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Akihiko Suzuki

Publications and source records attributed to Akihiko Suzuki.

17 recordsLinked to original sources
PubMed2006

Separate analysis of asialoglycoprotein receptors in the right and left hepatic lobes using (99m)Tc-GSA SPECT in patients with acute hepatic damage.

The asialoglycoprotein receptor (ASGPR) is abundantly expressed on the sinusoidal surfaces of hepatocytes. However, regional expression and clinical significance of the ASGPR in acute hepatic damage is presently unknown. Our aim was to clarify the clinical significance of the regional expression of ASGPR in human livers with acute hepatitis (AH) and fulminant hepatic failure (FHF). Eighteen volunteers, 42 patients with AH and 10 with FHF were studied using a newly developed, conventional (99m)Tc-GSA SPECT analysis. Using Cantlie's line as a guide, ASGPR expression was analyzed separately in the right and left hepatic lobes, as well as in the whole liver, using novel indices (the liver uptake ratio [LUR] and liver uptake density [LUD], which reflect the amount and density of ASGPRs in the liver, respectively). Mean LUR and LUD values for the whole liver and the right and left lobes decreased in accordance with the severity of acute hepatic damage. In the FHF group, the reduction in LUR and LUD values in the right lobes was more significant than in the left lobes. The LUR and LUD values for the whole liver correlated well with hepatic functional reserve and total bilirubin levels. The right LUR and LUD values in particular correlated well with these parameters. A time-course observation of 13 patients with either AH or FHF revealed that the expression of ASGPRs in the right lobe recovered faster than in the left. We first evaluated the regional expression of AGSPRs by (99m)Tc-GSA SPECT analysis in both AH and FHF patients, which is a clinically useful and reliable indicator for assessing the severity of regional hepatic damage and evaluating regional liver regeneration.

Journal Article↗
PubMed2006

Characteristics of rat bone marrow cells differentiated into a liver cell lineage and dynamics of the transplanted cells in the injured liver.

BACKGROUND: Bone marrow cells (BMCs) have been shown to differentiate into a liver cell lineage, but little is known about their dynamics following transplantation. BMCs were cultured to investigate the expression of liver-specific genes in vitro and transplanted into in vivo liver-injury models to elucidate their dynamics in the liver. METHODS: The mRNA expression of various liver-specific genes in BMCs cocultured with hepatocytes was analyzed using reverse transcription-polymerase chain reaction. BMCs from transgenic rats expressing green fiuorescent protein were transplanted into the spleen of rat liver-injury models induced with 2-acetylaminofiuorene (2-AAF) or carbon tetrachloride (CCl4). BMCs were also transplanted directly into livers treated with CCl4 to determine which route is better for transplantation. RESULTS: BMCs differentiated into a liver cell lineage in vitro and expressed mRNAs consistent with mature hepatocytes, including albumin. The transplanted BMCs were found in the liver in the CCl4-induced injury model, but not in the 2-AAF-induced model. The hepatocyte growth factor and fibroblast growth factor mRNA levels in the liver were significantly higher in the CCl4-induced model than in the 2-AAF-induced model. Migration of BMCs to the liver was more effective following injection into the liver, rather than into the spleen. CONCLUSIONS: Cultured BMCs differentiated into a liver cell lineage are a potential source for cell transplantation. Transplantation is successful in the severely injured liver with a high level of expression of mRNAs for growth factors. Injection of BMCs directly into the liver is the preferred route of administration.

2-Acetylaminofluorene↗
PubMed2005

Differentiation of rat bone marrow cells cultured on artificial basement membrane containing extracellular matrix into a liver cell lineage.

BACKGROUND/AIMS: Bone marrow (BM) cells have been shown to be capable of differentiating into a liver cell lineage in vitro. However, their differentiation and proliferation is poor, and the cell characteristics are poorly understood. METHODS: We cultured rat BM cells on an artificial basement membrane containing extracellular matrix (ECM) with hepatocyte growth factor (HGF). The expression of mRNA for liver-specific genes was analyzed by reverse transcription PCR. The expression of albumin and Musashi-1 by cultured cells was analyzed using a fluorescence-activated cell sorter (FACS). The proportions of albumin-positive cells when culture was performed with different concentrations of HGF were analyzed by FACS. RESULTS: On culture day 21, polygonal cells proliferated and formed cell colonies. These cells expressed mRNA for all the liver-specific genes analyzed, and showed heterogeneous differentiation, some cells expressing albumin, others expressing Musashi-1. Albumin-positive differentiated cells were large and rich in intracellular structures, while Musashi-1-positive undifferentiated cells had the opposite characteristics. Culturing cells with higher concentrations of HGF induced an increased proportion of albumin-positive cells. CONCLUSIONS: The results suggest that cell culture on an ECM with a high concentration of HGF increases the extent to which BM cells differentiate into a liver cell lineage and proliferate in vitro.

Albumins↗
PubMed2005

NAD(P)H oxidase plays a crucial role in PDGF-induced proliferation of hepatic stellate cells.

The proliferation of hepatic stellate cells (HSCs) is a critical step in hepatic fibrogenesis. Platelet-derived growth factor (PDGF) is the most potent mitogen for HSCs. We investigated the role of nonphagocytic NAD(P)H oxidase-derived reactive oxygen species (ROS) in PDGF-induced HSC proliferation. The human HSC line, LI-90 cells, murine primary-cultured HSCs, and PDGF-BB were used in this study. We examined the mechanism of PDGF-BB-induced HSC proliferation in relation to the role of a ROS scavenger and diphenylene iodonium, an inhibitor of NAD(P)H oxidase. We also measured ROS production with the aid of chemiluminescence. We showed that PDGF-BB induced proliferation of HSCs through the intracellular production of ROS. We also demonstrated that HSCs expressed key components of nonphagocytic NAD(P)H oxidase (p22phox, gp91phox, p47phox, and p67phox) at both the messenger RNA and protein levels. Diphenylene iodonium suppressed PDGF-BB-induced ROS production and HSC proliferation. Coincubation of H2O2 and PDGF-BB restored the proliferation of HSCs that was inhibited by diphenylene iodonium pretreatment. Phosphorylation of the mitogen-activated protein kinase (MAPK) family constitutes a signal transduction pathway of cell proliferation. Our data demonstrate that NAD(P)H oxidase-derived ROS induce HSC proliferation mainly through the phosphorylation of p38 MAPK. Moreover, an in vivo hepatic fibrosis model also supported the critical role of NAD(P)H oxidase in the activation and proliferation of HSCs. In conclusion, NAD(P)H oxidase is expressed in HSCs and produces ROS via activation of NAD(P)H oxidase in response to PDGF-BB. ROS further induce HSC proliferation through the phosphorylation of p38 MAPK.

Animals↗
PubMed2005

Pathology of pure hippocampal sclerosis in a patient with dementia and Hodgkin's disease: the Ophelia syndrome.

An archive autopsy case of a 50-year-old man who died of Hodgkin's lymphoma had a 4-year, 4-month history of dementia. After radiochemotherapy, the lymphoma subsided except for involvement of the spleen, but the dementia remained. Neuropathological examination revealed that the pathology was confined to the hippocampus, both hippocampi showing sclerosis without inflammation. Neurons of sector cornu ammonis (CA) 1 were completely lost whereas moderate neuron loss was also observed in sectors CA3 and 4, and the dentate gyrus. Neurons of sector CA2 were relatively well preserved and the subiculum was intact. There was no evidence of global hypoxia, or of neurodegenerative disorders with pathological changes affecting the hippocampus. Although there was a long preneoplastic history, and no inflammatory changes were found at autopsy, the present case of hippocampal sclerosis could be included in the category of paraneoplastic limbic encephalitis associated with Hodgkin's lymphoma or the Ophelia syndrome.

Adult↗
PubMed2005

Breast conserving surgery with primary volume replacement using a lateral tissue flap.

Breast conserving surgery (BCS) is now a standard surgical treatment for early breast cancer. The number of patients with tumors under 3 cm who underwent breast conserving surgery overtook the number of patients who underwent total mastectomy for the first time in Japan in 2003. We have been employing breast conserving surgery with primary reconstruction using a lateral tissue flap (LTF), and have performed breast conserving surgery for 266 patients from 1990 to 2002. The incidence of local relapse was 5.6%. Although we did not irradiate a low risk group of 101 patients, our method is not inferior to other reports in which all cases underwent irradiation. Primary reconstruction with LTF has three advantages. The first is that we can avoid poly-surgery for breast reconstruction. The second is that the volume of the graft is maintained longer than reconstruction with a musculo-cutaneous flap. The third is that patients can avoid allergic reactions or granulomas as seen with artificial prosthesies. In conclusion, breast conserving surgery with immediate volume replacement with a LTF is a reasonable surgical procedure and has the advantage of avoiding unnecessary surgical procedures for reconstruction and surgical invasion without delaying the diagnosis of local relapse. Moreover, an adequate assessment of risk can spare low risk groups irradiation.

Axilla↗
PubMed2005

Pathological aspects of core needle biopsy for non-palpable breast lesions.

Recently, the incidence of non-palpable or noninvasive breast cancer has increased. Consequently, criteria for choosing procedures to obtain pathological materials had changed. Fine needle aspiration biopsy cytology (FNA) and core needle biopsy (CNB) are both reliable procedures for detecting breast cancer. However, for non-palpable lesions, the diagnostic accuracy of CNB is higher. The main limits of FNA are the high rate of insufficient sampling and inability to determine invasiveness. CNB is an established alternative to surgical biopsy, and CNB can avoid excess surgical biopsies in a large number of patients. In addition to accurate histological diagnosis, there is interest in obtaining prognostic information from CNB, especially for patients being considered for preoperative (neoadjuvant) therapy. CNB provides useful information about histologic type and grade. However, an unavoidable problem of CNB is underestimation of invasion. On the other hand, there is good concordance in particular for estrogen receptor (ER) and progesterone receptor (PR) between CNB and surgical excision. Several aspects of CNB remains controversial, such as diagnosing papillary lesions by CNB, problems regarding tumor cell displacement after CNB, and management of lobular neoplasia (LN) on CNB.

Biopsy, Needle↗
PubMed2004

Expression of Notch signalling markers in bone marrow cells that differentiate into a liver cell lineage in a rat transplant model.

Notch signalling pathway plays an important role in cell differentiation. To investigate the implications of Notch signalling in the differentiation of rat bone marrow (BM) cells into a liver cell lineage, we used cultured BM cells to examine the mRNA expression of Musashi-1, which positively regulates Notch signalling, and made a transplant model to examine the protein expression of Notch signalling markers. For the in vivo experiment, BM cells were collected from transgenic rats expressing green fluorescence protein (GFP) and transplanted into the spleens of recipient rats, in which liver damage had been induced with carbon tetrachloride. The expression of Notch receptor 1 (Notch-1), Jagged-1 and Musashi-1, in the transplanted GFP-positive BM cells was investigated by immunohistochemistry. The expression of the liver-specific proteins, alpha-fetoprotein and cytokeratin19 was also investigated. Musashi-1 mRNA became detectable in the BM cells on culture day 7 in vitro. After transplantation, GFP-positive BM cells were observed in the portal areas of the recipient's livers. Notch-1, Jagged-1, Musashi-1, alpha-fetoprotein and cytokeratin19 were all expressed in the transplanted BM cells. These results suggest that the Notch signalling pathway plays a role in the differentiation of BM cells into a liver cell lineage.

Journal Article↗
PubMed2004

Collaboration of breast cancer clinic and genetic counseling division for BRCA1 and BRCA2 mutation family in Japan.

BACKGROUND: BRCA1 and BRCA2 mutations cause high breast cancer incidence rates as high as 80% Although prophylactic therapy is still controversial, several prophylactic therapies have been proposed and tried for BRCA1 and BRCA2 mutation carriers. Prophylactic surgery, chemo-prevention and precise screening have been proposed as prophylactic therapy. All BRCA1 and BRCA2 mutation carriers need knowledge about their disease and the countermeasures that are used to protect against onset of disease. Counseling plays an important role in this regard for people with genetic diseases. Therefore, collaboration between breast cancer clinics and genetic counseling services is the most important issue in clinical practice. Our group consists of three national universities and a general hospital. In this article we describe our trial to construct a clinical system against hereditary breast cancer as an interim report for the Japanese Ministry of Health, Labour and Welfare. PATIENTS AND METHODS: Twenty familial breast cancer patients were registered in this study. The whole sequence of BRCA1 and BRCA2 were analyzed. If pathological mutations were detected, their first degree families were introduced to the counseling division at each institute when candidates visited counseling divisions. RESULTS AND DISCUSSION: Four cases of a deleterious mutation in BRCA1 or BRCA2 were detected among 20 cases. Their first degree relatives are now under consideration for visiting counseling divisions. The clinical system described in this study should play a role to protect BRCA1 or BRCA2 mutation carriers in Japan.

Breast Neoplasms↗
PubMed2004

Transmission of hepatitis C virus quasispecies between human adults.

To elucidate how hepatitis C virus (HCV) with multiple variants (quasispecies) is transmitted and adapts to the host during infection, we compared nucleotide and deduced amino acid sequences from hypervariable region1 (HVR1) of the E2 gene of HCV between a donor and a recipient who developed hepatitis after a needlestick accident. Thirty clones from each subject were sequenced after PCR amplification, cloning, and purification of plasmid DNA from single colonies of transformed bacteria. Genetic analysis revealed that the recipient's viral sequences were much less diverse than the donor's. We found a single predominant HCV HVR1 clone of the recipient in 22/30 isolates with the same amino acid sequence, and mimic clones in 8/30 isolates with only one amino acid substitution. These were all absent in the donor, who had 21 highly diverse sequences. Phylogenetic analysis of virus E1/E2 gene sequences showed that the recipient's unique sequences were related to the population of variants from the donor, in whom one isolate had 96% similarity to the recipient's predominant amino acid sequence. These results suggest that a minor subset of the donor's HCV variants is selectively transmitted to the recipient, and that the selection determines the predominant variant in the new host.

Journal Article↗
PubMed2004

Increased neutrophils in bronchoalveolar lavage fluids from a patient with pulmonary edema associated with pheochromocytoma.

Pulmonary edema, both cardiogenic and noncardiogenic, has been reported as a manifestation of pheochromocytoma. We report a patient with pheochromocytoma complicated by acute pulmonary edema that appeared clinically noncardiogenic. The patient had an uncomplicated course and rapid resolution of pulmonary edema. Bronchoalveolar lavage fluids (BALF) showed a marked accumulation of neutrophils, suggesting involvement of neutrophil-mediated lung injury in noncardiogenic pulmonary edema associated with a pheochromocytoma.

Adrenal Gland Neoplasms↗
PubMed2003

Separate analysis of asialoglycoprotein receptors in the right and left hepatic lobes using Tc-GSA SPECT.

The asialoglycoprotein receptor (ASGPR) is abundantly expressed on the sinusoidal surfaces of hepatocytes. We aimed to clarify the clinical significance of the regional distribution of ASGPRs in the human liver, especially in chronic viral hepatitis. Eighteen volunteers, 34 patients with chronic hepatitis, and 33 patients with cirrhosis (11/Child-Pugh A, 11/Child-Pugh B, 11/Child-Pugh C) were studied using a newly developed, conventional technetium-99m-diethylenetriaminepentaacetic acid-galactosyl human serum albumin ((99m)Tc-GSA), single photon emission computed tomography (SPECT) method. Using Cantlie's line as a guide, ASGPR dynamics were analyzed separately in the right and left lobes, as well as in the whole liver, using novel indices (the liver uptake ratio [LUR] and the liver uptake density [LUD], which reflect the amount and density of ASGPRs in the liver, respectively). Mean LUR and LUD values for the whole liver and the right and left lobes decreased with increasing progression of chronic viral hepatitis. The LUR for the whole liver correlated well with parameters measuring the hepatic functional reserve and the platelet count. The right LUR correlated particularly well with conventional liver function tests, and comparison of the right LUD with histologic findings showed that it was a good indicator of periportal and/or bridging necrosis and fibrosis. In conclusion, our (99m)Tc-GSA SPECT method was clinically useful in evaluating regional hepatic function and the progression of chronic viral hepatitis using dynamic changes in ASGPRs.

Adult↗
PubMed2003

Toward understanding the natural history of ovarian carcinoma development: a clinicopathological approach.

OBJECTIVE: The natural history of the development of ovarian carcinoma is not known. It also remains undetermined whether ovarian carcinomas develop from benign and/or borderline malignant tumors or arise de novo from the ovarian surface epithelium. METHODS: To address these issues clinicopathologically, we reviewed the clinical charts of 543 patients with epithelial ovarian carcinoma and 252 patients with borderline tumors who underwent laparotomy at seven hospitals and collected patients whose clinical and transvaginal ultrasonography (USG) findings for adnexal regions 12 months or fewer prior to the surgery were available. Histological slides of the resected specimens were reexamined concerning the diagnosis and histological grade, as well as the presence or absence of benign- or borderline-like lesions adjacent to the carcinoma. RESULTS: Forty-nine patients had had gynecological examination with transvaginal USG 12 months or fewer prior to laparotomy. Among them, 35 had carcinomas (11 serous, 6 mucinous, 8 clear cell, 10 endometrioid) and 14 had borderline tumors (8 serous, 6 mucinous). Of the 35 patients with carcinoma, 19 (54%) had been followed up for benign-appearing cysts or endometriotic cysts. In these cases, serial USG examinations revealed an increase in size and/or appearance of the solid part of the cyst. In the remaining 16 (46%), however, there had been no apparent abnormalities in USG, and such cases occurred most frequently for serous carcinomas. CONCLUSIONS: Our findings suggest that approximately half of ovarian carcinomas develop secondarily from preexisting, benign-appearing cysts or endometriotic cysts, whereas the remaining half seem to develop suddenly from a normal-appearing ovary. This appears to be consistent with two possible pathways of ovarian carcinoma development; adenoma-carcinoma sequence and de novo carcinogenesis.

Adult↗
PubMed2003

[Treatment strategy for liver metastasis from breast cancer].

Distant metastases, including supraclavicular and parasternal lymph node metastases, were observed in about 23% of primary breast cancers in our institute. The liver was the primary site of metastasis in about 8% of cases. This rate was low compared with metastases to the bone, lung, and pleura. As treatment for metastatic lesions to other organs fails, metastatic frequency to the liver increases. As treatment, whole-body control with chemoendocrine therapy is fundamental. In chemotherapy, anthracyclines are the first choice and taxanes are the second, but the use of herceptin for herceptest-positive patients should be considered. Endocrine therapy should be adopted for patients with hormone receptor-positive tumors. Achieving a temporary partial response is possible, although cure is almost impossible. The prognosis of patients with metastasis to the liver is poor; the 3- and 5-year survival rates are 22% and 11%, respectively. We must emphasize the prevention of liver metastases by early detection using mass screening with mammography and neoadjuvant/adjuvant chemoendocrine therapy.

Aged↗
PubMedDate not supplied

Spleen-preserving distal pancreatectomy with preservation of the splenic artery and vein for intraductal papillary-mucinous tumor (IPMT): three interesting cases.

Preservation of the spleen at distal pancreatectomy has recently attracted considerable attention. Since our first trial and success with spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein for tumors of the pancreas and chronic pancreatitis, this procedure has been performed more frequently. Three patients with intraductal papillary-mucinous tumor underwent spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein. In this procedure, the splenic vein is identified behind the pancreas and the connective tissue membrane is cut longitudinally above the splenic vein. An important point is to remove the splenic vein from the pancreas from the body of the pancreas toward the spleen. In one patient with intraductal papillary-mucinous tumor in the body of the pancreas who had undergone distal gastrectomy for duodenal ulcer 32 years previously, residual proximal gastrectomy could be avoided with this procedure. In this case, the histological diagnosis was a pseudocyst, and epithelial dysplasia was found in other pancreatic ductuli. In another case, epithelia were borderline between hyperplasia and adenoma. In both of these cases, the histological diagnosis was different from the preoperative diagnosis. Even with advances in imaging techniques, diagnosis of a cystic lesion of the pancreas is still very difficult. Ordinary distal pancreatectomy with splenectomy would have been oversurgery in these two cases, which could be avoided using our procedure. Severe complications were not found in any of the three cases and the postoperative course was uneventful. The patients have been followed as outpatients without any recurrence. Spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein is easy and safe, and should be performed for some patients with intraductal papillary mucinous tumor of the pancreas.

Adenocarcinoma, Mucinous↗