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Biomedical subjects

A Nakao

Publications and source records attributed to A Nakao.

At least 73 records · Page 4Linked to original sources

Hepatitis C virus in blood and dialysate in hemodialysis.

The prevalence of hepatitis C virus (HCV) positivity among hemodialysis patients remains high compared with that of the healthy population, and thus the issue of safety and environmental protection must be addressed. The purpose of this study is to evaluate the dynamics of prehemodialysis and posthemodialysis blood HCV levels and HCV escape to spent dialysate. Because heparin has an inhibitory effect on the reverse-transcription polymerase chain reaction (RT-PCR) assay, a serine protease inhibitor (nafamostat mesilate) was used as the anticoagulant for hemodialysis. High-flux polysulfone membrane dialyzers were used; dialyzer reuse was not performed. Multicyclic RT-PCR was performed for the quantitative detection of HCV. To elucidate HCV escape to spent dialysate, a portion of total spent dialysate was continuously extracted in a sterile fashion using a minutely adjusted syringe pump. No HCV extravasation to spent dialysate was found, although HCV copy numbers were reduced to a statistically significant level in postdialysis blood compared with predialysis levels (P: < 0.05; n = 20). The need to establish standards for risk management in dialysis centers is evident. The data obtained in this study strongly suggest that to minimize the risk for HCV transmission, lower transmembrane pressure (TMP) should be used in the hemodialysis of HCV-positive patients, with fresh polysulfone dialyzers and dialysis settings of 180 to 250 mL/min for blood flow, 500 mL/min for dialysate flow, and less than 18.72 mm Hg for TMP.

Blood↗

Intraoperative ultrasonography by high-resolution annular array transducer for intraductal papillary mucinous tumors of the pancreas.

BACKGROUND: Intraductal papillary mucinous tumors of the pancreas (IPMT) spread along the main pancreatic duct (MPD) or branch duct, or both. It is important to intraoperatively determine the extent of IPMT lesions in the MPD to perform a successful operation. METHODS: This study included 27 consecutive patients with IPMT who were referred for operation and who had undergone endoscopic ultrasonography, endoscopic retrograde pancreatography, and computed tomography as a diagnostic examination. Intraoperative ultrasonography with a 7.5-MHz annular array transducer and a 7. 5-MHz conventional transducer was performed. All patients underwent operation, and the pathology was confirmed. Endoscopic ultrasonography, endoscopic retrograde pancreatography, intraoperative conventional ultrasonography, and intraoperative annular array ultrasonography results were correlated with those from a pathologic examination of the resected specimens. The diagnostic accuracy of these 4 modalities in the detection of IPMT lesions in the MPD and the branch duct was confirmed. RESULTS: The diagnostic criterion of IPMT lesions by intraoperative annular array ultrasonography was the presence of echogenic masses with irregular margins in the MPD or branch duct, or both. An IPMT lesion in the MPD was found in 22 of the 27 patients. Intraoperative annular array ultrasonography detected 5 cases of IPMT lesions in the MPD that could not be detected by endoscopic ultrasonography or endoscopic retrograde pancreatography. In 3 of 5 patients, pancreatic resection was extended to remove IPMT lesions. Intraoperative annular array ultrasonography detected 3 multifocal lesions that could not be detected by preoperative examinations. For the diagnosis of IPMT lesions in the MPD, the respective sensitivity, specificity, and overall accuracy of intraoperative annular array ultrasonography were 86%, 100%, and 89%; the respective values were 50%, 100%, and 59% for endoscopic retrograde pancreatography; 59%, 100%, and 67% for endoscopic ultrasonography, and 32%, 100%, and 44% for intraoperative conventional ultrasonography. For the diagnosis of IPMT lesions in the branch duct, the respective sensitivity, specificity, and overall accuracy of intraoperative annular array ultrasonography were 95%, 100%, and 96%. CONCLUSIONS: Intraoperative annular array ultrasonography is suitable for longitudinal scanning of the MPD, useful for accurate diagnosis of the extent of IPMT in the pancreas, and valuable for planning surgical strategy and successful operations for IPMT.

Adenocarcinoma, Mucinous↗

A family of multiple endocrine neoplasia type 2A with the RET proto-oncogene mutation in codon 618 (Cys-->Arg).

Multiple endocrine neoplasia type 2 (MEN-2) is a hereditary syndrome characterized by medullary thyroid carcinoma (MTC), pheochromocytoma and hyperplasia or adenoma of the parathyroid gland with hyperparathyroidism. Recent genetic studies have identified the presence of germline missense mutations in the RET proto-oncogene in almost 100% of MEN-2 patients. We report here three generations of one MEN-2 family with rare missense mutation at codon 618 (Cys-->Arg) of the RET proto-oncogene. The first patient was surgically treated at the age of 63 years but died of bone metastasis. His two children (29-year-old daughter and 25-year-old son) were treated surgically for MTC and neck lymph node metastasis. Germline mutations of the RET proto-oncogene of these three MTC patients and two children of the 29-year-old daughter (9-year-old female and 7-year-old male) were examined. Three MTC patients and the 9-year-old female possessed the mutation. The phenotype of the family with this rare point mutation of the RET proto-oncogene is reported.

Adult↗

Leiomyosarcoma arising in a remnant esophagus after esophagectomy: a case report.

We report an extremely rare case of leiomyosarcoma arising from a remnant esophagus. A 52-year-old Japanese man was referred to our hospital for treatment of a tumor arising from the remnant esophagus. Four years earlier, he underwent a subtotal esophagectomy for esophageal squamous cell carcinoma (well differentiated squamous cell carcinoma, T1N0M0 Stage I) located in the lower esophagus. After preoperative studies, partial esophagectomy with laryngeal preservation and reconstruction using a free graft from the jejunum were performed. Histopathological and immunohistochemical examination revealed leiomyosarcoma without metastasis. Immunohistochemical examination showed that most tumor cells were positive for smooth muscle actin and vimentin, but were negative for cytokeratin and S100. The deeply biopsied specimens are helpful for preoperative histological diagnosis. Mitotic activity has been considered an important criterion of malignancy. However, some cases with minimal mitosis in the tumor grow rapidly and were associated with poor prognosis. Therefore, we advocate that the clinical behavior is the only true indication of malignancy. We also provide a review of 64 cases of esophageal leiomyosarcoma reported in the Japanese literature with available data between 1969 and 1999, including the present case, and discuss their clinicopathological features. Asynchronous occurrence of leiomyosarcoma and squamous cell carcinoma in the esophagus is most unusual and has never been reported. Patients with infiltrating type leiomyosarcoma measuring more than 5 cm in diameter tend to have a poor prognosis. Chemotherapy did not exhibit any survival benefits. In the present patient, no recurrence has been noted for 23 months after surgery.

Carcinoma, Squamous Cell↗

Structural transition of d(G4T4G4) from antiparallel to parallel G-quartet induced by divalent cations.

We obtained thermodynamic parameters of an antiparallel G-quartet formation of d(G4T4G4) with 1 mM divalent cation (Mg2+, Ca2+, Mn2+, Co2+, or Zn2+). In addition, we also found that a higher concentration of a divalent cation induced a transition from an antiparallel to a parallel G-quartet structure. These results indicate that the divalent cations are a good tool for regulating the G-quartet structures and their stability.

Base Sequence↗

Expression of neural cell adhesion molecule in pancreatic cancer.

Neural cell adhesion molecule (NCAM) has been found to be a significant factor for survival in various solid tumors. In the present study, we examined the expression of NCAM in exocrine tumors of the pancreas by immunohistochemistry, using two monoclonal antibodies against NCAM and polysialic acid (MAB735). Expression of NCAM was seen mainly in the cytoplasm of the following cells: regenerating duct cells among neoplastic tissue, hyperplastic islet cells, intrapancreatic nerves and ganglia, as well as tumor cells. There was no reactivity with MAB735. We found a significant correlation between intense NCAM expression (i.e., expression in more than 50% of all tumor cell mass) and survival rates in tubular adenocarcinoma, particularly moderately differentiated tumors (p < 0.05). There was no statistically significant relation between NCAM reactivity and tumor stage or any of the clinicopathologic parameters described by the Japan Pancreas Society (p > 0.05). We conclude that the expression of NCAM in tubular adenocarcinoma of the pancreas, particularly in moderately differentiated tumors, has a significant impact on the overall patient survival.

Adult↗

[Acute subdural abscess due to mixed infection of Eikenella corrodens and Streptococcus constellatus].

Eikenella corrodens is a gram-negative, facultative anaerobic rod that frequently exists as part of normal human flora in the upper respiratory tract and gastrointestinal tract. Recently, E. corrodens is reported as a rare causative agent of empyematic lesion. We report a case of 10-year-old girl with acute subdural abscess. She developed a high grade fever, swelling of the left periorbital area, right sided partial seizure and hemiplegia. Brain CT and MRI showed left parietal subdural abscess. Because intravenous antibiotic therapy was not effective enough and her neurological symptoms progressed, surgical drainage was performed in order to decompress the brain and to determine the causative agents. Through careful bacterial cultures, E. corrodens and Streptococcus constellatus were detected from the subdural abscess. After the drainage operation and a three week course of appropriate chemotherapy, the abscess completely disappeared and no sequela remained.

Acute Disease↗

Effect of endotoxin on P-glycoprotein-mediated biliary and renal excretion of rhodamine-123 in rats.

The effects of Klebsiella pneumoniae endotoxin on the biliary excretion and renal handling of rhodamine-123 were investigated in rats at different times after intraperitoneal injection (1 mg/kg of body weight). The typical substrates for P glycoprotein, i.e., cyclosporine, colchicine, and erythromycin, inhibited the biliary clearance of rhodamine-123, whereas a substrate for organic cation transporter, cimetidine, did not inhibit clearance, suggesting that rhodamine-123 is transported mainly by P glycoprotein. The biliary, renal, and tubular secretory clearances of rhodamine-123 and the glomerular filtration rate significantly decreased 6 h after injection of endotoxin but returned to control levels by 24 h. These results suggest that endotoxin-induced decreases in P-glycoprotein-mediated biliary excretion and renal handling of rhodamine-123 were probably due to impairment of P-glycoprotein-mediated transport ability. Pretreatment with pentoxifylline (50 mg/kg) significantly inhibited endotoxin-induced increases in tumor necrosis factor alpha (TNF-alpha) levels in plasma, which ameliorated the endotoxin-induced reduction of the biliary excretion of rhodamine-123. It is likely that endotoxin-induced impairment of the transport of rhodamine-123 is caused, in part, by overproduction of TNF-alpha. The effect of endotoxin on the expression of P-glycoprotein mRNA in liver and kidneys of rats was investigated by using a reverse transcriptase PCR. The expression of Mdr1a mRNA in both liver and kidney decreased 6 h after endotoxin injection and returned to control levels after 24 h, whereas the expression of Mdr1b mRNA in liver increased at both times and that in kidney decreased at 24 h. These findings suggest that K. pneumoniae endotoxin dramatically decreases P-glycoprotein-mediated biliary and renal excretion of rhodamine-123 probably by decreasing the expression of Mdr1a, which is likely due to increased plasma TNF-alpha levels.

ATP Binding Cassette Transporter, Subfamily B↗

Oxidative and nitrosative stress in acute renal ischemia.

Generation of reactive oxygen species and nitric oxide in hypoxia-reperfusion injury may form a cytotoxic metabolite, peroxynitrite, which is capable of causing lipid peroxidation and DNA damage. This study was designed to examine the contribution of oxidative and nitrosative stress to the renal damage in ischemic acute renal failure (iARF). iARF was initiated in rats by 45-min renal artery clamping. This resulted in lipid peroxidation, DNA damage, and nitrotyrosine modification confirmed both by Western and immunohistochemical analyses. Three groups of animals were randomly treated with an inhibitor of inducible nitric oxide synthase (NOS), L-N(6)-(1-iminoethyl)lysine (L-Nil), cell-permeable lecithinized superoxide dismutase (SOD), or both. Each treatment resulted in amelioration of renal dysfunction, as well as reduced nitrotyrosine formation, lipid peroxidation, and DNA damage, thus suggesting that peroxynitrite rather than superoxide anion is responsible for lipid peroxidation and DNA damage. Therefore, in a separate series of experiments, a scavenger of peroxynitrite, ebselen, was administered before the reperfusion period. This treatment resulted in a comparable degree of amelioration of iARF. In conclusion, the present study provides the first attempt to elucidate the role of peroxynitrite in initiation of the cascade of lipid peroxidation and DNA damage to ischemic kidneys. The results demonstrate that L-Nil, lecithinized SOD, and ebselen treatments improve renal function due to their suppression of peroxynitrite production or its scavenging, consequently preventing lipid peroxidation and oxidative DNA damage.

Animals↗

Pharmacokinetics of cetirizine in chronic hemodialysis patients: multiple-dose study.

The serum concentration-time profiles of cetirizine were measured in 8 male end-stage renal failure (ESRF) patients on chronic hemodialysis (HD). Cetirizine (5 mg) was ingested three times a week during the predialysis period. Blood samples were drawn for basal level evaluation, before and after dialysis on 3 days per week, and before HD the following week. The serum levels of cetirizine were measured using a validated atmospheric-pressure ionization liquid chromatography-tandem mass spectrometry method. Basal levels of cetirizine in HD patients were confirmed to be 0 ng/ml. The predialysis levels of cetirizine on days 1, 3, 5, and 8 were (mean +/- SD) 2.74 +/- 7.76, 34.16 +/- 21.55, 35.58 +/- 13.43, and 22.47 +/- 12.92 ng/ml, respectively. The postdialysis levels of cetirizine 4-5 h after ingestion were as follows (ng/ml): day 1, 103.11 +/- 37.27; day 3, 131.34 +/- 51.18, and day 5, 136.48 +/- 48.72. Between dialysis sessions, no supplemental dosage was required to keep the therapeutic range of 14 ng/ml. In addition, the predialysis levels on day 8 were not statistically different from the basal levels. Evidence from the multiple-dose study supports the clinical use of cetirizine for ESRF patients on HD. Thus, it is concluded that a prescription of 5 mg cetirizine three times a week during the predialysis period will be the effective and safety renal dosage for ESRD patients on HD.

Adolescent↗

Establishment and characterization of a murine mast cell line derived from NC/Nga mice.

A cell line, termed NCJ, was established from the bone marrow-derived mast cells (BMMCs) of NC/Nga mice that are mouse models for atopic dermatitis. NCJ cells expressed FcepsilonRI and c-kit and showed a metachromasia of the granules with a toluidine blue-positive and safranin-negative staining pattern that is characteristic for immature-type mast cells. Interestingly, NCJ cells showed proliferation independent of IL-3, which was associated with constitutive phosphorylation of Raf-1 and Erk kinases. Although NCJ cells had several characteristics of mast cells, we failed to detect FcepsilonRI-mediated beta-hexosaminidase release and its histamine content. These findings indicated that NCJ cells represented a mast cell line with an immature phenotype and the ability to proliferate in the absence of mast cell growth factors. NCJ cells might thus be useful to study the molecular basis of mast cell proliferation.

Animals↗

Somatic gene alteration of AIB1 gene in patients with breast cancer.

AIB1 (amplified in breast cancer 1) is a coactivator which stimulates the transcriptional activity of the liganded-estrogen receptor (ER). It has been reported that AIBI gene is amplified and overexpressed in some breast cancer cell lines. AIB1 contains a stretch of homopolymeric glutamines (poly-Q). We reported that the poly-Q shows polymorphism, which provides an opportunity to study somatic gene alteration such as loss of heterozygosity (LOH). In the present study, we aimed to investigate the frequency of somatic gene alteration in Japanese patients with breast cancer. Amplification of AIB1 gene was detected only in 1 (2.6%) of 39 breast cancer tissues by DNA dot blot analysis. On the other hand, LOH was found in 2 (8%) breast cancer tissues out of 25 patients showing heterozygosity in peripheral blood mononuclear cells (PBMC). Taken together, both LOH and amplification of AIB1 gene were identified in breast cancer patients, raising the possibility that AIB1 have oncogenic as well as antioncogenic potential for the pathogenesis of breast cancer.

Adult↗

Successful resection of rectal carcinoma in an Evans' syndrome patient followed by predonisolone and high-dose immunoglobulin: report of a case.

A 69-year-old woman was admitted to our hospital because of anal bleeding and fatigue. The patient was previously diagnosed as having Evans' syndrome on the basis of hematological examination and had been treated with predonisolone for 8 years. On admission, severe anemia and thrombocytopenia were noted. Colonoscopy and Barium enema studies demonstrated an irregular tumor with hemorrhagic ulceration in the rectum, which was histopathologically confirmed as an adenocarcinoma. After red blood cells and platelets were transfused, and the patient was treated with high-dose gammaglobulin, predonisolone, and camostat mesylate, the platelet count gradually increased and hemolysis was well controlled. The patient then underwent Hartmann's operation and splenectomy without any postoperative complications. Predonisolone and high-dose immunoglobulin therapy in a rectal cancer burdened patient with Evans' syndrome is considered useful in combination with surgical treatment. This is the first case report of rectal carcinoma resection in a patient with Evans' syndrome.

Adenocarcinoma↗

Retroperitoneal hematoma associated with femoral neuropathy: a complication under antiplatelets therapy.

We report a case of retroperitoneal hematoma presenting as femoral nerve pulsy on antiplatelet therapy. The patient, a 78-year-old man who had undergone antiplatelet treatment using ticlopidine, was admitted to our hospital with complaints of sudden-onset low abdominal and back pain. Computed tomography showed an iso-density mass in the right retroperitoneum within the psoas muscle. We made a diagnosis of retroperitoneal hematoma compressing the femoral nerve and performed an operation to remove the hematoma in order to decompress the femoral neuropathy. Postoperatively, the patient rapidly recovered from the femoral neuropathy. In the particular case in which no antagonist against the ticlopidine is available, surgical decompression could produce a good outcome.

Aged↗

AIS overexpression in advanced esophageal cancer.

We examined AIS status in digestive tract cancers and found that all eight esophageal cancer cell lines (100%) showed AIS/TA-AIS gene overexpression, whereas 1 of 12 (8%) gastric cancer and 0 of 14 (0%) colon cancer cell lines showed AIS/TA-AIS gene expression. We then confirmed that the AIS gene, not the TA-AIS gene, was dominantly expressed in esophageal cancers by reverse transcription-PCR. AIS protein was also expressed in AIS gene-positive cell lines. Subsequently, we tested AIS gene expression in paired esophageal normal tissues and cancers. Twenty-five of 39 (64%) primary esophageal cancers demonstrated an obviously higher expression of AIS gene compared to paired normal tissues. Moreover, high AIS gene expression was significantly associated with lymph node metastases in esophageal cancer (P = 0.0271). These results suggested that AIS may be useful as a marker for advanced esophageal cancer.

Aged↗

Impact of tacrolimus and bone marrow augmentation on intestinal allograft survival and intragraft cytokine expression in rats.

Effects of simultaneous bone marrow transplantation (BMT) with a short course of tacrolimus on a heterotopic small bowel transplantation (SBT) were tested in a high responder rat combination of ACI (RT1avl) to LEW (RTIl). Intestinal allograft survival and changes of intragraft cytokine expression by this treatment were analyzed by reverse transcription polymerase chain reaction (RT-PCR). Only the treatment with donor specific BMT via portal vein plus a short course of tacrolimus (1.0 mg/Kg for 3 days) significantly prolonged allograft survival (mean +/- SD; 11.7 +/- 1.9 days), while the grafts were rejected at 4 to 8 days by other control treatments. More beneficial effect of donor type BMT via portal vein on allograft survival was achieved (19.0 +/- 2.2 days) by containing administration of a lower dose of tacrolimus (0.5 mg/Kg for 11 days). Both gene expression of IFN-gamma and infiltration of IFN-gamma-producing cells were strongly suppressed by this protocol, while tacrolimus treatment alone could not suppress IFN-gamma production. Tacrolimus treatment added with donor specific BMT down-regulated IL-12 and IFN-gamma transcript, resulted in a significant prolongation of intestinal allograft survival.

Animals↗