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Background/Aim: This study aimed to evaluate the association between the change in peripheral eosinophil count during postoperative pelvic radiotherapy and gastrointestinal (GI) toxicities in patients with cervical cancer. Patients and Methods: The medical records of 163 patients with cervical cancer who underwent postoperative concurrent chemoradiotherapy between 2000 and 2016 were analyzed. Results: Among the peripheral blood cell counts, transient elevation of the eosinophil count was observed during radiotherapy. Of the 163 patients, 117 developed grade ≥2 diarrhea during radiotherapy, and 25 patients developed grade ≥2 late GI toxicities. In multivariate analysis, the maximum eosinophil count and age emerged as independent predictors of grade ≥2 acute diarrhea during radiotherapy, while bowel bag V40 Gy and age were predictive of grade ≥2 late GI toxicities. Conclusion: Early detection of transient elevation of eosinophil may facilitate early treatment of acute diarrhea during radiotherapy.

Acid-tolerant yeasts often inhabit extremely acidic environments: mine drain-ages, hot springs, and even fermented foods. Some of them also possess the ability to neutralize acidic media. However, the examples of these yeasts that are already known were isolated from acidic environments. In this study, the isolation of acid-tolerant yeasts from natural neutral aquatic environments and the identification of yeasts able to neutralize an acidic medium (acid-neutralizing yeast) in Japan were carried out. Various kinds of acid-tolerant and acid-neutralizing yeasts were obtained. In a neutralizing test using an acidic casamino acid solution adjusted to a pH of 4.0 with sulfuric acid, the obtained acid-neutralizing yeasts elevated the pH to approximately 7.0, and their neutralizing abilities were similar to those of previously reported yeasts that had been isolated from acidic environments. These results showed that acid-tolerant yeasts and acid-neutralizing yeasts exist widely in neutral environments, and little difference was found in the neutralizing abilities of yeasts obtained from neutral environments in comparison to those obtained from acidic environments.

Objective The close relationship between fatty liver and metabolic syndrome suggests that individuals with fatty liver may have multiple coronary risk factors. In the present study, we investigated the relationships among fatty liver, abdominal fat distribution, and coronary risk markers. Methods and Results Eighty-seven pairs of men and 42 pairs of women who were matched for age and body mass index were enrolled in the present study. The obesity-related markers, abdominal fat distribution (examined by CT), and coronary risk markers were compared in subjects with and without fatty liver. The visceral fat area was significantly larger in the men with fatty liver than in the men without fatty liver. The plasma levels of triglyceride and low-density lipoprotein cholesterol (LDL-C), as well as the homeostasis model assessment-insulin resistance level, were higher in both males and females with fatty liver than in those without fatty liver, while the plasma levels of high-density lipoprotein cholesterol (HDL-C) and adiponectin were lower in the males and females with fatty liver. The plasma levels of apolipoprotein B, remnant-like particle cholesterol (RLP-C), and oxidized LDL were higher in men with fatty liver, but not in women with fatty liver. Conclusion Both males and females with fatty liver had lower insulin sensitivity, lower plasma levels of HDL-C and adiponectin, and higher triglyceride and LDL-C levels. However, the plasma levels of apolipoprotein B, RLP-C, and oxidized LDL were only higher and closely associated with fatty liver in men. Men with fatty liver had a higher risk of coronary disease than women with fatty liver.

The purpose of this paper is to consider methods of instruction in the proper use of conjunctions by Japanese learners of English by using corpus of English writing by Japanese university students and focusing on the role of conjunctions, which are considered to fulfill an important role in increasing cohesion. Three conjunctions were chosen for the analysis, and the Japanese, Chinese, Russian, Bulgarian and Turkish sub-corpora taken from the second version of the International Corpus of Learner English (ICLEv2) as well as a native speaker corpus LOCNESS-US were examined for the purpose of comparison. The analysis found that there is a statistically significant difference between native speakers of English and non-native learners of English regarding the use of above conjunctions as well as the sentence position in which they are used. The findings in this study has led us to the conclusion that, no matter what the mother tongue background of the English learner is, strategies are needed to increase cohesion of the text and correct use of conjunctions plays an important part in order to write texts that are logical and read like natural English.

Bacterial colonization in infancy is considered crucial for the development of the immune system. Recently, there has been a drastic increase in childhood allergies in Japan. Therefore, we conducted a prospective study with 56 infants on the relationship between gut microbiota in the first year of life and the development of allergies during the first 3 years. In the lactation period, organic acid producers such as Leuconostoc, Weissella and Veillonella tended to be underrepresented in subjects who developed food allergies (FA, n = 14) within the first two years. In the weaning period, children in the FA group were highly colonized by unclassified Enterobacteriaceae and two Clostridium species closely related to Clostridium paraputrificum and C. tertium, and the whole tree phylogenetic diversity index was significantly lower in the FA group. All of these differences in the weaning period were statistically significant, even after adjusting for potential confounding factors. A higher abundance of unclassified Enterobacteriaceae was also found in the other allergic group (n = 15), whereas the two Clostridium species were highly specific to the FA group. The mode of action of these Clostridium species in childhood food allergies remains unknown, warranting further investigation.

In the present study I investigate the use of lexical collocations in Japanese EFL learners' written English, with a special focus on the verb "take." I compare differences in the use of "take" in academic essays written by Japanese university students and by American university students, using the ICLE Japanese subcorpus as a learner corpus and LOCNESS as a reference corpus. I examined lexical collocations of "take" in terms of frequency, variety, overuse, and underuse. The results revealed that although the total frequency of "take" with noun combinations was higher in the Japanese EFL learner data, learners tended to overuse fixed expressions and did not use native-like collocations. The overall results suggest the need to expand collocational knowledge on the part of Japanese EFL learners, which may prove to be beneficial in producing more natural sentences. To achieve the above goal, I propose three suggestions in this paper. The first is that the process by which Japanese EFL students learn collocations needs to be clarified. The second is that collocational data retrieved from corpora should be put to use in classroom English texts. Lastly, there should be a greater awareness of the importance of teaching collocations to Japanese learners of English.

We investigated the correlation between fecal bacteria composition in early infancy and the prevalence of allergic diseases in late infancy. The fecal microbiota in the first 2 months was profiled using the 16S rRNA V6 short-tag sequences in the community and statistically compared between two groups of subjects who did and did not show allergic symptoms in the first 2 years (n = 11 vs. 11). In the allergic group, genus Bacteroides at 1 month and genera Propionibacterium and Klebsiella at 2 months were more abundant, and genera Acinetobacter and Clostridium at 1 month were less abundant than in the nonallergic group. Allergic infants who showed high colonization of Bacteroides and/or Klebsiella showed less colonization of Clostridium perfringens/butyricum, suggesting antagonism between these bacterial groups in the gastrointestinal tract. It was also remarkable that the relative abundance of total Proteobacteria, excluding genus Klebsiella, was significantly lower in the allergic than in the nonallergic group at the age of 1 month. These results indicate that pyrosequence-based 16S rRNA gene profiling is valid to find the intestinal microbiotal disorder that correlates with allergy development in later life.

Background Tubulointerstitial fibrosis (TIF) is seen as the final stage of progressive nephropathy, and the degree of TIF is reported to be a major determinant in renal outcomes. In recent years, epithelial-mesenchymal transition (EMT) and the zinc-finger transcription factor snail homolog 1 (Snai1) have each been implicated in the mechanism of TIF. The relationship between EMT and these transcription factors is unclear, however, so in this study we attempted to elucidate the correlation between the expression of Snai1 and clinical markers. Methods We performed immunohistochemical staining on human renal tissue obtained from patients with diabetic nephropathy (DN), IgA nephropathy (IgAN), minimal change disease (MCD) and minor glomerular abnormality (MGA) using anti-Snai1 and anti-vimentin antibodies. We counted Snai1-positive and Snai1/vimentin double positive tubular epithelial cells. Results Snai1 protein was mainly observed in the nuclei of flattened, damaged tubular epithelial cells, especially in IgAN and DN, and positive cell numbers were significantly higher in IgAN than in MGA, MCD or DN. Snai1/vimentin double staining showed that some vimentin-positive tubular epithelial cells also contained Snai1-positive nuclei, and double positive cell numbers were increased in IgAN and DN. Statistical analysis revealed positive correlations between Snai1/vimentin double positive cell numbers and proteinuria and creatinine in IgAN. Positive correlations were also seen between Snai1/vimentin double positive cell numbers and the severity of proteinuria in DN. Conclusions The results of this study indicate that Snai1 plays an important role in TIF in patients with progressive nephropathy.

The influence of antibiotic exposure in the early postnatal period on the development of intestinal microbiota was monitored in 26 infants including five antibiotic-treated (AT) subjects orally administered a broad-spectrum antibiotic for the first 4 days of life and three caesarean-delivered (CD) subjects whose mothers were intravenously injected by the similar type of antibiotics in the same period. The faecal bacterial composition was analysed daily for the first 5 days and monthly for the first 2 months. Terminal restriction fragment length polymorphisms in the AT subjects showed less diversity with the attenuation of the colonization of some bacterial groups, especially in Bifidobacterium and unusual colonization of Enterococcus in the first week than the control antibiotic-free infants (AF, n=18). Quantitative real-time PCR showed overgrowth of enterococci (day 3, P=0.01; day 5, P=0.003; month 1, P=0.01) and arrested growth of Bifidobacterium (day 3, P=0.03) in the AT group. Furthermore, after 1 month, the Enterobacteriaceae population was markedly higher in the AT group than in the AF group (month 1, P=0.02; month 2, P=0.02). CD infants sustained similar, although relatively weaker, alteration in the developing microbiota. These results indicate that antibiotic exposure at the beginning of life greatly influences the development of neonatal intestinal microbiota.

Objective Diabetic nephropathy (DN) is a common cause of end-stage renal disease. However, the precise mechanism of DN, which involves the role of lipid, is still not fully understood. Lectin-like oxidized LDL receptor-1 (LOX-1) is a type II single-transmembrane protein that binds oxidized low density lipoprotein (Ox-LDL). This study examined the expression of LOX-1 mRNA in renal tissues from type 2 diabetes patients with DN using in situ hybridization (ISH). Patients and Methods Renal tissues were obtained from 15 type 2 patients with DN and 5 minimal change nephrotic syndrome (MCNS), membranous nephropathy (MN) and normal human kidney (NHK). Glomerular and tubulointerstitial LOX-1 mRNA expression was evaluated by ISH. Results The cells positive for LOX-1 mRNA were identified in the glomeruli of DN, MCNS, MN and NHK, however, there was no positive signal in the tubulointerstitial area in MCNS and NHK. Some cells positive for LOX-1 mRNA were detectable in the tubulointerstitial area in DN and MN. In the results of glomerular staining, there was no significant difference between them. There was a significant correlation between the tubulointerstitial LOX-1 expression and the degree of the tubulointerstitial damage and urinary protein in DN. Conclusion Increased expression of LOX-1 mRNA in the tubulointerstitial area may be closely linked to the development and progression of human DN, and in particular the tubulointerstitial damage.

Objective The loss of podocytes has been reported to have a role in the onset and progression of diabetic nephropathy (DN). Although structural changes such as podocyte hypertrophy are considered to be associated with podocyte loss, the relationship has not been thoroughly investigated using human DN renal tissues. Methods The subjects were 17 patients with DN diagnosed histopathologically by renal biopsy. Immunostaining was performed with antibodies for Wilm's tumor 1 (WT1) and synaptopodin (SPD), which are markers of podocytes, to determine the number of podocytes and assess podocyte hypertrophy. Results The number of podocytes was decreased in DN patients compared with the controls. An inverse correlation was observed between the number of podocytes and both the urinary protein excretion and the extent of mesangial expansion. Podocyte hypertrophy was also more marked in DN patients compared with controls. Conclusion Based on these results, podocyte loss and hypertrophy were suggested to be involved in the development and progression of human DN.

This paper discusses two studies which examine the usage of countable and uncountable nouns in the International Corpus of Learner English (ICLE) error-tagged Japanese sub-corpus. The first study examines major tendencies in the misuse of countable and uncountable nouns as found in the above corpus. Next, the second study examines how learners lexically determine that a noun can be used in both countable and uncountable forms. As a result, errors are classified into 3 types: errors using an uncountable noun as a countable noun, errors using a countable noun as an uncountable noun, and errors occurring when deciding between countable and uncountable nouns depending on the context. Based on the results of the second study, errors related to determining when to use a noun as countable or uncountable depending on context account for over 60% of the errors revealing a major tendency in the misuse of these nouns. It indicates that Japanese learners of English tend to have a fixed notion that specific nouns, especially abstract nouns, are uncountable. Results of the two studies suggest that recognition of countability or uncountability by Japanese EFL learners may be affected by the concept of a noun's concreteness or abstractness.

In this study, the English learner corpora from four different language learner groups will be analyzed: Japanese, Chinese, Italian, and French speakers, as well as two native speaker corpora for the purpose of comparison with the learner data. The results revealed that varieties of the usage of "feel" in respective learner corpora have unique tendencies, and they did not necessarily conform to the tendencies in the native speaker data. Also, it was found that differences existed between the learner corpora and the native speaker corpora in terms of the usage of adverbs and modifiers that collocated with the verb "feel". For example, in the learner corpora, words that modified the verb "feel" and expressed strength of emotion were very limited in number compared with the native speaker corpora. On the other hand, the native speaker data showed a tendency of using various adverbs, modifiers, etc., modifying the verb "feel" and specifically describing strength of emotion, certainty and so forth. The results of this study reinforce the assertion that emotion language is strongly affected by the learners' first languages and their socio-cultural experiences.

Although emotional expression has been studied from the perspective of many different disciplines, the study of the use of learners' emotional expressions in SLA has not yet been fully explored. This paper explores the learners' use of emotional expressions in the Japanese, Chinese, French and Italian learner corpora in spoken English against that of native speakers. The results show that 1) the use of emotion vocabulary differed according to the learners' language background and 2) strategies used in expressing emotions also differed according to the learners' linguistic background. Overall, the results of this paper have proven that Japanese students as well as the other non-native students do try to express emotions, in fact more frequently than native speakers of English. The difference seems to lie in how well they can use a variety of emotional expressions and their supporting strategies. Providing students with sufficient exposure to emotional expressions and their supporting strategies should be one of the most important instructional goals to implement.

Layered Li1+yNixCo1−2xMnxO2 materials were prepared by a solid-state reaction at 950 °C for 10 h in air and characterized by various methods. The cell performance depended on the composition. The rate performance deteriorated as Co content (1 − 2x) decreased. On the other hand, it improved as excess Li content (y) increased. The change of cell performance associated with composition variations was closely related to both the structural disorder (cation mixing) and the electrical conductivity (volume resistivity). The degree of cation mixing depended greatly on Co content (1 − 2x). On the other hand, the volume resistivity depended greatly on excess Li content (y). In other words, the cell performance was improved by the reduction of cation mixing and volume resistivity. Only Ni K-edge X-ray absorption near edge structure (XANES) spectra showed edge shifts to higher energy due to the oxidation of Ni as either Co content (1 − 2x) or excess Li content (y) increased. The unit cell size decreased as either Co content (1 − 2x) or excess Li content (y) increased. They are probably caused by the change from Ni2+ ( r Ni = 0.69 A) to the smaller Ni3+ ( r N i 3+ = 0.56 A). From these results, it is assumed that the reduction of volume resistibity is closely related to the increase of Ni3+ concentration in Li1+yNixCo1−2xMnxO2.

We investigated the effect of T cell-dependent B cell activation on the production of IL-10 and IL-12 by peripheral blood mononuclear cells (PBMCs) obtained from patients with Graves' disease vs Hashimoto's thyroiditis, type 1 diabetes or normal controls. Incubation of PBMCs, from each of the subject groups, with a combination of anti-CD40 monoclonal antibodies and interleukin 4 (IL-4)-activated B cells, as shown by an increased level of soluble CD23. There was also a notable increase in the number of CD23(+)cells in PBMCs from patients with Graves' disease as compared to the other subject groups. This combination of B cell stimulants increased production of IL-10 in PBMCs obtained from patients with Graves' disease relative to those patients with Hashimoto's thyroiditis, type 1 diabetes, or the control subjects. The production of IL-12 showed wide variation that depended on the basal IL-12 level. In subjects with a low basal IL-12 level there was a positive correlation between the production of IL-12 and that of IL-10 from PBMCs stimulated with anti-CD40 antibodies plus IL-4. On the contrary, in the patients with a high basal IL-12 level, no change or a decrease of IL-12 production was observed after the stimulation. Thus, T cell-dependent B cell activation via a CD40 pathway triggers the overproduction of IL-10 and overcome the effect of IL-12 to shift the Th(1)/Th(2)balance to Th(2)dominance in patients with Graves' disease but not in Hashimoto's thyroiditis or type 1 diabetes.

Epicotyl segments(approximately 1 cm in length)of Vigna angularis(cv.Tanbadainagon)inoculated with Agrobacterium rhizogenes produced hairy roots and/or adventitious buds. Mikimopine and the predictable PCR band for rol gene were detected in the hairy roots, and plantlets obtained from the adventitious buds were negative for both products. These results suggested that the segments can induce the formation of adventitious buds without an infection of A.rhizogenes; therefore this possibility was examined. As a result, adventitious buds were formed from the segments on a hormone-free medium and promoted by low concentrations of 6-benzyladenine(BA) and 1-naphthaleneacetic acid(NAA). When the calli induced on the medium containing BA and/or NAA were transplanted onto the hormone-free medium, they induced an organogenic callus, which was growing with the formation of a green leaflike structure. Especially, the frequency of organogenic callus formations was very high in calli that had once produced adventitious buds. The development of shoots from organogenic callus was induced on the medium containing gellan gum with NAA. Shoots(more than 1 cm in length)cut from epicotyl segments and organogenic callus produced roots and developed actively on the hormone-free medium. The procedures obtained in the present study are useful for the genetic improvement of the plant via biotechnology.

Summary Suppression of the fibrinolytic activity plays an impotant role in the prevention of hemorrhage during pregnancy and labor. A hypofibrinolytic and hypercoagulable state may be established in the placenta during pregnancy. However, little infarcition is present in the normal placenta. This evidence demonstrates that the placenta maintains a fibrinolytic activity in spite of a hypercoagulation state. We studied the role of APC (activated protein C) on fibrinolysis in the placenta. (1) APC-PAI-1 (plasminogen activator inhibitor type-1) complexes were demonstrated in serum-free culture medium when human umbilical vein endothelial cells (HUVEC) were incubated with APC, indicating that PAI-1 was dissociated from receptor-bound uPA (urokinase type plasminogen activator) on the cell surface of HUVEC. This was also confirmed by enzyme-linked immunosorbent assay (ELISA), (2) APC antigen is located on the syncytiotrophoblast in first trimester placenta by immunohistochemistry. Taken together, these results suggest that APC could possibly play a significant role in fibrinolytic activity during early stages of gestation.

Objective: To increase the accuracy of the diagnosis of atypical squamous cells of undetermined significance (ASC-US), ASC-US were divided into high-risk human papillomavirus (HPV HR+) and non-high-risk HPV (HPV HR-) cases to analyze the significance of binucleated cells with compression. Study Design: ThinPrep specimens of ASC-US were examined. This study included 21 CIN and HPV HR+ (CIN+), 19 benign and HPV HR- (B-) and 10 benign and HPV HR+ (B+) cases. The number of cells were examined by defining binucleated cells with their nuclei pressing against each other as positive compression, and their relation to the relative light units (RLUs) of the DNA Hybrid capture 2 (HC2) was determined. Results: 95.2% of CIN+ and 15.8% of B- cases were compression positive, while 4.8% of CIN+ and 84.2% of B- cases were compression negative, which was significantly different. The average number of cells with positive compression was 5.7 ± 5.3 in CIN+, 2.0 ± 0.7 in B- and 5.5 ± 1.5 in B+ cases, with significant differences between CIN+ and B- and between B- and B+ cases. The number of compression-positive cells increased as HPV HC2 RLUs became higher. Conclusion: Positive compression is useful in determining ASC-US with HPV HR+. The identification of positive compression is highly practical because it can be observed morphologically.

Objective To determine the clinical usefulness of long-term intensive insulin therapy in Japanese patients with type 2 diabetes. Patients and methods Various clinical indicators and potential of withdrawal from insulin therapy were investigated in 20 type 2 diabetic patients receiving treatment in the outpatient clinic over a period of 8 years after starting intensive insulin therapy between April 1997 and March 1999. Results The mean glycated hemoglobin (HbA1c) was approximately 6.5%, and there was no significant increase in insulin dose over a period of 8 years after commencement of intensive insulin therapy. Withdrawal from insulin therapy could be sustained in previously untreated patients. Conclusion Our results indicated the clinical usefulness of intensive insulin therapy over the long term in Japanese patients with type 2 diabetes and that such therapy could be especially useful for previously untreated patients.

Background Alpha-actinin-4 is an actin filament crosslinking protein that interacts with intercellular adhesion molecules. Recent animal studies suggested that alpha-actinin-4 is an essential component of the glomerular filtration barrier. However, little is known about its expression in human diabetic nephropathy (DN). Methods Renal biopsy tissues were obtained from 17 patients with DN. We determined the mRNA and protein expression levels of alpha-actinin-4 by in situ hybridization and immunohistochemistry. The histopathological severity of DN was classified into two groups: mild and moderate mesangial expansion groups. We also measured urinary protein excretion and creatinine clearance. Results Podocytes were positively stained for alpha-actinin-4 mRNA and protein. In the glomeruli, the percentage of cells positive for alpha-actinin-4 mRNA was significantly lower in moderate mesangial expansion group than in mild mesangial expansion group and control. The percentage of immunohistochemically positive area for alpha-actinin-4 protein in moderate mesangial expansion group was significantly lower than in mild mesangial expansion group and control. The percentage of cells positive for alpha-actinin-4 mRNA and area positive for the protein correlated inversely with severity of proteinuria. Conclusion Our results suggest that low expression levels of alpha-actinin-4 mRNA and protein are linked to the progression of glomerulopathy and proteinuria in human DN.

Objective Membranous nephropathy (MN) is the most common cause of adult-onset nephrotic syndrome and its management is still controversial. The aim of this study was to determine the effectiveness of corticosteroid-alone therapy for controlling proteinuria in MN. Methods Twenty-three patients, which had moderate proteinuria (admission 24-hour urinary protein excretion 1.0 to 3.5 g/day) with primary MN were studied retrospectively. Results Thirteen patients received corticosteroid-alone therapy combined with rest and dietary therapy (steroid group), while the other 10 patients were treated with rest and diet alone (non-steroid group). These two groups did not differ with respect to their laboratory features at the time of admission. After discharge, 5 of 13 patients of the steroid group dropped out . Therefore, only 8 patients could be followed up. As the result, 5 of 8 patients (62.5%) achieved complete remission (CR) and 3 of 8 patients (37.5%) had incomplete remission (ICR), so none of the patients failed to improve. On the other hand, 3 of 10 patients of the non-steroid group dropped out. Then, 7 patients were followed up. None of the 7 patients showed improvement during follow-up and 5 of these 7 patients were started on corticosteroids. Finally, as this result, 4 of 5 patients (80%) could achieve CR by 2 years after hospital discharge. Moreover, in the remaining 2 patients from the non-steroid group, no remission could be achieved even 2 years after discharge. Conclusion These results suggest that long-term corticosteroid-alone therapy is beneficial for controlling proteinuria in patients with MN.

Endothelin-1 (ET-1) concentrations are increased in patients with diabetes mellitus, particularly those with diabetic retinopathy, or essential hypertension. We hypothesized that ET-1 might participate in the development and progression of diabetic microangiopathy. In this study, the effects of the angiotensin converting enzyme (ACE) inhibitor, enalapril maleate, on diabetic angiopathy were examined in streptozotocin (STZ)-induced diabetic (STZ-DM) rats by monitoring variations in renal function and ET-1 concentrations in blood and organ tissues. Significant increases in kidney weight and in concentrations of urinary albumin, N-acetyl-fl-d-glucosamidase (NAG) and serum ET-1 were observed in the STZ-DM rats as compared with the non-diabetic rats, and the concentration of ET-1 in the kidneys tended to be increased. Microscopic and electron microscopic analyses showed increased mesangial cell proliferation, matrix expansion and enlarged mesangial area in the kidney of the diabetic rats. After administration of the ACE inhibitor, increased concentrations of urinary albumin and NAG in the STZ-DM rats were reduced to the control values with a slight improvement in the electron microscopic changes. These data suggest that ET-1 may be involved in the development and progression of diabetic nephropathy and may explain, in part, why diabetes is liable to complicate hypertension. ACE inhibitor may help to restore diabetic nephropathy in the STZ-induced diabetic rats.

The possible role of abnormal T cell-dependent B-cell activation in Graves' disease was investigated by comparing lymphocyte subset distribution and the production of soluble CD8 (sCD8), sCD23, IL-10 and IL-12 by peripheral blood cells (PBMC) and thyroid-infiltrating lymphocytes (TL) in vitro. In TL, the percentage of CD8(+) cells was slightly higher and the sCD8 concentration was significantly higher than in PBMC. The ratio CD23(+) cells to CD20(+) cells (activated B/pan B cells) was increased in TL compared to PBMC from Graves' or normal controls, although the percentage of CD20(+) cells was decreased. Compared to PBMC in Graves' disease, the relative ratio of IL-10 to IL-12 release (IL-10/IL-12) by unstimulated TL was increased, despite a lack of significant difference between PBMC and TL in mean values for either IL-10 or IL-12 secretion. Incubating PBMC with a combination of anti-CD40 monoclonal antibodies and interleukin-4 (IL-4) resulted in B cell activation, reflected in an increase in the sCD23 level in both controls and Graves' patients, but especially prominent in the latter. Stimulation with anti-CD40 antibody and IL-4 also decreased the percentage of CD8(+) cells in PBMC but not TL from both Graves' disease and normal controls, and the percentage of CD8(+) cells in TL was higher than PBMC after the stimulation. The sCD23 concentration in TL was decreased compared to PBMC both in patients with Graves' disease and normal controls. However, in contrast to the increased responses observed in Graves' PBMC or normal controls after stimulation, sCD23 levels remained the same in stimulated TL from Graves' patients. This combination of B cell stimulants increased production of IL-10 in PBMC but not in TL obtained from patients with Graves' disease, and the increased IL-10/IL-12 ratio declined to a value no different from that in PBMC group after stimulation. Thus, T cell-dependent B-cell activation via a CD40 pathway may cause a shift in the Th(1)/Th(2) balance to Th(2) dominance in Graves' disease, while increased CD8(+) cells in TL may suppress sCD23 production and IL-10-producing Th(2) cells.

Physicochemical properties, drug release and stability of polymyxin B sulfate in an ointment prepared for the treatment of burn with use of o/w type emulsified base were studied. This ointment showed the equal consistency and spreadability to those of the commercial emulsified base for burn, and the washing-out time was appreciably shorter than that. The rate of the release of polymyxin B sulfate from the ointment was higher in the order of macrogol, emulsified and hydrophilic ointment. When polymyxin B sulfate were prepared with any of 3 ointment bases, their potencies lowered by about 10% when they were stored at 37°C for 2 months, but they were almost stable when stored at room temperature for a month