Biomedical subjects

M Furusawa

Publications and source records attributed to M Furusawa.

At least 19 recordsLinked to original sources

PubMed2005

Allograft glomerulitis: histologic characteristics to detect chronic humoral rejection.

The aim of this study was to clarify the histopathologic significance of allograft glomerulitis in chronic allograft nephropathy (CAN). Review of our renal allograft biopsy files revealed 140 specimens with CAN among 115 selected patients. They were classified into two groups: one had CAN with glomerulitis (group G), and the other was free of this finding (group NG). We evaluated the clinicopathologic parameters as follows: levels of serum creatinine and proteinuria in the biopsy; presence of circulating anti-donor antibodies; allograft failure rate; history of biopsy-proven acute cellular rejection (ACR) and acute humoral rejection (AHR); complications of ACR and chronic rejection (CR); and results of immunofluorescence studies for C4d and HLA-DR. The glomerulitis group showed a significantly greater incidence of CR complications, the presence of circulating anti-donor antibodies, and C4d deposition in peritubular and glomerular capillaries. This group also showed higher levels of serum creatinine and proteinuria, higher graft loss rate, and increased AHR incidence, although the differences were not significant. There was also no statistical significance in the HLA-DR expression on tubular epithelial cells. The present results strongly suggest that humoral factors may play an important role in the progression of glomerulitis in CAN. Therefore, we suspect that glomerulitis in CAN is one of the main histologic markers for CR. The presence of glomerulitis may represent humoral factor-dependent inflammation. It should be considered an important diagnostic criterion for CR in addition to double-contour formation and elastica disruptions with or without subendothelial inflammation (Banff '97).

ABO Blood-Group System↗

PubMed2004

Efficacy of IgM anti-blood type antibody monitoring by enzyme-linked immunosorbent assay after renal transplantation across the blood barrier: high-dose immunoglobulin administration blocks IgM rather than IgG anti-blood type antibodies.

We used an enzyme linked immunosorbent assay (ELISA) to investigate the presence of subtypes of anti-blood-type antibodies in patients with biopsy-proven humoral rejection after ABO-incompatible renal transplantation. High agglutinin IgG and IgM anti-blood type antibodies from 12 ABO-incompatible recipients with vascular rejection were separately assessed using an ELISA. Patients who exhibited excellent renal function despite high agglutinin titers of anti-blood-type antibodies(n = 8) were also examined. All 12 rejection patients exhibited highly elevated titers of IgG and IgM, while the eight stable patients exhibited only slightly elevated IgG titers, but not IgM. IgG and IgM titers did not change after plasmapheresis and steroid pulse therapy, whereas IVIg treatment significantly blocked both IgG and IgM, with IgM being blocked to a larger extent than IgG. Blocking of IgM seems to play an important role in improving ABO-incompatible grafts.

Antibodies, Anti-Idiotypic↗

PubMed2004

Histological analysis of late renal allografts of antidonor antibody positive patients with C4d deposits in peritubular capillaries.

The association of humoral immunity with late renal allograft dysfunction has recently been recognized, and many reports have revealed C4d deposits in peritubular capillaries (C4d in PTC), and the presence of serum antidonor HLA antibody in patients suffering from graft dysfunction, long time after transplantation. In this study, morphological changes in renal allograft biopsies more than 1 year after transplantation in 14 patients with C4d in PTC and serum antidonor antibody were investigated for the presence of chronic rejection (CR). In addition to the light microscope study, an electron microscope study was done to evaluate the multilayering of the peritubular capillary basement membrane (MLPTC). Histologically, only seven of 14 patients met the criteria of CR, and 71.4% (5/7) of CR patients had episodes of acute humoral rejection (AHR), coexisting with acute tubulointerstitial rejection. Peritubular capillaritis was observed in all patients, although it differed in severity. Transplant glomerulitis and interstitial inflammation were also observed in many patients: 71.4% (10/14) and 92.9% (13/14) respectively. MLPTC was observed in 12 patients (85.7%), but the severity of the MLPTC did not reflect the severity of peritubular capillaritis or any other histological features. The long-term outcomes of the patients CR, especially those with episodes of AHR, were poor, and two of them lost their graft functions. On the other hand, patients without CR had relatively favourable outcomes. In conclusion, we confirmed the diverse morphological changes of late renal allografts, which cannot be categorized as chronic humoral rejection (CHR), and such patients who do not have typical morphological changes such as CHR, should be followed-up on a long-term basis in order to clarify the significance of C4d on PTC in late renal allografts.

Adolescent↗

PubMed2001

AMY-1, a c-Myc-binding protein, is localized in the mitochondria of sperm by association with S-AKAP84, an anchor protein of cAMP-dependent protein kinase.

We have reported that a novel c-Myc-binding protein, AMY-1 (associate of Myc-1), stimulated the transcription activity of c-Myc. To access the molecular function of AMY-1, a two-hybrid screening of cDNAs encoding AMY-1-binding proteins was carried out with AMY-1 as a bait using a human HeLa cDNA library, and a clone encoding cAMP-dependent protein kinase anchor protein 149 (AKAP149), was obtained. AMY-1 was found to bind in vitro and in vivo to the regulatory subunit II binding region of AKAP149 and S-AKAP84, a splicing variant of AKAP149 expressed in the testis. AMY-1 was expressed postmeiotically in the testis, as S-AKAP84 was expressed. Furthermore, S-AKAP84 and regulatory subunit II, a regulatory subunit of cAMP-dependent protein kinase, made a ternary complex in cells, and AMY-1 was localized in the mitochondria of HeLa and sperm in association with AKAP149 and S-AKAP84, respectively. These results suggest that AMY-1 plays a role in spermatogenesis.

A Kinase Anchor Proteins↗

PubMed2001

Expression of xenoantigen transformed human cancer cells to be susceptible to antibody-mediated cell killing.

The carbohydrate epitope, alphaGal epitope, is known as a major xenoantigen. The epitope exists abundantly in non-primate mammals and has recently been found on C-type retroviruses. Humans and Old World monkeys have anti-alphaGal antibody, a natural antibody. The present study was performed to examine if the alphaGal epitope could be used as a new target of gene therapy against human cancer. Bovine alpha1-3 galactosyltransferase (alpha1-3 GT) cDNA which produces the alphaGal epitope was electrophoretically transfected into the human pancreatic cancer cell line, MIA PaCa-2 and the human hepatocellular carcinoma cell line, huH7. The expression of the alphaGal epitope was confirmed by flow cytometry, using specific binding with IB4 lectin conjugated with fluorescein isothiocyanate. Transfected MIA PaCa-2 cells and huH7 cells showed a positive log shift for the alphaGal epitope. Next, we examined whether human cancer cells expressing the alphaGal epitope could be lysed by natural antibodies using the complement-dependent cytotoxic cross-match test. The results showed that transfected MIA PaCa-2 cells and huH7 cells were effectively lysed by human natural antibodies, and the killing was observed with any serum irrelevant of blood type. The results indicate that transfection of the functional alpha1-3 GT gene into human cancer cells can lead to their transformation, making them susceptible to lysis by natural antibodies, and, thus, useful for gene therapy.

Animals↗

PubMed2001

Promotion of evolution by intracellular coexistence of mutator and normal DNA polymerases.

The efficient evolution of a population requires both genetic diversity and stable reproduction of advantageous genotypes. The accuracy of DNA replication guarantees the stable reproduction, while errors during DNA replication produce the genetic diversity. Thus, one key to the promotion of evolution is inherent in DNA replication. In bacteria, replication forks progress bidirectionally from the single origin of replication on a genome. One replication fork contains two DNA polymerase molecules so that four DNA polymerases simultaneously carry out the replication of a genome. It is generally believed that the fidelity of the intracellular DNA polymerases is identical (parity strategy). To test this, we examined the effects of the intracellular coexistence of a mutator polymerase with low fidelity and a normal polymerase with high fidelity on adaptive evolution (disparity strategy). From the analysis using genetic algorithms based on the bacterial replication, it was found that the population using the disparity strategy could further expand its genetic diversity and preserve the advantageous genotypes more profoundly than the parity population. This strongly suggests that bacteria replicating with a disparity strategy may undergo rapid evolution, particularly during severe environmental changes. The implications of the conspicuous adaptability of Escherichia coli mutator strains are discussed in this context.

Animals↗

PubMed2001

Stilbenoids in lianas of Gnetum parvifolium.

Five new stilbene dimers were isolated from the lianas of Gnetum parvifolium in addition to known stilbenoids. The structures of the compounds were established on the basis of spectroscopic evidence, including long-range coupling and nuclear Overhauser effect experiments, in NMR spectrum. Among the isolates, 2b-hydroxyampelopsin F showed potent inhibitory activity in the Maillard reaction.

Acetylation↗

PubMed2000

Establishment and characterization of a colonic epithelial cell line MCE301 from transgenic mice harboring temperature-sensitive simian virus 40 large T-antigen gene.

We produced an immortalized colonic epithelial cell line, MCE301, using fetal mice transgenic for the temperature-sensitive simian virus 40 large T-antigen gene. MCE301 cells showed epithelial-like morphology and maintained tight connections with neighboring cells. The cells grew at a permissive temperature (33 degrees C), but the growth of the cells was significantly prevented at the nonpermissive temperature (39 degrees C). The cells expressed large T-antigen at 33 degrees C but not at 39 degrees C. MCE301 cells were not transformed, as judged by the absence of anchorage-independent growth in soft agar gel and lack of tumor formation in nude mice. Electron microscopic studies showed that the cells formed microvilli-like structures on the cell surface and junctional complexes such as tight junctions and desmosomes between the cells. The cells expressed cytosketal (acidic cytokeratins and actin), basement membrane (laminin and collagen type IV) and junctional complex proteins (ZO-1 and desmoplakin I + II), as judged by specific antibodies. Fetal bovine serum, epidermal growth factor, insulin-like growth factor and insulin significantly increased the cell growth at 33 degrees C. Moreover, MCE301 cells expressed colonic mucin Muc2 mRNA as demonstrated by reverse transcriptase-polymerase chain reaction, indicating that the cells originate from mucus-secreting cells. Alkaline phosphatase, a brush border-associated enzyme, was detected in the cells. Sodium butyrate (2 mM), an inducer of cellular differentiation, markedly elevated alkaline phosphatase activity. Thus, the present mouse colonic epithelial cell line MCE301 possessing these unique characteristics should provide a useful in vitro model of colonic epithelium.

Alkaline Phosphatase↗

PubMed2000

AMY-1 is a trigger for the erythrocyte differentiation of K562 cells.

We have reported that a novel c-Myc binding protein, AMY-1, stimulated the transcription activity of c-Myc and was translocated from cytoplasm to nuclei in a c-Myc-dependent manner. Here, the role of AMY-1 in cell differentiation was examined. AMY-1 expression was up-regulated after differentiation induction of human K562 cells to erythrocyte cells by AraC, while c-Myc expression was rapidly down-regulated. K562 cell lines expressing exogenous AMY-1 were established, and these cells expressed a high level of epsilon-globin mRNA, a marker gene necessary for erythrocyte cell differentiation, without differentiation induction. The addition of AraC rapidly initiated differentiation in these cell lines, which continued to differentiate to erythrocyte cells possessing a high level of hemoglobin even after the decrease in AMY-1 expression. These results suggest that AMY-1 is a trigger for K562 cells to differentiate to erythrocyte cells and that AMY-1 may have a function independent of or different from c-Myc.

Antimetabolites, Antineoplastic↗

PubMed2000

Early glottic squamous cell carcinoma. Predictive value of MR imaging for the rate of 5-year local control with radiation therapy.

PURPOSE: To evaluate MR findings in early (T1 and T2 stages) glottic carcinomas and the predictive value of MR imaging for the rate of 5-year local control with radiation therapy. MATERIAL AND METHODS: Eighty-three patients with early glottic carcinomas were prospectively examined with MR at 1.5 T. MR investigation included unenhanced T1-weighted, T2-weighted, dynamic and contrast-enhanced T1-weighted images. Three patients with presumed advanced diseases on MR were initially treated with total laryngectomy and were excluded from the study. The remaining 80 patients were treated with radiation therapy with curative intent. Tumor detectability, size and relationship to the thyroid cartilage were determined on MR images. The MR findings were then correlated with the rate of local control. RESULTS: Forty-eight of 80 lesions (60%) were detected on MR imaging. All detected lesions but 1 demonstrated increased signal on T2-weighted images. The lesions were best delineated on dynamic images (statistically significant). The 5-year local control rate with radiation therapy was 72%. Univariate analysis revealed clinical T stage, MR detectability, tumor size and relationship to the thyroid cartilage as significant predictors. Multivariate analysis revealed that the relationship to the thyroid cartilage was an independent factor. CONCLUSION: MR provides prognostic information about the results of definitive radiation therapy. To evaluate the tumor extension in lesions detected on precontrast MR images, contrast-enhanced dynamic images should be obtained.

Adult↗

PubMed2000

Dynamic helical CT of T1 and T2 glottic carcinomas: predictive value for local control with radiation therapy.

BACKGROUND AND PURPOSE: Tumor volume and cartilage invasion have been suggested as prognostic factors of glottic carcinomas following definitive radiation therapy. Radiologic examinations provide additional information regarding the deep extension of tumor. We determined whether dynamic helical CT can predict local control of early (T1 and T2 stage) glottic carcinomas treated with definitive radiation therapy. METHODS: Sixty-eight patients with early glottic carcinoma evaluated on pretreatment dynamic helical CT were treated with definitive radiation therapy. Tumor detectability, maximum dimension, tumor volume, and involvement of anatomic subsites (anterior commissure, ventricle, subglottic region, and thyroid and arytenoid cartilages) were determined by consensus by three radiologists without previous knowledge of the clinical information. The CT findings were correlated with local control. RESULTS: The two-year local control rate was 76%; 91% for T1 and 60% for T2 lesions. Univariate analysis revealed clinical T stage, tumor detectability, maximum dimension, tumor volume, anterior commissure involvement, ventricle involvement, and thyroid cartilage involvement as significant prognostic factors. Thyroid cartilage involvement was an independent predictor by multivariate analysis. The lesions separate from the thyroid cartilage had a 95% probability of local control, whereas the lesions adjacent to the cartilage had only a 42% control rate. CONCLUSION: Dynamic helical CT provides prognostic information for the results of definitive radiation therapy. Patients with a tumor adjacent to the thyroid cartilage had an increased risk of local failure.

Adult↗

PubMed1999

A conspicuous adaptability to antibiotics in the Escherichia coli mutator strain, dnaQ49.

By repeating the cycle of mutagenesis and selection, the Escherichia coli dnaQ49 mutator acquired high level resistance to ampicillin (30,000 micrograms ml-1), streptomycin (26,000 micrograms ml-1) and ofloxacin (3000 micrograms ml-1). Under the strong pressure of ofloxacin, dnaQ49 also followed the history of mutations in the gyrase and topoisomerase i.v. genes previously observed in clinical isolates of quinolone-resistant E. coli. The results of these in vitro experiments suggest that naturally existing mutators may participate in the rapid acquisition of resistance to various antibiotics in patients. A possible mechanism for the occurrence of this adaptability is discussed with special reference to the property of mutagenesis accompanying DNA replication.

Amino Acid Sequence↗

PubMed1998

Optimal image resolution for digital storage of radiotherapy-planning images.

PURPOSE: To evaluate the quality of digitized radiation-planning images at different resolution and to determine the optimal resolution for digital storage. METHODS AND MATERIALS: Twenty-five planning films were scanned and digitized using a film scanner at a resolution of 72 dots per inch (dpi) with 8-bit depth. The resolution of scanned images was reduced to 48, 36, 24, and 18 dpi using computer software. Image qualities of these five images (72, 48, 36, 24, and 18 dpi) were evaluated and given scores (4 = excellent; 3 = good; 2 = fair; and 1 = poor) by three radiation oncologists. An image data compression algorithm by the Joint Photographic Experts Group (JPEG) (not reversible and some information will be lost) was also evaluated. RESULTS: The scores of digitized images with 72, 48, 36, 24, and 17 dpi resolution were 3.8 +/- 0.3, 3.5 +/- 0.3, 3.3 +/- 0.5, 2.7 +/- 0.5, and 1.6 +/- 0.3, respectively. The quality of 36-dpi images were definitely worse compared to 72-dpi images, but were good enough as planning films. Digitized planning images with 72- and 36-dpi resolution requires about 800 and 200 KBytes, respectively. The JPEG compression algorithm produces little degradation in 36-dpi images at compression ratios of 5:1. CONCLUSION: The quality of digitized images with 36-dpi resolution was good enough as radiation-planning images and required 200 KBytes/image.

Humans↗

PubMed1998

Establishment and characterization of tracheal epithelial cell lines, TM01 and TM02-3, from transgenic mice bearing temperature-sensitive simian virus 40 large T-antigen gene.

Murine tracheal epithelial cell lines, TM01 and TM02-3, were established from a primary culture of tracheal cells of adult transgenic mice bearing a temperature-sensitive simian virus (SV40) large T-antigen gene. Both TM01 and TM02-3 cells, which grew until confluent monolayers were formed, maintained tight contact with neighboring cells, and retained the characteristics of epithelial cells with microvilli on the surface. These cells grew at a permissive temperature (33 degrees C), but did not at a nonpermissive temperature (39 degrees C), indicating that TM01 and TM02-3 cells undergo temperature-sensitive growth. Large T-antigen was expressed only in the nuclei at 33 degrees C. Sepharose CL-4B column chromatography using a 14C-glucosamine hydrochloride, indicating that both cells produced high molecular weight glycoconjugates, and suggesting that these cells may originate from mucus-producing cells. TM01 cells expressed intercellular adhesion molecular-1 (ICAM-1) in both unstimulated and stimulated (1,000 U/ml tumor necrosis factor-alpha and 500 U/ml interferon-gamma) conditions, whereas TM02-3 cells expressed ICAM-1 only under stimulated conditions. We conclude that these cell lines may serve as a useful model to study the tracheal cell functions under defined in vitro conditions.

Animals↗

PubMed1998

Asymmetrical DNA replication promotes evolution: disparity theory of evolution.

Heredity is guaranteed by faithful DNA replication whereas evolution depends upon errors accompanying DNA replication. This contradiction existing between heredity and evolution cannot be resolved in an individual organism, but only in terms of a population, in that a delicate balance exists between wild type and variants in a population which is necessary for the survival of the species. Namely, there seems to be a key in the mechanism of DNA replication to solve some problems of evolution. DNA is replicated semiconservatively using the leading and discontinuous lagging strands. According to our 'disparity theory of evolution', the existence of a sufficient fidelity difference between the leading and lagging strands is advantageous in terms of evolution, because the diversity of genotypes is enlarged but genotypes that have occurred in the past are guaranteed. In theory, by artificially increasing the fidelity difference between the leading and lagging strand ('disparity mutator'), evolution is accelerated while avoiding the extinction of the population. Using a disparity mutator, we should be able to improve living things, including multicellular organisms, within constrained conditions. A double-stranded algorithm, which mimics the structure and replication manner of DNA, is promising for solving optimization problems.

Animals↗

PubMed1997

MR evaluation of radiation otomastoiditis.

PURPOSE: The purpose of this study was to evaluate the incidence of radiation otomastoiditis, on using T2-weighted magnetic resonance (MR) imaging, in relation to radiation fields, doses, intervals, and clinical symptoms after radiotherapy that included the temporal bone in the fields. METHODS AND MATERIALS: We performed follow-up MR examinations at various intervals after radiotherapy including the temporal bones for 270 ears of 114 patients with various diseases of the head and neck and intracranial regions. The middle ear and mastoid air cells on T2-weighted images were scored as follows; showing no high signal intensity, a local high signal intensity area, or a high signal intensity area occupying the entire middle ear and all mastoid air cells. The radiation fields as depicted on the lateral simulator films classed as anterior to the clival line, posterior to the clival line, or both. RESULTS: The incidence of radiation otomastoiditis depicted on T2-weighted MR images increased in the patients who had received irradiation doses of 50 Gy or more. In the patients with doses of less than 50 Gy, the incidence was 18% within 6 months following radiotherapy, 13% at between 6 and 12 months, and 8% after 12 months, whereas it was more than 50% at any period after radiotherapy in the patients with 50 Gy or more. The incidence of radiation otomastoiditis was quite high in the patients whose radiation fields included region both anterior and posterior to the clival line. CONCLUSION: The incidence of radiation otomastoiditis as demonstrated on T2-weighted MR images is increased at irradiation doses of 50 Gy or more. To reduce the incidence of severe radiation otomastoiditis, the irradiation fields of the temporal bone when the dose is 50 Gy or more should be limited to as small as possible. The clival line is considered to be a good landmark in reducing the irradiation field when doses of 60-70 Gy are delivered in curative radiotherapy.

Adolescent↗

PubMed1997

Role of dynamic MRI in the evaluation of head and neck cancers treated with radiation therapy.

PURPOSE: To study the usefulness of dynamic magnetic resonance imaging in the evaluation of head and neck cancers treated with radiation therapy. METHODS AND MATERIALS: Seventy-six patients (58 males and 18 females; ages 20-82) with head and neck cancers (10 nasopharyngeal carcinomas, 22 mesopharyngeal carcinomas, 10 hypopharyngeal carcinomas, 16 oral cavity carcinomas, 11 lingual carcinomas, and 7 laryngeal carcinomas) were treated by radiation therapy combined with concomitant low-dose cisplatinum. Magnetic resonance imaging (MRI) was performed before and 2 weeks after the irradiation in all cases. After bolus administration of gadopentetate dimeglumine (Gd-DTPA) (0.1 mmol kg), images were obtained every 30 s (repetition time 200 ms, echo time 16 ms) using a 1.5 or 0.5-T superconductive unit. Biopsy or surgery was performed after radiation therapy and the histologic findings were correlated with the MRI findings (T1, T2, dynamic, and enhanced T1). RESULTS: Complete remission, partial response, and no response were obtained in 18, 36, and 7 cases, respectively. Dynamic MRI correctly diagnosed 17 of the 18 complete remission cases, 33 of the 36 partial response cases, and all of the 7 no-response cases. The accuracy of dynamic MRI, T1-weighted image, T2-weighted image, and Gd-enhanced T1-weighted image was 94.4%, 68%, 82%, and 86%, respectively. CONCLUSION: Dynamic MRI proved to be useful in the evaluation of the radiation therapy of head and neck cancers.

Adult↗

PubMed1997

The effect of azelastine on acute radiation dermatitis in mice models.

PURPOSE: In our previous report we described the clinical value of azelastine, an oral antiallergic agent, as an inhibitor of radiation dermatitis. Here we studied the effect of azelastine on normal skin and tumor size after irradiation in a mouse model. METHODS AND MATERIALS: The modifying effects of azelastine on both the degree of radiation dermatitis and antitumoral effect of radiation therapy were investigated in the normal skin as well as in SCC VII tumors of C3H/He mice. The right hind legs, with or without tumors, were irradiated with 20-60 Gy at 0.62 Gy/min. Azelastine was administered via the mouse chow, and acute skin reactions and tumor growth curves were compared between the azelastine and control groups. RESULTS: The acute skin reactions of the azelastine group were significantly less prominent than those of the control group (p < 0.01). At a dose of 40 Gy the dose modification factors were 1.19-1.25. The tumor growth curves of the azelastine and control groups were almost identical, indicating that the treatment response of irradiation was not affected by administration of azelastine. CONCLUSIONS: Application of azelastine reduces the degree of acute radiation dermatitis without affecting the antitumoral effect of radiation therapy.

Animals↗