Predicting the characteristics of the aetiological agent for Kawasaki disease from other paediatric infectious diseases in Japan.

Although Kawasaki disease (KD), which was first reported in the 1960s, is assumed to be infectious, its aetiological agent(s) remains unknown. We compared the geographical distribution of the force of infection and the super-annual periodicity of KD and seven other paediatric infectious diseases in Japan. The geographical distribution of the force of infection, which was estimated as the inverse of the mean patient age, was similar in KD and other paediatric viral infections. This similarity was due to the fact that the force of infection was determined largely by the total fertility rate. This finding suggests that KD shares a transmission route, i.e. sibling-to-sibling infection, with other paediatric infections. The super-annual periodicity, which is positively associated with the sum of an infectious disease's incubation period and infectious period, was much longer for KD and exanthema subitum than other paediatric infectious diseases. The virus for exanthema subitum is known to persist across the host's lifespan, which suggests that the aetiological agent for KD may also be capable of persistent infection. Taken together, these findings suggest that the aetiological agent for KD is transmitted through close contact and persists asymptomatically in most hosts.

Predicting the characteristics of the aetiological agent for Kawasaki disease from other paediatric infectious diseases in Japan--ERRATUM.

In the above-mentioned article [1] there is an error in the penultimate heading in Table 4. The heading 'T predicted by equation (2)' should read 'T predicted by equation (7)'.

Long-term follow-up on soft and hard tissue levels following guided bone regeneration treatment in combination with a xenogeneic filling material: a 5-year prospective clinical study.

PURPOSE: In the present prospective study, bone augmentation by guided bone regeneration (GBR) in combination with bovine hydroxyapatite (BHA) as filling material was evaluated with regard to soft and hard tissue stability over time. MATERIALS AND METHODS: Implant survival, radiologic bone level (marginal bone level [MBL]), and clinical soft tissue parameters (marginal soft tissue level [MSTL]) were observed. Twenty patients received a total of 41 implants (Brånemark System, Nobel Biocare, Göteborg, Sweden) in conjunction with GBR treatment. The end point of the study was after 5 years following implant placement. RESULTS: The cumulative implant survival rate was 97.5% corresponding to one implant failure. The radiologic evaluation of the MBL demonstrated a crestal bone height above the level of the fixture head. The bone height decreased from -3.51 to -2.38 mm (p < .001). The MSTL was -1.52 mm at baseline and -1.15 mm at the 5-year follow-up (p < .04) demonstrating a stable submucosal crown margin throughout the study period. CONCLUSION: GBR treatment in combination with a xenogeneic filling material (BHA) is a viable treatment option in order to maintain stable hard and soft tissue levels in conjunction with augmentative procedure related to oral implant treatment.

Long-term results of surgical therapy for masticatory muscle tendon-aponeurosis hyperplasia accompanied by limited mouth opening.

Masticatory muscle tendon-aponeurosis hyperplasia is a new disease entity characterized by limited mouth opening due to contracture of the masticatory muscles, resulting from hyperplasia of tendons and aponeuroses. In the case of masseter muscle type, the face displays a square mandible configuration. Pharmacotherapy, occlusal splints and physical therapy are ineffective. This study evaluated the long-term results of aponeurectomy of the masseter muscle with coronoidectomy to release the temporal muscle tendon. The subjects were 10 patients who underwent surgery between 2000 and 2005. Mean maximum mouth opening before surgery was 21.8mm (range 17-29 mm). All patients received bilateral aponeurectomy of the masseter muscle and coronoidectomy. Three patients additionally underwent bilateral anglectomy for esthetic reasons. After discharge, one patient did not return to the hospital. Data from the other nine patients were analyzed. The mean duration of follow-up was 4 years. At final follow-up, the maximum mouth opening was >44 mm in four patients, 40-44 mm in three patients, and 35-39 mm in two patients. Overall satisfaction was excellent or good in all patients.

C-type natriuretic peptide activates a non-selective cation current in acutely isolated rat cardiac fibroblasts via natriuretic peptide C receptor-mediated signalling.

In the heart, fibroblasts play an essential role in the deposition of the extracellular matrix and they also secrete a number of hormonal factors. Although natriuretic peptides, including C-type natriuretic peptide (CNP) and brain natriuretic peptide, have antifibrotic effects on cardiac fibroblasts, the effects of CNP on fibroblast electrophysiology have not been examined. In this study, acutely isolated ventricular fibroblasts from the adult rat were used to measure the effects of CNP (2 x 10(-8) M) under whole-cell voltage-clamp conditions. CNP, as well as the natriuretic peptide C receptor (NPR-C) agonist cANF (2 x 10(-8) M), significantly increased an outwardly rectifying non-selective cation current (NSCC). This current has a reversal potential near 0 mV. Activation of this NSCC by cANF was abolished by pre-treating fibroblasts with pertussis toxin, indicating the involvement of G(i) proteins. The cANF-activated NSCC was inhibited by the compounds Gd(3+), SKF 96365 and 2-aminoethoxydiphenyl borate. Quantitative RT-PCR analysis of mRNA from rat ventricular fibroblasts revealed the expression of several transient receptor potential (TRP) channel transcripts. Additional electrophysiological analysis showed that U73122, a phospholipase C antagonist, inhibited the cANF-activated NSCC. Furthermore, the effects of CNP and cANF were mimicked by the diacylglycerol analogue 1-oleoyl-2-acetyl-sn-glycerol (OAG), independently of protein kinase C activity. These are defining characteristics of specific TRPC channels. More detailed molecular analysis confirmed the expression of full-length TRPC2, TRPC3 and TRPC5 transcripts. These data indicate that CNP, acting via the NPR-C receptor, activates a NSCC that is at least partially carried by TRPC channels in cardiac fibroblasts.

Surgical resection of solitary adrenal metastasis from esophageal carcinoma following esophagectomy.

The prognosis of esophageal carcinoma following esophagectomy is poor due to a high frequency of metastasis to periesophageal lymph nodes and distant organs. However, we experienced a case with good prognosis following resection of a solitary adrenal metastatic tumor. The patient was a 70-year-old man diagnosed with type 2 esophageal cancer (Lt-Ae, T2N1M0, Stage IIB) who was treated with esophagectomy. Eight months following surgery, solitary adrenal metastasis was detected by CT, and was resected. At 42 months follow-up he has had a good quality of life in the community without evidence of recurrence. To the best of our knowledge, only five cases with resected solitary adrenal metastases including our case, have been reported, and show a greater than 1-year survival. Consequently, we suggest that resection of solitary organ metastases is a good alternative, even following esophagectomy.

Changes in the awareness of oral health among new students newly enrolled at the University of Tokyo over the past 15 years.

OBJECTIVE: The aim of this study was to examine changes in awareness of oral health among Japanese university students. METHODS: Between 1990 and 2004, a total of 51,650 students newly enrolled at the University of Tokyo responded to an annual written questionnaire on oral health. RESULTS: (i) Approximately 60% of the students brushed their teeth twice a day. Female students brushed more frequently than male students. (ii) The percentage of students who brushed for 2-3 min per time decreased, while the percentage who brushed four or more minutes increased. (iii) The number of students who had learned how to brush properly increased. This trend was particularly clear-cut among male students, although the proportion of female students who had learned to brush properly remained higher than that of male students. (iv) The percentage of female students who sought treatment for malocclusion was higher than that of male students. The percentage of students who underwent orthodontic treatment increased from 11.6 to 19.7%. The percentage of female students who received orthodontic treatment was approximately twofold that of male students. (v) The percentage of students who had temporomandibular disorders was 0.7% in males and 1.5% in females. (vi) More than 40% of the students had periodontal diseases, with a higher prevalence among male students than female students. (vii) Approximately 20% of the students wanted to consult our service centre. CONCLUSIONS: The awareness of oral health among new undergraduates at the University of Tokyo has improved over the past 15 years.

A comprehensive analysis of loss of heterozygosity caused by hemizygous deletions in renal cell carcinoma using a subtraction library.

Several new loci were identified by a comprehensive analysis of loss of heterozygosity (LOH) using a subtraction library between matched normal and renal cell carcinoma (RCC) tissues. A total of 187 clones from the library, with a complexity of 1x10(4), were mapped, and 44 clusters of the mapped loci were subjected to LOH analysis using microsatellite markers. A total of 27 loci, which exhibited frequencies of LOH of at least 10% among 44 tumors, mostly clear-cell RCC, included several loci that were reported previously, such as, the von Hippel-Lindau gene, adenomatous polyposis coli, and interferon regulatory factor-1, as well as new loci, at 5q32-q34, 6q21-q22, 8p12, and others. These loci exhibited LOH among 11.8-93.8% of tumors, and most, if not all, were derived from the sites of hemizygous deletions. The minimum regions of LOH of chromosomes 5, 6, and 8 were 9.0, 10.3, and 0.775 Mb, respectively. The average distance between the cloned fragments on the chromosomes was 2.2 Mb in 187 clones, indicating that the minimum LOH size expected from this subtraction analysis was roughly 50 kb. Therefore, the strategy described here provides comprehensive analysis of LOH sites, which were mostly caused by hemizygous deletions.

Opsonin receptor expression on peritoneal exudative and circulatory neutrophils in murine acute pancreatitis.

Acute severe (necrotizing) pancreatitis is often associated with pancreatic or peripancreatic infection. Decreased bacterial clearance due to impaired immune defense may cause local infection. We investigated expressions of surface opsonin receptors (CD11b, complement receptor 3; CD32/CD16, immunoglobulin G Fc receptor) on local and circulatory neutrophils, in murine acute pancreatitis. The mild and severe forms of acute pancreatitis were induced by seven and 13 subcutaneous injections of caerulein, respectively. Peritoneal exudative and circulatory neutrophils were counted and assayed for receptor expressions by flow cytometry, serially at 1-72 hours after pancreatitis induction. Histologically, mild and severe forms showed edematous and necrotizing pancreatitis, respectively. The peritoneal exudative neutrophil count was greater in mild than in severe pancreatitis. Expressions of CD11b and CD32/CD16 on local neutrophils were upregulated early in mild pancreatitis. This upregulation was attenuated in severe pancreatitis. The circulatory neutrophil count was elevated in severe pancreatitis but was unchanged in mild pancreatitis. Opsonin receptor expression on circulatory neutrophils showed a transient, modest upregulation in the early phase of mild pancreatitis. Receptor-positive circulatory neutrophils showed a marked elevation that persisted throughout the course of severe pancreatitis. In conclusion, severe (necrotizing) pancreatitis is associated with reduced opsonin receptor expression on local neutrophils and enhanced expression on circulatory neutrophils, as compared with mild (edematous) pancreatitis. These changes may contribute to local infectious complications and multiple organ failure, in severe pancreatitis.

Initial and maintenance combination treatment with interferon-beta, MCNU (Ranimustine), and radiotherapy for patients with previously untreated malignant glioma.

Combined treatment with interferon-beta, MCNU (Ranimustine), and radiotherapy was assessed in patients with malignant glioma who had not received previous cytotoxic drug therapy. Forty-three patients up to 75 years old with histopathologically confirmed malignant glioma were studied. All patients had tumors measurable by neuroimaging, a Karnofsky performance score exceeding 40, and an expected survival exceeding 2 months. A response rate of 49% (21/45) was observed, including 6 complete remissions (14%) and 15 partial remissions (35%). Of the 43 patients who completed initial therapy, 19 were given sequential maintenance therapy. Survival time was much longer with than without maintenance therapy. Toxic side effects were moderate and did not substantially affect patients' general condition. We concluded that this combination therapy had a pronounced effect on untreated malignant glioma, particularly in patients whose initial therapy was followed up with maintenance therapy.

[Effectiveness of DeVIC chemotherapy for recurrent primary central nervous system lymphoma].

Six cases with recurrent or refractory primary central nervous system lymphoma were treated with a new chemotherapeutic regimen "DeVIC (dexamethasone, VP16, ifosfamide, carboplatin)". Five recurrent cases had a remission period for an average of 18 months after initial treatment, but relapse occurred. One refractory case had no response after initial treatment. Then these 6 cases were treated with 1-3 courses of DeVIC chemotherapy at intervals of 4 weeks. Two cases achieved complete remission, and 3 cases attained partial remission (response rate was 83%). One case showed no response after 1 course of DeVIC chemotherapy. However, in all cases re-relapse occurred 1-5 months after remission, and only 1 case is still alive. DeVIC chemotherapy produced a high response rate for recurrent central nervous system lymphoma, but re-relapse occurred after only a few months. The establishment of maintenance chemotherapy is required.

Clinicopathological study of oligodendroglial tumors: the effectiveness of interferon beta, ACNU/MCNU, and radiation (IAR/IMR) for anaplastic tumors.

The retrospective clinicopathological characteristics of oligodendroglial tumors were investigated in patients who underwent surgery, radiotherapy, and/or chemotherapy. Regarding oligodendroglioma and oligoastrocytoma without malignancy, patients who had undergone radiation therapy at a total dose of 40-50Gy had relatively long postoperative survival. Of these 15 patients, 6 showed signs of recurrence, and after additional treatment, 5 patients are still alive. On the other hand, regarding anaplastic oligodendroglial tumors, patients with anaplastic oligoastrocytoma responded well to combination chemotherapy with interferon beta, nitrosourea derivatives (ACNU/ MCNU), and radiation therapy (referred to as IAR/IMR) and survived longer than patients with anaplastic oligodendroglioma. In conclusion, patients with oligodendroglial tumors could survive longer by treatment involving surgery and radiotherapy. As for malignancy, cases of anaplastic oligoastrocytoma could be effectively treated by adjuvant therapy using IAR/IMR after surgery, but in cases of anaplastic oligodendroglioma, the response to IAR/IMR was not good, and another strategy of treatment should be recommended.

Efficacy of post operative adjuvant therapy with human interferon beta, MCNU and radiation (IMR) for malignant glioma: comparison among three protocols.

In order to develop ultimate adjuvant therapy for malignant gliomas, we analysed 77 patients with malignant gliomas (29 anaplastic astrocytomas (AAs) and 48 glioblastoma multiformes (GMs)) treated by three protocols of IMR therapy (human interferon-beta (HuIFN-beta), MCNU and radiation). In protocol 1 (n = 45: AA = 13, GM = 32), 1 x 10(6) IU of HuIFN-beta was administrated intravenously once a day for 7 days. On day 2, MCNU was administrated at a dose of 2 mg/kg b.w. intravenously and from day 3, radiation was started in five weekly fractions of 2 Gy for 6 weeks. Total dose was 60 Gy. Protocol 2 (n = 19: AA = 11, GM = 8) was comparable with protocol 1 except HuIFN-beta was administrated twice a day at a dose of 1 x 10(6) IU each. Protocol 3 (n = 13: AA = 5, GM = 8) differed from protocol 2 only in a high dose-hyperfractionated radiation which was given twice a day at a dose of 1.5 Gy each and for a total dose of 66 Gy. Antitumor effects were evaluated by survival and response rate determined by decrease of tumor size. Significant improvement was obtained in patients with AAs by protocol 2 and 3. Response rates of patients with AAs and GMs were 46.2% and 50% in protocol 1, 63.6% and 50% in protocol 2, and 80% and 50% in protocol 3, respectively. One and two year survival rates in AAs were 46.4% and 34.8% in protocol 1, both 75% in protocol 2, and both 100% in protocol 3. Survival rates in GMs were not different among them. Except of radiation necrosis, which was observed in 38.5% of the patients under protocol 3, there was no significant difference in the adverse effects among the three protocols. In the present study, the efficacy of IMR therapy for patients with malignant gliomas, especially for AAs, was cofirmed. We conclude that twice a day administrations of HuIFN-beta in combination with a high dose-hyperfractionated radiation provide increased efficacy in IMR therapy.

Src homology region 2 (SH2) domain-containing phosphatase-1 dephosphorylates B cell linker protein/SH2 domain leukocyte protein of 65 kDa and selectively regulates c-Jun NH2-terminal kinase activation in B cells.

Src homology region 2 (SH2) domain-containing phosphatase-1 (SHP-1) is a cytosolic protein tyrosine phosphatase containing two SH2 domains in its NH2 terminus. That immunological abnormalities of the motheaten and viable motheaten mice are caused by mutations in the gene encoding SHP-1 indicates that SHP-1 plays important roles in lymphocyte differentiation, proliferation, and activation. To elucidate molecular mechanisms by which SHP-1 regulates BCR-mediated signal transduction, we determined SHP-1 substrates in B cells using the substrate-trapping approach. When the phosphatase activity-deficient form of SHP-1, in which the catalytic center cysteine (C453) was replaced with serine (SHP-1-C/S), was introduced in WEHI-231 cells, tyrosine phosphorylation of a protein of about 70 kDa was strongly enhanced. Immunoprecipitation and Western blot analyses revealed that this protein is the B cell linker protein (BLNK), also named SH2 domain leukocyte protein of 65 kDa, and that upon tyrosine phosphorylation BLNK binds to SHP-1-C/S in vitro. In vitro kinase assays demonstrated that hyperphosphorylation of BLNK in SHP-1-C/S-expressing cells was not due to enhanced activity of Lyn or Syk. Furthermore, BCR-induced activation of c-Jun NH2-terminal kinase was shown to be significantly enhanced in SHP-1-C/S transfectants. Taken collectively, our results suggest that BLNK is a physiological substrate of SHP-1 in B cells and that SHP-1 selectively regulates c-Jun NH2-terminal kinase activation.

Comparative genomic sequencing identifies novel tissue-specific enhancers and sequence elements for methylation-sensitive factors implicated in Igf2/H19 imprinting.

A differentially methylated region (DMR) and endoderm-specific enhancers, located upstream and downstream of the mouse H19 gene, respectively, are known to be essential for the reciprocal imprinting of Igf2 and H19. To explain the same imprinting patterns in non-endodermal tissues, additional enhancers have been hypothesized. We determined and compared the sequences of human and mouse H19 over 40 kb and identified 10 evolutionarily conserved downstream segments, 2 of which were coincident with the known enhancers. Reporter assays in transgenic mice showed that 5 of the other 8 segments functioned as enhancers in specific mesodermal and/or ectodermal tissues. We also identified a conserved 39-bp element that appeared repeatedly within the DMR and formed complexes with specific nuclear factors. Binding of one of the factors was inhibited when the target sequence contained methylated CpGs. These complexes may contribute to the presumed boundary function of the unmethylated DMR, which is proposed to insulate maternal Igf2 from the enhancers. Our results demonstrate that comparative genomic sequencing is highly efficient in identifying regulatory elements.

Purification and characterization of a thermostable chitinase from Streptomyces thermoviolaceus OPC-520 and cloning of the encoding gene.

When Streptomyces thermoviolaceus OPC-520 was grown in a minimal medium with 1% chitin, three activity bands corresponding to proteins of 40 kDa (Chi40), 30 kDa (Chi30), and 25 kDa (Chi25) were detected. Among them, Chi30 was purified from the culture filtrate of the strain. The molecular mass was estimated to be 30 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and its isoelectric point was 3.8. The optimum pH and temperature of Chi30 were 4.0 and 60 degrees C, respectively. Chi30 was stable at pH 6-8 up to 60 degrees C. The gene encoding Chi30 (chi30) was cloned and its nucleotides sequenced. The open reading frame of chi30 encoded a protein consisting of 347 amino acids with a calculated molecular weight of 35,621. The mature Chi30 consisted of only a catalytic domain and showed a significant similarity with ChiA from S. coelicolor and ChiA from S. lividans. The existence of a 12-bp direct repeat sequence in the promoter region of chi30 was detected, which have been suggested to be involved in both chitin induction and glucose repression.

Family 19 chitinases from Streptomyces thermoviolaceus OPC-520: molecular cloning and characterization.

Family 19 chitinase genes, chi35 and chi25 of Streptomyces thermoviolaceus OPC-520, were cloned and sequenced. The chi35 and chi25 genes were arranged in tandem and encoded deduced proteins of 39,762 and 28,734 Da, respectively. Alignment of the deduced amino acid sequences demonstrated that Chi35 has an N-terminal domain and a catalytic domain and that Chi25 is an enzyme consisting of only a catalytic domain. Amino acid sequences of the catalytic domains of both enzymes, which are highly similar to each other, suggested that these enzymes belong to the family 19 chitinases. The cloned Chi35 and Chi25 were purified from E. coli and S. lividans as a host, respectively. The optimum pH of Chi35 and Chi25 were 5-6, and the optimum temperature of Chi35 and Chi25 were 60 and 70 degrees C, respectively. Chi35 bound to chitin, Avicel, and xylan. On the other hand, Chi25 bound to these polysaccharides more weakly than did Chi35. These results indicate that the N-terminal domain of Chi35 functions as a polysaccharide-binding domain. Furthermore, Chi35 showed more efficient hydrolysis of insoluble chitin and stronger antifungal activity than Chi25. In the polysaccharide-binding domain of Chi35, there are three reiterated amino acid sequences starting from C-L-D and ending with W, and the repeats were similar to xylanase (STX-I) from the same strain. However, the repeats did not show sequence similarity to any of the known chitin-binding domains and cellulose-binding domains.

Immediate and delayed implant placement into extraction sockets: a 5-year report.

BACKGROUND: As a complement to the earlier reported 3-year results from a prospective multicenter study of immediate and delayed placement of implants into fresh extraction sockets, the 5-year results are reported. PURPOSE: The purpose of this 5-year report was to evaluate the immediate and long-term success of implants placed into fresh extraction sockets, with respect to implant size and type, bone quality and quantity, implant position, initial socket depth, and reason for tooth extraction. MATERIALS AND METHODS: This paper presents the 5-year results of the original 12 centers that participated with 143 consecutively included patients. A total of 264 implants were placed either immediately after tooth extraction or after a short soft-tissue healing time (3-5 weeks). The patients were divided into five subgroups, depending on the type of insertion method used. RESULTS: The outcome demonstrated that the cumulative implant survival rate after 5 years of loading has not changed and remains 92.4% in the maxilla and 94.7% in the mandible. No difference in failure rates can be seen between the groups when relating the failures to insertion method. CONCLUSION: This prospective study demonstrated that placing Brånemark implants into fresh extraction sites can be successful over a period of 5 years of loading. One of the outcomes of the study shows that there is a clinical correlation between implant failure and periodontitis as a reason for tooth extraction, even if it is difficult to give it a casual association. It can be hypothesized that periodontitis affected tissues might have a negative local influence because of the presence of infrabony defects that could possibly increase the gap between bone and implant or jeopardize achievement of primary stability.

Idiopathic hypertrophic cranial pachymeningitis: clinicoradiological spectrum and therapeutic options.

OBJECTIVE: Idiopathic hypertrophic cranial pachymeningitis is a rare disease, of undetermined pathogenesis, that is characterized by inflammation and fibrosis of the dura mater. METHODS: We encountered six patients with idiopathic hypertrophic cranial pachymeningitis and analyzed their clinical presentations, radiological findings, and treatment. RESULTS: In the six patients, the main manifestations were cranial nerve palsies and headache. Three associations were present, namely optic neuropathy, Tolosa-Hunt syndrome, and diabetes insipidus. Gadolinium-enhanced magnetic resonance imaging was diagnostic, showing intense dural enhancement in a linear or nodular pattern. The responses to corticosteroid therapy were better for patients who exhibited linear, rather than nodular, dural enhancement. For one patient, surgical decompression of the superior orbital fissure provided lasting relief. The course of the disease followed one of three patterns, i.e., sustained remission, relapse with corticosteroid independence, or relapse with corticosteroid dependence. Pulse corticosteroid therapy provided significant relief, while reducing the daily corticosteroid requirement and avoiding side effects, for a corticosteroid-dependent relapsing patient. CONCLUSION: Idiopathic hypertrophic cranial pachymeningitis exhibits varied clinical courses. It is important to prevent irreversible cranial neuropathy during the active phase of the disease, using daily administration of corticosteroids, pulse corticosteroid therapy, or surgical decompression.

Synthesis of chitinase in Streptomyces thermoviolaceus is regulated by a two-component sensor-regulator system.

The chiS and chiR genes located upstream of the chitinase locus (chi40) on the chromosome of Streptomyces thermoviolaceus OPC-520 were cloned and sequenced. The deduced amino acid sequences revealed that ChiS (390 amino acids, 40.9 kDa) and ChiR (213 amino acids, 22 kDa) show significant sequence similarities to histidine kinases and response regulators, respectively, of typical prokaryotic two-component regulatory systems. The extracellular chitinase activity of Streptomyces lividans 66 (pTSR2 (bearing chiS, chiR and chi40)) was significantly enhanced by a high dosage of the chiS and chiR genes.