Histopathological features of the bronchi in severe bronchial asthma--a statistical analysis]

The aim of this study was to examine the histopathological features of the bronchi in patients with severe bronchial asthma. Seventy-four autopsy cases of death from severe bronchial asthma were analyzed statistically. The areas of the bronchial wall, smooth muscle, bronchial glands, basement membrane, and bronchial bore, were measured at the level of the subsegmental bronchi. Normal lungs from 34 autopsy cases without any respiratory pathology were used as controls. All of these areas but the last were significantly increased in severe bronchial asthma. The bronchial bore area was significantly decreased. Moreover, the above areas in low and moderate goblet cell hyperplasia cases were compared with those in high goblet cell hyperplasia cases. In the latter, the areas of the smooth muscle, bronchial glands and basement membrane were significantly elevated and those of the bronchial bore were significantly decreased. Finally, the areas of the bronchial bore, smooth muscle and bronchial glands were also compared between groups presenting with three different levels of basement membrane thickening, but no significant difference was noted. Further study to examine the precise morphological changes is needed to elucidate the characteristics of bronchi in severe bronchial asthma patients.     

Polymorphism of CCR5 affecting HIV disease progression in the Japanese population

Among several factors associated with HIV-1 disease progression, genetic polymorphism of CCR2, CCR5, and CXCR4 in HIV-1 infection has been found. Single-nucleotide polymorphisms (SNPs) in the CCR2, CCR5, and CXCR4 genes as well as a 32-base pair deletion in the open reading frame of the CCR5 gene are associated with HIV disease progression among Caucasians and African-Americans in North America and Europe. However, in populations other than Caucasians and African-Americans, SNPs have not been fully examined. In our study SNPs in CCR2 coding and CCR5 regulatory regions have been examined in 98 Japanese HIV-positive individuals. The alleles of CCR5 regulatory regions at -2135T and -2086G are associated with late onset of AIDS (p < 0.05; odds ratio for the early onset of AIDS, 0.502 and 0.404, respectively). In contrast to this, the allele of CCR5 at -2086A is associated with the early onset of AIDS (p < 0.05; odds ratio for the early onset of AIDS, 2.133). A haplotype including two alleles at -2135G and -2086G is associated with the late onset of AIDS (p < 0.05; odds ratio for the early onset of AIDS, 0.372). Thus we found that a CCR5 SNP and haplotype polymorphism affect HIV disease progression even in the Japanese population. This indicates that the CCR5 genetic polymorphism affecting disease progression should be studied in a wider range of population.     

CD3 down-regulating factor in sera and culture supernatants of leukaemic cells from patients with adult T cell leukaemia

Immunological abnormality of T lymphocytes in patients with adult T cell leukaemia (ATL) is characterized by abnormal expression of the 55 kD chain of the receptor for interleukin 2 (IL-2R/p55) (Tac), and the down-regulation of CD 3 expression. Using serum and culture supernatants of leukaemic cells from ATL patients (Group A) whose CD 3 expression was down-regulated and those (Group B) whose CD 3 was not low, the possible mechanism of CD 3 down-regulation on ATL cells was discussed. When PBMC from normal individuals were cultured with sera from ATL patients for 24 h, CD 3 expression revealed by mean fluorescent intensity (MFI) was down-regulated by sera from ATL patients in Group A (MFI: Pt 1 = 51.6 ± 4.5, Pt 2 = 48.0 ± 6.9, control = 96.5 ± 6.6), not by sera from patients in Group B (MFI: Pt 3 = 105.5 ± 7.9, Pt 4 = 102.5 ± 8.3, control = 96.5 ± 6.6). When normal PBMC were cultured with supernatants of leukaemic cells from ATL patients in Group A, this CD 3 down-regulating activity was also detected (MFI: Pt 1 = 78.0 ± 10.2, Pt 2 = 70.6 ± 8.7, control = 94.0 ± 6.6). By using gel-chromatography, the fractionated supernatants from ATL patients in Group A decreased CD 3 expression of normal PBMC significantly (MFI: Pt 1 = 22.9 ± 5.8, Pt 2 = 28.8 ± 7.4, control = 92.1 ± 9.6). This CD 3 down-regulating activity in fractionated supernatant was not inhibited by any lymphokine antibodies, anti-IL-1α antibody (Ab), anti-IL-1B Ab, anti-IL-2 Ab, anti-IL-3 Ab, anti-IL-4 Ab, anti-IL-6 Ab, anti-TNF-α Ab and anti-IFN-γ Ab. Any known cytokines (IL-1, IL-2, IL-3, IL-4, IL-6, TNF-α and IFN-γ) could not modulate CD 3 expression of normal PBMC. These findings suggested that there are novel factor(s) with CD 3 down-regulating activity in the serum and culture supernatant of ATL patient and those factor(s) are involved in progression of ATL.     

Relation of QT-interval variability to ventricular arrhythmias during percutaneous transluminal coronary angioplasty

The present study investigated the role of the dispersion of QT interval in percutaneous transluminal coronary angioplasty (PTCA)-induced ventricular tachyarrhythmias. Patients with effort angina without a previous myocardial infarction (n = 22), who had single-vessel disease of the anterior descending coronary artery (LAD), underwent PTCA if the coronary lesion was 75% or more stenosed in segment 6 or 7 of the LAD. The standard 12-lead ECG was continuously recorded during the procedure. Averaged QTc and QTac intervals, where QTac was the interval from the beginning of QRS complex to the nadir of T wave corrected by Bazett's formula, did not change significantly during PTCA. Of the 22 patients, 7 showed ventricular arrhythmias during PTCA. The maximum difference (deltaQTc) and the standard deviation (QTcSD) of the corrected QT interval in the standard 12-lead ECG increased significantly during PTCA in the 7 patients with ventricular arrhythmias, whereas they decrreased in the 15 patients without ventricular arrhythmias. deltaQTac and QTacSD were not affected by PTCA regardless of ventricular arrhythmias, which shows that the increases in the variation of the ventricular repolarization process play a role in PTCA-induced ventricular arrhythmias.     

Indication of aortocoronary by-pass for coronary arterial obstruction due to Kawasaki disease

Summary Six patients with coronary arterial lesions due to Kawasaki disease underwent aortocoronary by-pass grafting at our institute. Before surgery, all of them had been closely monitored for some years by means of selective coronary arteriography, thallium myocardial imaging, electrocardiography (treadmill and/or Holter), and two-dimensional echo cardiography. Based on this experience, we propose the following guidelines as an indication for aortocoronary by-pass in such patients. First, the following three conditions should be satisfied: 1) The progress of coronary arterial lesions has been documented by serial selective coronary arteriography; 2) redistribution to the perfusion defect has been detected on the delayed image in myocardial imaging; 3) no coronary arterial lesions distal to the graft site have been detected by coronary angiography. When these three conditions are satisfied, at least one of the following conditions must apply: 1) Localized stenosis in the left main trunk has progressed to critical stenosis; 2) there is occlusion of two or more vessels; 3) collateral vessels connecting to the peripheral portion of an occluded coronary artery arise from the peripheral part of a vessel with progressive localized stenosis; 4) progressive localized stenosis or critical stenosis has developed in the left anterior descending artery, in addition to significant stenosis in the right coronary artery.     

Effect of temporary school closure due to COVID-19 on musculoskeletal function in elementary school children

Objective: In 2020, coronavirus disease-2019 (COVID-19) became the cause of a pandemic. In response, the Japan Sports Agency issued warnings about secondary damage to health, such as the threat to physical and mental well-being due to the lack of exercise in this situation. In this study, we report on cross-sectional and longitudinal examinations of standing trunk flexion to evaluate how temporary long-term school closures affected musculoskeletal function in elementary school students.Patients and Methods: All children in one public elementary school in T-city during the school years 2019 and 2020 were included in this study. A digital forward flexion meter was used to measure standing trunk flexion.Results: In this study, 284 (284/289: 98.3%) and 266 (266/274: 97.1%) children in school years 2020 and 2019, respectively, were found to have valid data for cross-sectional analysis. The standing trunk flexion did not show significant differences between grades or sexes. In the longitudinal analysis, the results of the comparison of standing trunk flexion in children for two consecutive years revealed significant differences only between grades 3 and 4 (P<0.05) and between girls in grades 3 and 4 (P<0.01), but no significant differences in other grades or among boys or girls were observed.Conclusion: Initially, we expected that there would be a difference in the results of functional assessment using standing trunk flexion depending on the period of absence from school. However, the results of this study showed no significant changes in standing trunk flexion. Moreover, since children’s musculoskeletal functions may be affected by various factors during the COVID-19 pandemic, they should be carefully monitored in the future.     

Effects of dextran sulfates on the acute infection and growth stages of Toxoplasma gondii

Toxoplasma gondii is one of the most prevalent parasites, causing toxoplasmosis in various warm-blooded animals, including humans. Because of the broad range of hosts susceptible to T. gondii, it had been postulated that a universal component of the host cell surface, such as glycosaminoglycans (GAGs), may act as a receptor for T. gondii infection. Carruthers et al. (Infect Immun 68:4005–4011, 2000) showed that soluble GAGs have also been shown to disrupt parasite binding to human fibroblasts. Therefore, we investigated the inhibitory effect of GAGs and their analogue dextran sulfate (DS) on T. gondii infection. For up to 24 h of incubation after inoculation of T. gondii, the inhibitory effect of GAGs on T. gondii infection and growth inside the host cell was weak. In contrast, DS markedly inhibited T. gondii infection. Moreover, low molecular weight DS particularly slowed the growth of T. gondii inside host cells. DS10 (dextran sulfate MW 10 kDa) was the most effective agent in these in vitro experiments and was therefore tested for its inhibitory effects in animal experiments; infection inhibition by DS10 was confirmed under these in vivo conditions. In this report, we showed that DSs, especially DS10, have the potential of a new type of drug for toxoplasmosis.     

Mutation Analysis of the IL36RN Gene in 14 Japanese Patients with Generalized Pustular Psoriasis

Generalized pustular psoriasis (GPP) is a rare, potentially life threatening, and aggressive form of psoriasis, which is characterized by sudden onset with repeated episodic skin inflammation leading to pustule formation. Familial GPP is known to be caused by recessively inherited mutations in the IL36RN gene, which encodes interleukin 36 receptor antagonist (IL‐36Ra). In this article, we performed mutation analysis of the IL36RN gene in 14 Japanese patients with GPP, and identified mutations in two of these patients analyzed. One patient was compound heterozygous for mutations c.115+6T>C and c.368C>G (p.Thr123Arg), whereas the other carried compound heterozygous mutations c.28C>T (p.Arg10*) and c.115+6T>C in the IL36RN gene. Expression studies using total RNA from the patients’ skin revealed that the mutation c.115+6T>C resulted in skipping of exon 3, leading to a frameshift and a premature termination codon (p.Arg10Argfs*1). The protein structure analysis suggested that the missense mutation p.Thr123Arg caused misfolding and instability of IL‐36Ra protein. In vitro studies in cultured cells showed impaired expression of the p.Thr123Arg mutant IL‐36Ra protein, which failed to antagonize the IL‐36 signaling pathway. Our data further underscore the critical role of IL36RN in pathogenesis of GPP.