Biomedical subjects

M Ohta

Publications and source records attributed to M Ohta.

At least 73 records · Page 4Linked to original sources

PubMed2001

Compassionate use of humanized anti-HER2/neu protein, trastuzumab for metastatic breast cancer in Japan.

The HER-2/neu protein is thought to be a unique and useful target for antibody therapy of cancers overexpressing the HER-2/neu gene. The recombinant humanized anti-HER-2 monoclonal antibody, trastuzumab (Herceptin) was approved for clinical use in the US in 1998. In Japan, it was approved and later became available in June, 2001. We have treated 41 patients with metastatic breast cancer with trastuzumab purchased from the US. In this paper, the details of the patients we experienced are reviewed.

Adult↗

PubMed2001

Correlation between plasma endotoxin, plasma cytokines, and plasminogen activator inhibitor-1 activities in septic patients.

The objective of this study was to evaluate the relation between the clinical and plasma parameters and the changes in plasma endotoxin activity with 2 hours of endotoxin-adsorbing therapy using polymyxin B (PMX). A total of 88 consecutive patients were admitted for PMX treatment of severe sepsis or septic organ failure. Standard supportive care was continued without alteration during PMX treatment. Endotoxin, tumor necrosis factor-alpha (TNFalpha), interleukin-6 (IL-6), IL-10, and plasminogen activator inhibitor-1 (PAI-1) activities and clinical parameters were measured before, immediately after, and the day after PMX treatment. The mean APACHE II and III scores were 24.2 +/- 1.0 and 85.8 +/- 3.0, respectively. The 2-week survival rate was 51.1%. In survivors, TNFalpha, IL-6, IL-10, and PAI-1 activities were significantly decreased during the 2-hour PMX treatment, the following day, or both times. There was no significant change in the parameters, except for TNFalpha, after PMX in nonsurvivors. In the subgroup whose plasma endotoxin decreased more than 30%, IL-6, TNFalpha, and PAI-1 significantly decreased after 2 hours of PMX or the following day (or both), but all four parameters in nonsurvivors showed no significant change. Hence PMX adsorbed plasma endotoxins and contributed to reductions in plasma proinflammatory cytokine levels and to improved clinical parameters during the 2-hour treatment. Changes in these parameters correlated with changes in plasma endotoxin activity in survivors whose plasma endotoxin levels were adequately reduced.

APACHE↗

PubMed2001

Resolution of Escherichia coli O157:H7 that contaminated radish sprouts in two outbreaks by two-dimensional gel electrophoresis.

Two-dimensional gel electrophoresis (2-DE) was performed to examine exoproteins and periplasmic proteins of Shiga toxin-producing Escherichia coli (STEC) O157:H7 strains isolated from cases associated with radish sprouts in two outbreaks. We found that STEC O157:H7 released a large number of proteins into the medium during the stationary phase of growth, as observed with 2-DE. Although pulsed-field gel electrophoresis (PFGE) patterns of STECs NGY9 (RIMD0509894), a Sakai isolate; NGY33, a Gamagoori isolate; and NGY120, a Kanagawa isolate, were all the same, comparison of 2-DE patterns of exoproteins and periplasmic proteins clarified that NGY9 was distinct from NGY33, whereas NGY33 and NGY120 were of close lineage. We therefore suggest that 2-DE analysis of exoproteins and periplasmic proteins is a powerful epidemiological method with high resolution.

Bacterial Proteins↗

PubMed2001

Postantibiotic suppression effect of macrolides on the expression of flagellin in Pseudomonas aeruginosa and Proteus mirabilis.

The phenomenon of postantibiotic effect (PAE) encompasses not only the effects of bacterial growth inhibition but also the suppression of virulence factors. We tentatively designated the latter effect the postantibiotic suppression effect (PASE). The flagella of Gram-negative bacteria are involved in the development of biofilms. We measured the PASE of erythromycin (ERY) and azithromycin (AZM) on the expression of flagellin in Pseudomonas aeruginosa and Proteus mirabilis. Flagellin preparations were subjected to sodium dodecylsulfate (SDS) polyacrylamide gel electrophoresis (PAGE) analysis and the flagellin band was identified by N-terminal amino acid sequence analysis. We thus evaluated the flagellin by the intensity of the band. The mean durations of the PAE of ERY and AZM on bacterial growth were 0.9 and 2.0 h for P. mirabilis, and 0.6 and 2.7 h for P. aeruginosa, respectively. The PASE of these drugs on flagellin expression was also observed. The apparent PASEs of ERY and AZM on flagellin were up to 5 h for P. mirabilis and up to 6 h for P. aeruginosa after a single 0.5 x minimum inhibitory concentration (MIC) treatment for 5 h. Our results suggest that certain combinations of antibiotics may have prolonged suppressive effects on the expression of virulence factors in certain Gram-negative bacteria.

Anti-Bacterial Agents↗

PubMed2001

Foveal translocation with scleral imbrication in patients with myopic neovascular maculopathy.

PURPOSE: To report our surgical results of foveal translocation with scleral imbrication in patients with myopic neovascular maculopathy. DESIGN: Noncomparative, interventional, consecutive case series. METHODS: Ten eyes of 10 myopic patients with subfoveal neovascular membranes that had undergone foveal translocation with scleral imbrication were recruited for this retrospective study. Inclusion criteria were myopia 6.0 diopters or greater in refractive error (or axial length 26.5 mm or longer), subfoveal choroidal neovascularization, and preoperative best-corrected visual acuity of 20/100 or worse. None of these eyes had undergone prior laser photocoagulation or submacular surgery. The main outcome measures were surgical complications and postoperative visual function. RESULTS: Postoperatively, visual acuity had improved more than 3 lines in the logarithm of minimum angle of resolution (logMAR) measurement in all eyes. The mean preoperative, postoperative best, and final visual acuity were 0.12, 0.59, and 0.51, respectively. Of the 10 eyes, six achieved a postoperative final visual acuity of 20/40 or better. The mean postoperative foveal displacement was 0.78 disk diameter (range, 0.3--1.3 disk diameter). Two patients underwent a reoperation because of insufficient foveal displacement. Furthermore, one of these two patients required a third operation to reduce an excessive retinal fold involving the fovea induced by the second surgery. Of the 10 patients, two noted transient diplopia. This complaint, however, resolved over time as suppression developed. Although unintentional iatrogenic retinal tears formed intraoperatively in two eyes, these were successfully treated without serious complications. Postoperatively, mild retinal pigment epithelial changes were observed in all cases, but none led to significant deterioration of visual acuity during the follow-up period. All patients but one were followed for a minimum of 6 months. CONCLUSIONS: In eyes with myopic neovascular maculopathy, foveal translocation with scleral imbrication may be useful in improving visual acuity. Further refinements in surgical technique and assessment of the long-term complications will be needed to make this procedure safer and more useful.

Adult↗

PubMed2001

Formation of PCDDs and PCDFs during the combustion of polyvinylidene chloride.

In laboratory-scale combustion of polyvinylidene chloride (PVDC) with a quartz tubular furnace designed and fabricated to provide the desired combustion temperature and mixing state of combustion gas with air, it was found that at 800 degrees C or higher the level of polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans [corrected] (PCDDs/PCDFs) resulting from PVDC combustion was no higher than that from heating air alone, and thus far below the levels which resulted from PVDC combustion at 750 degrees C or lower. The results provide the first laboratory confirmation of the relation between PVDC incineration temperature and PCDD/PCDF formation, and of the primary importance of high temperature, turbulence for mixing between air and combustion gas, and sufficient residence time, as governing factors for the minimization of PCDD/PCDF formation in municipal solid waste incinerators.

Benzofurans↗

PubMed2001

Intravenous immunoglobulin for cranial polyneuropathy associated with Campylobacter jejuni infection.

This study reports the efficacy of i.v. immunoglobulin in a patient with cranial polyneuropathy resulting from Campylobacter jejuni infection who had high titers of serum IgG antibodies against gangliosides GD1a and GT1b in the acute phase. Treatment with i.v. immunoglobulin (400 mg/kg/day x 5 days) led to rapid partial resolution of his neurologic manifestations, but complete recovery was not obtained until 6 months later. The present case suggests that i.v. immunoglobulin therapy prevents further progression of the disease but that it may not shorten the clinical course of cranial polyneuropathy in some cases associated with Campylobacter jejuni infection.

Acute Disease↗

PubMed2001

Interleukin 8 and vascular endothelial growth factor -- prognostic factors in human gastric carcinomas?

Gastric carcinoma cells express potent angiogenic factors including vascular endothelial growth factor (VEGF). We previously reported that interleukin-8 (IL-8) acts as an angiogenic factor for human gastric carcinomas. More recently, we found that IL-8 upregulates matrix metalloproteinase-9 (MMP-9) expression and increases invasive activity of gastric carcinoma cells. The purpose of this study was to determine whether the expression of IL-8 and VEGF correlates with clinicopathological parameters in human gastric carcinomas. IL-8 and VEGF expression levels were measured by an enzyme-linked immunosorbent assay (ELISA) in 56 gastric carcinomas and the surrounding normal mucosa. Macroscopic and histopathological tumour findings, presence of metastasis and prognosis were obtained from the patient records and endoscopic, surgical and pathological reports. IL-8 protein levels were higher in most neoplasms than in the corresponding normal mucosal tissue. In contrast, VEGF expression in the tumours was similar to that in normal mucosa. The IL-8 level in the neoplasms correlated significantly with the depth of invasion, venous invasion and lymphatic invasion. VEGF expression in the tumours correlated well with the depth of invasion and lymph node metastasis. No correlation between IL-8 and VEGF expression in the tumours was observed. The survival rates of patients with tumours displaying high IL-8 and VEGF expression levels were significantly lower (P<0.05) than those of patients with tumours displaying low IL-8 and VEGF expression. The results suggest that IL-8 and VEGF may be independent and important prognostic factors in human gastric carcinomas.

Adult↗

PubMed2001

Isolation and characterization of a Na+/H+ antiporter gene from the halophyte Atriplex gmelini.

With a homologous gene region we successfully isolated a Na+/H+ antiporter gene from a halophytic plant, Atriplex gmelini, and named it AgNHX1. The isolated cDNA is 2607 bp in length and contains one open reading frame, which comprises 555 amino acid residues with a predicted molecular mass of 61.9 kDa. The amino acid sequence of the AgNHX1 gene showed more than 75% identity with those of the previously isolated NHX1 genes from glycophytes, Arabidopsis thaliana and Oryza sativa. The migration pattern of AgNHX1 was shown to correlate with H+-pyrophosphatase and not with P-type H+-ATPase, suggesting the localization of AgNHX1 in a vacuolar membrane. Induction of the AgNHX1 gene was observed by salt stress at both mRNA and protein levels. The expression of the AgNHX1 gene in the yeast mutant, which lacks the vacuolar-type Na+/H+ antiporter gene (NHX1) and has poor viability under the high-salt conditions, showed partial complementation of the NHX1 functions. These results suggest the important role of the AgNHX1 products for salt tolerance.

Amino Acid Sequence↗

PubMed2001

Physicochemical parameters responsible for the affinity of methotrexate analogs for rat canalicular multispecific organic anion transporter (cMOAT/MRP2).

PURPOSE: Canalicular multispecific organic anion transporter (cMOAT/MRP2) is known to exhibit a broad substrate specificity toward amphiphatic organic anions, including methotrexate (MTX). The present study aims to identify the physicochemical properties of MTX derivatives that correlate with recognition specificity by cMOAT/MRP2. METHODS: We examined the inhibitory effect of MTX and 24 analogs on the transport of [3H]-S-(2,4-dinitrophenyl)glutathione by cMOAT/MRP2. The affinity constants of these compounds were compared with their physicochemical parameters. The primary active transport of several compounds was also confirmed. RESULTS: The affinity constants closely correlated with the octanol/water partition coefficient (clogP), and a linear combination of polar and nonpolar surface areas. The affinity for cMOAT/MRP2 also closely correlated with the molecular weight, which also showed a significant correlation with nonpolar surface area and clogP. CONCLUSIONS: Recognition by cMOAT/MRP2 depends on a balance of dynamic surface properties between the polar and nonpolar regions of MTX analogs. The so-called "molecular weight threshold" for the cMOAT/MRP2 affinity of these compounds can be explained by their physicochemical parameters, especially their nonpolar surface areas.

Adenosine Triphosphate↗

PubMed2001

Sp1 is a key regulator of the PDGF beta-receptor transcription.

The mouse PDGF beta-receptor promoter is tightly controlled by NF-Y that binds to a CCAAT box located upstream of the initiation site [1, 2]. In this report, we show that Sp1 plays an essential role in the PDGF beta-receptor transcription. Within the upstream GC rich area there are two Sp1 binding sites located in close proximity to the CCAAT box. Deletion of the GC rich region resulted in a 50% decrease of the transcriptional activity of the promoter, and a complete loss of its responsiveness to over-expression of Sp1. There was an additive effect between NF-Y and Sp I in reporter activity when they were co-transfected together with the promoter-reporter construct. Furthermore, transfection of NF-Y failed to enhance transcriptional activity when the Sp1 binding sites were deleted from the promoter, suggesting an important role for Sp1 in this NF-Y controlled transcription. We have recently reported that c-Myc represses PDGF beta-receptor transcription through its interference with the transactivation activity of NF-Y [3]. In the case of p21(wafl/cip1) transcription, c-Myc was shown to repress its transcription by sequestering Sp1 [4]. However, we could not find any effect of Sp1 in the c-Myc-mediated repression on the PFDGF beta-receptor promoter, since the deletion of SpI binding sites could not attenuate the repression by c-Myc on the promoter activity.

3T3 Cells↗

PubMed2001

Direct screening of the IMP-1 metallo-beta-lactamase gene (blaIMP) from urine samples by polymerase chain reaction.

BACKGROUND: As Gram-negative bacterial isolates producing plasmid-mediated IMP-1 metallo-beta-lactamase usually demonstrate resistance to various broad-spectrum beta-lactams, including cephamycins and carbapenems, transmission and proliferation of these microorganisms in clinical settings could become a clinical threat in the near future. According to previous studies by the same authors, IMP-1-producing strains are usually isolated from urine samples. Therefore, in this study, a polymerase chain reaction (PCR) was applied for direct screening of the IMP-1 metallo-beta-lactamase gene in urine samples. METHOD: Urine samples were collected from 273 inpatients to whom various broad-spectrum beta-lactams, including carbapenems, had been administered in 57 hospitals in 1997. DNA templates for PCR analyses were prepared directly from 19 urine samples from which Serratia marcescens strains demonstrating high-level resistance (minimal inhibitory concentration > 128 microg/mL) to both ceftazidime and cefoperazone-sulbactam were later isolated. RESULTS: The IMP-1 metallo-beta-lactamase gene (blaIMP)-specific 578 bp fragments were able to be amplified successfully in eight of the 19 samples. In the seven strains isolated from the eight samples, the presence of blaIMP was also detected by a DNA hybridization analysis. The lower limit of the PCR method was determined as 1 x 10(2) CFU of blaIMP-bearing bacterial cells per 1 mL of urine sample. No false positive result was found. CONCLUSION: The PCR-aided direct screening of blaIMP is applicable to early recognition of IMP-1-producing bacteria in urine samples. This method would help to prevent nosocomial and interhospital transmission of this kind of hazardous bacteria, as well as the advancement of rigorous infection control.

Bacterial Proteins↗

PubMed2001

Use of various combinations of free, complexed and total prostate-specific antigen levels as predictors of the pathologic stage of prostate cancer.

BACKGROUND: The efficacy of various combinations of total, free and complexed prostate-specific antigen (PSA) levels were assessed to predict the pathologic stage of prostate cancer. METHODS: Total PSA (tPSA), free PSA (fPSA) and complexed PSA (cPSA) levels were measured preoperatively in 52 patients with clinical localized prostate cancer who had undergone radical prostatectomy. Pathologic stages were classified as: organ-confined (n = 27); capsular penetration (n = 14); seminal vesicle involvement (n = 8); involvement of the surgical margins (n = 10); and lymph node involvement (n = 3). RESULTS: The fPSA/tPSA and fPSA/cPSA ratios significantly differed between patients with organ-confined disease and non-organ-confined disease (P = 0.035, P = 0.033, respectively) and between those with favorable versus unfavorable pathology (P = 0.001, P = 0.014, respectively), but tPSA, cPSA, fPSA and the cPSA/tPSA ratio did not. Using a fPSA/tPSA cutoff level of 11%, the prediction of organ-confined disease would increase from 52 to 67% and the rate of predicting favorable pathology would increase from 42 to 62%. A fPSA/cPSA cutoff level of 12% would increase the rate of predicting organ-confined disease to 79% and the rate of predicting favorable pathology would increase to 69%. The positive predictive value of the fPSA/cPSA ratio was higher than that of the fPSA/tPSA ratio, although the receiver operating characteristic curve of the fPSA/cPSA ratio was not different from that of the fPSA/tPSA ratio. CONCLUSION: Although there was no predictive difference found between fPSA/tPSA and fPSA/cPSA ratio, both ratios may help predict the pathologic stage of prostate cancer.

Aged↗

PubMed2001

Antidepressant drug treatments induce glial cell line-derived neurotrophic factor (GDNF) synthesis and release in rat C6 glioblastoma cells.

Modulation of neurotrophic factors to protect neurons from damage is proposed as a novel mechanism for the action of antidepressants. However, the effect of antidepressants on modulation of glial cell line-derived neurotrophic factor (GDNF), which has potent and widespread effects, remains unknown. Here, we demonstrated that long-term use of antidepressant treatment significantly increased GDNF mRNA expression and GDNF release in time- and concentration-dependent manners in rat C6 glioblastoma cells. Amitriptyline treatment also increased GDNF mRNA expression in rat astrocytes. GDNF release continued for 24 h following withdrawal of amitriptyline. Furthermore, following treatment with antidepressants belonging to several different classes (amitriptyline, clomipramine, mianserin, fluoxetine and paroxetine) significantly increased GDNF release, but which did not occur after treatment with non-antidepressant psychotropic drugs (haloperidol, diazepam and diphenhydramine). Amitriptyline-induced GDNF release was inhibited by U0126 (10 microM), a mitogen-activated protein kinase (MAPK)-extracellular signal-related kinase (ERK) kinase (MEK) inhibitor, but was not inhibited by H-89 (1 microM), a protein kinase A inhibitor, calphostin C (100 nM), a protein kinase C inhibitor and PD 169316 (10 microM), a p38 mitogen-activated protein kinase inhibitor. These results suggested that amitriptyline-induced GDNF synthesis and release occurred at the transcriptional level, and may be regulated by MEK/MAPK signalling. The enhanced and prolonged induction of GDNF by antidepressants could promote neuronal survival, and protect neurons from the damaging effects of stress. This may contribute to explain therapeutic action of antidepressants and suggest new strategies of pharmacological intervention.

Amitriptyline↗

PubMed2001

Limited urinary concentration and damaged tubules in rats with a syngeneic kidney graft.

BACKGROUND: The underlying mechanisms of renal transplant dysfunction are poorly understood. There is little information on tubular function in kidney grafts. The cDNAs encoding kidney-specific cell surface proteins required for renal reabsorption of sodium (sodium cotransporter in thick ascending limb of Henle, rBSC1) and water (apical water channel in collecting duct, AQP2) have been recently identified. Since transcripts of these proteins are up-regulated in dehydration in association with maximal concentration of urine, we examined urinary concentrating ability and expression levels of mRNA of these proteins in kidney isografts. METHODS: Male Sprague-Dawley rats underwent syngeneic renal transplantation or unilateral nephrectomy (UNX) and were deprived of water for 24 hours at six weeks after the operation when histological and functional compensation of the intact kidney was complete. Blood and urinary samples were collected before and after dehydration. The amount of rBSC1 or AQP2 mRNA was measured using competitive polymerase chain reaction (PCR) by inducing a point mutation at the middle of PCR product for rBSC1 or by deleting 180 bp from 780 bp PCR product for AQP2, respectively. The protein expression was examined by Western blot analysis. RESULTS: Both groups of rats demonstrated the same levels of compensatory renal hypertrophy (approximately 60% weight increase) and plasma creatinine values. Histological examination revealed enlarged glomeruli and tubules, but no findings of ischemic damage, such as tubular atrophy or interstitial changes. Urinary concentration was noted in the UNX rats but not in rats with kidney grafts. Competitive PCR demonstrated that dehydration did not increase rBSC1 and AQP2 transcripts in rats with kidney transplantation. Immunoblot analysis confirmed that the marked increase of both rBSC1 and AQP2 proteins was noted only in the remnant kidney of dehydrated rats. CONCLUSIONS: Rats with kidney isografts have a limited capacity to concentrate urine and, at the same time, fail to increase rBSC1 and AQP2 transcripts. This suggests that there is a prolonged damage of renal tubules by ischemia or denervation of the donor kidney, both of which are inevitable in the transplantation procedure.

Animals↗

PubMed2001

Effect of a thick palatal appliance on muscular symptoms in craniomandibular disorders: a preliminary study.

Several treatment modalities for myofascial pain dysfunction syndrome (MPD) are being used at present. However, from the standpoint of patients' quality of life, it would be reasonable to seek a more effective treatment modality. This study aimed to show clinical data of a preliminary study regarding the effect of a thick palatal appliance, designed to fill the palatal concavity with a thick resin base, on muscular symptoms in eighteen MPD patients. Shown here are the clinical results of two volunteer patients using palatal appliances of two different thicknesses. In this study, MPD patents were divided into the three following groups: 1. no-treatment group; 2. thick palatal appliance group; and 3. medication group. Based on the results of this study, it was suggested that the thick palatal appliance could bring about early improvement of MPD syndrome. It is suggested that the thickness of the palatal plate was an important factor in obtaining the clinical effect.

Adult↗

PubMed2001

Structural analysis of sulfated N-linked oligosaccharides in erythropoietin.

We previously demonstrated that high-performance liquid chromatography with electrospray ionization mass spectrometry (LC/MS) equipped with a graphitized carbon column (GCC) is useful for the structural analysis of carbohydrates in glycoproteins. Using LC/MS with GCC, sulfated N-linked oligosaccharides were found in erythropoietin (EPO) expressed in baby hamster kidney cells. Sulfation occurs in a part of the N-linked oligosaccharides in the EPO. Sulfated monosaccharide residue in the sulfated N-linked oligosaccharide was determined by exoglycosidase digestion followed by sugar mapping by LC/MS. The linkage position and branch-location of the sulfate group in the tetraantennary oligosaccharide were analyzed by (1)H-nuclear magnetic resonance. It was suggested that sulfation occurs on the C-6 position of GlcNAc located in the GlcNAcbeta1-4Manalpha1-3 branch.

Animals↗

PubMed2001

A case with HER2-overexpressing breast cancer completely responded to humanized anti-HER2 monoclonal antibody.

This is a case report of a 57-year-old woman with a history of primary carcinoma of the right breast with metastases to the contralateral axillary lymph node. After a partial response (PR) was induced by high-dose chemotherapy with peripheral blood stem cell transplantation, she underwent mastectomy with biopsy of the bilateral axillary lymph nodes. Six months after surgery, the patient had multiple lung metastases. She was then treated with five cycles of fluorouracil, mitoxantrone and vindesine. Although a PR was achieved, further chemotherapy could not be given because of cardiac dysfunction. Since immunohistochemical staining for the HER2 gene product was strongly positive on the surface of primary tumor cells, humanized anti-HER2 monoclonal antibody (trastuzumab) was given intravenously. The metastatic lesion decreased in size and finally appeared to be only cicatricial. Twenty-one months after the initial administration of trastuzumab, the pulmonary lesion was excised. The pathological examination revealed no tumor cells in the resected specimen so further treatment was stopped. The relapse-free state has continued for 24 months after the pulmonary resection.

Antibodies, Monoclonal↗