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At least 37 records · Page 2Linked to original sources

PubMed2006

Surgical ventricular reverse remodeling in severe ischemic dilated cardiomyopathy: the relevance of the left ventricular equator as a prognostic factor.

OBJECTIVES: Surgical ventricular reverse remodeling has been shown to possibly improve hemodynamics and symptoms, but effects on long-term mortality are not established. No consistent data are available on which patients will benefit most from this procedure. This study was designed to analyze the predictors of long-term survival after surgical ventricular reverse remodeling in patients with ischemic cardiomyopathy. METHODS: Eighty-five patients who underwent surgical ventricular reverse remodeling between May 1991 and October 2003 were retrospectively analyzed. Left ventricular wall motion and left ventricular equatorial diameter were assessed by means of angioventriculography. Left ventricular ejection fraction and volumes were measured by means of echocardiography. Cox regression analysis was used in several combinations to create a final model for identifying predictors of death. RESULTS: Actuarial survival after 1, 3, 5, and 10 years was 89%, 79%, 75%, and 75%, respectively. New York Heart Association class improved from 2.9 +/- 1.0 to 1.3 +/- 0.5 (P < .0001), left ventricular ejection fraction increased from 27.6% +/- 6.3% to 43.0% +/- 10.1% (P < .0001), and left ventricular end-systolic volume index decreased from 89.6 +/- 27.6 mL/m2 to 56.5 +/- 34.5 mL/m2 (P < .0001). Multivariate analysis identified left ventricular equatorial diameter of 70 mm or greater (hazard ratio, 5.28; 95% confidence interval, 1.79-11.71; P = .020) and segmental akinesia (hazard ratio, 4.46; 95% confidence interval, 1.23-17.12; P = .024) as the only independent predictors of death. CONCLUSIONS: In this analysis of a single cohort of patients, surgical ventricular reverse remodeling improves the symptoms of ischemic cardiomyopathy, as well as left ventricular function, shape, and volume, with encouraging long-term outcomes, particularly in patients with dyskinesia. A left ventricular equatorial diameter of 70 mm or greater appears to be an important independent prognostic factor, which suggests the relevance of the left ventricular equatorial region for effective surgical reverse remodeling.

Adult↗

PubMed1993

Late effects of cardiomyoplasty on left ventricular mechanics and diastolic filling.

BACKGROUND: Dynamic cardiomyoplasty is a relatively new surgical procedure proposed for treatment of severe myocardial failure. Limited clinical experience suggests that this procedure reverses congestive heart failure, improving the long-term survival. METHODS AND RESULTS: In this investigation, the late effects (16.5 +/- 4.8 months after surgery) of cardiomyoplasty on left ventricular mechanics and diastolic filling were studied in eight male patients (mean age, 45 +/- 7 years). The investigation was performed with the myostimulator on and off (24 +/- 1 hours off) using a microtip catheter to obtain the left ventricular pressures simultaneously with Doppler (inflow velocities) and M-mode and two-dimensional echocardiographic recordings. Statistical comparisons were made with Student's t test for paired data. Dynamic cardiomyoplasty increased the maximal elastance (17 +/- 1 versus 21 +/- 1 mm Hg/cm, P = .006) and decreased the systolic wall stress (253 +/- 17 versus 190 +/- 12 g/cm2, P = .029). Left ventricular end-diastolic pressure decreased (27.1 +/- 2.8 versus 17.6 +/- 1.7 mm Hg, P = .019), as did end-diastolic circumferential wall stress (69 +/- 8 versus 37 +/- 5 g/cm2, P = .002). The chamber and muscle stiffnesses decreased (120 +/- 31 versus 52 +/- 11 mm Hg/cm, P = .017; 994 +/- 185 versus 426 +/- 76 g/cm2, P = .002, respectively). The pattern of left ventricular diastolic filling changed, with a decrease of early peak flow (231 +/- 20 versus 217 +/- 21 mL/s, P = .022), of deceleration time (163 +/- 28 versus 116 +/- 26 seconds, P = .001), and of flow area during rapid filling (105 +/- 15 versus 75 +/- 12 mL, P = .004) and an increase of flow area during atrial contraction (39 +/- 4 versus 88 +/- 9 mL, P = .001). CONCLUSIONS: Our detailed evaluation of left ventricular mechanics demonstrates that cardiomyoplasty has significant multiple beneficial effects on dilated myopathic heart.

Assisted Circulation↗

PubMed1998

Predominant expression of T helper 2 cytokines and altered expression of T helper 1 cytokines in long-term allograft survival induced by intrathymic immune modulation with donor class I major histocompatibility complex peptides.

BACKGROUND: We have recently demonstrated that three synthetic peptides corresponding to the alpha-helices of the alpha1 and alpha2 domains of the donor class I RT1.Aa molecule served as efficient CD4+ T-cell epitopes for indirect recognition of this molecule during cardiac allograft rejection in the PVG.R8-toPVG.1U rat strain combination. These peptides induce long-term graft survival when injected into the thymus 7 days before transplantation under the cover of transient immunosuppression with anti-rat lymphocyte serum. In this study, we analyzed intragraft cytokine gene expression to test whether immune deviation to the T helper (Th) 2 response is associated with long-term allograft survival in this model. METHODS: Intragraft cytokine gene expression was analyzed using a competitive reverse transcription polymerase chain reaction method we developed for this study. Cytokine gene expression was quantified in control allografts (n=5) with acute rejection and allografts from intrathymically manipulated recipients with acute rejection (n=5), delayed rejection (n=7), or no rejection (n=8). RESULTS: Long-surviving allografts expressed high levels of interleukin (IL)-4, IL-10, transforming growth factor (TGF)-beta, interferon (IFN)-gamma, and undetectable levels of IL-2. Allografts that were rejected in a delayed fashion expressed mostly IL-2, IFN-gamma, and TGF-beta with low or undetectable levels of IL-4 and IL-10. Acutely rejected allografts from unmanipulated controls or peptide-manipulated recipients expressed high levels of IL-2, IFN-gamma, TGF-beta and undetectable levels of IL-4 or IL-10. All allografts also expressed T-cell receptor Cbeta gene, providing evidence for the presence of T-cell infiltrates in the grafts. CONCLUSIONS: These observations demonstrate that acute graft rejection in this model is associated with the expression of Th1 cytokines, IL-2, and IFN-gamma, whereas long-term survival is associated with predominant expression of Th2 cytokines, IL-4, and IL-10. The expression of IFN-gamma in long-surviving allografts in the absence of IL-2 provides evidence for altered activation of the Th1 response in this intrathymic immune modulation model.

Animals↗

PubMed1995

Diagnosis, management, and survival of patients with leptomeningeal cancer based on cerebrospinal fluid-flow status.

BACKGROUND: The authors assessed cerebrospinal fluid (CSF) flow in patients with carcinomatous meningitis using technetium-99m-DTPA (Tc-99) ventriculography to determine the frequency of flow abnormalities, their reversibility with treatment, and the implications for successful therapy and survival. METHODS: Technetium-99m-DTPA flow studies were performed in 31 patients after placement of Ommaya reservoirs (Baxter, McGaw Park, IL). Two millicuries of Tc-99 were injected into the reservoir. Planar images of the head and entire spine were obtained after 10 and 30 minutes and after 1, 4, 6, and 24 hours. Follow-up studies were performed for 12 patients whose initial studies were abnormal or who developed complications of therapy. RESULTS: In 19 of the 31 patients (61%), ventricular-outlet, spinal, or convexity blocks were identified. In 11 of these 19 patients, focal radiotherapy to the site of the block restored normal flow. Survival among patients with initially normal, abnormal but correctable, and abnormal but uncorrectable CSF flow differed significantly (6.9, 13.0, and 0.7 months respectively; P < 0.001). Some patients who were treated intrathecally despite abnormal CSF flow experienced drug-related toxicity. CONCLUSIONS: Cerebrospinal fluid-flow blocks are common in patients with carcinomatous meningitis and may occur at the skull base, in the spinal canal, and over the convexities. These flow abnormalities often can be corrected with appropriately directed radiotherapy. If untreated, CSF tumor progression (protected site effect), neurotoxicity (high concentration effect), and systemic toxicity (reservoir effect) can occur, resulting in shortened survival and treatment-related morbidity. Therefore, intrathecal chemotherapy should be preceded by a radionuclide flow study and should be delayed if abnormal flow is documented until appropriate radiotherapy reestablishes normal flow.

Adolescent↗

PubMed2003

Reversibility of severe metabolic stress in stored platelets after in vitro plasma rescue or in vivo transfusion: restoration of secretory function and maintenance of platelet survival.

BACKGROUND: Determining reversible aspects of the platelet storage lesion may result in improved function and survival of transfused platelets. STUDY DESIGN AND METHODS: Using a model of high-dose (apheresis-derived) platelet concentrates (PC), functional changes imposed by transient adverse metabolic conditions (pH < 6.0 for 1-2 hr) that could be reversed by autologous plasma rescue followed by standard platelet storage were investigated. Whole-blood-derived PCs were transfused into a small number of normal volunteers to determine platelet recovery and survival. RESULTS: Without rescue, high-dose PCs developed severe in vitro functional derangements at the time of the pH nadir including 1) loss of resting morphology; 2) complete abrogation of osmotic recovery and platelet aggregation and glycoprotein IIb/IIIa up-regulation to agonist; and 3) decreased alpha-granule release. By contrast, spontaneous and agonist-induced binding of annexin V were unaffected by adverse metabolic conditions. Plasma rescue to an optimal pH improved morphology scores, stabilized osmotic recovery, and completely restored platelet secretory responses, as measured by aggregation, glycoprotein IIb/IIIa up-regulation, and alpha-granule release. In a limited number of studies, plasma rescue was accompanied by preserved in vivo platelet recovery and survival after autologous transfusion after 5 days of storage. CONCLUSION: Transient derangement of platelet metabolism, which does not increase membrane phosphatidylserine exposure, causes in vitro functional abnormalities that are fully reversed or stabilized by metabolic rescue. Preliminary data suggest that such rescued platelets may have normal posttransfusion recovery and survival.

Acidosis↗

PubMed2003

Prognostic significance of occult metastases in colon cancer.

PURPOSE: The purpose of this study was to determine the prognostic significance of occult lymph node metastases in colon cancer detected by cytokeratin 20 reverse transcription polymerase chain reaction. METHODS: Two hundred patients undergoing elective colonic resections were enrolled in the study. Lymph nodes from resected specimens were dissected fresh and assessed by both reverse transcription polymerase chain reaction and histopathology. Follow-up was undertaken for up to five years, and the major end point of death was recorded. Univariate survival analysis was performed by the log-rank method and the change-in-estimate method was used to construct multivariate analysis models for the effect of cytokeratin 20 reverse transcription polymerase chain reaction lymph node status on overall survival. RESULTS: A total of 2,317 lymph nodes from 200 patients were assessed by both histopathology and cytokeratin 20 reverse transcription polymerase chain reaction. Forty-eight of 141 (34 percent) histologically lymph node-negative patients had evidence of occult metastases by cytokeratin 20 reverse transcription polymerase chain reaction. An interim analysis was performed at a median of 42 (range, 23-75) months. Cytokeratin 20 reverse transcription polymerase chain reaction lymph node status was a highly significant predictor of overall survival (P < 0.0001) on univariate analysis. In addition, the number of reverse transcription polymerase chain reaction-positive lymph nodes was a significant predictor of survival in the histologically lymph node-negative group (P < 0.0001) on univariate analysis. On multivariate analysis cytokeratin 20 reverse transcription polymerase chain reaction lymph node status had independent prognostic significance for overall survival (P = 0.021; hazard ratio = 2.7) and the number of cytokeratin 20 reverse transcription polymerase chain reaction-positive lymph nodes was a significant predictor of overall survival in the histologically lymph node-negative group (P = 0.005; hazard ratio = 1.1-11.1). CONCLUSION: Cytokeratin 20 reverse transcription polymerase chain reaction has potential as a clinically useful marker for staging colorectal cancer. Further follow-up is required, but if the current trends continue, a study of the effect of adjuvant therapy in patients with occult metastases detected by cytokeratin 20 reverse transcription polymerase chain reaction is indicated.

Adenocarcinoma↗

PubMed2000

Thymidylate synthase quantitation and in vitro chemosensitivity testing predicts responses and survival of patients with isolated nonresectable liver tumors receiving hepatic arterial infusion chemotherapy.

BACKGROUND: Patients with isolated, nonresectable liver tumors may receive regional hepatic arterial infusion (HAI) chemotherapy with response rates of about 50%. The objective of this study was to investigate the value of thymidylate synthase (TS) determination in combination with in vitro chemosensitivity testing to predict the responses and survival of patients receiving HAI. METHODS: TS mRNA expression was quantitated using a reverse transcription-polymerase chain reaction technique with beta-actin as the internal standard. In vitro chemosensitivity testing was performed with tumor cell suspensions using the human tumor colony-forming assay (HTCA). RESULTS: An analysis of the test combination in 24 consecutive patients revealed that 77% (10 of 13) of the sensitive and 9% (1 of 11) of the resistant patients had complete or partial clinical responses. Sensitive patients were 8.5-fold more likely to respond (P = 0.0036) and displayed with 32 months (range, 5-75 months) a longer median survival than resistant patients with 17 months (range, 3-28 months, P = 0.003). Analysis of the Kaplan-Meier curves revealed that sensitive patients had a higher overall survival probability, as determined by the log rank test (P = 0.044). CONCLUSIONS: These results suggest that the clinical outcomes of patients receiving HAI therapy may be predictable with TS quantitation and HTCA. It is possible, therefore, that this combination may be used in the future to select patients with liver tumors who will benefit from HAI before the start of regional chemotherapy.

Adult↗

PubMed2005

Primary HIV-1 infection sets the stage for important B lymphocyte dysfunctions.

OBJECTIVES: To investigate the effects of primary HIV-1 infection (PHI) and of two antiretroviral therapies [highly active antiretroviral therapy (HAART) or reverse transcriptase inhibitors (RTI)] on activation, differentiation and survival of B cells. METHODS: Naive and memory B cells from three groups [PHI (31), chronic infection (26) and healthy donors (12)] were studied for surface expression of Fas, LAIR-1, CD70, intracellular expression of Bcl-2 and spontaneous apoptosis. Fluorescence activated cell sorting (IgD+IgM+CD19+CD27+) and short-term cell culture to analyse induction of CD25 on B cells were performed in five patients with PHI. Patients with PHI were sampled at baseline, and after 1 and 6 months of therapy. Results were analysed by parametric and non-parametric tests and by mathematical modelling. RESULTS: In PHI, B cells were significantly decreased; naive and memory B lymphocytes showed a high degree of activation, manifested by hypergammaglobulinaemia, altered expression of Fas and LAIR-1, and high rate of spontaneous apoptosis. Antiretroviral treatment improved the activation/differentiation status of B cells, reduced apoptosis to levels comparable to those in healthy individuals and restored the ability of B cells to respond to T cell-dependent activation. B cells showed slightly better recovery in patients taking HAART than in those taking RTI. Decreased IgM-positive memory B cells and lower induction of CD25 expression on B cells upon T cell activation at diagnosis of PHI was shown in five patients tested. These parameters normalized after 6 months of therapy. CONCLUSION: B cell dysfunctions found in chronic HIV-1 infection appear during PHI and initiation of antiretroviral therapy early during infection may help to preserve the B cell compartment.

Adolescent↗

PubMed1997

Stored blood--an effective immunosuppressive method for transplantation of kidneys from unrelated donors. An 11-year follow-up.

Thirty-seven patients were submitted to kidney transplantation after transfusion at 2-week intervals with 4-week stored blood from their potential donors. All patients and donors were typed for HLA-A-B and DR antigens. The patients were also tested for cytotoxic antibodies against donor antigens before each transfusion. The percentage of panel reactive antibodies (PRA) was determined against a selected panel of 30 cell donors before and after the transfusions. The patients were immunosuppressed with azathioprine and prednisone. Rejection crises were treated with methylprednisolone. The control group consisted of 23 patients who received grafts from an unrelated donor but who did not receive donor-specific pretransplant blood transfusion. The incidence and reversibility of rejection episodes, allograft loss caused by rejection, and patient and graft survival rates were determined for both groups. Non-parametric methods (chi-square and Fisher tests) were used for statistical analysis, with the level of significance set at P < 0.05. The incidence and reversibility of rejection crises during the first 60 post-transplant days did not differ significantly between groups. The actuarial graft and patient survival rates at five years were 56% and 77%, respectively, for the treated group and 39.8% and 57.5% for the control group. Graft loss due to rejection was significantly higher in the untreated group (P = 0.0026) which also required more intense immunosuppression (P = 0.0001). We conclude that transfusions using stored blood have the immunosuppressive effect of fresh blood transfusions without the risk of provoking a widespread formation of antibodies. In addition, this method permits a reduction of the immunosuppressive drugs during the process without impairing the adequate functioning of the renal graft.

Adult↗

PubMed2000

RU486 increases radiosensitivity and restores apoptosis through modulation of HPV E6/E7 in dexamethasone-treated cervical carcinoma cells.

OBJECTIVE: Cervical carcinoma tumors containing radioresistant cells are associated with decreased local control and survival. Therefore, strategies to increase cell kill during radiotherapy have a clear rationale. It was previously determined that treatment with the corticosteroid dexamethasone increased radioresistance and decreased apoptosis in C4-1 cervical carcinoma cells. The goal of this study was to determine whether hormone antagonists, specifically Mifepristone (RU486), could reverse the effects of dexamethasone on clonogenic survival and apoptosis following gamma-irradiation. METHODS: Cervical carcinoma cell line C4-1 cells were exposed to 1 microM dexamethasone in the presence or absence of 1 microM Mifepristone (RU486), a hormone antagonist, and irradiation. Cells were analyzed for steroid-dependent HPV E6/E7 mRNA expression (by Northern blot analysis), clonogenic survival, and apoptosis (by Annexin V staining and the DNA fragmentation assay). In addition, p53 protein levels were determined by Western blot analysis. RESULTS: The hormone antagonist RU486 reversed dexamethasone-dependent upregulation of E6/E7 mRNA and restored radiation-induced p53 expression, apoptosis, and clonogenic survival to levels similar to those observed following irradiation alone. CONCLUSION: RU486 reverses glucocorticoid-dependent upregulation of HPV E6/E7, which corresponds to restoration of p53 expression, and restores radiosensitivity and apoptosis following gamma-irradiation. Therefore, it appears that along with radiation, RU486 may be a beneficial agent in the treatment of hormone-reactive cervical tumors.

Apoptosis↗

PubMed2001

Interferon gamma inhibits growth of human pancreatic carcinoma cells via caspase-1 dependent induction of apoptosis.

BACKGROUND AND AIMS: The poor prognosis of pancreatic cancer is partly due to resistance to a broad spectrum of apoptotic stimuli. To identify intact proapoptotic pathways of potential clinical relevance, we characterised the effects of interferon gamma (IFN-gamma) on growth and survival in human pancreatic cancer cells. METHODS: IFN-gamma receptor expression and signal transduction were examined by reverse transcriptase-polymerase chain reaction (RT-PCR), immunoprecipitation, western blot analysis, and transactivation assays. Effects on cell growth and survival were evaluated in terms of cell numbers, colony formation, cell cycle analysis, DNA fragmentation, and poly(ADP ribose) polymerase (PARP) cleavage. RESULTS: All four pancreatic cancer cell lines examined expressed functional IFN-gamma receptors and downstream effectors, including the putative tumour suppressor interferon regulatory factor 1 (IRF-1). IFN-gamma treatment profoundly inhibited anchorage dependent and independent growth of pancreatic cancer cells. Cell cycle analyses revealed subdiploid cells suggesting apoptosis, which was confirmed by demonstration of DNA fragmentation and PARP cleavage. Time and dose dependency of apoptosis induction and growth inhibition correlated closely, identifying apoptosis as the main, if not exclusive, mechanism responsible for growth inhibition. Apoptosis was preceded by upregulation of procaspase-1 and accompanied by proteolytic activation. Furthermore, the caspase inhibitor z-vad-fmk completely prevented IFN-gamma mediated apoptosis. CONCLUSIONS: These results identify an intact proapoptotic pathway in pancreatic cancer cells and suggest that IRF-1 and/or procaspase-1 may represent potential therapeutic targets to be further explored.

Analysis of Variance↗

PubMed1997

Astrovirus survival in drinking water.

A method based on infection of CaCo-2 cultured cell monolayers (CC) and reverse transcription-PCR (RT-PCR) was developed for the specific detection of infectious astrovirus. The procedure was validated by titrating poliovirus stocks in parallel in CaCo-2 cells by determining the most probable number of cytopathogenic units and by cell culture and subsequent RT-PCR (CC-RT-PCR). CC-RT-PCR was then employed to measure the persistence of astrovirus suspended in dechlorinated tap water. After 60 days, the decay of astrovirus infectivity was 2 log units at 4 +/- 1 degrees C and 3.2 log units at 20 +/- 1 degrees C, while after 90 days, the titer reduction was 3.3 and 5 log units at 4 +/- 1 degrees C and 20 +/- 1 degrees C, respectively. Astrovirus decay in the presence of free chlorine (FC) was monitored by CC-RT-PCR. Residual infectivity was found after 2 h in the presence of 1 mg of FC/liter. Under these conditions, astrovirus shows a log titer reduction (LTR) or 4, while 0.5 mg of FC/liter induced an LTR of 2.4. The possibility of acquiring data on the survival of fastidious viruses in the environment opens new perspectives on the epidemiology of some significant infections transmitted by the fecal-oral route.

Astroviridae Infections↗

PubMed1985

Use of the extracranial-intracranial arterial bypass in the management of refractory vasospasm: a case report.

Cerebral arterial vasospasm after aneurysmal subarachnoid hemorrhage remains one of the major causes of morbidity and mortality in patients surviving the initial hemorrhage. Once established, no known method has been shown to reverse this process in humans. Although intravascular volume expansion and induced arterial hypertension have been shown to be effective in the reversal of neurological deficits secondary to vasospasm, a large proportion of patients remain refractory to these methods. We report one such case successfully managed by the establishment of an extracranial-intracranial anastomosis in an attempt to augment collateral flow.

Adult↗

PubMed2006

IgE-receptor activation induces survival and Bfl-1 expression in human mast cells but not basophils.

BACKGROUND: The contribution of mast cells to the pathology of allergic diseases are facilitated by their long life span in tissue and ability to regranulate. Bcl-2 genes are one of the main regulators of cell death and survival. The aim of this study was to elucidate the mechanisms responsible for mast cell survival in allergy. METHODS: Bcl-2 family gene expression in human mast cells and basophils was analyzed by ribonuclease protection assay and by reverse-transcriptase polymerase chain reaction. Cell survival was measured by mixing cells with the vital dye, trypan blue, and the number of living cells was enumerated. Apoptotic cells were measured by a Cell Death Detection ELISA. RESULTS: We found that cross-linking of FcepsilonRI on human cord blood cultured mast cells (CBCMCs) promoted cell survival and induced expression of the pro-survival gene Bfl-1. CBCMCs were found to express both Bfl-1 and Bfl-1S, two splicing variants of Bfl-1. Bfl-1 induction was mediated through Syk, PI3-kinase and intracellular calcium mobilization, since piceatannol, wortmannin and EDTA, respectively, significantly reduced Bfl-1 expression levels. In contrast to CBCMCs, no evidence was found for Bfl-1 expression and survival promotion in human basophils. CONCLUSIONS: Immunoglobulin E (IgE)-dependent activation-induced mast cell survival was correlated with Bfl-1 gene upregulation, providing a possible explanation for mast cell longevity in allergic reactions.

Basophils↗

PubMed2003

Support of retinal ganglion cell survival and axon regeneration by lithium through a Bcl-2-dependent mechanism.

PURPOSE: To explore whether lithium, a long-standing mood-stabilizing drug, can be used to induce expression of Bcl-2 and support the survival and regeneration of axons of retinal ganglion cells (RGCs). METHODS: Levels of expression of Bcl-2 in the retina were assessed with quantitative reverse transcription-polymerase chain reaction. To determine whether lithium directly supports the survival of and axon-regenerative functions of RGCs, various amounts of lithium were added to cultures of isolated RGCs. Anti-Thy1.2 antibodies-conjugated to magnetic beads were used to isolate the RGCs. In addition, retina-brain slice cocultures were prepared from tissues of Bcl-2-deficient or Bcl-2-transgenic mice and treated with various amounts of lithium. The effects of the expression of Bcl-2 on lithium-mediated functions were then analyzed. RESULTS: Normal mouse retina expressed very low levels of Bcl-2 after birth. Addition of lithium in the culture increased mRNA levels of Bcl-2 in retinas of postnatal mice in a dose-dependent manner. Moreover, lithium promoted not only the survival of RGCs but also the regeneration of their axons. Depleting or forcing the expression of Bcl-2 in RGCs eliminated the effects of lithium. CONCLUSIONS: Lithium supports both the survival and regeneration of RGC axons through a Bcl-2-dependent mechanism. This suggests that lithium may be used to treat glaucoma, optic nerve neuritis, the degeneration of RGCs and their nerve fibers, and other brain and spinal cord disorders involving nerve damage and neuronal cell loss. To achieve full regeneration of the severed optic nerve, it may be essential to combine lithium therapy with other drugs that mediate induction of a permissive environment in the mature central nervous system.

Animals↗

PubMed2003

Preoperative thallium scanning, selective coronary revascularization, and long-term survival after major vascular surgery.

BACKGROUND: Ischemia on thallium scanning is a strong predictor of long-term mortality in CAD patients. Whether coronary revascularization (CR) in patients with significant ischemia on preoperative thallium scanning (PTS) improves long-term survival after major vascular surgery has not been determined. METHODS AND RESULTS: The perioperative data, including PTS and subsequent CR in patients with moderate to severe reversible ischemia on PTS, and long-term survival of 502 consecutive patients who underwent 578 major vascular procedures were analyzed retrospectively. Patients with PTS who ultimately did not undergo the planned vascular operation were also studied. Cox regression and propensity score analyses were used to analyze survival. A total of 407 patients (81.1%) had PTS: 221 (54.3%) had no or mild defects (group I); 50 (12.3%) had moderate-severe fixed defects (group II); 62 (15.2%) had moderate-severe reversible ischemia yet did not undergo CR (group III); and 74 (18.2%) had moderate-severe reversible ischemia and subsequent CR by CABG (36) or PTCA (38; group IV). Patients who sustained major complications as a result of the preoperative cardiac workup were included in group IV. By multivariate analysis, age, type of vascular surgery, presence of diabetes, previous myocardial infarction, and moderate-severe ischemia on PTS independently predicted mortality (P=0.001, 0.009, 0.039, 0.006, and 0.029, respectively), and preoperative CR predicted improved survival (OR 0.52, P=0.018). Group IV had better survival than group III even when subdivided according to normal and reduced left ventricular function (OR 0.40 and 0.41, P=0.035 and 0.021, respectively). CONCLUSIONS: Long-term survival after major vascular surgery is significantly improved if patients with moderate-severe ischemia on PTS undergo selective CR.

Aged↗

PubMed2003

Characterization of pDJA1, a cardiac-specific chaperone found by genomic profiling of the post-ischemic swine heart.

BACKGROUND: Previously, we showed by subtractive hybridization in a swine model of ischemia/reperfusion that an upregulation of genes participating in mechanisms of cell survival is a potential genomic mechanism to tilt the balance from necrosis to functional reversibility. METHODS AND RESULTS: We present here the full-length sequencing and characterization of a novel gene that was found in this subtraction, encoding a cardiac-specific DnaJ-like co-chaperone that we call Pig DnaJ-like protein A1 (pDJA1). The expression of pDJA1 was found to be restricted to the heart, as opposed to skeletal muscle, liver, lung, kidney, aorta, stomach and spleen. Expression of pDJA1 is restricted to cardiac myocytes, as determined by in situ hybridization. The transcript is expressed more in the left ventricle than in the other cardiac chambers. Remarkably, expression of pDJA1 follows a transmural gradient in the left ventricle, with the highest level of expression in the subendocardium. Expression of pDJA1 slightly increased during an episode of ischemia, but increased by 4-fold during the following period of reperfusion. Adenovirus-mediated transduction of pDJA1 in isolated rat neonatal cardiac myocytes decreased by 65% the rate of apoptosis induced by staurosporine. CONCLUSION: Therefore, pDJA1 is a novel heart-specific, ventricle-enriched cardioprotective co-chaperone, which participates in the program of cell survival that limits irreversible damage in post-ischemic myocardium.

Adenoviridae↗

PubMed2006

Increase in DNA fragmentation and apoptosis-related gene expression in frozen-thawed bovine blastocysts.

Evaluation of apoptosis and expression level of apoptosis-related genes is useful for examining the variation in embryo quality according to environmental change. The objective of this study was to investigate DNA fragmentation and apoptosis-related gene expression patterns in frozen-thawed bovine blastocysts. In vitro produced day 7 blastocysts were frozen by two different vitrification methods (conventional 0.25 ml straw or MVC straw). After thawing, DNA fragmentation of surviving embryos was examined by TUNEL assay, and the expression patterns of their apoptotic genes (survivin, Fas, Hsp 70 and caspase-3) were evaluated using real-time quantitative reverse transcriptase polymerase chain reaction. In vitro survival rates of frozen-thawed embryos were higher following the MVC vitrification method (88.2% re-expanded at 24 h, 77.1% hatching at 48 h) than the conventional (C) vitrification method (77.0% re-expanded at 24 h, 66.7% hatching at 48 h). However, both vitrified methods resulted in a significantly higher apoptotic index (C vitrification method 11.9%, MVC vitrification method 11.0%) than in non-frozen embryos (3.0%). Expression levels of survivin, Fas, caspase-3, and Hsp 70 were also increased in the frozen-thawed embryos compared with non-frozen embryos. These results indicate that the cryopreservation procedure might cause damage that results in an increase in DNA fragmentation and apoptosis-related gene transcription, reducing developmental capacity of frozen-thawed embryos.

Animals↗