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The aim of this study was to investigate the risk factors affecting long-term prognosis of autotransplantation of third molars with complete root formation in males at dental clinics. Participating dentists were requested to provide information on transplantations they had undertaken from 1 January 1990 to 31 December 2010. Data on a total of 708 teeth from 637 patients were collected. After data screening and elimination, participants of this study consisted of 183 teeth of 171 males ranging from 20 to 72 years of age (mean age, 44·8 years). The cumulative survival rate was 86·0% at the 5-year mark, 59·1% at 10 years and 28·0% at 15 years. The mean survival time was 134·5 months, as calculated by the Kaplan-Meier method. Single factor analysis using the log-rank test showed that the following factors had significant influence (P < 0·05) on survival of transplanted teeth: periodontal disease as the reason for recipient site tooth extraction, fewer than 25 present teeth and Eichner index Groups B1 to C. Cox regression analysis examined five factors: age, smoking habit, recipient site extraction caused by periodontal disease, fewer than 25 present teeth and Eichner index. This analysis showed that two of these factors were significant: fewer than 25 present teeth was 2·63 (95% CI, 1·03-6·69) and recipient site extraction caused by periodontal disease was 3·80 (95% CI, 1·61-9·01). The results of this study suggest that long-term survival of transplanted teeth in males is influenced not only by oral bacterium but also by occlusal status., (© 2012 Blackwell Publishing Ltd.)

The aim of this study was to investigate the usage of tooth autotransplantation in dental clinics which offer the treatment and evaluate its practicality. Participating dentists were requested to provide information on transplantations they had undertaken from 1 January 1990 to 31 December 2010. A total of 614 teeth from 552 patients (37 dentists) ranging in age from 17 to 79 (mean age: 44·1) were examined. Cumulative survival rate and mean survival time were calculated using the Kaplan-Meier method, and log rank test was used for analysis of factors. The mean number of autotransplantation patients per clinic per year was 1·4. Upper third molars constituted 36·8% of donor teeth, while 37·1% were lower third molars. The lower first molar region was the most common recipient site at 32·6%, followed by the lower second molar region (28·0%). Prosthodontic treatment of transplanted teeth involved coverage with a single crown (72·5%) and abutment of bridge (18·9%). A total of 102 transplanted teeth were lost owing to complications such as attachment loss (54·9%) and root resorption (25·7%). The cumulative survival rate in cases where donor teeth had complete root formation was 90·1% at 5 years, 70·5% at 10 years and 55·6% at 15 years. The mean survival time was 165·6 months. Older age was a significant risk factor (P < 0·05) for survival. In cases where suitable donor teeth are available, autotransplantation of teeth may be a plausible treatment option for dealing with missing teeth in dental clinics., (© 2011 Blackwell Publishing Ltd.)

In investigating the biological activities of bone marrow mesenchymal stem cells (BMMSCs), an important task is cell sorting of effective BMMSCs. In the present study, we examined the usefulness of CD271 as a cell surface marker of BMMSCs. Specifically, we investigated (1) CD271 expression before and after freezing, (2) difference between the CD271(+) and CD271(-) fractions regarding calcium formation level after bone differentiation, and (3) method of harvesting effective BMMSCs from marrow tissue. CD271 was partially expressed in cryopreserved BMMSCs (CBMMSCs). We used CD271 in separating CBMMSCs into different cell groups and compared the calcium formation levels between the CD271-expressed and CD271-nonexpressed groups. A significant amount of BMMSCs existed even in the CD271(-) fraction, and the calcium formation level was high in 4 of 5 CD271(-) fraction specimens. The same investigation was conducted on nonfrozen BMMSCs. No major difference was found in CD271 expression compared with CBMMSCs. However, the calcium formation level of the CD271(+) fraction was higher in 3 of 5 specimens. We presumed that CD271 expression might have been substantially changed during culture and cryopreservation. We compared the method of directly culturing bone marrow tissue and that of washing the sample before culture and confirmed that the calcium formation level of BMMSCs was higher when the marrow tissue was washed before culture.

To increase the bond strength of CAD/CAM-fabricated, leucite-reinforced glass ceramics with a resin cement, the effects of the following were investigated: surface modification by tribochemical (TBC) treatment, followed by combined application of a silane coupling agent and a functional monomer as a primer. Bond strength was evaluated by a shear bond test. It was found that a silane coupling agent was useful for all the surfaces, particularly for the TBC-treated surface. This was because of the presence of a silica layer on the modified surface. The combination of a silane coupling agent and a functional monomer on the TBC surface allowed marked improvement in bonding, whereby the bonding endured 20,000 cycles of thermal cycling. Therefore, TBC treatment in combination with a silane coupling agent and a functional monomer as a primer substantially increased the bond strength of CAD/CAM-fabricated glass ceramics with resin cement, if the treatment conditions were appropriate.

A 34-year-old female was referred to our hospital for the evaluation of atypical lymphocytosis. Leukocyte count at diagnosis was 17,900/microl with 58% atypical lymphocytes having a convoluted nucleus and prominent nucleoli. Because the leukocyte count increased to 43,600/microl, the patient was treated with 2'deoxycoformycin followed by CHOP combination chemotherapy. However, both treatments failed to achieve remission. We planned an allogeneic bone marrow transplantation from an HLA-matched unrelated donor. The patient was treated with Ara-C and etoposide before conditioning to decrease the high leukemia burden. After administration of total body irradiation (12 Gy in six fractions) and cyclophosphamide (total dose of 120 mg/kg) unmanipulated marrow cells were infused. Under prevention of GVHD by CsA and short-term MTX, leukocyte engraft was prompt at day 16, and acute GVHD grade II was observed. Because 9.4% of residual recipient type T-cells was seen with STR analysis on day 22, we decreased the dose of Cs'A. After the occurrence of mild acute GVHD, the residual T-cell number decreased. The patient is still in complete remission for up to 22 months after BMT. We conclude that allogeneic SCT is effective for the treatment of T-PLL.

Secondary bone grafting in the alveolar cleft is one of the most important treatment modalities for patients with a cleft lip and palate. In children, however, harvesting a sufficient amount of bone graft from the donor site is difficult, and the procedure imposes a heavy burden on the patients. This problem may be resolved if autologous transplantation can be performed using a cell-hybrid type of artificial bone prepared with the patient's own bone marrow cells through a tissue engineering technique. In the current study, we examined the possibility of achieving such an autologous transplantation using cryopreserved human bone marrow cells. Human bone marrow cells were grown in culture and cryopreserved, and the cells preserved for 3 years and the cells preserved for 3 months were then thawed and recultivated. In one experiment, the recultivated cells were seeded onto a complex composed of porous hydroxyapatite and bone morphogenetic protein (BMP), and the complex was grafted subcutaneously in nude mice. In another experiment, the cells were seeded onto the porous hydroxyapatite and cultivated for 10 days before grafting in a medium supplemented with BMP. The bone formation potential of the cells was compared between these two experiments. Formation of mature bone was observed 2 weeks after transplantation in the former experiment, whereas only scarce bone formation was evident 4 weeks after transplantation in the latter experiment. It is therefore assumed that exposing the cultured human bone marrow cells to a high concentration of BMP in vivo strongly promotes bone formation.

The voltage-gated sodium channel type II alpha polypeptide gene (SCN2A) R188W mutation with channel dysfunction was recently identified in a patient with febrile and afebrile seizures. A possible association between SCN2A R19K polymorphism and febrile seizures (FS) associated with afebrile seizures including generalized epilepsy with febrile seizures plus (GEFS+) was also noted. We attempted to identify the R188W mutation and confirm association of the R19K polymorphism in 93 Japanese patients with FS, 35 Japanese patients with FS associated with afebrile seizures including GEFS+, and 100 control subjects. The R188W mutation was not found. There were no significant differences in genotype or allele frequencies of the R19K polymorphism between groups. Our study failed to provide evidence supporting a causal relation between the SCN2A mutation/polymorphism and FS or FS associated with afebrile seizures including GEFS+ in the Japanese population., (Copyright 2002 Elsevier Science Ireland Ltd.)

The ability of CD34+ leukemic cells to differentiate to dendritic cells (DCs) was investigated in 18 acute myeloid leukemia (AML) and 4 lymphoid leukemia (ALL) patients. The generation of DCs was determined by the expression of DC-associated CD1a or CD83 (more than 30%) with costimulatory molecules, by CD80 antigens (>20%), and by the exhibition of allostimulatory activity. In the AML patients, allostimulatory mature DCs were generated from 3 of 9 M0 or M1, 2 of 5 M2,2 of 4 M4 or M5, and 3 of 4 ALL (L2) cases. In total, DCs were more efficiently induced from cases expressing over 75% of CD34+ among whole bone marrow mononuclear cells (8 of 12), compared with those under 75% (2 of 10; P < .05). B-cell (CD19), natural killer (NK)-cell (CD56), or T-cell (CD7) lineage markers, which were aberrantly expressed on the blasts, were rarely found on leukemic DCs at the end of the culture period, and myeloid (CD13, CD33), not lymphoid (CD10), markers were shown on ALL-derived DCs. In Philadelphia chromosome-positive ALL or AML patients with t (8;21), DCs were confirmed to be of leukemic origin by fluorescence in situ hybridization analysis.

A 61-year-old woman had been treated for multiple myeloma for 4 years when she developed abdominal pain. Ultrasonography and computed tomography revealed a tumor in the abdomen. Positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) showed increased FDG uptake in the tumor. In previous bone marrow lesions, which were in clinical remission after chemotherapy and radiotherapy, abnormal FDG uptake was not recognized. Pathological examination after surgery revealed the tumor to be a plasmacytoma of the duodenum. Plasmacytoma of the duodenum is rare but can be seen during the clinical course of multiple myeloma. A few reports have described FDG PET findings of plasmacytoma. Those previous reports and our present case suggest a potential value of FDG PET in the evaluation of multiple myeloma.

We previously developed a system using murine strome (HESS-5), which could expand umbilical cord blood (UCB) stem and progenitor cells, especially CD34+/38- cells, in the presence of human recombinant cytokines. In this study, the ability of expanded UCB- or bone marrow (BM)-CD34+ cells to differentiate into dendritic cells (DCs) was examined. DCs could be induced either from short or long term cultured CD34+ cells after switching the cytokines from Flk-2/Flt-3 ligand, stem cell factor (SCF), thrombopoietin (TPO) to granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) (immature type) plus tumor necrosis factor (TNF)-alpha with stimulation by CD40L transfectant (mature type). Each immature or mature UCB-DCs showed a dextran uptake or a potent allo-T lymphocytes proliferative ability, respectively. Furthermore, those DCs from BM significantly stimulated auto-T lymphocytes in an antigen (varicella zoster virus) specific manner. In conclusion, a novel culture system using HESS-5 is useful to support a rapid and sustained generation of primitive myeloid cells which can develop into functional DCs.

Objective: We examined cell subsets with respect to cutaneous graft-vs-host disease by cell sorting selection of subsets of human mononuclear cells and injecting the subsets subcutaneously in a mouse model., Materials and Methods: Cell suspensions containing cultured human epidermal cells and dermal fibroblasts from a single donor mixed with lymphoid cell subsets positively selected using the FACSVantage cell sorting instrument and/or MACS cell isolation kits from unrelated individuals were injected into immunodeficient mice. This model is known to generate human skin with histologic findings similar to human graft-vs-host disease., Results: Donor T-cell subsets CD4(+) and CD8(+) plus either host or donor CD14(+) cells were necessary to cause acute cutaneous graft-vs-host disease. Although graft-vs-host disease can result from recognition of class I antigens expressed on human cutaneous cells by donor peripheral blood mononuclear cells, additional recognition of class II antigens expressed on host mononuclear cells resulted in more severe histologic manifestations. Dendritic cells that differentiated from donor and host monocytes also showed competent accessory cell function in this system., Conclusions: Based on this model, human cutaneous graft-vs-host disease was caused by donor CD4(+) cells and CD8(+) cells activated through recognition of host antigens, including class I and class II antigens presented by either donor or host CD14(+) cells or dendritic cells.

A 23-year-old man first visited a local hospital in 1998 because of exertional dyspnea. Peripheral blood examination revealed mild leukocytosis with 82% eosinophils, and he was treated with prednisolone. As the eosinophilia did not improve, he was referred to Tokai University Hospital in March 1999 for further diagnosis and treatment. The patient was diagnosed as having hypereosinophilic syndrome (HES) because of unexplained hypereosinophilia persisting for more than 6 months, resulting in cardiac dysfunction. His disease was progressive in spite of immunosuppressive therapy, interferon-alpha and cytotoxic chemotherapy. Since he had an HLA-identical brother, allogeneic bone marrow transplantation (BMT) was performed in October 1999. After completion of the immunosuppressive therapy on day 79 after BMT, the number of eosinophils gradually increased again. Although we suspected recurrence of the disease, DNA fingerprinting revealed that the peripheral granulocytes were 100% donor type. An increase of interleukin-5 (IL-5) produced by peripheral lymphocytes and a decrease of the Th1/2 ratio suggested that the eosinophilia was related to GVHD. The eosinophilia was eventually controlled by cyclosporin. We conclude that DNA fingerprinting and examination of the IL-5 level and Th1/2 ratio are useful for differentiating between relapse and GVHD in cases of eosinophilia occurring after BMT for HES.

The ability of leukemic cells to differentiate to mature dendritic cells (DCs) was investigated in six acute myelomonocytic or monocytic leukemia cases. It was found that CD14 positive cells were more efficiently changed to CD83 positive mature typed DCs with granulocyte-macrophage colony-stimulating factor (GM-CSF)/interleukin-4 (IL-4) and tumor necrosis factor alpha (TNF-alpha) compared with CD14 negative cells. Such leukemia derived DCs expressed a sufficient level of costimulatory molecules (CD80 and CD86), and were shown to be monoclonal based on an the X-inactivation analysis. They also stimulated not only allo- but auto-T lymphocytes, which thereafter became cytotoxic T lymphocytes (CTLs).

Human bone marrow (BM) or mobilized peripheral blood (mPB) CD34(+) cells have been shown to loose their stem cell quality during culture period more easily than those from cord blood (CB). We previously reported that human umbilical CB stem cells could effectively be expanded in the presence of human recombinant cytokines and a newly established murine bone marrow stromal cell line HESS-5. In this study we assessed the efficacy of this xenogeneic coculture system using human BM and mPB CD34(+) cells as materials. We measured the generation of CD34(+)CD38(-) cells and colony-forming units, and assessed severe-combined immunodeficient mouse-repopulating cell (SRC) activity using cells five days after serum-free cytokine-containing culture in the presence or the absence of a direct contact with HESS-5 cells. As compared with the stroma-free culture, the xenogeneic coculture was significantly superior on expansion of CD34(+)CD38(-) cells and colony-forming cells and on maintenance of SRC activity. The PKH26 study demonstrated that cell division was promoted faster in cells cocultured with HESS-5 cells than in cells cultured without HESS-5 cells. These results indicate that HESS-5 supports rapid generation of primitive progenitor cells (PPC) and maintains reconstituting ability of newly generated stem cells during ex vivo culture irrespective of the source of samples. This xenogeneic coculture system will be useful for ex vivo manipulation such as gene transduction to promote cell division and the generation of PPC and to prevent loss of stem cell quality.

Cell numbers limit the widespread clinical use of cord blood (CB) for gene therapy and marrow replacement in adults; a simple and effective method for ex vivo expansion of CB primitive progenitor cells (PPC) is required. Recently, the combination of thrombopoietin (TPO) and Flk-2/Flt-3 ligand (FL-2) was reported to support slow proliferation of CB-PPC in stroma-free liquid culture. We established a novel culture system in which the murine stromal cell line HESS-5 dramatically supports the rapid expansion of cryopreserved CB-PPC in synergy with TPO/FL-2. Furthermore, while HESS-5 cells directly adhered to human progenitors during culture, the cultured human cells could easily be harvested without contamination by HESS-5 cells. Within 7 days of culture, a 100-fold increase in CD34bright/CD38dim cells was obtained in serum-containing culture. When HESS-5 cells were physically separated from human progenitor cells in the presence of TPO/FL-2, synergy was blocked, suggesting that HESS-5 cells support proliferation of PPC by direct cell-to-cell interaction. The hematopoietic-supportive effects of this xenogeneic coculture system were then assessed in a very short-term (5 days) serum-free culture. Expansion was further enhanced by addition of stem cell factor (SCF) or interleukin-3 (IL-3). As a result, a 50- to 100-fold increase in CD34bright/CD38dim cells was noted. Colony-forming units in culture (CFU-C) and mixed colonies (CFU-GEMM) were enhanced by 10- to 30-fold and 10- to 20-fold, respectively. Moreover, generation of long-term-culture-initiating cells (LTC-IC) from CD34bright/CD38dim cells was amplified by 25-fold. The severe-combined immunodeficient (SCID) mouse-repopulating cell (SRC) assay confirmed extensive ability of the expanded cells to reconstitute long-term hematopoiesis. These results indicate that this xenogeneic coculture system, in combination with human cytokines, can rapidly generate PPC from cryopreserved CB.

Increases in height were reported in children chronically exposed prenatally and postnatally to D2 receptor-blocking drugs. A possible haplotypic association between stature and the DRD2 gene was also reported. In this study, we examined linkage between stature and DRD2 by genotyping a dinucleotide repeat polymorphism in 79 sib-pairs aged 8-17 years. An association between stature and a putative functional polymorphism in the promoter region of the DRD2 gene was examined in the sib-pairs and in 125 unrelated male adults. All the subjects were Japanese. Linkage (p = 0.004, SIBPAL) and an association (p = 0.009, paired t-test, in the sib-pairs; p = 0.006, ANOVA, in the adults) with stature were suggested. These findings indicate that DRD2 is one of the genes that contribute to heritability of stature.

To determine the frequency of familial hypoalphalipoproteinemia in the general population due to mutation of the apolipoprotein A-I (apo A-I) gene, we analyzed sequence variations in the apo A-I gene. The subjects were 67 children with a low high-density lipoprotein (HDL) cholesterol level (

We describe a Japanese boy with ring chromosome 18 in whom abnormal myelination was observed on magnetic resonance imaging. Cytogenetic investigation revealed 46, XY, r(18) (p11.2 q21.33). T2-weighted magnetic resonance imaging scan of the brain demonstrated high signal intensity consistent with abnormal myelination. Microsatellite marker analysis of DNA demonstrated only one copy of the myelin basic protein gene, derived from the mother. The present case indicates that a hemizygous state for the myelin protein gene may be related to the abnormal myelination.

The effectiveness of a school-based intervention trial for the primary prevention of cardiovascular disease was studied by measuring cardiovascular risk factors in 701 children with intervention and 663 children without intervention. Outcomes were assessed using preintervention measures at 10 years old (fall 1991) and follow-up measures at 13 years old (fall 1994). In girls with intervention, HDL-cholesterol level was significantly higher and atherogenic index was significantly lower than that in girls without intervention. In obese girls with intervention, frequency of reduced obesity index was significantly higher than that in obese girls without intervention. In boys, however, body size and cholesterol measures did not differ significantly between intervention groups and nonintervention groups. These results indicate that school-based intervention for cardiovascular health can produce a reduction in risk factors for atherosclerosis in girls over a period of 3 school years.

Basal cell carcinoma, which accounts for 70%-80% of all cutaneous malignancies in the United States, has increased recently in Japan. We compared methods for reconstruction after surgery for basal cell carcinoma, which is expected to increase further in the future. Thus patients who underwent reconstruction after surgery for basal cell carcinoma of the nose using medial forehead flaps and nasolabial flaps were selected, and the effectiveness of these flaps was compared by taking the size and location of the tissue defect into consideration. As a result, possibly because of anatomical and histological differences of the face between Caucasians and Asians, better results were obtained with nasolabial flaps than with median forehead flaps.

To understand the relevance of allergy to the development of asthma in children, we examined basophil histamine release (HR) with Df antigen, blood eosinophil counts, serum eosinophil cationic protein (ECP) levels, and bronchial responsiveness to methacholine (PC20) in three groups of children, including 36 asthmatics with high RAST titre for Df (group 1), 36 non-asthmatics with similarly high RAST titre for Df (group 2) and 21 non-asthmatics with negative RAST titre for Df (group 3). The amount of Df antigen inducing 50% HR from basophils did not vary significantly between group 1 and 2 (P > 0.05), while none of the cells responded to higher concentrations of Df in group 3. The mean number of blood eosinophils and level of serum ECP were highest in group 1, and lowest in group 3, with group 2 being intermediate, and the differences were significant between all three groups (P < 0.01). The mean PC20 value was the lowest in group 1, intermediate in group 2, and the highest in group 3, and the differences were significant between all three groups (P < 0.01). While correlation studies showed that PC20 values of group 2 subjects significantly correlated with their eosinophil numbers (r = -0.48, P < 0.01) and ECP levels (r = -0.49, P < 0.01), such correlations were not found in group 1 subjects. These results suggest that the degree of the eosinophilic inflammation caused by the allergic reaction to mites is an important factor in determining the clinical expression of asthma in atopic subjects.

Knee joints affected by rheumatoid arthritis (RA) were randomized to either arthroscopic or open synovectomy, and the postoperative results were compared retrospectively. The materials consisted of 58 patients with 75 surgically treated knees. Arthroscopic synovectomy was performed on 37 knees of 30 patients, who were followed for five years and four months on average. Open synovectomy was performed on 38 knees of 28 patients, who were followed for five years and five months on average. The results were evaluated for ; recurrence of synovitis ; duration of the symptom-free period ; progressive bone changes on radiography ; range of motion (ROM) ; duration of hospital stay ; duration of surgery. Due to the less invasive surgical procedure, arthroscopic synovectomy resulted in less post operative pain, and there was no restriction of ROM after surgery, no need for postoperative rehabilitation, shorter hospital stay, lower incidence of osteoarthritic changes, and earlier return to the daily life. However, as synovial membrane removal was unavoidably insufficient, the effect of surgery lasted for only 18 months on average and recurrence of synovitis was observed in 73 % of patients. Open synovectomy meant relatively greater invasion and postoperative pain. Due to the restricted ROM in some cases, postoperative treatment was required and the hospital stay tended to be prolonged. Nevertheless, the recurrence rate was only 37 % during follow-up and the effect of surgery persisted for an average of 75 months, much better than that of arthroscopic synovectomy. In the treatment of RA knees, the indications for arthroscopic and open synovectomies should be carefully studied in the light of the merits and for demerits of each procedure.

A novel complex mutation with the presence of both deletion and insertion in very close proximity in the same region was detected in exon 8 of the LDL receptor gene from two apparently unrelated Japanese families with familial hypercholesterolemia (FH). In this mutant LDL receptor gene, the nine bases from nucleotide (nt) 1115 to nt 1123 (AGGGTGGCT) were replaced by six different bases (CACTGA), and consequently the four amino acids from codon 351 to 354, Glu-Gly-Gly-Tyr, were replaced by three amino acids, Ala-Leu-Asn, in the conserved amino acid region of the growth factor repeat B of the LDL receptor. The nature of the amino acid substitution and data on the families suggest that this mutation is very likely to affect the LDL receptor function and cause FH. The generation of this complex mutation can be explained by the simultaneous occurrence of deletion and insertion through the formation of a hairpin-loop structure mediated by inverted repeat sequences. This this mutation supports the hypothesis that inverted repeat sequences influence the stability of a given gene and promote human gene mutations.

Total cholesterol levels, obesity index and blood pressure were measured in 6,278 school-age children living in Ibaraki Prefecture in 1991, and children with high risk for atherosclerosis were identified. The frequencies of the school-age children with hypercholesterolemia (total cholesterol > or = 200 mg/dl), obesity (obesity index > or = 40%) or hypertension were 7%, 5%, 1%, respectively. In half of the area where the children lived, lipid measurements were also obtained in the parents of hypercholesterolemic children. Twenty-nine out of ninety fathers (32%) and 22 out of 140 mothers (16%) were hypercholesterolemia (total cholesterol > or = 240 mg/dl). Among them five families of familial hypercholesterolemia were diagnosed. Seventy children with hypercholesterolemia and 81 obese children, who were screened and received health counseling, were re-examined after one year. The levels of LDL-cholesterol, triglyceride and atherogenic index were significantly decreased and HDL cholesterol level was significantly increased in the children with hypercholesterolemia. Obesity index, triglyceride level and atherogenic index were significantly decreased and HDL cholesterol level was significantly increased in the children with obesity. In addition, the frequencies of the children with dyslipidemia or liver dysfunction were significantly decreased in the obese children after one year. These data suggested that the screening system and the plans after the examinations described here were effective in reducing risk factors for atherosclerosis in children.

Three hundred and twenty nine obese children (206 boys, 123 girls) whose obesity index were above 40% were screened among 6,278 school-age children living in Ibaraki Prefecture. Six hundred and fifty-eight school-age children without obesity were used as controls. The mean levels of total cholesterol and triglyceride of obese boys were significantly higher than those of control boys. The mean levels of HDL-cholesterol of both boys and girls with obesity were significantly lower than those of controls. Hypercholesterolemia, hypertriglyceridemia and hypoalphalipoproteinemia in the boys with obesity were significantly more frequent than those in control boys. In the girls with obesity, hypoalphalipoproteinemia was significantly more frequent than that in control girls. Liver dysfunction (GPT > or = 40 IU/l) in obese children was significantly more frequent than in controls: Although none of controls had liver dysfunction, 24.8% of obese boys and 11.4% of obese girls had liver dysfunction. These findings indicated that atherogenic dyslipidemias and liver dysfunction were common in Japanese school-age children with obesity, especially in boys.

Primary hypoalphalipoproteinemia is associated with atherosclerosis and exhibits significant familial aggregation. To reveal the presence of autosomal dominant hypoalphalipoproteinemia due to a completely defective apolipoprotein A-I gene, the apolipoprotein A-I gene was analyzed in a Japanese family with low levels of HDL cholesterol and apolipoprotein A-I. An insertion of a C in the region of the seven C run between codons 3 and 5 was detected in the apolipoprotein A-I gene. The heterozygous state for the mutation was associated with approximately 50% of the normal HDL cholesterol levels and of the normal apolipoprotein A-I levels. The data suggest that a part of familial hypoalphalipoproteinemia might be an autosomal dominant trait due to a completely defective apolipoprotein A-I gene.

To assess the relationship between relatively severe hereditary hypercholesterolemia with Achilles tendon xanthomas and the defect of the low density lipoprotein (LDL) receptor gene, family studies were carried out in 17 hypercholesterolemic families. In 16 out of the 17 families, hypercholesterolemia co-segregated with four different gross rearrangements, six different restriction fragment length polymorphism (RFLP) haplotypes, or an abnormal TaqI band of the LDL receptor gene. These findings are compatible with the interpretation that hypercholesterolemia is caused by defective LDL receptor genes, and that the origin of the mutant LDL receptor genes in Japanese generally differs among different pedigrees. In the remaining family, the proband and his sibling, both having relatively severe hypercholesterolemia and Achilles tendon xanthomas, shared an RFLP haplotype, although the proband's other sibling with moderate hypercholesterolemia but without Achilles tendon xanthomas did not. The mutant gene for familial defective apolipoprotein B-100 was not detected in the 17 probands. These data suggest that most, if not all, of the relatively severe hereditary hypercholesterolemia associated with Achilles tendon xanthomas is caused by a defect of the LDL receptor gene.

To investigate the association of apolipoprotein (APO) E4 and hypercholesterolemia in children, we studied the APOE phenotypes of 51 school-age children with hypercholesterolemia and of 51 age, sex and obesity index-matched controls with normocholesterolemia by two-dimensional gel electrophoresis APOE4 was present in 21 of 51 hypercholesterolemic children (41.2%), and in nine of 51 control subjects (17.6%). The difference was significant (p less than 0.01). This finding indicates that APOE4 is associated with hypercholesterolemia in children.

Ninety-one children were determined to have hypercholesterolemia from a screening of 1,469 school children in the community near University of Tsukuba, and family studies of these children were performed. More than 50% of the parents participated in the study. The mean cholesterol levels of parents of hypercholesterolemic children were significantly higher than that of controls. Hypercholesterolemia in parents of hypercholesterolemic children was more frequent than that in controls. Nine families with autosomal dominant hyperlipidemia including familial hypercholesterolemia and familial combined hyperlipidemia were detected by further family studies. These results indicate that genetic factors are important as causes of hypercholesterolemia of school children and that family studies of hypercholesterolemic children is an efficient method for screening for persons with increased risk for cardiovascular diseases.

A 2-year-old boy, whose clinical abnormalities included growth retardation(3rd percentile), mild mental retardation (DQ = 67), microcephaly, hypertelorism, strabismus, prominent nasal bridge, stubby nose, pointed chin, undescended testes and hydronephrosis, had a ring chromosome 10. Using high-resolution banding technique, the breakpoints were decided at p15.3 and q26.3 of chromosome 10. The clinical features observed in this case were common in 8 other cases with ring chromosome 10 previously reported. Thus, the terminal deletion of both arms of chromosome 10 seems to be the cause of the specific clinical abnormalities. When a patient has the clinical common abnormalities above mentioned, ring chromosome 10 syndrome will be suspected before chromosome analysis.