Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Reverse Survival Method”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 253 records · Page 14Linked to original sources
PubMed2005

Combined high cervical spine and brain stem injuries: a complex and devastating injury in children.

BACKGROUND: In young children, high cervical spine injuries (HCSI) can result in inaugural reversible, cardiac arrest or apnea. We noted in children sustaining such injuries an unusual incidence of associated brain stem injuries and defined a special pattern of combined lesions. METHODS: Children with HSCI surviving inaugural cardiac arrest/apnea were selected for a retrospective analysis of a trauma data bank. Epidemiologic, clinical, and radiological characteristics, and outcome were reviewed and compared with those of the rest of the trauma population with severe neurologic injuries (defined by a Glasgow Coma Scale < 8). RESULTS: Thirteen children with HCSI above the C3 spinal level and inaugural cardiac arrest/apnea were identified and compared with 819 severely head injured children without HSCI. Mean age was 4.7 +/- 2.9 years, and median Glasgow Coma Scale was 3 (3-6) after resuscitation. Initial standard x-ray views missed spine injuries in 6 patients. Spiral computed tomographic (CT) scan showed cervical fracture-dislocations associated with diffuse brain lesions and brain stem injury in all patients. Children with combined lesions had more frequent severe facial and skull base fractures compared with the rest of the population. They also were younger and sustained more frequent severe distracting injury to the neck than the rest of the population. Mortality rate (69%) was 2.6-fold higher than that observed in children without HCSI. In survivors, none demonstrated spinal cord injury resulting in persistent peripheral neurologic deficits, but only one achieved a good recovery. CONCLUSIONS: Combined HCSI and brain stem injuries must be suspected in young children sustaining a severe distracting injury to the craniocervical junction. Early recognition of these catastrophic injuries by systematic spiral cervical spine and brain stem computed tomographic scan evaluation is mandatory.

Algorithms↗
PubMed2000

Construction of a non-tumorigenic rat hepatocyte cell line for transplantation: reversal of hepatocyte immortalization by site-specific excision of the SV40 T antigen.

BACKGROUND/AIMS: Hepatocytes immortalized with a temperature-sensitive SV40 large T antigen (SV40Tag) function as well as primary hepatocytes following transplantation to reverse hepatic encephalopathy and improve survival in rodents with liver failure. The continued presence of SV40Tag in the conditionally immortalized hepatocytes may increase the risk of malignant tumor growth in transplant recipients. METHODS: We immortalized hepatocytes using a recombinant retrovirus containing the gene encoding SV40Tag flanked by loxP recombination target sites. Excision of SV40Tag from immortalized cells could then be accomplished by site-specific recombination with Cre-recombinase. RESULTS: Cells immortalized with this recombinant virus expressed SV40Tag and doubled in number every 48 h. After excision of the gene encoding SV40Tag with Cre-recombinase, cells stopped growing, DNA synthesis fell by 90%, and production of liver-specific mRNAs was either increased or became newly detectable. In addition, the morphology and epithelial cell polarity of the cells became more characteristic of differentiated hepatocytes. To determine their malignant potential, immortalized hepatocytes were transfected to express a second oncogene, activated H-ras. SV40Tag+/H-ras+-immortalized cells were capable of anchorage-independent growth and developed into tumors when injected in severe combined immunodeficiency mice. While Cre-recombinase delivery by recombinant adenovirus infection was not 100% efficient, when SV40Tag excision occurred anchorage-independent growth stopped and tumor formation in immunodeficient mice was abolished. Immortalized hepatocytes also contained the gene encoding herpes simplex virus thymidine kinase and treatment with ganciclovir produced complete regression of established tumors in mice. CONCLUSIONS: These studies extend previous work that indicates that a transplantable hepatocyte cell line could be developed for clinical use.

Animals↗
PubMed2003

Isolation of differentially expressed genes in conceptuses and endometrial tissue of sows in early gestation.

The implantation period is a critical time for embryonic survival in pigs. During this period, numerous growth factors are secreted by the conceptuses and the uterine endometrium in order to establish pregnancy and to provide a proper environment for embryonic development. It is well known that the Chinese Meishan sows have a larger litter size when compared with occidental sows mainly because of a superior embryonic survival rate. As a further step toward understanding the mechanisms involved in embryonic survival, we used a suppression subtractive hybridization technique to identify genes that were differentially expressed in Meishan-Landrace conceptuses and endometrial tissue at Day 15 of gestation when compared with conventional Landrace sows. Of the 1000 subtractive clones isolated from each library, 137 endometrial and 166 conceptus-enriched cDNAs were single-pass sequenced and examined by BLAST analysis for identification. Sixty-two percent of the clones found in the endometrial library and 78% of the clones found in the conceptus library showed homology with known genes. Among these genes, the 20 most relevant to embryonic survival based on the available literature were validated through real-time reverse-transcriptase polymerase chain reaction (RT-PCR) analysis. Our results show that suppression subtractive hybridization is a powerful method applicable in identifying putative candidate genes that might be used for selection of high litter-size breeds.

Animals↗
PubMed2004

Survivin is an independent prognostic marker for risk stratification of breast cancer patients.

BACKGROUND: Results in previous qualitative studies of the association of the apoptosis inhibitor survivin with prognosis of breast cancer patients have been contradictory. METHODS: Survivin mRNA was measured by quantitative TaqMan reverse transcription-PCR in 275 breast cancer tissues from patients with operable tumors and was correlated with established clinicopathologic factors, relapse-free survival [(RFS); 102 events], and overall survival [(OS); 81 events]. RESULTS: High survivin mRNA concentrations were found mainly in tissues from younger patients and in high-grade cancer tissues. High survivin concentrations were most strongly associated with estrogen receptor- or progesterone receptor-negative tumors. In univariate Cox regression analysis for RFS, survivin concentrations were significantly associated with poor prognosis with a hazard ratio (HR) of 1.99 (95% confidence interval, 1.31-3.02; P = 0.001) for every 10-fold increase in expression. For OS, a significant contribution of survivin to poor prognosis was found with a HR of 2.76 (1.67-4.55; P <0.001). Multivariate analyses were performed including established clinicopathologic factors. For RFS, age (P = 0.027), nodal category (P <0.001), and survivin [HR = 1.78 (1.18-2.68); P = 0.006] contributed significantly to the model. For OS, only nodal category (P <0.001) and survivin [HR = 3.05 (1.83-5.10); P <0.001] were significant. CONCLUSION: Survivin demonstrates a strong, independent, association with poor prognosis. Survivin might be used as a new marker to stratify breast cancer patients for more optimal treatment modalities, or it could be a promising new target for therapy.

Biomarkers, Tumor↗
PubMedDate not supplied

[A study of initial antiretroviral therapy effectiveness, survival and safety in HIV+ patients].

OBJECTIVE: To study initial antiretroviral therapies indicated for HIV-infected patients during the 2001-2003 period regarding effectiveness, survival and safety. METHOD: A descriptive, retrospective study of clinical and drug-related variables of naïve HIV-infected patients through pharmacotherapeutic history. RESULTS: Mean CD4+ lymphocytes counts were 209.6 cells/mm3. Pneumonia by Pneumocystis carinii was the most commonly found condition at antiretroviral treatment onset. Most commonly used therapies included those based on a non-nucleoside reverse transcriptase inhibitor (NNRTI) combined with two nucleoside reverse transcriptase inhibitors (NRTIs). The longest mean survival was achieved by using combinations of three nucleoside reverse transcriptase inhibitors. The primary reason for initial antiretroviral therapy discontinuation were adverse effects, with stavudine exhibiting the poorest tolerability. CONCLUSIONS: Therapies based on non-nucleoside reverse transcriptase inhibitors and protease inhibitors (PIs) have shown similar effectiveness to increase CD4+ cell counts. Regarding viral load decreases, protease inhibitors were most effective. Therapies using three nucleoside reverse transcriptase inhibitors resulted in peak survival.

Adult↗
PubMed2006

Kinetic analysis of the protection afforded by reversible inhibitors against irreversible inhibition of acetylcholinesterase by highly toxic organophosphorus compounds.

In organophosphate poisoning, the underlying mechanism of the therapeutic efficacy of carbamate prophylaxis, which was successfully tested in animal experiments, still awaits complete understanding. In particular, it is unclear whether survival is improved by increased acetylcholinesterase activity during the acute phase, when both carbamate and organophosphate are present. This question should be solved experimentally by means of a dynamically working in vitro model. Immobilized human erythrocytes were continuously perfused while acetylcholinesterase activity was monitored in real-time by a modified Ellman method. The concentrations of reversible inhibitors and of paraoxon were varied to assess the influence of both components on the enzyme activity under steady-state conditions. Physostigmine, pyridostigmine and huperzine A were tested for their prophylactic potential. Upon pretreatment with these reversible inhibitors the enzyme was inhibited by 20-90%. Additional perfusion with 1 microM paraoxon for 30 min resulted in a residual activity of 1-4%, at low and high pre-inhibition, respectively. The residual activity was significantly higher than in the absence of reversibly blocking agents (0.3%). After discontinuing paraoxon, the activity increased even in the presence of the reversible blockers. Stopping the reversibly blocking agents resulted in 10-35% recovery of the enzyme activity, depending on the degree of pre-inhibition. The experimental results agreed with computer simulations upon feeding with the essential reaction rate constants, showing that physostigmine was somewhat superior to pyridostigmine in enhancing residual activity in the presence of 1 microM paraoxon for 30 min. The model predicts that inhibitors with a faster dissociation rate, e.g. huperzine A, may be superior in case of a 'hit-and-run' poison such as soman.

Acetylcholinesterase↗
PubMed2006

Survivin and glycodelin transcriptional activity in node-positive early breast cancer: mRNA expression of two key regulators of cell survival.

INTRODUCTION: Glycodelin and survivin are key polypeptide regulators of cellular proliferation, apoptosis and angiogenesis. In view of contradictory reports on their functional role in tumors, we studied their transcriptional levels in localized breast cancer. PATIENTS AND METHODS: Glycodelin and survivin messenger ribonucleic acid (mRNA) was isolated and amplified by quantitative reverse-trancription PCR from paraffin-embedded breast carcinomas of 275 women. A normalized score was calculated by the use of GAPDH, RPL37A reference genes and was correlated with clinicopathologic/molecular parameters and patient outcome. RESULTS: A total of 272 patients were eligible, most harbored stage III node-positive breast carcinomas larger than 2 cm. Glycodelin mRNA was expressed in 68 patients (25%), more frequently in premenopausal women (P = 0.01) and those with HER2 mRNA-positive tumors (P = 0.02). Survivin mRNA was present in 263 tumors (97%) and its levels correlated significantly with high nuclear grade, VEGF mRNA and p53 mRNA presence (P < 0.05). At a median follow-up of 64 months, neither glycodelin nor survivin mRNA expression demonstrated prognostic utility for overall or disease-free survival at univariate and multivariate analysis. CONCLUSIONS: Glycodelin and survivin transcriptional activity are associated with adverse clinicopathologic and molecular characteristics of node-positive primary breast cancer but do not predict patient outcome. Further study is needed for illumination of their functional roles in tumorigenesis.

Adult↗
PubMed2002

Quantitation of calcitonin gene-related peptide mRNA and neuronal cell death in facial motor nuclei following axotomy and 633 nm low power laser treatment.

BACKGROUND AND OBJECTIVES: A persistent increase in calcitonin gene-related peptide (CGRP) immunoreactivity in motoneurons may serve as an indicator for regeneration after peripheral nerve injury [Borke et al., J Neurocytol 1993;22:141-153]. STUDY DESIGN/MATERIALS AND METHODS: We examined the effects of low power laser treatment (633 nm) on axotomy-induced changes in alpha-CGRP mRNA and long-term neuronal survival in facial motoneurons. A quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay for alpha-CGRP mRNA was used to detect changes in the response to axotomy and laser irradiation. Cell counts of neurons in injured and non-injured facial motor nuclei of laser-treated and non-treated rats were done to estimate neuronal survival. RESULTS: A 10-fold increase (P < 0.0001) in mRNA for alpha-CGRP at 11 days post-transection and an almost threefold increase (P < 0.0001) in neuronal survival at 6-9 months post-transection were found in 633 nm light treated rats. DISCUSSION: These findings demonstrate that 633 nm laser light upregulates CGRP mRNA and support the theory that laser irradiation increases the rate of regeneration, target reinnervation, and neuronal survival of the axotomized neuron.

Animals↗
PubMed1998

No evidence of infection with porcine endogenous retrovirus in recipients of porcine islet-cell xenografts.

BACKGROUND: The study of whether porcine xenografts can lead to porcine endogenous retrovirus (PERV) infection of recipients is critical for evaluating the safety of pig-to-man xenotransplantation. PERV is carried in the pig germline, and all recipients of porcine tissues or organs will be exposed to the virus. METHODS: We studied 10 diabetic patients who had received porcine fetal islets between 1990 and 1993, looking for evidence of PERV infection by using PCR serology, PCR, and reverse transcriptase assays. Prolonged xenograft survival (up to a year) was confirmed in five patients by porcine C-peptide excretion and detection of pig mitochondrial DNA (mtDNA) in serum. FINDINGS: Despite the evidence for extended exposure to pig cells and despite concomitant immunosuppressive therapy, we were unable to detect markers of PERV infection in any patient. Screening for two PERV sequences in peripheral blood lymphocytes collected 4-7 years after the xenotransplantation was negative. Markers of PERV expression, including viral RNA and reverse transcriptase, were undetectable in sera from both early (day 3 to day 180) and late (4-7 years) time points. Western blot analysis for antibodies was consistently negative. INTERPRETATION: These results suggested the absence of PERV infection in these patients. Also this study establishes a minimum standard for post-transplant surveillance of patients given porcine xenografts.

Adult↗
PubMed2003

Suppression of testosterone stimulates recovery of spermatogenesis after cancer treatment.

It is important to develop methods to prevent or reverse the infertility caused by chemotherapy or radiation therapy for cancer in men. Radiation and some chemotherapeutic agents kill spermatogonial stem cells, but we have shown that these cells survive in rats, although they are unable to differentiate. There is evidence that this phenomenon also occurs in men. The block to spermatogonial differentiation in rats is caused by some unknown change, either in the spermatogonia or the somatic elements of the testis, such that testosterone inhibits spermatogonial differentiation. In the rat, the spermatogenesis and fertility lost following treatment with radiation or some chemotherapeutic agents can be restored by suppressing testosterone with gonadotropin releasing hormone (GnRH) agonists or antagonists, either before or after the cytotoxic insult. The applicability of this procedure to humans is still unknown. Some anticancer regimens may kill all the stem cells, in which case the only option would be spermatogonial transplantation. However, in some cases stem cells survive and there is one report of stimulation of recovery of spermatogenesis with hormonal treatment. Clinical trials should focus on treating patients with hormones during or soon after anticancer treatment. The hormone regimen should involve suppression of testosterone production with minimum androgen supplementation used to improve the diminished libido.

Animals↗
PubMed2005

Inhibition of growth of experimental human and hamster pancreatic cancers in vivo by a targeted cytotoxic bombesin analog.

OBJECTIVES: Targeting anticancer agents to receptors for peptide hormones such as bombesin/gastrin-releasing peptide (GRP) on tumor cells increases the efficacy and lowers the toxicity of cancer therapy. We studied the expression of bombesin/GRP receptors in 6 experimental pancreatic cancers and evaluated tumor inhibition in vivo produced by targeted chemotherapy with the cytotoxic bombesin analog AN-215. METHODS: Nude mice with xenografts of Panc-1, CFPAC-1, Capan-1, Capan-2, MiaPaCa-2, and SW-1990 human ductal pancreatic cancers, as well as hamsters with nitrosamine-induced pancreatic cancers, were treated with AN-215 or its cytotoxic radical 2-pyrrolinodoxorubicin (AN-201) for 7 to 12 weeks. Tumor growth reduction and survival were analyzed, and cell proliferation rate and apoptosis were examined by histologic methods. Bombesin/GRP receptors on the tumors were studied by ligand-binding assays and their mRNA expression was studied by reverse transcriptase-polymerase chain reaction. RESULTS: All tumors expressed mRNA for subtype 1 bombesin/GRP receptor, but MiaPaCa-2, and in one experiment, SW-1990 tumors did not show binding sites for bombesin. AN-215 powerfully inhibited the growth of all pancreatic cancers that expressed functional receptors for bombesin/GRP. AN-201 was less effective on most tumors and somewhat more toxic than AN-215. CONCLUSIONS: Bombesin/GRP receptors are expressed on most ductal pancreatic carcinoma cell lines and can be used for targeted chemotherapy with the cytotoxic bombesin analog AN-215.

Animals↗
PubMed1997

Antiretroviral therapy for human immunodeficiency virus infection in 1997.

It has become clear that the acquired immunodeficiency syndrome follows continuous replication of the human immunodeficiency virus (HIV) and a decrease in immune capability, most obviously a decline in the number of CD4 lymphocytes. An understanding of key elements in the infectious life cycle of HIV has led to the development of potent antiretroviral drugs selectively targeting unique reverse transcriptase and protease enzymes of the virus. Completed clinical trials have shown that antiretroviral therapy for HIV infection, begun early, reduces viral replication and reverses the decline in CD4 lymphocyte numbers. Recent studies of combination therapies have shown that decreases in plasma HIV viremia to low levels and sustained increases in CD4 cell numbers are associated with longer survival. Potent combination regimens including protease inhibitors and non-nucleoside reverse transcriptase inhibitors suppress detectable viral replication and have demonstrated clinical benefits in patients with advanced disease. Progress in antiretroviral therapy and methods to monitor responses to treatment are providing new hope in the treatment of HIV infection.

CD4 Lymphocyte Count↗
PubMed2001

Down regulation of the tumor suppressor gene maspin in breast carcinoma is associated with a higher risk of distant metastasis.

BACKGROUND: Maspin (mammary serpin) is a relatively novel serine protease inhibitor with tumor suppressing function in breast cancer. Maspin expression was found in normal breast epithelial cells, but was decreased during tumor progression. Only a few systematic analyses of this phenomenon have been undertaken so far. In this study we developed specific nested reverse transcription polymerase chain reaction (RT-PCR) conditions for the detection of maspin expression in human breast carcinoma and assessed maspin's association with the clinical behavior of primary breast cancers. METHODS: Tumor specimens obtained from 45 primary breast cancer patients were analyzed for maspin expression by a nested RT-PCR assay. Recurrence free survival was evaluated and correlated to maspin expression. RESULTS: The maspin transcript was detected in 29 (64%) breast cancer specimens whereas no expression was found in 16 (36%) cancer specimens. This expression was unrelated to any of the established prognostic factors. However, 6 out of 8 patients who developed distant metastasis (lymph nodes, lung, liver, bone, pleura) within 3 yr after their initial diagnosis showed no maspin expression of the primary breast cancer (p < 0.05). CONCLUSIONS: The lack of maspin expression in breast cancer seems to be associated with a short disease free survival and supports maspin's function as an indicator of tumor aggressiveness and metastatic potential. Nested RT-PCR is a sensitive method to determine maspin expression in human breast cancer tissue.

Adult↗
PubMed2005

[The reverse first dorsal metatarsal artery flap for the defects of the distal foot].

OBJECTIVE: To explore a new method to reconstruct the defect of the distal foot. METHODS: A distally based dorsum pedis island flap pedicled with the first dorsal metatarsal artery was designed and transferred to the defect of the distal foot. RESULTS: Five patients were treated with this flap, which ranged from 2 cm x 4 cm to 6 cm x 7 cm in size. Four flaps survived completely, one flap had marginal necrosis and healed after conservative therapy. CONCLUSIONS: The reverse first dorsal metatarsal artery flap, with good blood circulation and easy manipulation, is a good option for the defects of the distal foot.

Adolescent↗
PubMed2004

Persistent evidence of circulating tumor cells detected by means of RT-PCR for CEA mRNA predicts early relapse: a prospective study in node-negative breast cancer.

BACKGROUND: In 100 consecutive patients with node-negative breast cancer who underwent curative surgery, we prospectively tested whether detection of circulating tumor cells in peripheral blood by means of reverse transcription-polymerase chain reaction for carcinoembryonic antigen (CEA) messenger RNA (mRNA) could predict patient outcomes. METHODS: We performed reverse transcription-polymerase chain reaction in blood samples taken before surgery and in repeat samples taken 2 to 3 weeks after surgery. Univariate and multivariate analyses of relapse-free survival were performed. RESULTS: Patients with CEA mRNA in preoperative samples had poorer survival rates than those who had no detectable CEA mRNA. The worst survival rate was seen in those with CEA mRNA in both pre- and postoperative samples. Stepwise multivariate analysis selected CEA mRNA expression pattern (P=.001; relative risk=0.69) and histologic tumor grade (P=.002; relative risk=1.35) as independent prognostic factors for disease-free survival. CONCLUSIONS: Molecular detection of CEA mRNA in both pre- and postoperative blood samples is an independent, negative prognostic factor in patients with node-negative breast cancer undergoing curative surgery.

Adult↗
PubMed2005

Expression and prognostic value of tuberous sclerosis complex 2 gene product tuberin in human pancreatic cancer.

BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutation of either of 2 tumor suppressor genes, TSC1 or TSC2, which encode hamartin and tuberin, respectively. Several studies have shown that tuberin functions independently of hamartin and inhibits signaling pathways via the mammalian target of rapamycin, a critical regulator of cell proliferation. Recent studies have revealed that the signaling pathways regulating the mammalian target of rapamycin such as Akt and S6K1 are frequently activated in pancreatic cancer. We hypothesized that tuberin might be involved in the proliferation and survival of pancreatic cancer cells. METHODS: We immunohistochemically examined the expression of tuberin in 42 pancreatic cancerous and noncancerous pancreatic tissue specimens using an antituberin antibody. The correlations between tuberin expression and various clinicopathologic features, including survival, were evaluated. Reverse transcriptase-polymerase chain reaction was performed to evaluate the level of tuberin expression in paired samples of pancreatic cancer and noncancerous tissue. RESULTS: Twenty-four of the 42 pancreatic cancer samples (57%) were negative for tuberin expression. The patients with tuberin-negative tumors had a significantly higher incidence of pT3 or pT4 disease (primary tumor extent by the TNM classification) than those with tuberin-positive tumors (P = .024). Female patients had a significantly higher incidence of tuberin-positive tumors than male patients (P = .014). The survival rate of the tuberin-positive group tended to be better than that of the tuberin-negative group, but there was no significant difference (P = .4). Expression of TSC2 in cancer tissue was lower than in the corresponding noncancerous tissue for 7 of the 9 samples examined. CONCLUSIONS: This study demonstrates that reduced expression of tuberin might be involved in the progression of pancreatic cancer. Accordingly, tuberin may provide a new therapeutic target in patients with this type of cancer.

Aged↗
PubMed2006

Effects of minocycline and doxycycline on cell survival and gene expression in human gingival and periodontal ligament cells.

OBJECTIVES AND BACKGROUND: Periodontitis is an infectious disease in the gingival crevice caused by periodontopathic bacteria, including Porphyromonas gingivalis, Prevotella intermedia, Actinobacillus actinomycetemcomitans, and Tennerella forsythensis, and antibacterial agents are directly administered to the site of infection to treat it. To maximize the therapeutic effects while reducing the adverse effects, the antibacterial agents should be administered at concentrations greater than their MIC(90) doses required to inhibit the growth of 90% of periodontopathic bacteria and the administration should not damage the periodontal tissue. One approach for estimating cellular damage in the periodontal tissue caused by the administration is to assay cytological damages following exposures of cultured human cells derived from periodontal tissues to antibacterial agents. In the present study, we investigated the cytotoxic effect of minocycline (MINO) and doxycycline (DOX) by using a human gingival fibroblast cell line, a human gingival epithelial cell line, and a human periodontal ligament fibroblast cell line. We also used these cell lines to study the effect of MINO or DOX on the mRNA and protein expressions of genes associated with the differentiation of fibroblasts and the proliferation, differentiation, or cellular adhesion important to the epithelial regeneration of the periodontal attachment. METHODS: The cytotoxic effect of MINO or DOX was measured as a decrease in cell survivals. The effects of these antibiotics on the mRNA and protein expressions in the cell lines were studied by reverse transcription-polymerase chain reaction (RT-PCR) and western blot analyses, respectively. RESULTS: The maximum concentration of MINO or DOX that has little effect on the cell survivals and the mRNA and protein expressions of genes for alkaline phosphatase, type I procollagen, keratinocyte growth factor receptor, keratin 18 or 8/18, integrin beta1, integrin beta4, and laminin 5gamma2 was 10 or 30 microm, respectively, which are greater than their MIC(90) doses against periodontopathic bacteria described above. CONCLUSIONS: These findings suggest that little, if any, cellular damage would be expected with topical administration of MINO or DOX to the periodontal pocket at a dose equivalent to the MIC(90). It is important to note, however, that the extrapolation of these findings to in vivo conditions has yet to be undertaken.

Administration, Topical↗
PubMed2000

Specific suppression of interleukin 2 biosynthesis by synthetic antisense oligodeoxynucleotides does not influence allograft rejection.

BACKGROUND: Interleukin (IL)-2 supplementation can reverse both blood transfusion-induced tolerance to kidney allografts and spontaneous tolerance to liver allografts in rats. Moreover, IL-2 expression is frequently suppressed in models of allograft tolerance. The failure of IL-2 biosynthesis might therefore play a critical role in tolerance induction. METHODS: Three antisense oligodeoxynucleotides (AS-1, AS-2, AS-3) to rat IL-2, and a control oligo (C-1) consisting of a scrambled version of AS-1, were evaluated for gene-specific suppression of IL-2 biosynthesis in vitro and in vivo, and for their effects on kidney allograft survival. Reverse transcriptase-polymerase chain reaction and IL-2 protein assays were used to assay concanavalin A-driven IL-2 biosynthesis by lymph node lymphocytes in vitro. PVG recipients of Dark Agouti kidney allografts were treated with the oligos. Graft survival and IL-2 biosynthesis by reverse transcriptase-polymerase chain reaction in spleen and graft biopsy specimens were assessed. RESULTS: The AS-1 oligo, but not the AS-2, AS-3 or C-1 oligos, suppressed concanavalin A-driven IL-2 biosynthesis for the 4 days of culture. This effect was dependent on delivery of the AS-1 oligo with lipofectamine. Supplementation with exogenous IL-2 reversed the suppression of lymphocyte proliferation in AS-1-treated cultures. Administration of AS-1 intravenously at 10 mg/kg/day to PVG recipients of Dark Agouti kidney allografts suppressed IL-2 (but not IL-6, interferon-gamma, or tumor necrosis factor-alpha) synthesis in the grafts of seven of nine rats, as measured in biopsy specimens taken at days 2-7. By contrast, all nine control grafts strongly expressed IL-2. However, neither graft histopathology nor graft survival was affected. CONCLUSIONS: Antisense oligonucleotides can powerfully suppress IL-2 biosynthesis in vitro and in allograft recipients in vivo, but this does not affect kidney allograft rejection.

Animals↗