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Objectives: In April 2020, the Japanese government declared a state of emergency owing to the outbreak of the novel coronavirus disease (COVID-19) pandemic, which resulted in reduced workforce and job losses. Furthermore, income is one of the most consistent predictors of dental visits. Therefore, this study examined the association between income changes and dental clinic visits during the COVID-19 state of emergency in Japan. Methods: An online, self-reported cross-sectional survey about health activities including dental visits during the first COVID-19 state of emergency was conducted in Osaka, Japan (June 23 to July 12, 2020). Among participants with toothaches, the assessment for the association between “refrained from visiting a dentist despite wanting treatment for toothache during the state of emergency (refrained treatment)” and income changes before and after the state of emergency using a multivariate Poisson regression model adjusted for sex, age, self-rated health, frequency of regular dental visits, and employment status. Results: Among 27,575 participants, 3,895 (14.1%) had toothaches, and 1,906 (6.9%) reported refrained treatment. Among people with decreased income (n = 8,152, 29.6% of overall participants), the proportions of the refrained treatment group were 8.0% (income decreased by 1%–49%), 9.9% (50%–99% decreased), and 9.1% (100% decreased). Among participants with toothache, after adjusting for all variables, compared with participants with no income change, we observed significantly higher prevalence ratios (PRs) for refrained treatment in those who experienced a decreased income owing to COVID-19 (1%–49% decrease: PR = 1.08; 95% confidence interval [CI], 1.005–1.17; 50%–99% decrease: PR = 1.18; 95% CI, 1.06–1.32; 100% decrease: PR = 1.18; 95% CI, 1.04–1.33). Conclusion: Decreased income was associated with refrained dental treatment during the COVID-19 state of emergency in Osaka, Japan. The economic damage related to the COVID-19 pandemic could lead to oral health inequalities. Knowledge Transfer Statement: Our study found that individuals with decreased income owing to COVID-19 before and after the state of emergency showed significantly higher prevalence ratios for refraining from visiting a dentist despite wanting treatment for toothache. We believe that our study makes a significant contribution because it provides novel, basic data that economic damages related to the COVID-19 pandemic might expand to oral health inequalities.

Accurate assessment of renal function is essential for determining serum vancomycin (VCM) concentration. Creatinine clearance (Ccr)-calculated using the Cockcroft and Gault (CG) equation-can be used to evaluate renal function for determining VCM dosage. However, Ccr-based evaluation may not be an accurate representation of the renal function in the elderly. Herein, we examine the effectiveness of estimated glomerular filtration rate (eGFR) calculated using the Berlin Initiative Study-1 (BIS1) equation, for predicting the serum VCM concentration. Herein, we retrospectively analyzed patients (aged ≥ 75 years) who had received VCM. Serum VCM concentration was predicted based on Ccr and eGFR. eGFR was calculated using the Japanese equation for eGFR (eGFR

The coronavirus disease 2019 (COVID-19) pandemic has become a major public health problem. Dental procedures that generate aerosols are considered to impose a high risk of infection; therefore, dental professionals, such as dentists and dental hygienists, may be at high risk of viral transmission. However, few studies have reported COVID-19 clusters in dental care settings.To investigate whether dental and oral/maxillofacial procedures are associated with the occurrence of COVID-19 clusters and measures taken to prevent nosocomial infection in dental clinics.An online questionnaire survey on clinical activities (administrative control), infection control measures (environmental/engineering control, personal protective equipment, etc.), and confirmed or probable COVID-19 cases among patients and clinical staff was administered to the faculties of the dental and oral/maxillofacial surgical departments of university hospitals.Fifty-one faculty members completed the questionnaire. All members were engaged in the treatment of dental and oral surgical outpatients and actively implemented standard precautions. Fourteen faculty members treated patients with COVID-19, but no infections transmitted from the patients to the medical staff were observed. In seven facilities, patients were found to have the infection after treatment (medical staff came in close contact), but there was no transmission from patients to medical staff. Four facilities had medical staff with infections, but none of them exhibited disease transmission from staff to patients.COVID-19 clusters are unlikely to occur in dental and oral surgical care settings if appropriate protective measures are implemented.

The IAEA fundamental safety objective is ‘to protect people and the environment from harmful effects of ionizing radiation’ and this must be done ‘without unduly limiting the operation of facilities or the conduct of activities that give rise to radiation risks’, while ensuring that people and the environment, present and future are protected against radiation risks (IAEA 2006 Fundamental Safety Principles, Safety Fundamentals No. SF-1). In addition, ‘protective actions to reduce existing or unregulated radiation risks must be justified and optimized’ (IAEA 2006 Fundamental Safety Principles, Safety Fundamentals No. SF-1). An international system of radiological protection can be applied such that processes, such as remediation, can be systematically undertaken to address the wide range of ‘existing exposure situations’ present globally. In doing so, decisions made regarding actions undertaken can be demonstrated to be ‘justified’ and ‘optimized’ (i.e. balanced), such that the amount of effort should be commensurate with the risk (applying a ’graded approach’). In addition, protection of people and the environment can be demonstrated by comparing the actual exposure to appropriate criteria over the lifetime of remediation. This paper provides an overview of the current IAEA safety standards on remediation of sites or areas contaminated with residual radioactive material within the international system of radiological protection and provides practical examples of their application through case studies considered in IAEA international model validation programs.

Summary Annual intravenous administration of zoledronic acid is used in the treatment of osteoporosis. A mathematical model was developed to predict bone mineral density up to 2 years after two annual doses of zoledronic acid from the early values of a bone resorption marker in osteoporosis patients. Introduction The measurement of bone mineral density (BMD) has been used as a surrogate marker instead of the observation of incident fractures to detect the efficacy of treatment. However, this method requires a long time to obtain significant changes. On the other hand, bone resorption markers respond to bone resorption inhibitors within a few weeks. Therefore, the aim of this study was to develop a mathematical model predicting long-term BMD after two annual doses of zoledronic acid (ZOL) using the early response of a bone resorption marker in osteoporosis patients. Methods The model was constructed using 3410 tartrate-resistant acid phosphatase 5b (TRACP-5b) serum concentrations and 1146 lumbar spine (L2-L4) BMD values from 306 patients with primary osteoporosis. A mathematical model was developed to describe the time-dependent profiles of TRACP-5b and BMD. Results The percentage changes from baseline of the BMD (%BMD) at up to 2 years were predicted from patients’ baseline BMD and baseline and 12-week TRACP-5b values by the model obtained. The simulated 90% prediction interval almost covered the observed %BMD distribution at each time point, and the predictions were comparable to the observed %BMD. Conclusions This is the first model to predict BMD for up to 2 years following two annual doses of ZOL using patients’ background characteristics and the early response of TRACP-5b. This model allows us to inform patients at the initial stage of ZOL treatment of their predicted response to treatment. Electronic supplementary material The online version of this article (10.1007/s00198-018-4376-1) contains supplementary material, which is available to authorized users.

To assess compliance with the Japanese antiemetic guidelines for chemotherapy-induced nausea and vomiting (CINV), the frequencies of CINV occurrence and use of antiemetic rescue medications were examined in patients with hematological malignancy. A total of 40 patients with hematologic malignancy were eligible in this study. This study was performed in the Department of Hematology, Kyushu University Hospital, as a subgroup analysis from a nationwide, multicenter prospective cohort study conducted by the CINV Study Group of Japan. In the patients with hematological malignancy, the guideline compliance rate was 45 %. Five patients (22.7 %) experienced vomiting during the observation period after receiving non-guideline-consistent antiemetic prophylaxis, whereas no patient experienced vomiting after receiving guideline-consistent antiemetic prophylaxis. The study was not sufficiently powered to reach a statistical significance in its frequency of occurrence between the compliance and non-compliance groups. In the entire study period, 8 out of 40 patients required rescue medication, but there was no association between the status of compliance and the antiemetic guidelines. A total of 22 (55.0 %) patients achieved complete response, which was defined as no vomiting and no use of antiemetic rescue medication, during the study period. The rate of compliance with the prophylactic antiemetic treatment guidelines seemed to be low in patients with hematological malignancy, although the status of the guideline compliance did not always influence the antiemetic effects.

SummaryBackground Vonoprazan is a new potassium-competitive acid blocker for treatment of acid-related diseases. Aim To conduct two randomised-controlled trials, to evaluate the non-inferiority of vonoprazan vs. lansoprazole, a proton pump inhibitor, for treatment of gastric ulcer (GU) or duodenal ulcer (DU). Methods Patients aged ≥20 years with ≥1 endoscopically-confirmed GU or DU (≥5 mm white coating) were randomised 1:1 using double-dummy blinding to receive lansoprazole (30 mg) or vonoprazan (20 mg) for 8 (GU study) or 6 (DU study) weeks. The primary endpoint was the proportion of patients with endoscopically confirmed healed GU or DU. Results For GU, 93.5% (216/231) of vonoprazan-treated patients and 93.8% (211/225) of lansoprazole-treated patients achieved healed GU; non-inferiority of vonoprazan to lansoprazole was confirmed [difference = −0.3% (95% CI −4.750, 4.208); P = 0.0011]. For DU, 95.5% (170/178) of vonoprazan-treated patients and 98.3% (177/180) of lansoprazole-treated patients achieved healed DU; non-inferiority to lansoprazole was not confirmed [difference = −2.8% (95% CI −6.400, 0.745); P = 0.0654]. The incidences of treatment-emergent adverse events were slightly lower for GU and slightly higher for DU with vonoprazan than with lansoprazole. There was one death (subarachnoid haemorrhage) in the vonoprazan group (DU). The possibility of a relationship between this unexpected patient death and the study drug could not be ruled out. In both studies, increases in serum gastrin levels were greater in vonoprazan-treated vs. lansoprazole-treated patients; levels returned to baseline after treatment in both groups. Conclusions Vonoprazan 20 mg has a similar tolerability profile to lansoprazole 30 mg and is non-inferior with respect to GU healing and has similar efficacy for DU healing.

This article describes recent developments in licensing and reimbursement policies in the EU, US, and Japan, examines causes of changes and compares differences and projects trends. With respect to licensing, the European Medicines Agency (EMA), US Food and Drug Administration (FDA), and Japan's Pharmaceuticals and Medical Devices Agency (PMDA) are committed to rigorous evaluation of pharmaceuticals in advance of market access with feedback from postmarket experience. The EMA is exploring integrated adaptive pathways for licensing, with formal pilot tests to provide a practical proof of concept. The FDA is augmenting traditional licensing procedures through reforms including Breakthrough Product Designation. The PMDA is implementing reforms to foster innovation and earlier patient access through its Sakigake strategy and licensing reforms on regenerative medicines. With respect to reimbursement, several generalizations emerge. Relative to US counterparts, EU payers typically set higher standards for evidence of effectiveness as a condition of reimbursement, impose tougher limits on reimbursement by indication, and drive harder deals in negotiations over prices.

The antiemetic effects and safety of granisetron and palonosetron against chemotherapy-induced nausea and vomiting (CINV) were retrospectively evaluated in patients with non-Hodgkin lymphoma receiving bendamustine-based chemotherapy. A total of 61 patients were eligible for this study. Before starting the bendamustine-based chemotherapy, granisetron or palonosetron were intravenously administered with or without aprepitant and/or dexamethasone. The proportions of patients with complete control (CC) during the overall (during the 6 days after the start of the chemotherapy), acute (up to 2 days), and delayed (3 to 6 days) phases were assessed. CC was defined as complete response with only grade 0-1 nausea, no vomiting, and no use of antiemetic rescue medication. Granisetron or palonosetron alone were administered to 9 and 19 patients, respectively. Aprepitant and/or dexamethasone were combined with granisetron and palonosetron in 28 and 5 patients, respectively. Acute CINV was completely controlled in all patients. Both granisetron monotherapy and palonosetron combination therapy could provide good control of delayed CINV, although the CC rates during the delayed and overall phases were not significantly different among mono- and combination therapy of the antiemetics. There was no significant difference in the frequencies of adverse drug events between the granisetron and palonosetron treatment groups. The present study showed that the antiemetic efficacy and safety of granisetron-based therapy were non-inferior to those of palonosetron-based therapy. Taken together with treatment costs, granisetron monotherapy would be adequate to prevent CINV in patients with non-Hodgkin lymphoma receiving bendamustine-based chemotherapy.

SummaryBackground Proton pump inhibitors (PPIs) are widely used for the treatment of acid-related diseases. Vonoprazan is a member of a new class of acid suppressants; potassium-competitive acid blockers. Vonoprazan may thus be an alternative to PPIs. Aim To evaluate efficacy, rapidity and duration of acid-inhibitory effects of vonoprazan vs. two control PPIs, esomeprazole and rabeprazole, in 20 healthy Japanese adult male volunteers with CYP2C19 extensive metaboliser genotype. Methods In this randomised, open-label, two-period cross-over study, vonoprazan 20 mg and esomeprazole 20 mg (Study V vs. E) or rabeprazole 10 mg (Study V vs. R) were orally administered daily for 7 days. Primary pharmacodynamic endpoint was gastric pH over 24 h measured as percentage of time pH ≥3, ≥4 and ≥5 (pH holding time ratios; HTRs) and mean gastric pH. Results Acid-inhibitory effect (pH4 HTR) of vonoprazan was significantly greater than that of esomeprazole or rabeprazole on both Days 1 and 7; Day 7 difference in pH4 HTR for vonoprazan vs. esomeprazole was 24.6% [95% confidence interval (CI): 16.2–33.1] and for vonoprazan vs. rabeprazole 28.8% [95% CI: 17.2–40.4]. The Day 1 to Day 7 ratio of 24-h pH4 HTRs was >0.8 for vonoprazan, compared with 0.370 for esomeprazole and 0.393 for rabeprazole. Vonoprazan was generally well tolerated. One vonoprazan subject withdrew due to a rash which resolved after discontinuation. Conclusions This study demonstrated a more rapid and sustained acid-inhibitory effect of vonoprazan 20 mg vs. esomeprazole 20 mg or rabeprazole 10 mg. Therefore, vonoprazan may be a potentially new treatment for acid-related diseases.

PurposeTo report the results of subconjunctival ologen Collagen Matrix implantation to manage ocular hypotony after filtration glaucoma surgery.Patients and methodsThis retrospective observational case series included 12 consecutive implantations of ologen in nine eyes of nine Japanese subjects (five men, four women; mean age±SD, 72.1±12.7 years) who underwent subconjunctival implantation of the device to treat hypotony after glaucoma filtration surgery. Demographic data and surgical results were collected by chart review.ResultsThe subjects included six patients who underwent trabeculectomy and three who underwent an EX-PRESS shunt surgery. The duration between the last glaucoma surgery and the initial ologen implantation was longer than 2 years in seven (78%) eyes. Bleb leakage in five (56%) eyes preoperatively stopped in all cases by 8 days after the device implantation. After the initial implantation, three (33.3%) eyes required a second implantation of ologen because of insufficient efficacy. After a mean follow-up of 12.6±6.8 months, the mean preoperative intraocular pressure (IOP) of 3.8±2.7 mmHg increased significantly (P=0.0001) to 9.0±3.2 mmHg; no eye required glaucoma medication to control the IOP. No vision-threatening complications developed in association with the treatment.ConclusionWhen conservative management failed, subconjunctival implantation of ologen Collagen Matrix in combination with bleb revision can be a useful therapeutic option for ocular hypotony after glaucoma filtration surgery.

Replication-competent oncolytic viruses hold great potential for the clinical treatment of many cancers. Importantly, many oncolytic virus candidates, such as reovirus and myxoma virus, preferentially infect cancer cells bearing abnormal cellular signaling pathways. Reovirus and myxoma virus are highly responsive to activated Ras and Akt signaling pathways, respectively, for their specificity for viral oncolysis. However, considering the complexity of cancer cell populations, it is possible that other tumor-specific signaling pathways may also contribute to viral discrimination between normal versus cancer cells. Because carcinogenesis is a multistep process involving the accumulation of both oncogene activations and the inactivation of tumor suppressor genes, we speculated that not only oncogenes but also tumor suppressor genes may have an important role in determining the tropism of these viruses for cancer cells. It has been previously shown that many cellular tumor suppressor genes, such as p53, ATM and Rb, are important for maintaining genomic stability; dysfunction of these tumor suppressors may disrupt intact cellular antiviral activity due to the accumulation of genomic instability or due to interference with apoptotic signaling. Therefore, we speculated that cells with dysfunctional tumor suppressors may display enhanced susceptibility to challenge with these oncolytic viruses, as previously seen with adenovirus. We report here that both reovirus and myxoma virus preferentially infect cancer cells bearing dysfunctional or deleted p53, ATM and Rb tumor suppressor genes compared to cells retaining normal counterparts of these genes. Thus, oncolysis by these viruses may be influenced by both oncogenic activation and tumor suppressor status.

Background: The prolonged bed-rest required achieving hemostasis after splanchnic angiography and interventional procedures can be avoided if the upper limb arteries are used. In such procedures, the use of long sheaths capable of reaching the descending aorta may be advantageous. Purpose: To analyze the results of procedures that utilizes an upper-limb-artery approach and long sheaths. Material and Methods: Two hundred forty-two patients with a mean age of 64 years underwent splanchnic angiography and interventional procedures via an upper limb artery using a long sheath (85 cm, 4-French). Repeat examinations were performed on 48 patients and the total number of examinations was 296. The records of these 296 examinations were reviewed and the success rate and complications were evaluated. Results: Overall, 295 of 296 (99.7%) examinations were successful, and one (0.3%) failed. Complications and side effects occurred in six cases (2.0%), a painful sheath manipulation occurred in two examinations (0.7%), and arterial occlusion (including temporary occlusion), hematoma of the puncture site, and pseudoaneurysm occurred in two (0.7%), one (0.3%), and one (0.3%) patient, respectively. Conclusion: The use of a long sheath capable of reaching the descending aorta enables the performance of splanchnic angiography and interventional procedures via the upper limb arteries.

The development of new neutron sources for BNCT applications, based on particle accelerators is currently underway all over the world. Though nuclear reactors were used for a long time as the only neutron source available having the requested flux levels, the accelerator-based ones have recently been investigated on the other hand due to its easy-to-use and acceptable performances. However, when using an accelerator, various secondary particles would be emitted which forms a troublesome background. Moreover, the neutrons produced have usually an energy spectrum somewhat different from the requested one and thus should be largely moderated. An additional issue to be taken into account is the patient positioning, which should be close to the neutron source, in order to take advantage of a neutron flux level high enough to limit the BNCT treatment time within 1 h. This implies that, inside a relatively narrow space, neutrons should be moderated, while unnecessary secondary particles should be shielded. Considering that a background-free neutron field from an accelerator-driven neutron source dedicated to BNCT application is generally difficult to be provided, the characterization of such a neutron field will have to be clearly assessed. In the present study, a low energy neutron spectrometer has been thus designed and is now being developed to measure the accelerator-based neutron source performance. The presently proposed spectrometer is based on a 3 He proportional counter, which is 50 cm long and 5 cm in diameter, with a gas pressure of 0.5 MPa. It is quite unique that the spectrometer is set up in parallel with the incident neutron beam and a reaction depth distribution is measured by it as a position sensitive detector. Recently, a prototype detector has been developed and the signal test is now underway. In this paper, the feature of the accelerator-based neutron sources is outlined and importance of neutron field characterization is discussed. And the developed new low energy neutron spectrometer for the characterization is detailed.

Summary. Background: Tissue factor pathway inhibitor (TFPI) is a physiological protease inhibitor that inhibits the initial reactions of the extrinsic blood coagulation pathway. Most TFPI in human plasma is associated with lipoproteins; however, the most functionally active form is thought to be the free, full-length form (f-pTFPI). Cell culture derived TFPI and recombinant TFPI (rTFPI) exhibit variations in their respective anticoagulant activity, which may be caused by post-translational modifications, such as the frequent differences in sugar chain structures among recombinant proteins. Sugar chain structures in rTFPI expressed in Chinese hamster ovary (CHO) cells have been reported previously, but those of plasma TFPI have not been. Objectives: To purify f-pTFPI and analyze the sugar chain structures. Results and conclusion: f-pTFPI was purified to homogeneity from blood plasma using a combination of anion-exchange, heparin affinity, immunoaffinity, and reversed-phase chromatographies, resulting in a yield of 76%. f-pTFPI showed a partially phosphorylated glycoprotein comprising a total of 276 amino acids by peptide mapping. The sugar chain structures were analyzed by two-dimensional sugar mapping combined with exoglycosidase digestion of the pyridylamino sugar chains and the following results were obtained. (Sialyl) Galβ1-3GalNAc was linked to Thr175, partially to Thr14 and Ser174; sialyl complex-type sugar chains to Asn117 and Asn167, whereas Asn228 was not glycosylated. Neuraminidase-resistant acidic sugar chains including sulfated sugar chains were not observed significantly. The protease inhibitory activities of f-pTFPI towards activated factor (F) X and tissue factor-activated FVII complex were identical to those of full-length rTFPI expressed in CHO cells.

Alanine:glyoxylate aminotransferase 2 (AGXT2; EC 2.6.1.44) degrades asymmetric dimethylarginine (ADMA), a competitive inhibitor of nitric oxide (NO) synthase. Increased ADMA, reduced NO, and hypertension are shown in Agxt2 knockout mice. There are four single nucleotide polymorphisms (rs37370, rs37369, rs180749, and rs16899974) with which AGXT2 activity changes in humans and may be related to vulnerability of vascular sclerosis. To examine the relationship between them, we studied the functional haplotypes of the AGXT2 gene and decided their relationship with arteriosclerotic changes via carotid intima-media thickness (carotid IMT) in Japanese subjects. Genotyping of those polymorphisms and the carotid IMT in 1,426 Japanese subjects were then evaluated. Subjects with C-A-A-A haplotype (rs37370, rs37369, rs180749, rs16899974) showed low AGXT2 activity (P0.0001; Pearson’s correlation coefficients: 0.497). The C-A-A-A haplotype was significantly associated with mean carotid IMT (P=0.049) and max carotid IMT (P=0.004). Subjects with two C-A-A-A haplotypes exhibited thicker mean carotid IMT (P=0.022) and maximum carotid IMT (P=0.001). In multiple regression analysis, subjects with two C-A-A-A haplotypes were independently and positively associated with mean carotid IMT (P=0.02) and maximum IMT (P=0.005) after correction. There was a significant correlation between the functional variants in the AGXT2 gene and carotid IMT in Japanese. The AGXT2 genotype may be an important factor underlying atherosclerosis.

AIM The aim of this study was to investigate the influence of changes in insulin resistance and early insulin secretion on the insulin secretagogic effects of nateglinide. METHODS Oral glucose tolerance testing (OGTT, 75 g) was performed in obese patients before and after weight loss on 2 consecutive days (first day OGTT without nateglinide, second day OGTT with nateglinide), to compare any weight loss associated changes in the nateglinide-induced insulin response to glucose loading. RESULTS Reductions in visceral fat, liver fat, skeletal muscle fat and homeostasis model assessment (HOMA)-R due to weight loss were associated with increased Delta insulin 30 min/Delta glucose 30 min (DeltaI30/DeltaG30), and reduced area under the curve (AUC) for plasma glucose as seen in OGTT results. Results from OGTT showed that nateglinide administration was associated with reductions in plasma glucose AUC, both before and after weight loss. Before weight loss, although there was a significant elevation of DeltaI30/DeltaG30 associated with nateglinide treatment, no major change in the insulin-secreting dynamics after glucose loading was observed. After weight loss, nateglinide administration produced a significant increase in DeltaI30/DeltaG30, with insulin secretion peaking more quickly. CONCLUSION Insulin response to nateglinide after glucose loading varied greatly in conjunction with weight loss. This may be accounted for not only by the enhancement of early insulin response to nateglinide associated with the improvement of early insulin response with weight loss but also by the reduced visceral fat, which in turn led to reduced levels of free fatty acids in portal blood and hepatic triglycerides, as well as increased hepatic insulin clearance.

Summary Background Although there have been several reports on the prevalence of atopic dermatitis (AD) in Japanese schoolchildren based on questionnaires, there has been no nation-wide study of the frequency of this condition diagnosed by dermatologists in regular health check-ups of schoolchildren. Objectives The objective of this work was to evaluate precisely the prevalence of AD in elementary schoolchildren in Japan based on regular health check-ups by dermatologists. Methods In 2001/2, elementary schoolchildren: first graders (age 6–7 years) and sixth graders (age 11–12 years) were examined by dermatologists in eight prefectures of Japan (Hokkaido, Iwate, Tokyo, Gifu, Osaka, Hiroshima, Kochi and Fukuoka). In each prefecture, public elementary schools were randomly selected from urban and rural districts. We planned to examine about 700 schoolchildren in each of urban first, urban sixth, rural first and rural sixth grades from the eight areas, a total of 22 400 children (700 × 4 × 8). AD was diagnosed by the dermatologists based on the Japanese Dermatological Association criteria for the disease. Results The point prevalence of AD was 11·2% overall (2664 of 23 719) ranging from 7·4% (Iwate) to 15·0% (Fukuoka) in the eight areas. Seventy-four per cent, 24%, 1·6% and 0·3% of those afflicted were in the mild, moderate, severe and very severe groups, respectively. Overall, the prevalence of first graders was slightly higher than that of sixth graders (11·8% vs. 10·5%, P

The increased susceptibility to infection following splenectomy has been well documented. We report here, a case of brain abscess developed five years after splenectomy in a patient with idiopathic thrombocytopenic purpura (ITP). A 65-year-old woman was admitted to our hospital because of fever, mental disorientation, and weakness in August, 1999. She had been followed with diagnoses of essential hypertension and type 2 diabetes mellitus (DM) since 1988. The patient was diagnosed as having ITP in 1992, and then underwent splenectomy in 1994. Monoclonal gammopathy of undetermined significance (MGUS) of IgG, lambda type was found in February 1999. Though high grade fever persisted after admission, blood cultures were negative. Antibiotics were given without a satisfactory effect. Right hemiparesis and worsening of consciousness developed subsequently. Contrast enhanced cranial computed tomography (CT) disclosed a ringed enhanced low density mass in the left parieto-occipital lobe compatible with a diagnosis of brain abscess. Surgical drainage was performed and 20 ml of pus was obtained. No primary infectious focus of the brain abscess was detected with intensive examinations.

Object. The purpose of this paper is to report the long-term results of gamma knife radiosurgery (GKS) for low-grade astrocytomas. Methods. Fifty-one patients with low-grade astrocytomas treated with GKS and followed for more than 24 months are reported. Of the 51 patients, 12 harbored Grade I astrocytomas in and around the visual pathways and hypothalamus. The remaining 39 harbored Grade II astrocytomas. The mean patient age at time of GKS was 9.8 years for patient with Grade I and 30.9 years for those with Grade II astrocytomas. The mean tumor diameter was 25.4 mm for Grade I and 23.7 mm for Grade II tumors. The mean margin dose was 12.5 Gy for Grade I and 15.7 Gy for Grade II tumors. In the mean follow-up period of 27.6 months, both Grade I and Grade II astrocytomas responded well to GKS. Grade I astrocytomas had a response rate of 50% and a control rate of 91.7%. Grade II astrocytomas had a 46.2% response rate and an 87.2% control rate. Statistical analyses concerning the efficacy and related factors showed a significantly better response for patients 10 years of age or older with Grade I and those with a follow-up period of more than 24 months. Complications included radiation-induced edema in 18 (35.3%) of 51 cases, cyst formation or enlargement in five (9.8%), and transient tumor enlargement in three (5.9%). Conclusions. Radiosurgery can play an important role in the treatment of low-grade astrocytomas, and complete cure of these tumors is expected in at least some of the cases.

The risk of preterm delivery ( < 37 weeks of gestation) is approximately nine times higher in women with multifetal pregnancies than in women with singleton pregnancies. However, it is possible that the risk will vary according to gestational week. To assess the risk of premature birth within 1 week by gestational age among multifetal pregnancies and compare the estimated risk with that of singleton pregnancies, we analyzed 6 036 475 infants born in singleton pregnancies and 90 887 infants born in multifetal pregnancies in Japan ( ≥ 22 weeks) over the 5-year period 1989–1993. An estimate of the risk of birth within 1 week at gestational week n was obtained by dividing the number of infants delivered at gestational week n by the number of infants delivered at or beyond gestational week n. The risk at 22 weeks was 0.9 per 1000 fetuses for singleton pregnancies and 5.0 per 1000 for multifetal pregnancies. The risk remained relatively stable until 27 weeks of gestation, then sharply increased toward 36 weeks of gestation in both singleton and multifetal pregnancies. The odds ratio for birth within 1 week for fetuses of multifetal pregnancies compared with fetuses of singleton pregnancies was 5.9 (95% CI, 5.4–6.5) at 22 weeks of gestation, increasing gradually with increasing gestational age until 33 weeks of gestation (13.7; 95% CI, 13.1–14.2) but declining thereafter to 8.8 (95% CI, 8.6–8.9) at 36 weeks of gestation. Results of data analysis for each year of the 5-year period did not differ substantially. Twin Research (2000) 3, 2–6.

The cDNA encoding bovine interleukin 6 (IL-6) was obtained from messenger RNA extracted from lipopolysaccharide-stimulated bovine Kupffer cells by the reverse transcription polymerase chain reaction (RT/PCR), and cloned into the baculovirus vector pVL 1392. Insect cells (Sf21AE derived from Spodoptera frugiperda) infected with the recombinant baculovirus secreted a large amount of 23.7 kD protein into the culture medium. This protein was capable of causing increased haptoglobin production and decreased albumin production in primary cultured bovine hepatocytes. The swine and human IL-6s were also able to decrease albumin production in bovine hepatocytes. This recombinant IL-6 did not stimulate the proliferation of 7TD1 cells (a murine IL-6-dependent cell line), whereas the recombinant swine IL-6 which was expressed in the same baculovirus system, and recombinant human IL-6 derived from Escherichia coli were each capable of stimulating proliferation of 7TD1 cells, respectively. This suggests a species restriction between bovine IL-6 and murine IL-6 dependent cell lines.

Leukocyte protein tyrosine phosphatase (LC-PTP)/hemopoietic PTP is a human cytoplasmic PTP that is predominantly expressed in the hemopoietic cells. Recently, it was reported that hemopoietic PTP inhibited TCR-mediated signal transduction. However, the precise mechanism of the inhibition was not identified. Here we report that extracellular signal-regulated kinase (ERK) is the direct target of LC-PTP. LC-PTP dephosphorylated ERK2 in vitro. Expression of wild-type LC-PTP in 293T cells suppressed the phosphorylation of ERK2 by a mutant MEK1, which was constitutively active regardless of upstream activation signals. No suppression of the phosphorylation was observed by LC-PTPCS, a catalytically inactive mutant. In Jurkat cells, LC-PTP suppressed the ERK and p38 mitogen-activated protein kinase cascades. LC-PTP and LC-PTPCS made complexes with ERK1, ERK2, and p38α, but not with the gain-of-function sevenmaker ERK2 mutant (D321N). A small deletion (aa 1–46) in the N-terminal portion of LC-PTP or Arg to Ala substitutions at aa 41 and 42 resulted in the loss of ERK binding activity. These LC-PTP mutants revealed little inhibition of the ERK cascade activated by TCR cross-linking. On the other hand, the wild-type LC-PTP did not suppress the phosphorylation of sevenmaker ERK2 mutant. Thus, the complex formation of LC-PTP with ERK is the essential mechanism for the suppression. Taken collectively, these results indicate that LC-PTP suppresses mitogen-activated protein kinase directly in vivo.

The serum thrombopoietin (TPO) levels in 61 idiopathic thrombocytopenic purpura (ITP) patients were found to be slightly increased compared with those of 29 normal subjects. The TPO levels of the 15 ITP patients who had a poor response to steroid therapy (i.e. an unchanged platelet count) were higher than those of the 22 ITP patients who had a good response to steroid therapy (i.e. an increased platelet count) and the normal subjects. The TPO levels in the 15 ITP patients whose platelet count was higher than 10 x 10(4)/microl after the discontinuation of steroid therapy significantly higher than those of the normal subjects. The platelet-associated immunoglobulin G (PAIgG) levels in the ITP patients who had a poor response to steroid therapy were slightly increased compared with the normal subjects and the ITP patients who had a good response to the steroid therapy and the nine ITP patients who did not undergo the steroid therapy. The serum TPO level was negatively correlated only with the megakaryocyte count in the ITP patients, and the megakaryocyte count in the ITP patients who had good responses to the steroid therapy was higher than that in those who had poor responses. These data suggest that serum TPO levels might be important for the prediction of the outcome of ITP patients who receive steroid therapy.

We report an unusual case of a 13-year-old girl with a benign osteoma associated with a cholesteatoma in the external auditory canal and serous otitis media. The osteoma was located in the antero-inferior wall of the right external auditory canal. A cholesteatoma was present between the osteoma and the tympanic membrane. Computed tomography revealed a soft tissue density within the external auditory canal and in the middle ear cleft. The shadow in the middle ear cleft was considered to represent the serous otitis media. Surgical removal of the osteoma and cholesteatoma proved successful, and no recurrences or complications have occurred in the first year postoperatively.

Fluid-attenuated inversion recovery (FLAIR) imaging of hepatic hemangiomas (10 patients, 16 lesions) and hepatic cysts (8 patients, 10 lesions) was performed. All hemangiomas were hypointense on T1-weighted images and hyperintense on T2-weighted images. With Gd-DTPA (0.1 mmol/kg), all hemangiomas were enhanced but not all cysts. It was necessary to perform contrast enhanced imaging to differentiate hepatic hemangiomas from hepatic cysts. However, on FLAIR imaging, hepatic hemangiomas were strongly hyperintense and 9 of the 10 hepatic cysts were isointense. One of the hepatic cysts was slightly hyperintense. FLAIR images were useful in differential diagnosis of hepatic hemangiomas and hepatic cysts without using Gd-DTPA.

The pharmacological effects of Oren-gedoku-to (OGT), a Japanese-Chinese traditional herbal medicinal mixture on lipid biosynthesis were investigated in cultured human hepatocyte HepG2 cells. The addition of OGT (0.5 and 4.2 mg/ml), which had no effect on cell proliferation and cellular protein content, caused a marked decrease in the cellular cholesterol content, particularly cholesteryl ester content following 24 h incubation. The incorporation of 14C-oleate into cellular cholesteryl ester fraction was also reduced remarkably during incubation for 6 and 24 h. The effects of OGT, its components and its main active chemicals on acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity were studied in vitro to explore the mechanism by which OGT inhibits cholesteryl ester formation. The data confirmed that OGT, in a dose-dependent manner, and its components (Scutellaria baicalensis, Coptis japonica, Gardenia jasminoides and Phellodendron amurense) remarkably inhibit ACAT activity. Among the main active chemicals of OGT, baicalein, a kind of flavonoid, decreased ACAT activity in a dose-dependent fashion from the level of 10(-6)M. These results strongly suggest that OGT reduces the cholesteryl ester formation in human hepatocytes by inhibiting ACAT, and that baicalein may, in part, be responsible for ACAT inhibition.

Insulin allergy is a not uncommon condition even though human insulin and insulin analogues are widely used. However, the development of insulin allergy after bone marrow transplantation has not been reported.A 44-year-old Japanese woman had aplastic anaemia and secondary haemochromatosis. She was diagnosed with having diabetes at age 32 years and had been treated with human insulin. At age 34 years, bone marrow transplantation was performed. One year later, a rash and urticaria appeared immediately after insulin injections. Intracutaneous tests were positive for both human insulins and analogues, whereas the test for protamine was negative. Furthermore, an IgE-radioallergosorbent test against insulin was positive. Thus, we diagnosed the patient with having an IgE-mediated type I allergy against insulin. Insulin therapy with insulin aspart, which showed the least skin reaction, was continued and the insulin allergy disappeared in 7 years.This is the first description of insulin allergy after bone marrow transplantation. Our case underscores the effects of bone marrow cells on IgE-mediated type I allergy for insulin.

OBJECTIVE--To assess the relationship between HLA-DRB1 genotypes and the progression of bone destruction in Japanese patients with RA. METHODS--The HLA-DRB1 alleles were determined by polymerase chain reaction and allele specific oligonucleotide probe techniques in 160 Japanese patients with RA. HLA-DR 0101, 0401, 0404, 0405, 1001 and 1402 were regarded as susceptible alleles of RA according to previous reports. Patients were classified into three groups (S/S, S/N and N/N group), based on the possession of two, one or no susceptible factor. The grading of radio-graphic changes in the wrists and fingers were evaluated by Larsen's criteria. The radiographic grades were first compared with the results of genotyping in the 160 cross sectional cases. A retrospective study was then conducted on a subgroup consisting of 57 cases taken from the 160 cases used for the cross sectional study. RESULTS--In the scatter diagram of the 160 cross sectional cases expressing the relationship between the stage of bone destruction and duration of RA, the regression line and the 95% confidence intervals separated the S/S group from the S/N and N/N groups in the early phase of development of bone destruction. In the retrospective study on the 57 cases the median years taken to development to stage V in the wrists after the onset of symptoms were 13.1 in the patients in the S/S group, 22.7 in the S/N group and 23.0 in the N/N group. The difference observed between the S/S and S/N group, and between the S/S and N/N group were statistically significant (p < 0.01), but that between the S/N and N/N groups was not. Thus the bone destruction in the wrists and fingers progressed more rapidly in the S/S group than in the S/N and N/N groups; and the rheumatoid susceptible alleles of HLA-DRB1 can be considered to be genetically recessive to the non-susceptible alleles in the progression of bone destructions in the wrists and fingers. CONCLUSION--Genotyping of HLA-DRB1 can be a useful prognostic marker in the early phase of RA.

A 62-year-old female was admitted to our hospital for investigation of acute progressive renal insufficiency and a systemic inflammatory reaction, despite treatment with several antibiotics. Laboratory data revealed severe renal insufficiency and positive titers for the myeloperoxidase anti-neutrophil cytoplasmic and anti-glomerular basement membrane antibodies. The deterioration of her general status did not allow us to perform the renal biopsy. Although corticosteroid therapy, hemodialysis, and plasma exchange were concomitantly initiated, pulmonary hemorrhage occurred several days after admission. Mechanical ventilation support was provided and continuous hemodiafiltration was carried out, following which the respiratory failure improved immediately. However, she developed clinical depression and suicidal behavior under the intensive therapy. Therefore, plasma exchange was discontinued and corticosteroid was tapered as quickly as possible. Four months after admission, platelet transfusion and short-term mechanical ventilation support improved the pulmonary hemorrhage; however, her mental status deteriorated despite psychiatric consultation and treatment with a tranquilizer. Thereafter, severe and serious systemic infection due to various pathogens including Staphylococcus aureus, Cytomegalovirus, Pneumocystis jiroveci, Pseudomonas aeruginosa, and Bacteroides recurred, and she died from systemic invasive aspergillosis (IA). We suspected severe immunosuppression caused by various factors, such as predonisolone administration, chronic renal failure on maintenance hemodialysis, depression, and malnutrition due to chronic inflammation and granulocytopenia as a side effect of ganciclovir. When treating rapidly progressive glomerulonephritis, immunosuppressive status should be carefully monitored regarding not only the dosage of therapeutic regimen but also the mental health status and nutrition of the patient.

In sheep and goats, the primer pheromone produced by the male induces out-of-seasonal ovulation in anoestrous females, the so-called 'male effect.' Because the initial endocrine event following reception of the pheromone is the stimulation of pulsatile luteinising hormone (LH) secretion, the central target of the pheromone is considered to be the putative gonadotrophin-releasing hormone (GnRH) pulse generator. Using electrophysiological techniques to record multiple-unit activity (MUA) in close proximity to kisspeptin neurones in the arcuate nucleus (ARC) of Shiba goats, we found that bursts (volleys) of MUA occur at regular intervals, and repetitive bursts are invariably associated with discrete pulses of LH, suggesting that the ARC kisspeptin neurones may be the intrinsic source of the GnRH pulse generator. A brief exposure of female goats to the pheromone immediately elicited an instantaneous rise in MUA, which is followed by an MUA volley and an accompanying LH pulse, indicating that the pheromone signal is transmitted to a subset of the ARC kisspeptin neurones to activate them. Because it has been suggested that the neurokinin B and dynorphin coexpressed in those neurones play critical roles in generating rhythmic bursts, they may be involved in the intracellular pheromone actions that are responsible for inducing the GnRH pulse.

We describe a case of Stanford type A acute aortic dissection. Replacement of the ascending aorta and aortic arch was performed using an "arch 1st technique". Following the completion of replacement, hypotension of the left superficial temporal artery pressure was detected. Ultrasonography revealed dissection of the left common carotid artery (LCCA) and compressive occlusion of the true lumen. Reconstruction of the LCCA was performed in the neck. The patient did well after the operation without any neurological abnormalities.

The approach that should be used for an anterior apical tumor still remains controversial. Since a modified open door method was very useful for the widening of the surgical field in a recent patient with an anterior apical tumor, an outline of this case is reported. The patient was a 66-year-old male with squamous cell carcinoma of the anterior apical region of the right lung (suspected to be invading the thoracic wall, cT3N1M0). After a midline sternal incision with a right unilateral collar incision, the medial half of the right clavicle and a few cm of the right 1st rib on the sternal side were resected to sufficiently expose the area from the right brachiocephalic trunk to around the subclavicular artery and vein, where invasion was suspected. This treatment facilitated widening of the visual field around the site of tumor invasion and made safe right upper lobectomy + combined thoracic wall resection + ND2a possible. In this patient, anterolateral incision at the 4th intercostal level, which is made using the original open door method, could be avoided, probably minimizing surgical invasion.

An adult case of right-sided Bochdalek hernia complicating intrathoracic intestinal strangulation is presented. Formation of this rare right-sided diaphragmatic hernia was facilitated by coexistent hypoplasia of the medial segment of left hepatic lobe. Computed tomography showed characteristic findings such as dilated small intestine with convergence of mesenteric folds in the thorax, which was highly diagnostic of intestinal strangulation due to diaphragmatic hernia.

Primary mucoepidermoid carcinoma of the thymus developing in an 80-year-old Japanese man is described. This is the third case report of this rare tumour which was diagnosed following fine needle aspiration cytology (FNAC) of a metastatic lesion in the left humerus. FNA showed the typical cytological findings of mucoepidermoid carcinoma, that is the presence of squamous, glandular and intermediate neoplastic cells. Histology at autopsy confirmed these findings.

Myosin light chain kinase (MLCK) plays a pivotal role in regulation of cellular functions, the evidence often relying on the effects of extracelluarly administered drugs such as ML-9. Here we report that this compound exerts non-specific inhibitory actions on the TRPC6 channel, a transient receptor potential (TRP) protein.Macroscopic and single channel currents were recorded from transfected HEK293 cells by patch-clamp techniques.Cationic currents elicited by carbachol (CCh; 100 microM) in HEK293 cells overexpressing murine TRPC6 (I(TRPC6)) were dose-dependently inhibited by externally applied ML-9 (IC(50)=7.8 microM). This inhibition was voltage-dependent and occurred as fast as external Na(+) removal. Another MLCK inhibitor, wortmannin (3 microM), and MLCK inhibitory peptides MLCK-IP(11-19) (10 microM) and -IP(480-501) (1 microM) showed little effects on I(TRPC6) density and the inhibitory efficacy of ML-9. The extent of the inhibition also unchanged with co-expression of wild-type or a dominant negative mutant of MLCK. Inhibitory effects of ML-9 on I(TRPC6) remained unaffected whether TRPC6 was activated constitutively or by a diacylglycerol analogue OAG (100 microM). Similar rapid inhibition was also observed with a ML-9 relative, ML-7. Intracellular perfusion of ML-9 via patch pipette, dose-dependently suppressed I(TRPC6). In inside-out patch configuration, bath application of ML-9 (and ML-7) rapidly diminished approximately 35pS single TRPC6 channel activities. Contrarily, currents due to TRPC7 expression were rapidly enhanced by externally applied ML-9 and ML-7, which was not prevented by MLCK inhibitory peptides.These results strongly suggest that ML compounds inhibit TRPC6 channels via a mechanism independent of inhibition of MLCK activity.

Cultivated limbal stem cell transplantation is being used as a current treatment modality for limbal stem cell deficiency. However, use of allogenic biological material as substrate is associated with risks of transmission of certain diseases and allograft rejection. Therefore development of non-toxic biodegradable synthetic polymers is important. We undertook this study to evaluate the use of a synthetic polymer Mebiol gel as a substrate for the growth of limbal phenotype cells and cornea phenotype cells from limbal explants.Human cadaveric limbal explants cells were cultivated on Mebiol gel. The proliferative capacity of cultivated cells was analyzed with thymidine incorporation studies. Immunostaining for presumed limbal stem cell association markers and cornea differentiation markers was performed and confirmed with reverse transcription (RT-PCR).The limbal explants underwent proliferation in vitro. The cultivated cells expressed the presumed limbal stem cell association markers (ABCG2 and p63), the transient amplifying cell markers (connexin 43, integrin alpha9) and the cornea differentiation marker (K3). RT PCR confirmed the immunohistochemical data.Our findings showed that the synthetic polymer Mebiol gel was able to support limbal explant proliferation. The cultured cells expressed presumed limbal stem cell association markers, transient amplifying cells and cornea phenotype markers. Mebiol Gel can be used as a scaffold for growing limbal explants.

Anaphylactic shock related to aprotinin has been reported to be induced exclusively in the presence of IgE antibody. And the possibility of anaphylactic shock induced by anti-aprotinin IgG antibody alone was controversial. In this paper, we describe the first case of anaphylactic shock induced by aprotinin-specific IgG antibody alone. A 55-year-old man underwent surgical repair of the descending aorta with the use of aprotinin at 2 months after first aprotinin usage. Immediately after initiation of cardiopulmonary bypass with the continuous infusion of aprotinin, clinical symptoms of anaphylactic reaction were found. Postoperative drug lymphocyte stimulation test for aprotinin and aprotinin-specific IgE antibody were negative, but aprotinin-specific IgG antibody was 163 mg/l and positive.

Canonical transient receptor potential7 (TRPC7) is the seventh identified member of the mammalian TRPC channel family, comprising nonselective cation channels activated through the phospholipase C (PLC) signaling pathway. TRPC7 is directly activated by diacylglycerol (DAG), one of the PLC products, having high sequence homologywith TRPC3 and TRPC6, which are also activated by DAG. TRPC7 shows unique properties of activation, such as constitutive activity and susceptibility to negative regulation by extracellular Ca2+. Although the physiological importance of TRPC7 in the native environment remains elusive, TRPC7 would play important roles in Ca2+ signaling pathway through these characteristic features.

A 48-year-old male consulted the department of respiratory medicine for right precordial pain occurring from the beginning of May 2004. Chest X-ray indicated a tumorous shadow in the right upper lung field and a large left lung cyst. Although chest wall infiltration was suspected based on computed tomography (CT) demonstrating a mass lesion in the right S2, there was no significant swelling of the mediastinal lymph node. On the left side, the lung was markedly compressed by a large cyst in the left upper lobe. Since bronchoscopy failed to establish a definitive diagnosis, the patient was referred to our department for surgery based on a suspicion of malignant pulmonary tumor. Considering both the risk of perioperative complications due to the left cystic lesion at surgery for right lung lesion and the improvement of respiratory function by removing cystic lesion of the left lung, the left side operation was preceded by the right side. Although postoperative examinations of respiratory function did not demonstrate any particular improvement, the results of selective right pulmonary artery obstruction test supported the possibility of pulmonary lobectomy. Therefore, the right upper lobectomy and ND 2a mediastinal dissection combined with chest wall resection was subsequently performed. Postoperative pathological diagnosis revealed that the tumor was a stage IIB large cell carcinoma of pT3N0M0 with costal infiltration.

To evaluate the risk of rupture of a 77 mm thrombosed popliteal artery aneurysm (PAA) in an 82-year-old woman, the aneurysm was percutaneously punctured and the intrathrombotic pressure (ITP) was measured preoperatively. The percentage of the mean ITP to the mean brachial artery pressure was 80%. The aneurysm was judged to have the risk of rupture, and replacement with a prosthetic graft was performed. The percentages of the mean ITP to the mean radial artery pressure and to the mean femoral artery pressure measured intraoperatively were 83% and 71%, respectively, which approximated to the percentage measured preoperatively. PAA may have the risk of rupture even though thrombosed, and preoperative measurement of the ITP might be useful to decide surgical indication.

In both superficial and deep femoral artery involvement, where angioplasty of the former is not suitable or feasible, angioplasty of the latter seems to be the method of choice and is a less invasive and efficient treatment particularly for limb threatening ischemia, an appropriate obstruction morphology provided. The authors describe a case of a 73-year-old man, with a rest pain of the foot and intermittent cyanosis of the toe, who underwent stent placement with transluminal angioplasty for severe stenosis in the deep femoral artery with the occluded superficial femoral and popliteal artery. The patient's ankle brachial index was remarkably increased from 0.25 to 0.61, and the preoperative symptoms were improved.

The swine interleukin-4 (SwIL-4) cDNA was cloned by RT-PCR. It was expressed using an expression vector pQE30 in E. coli, a baculovirus AcNPV vector pVL1392 in insect cells, and a pCAGGS vector in mammalian cells. The rSwIL-4 proteins expressed from bacteria and insect cells were purified using a chelating affinity column and a mAb-coupled immunoaffinity column. The amount of the products and their bioactivities were compared. All recombinant cytokines were efficiently reacted with the specific antibodies and the molecular weight of rSwIL-4 was approximately 16 kDa in E. coli, 15 and 18 kDa in insect cells, and 15 and 20 kDa in mammalian cells. Variations of molecular weight observed in insect and mammalian cells were probably due to different modification ways of glycosylation. All these recombinant proteins retained their antigenicity and were biologically active in inducing human TF-1 cell proliferation in vitro. The simple purification method will make it possible to evaluate the in vitro and in vivo effects of IL-4 in pigs.

The present study investigated the expression of Toll-like receptor (TLR) 2, TLR4, cluster of differentiation (CD) 14 and CD1a in human periodontitis gingiva using immunohistochemical methods. The specimens were classified according to the degree of inflammation into three groups (mild, moderate and severe). We established three zones in which to evaluate the ratios of TLR2-, TLR4-, CD14- and CD1a-positive cells to total cells in the connective tissues of each section. TLR2 and TLR4 were expressed in human periodontal tissues, and the ratio of TLR2-positive cells was highest overall in zone 1 (connective tissue subjacent to pocket epithelium) of the severe group and that of TLR4-positive cells was higher in the severe group than in the other groups. These results suggest that TLR2 and TLR4 participate in the innate immune response to stimulation by bacterial products in periodontal tissues. The ratio of CD14-positive cells was lowest overall in zone 1 of the severe group and that of CD1a was higher in the severe group than in the other groups. These results suggest that CD14 may be down-regulated during the development of inflammation and/or dendritic cells might infiltrate chronically inflamed gingival tissue.

The study was designed to test the angle independence of a dynamic three-dimensional digital colour Doppler method for laminar flow measurement. The technique acquired three-dimensional data by rotational acquisition and used surface integration of Doppler vector velocities and flow areas in time and space for flow computation.A series of pulsatile flows (peak flow 55-180 ml/s) through a curved tube were studied with reference flow rates obtained using an ultrasonic flow meter. Colour Doppler imaging was performed at three angles to the direction of flow (20 degrees, 30 degrees, 40 degrees), using a multiplane transoesophageal probe controlled by an ATL HDI5000 system. Integration of digital velocity vectors over a curved three-dimensional surface across the tube for each of the 11 flow rates at each angle was performed off-line to compute peak flow.Peak flow rates correlated closely (r=0.99) with the flow meter with the mean difference from the reference being -0.8+/-2 x 4 ml/s, 0.9+/-2.6 ml/s, 1.0+/-2 x 3 ml/s for 20 degrees, 30 degrees and 40 degrees respectively. Comparison of the three angle groups showed no significant differences (P=0.15, ANOVA). When sampled obliquely, the flow area on the curved surface increased while the velocities measured decreased.Surface integration of velocity vectors to compute three-dimensional Doppler flow data is less angle dependent than conventional Doppler methods.

A new method of stabilizing the nasal endotrascheal tube was described. The tube was secured to the anterior portion of the nasal septum with braided silk thread, which was tightened over the rubber tube to keep air route of the cuff open. There found no complications such as unplanned extubation, necrosis and infections of the nasal septum.