Biomedical subjects

Hirofumi Yamada

Publications and source records attributed to Hirofumi Yamada.

15 recordsLinked to original sources

PubMed2006

Electrospray deposition, model, and experiment: toward general control of film morphology.

Poly(vinylidene fluoride) film formation with electrospray deposition has been studied with support of a droplet evaporation model. The input parameters of the model consist basically of the solvent, the solute concentration, the flow rate, and the solution conductivity. The model provides the droplet size, the solute concentration, the droplet velocity, and the shear stress of the droplet at impact as a function of the distance between the nozzle and the substrate. With some additional experimental information such as the size change of the film with spray distance and the viscosity of the solution, the growth rate of the film and the shear rate of the droplet at impact can be determined. Growth rate is shown to define distinct regimes of film formation. In those regimes, only a single factor or a limited number of factors controls the film morphology. The most important factors include the shear rate and the surface energy. It is found that at a specific range of growth rates only the shear rate determines the morphology of the polymer film. Growth rate, as the defining quantity of film morphology, is not limited to polymer solutions. Therefore, the growth rate, in combination with the control factors mentioned above, functions as a general framework through which understanding and control of film formation with electrospray deposition can be improved.

Journal Article↗

PubMed2005

Eukaryotic RNases H1 act processively by interactions through the duplex RNA-binding domain.

Ribonucleases H have mostly been implicated in eliminating short RNA primers used for initiation of lagging strand DNA synthesis. Escherichia coli RNase HI cleaves these RNA-DNA hybrids in a distributive manner. We report here that eukaryotic RNases H1 have evolved to be processive enzymes by attaching a duplex RNA-binding domain to the RNase H region. Highly conserved amino acids of the duplex RNA-binding domain are required for processivity and nucleic acid binding, which leads to dimerization of the protein. The need for a processive enzyme underscores the importance in eukaryotic cells of processing long hybrids, most of which remain to be identified. However, long RNA-DNA hybrids formed during immunoglobulin class-switch recombination are potential targets for RNase H1 in the nucleus. In mitochondria, where RNase H1 is essential for DNA formation during embryogenesis, long hybrids may be involved in DNA replication.

Amino Acid Sequence↗

PubMed2005

Incarcerated recurrent rectal prolapse with ileal strangulation: report of a case.

We report a rare case of incarcerated rectal prolapse with ileal strangulation occurring after a Gant-Miwa procedure with anal encircling (Thiersch's procedure) for recurrent rectal prolapse. The patient was a 78-year-old woman who presented to our outpatient clinic the day after sudden rectal protrusion had occurred. She had undergone a Gant-Miwa procedure for rectal prolapse 4 years previously, and another Gant-Miwa procedure with anal encircling for recurrent rectal prolapse 18 months earlier. The patient attempted to reduce the prolapse manually, but was unsuccessful. On admission, a 10 x 4-cm semispherical mass was observed extra-anally, with a necrotic surface. We performed an emergency laparotomy, which rerealed a prolapse of the anterior wall of the rectum with part of the ileum protruding into the sac formation. Thus, we resected the incarcerated ileum followed by primary anastomosis and proctectomy (Hartmann's procedure) with good results. This case demonstrates that ileal strangulation can occur as a complication of rectal prolapse recurrence after perineal repair.

Aged↗

PubMed2004

Glyceraldehyde 3-phosphate dehydrogenase is a novel autoantigen leading autoimmune responses to proliferating cell nuclear antigen multiprotein complexes in lupus patients.

Using 2-dimensional electrophoresis and ion-pair chromatography, we have identified elements of proliferating cell nuclear antigen (PCNA) multiprotein complexes that are reactive to antibodies in sera from patients with systemic lupus erythematosus. Among the various elements of the complexes, a 37 kDa protein (PI 8.5) that specifically reacted with SLE sera, but not with sera from patients with other connective tissue diseases, was identified as glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Immunoblot analysis showed that SLE sera reactive with the 37 kDa protein specifically reacted with GAPDH, as did anti-GAPDH mAbs. The purified autoantibodies to GAPDH from lupus serum showed both nuclear speckled and cytoplasmic staining patterns in immunofluorescence on Hep-2 cells. In addition, enzyme-linked immunosorbent assay (ELISA) revealed the presence of anti-GAPDH autoantibodies in 47% of lupus patients. Longitudinal analysis of the reactivity of lupus sera to PCNA complexes showed the autoimmune response to spread from GAPDH to other elements of PCNA complexes, and the presence of anti-GAPDH antibodies was significantly correlated with increased levels of serum PCNA. Taken together, these findings suggest that GAPDH interacting with PCNA in association with its cellular function is a novel autoantigen recognized by lupus sera, and that GAPDH thus plays an important role in the induction of autoimmune responses against the PCNA complex.

Animals↗

PubMed2004

Anorectal agenesis with a rectourethral fistula diagnosed in an adult: report of a case.

We report an unusual case of anorectal agenesis with a rectourethral fistula diagnosed in a 48-year-old man. The patient presented after noticing hematuria, although he had been aware of urinary leakage from his colostomy with occasional fecal urine for about 4 years. He had had a double-barrel colostomy created soon after birth for an imperforate anus, with revision at the age of 4 years to correct a prolapse of the stoma, but his malformation had never been repaired. We performed a physical examination, which did not reveal a perineal fistula, but urethrocystography demonstrated high anorectal agenesis with a rectourethral fistula. Thus, we resected the rectourethral fistula and created an end-colostomy. The patient had an uneventful postoperative course, and was discharged in good health on postoperative day 19. To our knowledge, this is the oldest patient to be diagnosed with anorectal agenesis and undergo resection of a rectourethral fistula.

Anus, Imperforate↗

PubMed2004

Anticyclic citrullinated peptide antibodies in patients with mixed connective tissue disease.

The clinical significance of anticyclic citrullinated peptide (CCP) antibodies in patients with mixed connective tissue disease (MCTD) was assessed. Altogether, 86 sera from MCTD patients, 96 from rheumatoid arthritis (RA) patients, 42 from systemic lupus erythematosus (SLE) patients, 23 from systemic sclerosis (SSc) patients, 21 from polymyositis/dermatomyositis (PM/DM) patients, and 17 from those with Sjögren's syndrome (SjS) were tested for anti-CCP antibodies using an enzyme-lined immunosorbent assay. Among the 96 RA patients, anti-CCP antibodies were detected in 85%, with the frequency being significantly higher than in MCTD, SLE, SSc, PM/DM, and SjS patients (9%, 14%, 13%, 14%, and 18%, respectively; P < 0.001). Among eight MCTD patients who fulfilled the diagnostic criteria for RA, only 50% had anti-CCP antibodies, and the prevalence was significantly lower than for all RA patients (p < 0.01). All eight patients who fulfilled the criteria for RA had overlap of SLE and SSc, except one patient, whereas the four anti-CCP-positive patients who did not fulfill the criteria for RA had SjS without overlapping features of SLE and SSc; moreover, most of their antibody titers were low. These results suggested that anti-CCP antibodies are associated with RA in MCTD patients, but careful diagnosis of RA is required if patients with low titers of anti-CCP antibodies lack overlapping SLE and SSc.

Journal Article↗

PubMed2004

Autoimmune response to proteasome activator 28alpha in patients with connective tissue diseases.

OBJECTIVE: To determine the autoimmune response against proteasome activator 28alpha (PA28alpha) in patients with various connective tissue diseases, and to compare the immunoreactivity between anti-PA28alpha and anti-Ki antibodies. METHODS: Serum samples were obtained from 219 patients with various connective tissue diseases. cDNA encoding full-length human PA28alpha and Ki were produced by polymerase chain reaction. Antigens were expressed as glutathione S-transferase (GST) fusion proteins. The immunoreactivity of serum for PA28alpha and Ki was studied by Western blotting. An inhibition test was performed by ELISA using purified Ki antigen. RESULTS: Anti-PA28alpha> antibody was detected in serum from 23% of patients with systemic lupus erythematosus (SLE) and 24% with Sjögren's syndrome (SS). These rates were significantly higher than those for the other rheumatic diseases. Since both PA28alpha and Ki are elements of the PA28 complex and their amino acid sequences share 40.2% homology, immunoreactivity to PA28alpha was studied further. Among 27 anti-Ki positive serum samples, 13 samples (48%) also reacted with PA28alpha, suggesting a relationship between anti-PA28alpha and anti-Ki antibodies. To investigate whether this finding was due to the presence of cross-reacting epitopes for PA28alpha and Ki antigens, an inhibition test was performed by ELISA. The reactivity to purified Ki antigen was not inhibited by preincubation with recombinant PA28alpha. CONCLUSION: Detection of anti-PA28alpha antibody was significantly higher in serum from patients with SLE and SS. The relationship between anti-PA28alpha and Ki antibodies suggests the importance of an antigen-driven system in the induction of an autoimmune response to PA28 complex.

Antibody Specificity↗

PubMed2004

[Tumoral dihydropyrimidine dehydrogenase expression and efficacy of 5-fluorouracil plus leucovorin plus UFT therapy in patients with colorectal cancer].

The purpose of this study was to examine the relation between tumoral expression of dihydropyrimidine dehydrogenase (DPD), the rate limiting enzyme of the degradation pathway 5-fluorouracil (5-FU), and the efficacy of 5-FU based chemotherapy for colorectal cancer. Twenty-eight colorectal cancer patients who had underwent noncurative resection (n = 16) or had developed recurrence (n = 12) were enrolled. All patients were given 5-FU plus leucovorin intravenously and UFT (1 M Tegafur, 4 M Uracil) perorally. The expression levels of the DPD in the primary lesions were determined by the enzyme-linked immunosorbent assay. Group A (n = 10) consisted of one patient with complete response, 4 with partial response, and 5 with no change (time to disease progression (TTP) > = 90 days). Group B (n = 18) consisted of 14 patients with progressive disease and 4 with NC (time to progression, < 90 days). The tumoral DPD levels did not differ between the groups (p = 0.58). There were no effective cases (n = 6) whose tumoral DPD levels were equal to or more than 83.2 U/mg protein (high DPD expression). There were marked overlaps in the DPD levels between the two groups whose DPD levels were less than 83.0 U/mg protein (moderate or low expression). These results suggest that high expression of tumoral DPD would be predictive to failure of fluoropyrimidine-based treatment. However, it is unlikely to set the optimal cutoff value for predicting the efficacy of this type of chemotherapy.

Adult↗

PubMed2004

Autoimmune response to proteins of proliferating cell nuclear antigen multiprotein complexes in patients with connective tissue diseases.

OBJECTIVE: To analyze the autoimmune response to the proliferating cell nuclear antigen (PCNA) multiprotein complex in patients with connective tissue diseases (CTD). METHODS: The PCNA complex was purified by affinity chromatography using anti-PCNA monoclonal antibodies. Then 196 serum samples from patients with systemic lupus erythematosus (SLE) and 82 from patients with other CTD were tested for reactivity with the complex by immunoblotting. RESULTS: Of 196 SLE sera, 61 (31%) reacted with at least one component of the PCNA complex, and most reactive sera contained autoantibodies to several components of the complex. Autoantibodies to PCNA complex were less common in patients with other CTD, and most of their sera reacted only with one or a few proteins in the complex. Two out of 20 scleroderma sera reactive with 100, 85, and 70 kDa proteins in the PCNA complex also had autoantibodies to topoisomerase I (topo I) antibodies, which is an element of the complex. These findings suggest that the autoimmune response to the PCNA complex was specific for SLE. Anti-PCNA complex antibodies were associated with an increased serum level of PCNA detected by ELISA. The spreading of the autoimmune response to the elements of the complex was observed in parallel with the increased serum PCNA level when a series of sera from a lupus patient were tested longitudinally. In addition, anti-PCNA complex antibodies were significantly correlated with lupus erythematosus cells. CONCLUSION: The "antigen-drive" system may play a crucial role in inducing the autoimmune response to the PCNA complex in patients with SLE.

Autoimmunity↗

PubMed2003

Fatal deep vein thrombosis after allogeneic reduced intensity hematopoietic stem cell transplantation for the treatment of metastatic gastric cancer.

A 61-year-old man received reduced intensity stem cell transplantation (RIST) for the treatment of metastatic gastric cancer. The cytoreductive course of RIST was uneventful until day 0, when fever suddenly developed and his performance status deteriorated. Edema developed in the bilateral lower extremities by day 7, which was diagnosed by Doppler ultrasonography as deep vein thrombosis (DVT) involving the femoral veins to the inferior vena cava. While the edema improved with anticoagulation treatment, gastrointestinal graft-versus-host disease (GVHD) followed on day 13. Diarrhea subsided spontaneously, but hypoalbuminemia persisted, with the subsequent development of oliguria and jaundice on day 18. He died of sepsis on day 30, without any evidence of cancer progression. This case demonstrates that DVT is a potentially significant problem following RIST for solid tumors.

Anticoagulants↗

PubMed2003

Selective inhibitory DNA aptamers of the human RNase H1.

Human RNase H1 binds double-stranded RNA via its N-terminal domain and RNA-DNA hybrid via its C-terminal RNase H domain, the latter being closely related to Escherichia coli RNase HI. Using SELEX, we have generated a set of DNA sequences that can bind efficiently (K(d) values ranging from 10 to 80 nM) to the human RNase H1. None of them could fold into a simple perfect double-stranded DNA hairpin confirming that double-stranded DNA does not constitute a trivial ligand for the enzyme. Only two of the 37 DNA aptamers selected were inhibitors of human RNase H1 activity. The two inhibitory oligomers, V-2 and VI-2, were quite different in structure with V-2 folding into a large, imperfect but stable hairpin loop. The VI-2 structure consists of a central region unimolecular quadruplex formed by stacking of two guanine quartets flanked by the 5' and 3' tails that form a stem of six base pairs. Base pairing between the 5' and 3' tails appears crucial for conferring the inhibitory properties to the aptamer. Finally, the inhibitory aptamers were capable of completely abolishing the action of an antisense oligonucleotide in a rabbit reticulocyte lysate supplemented with human RNase H1, with IC50 ranging from 50 to 100 nM.

Animals↗

PubMed2003

[Results of prophylactic hepatic arterial chemotherapy for liver metastases of Dukes C colorectal cancer--correlation with tumoral expression of dihydropyrimidine dehydrogenase, thymidylate synthase, p53, or orotate phosphoribosyl transferase].

The purpose of this study was (1) to disclose data from a non-randomized trial of prophylactic hepatic arterial chemotherapy for liver metastases from Dukes'C colorectal cancer, (2) to examine the influence of the expression of dihydropyrimidine dehydrogenase (DPD), thymidylate synthase (TS), and p53 in the primary lesion on this chemotherapy, and (3) to examine the expression of orotate phosphoribosyl transferase (OPRT) mRNA levels in the cases of recurrence included in this study. Patients who underwent curative resection of Dukes'C colorectal cancer between November 1996 and April 2000 were examined. After curative resection, patients were non-randomly divided into two groups after obtaining their informed consent: Hepatic arterial infusion (HAI) group patients (n = 28) were given 5-FU (500 mg/body for 1 h per week, repeated 50 times) via the hepatic artery and peroral UFT-E after resection of Dukes'C colorectal cancer. Control group patients (n = 21) received UFT-E alone. Liver metastasis-free survival did not differ between the groups. Immunohistochemical examinations revealed that the expression of tumoral DPD or p53 was unlikely to affect the hepatic recurrence, although patients with a low expression of TS tended to have better survival in both groups. However, multivariate analysis by the Cox proportional hazard model revealed that a significant prognostic factor influencing the hepatic recurrence is extensive venous invasion. Expression levels of OPRT mRNA, measured in tumors of patients with recurrence (n = 6 for the HAI group; and n = 4 for the control group) were not significantly different between the groups. These results suggest that (1) intermittent hepatic arterial infusion of 5-FU in addition to oral UFT-E was not more useful than administration of UFT alone, and (2) the expression of DPD, TS, p53, and OPRT in the primary lesion was unlikely to affect the prognosis of patients included in this study.

Adult↗

PubMed2002

Autoimmune responses to proliferating cell nuclear antigen multiprotein complexes involved in cell proliferation are strongly associated with their structure and biologic function in patients with systemic lupus erythematosus.

OBJECTIVE: To analyze the reaction of lupus sera with proliferating cell nuclear antigen (PCNA) multiprotein complexes (PCNA complexes), which are part of the protein machinery involved in cell proliferation. METHODS: PCNA complexes were purified from rabbit thymus extract by affinity chromatography using anti-PCNA monoclonal antibodies (TOB7, TO17, and TO30); monomeric and trimeric PCNA forms (AK-PCNA) were purified using anti-PCNA serum AK. The reactions to these antigens of 10 anti-PCNA-positive and 40 anti-PCNA-negative sera selected from 560 lupus patients were tested by immunoblotting, immunoprecipitation, and enzyme-linked immunosorbent assays (ELISAs). RESULTS: With one exception (serum OK), anti-PCNA-positive sera reacted exclusively with only the 34-kd polypeptide. In contrast, 14 of 40 anti-PCNA-negative sera reacted with multiple proteins within PCNA complexes. Most anti-PCNA-positive sera probably recognize as epitopes the binding sites for other proteins on PCNA, which are likely hidden when PCNA is complexed with other proteins. As a consequence, only serum OK reacted with the PCNA complex in a series of ELISAs. Using AK-PCNA as a competitive inhibitor, it was determined that serum OK reacts with both the 58-kd polypeptide and the 34-kd PCNA within complexes. Together with the results of a longitudinal analysis, these results suggest that the immune system of patient OK likely recognized the complexed PCNA protein, after which the autoimmune response spread to other elements of the complexes. CONCLUSION: Intermolecular-intrastructural help, leading to the spread of autoimmune response from PCNA to other proteins associated with its biologic function, plays a crucial role in the induction of the autoimmune response seen in lupus patients.

Antibodies, Monoclonal↗

PubMed2002

Ferroelectric molecular films for nanoscopic ultrahigh-density memories.

The formation and visualization of nanometer-scale polarized domains in ultrathin ferroelectric molecular films by scanning-probe microscopy are described. These operations to the ferroelectric domains correspond to the "writing" and the "reading" process, respectively, for the data-storage application. In addition, nanometer-scale structures and the local electrical properties of the local domains, including the interface effect, are discussed. The achieved minimum diameter of the written ferroelectric domains was 30 nm. The size of the "recording" dot corresponds to the recording density of about 230 Gbit/in.(2). The "erasing" process by switching domains was also demonstrated. Furthermore, nanometer-scale ferroelectric domains using VDF oligomer molecular films were successfully formed, which has opened the way to the control of single molecular dipoles.

Iron↗

PubMed2002

[Hepatic recurrence after prophylactic hepatic arterial infusion of 5-fluorouracil for Dukes' C colorectal cancer--correlation with the expression of dihydropyrimidine dehydrogenase in the primary tumor].

PURPOSE: The purpose of this study was twofold: (1) to disclose the intermediate outcome of a non-randomized trial of prophylactic hepatic arterial infusion chemotherapy (PHAI) for curatively resected Dukes' C colorectal cancer performed between November 1996 and April 2000, and (2) to examine the relationship between the expression of dihydropyrimidine dehydrogenase (DPD) in tumor tissue and the efficacy of this chemotherapy. PATIENTS AND METHODS: The oncological outcomes were compared between patients (n = 28) receiving PHAI (5-FU: 500 mg/body/w x 50 cycles) plus oral administration of UFT-E (400 mg/body/day, for 24 months) and those (n = 21) receiving UFT-E alone. The levels of tumoral DPD were determined in a total of 43 patients (n = 25, PHAI group; n = 18, control group) by an enzyme-linked immunosorbent assay. RESULTS: Seven (25%) in the PHAI group and four (19%) in the control group developed liver metastasis postoperatively. The liver metastasis-free survival was not different between the groups (p = 0.94). When the analysis was restricted to patients who developed liver metastasis, the duration from surgery to detecting liver metastasis tended to be longer in the PHAI group (p = 0.09). In addition, the overall survival tended to be better in the PHAI group (p = 0.12). In the control group, the level of DPD was higher in patients who developed liver metastases (n = 4) than in those who did not (n = 14, p = 0.04). However, in the PHAI group, the level of DPD was not different regardless of the occurrence of liver metastases (p = 0.30). CONCLUSIONS: These results suggest that (1) PHAI is unlikely to improve the prognosis of Dukes' C patients remarkably, and (2) the efficacy of this regimen cannot be predicted by determining the levels of tumoral DPD.

Administration, Oral↗