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論叢(Article), シンポジウム『同志社にとっての1876年』(Symposium:the meaning of 1876 for Doshisha)

The disruption of circadian rhythm is closely related to mood disorders in night-shift workers, and a similar situation may occur in postpartum mothers. However, the situations of postpartum mothers remain largely unknown because of a lack of an appropriate circadian phase marker in the clinical setting. This study aimed to evaluate whether salivary melatonin concentration at awakening can identify misalignment between awakening time and the biological clock system, which might be associated with depressive mood in some mothers. Ninety-eight healthy mothers who were currently the primary parental caregivers were recruited at 1 month after delivery. All mothers completed the Edinburgh Postnatal Depression Scale (EPDS) and wore an actigraphy watch at home for 3 consecutive days to determine nocturnal sleep variables. While wearing the actigraphy watch, they also collected saliva samples during the awakening period for a melatonin concentration assay. The results indicated that daily salivary melatonin levels after 30 min of awakening (hereafter, melatonin levels) were positively correlated with sleep onset time and negatively correlated with sleep offset time and total sleep time. Six mothers with an EPDS score of ≥9 (the cutoff value for Japanese women at high risk for postnatal depression) had an average melatonin level of either4 pg/ml or16 pg/ml for 3 d. Mothers with melatonin levels4 pg/ml or16 pg/ml tended to have elevated EPDS scores (4.93 ± 2.95 or 4.20 ± 2.93, mean ± standard deviation) compared with mothers with melatonin levels between 4 and 16 pg/ml (3.00 ± 2.12

Pustulotic arthro-osteitis (PAO) is a major complication of palmoplantar pustulosis (PPP). In orthopedic surgery outpatient clinics, PPP patients with osteoarticular symptoms are seen frequently, but PAO's clinical features remain not well known. To determine Japanese patients' clinical features and treatment status with PAO, we conducted a single-center retrospective epidemiologic survey. Clinical features, including gender, age, smoking habit, the onset pattern, interval between skin manifestation and osteoarticular symptoms, and the incidence of sternoclavicular joint lesions, axial and peripheral joint lesions, were examined. The association between physical status and image findings by X-ray, computed tomography, bone scintigraphy with Technetium99 , or magnetic resonance imaging was evaluated. The distribution pattern of peripheral joint lesions and the treatment status were evaluated. We identified 51 patients, 10 men and 41 women, with PAO. The average age was 48 years and 59% were smokers. The frequency of onset patterns was skin-leading type (63%), simultaneous onset (18%), and osteoarticular leading type (16%). The average interval between skin involvement and osteoarticular involvement in skin-leading type was significantly longer than that in osteoarticular leading type (7.1 years vs. 2.0 years). A sternoclavicular joint (SCJ) lesion was detected in 65% cases, and the physical findings of SCJ were significantly related to the image findings. Axial and peripheral joint lesions were detected in the same ratio (23 cases, 45%). In the peripheral joints, the finger joint was the most common (26%), followed by the shoulder joint (21%). Patients were treated with nonsteroidal anti-inflammatory drugs (76%), followed by conventional synthetic disease-modifying antirheumatic drugs (DMARDs) (29%) and biological DMARDs (9.8%). Tonsillectomy was performed in 11 cases. In conclusion, PAO more frequently involves SCJ in middle-aged women who smoke. Given that osteoarticular leading type was detected in 16% cases, seronegative oligoarthritis patients should be monitored for PPP, leading to a diagnosis of PAO.

This study examined the effectiveness of heart rate variability (HRV) biofeedback intervention for reduction of psychological stress in women in the early postpartum period. On postpartum day 4, 55 healthy subjects received a brief explanation about HRV biofeedback using a portable device. Among them, 25 mothers who agreed to implement HRV biofeedback at home were grouped as the biofeedback group, and other 30 mothers were grouped as the control group. At 1 month postpartum, there was a significant decrease in total Edinburgh Postnatal Depression Scale score (P

Porous β-tricalcium phosphate (TCP) displays osteoinductivity in certain animals in the absence of osteoinductive agents. We evaluated whether the microstructure may be an important determinant of osteoinduction, and also investigated how bone formation was promoted using β-TCP combined with bone marrow aspirates. We prepared two types of β-TCP, namely, β-TCP A, which possessed interconnected macropores and micropores, and β-TCP B, which possessed macropores but had less detectable micropores. These were implanted with or without marrow in canine muscles. Bone formation and the resorption of each β-TCP implant were evaluated histologically. Newly formed bone began to appear at day 42 in the implants of β-TCP A alone, but the implants of β-TCP B alone did not show any bone formation by day 42. Meanwhile, bone formation was already evident on day 14 by loading with bone marrow aspirates with or without micropores. By immunohistochemistry, the number of cathepsin K-positive cells (osteoclasts) increased as time passed in the implants of β-TCP A alone, while the number of the osteoclasts did not change obviously in the implants of β-TCP B alone from day 14 to 56. Reticular fibrils were evident within the β-TCP A, and were barely observed in the β-TCP B in the silver impregnation. The present result would bring about the possible role to enhance the importance of the surface microstructure for the better osteoinductivity. Our findings suggest that the combination of porous β-TCP and bone marrow facilitates bone formation.

BACKGROUND Acquired hemophilia A is rarely found in association with myeloproliferative neoplasms, such as the JAK2 kinase V617F mutation-positive chronic neutrophilic leukemia (CNL). CASE REPORT An 80-year-old Japanese male was diagnosed with acquired hemophilia A. He had compartment-like symptoms due to soft tissue hemorrhage in his left forearm and right lower extremity. A blood examination showed neutrophilia with a white blood cell count of 31,900/μL (91.9% neutrophils), an activated partial thromboplastin time of 69.0 seconds, coagulation factor VIII (FVIII) < 1.0%, and anti-FVIII inhibitor, 190 BU/mL. The bleeding episodes were controlled with intravenous activated prothrombin complex concentrate (FEIBA(®)) followed by recombinant factor VIIa (NovoSeven(®)). In addition, oral prednisolone (maximum dose, 30 mg/day) plus four doses of rituximab effectively suppressed anti-FVIII inhibitor levels while simultaneously reducing the neutrophil count. CNL with the JAK2 kinase V617F mutation was identified as the underlying disease. CONCLUSION This report describes the effectiveness of a combination of prednisolone and rituximab in managing acquired hemophilia A in an elderly man with a rare case of JAK2 kinase V617F mutation-positive CNL.

When elderly patients present with persistent thrombocytosis, myeloproliferative disease, iron-deficiency anemia or post-splenectomy status are suspected along with autoimmune diseases. Reported here are the cases of two elderly patients with persistent thrombocytosis due to hyposplenia, which is very rarely diagnosed in old age. Case 1 was a 72-year-old man whose thrombocytosis was due to non-familial type isolated congenital asplenia. Case 2 was a 74-year-old man whose thrombocytosis was caused by an atrophied spleen resulting from perforated stomach ulcer-related panperitonitis that had been treated 20 years previously. Both patients had thrombocyte counts exceeding >500,000/μl in association with small vestigial spleen tissue on a computed tomography scan and positive Howell–Jolly bodies on the blood smear. A correct diagnosis is essential for the management of persistent thrombocytosis.

がん疼痛に対し, ケタミンが使用されることは多い. 今回われわれは, 多発性骨髄腫の仙骨髄外転移による難治性の臀部痛の症例に対し, 複方オキシコドン注射液に加え, ケタミンを併用し, せん妄が惹起された1例を経験したので報告する. ケタミンを4 mg/時で経静脈的に開始した30時間後からせん妄が惹起され, 36時間後には疼痛の増悪の訴えが表出したため, オキシコドンのレスキューに加え, 2 mgのケタミンを急速に追加投与した. 投与直後, 過活動性せん妄が急激に出現したため, ケタミンの投与を中止した. 中止翌日には, せん妄が改善していた. 今回, このような少量のケタミンで過活動性せん妄が惹起された原因として, チトクロームP 450 (CYP) 3A4阻害作用を有する抗真菌薬のボリコナゾールが投与されていたことにより, ケタミンの副作用が強く出たことが考えられた. ケタミンを使用する際には, CYP阻害薬との薬物間相互作用に十分な注意を要する.

We report four cases of adult-onset Langerhans cell histiocytosis (LCH) with central nervous system (CNS) lesions in the hypothalamic-pituitary region. The first clinical symptoms were diabetes insipidus (two patients), hypothyroidism (one patient), and decreased libido/erectile dysfunction (one patient). Diagnosis was delayed as the CNS lesion was not initially suspected to be secondary to LCH, with a median time from symptom onset to treatment of 3.0 (range

We report here, our experience of seven patients with epithelioid sarcomas and their serum CA 125 levels, as well as the results of an in vitro and in vivo study of CA 125 expression in epithelioid sarcoma cells and xenografts using three epithelioid sarcoma cell lines.In the clinical study, the serum CA 125 levels of seven epithelioid sarcoma patients were examined at multiple time points. Expression of the MUC16 gene that encodes the CA 125 sequence was examined using RT-PCR methods in three epithelioid sarcoma cell lines, FU-EPS-1, SFT-8606 and NEPS, and the CA 125 protein in each cell lysate was examined by Western blot using anti-CA 125 clone OC125 antibody. The concentration of CA 125 in the conditioned medium of each cell line was also measured.In five of the seven epithelioid sarcoma patients, CA 125 levels reflected regression and progression of their disease. The CA 125 concentrations in the conditioned medium of FU-EPS-1, SFT-8606 and NEPS cells were 259, 252, and 6 U/ml, respectively. Strong expression of MUC16 mRNA was shown in FU-EPS-1 and SFT-8606 cells: correspondingly, a thick band was observed by Western blot analysis in only FU-EPS-1 and SFT-8606 cells.We concluded that epithelioid sarcoma cells produce and secrete CA 125 into the blood serum and that the elevation of serum CA 125 correlates with disease progression. Therefore, measuring the serum CA 125 level should provide an useful index for diagnosing and monitoring the course of epithelioid sarcoma.

We report on a case of a solitary fibrous tumor that developed in the thigh of an 82-year-old woman. The tumor was composed of areas of high-grade sarcoma and typical solitary fibrous tumor. Its karyotype was: 70,XXX,+X[4],+1[2],add(1)(p36)[4],add(1)[2],+2[4],-3[4],+6[4],add(6)(p11)x2[4],+7[4],+9[3],-11[4],-12[4],-13[4],add(13)(p11)x2[4],-14[4],+15[4],-16[3],-17[4],-19[4],+20,[4],+21[4],+22[2],+mar1x2[4][cp4].

Dedifferentiated chondrosarcoma is a rare, highly malignant variant of chondrosarcoma in which a high-grade sarcoma coexists with a low-grade chondroid tumor. We herein review a case of dedifferentiated chondrosarcoma with an osteosarcoma omit component that occurred in the distal femur of a 38-year-old man. We established the cell line (NDCS-1) from a pleural effusion of the metastatic lung tumor. The cell line was characterized by a the G-banded karyotype, polymerase chain reaction (PCR) single-strand conformation polymorphism analysis, spectral karyotyping, and reverse transcriptase PCR (RT-PCR). The tumor exhibited complex karyotypes and a high frequency of chromosomal amplication with p53 mutation. This tumor revealed an osteoblastic and chondroblastic character in vitro and in severe combined immunodeficiency mice. The expression and phosphorylation of platelet-derived growth factor receptor-beta, which seemed to play a major role in the malignant phenotype of chondrosarcoma, was confirmed by RT-PCR and Western blotting. To our knowledge, this is the first report of the establishment of a human dedifferentiated chondrosarcoma.

We report two cases of primary cold agglutinin disease (CAD) associated with megaloblastic anemia in Japanese elderly patients. Case 1 was a 67-year-old male and Case 2 was a 55-year-old male. Both patients were diagnosed with primary CAD, with continuously high cold agglutinin titers (1 : >8,192 and 1 : 16,834, resp.), monoclonal IgM-kappa light chains, and no underlying disease. In addition, both patients had megaloblastic anemia due to vitamin B12 deficiency. One patient received rituximab and both received vitamin 12 supplementation. To date, no cooccurrence of primary CAD and megaloblastic anemia has been emphasized. Thus, the association of these hematological diseases may be incidental; however, given that CAD is an autoimmune disease which may show antibodies against intrinsic factor and gastric parietal cells, this association was thought to be probably not a coincidence. Clinicians should be aware of the possible simultaneous presence of autoimmune hemolytic/megaloblastic anemia in patients with primary CAD.

Immature-type natural killer (NK) cell leukemia is rare and heterogeneous, and is variously classified as myeloid/NK cell precursor acute leukemia, myeloid/NK cell acute leukemia, or blastic NK cell lymphoma/leukemia [1–3]. Scott et al. [1] first described 20 cases of adult de novo acute myeloid leukemia showing a CD16/CD33/CD34/ CD56/HLA-DR phenotype. A few additional cases have since been reported, including that presented in this journal [4]. However, Suzuki et al. [2, 3] characterized myeloid/ NK cell precursor acute leukemia as a distinct entity, with a CD7/CD56/CD34/HLA-DR phenotype. Thus, myeloid/NK cell leukemia showing the CD7/CD56/ CD34/HLA-DR phenotype is considered to be more mature than myeloid/NK cell precursor leukemia [3]. Here, we report a case of myeloid/NK cell acute leukemia developing after chemoradiotherapy and with morphologically distinct characteristics. In March 2013, a 63-year-old man presented with poor appetite, lassitude, chest pain, and ophthalmic pain. He had undergone chemoradiotherapy (irradiation with 69.6 Gy/37 Fr and chemotherapy with cumulative doses of 280 mg/body carboplatin and 4,000 mg/body 5FU) for hypopharyngeal squamous cell carcinoma 5 months before referral. His complaints resolved gradually within 1 month; however, he developed anemia (Hb, 7.3 g/dL), thrombocytopenia (platelet count, 36 k/lL), and high lactate dehydrogenase (LDH, 836 IU/ L) in early April 2013. His condition rapidly deteriorated thereafter and he suffered respiratory distress and hepatic/ renal failure. There were no skin lesions, lymphadenopathy, or hepatosplenomegaly. No symptoms suspecting CNS disease were present. Repeat transfusions of red blood cells and platelets were performed. Blood analysis showed the following: white blood cell counts, 3,100/lL (5 % abnormal cells); Hb, 8.7 g/dL; platelet count, 63 K/lL; serum CRP, 2.89 mg/dL; aspartate aminotransferase (AST, 4,169 IU/L); alanine aminotransferase (ALT, 1,191 IU/L); LDH, 6,014 IU/L; total bilirubin, 6.2 mg/dL; direct bilirubin, 4.3 mg/dL; ferritin, 1,036 ng/mL; BUN, 48.2 mg/ dL; creatinine, 3.51 mg/dL; and uric acid, 19.6 mg/dL. The patient then developed coagulopathy, with a plasma D-dimer 2.7 lg/mL (normal \1.0 lg/mL), fibrinogen 140 mg/dL (normal 146–380 mg/dL) and antithrombin-III level of 33 % (normal 80–125 %). The bone marrow smear was cellular and showed 77 % blasts, which possessed round or oval nuclei with prominent nucleoli and a deeply stained cytoplasm with protrusions (mimicking plasmacytoid/megakaryoblastoid cells), some of which (6 %) showed weak staining for myeloperoxidase but stained negative for Periodic Acid-Schiff and iron. There were no azurophilic granules. In addition, we noted very large fishshaped blasts containing numerous nucleoli, large cells with mitotic figures, and unevenly divided binuclear blasts (Fig. 1a–d), Flow cytometry showed that bone marrow blasts were CD33 (80 %)/CD56 (96 %) but CD4 (\5 %)/CD7 (\5 %)/CD13 (\5 %)/CD34 (\5 %)/ CD41 (\5 %)/CD61 (\5 %) and HLA-DR (\5 %). Thus, the diagnosis of myeloid/NK cell leukemia was S. Imashuku (&) N. Kudo Division of Hematology, Takasago-seibu Hospital, 1-10-41 Nakasuji, Takasago 676-0812, Japan e-mail: shinim95@mbox.kyoto-inet.or.jp

The outcome for patients with Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) has improved significantly since the introduction of HLH-94 type immunochemotherapy [1]; however, treatment of EBV-HLH remains difficult in patients with chronic active EBV infection (CAEBV), a form of T or natural killer (NK) cell lymphoproliferative disease (LPD). [2, 3]. Although rituximab is effective as a pre-emptive B celldirected therapy for patients with XLP1-related EBV-HLH or severe EBV-HLH, in which EBV resides within B cells, [4–7] it has been thought to be inapplicable to Asian EBVHLH patients harboring EBV-infected T or NK cells. Here, testing the hypothesis that EBV may initially reside in B cells and may continue to produce virus particles and infect T or NK cells, we employed a combination of rituximab and HLH-94 type immunochemotherapy in the initial treatment of a 64-year-old Japanese male with EBV-NKLPD-associated HLH. The patient was referred to us with fever of unknown etiology. He had been suffering from influenza A infection and had remained febrile for nearly two weeks. His past history showed that the patient had suffered an episode of fever of unknown origin five months earlier, which had been associated with high serum IgG levels; therefore, one of the referring physicians suspected collagen disease, although no definitive diagnosis was made. On admission, the patient was febrile ([39.0 C) and suffering from diarrhea. Computed tomography revealed splenomegaly, but there was no evidence of adenopathy. Blood analysis revealed the following: WBC, 3,000/lL; Hb, 10.8 g/dL; platelet count, 71,000/lL; serum aspartate aminotransferase, 225 U/L; alanine aminotransferase, 116 U/L; lactate dehydrogenase, 1,050 U/L; total bilirubin, 1.6 mg/dL, total protein, 8.2 g/dL; albumin, 2.6 g/dL; BUN, 22.7 mg/dL; creatinine, 1.36 mg/dL; CRP, 7.23 mg/dL; ferritin, 17,282 ng/mL; sIL-2R, 14,700 U/mL; b-2-microglobulin, 12.6 mg/L; total cholesterol, 78 mg/dL; IgG, 4,116 mg/dL; IgA, 337 mg/dL; IgM, 68 mg/dL; anti-nuclear antibodies (ANA), [ 2,560; anti-DNA antibodies, \ 7; plasma fibrinogen, 207 mg/dL; and D-dimer, 42.7 lg/mL. In terms of hypergammaglobulinemia, the kappa/lambda ratio was 1.2 and neither M-protein nor Bence Jones protein was positive. No specific collagen disease was identified. The clinical features and laboratory data were compatible with the diagnostic criteria for HLH. The patient was diagnosed provisionally with collagen disease-related HLH and treated with oral prednisolone (PSL 30 mg/day). However, the high fever continued and he developed severe coagulopathy associated with a marked reduction in platelet count (21,000/lL), fibrinogen (\50 mg/dL) and anti-thrombin III (AT-3; 63 %) levels; therefore, he received gabexate S. Imashuku (&) N. Kudo Division of Hematology, Takasago-seibu Hospital, 1-10-41 Nakasuji, Takasago 676-0812, Japan e-mail: shinim95@mbox.kyoto-inet.or.jp

Natural killer (NK) cells were proposed to play an important role in the pathogenesis of human T-cell lymphotropic virus type 1- (HTLV-1-) associated neurologic disease. Our patient was a 77-year-old Japanese man, who had been treated for infective dermatitis associated with HTLV-1 for nearly 10 years. When referred to us, he had facial eczema/edema as well as extensive dermatitis at the neck/upper chest and nuchal area/upper back regions. Dermal lesions had CD3+CD4+ cells, but no NK cells. Flow cytometry of his peripheral blood showed a phenotype of CD2+ (97%), CD3+ (17%), CD4+ (12%), CD7+ (94%), CD8+ (6%), CD11c+ (70%), CD16+ (82%), CD19+ (0%), CD20+ (0%), CD56+ (67%), HLA-DR+ (68%), and NKp46+ (36%). Absolute numbers of CD56+NK cells in the peripheral blood were in a range of 986/μL–1,270/μL. The expanded NK cells in the peripheral blood are considered to be reactive, to maintain the confinement of the HTLV-1-positive CD4+ cells in the skin, and to prevent the progression of the disease.

To detect the presence of cancer cells in peripheral and mesenteric blood and to examine their relationship to prognosis in colorectal cancer patients undergoing curative surgery, we examined cytokeratin 19 and 20 mRNA in peripheral and mesenteric venous blood. Using reverse transcriptase polymerase chain reaction, cytokeratin 19 and 20 mRNA was amplified in peripheral and mesenteric blood samples obtained from 35 colorectal cancer patients who underwent curative surgery. Cytokeratin 19 or 20 mRNA in peripheral or mesenteric blood samples was detected in 18 of 35 cases (51%). There was no significant difference in Dukes' staging between the positive and negative groups. The median follow-up period was 56 months. In the positive group six patients (33%) showed recurrences. One patient (6%) showed recurrence in the negative group. The recurrence rate was significantly higher in the positive group than in the negative group. Five-year disease-free survival was significantly better in the negative group than in the positive group (94% vs. 65%). The detection of cytokeratin 19 or 20 mRNA in peripheral or mesenteric blood is thus associated with the prognosis for colorectal cancer patients undergoing curative surgery. Although the presence of these mRNAs in blood samples is a prognostic marker, the clinical utility of this assay is questionable because of the low recurrence rate in the positive group.

There is a well-known correlation between Herpes simplex (HSV) infection and erythema multiforme (EM). More recently, in Japan, it was found that Chlamydia pneumoniae (Cp) may promote the development of EM. All cases of Cp infection-associated EM that had been diagnosed in our clinic over the past two years (from 2011 to 2012) were analyzed. Cp infection was diagnosed on the basis of a significant increase (&gt, 2.00) in anti-Cp IgM titers, as measured by the HITAZYME-ELISA test. There were 7 cases of Cp-EM, one male and 6 females. Median age was 13 years (range 3-29 years). It is recommended that the possible involvement of Cp infection, besides HSV or Mycoplasma pneumoniae infections, should be considered in all cases of EM.

In Japan, although oral oxycodone is widely used for cancer pain treatment, there is no injection preparation of oxycodone used as a single ingredient. Only the compound injection of oxycodone and hydrocotarnine has received approval. Subcutaneous administration of the drug is approved, but there are few efficacy and safety reports about its intravenous administration. We compared 245 patients(187 intravenous administration patients and, 58 subcutaneous administration patients)to whom the compound injection of oxycodone and hydrocotarnine was administered from April, 2008 to September, 2011, in order to investigate the drug's efficacy and safety. The reasons for injection were the impossibility of oral administration in 105 patients, a need for dose adjustment in 56 patients, and that other drugs were not as effective in 37 patients, and side effect reduction in 33 patients. The average change in the numeric rating scale(0-10)was 3. 7→1. 8 in intravenous administration, and 3. 4→1. 2 in subcutaneous administration. The incidence of main adverse events(intravenous administration/subcutaneous administration)were constipation(37%/28%), vomiting(31%/34%), and somnolence(52%/50%). There was no significant difference in efficacy and safety. The conversion ratio differed in a case due to a change, and about 20 to 40% of addition was needed within four days after the start. It is considered that compound injection of oxycodone and hydrocotarnine is effective for cancer pain treatment.

Although it is well known that an excess of iodide suppresses thyroid function and blood flow in vivo, the underlying molecular mechanisms are not fully known. The functional effect of iodide occurs at multiple steps, which include inhibition of sodium/iodide symporter (NIS) expression, transient block of organification, and inhibition of hormonal release. The vascular effect likely involves suppression of the vascular endothelial growth factor (VEGF) gene. In this report, we show that excess iodide coordinately suppresses the expression of the NIS and VEGF genes in FRTL-5 thyroid cells. We also demonstrate that the mechanism of iodide suppression of NIS gene expression is transcriptional, which is synergized by the addition of thyroglobulin. Based on the findings of reporter gene assays and electrophoretic gel mobility shift analysis, we also report two novel DNA binding proteins that responded specifically to iodide and modulated NIS promoter activity. The results suggest that excess iodide affects thyroid vascular function in addition to iodide uptake. This study provides additional insights into the mechanism of action of excess iodide on thyroid function.

Aim: In order to clarify the sources of chronic HBV (hepatitis B virus) infection in children after the implementation of an “at-risk” strategy in Japan, chronically infected children were assessed. In addition, chronically infected children born to HBsAg-negative mothers and their family members were assessed to identify the sources of HBV transmission. Methods: Fifty-seven children who tested HBsAg-positive after the initiation of a mother-to-child transmission prevention program were enrolled in this study. The full-genome HBV DNA sequence was analyzed to confirm the transmission sources. Results: Of the 57 patients, 37 (65%) were born to HBV carrier mothers. The remaining 20 (35%) patients were born to HBsAg-negative mothers. Fourteen of these patients had HBV carrier fathers, and 2 patients, who were siblings, did not have an HBV carrier father. The remaining 4 patients had no family members with HBV infection. Phylogenetic tree analysis confirmed that father-to-child transmission and sibling-to-sibling transmission occurred in 3 families and 1 family, respectively. Conclusion: Although vaccine failure of mother-to-child transmission was the major cause of chronic HBV infection in children, father-to-child transmission was the second most common mode of transmission. In addition, sibling-to-sibling transmission was found. Unless at-risk individuals and groups can be accurately identified to prevent horizontal transmission, the introduction of universal vaccination is essential for achieving the elimination of HBV infection in Japan.

Activating Gs a mutations have been identified in most instances of fibrous dysplasia (FD). This mutation leads to consistently elevated intracellular cyclic adenosine monophosphate (cAMP) levels, with various biological consequences. The development of secondary sarcoma in FD is a rare but well-established phenomenon. This finding raised the possibility that a common gene mutation exists in these tumors.The expression of the Gs a mutation was examined in 16 cell lines and 173 musculoskeletal tumor tissues, including 13 cases of FD, via RT-PCR and sequence analysis.No expression of a Gs a mutation was detected in any cell line or clinical tissue sample, excluding FD tissues. Direct sequence analysis demonstrated results identical to those of RT-PCR.Activating Gs a mutation rarely occurs in musculoskeletal tumors other than FD. The occurrence of most sarcomas displays no correlation with Gs a mutations.

The aim of the study was to examine the chronological histology of osteoinduction of highly purified beta-tricalcium phosphate (beta-TCP) implanted in dog dorsal muscles. Specimens were harvested on days 14, 28, 42, 56, 112 and 168 after implantation, and were analyzed by hematoxylin and eosin (HE) staining, tartrate-resistant acid phosphatase (TRAP) staining, immunohistochemistry, in situ hybridization, and silver impregnation. After day 28, abundant TRAP- and cathepsin K-positive multinucleated cells adhered to beta-TCP, suggesting that these cells are osteoclasts that can resorb beta-TCP. On day 56, new bone was formed and alpha1 chain of type I procollagen mRNA-positive osteoblasts lined the newly formed bone. Silver impregnation showed abundant collagen fibrils within the beta-TCP micropores. These results suggest that micropores function as a storage space for extracellular matrix components, including collagen. Newly formed bone never degenerated in the late stage, suggesting that beta-TCP has good biocompatibility and this material retains the conditions appropriate for osteointegration and bioresorption. In conclusion, beta-TCP has osteoinductivity after implantation in dog dorsal muscles without use of bone marrow cells or osteoinductive cytokines. The appearance of a large number of active osteoclasts precedes new bone formation.

Urinary excretion of mefenamic acid (MA) and its two oxidative metabolites, M-I (3'-hydroxymethyl derivative) and M-II (3'-carboxyl derivative), and their glucuronides was investigated in preterm infants undergoing MA therapy. MA was given orally at a dose of 2 mg/kg and the dose was repeated every 24 h a maximum of three times. Urine was collected for up to 5 d after the last dose, and MA and the metabolites were determined by a newly developed HPLC. The cumulative amounts of MA and the metabolites excreted in the urine varied from 7 to 46% of the total dose administered, and were less than those reported in adults and children. Significant correlation was observed between the plasma half-life of MA and the cumulative amount of MA and the metabolites excreted in the urine. These results suggest that long plasma half-lives of MA observed in preterm infants are due mainly to low activity of drug metabolizing enzyme(s). In an infant who received the two regimens of MA therapy about 2 weeks apart, the plasma half-life of MA was shortened and the urinary excretion of the MA metabolites including their glucuronides was greatly increased during this period. It is suggested that the activities of both cytochrome P-450(s) and glucuronyltransferase(s) related to MA metabolism rapidly increased during the first month of the infant's life.

Prominent osteoconductive activity and the biodegradable nature of commercially available beta-tricalcium phosphate ( β -TCP, OSferion ® ) have been documented in animal experiments. We analyzed four cases of involving grafted OSferion ® in human bone with respect to histological features by routine hematoxylin and eosin staining, silver impregnation, immunohistochemistry and in situ hybridization. OSferion ® affords early bioresorption by osteoclasts, vascular invasion of macropores and osteoblastic cell attachment on the surface on the ceramic surface 14 days after grafting. Prominent bone formation and direct bone connection between preexisting bone and OSferion ® were evident 28 days after grafting. Nearly the entire TCP surface was covered by lamellar bone; additionally, active osteoblastic lining and attachment of the osteoclast-like giant cells were not observed 72 weeks after grafting. Silver impregnation revealed the presence of collagen fibrils within probable micropores of OSferion ® .

The aim of this study was to examine the chronological histology associated with highly purified beta-tricalcium phosphate (beta-TCP) implanted in the rat femoral condyle. Specimens were harvested on days 4, 7, 14, 28 and 56 after implantation, and were analyzed by tartrate-resistant acid phosphatase (TRAP) staining, immunohistochemistry of the ED1 protein as a marker of the phagocyte system, and in situ hybridization with digoxigenin-labeled alpha1 chain of type I procollagen (COL1A1), osteopontin and osteocalcin. beta-TCP was resorbed in a chronological manner. Although new bone was not observed on day 4, fibroblast-like cells around beta-TCP were positive for COL1A1 and osteopontin mRNA. New bone formation presented after day 7. In the double-staining for OPN and ED1 on day 7, most cells around beta-TCP were positive for either osteopontin mRNA or ED1 protein. However, there were some doubly positive multinucleated cells, suggesting that they belonged to the mononuclear phagocyte system. After day 28, the implanted region was replaced with bone marrow. Multinucleated TRAP-positive and ED1-positive cells which adhered to beta-TCP at all stages seemed to be osteoclasts and they continuously resorbed beta-TCP. beta-TCP has a good biocompatibility since both bioresorption and bone formation started at an early stage after implantation.

A 77-year-old male was admitted to hospital after suffering a pelvic bone fracture in a road traffic accident and was incidentally found to have IgG-kappa-type multiple myeloma with hypercalcemia. The patient was also noted to be hypokalemic and had low HCO3 (-), with possible damage to the distal tubules in the kidneys. When the treatment was begun with bortezomib/dexamethasone/elcatonin and sodium bicarbonate (NaHCO3) in normal saline (equivalent to a daily sodium dose of 200 millimoles per liter [mmol/L]), the patient was in a state of poor oral fluid intake. The patient developed hypernatremia and hyperchloremia, with a peak serum sodium and chloride levels of 183 mmol/L and 153 mmol/L, respectively, at the sixth day after the start of treatment. Following the switch of the intravenous infusions from normal saline to soldem 1 and soldem 3 solutions, these high-electrolyte levels gradually returned to normal over the next 7 days. Although the patient showed disturbed consciousness (Japan Coma Scale = JCS-I-3) during the period of electrolyte abnormality, he eventually fully recovered without sequelae. In this patient, we successfully managed the severe hypernatremia/hyperchloremia, caused by the combined effects of intravenous saline burden in a state of poor oral fluid intake, during the treatment for IgG-kappa type multiple myeloma.

We report here on a 60-year-old male with alcohol-related macrocytic anemia. He was hospitalized on three occasions with hemoglobin < 9.0 g/dL and mean corpuscular volume > 130 fL. Careful history taking and observation of his blood status led us to make a correct diagnosis. At the time of each of his admissions, only with bed rest and abstinence from alcohol did our patient dramatically show spontaneous recovery of anemia in association with a rapid decline of serum γ-glutamyl transpeptidase values. It is well recognized that marrow abnormalities in alcoholic patients are reversible. Physicians should be aware that there is a subset of patients with macrocytic anemia that could be improved without medication.

Insoluble α- d -glucan, previously formed on a glass surface from sucrose by the action of cell-free d -glucosyltransferases of Streptococcus sobrinus OMZ176, was significantly removed by a purified preparation of endo-(1→3)-α- d -glucanase (mutanase) from a strain of Pseudomonas sp. Almost complete dissociation of adherent glucan occurred at the highest enzyme concentration (40 mU/mL) tested. Synthesis and de novo adherence on glass of the glucan was markedly inhibited by the presence of mutanase, even at low concentrations (4 mU/mL or less). When compared to native glucan, the mutanase-modified glucan samples (a) contained lower proportion of d -(1→3) linkages; (b) showed lower susceptibility to mutanase and higher susceptibility to (1→6)-α- d -glucanase (dextranase); (c) contained larger amounts of low-molecular-weight fractions; (d) had lower intrinsic viscosities; (e) showed higher S. sobrinus cell-agglutinating activities; and (f) consisted of looser entwinement of coalescent single-stranded fibrils (a major component) and shorter double-stranded fibrils (a minor one).