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M Hagihara

Publications and source records attributed to M Hagihara.

At least 37 records · Page 2Linked to original sources

[The state of the art of the computer applications in clinical laboratory medicine].

For all kinds of purposes, a huge amount of data are processed at a clinical laboratory, including not only letters and numerical values, but also waves and graphics. So various computer applications have been developed for it, although only a small part of them has survived through severe use in practice. They have to cope with many exceptions that will occur at any time, and also to adapt progressive changes in medicine and in needs to medicine, otherwise they cannot increase the productivity of their users, rather they will decrease it. To avoid such failures, (1) one should make a comprehensive system analysis before planning, (2) one should understand completely what will happen at the user interface of the system, (3) one should make systems so flexible that they can adapt the alteration of needs of their users. This paper present some outstanding examples that are used or are going to be used successfully in each practical application of laboratory medicine, and point out the key factors of each success.

Clinical Laboratory Information Systems↗

Evidence of long-term survival of donor-derived cells after limbal allograft transplantation.

PURPOSE: Severe destruction of the corneal limbus causes conjunctival invasion and subsequent visual loss. Limbal allograft transplantation (LAT) was recently proposed for the treatment of these disorders. However, whether the method functions as a stem cell transplantation of the corneal epithelium remains unclear. This study provided evidence that donor-derived corneal epithelial cells survive long after LAT. METHODS: Epithelial cells on the paracentral cornea in patients who have undergone LAT were subjected to fluorescence in situ hybridization (FISH) and polymerase chain reaction restriction fragment length polymorphism (RFLP) analysis. X and Y chromosomes were detected using sex chromosome-specific probes in the FISH analysis, and HLA-DPBI antigens were examined in the RFLP analysis. Eyes receiving conventional penetrating keratoplasty (PKP) served as controls. RESULTS: Donor-derived epithelial cells were detected in three of five eyes (60.0%) in the FISH analysis and in seven of nine eyes (77.8%) in the RFLP analysis. Among these eyes, one and three eyes in the FISH and RFLP analysis, respectively, had both donor- and recipient-derived cells. In control PKP eyes, none of the eyes in the FISH analysis and one of eight eyes (12.5%) in the RFLP analysis had donor-derived cells. CONCLUSIONS: These results suggest that donor-derived cells survive much longer after LAT than those after PKP, and that LAT may function as stem cell transplantation of the corneal epithelium.

Adolescent↗

The impact of HLA-A matching in corneal transplantation.

Previously, we have reported the results of our retrospective study on the effect of HLA class II allele matching on the outcome of corneal transplant. Here, we demonstrate our findings of the study for HLA class I allele matching in the same study subjects. Eighty transplant recipients were typed for HLA-A, and 79 transplant recipients were typed for HLA-B alleles, by PCR-SSOP. The association between HLA class I allele matching and 1-year rejection-free graft survival was evaluated. When a total of 79 transplant recipients were subdivided into groups with matching (one to four alleles matched) and without matching (no allele matched) for HLA class I (HLA-A and -B), a significantly higher rate of 1-year rejection-free graft survival was detected in transplant recipients with matching, compared with those without matching (p=0.0258). We have found that matching for at least one HLA class I allele was more beneficial especially in high-risk transplant recipients (p=0.0076). Also, an analysis of matching for each locus separately, detected that, HLA-A matching was significantly associated with a higher rate of 1-year rejection-free graft survival. Transplant recipients with HLA-A matching (one or two-alleles matched) had significantly higher rejection-free graft survival compared with those without matching (no allele matched), when high- and low-risk groups were analyzed together (p=0.0099). Furthermore, matching for HLA-A allele was significantly beneficial compared with no matching in high-risk transplant recipients (p=0.0154). Nevertheless, no significant effect of HLA-B matching was detected. We conclude that HLA class I, especially HLA-A matching has a beneficial effect for corneal transplant outcome.

Alleles↗

Female sterility in mice lacking the basigin gene, which encodes a transmembrane glycoprotein belonging to the immunoglobulin superfamily.

Basigin (Bsg) is a transmembrane glycoprotein belonging to the immunoglobulin superfamily. Bsg knock-out mice exhibit infertility of both sexes. Based on limited results, defective implantation has been considered to be the cause of the female infertility. We demonstrate here that disruption of the Bsg gene produces the failure of female reproductive processes including not only implantation but also fertilization. Bsg mRNA expression in cumulus cells and basolateral localization of the Bsg protein in the endometrial epithelium further support the importance of Bsg in these processes.

Animals↗

HLA-A*24-B*07-DRB1*01 haplotype implicated with genetic disposition of peak bone mass in healthy young Japanese women.

HLA exhibits the most extensive polymorphism of any of the known human genes and is known as a genetic marker which allows genetic background of many diseases and physical phenomena. In this study, we, therefore, tried to investigate the regulation of HLA polymorphism and peak bone mass (PBM) in order to elucidate the genetic backgrounds of bone metabolism in young women. Subjects were 67 healthy young Japanese women (average age: 23.6 +/- 2.6 years, Body Mass Index (BMI): 19.9 +/- 2.0 who were randomly chosen. Allelic polymorphisms in HLA class I (HLA-A and -B) and HLA-class II (DRB1) were investigated by PCR-SSOP and PCR-SSP. Vitamin D Receptor (VDR) and Estrogen Receptor (ER) gene polymorphisms were also analyzed. Lifestyle factors, such as exercise and nutrition, were examined by questionnaire. Bone mineral density was examined using with Lunar DPX-L. Subjects who possessed HLA-B*07 had a significantly lower PBM than those without B*07 (p < 0.05). All subjects were divided into 3 groups according to HLA haplotypes linked with HLA-B*07, as follows: A*24(+/-)B*07(-)DRB1*01(+/-), A*24(+)B*07(+)DRB1*01(-), and A*24(+)B*07(+)DRB*01(+). There were no significant differences between these three groups in factors that affect bone metabolism, such as age, age at menarche, BMI, calcium intake, exercise habits, VDR or ER allele frequency. The HLA-A*24-B*07-DRB1*01 haplotype had a significantly lower Z score in the lumbar spine compared with subjects without this haplotype (p < 0.05). When the Z score was divided by values higher or lower than +1 or -1, all 3 subjects whose Z score was lower than -1.0 were found to have the HLA-A*24-B*07-DRB1*01 haptotype. A significant association between HLA-A*24-B*07-DRB1*01 and Z score < -1 was found (Yate's correction chi(2) = 10.82, p = 0.001, RR = 204). In conclusion, the HLA-A*24-B*07-DRB*01 haplotype can be considered a new genetic marker implicated with low PBM in healthy young Japanese women.

Adult↗

T-cell clonal change after allo-kidney transplantation in humans.

Whether T cells circulating peripherally express changes at a clonal level after renal transplantation is uncertain. To clarify this issue, we analyzed T-cell clonality of peripheral blood lymphocytes (PBLs) in 12 renal transplant recipients by a novel polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) method that can discriminate T-cell clones with different T-cell receptor (TCR) Vbeta motifs. The PCR-SSCP study showed that after transplantation, only a few distinct T-cell clonotypes accumulated in the absence of clinical episodes, irrespective of the compatibility of HLA antigens. In contrast, various T-cell clones appeared in cases of acute rejection (AR) and infection. These subsided immediately after the AR was resolved; however, they remained long after the resolution of the infection. In a case of AR followed by an infectious episode, distinct T-cell clones appeared concomitantly with each episode. Several of them disappeared or remained thereafter. In one case, significant numbers of accumulating bands were observed by in-vitro stimulation by mixed lymphocyte reaction (MLR); several were identical to those found in vivo. However, some of those that did not appear in vitro were apparent in vivo. In conclusion, the appearance of T-cell clonotypes at a peripheral level indicates the existence of immunologically activated T-cell clones, which were significantly affected by immunosuppressive therapy. It was also determined that the T-cell immune system is much more complicated in vivo than in vitro.

Abscess↗

Participation of oligomerization through C-terminal D domain region of Sp1 in DNA binding.

Transcription factor Sp1 is a Cys2His2-type zinc finger protein that specifically binds to GC-boxes on numerous viral and cellular genes. In this study, we prepared several Sp1 mutant peptides Sp1 (530-696) containing zinc finger region and the domain D, and Sp1 (530--623) containing only zinc finger region, and then investigated the participation of the C-terminal domain D of Sp1 for GC-box binding. Gel mobility shift assays demonstrate that Sp1 (530--696) evidently shows DNA-binding modes different from Spl (530--623) and that the Sp1 mutant containing the domain D self-interacts directly. Domain D may play an important role in the synergistic activation of Sp1 by the stacking of tetramers. A novel model for Sp1 oligomerization has also been proposed.

Amino Acid Sequence↗

Stage-specific localization of basigin, a member of the immunoglobulin superfamily, during mouse spermatogenesis.

Ablation of the transmembrane glycoprotein basigin leads to azoospermic mice, indicating that this gene is essential for spermatogenesis. To examine the functions of basigin in the testis, the precise localization of basigin during spermatogenesis was examined immunohistochemically. In the adult mouse testis, basigin immunoreactivity appeared on the cell surface of leptotene spermatocytes and gradually increased in intensity during the meiotic prophase. Cytoplasmic staining, as well as cell surface staining, was detected in spermatids. The most conspicuous reactivity was found in the spermatids at steps 9-11 and in the flagella of spermatids. Immuno-electron microscopic analysis demonstrated that basigin was localized not only on the plasma membranes of spermatocytes and spermatids, but also on the plasma membrane of the Sertoli cell processes which contact the spermatocytes and spermatids. Basigin immunoreactivity was also detected during postnatal development in spermatocytes and spermatids but not in spermatogonia. Experimental cryptorchid testes which contain only spermatogonia and Sertoli cells in the seminiferous epithelium showed no basigin immunoreactivity. Seven days after surgical reversal of the cryptorchid testis, spermatocytes reappeared in the tubules, along with basigin immunoreactivity. Furthermore, in sterile mutant mice, in which neither spermatocytes nor spermatids were generated, no basigin immunoreactivity was detected in the seminiferous tubules. These findings indicate that expression of basigin is concomitant with appearance of spermatocytes in the seminiferous tubule, and suggest that basigin is involved in the interaction between Sertoli cells and germ cells at specific stages of spermatogenesis.

Animals↗

[Allogeneic bone marrow transplantation in children from related donors other than HLA-identical siblings].

Thirty-five children with poor-prognosis disease underwent allogeneic bone marrow transplantation (BMT) from related donors other than HLA identical siblings (parents in 18 cases, non-identical siblings in 14, and other relatives in 3). Phenotypically identical donors were involved in 12 cases, donors with one mismatched locus in 17, and donors with two or more mismatched loci in 6. Thirty-two of the children received total-body irradiation as part of their conditioning regimen, followed by unpurged marrow-cell infusions (averaging 4.09 x 10(8) cells/kg). Methotrexate and cyclosporin were administered for graft-versus-host disease (GVHD) prophylaxis; 15 of the children also received antithymocyte globulin (ATG) infusions. The effective graft rate for the group was 84. 8%; of 5 patients who experienced rejections, 4 had non-malignant diseases. The incidence of grade II-IV acute GVHD was 48.4%, significantly higher than that for groups that received allogeneic BMT from matched sibling donors. Three children (8.8%) died of severe GVHD. The incidence of acute GVHD in phenotypically matched patients was the same as that in the one-locus mismatched cases. MLC reactivity affected the incidence of acute GVHD (60.0% MLC-positive, 28.6% negative). ATG reduced the severity of acute GVHD. The event-free survival rate was 40.8 +/- 8.5% for the entire group (N = 35; 32.9 +/- 10.5% for the 22 children with malignancies, and 53.8 +/- 13.8% for the 13 with non-malignant diseases). Despite the risk of severe GVHD, allogeneic BMT from related donors other than HLA-identical siblings seems to be an effective treatment for patients with poor-prognosis diseases.

Acute Disease↗

Association between HLA-DPB1 matching and 1-year rejection-free graft survival in high-risk corneal transplantation.

We analyzed the effect of matching for HLA class II alleles on corneal graft outcome in a single-center, retrospective study from January 1991 through April 1996. The study involved 81 transplant recipients at high and low risk of corneal graft rejection, who were typed by the polymerase chain reaction-restriction fragment length polymorphism method and who completed at least 1-year of follow-up. The DRB1, DQB1, and DPB1 alleles were analyzed together and transplant recipients were subdivided into groups with matching (one to four alleles matched in the high risk or one to five alleles matched in the low risk) and without matching (no allele matched) for HLA class II. A significantly higher rate of 1-year rejection-free graft survival was revealed in high-risk transplant recipients with matching, compared with those without matching (P=0.0238). We have shown that matching for at least one HLA class II allele was actually beneficial in high-risk transplants. An analysis of matching for each allele separately, detected that only HLA-DPB1 matching was significantly associated with a higher rate of 1-year rejection-free graft survival in high-risk transplant recipients with matching (one or two alleles matched) compared with those without matching (no allele matched) (P=0.0139). In particular, matching for one DPB1 allele was significantly beneficial compared with no matching (P=0.0140). There was no significant effect of HLA-DRB1 and -DQB1 matching (P=0.3177 and P=0.2878, respectively). Furthermore, a strong association between DPB1 matching and 1-year rejection-free graft survival was observed in DRB1-incompatible high-risk transplant recipients (P=0.0308). Nevertheless, no significant effect of DPB1 matching was detected in DQB1-incompatible transplant recipients. Our findings indicate that HLA class II DNA typing is clinically relevant for corneal transplant recipients and that especially HLA-DPB1 matching has a beneficial effect in high-risk corneal transplantation.

Adolescent↗

Synchronous decline of serum-soluble HLA class I antigen and beta-cell function in insulin-dependent diabetes mellitus.

Serum-soluble HLA class I molecules (sHLA) have immunomodulatory functions and their serum levels correlate with the HLA class I phenotype. We studied longitudinal changes of serum sHLA levels in insulin-dependent diabetes mellitus (IDDM). A total of 198 serum samples were obtained from 40 IDDM patients before and after IDDM onset. sHLA was assayed by a sandwich ELISA. sHLA levels in IDDM patients at the initiation of insulin therapy (IDDM onset) were markedly reduced compared with those in normal controls (334.2 +/- 26.3 ng/ml vs 492.4 +/- 55.5 ng/ml, mean +/- SEM, P = 0.0038). They fell sharply during 6 months before and after the onset of IDDM. The dynamic profile of sHLA and the time course of beta-cell loss were different between IDDM patients with and without HLA-A24. In those with HLA-A24, sHLA became significantly lower than normal controls with HLA-A24 at IDDM onset. Recovery of their sHLA values occurred at 3 years from IDDM onset. On the other hand, in those without HLA-A24, sHLA levels began to decrease since the onset of IDDM and became significantly lower than normal controls without HLA-A24 at 4 years after the onset. Recovery of sHLA occurred at more than 6 years from the onset. An early (within 18 months), complete loss of beta-cell function occurred in 5 of 13 IDDM patients with HLA-A24 compared with 1 of 14 of those without HLA-A24 (P = 0.077). A late (more than 36 months after the onset of IDDM), complete loss of beta-cell function occurred in 7 of 14 IDDM patients without HLA-A24 but in none of 13 of those with HLA-A24 (P = 0.0058). These results indicate that the decline of sHLA is synchronous with massive beta-cell destruction, and that these events occur during a short period in IDDM patients with HLA-A24, whereas they occur during a relatively long period in those without HLA-A24.

Adolescent↗

Serum concentrations of soluble HLA-class I and CD8 forms in patients with viral hepatic disorders.

Soluble HLA-class I and CD8 molecules were determined by sandwich ELISA in patients with viral-induced hepatic disorders. As a whole, the patients with hepatic disorders (acute hepatitis: AH; chronic hepatitis: CH; liver cirrhosis: LC; hepatocellular carcinoma: HCC) showed higher sHLA-class I and sCD8 levels than normal controls (P < 0.001). AH patients had the highest sHLA-class I levels (mean, 3513 +/- 2112 ng/ml), followed by CH (2896 +/- 1290 ng/ml), LC (2293 +/- 1266 ng/ml), and HCC (2221 +/- 1212 ng/ml) sCD8 levels wer highest in AH, followed by HCC, LC, and CH, in that order. Among histologically defined C virus-positive patients, sHLA-I levels were higher in those with chronic active hepatitis (CAH) 2A (3802 +/- 1124 ng/ml) than in those with chronic persistent hepatitis (CPH; 2200 +/- 711 ng/ml; P < 0.01), the levels then decreased as the disease progressed (CAH2B, 3564 +/- 1783 ng/ml, LC, 2376 +/- 1265 ng/ml). In contrast, sCD8 values showed little difference among the disorders. sHLA-class I levels showed a positive correlation with sCD8 values both in whole patients and in patients with AH (P < 0.01), but no correlation was shown, in any patients, with biochemical parameters such as GPT and GOT. These findings, taken together, suggest that hepatic destruction is not the only cause of sHLA-class I production, but that sHLA-class I levels, together with sCD8 levels, may reflect immunological activity in hepatic disorders.

CD8 Antigens↗