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We report the first case with COVID-19-like acute respiratory distress syndrome after mRNA-1273 SARS-CoV-2 vaccination. An 88-year-old woman developed dyspnea several hours after vaccination with the second dose of mRNA-1273. She was hospitalized on day nine due to worsening dyspnea. Chest computed tomography showed bilateral ground-glass opacities and consolidations, mainly in the peripheral lung areas. Repeat polymerase chain reaction tests for SARS-CoV-2 were negative, although the serum level of antibodies against spike protein was extremely elevated. Her condition did not improve with high-dose corticosteroids and high-flow nasal cannula oxygen therapy; she died on day 18. Autopsy findings revealed very early-phase diffuse alveolar damage in the whole lung without other lung diseases. The clinical and pathological findings suggested vaccine-induced acute respiratory distress syndrome. Serological and pathological tests might be useful to differentiate the disease from COVID-19., Competing Interests: Conflict of Interest Department of Infectious Disease and Respiratory Medicine of Yokohama Municipal Citizen's Hospital, to which Yukihiro Yoshimura, Hiroaki Sasaki, Nobuyuki Miyata, Kazuhito Miyazaki, and Natsuo Tachikawa belong, have received research funding from three companies, Gilead Sciences, Inc., Eli Lilly Japan K.K, and Ono Pharmaceutical Co., Ltd. in the last two years., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Osteoblasts participate in both bone formation through the synthesis of extracellular matrix and osteoclast differentiation through the expression of osteoclast differentiation factor. Osteoblasts communicate with each other via gap junctions (GJ), which enable small molecules, such as cAMP, to move to adjacent cells. Therefore, we focused on the role of cAMP propagation between osteoblasts via GJ in the osteoclast-supporting activity of osteoblasts. Osteoclast-supporting activity was evaluated by a co-culture system of osteoblasts with bone marrow-derived mononuclear cells. In this system, ablation of Gja1, a gene encoding connexin 43, in osteoblasts promoted osteoclastogenesis induced by prostaglandin E 2 (PGE 2 ). A phosphodiesterase 4 inhibitor increased both osteoclastogenesis and the intracellular cAMP concentration ([cAMP] i) in osteoblasts. Individual cell analysis of [cAMP] i in osteoblasts revealed different responses of each osteoblast to PGE 2 . Moreover, measurement of real-time [cAMP] i demonstrated cAMP movement from cell to cell via GJ. The inhibition of GJ resulted in the upregulation of [cAMP] i in osteoblasts stimulated by PGE2. This study suggested that GJ intercellular communication exerts protective effects against excess osteoclastogenesis via cAMP movement between osteoblasts., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Lymphoma has been reported to worsen the prognosis of COVID-19 partly because it disturbs the normal production of antibodies. We treated a man with mantle cell lymphoma treated with rituximab, who developed severe COVID-19 with viral shedding that lasted for 78 days. He stayed in the intensive care unit for 28 days and did not respond to any treatment against COVID-19. His increased oxygen demand at rest eventually resolved despite the absence of anti-SARS-CoV-2-IgG. This case illustrates that recovery from COVID-19 can occur without antibody production, and that even patients with an inability to produce antibodies can recover from severe COVID-19. It also illustrates that lymphoma patients who develop severe COVID-19 while on rituximab therapy can recover from a prolonged viral shedding state if the acute lung injury can be overcome., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Vaccination is one of the most important tools to control the COVID-19 pandemic. However, there is little information on the antibody response in humans after the COVID-19 vaccination., Methods: This single-center, prospective study was conducted in Yokohama, Japan. We included health care workers who had received two doses of COVID-19 vaccination (BNT162b2) 21 days apart. We measured serum immunoglobulin G (IgG) to nucleoprotein and spike protein of SARS-CoV-2 with commercially available kits before and 7, 14, and 35 days after the first dose of vaccination., Results: A total of 104 workers participated in this study. Of these, 7 participants were seropositive with antibodies to spike protein at baseline and 4 of the 7 seropositive participants had COVID-19 history. The mean level of IgG to spike protein (QT) was 45.2, 1219, 2845, and 23489 AU/mL at baseline, on days 7, 14, and 35, respectively, although the values for nucleoprotein (NG) were 0.2, 0.21, 0.22, and 0.19 S/C, respectively. On day 7, QT in seropositive participants at baseline was elevated, whereas it was not elevated in seronegative participants at baseline until day 14., Conclusions: QT was elevated over the cutoff in all the participants at day 35, but NG did not change between baseline and day 35., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Introduction: The epidemiology of infectious diseases in Japan remains undefined despite the increasing tourism. GeoSentinel, an epidemiological surveillance system for reporting imported infectious diseases, has only two participating facilities in Japan. Although the number of infectious diseases is reported by the National Institute of Infectious Diseases, there is no detailed clinical information about these cases. Therefore, we established J-RIDA (Japan Registry for Infectious Diseases from Abroad) to clarify the status of imported infectious diseases in Japan and provide detailed information., Methods: J-RIDA was started as a registry of imported infectious diseases. Case registration began in October 2017. Between October 2017 and September 2019, 15 medical institutions participated in this clinical study. The registry collected information about the patient's age, sex, nationality, chief complaint, consultation date, date of onset, whether visit was made to a travel clinic before travel, blood test results (if samples were collected), travel history, and final diagnosis., Results: Of the 3046 cases included in this study, 46.7% to Southeast Asia, 13.0% to Africa, 13.7% to East Asia, 11.5% to South Asia, 7.5% to Europe, 3.8% to Central and South America, 4.6% to North America, 3.9% to Oceania, and 2.8% to Central and west Asia. More than 85% of chief complaints were fever and general symptoms, gastrointestinal symptoms, respiratory symptoms, or dermatologic problems. The most common diseases were travelers' diarrhea, animal bite, upper respiratory infection, influenza, and dengue fever., Conclusions: We summarized two-year cases registered in Japan's imported infectious disease registry. These results will significantly contribute to the epidemiology in Japan., Competing Interests: Declaration of competing interest None declared., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: A large COVID-19 outbreak occurred on the cruise ship Diamond Princess in February 2020. Little information has been reported about the clinical characteristics of the patients., Methods: This single-center, retrospective, observational study was conducted in Yokohama, Japan. We included symptomatic patients who were infected on the ship and admitted to our hospital between 5 and 19 February 2020. All the cases were confirmed with SARS-CoV-2 infection by polymerase chain reaction (PCR)., Results: We confirmed 17 cases. The average age was 69 years; 10 patients were Asian and 7 were Caucasian. Eleven patients had one or more chronic diseases. The major symptoms were cough and fever. Chest computed tomography (CT) scans found bilateral ground-glass opacities predominantly in the peripheral area, which were similar to reports from cases in China. C-reactive protein (CRP) levels were higher in severe and critical cases than in mild to moderate cases. The moderate to severe cases reached symptomatic resolution; one of the three critical cases resulted in death due to multiple organ failure. SARS-CoV-2 was detected by PCR at an average of 7 days after symptomatic resolution., Conclusions: Cough and fever, increased blood CRP levels, and CT findings of bilateral ground-glass opacities predominantly in the peripheral lung were characteristic of the COVID-19 cases in this study. These findings were compatible with those of previous reports., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Toxoplasma gondii is an obligate intracellular protozoan that causes toxoplasmic encephalitis (TE) in immunocompromised patients. We describe a case of a 29-year-old Japanese man presenting with headache and vomiting. He had previously been diagnosed with human immunodeficiency virus infection. Magnetic resonance imaging identified some nodules in his brain. We suspected TE and began treatment successively with parenteral trimethoprim-sulfamethoxazole (TMP/SMX) plus clindamycin. After that, we switched to pyrimethamine plus sulfadiazine (PMT/SDZ) because these drugs are the first-line treatment for TE. Because the patient experienced nausea and vomiting, PMT/SDZ was replaced with TMP/SMX, atovaquone, and clindamycin. However, the patient could not tolerate them owing to their adverse reactions. Thus, we attempted oral desensitization to TMP/SMX to treat his TE. We began desensitization with 0.4/2 mg of TMP/SMX. The patient experienced morbilliform rash and elevated aminotransferase levels. Therefore, we administered a glycyrrhizin and an antihistamine and continued the last tolerable dose until these symptoms improved. After 37 days, we achieved desensitization to 160/800 mg of TMP/SMX, and the patient's symptoms improved. After using nested-polymerase chain reaction to identify T. gondii DNA in his frozen cerebrospinal fluid, which was collected at admission, his diagnosis was confirmed as TE. This might be the first case to attempt desensitization to TMP/SMX to treat TE., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The number of patients returning from or staying abroad is likely to increase in the future. We performed a retrospective study of patients returning from abroad in our travel clinic in Japan. All patients presenting within 6 months of traveling abroad between 2004 and 2014 were included in the present study. A total of 2374 (mean age, 35 years) patients were seen by doctors specializing in treating infectious diseases. Of these, 918 were females and 87 of them lived abroad. Diagnoses and exposure regions were recorded for all patients. The most frequent region visited before attending our clinic was Southeast Asia (n = 1050, 44%), with a median duration for staying abroad of 8 days. The major purposes for overseas travel were tourism (n = 1302, 55%) and business (n = 684, 29%). Of the 2399 individual diagnoses made, the most frequent were diseases of the gastrointestinal system (n = 1083, 45%), skin and soft tissue (n = 440, 18%), systemic febrile disease without specific systems (419, 18%), and the respiratory system (353, 15%). The relative incidences of specific diseases changed drastically due to significant disease outbreaks, such as pandemic influenza in 2009. Exposure regions remained relatively constant throughout the study period, except for Japan. Vaccine-preventable diseases accounted for 5.3% of all the diseases, and 402 (26%) patients received pre-travel consultation and prophylaxis with vaccines and/or anti-malarial drug. We should make an effort to make more people notice the risk of travel and properly perform prophylaxis., (Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Subjective adverse reactions to metronidazole were analyzed in 111 patients with amebiasis. Metronidazole was administered to 36 patients at a daily dose of 2250 mg and 75 patients at daily doses lower than 2250 mg. The reactions reported included nausea without vomiting in 11 (9.9%) patients, nausea with vomiting in 2 (1.8%), dysgeusia in 2 (1.8%), diarrhea in 1 (0.9%), headache in 1 (0.9%), numbness in 1 (0.9%), dizziness in 1 (0.9%), urticaria in 1 (0.9%), exanthema in 1 (0.9%), and discomfort in 1 (0.9%). Nausea was reported by 28% (10/36) of the patients receiving metronidazole at a daily dose of 2250 mg and 4% (3/75) of the patients receiving lower daily doses. The duration of the metronidazole administration in days was not associated with the appearance of nausea. No life-threatening adverse reactions were identified, and good clinical therapeutic effects were observed in 96% (107/111) of the patients. While metronidazole appears to be a safe anti-protozoal agent for patients with amebiasis, our results indicate that a daily metronidazole dose of 2250 mg is excessive for amebiasis, as it often induces nausea., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

A 41-year-old woman became ill with acute hepatitis B after gynecological surgery performed by a surgeon who was hepatitis B surface antigen positive. The surgeon was positive for hepatitis B e antigen, and HBV DNA concentrations in the serum, saliva, and sweat of the surgeon were very high. HBV genotype and partial HBV DNA sequences from the HBV-infected surgeon were identical to those in the HBV-infected patient. Extensive research by the committee including infection control and prevention specialists judged the source of infection to be a surgeon infected with HBV. Transmission of HBV from a healthcare worker to patients who are not immune to HBV can actually happen. This case report illustrates the importance of a stringent policy of a nationwide HBV universal vaccination program.

Cytomegalovirus (CMV) retinitis with idiopathic CD4(+) T lymphocytopenia (ICL) is rare and difficult to control. We report a first case for long-term control of CMV retinitis with ICL using interleukin-2 (IL-2) therapy and succeeded in discontinuation of anti-CMV therapy. A 49-year-old Japanese woman was diagnosed with ICL based on low CD4(+) count (72/μl), negative for HIV-1 and -2 antibodies, and absence of any defined immunodeficiency diseases or immunosuppressive therapy. PCR test of the aqueous humor in the right eye was suggestive of CMV retinitis. She was treated with systemic ganciclovir, but after several relapses of CMV retinitis, rhegmatogenous retinal detachment appeared in the right eye and she became blind in that eye. Three years later, she developed CMV retinitis in the left eye. Although she received systemic and focal anti-CMV treatments, the retinitis showed no improvement. Finally, retinal detachment occurred, and she underwent vitrectomy. IL-2 was injected to increase CD4(+) counts. Because of hyperpyrexia, blepharedema, central scotoma, and color anomaly, we changed to low-dose IL-2 therapy with no side effects. Finally, we succeeded in increasing the CD4(+) count to more than 200/μl after discontinuation of low-dose IL-2 therapy. CMV retinitis never recurred after discontinuation of anti-CMV therapy, with good visual acuity of 20/20 in the left eye. She developed blindness of the first affected right eye, whereas the visual acuity of the left eye remains excellent more than 12 years after the onset of CMV retinitis through the combined use of anti-CMV therapy, IL-2 therapy, and vitrectomy.

Although a limited duration of immune activation of structured treatment interruptions (STIs) has been reported, the immune escape mechanism during STIs remains obscure. We therefore investigated the role of three immunodominant cytotoxic T lymphocyte (epitopes) in 12 HLA-A*2402-positive patients participating longitudinally during the clinical study of early antiretroviral treatment (ART) with five series of structured treatment interruptions (STIs). The frequency of HLA-A*2402-restricted CTLs varied widely and a sustained CTL response was rarely noted. However, a Y-to-F substitution at the second position in an immunodominant CTL epitope Nef138-10 (Nef138-2F), which was previously demonstrated as escape mutation, was frequently detected in seven patients primarily and emerged in the remaining five patients thereafter, and the existence of escape mutations was correlated with high pVL levels early in the clinical course. These findings suggest that escape mutation in the immunodominant CTL epitope may be one of the mechanisms to limit HIV-1-specific immune control in STIs.

Signal transducer and activator of transcription 3 (STAT3) is a DNA-binding transcription factor activated by multiple cytokines and interferons. High expression of STAT3 has also been implicated in cancer and lymphoma. Here, we show a case of B cell lymphoma in which a defective human immunodeficiency virus 1 (HIV-1) integrated upstream of the first STAT3 coding exon. The lymphoma cells with anaplastic large cell morphology formed multiple nodular lesions in the lung of an acquired immunodeficiency syndrome (AIDS) patient with Kaposi's sarcoma. The provirus had a 5' long terminal repeat (LTR) deletion, but the 3' LTR had stronger promoter activity than the STAT3 promoter in reporter assays. Immunohistochemistry showed increased expression of STAT3 in the nuclei of lymphoma cells. Transfection of STAT3 resulted in transient cell proliferation in primary B cells in vitro. Although this is a very rare case of HIV-1-integrated lymphoma, these data suggest that up-regulation of STAT3 caused by HIV-1 integration resulted in the development of B cell lymphoma in this special case.

Recent introduction of highly active antiretroviral therapy (HAART) is reported to have reduced the incidence of lymphoma among HIV-infected individuals. A clinicopathological study was performed on 86 AIDS-related lymphoma patients who were treated in Tokyo area from 1987 to 2005. The incidence of lymphoma detected by autopsy was 27% (53 cases/198 autopsies). Diffuse large B cell lymphoma was the most predominant histological subtype throughout the period (78%). Burkitt's lymphoma (BL) increased from 2% in the pre-HAART era (before end-1997) to 13% in the HAART era, whereas incidence of BL did not vary between HAART users and non-users. Epstein-Barr virus (EBV)-positive lymphoma decreased from 88% in the pre-HAART era to 58% in the HAART era, but did not differ significantly between HAART users (73%) and non-users (74%). Nodal involvement of lymphoma increased from 14% in the pre-HAART era to 50% in the HAART era; however, central nervous system involvement decreased from 62 to 38%. Kaposi's sarcoma-associated herpesvirus infection was rare (4%) among all cases. These data suggest that HAART might play a partial role in these changes, and the alteration in immunological backgrounds, such as EBV prevalence, is suggested as another leading cause of these changes in Japanese AIDS-related lymphoma.

Efavirenz (EFV) is metabolized by cytochrome P450 2B6 (CYP2B6) in the liver. We analyzed the genotypes of CYP2B6 and their contribution to plasma EFV concentrations in 35 EFV-treated patients in International Medical Center of Japan. The mean plasma EFV concentration of patients with CYP2B6 *6/*6 (Q172H and K262R) (25.4+/-7.5 microM, +/-SD, n = 2) was significantly higher than that of patients with genotypes *6 heterozygote (9.9+/-3.3 microM, n = 10) or without alleles *6 (8.0+/-2.6 microM, n = 23) (p < 0.0001). To confirm our result, we further analyzed nine patients (three with high EFV concentrations and arbitrarily selected six with normal EFV concentrations) treated in Osaka National Hospital, and it resulted that the only three patients with the high concentrations were the *6/*6 holder. EFV dose could be decreased in those patients harboring the genotype to reduce toxicity with compromising potency, representing the first step of the Tailor-Made therapy of HIV-1 infection.

Background: 14-3-3 proteins are major evolutionarily conserved cytosolic proteins that regulate signal transduction, apoptosis and neurotransmitter synthesis. Five homologous 14-3-3 isoforms, beta, gamma, zeta, epsilon and eta, are reported in mammalian neurones. To elucidate the diagnostic value of 14-3-3 in cerebrospinal fluid (CSF), a highly specific antibody against each isoform and studies on the isoform patterns in patients with neuronal destruction are needed., Methods: In this study, we raised isoform-specific antibodies against 14-3-3 proteins and established a semiquantitative method of identification of each isoform by Western immunoblotting., Results: We found that three isoforms, 14-3-3 epsilon, gamma and zeta, appeared in the CSF of HIV patients with AIDS dementia complex or cytomegalovirus encephalitis, but not in AIDS patients without neurological symptoms or the non-HIV patients examined. The isoform patterns in AIDS patients were different from those reported in Creutzfeldt-Jakob disease and herpes simplex encephalitis, suggesting that the isoform patterns may facilitate the differential diagnosis. A high frequency of 14-3-3 in CSF was observed in seriously ill AIDS patients, particularly those with CD4 levels of less than 20 mm(3)., Conclusion: These findings suggested that 14-3-3 proteins were released from destroyed neural cells and are useful real-time markers of the rate and amount of neural cell destruction in these patients.

The cause and origin of Kaposi's sarcoma (KS) remain an enigma. Recently, Chang et al. reported a DNA fragment resembling human gamma herpesvirus that was specifically associated with KS tissue. In this paper, we report examination of three Japanese patients for presence of the KS-associated herpesvirus-like (KSHV) sequences. KSHV sequences were present in two of these patients, but could not be confirmed in the third because of DNA degradation. The KSHV sequences appeared to be present mainly in those tissues with KS invasion. Our results further demonstrate the presence of KSHV in KS lesions and support its role in the pathogenesis of KS., (Copyright © 1995 Japanese Society of Chemotherapy and the Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)