VALIDITY OF ACTIVITY INDICES IN ULCERATIVE COLITIS: COMPARISON OF CLINICAL AND ENDOSCOPIC INDICES

Aim: Various different clinical indices (CI) and endoscopic indices (El) have been used to evaluate the clinical disease activity of ulcerative colitis (UC). However, no standardized CI or El of UC has been established. The aim of the present study was to determine whether or not any of the CI and/or EI for assessing the disease activity of UC could be established as a standard. Methods: The most frequently used CI and EI were identified from 100 published clinical trials dealing with UC, and representative CI and El were selected. Seventy‐four patients were enrolled in this study and their CI and El were assessed prior to treatment and at 2, 4 and 8 weeks after treatment. Furthermore, changes over time and relationships among the indices were analyzed. In this study, the clinical activity index (CAI), the disease activity index (DAI), the Lichtiger index (LI) and the Seo index were selected as the representative CI, and the Baron score and the Rachmilewitz endoscopic index (REI) were selected as the representative EI. Results: A significant decrease in all the CI and El was observed after treatment, as compared with the baseline values. Moreover, there were positive relationships among the CI and between the CI and El. Conclusion: Our results demonstrated that all the CI and El examined were almost equally useful for evaluating disease activity in UC patients. Further studies may help to determine which of the indices is the most suitable for use in UC clinical trials.     

Simultaneous surgery for chronic aortic dissection and adrenal adenoma with primary aldosteronism

A 38-year-old man had Stanford type B chronic aortic dissection. Blood pressure was diffi cult to control, and further examination revealed primary aldosteronism. Magnetic resonance images showed a 1-cm nodule in the left adrenal gland. Graft replacement for aortic dissection under extracorporeal circulation and resection of the left adrenal gland were undertaken simultaneously. The postoperative course was uneventful, and blood pressure was controlled without antihypertensive drugs.     

Epitope mapping of capsid proteins VP2 and VP3 of infectious bursal disease virus

Summary Twenty hybridoma cell lines producing monoclonal antibodies (MAbs) against serotype 1 infectious bursal disease virus (IBDV) of GBF-1 and the attenuated GBF-1E strains were produced. The MAbs recognized major structural proteins VP2 and VP3. MAb recognition sites were mapped using recombinantEscherichia coli clones which expressed N-terminal and (or) C-terminal truncated virus antigens, and competitive-binding assays. At least 3 conformation-dependent serotype 1 specific virus neutralizing antigenic sites and a linear antigenic site were defined on VP2 and VP3, respectively. Two of the conformational virus neutralizing antigenic sites were localized in the central area of VP2 consisting of 156 amino acid residues, and the linear epitope was localized in C-terminal 105 amino acid residues of VP3. Another conformational virus neutralizing antigenic site recognized with the virus neutralizing MAb GK-5 was not defined because GK-5 did not react with virus antigen expressed in recombinantE. coli. The conformational antigenic site was supposed to be composed of tertiary or quaternary protein structure, which may not be constructed in recombinantE. coli.     

Glucose-6-phosphate dehydrogenase (G6PD) mutations in Myanmar: G6PD Mahidol (487G>A) is the most common variant in the Myanmar population

We conducted a survey of malaria diagnoses and treatments in remote areas of Myanmar. Blood specimens from more than 1,000 people were collected by the finger-prick method, and 121 (11%) of these people were found to be glucose-6-phosphate dehydrogenase (G6PD) deficient. Of these 121, 50 consented to analysis of the G6PD genome. We read the G6PD sequences of these subjects and found 45 cases of G6PD Mahidol (487G>A), two of G6PD Coimbra (592C>T), two of G6PD Union (1360C>T), and one of G6PD Canton (1376G>T). Taken together with data from our previous report, 91.3% (73/80) of G6PD variants were G6PD Mahidol. This finding suggests that the Myanmar population is derived from homogeneous ancestries and are different from Thai, Malaysian, and Indonesian populations.     

JAK inhibitor has the amelioration effect in lupus-prone mice: the involvement of IFN signature gene downregulation

Background

We previously reported that JAK–STAT-pathway mediated regulation of IFN-regulatory factor genes could play an important role in SLE pathogenesis. Here, we evaluated the efficacy of the JAK inhibitor tofacitinib (TOFA) for controlling IFN signalling via the JAK–STAT pathway and as a therapeutic for SLE.

Results

We treated NZB/NZW F1 mice with TOFA and assessed alterations in their disease, pathological, and immunological conditions. Gene-expression results obtained from CD4⁺ T cells (SLE mice) and CD3⁺ T cells (human SLE patients) were measured by DNA microarray and qRT-PCR. TOFA treatment resulted in reduced levels of anti-dsDNA antibodies, decreased proteinuria, and amelioration of nephritis as compared with those observed in control animals. Moreover, we observed the rebalance in the populations of naïve CD4⁺ T cells and effector/memory cells in TOFA-treated mice; however, treatment with a combination of TOFA and dexamethasone (DEXA) elicited a stronger inhibitory effect toward the effector/memory cells than did TOFA or DEXA monotherapy. We also detected decreased expression of several IFN-signature genes Ifit3 and Isg15 in CD4⁺ from SLE-prone mice following TOFA and DEXA treatment, and IFIT3 in CD3⁺ T cells from human patients following immunosuppressant therapy including steroid, respectively.

Conclusion

Modulation of type I IFN signalling via JAK–STAT inhibition may exert a beneficial effect in SLE patients, and our results suggest that TOFA could be utilised for the development of new SLE-specific therapeutic strategies.

     

Expression of vascular endothelial growth factor in normal pituitary cells and pituitary adenomas producing adrenocorticotropic hormone

Vascular endothelial growth factor (VEGF) induces endothelial cell proliferation and an increase in capillary permeability. Because the anterior pituitary gland and pituitary adenomas are highly vascular, expression of VEGF was examined immunohistochemically. Some normal pituitary cells stained positively for VEGF, and restaining for ACTH, prolactin, TSH, LH, FSH, and S-100 protein after VEGF staining revealed that almost all cells staining positively for ACTH also stained for VEGF. Only adenomas staining positively for ACTH stained for VEGF. These results suggest that VEGF is produced by normal pituitary cells and adenomas producing ACTH.     

Maintenance of chloroplast-derived sequences in the mitochondrial DNA of Gramineae

Evidence for the transfer of DNA from the chloroplast to the mitochondrion has been reported in many higher plants and, in most cases, the transferred chloroplast genes do not have the ability to encode functional products as a consequence of base substitutions and/or multiple rearrangements. We reported previously that the sequence of one end of a chloroplast-derived (ct-derived) fragment of DNA that contained the rps19 and trnH genes has been maintained in most gramineous plants and that its presence seems to be correlated with gene expression in this region. In the present study, we have investigated whether or not the ct-derived sequences in mitochondrial DNA (mtDNA) from some gramineous plants and species of Oryza are conserved, and whether or not such conservation is related to gene expression in these regions. We identified two junctions between ct-derived and mitochondrial sequences that were conserved among some gramineous plants. Around these regions, we found a ct-derived gene for tRNA and the promoter of a mitochondrial gene on the ct-derived sequences, respectively, and these regions were transcribed through the junctions. This result indicates that the junctions and/or regions that are transcribed and functional in mitochondria have been strongly conserved and maintained during their evolution. In Oryza, some junctions between ct-derived and mitochondrial sequences were conserved and other junctions were not. These variations seem to have been caused by deletions and/or rearrangements, and appear to be specific to the type of genome. In the case of Oryza, the timing of deletions and/or rearrangements of ct-derived sequences is likely to have coincided with the divergence of the various genome types. Received: 24 July / 13 August 1997     

Analysis and typing of the vacA gene from cagA-positive strains of Helicobacter pylori isolated in Japan.

Approximately 50% of Helicobacter pylori strains produce a cytotoxin that is encoded by vacA and that induces vacuolation of eukaryotic cells. Mosaicism in vacA alleles was reported, and there are three different families of vacA signal sequences (s1a, s1b, and s2) and two different families of middle-region alleles (m1 and m2). In addition, the vacA genotype of a strain is associated with its cytotoxin phenotype and its capacity to induce peptic ulceration. To clarify the strain diversity of H. pylori in Japan, 87 Japanese clinical isolates of H. pylori (40 from patients with chronic atrophic gastritis, 25 from patients with duodenal ulcer, 16 from patients with gastric ulcer, 3 from patients with both duodenal and gastric ulcers, and 3 from patients with intestinal type gastric cancer) were characterized by vacA typing by PCR and DNA sequencing. Eighty-four of the 87 isolates were s1a/m1, one was s1b/m1, and two could not be typed. Moreover, all isolates in this study were cagA positive. There were no distinct differences between the cytotoxin-producing strains and cytotoxin-nonproducing strains within the 0.73-kb middle region. Japanese strains were highly homologous, with more than 96% identity in this region, in which maximum divergence has been reported. In addition, there were no associations between the specific vacA types and the level of in vitro cytotoxin activity or the clinical consequences. These results indicate that the cagA-positive, s1a/m1-type strains are common in Japan, regardless of the vacA phenotype or clinical outcome.     

Eosinophilopoietic factors prime eosinophils for increased interleukin-8 generation

Recent studies have identified eosinophils as a cellular source of various cytokines, indicating that eosinophils play not only an effector role but also a regulatory role within the allergic inflammatory cell network. Because eosinophilopoietic factors are known to stimulate various functions of eosinophils, we examined the effect of interleukin (IL)-5 on chemoattractant-induced IL-8 generation from eosinophils. Although IL-5 alone induced little or no IL-8 production from eosinophils, short-term preincubation with IL-5 markedly enhanced the eosinophil IL-8 generation caused by C5a plus cytochalasin B (CB). IL-3 also potentiated C5a-induced IL-8 generation. Both factors were active at picomolar concentrations. Furthermore, competitive polymerase chain reaction (PCR) experiments revealed that the enhancement occurred at the pretranslational level. Since eosinophils in allergic inflammation are believed to be activated by these eosinophilopoietic factors, eosinophil-derived cytokines may play more important roles in the allergic inflammatory cell network than has been previously supposed.     

Multilayered structure of the basal lamina of the tubuli recti in normal mice

Previous studies have demonstrated that the blood-testis barrier (BTB) at the tubuli recti (TR) and the rete testis (RT) is less complete than at the seminiferous tubules (ST). However, there has been no report focusing on the basal lamina, which is an important component of the BTB at both TR and RT. In the present study, we performed electron microscopic observation of the basal lamina at the TR and RT, in comparison with that of those of the ST in normal mice. The results showed that the basal lamina of modified Sertoli cells at the TR segment exhibited a wavy and multilayered structure, but the Sertoli cells of ST and the epithelium of RT had an almost flat and singlelayered basal lamina. It was also noted that wide gaps existed between the modified Sertoli cells, the basal lamina of the epithelial layer, and the myoid cell layer at the middle TR segment. This characteristic structure of the basal lamina of the TR epithelial layer may be one of the factors for its incomplete BTB.