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PubMed2003

Differential c-Myc responsiveness to B cell receptor ligation in B cell-negative selection.

Responsiveness of c-Myc oncogene to B cell receptor ligation has been implicated in the induction of apoptosis in transformed and normal immature B cells. These studies provided compelling evidence to link the c-Myc oncogene with the process of negative selection in B-lymphocytes. However, in addition to apoptosis, B cell-negative selection has been shown to occur by secondary Ig gene rearrangements, a mechanism called receptor editing. In this study, we assessed whether differential c-Myc responsiveness to B cell receptor (BCR) ligation is associated with the mechanism of negative selection in immature B cells. Using an in vitro bone marrow culture system and an Ig-transgenic mouse model (3-83) we show here that c-Myc is expressed at low levels throughout B cell development and that c-Myc responsiveness to BCR ligation is developmentally regulated and increased with maturation. Furthermore, we found that the competence to mount c-Myc responsiveness upon BCR ligation is important for the induction of apoptosis and had no effect on the process of receptor editing. Therefore, this study suggests an important role of c-Myc in promoting and/or maintaining B cell development and that compartmentalization of B cell tolerance may also be developmentally regulated by differential c-Myc responsiveness.

Animals↗
PubMed2004

MHC-restricted Ig V region-driven T-B lymphocyte collaboration: B cell receptor ligation facilitates switch to IgG production.

B cells spontaneously process their endogenous Ig and present V region peptides on their MHC class II molecules. We have here investigated whether B cells collaborate with V region-specific CD4+ T cells in vivo. By use of paired Ig L chain-transgenic and TCR-transgenic mice and cell transfer into normal hosts, we demonstrate that B cell presentation of a V(L) region peptide to CD4+ T cells results in germinal centers, plasma cells, and Ab secretion. Because the transgenic B cells have a fixed L chain but polyclonal H chains, their B cell receptor (BCR) repertoire is diverse and may bind a multitude of ligands. In a hapten-based system, BCR ligation concomitant with V region-driven T-B collaboration induced germinal center formation and an IgM --> IgG isotype switch. In the absence of BCR ligation, mainly IgM was produced. Consistent with this, prolonged V region-driven T-B collaboration resulted in high titers of IgG autoantibodies against ubiquitous self-Ags, while natural-type Abs against exotic bacteria remained IgM. Taken together, V region-driven T-B collaboration may explain induction of natural IgM Abs (absence of BCR ligation) and IgG autoantibodies (BCR ligation by autoantigen) and may be involved in the development of autoimmunity.

Animals↗
PubMed2004

Architectural changes in the TCR:CD3 complex induced by MHC:peptide ligation.

A hallmark of T cell activation is the ligation-induced down-modulation of the TCR:CD3 complex. However, little is known about the molecular events that drive this process. The CD3 zeta-chain has been shown to play a unique role in regulating the assembly, transport, and cell surface expression of the TCR:CD3 complex. In this study we have investigated the relationship between CD3zeta and the TCRalphabetaCD3epsilondeltagamma complex after ligation by MHC:peptide complexes. Our results show that there is a significant increase in free surface CD3zeta, which is not associated with the TCR:CD3 complex, after T cell stimulation. This may reflect dissociation of CD3zeta from the TCRalphabetaCD3epsilondeltagamma complex or transport of intracellular CD3zeta directly to the cell surface. We also show that MHC:peptide ligation also results in exposure of the TCR-associated CD3zeta NH2 terminus, which is ordinarily buried in the complex. These observations appears to be dependent on Src family protein tyrosine kinases, which are known to be critical for efficient T cell activation. These data suggest a mechanism by which ligated TCR may be differentiated from unligated TCR and selectively down-modulated.

Amino Acid Sequence↗
PubMed2006

OX40 ligation of CD4+ T cells enhances virus-specific CD8+ T cell memory responses independently of IL-2 and CD4+ T regulatory cell inhibition.

We have previously shown that CD4(+) T cells are required to optimally expand viral-specific memory CD8(+) CTL responses using a human dendritic cell-T cell-based coculture system. OX40 (CD134), a 50-kDa transmembrane protein of the TNFR family, is expressed primarily on activated CD4(+) T cells. In murine models, the OX40/OX40L pathway has been shown to play a critical costimulatory role in dendritic cell/T cell interactions that may be important in promoting long-lived CD4(+) T cells, which subsequently can help CD8(+) T cell responses. The current study examined whether OX40 ligation on ex vivo CD4(+) T cells can enhance their ability to "help" virus-specific CTL responses in HIV-1-infected and -uninfected individuals. OX40 ligation of CD4(+) T cells by human OX40L-IgG1 enhanced the ex vivo expansion of HIV-1-specific and EBV-specific CTL from HIV-1-infected and -uninfected individuals, respectively. The mechanism whereby OX40 ligation enhanced help of CTL was independent of the induction of cytokines such as IL-2 or any inhibitory effect on CD4(+) T regulatory cells, but was associated with a direct effect on proliferation of CD4(+) T cells. Thus, OX40 ligation on CD4(+) T cells represents a potentially novel immunotherapeutic strategy that should be investigated to treat and prevent persistent virus infections, such as HIV-1 infection.

Apoptosis↗
PubMedDate not supplied

Tubal ectopic pregnancy after bilateral tubal ligation: A case report.

BACKGROUND: Tubal ligation is a common method of contraception, and pregnancy after this method of sterilization is uncommon. We here present a report of Tubal pregnancy after a Bilateral Tubal Ligation (BTL). METHOD: The case notes of a 35 year Nigerian female who presented with a tubal pregnancy after BTL and a review of literature on the subject was used. RESULT: A 35-year-old para 4=0 had bilateral tubal ligation during caesarean section for her last childbirth. She presented 3 years later with a six weeks history of irregular vaginal bleeding and lower abdominal pain and had a laparotomy for a right tubal ectopic pregnancy. CONCLUSION: Ectopic pregnancy after bilateral tubal ligation is uncommon. Females who undergo BTL should be adequately counseled on the possibility of failure of this procedure for contraception.

Adult↗
PubMed1999

Neuronal nitric oxide synthase mRNA upregulation in rat sensory neurons after spinal nerve ligation: lack of a role in allodynia development.

Pharmacological evidence suggests a functional role for spinal nitric oxide (NO) in the modulation of thermal and/or inflammatory hyperalgesia. To assess the role of NO in nerve injury-induced tactile allodynia, we examined neuronal NO synthase (nNOS) expression in the spinal cord and dorsal root ganglia (DRG) of rats with tactile allodynia because of either tight ligation of the left fifth and sixth lumbar spinal nerves or streptozotocin-induced diabetic neuropathy. RNase protection assays indicated that nNOS mRNA (1) was upregulated in DRG, but not spinal cord, neurons on the injury side beginning 1 d after nerve ligation, (2) peaked (approximately 10-fold increase) at 2 d, and (3) remained elevated for at least 13 weeks. A corresponding increase in DRG nNOS protein was also observed and localized principally to small and occasionally medium-size sensory neurons. In rats with diabetic neuropathy, there was no significant change in DRG nNOS mRNA. However, similar increases in DRG nNOS mRNA were observed in rats that did not develop allodynia after nerve ligation and in rats fully recovered from allodynia 3 months after the nerve ligation. Systemic treatment with a specific pharmacological inhibitor of nNOS failed to prevent or reverse allodynia in nerve-injured rats. Thus, regulation of nNOS may contribute to the development of neuronal plasticity after specific types of peripheral nerve injury. However, upregulation of nNOS is not responsible for the development and/or maintenance of allodynia after nerve injury.

Animals↗
PubMed2000

CD38 ligation inhibits normal and leukemic myelopoiesis.

CD38 is a transmembrane molecule whose expression varies during hematopoietic cell differentiation. We used stroma-supported cultures of human myeloid cells to assess the effects of CD38 ligation on myeloid differentiation. In 8 experiments with CD34(+ )cells purified from normal bone marrow or cord blood, flow cytometry used with antibodies to CD34 and myeloperoxidase (MPO) identified 4 cell populations after 7 days of culture. Addition of anti-CD38 (T16) to the cultures induced a profound reduction of the most mature (CD34(-)MPO(++)) cell population, which includes promyelocytes, myelocytes and metamyelocytes; mean (+/- SD) cell recovery was 12.8% +/- 9.8% of that in parallel cultures with an isotype-matched control antibody. The suppressive effect of CD38 ligation on phenotypically more immature normal cells was inconsistent but generally less pronounced. Recovery of CD34(++)MPO(-) cells was 63.3% +/- 24.4%, recovery of CD34([+/-] )MPO(- )cells was 95.3% +/- 35.1%, and recovery of CD34(-)MPO(+) cells was 42.0% +/- 18.7% of that in control cultures. However, anti-CD38 suppressed recovery of cells obtained from 6 patients with CD38(+) acute myeloid leukemia; after 7-day cultures, cell recovery was 25.2% +/- 21.7% of that in control cultures. Cell recovery was also reduced by F(ab')(2) or Fab fragments of anti-CD38. CD38 ligation dramatically suppressed recovery of murine 32D myeloid cells transfected with human CD38 and cocultured with stroma (3.8% +/- 7.3%; n = 7). CD38 ligation of CD38( + )32D cells also induced cell aggregation, tyrosine kinase activity, and Ca(++) influx. We conclude that CD38 mediates signals that culminate in suppression of myeloid cell growth and survival. (Blood. 2000;95:535-542)

ADP-ribosyl Cyclase↗
PubMed2000

Spontaneous apoptosis in neutrophils is associated with downregulation of HLA Class I and is prevented by ligation of Class I.

In many types of cells, ligation of human leukocyte antigens (HLA) Class I molecules with specific mAbs results in the transduction of signals that trigger different cell functions. We have investigated the effects of Class I ligation in human neutrophils. After several hours in culture, neutrophils split spontaneously into two subpopulations, one with normal and the other with reduced levels of Class I. The latter subpopulation displayed high binding capacity for Annexin V, showed a hypodiploid peak, electrophoretic DNA fragmentation, and morphological features of apoptotic cells. The addition of drugs known to delay apoptosis (GM-CSF or cAMP) resulted in a reduction of Class I modulation. Furthermore, ligation of surface Class I with F(ab')2 fragments of the anti-Class I mAb W6/32 resulted in a delay in the progression of apoptosis. These data indicate that this surface Class I molecule is a marker of age-related apoptosis, and the ligation of these molecules results in the transduction of a signal that inhibits apoptosis. Thus, the downregulation of HLA Class I molecules in aging neutrophils prevents their halting the apoptotic process.

Adult↗
PubMed1976

[The psychological results of tubal ligation as definitive method of contraception (author's transl)].

The cases of tubal ligation at the University Department of Tubingen and the University Department of Giessen during the last few years were reviewed. In most cases the psychological results of the procedure is positive and results in an improved partner relationship in most cases, provided that the procedure was the result of a mature decision by the couple. Tubal ligation in the puerperium is more favorable than in conjunction with the Caesarean Section. Interval sterilization shows the best results. A thorough discussion by the physician and if possible a psychological discussion should take place prior to the tubal ligation since both are important aids in the decision. The social indication should be clearly defined and the responsibility of the couple should be emphasized. A well defined and documented task for the clinical practice of prior physician and psychological discussion of tubal ligation is the basis of a present prospective study at the University Department for Women in Tubingen which is designed to show the positive psychological effects on the couple.

Adult↗
PubMed1999

[Experimental study on head and neck hemodynamics after ligation of jugular veins].

OBJECTIVE: To study alteration of neck hemodynamics after ligation of jugular veins during radical neck dissection. METHODS: 4 rhesus monkeys were selected to simulate the human bilateral radical neck dissection. After operation, the jugular veins were ligated or loosen and the blood stream quantities and blood pressure of jugular veins and arteries were measured simultaneously. RESULTS: The hemodynamic index would changed after jugular vein was ligated, the more the jugular veins were ligated, the greater effects the hemodynamics index of jugular veins were occurred, but there was little effect on arteries. CONCLUSION: The external jugular veins have the effect of compensating cerebral venous outflow after removing the internal jugular veins, and the external jugular veins should be conserved when bilateral or unilateral radical neck dissection was done.

Animals↗
PubMed1992

Intrinsic intermolecular DNA ligation activity of eukaryotic topoisomerase II. Potential roles in recombination.

Drosophila melanogaster topoisomerase II is capable of joining phi X174 (+) strand DNA that it has cleaved to duplex oligonucleotide acceptor molecules by an intermolecular ligation reaction (Gale, K. C. and Osheroff, N. (1990) Biochemistry 29, 9538-9545). In order to investigate potential mechanisms for topoisomerase II-mediated DNA recombination, this intrinsic enzyme activity was further characterized. Intermolecular DNA ligation proceeded in a time-dependent fashion and was concentration-dependent with respect to oligonucleotide. The covalent linkage between phi X174 (+) strand DNA and acceptor molecules was confirmed by Southern analysis and alkaline gel electrophoresis. Topoisomerase II-mediated intermolecular DNA ligation required the oligonucleotide to contain a 3'-OH terminus. Moreover, the reaction was dependent on the presence of a divalent cation, was inhibited by salt, and was not affected by the presence of ATP. The enzyme was capable of ligating phi X174 (+) strand DNA to double-stranded oligonucleotides that contained 5'-overhang, 3'-overhand, or blunt ends. Single-stranded, nicked, or gapped oligonucleotides also could be used as acceptor molecules. These results demonstrate that the type II enzyme has an intrinsic ability to mediate illegitimate DNA recombination in vitro and suggests possible roles for topoisomerase II in nucleic acid recombination in vivo.

Adenosine Triphosphate↗
PubMed2003

[Self-ligating edgewise brackets. An overview].

During the last years both the manufactures and the orthodontists seem to show an increased interest in self-ligating brackets. This paper aims to present the history of self-ligating systems, to describe the three mostly used bracketsystems and to review the relevant literature. It seems from the existing data that self-ligating brackets have certain advantages over conventionally ligated brackets. However, the data are still thin and a high need for well designed clinical trials exist.

Dental Stress Analysis↗
PubMedDate not supplied

The efficacy of endoscopic ligation for the prevention of variceal rebleeding in cirrhotic patients according to the hepatocellular function.

BACKGROUND/AIMS: Endoscopic variceal ligation is considered the leading therapy for the prevention of variceal rebleeding in cirrhotic patients. However, the efficacy of this method in cirrhotic patients with poor hepatocellular function is not well-known yet. The aim of this study is to compare the efficacy of endoscopic variceal ligation for the eradication of esophageal varices, rebleeding and mortality rates, based on hepatocellular function, as graded by Child-Pugh. METHODOLOGY: Between June 1996 and December 2001, 163 consecutive cirrhotic patients were submitted to band ligation at our Department. Of these cases, 128 patients with previous variceal bleeding (mean age = 50.7 years; 90 males and 38 females) were followed-up. 55 patients were graded as Child A, 49 as Child B and 24 as Child C. RESULTS: The mean follow-up period for all groups was 17.3 months. Varices were eradicated in 82.7% (86 of 104 cases) of Child A/B cirrhotic patients and in 54.2% (13 of 24 cases) of Child C cases (p=0.0061). Eradication was achieved after a mean of 3.7 sessions, and no difference was observed among the groups. Varices recurred in 38.4% (38 of 99 cases) of the patients, presenting no difference among the different Child classes. However, there was a trend to a higher rebleeding rate among patients with variceal recurrence (21% vs. 8.2%, p=0.075). Rebleeding occurred in 20.2% (21 of 104 cases) of Child A/B cirrhotics and in 41.7% (10 of 24 cases) of Child C patients (p=0.001 log-rank test). The mortality rate was 13.5% (14 of 104 cases) among Child A/B patients and 37.5% (9 of 24 cases) among Child C cases (p=0.0135). CONCLUSIONS: Endoscopic variceal ligation is an effective method for the prevention of rebleeding in patients with better liver function. Child C patients had a poor response to treatment. These patients, in a statistically significant fashion, had a worse eradication rate and greater rebleeding and mortality rates than Child A/B patients.

Endoscopy↗
PubMed1992

Incidence of hypotension induced by spinal anesthesia with xylocaine for cesarean section and postpartum tubal ligation.

The incidence of hypotension induced by spinal anesthesia in 154 ASA class I or II patients having Cesarean section and postpartum bilateral tubal ligation was studied. Xylocaine (2%) 60-65 mg was used for spinal anesthesia. There was 41.0% of patients in Cesarean section group developed hypotension induced by spinal anesthesia, and 13.5% in tubal ligation group. We found no correlation between the time after delivery and the occurrence of hypotension induced by spinal anesthesia. In addition, 20.3% of the patients in tubal ligation group required intravenous narcotics because of inadequate sensory blockade during skin incision, but only 9.0% in Cesarean section needed the same supplement which was due to visceral pain during intra-abdominal manipulation. We conclude that spinal anesthesia with 2% xylocaine is safe and effective in both Cesarean section and postpartum tubal ligation although a significant difference of spinal hypotension existed.

Adult↗
PubMedDate not supplied

Effect of band ligation on portal hypertensive gastropathy and development of fundal varices.

BACKGROUND: Use of endoscopic therapies for esophageal varices has resulted in increased prevalence of fundal varices and severe portal hypertensive gastropathy. This study was meant to compare the effect of band ligation and sclerotherapy on development of fundal varices and portal hypertensive gastropathy. METHODS: Patients with esophageal varices presenting in the endoscopy unit of Shiakh Zayed Hospital, with at least one previous endoscopy were included. Patient's past record was reviewed for findings and type of treatment given for varices during first endoscopy, number of endoscopies till date, number of esophageal varices band ligation (EVBL) or sclerotherapy sessions. All patients underwent upper GI endoscopy and findings were recorded. Type of treatment patient rendered during first endoscopy either EVBL or sclerotherapy was correlated to the presence of fundal varices and severity of portal hypertensive gastropathy observed on present endoscopy, using Chi square test (chi2). RESULTS: Eighty one patients were included. Mean age of patients was 48.70 +/- 12.63. Esophageal varices band ligation was carried out during first endoscopy in 49 (60.5%) patients and sclerotherapy in 31 (38.2%) patients. On fresh endoscopy, fundal varices were seen in 25 (30.8%) patients. Severe portal hypertensive gastropathy was found in 26 (32.1%) and mild in 54 (66.7%) patients. Severity of portal hypertensive gastropathy and presence of fundal varices in recent endoscopy was significantly more in patients with EVBL in first endoscopy. CONCLUSION: Band ligation of esophageal varices is associated with more frequent development of fundal varices and worsening of portal hypertensive gastropathy compared to sclerotherapy.

Esophageal and Gastric Varices↗
PubMedDate not supplied

[Indications for bilateral ligation of the uterine arteries and the hypogastric arteries in refractory obstetrical hemorrhages].

The author describes the various indications for obstetric hemostatic vascular ligations accepted today by specialists. In serious post-partum uterine hemorrhage due to pathology of contraction and or retraction of the uterus, hemorrhage refractory to classical conservative treatment, specialists use either bilateral ligation of the uterine arteries at the site of their ascending branches, or bilateral ligation of the anterior branch of the internal iliac artery (BLILA), sometimes thus avoiding hemostatic hysterectomy. However hemostatic vascular ligations may be attempted only rarely, in particular when hemostasis procedures follow one after the other in the absence of an immediate threat to the mother's life. Prophylactic BLILA may be performed immediately after hemostatic hysterectomy (as a complement before closing the abdominal wall). It thus guarantees hemostasis and avoids the possibility of reoperation to achieve hemostasis, which could be fatal. BLILA performed at the postoperative (posthysterectomy) stage, during hemostatic reoperation, is of a curative nature and is effective only when hemorrhage is coming from a branch of the internal iliac artery. In severe post-partum hemorrhage coming from the peri-uterine regions supplied by the internal iliac arteries, only BLILA may be useful when local surgical hemostasis is ineffective or impossible.

Female↗
PubMed1987

Contrasting patterns of DNA strand breakage and ADP-ribosylation-dependent DNA ligation during granulocyte and monocyte differentiation.

Previous studies have shown that structural changes in DNA, including the ligation of pre-existing DNA breaks and the opening and closure of new breaks, occur shortly after exposure of granulomonocytic precursors (CFU-GM) to granulocyte-macrophage colony stimulating activity (GM-CSA). Monocytic differentiation of CFU-GM is selectively inhibited by compounds known to inhibit the nuclear enzyme ADP-ribosyl transferase (ADPRT). Since this enzyme, which transfers ADP-ribose units to chromatin proteins, is known to activate DNA ligase, we attempted to determine whether ligation of one or both types of DNA break is required for monocytic differentiation. Breaks in DNA were examined using the nucleoid sedimentation technique in which DNA breaks cause loss of DNA supercoiling in nucleoids and concomitant changes in their sedimentation through neutral sucrose gradients. We here report that two distinct patterns of DNA strand breakage and ligation are associated with differentiation to the granulocyte and monocyte lineages. Monocytic inducers (phorbolester and vitamin D3) predominantly produce closure of pre-existing strand breaks, whereas granulocytic inducers (granulocyte colony stimulating activity, G-CSA; retinoic acid) cause opening and closure of new breaks. Only ligation of the pre-existing breaks is highly sensitive to inhibition by 3-methoxybenzamide (a potent ADPRT inhibitor), and only monocytic differentiation is impaired by addition of this compound. These findings suggest that DNA structural changes may be directly involved in granulocyte-macrophage switching.

Adenosine Diphosphate Ribose↗
PubMed1988

Thermography of gluteal regions after hypogastric artery ligation.

Thermographic examination of buttocks of 7 patients after hypogastric artery ligation using non-absorbable suture has been performed. In 6 patients the possibility of eventual recanalization has been eliminated by aortography, in 1 patient by pelvic angioscintigraphy. Repeated thermographic examination of 3 patients after bilateral ligation has shown no anomalous results. In 1 among 4 patients after unilateral ligation a cooler area could be repeatedly observed on the ipsilateral side. Thermography, in combination with other methods of examination, seems to be suitable for complex study of the state of circulation after hypograstric artery ligation, performed to stop a life-threatening hemorrhage.

Adult↗