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Biomedical subjects

Michihiro Suzuki

Publications and source records attributed to Michihiro Suzuki.

At least 19 recordsLinked to original sources

Molecular epidemiology of hepatitis A virus in metropolitan areas in Japan.

BACKGROUND: Transmission routes of hepatitis A virus (HAV) in Japan have changed. The present study investigated changes of transmission routes in relation to genetic drift. METHODS: All 60 patients who were admitted between 1993 and 2003 with a diagnosis of hepatitis A were retrospectively analyzed. Nucleotide sequences of the VP1/2A region of the HAV recovered from their sera were determined. RESULTS: The suspected transmission routes were household contact, 19 (31%); food or waterborne, 16 (27%); homosexual activity, 11 (18%); international travel, 4 (7%); and unknown 10. (17%). The 11 patients presumably infected through homosexual activity were found exclusively in 1998 and 1999. The proportion of patients exposed through homosexual behavior and household contact was higher in those 2 years than in other years. Nucleotide sequences could be determined for 58 patients. Fifty-seven of the 58 sequences belonged to genotype IA HAV, with less than 10% nucleotide diversity. Of the 27 sequences isolated during 1998 and 1999, 25 had an identical nucleotide sequence regardless of the suspected transmission route. In contrast, sequences obtained in the other years differed from one another. A phylogenetic tree constructed from sequences recovered from patients without a history of travel abroad showed several clusters. CONCLUSIONS: Our results suggest that (1) HAV acquired through homosexual activity may be transmitted to nonhomosexual individuals; (2) hepatitis A in metropolitan areas in Japan is caused mainly by sporadic infection with genotype IA HAV; and (3) several subtypes of genotype IA HAV are endemic in Japan.

Adult↗

Obstructive jaundice caused by secondary pancreatic tumor from malignant solitary fibrous tumor of pleura: a case report.

A 77-year-old man on systemic chemotherapy against postoperative bilateral multiple lung metastases of malignant solitary fibrous tumor of the pleura suffered from pruritus and jaundice. Blood examination showed elevated levels of hepatobiliary enzymes. Abdominal computed tomography showed a tumor with peripheral enhancement in the pancreatic head, accompanied with the dilatation of intra- and extra-hepatic bile ducts. He was diagnosed as having obstructive jaundice caused by a pancreatic head tumor. The pancreatic head tumor was presumably diagnosed as the metastasis of malignant solitary fibrous tumor of the pleura, because the findings on the pancreatic head tumor on abdominal CT were similar to those on the primary lung lesion of malignant solitary fibrous tumor of the pleura. The pancreatic tumor grew rapidly after the implantation of metallic stent in the inferior part of the common bile duct. The patient died of lymphangitis carcinomatosa of the lungs. Autopsy revealed a tumor that spread from the pancreatic head to the hepatic hilum. Microscopically, spindle-shaped cells exhibiting nuclear atypicality or division together with collagen deposition were observed. Immunohistochemically the pancreatic head tumor cells were negative for staining of alpha-smooth muscle actin (alpha-SMA) or CD117, but positive for vimentin, CD34 and CD99. These findings are consistent with those on malignant solitary fibrous tumor of the pleura. We report the first case of obstructive jaundice caused by a secondary pancreatic tumor from malignant solitary fibrous tumor of the pleura.

Aged↗

Risk factors for retinopathy associated with interferon alpha-2b and ribavirin combination therapy in patients with chronic hepatitis C.

AIM: To elucidate the frequency and risk factors for retinopathy in patients with chronic hepatitis C who are treated by interferon-ribavirin combination therapy. METHODS: We prospectively analyzed 73 patients with histologically confirmed chronic hepatitis C, who underwent combination therapy for 24 wk. Optic fundi were examined before, and 2, 4, 12 and 24 wk after the start of combination therapy. RESULTS: Fourteen patients (19%) developed retinopathy, which was initially diagnosed by the appearance of a cotton wool spot in 12 patients. Retinal hemorrhage was observed in 5 patients. No patient complained of visual disturbance. Retinopathy disappeared in 9 patients (64%) despite the continuation of combination therapy. However, retinopathy persisted in 5 patients with retinal hemorrhage. A comparison of the clinical background between the groups with and without retinopathy showed no significant differences in age, gender, viral genotype, RNA level, white blood cell count, platelet count, prothrombin time, complications by diabetes mellitus or hypertension, or pretreatment arteriosclerotic changes in the optic fundi. However, multiple logistic regression analysis revealed that complication by hypertension was observed with a high frequency in the group with retinopathy (P = 0.004, OR = 245.918, 95% CI = 5.6-10786.2). CONCLUSION: Retinopathy associated with combination therapy of interferon alpha-2b and ribavirin tends to develop in patients with hypertension.

Adult↗

Safer endoscopic gastric mucosal resection: preoperative proton pump inhibitor administration.

BACKGROUND AND AIM: Control of bleeding is crucial in improving the safety of endoscopic mucosal resection (EMR), and intragastric acidity has a great impact on hemostasis and blood coagulation. Proton pump inhibitors (PPI) are potent suppressors of gastric acid; however, PPI need to be continuously administered orally for several days, and thus initial effects may be insufficient if PPI is only administered immediately after EMR. The aim of this study was to determine whether preoperative administration of PPI prior to EMR can elevate intragastric acidity, facilitate better control of intraoperative bleeding (complete coagulation and hemostasis), prevent postoperative bleeding, and facilitate healing of artificial ulcers. METHODS: A randomized clinical study was conducted in which EMR was performed with or without 1 week of preoperative PPI administration. RESULTS: Artificial ulcers created by EMR healed more rapidly in patients who received preoperative PPI. CONCLUSIONS: The results of the study suggest that preoperative administration of PPI before EMR is useful for controlling and preventing bleeding, and for facilitating the healing of artificial ulcers.

Adenoma↗

Hepatocellular carcinoma with silent and cirrhotic non-alcoholic steatohepatitis, accompanying ectopic liver tissue attached to gallbladder.

A 70-year-old man had been obese since youth. He had been treated for hypertension and diabetes mellitus. An abdominal ultrasound showed a mass in the liver. He was admitted to St Marianna University School of Medicine Hospital for further evaluation. There was no history of alcohol use, and hepatitis viral markers and autoantibodies were all negative. Several imaging studies showed overt hepatocellular carcinoma (HCC). Transcatheter arterial embolization was performed, followed by surgical resection. Histopathological examination revealed moderately differentiated HCC. The non-tumor areas had pseudolobules in a diffuse pattern similar to alcoholic cirrhosis. The histological findings in the ectopic liver tissue attached to the gallbladder, which was also resected during surgery, were that there was no cirrhosis, but fine fibrosis with inflammatory cell infiltration of sinusoids. These findings were consistent with non-alcoholic steatohepatitis (NASH). There was probably a progression of similar findings that had developed into cirrhosis. These findings confirmed a diagnosis of HCC, cirrhosis, and underlying NASH in this patient. The present case is important for investigation of the development into cirrhosis and carcinogenesis of NASH. The present case demonstrates the importance of evaluating obese patients with fatty liver for underlying NASH and ongoing follow up for development of cirrhosis and HCC.

Aged↗

Pancreatic involvement in chronic viral hepatitis.

AIM: To elucidate the frequency and characteristics of pancreatic disorders in the course of chronic viral hepatitis. METHODS: We prospectively assessed the serum pancreatic enzyme levels and imaging findings in patients with chronic viral hepatitis and healthy control subjects. RESULTS: Serum amylase (t-Amy), salivary amylase (s-Amy), pancreatic amylase (p-Amy) and serum lipase levels were higher in hepatitis patients in comparison to control subjects. However, in asymptomatic viral carriers, only the serum t-Amy levels were higher than those of the controls. The levels of each enzyme rose with the progression of liver disease in patients with hepatitis B or C; whereas the levels of each enzyme within the same clinical stage of the disease did not differ between patients diagnosed with either hepatitis B or hepatitis C virus. Imaging findings demonstrated chronic pancreatitis in only 1 out of 202 patients (0.5%). CONCLUSION: Our data suggest that serum levels of pancreatic enzymes increase with the progression of liver disease in patients diagnosed with viral hepatitis. Pancreatic disease, asymptomatic in most cases, may represent an extrahepatic manifestation of chronic viral hepatitis.

Adult↗

Solid variant of aneurysmal bone cyst of the cervical spine.

STUDY DESIGN: A case of the solid variant of aneurysmal bone cyst affecting the posterior component of the fourth cervical vertebra is reported. Imaging studies showed an expansile destructive lesion. After curettage, autologous iliac bone grafting with posterior fusion was performed. There was no sign of local recurrence 2 years after surgery. OBJECTIVES: To emphasize the occurrence of the solid variant of aneurysmal bone cyst in the cervical spine. SUMMARY OF BACKGROUND DATA: The solid variant of aneurysmal bone cyst is rare, and only 12 cases occurring in the vertebrae, including 3 in the cervical vertebrae, have been reported. The condition is difficult to diagnose radiologically before biopsy or surgery. METHODS: A 9-year-old girl presented with pain in the nape of the neck without any neurologic deficit. She was found to have the solid variant of aneurysmal bone cyst in the posterior component of the fourth cervical vertebra, which had destroyed the lamina and spinous process. Part of the posterior aspect of the C4 vertebral body was also involved. Curettage of the lesion was performed, and the defect in the posterior component of the vertebra was reconstructed using an autologous iliac bone graft with posterior fusion using a halo vest. RESULTS: Magnetic resonance imaging disclosed a homogeneous low intensity mass at the lamina, spinous process, and vertebral body of C4 on T1-weighted images. The mass showed heterogeneous high signal intensity on Gd-enhanced images. Histologically, the resected specimen showed predominant fibroblastic proliferation, with minor foci of reactive osteoid formation and an area of osteoclast-like giant cells. Neither cellular atypia nor mitotic figures were evident. There was no sign of local recurrence 2 years after surgery. CONCLUSIONS: The solid variant of aneurysmal bone cyst should be included in the differential diagnosis of any lytic expansile lesion of the spine, even though it is a destructive lesion. Gd-enhanced magnetic resonance imaging may be helpful for distinguishing the solid variant from conventional aneurysmal bone cyst.

Bone Cysts, Aneurysmal↗

Identification of a new autoantibody in patients with chronic hepatitis.

To comprehensively study autoantibodies in patients with chronic hepatitis (CH), especially those with hepatitis C virus (HCV) infection, proteins extracted from HepG2 cells were separated by two-dimensional electrophoresis. Spots reacting with sera from 15 patients with CH-C were detected by Western blotting. Proteins extracted from the spots were subjected to mass spectroscopy for identification by mass fingerprinting. Antigenicity of the proteins identified was confirmed by Western blotting and enzyme-linked immunoabsorbent assay. The localization of the autoantigens so detected was investigated by immunohistochemistry. Among 20 protein spots detected, four were identified as actin, heat shock protein (HSP) 70, HSP60, and a novel protein (hepalaminin). Hepalaminin consists of two domains of laminin beta-2 and a specific domain. Autoantibodies against the specific domain were detected in 60.8% of patients with CH-C, 37.7% of those with CH-B, 42.3% of those with autoimmune CH, 28.6% of nonalcoholic steatohepatitis, 10.0% of asymptomatic HCV carriers, but in no healthy volunteers. Antihepalaminin positivity in CH-C and CH-B was related to histologic grading. Immunohistochemical staining demonstrated that hepalaminin is present in the cytoplasm of hepatocytes and cholangiocytes but not of fibroblasts or the vascular epithelium. Hepalaminin is a novel protein expressed in hepatocytes and cholangiocytes. Autoimmunity to this protein may exacerbate inflammation in chronic viral hepatitis.

Amino Acid Sequence↗

Role of hepatitis B virus in hepatocarcinogenesis in alcoholics.

BACKGROUND: The pathogenesis of hepatocellular carcinoma (HCC) in alcoholics is not understood well. Occult hepatitis B virus (HBV) infection may have some roles. METHODS: We compared the clinical features of HCC in patients with and without a history of excessive alcohol consumption. For hepatitis B surface antigen (HBsAg)-negative, anti-hepatitis C virus (HCV)-negative (NBNC) patients, HBV DNA in the tumor was detected by polymerase chain reaction (PCR)-Southern blotting. Integrated and episomal forms of HBV DNA were detected using agarose gel electrophoresis after nested PCR and were quantified by real-time PCR. RESULTS: For patients who were anti-HCV positive in serum, the age at diagnosis of HCC was lower for alcoholics than nonalcoholics. For serum HBsAg-positive patients and those who were NBNC, the age at diagnosis of HCC was the same for alcoholics and nonalcoholics. The numbers of tumors and of patients with vascular invasion did not differ between alcoholics and nonalcoholics in any subset. In three NBNC-HCC patients with a history of alcohol abuse, HBV DNA was detected in the tumor. Integrated HBV DNA was detected in one patient, and the episomal form of HBV DNA was detected in two patients. CONCLUSION: HBV may be found in episomal and integrated forms in the chromosomal DNA of the livers of habitual drinkers who are negative for HBsAg and anti-HCV and may have a direct role in hepatocarcinogenesis.

Aged↗

Strategy for hepatic hyperplastic nodules in heavy drinkers.

BACKGROUND: Increased detection of nodular lesions that have not yet been definitively diagnosed as hepatocellular carcinoma (HCC) has occurred with the use of advanced imaging techniques. In heavy drinkers, the differential diagnosis between a hyperplastic nodule and early HCC on the basis of results of fine-needle biopsy is often difficult. Negation of diagnosis of HCC after surgical resection has been reported, and nodular lesions have been found to decrease during follow-up observation. On the basis of findings, a suitable strategy for the management of such lesions is suggested. METHODS: We identified six patients who had hepatic nodular lesions on ultrasonography and were heavy drinkers. This group included five men and one woman with a mean age of 45.3 +/- 3.8 years. Two patients had solitary lesions; four had multiple lesions, and of these, two were hepatitis C virus antibody positive (C+). In the five men, the nodular lesions were detected during hospitalization for ruptured or prophylactic treatment of gastroesophageal varices. RESULTS: Five of the six patients had hypervascular lesions characterized by increased hepatic artery blood flow. However, dynamic computed tomography and magnetic resonance imaging studies during late-phase imaging could not confirm any decrease in portal blood flow. HCC was diagnosed by detailed imaging studies and liver biopsy in one C+ patient with a solitary nodule. In two of the other four patients, imaging findings were compatible with hypervascular HCC. Findings on liver biopsy do not always permit an easy differential diagnosis between a regenerative lesion (hyperplastic nodule) and a dysplastic or neoplastic lesion. One patient with a hypovascular lesion was C+, and liver biopsy showed a dysplastic nodule. CONCLUSION: Heavy drinkers with alcoholic liver disease often develop hypervascular, hyperplastic nodules. The accurate diagnosis of these nodules requires careful consideration of clinical factors, including a combination of images and histologic examination. However, some cases were still difficult to distinguish between HCC by applying advanced imaging techniques and biopsy results.

Adult↗

A rapid biosensor chip assay for measuring of telomerase activity using surface plasmon resonance.

Considerable interest has been focused on telomerase because of its potential use in assays for cancer diagnosis, and for anti-telomerase drugs as a strategy for cancer chemotherapy. A number of assays based on the polymerase chain reaction (PCR) have been developed for evaluation of telomerase activity. To overcome the disadvantages of the conventional telomerase assay [telomeric repeat amplification protocol (TRAP)] related to PCR artifacts and troublesome post-PCR procedures, we have developed a telomeric repeat elongation (TRE) assay which directly measures telomerase activity as the telomeric elongation rate by biosensor technology using surface plasmon resonance (SPR). 5'-Biotinylated oligomers containing telomeric repeats were immobilized on streptavidin-pretreated dextran sensor surfaces in situ using the BIACORE apparatus. Subsequently, the oligomers associated with the telomerase extracts were elongated in the BIACORE apparatus. The rate of TRE was calculated by measuring the SPR signals. We examined elongation rates by the TRE assay in 18 cancer and three normal human fibroblast cell lines, and 12 human primary carcinomas and matching normal tissues. The elongation rates increased in a concentration- and time-dependent manner. Those of cancer cells were two to 10 times higher than fibroblast cell lines and normal tissues. Telomerase activities and its inhibitory effects of anti-telomerase agents as measured by both the TRE and TRAP assays showed a good correlation. Our assay allows precise quantitative comparison of a wide range of human cells from somatic cells to carcinoma cells. TRE assay is suitable for practical use in the assessment of telomerase activity in preclinical and clinical trials of telomerase-based therapies, because of its reproducibility, rapidity and simplicity.

Cell Line↗

Detection, using a novel method, of a high prevalence of cryoglobulinemia in persistent hepatitis C virus infection.

To elucidate precisely the prevalence and significance of cryoglobulinemia in hepatitis C, we examined the prevalence of serum cryoglobulin (CG) among 232 consecutive hepatitis C virus carriers (23 asymptomatic carriers, 164 with chronic hepatitis, 45 with cirrhosis), 30 consecutive hepatitis B virus carriers and 100 age- and sex-matched healthy volunteers. We used a gel-diffusion procedure that detects CG with greater sensitivity and specificity than the conventional precipitation method. Among the 232 patients, 166 were tested for the presence or absence of CG by the precipitation method also, which showed 60 (36.1%) patients to be positive for CG. On the other hand, 164 of the 232 patients (70.7%) were positive for CG using the diffusion method. 5 (16.7%) of the 30 HBV carriers and 2 (2%) of the healthy volunteers also were positive for CG using the gel-diffusion procedure. CG was detected more frequently among the patients with chronic hepatitis or cirrhosis than the asymptomatic carriers. In spite of the high prevalence of CG positivity, only one patient had symptoms related to cryoglobulinemia. Positivity for CG was not related to viral serogroup, viral load or the presence of antinuclear antibody, but it was related closely to CH50: 58 of 63 (92.1%) patients with lower levels of CH50 were positive for serum CG. In conclusion, cryoglobulinemia is a very common feature of chronic hepatitis C.

Journal Article↗

Autoantibodies to CD69 in patients with chronic hepatitis type C: a candidate marker for predicting the response to interferon therapy.

OBJECTIVE: To understand the autoimmunity associated with chronic hepatitis C (CHC), we investigated autoantibodies (autoAbs) to CD69. METHODS: With this aim, we tested the reactivity of serum samples from patients with CHC and asymptomatic carriers of hepatitis C virus (HCV), as well as from patients with chronic hepatitis B (CHB) and autoimmune hepatitis (AIH), to recombinant CD69 molecules. RESULTS: Frequencies of anti-CD69 autoAbs were 38.7% in CHC, 15.8% in AIH and 12.3% in CHB. None of the tested asymptomatic HCV carriers had autoAbs to CD69. It is important clinically that the presence of anti-CD69 autoAbs was found to be associated with a poor response to interferon-alpha (IFN-alpha) therapy. In the epitope analysis, multiple epitopes were mapped on CD69, indicating antigen-driven production of the autoAbs. CONCLUSION: We evidenced existence of anti-CD69 autoAbs in patients with CHC, and found that the anti-CD69 autoAb may have potential for predicting responses to IFN-alpha therapy.

Adult↗

Increase in dephosphorylation of the heavy neurofilament subunit in the monkey chronic glaucoma model.

PURPOSE: To investigate the phosphorylation of the heavy neurofilament subunit (NF-H), which could be deeply involved in axonal transport of retinal ganglion cells (RGCs), in an experimental glaucoma model of chronic elevation of intraocular pressure (IOP) in monkeys. METHODS: One eye in adult monkeys was randomly selected for laser treatment, and IOP was maintained between 30 and 40 mm Hg throughout the experiment. The eyeballs with the optic nerve and optic chiasm were enucleated as one tissue and were subject to immunocytochemical observation, using two NF-H-specific antibodies, NF-200 and SMI31. NF-200 reacts with both phosphorylated and dephosphorylated NF-H, whereas SMI reacts only with phosphorylated NF-H. Ratios of SMI31-positive to NF-200-positive areas were calculated for quantitative evaluation of phosphorylation status. Specimens from the retina, lamina cribrosa (LC), post-LC, and optic chiasm were evaluated separately. Phosphorylation of NF-H at the retina and optic nerve head was compared between specimens from temporal retina and nasal retina, or between temporal and nasal regions of the optic disc. The status of phosphorylation was confirmed by Western blot analysis. RESULTS: An enlargement of the disc cup was observed on the temporal side, and the superior and inferior poles were preferentially involved in the neuronal damage in laser-treated eyes. Most NF-Hs in the control eyes were phosphorylated in all investigated regions, whereas those in the glaucomatous eyes were significantly dephosphorylated, and NF-Hs in the temporal region were significantly dephosphorylated compared with those in the nasal region. At the optic chiasm, NF-Hs in axons traveling from laser-treated eyes were highly dephosphorylated, and the extent of NF-H dephosphorylation corresponded to the degree of glaucoma-induced axonal damage. Western blot analysis showed the change in the phosphorylation of NF-Hs. CONCLUSIONS: NF-Hs in RGC axons are dephosphorylated by elevated IOP, which may be deeply involved in glaucoma-induced damage to axonal transport.

Animals↗

Comparison between isopropyl unoprostone and latanoprost by prostaglandin E(2)induction, affinity to prostaglandin transporter, and intraocular metabolism.

The pharmacological differences between isopropyl unoprostone (referred to as unoprostone) and latanoprost, concerning their induction of endogenous prostaglandin E(2)(PGE(2)) and affinity to a human prostaglandin transporter (PGT), were investigated. Freshly dissected bovine iris tissues were incubated with major intraocular metabolites of unoprostone, M1 and M2, acid of latanoprost, or PGF(2 alpha), and PGE(2)induction was measured. Affinities of M1, M2, latanoprost, acid of latanoprost, and PGF(2 alpha)to PGT molecule were measured using PGT-cDNA transfected HeLa cells by an isotopic influx assay.(3)H-unoprostone was incubated with freshly prepared serum, aqueous humor, or frozen stored fetal bovine serum (FBS), and the radioactivity of supernatants was measured to investigate their metabolism of(3)H-unoprostone.M2, acid of latanoprost, and PGF(2 alpha)significantly increased a release of PGE(2)compared with the control. 10 microM indomethacin completely inhibited PGE(2)induction by acid of latanoprost and PGF(2 alpha), while 100 microM indomethacin was required to inhibit PGE(2)induction completely by M1 and M2. Unoprostone, M1, M2, and latanoprost showed little affinity to PGT, while acid of latanoprost had an affinity to PGT. Freshly prepared serum and aqueous humor metabolized unoprostone, but frozen stored FBS did not. The release of endogenous PGE(2)may play an important role of action by means of PG analogs, and differences in indomethacin-related inhibition of PGE(2)release and in affinities to PGT may in part cause their different actions.

Adult↗