[Revascularization of the deep femoral artery and its inflow vessels to treat critical limb ischemia in patients with thromboangiitis obliterans:a report of 9 cases].

Objective: To examine the effectiveness of revascularization of the deep femoral artery and its inflow vessels to treat critical limb ischemia in patients with thromboangiitis obliterans (TAO). Methods: The clinical data of 9 TAO patients with critical limb ischemia who underwent deep femoral artery and its inflow revascularization from January 2018 to October 2020 at Department of Vascular Surgery, the First Medical Center, People's Liberation Army General Hospital were retrospectively analyzed.There were all males, aged from 26 to 50 years with onset time from 1 to 7 years.All patients had severe rest pain, and 4 had ischemic ulcers or gangrene.All patients had occlusion of the deep femoral artery origins and(or) its inflow tracts, including 2 ipsilateral common iliac artery occlusion, 4 ipsilateral external iliac artery occlusion, 7 common femoral artery occlusion, and 8 deep femoral artery origins, without the involvement of the contralateral common femoral artery or its inflow tracts.Surgical procedures included femoral endarterectomy with thrombectomy, merge suture, and bypass.Technical success rate, rest pain relief, ulcer healing, patency, amputation rate, and long-term prognosis were recorded. Results: The overall technical success rate was 9/9, including 8 femoral endarterectomies with thrombectomy (with 4 patch-angioplasty with the great saphenous vein, 1 merge suture, and 3 simple sutures), 4 femoral-femoral bypasses with artificial vessels, and 1 superficial femoral artery bypass with the great saphenous vein.Rest pain disappeared after the operation immediately.The follow-up time was 10 to 44 months.All patients survived.The semi-annual patency rate was 9/9, and the one-year patency rate was 6/8.Except for one patient with significantly reduced but unhealed dorsalis ulcer up to now due to continuous heavy tobacco exposure after surgery, all others had no rest pain occurred or recurrence of foot ulcers during the follow-up.Among the 8 patients, 3 cases with recent claudication had continuous moderate tobacco exposure (10 to 20 cigarettes per day or severe passive smoking). Conclusions: For patients with thromboangiitis obliterans involved in the deep femoral artery or its inflow vessels, revascularization should be the primary choice and a good long-term prognosis is promising.Postoperative tobacco exposure (including passive smoking) is of great impact on the prognosis of TAO patients, and smoking cessation education must be reemphasized and reinforced.

Protective effects of miRNA-589 on cerebral ischemia-reperfusion injury.

To uncover the potential influence of microRNA-589 (miRNA-589) on cerebral ischemia-reperfusion injury (IRI) and the underlying mechanism, BV2 cells were stimulated by lipopolysaccharide (LPS) or conditioned medium (CM) of primary cortical neurons undergoing oxygen-glucose deprivation (OGD). Regulatory effects of miRNA-589 on the release of inflammatory factors in BV2 cells induced with LPS or CM of primary cortical neurons undergoing OGD were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). The interaction between miRNA-589 and TRAF6 was finally assessed by dual-luciferase reporter gene assay. MiRNA-589 was downregulated in BV2 cells induced with LPS or CM of primary cortical neurons undergoing OGD. Overexpression of miRNA-589 reduced the release of inflammatory factors in LPS or CM-induced BV2 cells. TRAF6 was verified to be the downstream gene of miRNA-589, and its level was negatively regulated by miRNA-589. MiRNA-589 is downregulated following cerebral IRI and alleviates inflammatory response through negatively regulating TRAF6.

[Expression and clinical significance of MIIP and PAK1 in endometrial carcinoma].

Objective: To investigate the expressions of migration and invasion inhibitory protein (MIIP) and p21-activated kinase 1 (PAK1) in endometrial carcinoma (EC) and their correlation with clinicopathological features. Methods: The protein levels of MIIP and PAK1 in 135 paraffin-embedded EC tissues, 55 atypical hyperplasia of endometrium (AHE) and 88 normal endometrium (NE) tissues were quantified by immunohistochemistry, the clincial significance and the relationship of these two proteins were also analyzed. Results: The positive rates of MIIP expression in NE, AHE and EC tissues were 52.3%(46/88), 41.8% (23/55) and 34.8% (47/135), respectively. The expression of MIIP in EC was significantly lower than that of MIIP in NE (P<0.05). The positive rates of PAK1 expression in NE, AHE and EC tissues were 45.5% (40/88), 50.9% (28/55) and 62.2% (84/135), respectively. The expression of PAK1 in EC tissues was significantly higher than that of PAK1 in NE tissues (P<0.05). The expression of MIIP in EC tissues was significantly associated with myometrial invasion, International Federation of Gynaecology and Obstetrics (FIGO) stage and lymph node metastasis (P<0.05). The expression of PAK1 in EC tissues was significantly related with differentiation, myometrial invasion, FIGO stage and lymph node metastasis (P<0.05). The expressions of MIIP and PAK1 in EC tissues were marginally related with the overall survival of patients (P=0.092, P=0.052). The expression of MIIP in EC was negatively correlated with PAK1 (r=-0.329, P<0.001). Conclusions: The down-regulation of MIIP and up-regualtion of PAK1 paticipate in the initiation and development of EC, which are correlated with the poor prognosis of EC. The protein expression of MIIP is inversely related with PAK1 in EC.

Multiple variants in 5q31.1 are associated with systemic lupus erythematosus susceptibility and subphenotypes in the Han Chinese population.

BACKGROUND: A previous study provided evidence for a genetic association between PPP2CA on 5q31.1 and systemic lupus erythematosus (SLE) across multi-ancestral cohorts, but failed to find significant evidence for an association in the Han Chinese population. OBJECTIVES: To explore the association between this locus and SLE using data from our previously published genome-wide association study (GWAS). METHODS: Single-nucleotide polymorphisms (SNPs) rs7726414 and rs244689 (near TCF7 and PPP2CA in 5q31.1) were selected as candidate independent associations from a large-scale study in a Han Chinese population consisting of 1047 cases and 1205 controls. Subsequently, 3509 cases and 8246 controls were genotyped in two further replication studies. We then investigated the SNPs' associations with SLE subphenotypes and gene expression in peripheral blood mononuclear cells. RESULTS: Highly significant associations with SLE in the Han Chinese population were detected for SNPs rs7726414 and rs244689 by combining the genotype data from our previous GWAS and two independent replication cohorts. Further conditional analyses indicated that these two SNPs contribute to disease susceptibility independently. A significant association with SLE, age at diagnosis < 20 years, was found for rs7726414 (P = 0·001). The expression levels of TCF7 and PPP2CA messenger RNA in patients with SLE were significantly decreased compared with those in healthy controls. CONCLUSIONS: This study found evidence for multiple associations with SLE in 5q31.1 at genome-wide levels of significance for the first time in a Han Chinese population, in a combined genotype dataset. These findings suggest that variants in the 5q31.1 locus not only provide novel insights into the genetic architecture of SLE, but also contribute to the complex subphenotypes of SLE.

[Clinical application of adult comorbidity evaluation-27 in endometrial cancer].

Objective: To investigate the significant role of the clinical application of adult comorbidity evaluation-27 (ACE-27) in endometrial cancer (EC). Methods: A total of 847 EC patients were included during Jan. 1985 to Dec. 2015 from Tianjin Medical University General Hospital. The clinical data of the patients were collected and analyzed retrospectively. All of the patients were received operation with no chemotherapy and radiotherapy before operation. The average age was 57.6 years old (range from 25 to 85 years old). The average follow-up period was 59.0 months (range from 2 to 312 months). The comorbidity of the patients was evaluated by ACE-27. EC patients survival was analyzed by Kaplan-Meier survival curve. The relationship between the prognosis of EC and ACE-27, age, body mass index (BMI) , pathological characteristic were showed by Cox modeling. Results: (1) The patient number of score 0, 1, 2 and 3 of ACE-27 in EC patients were respectively 311 (36.7%), 263 (31.1%), 132 (15.6%) and 141 (16.6%) cases. (2) Kaplan-Meier survival curve analysis showed that overall survival time of EC patients was gradually decreased as increased score of ACE-27 (χ2=19.003, P=0.000) . In the patients of BMI<25 kg/m2 and BMI 25-<30 kg/m2, International Federation of Gynecology and Obstetrics (FIGO) stage Ⅰ, endometrial adenocarcinoma type and the overall survival time of those EC patients were gradually decreased as increased score of ACE-27 (P<0.05) . However, there was no statistically significant difference in overall survival time for patients with BMI ≥30 kg/m2, FIGO stage with Ⅱ-Ⅳand non-endometrial adenocarcinoma type (P>0.05). Per unvariate logistic modeling showed that the risk of death in score 3 of ACE-27 was increased compared with score 0 of ACE-27 (OR=2.53, P=0.000) . The overall survival time in EC patients with aged 50-59, 60-69 and ≥70 years old, BMI 25-<30 kg/m2 and ≥ 30 kg/m2, G3, FIGO stage Ⅱ-Ⅳ and non-endometrial adenocarcinoma type were significantly decreased compared with those aged <50 years old, BMI < 25 kg/m2, G1, FIGO stage Ⅰ and endometrial adenocarcinoma type (all P<0.05) . Further we found that postoperative chemotherapy or radiotherapy rate were decreased for EC patients with FIGO staging Ⅲ or Ⅳ as the increase of ACE-27 score, but there was no statistically significant difference (P>0.05). (3) Per multivariate logistic modeling showed that the risks of death in score 3 of ACE-27 was increased compared with score 0 of ACE-27 among age-adjusted, BMI, histological grade, FIGO stage and pathologic type (OR=2.40, P=0.000) . Per multivariate logistic modeling showed that, the overall survival time in EC patients with aged 60-69 and ≥70 years old, BMI 25-<30 kg/m2 and ≥30 kg/m2, FIGO stage Ⅲ-Ⅳ and non- endometrial adenocarcinoma type remain significantly decreased compared with those aged <50 years old, BMI<25 kg/m2, FIGO stage Ⅰ and endometrial adenocarcinoma type (P<0.05) , but there was no statistically significant difference in histological grade (P>0.05). Conclusions: ACE-27 may become one of the factors of predictive therapy and the prognosis for EC patients. The detailed clinical data of comorbidity should be collected to evaluate prognosis and therapy plan.

MicroRNA-181b expression in prostate cancer tissues and its influence on the biological behavior of the prostate cancer cell line PC-3.

We examined microRNA-181b (miRNA) expression in prostate cancer tissues and its effect on the prostate cancer cell line PC-3. Tissues from 27 cases of prostate cancer and 30 samples of normal human prostate were collected by surgical removal. Total miRNA was extracted, and the relative expression of miR-181b was quantified using RT-PCR. miR-181b ASO was transfected into prostate cancer PC-3 cells. miR-181b expression in transfected and non-transfected cells was measured using RT-PCR. Changes in cell apoptosis were measured using flow cytometry. MTT and cell growth curve methods were used to assess the influence of miR-181b expression on cell proliferation. The changes in cell invasive ability in vitro were detected using the Transwell chamber method. miR-181b was up-regulated in the prostate cancer tissues compared with the normal prostate samples. It was down-regulated after miR-181b ASO transfection into the prostate cancer PC-3 cells. Down-regulation of miR-181b in the PC-3 cell induced apoptosis, inhibited proliferation, and depressed invasion of PC-3 cells in vitro. As miR-181b is over-expressed in prostate cancer, its down-regulation could have potential as gene therapy for prostate cancer by inducing apoptosis, inhibiting proliferation and depressing invasion by cancer cells.

A single-nucleotide polymorphism rs4639966 in 11q23.3 is associated with clinical features of systemic lupus erythematosus in the Chinese population.

In our previous genome-wide association study (GWAS), we identified an association signal of the single-nucleotide polymorphism (SNP) rs4639966 (p = 1.25 × 10(-16), odds ratio [OR] = 1.29) within 11q23.3. The aim of this study was to investigate its relationship with disease subphenotypes, including renal nephritis, photosensitivity, antinuclear antibody (ANA), age at diagnosis, malar rash, discoid rash, immunological disorder, oral ulcer, hematological disorder, neurological disorder, serositis, arthritis and vasculitis. In this study, we used 4199 cases and 8255 controls from our previous GWAS to explore the association between 11q23.3 with subphenotypes of systemic lupus erythematosus (SLE). Data were analyzed with PLINK 1.07 software. Significant associations were found for the SNP rs4639966 of 11q23.3 with SLE of age at diagnosis <20 years (OR = 1.18, p = 0.0049), malar rash (OR = 1.13, p = 0.01) and vasculitis (OR = 1.17, p = 0.02). The study suggested that 11q23.3 might not only play important roles in the development of SLE, but also contribute to the complex phenotypes of SLE.

TNIP1, SLC15A4, ETS1, RasGRP3 and IKZF1 are associated with clinical features of systemic lupus erythematosus in a Chinese Han population.

Systemic lupus erythematosus (SLE) is an autoimmune disease with heterogeneous clinical manifestations influenced by genetic and environmental factors. Five novel susceptibility genes (TNIP1, SLC15A4, ETS1, RasGRP3 and IKZF1) for SLE have been identified in a recent genome-wide association study of a Chinese Han population. This study investigated their relationships with disease subphenotypes, including renal nephritis, photosensitivity, antinuclear antibody (ANA), age at diagnosis, malar rash, discoid rash, immunological disorder, oral ulcer, hematological disorder, neurological disorder, serositis, arthritis and vasculitis. Significant associations were found for the single nucleotide polymorphism rs10036748 of TNIP1 with photosensitivity (odds ratio (OR) = 0.87, p = 0.01) and vasculitis (OR = 1.18, p = 0.04); rs10847697 of SLC15A4 with discoid rash (OR = 1.18, p = 0.02); rs6590330 of ETS1 with SLE of age at diagnosis <20 years (OR = 1.24, p = 8.91 x 10(-5)); rs13385731 of RasGRP3 with malar rash (OR = 1.20, p = 0.01), discoid rash (OR = 0.78, p = 0.02) and ANA (OR = 0.72, p = 0.004); rs4917014 of IKZF1 with renal nephritis (OR = 1.13, p = 0.02) and malar rash (OR = 0.83, p = 0.00038), respectively. The study suggested that these susceptibility genes might not only play important roles in the development of SLE, but also contribute to the complex phenotypes of SLE.

Nucleoside restoration of heat resistance and suppression of glucose-regulated protein synthesis by glucose-deprived L929 cells.

Depriving cultured cells of glucose increases glucose-regulated protein synthesis, suppresses heat shock protein synthesis, and increases sensitivity to killing by hyperthermia. The present study shows that supplementation of glucose-free culture medium with uridine or a number of other nucleosides reverses all these effects of glucose deprivation. Uridine is more effective in this regard than equimolar concentrations of glucose, and ribose is relatively ineffective. Uridine does not suppress glucose-regulated protein synthesis that has been induced by glycosylation inhibitors, calcium chelation, or anoxia. We infer from these data that the effects of glucose deprivation may result from inhibition of ribonucleoside synthesis and that ribonucleosides may be directly involved in regulating glucose-regulated protein and heat shock protein synthesis as well as in protecting cells against hyperthermic cytotoxicity.

Relationship between p53 gene mutation and protein expression: clinical significance in transitional cell carcinoma of the bladder.

Although the mutated p53 gene has been postulated to induce immunohistochemically-detectable p53 protein, reports regarding the relationship between p53 mutation and p53 protein expression have been contradictory. This study investigated the relationship between p53 mutations and p53 expression and their clinical significance for patients with transitional cell carcinoma of the bladder. Eighty-seven transitional cell carcinoma of the bladder were analyzed by immunohistochemistry (IHC) for p53 nuclear accumulation, and the results compared to mutations detected in the p53 gene evaluated by polymerase chain reaction single-strand conformation polymorphism (SSCP) and DNA sequence analysis. By p53 IHC analysis, positive p53 staining was observed in 50 (57.5%) of the 87 tumors. The specificity of IHC, defined as a percentage of IHC negative (<20%) tumors among tumors without mutation, was 94.6%. Despite the good concordance between p53 mutation and p53 protein expression (p<0.0001), 48.0% (24/50) of the tumors showed p53 overexpression without mutation, and 2 (5.4%) tumors with mutation showed no p53 immunoreactivity. Patients with higher grade (grade 3), stage (stages pT2-4), and p53 mutations had a poorer prognosis by Kaplan-Meier survival analysis. A Cox univariate analysis found that grading (hazard ratio 3.139; p=0.002), staging (hazard ratio 3.832; p=0.0005) and p53 mutation (hazard ratio 2.498; p=0.013) were significant variables in these patients, but no variable was independently associated with an increased survival of bladder carcinoma by multivariate analysis. We found that a 20% cut-off level of p53 overexpression showed the highest correlation with prognosis and p53 mutation, however, p53 overexpression and mutation were not superior to staging as prognostic markers. These data suggest that careful assessment of the TNM staging system remains the most reliable predictive indicator of survival for patients with transitional cell carcinoma of the bladder.

The epidemiology of a measles outbreak on a remote offshore island near Taiwan.

In September-October 1985, a measles outbreak occurred among elementary school students on a small offshore island near Taiwan. The outbreak began with nosocomial transmission of measles in a hospital emergency room on the main island of Taiwan. Four distinct generations of transmission occurred among elementary school children an their household contacts. Elementary school children were susceptible to measles because they were born after the last major outbreak, but before measles vaccine was locally available. Low immunization rates and low vaccine efficacy contributed to the spread of measles among preschool-age household contacts.

The role of reduced nicotinamide adenine dinucleotide phosphate in glucose- and temperature-dependent doxorubicin cytotoxicity.

The mechanism of doxorubicin resistance induced by glucose deprivation was examined using an L929 cell system. Resistance developed even when the synthesis of glucose-regulated proteins was suppressed by supplementing glucose-deprived cultures with uridine. Resistance was also not correlated with pyruvate availability, with DNA strand breaks, or with intracellular drug or nucleotide levels. However, intracellular concentrations of reduced nicotinamide adenine dinucleotide phosphate (NADPH) decreased to undetectable levels in glucose-deprived cells with or without uridine supplementation. NADPH depletion induced by treating glucose-fed cells with low concentrations of methylene blue afforded the same degree of protection as glucose deprivation, and normal sensitivity could be restored to glucose-deprived cells by adding NADPH to the culture medium. These results suggest that decreased NADPH availability is responsible for the doxorubicin resistance induced by glucose deprivation. Although drug uptake and NADPH production increased with temperature, these effects could not fully account for the > 1000-fold decrease in clonogenic survival observed over the 25 degrees-37 degrees C temperature range. Similarly, manipulation of NADPH levels confirmed a role for drug bioreduction in the cytotoxic mechanism but did not suggest that NADPH availability was rate-limiting for this process at any temperature employed.

Photodynamic enhancement of doxorubicin cytotoxicity.

Argon ion laser irradiation at 514.1 nm and 488 nm dramatically increased doxorubicin cytotoxicity in an L929 cell clonogenic survival assay. The cytotoxicity was dependent on both the drug concentration and the total light energy delivered such that at 5 micrograms doxorubicin/ml and 800 J/cm2, cytotoxicity was enhanced by a factor of > 10(4) relative to that achieved with drug alone. Irradiation times in excess of 2 min and power densities in excess of 100 J/cm2 were required to produce the effect. Beyond this 2-min limit, cytotoxicity was not related to the duration of exposure if the total energy delivered was held constant. The ability of catalase and superoxide dismutase to abolish completely the increase in cytotoxicity produced by laser irradiation suggests that the cytotoxic mechanism may depend on the generation of active oxygen species by the photodynamically excited drug.

Mechanism of action and spectrum of cell types susceptible to doxorubicin photochemotherapy.

We have shown that, whereas argon ion laser irradiation alone is not cytocidal for L929 cells, it greatly increases the cytotoxicity of intracellular doxorubicin. The present study showed that light enhancement of doxorubicin cytotoxicity was not restricted to stock L929 cells, but could also be demonstrated using L929 cells selected for doxorubicin resistance and several standard cell lines that are relatively resistant to doxorubicin prior to selection. Light-enhanced cytotoxicity resulted in extensive nuclear DNA loss and was strongly inhibited by anoxia. These findings suggest that the mechanism by which light exposure enhances doxorubicin cytotoxicity involves DNA damage by intranuclear generation of reactive oxygen species.

Mechanism of action and spectrum of cell lines sensitive to a doxorubicin-transferrin conjugate.

A transferrin-doxorubicin conjugate exhibited greatly increased cytotoxicity relative to unconjugated doxorubicin toward a variety of cultured tumor cell lines. An L929 cell line selected for doxorubicin resistance was as sensitive to the transferrin-doxorubicin conjugate as was the parental unselected line. Quantitative measurements of doxorubicin fluorescence in single L929 cells showed that uptake was similar in amount when cells were exposed to equivalent concentrations of doxorubicin presented either free or as the transferrin-doxorubicin conjugate. However, unconjugated drug fluorescence was distributed in membranes, cytoplasm and nucleus, whereas conjugate fluorescence was confined mainly to the cytoplasmic compartment. In as much as NADPH-dependent free radical formation is a known mechanism of doxorubicin cytotoxicity, localization in the vicinity of NADPH production might facilitate this cytotoxic pathway. Neither cytotoxicity nor uptake of the conjugate quantified by doxorubicin fluorescence was significantly blocked by excess free transferrin, and the conjugate was not concentrated in the plasma membrane at 4 degrees C. These findings suggest that conjugate internalization is not entirely dependent on transferrin receptor binding.

Clinical significance of p53, MDM2 and bcl-2 expression in transitional cell carcinoma of the bladder.

We investigated the prognostic and predictive relevance of p53, MDM2, and bcl-2 protein expression in patients with transitional cell carcinoma (TCC) of the bladder. The expression of p53, MDM2 and bcl-2 protein was studied by immunohistochemical methods in paraffin-embedded specimens from 119 patients whose clinicopathologic data confirmed TCC of the bladder. Multivariate analyses of prognostic factors were performed, and correlations with classical clinicopathologic parameters were examined. Sixty-one, 12, and 17% of cases were considered positive for expression of p53, MDM2 and bcl-2, respectively. p53 expression correlated with stage (p=0.0209), but not MDM2 and bcl-2 with any clinicopathologic parameters. In Cox's regression analysis, staging demonstrated a statistically worse prognosis (hazard ratio 1.636; p=0.0059) while bcl-2 (hazard ratio 0.179; p=0.0474) expression showed favorable prognosis in stage T2-4 invasive TCC of the bladder. Co-expression with p53/MDM2 (hazard ratio 0.367; p=0.0401) and p53/bcl-2 (hazard ratio 3.487; p=0.0111) overexpression were associated with favorable and unfavorable prognosis in stage T2-4 invasive TCC of the bladder, respectively. Our results indicate that staging is the most useful parameter to predict clinical outcome in patients with TCC of the bladder. Determinations of bcl-2 and co-expression p53/MDM2 and p53/bcl-2 may be useful for predicting tumor behavior and prognosis in stage T2-4 invasive type TCC of the bladder.

Glycemia and exercise training alter glucose transport and GLUT4 in the Zucker rat.

The purpose of this study was to determine the effects of chronic hyperglycemia and/or exercise training on the muscle concentration of the insulin-responsive glucose transporter protein, GLUT4, and on maximally insulin-stimulated hindlimb muscle glucose transport. Five-wk-old lean and obese Zucker rats were randomly assigned to sham-operated control (CTL) or 90% pancreatectomized (PX) groups. Obese-PX animals were further randomized into sedentary or exercise trained groups (15-wk treadmill running for 2 h.d-1, 5 d.wk-1, 15% grade, at 15-18 m.min-1). Muscle GLUT4 protein content and maximally insulin-stimulated glucose transport were determined in gastrocnemius, plantaris, and soleus muscles. At 20 wk, lean-PX displayed mild fasting hyperglycemia but normal insulin levels. Obese-PX rats had insulin levels similar to lean-CTL rats but had severe hyperglycemia. Hyperglycemia in lean-PX was associated with a 28% decrease in maximal glucose transport and a 65% decrease in muscle GLUT4 (P < 0.05) compared with lean-CTL. In obese-PX, maximal glucose transport was not affected, but muscle GLUT4 was reduced by 62% (P < 0.05) compared to obese-CTL. Exercise training obese-PX reduced hyperglycemia, increased maximal glucose transport by 45%, and increased muscle GLUT4 by > 2-fold (P < 0.05) compared with obese-CTL. Thus, hyperglycemia associated with PX may be an important factor in the reduction of muscle GLUT4 levels in lean and obese rats. The reduced GLUT4 was accompanied by reduced maximal glucose transport in lean but not obese rats. Exercise training reduced hyperglycemia, normalized glucose transport, and increased muscle GLUT4 in obese-PX.(ABSTRACT TRUNCATED AT 250 WORDS)

Transient inhibition of L929 cell mitosis and locomotion by argon ion laser irradiation.

Argon ion laser irradiation of L929 cells transiently inhibits both entry into and passage through mitosis without affecting clonogenic survival. Anaphase mitotic figures virtually disappear from irradiated cell monolayers although prophase + metaphase mitotic figures can still be identified. The total number of mitotic figures does not change significantly and time-lapse video recording shows that cells do not enter mitosis following irradiation. This effect is dependent on light dose within the 900-2700 J/cm2 range and persists for 10-48 h depending on the initial light exposure. Inhibition of cell locomotion and subsequent recovery were observed to occur over a similar time course. The possible contribution of these phenomena must be considered whenever biological systems are exposed to argon ion laser irradiation.

Cefixime absorption kinetics after oral administration to humans.

Cefixime (CFX) absorption kinetics after oral administration to humans was studied. Four distinct models, incorporating a delay of absorption and first-order elimination kinetics, i.e. first-order absorption (M1), zero-order absorption (M0), Michaelis-Menten type absorption (MM) and Michaelis-Menten type absorption with 'an absorption window' (MM-delta t) were used to fit concentration data of CFX in 10 Chinese men following an oral dose of 400 mg. r2 and AIC were selected as measures of goodness-of-fit. The results show that the MM-delta t model provided a better fit than the other three models. The kinetic parameters were estimated as follows: Vmax' = 10.80 +/- 3.80 mg.l-1.h-1; K(m)' = 88.31 +/- 2.75 micrograms.ml-1; delta t = 4.75 +/- 0.85 h; T1/2 = 4.20 +/- 0.92 h; Tmax = 5.20 +/- 0.92 h; and Cmax = 6.04 +/- 1.70 mg.l-1.

Zinc finger protein 637 protects cells against oxidative stress-induced premature senescence by mTERT-mediated telomerase activity and telomere maintenance.

Oxidative stress is believed to be an important inducer of cellular senescence and aging. Zinc finger protein 637 (Zfp637), which belongs to the Krüppel-like protein family, has been hypothesized to play a role in oxidative stress. Nevertheless, the precise function of Zfp637 has seldom been reported, and it remains unclear whether Zfp637 is involved in oxidative stress-induced premature senescence. In this study, we show that the endogenous expression levels of Zfp637 and mouse telomerase reverse transcriptase (mTERT) are downregulated during oxidative stress-induced premature senescence and in senescent tissues from naturally aged mice. The overexpression of Zfp637 markedly increases mTERT expression and telomerase activity, maintains telomere length, and inhibits both H2O2 and D-galactose-induced senescence accompanied by a reduction in the production of reactive oxygen species (ROS). In contrast, the knockdown of Zfp637 significantly aggravates cellular senescence by downregulating mTERT and telomerase activity, accelerating telomere shortening, and increasing ROS accumulation. In addition, the protective effect of Zfp637 against premature senescence is abrogated in the absence of mTERT. We further confirm that Zfp637 binds to and transactivates the mTERT promoter (-535/-502) specifically. As a result, the mTERT-mediated telomerase activity and telomere maintenance are responsible for the protective effect of Zfp637 against oxidative stress-induced senescence. We therefore propose that Zfp637 prevents oxidative stress-induced premature senescence in an mTERT-dependent manner, and these results provide a new foundation for the investigation of cellular senescence and aging.