Search PubMed⌕ Search

Biomedical subjects

M Muramatsu

Publications and source records attributed to M Muramatsu.

At least 19 recordsLinked to original sources

Expression of glutamine synthetase and cell proliferation in human idiopathic epiretinal membrane.

BACKGROUND/AIM: The mechanisms of the cellular origin and cell proliferation in the idiopathic epiretinal membrane (ERM) are unsolved. The aim of this study was to examine the expression of cell cycle related molecules and glutamine synthetase (GS), which is expressed in Müller cells and their processes, in ERM tissues. METHODS: The ERMs were surgically removed using pars plana vitrectomy. Formalin fixed, paraffin embedded ERM tissues were analysed by immunohistochemistry with anti-cyclin D1, p27 (KIP1), proliferating cell nuclear antigen (PCNA), and GS antibodies. RESULTS: The histopathological findings showed that all the ERMs consisted of oval or spindle mononuclear cells with thin collagen-like tissues. Immunoreactivity for GS was detected in collagen-like tissues of ERM, presenting a continuous, isodense pattern. GS immunopositive cells in all cases expressed PCNA in their nuclei. Nuclear immunoreactivity for cyclin D1 was noted in the ERM constituent cells, whereas p27 (KIP1) positive nuclei were not detected. CONCLUSION: Cyclin D1 and PCNA were expressed in the idiopathic ERM, which was mainly derived from Müller cells and extensions of their processes.

Aged↗

Baseline glomerular sclerosis influences morphological changes, but not level of serum creatinine.

The aim of this study was to investigate whether glomerular sclerosis (GS) at the time of engraftment affects subsequent morphology and clinical course of renal allografts. Eighty-one renal transplant recipients were recruited for this study. Protocol biopsies of the renal allografts were performed at engraftment, as well as at 1, 3, 5, and 7 years after transplantation. All cases were divided into 2 groups based on the presence of GS at engraftment, namely, non-GS and GS groups. Morphological changes in the renal allografts were graded from 0 to 3+ based on the severity of chronic allograft nephropathy (CAN) of the Banff classification based on 5 factors: percentage of GS, extent of interstitial fibrosis, tubular atrophy, arterial intimal thickening, and arteriolar hyalinosis. Furthermore, the level of serum creatinine (s-Cr) at each year was examined by recipient age and gender, donor age and gender, type of donor (living/cadaver), delayed graft function, acute rejection within 1 year after transplantation, mean blood pressure, and use of calcineurin inhibitors as well as the presence of GS at engraftment. The extent of GS at engraftment significantly correlated with donor age (P = .0038) but with a weak correlation coefficient. Although the severity of CAN developed gradually in both non-GS and GS groups, differences in morphological changes at engraftment between the 2 groups persisted throughout 7 years. Donor age and recipient gender influenced s-Cr significantly. In conclusion, the presence of GS at engraftment aggravates subsequent morphological changes and affects short-term but not long-term allograft prognosis.

Adolescent↗

Reversibility from delayed hyperacute rejection in ABO-incompatible renal transplantation: histopathological findings of renal allograft biopsy.

ABO-incompatible renal transplantation (ABOIRTx) tend to lead to blood type antibody-mediated rejection, the so-called delayed hyperacute rejection (DHAR), which results in short-term graft loss. To clarify the accurate incidence and prognostic value of DHAR among ABOIRTx, we reviewed biopsy specimens obtained from ABOKTx allografts with abrupt dysfunction during the early period after transplantation. Among 74 ABOIRTx patients, 34 patients displayed allograft dysfunction within 14 days following transplantation. The biopsy specimens were classified based on the Banff schema. The pathological diagnosis of ABO blood type antibody-mediated humoral rejection (ABO-AMHR) was made by the following 3 findings: Specimens with all of above-mentioned findings were categorized as severe ABO-AMHR; those with at least one findings, were categorized as mild ABO-AMHR. All patients were treated with steroid pulse therapy and/or modification of other immunosuppressants. Group 1 consisted of severe ABO-AMHR (n = 6); group 2 consisted of mild ABO-AMHR (n = 5); group 3 consisted of acute cellular rejection (n = 3); group 4 consisted of recovery phase of ATN (n = 11); group 5 consisted of calcineurin inhibitor toxicity (n = 2); and group 6 consisted of normal histology (n = 5). One of 6 patients (16%) in group 1 lost the graft because of DHAR irreversible by antirejection and anticoagulation therapy. However, there has been no clear definition of histpathological criteria for DHAR after ABO-incompatible kidney transplantation. The definition must prognosticate whether the rejection process is reversible.

ABO Blood-Group System↗

The pathologic impact of tacrolimus on protocol biopsy in renal transplant patients with basiliximab-based immunosuppression.

Forty-two ESRD patients underwent renal transplantation using basiliximab (mean age: 30.6 +/- 18.6 years at transplantation; male: 50%; ESRD duration: 51.6 +/- 13.0 months) between February, 2000 and July, 2003. All patients had a protocol biopsy on the day of transplant, on discharge from the hospital (35.5 +/- 13.2 days), and at 1 year after transplant. The immunosuppression included a calcineurin inhibitor, basiliximab, mycophenolate mofetil (MMF), and methylprednisolone. While 16 patients used tacrolimus (FK group: 29.4 +/- 16.6 years old), 26 patients used cyclosporine (CsA group: 31.4 +/- 20.1 years old). Protocol biopsies were graded according to the Banff 97 classification. The incidence of acute rejection episodes within 1 year was greater in the CsA (15%) than the FK group (6%). Serum creatinine at hospital discharge was similar (CsA: 1.01 +/- 0.59 mg/dL, FK: 0.97 +/- 0.49, p = .18); however creatinine at 1 year differed significantly (CyA: 1.22 +/- 0.88 mg/dL, FK: 0.92 +/- 0.39, P = .03). There was a trend toward an increase in the score of interstitial inflammations in the CsA group, while it remained constant in the FK cohort (P = .05 at 1 year between the two groups). Other pathologic scores (t, ci, ct, cv, ah) did not differ between the groups at 1 year. Although there were no differences in the demographics between the two groups, there were several trends toward better renal function in the FK group.

Antibodies, Monoclonal↗

First living related kidney transplantation results in excellent outcomes for small children.

OBJECTIVE: The aim of this study was to evaluated the outcomes of living related kidney transplantation in small children. MATERIALS AND METHODS: Ten pediatric patients with body weights less than 10 kg received parental kidney transplants (five mothers and five fathers). An intra-abdominal approach was used in nine children and a retroperitoneal approach in one child. Bilateral, left, or right nephrectomy was performed in seven, two, and one child, respectively. Immunosuppression consisted of either cyclosporine (n = 7) or tacrolimus (n = 3) with either mizoribine (n = 4) or mycophenolate mofetil (MMF) (n = 5) or azathioprine (n = 1), and methylprednisolone (n = 10). Antilymphocyte globulin was used in the first series of four children; basiliximab in the most recent five children. RESULTS: All renal allografts functioned immediately after transplantation despite the mismatched size of the large renal allografts. Nine of 10 children were alive with a functional allograft at 6 to 196 months posttransplantation. One child died of intra-abdominal bleeding 5 days posttransplantation. One child has suffered chronic allograft nephropathy 11 years posttransplantation (serum creatinine 3.3 mg/dL). The remaining eight children display good renal function (serum creatinine = 0.2 to 1.43 mg/dL). Steroids were withdrawn in eight of nine children; one child continues on alternative-day therapy. One child (LD55) exceeded the mean standard height. The most recent height standard deviation (SD) scores were superior (-1.75 +/- 1.39 [-3.83 to 0.54]; P < .0082) to those at transplantation (-2.91 +/- 0.79 [-2.00 to -4.14]). CONCLUSIONS: The outcomes of living related kidney transplantation in small children were excellent despite the operative risks and the difficulty of cardiovascular and fluid management. Transplantation for small children appears to result in much better quality of life and growth than dialysis.

Antibodies, Monoclonal↗

Haplotyping of TNFalpha gene promoter using melting temperature analysis: detection of a novel -856(G/A) mutation.

Tumor necrosis factor alpha (TNFalpha) is a potent cytokine with a wide range of pro-inflammatory activities and plays a critical role in the pathogenesis of a number of infectious, inflammatory, autoimmune, and metabolic diseases. We determined four single-nucleotide polymorphisms (SNPs), -1031(C/T), -863(C/A), -857(C/T), and -308(G/A) in the TNFalpha promoter region using melting temperature analysis, among 1451 geriatric autopsy samples. Two adjacent SNPs, -863(C/A) and -857(C/T), were directly assayed by a single probe reaction, which correctly determined three of four expected haplotypes. Sequence confirmation related that the most rare haplotype (8/2902 chromosomes, frequency: 0.26%) contains a novel mutation of -856(G/A), instead of the predicted haplotype. These results indicate that melting temperature analysis provides a robust method to determine the polymorphisms in the TNFalpha promoter.

Haplotypes↗

Elevations of AGE and vascular endothelial growth factor with decreased total antioxidant status in the vitreous fluid of diabetic patients with retinopathy.

BACKGROUND/AIMS: Advanced glycation end product (AGE) induces vascular endothelial growth factor (VEGF) expression in cell culture and animal models, being considered to be involved in development of diabetic retinopathy; oxidative stress also has a part in diabetic retinopathy. However, the interrelations between AGE, VEGF, and oxidative stress remain to be elucidated. In this study, vitreous AGE, VEGF, and total antioxidant levels in were determined in diabetic patients with retinopathy, and the relations among them investigated. METHODS: ELISA (enzyme linked immunosorbent assay) was used to determine the vitreous levels of AGE and VEGF in 41 patients with diabetic retinopathy and 28 non-diabetic control subjects. Total antioxidant levels in vitreous of 20 diabetic patients and 18 controls were also analysed by ELISA. RESULTS: The vitreous levels of AGE and VEGF were significantly higher in diabetic patients than in control subjects (p<0.01 for both). There was a significant correlation between the vitreous AGE and VEGF levels (p<0.001). Total antioxidant status was decreased in vitreous in patients with diabetes compared with the controls (p<0.01). Furthermore, both AGE and VEGF levels were inversely correlated with the total antioxidant status (p<0.01 and p<0.05, respectively). CONCLUSION: This study suggests that AGE and decreased total antioxidant status may contribute to the pathogenesis of diabetic retinopathy via induction of VEGF.

Adult↗

Gene expression profile in rat pancreatic islet and RINm5F cells.

To clarify tissue-specificity of pancreatic beta cells, comparison of mRNA expression in various conditions of the tissue of multiple organisms is important. Although the developed methodologies for mRNA monitoring such as microarray, rely on the growth of dbEST (database of expressed sequence tag), a large number of unknown genes in the genome, especially in the rat, have not been shown to be expressed. In this study, we have established the first database of ESTs from rat pancreatic islet and RINm5F cells. Two cDNA libraries were constructed using mRNAs from rat pancreatic islet and RINm5F cells to cover a wider spectrum of expressed genes. Over 40,000 clones were randomly selected from the two libraries and partially sequenced. The sequences obtained were subjected to BLAST database analyses. This large-scale sequencing generated 40,710 3'-ESTs. Clustering analysis and homology search of nucleotide and peptide databases using both 3'- and 5'-ESTs revealed 10,406 non-redundant transcripts representing 4078 known genes or homologs and 6328 unknown genes. To confirm actual expression, the unknown sequences were further subjected to dbEST search, resulting in the identification of 5432 significant matches to those from other sources. Interestingly, of the remaining sequences showing no match, 779 were found to be encoded by exon-intron organization in the corresponding genomic sequences, suggesting that these are newly found as actually expressed in this study. Since many genes are up- or down-regulated in differing conditions, applications of the expression profile should facilitate identification of the genes involved in cell-specific functions in normal and disease states.

Animals↗

BK virus nephropathy in a patient with ABO-incompatible renal transplantation.

A 43-year-old woman with end-stage renal disease originating from IgA nephropathy entered chronic haemodialysis therapy. She then received an ABO-incompatible living related renal transplantation. Initial immunosuppression consisted of azathioprine, methylprednisolone and tacrolimus. At 155 days after transplantation, the azathioprine was changed to mycophenolate mofetil for continuous graft dysfunction. Furthermore, a total of three courses of anti-rejection therapy was given. At 665 days after transplantation, diagnosis of BK-virus nephropathy was made by immunohistochemical analysis and viral DNA assay. Therefore the immunosuppression therapy was reduced for graft dysfunction. All five renal biopsy specimens were examined retrospectively in order to determine when the BK virus nephropathy had developed. The expressions of SV40 large T antigens were detected from the third (117 days) to the fifth (665 days) biopsies, with increasing numbers of SV40 large T antigen positive cells. In addition, many cells contained inclusion bodies which were already present in the urinary sediment for 3 months post-transplantation. Although it is difficult to make a diagnosis of early stage of BKVN, we have to consider with caution if urinary cells with inclusion body are seen. Awareness of BKVN at the earliest opportunity is important in order to avoid over-immunosuppression.

Adult↗

Application of discordant sib-pair linkage analysis for mapping minor histocompatibility antigen loci in a novel graft-vs-host-disease model.

Graft-vs-host disease (GVHD) is an adverse effect of allogenic bone marrow transplantation. Although a major cause of GVHD following bone marrow transplantation is incompatibility of major histocompatibility antigen (human leukocyte antigen, HLA) in donor-recipient pairs, the incompatibility of minor histocompatibility antigen (mHa) is known as another cause, especially in HLA-matched donor-recipient pairs. In 1998, Lunetta and Rogus proposed the use of discordant sib-pair (DSP) linkage analysis for detecting mHa and calculated the statistical power using the GVHD model, assuming single mHa locus with multiple alleles. Recently, we proposed a different GVHD model, assuming multiple mHa loci with two alleles (biallelic), considering the single-nucleotide polymorphisms. When the effect of each mHa locus on the occurrence of GVHD is independent, the possible triangle for DSP proposed by Lunetta and Rogus is not optimum, but a new possible triangle, named here as GVHD region, is needed. We evaluated, based on Monte Carlo simulation, the test criteria [log of odds (lod) score cutoffs] and power of DSP using the GVHD region for various parameter sets. The GVHD region showed a higher power than the DSP and entire regions in plausible situations. Our results suggest that the application of GVHD region to DSP is effective for the screening of mHa loci.

Genetic Linkage↗

Changes in the distribution pattern of gelatin-binding protein of 28 kDa (adiponectin) in myocardial remodelling after ischaemic injury.

AIMS: Gelatin-binding protein of 28 kDa (GBP28) is a collagen-like plasma protein having a binding capacity with collagens. We investigated GBP28 role on myocardial remodelling as well as the diagnostic significance of GBP28 immunostaining in myocardial infarction. METHODS AND RESULTS: Myocardial tissues obtained from 47 autopsied hearts with infarction were immunostained with antibodies against GBP28, fibronectin, type III and IV collagens, and prolyl 4-hydroxylase. GBP28 was distributed in interstitium of infarcted lesions at an early stage. GBP28 was linearly found both along the border with vital myocardium and at the periphery of surviving cardiomyocyte around the lesion at granulative stage. However, it was not observed in the scar. GBP28 distribution patterns were similar to those of fibronectin in infarcted lesions and those of type IV collagen at the periphery of cardiomyocyte. Type III collagen was not recognized in the early-stage lesion but increased along with scar maturation. Prolyl 4-hydroxylase was found in surviving cardiomyocytes around the lesion during all stages and in interstitial cells appeared in granulation tissue. CONCLUSION: GBP28 plays a role as a scaffold of newly formed collagen in myocardial remodelling after ischaemic injury, and GBP28 immunostaining may assist in a diagnosis of healing stage.

Adiponectin↗

Spontaneous haemorrhage into metastatic brain tumours after stereotactic radiosurgery using a linear accelerator.

OBJECTIVE: To determine the incidence and clinical characteristics of spontaneous haemorrhage into metastatic brain tumours after radiosurgery. METHODS: Intratumour haemorrhage rate, clinical features, and treatment were evaluated in 54 patients with 131 brain metastases of varying origin who were treated using linear accelerator radiosurgery. The marginal dose was maintained constant at 20 or 25 Gy, irrespective of tumour size. RESULTS: Haemorrhage was identified in 7.4% of the metastases (five tumours in four patients) before radiosurgery and in 18.5% (10 tumours in 10 patients) after radiosurgery. In three cases, haemorrhage into the tumour after radiosurgery was symptomatic. Half the haemorrhages occurred within one month of radiosurgery. The changes in tumour size observed at the time of haemorrhage were an increase in one tumour, no change in five, and a decrease in four. Haemorrhage into a tumour after radiosurgery was more likely to occur in female patients, in tumours with a larger volume on pretreatment neuroimaging, and in tumours treated with a larger number of isocentres or a higher maximum dose. Haemorrhagic features in the patients or their tumours on presurgical assessment were not disposing factors to haemorrhage after radiosurgery. CONCLUSIONS: When larger brain metastases are aggressively treated by radiosurgery, better local control may be attained but there may also be a higher risk of haemorrhage soon after the treatment.

Adult↗

Expression of estrogen, progesterone and androgen receptors in the oviduct of developing, cycling and pre-implantation rats.

To determine expression and localization of receptors for estrogen (ER), progesterone (PR) and androgen (AR), detailed immunohistochemical evaluations were performed in the Sprague-Dawley rat oviduct during pre- and neonatal development, estrous cycle and pre-implantation period. In addition, real-time RT-PCR studies were conducted to evaluate changes in ERalpha, ERbeta, total PR (PR-A+B), PR-B and AR mRNA expressions. All receptors except for ERbeta were detected in epithelial, and stromal or mesenchymal cells of the fetal and neonatal oviduct, and increased with development. During the estrous cycle and early pregnancy, ERalpha and PR-A+B were expressed in epithelial, stromal and muscle cells throughout the oviduct region, and showed changes in expression predominantly in the isthmus. Only a few epithelial cells in the infundibulum (inf) and ampulla (AMP) showed ERbeta staining. AR was detected in stromal and muscle cells throughout the oviduct region, and in epithelial cells of the inf/AMP. Taken together, ERalpha, PR-A+B and AR were detected in the epithelium of the inf/AMP region, but all of these receptors were expressed in a distinct subset of epithelial cells which were negative for beta-tubulin IV, a ciliated epithelial cell marker. These results contribute to a better understanding of the respective roles of ERs, PRs and AR in the rat oviduct.

Animals↗