長崎市内に発生したアデノウイルス3型に因る咽頭結膜熱の流行

In summer, 1966, the patients of acute respiratory illness characterized by elevated fever, pharyngitis and/or conjunctivitis were observed among school-children at Nagasaki city. All patients had history of swimming to pool on end of July, and the number of cases increased rapidly on beginning of August. The etiologic diagnosis of the epidemic was made by virus isolation and serologic investigation on patients visited hospitals, and adenovirus was isolated in HeLa cell cultures from those patients and virus isolation rate was 41% of 54 cases. Isolated viruses were all identified as type 3 using a rabbit antiserum against adenovirus type 3. A significant rising of antibodies on complement-fixing and neutralizing tests was each 77%. and 94% of acute and convalescent sera collected from 54 cases. Thirty-four of 54 cases was diagnosed by virus isolation or serologic investigation as adenovirus type 3 infection.1966年7月下旬から8月上旬にかけて 長崎市内の学童の間で咽頭結膜熱様疾患の多発が気付かれた。38℃以上40℃に及ぶ発熱を主訴とし、咽頭炎、結膜炎を伴う患者が50%以上に認められ、下痢、嘔吐などの消化器症状をも伴っていた。市内の病院を訪れた54名の外来患者からウイルス分離検体として、咽頭拭液及び糞便を採取し、HeLa細胞を用いた組織培養法により、患者54名中22名(41%)、検体別では咽頭拭液52件中16株(31%)、糞便32件中14株(44%) 計30株のウイルスを分離することが出来た。臨床像及びHeLa細胞による細胞変性効果からアデノウイスルが推定され、アデノウイルス3型の免疫血清を用いて、中和反応による同定試験を行った結果、分離ウイルスはすべてアデノウリルス3型であることを確認した。又、血清学的検査を行う為に、患者の急性期及び回復期のペア血清を採取できた17件について、補体結合試験及び中和試験を行った結果、補体結合抗体では1７件中13件(77%)、中和抗体については17件中16件(94%)にアデノウイルス3型に対する有意の抗体上昇を認めた。ウイルス分離陽性或は血清抗体陽性であった患者の殆どは、長崎市内の南部にある網場プール及び東高校プールで7月20日から8月11日の間に遊泳の形跡があり、この咽頭結膜熱の病院はプールを介するアデノウイルス3型に因る感染である事を証明した

Relationships between activity of daily living, and oral cavity care and the number of oral cavity microorganisms in patients with cerebrovascular diseases

We examined the relationships among the activity of daily living (ADL), oral cavity care, and the number of oral cavity microorganisms in 40patients with cerebro-vascular diseases (CVD). The CVD patients were classified into 4groups, I, II, III and IV based on their ADL and the method used for oral cavity care. The ADL was highest in group I and lowest in group III. Only the patients of only group III could not eat by themselves and were receiving naso-esophageal feeding. Oral cavity care was performed by the patients themselves in groups I and IV, but was performed by caregivers in groups II and III. The group IV patients had no teeth, but could eat by themselves using full dentures. The numbers of microorganisms in the pharyngeal swabs from the 4groups were measured and expressed as colony-forming units (cfu). The numbers of both Staphylococci spp. and Candida spp. were significantly higher in group III than in the other groups. Moreover, Pseudomonas aeruginosa was isolated only from patients of group III (in about 66%). The oral cavity care by caregivers was almost the same in groups II and III, but the numbers of oral cavity microorganisms were significantly higher in group III than in group II. These results indicated that microorganisms grow more easily in the oral cavities of CVD patients with low ADL compared with CVD patients with higher ADL, and that eating is thought to be important for the prevention of an increase of microorganisms in the oral cavity

Stress Tolerance in Subjects with Myocardial Infarction

In our course of surveys to study the relationship between stress and myocardial infarction (MI), we have investigated whether stress tolerance may play a significant role when MI develops. To elucidate the possible role of stress tolerance, we examined 96 patients with MI (68 men and 28 women, age 40-90 years) with a stress tolerance check list in which stress tolerance was quantified as total points for 20 self-evaluated items, each scored between 1 and 4 points. Their scores were compared with control values obtained from persons not suffering from MI, and further analyzed by dividing them into 3 groups according to their grade of stress tolerance; that is, low (39 or less in score), moderate (40-49) and high (50-80). The mean stress tolerance score (± SD) was significantly lower in the 96 MI patients (49.5 ± 8.90 points) than in the controls (60.8 ± 7.3 points). The stress tolerance grade was low in 13 of the 96 (13.5%), moderate in 34 (35.5%) and high in 49 (51.0%). In MI patients, lowly or moderately stress-tolerant persons were significantly higher in percentage (49.0%) than in the controls (6.3%). These results clearly indicate that low stress tolerance is a risk factor in the development of MI

Prospective Study of Gefitinib Readministration After Chemotherapy in Patients With Advanced Non-Small-Cell Lung Cancer Who Previously Responded to Gefitinib

The present study was designed to prospectively evaluate the clinical efficacy of gefitinib readministration in patients with advanced non-small cell lung cancer who responded well to initial gefitinib, followed by cytotoxic chemotherapy. Twenty subjects were enrolled, and 3 and 6 patients achieved partial response and stable disease, respectively. These findings provide valuable information for the management of previous gefitinib responders. Introduction: Salvage treatment for acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitor in patients with non-small-cell lung cancer is a matter of clinical concern. Several retrospective reports have indicated the usefulness of epidermal growth factor receptor tyrosine kinase inhibitor readministration; however, there have been few prospective studies. Materials and Methods: This study was designed to prospectively evaluate the clinical efficacy of gefitinib readministration in patients with advanced or metastatic non-small-cell lung cancer who responded well to initial gefitinib treatment. The subjects received at least 1 regimen of cytotoxic chemotherapy after progressive disease with the initial gefitinib therapy. Gefitinib administration (250 mg/d, orally) was started after progressive disease with the previous chemotherapeutic regimen. The primary endpoint in the present study was the response rate. Results: Twenty patients were enrolled between April 2007 and May 2011. Three patients achieved partial response, and 6 showed stable disease. Thus, the overall response rate and disease control rate of gefitinib readministration were 15% (95% Cl, 3.21-37.9) and 45% (95% Cl, 23.1-68.5), respectively. Median progression-free survival and overall survival from the start of gefitinib readministration were 2.0 months (95% Cl, 0.9-3.1 months) and 12.0 months (95% Cl, 8.0-16.0 months), respectively. Conclusion: These results suggest that gefitinib readministration may be an option, albeit with a low response rate and short progression-free survival, for patients who responded well to initial gefitinib followed by systemic chemotherapy. These findings provide valuable information for the management of previous gefitinib responders.ArticleCLINICAL LUNG CANCER. 13(6):458-463 (2012)journal articl

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target