligation group after pancreaticoduodenectomy were 19 per cent and 77 per cent and after distal pancreatectomy were 4 per cent and 9 per cent respectively. After pancreaticoduodenectomy with pancreaticojejunostomy the mortality was 18 per cent with a morbidity of 33 per cent. It is concluded that distal pancreatectomy with duct ligation is a relatively safe procedure, while after pancreaticoduodenectomy the morbidity is significantly reduced (P less than 0.001) by a pancreaticojejunostomy.

Duodenum↗
PubMed1985

Appendicectomy: assessment of stump invagination versus simple ligation: a prospective, randomized trial.

The appendix stump was ligated and doubly invaginated in 374 patients and was simply ligated in 361 in a prospective, randomized trial of 735 consecutive appendicectomies. The two groups were similar with respect to sex, age, degree of appendiceal inflammation and antibiotic treatment. The incidence of wound infection and postoperative pyrexia and the postoperative hospital stay showed no significant intergroup difference. The median operating time was slightly shorter in the group without invagination. Simple ligation facilitates and shortens appendicectomy. It produces no deformation of the caecal wall that subsequently may be mistaken for a caecal neoplasm. Simple ligation is therefore recommended as standard procedure in appendicectomy.

Appendectomy↗
PubMed2007

Outcome following bypass, and proximal and distal ligation of popliteal aneurysms.

BACKGROUND: The aim of this study was to describe early and late results of proximal and distal ligation for popliteal aneurysm (PA), combined with bypass, with particular reference to the fate of the excluded aneurysm. METHODS: Of a cohort of 116 patients with PAs, 66 were treated with bypass and ligation. Graft patency was determined by duplex surveillance. In addition, 17 patients with bypassed PAs underwent a total of 33 duplex scans to determine flow within the aneurysm and change in size. RESULTS: For initially patent PAs, 3-, 5- and 8-year primary bypass graft patency was 78, 78 and 51 per cent respectively. These rates were not statistically significantly different from those following bypass for thrombosed PA, 3- and 5-year primary patency being 72 and 65 per cent respectively. No PA produced further symptoms after bypass and ligation. No flow was seen in any aneurysm at follow-up. Only one showed an increase in size. CONCLUSION: Proximal and distal ligation with bypass produced satisfactory long-term patency with good exclusion of the PA.

Aneurysm↗
PubMedDate not supplied

TNF-alpha and leptin in experimental liver fibrosis models induced by carbon tetrachloride and by common bile duct ligation.

In this study we investigated TNF-alpha and leptin levels in two different liver fibrosis models induced by carbon tetrachloride (CCl(4)) and common bile duct ligation (CBDL). A total of 36 male rats of Albino-Wistar strain were allocated to three groups. One of the groups was the control. The second group received 0.15 ml 100 g(-1) CCl(4) subcutaneously for 6 weeks, 3 days per week. The third group underwent common bile duct ligation (CBDL) and was monitored for 4 weeks. Histopathological investigation included fibrosis, steatosis and inflammation. Serum IL-6 and TNF-alpha levels were analysed by ELISA methods and leptin was analysed by RIA. Fibrosis and steatosis increased significantly in the CCl(4) group in comparison with the CBDL group (p < 0.01; p < 0.001). Leptin and TNF-alpha levels in CCl(4) group were higher than those in the CBDL and control groups (p < 0.05). TNF-alpha and leptin levels were not related to each another in either the CCl(4) group or the CBDL group (r=0.22, p > 0.05; r=0.19, p > 0.05). The IL-6 level was higher in the CCl(4) group in relation to severity of inflammation (p < 0.05). TNF-alpha and leptin levels were higher in animals with liver fibrosis induced by CCl(4), than they were in those whose liver fibrosis was induced by common bile duct ligation. Leptin and TNF-alpha may be less effective on the development of liver fibrosis in the group which underwent common bile duct ligation.

Animals↗
PubMed2004

Effects of spinal nerve ligation on immunohistochemically identified neurons in the L4 and L5 dorsal root ganglia of the rat.

This study examined the effect of spinal nerve ligation on different populations of immunohistochemically identified neurons in the dorsal root ganglia (DRG) of the rat. The optical fractionator method was used to count neurons in the ipsilateral L4 and L5 DRG 1-20 weeks after ligation of the L5 and L6 spinal nerves, sham surgery, or no surgery. One week after ligation, neurons in the L5 DRG that were labeled by IB4, a marker of unmyelinated primary afferent neurons, were largely absent. The numbers of IB4-labeled neurons then progressively increased to reach control values by 20 weeks. A smaller, sustained decrease occurred in the number of small-, medium- and large-sized neurons immunoreactive for calcitonin gene-related peptide (CGRP), a marker for peptidergic primary afferents, in the L5 DRG. There was a proportionately greater decrease in the numbers of medium- to large-sized CGRP-like immunoreactive neurons. The number of myelinated afferents in the L5 DRG, identified by their staining for neurofilament protein (N52), did not change after ligation. However, closer examination revealed a significant decrease in the numbers of large-sized neurons, coupled with an increase in the numbers of small- to medium-sized neurons, and the appearance of a novel population of very small-sized neurons labeled by N52. The numbers and cell size distributions of IB4-labeled, CGRP-like immunoreactive, and N52-labeled neurons were unchanged in the adjacent L4 DRG. Unlike the L5 DRG, injury-induced changes in the expression of various receptors, neurotransmitters and neurotrophic factors in the L4 DRG are not confounded by a change in the immunohistochemical phenotype of primary afferent neurons.

Animals↗
PubMedDate not supplied

Chronic bile duct ligation in the dog: hemodynamic characterization of a portal hypertensive model.

Splanchnic and systemic hemodynamics were measured in six normal dogs and in 18 dogs that had the bile ducts ligated for a period of 8 weeks. In the bile duct-ligated dogs, there was a decrease in arterial pressure (110 +/- 4 mm Hg vs. normal 136 +/- 6 mm Hg; p less than 0.005) and peripheral vascular resistance (4.60 +/- 0.38 vs. 6.28 +/- 0.38 dynes-sec-cm-5; p less than 0.02), and an increase in cardiac index (129 +/- 7 vs. 98 +/- 9 ml per min per kg; p less than 0.05). The splanchnic hemodynamic characteristics in the bile duct-ligated dogs included an increase in portal venous pressure (13.3 +/- 0.6 mm Hg vs. 6.7 +/- 0.5 mm Hg; p less than 001) and wedged hepatic venous pressure (14 +/- 1.2 mm Hg), the development of extensive portal-systemic shunting (49 +/- 10 vs. 0.03 +/- 0.01%; p less than 0.01), and a decrease in portal venous flow (194 +/- 21 ml per min vs. 427 +/- 21 ml per min; p less than 0.001). This study demonstrated that chronic bile duct-ligated dogs develop sinusoidal portal hypertension with extensive portal-systemic shunting and a hyperdynamic systemic circulation. These findings closely resembled hemodynamic abnormalities observed in human cirrhosis and suggest that this model is useful in physiopathological and pharmacological studies of portal hypertension.

Animals↗
PubMed1993

Hepatic blood volume responses and compliance in cats with long-term bile duct ligation.

Hepatic capacitance responses were compared in sham-operated and 14-day bile duct-ligated cats under pentobarbital anesthesia. Both groups were subjected to splenectomy and had the anterior hepatic nerve plexus sectioned to allow stimulation; the posterior plexus was intact. Blood volume compensation for hemorrhage was reduced in the bile duct ligation group compared with the control group: The liver compensated for 20.1% and 10.6% of blood loss, respectively. Portal hypertension did not exist and hepatic compliance was unaltered despite the presence of severe biliary hyperplasia, portal tract distortion and fibrosis. The capacitance responses to hemorrhage in the bile duct ligation group were accounted for entirely by a passive compliant response to reduced portal pressure, whereas the sham surgery group showed an additional active component. Responses of liver volume and venous resistance to norepinephrine were normal, but responses to nerve stimulation were reduced. The nerve dysfunction was not universal; reflex arterial blood pressure response to carotid occlusion was normal. The data suggest that hepatic blood volume responses to hemorrhage is mediated by passive compliant responses to reduced portal pressure (stressed volume) and active responses (unstressed volume) to nerve stimulation but that long-term bile duct ligation produces selective hepatic neuropathy resulting in loss of the active component.

Animals↗
PubMed1987

Acidic phospholipids, diacylglycerols, and free fatty acids in gerbil brain: a comparison of ischemic changes resulting from carotid ligation and decapitation.

The levels of brain acidic phospholipids (poly-PI, PI, PA, and PS), DG, and FFA and their acyl group profiles were determined after induction of ischemia in gerbils by ligation of the common carotid arteries and decapitation. Ischemia induced by both procedures resulted in a significant decrease in poly-PI (20% for 1-min decapitation and 1-min ligation). Except for a 16% increase in PI in the 5-min decapitation group, no apparent change was found in other phospholipids after either ischemic condition. The level of DG was increased one- and three-fold after 1 and 5 min, respectively, of decapitative ischemic treatment. Ligation of the carotid arteries for 1 min resulted also in a one-fold increase in the DG level. The decapitative model resulted in a one- and five-fold increase in FFA level (with respect to 1 and 5 min, respectively), whereas ligation for 1 min resulted in an increase of 42% of the FFA. The acyl groups of poly-PI and PI in the control gerbil brain are enriched in 18:0 and 20:4, but those of DG, FFA, and PA have a higher proportion of 16:0 besides 18:0 and 20:4. However, a preferential increase in the proportion of 18:0 and 20:4 was shown for the DG and FFA in both types of ischemic treatments. It is concluded from the results that both models of ischemic treatment elicit a similar decrease in poly-PI and increase in DG, but differ in the amount of FFA release. The higher level of FFA release in the decapitative model suggests that other biochemical mechanisms may be activated to cause the additional release.

Animals↗
PubMed1979

Effect of infusion chemotherapy and hepatic artery ligation on normal liver: experimental study in the cat.

The effects of arterial infusion with chemotherapy alone or in combination with hepatic artery ligation on the normal liver of the cat were studied. Early in the course of treatment cats receiving chemotherapy infusion only appeared sicker than animals in other groups. Yet only 1 of 5 cats was dead at 12 weeks. In contrast, 4 of 6 animals that had hepatic artery ligation and chemotherapy infusion, and 3 of 6 that had ligation of the hepatic artery only, died during the same period of follow-up. Progressive liver damage after dearterialization accounted for the high mortality rate. Histologic examination of liver biopsies taken from animals in these latter groups revealed marked destruction of the parenchyma. These changes were more extensive in animals treated by a combination of hepatic artery ligation and chemotherapy infusion. To avoid the injurious effects of permanent interruption of the hepatic arterial flow on normal liver tissue an alternative method of hepatic dearterialization is currently under investigation.

Animals↗
PubMed1981

Serum alpha-fetoprotein in rats after ligation of the common bile duct: relation to ductular cell (oval cell) proliferation.

Serum AFP levels were measured by radio-immunoassay in rats at various periods after ligation and section of the common bile duct and after sham-ligation. Transient elevations of serum AFP reaching statistically significant levels occurred at 3 to 10 days, 17 days and 28 days after ligation of the common bile duct but not in sham-operated rats. The peak elevations of serum AFP followed waves of mitosis in both the ductular cells and the hepatocytes as measured by autoradiography. Proliferation of hepatocytes, however, remained minor when compared to ductular cell multiplication. Ultra-structural and histochemical studies of the liver clearly distinguished ductular (oval) cells from hepatocytes and provided no evidence of transition from ductular cells to hepatocytes. Our findings suggest that ductular cell proliferation in the rat induced by ligation of the common bile duct may produce elevations in the serum AFP.

Animals↗
PubMed1997

Chronic spinal nerve ligation induces changes in response characteristics of nociceptive spinal dorsal horn neurons and in their descending regulation originating in the periaqueductal gray in the rat.

We studied whether a chronic neuropathy induced by unilateral spinal nerve ligation changes the response characteristics of spinal dorsal horn wide-dynamic range (WDR) neurons or their periaqueductal gray (PAG)-induced descending modulation. Experiments were performed in rats with behaviorally demonstrated allodynia induced by spinal nerve ligation and in a group of nonneuropathic control rats. The stimulus-response functions of WDR neurons for mechanical and thermal stimuli and the modulation of their peripherally evoked responses by electrical stimulation of the PAG were determined under pentobarbital anesthesia. The results showed that neuropathy caused a significant leftward shift in stimulus-response functions for mechanical stimuli. In contrast, stimulus-response functions for noxious heat stimuli in the neuropathic limb were, if anything, shifted rightward, although this shift was short of statistical significance. In neuropathic rats, PAG stimulation produced a significantly stronger attenuation of spinal neuronal responses induced by noxious heat in the unoperated than in the operated side. At the intensity that produced attenuation of noxious heat stimuli, PAG stimulation did not produce any significant change in spinal neuronal responses evoked by mechanical stimuli either from the operated or the nonoperated hindlimb of the neuropathic rats. Spontaneous activity of WDR neurons was higher in the operated side of neuropathic rats than in control rats. Afterdischarges evoked by peripheral stimuli were observed in 1/16 of the WDR neurons ipsilateral to spinal nerve ligation and not at all in other experimental groups. The WDR neurons studied were not activated by innocuous or noxious cold stimuli. The results indicate that spinal nerve ligation induces increased spontaneous activity and enhanced responses to mechanical stimuli in the spinal dorsal horn WDR neurons, whereas noxious heat-evoked responses are not significantly changed or if anything, attenuated. Moreover, the inhibition of noxious heat stimuli by PAG stimulation is attenuated in the neuropathic side. It is proposed that the observed changes in the response characteristics of the spinal dorsal horn WDR neurons and in their descending modulation may contribute to the neuropathic symptoms in these animals.

Animals↗
PubMed1994

Longitudinal changes in myocardial basic fibroblast growth factor (FGF-2) activity following coronary artery ligation in the dog.

Although fibroblast growth factor has been identified in normal and ischemic myocardium, temporal changes in mitogenic activity due to fibroblast growth factors in ischemic tissue have not been well established, nor has correlation been made with the known early increases in coronary collateral flow. This study sought to measure fibroblast growth factor activity in myocardium after coronary ligation. Accordingly the left anterior descending coronary artery of dogs was ligated and coronary collateral flow measured with radioactive microspheres. The heart was arrested after 2 h (four dogs), 1 week (four dogs), 2 weeks (three dogs), or 8 weeks (four dogs). Just before arrest collateral flow was again measured with radioactive microspheres, and the perfusion territory of the ligated vessel was demarcated with an intracoronary injection of Evans blue. The stained ischemic region was separated into central and peripheral portions. A transmural sample was removed from each portion for quantitation of tissue radioactivity and the rest was used for isolation of fibroblast growth factor and the measurement of mitogenic activity with vascular endothelial cells. To determine which fibroblast growth factor (FGF-1 or FGF-2) was being produced by the myocardium, aliquots of the isolated protein were first treated with specific antibodies to FGF-1 or FGF-2 before being assayed for mitogenicity. Coronary collateral flow did not change between 5 min and 2 h following coronary ligation, but was significantly increased at later time points. The ischemic/normal myocardial basic fibroblast growth factor mitogenic activity ratio in the peripheral ischemic tissue was increased after 2 h of ischemia (1.41 +/- 0.34), but the increase was not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1999

Hepatocyte growth factor supply accelerates compensatory hypertrophy caused by portal branch ligation in normal and jaundiced rats.

BACKGROUND: Hepatocyte growth factor (HGF), first identified as the most potent mitogen for hepatocytes, significantly stimulates liver regeneration after hepatectomy. In this report, we examined whether HGF is also useful in accelerating compensatory hypertrophy caused by portal branch ligation in normal and jaundiced rats. MATERIALS AND METHODS: Normal and reversible obstructive jaundiced rats underwent portal ligation of the left lateral and median branches, which supply approximately 70% of the total volume of the liver. Simultaneously, the animals were continuously treated with either recombinant human HGF (rhHGF) or vehicle alone via an intraperitoneally implanted osmotic pump. Two and four days after portal ligation, the degree of compensatory hypertrophy in unoccluded lobes was examined by measuring the wet weight ratios of the unoccluded lobes to the whole liver and the 5-bromo-2'-deoxyuridine labeling index of hepatocytes in each group. RESULTS: The HGF treatment significantly increased the wet weight ratios and the DNA synthesis in nonoccluded lobes 2 and 4 days after portal ligation in both normal and jaundiced rats. Moreover, rhHGF supply promptly decreased serum total bilirubin level in jaundiced rats. CONCLUSIONS: Continuous rhHGF administration not only accelerates compensatory hypertrophy in normal and jaundiced rats but also ameliorates hyperbilirubinemia in jaundiced rats.

Adaptation, Physiological↗
PubMed1978

Morphological and functional changes in the tight junctions of the bile canaliculi induced by bile duct ligation.

Thin sections after bile duct ligation showed that the depth of tight junctions appeared to increase and that the distance between individual punctate contacts appeared to become irregular and wider than in controls. The freeze fracture replicas clearly demonstrated these changes in the tight junction morphology. Changes were noted most conspicuously in the tight junction three weeks after ligation. Measurements of the junctional morphology in control and ligated specimens showed that the junctional depth had increased two fold in the latter, whereas the number of strands had scarcely changed. Lanthanum tracer experiments showed that the tight junctions did not permit the passage of the tracer in normal nor ligated rats. It was concluded that the mechanism of obstructive jaundice could not be related to changes in junctional morphology causing increased junctional permeability.

Animals↗
PubMed1995

Necrotizing fasciitis following postpartum tubal ligation. A case report and review of the literature.

Necrotizing fasciitis is a rare, but devastating subcutaneous bacterial infection which occurs following breaks in skin integrity, either natural, post traumatic or post surgical. Although it has been described following many surgical procedures, necrotizing fasciitis has not been previously described following postpartum tubal ligation. Necrotizing fasciitis was diagnosed four days after an uncomplicated postpartum tubal ligation via an infraumbilical incision. Rapid surgical debridement with broad spectrum antibiotic coverage provided successful therapy. Postpartum tubal ligation is one of the most common surgical procedures in obstetrics and gynecology, thus reports of complications resulting from this procedure are quite relevant to clinical practice. We present here the first reported case of necrotizing fasciitis following postpartum tubal ligation through an infraumbilical incision.

Adult↗