Studies on so called "Umayado Disease" 1. About its Etiological and Clinical items

I have made researches on the kernel of an eruptive febrile disease which is usually seen, exceptionally in summer, at Aioi-mura, Okawa-gun, the eastern part of Kagawaken. The nature of this disease was unknown but I have succeeded in the isolation of Rickettsia from a patient, and made it clear that bacteriological natures and the Rickettsia isolated are identical with Rickettsia tsutsugamushi (orientalis). A similar disease in Tsuda-cho, Okawa-gun has been proved also to be Tsutsugamushi disease. while it can be seen in winter. This proves that there is a serious kind of Tsutsugamushi disease that develops in summer and a comparatively mild kind that develops in winter. The following shows the research I have made through clinical findings on each of the different types of tsutsugamushi disease. 1. Both Aioi-mura and Tsuda-cho are topographically located near the sea. It is usually the case that the patients houses are situated in lower land districts. 2. It develops only in summer in Aioi-mura with the duration of months from June to September. 3. It develops irrespective of age. In the block of Umayado (Aza Umayado) and Sakamoto (Aza Sakamoto) of Aioi-mura, I have found all the people, regardless of their ages, exposed in their home to the attack of the disease. 4. People of the contaminated areas are engaged in farming with fishing as their side job. Almost none of them raise pigs. This shows that pigs are not the cause of it. It is not as yet clear whether it is from the migratory birds. 5. No relation of cause and effect can be found between the occupation of the villagers snd the outbreak of the disease of the patients. 6. Clinical findings of the patients Mr. Mitani who had the disease in summer in Aioimura, and Mr. Tanizawa, in winter in Tsuda-cho are both found to be the same with those of Tsutsugamushi disease, and antibiotics especially the Terramycin is effective for it. Serums of the patients agglutinated the OXK remarkably, and assurance of the rising of the agglutination titers shows that it does not differ from the Tsutsugamushi disease. 7. The antibiotics especially the Chloromycetin and Terramycin are very effective. With these antibiotics the fever goes down. After the fever drops, it is difficult to isolate the Rickettsia from the blood. In brief, I have analyzed the clinical findings of de-velopment of "Umayado Disease", a local eruptive febrile disease, and at the same time, classified the peculiar local type of Tsutsugamushi disease according to the clinical findings into the summer type and the winter one. This leads to the fact that in a single prefecture and moreover at the places quite close to each other there can be seen a serious and a mild type of Tsutsugamushi disease in summer and winter respectively, which I think is sure to contribute to the study on the distribution and epidemic researches of Tsutsugamushi disease

Transcriptome Analysis Reveals Key Genes Involved in Weevil Resistance in the Hexaploid Sweetpotato

Because weevils are the most damaging pests of sweetpotato, the development of cultivars resistant to weevil species is considered the most important aspect in sweetpotato breeding. However, the genes and the underlying molecular mechanisms related to weevil resistance are yet to be elucidated. In this study, we performed an RNA sequencing-based transcriptome analysis using the resistant Kyushu No. 166 (K166) and susceptible Tamayutaka cultivars. The weevil resistance test showed a significant difference between the two cultivars at 30 days after the inoculation, specifically in the weevil growth stage and the suppressed weevil pupation that was only observed in K166. Differential expression and gene ontology analyses revealed that the genes upregulated after inoculation in K166 were related to phosphorylation, metabolic, and cellular processes. Because the weevil resistance was considered to be related to the suppression of larval pupation, we investigated the juvenile hormone (JH)-related genes involved in the inhibition of insect metamorphosis. We found that the expression of some terpenoid-related genes, which are classified as plant-derived JHs, was significantly increased in K166. This is the first study involving a comprehensive gene expression analysis that provides new insights about the genes and mechanisms associated with weevil resistance in sweetpotato

Pharmacokinetics of Weekly Paclitaxel and Feasibility of Dexamethasone Taper in Japanese Patients with Advanced Non–small Cell Lung Cancer

AbstractPurposeWeekly paclitaxel combined with a platinum-based agent has been advocated as an alternative regimen for patients with advanced non–small cell lung cancer (NSCLC). Limited studies exist on the tolerability of weekly paclitaxel in Japanese patients with advanced NSCLC. Furthermore, the feasibility of dexamethasone taper in the premedication regimen for weekly paclitaxel has not been examined in these patients. To address this issue, we assessed the maximum tolerated dose, dose-limiting toxicity, and pharmacokinetics of weekly paclitaxel in Japanese patients with advanced NSCLC in a dose-escalation Phase I trial and examined the feasibility of dexamethasone taper in these patients.MethodsWeekly 1-hour infusions of paclitaxel were administered at doses of 80 to 120 mg/m2 (dose escalation of 20 mg/m2). The 7-week treatment cycle consisted of 6 infusions followed by a 2-week treatment interval. Pharmacokinetics were assessed during the first cycle. Dexamethasone was commenced at 16 mg and doses were successively halved if hypersensitivity reactions were absent.FindingsA total of 15 patients with either Stage IIIB or IV NSCLC were enrolled. Although no dose-limiting toxicity was observed at 120 mg/m2, 4 of 6 patients with peripheral neuropathy required discontinuation of treatment. The maximum accepted dose and the recommended dose were 120 and 100 mg/m2, respectively. No grade ≥3 adverse events were observed at 100 mg/m2. The maximum drug concentration and AUC correlated with dose escalation. The pharmacokinetic parameters after the first and sixth infusions were similar, indicating that repeated administration of paclitaxel did not result in drug accumulation or affect its pharmacokinetic profile. Partial response was observed in 3 of 15 patients. Plasma adrenocorticotropic hormone and cortisol levels decreased during treatment but approached baseline levels after a dexamethasone-free interval.ImplicationsWeekly paclitaxel at 100 mg/m2 given as a 1-hour infusion for 6 weeks followed by a 2-week treatment interval was well tolerated by Japanese patients with advanced NSCLC. Dexamethasone taper was feasible in these patients, and no clear trend in plasma adrenocorticotropic hormone or cortisol levels was observed

TPO-RA improved ITP induced by atezolizumab

Immune checkpoint inhibitors (ICIs) have shown impressive anti-tumor effects against multiple types of malignancies. Among the wide variety of immune-related adverse events (irAEs), immune-related thrombocytopenia (ITP) is relatively rare but often clinically significant and life-threatening. However, the appropriate treatment for severe ITP has not been determined. We herein report an 82-year-old male patient with non-small-cell lung cancer who developed severe ITP three weeks after starting the third course of atezolizumab. The initial combination therapy with high-dose prednisolone, intravenous immunoglobulin and platelet transfusion was ineffective. However, additional treatment with eltrombopag, a thrombopoietin receptor agonist, resulted in remarkable improvement in the thrombocytopenia

Applications of a novel biodetection system to saliva using protein fingerprints with data processing

A fundamental method has been developed focusing on a facile and rapid examination of periodontal disease. Periodontal disease is an oral disease thought to affect 80% of adults, and early detection with treatment is desirable for the improvement of the quality of life. Unfortunately conventional methods are not consistent as the disease is caused by a number of bacteria and detection relies on the skills of the dentist. Thus an objective detection system is required. We have performed an experiment on saliva using a novel biodetection system, designated PepTenChip®. A disease model for saliva was prepared using a specimen from a healthy subject and a mixture of hemoglobin (f-Hb) and lactate dehydrogenase (LDH), which is used as a periodontal disease marker protein with healthy saliva. PepTenChip® is a peptide microarray in which fluorescent labelled structured peptides are immobilized on a novel amorphous carbon substrate. Since the peptides used as capture molecules are fluorescently labelled, labeling of analytes is not necessary. The fluorescence intensity change before and after application of analytes are detected rather than the ON/OFF detection common to conventional microarrays using a set of antigen-antibody. The fluorescence intensity value changes according to the concentration of captured protein allowing the generation of protein fingerprint (PFP) and dendrograms. The present method does not rely on a "one to one" interaction, unlike conventional biodetection, and advantages can be envisaged in the case of an undefined or unknown cause of disease. The statistical analyses, such as multivariate analyses, allow classification of the type of proteins added in saliva as mimetics of disease. PepTenChip® system is useful and convenient for examination of periodontal disease in health care

Comparative Chemotherapeutic Efficacy in Non-small Cell Lung Cancer Patients with Postoperative Recurrence and Stage IV Disease

BackgroundWhether chemotherapy would be equally effective in non-small cell lung cancer patients with stage IV disease (group A) and postoperative recurrence (group B) remains unclear.Patients and MethodsIn a total of 642 non-small cell lung cancer patients with distant metastases treated by chemotherapy, the baseline patient characteristics, responses to chemotherapy and survival were compared between group A (n = 480) and group B (n = 162).ResultsAdenocarcinoma was the predominant histologic type, accounting for 78% of the patients in group A and 90% of the patients in group B (p < 0.001). Bone and brain metastases were more common in group A (p = 0.034 and p = 0.014, respectively), although pulmonary metastases were more common in group B (p < 0.001). The chemotherapy regimens used for the treatment did not differ between groups A and B. The response rates in group A and group B were 32 and 33%, respectively (p = 0.65). In contrast, the median progression-free survival (5.5 versus 4.2 months, p = 0.0065) and overall survival (21.3 versus 13.3 months, p < 0.001) were better in group B than in group A.ConclusionSurvival was superior in patients with postoperative recurrence than in those with stage IV disease, although the two groups showed comparable responses to chemotherapy

Perspectives of non-specialists on the potential to serve as ethics committee members

Objective: In Japan, under the new Clinical Trials Act pertaining to investigator-initiated clinical trials that came into effect on 1 April 2018, review boards should review proposed clinical trials while considering written opinions from specialists. Additionally, involvement of non-specialists is mandatory, and attention is being placed on their effective contributions. This study was performed to determine representative key issues with which to promote these contributions. Methods: This qualitative study was conducted in 2018 using a focus group interview of six non-specialists regarding perspectives on clinical research itself and research ethics committees. Results: For perspectives on clinical research itself, 33 codes were established and sorted into 2 categories and 6 subcategories relating to ambivalence toward clinical research. For perspectives on research ethics committees, 54 codes were established and sorted into 3 categories and 10 subcategories relating to the theme “knowledge and an environment that promotes non-specialist members’ participation.” One notable result was the willingness of participants to obtain details about a study should they be selected. Conclusions: The results suggest that detailed explanation of a particular study would encourage non-specialist members to participate in a clinical research review committee. Education aimed at non-specialist participation should therefore be considered in future studies

Multidisciplinary treatment of skeletal muscle metastasis from lung cancer : A case of triceps muscle metastasis of lung squamous cell cancer

A 62-year-old Japanese man presented a hard and painful intramuscular mass in the right upper arm during the chemotherapy for lung squamous cell carcinoma. Initially, this mass containing fluid accumulation was treated by radiotherapy and antibiotics as a muscle metastasis suspected to be complicated with local infection. However, because the swelling and pain of his right arm did not improve, he underwent a surgical debridement of the mass. These local treatments succeeded in relieving the patient's symptoms for a while. However, after temporary remission, the recurrence tumor developed the paralysis of right radial nerve and ulnar nerve in his upper arm. Despite further combined therapy including drainage, additional radiotherapy, and chemotherapy, paralysis made his performance status deteriorated. He was eventually discontinued aggressive treatment due to worsened general condition. We herein report a case of lung cancer followed unusual course due to muscle metastasis in the triceps muscle. Because the paralysis caused by muscle metastasis can be the factor to deteriorate the performance status of patient, the combined therapy including antibiotics, debridement, radiotherapy and chemotherapy as early as possible should be considered to avoid its risk

Efficacy and safety of second-line chemotherapy for patients with advanced non-small cell lung cancer complicated by interstitial lung disease

Background: Treatment of non-small cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) is limited because of the risk of its acute exacerbation (AE). Furthermore, the efficacy and safety of second-line chemotherapy for these patients is unclear. Methods: To investigate the efficacy and safety of second-line chemotherapy for NSCLC patients with ILD, we retrospectively reviewed patients who were treated at our institute between April 2010 and December 2018. Results: Thirty-five patients received two or more regimens. Thirty-four patients were male and the median age at the initiation of second-line chemotherapy was 70 years. Almost all patients had a smoking history. Fourteen patients had adenocarcinoma and 15 had squamous cell carcinoma histology. Stages III and IV were observed in 20 and 11 patients, respectively. With respect to the type of ILD, 12 patients had usual interstitial pneumonia (UIP). The overall response rate and disease control rate were 11.4 and 68.6%, respectively. The median progression-free and median overall survival were 4.1 and 6.4 months, respectively. The AE of ILD was observed in eight patients, five of whom died. UIP and low percentage vital capacity were detected as significant risk factors for the AE of ILD. Conclusion: Second-line chemotherapy among patients with NSCLC complicated by ILD showed a certain effectiveness, but some patients experienced the AE of ILD, which may lead to death. The risk of the AE of ILD must be considered especially for patients with UIP and low percentage VC

Correlation between immune-related adverse events and therapeutic effects of nivolumab in patients with malignant pleural mesothelioma

Background: Nivolumab is used for the treatment of malignant pleural mesothelioma (MPM). However, immune-related adverse events (irAEs) occur in patients treated with nivolumab. Several studies have reported the correlation between irAEs and therapeutic effects of immune checkpoint inhibitor, but none have reported the correlation in MPM. Here we report a retrospective study which shows the correlation between irAEs and therapeutic effects of nivolumab in patients with MPM. Methods: This study included patients treated with nivolumab at Tokushima University Hospital from February 2009 to September 2021. We retrospectively reviewed the medical records to evaluate the several clinical factors, such as the presence or absence of irAEs, their severities, progression-free survival (PFS), overall survival (OS) or objective response to the treatment. Results: Eleven patients received treatment with nivolumab. Objective response rate was 18.2% and the disease control rate was 90.9%. Median PFS was 6.8 months (95% confidence interval, 1.3 to 11.9 months) and median OS was 15.2 months (95% confidence interval, 8.9 to 21.5 months). IrAEs occurred in eight patients (72.7%), and grade ≥ 2 irAEs occurred in six patients (54.5%). PFS and OS were significantly longer in the grade ≥ 2 irAEs group than in grade < 2 irAEs group (median PFS 13.6 vs. 3.8 months, p = 0.0093; median OS not reached vs. 8.6 months, p = 0.0108). Conclusions: This is the first study to report the correlation between irAEs and therapeutic effects in patients with MPM. Because the presence of irAEs may be associated with a favorable clinical outcome, early detection and appropriate management of irAEs will increase the therapeutic benefits to patients