Biomedical subjects

J C Wu

Publications and source records attributed to J C Wu.

At least 73 records · Page 4Linked to original sources

PubMed2000

Seroprevalence of GB virus C/hepatitis G virus-RNA and anti-envelope antibody in high-risk populations in Taiwan.

BACKGROUND: GB Virus C (GBV-C)/hepatitis G virus (HGV) was identified in 1995-1996 as a transfusion-transmissible virus. The diagnosis of GBV-C/HGV infection is based on the detection of GBV-C/HGV-RNA by using polymerase chain reaction. Recently, an enzyme immunoassay detecting the antibodies to the viral protein, E2 envelope protein (anti-envelope) of GBV-C/HGV, has been developed. METHODS: Serum GBV-C/HGV-RNA and anti-envelope antibody were determined in 76 cases of intravenous drug users (IVDU), 76 patients with regular hemodialysis and in 80 prostitutes to evaluate the GBV-C/HGV infection rate among high-risk populations in Taiwan. Seventy-six healthy blood donors were randomly selected and were used as a control group. RESULTS: The prevalence of GBV-C/HGV-RNA in high-risk populations was 33% for IVDU, 16% for patients with hemodialysis and 13% for prostitutes, which was significantly higher than the 3% obtained in the control group (P < 0.05 for all groups). The prevalence of anti-envelope antibody was 13% for IVDU, 21% for patients with hemodialysis and 23% for prostitutes, which was not significantly different from the control group (11%). Among the 99 subjects who had positive GBV-C/HGV markers, 97 were tested for exclusive positivity for either GBV-C/HGV-RNA or anti-envelope antibody. CONCLUSIONS: The presence of serum anti-envelope antibody usually indicates the clearance of serum GBV-C/HGV-RNA in patients infected with GBV-C/HGV. GBVirus-C/HGV infection in high-risk populations, determined by the presence of serum GBV-C/HGV-RNA, may underestimate the true level of past and present infection.

Adult↗

PubMed2000

Immunohistochemical differentiation of hepatitis D virus genotypes.

Determination of hepatitis D virus (HDV) genotypes is epidemiologically and clinically important. Phylogenic analysis based on sequencing analysis of multiple HDV strains isolated from sera of patients is not convenient for mass screening in routine laboratories. This study was designed to develop genotype-specific antibodies against hepatitis delta antigen (HDAg) and to apply these antibodies for immunohistochemical differentiation of HDV genotypes in formalin-fixed, paraffin-embedded liver biopsies of patients. Divergence in the carboxyl-terminal 19 amino acids of the large HDAg between genotypes I and II is more than 70%. Peptides covering these residues were conjugated to keyhole limpet hemocyanin and were used for immunization. The generated antibodies were confirmed for their specificity by binding to type-specific HDAgs expressed in DNA-transfected Huh-7 hepatoma cells. Liver biopsies from 6 patients who had dominant genotype I HDV and 33 patients who had dominant genotype II HDV in sera were stained with these antibodies. The accuracy for these antibodies was 94.9%, and the agreement between dominant HDV genotypes in serum and dominant hepatic HDV genotypes based on HDAg staining was nearly perfect (kappa = 0.83). In summary, the carboxyl-terminal 19 amino acids of the large HDAg can be used as immunogens to generate genotype-specific antibodies. These antibodies were proven to be useful in immunohistochemical differentiation of HDV genotypes in liver biopsies.

Amino Acid Sequence↗

PubMed2000

DNA-Based immunization produces Th1 immune responses to hepatitis delta virus in a mouse model.

Hepatitis delta virus (HDV) superinfection is one of the major causes of fulminant hepatitis in endemic areas of hepatitis B virus (HBV) infection. Currently, there is no effective treatment or vaccine against HDV superinfection. DNA-based immunization is a promising antiviral strategy to prevent or treat persistent viral infections. In this study, we investigated the immunological effects of DNA vaccines against HDV in BALB/c mice. Plasmid (pD) encoding large hepatitis D antigen (L-HDAg), or plasmid (pS/pD) coexpressing hepatitis B surface antigen (HBsAg) and L-HDAg, were injected into mice intramuscularly. The seroconversion rate, anti-HBs levels, anti-HDV titers, T-cell proliferation responses, and T-helper (Th)-release cytokine profiles were analyzed. Mice immunized with plasmids, pS/pD or pD, produced low, but significant, titers of anti-HDV antibodies. In contrast, pS/pD induced much stronger anti-HBs titers in the immunized animals. Interestingly, splenic lymphocytes derived from pS/pD-inoculated mice demonstrated significant proliferation responses to recombinant HBsAg and HDAg, and resulted in a Th1-like immune response as suggested by the production of interferon gamma (INF-gamma) and interleukin-2 (IL-2), but not IL-4. The splenic lymphocyte derived from the pD-inoculated mice showed a similar Th1 response to the stimulation of HDAg, but not to HBsAg. In conclusion, our results suggest that DNA vaccines against HDV can induce significant cellular immune responses with a Th1 preference. HBV and HDV coimmunization can be performed by DNA vaccines. These results are promising for the future development of prophylactic and therapeutic HDV vaccines.

Animals↗

PubMed2000

Diabetes mellitus as a risk factor of liver cirrhosis in patients with chronic hepatitis B virus infection.

Liver cirrhosis may occur in chronic hepatitis B surface antigen (HBsAg) carriers. Diabetes mellitus (DM)-associated chronic hepatitis may also occasionally lead to cirrhosis; however, its role in the course of chronic HBsAg carriers has not been studied. A cohort of 500 HBsAg carriers (398 men; mean age at entry, 42 +/- 15 years) were followed up longitudinally. After a mean follow-up of 5.8 +/- 3.3 years, 71 (14.2%: 70 men) patients developed cirrhosis. Increased risks of cirrhosis were found among men and the elderly (p < 0.001). Fifteen (21.1%) cirrhotic patients were noted to have had DM for 2-15 years before the development of cirrhosis. By contrast, only eight (1.9%; p < 0.001 ) of the patients without cirrhosis developed DM. When cirrhotic patients were compared to 102 age- and sex-matched non-cirrhotic controls, DM and elevation of serum alanine transaminase levels were found to be independent factors associated with the advent of cirrhosis in multivariate analysis. Other factors, including acute exacerbation, bridging hepatic necrosis, and superinfection by hepatitis C or D viruses, were insignificant. Our results suggest that DM may play a role in the progression to liver cirrhosis in chronic HBsAg carriers. High-risk subjects should be closely monitored for late complications.

Adult↗

PubMed2000

Factors predictive of liver cirrhosis in patients with chronic hepatitis B: a multivariate analysis in a longitudinal study.

OBJECTIVE AND DESIGN: Chronic hepatitis B virus (HBV) infection may lead to liver cirrhosis; however, factors associated with the development of cirrhosis have been incompletely studied. A total of 516 patients with chronic hepatitis B were followed up longitudinally to determine their outcome. METHODS: The clinical and pathological features were compared between those with and without cirrhosis occurrence. The risk factors were analysed, and the probability of the development of cirrhosis was estimated. RESULTS: During a mean follow-up period of 5.7 +/- 3.4 years (range 1-17 years), cirrhosis occurred in 71 patients, with a calculated annual incidence of 2.4%. Older age (> 45 years) at entry, male gender, persistent hepatitis (> 1.5-fold rise of serum alanine aminotransferase levels for at least one year) and diabetes mellitus were identified as independent risk factors of cirrhosis in a multivariate analysis (odds ratios 8.0, 19.3, 2.0 and 5.2, respectively; P values all < 0.05). A logistic regression equation was used to predict the probability of cirrhosis occurrence, which was as high as 76.6% when all risk factors were present. Acute exacerbation or super-infection by hepatitis C or D viruses were not significant predictors. Patients with subsequent cirrhosis had higher initial hepatic histological necro-inflammatory activities when compared to age- and sex-matched non-cirrhotic controls (Knodell's scores: 8.2 +/- 2.4 versus 6.0 +/- 4.1, P< 0.05). CONCLUSIONS: Patients who were elderly, male, diabetic or had a history of persistent and histologically severe hepatitis were at increased risks of liver cirrhosis. Aggressive anti-viral therapy may be needed for these patients and they should be closely monitored for HBV-related late complications.

Adult↗

PubMed2000

Imaging of dopamine transporters with technetium-99m TRODAT-1 and single photon emission computed tomography.

The authors wanted to evaluate the usefulness of 99Tcm-TRODAT-1 as an imaging agent for measuring changes in dopamine transporter concentrations in Parkinson disease (PD) and correlate the findings to the severity of the disease as measured by the Hoehn and Yahr scale (H/Y). Twenty-two healthy volunteers and 27 patients with PD of H/Y stage I-IV were evaluated. Acquisitions were performed 2 hours after injection of 99Tcm-TRODAT-1. Regions of interest were drawn over the striatum and the cerebellum, and the ratios of striatum-to-cerebellum (ST/CB) were calculated. Patients with PD showed a significant decrease in the striatal uptake of 99Tcm-TRODAT-1 compared to healthy volunteers, and the ST/CB ratios were closely related to the stage of PD. The present study demonstrates that it is possible to visualize and quantify changes in dopamine transporter in the striatum of patients with PD using 99Tcm-TRODAT-1 and SPECT with good correlation to H/Y stage and unified Parkinson's disease rating scale (UPDRS) scale.

Adult↗

PubMed2000

Diagnostic value of immunoglobulin G (IgG) and IgM anti-hepatitis E virus (HEV) tests based on HEV RNA in an area where hepatitis E is not endemic.

Acute hepatitis E (AHE) has rarely been reported in industrialized countries, but the rate of seroprevalence of hepatitis E virus (HEV) antibodies (anti-HEV) is inappropriately high. The sensitivity and specificity of the assay used to test for immunoglobulin G (IgG) and IgM anti-HEV have not been well established in areas where hepatitis E is not endemic (hereafter referred to as "nonendemic areas"). We collected serum samples from 13 AHE patients, 271 healthy subjects, and 160 other liver disease patients in Taiwan to test for HEV RNA by reverse transcription (RT)-PCR and for IgG and IgM anti-HEV by enzyme-linked immunosorbent assays. The sensitivities of IgG and IgM anti-HEV (relative to RT-PCR) were 86.7 and 53.3%, respectively. The specificities of IgG and IgM anti-HEV assays for diagnosing AHE were 92.1 and 98.6%, respectively. The rate of seroprevalence of IgG anti-HEV was 11% among healthy subjects in this nonendemic area, and it increased with age. In summary, IgG anti-HEV is a good diagnostic test for screening for AHE in nonendemic areas. The high rate of prevalence of anti-HEV in healthy subjects indicates that subclinical infection may exist.

Acute Disease↗

PubMed2000

Preferentially deleted chromosome region 9p21 in large hepatocellular carcinomas.

The role of somatic deletions in chromosome 9 and chromosome 22 loci in hepatocellular carcinomas (HCC) was studied. Twenty-one paired HCC and adjacent tumor-free liver tissue samples were examined for loss of heterozygosity at six chromosome 9 and ten chromosome 22 loci. Among informative cases, the highest LOH rates were observed at 9p21 (40% or 4/10 at IFNA) and 9q23 (23% or 3/13 at D9S318). Our observed LOH rate at 9p21 was significantly higher than the background level previously reported for the same tumor type. Clinical data indicate that chromosome 9p21 deletions occurred preferentially in larger tumors (>5 cm diameter). However, a sequence analysis of the MTS1 gene coding region in cases of 9p21 LOH did not reveal any change, suggesting another tumor suppressor gene as the LOH target.

Aged↗

PubMed2000

Clinical and epidemiological implications of swine hepatitis E virus infection.

In nonendemic areas, most patients with acute hepatitis E were infected through traveling to endemic areas. However, some patients did not have a history of foreign travel before infection. Furthermore, high seroprevalence rates of antibody to hepatitis E virus (anti-HEV) were found in the general adult population in some countries without any recorded outbreak of hepatitis E. The significance of anti-HEV assay in these subjects remains obscure. To study if swine might be a source of HEV infection, HEV was tested in sera of 235 pigs in Taiwan, and from 5 patients with acute HEV infection who either denied or did not provide any foreign travel history. Three (1.3%) pigs had detectable swine HEV RNA. The swine and human HEV strains from Taiwan formed a monophyletic group, distinct from three previously reported groups: the United States human and swine HEV strains, the Mexico strain, and the largest group composed of the Asian and the African strains. The identity of nucleotide sequences was 84-95% between swine and human HEV strains in Taiwan, and 72-79% between Taiwan strains and those from different areas. The predicted amino acid sequence of a Taiwan swine HEV strain within the peptide 3-2 used in commercial anti-HEV assay showed a high identity (91-94%) with those of other human and swine HEV strains. Swine may be a reservoir of HEV and subclinical swine HEV infection may occur. Cross-reactivity of current anti-HEV assay may account for the high prevalence rate of anti-HEV in the general population in nonendemic areas.

Adult↗

PubMed2000

Clinical significance of changes in serum hepatitis B virus DNA titer in patients with chronic hepatitis B treated with interferon.

BACKGROUND: Interferon (IFN) has been used in the treatment of patients with chronic hepatitis B virus (HBV) infection. Nonetheless, the changes in serum HBV DNA titer during IFN treatment and the effect of these changes on the therapeutic results have not been well studied. METHODS: Twenty patients with chronic hepatitis B who were positive for serum hepatitis B e antigen (HBeAg) and HBV DNA received IFN-alpha 2a 4.5 million units by subcutaneous injection three times a week for 24 weeks. Twenty age- and sex-matched patients with chronic hepatitis B were selected as a control group. Treatment response was defined as the normalization of serum alanine aminotransferase (ALT) and the seroconversion of serum HBeAg 24 weeks after discontinuation of the IFN treatment. Serum HBV DNA was measured using the branched DNA (bDNA) signal amplification assay. RESULTS: There was no significant difference in pretreatment mean serum ALT and HBV DNA titer in either the IFN-treated or the control group. Treatment response was found in six (30%) of 20 IFN-treated patients and in four (20%) of 20 control patients (p > 0.05). Serum HBV DNA titer fell after IFN treatment and remained undetectable only in patients with final treatment response. Serum HBV DNA was negative at week 12 of the IFN treatment in four (67%) of six patients with treatment responses, significantly higher than in none (0%) of 14 patients without a treatment response (p = 0.001). Multivariate logistic regression revealed that the negativity of serum HBV DNA at week 12 of the IFN treatment successfully predicted treatment response. CONCLUSIONS: Thirty percent of the patients with chronic hepatitis B responded to IFN-alpha 2a 4.5 million units subcutaneously injected three times a week for 24 weeks. Negativity of serum HBV DNA measured by bDNA assay at week 12 of the IFN treatment may suggest a beneficial treatment outcome.

Adult↗

PubMed2000

Impact of hepatitis B and C virus infection on the outcome of kidney transplantation in Chinese patients.

BACKGROUND: There has been improvement in kidney transplantation over the years; however, the impact of hepatitis B and C virus (HBV, HCV) infection on the long-term outcome of kidney transplant is still controversial. METHODS: A total of 113 patients who received renal allografts from 1986 to 1998 were analyzed. Nine were positive for both hepatitis B surface antigen (HBsAg) and antibody to HCV (anti-HCV) (Group 1), 20 were HBsAg-positive and anti-HCV-negative (Group 2), 30 were HBsAg-negative and anti-HCV-positive (Group 3) and 54 were negative for both markers (Group 4). The outcome and survival were compared among the four groups of patients. RESULTS: The mean follow-up period was 5.1 +/- 3.2 years (range, 0.5-13 years) for all patients. Group 2 patients had significantly higher liver-related complications (35% vs 0%, p < 0.0001) and liver-related deaths (20% vs 0%, p = 0.004) than did Group 4 patients. Among all, four HBsAg-positive patients had fulminant hepatitis and died within two years of transplantation. Three (Group 2) of the patients who died were seropositive for hepatitis B e antigen and/or HBV DNA and none had a history of or positive serologic marker to indicate hepatitis of other etiologies. The remaining patient (Group 1) had evidence of superinfection of HCV. Liver cirrhosis occurred in one, two and one patient in Groups 1, 2 and 3, respectively, and hepatocellular carcinoma occurred in two and one patient in Groups 2 and 3, respectively. Despite high liver-related mortality in HBV-infected patients, paradoxically, no significant differences among the four groups in the long-term graft and patient survivals were demonstrated. The presence of HBsAg or anti-HCV was not associated with a poor prognosis of survival as determined by Cox regression analysis. CONCLUSIONS: HBV or HCV infection is not a contraindication to kidney transplantation in Chinese patients. However, it should be noted that serious liver-related complications may occur and limit survival in HBV- and/or HCV-infected patients after kidney transplantation.

Adolescent↗

PubMed2000

TT virus infection among hemodialysis patients at a medical center in Taiwan.

Although the association between TT virus (TTV) infection and hepatitis is controversial, the high prevalence of TTV infection in healthy blood donors and even higher rate among frequently transfused patients poses a potential threat to public health and clinical care. In addition, there is a lack of data concerning the prevalence and mode of transmission of TTV infection in different subpopulations in Taiwan. In the present study, we investigated the prevalence of TTV infection in 111 uremic patients receiving regular hemodialysis in a single hospital in Taiwan. Blood samples were collected and analyzed using a seminested polymerase chain reaction (PCR) designed to amplify a 271 base-pair DNA fragment. The results show that the overall TTV positive rate in uremic patients in our hospital was 61% (68/111), which was much higher than the reported TTV prevalence rate among the normal population (ranging from 1%-12%). The results of analysis of the demographic and clinical characteristics of the patients indicate that blood transfusion may play an important role in TTV transmission (p < 0.05). In addition, the hepatitis B positive rate was significantly lower in TTV positive patients. However, liver function tests were not significantly different between TTV positive and TTV negative patients. The results of the present study suggest that blood transfusion plays an important role in TTV transmission in uremic patients.

Adult↗

PubMed2000

Characterization of a highly glycopeptide-resistant Enterococcus gallinarum isolate.

BACKGROUND AND PURPOSE: Adequate treatment of emergency infection involving antibiotic-resistant bacteria such as vancomycin-resistant Enterococcus requires a convergence of clinical and bacteriologic techniques. An isolate of Enterococcus gallinarum, designated as TSGH63, is known to be uncommonly vancomycin-resistant. This study investigated the genetic determinant for this unique characteristic. METHODS: After completing the conventional identification and sensitivity tests, the genomic content of E. gallinarum TSGH63 was extracted and analyzed by pulse-field electrophoresis. A set of specific primers for vanA, vanB, vanC1, and vanC2/C3 genes was then applied in a multiplex polymerase chain reaction (PCR) to differentiate its genetic content. To locate the determinant for high vancomycin resistance, the electrophoresis profile was further analyzed by Southern blot using the digoxigenin (DIG)-labeled vanA gene probe. Finally, interspecies transfer of the vancomycin-resistance determinant of E. gallinarum TSGH63 was tested by a conjugation experiment in vitro. RESULTS: A 50-kb plasmid was identified in the analysis of the genomic extract of E. gallinarum TSGH63 by pulse field electrophoresis. Using multiplex PCR, we demonstrated that E. gallinarum TSGH63 harbors a vanA gene in addition to a vanC1 gene. The DIG-labeled vanA gene-specific probe bound to the plasmid exclusively on the Southern blot. The plasmid-carried vanA gene, but not the vanC1 gene, was found to be transferable from TSGH63 to E. faecalis JH2-2 by conjugation in vitro. CONCLUSIONS: This is the first report of isolation of E. gallinarum with a high level of resistance to glycopeptides in Taiwan. The demonstrated interspecies transfer of the vancomycin-resistance gene highlights the importance of stringent control of the use of vancomycin.

Conjugation, Genetic↗

PubMed2000

Clinical, virologic and pathologic significance of elevated serum gamma-glutamyl transpeptidase in patients with chronic hepatitis C.

BACKGROUND: Elevated serum gamma-glutamyl transpeptidase (GGT) is often seen in patients with chronic hepatitis C virus (HCV) infection and is associated with a poor response to interferon treatment. The pathogenesis of these phenomena is unclear. Therefore, we assessed the prevalence of elevated serum GGT in Chinese patients with chronic hepatitis C and evaluated the clinical, biochemical, virologic and histologic features of this phenomenon. METHODS: One hundred and twelve patients with biopsy-proven chronic hepatitis C were enrolled. Patients who were habitual alcohol drinkers, alcoholics or had diabetes mellitus were excluded. RESULTS: Forty-three (38.4%) of 112 patients had elevated serum GGT (> 60 U/l). Patients with elevated serum GGT had significantly higher serum levels of alanine and aspartate aminotransferases, alkaline phosphatase and total bilirubin, significantly higher histologic scores of liver lobular necro-inflammation and fibrosis when compared to patients with normal serum GGT. Elevated serum GGT was not correlated to serum HCV RNA titer or HCV genotype. Multivariate logistic regression analysis showed that a histologic fibrotic score > or = 2 was the only significantly independent predictor associated with elevated serum GGT. Fifty-seven of 112 patients completed a six-month course of interferon treatment. Patients with elevated serum GGT had a significantly lower sustained response rate to interferon when compared to patients with normal serum GGT (8% vs 30%, p = 0.042). CONCLUSIONS: Elevated serum GGT in chronic hepatitis C patients was frequently associated with more severe hepatic fibrosis or cirrhosis and may, in part, account for poor response to interferon therapy.

Adult↗

PubMed2000

Resolution of refractory hepatic hydrothorax after chemical pleurodesis with minocycline.

Management of refractory hepatic hydrothorax is a challenge to physicians in clinical practice. We reported two patients with hepatic hydrothorax, non-alcoholic cirrhosis and rapidly recurring pleural effusion. They failed to improve with diuretics and repeated thoracentesis. Refractory hepatic hydrothorax was successfully treated by minocycline-induced pleural symphysis. After pleurodesis, ventilatory function returned to normal in both patients. No recurrence of pleural effusion was noted. We suggest that minocycline pleurodesis is an alternative treatment for refractory hepatic hydrothorax because it is simple, safe and effective.

Aged↗

PubMed2000

Limb myorhythmia in association with hypertrophy of the inferior olive: report of two cases.

We report on 2 patients who uncommonly developed isolated limb myorhythmia in association with inferior olive hypertrophy (IOH) after an acute stroke in the brain stem. A slow tremor presented in the proximal upper limbs predominantly when at rest. It was aggravated by outstretched arms and by active hand movements. The surface electromyogram (EMG) recorded simultaneous activities over the agonist and antagonist muscles with a rate of 3.5 Hz and 2.5 Hz in 2 patients respectively. In the first patient, bilateral limb myorhythmia presented 12 months after the brain stem stroke, and both inferior olives were hypertrophic. In the second patient, unilateral limb myorhythmia developed in the left hand 7 months after right pontine hemorrhage, and only the right inferior olive was hypertrophic. These findings indicate that limb myorhythmia commencing after brain stem insult is anatomically and temporally related to hypertrophy of the contralateral inferior olive. Based on our 2 patients and previously reported cases, we propose that a possible causal relationship exists between limb myorhythmia and contralateral IOH, although its pathophysiological mechanisms remain to be established. We suggest that, similar to palatal myoclonus, isolated limb myorhythmia is within the clinical spectrum of IOH.

Brain Stem↗

PubMed2000

Quantitative PET scan findings in carbon monoxide poisoning: deficits seen in a matched pair.

Quantitative positron emission tomography (PET) was utilized to establish the degree and localization of central nervous system dysfunction in 2 adult patients 3 years status postchronic carbon monoxide poisoning. The individual PET scans were compared against a composite scan made up of 32 normals using a z transformation statistical parametric map. Neuropsychological findings indicated marked anterior frontal lobe syndrome in the context of far-above-average intelligence, memory, and language. They also showed manifest frontal symptoms in activities of daily living that resulted in vocational disability in each case. PET analysis revealed substantially decreased metabolism in the orbitofrontal and dorsolateral prefrontal cortex as well as in areas of the temporal lobe for each individual. Individual scans were very similar and consistent with patient's presenting symptoms, and changed life circumstances. This report represents the first quantitative functional neuroimaging study relevant to carbon monoxide poisoning.

Clinical Conference↗

PubMed1999

Effects of hyperthermia on the cytoskeleton and focal adhesion proteins in a human thyroid carcinoma cell line.

Hyperthermia is reported to act as a sensitizer to chemotherapeutic drugs in the treatment of cancer. Thyroid follicular carcinoma were used to elucidate the effects of hyperthermic treatment (41-43 degrees C) on cell morphology, cytoskeleton, and the focal adhesion complex. The critical temperature that resulted in inhibition of cell proliferation as the cell number in the same area did not increase over a 23 h time course and irreversible changes in cell morphology was 42-43 degrees C. An immunofluorescence study on heat-treated cells (43 degrees C, 1-5 h) demonstrated that depolymerization of actin filaments, intermediate filaments, and microtubules accounted for the rounding-up of cells and detachment from the substratum. Characteristic staining patterns for integrin alphav, focal adhesion kinase, and vinculin were noted in untreated cells, but the immunoreactive intensities for these proteins became weaker with time of heat treatment. Anti-phosphotyrosine staining revealed less immunoreactivity in the focal adhesions in treated cells compared with control cells. The disappearance of integrin alphav from the cell surface may result in inhibition of integrin-mediated activation of focal adhesion kinase, which results in dephosphorylation of focal adhesion components and its disassembly. These results indicate that hyperthermia induces disruption of integrin-mediated actin cytoskeleton assembly and, possibly, of other integrin-mediated signaling pathways.

Actins↗