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PubMed1985

Retrospective study of histological features of acute rejection in renal allografts and comparison with circulating T cell populations.

The histological severity of acute rejection in renal allografts was determined for 39 rejection episodes in 30 renal transplant recipients. Data were compared with the peripheral blood T cell subset ratios measured before and at the onset of the rejection episode. T cell subset ratios showed no correlation with the histological severity of rejection, nor with the reversibility of the rejection episode. The grade of histological rejection on biopsy was predictive of graft survival. We conclude that renal biopsy remains the best method for determining the severity and outcome of acute allograft rejection episodes.

Adolescent↗
PubMed1997

Vinorelbine chemotherapy in non small cell lung cancer: experience in elderly patients.

This study involved 25 elderly (> 65 years old) patients (pts) with unresectable non small cell lung cancer (NSCLC) who were not eligible for polychemotherapy. The diagnosis of NSCLC was histologically or cytologically documented, and all of them had measurable or evaluable disease. The median age of the patients was 71 (range 65-77); 9 had been pretreated. The pts received 25 mg/m2 of vinorelbine weekly or bi-weekly depending on the results of blood tests. The treatment continued until disease progression or tolerance. No complete response was achieved: 3 pts (12%) had a partial response (RP) (8-12-14 months), 13 (52%) stable disease (SD) with an improvement in symptoms, such as cough and/or pain, and 9 pts (36%) progressed. Compliance with the therapy was acceptable. The main toxicity was hematological: neutropenia was observed in 16 pts, with only 1 case of grade 4 neutropenia without sepsis; grade 1-2 anemia occurred in 8 patients. The other toxicities included grade 1-2 neurotoxicity in 8 pts, chemical phlebitis in 2 pts and grade 3 cardiotoxicity reversible with medical treatment in 1 patient. The median survival time was 10 months (lower quartile 5 months, upper quartile 23 months) (Kaplan and Meyer method). Vinorelbine can be considered a rational choice in elderly pts with advanced NSCLC who are not suitable for aggressive polychemotherapy, with the aim of improving their quality of life in terms of symptoms and outpatient treatment.

Aged↗
PubMedDate not supplied

Routine cryopreservation of kiwifruit (Actinidia spp) germplasm by encapsulation-dehydration: importance of plant growth regulators.

The encapsulation-dehydration protocol was optimized for an in vitro cultured hybrid Actinidia arguta x A. deliciosa. Shoot tips from 14-d reactivated mononodal microcuttings were embedded, transferred to liquid culture medium whose sucrose concentration was daily increased (0.3, 0.5, 0.75 M) and then kept at 0.75 M for 2 or 4 d. Dehydration on silica gel was monitored to 20+/-1.5% residual water content (dry weight basis), allowing direct quenching in liquid nitrogen and rewarming at room temperature. Differential scanning calorimetry analysis underlined the importance of reversible glass transition in shoots for survival. Regrowth ranged from 85% to 95%. Growing shoot tips showed no phenotypic abnormalities. Rooting was also achieved. This method was routinely applied to diploid A. chinensis and A. eriantha, and to several diploid hybrids, yielding over 70% regrowth. A slight decrease in sucrose molarity (0.65 M) allowed tetraploid A. chinensis and A. chrysantha x A. arguta to survive dehydration, but not quenching in LN. For A. deliciosa cv Hayward and cv Tomuri, normal regrowth after cryopreservation was achieved only after modification of the pre- and post-culture media, highlighting the importance of monitoring plant growth regulator balance, principally at the post-thaw recovery step.

Actinidia↗
PubMed1999

Thrombospondin-1 expression and clinical implications in malignant pleural mesothelioma.

BACKGROUND: The role of thrombospondin-1 (TSP-1) in tumor angiogenesis and progression is controversial. The authors assessed the impact of TSP-1 as a prognostic indicator in malignant pleural mesothelioma (MPM). METHODS: TSP-1 expression was assessed by reverse transcriptase-polymerase chain reaction using 5 normal pleural samples, 78 MPM tumors, and 43 surrounding normal lung samples. In MPM tumors, vascular endothelial growth factor (VEGF) expression also was examined. Differences between different valuables were analyzed using the Mann-Whitney U test. Survival curves were obtained by the Kaplan-Meier method and the survival rate was assessed by the log rank test. RESULTS: TSP-1 was highly expressed in 74 of the 78 MPM tumors (95%) with a mean value of 2.27 +/- 0.42 compared with normal pleura (0.50 +/- 0.06) and surrounding normal lung (0.96 +/- 0.20) (P = 0.05 vs. normal pleura and P = 0.0006 vs. surrounding normal lung). The mean TSP-1 expression was significantly greater in high VEGF-expressing tumors (2.63 +/- 0.51) compared with low VEGF-expressing tumors (1.17 +/- 0.39; P < 0.0001) and TSP-1 expression was lower in patients with TNM Stage III/IV disease (n = 60) (1.85 +/- 0.37) than in patients with Stage I/II disease (n = 13) (4.46 +/- 1.74) (P = 0.025). The TSP-1 expression levels in tumors with lymph node metastases were significantly lower than in those without lymph node metastases (P = 0.0305). Although high TSP-1 expression was associated with good prognosis in patients with low VEGF-expressing tumors, TSP-1 itself appeared to have no overall impact on survival. The methylation status of a CpG island associated with the TSP-1 promoter was evident in MPM tumor samples despite high levels of TSP-1 mRNA expression. CONCLUSIONS: TSP-1 is overexpressed in MPM tumors but its expression is of little value as a prognostic indicator in MPM. However, the relations between TSP-1 and VEGF in MPM merit further investigation for possible innovative therapeutic interventions.

Adult↗
PubMed2002

[The application of arterialized venous digital island flap in fingertip reconstruction].

OBJECTIVE: To introduce an operation for fingertip reconstruction. METHODS: The vascularity of the reverse dorsal island flap is augmented by performing an arteriovenous anastomosis between the dorsal vein in the flap and a digital artery at the fingertip. The flap was used in ten patients for reconstruction of their fingertip defects. RESULTS: All the ten flaps survived and the appearance was good. CONCLUSION: The method is easy except for the necessity of performing standard microvascular surgery. The flap is a good option for repairing fingertip defects.

Adult↗
PubMed2005

Effects of p,p'-dichlorodiphenyldichloroethylene on the expressions of transferrin and androgen-binding protein in rat Sertoli cells.

The mechanisms of reproductive malfunction of male mammals caused by 2,2-bis(4-chlorophenyl)-1,1-dichloroethylene (p,p'-DDE, hereafter DDE) remain unknown. To explore the effects of DDE on the expressions of transferrin (Tf) and androgen-binding protein (ABP), we isolated Sertoli cells from healthy immature rats (18-20 days SD rats), set up Sertoli cell cultures, evaluated the toxicity, and measured the expression levels of mRNA of Tf and ABP genes by the one-step reverse transcriptase polymerase chain reaction method after cultured Sertoli cells were in vitro exposed to DDE at different concentrations for 24 h. The results showed that the number and survival rate of Sertoli cells decreased sharply with increased doses of DDE. The expression level of Tf mRNA decreased, whereas ABP mRNA increased gradually with increased DDE doses. There existed an obvious dose-effect relationship between the concentration of DDE and the expression levels of Tf mRNA and ABP mRNA. These findings suggest that DDE may inhibit the expression of Tf and up-modulate expression of ABP in cultured rat Sertoli cells.

Androgen-Binding Protein↗
PubMed2003

[Completely reversed acute rejection episodes do not influence the long-term renal allograft survival].

OBJECTIVE: To assess the influence of times and duration of acute rejection episodes and the effect of antirejection therapy in renal transplantation recipients on the long-term survival of renal allograft. METHODS: The clinical data of 946 patients who received renal transplantation were analyzed to analyze the survival of renal allograts in different conditions: times of rejection episode, time of onset of acute rejection, and effect of antirejection therapy by life table and Wilcoxon test, and to identify the risk factors through Cox regression analysis. RESULTS: During the follow-up with a range of 3 approximately 158 months acute rejection occurred in 172 patients. The 946 cases of kidney transplantation were divided into rejection free group (NAR, n = 774), one time rejection group (1AR, n = 159), and twice and more rejection group (2AR, n = 13) according to the times of rejection. The 1AR group was subdivided into completely reversed group (CAR) and incompletely reversed group (1AR). The 1AR cases were subdivided into early-stage rejection group (EAR, with episode within 90 days after transplantation, n = 112) and late-stage rejection group (LAR, with episode 90 days later transplantation, n = 47) according to the onset time of rejection episode. The five-year survival rate was 70.9% in the AR group (n = 172) and was 93.3% in the NAR group (P < 0.000 1). The ten-year survival rate of renal allografts was 29.8% in the AR group, and was 83.3% in the NAR group (P < 0.000 1). The 5-year survival rate of renal allograft was less than 30% in the 2AR group, significantly lower than those in the NAR and IAR groups (P < 0.000 1 and P< 0.003). The 5-year survival rate of renal allograft was 89.0% in the EAR group, significantly higher than that in the LAR group (48.9%, P < 0.000 1). The 8-year survival rate was 84.3% in the EAR group, significantly higher than that in the LAR group (32.1%, P < 0.000 1). Both the survival rates of renal allograft in the EAR and LAR groups were significantly lower than that in the NAR group (P = 0.025 and P < 0.000 1). The condition had been completely reversed in 95 patients and incompletely reversed in 54 patients, and failed to be improved in 10 patients out of the 159 cases in the IAR group after antirejection therapy. The 5-year survival rate of renal allograft was 93.9% in the CAR group, significantly higher than that in the IAR group (63.1%, P < 0.000 1) but not significantly different from that in the NAR group (P = 0.96). The 8-year survival rate of renal allograft was 89.2% in the CAR group, significantly higher than that in the IAR group (41.4%, P < 0.000 1) but not significantly different from that in the NAR group (P = 0.96). The time of rejection onset was not the main factor effecting survival rate of grafts. The main risk factor influencing the long-term survival of renal allograft was the therapeutic effect after the onset of rejection with a risk rate of 3.14. CONCLUSION: The acutely rejected renal allografts have poor long-term survival. The long-term survival rate of renal allograts with acute rejection that occurs only once and is completely recovered after antirejection therapy is not significantly different from that of the renal allografts in NAR group.

Acute Disease↗
PubMed1999

Prolongation of heart xenograft survival in a hamster-to-rat model after therapy with a rationally designed immunosuppressive peptide.

BACKGROUND: Modification of the aminoacid sequence of peptides derived from the HLA class I heavy chain in combination with computer rational design resulted in the development of a peptide, RDP1258, with enhanced immunosuppressive activity. METHODS: We evaluated the activity of this peptide, analyzing infiltrate by immunohistology and cytokine transcripts by reverse transcriptase-polymerase chain reaction method, in a hamster-to-rat xenograft model where recipients were treated with cobra venom factor (CVF) and peptide. RESULTS: Although CVF or peptide alone had no effect, a combination of CVF/peptide RDP1258 resulted in a significant prolongation of graft survival (7.9+/-1 vs. 4.5+/-0 and 3.5+/-0 days, P<0.001). This effect was associated with an increased expression of heme oxygenase 1 (HO-1) in spleen, a significant reduced graft infiltrate, and a decrease of tumor necrosis factor-alpha mRNA transcripts (P<0.05) compared with CVF-treated recipients (1.6+/-0.07 vs. 3.3+/-0.3%, P=0.001) on day 3 after transplantation. CONCLUSION: These observations are consistent with the observation that up-regulation of HO-1 results in inhibition of immune effector functions and suggest that the peptide acts, at least partially, through HO-1 regulation.

Animals↗
PubMed1981

Factors affecting sperm motility. VIII. Velocity and survival of human spermatozoa as related to temperatures above zero.

The effect of temperature on motility and survival of ejaculated human spermatozoa was investigated with the aid of the multiple exposure photography (MEP) method for objective sperm motility determination. Fresh specimens from healthy donors were analyzed while being heated or cooled gradually, or during their storage at various temperatures from 0 to 48 degrees C. Sperm velocity increased steadily from zero to 50.4 nm/sec between freezing point and body temperature. Thereafter, their activity dropped dramatically and total immobilization occurred at 45 degrees C. The induced immobilization was reversible providing exposure to those extreme temperatures was short enough to prevent permanent damage. Sperm survived up to 24-48 h when stored at 23 degrees C, while at body temperature, their survival in vitro was much shorter and rarely extended beyond 12 h. Their longevity was still shorter at higher or lower temperatures, especially when approaching 48 degrees C. With the aid of the combined supravital staining and MEP methods it was found that temperatures of extreme levels induced mainly immobilization rather than a spermicidic effect. The possible mechanism of thermal effect on sperm motility and some of its practical implications are discussed.

Cell Survival↗
PubMed2003

Elevated expression of valosin-containing protein (p97) in hepatocellular carcinoma is correlated with increased incidence of tumor recurrence.

PURPOSE: Valosin-containing protein (VCP; also known as p97) has been shown to be associated with antiapoptotic function and metastasis via activation of the nuclear factor-kappaB signaling pathway. In this study, association of VCP expression with recurrence of hepatocellular carcinoma (HCC) and patient survival was examined. PATIENTS AND METHODS: VCP expression in 170 patients (139 male and 31 female) with ages ranging from 31 to 81 years (median, 61 years) was analyzed by quantitative reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry, in which staining intensity in tumor cells was categorized as weaker (level 1) or equal to or stronger (level 2) than that in endothelial cells. RESULTS: Immunohistochemically, 57 patients (35.2%) showed level 1, and 105 patients (64.8%) showed level 2, VCP expression. Quantitative RT-PCR analysis revealed higher VCP mRNA expression in level 2 patients (n = 7) than level 1 (n = 4) (P <.05). Patients with VCP-level 2 HCC showed higher rate of portal vein invasion in the tumor (P <.01) and poorer disease-free and overall survival (P <.0001 and P <.05, respectively) compared with level 1 patients. Multivariate analysis revealed VCP expression level, tumor multiplicity, and degree of fibrosis in the noncancerous liver tissue to be independent prognosticators for disease-free and overall survival. VCP level was an indicator for disease-free survival in each early- (I and II) and advanced- (III and IV) stage group of pathologic tumor-node-metastasis classification (P <.001 and P <.01, respectively). CONCLUSION: VCP expression level has prognostic significance for disease-free and overall survival of patients with HCC.

Adenosine Triphosphatases↗
PubMed1998

Effect of inhibition of ornithine decarboxylase activity in a model of acute hepatocellular necrosis.

OBJECTIVE: The effect of blockade of the enzyme ornithine decarboxylase by difluoromethylornithine (DFMO) on hepatocellular necrosis and survival in rats treated with thioacetamide (TAA) was investigated. DESIGN: In one experiment, the effect of DFMO on survival of rats with TAA-induced acute hepatocellular necrosis was determined. In another experiment, blood and liver specimens were obtained from DFMO or saline-treated rats 24 h after the administration of TAA for determinations of serum alanine aminotransferase (ALT) and liver content of polyamines and microsomal cytochrome P-450 and for assessment of hepatic histology. METHODS: Liver polyamines were determined by reversed-phase HPLC and microsomal cytochrome P-450 content by dithionite-difference spectroscopy of CO-treated homogenates. The severity of hepatocellular necrosis was scored blindly. RESULTS: TAA-treated rats that received DFMO survived longer than saline-treated controls (P < 0.01). Serum ALT and liver putrescine concentrations were lower and the histological severity of acute hepatocellular necrosis was less in DFMO-treated rats with TAA-induced hepatocellular necrosis than in saline-treated controls (P < 0.05, P < 0.01 and P < 0.05, respectively). Total cytochrome P-450 levels were similar in DFMO and saline-treated rats with TAA-induced hepatocellular necrosis. CONCLUSIONS: DFMO increases survival in TAA-induced fulminant hepatic failure by decreasing the severity of acute hepatocellular necrosis. The beneficial effects of DFMO do not appear to be mediated by its effects on polyamine metabolism, but may be attributable to an effect of DFMO on thioacetamide metabolism or on an alternative pathway of ornithine metabolism.

Animals↗
PubMed2005

Advancing immunosuppression therapy to counter the progression of cardiac allograft vasculopathy.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is the major cause of late mortality in heart transplant recipients. Because immunosuppressive therapy has been convincingly shown to suppress cellular rejection and prolong cardiac allograft survival, we assessed the efficacy of advancing immunosuppressive therapy in reversing or delaying CAV by switching azathioprine to combination mycophenolate mofetil and prednisone (MMF-P). METHODS AND RESULTS: Seventeen adult posttransplant patients, whose CAV was prospectively approached with the MMF-P protocol, were studied. The development of significant CAV was declared on the index coronary angiogram and the MMF-P protocol was instituted. The degree of occlusion for all coronary lesions was quantitated for the index angiogram, and for the angiograms performed 1 year before (baseline) the index angiogram and annually for 2 years after the index angiogram (MMF-P years 1 and 2). There was a significant change in percent occlusion over time (P < .001). Percent occlusion increased significantly from the baseline year to the index CAV year, but then decreased significantly from the index CAV year to the MMF-P treatment years 1 and 2. CONCLUSION: Advancing immunosuppression with MMF-P can delay the progression of and partially reverse lumen narrowing of CAV in heart transplant recipients.

Azathioprine↗
PubMed1983

Human amnion in the management of chronic ulceration of the lower limb: a clinico-pathologic study.

This study shows that unmodified human amnion can make a useful contribution to the management of venous ulceration. By suppressing infection, and, by providing a healthy granulating surface, it significantly reduces the pre-skin graft preparation time, when compared with a conventional method of treatment. However, it does not seem to significantly influence the prospects of graft take, or of long term graft survival, in this comparison. A reversion towards normal of local vasculature, as characterized by vessel wall thinning and widening of the lumen, appears to be a significant tissue change induced by amnion treatment. Such a change may have considerable relevance in any analysis of the basis of the therapeutic efficacy of amnion.

Aged↗
PubMed2004

[Methods for assessing cognitive function utilizing operant tasks in rats].

Most human behaviors (responses) are volitional, the frequency of which is changed based on stimulus presentations contingent upon the response, that is, operant behavior. It is considered that the findings on cognitive functions based on operant behaviors are more reliable in extrapolating the results to humans. Impairment of memory function, most notably the impairments of working memory and attention, is an important research focus to elucidate the mechanism underlying the core syndrome of Alzheimer's disease. Among various methods to measure working memory and attention, a delayed matching-to-sample paradigm utilizing operant chambers equipped with 3 levers and a choice reaction time paradigm have been proven to be very useful. Aside from these, adaptation to new environment is an important function for survival, and its impairment has been considered to be one of the factors inducing psychiatric disorders. Preclinical methods to measure the adaptation ability include a position reversal learning paradigm utilizing 2-lever operant chambers. Since the findings of studies on cognitive functions utilizing operant behaviors have been in good correlation with clinical findings, it would serve as a good strategy for elucidating the causes of such disorders as well as developing therapeutic agents.

Adaptation, Psychological↗
PubMed1995

Reverse temporalis muscle flap: treatment of large anterior cranial base defect with direct intracranial-nasopharyngeal communication.

Inadequately managed frontal sinus fracture or sinusitis can pose a major problem of intracranial-nasopharyngeal communication. Life-threatening ascending infection of the intracranium is inevitable unless the intracranium is separated from the nasopharynx. In five patients with frontal bone defect associated with direct intracranial-nasopharyngeal communication, the authors used reverse temporalis muscle flap based on the superficial temporal vessels to obliterate the nasocranial communication. With the authors' method, the nasocranial communication were sealed off permanently, and the ascending infection from intracranial-nasopharyngeal communication was controlled successfully. The reverse temporalis muscle flap, which survives by reversed arterial flow through the vascular connection, exists between the superficial temporal artery and the deep temporal artery in the region of temporalis muscle origin. The reverse temporalis muscle flap is versatile and is recommended especially when other local flaps are not available to obliterate the nasocranial communication.

Adult↗
PubMed1998

Induction of long-term remission in advanced hepatocellular carcinoma with percutaneous isolated liver chemoperfusion.

OBJECTIVE: The aim of this study was to report the long-term results of percutaneous isolated liver chemoperfusion with hepatic venous isolation and charcoal hemoperfusion (HVI-CHP) in patients with multiple advanced hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: The results of conventional chemotherapy including regional and systemic chemotherapy in patients with HCC remain dismal, and long-term survivors after treatment are rare among patients with multiple advanced HCC. In an effort to improve this situation, we previously developed a novel system of percutaneous isolated liver chemoperfusion with HVI-CHP. METHODS: Doxorubicin (60 to 150 mg/m2) was administered via the hepatic artery, under conditions of extracorporeal drug elimination by HVI-CHP in 28 consecutive patients with advanced HCC (39 total treatments). Hepatic venous isolation and charcoal hemoperfusion was accomplished mainly by the single catheter technique using a newly developed 4-lumen-balloon catheter, which was used to isolate and capture total hepatic venous outflow and, at the same time, to direct the filtered blood to the right atrium. RESULTS: Complete remission was achieved in five patients, of which four received repeated treatments (two or three times). Although 1 of 5 patients with complete remission died of pulmonary metastases at 8 months, the other 4 remain healthy and free of disease at 20, 24, 27, and 42 months after the first treatment. Partial responses were observed in 12 patients. Duration of response in responders (complete and partial) with repeated treatments was significantly longer than that with a single treatment (p = 0.01). The overall survival rate by the Kaplan-Meier method was 39.7% at 5 years. The treatments were well-tolerated, and the primary side effects were mild to moderate chemical hepatitis and reversible myelosuppression. CONCLUSIONS: The results suggest that percutaneous isolated liver chemoperfusion with HVI-CHP is an effective palliative treatment in the majority of patients and yields long-term complete remission in some patients with multiple advanced HCC.

Adult↗
PubMed1999

Low dose hypersensitivity in the T98G human glioblastoma cell line.

PURPOSE: To examine the low dose-response of a human radioresistant glioblastoma cell line (T98G) using two different methods to measure surviving fraction and to define the influence of cell cycle phase on this response. MATERIALS AND METHODS: The survival of cells following exposure to single very low doses of X-rays in vitro was measured using either the Dynamic Microscopic Image Processing Scanner (DMIPS) or a Cell Sorter (CS). The DMIPS was also used to measure the low dose survival response of T98G cells following manipulation of their progression through the cell cycle. RESULTS: With both methods, T98G demonstrated marked low dose hyper-radiosensitivity (HRS) and the two methods produced very similar data in the low dose region of the survival curve. However, the CS protocol produced less variable results and was the more efficient method of generating low dose data. HRS was also demonstrated when these cells were irradiated while held in reversible arrest in the G1 phase of the cell cycle, but the effect was less marked than in the asynchronous population. CONCLUSIONS: T98G glioblastoma cells demonstrate marked HRS, which is a characteristic of the whole population rather than being due to the influence of a small subpopulation of hyper-radiosensitive cells within a particular phase of the cell cycle.

Cell Cycle↗
PubMed1997

Presence of circulating prostate cells in the bone marrow of patients undergoing radical prostatectomy is predictive of disease-free survival.

PURPOSE: To determine whether the presence of circulating prostate cells in the bone marrow is associated with disease-free survival in patients undergoing radical prostatectomy. MATERIALS AND METHODS: We evaluated the bone marrow of 86 patients with clinically localized prostate cancer treated by radical prostatectomy for the presence of circulating prostate cells using reverse-transcriptase polymerase chain reaction (RT-PCR) amplification of prostate-specific antigen (PSA) mRNA. Follow-up duration ranged from 1 to 43 months (mean, 15.4). RESULTS: Two of 47 patients (4%) with negative RT-PCR PSA results and 10 of 39 patients (26%) with positive RT-PCR PSA results have had disease recurrence. Patients whose RT-PCR PSA results were positive had a significantly shorter disease-free survival period than those patients with negative RT-PCR PSA results (P = .004). RT-PCR status correlated significantly with serum PSA level (P = .001) and pathologic stage (P = .003). Based on Cox's proportional hazards models, RT-PCR status was found to be a significant predictor of disease-free survival. However, after controlling for PSA level, RT-PCR status was not significant in predicting disease-free survival. CONCLUSION: RT-PCR PSA of bone marrow may be a useful pretreatment prognostic test for patients undergoing radical prostatectomy. Currently, this test should not be used to determine if patients receive definitive local therapy.

Adenocarcinoma↗