Biomedical subjects

Yuji Yamamoto

Publications and source records attributed to Yuji Yamamoto.

At least 73 records · Page 4Linked to original sources

PubMed2002

Temperature-related change in the properties relevant to drug delivery of poly(ethylene glycol)-poly(D,L-lactide) block copolymer micelles in aqueous milieu.

The block copolymers of poly(ethylene glycol) and poly(D,L-lactide) (PEG-PDLLA), the latter having a glass transition temperature (T(g)) around the physiological condition, was self-assembled into polymer micelles with a narrow and unimodal distribution in aqueous milieu either by dialysis or by the ultrasonication-aided dispersion method. The 1H NMR measurement of the PEG-PDLLA micelles in D(2)O revealed a gradual increase in the chain mobility of PDLLA segment in the core of the micelles at a temperature range above the T(g) of PDLLA. The critical association concentration (c.a.c.) of the PEG-PDLLA micelles was determined at various temperatures (25-55 degrees C) using pyrene as a probe to monitor the change in the polarity of the microenvironment in the micelle. An Arrhenius plot of the c.a.c. (ln(c.a.c.) versus 1/T) exhibited a break near T(g) of PDLLA. In sharp contrast with the linear decrease in ln(c.a.c.) versus 1/T in the region above the T(g), there was observed an almost constant c.a.c. (7-8 mg/l) regardless of the temperature change below the T(g). Furthermore, the chain exchange reaction between micelles was investigated based on the migration of the end-tagged block copolymers (alpha-lactosyl-PEG-PDLLA and omega-pyrenyl-PEG-PDLLA). The change in the binding affinity of the fluorescent micelles toward the RCA-1 lectin immobilized column was monitored with time to estimate the chain exchange. Consequently, appreciable acceleration in the chain exchange rate was revealed by increasing the surrounding temperature indicating the core mobility to be a substantial factor for inter-micellar chain migration. These results indicate that the engineering of the thermal characteristics of the core-forming segment of the block copolymer should be one of the crucial factors for optimizing the properties of the polymer micelles used for drug delivery.

Deuterium Oxide↗

PubMed2002

Multicompartmental distribution of the tuberous sclerosis gene products, hamartin and tuberin.

Mutations of the TSC1 and TSC2 genes give rise to the clinical disorder of tuberous sclerosis characterized by the development of hamartomas predominantly affecting the central nervous system, kidney, skin, lung, and heart. The function of the gene products, hamartin and tuberin, is not well understood but we have previously suggested a role in vesicular transport. To define the subcellular compartment(s) involved with these two proteins, biochemical characterization of hamartin and tuberin was performed in primary tissues and cell lines. Fractionation of cell lysates identified both proteins in the cytosolic, microsomal, and cytoskeletal compartments. In each of these fractions, hamartin and tuberin formed a stable complex in coimmunoprecipitation analyses. Further, they colocalized extensively in discrete, vesicular structures in the cytoplasm. Within the microsomal compartment, hamartin and tuberin behaved as peripheral membrane proteins that associate with the cytosolic leaflet of membranous domains. Immunoisolation of tuberin-bound vesicles using magnetic beads showed an enrichment of rap1, rab5, and caveolin-1, all of which have been found in specialized lipid microdomains, caveolae. Our data suggest that hamartin and tuberin are multicompartmental proteins that partially reside in caveolin-1-enriched structures and potentially affect their signaling.

Animals↗

PubMed2002

Is there a role for nontraditional resection of early gastric cancer?

Current trends in the treatment of gastric cancer indicate the emergence of a more sophisticated approach, with tailored therapy applied to individual cases. Treatment includes a broader spectrum of therapeutic options (Fig. 3), including EMR, laparoscopic or laparoscopy-assisted surgery, modified radical surgery, and typical radical surgery with lymph node dissections. Precise characterization of the lesions, especially the depth of invasion in the gastric wall, its size, histology and whether there is ulceration, is the key to successful treatment of N0 mucosal cancer. Micrometastasis and metastasis at the molecular level are issues that require further investigation. Laparoscopic surgery may be more widely accepted. The limitations of nodal dissection based on the concept of a sentinel node should be carefully evaluated in future studies. [figure: see text] Many treatment options, ranging from minimally invasive surgery to D2 node dissection, are available to the surgical oncologist who is treating EGC. As more information is gathered, surgeons will be better able to select patients who are good candidates for minimal surgical procedures.

Gastrectomy↗

PubMed2002

Typing of Y chromosome single nucleotide polymorphisms in a Japanese population by a multiplexed single nucleotide primer extension reaction.

We have developed a new method for typing single nucleotide polymorphisms (SNPs) on the human Y chromosome based on a multiplexed single nucleotide primer extension. This method has the advantage that several SNPs are typed rapidly and simultaneously. We examined 15 different SNP loci on Y chromosome, M9, M105, M122, M125, M128, M130, SRY465, IMS-JST006241, IMS-JST006841, IMS-JST002611, IMS-JST003305, IMS-JST008425, IMS-JST021354, IMS-JST021355 and IMS-JST055457, in 159 Japanese males. From the typing results of these 15 loci, we found 13 haplotypes. Gene diversity for each locus ranged from 0.025 to 0.486 and the haplotype diversity was estimated to be 0.838. This method could be readily applied for personal identification and paternity testing.

Journal Article↗

PubMed2002

Cyclooxygenase-2 mRNA is up-regulated in cirrhotic or chronic hepatitis liver adjacent to hepatocellular carcinoma.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is unique in that its carcinogenesis is related to inflammatory changes and regenerative activities in the background liver. Although there are some data on cyclooxygenase (COX)-2 expression in HCC by immunohistochemical studies, little is known about the possible role of COX-2 in inducing hepatitis and/or carcinoma. To elucidate whether COX-2 is involved in a part of these processes, we attempted to examine COX-2 mRNA both in the adjacent non-tumoral liver and in HCC. METHODS: Twenty-two matched sets of adjacent liver and HCC specimens were analyzed for COX-2 mRNA expression using a real-time quantitative reverse transcription polymerase chain reaction. Cyclooxygenase-2 protein expression was also determined by immunohistochemistry. RESULTS: Cyclooxygenase-2 mRNA expression was significantly higher in the adjacent liver than in HCC (P = 0.016). Cyclooxygenase-2 mRNA expression in adjacent liver tissues was positively correlated with the modified histological activity index scores (r = 0.575, P = 0.006), the serum alanine aminotransferase levels (r = 0.536, P = 0.010), and the Ki-67 labeling indices (r = 0.698, P = 0.001). In contrast, COX-2 mRNA expression in HCC was not correlated with any of the clinicopathological features. CONCLUSIONS: Cyclooxygenase-2 is expressed at higher levels in the adjacent liver than in HCC, and it may be associated with high levels of necroinflammation and regeneration in the background liver. Conversely, COX-2 may have a lesser role in the progression of HCC.

Aged↗

PubMed2002

Possible involvement of increased glycoxidation and lipid peroxidation of elastin in atherogenesis in haemodialysis patients.

BACKGROUND: Glycoxidation and lipid peroxidation products accumulate in collagen of various tissues in haemodialysis patients with end-stage renal disease (ESRD). The purpose of this study was to test the hypothesis that increased glycoxidation and lipid peroxidation of aortic elastin is implicated in the cardiovascular complications, particularly atherosclerosis, of chronic haemodialysis patients. METHODS: Post-mortem aortic samples were obtained from 16 deceased subjects, including chronic haemodialysis patients (group 1 n=6, age 64.7+/-11.4 years) and control subjects (group 2 n=10, age 61.1+/-10.4 years). The samples were divided into three vessel wall sites: atherosclerotic intima, lesion-free intima, and media. They were sequentially treated with 0.01 M phosphate-buffered saline, collagenase, and elastase to obtain three fractions, namely soluble (SF), collagen (CF), and elastin (EF) fractions, respectively. Using spectrophotofluorometry, the pentosidine- and malondialdehyde (MDA)-linked fluorescence of these fractions was measured at wavelengths 335/385 and 390/460 (excitation/emission), respectively. RESULTS: Samples from haemodialysis patients (group 1) exhibited a significant increase in both pentosidine- and MDA-linked fluorescence of EF in atherosclerotic intima, lesion-free intima, and media samples, compared with samples from control subjects (group 2). In group 1, the levels of pentosidine- and MDA-linked fluorescence of EF were highest in atherosclerotic intima among the three aortic sites. Interestingly, in both groups, the levels of pentosidine- and MDA-linked fluorescence of EF were significantly higher than those of CF in all aortic sites. There was a strong correlation between the levels of pentosidine- and MDA-linked fluorescence in CF and EF for all aortic sites. In group 1, the pentosidine- and MDA-linked fluorescence levels of EF correlated significantly with the duration of haemodialysis in lesion-free intima and media. CONCLUSIONS: Our study provides the first biochemical evidence for a close link between aortic elastin glycoxidation and lipid peroxidation. In addition, we demonstrated high levels of these products in the aortic elastin of haemodialysis patients with ESRD. Our findings support the hypothesis that modification of aortic elastin by glycoxidation and lipid peroxidation may contribute to the development of vascular complications, particularly atherosclerosis, in patients with end-stage renal failure.

Arteriosclerosis↗

PubMed2002

A frameshift mutation of beta subunit of epithelial sodium channel in a case of isolated Liddle syndrome.

BACKGROUND: Liddle syndrome is an autosomal dominant form of salt-sensitive hypertension caused by mutations in the epithelial sodium channel expressed in the distal nephron playing an essential role in Na absorption. All reported mutations in Liddle syndrome are either missense mutations or frameshift mutations destroying the PY motif closer to the C-terminus of the beta or gamma subunits causing the situation that the epithelial sodium channels are not degraded and sodium is pooled and thus hypertension and hypokalemia are caused. METHODS: We sequenced the C-terminus of the beta or gamma subunits of the epithelial sodium channel in a Japanese family of a patient clinically diagnosed as having Liddle syndrome. RESULTS: As a result, we found in the proband, a frameshift mutation of the beta subunit caused by a single cytosine insertion at the codon 595, introducing a new stop codon at 605 and deleting the last 34 amino acids from the normally encoded protein. CONCLUSION: This mutation is carried by neither parent (with paternity proven) and hence confirms this has occurred as a event within this family.

Adolescent↗

PubMed2002

An iron-binding protein, Dpr, from Streptococcus mutans prevents iron-dependent hydroxyl radical formation in vitro.

The dpr gene is an antioxidant gene which was isolated from the Streptococcus mutans chromosome by its ability to complement an alkyl hydroperoxide reductase-deficient mutant of Escherichia coli, and it was proven to play an indispensable role in oxygen tolerance in S. mutans. Here, we purified the 20-kDa dpr gene product, Dpr, from a crude extract of S. mutans as an iron-binding protein and found that Dpr formed a spherical oligomer about 9 nm in diameter. Molecular weight determinations of Dpr in solution by analytical ultracentrifugation and light-scattering analyses gave values of 223,000 to 292,000, consistent with a subunit composition of 11.5 to 15 subunits per molecule. The purified Dpr contained iron and zinc atoms and had an ability to incorporate up to 480 iron and 11.2 zinc atoms per molecule. Unlike E. coli Dps and two other members of the Dps family, Dpr was unable to bind DNA. One hundred nanomolar Dpr prevented by more than 90% the formation of hydroxyl radical generated by 10 microM iron(II) salt in vitro. The data shown in this study indicate that Dpr may act as a ferritin-like iron-binding protein in S. mutans and may allow this catalase- and heme-peroxidase-deficient bacterium to grow under air by limiting the iron-catalyzed Fenton reaction.

Bacterial Proteins↗

PubMed2002

Allele frequencies of single nucleotide polymorphisms in the second exon of the myoglobin gene among the Japanese.

The difference in the allele frequencies of two single nucleotide polymorphisms (SNPs) in the second exon of the myoglobin gene between Japanese and other populations is reported. These SNPs are the substitutions of (A79G) and (T109C), and they were investigated by a single polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis followed by direct sequencing. The substitutions were always linked and two alleles were found in the samples used: the A-T allele with no substitution at positions (79A) and (109T) and the G-C allele with substitutions of (79G) and (109C). The frequencies of these alleles were 0.755 and 0.245, respectively, and they were found to be in Hardy-Weinberg equilibrium. The distribution of alleles in the Japanese population was significantly different from that reported among whites, blacks, and Hispanics (p < 0.0001).

Alleles↗

PubMed2002

Evaluation of a method for typing the microsatellite D12S391 locus using a new primer pair and capillary electrophoresis.

We describe a modified method for typing a polymorphic microsatellite D12S391 locus by PCR using a newly designed primer pair. This primer pair produces shorter D12S391 amplified fragments (104-156 bp) than the primer pair originally described by Lareu et al. (209-261 bp). The detection system for the D12S391 locus using the new primer pair and capillary electrophoresis (CE) analysis was evaluated using various forensic samples. The typing results from 70 DNA samples using the new primer pair and the original primer pair were completely identical. One hundred twenty-five amplified fragments from D12S391 alleles were sized correctly within +/- 0.25 bp of the D12S391 allelic ladder. A rare allele, 19.3, previously found only in Caucasians, was found for the first time in a Japanese subject, and it was clearly distinguished from allele 20 by the CE analysis. This detection system was sensitive and could detect D12S391 types from 16 pg of genomic DNA, and from a minor component at a ratio of 1:10 in mixed samples. This system was more useful for the analysis of degraded DNA than was the method using the original primer pair, and could detect D12S391 types from bloodstains that had been stored for 26 years. In addition, the specificity of the method was demonstrated using nonhuman DNA.

Alleles↗

PubMed2002

A case of suffocation by an advertising balloon filled with pure helium gas.

We encountered a rare case of suffocation by an advertising balloon filled with pure helium gas. Suffocation caused by inhalation of atmosphere lacking in oxygen is not exceptional, but reports of death by suffocation due to a pure inert gas such as helium are very rare. In this case, the balloon mooring on the ground was enclosed, warning signs were displayed, and it was clear that entering the balloon filled with an atmosphere lacking in oxygen was extremely dangerous and should not be done; the accident did, however, occur. Accidents of this kind may occur in the future unless appropriate education and countermeasures are taken.

Accidents↗

PubMed2002

Dietary fiber suppresses elevations of uric acid and allantoin in serum and urine induced by dietary RNA and increases its excretion to feces in rats.

This study was performed to examine the effects of several kinds of dietary fibers (DF) with different physical properties on dietary RNA metabolism. Male Wistar strain rats, 4 wk old, were fed diets with or without a 3% yeast RNA and a 5% DF (cellulose, chitin, chitosan, inulin, and xanthan gum) for 20 d (Experiment 1) or 5 d (Experiment 2). Feeding DF tested lowered the serum uric acid and allantoin concentrations and the urinary excretions of their compounds and increased the amount of RNA excreted into the feces compared with fiber-free. The water-holding capacity and nucleotide adsorption of chitin and chitosan in acidic solutions were higher than those of cellulose. The digestion rate of RNA by RNase A in vitro was found to be lower in the DF tested than in fiber-free. The decrease was remarkable in chitosan and xanthan gum. The uptakes of 14C-labeled adenosine and adenosine 5'-monophosphate (5'-AMP) in the rat jejunum were markedly decreased in regard to chitosan and xanthan gum in comparison with the fiber-free. These phenomena suggest that DF with high viscosity is more strongly associated with the suppression of RNA digestion by RNase A and the depression of the uptake of purine compounds to jejunum. The present results reveal that the elevation of serum uric acid concentration induced by dietary RNA can be suppressed by DF in rats.

Adsorption↗

PubMed2002

[Rupture of previously documented asymptomatic unruptured aneurysms--aneurysm size: risk factor for aneurysm rupture].

The natural history of asymptomatic unruptured aneurysms is not clear. We conducted a follow up study of 100 patients (since 1993) with 122 asymptomatic unruptured aneurysms that had not been operated on. We report five patients with previously documented asymptomatic unruptured aneurysms smaller than 10 mm in diameter that subsequently ruptured. Among the 100 patients, five had suffered subarachnoid hemorrhage (SAH) due to rupturing of an aneurysm. Of the 5 cases, 1 was male and 4 were female, with ages ranging from 59-73 years (mean age, 68 years). The aneurysms were on the MCA in 3, on the BA-SCA in 1, on the IC-PC in 1. The maximal diameter of the aneurysms at diagnosis ranged from 4.5 to 8 mm. The period from discovery to SAH was from 4 to 69 months and the cumulative rate of rupture of the aneurysms was 1.5 percent per year. Four of the 5 cases increased in size after the rupture. In our series, 2 of the 5 cases showed enlargement and the development of an aneurysmal bleb in the follow up MRA and 3D-CTA. The present study demonstrates that five asymptomatic unruptured aneurysms less than 10 mm in diameter subsequently ruptured. We ought to seriously consider the assertion published in the New England Journal of Medicine (Dec. 10, 1998), that unruptured aneurysms less than 10 mm in diameter have a very low probability of subsequent rupture.

Aged↗

PubMed2002

[Recurrence of right breast cancer at the thoracic wall successfully treated with intra-arterial infusion of doxorubicin hydrochloride--a case report].

We report a recurrent case of breast cancer successfully treated with intra-arterial infusion of doxorubicin hydrochloride (ADM) combined with systemic CAF therapy. The patient, a 37-year-old woman, was diagnosed with a recurrence at the thoracic wall 55 months after curative resection for right breast cancer. She was treated with intra-arterial infusion chemotherapy of ADM, 30 mg, combined with systemic CAF therapy of cyclophosphamide, 100 mg from days 1 to 14, ADM, 30 mg on days 1 and 8, and 5-fluorouracil, 500 mg on days 1 and 8, as one course. Two courses of the treatment resulted in a complete response of the tumor. This result suggests that local and systemic chemotherapy could be effective for the treatment of local recurrence of breast cancer.

Adult↗

PubMedDate not supplied

Spleen-preserving laparoscopic distal pancreatectomy for cystic adenoma.

For borderline malignant diseases of the pancreas such as cystic adenoma, partial pancreatectomy or pancreatoduodenectomy including pylorus-preserving pancreaticoduodenectomy have been performed depending on tumor location under large median laparotomy. To investigate the feasibility of a technique with minimal skin incision, while retaining safety equivalent to conventional resection of the pancreatic tail, by making use of the advantages of laparoscopic procedure, we performed a minimally invasive laparoscopic resection of the pancreatic tail with preservation of the spleen. A 69-year-old woman underwent surgery for a diagnostic therapy for a cystic lesion of the pancreatic tail. The procedure was performed as follows: All procedures were performed completely laparoscopically under CO2 insufflation. After dissection of the omentum, laparoscopic ultrasound was performed to identify the location of the tumor and splenic vessels. The splenic hilus was dissected with preservation of the splenocolic ligament to maintain the lower blood supply to the spleen. The left gastroepiploic artery and the short gastric arteries and veins could be preserved. After division of the splenic hilus, the splenic artery and vein were identified from behind the pancreas by being held up and dissected individually by intracorporeal ligation by 3-0 Nylon. Then, pancreatic transection was performed 1 cm proximal to the tumor with the Endo-GIAII. The duration of operation was 4.5 hours. Intraoperative blood loss was under 50 mL. Histological examination revealed mucinous cytadenoma. She could walk the day after surgery and was discharged from the hospital uneventfully. CT prior to discharge from the hospital revealed sufficient blood flow in the spleen. Thus, it may be feasible to select laparoscopic spleen-preserving distal pancreatectomy as a first choice for diagnostic therapy for cystic lesions of the pancreatic tail.

Aged↗

PubMedDate not supplied

Does pancreaticosplenectomy contribute to better survival?

BACKGROUND/AIMS: This study was conducted to clarify the impact of pancreaticosplenectomy on the prognosis of patients with gastric carcinoma. METHODOLOGY: Two hundred and seventy-two patients who underwent total gastrectomy with distal pancreatectomy and splenectomy were retrospectively reviewed. RESULTS: Lymph node metastases at the splenic hilum (#10) and along the splenic artery (#11) occurred in 12.4% and 19.2% of cases, respectively. The 5-year survival rate of those without metastasis at #10 was 62.8%. Once nodal metastasis occurred, the prognosis became very poor; only 18.2% in those with a single positive node and 15.4% of those with two or more positive nodes at this location survived 5 years. Similar trends in survival were observed with respect to nodes at #11. When stratified by nodal status as currently determined by microscopic examination, pancreaticosplenectomy saved 4.5% of patients with positive nodes, but was insufficient in 17.3% of cases and was not necessary in the 78.2% of cases who were node negative at these locations. CONCLUSIONS: The data indicate that pancreaticosplenectomy can save some patients with positive nodes in these regions; however, the small survival benefit does not provide a basis for the general application of this highly morbid procedure. To further evaluate these results in a randomized study, selection of a subset of patients who are likely to have metastasis is the key.

Gastrectomy↗

PubMedDate not supplied

Platelet-derived endothelial cell growth factor (PD-ECGF) is up-regulated in human hepatocellular carcinoma (HCC) and the corresponding hepatitis liver.

BACKGROUND/AIMS: Platelet-derived endothelial cell growth factor (PD-ECGF) is one of the angiogenic factors. The aim of this study was to examine the PD-ECGF concentrations in hepatocellular carcinoma, background liver, and normal liver tissues, and to elucidate their significance on clinicopathological outcomes. METHODOLOGY: The concentration of PD-ECGF in the tissue extract was determined by enzyme-linked immunosorbent assay. RESULTS: PD-ECGF concentrations were significantly higher in hepatocellular carcinoma and background liver tissues compared with normal control liver (p = 0.003, p = 0.001, respectively). PD-ECGF concentrations in hepatocellular carcinoma tissues were positively correlated with intratumoral arteriole densities (r = 0.667, p = 0.009), and were higher in less differentiated carcinomas (p = 0.039). However, tumor PD-ECGF concentration did not affect the patients' disease-free survival rates. Those in the background liver tissues were positively correlated with histological activity index scores (r = 0.650, p = 0.001) and serum alanine aminotransferase levels (r = 0.0452, p = 0.035). CONCLUSIONS: PD-ECGF is up-regulated in hepatocellular carcinoma and the corresponding hepatitis liver. The PD-ECGF concentrations in hepatocellular carcinoma correlated positively with microvessel density, lower differentiation, yet not with patients' prognosis. The concentrations of PD-ECGF in the corresponding hepatitis liver correlated positively with the degree of active hepatitis.

Alanine Transaminase↗

PubMedDate not supplied

Is bursectomy necessary for patients with gastric cancer invading the serosa?

BACKGROUND/AIMS: To confirm the impact of bursectomy on survival, we reviewed the clinical records of patients who underwent radical total gastrectomy with bursectomy for gastric cancer invading the serosa, with special reference to the location of tumor invasion. METHODOLOGY: From the records, patients were selected for this retrospective cohort study according to the following criteria: (a) Invasion beyond the serosal surface, (b) No metastases to liver, peritoneum, or distant organs, (c) Negative for peritoneal lavage cytology, and (d) Patients underwent curative D2 total gastrectomy with complete omental bursectomy. A total of 134 patients were eligible. These patients were divided into a group I which included patients with tumors that invaded only the posterior wall and a group II which included those with others. Survival was examined by uni- and multivariate analyses. RESULTS: Survival rates at 3 and 5 years were 67.3% and 53.0% for group I and 68.8% and 53.8% for group II. There was no significant difference in the survival between the two groups (p=0.969), even if survival was stratified by various clinicopathological factors. Multivariate analyses demonstrated that the significant independent factors for the survival were macroscopic type and lymph node metastasis. Location of the invasion was not a significant factor. CONCLUSIONS: These results suggested that bursectomy did not inhibit the spreading of tumor cells into the retro-stomach space. There might be no survival benefit of bursectomy in patients with gastric cancer.

Adult↗