Feeding catheter gastrostomy with the round ligament of the liver prevents mechanical bowel obstruction after esophagectomy.

Jejunostomy, which requires the fixation of the jejunum to the abdominal wall, is commonly used as an enteral feeding access after esophagectomy. However, this procedure sometimes causes severe complications, such as mechanical bowel obstruction. In 2009, we developed a modified approach to insert an enteral feeding tube through the reconstructed gastric tube using the round ligament of the liver. The aim of this study is to investigate the usefulness of this approach as compared to the approach through jejunostomy. Between January 2005 and March 2015, 420 patients with thoracic esophageal cancer underwent esophagectomy via thoracotomy and laparotomy. Of these, 214 underwent feeding jejunostomy (FJ group) and 206 patients underwent feeding via gastric tube with round ligament of the liver (FG group). Catheter-related complications, other postoperative complications, and mortality were compared between the two groups. The incidence of catheter site infection during catheterization in the FG group was significantly lower (n = 1/206, 0.5%) compared to the FJ group (n = 11/214, 5.1%) (P < 0.01). The postoperative bowel obstruction did not occur in the FG group, while it occurred in eight patients (3.7%) in the FJ group (P < 0.01). The incidences of other catheter-related and postoperative complications were similar between the two groups. Feeding catheter gastrostomy with the round ligament of the liver can be a useful enteral feeding access after esophagectomy, because the incidence rate of severe catheter-related complications, such as surgical site infection and mechanical obstruction tend to be lower with this technique compare to jejunostomy.

Randomized clinical trial of the effect of perioperative synbiotics versus no synbiotics on bacterial translocation after oesophagectomy.

BACKGROUND: The impact of perioperative synbiotics on bacterial translocation and subsequent bacteraemia after oesophagectomy is unclear. This study investigated the effect of perioperative synbiotic administration on the incidence of bacterial translocation to mesenteric lymph nodes (MLNs) and the occurrence of postoperative bacteraemia. METHODS: Patients with oesophageal cancer were randomized to receive perioperative synbiotics or no synbiotics (control group). MLNs were harvested from the jejunal mesentery before dissection (MLN-1) and after the restoration of digestive tract continuity (MLN-2). Blood and faeces samples were taken before and after operation. Microorganisms in each sample were detected using a bacterium-specific ribosomal RNA-targeted reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) method. RESULTS: Some 42 patients were included. There was a significant difference between the two groups in detection levels of microorganisms in the MLN-1 samples. Microorganisms were more frequently detected in MLN-2 samples in the control group than in the synbiotics group (10 of 18 versus 3 of 18; P = 0·035). In addition, bacteraemia detected using RT-qPCR 1 day after surgery was more prevalent in the control group than in the synbiotics group (12 of 21 versus 4 of 21; P = 0·025). Neutrophil counts on postoperative days 1, 2 and 7 after surgery were all significantly higher in the control group than in the synbiotics group. CONCLUSION: Perioperative use of synbiotics reduces the incidence of bacteria in the MLNs and blood. These beneficial effects probably contribute to a reduction in the inflammatory response after oesophagectomy. REGISTRATION NUMBER: ID 000003262 (University Hospital Medical Information Network, http://www.umin.ac.jp).

Cross talk between hedgehog and epithelial-mesenchymal transition pathways in gastric pit cells and in diffuse-type gastric cancers.

We previously reported hedgehog (Hh) signal activation in the mucus-secreting pit cell of the stomach and in diffuse-type gastric cancer (GC). Epithelial-mesenchymal transition (EMT) is known to be involved in tumour malignancy. However, little is known about whether and how both signallings cooperatively act in diffuse-type GC. By microarray and reverse transcription-PCR, we investigated the expression of those Hh and EMT signalling molecules in pit cells and in diffuse-type GCs. How both signallings act cooperatively in those cells was also investigated by the treatment of an Hh-signal inhibitor and siRNAs of Hh and EMT transcriptional key regulator genes on a mouse primary culture and on human GC cell lines. Pit cells and diffuse-type GCs co-expressed many Hh and EMT signalling genes. Mesenchymal-related genes (WNT5A, CDH2, PDGFRB, EDNRA, ROBO1, ROR2, and MEF2C) were found to be activated by an EMT regulator, SIP1/ZFHX1B/ZEB2, which was a target of a primary transcriptional regulator GLI1 in Hh signal. Furthermore, we identified two cancer-specific Hh targets, ELK1 and MSX2, which have an essential role in GC cell growth. These findings suggest that the gastric pit cell exhibits mesenchymal-like gene expression, and that diffuse-type GC maintains expression through the Hh-EMT pathway. Our proposed extensive Hh-EMT signal pathway has the potential to an understanding of diffuse-type GC and to the development of new drugs.

Impairment of AMPA receptor function in cerebellar granule cells of ataxic mutant mouse stargazer.

The spontaneous recessive mutant mouse stargazer (stg) begins to show ataxia around postnatal day 14 and display a severe impairment in the acquisition of classical eyeblink conditioning in adulthood. These abnormalities have been attributed to the specific reduction in brain-derived neurotrophic factor (BDNF) and the subsequent defect in TrkB receptor signaling in cerebellar granule cells (GCs). In the stg mutant cerebellum, we found that EPSCs at mossy fiber (MF) to GC synapses are devoid of the fast component mediated by AMPA-type glutamate receptors despite the normal slow component mediated by NMDA receptors. The sensitivity of stg mutant GCs to exogenously applied AMPA was greatly reduced, whereas that to NMDA was unchanged. Glutamate release from MF terminals during synaptic transmission to GCs appeared normal. By contrast, AMPA receptor-mediated EPSCs were normal in CA1 pyramidal cells of the stg mutant hippocampus. Thus, postsynaptic AMPA receptor function was selectively impaired in stg mutant GCs, although the transcription of four AMPA receptor subunit genes in the stg GC was comparable to the wild-type GC. We also examined the cerebellum of BDNF knockout mice and found that their MF-GC synapses had a normal AMPA receptor-mediated EPSC component. Thus, the impaired AMPA receptor function in the stg mutant GC is not likely to result from the reduced BDNF-TrkB signaling. These results suggest that the defect in MF to GC synaptic transmission is a major factor that causes the cerebellar dysfunction in the stg mutant mouse.

Cloning and sequencing of the gene cluster encoding two subunits of membrane-bound alcohol dehydrogenase from Acetobacter polyoxogenes.

The membrane-bound alcohol dehydrogenase (ADH) from Acetobacter polyoxogenes NBI1028 is composed of a 72 kDa subunit and a 44 kDa cytochrome c subunit. The amino acid sequences of the two regions of the 72 kDa subunit were determined to prepare oligonucleotides for the purpose of amplification of a DNA fragment corresponding to the intermediate region by the polymerase chain reaction. A 0.5 kb DNA fragment thus amplified was used as the probe to clone a 7.0 kb PstI fragment coding for the whole 72 kDa subunit. Nucleotide sequencing and immunoblot analysis revealed that the cloned fragment contained the full structural genes for the 72 kDa and the 44 kDa subunits and they were clustered with the same transcription polarity. The predicted amino acid sequence of the gene for the 72 kDa subunit showed homology with that of the 72 kDa subunit from ADH of A. aceti and those of methanol dehydrogenase from methylotrophic bacteria. The 72 and 44 kDa subunits contained one and three typical haem binding sequences, respectively.

Cloning and sequencing the recA+ genes of Acetobacter polyoxogenes and Acetobacter aceti: construction of recA- mutants of by transformation-mediated gene replacement.

The recA+ gene of Acetobacter polyoxogenes was cloned as a gene that conferred methyl methanesulfonate resistance (MMSR) on the RecA- Escherichia coli HB101. The cloned recA+ gene also conferred (i) resistance to UV irradiation, (ii) enhanced intrachromosomal recombination, and (iii) permitted prophage phi 80 induction in E. coli recA- lysogens. Nucleotide sequence determination revealed that the recA product consists of 348 amino acids (aa) corresponding to 38 kDa, and shows significant similarity to RecA proteins from other Gram- bacteria. Next, a portion of recA from Acetobacter aceti was cloned by using polymerase chain reaction with oligodeoxyribonucleotide primers design based on the A. polyoxogenes recA sequence. Due to availability of efficient host-vector and transformation systems in A. aceti, recA mutants of A. aceti were obtained by transformation-mediated gene replacement with the cloned A. aceti recA gene which was inactivated by insertion of the kanamycin-resistance-encoding gene from pACYC177. The recA mutants obtained in this way showed similar phenotypes to those of E. coli recA strains, such as increased sensitivity to MMS and to UV irradiation, and decreased homologous recombination.

Improved immunohistochemical detection of postsynaptically located PSD-95/SAP90 protein family by protease section pretreatment: a study in the adult mouse brain.

Postsynaptic density (PSD)-95, SAP102, and Chapsyn-110 are members of the PSD-95/SAP90 protein family, which interact with the C-terminus of N-methyl-D-aspartate (NMDA) receptor and shaker-type potassium channel subunits. Here we report that appropriate section pretreatment with pepsin has led to qualitative and quantitative changes in light microscopic immunohistochemical detection of the protein family. First, pepsin pretreatment lowered the concentration of affinity-purified primary antibodies, while it greatly increased the intensity of immunoreactions. Second, the resulting overall distributions of PSD-95, SAP102, and Chapsyn-110 in the adult mouse brain were consistent with their mRNA distributions. Third, instead of the reported patterns of somatodendritic labeling, tiny punctate staining in the neuropil became overwhelming. Fourth, many PSD-95-immunopositive puncta were apposed closely to synaptophysin-positive nerve terminals and overlapped with NMDA receptor subunits. By postembedding immunogold, the PSD-95 antibody was shown to label exclusively the postsynaptic density at asymmetrical synapses. Based on these results, we conclude that antibody access and binding to the postsynaptically located PSD-95/SAP90 protein family are hindered when conventional immunohistochemistry is adopted, and that pepsin pretreatment effectively unmasks the postsynaptic epitopes. On the other hand, PSD-95 in axon terminals of cerebellar basket cells, where high levels of potassium channels are present, was detectable irrespective of pepsin pretreatment, suggesting that PSD-95 antibody is readily accessible to the presynaptic epitopes. Consequently, the present immunohistochemical results have provided light microscopic evidence supporting the prevailing notion that the PSD-95/SAP90 protein family interacts with NMDA receptor subunits and potassium channel subunits.

Dynamic transformation of Bergmann glial fibers proceeds in correlation with dendritic outgrowth and synapse formation of cerebellar Purkinje cells.

Bergmann glia (BG) are unipolar cerebellar astrocytes, whose radial (or Bergmann) fibers associate with developing granule cells and mature Purkinje cells (PCs). In the present study, we investigated the morphodifferentiation of BG by immunohistochemistry for glutamate transporter GLAST and electron microscopy. GLAST was expressed widely in cerebellar radial glia/astrocytes during fetal and neonatal periods and became concentrated in BG postnatally. During the second postnatal week when PC dendrites grow actively, GLAST immunostaining revealed dynamic cytologic changes in Bergmann fibers in a deep-to-superficial gradient; Bergmann fibers traversing the external granular layer were stained as rod-like fibers, whereas in the molecular layer, the rod-like pattern was gradually replaced with a reticular meshwork. At postnatal day 10, the superficial rod-like domain was composed of glial fibrillary acidic protein (GFAP)-positive/GLAST-positive straight fibers, forming cytoplasmic swellings and short filopodia. Along this domain, the tip of growing PC dendrites ascended vertically and entered the base of the external granular layer. The deeper reticular domain of Bergmann fibers was characterized by active expansion of GFAP-negative/GLAST-positive lamellate processes, which surrounded PC synapses almost completely. Therefore, the transformation of Bergmann fibers proceeds in correlation with dendritic differentiation of PCs. The intimate PC-BG relationships during cerebellar development raise the possibility that a preexisting glial shaft could serve as a structural substrate that directs dendritic outgrowth toward the pial surface, whereas the successive formation of a reticular glial meshwork should lead to structural maturation of newly formed PC synapses.

Identification and characterization of novel developmentally regulated neural-specific proteins, BRINP family.

Processes of neuronal differentiation involve activation of a set of neuronal specific genes and cessation of cell proliferation in postmitotic neurons. Previous studies revealed that bone morphogenetic protein (BMP) and retinoic acid (RA) play important roles in the differentiation of peripheral sympathetic neurons such as the synergistic induction of responsiveness to specific neurotrophic factors. In the present study, while trying to clarify the mechanism of the BMP/RA-actions, we identified a novel neural-specific protein, BMP/RA-inducible neural-specific protein-1 (BRINP1) which shows no similarity to other known proteins. Subsequently, two homologous proteins, BRINP2 and BRINP3, making up the BRINP family, are identified. Individual BRINP genes have distinct regulatory mechanisms of expression within the nervous system. In rodent brain, BRINP1 is expressed from earlier developmental stage, i.e. E9.5, and widely expressed in various neuronal layers and nuclei of the adult animal, while BRINP2 and BRINP3 were detectable from E11.5 and expressed in rather limited regions in a complementary manner. During the course of perinatal development of sympathetic neurons, BRINP1 is induced from earlier embryonic stage and further increased toward adult stage, while BRINP3 expressed from earlier stage is replaced by BRINP2 expression which increases postnatally in accordance with the action of BMP2 and RA. Furthermore, when expressed in nonneuronal cells, all three BRINP family proteins suppressed the cell cycle progression. Possible physiological functions of BRINP family members in the development of the nervous system are discussed.

Nucleotide sequence of the membrane-bound aldehyde dehydrogenase gene from Acetobacter polyoxogenes.

The nucleotide sequence of the membrane-bound aldehyde dehydrogenase (ALDH) gene from an industrial vinegar producer, Acetobacter polyoxogenes, was determined. Comparison of the sequence with the NH2-terminal amino acid sequence of the mature ALDH and determination of the actual translational initiation codon by means of in vitro manipulation of the upstream and proximal regions of the cloned gene showed that ALDH was primarily translated as a 773-amino-acid protein and that the 44-amino-acid sequence at the NH2-terminus, which probably serves as a signal peptide, was processed during maturation and localization in the membrane. When ALDH was expressed in a large quantity in Escherichia coli cells after the coding region had been placed downstream of the lac promoter, the ALDH protein, which still contained the signal peptide and had no ALDH activity, was localized in the membrane fraction.

Down-regulated expression of glutamate transporter GLAST in Purkinje cell-associated astrocytes of reeler and weaver mutant cerebella.

The glutamate transporter plays an important role in rapid removal of glutamate from the synaptic cleft. Glutamate transporter GLAST is highly expressed in the Bergmann glia (BG), a unipolar cerebellar astrocyte associated structurally and functionally with Purkinje cells (PCs). Here we investigated the expression and localization in the reeler and weaver mutant cerebella with disorganized cytoarchitecture and disrupted synaptic circuitry. In the cortex of both cerebella, GLAST-expressing cells were astrocytes associating PCs; they were located around PC somata and primary dendrites, and extended glial fibrillary acidic protein (GFAP)-immunopositive processes surrounding PC somata and dendrites. Additional signals were detected in astrocytes of the reeler subcortex; they were dispersed among ectopic PCs and had GFAP-positive processes apposing to PC somata and stunted dendrites. Therefore, GLAST expression in PC-associated astrocytes was conserved in these mutants. Compared to the wild-type BG, however, the transcription level in individual mutant astrocytes was significantly reduced to about one-third level in the reeler and weaver cortex or one-sixth level in the reeler subcortex. Taking previous results on remarkable up-regulation during dendritogenic/synaptogenic stages and down-regulation following experimental glutamatergic denervation, it is suggested that GLAST expression in cerebellar astrocytes is regulated correlatively with cytological and/or synaptic differentiation of neighboring PCs.

Distinct spatiotemporal expression of mRNAs for the PSD-95/SAP90 protein family in the mouse brain.

PSD-95 (SAP90), SAP102 and Chapsyn-110 (PSD-93) are members of the membrane-associated guanylate kinase family, and interact with N-methyl-D-aspartate (NMDA) receptor NR2A (GluRepsilon1) and NR2B (GluRepsilon2) subunits and with Shaker-type K+ channel subunits to cluster into a channel complex. In the present study, we examined their expression in developing and adult mouse brains by in situ hybridization with antisense oligonucleotide probes. PSD-95 and SAP102 mRNAs were prominently expressed at embryonic day 13 (E13) in the mantle zone of various brain regions, where NMDA receptor NR2B subunit mRNA is expressed at high levels. In the early postnatal period when active synaptogenesis takes place, both mRNAs became elevated and concentrated in the telencephalon and cerebellar granular layer, where NR2A and/or NR2B subunit mRNAs are abundantly expressed. Chapsyn-110 mRNA was, though at low levels, found over the mantle zone of embryonic brains, and the level was progressively increased in the telencephalon starting at perinatal stages. The spatial and temporal correlations in the brain in vivo suggest that the PSD-95/SAP90 protein family can interact with NMDA receptor subunits to cluster them into channel complex at both synaptic and non-synaptic sites before, during and after synaptogenic stages.

Developmental changes in expression of the three ryanodine receptor mRNAs in the mouse brain.

Ryanodine receptors (RyR) are Ca(2+)-induced Ca(2+) release channels located on the endoplasmic reticulum, and consist of three isoforms, termed RyR1-3. We examined their expression in developing mouse brains by in situ hybridization. During the embryonic stage, RyR1 mRNA levels were highest in the rostral cortical plate, whereas RyR3 mRNA was most prominent in the caudal cortical plate and hippocampus. Initially, low levels of RyR2 mRNA were distributed in the diencephalon and brainstem. However, from postnatal day 7 onward, RyR2 mRNA became the major isoform in many brain regions, while RyR1 mRNA became prominent in the dentate gyrus and Purkinje cell layer. Postnatal down-regulation in the caudal cerebral cortex restricted RyR3 mRNA expression to the hippocampus, particularly the CA1 region. Therefore, RyR expression undergoes dynamic changes during the early postnatal period, when neurons are undergoing structural and functional differentiation.

Differential palmitoylation of two mouse glutamate receptor interacting protein 1 forms with different N-terminal sequences.

Glutamate receptor interacting protein (GRIP) is a member of the PDZ domain-containing protein family that is localized in the postsynaptic density area. This protein has been reported to interact specifically with the C-termini of AMPA-selective glutamate receptor channel subunits, GluRalpha2 and GluRalpha3 through its PDZ domains. To clarify the physiological functions of GRIP, we cloned mouse GRIP1, and found that there are three sites for alternative splicing and two putative translational start codons by characterizing GRIP1 cDNA clones and reverse transcription-polymerase chain reaction products. Metabolic labeling of COS-7 cells expressing two N-terminal GRIP1 proteins demonstrated that these proteins differed in their pattern of palmitoylation. These findings suggested that the molecular diversity of GRIP1 underlies the localization and functional heterogeneity of this protein.

Clinicopathologic characteristics and survival of patients with clinical Stage I squamous cell carcinomas of the thoracic esophagus treated with three-field lymph node dissection.

OBJECTIVE: Clinicopathologic characteristics and survival rates of patients with clinical Stage I tumors treated with three-field lymph node dissection have not been well investigated. This report documents the results of a series of cases of clinical Stage I squamous cell carcinomas treated with this surgical procedure in our institute. METHODS: From January 1988 to March 1997, 326 patients with carcinomas of the thoracic esophagus underwent transthoracic esophagectomy with three-field lymph node dissection. Two hundred and ninety-seven (91%) of these had squamous cell carcinomas. Fifty-seven (18%) patients with clinical Stage I squamous cell carcinomas of the thoracic esophagus were retrospectively reviewed here. RESULTS: Among 57 clinical Stage I squamous cell carcinomas, ten (18%) were diagnosed as T1-mucosal and 47 (83%) as T1-submucosal. Seventy percent of the patients with clinical T1-mucosal tumors had additional primary esophageal lesions. The operative morbidity and in-hospital mortality rates were 63 and 0%, and the overall 1-, 3-, 5-, and 10-year survival rates were 95, 86, 78, and 70%, respectively. Of the 57 tumors assessed pathologically, 12 (21%) were T1-mucosal, 42 (74%) were T1-submucosal, and three (5%) were T2. Nineteen (33%) exhibited lymph node metastasis. The 1-, 3-, 5-, and 10-year survival rates for patients with lymph node metastasis were 90, 79, 73, and 58%, respectively, as compared with 97, 90, 80, and 76, respectively for patients without lymph node metastasis (P=0.24). The accuracy of preoperative staging, based on both wall penetration and the status regarding lymph node metastasis, was 63%. With reference to the 1997 UICC-TNM staging system, 36 (63%) were pStage I, two (4%) were pStage IIA, 18 (28%) were pStage IIB, and three (6%) were pStage IVB. The 1-, 3-, 5-, and 10-year survival rates for patients with pStage I disease were 97, 92, 85, and 81%, respectively. In those with pStage II or IV disease, the values were 91, 76, 65, and 52%, respectively. CONCLUSIONS: Three-field lymph node dissection may be indicated even for patients with clinical Stage I squamous cell carcinoma requiring surgical intervention because this surgical procedure provides for possible cure by removing unsuspected lymph node metastasis.

Pulmonary hypertension associated with systemic lupus erythematosus: predominantly thrombotic arteriopathy accompanied by plexiform lesions.

We report an autopsy case of pulmonary hypertension associated with systemic lupus erythematosus in a 48-year-old woman. After 8-year follow-up under a definite diagnosis of systemic lupus erythematosus, she experienced gradually developing exertional dyspnea with palpitation. Her chest x-ray showed clear lung fields with marked cardiac enlargement. A right cardiac catheterization revealed a pulmonary arterial pressure of 74/30 mm Hg (mean: 47). She was treated with repeated plasmapheresis, oral corticosteroid, and immunosuppressant without improvement, and she died suddenly, 23 days after admission. Pathological examination revealed that small pulmonary arteries and arterioles were diffusely involved by florid thrombotic lesions, which were characterized by intimal eccentric fibrous thickening, luminal occlusion with recanalization, and occasional fresh thrombi. In addition, some arteries showed plexiform lesions coexistent with intimal thrombotic lesions. Concentric laminar intimal fibrosis was not seen. No significant parenchymal change was seen. Our study not only adds a rare case of thrombotic pulmonary hypertension associated with systemic lupus erythematosus, but also suggests that plexiform lesions can occur in association with thrombotic arteriopathy.

A clinicopathological study of ameloblastomas.

72 cases of ameloblastoma were obtained from the files of the Department of Pathology, School of Dentistry, Aichi-Gakuin University for the years January 1970 through December 1983. The cases were analyzed with respect to sex, age, duration, site histopathology, and treatment. Of 72 patients, 63 had no previous therapy, while 9 received their initial treatment elsewhere. There were 38 males and 34 females, a ratio of 1.2: 1. At the time of diagnosis, the ages of all patients ranged from 11 to 71 years, with an average of 36.6 years. About 65% of patients were in the 2nd, 3rd, and 4th decades of life. The duration of symptoms varied from 2 days to 5 years, with an average of 12.6 months. 69 cases occurred in the mandible, with the molar-ramus region being the most frequent site of involvement. Only 3 were found in the maxilla. The left side of the mandible was affected 1.6 times more frequently than the right. Histopathologically, 44 cases were of the plexiform type, 15 the follicular, 10 the acanthomatous, and 2 the basal cell type. Only 1 case was of the granular cell type. Most of the findings in the present study agreed with previous available data from the literature on ameloblastomas.

Nondestructive prediction method for yolk:albumen ratio in chicken eggs by computer image analysis.

The purpose of this study was to develop a nondestructive prediction method for the yolk: albumen ratio by computer image analysis for candling inspection. Twenty-two to 49 eggs per line were randomly sampled from four chicken lines. After weighing the eggs, the eggs were illuminated by an overhead projector beam through a small hole in dark room. Video images were taken of the eggs from four directions, the eggs rotated each time by 90 degrees. The eggs were broken for measuring egg traits, including the yolk:albumen ratio. The average value obtained from four directions was used for statistical analysis. The ratio of the number of pixels of light and dark parts (light: dark ratio), and the CV of red (R), green (G), and blue (B) components for the whole egg and for light and dark parts of the egg were calculated and defined as image analysis traits. Correlation coefficients between the yolk: albumen ratio and CV of R and G components of the whole egg were significant (0.42 to 0.79) in all the lines. The determination coefficient of multiple regression of the yolk:albumen ratio on the CV of R and G components of the whole egg and the light:dark ratio was 0.83. Observed and predicted yolk:albumen ratios were classified into five levels. The ratio of zero difference between observed and predicted values was 76.1%, and the percentage of 0 to +/- 1 difference between observed and predicted values was 100.0%. The image analysis method accurately predicted the yolk:albumen ratio without breaking the egg.

[Change of housing environment and withdrawal of corticosteroid as treatments of atopic dermatitis].

For the purpose of searching for the factors for improvement in cutaneous lesions of atopic dermatitis, we evaluated two factors, namely, change in the housing environment and withdrawal of corticosteroid in a group of patients whose clinical course had been observed for more than one year. The condition of illness was judged by a combination of VAS scoring of cutaneous lesions, laboratory data (IgE, LDH, eosinophil) and evaluation by the patient himself. The results showed a significant difference (p = 0.143) by Fisher's direct probability for the tendency to improve in the group in which the housing environment had changed and p = 0.266 for the tendency to improve in the group in which corticosteroid was withdrawn. When the tendency to improve by either change in the housing environment or corticosteroid withdrawal was examined, the p value was 0.028 at 5% level of significance. That is, the findings in this study suggest that atopic dermatitis will improve in the presence of either or both of these two factors at 5% level of significance. Factors regulating the condition of illness in atopic dermatitis are diverse. Analysis using only one of these factors cannot easily show a statistically significant difference. So studies involving two or more factors are needed.

C/EBP homologous protein contributes to cytokine-induced pro-inflammatory responses and apoptosis in ß-cells.

Induction of the C/EBP homologous protein (CHOP) is considered a key event for endoplasmic reticulum (ER) stress-mediated apoptosis. Type 1 diabetes (T1D) is characterized by an autoimmune destruction of the pancreatic ß-cells. Pro-inflammatory cytokines are early mediators of ß-cell death in T1D. Cytokines induce ER stress and CHOP overexpression in ß-cells, but the role for CHOP overexpression in cytokine-induced ß-cell apoptosis remains controversial. We presently observed that CHOP knockdown (KD) prevents cytokine-mediated degradation of the anti-apoptotic proteins B-cell lymphoma 2 (Bcl-2) and myeloid cell leukemia sequence 1 (Mcl-1), thereby decreasing the cleavage of executioner caspases 9 and 3, and apoptosis. Nuclear factor-κB (NF-κB) is a crucial transcription factor regulating ß-cell apoptosis and inflammation. CHOP KD resulted in reduced cytokine-induced NF-κB activity and expression of key NF-κB target genes involved in apoptosis and inflammation, including iNOS, FAS, IRF-7, IL-15, CCL5 and CXCL10. This was due to decreased IκB degradation and p65 translocation to the nucleus. The present data suggest that CHOP has a dual role in promoting ß-cell death: (1) CHOP directly contributes to cytokine-induced ß-cell apoptosis by promoting cytokine-induced mitochondrial pathways of apoptosis; and (2) by supporting the NF-κB activation and subsequent cytokine/chemokine expression, CHOP may contribute to apoptosis and the chemo attraction of mononuclear cells to the islets during insulitis.