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Biomedical subjects

M Fukuda

Publications and source records attributed to M Fukuda.

At least 1,603 records · Page 89Linked to original sources
PubMedDate not supplied

Surface roughness of cellulose hollow fiber dialysis membranes and platelet adhesion.

A great deal of research has been conducted focusing on membrane materials with reference to their blood compatibility, but blood compatibility is influenced both by the material used in membranes and their structure, and by the flow conditions at the membrane surface. Accordingly, the relationship between membrane surface roughness and hemocompatibility has been evaluated using five types of membranes of differing surface roughness by evaluating the inner surfaces of the hollow fibers by atomic force microscopy (AFM) and by measuring platelet adhesion ratios using bovine blood. The yield stress, which equates to flow characteristics, was also evaluated using a glycerol suspension of polymethylmethacrylate (PMMA), a Bingham fluid. It was found that membranes having rough surfaces had high platelet adhesion ratios and poor hemocompatibility, whereas those with smoother surfaces had lower platelet adhesion ratios and better hemocompatibility. Measurement of the yield stresses for these membranes revealed higher values for those with rough surfaces, and lower values for those with smoother polyethylene glycol (PEG) grafted surfaces. This suggests that flow conditions at the membrane surface differ according to its surface roughness, and that this difference in flow conditions also influences hemocompatibility.

Cellulose↗
PubMedDate not supplied

Prognostic significance of TEL/AML1 fusion transcript in childhood B-precursor acute lymphoblastic leukemia.

PURPOSE: A retrospective study was conducted to investigate the prognostic significance of TEL/AML1 fusion resulting from a cryptic t(12;21) in Japanese patients with childhood B-precursor acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: Leukemic samples from 144 children with newly diagnosed ALL (104 with CD10-positive B-precursor ALL, 11 with CD10-negative B-precursor ALL, 5 with B-ALL, and 24 with T-ALL) were analyzed by reverse-transcription polymerase chain reaction. RESULTS: The frequency of patients with TEL/AML1 was 16% (23 of 144) and all patients with TEL/AML1 also had CD10-positive B-precursor ALL. TEL/AML1 was not found in any samples from the patients with T-ALL, B-ALL, or CD10-negative B-precursor ALL. Among patients with CD10-positive B-precursor ALL, age, initial white blood cell count, and immunophenotype did not differ with TEL/AML1 positivity, although the patients were predominantly male (p < 0.01). Clinical outcomes of 94 patients treated with recent protocols were analyzed. Five of the 21 (23.8%) patients with TEL/AML1 relapsed and 4 of these relapsed > 24 months after diagnosis. Although the overall 5-year survival rate was better among patients with TEL/AML1 fusion transcript than among those without it (87.3 +/- 8.7% versus 75.9 +/- 5.8%, respectively), the 5-year disease-free survival (DFS) rates of patients with TEL/AML1 fusion transcript and those without it were similar (64.0 +/- 13.5% versus 69.1 +/- 6.3%, respectively). However, for 57 patients treated with the latest intensive protocol, the 4-year DFS rate was much higher for the patients with TEL/AML1 fusion transcript than for those without it (100.0% v.s. 69.6 +/- 8.4%, respectively, p = 0.1472). CONCLUSIONS: This study confirmed that TEL/AML1 gene fusion is the most common genetic event in pediatric ALL in Japan and is restricted to CD10-positive B-precursor ALL. Moreover, it was associated with an improved survival rate among patients treated with intensive therapy. Therefore, these data suggest that the patients with TEL/AML1 may not necessarily be candidates for less aggressive treatment.

Adolescent↗
PubMedDate not supplied

Monitor peptide (rat pancreatic secretory trypsin inhibitor) directly stimulates the proliferation of the nontransformed intestinal epithelial cell line, IEC-6.

BACKGROUND/AIMS: The growth-stimulating activity of monitor peptide [rat pancreatic secretory trypsin inhibitor (PSTI)-61] was evaluated in the rat intestinal epithelial cell line IEC-6. In response to food intake, monitor peptide induces cholecystokinin release and the subsequent secretion of pancreatic enzyme into the rat small intestine. METHODS: Monitor peptide was purified from rat bile-pancreatic juice. The proliferation of IEC-6 cells was determined by both counting cell number and [3H]-thymidine incorporation. Ornithine decarboxylase (ODC) activity was assessed by radiometric technique using L-[1-14C]-ornithine. RESULTS: Monitor peptide (10(2)-10(5) ng/ml) induced a significant increase in the incorporation of [3H]-thymidine into IEC-6 cells, and this effect was observed in a dose-dependent manner. A significant increase in the cell number was also observed. An antibody specific for the synthetic NH2-terminal fragment of monitor peptide completely abrogated the growth-stimulating effects of this peptide. In addition, monitor peptide effectively increased the ODC activity of IEC-6 cells. CONCLUSIONS: These results indicate that monitor peptide stimulates the growth of intestinal epithelial cells, and suggest that polyamine metabolism may be involved in this mechanism of growth induction.

Animals↗
PubMedDate not supplied

The effect of hyperthermia on murine leukaemia cells in combination with photodynamic therapy.

Mouse leukaemia L1210 cells were subjected to hyperthermia (43.0 +/- 0.05 degrees C, water bath) and photodynamic therapy (50 micrograms/ml haematoporphyrin derivative (HpD), 630 +/- 5 nm at 0.1 mW/cm2) for varying lengths of treatment time in different sequences. Dose-response curves showed that the two modalities interact to make the combination more cytotoxic than the sum of the separate individual treatments, and that a determining factor is the intracellular concentration of HpD of tumour cells during hyperthermia. High cytotoxic (synergistic) effects of photodynamic therapy (PDT) were obtained when PDT was performed after hyperthermia following HpD administration. However, only additive cytotoxic effects were found, when hyperthermia was performed after HpD administration and PDT. These cytotoxic data were supported by DNA damage (the increase in single-stranded DNA) as revealed by flow cytometry in cells stained with acridine orange (AO). These in vitro experiments suggest that clinical applications of PDT after hyperthermia with HpD injection might be useful.

Animals↗
PubMedDate not supplied

Allelic loss on the short arm of chromosome 8 in oral squamous cell carcinoma.

Allelic deletions on the short arm of chromosome 8 (8p) are frequent events in many different types of malignant tumors, including head and neck tumors and oropharyngeal cancers. These regions are thought to harbor tumor suppressor genes. However, there has been no detailed analysis of loss of heterozygosity (LOH) on the chromosome arm 8p in oral squamous cell carcinoma (SCC). In order to estimate details of 8p loci involved in oral SCC, 32 patients with oral SCCs were examined for the LOH state 8p by PCR-LOH assay using 14 microsatellite markers. Based on our results a detailed deletion map of 8p showed LOH in at least one of the loci tested in 62.5% (20 of 32) of patients; and microsatellite instability (MI) was observed in 50% (16 of 32). The frequent LOH on this chromosome arm was identified at D8S87 and D8S258, mapped on 8p12 and 8p22, respectively. Fisher's exact test revealed no significant statistical correlation between the incidence of LOH or MI and clinicopathological features. Our observations indicate that the short arm of chromosome 8 may play a role in the pathogenesis of oral SCC; and that the two loci identified in this study may be tumor suppressor gene loci on 8p.

Carcinoma, Squamous Cell↗
PubMedDate not supplied

Prognostic value of numerical aberrations of chromosome 17 in differentiated gastric cancer: evaluation by multivariate regression analysis.

Using in situ hybridization with a chromosome-specific DNA probe, we investigated the numerical aberrations of chromosome 17 in differentiated gastric cancers. In 75 cancers that invaded the submucosal or deeper layer, the frequency of an increased hybridized signal (hyperdiploid nuclei) on chromosome 17 was significantly associated with lymph node metastasis. Multivariate analysis showed that the classification of numerical aberration (disomy and polysomy) based on the percentage of hyperdiploid nuclei was an independent prognostic factor for the postoperative survival of 58 patients with invasive gastric cancer treated with radical gastrectomy. Thus, numerical aberrations of chromosome 17 may be a useful prognostic indicator of differentiated gastric cancer.

Adenocarcinoma↗
PubMedDate not supplied

The DNA-instability test as a specific marker of malignancy and its application to detect cancer clones in borderline malignancy.

Recent progress in cytogenetic and biochemical mutation assay technologies has enabled us to detect single gene alterations and gross chromosomal rearrangements, and it became clear that all cancer cells are genetically unstable. In order to detect the genome-wide instability of cancer cells, a new simple method, the DNA-instability test, was developed. The methods to detect genomic instability so far reported have only demonstrated the presence of qualitative and quantitative alterations in certain specific genomic loci. In contrast to these commonly used methods to reveal the genomic instability at certain specific DNA regions, the newly introduced DNA-instability test revealed the presence of physical DNA-instability in the entire DNA molecule of a cancer cell nucleus as revealed by increased liability to denature upon HCl hydrolysis or formamide exposure. When this test was applied to borderline malignancies, cancer clones were detected in all cases at an early-stage of cancer progression. We proposed a new concept of "procancer" clones to define those cancer clones with "functional atypia" showing positivities for various cancer markers, as well as DNA-instability testing, but showing no remarkable ordinary "morphological atypia" which is commonly used as the basis of histopathological diagnosis of malignancy.

Animals↗
PubMedDate not supplied

Placement of endosseous implants into bone-grafted alveolar clefts: assessment of bone bridge after autogenous particulate cancellous bone and marrow graft.

The objective of this study was to evaluate the bone quantity of alveoli grafted with autogenous particulate cancellous bone and marrow for implant placement in patients with alveolar clefts. Bone height, bone width, and interdental alveolar crest level were evaluated using computed tomography and periapical radiographs. The grafted alveoli underwent resorption 3-dimensionally, and the interdental alveolar crest level also decreased. The latter seemed to be the critical factor for implant surgery, as almost half of the grafted alveoli required another bone graft within 24 months after the original bone graft to increase the interdental alveolar crest level for endosseous implant placement. These data suggest that alveoli grafted with particulate cancellous bone and marrow are suitable for implant placement, but that the loss of width and height of the bone bridge must also be considered.

Adolescent↗
PubMedDate not supplied

The 5-HT2 receptor antagonist sarpogrelate reduces urinary and plasma levels of thromboxane A2 and urinary albumin excretion in non-insulin-dependent diabetes mellitus patients.

1. Therapeutic effects of a 5-HT2 receptor antagonist sarpogrelate on microalbuminuria and thromboxane (TX)A2 biosynthesis were examined in non-insulin-dependent diabetes mellitus (NIDDM) patients. 2. In protocol I, the ankle-brachial pressure index (API; an indicator of peripheral blood flow) and urinary albumin excretion (UalbV; an indicator of renal function) were determined in 42 NIDDM patients who had been treated with 300 mg/day sarpogrelate for 8 weeks. In an analysis of the results, the NIDDM patients were divided into four groups based on the severity of either vasculopathy or nephropathy as follows: group A, API < 0.9, UalbV > or = 100 mg/day; group B, API < 0.9, UalbV < 100 mg/day; group CAPI > or = 0.9, UalbV > or = 100 mg/day; and group D, API > or = 0.9, UalbV < 100 mg/day. 3. In protocol II, 10 NIDDM patients with UalbV values > 100 mg/day were divided into two groups to further confirm the effect of sarpogrelate on albuminuria: group E, the sarpogrelate treatment group (n = 5); and group F, the no treatment group (n = 5). 4. In protocol I, the incidence of a cold sensation in the lower extremities was reduced from 45.2 to 21.4% following sarpogrelate treatment. In patients with UalbV > or = 100 mg/day (groups A and C), UalbV was significantly decreased independent of API, while it did not change in patients with UalbV < 100 mg/day (groups B and D). Plasma TXB2 levels were significantly decreased following sarpogrelate treatment, whereas plasma 6-keto-prostaglandin F1 alpha levels were not. 5. In protocol II, in the sarpogrelate treatment group (group E), albuminuria was significantly improved and both plasma levels TXB2 and urinary TXB2 excretion were significantly decreased. In contrast, in the untreated group (group F), neither plasma levels TXB2 nor urinary TXB2 excretion was changed. 6. In conclusion, microalbuminuria was improved by treatment with the 5-HT2 receptor antagonist sarpogrelate independent of latent vasculopathy. Blockade of 5-HT2 receptors is suggested to be beneficial for the treatment of nephropathy in NIDDM patients. It is possible that the inhibition of TXA2 biosynthesis is involved in the therapeutic effect of 5-HT2 receptor antagonists.

Albuminuria↗
PubMedDate not supplied

Thymidylate synthase levels as a therapeutic and prognostic predictor in breast cancer.

5-Fluorouracil (5-FU) is a commonly used adjuvant therapeutic drug in treating breast cancer. 5-FU is metabolically converted to 5-fluorouracil-2'-deoxyuridine-5'-monophosphate-(FdUMP) which is believed to inhibit DNA synthesis in neoplastic cells by forming a tightly bound ternary complex with thymidylate synthase (TS). In the present study, we examined the possible relationship between TS levels and clinico-pathologic and prognostic features in breast disease. Mean TS levels of 2.9 pmol/g, 6.1 pmol/g, and 23.1 pmol/g were obtained in cases of benign breast disease (3 cases), primary breast cancer (115 cases), and recurrent tumors (4 cases), respectively. In breast cancer, mean TS levels significantly correlated with S-phase fraction (SPF), DNA polymerase a and lymphatic invasion. Thus, TS levels in breast cancer significantly reflected cell proliferation and malignancy. Regarding the survival rate, patients with TS values above 10 pmol/g showed an unfavorable prognosis. The effectiveness of adjuvant 5-FU derivatives chemotherapy was reflected in a higher disease-free survival rate in node (+) cases showing TS levels between 5 and 10 pmol/g (p < 0.1), but not in node (-) cases. In conclusion, TS levels in neoplastic tissues of the breast were highest in recurrent tumors, followed by those in primary cancer, benign breast disease and in breast cancer which reflected proliferative activity. Breast cancers with extremely high TS levels were accompanied by an unfavorable prognosis; however, those with moderately high TS levels tended to respond to adjuvant chemotherapy with 5-FU derivatives.

Adult↗
PubMedDate not supplied

Photodynamic therapy based on combined use of 5-aminolevulinic acid with a pheophorbide-a derivative for murine tumors.

BACKGROUND: 5-Aminolevulinic acid (5-ALA)-based photodynamic therapy (PDT) appears to be a promising cancer treatment modality. Here, we investigated whether enhancement of 5-ALA-PDT by combining another photosensitizer, a pheophorbide-a derivative (PH-1126), is an option. MATERIALS AND METHODS: PH-1126 (2.5, 5 or 10 mg/kg.bw) and 5-ALA (168 mg/kg.bw) were injected i.p. into C3H/HeN mice bearing squamous cell carcinoma (SCC) or BALB/c nude mice bearing L5178Y lymphoma. Afterwards, these mice received laser irradiations (630 nm for 5-ALA and 650 nm for PH-1126) with a total dose of 88 J/cm2. The results showed that PDT with 5-ALA plus PH-1126 at a low dose (2.5 mg/kg.bw) were well tolerated by both animal models, with resultant synergistically enhanced inhibition of tumor growth and/or survival advantage for the treated animals. CONCLUSION: This study demonstrated the usefulness of the combination of a low dose PH-1126 with 5-ALA for PDT of experimental tumors in vivo.

Aminolevulinic Acid↗
PubMedDate not supplied

Immunohistochemical detection of cytokeratin 18 and its neo-epitope in Warthin's tumor (adenolymphoma) of the parotid glands.

An immunohistochemical method using a monoclonal antibody M30 (MAb M30), which reacts with the product released by cleavage of cytokeratin 18 (CK18) by activated caspase, was used to investigate the presence and extent of apoptosis in 36 cases of Warthin's tumor (WT) of the parotid glands. The distribution of CK18 in WT was also determined and compared with that of the product detected by MAb M30. In WT, CK18 was observed mainly in the tumor cells of duct-like structures, but not in the cells of lymphatic tissues. Positive MAb M30 reaction products were found in luminal contents, duct-like structures and the cytoplasm of some macrophages in lymphatic areas near the duct-like structures in WT. These findings indicated that apoptotic cells are phagocytosed and eliminated as waste by macrophages. It is suggested that a mechanism which regulates the balance of proliferative activity and apoptosis may be closely linked to the growth of WT.

Adenolymphoma↗
PubMedDate not supplied

Changes in peritoneal equilibration test values during long-term peritoneal dialysis in peritonitis-free children.

Little is known about the changes in peritoneal equilibration test (PET) values in children on long-term peritoneal dialysis (PD). In the present study, a PET was carried out every 6 months in 39 children (mean age 8.8 +/- 5.5 years) undergoing PD for 6 to 85 months (mean 36.9 +/- 23.1 months). Patients experiencing peritonitis were excluded. Both D/P creatinine (dialysate-to-plasma ratio of creatinine at 4 hours) and D/D0 glucose (ratio of dialysate glucose at 4 hours' dwell time to dialysis glucose at 0 dwell time) were measured 195 times in this series of patients. No remarkable change was found for D/P creatinine or D/D0 glucose during the first 24 months of PD but thereafter, D/P creatinine increased gradually and D/D0 glucose decreased gradually. Mean D/P creatinine increased significantly after the first 24 months of PD: from 0.66 +/- 0.12 during the first 24 months, to 0.70 +/- 0.09 after 25 months and more of PD (p = 0.0051). Mean D/D0 glucose decreased significantly after 24 months of PD: from 0.42 +/- 0.09 during the first 24 months, to 0.38 +/- 0.08 after 25 months and more of PD (p = 0.0015). The most significant change for both D/P creatinine and D/D0 glucose occurred after 24 months of PD. It seems reasonable to consider the mean PET values at 24 months of PD as the standard PET values.

Adolescent↗
PubMedDate not supplied

Expression of granulocyte colony-stimulating factor receptor and platelet-derived endothelial cell growth factor in oral and oropharyngeal precancerous lesions.

Epithelial hyperplasia and dysplasia have been diagnosed as precancerous lesions and have been discussed in relationship to carcinogenesis. We analyzed the immunohistochemical expression of granulocyte colony-stimulating factor receptor (G-CSFR) and platelet-derived endothelial cell growth factor (PD-ECGF) in oral and oropharynx; 33 samples of normal epithelium, 28 samples of hyperplasia, 16 samples of dysplasia and 58 samples of squamous cell carcinoma. Also, we examined mean vessel density (MVD) by using CD34 staining and proliferating cell nuclear antigen (PCNA) staining. Dysplasia and head and neck Squamous Cell Carcinoma (SCC) exhibited higher G-CSFR expression and MVD than normal or hyperplastic epithelium (p <0.01). In the PD-ECGF staining, significant differences were found between SCC and normal epithelium, hyperplasia and dysplasia (p<0.001). In dysplasia and hyperplasia, PD-ECGF expression was significantly correlated with PCNA expression (r=0.345, p=0.025), however it was not correlated with the MVD. G-CSFR expression was not correlated with either PCNA or MVD. These results suggest that G-CSFR and PD-ECGF might be concerned with different carcinogenesis pathways of the squamous cells in the oral region and that PD-ECGF may be concerned with epithelial proliferation rather than angiogenesis.

Adult↗
PubMedDate not supplied

Detection of non-papillary, non-invasive transitional cell G1 carcinoma as revealed by increased DNA instability and other cancer markers.

The method to reveal DNA-instability as demonstrated by immunohistochemical staining with anti-cytidine antibody after acid hydrolysis (DNA-instability test) was used as a marker of malignancy. The test was applied to paraffin-embedded sections taken from 15 urinary bladders, renal pelvic cavities, and ureters bearing multiple carcinoma in situ (CIS) and totally 31 papillary urothelial cancers. The serial sections of the same tissues were also subjected to immunohistochemical staining for PCNA, p53, DFF45, and VEGF. The DNA-instability test was positive in 100% cancer lesions irrespective of the grades, and apparently normal urothelium, and hyperplastic and dysplastic urothelial lesions also showed the areas with clones positively stained with DNA-instability testing, and the percent numbers of positive areas in them were 28.3%, 37.7%, and 61.5%, respectively. These clones, which were present in apparently normal urothelium and in hyperplastic and dysplastic urothelial lesions, showed higher percent values of PCNA-positive-cells, in comparison to the values estimated in the areas with negatively stained DNA-instability testing, and the former values were statistically not different from those in carcinoma lesions. Furthermore, the percent numbers of areas positive for p53, DFF45, and VEGF, with positive DNA-instability testing were also much higher than those with negative DNA-instability testing in apparently normal urothelium, and hyperplastic and dysplastic urothelial lesions, and the former values were again comparable to those in cancer lesions with no statistical differences. These clones were regarded as already being malignant and should be the direct precursors of progressed cancer lesions. They will make progression through two different pathways, one to papillary non-invasive G1 cancers by neovascularization induced by paracrine secretion of VEGF, and another to flat CIS G2 without secretion of VEGF; thus the clones should be regarded as non-papillary, non-invasive Gl TCC, or CIS G1. It should be always taken into account that the probability for apparently normal urothelium, and hyperplastic and dysplastic urothelial lesions to contain cancer clones, will be high already, especially in tumor-bearing bladders.

Biomarkers, Tumor↗
PubMedDate not supplied

Pathogenesis of calcium crystal deposition in the ligamentum flavum correlates with lumbar spinal canal stenosis.

OBJECTIVE: To investigate the histological and immunohistochemical properties of degenerative changes and calcium crystal deposition in the lumbar ligamentum favum. METHODS: We examined the ligamentum flavum harvested from 119 surgical cases with symptomatic lumbar spinal stenosis. Sections of the ligament were examined by scanning electron microscopy (SEM), energy dispersive X-ray micro-analysis, and were immunostained for S-100 protein, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and CD34. The results were compared with those of ligament tissue harvested from 10 cases of lumbar disc herniation. RESULT: The elastic fibres of the ligamentum favum showed regular, or sometimes irregular, and fragmented fibre bundles. Large areas of fibrosis with reduced elastic component and increased collagenous tissue were frequently seen in the degenerated ligaments. Calcium crystal deposits were observed in these fibrous ligaments, associated with many hypertrophic chondrocytes, and with small blood vessel formation. These chondrocytes stained positively for S-100 protein, VEGF and bFGF Calcium pyrophosphate dihydrate crystals were identified in the calcium deposit area. CONCLUSION: We believe that rupture of elastic fibre bundles is the first change to occur in degeneration of the ligamentum favum. Calcium crystal deposition was seen within these fibrous and chondrometaplastic areas. Hypertrophic chondrocytes regulate crystal formation and tissue reconstruction by secreting cytokines.

Adult↗