Age in months and birth order in infant nonfatal injuries: A retrospective cohort study.

Objective: To examine the age in months at which infants visited outpatient clinics or emergency rooms for the first time for nonfatal injuries and to identify risk factors for the occurrence of these injuries. Study design: Retrospective cohort study. Methods: We used a health insurance claims database in Japan. Infants born between April 2012 and December 2014 were identified and followed until 12 months of age. We identified their first visit to outpatient clinics or emergency rooms because of nonfatal injuries (wounds/fractures, foreign bodies, and burns). Cox regression analysis was used to examine the association of nonfatal injuries with infants' sex, birth order, and parental age. Results: We identified 46,431 eligible infants. Of these, 7606 (16.4%) were brought to an outpatient clinic or emergency room for nonfatal injuries within 12 months of birth. Of the 7,606, 21.7% were aged ≤4 months and 44.7% â€‹≤ â€‹7 months. First-born infants were more likely to have wounds/fractures and burns. Conclusion: One-fifth of first nonfatal infant injuries occurred within 4 months of age. Healthcare providers should provide early education about injury prevention, especially to caregivers of first-born infants.

Natriuretic peptide receptor A is related to the expression of vascular endothelial growth factors A and C, and is associated with the invasion potential of tongue squamous cell carcinoma.

Natriuretic peptide receptor A (NPRA) is one of the natriuretic peptide receptors. NPRA has been reported to play a role in the carcinogenesis of various tumours, as well as functional roles in renal, cardiovascular, endocrine, and skeletal homeostasis. The clinicopathological significance of NPRA in tongue squamous cell carcinoma (TSCC) was examined in this study. The overexpression of NPRA was more frequent in TSCC (21/58, 36.2%) than in the normal oral epithelium (0/10, 0%) (P<0.05). It was also more frequently observed in cancers with higher grades according to the pattern of invasion (grades 1-2 vs. grades 3-4, P<0.01). Additionally, there was a tendency towards an association between the N classification and NPRA expression (N0 vs. N1-2, P=0.06). Significant correlations were also observed between the expression of NPRA and that of VEGF-A (P<0.001) and VEGF-C (P<0.001). The high-NPRA expression group had a significantly poorer prognosis, with a 5-year disease-specific survival rate of 39.7%, compared to 97.0% in the low-expression group (P<0.001). Multivariate analysis suggested that the overexpression of NPRA may also be an independent prognostic factor (P<0.05). In conclusion, NPRA is associated with VEGF expression levels, invasion, and metastasis, and may be a prognostic factor in TSCC patients.

TNF-α-induced IL-6 and MMP-9 expression in immortalized ameloblastoma cell line established by hTERT.

OBJECTIVE: Ameloblastoma (AM) shows locally invasive behaviour. However, biological investigations regarding regulation of gene expression associated with AM pathological features are difficult to perform, because AM cells can be passaged for a few generations due to senescence. We report a newly established immortalized AM cell line, AMB cells, by transfection with human telomerase reverse transcriptase (hTERT). Furthermore, we examined whether TNF-α modulates bone resorption-related genes, IL-6 and MMP-9 in cooperation with TGF-ß or IFN-γ. MATERIALS AND METHODS: Following transfection of an hTERT expression vector into AM cells using a non-viral method, the effects of cytokines on the expressions of IL-6 and MMP-9 mRNA were examined using real-time PCR. TNF-α-induced NF-κB activity was examined by western blotting and transcription factor assays. RESULTS: AMB cells continued to grow for more than 100 population doublings. Stimulation with TNF-α increased IL-6 and MMP-9 mRNA expressions, as well as NF-κB activation. Furthermore, TGF-ß and IFN-γ dramatically increased TNF-α-mediated expressions of MMP-9 and IL-6 mRNA, respectively, while those responses were suppressed by NF-κB inhibitor. CONCLUSION: We established an immortalized AM cell line by hTERT transfection. TNF-α-mediated regulation of MMP-9 and IL-6 via NF-κB may play an important role in the pathological behaviour of AMs, such as bone resorption.

Predictors of obstructive sleep apnoea-hypopnea severity and oral appliance therapy efficacy by using lateral cephalometric analysis.

Obstructive sleep apnoea-hypopnea (OSAH) is a common disorder characterised by repetitive complete or partial closure of the upper airway during sleep, which results in sleep fragmentation and oxygen desaturation. There is growing interest in the use of oral appliances (OAs) to treat OSAH. The purpose of this study was to clarify the cephalometric factors that are associated with OSAH severity and that predict the outcome of OA therapy. Two hundred nine patients with OSAH were recruited and analysed retrospectively. They had a polysomnographically documented apnoea-hypopnea index (AHI) of more than five respiratory events per hour. Lateral skull radiographs were used for cephalometric analysis. Only 67 of the 209 recruited patients underwent a second polysomnography (PSG) to evaluate the efficacy of OA therapy. In all recruited patients, the angle formed by the subspinal point (A) to the nasion (N) to the supramental point (B) (i.e. ANB angle) and the distance between the mandibular plane and hyoid bone (MP-H) were predictive factors of OSAH severity. In only 67 patients underwent PSG with an OA, the mean rate of decrease in the AHI was 47·8 ± 29·1%. OA therapy effectively treated OSAH in some patients with a very severe form of OSAH. However, patients who had a high position of the hyoid bone had a poor response to OA therapy. This study suggested that cephalometric analysis is useful for predicting OSAH severity and OA therapy efficacy.

A clinicopathological study of perineural invasion and vascular invasion in oral tongue squamous cell carcinoma.

The risk factors for recurrence of head and neck cancer are classified as being of high or intermediate risk. Those of intermediate risk include multiple positive nodes without extracapsular nodal spread, perineural/vascular invasion, pT3/T4 primary tumours, and positive level IV/V nodes. However, little evidence is available to validate these intermediate risk factors. We analyzed perineural/vascular invasion in 89 patients who underwent radical surgery for oral tongue squamous cell carcinoma, whose records were reviewed retrospectively. Perineural invasion was found in 27.0% of cases and vascular invasion in 23.6%; both had a strong relationship with histopathological nodal status (P = 0.005). The 5-year disease-specific survival (DSS) and overall survival rates of patients with perineural invasion were significantly lower than those of patients without perineural invasion (P < 0.001 and P = 0.002, respectively). The 5-year DSS of UICC stage I and II cases with perineural/vascular invasion was significantly lower than those without (P < 0.001 and P = 0.008, respectively). Perineural invasion and vascular invasion are risk factors for regional metastasis and a poor prognosis. We recommend elective neck dissection when perineural/vascular invasion is found in clinical stage I and II cases. The accumulation of further evidence to consider intermediate risks is required.

Itraconazole inhibits TNF-α-induced CXCL10 expression in oral fibroblasts.

OBJECTIVE: Itraconazole (ICZ) has a broad spectrum of antifungal activity including a wide range of Candida spp. TNF-α, an inflammatory cytokine associated with Th1-mediated oral inflammatory disease, enhances inflammatory mediators, such as CXCR3-agonistic chemokines including CXCL10. We examined the anti-inflammatory potential of ICZ against TNF-α-induced chemokines in oral fibroblasts. MATERIALS AND METHODS: We investigated the effects of ICZ on mRNA expressions of various TNF-α-induced chemokines in immortalized oral keratinocytes (RT7) and oral fibroblasts (GT1) using quantitative PCR analysis. Subsequently, the effects of ICZ and fluconazole (FLZ) on TNF-α-induced CXCL10 proteins in GT1 and primary fibroblasts were examined using enzyme-linked immunosorbent assays (ELISA). The effect of ICZ on signal transduction protein phosphorylation involved in CXCL10 production from TNF-α-stimulated GT1 was examined by western blotting. RESULTS: ICZ inhibited TNF-α-induced CXCL10 mRNA in GT1, but not RT7. Although ICZ did not affect TNF-α-induced IL-8 mRNA, the mRNAs of TNF-α-induced CXCR3-agonistic chemokines such as CXCL9 and CXCL11 were inhibited by ICZ in GT1. TNF-α-induced CXCL10 protein production in GT1 and primary fibroblasts was inhibited by ICZ, but not FLZ. Finally, ICZ inhibited TNF-α-induced phosphorylation of c-JUN, which is related to CXCL10 production by TNF-α-stimulated GT1. CONCLUSION: ICZ may be useful as therapy for Th1-mediated oral inflammatory disease.

Benefits of maxillectomy with internal dissection of the masticator space by transmandibular approach in the surgical management of malignant tumours of the upper gingiva and hard palate: a clinical review of 10 cases.

The aim of this study was to review patients with tumours extending to the posterior portion of the upper gingiva and hard palate, and to evaluate the postoperative outcomes. Ten consecutive patients with tumours in the upper gingiva and hard palate, who underwent maxillectomy with internal dissection of the masticator space by the transmandibular approach, were reviewed retrospectively. Among the 10 patients, the pathological diagnosis was squamous cell carcinoma in seven, adenoid cystic carcinoma in one, malignant melanoma in one, and osteosarcoma in one. Loco-regional control was achieved in eight of nine patients (88.9%). Three patients had residual moderate trismus. Cosmetic issues were not noted in any patient. En bloc resection of the maxilla with the internal portion of the masticator space and neck through the parapharyngeal space by the transmandibular approach is a useful and satisfactory technique for the excision of a tumour with involvement of the posterior portion of the upper gingiva and hard palate.

Membrane fouling caused by sub-micron particles in a mixed liquor suspension of an MBR.

Membrane fouling needs to be mitigated for widespread use of membrane bioreactors (MBRs). It has been pointed out that particles with small sizes found in supernatants (sub-micron particles) of mixed liquor suspensions of MBRs are important in the evolution of membrane fouling of this technology. However, information on characteristics of sub-micron particles in MBRs is still insufficient. In this study, a pilot-scale MBR treating municipal wastewater was used to investigate and characterize sub-micron particles in an MBR and to identify the size fraction(s) responsible for irreversible fouling in an MBR. It was clearly shown that characteristics of sub-micron particles in the MBR varied considerably depending on their sizes. Results of Fourier transform infrared (FTIR) analysis and monosaccharide analysis suggested that irreversible fouling in this study was mainly caused by the specific size fraction of 0.1-0.45 µm, which was close to the size of micropores of the membrane used. Pore plugging might explain this to some extent.

Characteristics of family caregivers with sleep dissatisfaction in Japan: identification using CHAID dendrograms.

The rapid increase in the population of the elderly has raised several social issues. The current study focused on sleep dissatisfaction in family caregivers to identify family caregivers with a heavy care burden. This study aimed to detect the characteristics of caregivers who are most likely to have sleep dissatisfaction. A chi-squared automatic interaction detection technique was used to analyze data collected from 92 research care managers who collected demographic and sleep dissatisfaction information from 280 caregivers and their care recipients. Caregivers whose care recipients were unstable and bedridden were most likely to have sleep dissatisfaction. When care recipients were not stable or non-bedridden, had severe dementia symptoms, and were physically independent, their caregivers were the second most likely to have sleep dissatisfaction. When care recipients were not stable or non-bedridden, had moderate dementia symptoms, and did not need help in transferring, their caregivers had the lowest risk of sleep dissatisfaction. Although many recent studies have found a high prevalence of insomnia among the elderly, describing the characteristics of caregivers who are most likely to have sleep dissatisfaction is a significant challenge. When care recipients are physically independent, the severity of the recipient's dementia symptoms relates to the caregiver's dissatisfaction with his/her sleep. In physically dependent care recipients, the severity of the recipient's dementia did not contribute to the caregiver's dissatisfaction with his/her sleep.

Chemopreventive activity of sesquiterpene lactones (SLs) from yacon against TPA-induced Raji cells deformation.

Yacon is a medicinal plant used as a traditional medicine by the natives in South America. In Japan, it becomes popular as a health food. Sesquiterpene Lactones (SLs) from yacon leaves were investigated and the active SLs such as enhydrin, uvedalin and sonchifolin, bearing alpha-methylene-gamma-lactone and epoxides as the active functional groups, were identified by 1H-6000 MHz-NMR. Chemopreventive and cytotoxic activities were determined using different primary screening methods. In this study, all tested SLs strongly inhibited TPA-induced deformed of Raji cells. The IC50 values of yacon SLs from anti-deforming assay were 0.04-0.4 microM. Interestingly, yacon SLs showed more potential of chemo preventive activity than both curcumin and parthenolide. However, the cytotoxicity on Raji cells was observed at high concentration of yacon SLs. The degree of anti-deformation was ranked in order: enhydrin >uvedalin >sonchifolin >parthenolide >curcumin. As according to structure-activity relationship, the high activities of enhydrin, uvedalin and sonchifolin may be due to the 2-methyl-2-butenoate and its epoxide moiety.

Re-evaluation of heterogeneity in HLA-B*510101 associated with Behçet's disease.

Behçet's disease (BD) is a chronic inflammatory disease characterized by oral aphthous ulcers, genital ulcers, uveitis and skin lesions. Etiology and pathogenesis of BD are not fully elucidated, but the association with human leukocyte antigen (HLA)-B51 or B*5101 has been repeatedly reported. Previous studies have shown that there are few sequence variations in the protein-coding region of B51, while there is a report on many variations in the 5'-flanking region and intron. In this study, HLA-B*5101 gene from 37 individuals including Japanese, Turkish, Jordanian and Iranian patients and healthy controls were fully sequenced to further clarify the B*5101 gene in association with BD. We found that all the patients and healthy controls carried B*510101 with no variation in the 5'-flanking region, exon and intron. However, seven polymorphisms were found in the 3'-flanking region. These polymorphisms composed of six haplotypes that were shared and stretched over the ethnic groups, suggesting that the susceptibility to BD was conferred by the B*510101 itself and not by any genes in linkage disequilibrium with B*510101. In addition, phylogenetic analyses of B*510101 showed that the 3'-flanking sequences followed an evolutional divergence differently from that of the other regions, implying that a unifying selection might operate to conserve B*510101.

HLA-DPbeta chain may confer the susceptibility to hepatitis C virus-associated hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a heart muscle disease characterized by hypertrophy and diastolic dysfunction of cardiac ventricles. It is suggested that one possible aetiology of HCM is the hepatitis C virus (HCV) infection, but molecular mechanisms underlying development of HCV-associated HCM (HCV-HCM) remains unknown. Because the human leucocyte antigen (HLA) molecule is involved in the control of progression/suppression of viral infection, extensive HLA allelic diversity may modulate the post-infectious course of HCV and pathogenesis of HCV-HCM. Here we undertook a case-control study with 38 patients with HCV-HCM and 132 unrelated healthy controls to reveal the potential impact of polymorphisms in seven classical and two non-classical HLA genes on the pathogenesis of HCV-HCM. It was found that DPB1*0401 and DPB1*0901 were significantly associated with increased risk to HCV-HCM in dominant model (P < 0.028, OR = 3.94, 95% confidence interval (CI) = 1.19, 13.02) and in recessive model (P < 0.007, OR = 9.85, 95% CI = 1.83, 53.04), respectively. The disparity in the gene-dose effect by two susceptible DPB1 alleles may be attributable to the difference between the susceptible (36 A and 55 A) and resistant (8L, 9F, 11G, 57E and 76M) residue-combination consisting of DPbeta anchor pocket for antigenic peptide-binding. These results implied that the HLA-DP molecules with specificity pocket appropriate for HCV antigen(s) might confer the progressive process of HCM among the HCV-infected individuals.

Lack of association between LTA and LGALS2 polymorphisms and myocardial infarction in Japanese and Korean populations.

To investigate the recently reported associations of polymorphisms in lymphotoxin-alpha (LTA) and galectin-2 (LGALS2) with myocardial infarction (MI), we analyzed a single nucleotide polymorphism of LTA (LTA 252A>G in LTA intron 1) and that of LGALS2 (LGALS2 3279C>T in LGALS2 intron 1) in Japanese and Korean populations. Although significant associations with MI were not observed in either population, we found that LTA 252GG was significantly associated with the severity of the disease for both the Japanese and Korean populations (P=0.017 and P=0.001, respectively). On the other hand, the polymorphism of LGALS2 was not associated with the severity of coronary atherosclerosis. These observations showed that, while the LTA 252GG genotype might modify the development of coronary atherosclerosis, the relation of LTA and LGALS2 to MI itself remained much less certain.

Synergistic effects of meloxicam and conventional cytotoxic drugs in human MG-63 osteosarcoma cells.

Cyclooxygenase-2 (COX-2) inhibitors have been shown to exert inhibitory effects on many types of malignant tumors and several groups have suggested that COX-2 inhibitors enhance the cytotoxic effects of other anti-cancer agents. We previously reported that meloxicam has an anti-tumorigenic effect on COX-2-expressing osteosarcoma cells. In the current study, we evaluated the synergy between meloxicam and cisplatin (CDDP), doxorubicin (DXR) and 4-hydroperoxy ifosfamide (4OOH-IFM), using the human osteosarcoma cell line, MG-63. Cytotoxicity was determined using 3-(4,5'-dimethylthiazol-2-yl)-2,5'-diphenyltetrazolium bromide (MTT) assays, and isobolographic analysis was used to evaluate any synergy. Apoptotic activity was determined by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL), and by evaluating Bax and Bcl-2 expression levels using real-time RT-PCR and western blotting analysis. Cell cycling was evaluated by flow cytometry. The cytotoxic effects of CDDP and DXR were enhanced synergistically in the presence of meloxicam and were partially due to an increase in apoptosis. By contrast, meloxicam enhanced neither the cytotoxic nor the apoptotic activity of 4OOH-IFM. Combining meloxicam with DXR significantly up-regulated Bax expression, whereas it down-regulated Bcl-2 expression in combination with CDDP. Furthermore, the number of cells in the G2/M phase was significantly increased in DXR-treated samples by the addition of meloxicam, but not in CDDP-treated or 4OOH-IFM-treated samples. These results suggest a potential clinical application of meloxicam in combination with cytotoxic drugs in patients with COX-2-positive osteosarcoma.

The haplotype block, NFKBIL1-ATP6V1G2-BAT1-MICB-MICA, within the class III-class I boundary region of the human major histocompatibility complex may control susceptibility to hepatitis C virus-associated dilated cardiomyopathy.

Cardiomyopathy is a heart muscle disease with impaired stretch response that can result in severe heart failure and sudden death. A small proportion of hepatitis C virus (HCV)-infected patients may be predisposed to develop dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). The molecular mechanisms involved in the predisposition remain unknown due in part to the lack of information on their genetic background. Because the human leukocyte antigen (HLA) region has a pivotal role in controlling the susceptibility to HCV-induced liver disease, we hypothesized that particular HLA alleles and/or non-HLA gene alleles within the human major histocompatibility complex (MHC) genomic region might control the predisposition to HCV-associated DCM (HCV-DCM) and/or HCV-associated HCM (HCV-HCM). Here, we present mapping results of the MHC-related susceptibility gene locus for HCV-associated cardiomyopathy by analyzing microsatellite and single nucleotide polymorphism markers. To delineate the susceptibility locus, we genotyped 44 polymorphic markers scattered across the entire MHC region in a total of 59 patients (21 HCV-DCM and 38 HCV-HCM) and 120 controls. We mapped HCV-DCM susceptibility to a non-HLA gene locus spanning from NFKBIL1 to MICA gene loci within the MHC class III-class I boundary region. Our results showed that HCV-DCM was more strongly associated with alleles of the non-HLA genes rather than the HLA genes themselves. In addition, no significant association was found between the MHC markers and HCV-HCM. This marked difference in the MHC-related disease susceptibility for HCV- associated cardiomyopathy strongly suggests that the development of HCV- DCM and HCV-HCM is under the control of different pathogenic mechanisms.

HLA class II DPB1, DQA1, DQB1, and DRB1 genotypic associations with occupational allergic cough to Bunashimeji mushroom.

We previously reported that two-third of workers in a Bunashimeji mushroom (Hypsizigus marmoreus) farm complained of respiratory allergic symptoms, but one-third workers did not suffer from such symptoms even when working for a long period. CD4+ T-helper (Th) cells increased, and Th2/Th1 ratio increased in the allergic workers. To address these immunological backgrounds, we have investigated whether there is any relationship between mushroom allergy and human leukocyte antigen (HLA) class II alleles of DPB1, DQA1, DQB1, and DRB1 by using the polymerase chain reaction-restriction fragment length polymorphism (RFLP) and sequencing-based typing methods. We observed that the allele frequencies of DQA1*0103, DQB1*0601, and DRB1*0803 were significantly higher in the workers having no allergic symptoms than allergic workers (DQA1*0103: 57 vs 25%, DQB1*0601: 49 vs 14%, and DRB1*0803: 29 vs 0%). However, this phenomenon was not seen in workers producing another kind of mushroom, Honshimeji (Lyophyllum aggregatum). The HLA-DRB1*0803 allele alone, the DRB1*0803, DQA1*0103, DQB1*0601 haplotype, or both were negatively associated with allergy to Bunashimeji, and these alleles might be involved in the prevention of Bunashimeji mushroom-specific respiratory allergy.

Molecular analysis of HLA allele frequencies and haplotypes in Baloch of Iran compared with related populations of Pakistan.

The extreme polymorphism in different loci of the human leukocyte antigen (HLA) system has been used as an invaluable tool for anthropological studies. Determination of HLA allele and haplotype frequencies in different ethnic groups is useful for population genetic analyses and the study of genetic relationships among them. In the present study, molecular analysis of HLA-A, -B, -C, -DQA1, -DQB1, and -DRB1 genes has been used to assign HLA allele and haplotype frequencies in 100 unrelated healthy individuals from the Baloch ethnic group of Iran. The results were compared with Baloch and other ethnic groups in the neighboring Pakistan. The results of this study showed that the most frequent HLA class I alleles were A*02011 (20.2%), B*4006 (11.1%), and C*04011 (28.6%). The most common HLA class II alleles were DQA1*0101/2 (42.5%), DQB1*0201 (32%), and DRB1*0301 (29%). Three-locus haplotype analysis revealed that A*11011-B*4006-C*15021 (5.8%) and DQA1*0501-DQB1*0201-DRB1*0301 (22.1%) were the most common HLA class I and II haplotypes, respectively, in this population. Neighbor-joining tree based on DA genetic distances and correspondence analysis according to HLA-A, -B, -DQB1, and -DRB1 allele frequencies showed that Baloch of Iran are genetically very close to Baloch and Brahui of Pakistan. This may reflect an admixture of Brahui and Baloch ethnic groups of Pakistan in the Balochistan province of Iran.

Embryology of the upper limb: the molecular orchestration of morphogenesis.

Accumulating data on the molecular interactions that occur during limb development have greatly enhanced our understanding of the process of limb morphogenesis. In this chapter, the key morphologic events are described, the broad categories of molecules involved are defined, the known molecular cascades and specific pathways that orchestrate limb development are reviewed. In addition, cascades disrupted by known genetic mutations associated with limb malformations are identified.

Association of polymorphic MHC microsatellites with GVHD, survival, and leukemia relapse in unrelated hematopoietic stem cell transplant donor/recipient pairs matched at five HLA loci.

In order to determine whether matching/mismatching for microsatellite polymorphism provides useful information on acute graft-vs-host disease (GVHD), survival, and leukemia relapse in hematopoietic stem cell (HSC) transplantation, we genotyped for polymorphisms at 13 microsatellite loci within the major histocompatibility complex (MHC) of 100 unrelated HSC transplant donor-recipient pairs who were matched at five classical human leukocyte antigen (HLA) loci. A high percentage of allele matching was obtained for five microsatellite loci, DQCARII (96%), MICA (93%), MIB (89%), C1-3-1 (93%), and D6S510 (97%), that are localized within 100 kb of the HLA-DR, HLA-DQ, HLA-B, HLA-C, or HLA-A locus. In contrast, the other eight microsatellites are located farther away from the HLA classical loci and have much lower percentages of allele matching [e.g. tumor necrosis factor a (TNFa) (73%), TNFd (74%), D6S273 (64%), C3-2-11 (46%), C5-3-1 (50%), C5-4-5 (63%), C5-2-7 (68%), and D6S265 (81%)]. Therefore, there were at least eight microsatellite markers with relatively high percentages of mismatches in the donor/recipient pairs with acute or chronic GVHD, poor graft survival, and leukemia relapse. However, there were no statistically significant associations between mismatched donor-recipient pairs at the 13 microsatellite loci and acute or chronic GVHD, graft survival, and leukemia relapse. Nevertheless, allele matching at the microsatellite TNFd locus near the TNFa gene was found by the Fisher's exact double-sided test to be significantly associated with decreased survival in the grade III/IV acute GVHD group. Overall, these results suggest that the matching of microsatellite polymorphisms within the HLA region, especially the ones farthest from the classical HLA loci, was not useful indicator for the outcome of HSC transplantation from unrelated donors. In this regard, the future determination of the genome-wide microsatellite genotypes in HLA-matched donor-recipient pairs, outside the MHC, may be a better possibility for identifying minor histocompatibility genes in linkage disequilibria with microsatellites as potential predictive markers for the occurrence of acute GVHD and survival rate in HSC transplantation.