コロナの後遺症

Patients often report various symptoms after recovery from acute COVID-19. These symptoms are called Long COVID. Although coronaviruses have been mutated and changes in infectivity have been noted, there have been no reports of differences in symptoms of Long COVID between strains of coronaviruses. In order to examine the differences in sequelae caused by different viral strains, we examined the age, sex, and symptoms of patients who visited the outpatient clinic of Hakuai Memorial Hospital from July 2021 to October 2022, and classified these patients into three periods（Period I : July to December, Period II : January to May, and Period III : June to October）. month） Period I corresponded to the pre-Delta strain, Period II to the Omicron strain, and Period III to the subtype. There were 401 patients, 45 in stage I（21 males, 24 females, average age of 41 years）, 178 in stage II（70 males, 108 females, average age 42.7 years）, and 178 in stage III（74 males, 104 females, average age 42.8 years）. Women tended to be more numerous than men. Most of the patients had been vaccinated, and 22 had not been vaccinated. The place of care after the diagnosis of COVID infection was examined, and 42％ of the inpatients were hospitalized in Period I, while most patients in Periods II and III recuperated at home or in hotels. The age distribution of the patients showed that most of them were between 30 and 70 years old, indicating a trend toward middle-aged and older persons. This trend was the same for all stages from stage I to stage III. Their symptoms are very varied. Patients with cough, phlegm, and pharyngeal discomfort being more common in stage II and stage III. while olfactory and respiratory disturbances were more common in stage I. Long-term patients were mostly malaise and memory impairment, and many of them were mild cases at the onset of the disease. Symptoms of the patients were often related to various medical departments, and it was considered important to collaborate with them. It is also important to avoid infection because sequelae can develop even in those with mild symptoms

Protease-induced leukocyte chemotaxis and activation: roles in host defense and inflammation

The migration of leukocytes such as neutrophils, monocytes and lymphocytes into inflamed lesions is one of the critical events of inflammation. Although the traditional function of neutrophil-derived antimicrobial proteases is to ingest and kill bacteria, some neutrophil serine proteases have been shown to induce leukocyte migration and activation. Mast cell-derived chymase also has the chemotactic activity for leukocytes. During the acute phase of inflammatory and allergic diseases, the predominantly migrated cells are neutrophils and mast cells, respectively, and in the subsequent chronic phase, monocytes and lymphocytes are mainly migrated. The chemotactic activity for monocytes and lymphocytes of neutrophil-derived serine proteases and mast cell-derived chymase may have a role in switching acute inflammation to chronic inflammation and delayed-type hypersensitivity. Recently, aminopeptidase N and endothelin were shown to induce chemotactic migration of leukocyes. Thus, protease-induced leukocyte chemotaxis and activation may play an important role in immunologic events of inflammatory and allergic diseases

Age-related increase of autoantibodies to interleukin 1α in healthy Japanese blood donors

Although autoantibodies to interleukin-1α (IL-1α autoantibodies) are known to be present in sera of apparently healthy humans, their frequency of occurrence and significance are unclear. To determine the prevalence of detectable IL-1α autoantibodies in normal human blood, we screened the plasma of blood donors (6290 subjects : 3977 men and 2313 women, ages 16 to 64 yr) by a radioimmunoassay which we developed using a method that could detect over 5 ng/ml. Moreover, we investigated immunoglobulin class of IL-1α autoantibodies and also their function. IL-1α autoantibodies were detected in 14.6% of the 6290 donors. Their frequency was higher in males than females (16.6% vs.11.2%, p<0.01) and increased with age in both sexes. The proportion of subjects with a high IL-1α autoantibodies titers also increased with age. We showed that IL-1α autoantibodies were of the IgG class and that they had neutralizing function to IL-1α by receptor assay. Neutralizing activity was only shown in plasma with concentration of IL-1α autoantibodies, the level of which was over 1000 ng/ml. The affinity of the IL-1α autoantibodies in plasma was between 2.1 X 10-10and 1.2 X 10-9 M (mean 6.4 X 10-10M). Our results provide a basis for comparison with IL-1α autoantibodies prevalence between healthy states and disease states, and suggest that IL-1α autoantibodies may play a significant role in modulating the effects of excessive IL-1α at local site or in systemic regions

A case of sarcoidosis associated with chronic eosinophilic pneumonia

A 38-year-old man was hospitalized in our university hospital because of pulmonary opacities with bilateral hilar and mediastinal lymphadenopathy seen on chest radiograph. Eosinophilia was observed in the circulation and bronchoalveolar lavage (BAL) fluid. Histological examination revealed noncaseating epithelioid granulomas and eosinophilic infiltration in the lung. Based on these findings, a diagnosis of sarcoidosis combined with chronic eosinophilic pneumonia was made. The infiltrates on chest radiograph and BAL eosinophilia were promptly reduced with corticosteroid therapy, but only mild reduction was observed in diffuse nodular shadows and hilar and mediastinal lymphadenopathy, and high amounts of lymphocytes in BAL fluid remained. Increased IFN-γ, IL-4 and IL-5 were detected in the BAL fluid, and corticosteroid therapy reduced IL-4 and IL-5 (Th-2 cytokines) but not IFN-γ(Th-1 cytokine). These cytokine levels in BAL fluid were intimately correlated with the clinical course of sarcoidosis and chronic eosinophilic pneumonia

Thrombin stimulates platelet-derived growth factor release by alveolar macrophages in rats : significance in bleomycin-induced pulmonary fibrosis

Thrombin is a multifunctional enzyme generated at sites of vascular injury, and is known to be increased in the lungs in some types of fibrotic lung disease. In this study, to determine whether thrombin is associated with fibroblast growth and pulmonary fibrosis in these disorders, we examined whether a growth factor for fibroblasts (platelet-derived growth factor, PDGF) was released by thrombin-stimulated alveolar macrophages (AM). The culture supernatants of rat AM stimulated with 1 or 10 U/ml of thrombin showed a significant increase in fibroblast growth-stimulating activity (FGA). Pretreatment of the AM supernatant with anti-PDGF-AA antibody significantly decreased the FGA, but pretreatment with anti-PDGF-BB antibody did not. The supernatants of AM stimulated with thrombin also increased the growth of fibroblasts from the lungs of rats with bleomycin-induced lung injury. These results indicate that thrombin stimulates AM to release PDGF-AA, which is responsible, at least in part, for fibroblast growth and the development of pulmonary fibrosis in some types of fibrotic lung disease

Interleukin-8 in bronchoalveolar lavage fluid of patients with diffuse panbronchiolitis or idiopathic pulmonary fibrosis

This study was designed to clarify the contribution of IL-8 as a specific neutrophil chemotactic factor in the human respiratory tract in various pulmonary diseases. The neutrophil chemotactic activity(NCA), neutrophil counts and IL-8 concentration in the bronchoalveolar lavage fluid (BALF) obtained from normal volunteers (NV), control patients (CP), patients with diffuse panbronchiolitis (DPB) and patients with idiopathic pulmonary fibrosis (IPF) were examined. Neutrophil counts, NCA and IL-8 concentration in BALF obtained from patients with DPB or IPF was significantly higher than that from NV or CP. The IL-8 concentration correlated with neutrophil count and also correlated with NCA in BALF from patients with IPF, whereas there was no correlation between these factors in BALF from DPB. These results suggest that the contribution of IL-8 to neutrophil accumulation of the lower respiratory tract is different between IPF and DPB

Complete and durable response of pulmonary large-cell neuroendocrine carcinoma to pembrolizumab

Background: Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare and aggressive tumor with a poor prognosis and standard therapy has not yet been established. Case: A 65-year-old male with a cough for 2 months presented to our hospital. He was clinically diagnosed with non small cell lung cancer cT3N1M0 stage IIIA and underwent right pneumonectomy. The final diagnosis was pulmonary LCNEC pT3N1M0 stage IIIA. Multiple subcutaneous masses were detected 4 months after surgery, and biopsy revealed postoperative recurrence and metastasis. Chemotherapy with carboplatin plus etoposide was initiated. Subcutaneous masses increased and multiple new brain metastases developed after two cycles. Additional tests revealed that epidermal growth factor receptor and anaplastic lymphoma kinase were negative, and the programmed death ligand 1 (PD-L1) expression rate in tumor cells was 40% (22C3 clones). The primary cells infiltrating the tumor were CD3-positive T cells and CD138-positive plasma cells. Second-line treatment with pembrolizumab was started. The shrinkage of subcutaneous masses was observed after one cycle, and the tumor had completely disappeared after six cycles. Treatment was continued for approximately 2 years. This response has been maintained for 4 years and is still ongoing. Conclusion: Pembrolizumab may be used as a treatment option for pulmonary LCNEC