[Clinical study of digital six-axis external fixation frame based on CT data for tibiofibular fractures].

Objective: To investigate the clinical effect of applying the digital six-axis external fixation frame based on CT data in the treatment of tibiofibular fractures. Methods: The clinical data of 43 patients with tibiofibular fractures treated by the self-developed digital six-axis external fixation frame based on CT data at Integrated Orthopedic Department of Traditional Chinese Medicine (TCM) and Western Medicine,HongHui Hospital from January 2018 to January 2021 were retrospective analysis.There were 27 males and 16 females,aged (36.0±9.4) years(range:25 to 50 years).AO classification:15 cases of 42A,11 cases of 42B, and 17 cases of 42C.There were 7 open fractures and Gustilo fracture classification:2 cases of type Ⅰ,4 cases of type Ⅱ,and 1 case of type Ⅲ.The two or three plane rings were connected with six connecting rods to form a complete six-axis external fixation frame,and the distal and proximal fracture blocks were connected to the distal and proximal rings by fixation pins,and the lengths of the six connecting rods needed to be adjusted were calculated by using the supporting software according to the CT data after surgery,and then the lengths of the connecting rods were adjusted one by one to complete the reduction of the fracture. The reduction accuracy of this six-axis external fixation brace was evaluated by measuring postoperative radiographs; postoperative recovery and complications were collected,the time of brace removal was recorded,and the function of the affected limb was evaluated according to the Johner-Wruhs score at the final follow-up. Results: Postoperative radiographs showed that all patients achieved satisfactory reduction with lateral displacement(M(IQR)) of 2.3(2.5) mm (range:0.3 to 7.3 mm),anteroposterior displacement of 2.1 (2.4) mm (range:0.3 to 5.7 mm),anteroposterior angulation of 2.5(2.4)°(range:0 to 5°),internal and external angulation of 2.1(1.5)°(range:0 to 4°), and no significant internal or external rotational deformity was detected on the exterior.On the second postoperative day,all patients were able to walk with partial weight-bearing on crutches. All 43 patients were followed up for more than 6 months,with a follow-up period of (33.3±7.3) weeks (range:24 to 42 weeks).The external fixation frame was removed after the fracture healed.The external frame was removed at 20(3)weeks (range:18 to 25 weeks) postoperatively. Up to the final follow up, no secondary fracture occurred in any of them.The Johner-Wruhs score of the affected limb at the last follow-up was excellent in 39 cases and good in 4 cases. Conclusion: The digital six-axis external fixator based on CT data for tibiofibular fractures has the advantages of precise reduction,firm fixation,simple operation,rapid fracture healing,and minimal trauma, which is a minimally invasive method for treating tibiofibular fractures,especially suitable for patients with poor skin and soft tissue conditions such as open injuries.

[Epidemiological investigation on a cluster epidemic of COVID-19 in a collective workplace in Tianjin].

Objective: To investigate and analysis the epidemiological characteristics of a cluster epidemic of COIVD-19 in a collective workplace in Tianjin, evduate the prevention and control measures based on limited evidence and experience in early period of COVID-19 epidemic. Methods: Descriptive research method was used to describe the distribution and other epidemiological characteristics of the cluster cases of COVID-19. Results: Since the onset of the first index case on January 15, ten confirmed COVID-19 cases had occurred in the workplace, and the epidemic had spread from the workplace to 4 families, infecting 7 family members. The median age of 17 cases was 55 (19-79) years. All the 10 employee cases were males, and in the family cases, 3 were males and 4 were females. Of the employee cases, 8 worked in CW workshop and 2 worked in administrative office building. The median exposure-onset interval of all the cases was 4 days, and the median exposure-onset interval was 4.5 days in the employee cases and 4 days in the family cases. The median onset-medical care seeking interval was 4 days in the non-isolated cases, 2.5 days in the cases with home isolation after onset, and 0.5 day in the cases with home isolation before onset. Conclusions: The clustering of COVID-19 cases was observed in this workplace in Tianjin, which affected 4 families. In the early stage of the epidemic, accurate and rapid blocking and control measures can completely prevent the large-scale spread of COVID-19.

Linc-UBC1 stimulates the metastasis and progression of ovarian cancer via downregulating p53 level.

OBJECTIVE: To elucidate the role of linc-UBC1 in regulating the metastasis and progression of ovarian cancer (OC) by downregulating the p53 level. PATIENTS AND METHODS: Relative levels of linc-UBC1 in OC tissues and paracancerous tissues were determined by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Differential expressions of linc-UBC1 in OC tissues with different tumor staging or tumor sizes were detected as well. Receiver operating characteristic (ROC) curves were introduced for assessing the diagnostic value of linc-UBC1 in OC. After silence of linc-UBC1, proliferative and migratory abilities of HO8910 and HEY cells were evaluated. Subcellular distribution of linc-UBC1 was analyzed. The interaction between linc-UBC1 and p53 was explored through the RNA immunoprecipitation (RIP) assay. At last, rescue experiments were conducted to uncover the role of linc-UBC1/p53 regulatory loop in influencing the progression of OC. RESULTS: Linc-UBC1 was upregulated in OC and its level negatively correlated to that of p53. Linc-UBC1 level was higher in OC patients with advanced TNM staging or larger tumor size. Linc-UBC1 was mainly distributed in the nucleus. Silence of linc-UBC1 attenuated proliferative and migratory abilities of HO8910 and HEY cells. RIP assay verified that linc-UBC1 could inhibit the transcription of p53. Knockdown of p53 could partially reverse the regulatory effects of linc-UBC1 on regulating the progression of OC. CONCLUSIONS: Linc-UBC1 is upregulated in OC tissues and cells. It stimulates the proliferation and metastasis of OC by downregulating p53 level, thus exerting a carcinogenic role.

[Investigation on the status of multidrug-resistant gram-negative bacteria induced by occupational exposure among medical staff in ICU].

Objective: To understand the natural carriage status of multidrug resistant gram-negative bacteria in ICU medical personmel and control growp of 69 hospitals in Tianjin. Methods: From April 2007 to October 2016, 2902 samples of nasal vestibule and hand swabs were collected from 1296 ICU medical personmel and 155 non medical personmel (control group) , and 14 kinds of antimicrobial agents were used to test the sensitivity of gram-negative bacilli. Results: 332 Gram-negative bacteria were isolated from medical personmel, of which 139 were multidrug resistant; 70 gram-negative bacteria were isolated from control group, and 20 of which were multidrug resistant. There was no significant difference (P>0.05) in the incidence of nasal vestibular colonization between medical personmel group (231/1296) and control group (32/155) . The control group (38/155) had a higher rate of hand bacteria carriage than medical staff group (101/1296) (P<0.01) . The proportion of multidrug resistant gram-negative bacteria was 28.57% (20/70) in control group, which was significantly lower than medical personmel group (41.87%, 139/332) (P<0.05) . Conclusion: For the nasal vestibule, the medical personnel and control guoup have the same gram-negative bacteria carrying rate, but the multidrug resistant bacteria isolation rate from the medical staff group are significantly higher which may due to vocational contamination of pathogen in ICU; while the gram-negative bacteria in the hands of the medical staff group are significantly lower than those of the control group, which might attribute to the difference of hand sanitation technique of two groups.

Optic Nerve Crush Induces Changes of Hydrogen Sulfide Synthases Expression in the Rat Retina.

OBJECTIVES: To investigate the expression changes of the hydrogen sulfide synthases cystathionine γ-lyase （CSE）, cystathionine ß-synthase （CBS）, and 3-mercaptopyruvate sulfurtransferase （3-MST）, after optic nerve crush （ONC） in rat the retina. METHODS: The rat model of ONC was established. Rats were divided into normal control, ONC, and sham control groups. Histopathologic changes in retina, the number of retinal ganglion cells （RGC） and retinal thickness of inner part （RTIP） were measured. The changes of CSE, CBS and 3-MST mRNA expression were detected with quantitative real-time PCR. RESULTS: The retinal histostructure was normal in normal controls and with minor changes in sham controls, respectively. Compared with sham group, significant retina damages were found in the ONC group： a time-dependent reduction of RGC number and RTIP. Expressions of CSE, CBS and 3-MST mRNA in rat retina were detected in normal control. Compared with normal controls, the expressions of CSE, CBS and 3-MST mRNA did not show any significant changes in the sham controls. Compared with sham controls, CBS mRNA expressions showed a time-dependent increase at 3 d, 7 d and 14 d after crush in the ONC group; CSE mRNA expressions increased to the peak at 3 d and then slightly reduced at 14 d after crush; 3-MST mRNA expressions showed the trend of increase at 3 d and 7 d and then enhanced remarkably at 14 d after crush. CONCLUSIONS: Hydrogen sulfide synthases CSE, CBS and 3-MST expressions were up-regulated in rat retina following ONC, which may cause an increase in local endogenous hydrogen sulfide production in the retina and a compensatory protective effect.

Presence, distribution and molecular epidemiology of multi-drug-resistant Gram-negative bacilli from medical personnel of intensive care units in Tianjin, China, 2007-2015.

BACKGROUND: Multi-drug-resistant Gram-negative bacteria (MDRGNB) have become an important cause of nosocomial infection in intensive care units (ICUs). AIMS: To investigate the molecular epidemiology of MDRGNB isolated from medical personnel (MP) and non-medical personnel (NMP) at 69 ICUs in Tianjin, China. METHODS: From April 2007 to October 2015, 2636 nasal and hand swab samples from 1185 MP and 133 NMP were cultured for GNB (including MDRGNB), meticillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). The susceptibilities of GNB to 14 antimicrobial agents were determined, and 80 MDRGNB were characterized using pulsed-field gel electrophoresis (PFGE) and dendrogram analysis. FINDINGS: In total, 301 GNB were identified in 269 MP, including 109 MDRGNB isolates in 104 MP. Forty-two GNB were isolated from 39 NMP, which included 20 NMP with MDRGNB. Overall, 8.8% of MP were colonized with MDRGNB, which greatly exceeded colonization rates with MRSA (0.9%) and VRE (0.1%). Three pairs of Klebsiella pneumoniae and one pair of Enterobacter aerogenes were indistinguishable from each other, but the majority of isolate tests had distinct PFGE profiles. CONCLUSIONS: The prevalence of MDRGNB was high among ICU MP in Tianjin, and greatly exceeded that of VRE and MRSA. There was no difference in the rates of nasal carriage of MDRGNB between MP and NMP, but NMP were significantly more likely to have hand colonization with MDRGNB. PFGE profiles showed that there was only limited sharing of strains of MDR E. aerogenes and K. pneumoniae between personnel.

Government Response to the Discovery of a Rabies Virus Reservoir Species on a Previously Designated Rabies-Free Island, Taiwan, 1999-2014.

Taiwan had been considered rabies free since 1961. In 2013, Taiwan confirmed the detection of rabies virus in wild Taiwan ferret-badgers. Up to December 2014, there have been 423 rabies-confirmed ferret-badgers and three cases of spillover infection into non-reservoir hosts. Genetic analysis indicates that TFBV is distinct from all other known rabies virus variants. To date, ferret-badger rabies is known to occur only in China and Taiwan. The temporal dynamics of rabid ferret-badgers in Taiwan suggests that the epizootic appears to have subsided to enzootic levels as of December 2014. According to the current epidemiologic data, there is only one TFBV strain in Taiwan. TFBV is still sequestered to the mountainous regions. Humans are at risk mainly through exposure to the virus from infected domestic meso-carnivores, mainly dogs and cats. Dogs and cats should be vaccinated to establish an immunological barrier to stop the spread of the disease from mountainous regions to domestic meso-carnivores.

Interleukin-10 polymorphisms associated with susceptibility to acute myeloid leukemia.

We investigated the association between polymorphisms in interleukin-10 (IL-10) -1082G/A (rs1800896), -819T/C (rs1800871), and -592A/C (rs1800872) and the risk of acute myeloid leukemia (AML) in a Chinese population. A total of 167 primary AML cases and 328 healthy control subjects were recruited at the First People's Hospital of Yunnan Province between March 2009 and January 2012. The polymorphisms rs1800896, rs1800871, and rs1800872 were genotyped by polymerase chain reaction-restriction fragment length polymorphism. Multivariate regression analyses showed that subjects carrying the rs1800871 CC genotype and C allele had a significantly increased risk of AML, with adjusted odds ratios (95% confidence intervals) of 1.72 (1.01-2.97) and 1.38 (1.04-1.81), respectively. Those carrying the rs1800872 G allele had a slightly increased risk of AML, with an adjusted odds ratio (95% confidence interval) of 1.30 (1.01-1.72). Moreover, genotyping results demonstrated that subjects carrying both the rs1800871 C allele and rs1800872 G allele had a moderately increased risk of AML, indicating that the 2 genotypes had a synergistic effect on AML risk (odds ratio = 2.03, 95% confidence interval = 1.24- 3.15). Our results demonstrated that polymorphisms in rs1800871 and rs1800872 enhance the risk of AML, and these 2 single nucleotide polymorphisms have a synergistic effect on AML risk.

Facial bone vibration in resonant voice production.

PURPOSE: This study investigated whether resonant voice training would enhance facial bone vibration during resonant voice production. METHODS: Twelve normal healthy participants undertook four sessions of resonant voice training, each lasted for 30 minutes. Piezoelectric accelerometer was used to measure the vibratory level on the face (nasal bridge and upper lip) and the perilaryngeal area during the production of nasal consonant /m/ and vowels /a/, /i/, and /u/ before and after the resonant voice training. The extents of vibration of these four sounds among these three sites were compared. RESULTS: Significant increase in facial bone vibration following resonant voice training was found. The nasal bridge showed a significantly larger magnitude of increase when compared with that at the upper lip. Different sounds were also found to facilitate different magnitude of facial bone vibration. Greater magnitude of facial bone vibration was found with the phonation of /m/, /i/, and /u/ when compared with the phonation of /a/. CONCLUSION: Resonant voice training facilitated an increase in facial bone vibration, more so at the nasal bridge area than around the upper lip. This is hypothesized to contribute to the improved resonant voice production. Sounds that involve relatively restricted oropharyngeal cavities facilitated a greater extent of facial bone vibration during resonant voice production.

Residue depletion of decoquinate in chicken tissues after oral administration.

A rapid, sensitive, and reliable high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed and validated for the analysis of decoquinate in chicken tissues. The compounds were extracted using acetonitrile by liquid-liquid extraction (LLE) and purified with an Oasis(™) HLB solid-phase extraction (SPE) cartridge. Chromatographic separation was performed on an XTerra C18 reversed-phase column with a mobile phase of water containing 0.1% formic acid and acetonitrile. The analyte was detected by tandem quadrupole mass spectrometry after positive electrospray ionization by multiple reaction monitoring. The detection and quantitation limits were 1 and 2.5 µg/kg, respectively. The recoveries of edible tissues ranged from 85.3% to 104.9%, with relative standard deviations (RSD) lower than 10.4%. The depletion profile of decoquinate was studied in healthy chickens after oral administration of feed containing 27.2 mg/kg decoquinate for 10 consecutive days. The residue concentrations of decoquinate in chicken muscle and liver were detected using the developed method. The highest residue concentrations were attained 0.25 day post-treatment, and decoquinate residues were still detected 5 days postmedication in the tissues examined. The developed method has been successfully applied to the depletion study of decoquinate in chicken tissues. The recommended withdrawal period with oral administration based on our research is 3 days.

Vibratory and perceptual measurement of resonant voice.

PURPOSE: This study set out to investigate whether there existed a correlation between auditory-perceptual judgment of resonant voice and the physical vibration in the facial bone. The magnitude of bone vibration in the facial bone during different types of voice production (resonant vs nonresonant vs strained voices) was also investigated. METHOD: Thirty-six healthy normal subjects produced three types of phonations: resonant voice, habitual nonresonant voice, and strained voice. A piezoelectric accelerometer was used to measure the vibrations in the nasal bridge and the perilaryngeal area during the phonation. Seventy-two selected nasal sounds (/ma/) produced under the resonant voice condition by these speakers were rated by two experienced speech pathologists on the magnitude of auditory-perceptual resonance using an 11-point equal-appearing interval scale. The magnitude of bone vibration was also compared across the three voice types. RESULTS: Significant moderate correlations were found between the physical bone vibration and the auditory-perceptual rating of resonant voice at the nasal bridge of the facial bone (0.6). Resonant voice, compared with the strained and nonresonant voice types, was also found to have a significant increase in the magnitude of facial bone vibration. Nasal stimuli, compared with nonnasal stimuli, facilitated greater bone vibration during resonant voice production. CONCLUSION: Piezoelectric accelerometer, as an objective quantitative tool, measures reliably the extent of bone vibration in resonant voice phonation. It is a useful tool for determining the bone vibration in relation to resonant voice.

Inhibitory effects of epidermal growth factor on progesterone production of ovarian granulosa cells in Tsaiya duck (Anas platyrhynchos var. domestica).

1. The purpose of this study was to investigate the effects of epidermal growth factor (EGF) on progesterone (P(4)) secretion from ovarian granulosa cells in Tsaiya ducks (Anas platyrhynchos var. domestica). 2. We obtained the largest (F1) follicle from Tsaiya duck, the granulosa layer was separated and the cells were isolated according to their proximity to the germinal disc. 3. The granulosa cells were cultured in vitro, the culture media and the cells were used to determine P(4) and steroidogenic enzyme concentrations, respectively. 4. P(4) concentrations were decreased in cultured granulosa cells taken proximal to the germinal disc (GD) compared to those distal to the germinal disc (NGD). 5. EGF inhibited both basal and ovine luteinising hormone (oLH)-induced P(4) concentrations. It also inhibited the P(4) secretion via protein kinase A (PKA) pathway when cultured with GD and NGD granulose cells (mixed together) in vitro. 6. Western blot results showed decreased concentrations of cytochrome P450 side-chain cleavage (P450scc) enzyme, 3ß-hydroxysteroid dehydrogenase (3ß-HSD) enzyme and steroid acute regulatory (StAR) protein expression, when the cells were co-treated with EGF and oLH. 7. The inhibitory effect of oLH-induced P(4) production was attenuated by EGF by the addition of MAP-erk kinase (MEK) inhibitor (PD98059) suggests EGF may inhibit P(4) production by affecting via the mitogen-activated protein kinase (MAPK) pathway.

The pharmacokinetics of nitazoxanide active metabolite (tizoxanide) in goats and its protein binding ability in vitro.

The pharmacokinetics of tizoxanide (T), the active metabolite of nitazoxanide (NTZ), and its protein binding ability in goat plasma and in the solutions of albumin and alpha-1-acid-glycoprotein were investigated. The plasma and protein binding samples were analyzed using a high-performance liquid chromatography (HPLC) assay with UV detection at 360 nm. The plasma concentration of T was detectable in goats up to 24 h. Plasma concentrations vs. time data of T after 200 mg/kg oral administration of NTZ in goats were adequately described by one-compartment open model with first order absorption. As to free T, the values of t(1/2Ka), t(1/2Ke), T(max), C(max), AUC, V/F((c)), and Cl((s)) were 2.51 +/- 0.41 h, 3.47 +/- 0.32 h, 4.90 +/- 0.13 h, 2.56 +/- 0.25 microg/mL, 27.40 +/- 1.54 (microg/mL) x h, 30.17 +/- 2.17 L/kg, and 7.34 +/- 1.21 L/(kg x h), respectively. After beta-glucuronidase hydrolysis to obtain total T, t(1/2ke), C(max), T(max), AUC increased, while the V/F((c)) and Cl((s)) decreased. Study of the protein binding ability showed that T with 4 microg/mL concentration in goat plasma and in the albumin solution achieved a protein binding percentage of more than 95%, while in the solution of alpha-1-acid-glycoprotein, the percentage was only about 49%. This result suggested that T might have much more potent binding ability with albumin than with alpha-1-acid-glycoprotein, resulting from its acidic property.

Adsorption and recovery of Cu (II) with polysulphone microcapsules containing chitosan gel.

Polysulphone (PSF) microcapsules (PSF-CTS) containing chitosan gel with higher mechanical stability and anti-biodegradability were prepared using a novel surface coating method. The thickness and microstructures of the polysulphone coating layer were analysed by SEM. The experiments to examine the mechanical improvement of the encapsulated gel beads were carried out. The adsorption for Cu2+ and regeneration properties of unencapsulated and encapsulated gel beads were also tested. The results showed that the mechanical strength of the encapsulated gel beads was significantly enhanced. However, this improvement led to a decrease of the adsorption kinetics due to the increase of the mass transfer resistance. The potentially available methods are suggested to reduce mass transport resistance through the PSF coating layer.

[A comparative study on wound healing treated by different doses of bovine basic fibroblast growth factor (bFGF)].

OBJECTIVE: To explore the optimal dosage and method of bFGF application on surgical wound for accelerating its healing. METHODS: Laceration wounds on the extremities of 73 patients were served as the target. The wounds were applied with three different doses of bFGF (75 Au/cm(2), 150 Au/cm(2), 300 Au/cm(2)) and with three application methods, i.e. once a day, three times a day and once a day with moistening. Normal saline with 0.5% metronidazol was employed as control agents. The wound healing time in every groups was recorded in days and compared with each other. RESULTS: When compared to each other, the wound healing time (day) was much shorter (P < 0.05) with bFGF application in dose of 75 similar 300 Au/cm(2). There were also obvious differences in wound healing time among groups treated with the same dose but with different methods (P < 0.01). In addition, three times a day and once a day with moistening of bFGF application could further shorten the wound healing time. CONCLUSION: Compared to the dosage of the agent, the frequency and method of bFGF application seemed more important for its optimal effects. In view of the convenience, feasibility and economy, once a day with moistening was recommended for clinical application.

[Characters of two gravity-related esterases in carrot callus cells].

On the basis of identification of two gravity-related esterases (grEST1 and grEST2) in carrot callus cells (Cai et al. 1998), we continued the study of the characteristics of these two esterases. They have the very special characteristic of SDS resistance. Their activities could be inhibited partially by deoxycholate. beta-Phenylpropionic acid, AgNO3 and CuSO4 had no inhibitory effect on their activities. The activities of grEST1 and grEST2 could be decreased by ascorbic acid and cysteine, and the influence by cysteine was particularly obvious. The molecular weights of grEST1 and grEST2 were shown to be near the ranges of 49-66 kD and 43-59 kD respectively by non-denaturing electrophoresis containing deoxycholate, Triton X-100 and SDS respectively, and the isoelectric points were approximately pH 5.4 and 4.9 respectively. Besides, grEST1 and grEST2 were found in the fraction precipitating at value between 30% and 40% saturation with (NH4)2SO4.

Synthesis and structure-activity relationships of 2-pyrazinylcarboxamidobenzoates and beta-ionylideneacetamidobenzoates with retinoidal activity.

The structure-activity relationships of two series of novel retinoids (2-pyrazinylcarboxamidobenzoates and beta-ionylideneacetamidobenzoates) have been investigated by evaluating their ability to induce differentiation in both human promyelocytic leukemia (HL60) cells and mouse embryonal carcinoma (P19) cells. The most active compound (ED50 = 8.3 x 10(-9) M) of the 2-pyrazinylcarboxamidobenzoates is 4-[2-(5,6,7,8-tetrahydro-5,5,8, 8-tetramethylquinoxalyl)carboxamido]benzoic acid (9u), while the most active analogue of the beta-ionylideneacetamidobenzoates is 4-[3-methyl-5-(2',6',6'-trimethyl-1'-cyclohexen-1'-yl)-(2E, 4E)-pentadienamido]benzoic acid (10a, ED50 = 3.2 x 10(-8) M). Our studies identify an absolute requirement for the carboxylic acid moiety on the aromatic ring to be para relative to the amide linkage for activity. Benzoate substitutions in the ortho position relative to the terminal carboxylate (9d,k,r) are well-tolerated; however, a methoxy substituent meta relative to the terminal carboxylate gives rise to only weakly active analogues (9x). Conformational studies (NMR, X-ray crystallography) of the 2-pyrazinylcarboxamidobenzoates indicate that the preferred conformation exhibits a trans-amide bond and an internal hydrogen bond between the quinoxaline N1 and HN amide which locks the torsional angle between C2 and CO in the s-trans conformation. N-Methylation (9y) results in loss of activity. Studies indicate that there is now a cis-amide bond present which redirects the carboxylate toward the pharmacophoric gem-dimethyl groups. The distance between the gem-dimethyl group and the terminal carboxylate appears to be too short to activate the retinoid receptor. N-Methylation in the beta-ionylideneacetamidobenzoate series (10c) also results in the formation of a cis-amide bond and loss of activity.

Taxol induces concomitant hyperphosphorylation and reorganization of vimentin intermediate filaments in 9L rat brain tumor cells.

Taxol, a microtubule stabilizing agent, has been extensively investigated for its antitumor activity. The cytotoxic effect of taxol is generally attributed to its antimicrotubule activity and is believed to be cell cycle dependent. Herein, we report that taxol induces hyperphosphorylation and reorganization of the vimentin intermediate filament in 9L rat brain tumor cells, in concentration- and time-dependent manner. Phosphorylation of vimentin was maximum at 10(-6) M of taxol treatment for 8 h and diminished at higher (10(-5) M) concentration. Enhanced phosphorylation of vimentin was detectable at 2 h treatment with 10(-6) M taxol and was maximum after 12 h of treatment. Taxol-induced phosphorylation of vimentin was largely abolished in cells pretreated with staurosporine and bisindolymaleimide but was unaffected by H-89, KT-5926, SB203580, genistein, and olomoucine. Thus, protein kinase C may be involved in this process. Hyperphosphorylation of vimentin was accompanied by rounding up of cells as revealed by scanning electron microscopy. Moreover, there was a concomitant reorganization of the vimentin intermediate filament in the taxol-treated cells, whereas the microtubules and the actin microfilaments were less affected. Taken together, our data demonstrate that taxol induces hyperphosphorylation of vimentin with concomitant reorganization of the vimentin intermediate filament and that this process may be mediated via a protein kinase C signaling pathway.