Anti-SARS CoV-2 IgG in COVID-19 Patients with Hematological Diseases: A Single-center,Retrospective Study in Japan

Objective Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread globally. Although the relationship between anti-SARS-CoV-2 immunoglobulin G (IgG) antibodies and COVID-19 severity has been reported, information is lacking regarding the seropositivity of patients with particular types of diseases, including hematological diseases. Methods In this single-center, retrospective study, we compared SARS-CoV-2 IgG positivity between patients with hematological diseases and those with non-hematological diseases. Results In total, 77 adult COVID-19 patients were enrolled. Of these, 30 had hematological disorders, and 47 had non-hematological disorders. The IgG antibody against the receptor-binding domain of the spike protein was detected less frequently in patients with hematological diseases (60.0%) than in those with non-hematological diseases (91.5%; p=0.029). Rituximab use was significantly associated with seronegativity (p=0.010). Conclusion Patients with hematological diseases are less likely to develop anti-SARS-CoV-2 antibodies than those with non-hematological diseases, which may explain the poor outcomes of COVID-19 patients in this high-risk group.     

Comparison of the effective intensity of transcutaneous electrical nerve stimulation contralateral to a pain site for analgesia

[Purpose] This study aimed to compare the effectiveness of transcutaneous electrical nerve stimulation contralateral to the pain site for analgesia to identify the effective stimulation intensity. [Participants and Methods] Ten healthy adult females were recruited for the study. The same heat stimulation was applied to the left wrist joint of each participant to induce pain, serving as the control. Transcutaneous electrical nerve stimulation was then randomly administered to the right wrist, corresponding to the same dermatome contralateral to the painful site, at the intensities of comfortable stimulation, pain threshold, and maximum pain. The effect of transcutaneous electrical nerve stimulation was assessed using a Visual Analogue Scale and by analysis of heart rate variability. [Results] The Visual Analogue Scale score was significantly lower after stimulation with the maximum pain intensity than that for control, and there were no significant differences among the intensities of comfortable stimulation, pain threshold, and maximum pain. No significant differences were found among the groups in terms of high and low-to-high frequency components. [Conclusion] Transcutaneous electrical nerve stimulation at the maximum pain intensity to the dermatome area contralateral to that of the dorsal pain site of the left wrist was considered effective.     

Mortality among persons with a history of Kawasaki disease in Japan: Can paediatricians safely discontinue follow-up of children with a history of the disease but without cardiac sequelae?

Aim: To clarify the question of whether patients with Kawasaki disease suffer a higher mortality rate after the incidence of the disease in comparison with age-matched healthy individuals. Methods: Between July 1982 and December 1992, 52 collaborating hospitals collected data on all patients having a new, definite diagnosis of Kawasaki disease. Patients were followed up until 31 December 2001 or their death. The expected number of deaths was calculated from Japanese vital statistics data and compared with the observed number. Results: Of 6576 patients enrolled, 29 (20 males and 9 females) died. The standardized mortality ratio (SMR: the observed number of deaths divided by the expected number of deaths based on the vital statistics in Japan) was 1.15 (95% CI: 0.77-1.66). In spite of the high SMRs during the acute phase, the mortality rate was not high after the acute phase for the entire group of patients. Although the SMR after the acute phase was 0.75 for those without cardiac sequelae, six males (but none of the females) with cardiac sequelae died during this period; and the SMR for the male group with cardiac sequelae was 1.95 (95% CI: 0.71-4.25). The mortality from congenital anomalies of the circulatory system was elevated, but no increase in cancer deaths was observed.

Conclusion: Although it was not statistically significant, the mortality rate among males with cardiac sequelae due to Kawasaki disease appeared to be higher than in the general population. On the other hand, the mortality rates for females with the sequelae and both males and females without sequelae were not elevated.     

Chronic effects in mice caused by oral administration of sublethal doses of azaspiracid, a new marine toxin isolated from mussels.

Toxicological effects of orally administered azaspiracid (AZA), a new toxin isolated from mussels, were investigated. First, a total of 25 mice were administered AZA twice at 300-450 microg/kg doses and observed for recovery processes from severe injuries. Slow recoveries from injuries were revealed: erosion and shortened villi persisted in the stomach and small intestine for more than 3 months: edema, bleeding, and infiltration of cells in the alveolar wall of the lung for 56 days; fatty changes in the liver for 20 days; and necrosis of lymphocytes in the thymus and spleen for 10 days. Secondly, low doses of AZA (50, 20, 5 and 1 microg/kg) were administered twice a week up to 40 times to four groups of mice. Many mice, nine out of ten at 50 microg/kg and three out of ten at 20 microg/kg, became so weak that they were sacrificed before completion of 40 injections. All these mice showed interstitial pneumonia and shortened small intestinal villi. Most importantly, lung tumor were observed in four mice, one out of ten (10%) at 50 microg/kg and three out of ten (30%) at 20 microg/kg. Tumors were not observed in 11 mice treated at lower doses and in 19 control mice. Hyperplasia of epithelial cells was also observed in the stomach of six mice out of ten administered at 20 microg/kg.     

Suppression of Sympathetic Nervous System Attenuates the Development of Two-Kidney, One-Clip Goldblatt Hypertension

Purpose

This study tried to assess the possible contribution of the sympathetic nervous system to the onset of two-kidney, one-clip (2K-1C) Goldblatt hypertension.

Materials and Methods

The effect of chlorisondamine administration with or without subsequent splanchnicotomy on the development of hypertension was examined in 2K-1C rats with special reference to norepinephrine synthesis.

Results

The 2K-1C rats were treated either with chlorisondamine or chlorisondamine plus subsequent splanchnicotomy, so that the development of hypertension was effectively arrested for 4 weeks. An apparently high rate of release of norepinephrine in 2K-1C rats was reduced by treatment with chlorisondamine plus splanchnicotomy. A similar trend was also seen in plasma norepinephrine concentration and norepinephrine clearance, to a lesser extent. There were significant positive relationships between percent change of systolic blood pressure and apparent rate of release of norepinephrine, plasma norepinephrine concentration and norepinephrine clearance in 2K-1C rats and 2K-1C + chlorisondamine + splanchnicotomy rats. There were no significant relationships in these parameters in sham-treated rats.

Conclusion

Increased sympathetic innervation appears to participate in the development of 2K-1C Goldblatt hypertension.     

Adenoviral E1A suppresses secretory leukoprotease inhibitor and elafin secretion in human alveolar epithelial cells and bronchial epithelial cells

BACKGROUND: An imbalance between neutrophil protease and surrounding antiprotease levels has been shown to be important in the pathogenesis of chronic obstructive pulmonary disease (COPD). Adenoviral E1A DNA and protein are frequently detected in the lungs of COPD patients. As secretory leukoprotease inhibitor (SLPI) and elafin/skin-derived antileukoproteinase (SKALP) are locally produced in the lung and inhibit neutrophil elastase activity, we hypothesized that adenoviral E1A might affect the production of these antiproteases. OBJECTIVES: To examine the effect of E1A on SLPI and elafin/SKALP secretion in A549 (alveolar epithelial) cells and primary human bronchial epithelial (HBE) cells. METHODS: SLPI and elafin/SKALP were quantitated from cell culture supernatants using an ELISA. SLPI mRNA expression was examined by Northern blotting, and SLPI promoter activity was measured using a reporter gene assay. RESULTS: E1A significantly suppressed SLPI and elafin/SKALP secretion by A549 cells upon interleukin (IL)-1beta stimulation. E1A also suppressed SLPI and elafin/SKALP secretion by HBE cells. SLPI mRNA expression in A549 cells was suppressed by E1A regardless of IL-1beta stimulation. IL-1beta-induced SLPI promoter activity was suppressed by E1A gene transfection into A549 cells. CONCLUSIONS: Our findings of adenoviral E1A-mediated suppression of SLPI and elafin/SKALP secretion suggest that E1A may be involved in the enhancement of alveolar damage and play a role in the COPD process.     

Tumor-associated macrophages and angiogenesis in early stage esophageal squamous cell carcinoma

Background

The association between angiogenesis and tumor-associated macrophages (TAMs) is unclear. Mononuclear cell infiltration was reported to induce angiogenesis in early stage esophageal squamous cell carcinoma (ESCC).

Methods

The study materials included 14 samples of normal squamous epithelium, 11 samples of low-grade intraepithelial neoplasia, and 64 samples of superficial esophageal cancer (M1 and M2 cancer 27; M3 or deeper cancer 37). We assessed microvessel density (MVD) using CD34 and CD105 immunostaining and monocyte count (MC) using CD68 and CD163 immunostaining in relation to the histological type or grade of mononuclear cell infiltration, as well as the correlation between MVD and MC.

Results

MVD and MC increased in accordance with histological type, and the differences were significant (P < 0.001). MVD and MC were significantly higher in M1 and M2 lesions than in normal squamous epithelium (P < 0.05). MVD (CD34 and CD105) and MC (CD68 and CD163) were significantly correlated with the degree of mononuclear cell infiltration (P < 0.001), and there was a strong correlation between MC assessed using CD68 and MC assessed using CD163 (rS = 0.93, P < 0.001). The CD163/CD68 ratio did not differ significantly according to histological type. There was a significant correlation between MVD assessed using CD105 and MC assessed using CD68 (rS = 0.69, P < 0.001) and CD163 (rS = 0.67, P < 0.001). MVD assessed using CD34 was also significantly correlated with MC assessed using both CD68 (rS = 0.59, P < 0.001) and CD163 (rS = 0.57, P < 0.001).

Conclusion

The number of TAMs is significantly associated with the development of neovasculature in the early stage of ESCC progression.

     

Mechanical properties of new self-adhesive resin-based cement

PurposeThe aim of this study was to compare the bonding strength, flexural strength, elastic modulus, water absorption and the expansion after water storage of new self-adhesive resin cements to commercially available dental cements.MethodsTwo types (hand-mix and auto-mix) of new self-adhesive resin cements (SAC-H and SAC-A, Kuraray Medical), one conventional resin cement (Panavia F2.0), three self-adhesive resin cements (Relyx Unicem, Maxcem and G-Cem), and two resin-modified glass-ionomer cements (Fuji Luting S and Vitremer) were used. Shear bond strengths, flexural strengths and elastic moduli (ISO 4049), water absorption (ISO 4049), and the expansion rate after water storage were investigated.ResultsBoth SAC-H and SAC-A provided adhesion to enamel and dentin, and had the same bond strength to gold alloy and zirconia as conventional resin cements. SAC-H and SAC-A had greater flexural strengths (86.4–93.5 MPa) than commercial self-adhesive resin cements or glass-ionomer cements. The elastic moduli of self-adhesive and glass-ionomer cements were 5.2–7.4 GPa and 2.3–3.4 GPa, respectively. The water absorption of SAC-H and SAC-A (26.3–27.7 μg/mm³) were significantly lower than commercial self-adhesive resin cements. SAC-H and SAC-A showed significantly lower expansion rates (0.17–0.26%) than commercial self-adhesive cements and glass-ionomer cements after 4 weeks water storage.ConclusionsIt is suggested that the new self-adhesive resin cements exhibited a favorable bonding capability and mechanical properties.