Biomedical subjects

Shiu-Feng Huang

Publications and source records attributed to Shiu-Feng Huang.

At least 19 recordsLinked to original sources

PubMed2005

High-frequency Alu-mediated genomic recombination/deletion within the caspase-activated DNase gene in human hepatoma.

The Alu repetitive elements, which constitute 10% of human genome, may serve as bridges for genomic recombination. However, their roles in tumorigenesis remain to be elucidated. Caspase-activated DNase (CAD), whose gene (hCAD) is mapped at chromosome 1p36, a region frequently displaying hemizygote deletion in many human cancers, is the key enzyme for nucleosome fragmentation during apoptosis. Recently, we detected many aberrant mRNAs for hCAD in many human hepatoma cells. To elucidate the genetic basis leading to the mRNA aberration, we used PCR-based chromosome walking to clone the corresponding genomic DNA identifying a novel Alu/Alu homologous recombination/deletion within hCAD in HepG2 and Hep3B cells. We then detected similar recombination events in 13 out of the 20 hepatoma tissues and in eight of the para-cancerous cirrhotic livers. The recombination was inclined to occur in males (P=0.031) and had marginal association with high-grade hepatoma (P=0.070) and tumor recurrence (P=0.070). The recombination caused exon-3 deletion, which in turn led to exon-3 skipping or replacement with a partial Alu-sequence, and consequential C-truncation of CAD. Our findings of high frequency of Alu-mediated hCAD deletion in human hepatoma not only underscore the implication of hCAD in hepatocarcinogenesis, but also highlight the potential roles of human repetitive sequences in mediating genome instability in human cancers.

Alu Elements↗

PubMed2005

Type II collagen gene variants and inherited osteonecrosis of the femoral head.

BACKGROUND: Avascular necrosis of the femoral head (ANFH) causes disability that often requires surgical intervention. Most cases of ANFH are sporadic, but we identified three families in which there was autosomal dominant inheritance of the disease and mapped the chromosomal position of the gene to 12q13. METHODS: We carried out haplotype analysis in the families, selected candidate genes from the critical interval for ANFH on 12q13, and sequenced the promoter and exonic regions of the type II collagen gene (COL2A1) from persons with inherited and sporadic forms of ANFH. RESULTS: We identified a G-->A transition in exon 50 of COL2A1 in affected members of a four-generation family with ANFH. This transition predicts the replacement of glycine with serine at codon 1170 in a GXY repeat of type II collagen. Another pedigree was shown to harbor the same transition, but the mutant allele occurred on a different haplotype background. In a third family, a G-->A transition in exon 33 of the gene, causing a glycine-to-serine change at codon 717, was detected. No mutation was found in the COL2A1 coding region in sporadic cases of ANFH. CONCLUSIONS: All the patients with familial ANFH whom we studied carried COL2A1 mutations. In families with ANFH, haplotype and sequence analysis of the COL2A1 gene can be used to identify carriers of the mutant allele before the onset of clinical symptoms, allowing the initiation of measures that may delay progression of the disease.

Adult↗

PubMed2005

Novel prognostic value of nuclear epidermal growth factor receptor in breast cancer.

Epidermal growth factor receptor (EGFR) has been detected in the nucleus of cancer cells and primary tumors for decades. While localized in the nucleus, EGFR functions as a transcriptional regulator resulting in the activation of the cyclin D1 gene. Despite nuclear accumulation of EGFR is linked to increased DNA synthesis and proliferative potential, the pathological significance of nuclear EGFR, however, remains uninvestigated. Furthermore, expression of EGFR has not provided a consistent predictive value for survival of breast cancer patients. Here, we analyzed 130 breast carcinomas via immunohistochemical analyses for the levels of nuclear and non-nuclear EGFR. We found 37.7% of the cohort immunostained positively for nuclear EGFR and 6.9% with high levels of expression. Importantly, Kaplan-Meier survival analysis and log-rank test revealed a significant inverse correlation between high nuclear EGFR and overall survival (P = 0.009). Expression of nuclear EGFR correlated positively with increased levels of cyclin D1 and Ki-67, both are indicators for cell proliferation. In contrast, expression of non-nuclear EGFR did not significantly correlate with those of cyclin D1 and Ki-67 or the overall survival rate. In addition, we analyzed 37 oral squamous carcinomas for EGFR expression and found 24.3% of the cases to contain moderate/high levels of nuclear EGFR. Taken together, our findings indicate pathological significance of nuclear EGFR and may have important clinical implication.

Breast Neoplasms↗

PubMed2005

Intrahepatic cholangiocarcinoma escapes from growth inhibitory effect of transforming growth factor-beta1 by overexpression of cyclin D1.

Transforming growth factor-beta1 (TGF-beta1) is involved in tumor progression by promoting angiogenesis or suppressing the immune system; yet TGF-beta1 also has a growth-inhibitory effect on epithelial cells including carcinoma cells. Several mechanisms of impaired TGF-beta1 responsiveness of carcinoma cells have been reported. In this study, we examined how TGF-beta1 participates in the development and progression of intrahepatic cholangiocarcinoma (ICC) associated with hepatolithiasis, and how ICC cells escape from growth inhibitory effect of TGF-beta1. A total of 40 cases of hepatolithiasis were studied, including 16 cases of ICC, and in vitro studies were conducted with cultured murine non-neoplastic biliary epithelial cells (MBEC) and three ICC cell lines. Immunohistochemically, TGF-beta1 was expressed in mononuclear cells and mesenchymal cells around the stone-containing bile ducts and invasive ICC, and also in biliary epithelial cells (hyperplastic and precursor lesions, and ICC). TGF-beta type II receptor (TbetaR-II) was constantly expressed on biliary epithelial cells irrespective of biliary lesions. In cell culture studies, TGF-beta1 significantly inhibited proliferation of MBEC via downregulation of cyclin D1, cdk4, and cdk6, while TGF-beta1 did not influence the proliferation of ICC cells. After suppression of cyclin D1 expression in one ICC cell line using cyclin D1 small interfering RNA, TGF-beta1 significantly inhibited the proliferation of ICC cells. In conclusion, high levels of TGF-beta1 around ICC or its precursors may be involved in development and progression of ICC in hepatolithiasis. ICC cells could escape the growth inhibitory effect of TGF-beta1 by overexpression of cyclin D1.

Cell Division↗

PubMed2004

High frequency of epidermal growth factor receptor mutations with complex patterns in non-small cell lung cancers related to gefitinib responsiveness in Taiwan.

PURPOSE: Epidermal growth factor receptor (EGFR) mutations related to gefitinib responsiveness in non-small cell lung cancer have been found recently. Detection of EGFR mutations has become an important issue for therapeutic decision-making in non-small cell lung cancer. EXPERIMENTAL DESIGN: Mutational analysis of the kinase domain of EGFR coding sequence was done on 101 fresh frozen tumor tissues from patients without prior gefitinib treatment and 16 paraffin-embedded tumor tissues from patients treated with gefitinib. Detection of phosphorylated EGFR by immunoblot was also done on frozen tumor tissues. RESULTS: The 101 non-small cell lung cancer tumor specimens include 69 adenocarcinomas, 24 squamous cell carcinomas, and 8 other types of non-small cell lung cancers. Mutation(s) in the kinase domain (exon 18 to exon 21) of the EGFR gene were identified in 39 patients. All of the mutations occurred in adenocarcinoma, except one that was in an adenosquamous carcinoma. The mutation rate in adenocarcinoma was 55% (38 of 69). For the 16 patients treated with gefitinib, 7 of the 9 responders had EGFR mutations, and only 1 of the 7 nonresponders had mutations, which included a nonsense mutation. The mutations seem to be complex in that altogether 23 different mutations were observed, and 9 tumors carried 2 mutations. CONCLUSIONS: Data from our study would predict a higher gefitinib response rate in lung adenocarcinoma patients in Chinese and, possibly, other East Asian populations. The tight association with adenocarcinoma and the high frequency of mutations raise the possibility that EGFR mutations play an important role in the tumorigenesis of adenocarcinoma of lung, especially in East Asians.

Adenocarcinoma↗

PubMed2004

Evaluation of prognosis for malignant rectal gastrointestinal stromal tumor by clinical parameters and immunohistochemical staining.

PURPOSE: The aim of this study was to identify associated prognostic factors influencing the outcome of curative resection of rectal gastrointestinal stromal tumor. PATIENTS AND METHODS: Diagnostic immunohistochemical staining with CD34, CD117, S-100, desmin, and muscle-specific actin was performed in 46 consecutive patients with previously diagnosed rectal leiomyosarcoma who underwent curative resection from 1979 to 1999. CD44, Bcl-2, P53, and Ki-67 staining were performed on tumors rediagnosed as gastrointestinal stromal tumor for the prognostic evaluation. RESULTS: There were 42 (91.3 percent) patients with rectal gastrointestinal stromal tumor (18 females and 24 males; mean age, 58.4 years). Twenty-nine patients underwent radical surgical resections, such as abdominoperineal resection or low anterior resection, whereas the other 13 patients underwent wide local excision, such as transrectal excision or Kraske's operation. Sixteen tumors were classified as high-grade gastrointestinal stromal tumors, and 26 as low-grade. No tumor had a positive P53 stain. Twenty-seven patients (64.3 percent) developed recurrence or metastasis postoperatively (median follow-up, 52 months). The one-year, two-year, and five-year disease-free survival rates were 90.2 percent, 76.7 percent, and 43.9 percent, respectively. Of these patients with recurrence, subsequent resections in 12 patients with local recurrence, transarterial tumor embolism or STI-571 chemotherapies in 3 patients with distant mestastases were performed. The one-year, two-year, and five-year overall survival rates were 97.4 percent, 94.3 percent, and 83.7 percent, respectively. Bcl-2 (P = 0.007) and histologic grade (P = 0.05) in disease-free survival analysis and age < 50 years (P = 0.03) and tumor size > 5 cm (P = 0.02) in overall survival analysis were independent prognostic factors. The group with wide local excision had a higher local recurrence rate than that of the radical resection group (77 percent vs. 31 percent, P = 0.006), despite smaller tumors (4.5 vs. 7.2 cm, P = 0.05). There was no difference in the incidence of distant metastasis between the two groups. CONCLUSION: Younger age (< 50 years), higher histologic tumor grade, positive Bcl-2 status, and larger tumors (> 5 cm) were factors associated with significantly poorer prognoses for rectal gastrointestinal stromal tumor. Radical resection was superior to wide local excision in the prevention of local recurrence, but not that of distant metastases.

Adult↗

PubMed2004

Correlation of MYCN amplification with MCM7 protein expression in neuroblastomas: a chromogenic in situ hybridization study in paraffin sections.

Amplification of the MYCN oncogene in neuroblastomas is generally associated with a more aggressive clinical course. Recently, 1 of the minichromosome maintenance proteins, MCM7, was found to be a direct target of the MYCN transcription factor in neuroblastoma. To confirm this correlation, chromogenic in situ hybridization (CISH) to detect MYCN amplification and immunohistochemical staining for MCM7 protein expression were performed on paraffin tissue sections of 26 neuroblastomas cases and of 4 recurrences of these tumors. Seven of the primary tumors showed MYCN amplification, and all were stage 3 or 4 tumors. Only 4 of these showed MCM7 overexpression. However, 11 primary tumors overexpressed MCM7. The 4 patients with MCM7 expression associated with MYCN amplification all died from the tumor. In contrast, the 7 patients with MCM7 overexpression but no MYCN amplification were all younger than 1 year of age and have shown good survival. This suggests that MCM7 overexpression by itself is not related to a poorer prognosis as is MYCN amplification. In addition, the 4 pairs of primary and recurrent tumors all showed changes in MCM7 expression from negative to positive, whereas none of them had MYCN amplification. This study showed that MCM7 overexpression is not necessarily correlated with MYCN amplification or an aggressive clinical course. Interpretation of the results of CISH was quite easy and straightforward because the preparations were viewed with an ordinary light microscope with good preservation of the tissue morphology.

Adolescent↗

PubMed2004

Frequent p16ink4a inactivation is an early and frequent event of intraductal papillary neoplasm of the liver arising in hepatolithiasis.

Intraductal papillary neoplasm of the liver (IPNL) is a precursor lesion of intrahepatic cholangiocarcinoma (ICC) arising in hepatolithiasis. In this study, 98 foci of IPNL identified in 39 surgically resected hepatolithiatic livers were investigated for expression of p16INK4a, cyclin D1, p21WAF1/CIP1, p53, mouse double-minute 2 (MDM2), and pRb. In addition, methylation-specific polymerase chain reaction (MSP) for p16 INK4a promoter region was performed in these foci. Nonneoplastic bile ducts from 11 hepatolithiatic livers, 5 histologically normal livers, and 9 cases of nonpapillary conventional ICC were used as controls. Decreased expression of p16INK4A was seen in IPNL group 1 with mild dysplasia and continued along the progression of IPNL to ICC. The expression of cyclin D1, p21WAF1/CIP1,and pRb gradually increased along the progression of IPNL to ICC and became significantly high in IPNL of group 3 (carcinoma in situ). The expression of p53 and MDM2 was increased in IPNL group 3 and group 4 with evident invasive carcinoma. MSP revealed that 54.6% of 44 IPNL foci harbored p16INK4a promoter hypermethylation, and such foci were significantly correlated with decreased expression of p16INK4a protein. Ki-67 labeling index exhibited a stepwise increase from IPNL group 1 to group 4. We conclude that p16INK4a inactivation, due mainly to its promoter hypermethylation, is a frequent and early event of IPNL and may be responsible for genetic and epigenetic alterations of other cell cycle regulators in IPNL.

Adenoma, Bile Duct↗

PubMed2004

Thalidomide salvages lethal hepatic necroinflammation and accelerates recovery from cirrhosis in rats.

BACKGROUND/AIMS: The authors investigated the feasibility of thalidomide employed to treat liver fibrosis. METHODS: A cirrhotic model was established using Sprague-Dawley rats fed thioacetamide. Thalidomide-treated group was given thalidomide (10mg/kg/day) intraperitoneally for 10 consecutive days. Mortality, histopathological changes, TNFalpha, TGFbeta1, TIMP-1 and TIMP-2 were determined. Expression of TNFalpha and TGFbeta1 mRNA of Kupffer's cells derived from the experimental rats were determined. RESULTS: The mortality rates of thalidomide-treated group and vehicle-treated group were 8 and 32%, respectively. The total Knodell score of thalidomide-treated rats was lower than those of vehicle-treated rats. Micro-nodular cirrhosis resolved grossly in thalidomide-treated rats on day 28; while vehicle-treated rats continued to display uneven liver surface on day 28. Expression of TNFalpha, TGFbeta1, TIMP-1, and TIMP-2 was decreased in thalidomide-treated rats compared to those treated with vehicles. Finally, the expression of TNFalpha and TGFbeta1 mRNA of Kupffer's cells derived from rats treated with thalidomide were much lower than those treated with vehicle. CONCLUSIONS: Thalidomide salvages lethal hepatic necroinflammation, accelerates recovery from cirrhosis in rats, and works by suppressing of TNFalpha and TGFbeta1 production of Kupffer's cells.

Animals↗

PubMed2004

Ultrasound biomicroscopy in pigmented conjunctival cystic nevi.

PURPOSE: To report the use of ultrasound biomicroscopy in the clinical diagnosis and management of pigmented conjunctival cystic nevi. METHOD: Two patients, aged 11 and 18 years, with rapidly growing raised conjunctival melanocytic lesions suspected to be inflamed juvenile conjunctival nevus underwent ultrasound biomicroscopic and histopathologic examinations. RESULTS: Ultrasound biomicroscopic examination of the lesions revealed multiple areas of cystic tissue, which is compatible with pathologic finding of compound nevus with epithelial inclusion cysts formation. Furthermore, clear interface was found between the mass and the underlying sclera. CONCLUSION: Pigmented conjunctival nevi may obscure cysts under slit-lamp examination. Ultrasound biomicroscopy is a useful diagnostic adjunct to distinguish cysts in conjunctival lesions. Additionally, this technique may be helpful in delineating the extent of lesions prior to excision biopsy.

Child↗

PubMed2004

Adjunctive treatment with interferon alpha-2b may decrease the risk of papilloma-associated conjunctival intraepithelial neoplasm recurrence.

PURPOSE: To report a case of bilateral papilloma virus-positive conjunctival intraepithelial neoplasm and the treatment results of using adjunctive interferon alpha-2b. METHODS: Case report and literature review. RESULTS: A 73-year-old man underwent subtotal excisional biopsy of the 270-degree gelatinous limbal lesion of the right eye to avoid creating a limbal deficiency and cicatricial change. Total excisional biopsy of the temporal elevated leukoplakic limbal lesion was performed on his left eye. Histology examination showed bilateral intraepithelial neoplasia, and human papilloma virus-16 and -18 were detected by polymerase chain reaction in both lesions. Two supplemental perilesional injections of interferon alpha-2b in the right eye were given, and the residual mass decreased in size gradually and completed clinical resolution 7 weeks following initial surgery. Although no recurrence was noticed in the right eye, recurrence of the conjunctival intraepithelial neoplasm lesion was noticed in the left eye. CONCLUSION: Adjunctive therapy might lower CIN recurrence rate, especially in extensive lesions, when surgical excision cannot ensure a tumor-free margin. Our bilateral case provided a good control example for the recurrence with or without adjunctive therapy.

Aged↗

PubMed2004

Severe intrahepatic cholestasis in an elderly patient with primary amyloidosis and colon adenocarcinoma.

Hepatic involvement in primary amyloidosis (AL type) is not rare but is often clinically silent. However, presentation with jaundice in AL-type amyloidosis is rare, with an incidence of less than 5% reported in the literature. It is considered to be a preterminal sign. We herein report on a case of primary hepatic amyloidosis presenting with severe intrahepatic cholestasis. Viral, drug, alcohol, and autoimmune etiologies were all excluded. A liver biopsy was performed because of unexplained cholestatic jaundice for 3 months. The pathology showed hepatic amyloidosis with extensive amyloid deposition in the expanded portal tracts and sinusoidal space. The patient received supportive treatment only, because of persistent jaundice, coexistent colon cancer with para-aortic lymph node metastasis, and possibly peritoneal carcinomatosis. Unfortunately, the patient died of sepsis 10 months after the onset of jaundice. We suggest that hepatic amyloidosis must be considered in the differential diagnosis of unexplained cholestatic jaundice.

Adenocarcinoma↗

PubMed2004

Pulmonary lymphangioleiomyomatosis: a clinicopathological analysis of ten cases.

BACKGROUND: Lymphangioleiomyomatosis (LAM) of the lung is a very rare disease of unknown etiology which occurs particularly in women of childbearing age. So far, there have been very few reports of LAM in Taiwan. METHODS: Data on all patients with a clinical or pathological diagnosis of LAM in Chang Gung Memorial Hospital from 1990 to 2001 were collected from the pathology files or by consultation with thoracic surgeons, chest physicians, and radiologists of this institution. Cases were confirmed by lung biopsy and high-resolution computed tomographic scanning. Clinical data were obtained from patients' charts. Additional immunostaining for HMB-45 antigen, estrogen receptor, and progesterone receptor was carried out for cases with available paraffin blocks. RESULTS: In total, 10 patients confirmed with a diagnosis of LAM and adequate clinical follow-up information were found from 1991 to 2001. All were females of fertility age. The follow-up periods ranged from 18 to 167 months. Six patients received hormonal therapy. According to the pulmonary function tests and clinical symptoms, 6 patients were in stable condition and 4 showed slow progression of disease by the time of the last follow-up. Two patients died after lung transplantation and abdominal surgery for retroperitoneal LAM, respectively, at another medical center. CONCLUSIONS: The clinicopathological features of our series are similar to those reported from other countries. The clinical course was slowly progressive with no significant response to hormonal therapy. Lung biopsies are important for a diagnosis, but the size and location of the biopsy specimens greatly affect the diagnostic reliability.

Adult↗

PubMed2004

Infantile-onset glycogen storage disease type II (Pompe disease): report of a case with genetic diagnosis and pathological findings.

Glycogen storage disease type II (GSD-II), also known as Pompe disease, is a rare autosomial recessive disease due to deficiency of lysosomal acid alpha-glucosidase (GAA). The infantile-onset form is the most severe, and most patients present with hypotonia and cardiomyopathy in early infancy. We report on a typical case of Pompe disease in a patient who died at 8 months of age due to aspiration pneumonia and hypertrophic cardiomyopathy. Genetic studies showed deficient GAA activity and mutation of the GAA gene with Gly615Arg (exon 13, G1845A). On autopsy, glycogen had markedly accumulated in the liver, myocardium and skeletal muscle. The neurons of the anterior horn of the spinal cord and medulla were also involved, but the cortex was spared. These neurological-histologic findings may explain the clinical features of poor motor function, decreased deep tendon reflexes and lack of mental retardation.

Base Sequence↗

PubMed2003

Interleukin-6 acts as an antiapoptotic factor in human esophageal carcinoma cells through the activation of both STAT3 and mitogen-activated protein kinase pathways.

The production of interleukin-6 (IL-6) has been discovered in a variety of human tumors. Here we report the expression of IL-6, IL-6 receptor alpha (IL-6Ralpha), and gp130 in human esophageal carcinoma tissues. We further demonstrate that IL-6 protects an esophageal carcinoma cell line CE48T/VGH from apoptosis induced by staurosporine. IL-6 stimulation induced a rapid phosphorylation of gp130 and STAT3, and a dominant-negative STAT3 completely abolished the antiapoptotic effect. IL-6 also activated ERK 1/2 in CE48T/VGH cells. Inhibition of the ERK activation by PD98059 and transfection of a dominant-negative ERK2 completely blocked the protection of IL-6 against apoptosis. Thus, both STAT and MAP kinase pathways are responsible for the IL-6-delivered survival signal in human esophageal carcinoma cells. In contrast, PI3-K inhibitors only partially attenuated the effect of IL-6, suggesting that PI3-K does not play a major role in the antiapoptotic signal of IL-6 in our system. To investigate whether IL-6 could induce the production of antiapoptotic molecules, proteins of the Bcl-2 family were measured. While Bcl-2, Bcl-x(L,), and Bax were not affected, Mcl-1 was induced by IL-6 in human esophageal carcinoma cells. Our results suggest that IL-6 may contribute to the progression of esophageal cancers in an autocrine or paracrine manner.

Apoptosis↗

PubMed2003

Novel point mutations in complete androgen insensitivity syndrome with incomplete müllerian regression: two Taiwanese patients.

UNLABELLED: Complete androgen insensitivity syndrome (CAIS) is a relatively rare X-linked disorder caused by androgen receptor gene (AR) mutations that result in complete impairment of genital virilisation. In these individuals, no müllerian derivatives are usually found; however, several sporadic cases of CAIS with müllerian remnants have been reported. In this paper, we report two novel point mutations of the AR gene resulting in two cases of CAIS with incomplete müllerian regression. Molecular studies of cases 1 and 2 showed novel missense mutations of the AR gene, with a methionine to threonine substitution at codon 749 (base 2608 T-->C) in exon 5 and a methionine to lysine substitution at codon 787 (base 2722 T-->A) in exon 6. Both patients received bilateral gonadectomy and inguinal hernia repair. The excised gonads proved to be testes with incomplete regression of the müllerian structures. CONCLUSION: Müllerian structures can be present in androgen insensitivity syndrome and the presence of a uterus therefore does not exclude this disorder. Further study of these patients may promote a better understanding of the pathogenesis.

Androgen-Insensitivity Syndrome↗

PubMed2003

Antisense overexpression of BMAL2 enhances cell proliferation.

To identify genes that are frequently downregulated in hepatocellular carcinoma (HCC), a panel of putative underexpressed genes was first established by an in-house cDNA macroarray method. Two different assays, semiquantitative RT-PCR combined with Northern analysis and customized cDNA microarray analysis, were used to screen through these genes and the results were compared. Several genes, some with unknown function, were confirmed to be downregulated by both the methods. The effect of a downregulated gene, BMAL2, on cell proliferation was examined. Overexpression of antisense BMAL2 RNA in 293EBNA cells resulted in reduced cell cycle time, increased plating efficiency in soft agar, diminished TNF-alpha-induced increment of CPP32/caspase-3 activity, and a reduced proportion of cells in the G2 phase with a concomitantly increased proportion of cells in the S phase. In conclusion, by combining three different methods, we have obtained a panel of frequently down regulated genes in HCC, including BMAL2. Antisense overexpression of BMAL2 enhances cell proliferation.

ARNTL Transcription Factors↗

PubMed2003

Expression of deleted in malignant brain tumor-1 (DMBT1) molecule in biliary epithelium is augmented in hepatolithiasis: possible participation in lithogenesis.

Deleted in malignant brain tumor-1 (DMBT1) is a mucin-like molecule participating in mucosal immune defense. Given that bovine gallbladder mucin, which accelerates cholesterol crystallization, is a DMBT1 homolog, DMBT1 expression was examined immunohistochemically in biliary epithelial cells in livers with hepatolithiasis (N = 25), primary sclerosing cholangitis (N = 7), large bile duct obstruction (N = 12), and control normal livers (N = 10). DMBT1 protein was determined in the hepatic bile samples of hepatolithiasis (N = 12) and other hepatobiliary diseases (N = 8) by immunoblot. While DMBT1 was faintly expressed in normal livers (20%), it was significantly augmented in hepatolithiasis (76%) (P < 0.05). DMBT1 was mildly expressed in primary sclerosing cholangitis and large bile duct obstruction. DMBT1 protein was detected frequently in hepatic bile samples of hepatolithiasis (50%) (P < 0.05), but in the other bile samples. The percentage of cholesterol in intrahepatic calculi was significantly higher in the patients with DMBT1-positive bile. Augmented expression and secretion of DMBT1 in intrahepatic large bile ducts in hepatolithiasis suggests its role in lithogenesis.

Agglutinins↗