Rheumatology: 7. Basics of therapy.
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Analgesics, Non-Narcotic↗
Biomedical subjects
S H Huang
Publications and source records attributed to S H Huang.
Water clusters in life.
The role of water in chemical, biochemical and cellular events has only been recognized as a universal solvent. The conventional wisdom holds that water is a passive agent in biological interaction. However, more and more researchers regard water as an active component in biochemical reactions and hence occupy a crucial role in life. We propose that the active component of water is due to the existence of stable water clusters in aqueous solutions. Our research demonstrated that stable water clusters could be produced in very dilute inorganic and organic water solutions, and also isolated from biological fluids such as bovine serum. Stable water clusters may play an important role in physiological and pathological processes of life.
Animals↗
Escherichia coli K1 aslA contributes to invasion of brain microvascular endothelial cells in vitro and in vivo.
Neonatal Escherichia coli meningitis remains a devastating disease, with unacceptably high morbidity and mortality despite advances in supportive care measures and bactericidal antibiotics. To further our ability to improve the outcome of affected neonates, a better understanding of the pathogenesis of the disease is necessary. To identify potential bacterial genes which contribute to E. coli invasion of the blood-brain barrier, a cerebrospinal fluid isolate of E. coli K1 was mutagenized with TnphoA. TnphoA mutant 27A-6 was found to have a significantly decreased ability to invade brain microvascular endothelial cells compared to the wild type. In vivo, 32% of the animals infected with mutant 27A-6 developed meningitis, compared to 82% of those infected with the parent strain, despite similar levels of bacteremia. The DNA flanking the TnphoA insertion in 27A-6 was cloned and sequenced and determined to be homologous to E. coli K-12 aslA (arylsulfatase-like gene). The deduced amino acid sequence of the E. coli K1 aslA gene product shows homology to a well-characterized arylsulfatase family of enzymes found in eukaryotes, as well as prokaryotes. Two additional aslA mutants were constructed by targeted gene disruption and internal gene deletion. Both of these mutants demonstrated decreased invasion phenotypes, similar to that of TnphoA mutant 27A-6. Complementation of the decreased-invasion phenotypes of these mutants was achieved when aslA was supplied in trans. This is the first demonstration that this locus contributes to invasion of the blood-brain barrier by E. coli K1.
Amino Acid Sequence↗
Urinary tract infection in febrile infants younger than eight weeks of Age.
OBJECTIVE: To assess the usefulness of laboratory parameters, including peripheral white blood cell (WBC) count, C-reactive protein (CRP) concentration, erythrocyte sedimentation rate (ESR), and microscopic urinalysis (UA), for identifying febrile infants younger than 8 weeks of age at risk for urinary tract infection (UTI), and comparison of standard UA and hemocytometer WBC counts for predicting the presence of UTI. METHODS: A total of 162 febrile children <8 weeks of age were enrolled in this prospective study. All underwent clinical evaluation and laboratory investigation, including WBC count and differential; ESR; CRP; blood culture; a lumbar puncture for cell count and differential, glucose level, protein level, Gram stain, and culture; and a UA and urine culture. All urine specimens were obtained by suprapubic aspiration and microscopically analyzed with standard UA as well as with hemocytometer WBC counts. Quantitative urine cultures were performed. Sensitivity, specificity, accuracy, likelihood ratios, and receiver operating characteristic (ROC) curves were determined for each of the screening tests. RESULTS: There were 22 positive urine culture results of at least 100 colony-forming unit/mL. Eighteen of these 22 patients were males, and all were uncircumcised. There were significant differences for pyuria >/=5 WBCs/hpf, pyuria >/=10 WBC/microL, CRP >20 mg/L, and ESR >30 mm/hour between culture-positive and culture-negative groups (P <.05). The ROC area for hemocytometer WBC count, standard UA, peripheral WBC count, ESR, and CRP concentration were.909 +/-.045,.791 +/-.065,.544 +/-.074,. 787 +/-.060, and.822 +/-.036, respectively. The ROC curve analysis indicates that the CRP, ESR, and standard UA were powerful but imperfect tools with which to discriminate for UTI in potentially infected neonates. Hemocytometer WBC counts had the highest sensitivity, specificity, accuracy, and likelihood ratios for identifying very young infants with positive urine culture results. For all assessments, hemocytometer WBC counts were significantly different, compared with the standard urinalysis. ESR, CRP, and peripheral WBC counts were not helpful in identifying UTI in febrile infants. CONCLUSION: UTI had a prevalence of 13.6% in febrile infants <8 weeks of age. The CRP, ESR, and standard UA were imperfect tools in discriminating for UTI, and the sensitivity of these laboratory parameters was relatively low. Hemocytometer WBC count was a significantly better predictor of UTI in febrile infants.
Female↗
Comparison of bilevel positive airway pressure and volume ventilation via nasal or facial masks in patients with severe, stable COPD.
BACKGROUND: In the past decade, noninvasive positive pressure ventilation (NIPPV) has been successfully used in chronic obstructive pulmonary disease (COPD) with acute exacerbation. Nonetheless, its effect in stable COPD remains controversial. Theoretically, differences in the mode of ventilation such as pressure versus volume preset, or interfaces such as nasal versus full facial mask could have an impact on the efficacy of NIPPV. Few published studies have focused on this topic. METHODS: In this crossover study, bilevel positive airway pressure (BiPAP) for pressure preset ventilation or PLV-100 as a home-care volume preset ventilator was used via a nasal or facial mask in 12 patients with stable hypercapnic COPD. The four types (2 ventilators and 2 masks) of NIPPV were used for 20 minutes each, with a randomized sequence. The patient breathed spontaneously for 10 minutes before and between each type of NIPPV as a baseline for comparison. RESULTS: Respiratory rate, tidal volume, pulse rate, Borg scale and phase angle were all significantly improved during BiPAP ventilation via either a nasal or facial mask (p < 0.05 for all). Suppression of inspiratory muscle activity was obvious, although not statistically significant. In contrast, inspiratory muscle activity, phase angle and respiratory rate increased and tidal volume decreased significantly during PLV-100 ventilation with either nasal or facial masks (p < 0.05 for all). Peak expiratory flow rate and maximum inspiratory and expiratory mouth pressures remained unchanged after each type of NIPPV. CONCLUSIONS: For patients with stable hypercapnic COPD, short-term use of BiPAP via either a nasal or facial mask markedly rests the inspiratory muscles, improves the respiratory pattern and reduces the sense of dyspnea for patients. In contrast, short-term use of PLV-100 via either a nasal or facial mask worsens the above parameters.
Aged↗
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↗
The essential role of Saccharomyces cerevisiae CDC6 nucleotide-binding site in cell growth, DNA synthesis, and Orc1 association.
Saccharomyces cerevisiae Cdc6 is a protein required for the initiation of DNA replication. The biochemical function of the protein is unknown, but the primary sequence contains motifs characteristic of nucleotide-binding sites. To study the requirement of the nucleotide-binding site for the essential function of Cdc6, we have changed the conserved Lys114 at the nucleotide-binding site to five other amino acid residues. We have used these mutants to investigate in vivo roles of the conserved lysine in the growth rate of transformant cells and the complementation of cdc6 temperature-sensitive mutant cells. Our results suggest that replacement of Lys with Glu (K114E) and Pro (K114P) leads to loss-of-function in supporting cell growth, replacement of the Lys with Gln (K114Q) or Leu (K114L) yields partially functional proteins, and replacement with Arg yields a phenotype equivalent to wild-type, a silent mutation. To investigate what leads to the growth defects derived from the mutations at the nucleotide-binding site, we evaluated its gene functions in DNA replication by the assays of the plasmid stability and chromosomal DNA synthesis. Indeed, the K114P and K114E mutants showed the complete retraction of DNA synthesis. In order to test its effect on the G1/S transition of the cell cycle, we have carried out the temporal and spatial studies of yeast replication complex. To do this, yeast chromatin fractions from synchronized culture were prepared to detect the Mcm5 loading onto the chromatin in the presence of the wild-type Cdc6 or mutant cdc6(K114E) proteins. We found that cdc6(K114E) is defective in the association with chromatin and in the loading of Mcm5 onto chromatin origins. To further investigate the molecular mechanism of nucleotide-binding function, we have demonstrated that the Cdc6 protein associates with Orc1 in vitro and in vivo. Intriguingly, the interaction between Orc1 and Cdc6 is disrupted when the cdc6(K114E) protein is used. Our results suggest that a proper molecular interaction between Orc1 and Cdc6 depends on the functional ATP-binding of Cdc6, which may be a prerequisite step to assemble the operational replicative complex at the G1/S transition.
Adenosine Triphosphate↗
Comparison of invasive and noninvasive tests for detecting Helicobacter pylori infection in bleeding peptic ulcers.
BACKGROUND: Eradication of Helicobacter pylori infection has been shown to prevent recurrent bleeding from peptic ulcers. However, the detection rate for H pylori infection seems to be underestimated in this group of patients and has been scarcely investigated. METHODS: Eighty patients with bleeding peptic ulcer were studied for evidence of H pylori infection. Seventy-seven of these patients were enrolled as having H pylori infection after any one of the following 3 tests were positive: culture, histologic study, or any 2 of rapid urease test (CLO test), carbon 13-labeled urea breath test (UBT), and serologic examination. Fresh blood or blood-containing material in the gastric antrum was noted by panendoscopy in 22 patients (group A). In the remaining 55 cases there was no blood in the antrum (group B). RESULTS: The sensitivities of the CLO test, bacterial culture, histologic study, 13C-labeled UBT, and immunoglobulin G serologic test were 45.5%, 36.4%, 77.2%, 95.4%, and 100% in group A, respectively, and 70.9%, 40.0%, 70.9%, 92.7%, and 96.4%, respectively, in group B. There was a statistically significant difference between the sensitivities found for CLO test and 13C-labeled UBT (p < 0.05). Of these 5 tests, only the sensitivity of the CLO test showed a statistically significant difference between groups A and B (p < 0.05). A delayed positive CLO test result was recorded in 13 patients (3 in group A, 10 in group B). CONCLUSION: Noninvasive tests seemed to be more sensitive than invasive tests in detecting H pylori infection in patients with bleeding peptic ulcers. Blood in the antrum might reduce the sensitivity of the CLO test but have no effect on the other tests. The CLO test should be observed for more than 24 hours because of the possibility of a delayed positive result in some patients with bleeding peptic ulcers.
Adult↗
Expression of the cadherin-catenin complex in well-differentiated human thyroid neoplastic tissue.
E-cadherin is a member of the cadherin family that plays a major role in epithelial integrity and tumorigenesis. Catenins are a group of cytoplasmic proteins that regulate the intracellular anchorage of cadherin and are required for the linkage between cadherin and the actin cytoskeleton. Loss of E-cadherin contributes to the pathogenesis in tumor invasion and gives a poor prognosis. In order to investigate the adhesion property of intercellular junctions in thyroid tumors, expression of alpha-,beta, and gamma-catenin should also be studied. A correlation between these molecular markers and malignancy would be useful as a preoperative diagnostic test for thyroid neoplasms. The expression of E-cadherin, alpha-, beta-, and gamma-catenin were studied in normal and neoplastic thyroid tissue by immunofluorescence microscopy and Western blot analysis. In the normal thyroid and in nodular goiter, and follicular adenoma, staining for E-cadherin, alpha-, beta-, and gamma-catenin was seen mainly at the lateral surface of epithelial cells in the follicle and the presence of these molecules was confirmed by Western blot analysis. Follicular carcinoma tissue stained positive for E-cadherin and alpha-catenin, but the results of beta- and gamma-catenin immunostaining were highly variable, with beta-catenin being absent in most follicular carcinomas (8/10) and gamma-catenin being absent in some follicular carcinomas (3/10). These results suggest that E-cadherin expression was not reduced during the pathogenesis of differentiated thyroid malignancies. Impairment of the cadherin-catenin complex at the cell junction may contribute to the malignant progression of differentiated thyroid neoplastic tissue.
Adult↗
Sagittal craniosynostosis outcome assessment for two methods and timings of intervention.
A retrospective quantitative analysis of 40 infants who underwent surgery for sagittal craniosynostosis was conducted to determine whether any difference in outcome, with respect to cranial index (cranial width/cranial length x 100), could be associated with either the age at surgery or the extent of the operation. Children < or = 13 months old at surgery and for whom there were archived computed tomography digital data preoperatively, perioperatively, and 1 year postoperatively were studied. For statistical analysis, the operation was classified as either extended strip craniectomy or subtotal calvarectomy, and the age at operation was either < or = 4 months or > 4 months. Twenty-eight patients underwent extended strip craniectomy at a mean age of 5.1 months. Their mean cranial index preoperatively was 67 versus 71 at 1 year postoperatively (p < 0.0001). Of extended strip craniectomy patients, 15 were operated on at age < or = 4 months (mean = 2.9 months) and 13 at age > 4 months (mean = 7.6 months). Mean cranial indices for age at operation groups did not achieve age-appropriate normal range values 1 year postoperatively for either group, and there was no significant difference between the mean percentages of improvement achieved (p = 0.143). Twelve patients underwent subtotal calvarectomy at a mean age of 5.2 months. Their mean cranial index preoperatively was 66 versus 74 at 1 year postoperatively (p < 0.0001). The mean cranial index in this group reached age-appropriate normal range values 1 year postoperatively. The percentage improvement in cranial index 1 year after subtotal calvarectomy was greater than after extended strip craniectomy (p = 0.003). Extended strip craniectomy for sagittal craniosynostosis does not achieve normal cranial width:length proportions, even when performed before 4 months of age. Subtotal calvarectomy for sagittal craniosynostosis does achieve normal cranial width:length proportions in the majority of the children, at least when performed within the first 13 months of life.
Craniosynostoses↗
Identification and characterization of a novel Ibe10 binding protein that contributes to Escherichia coli invasion of brain microvascular endothelial cells.
The molecular basis of Escherichia coli traversal of the blood-brain barrier in the development of E. coli meningitis is not well understood. We have previously shown that a novel Ibe10 protein found in cerebrospinal fluid isolates of E. coli is necessary for invasion of the brain microvascular endothelial cells (BMEC) that constitute the blood-brain barrier both in vitro and in a newborn rat model of hematogenous meningitis. Here we identified a novel Ibe10 binding molecule/receptor (Ibe10R) on both bovine BMEC (HBMEC) and human BMEC (HBMEC) that is responsible for invasion by E. coli. Ibe10R, an approximately 55-kDa protein, was purified from BBMEC by Ibe10-Ni-Sepharose affinity chromatography. Bovine Ibe10R, as well as polyclonal antibodies to Ibe10R, blocked E. coli invasion of BBMEC very effectively. The N-terminal amino acid sequence of Ibe10R showed 75% homology to serum albumin. However, the amino acid sequence of an Ibe10R fragment generated by limited enzymatic digestion did not reveal homology to any other proteins, suggesting that Ibe10R represents a novel albumin-like protein. Immunocytochemical analysis of BBMEC using anti-Ibe10R antibody suggested that only a subset of cultured BBMEC express Ibe10R on their surface. Enrichment of Ibe10R-positive BBMEC by fluorescence-activated cell sorting with anti-Ibe10R antibody resulted in enhanced invasion by E. coli. The anti-Ibe10R antibody raised against bovine Ibe10R also blocked E. coli invasion of HBMEC very effectively. Interestingly, anti-Ibe10R antibody affinity chromatography of HBMEC membrane proteins revealed a smaller protein with an approximate molecular mass of 45 kDa. These results suggest that the Ibe10 of E. coli interacts with a novel BMEC surface protein, Ibe10R, for invasion of both BBMEC and HBMEC.
Animals↗
Identification and characterization of an Escherichia coli invasion gene locus, ibeB, required for penetration of brain microvascular endothelial cells.
Escherichia coli K1 is the most common gram-negative organism causing neonatal meningitis, but the mechanism by which E. coli K1 crosses the blood-brain barrier is incompletely understood. We have previously described the cloning and molecular characterization of a determinant, ibeA (also called ibe10), from the chromosome of an invasive cerebrospinal fluid isolate of E. coli K1 strain RS218 (O18:K1:H7). Here we report the identification of another chromosomal locus, ibeB, which allows RS218 to invade brain microvascular endothelial cells (BMEC). The noninvasive TnphoA mutant 7A-33 exhibited <1% the invasive ability of the parent strain in vitro in BMEC and was significantly less invasive in the central nervous system in the newborn rat model of hematogenous E. coli meningitis than the parent strain. The TnphoA insert with flanking sequences was cloned and sequenced. A 1,383-nucleotide open reading frame (ORF) encoding a 50-kDa protein was identified and termed ibeB. This ORF was found to be 97% identical to a gene encoding a 50-kDa hypothetical protein (p77211) and located in the 13-min region of the E. coli K-12 genome. However, no homology was observed between ibeB and other known invasion genes when DNA and protein databases in GenBank were searched. Like the TnphoA insertion mutant 7A-33, an isogenic ibeB deletion mutant (IB7D5) was unable to invade BMEC. A 7. 0-kb locus containing ibeB was isolated from a LambdaGEM-12 genomic library of E. coli RS218 and subcloned into a pBluescript KS vector (pKS7-7B). pKS7-7B was capable of completely restoring the BMEC invasion of the noninvasive TnphoA mutant 7A-33 and the ibeB deletion mutant IB7D5 to the level of the parent strain. More importantly, the ibeB deletion mutant IB7D5 was fully complemented by pFN476 carrying the ibeB ORF (pFN7C), indicating that ibeB is required for E. coli K1 invasion of BMEC. Taken together, these findings indicate that several E. coli determinants, including ibeA and ibeB, contribute to crossing of the blood-brain barrier.
Amino Acid Sequence↗
The gene locus yijP contributes to Escherichia coli K1 invasion of brain microvascular endothelial cells.
Most cases of Escherichia coli meningitis develop as a result of hematogenous spread, but it is not clear how circulating E. coli crosses the blood-brain barrier. A TnphoA mutant of E. coli K1 RS218 was shown to be significantly less invasive than its parent strain in bovine and human brain microvascular endothelial cells (BMEC), which constitute the blood-brain barrier. More importantly, traversal of the blood-brain barrier was significantly less with this mutant than with the parent strain in newborn rats with experimental hematogenous meningitis. A DNA segment containing the TnphoA insertion site was cloned from RS218, and the cloned DNA complemented the TnphoA mutant in invasion of BMEC. Nucleotide sequence revealed a near identity to that of a hypothetical yijP gene (also called f577) in the E. coli K-12 genome. Sequence analysis indicated that the E. coli K1 yijP gene likely encodes a 66. 6-kDa membrane protein. Deletion and complementation experiments indicated that the yijP gene was involved in E. coli K1 invasion of BMEC, i.e., the invasive ability of E. coli K1 was significantly reduced after yijP was deleted and was restored by complementation with a plasmid containing the yijP open reading frame. This is the first demonstration that the yijP gene locus plays a role in the pathogenesis of E. coli K1 meningitis.
Animals↗
A case of extraadrenal pheochromocytoma associated with adrenal cortical nodular hyperplasia and papillary thyroid carcinoma.
A 64-year-old woman was admitted in November, 1996 for fluctuating blood pressure. There was multinodular goiter in her neck. High urine VMA and serum aldosterone were noted. Computed tomography showed an oval lesion in the left adrenal gland. Left adrenalectomy was performed and the pathology was proved to be adrenal cortical nodular hyperplasia. Fluctuating blood pressure and high urine VMA persisted after the operation. CT scan of the abdomen revealed a soft tissue mass in lower abdomen. The patient was admitted again in September, 1997. Laboratory examinations showed normal serum aldosterone, normal plasma renin activity and high urine VMA. Aspiration cytology of the thyroid gland disclosed papillary thyroid carcinoma. [131I]-metaiodobenzylguanidine image revealed a high uptake lesion in the right L-3 paravertebral area. Tumor excision and thyroidectomy were performed. The pathology was reported as extraadrenal pheochromocytoma and papillary thyroid carcinoma. Papillary thyroid carcinoma is rarely associated with pheochromocytoma. To our knowledge, this paper is the first report of a patient with extraadrenal pheochromocytoma associated with papillary thyroid carcinoma and adrenal cortical nodular hyperplasia.
Adrenal Cortex↗
Combination of color Doppler ultrasonography and ultrasound-guided fine-needle aspiration cytology for localization of parathyroid lesions.
We examined the usefulness of color Doppler ultrasonography combined with ultrasound-guided fine-needle aspiration cytology (FNAC) for preoperative localization of parathyroid lesions in patients with hyperparathyroidism. Twenty-eight patients (19 men, 9 women; mean age, 56 years) with clinical and laboratory evidence of hyperparathyroidism underwent preoperative color Doppler ultrasonography and ultrasound-guided FNAC prior to surgery. On ultrasonography, the parathyroid lesions were anechoic or hypoechoic, located behind or at the margin of the thyroid gland, and mimicked blood vessels in some cases. On color Doppler ultrasound, parathyroid lesions showed little or no vascularity. They were easily differentiated from blood vessels, thus improving the safety of ultrasound-guided FNAC. Thirty-four (76%) of 45 surgically confirmed parathyroid lesions were detected with ultrasonography in 21 (75%) of the patients. There was no significant difference in the detection rates of lesions in the right upper, right lower, left upper, and left lower parathyroid glands. Eight (29%) patients had coexisting thyroid lesions. FNAC of the ultrasound-detected abnormalities provided preoperative confirmation that they were parathyroid lesions. In conclusion, our findings show that color Doppler ultrasonogrphy in combination with ultrasound-guided FNAC is useful for preoperative localization of parathyroid lesions.
Biopsy, Needle↗
Ankle arthrodesis: internal non-compression arthrodesis versus internal compression arthrodesis.
Ankle arthrodesis is still considered to be the standard treatment for most disabling types of ankle arthritis, but fusion methods are varied. We report our experience of ankle arthrodesis and compare a group of 34 cases treated by Blair's non-compression arthrodesis to another group of 32 cases treated by internal compression arthrodesis using two crossed screws. The same surgeon performed all the operations. The Blair's non-compression arthrodesis group included 21 males and 13 females with an average age of 42 y/o (range 18-70 y/o) and an average follow up period of 38.6 months (range 26-62 months). The union rate was 91.2% and the average union time was 5.6 months (range 2-10 months). There were three cases of non-union. The cross-screw compression arthrodesis group included 20 males and 12 females with an average age of 45 y/o (range 20-86 y/o) and an average follow up period of 38.3 months (range 15-81 months). The union rate was 96.9% and the average union time was 2.7 months (range 1.5-4.4 months). There was one case of non-union. We conclude that our cross-screws compression arthrodesis with its shorter fusion time was found to be superior to the Blair's non-compression arthrodesis.
Adult↗
De novo RET proto-oncogene mutation in a patient with multiple endocrine neoplasia type 2B.
We report a case of multiple endocrine neoplasia type 2B (MEN 2B) with de novo RET proto-oncogene mutation. The patient, a 23-year-old Taiwanese woman, was admitted for treatment of recurrent medullary thyroid cancer (MTC) 7 years after a total thyroidectomy. Mucosal neuromas and marfanoid appearance were also noted. Because MEN 2B was suspected, the patient and her family members underwent genetic analysis. A heterozygous germline mutation at codon 918 (ATG-->ACG) of the proto-oncogene RET was detected in the patient. This mutation was considered de novo, as it was not detected in either of her parents or her siblings. The patient underwent surgery for removal of the recurrent tumor. Although no pheochromocytoma was noted, regular follow-up is necessary because of persistent hypercalcitoninemia.
Adult↗
Distribution of the cadherin-catenin complex in normal human thyroid epithelium and a thyroid carcinoma cell line.
E-cadherin is the major cell-cell adhesion molecule expressed by epithelial cells. Cadherins form a complex with three cytoplasmic proteins, alpha-, beta-, and gamma-catenin, and the interaction between them is crucial for anchoring the actin cytoskeleton to the intercellular adherens junctions. The invasive behavior of cancer cells has been attributed to a dysfunction of these molecules. In this study, we examined the distribution of the cadherin-catenin complex in a Chinese human thyroid cancer cell line, CGTH W-2, compared with that in normal human thyroid epithelial cells. In the normal cells, using immunofluorescence staining, E-cadherin and alpha-, beta-, and gammm-catenin were found to be localized at the intercellular junction and appeared as 135, 102, 90, and 80 kD proteins on Western blots. In CGTH W-2 cells, no E-cadherin and gamma-catenin immunoreactivity was detected by immunofluorescence or Western blotting; alpha- and beta-catenin were detected as 102 and 90 kD proteins on blots but gave a diffuse cytoplasmic immunofluorescence staining pattern in most cells, while beta-catenin was also distributed throughout the cytoplasm in most cells but was found at the cell junction in some, where it colocalized with alpha-actinin. The present data indicate that the loss of cell adhesiveness in these cancer cells may be due to incomplete assembly of the cadherin-catenin complex at the cell junction. However, this defect did not affect the linkage of actin bundles to vinculin-enriched intercellular junctions.
Actinin↗