Prolonged viral shedding of SARS-CoV-2 in an immunocompromised patient.

The duration of viral shedding of SARS-CoV-2 is usually less than 10 days. We experienced a COVID-19 case with prolonged viral shedding for 2 months. His cell mediated immunity has been depressed (CD4+T cell <100/µl) due to advanced malignant lymphoma and chemotherapy which had been completed 4 months prior to the onset of symptoms of COVID-19. We administered several treatments against COVID-19, however the results of Polymerase Chain Reaction (PCR) from nasopharyngeal specimens remained positive to SARS-CoV-2 for 2 months. Moreover, virus isolation assays performed on Day 59 also remained positive. He was finally discharged on Day 69 with two consecutive negative PCR results for SARS-CoV-2. Immunocompromised status may prolong viral shedding and it is therefore important for the clinician to take into account this when assessing such patients.

Graphiumins, new thiodiketopiperazines from the marine-derived fungus Graphium sp. OPMF00224.

Eight new thiodiketopiperazines, designated as graphiumins A to H (1-8), were isolated along with bisdethiobis(methylthio)-deacetylaranotin (9) and bisdethiobis(methylthio)-deacetylapoaranotin (10) from the culture broth of the marine-derived fungus Graphium sp. OPMF00224. The structures of the graphiumins were elucidated based on spectroscopic analyses (1D and 2D NMR data, ROESY correlations and CD data) and chemical methods. The absolute configuration of the common (3S)-3-hydroxy-octanoyl acid residue in 1, 3 and 4 was determined by hydrolysis, benzoyl derivatization and HPLC analysis using a chiral column. Five graphiumins moderately inhibited yellow pigment production by methicillin-resistant Staphylococcus aureus.

Bafilomycin L, a new inhibitor of cholesteryl ester synthesis in mammalian cells, produced by marine-derived Streptomyces sp. OPMA00072.

Marine-derived Streptomyces sp. OPMA00072 was found to produce inhibitors of the synthesis of neutral lipids in a cell-based assay using Chinese hamster ovary (CHO) cells. A new 16-membered macrolide named bafilomycin L (BFL) (1) was isolated along with the known structurally related bafilomycin C1 (BFC1) (3) from the culture broth of the actinomycete by solvent extraction, octadecylsilyl column chromatography and HPLC. BFL inhibited cholesteryl ester (CE) synthesis in CHO cells with an IC50 value of 0.83 nM and also in mouse peritoneal macrophages with an IC50 of 6.1 nM. In addition, BFL blocked cellular acidification in HeLa cells by interfering with vacuolar H(+)-ATPase (V-ATPase) as well as other bafilomycins. These data strongly suggest that BFL disturbed the lysosome function to block cholesterol metabolism, leading to the inhibition of CE accumulation in mammalian cells.

[A case of calcinomatous polyarthritis presenting rheumatoid arthritis-like polyarthritis as the initial symptom of gastric cancer].

We report a case of calcinomatous polyarthritis presenting rheumatoid arthritis-like polyarthritis as the initial symptom of gastric cancer. A 79-year-old male visited to our hospital with complaint of pain and swelling of multiple joints including bilateral hands, bilateral knees, elbows and small joints of fingers. He also complained of neck and back stiffness. Both of rheumatoid factor test and anti-cyclic citrullinated peptide antibody were negative. Non-steroidal anti-inflammatory drug did not relieve his arthritic pain. He showed anorexia, body weight loss and was anemic. Upper gastrointestinal endoscopic evaluation demonstrated a gastric cancer. The patient underwent subtotal gastrectomy. Within 1 week after the subtotal gastrectomy, both polyarthritis and stiffness started to improve. The polyarthritis in this case was diagnosed as calcinomatous plyarthritis for its features. Paraneoplastic rheumatism remains a rare event, but knowledge of it is essential for early diagnosis of underlying cancer.

Polymyositis associated with autoimmune hepatitis, primary biliary cirrhosis, and autoimmune thrombocytopenic purpura.

We describe a 40-year-old woman with polymyositis (PM) who developed autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and autoimmune thrombocytopenic purpura (AITP) concurrently. About 4 years earlier, she suffered from muscle weakness probably due to PM. When she visited our hospital, she had polyarthritis, myalgia, symmetrical proximal limb-muscle weakness, elevated muscle enzymes, and myogenic abnormalities on electromyogram. Pathological findings obtained by muscle biopsy showed histological findings consistent with PM. Her serum liver enzymes were also elevated. The histology obtained by liver biopsy revealed the mixture findings of chronic active hepatitis and biliary cirrhosis. As antibodies to mitochondria M2 and liver/kidney microsome type 1 (LKM-1) were present, we concluded her liver disease was due to an overlap of AIH and PBC. Furthermore, purpura on the legs with thrombocytopenia appeared in parallel with liver dysfunction. She was diagnosed as having AITP by clinical and laboratory findings. Her serum showed a speckled pattern in immunofluorescence antinuclear antibody testing, but the antigen specificities were distinct from those of the known myositis-related autoantigens. This is a first case report of PM accompanied by AIH, PBC, and AITP. It was notable that there was an overlap of disease-associated immunological findings and immunogenetic backgrounds. This case provides a possible insight into the mechanisms and interplay of autoimmune diseases.

[A case of slowly progressive type 1 diabetes mellitus developing myeloperoxidase-specific anti-neutrophil cytoplasmic antibody-associated vasculitis with hypertrophic pachymeningitis manifesting as multiple cranial nerve palsy].

We report a 63-year-old man with a 35-year history of slowly progressive type 1 diabetes mellitus (SPIDDM), complicated with myeloperoxidase-specific anti-neutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitis presenting alveolar hemorrhage and pachymeningitis. The patient was first diagnosed as having DM at age of 28 years old and deteriorated secretion of insulin and the typical clinical course led us to the diagnosis of SPIDDM. When he was 58 years old, he suffered from fever, headache, and alveolar hemorrhage. He was diagnosed as having MPO-ANCA associated vasculitis based on a high titer of MPO-ANCA and histological findings of lung biopsy. Treatment with steroid pulse therapy, followed by oral prednisolone and oral cyclophosohamide, resulted in clinical improvement. Five years later, he complained of double vision. A gadolinium-enhanced magnetic resonance imaging (MRI) study of the brain showed normal. Two months later, he developed right cranial nerve V~XII palsy. A second MRI study revealed thickening of the right temporal region and cerebellar dura mater, leading us to the diagnosis of hypertrophic pachymeningitis. He responded well to oral prednisolone (50 mg/day) and intravenous cyclophosohamide (500 mg). This is the first case report of SPIDDM complicated with MPO-ANCA-associated vasculitis, manifesting as alveolar hemorrhage and hypertrophic pachymeningitis.

[A case report of a HIV-infected patient, who was denied to return home because of his psychological complications along with hepatocellular carcinoma].

Although a social support system has been developed in recent times, some of the difficult cases which complicate serious diseases due mainly to lack of family care power, have been reported. We experienced one HIV-infected patient who suffered from hepatic carcinoma and had been taken care of at home, but he was denied to return home after hospitalization. It has been reported that the management of homecare station has become worsened and the number of stations has been decreasing in various locations. If the patients were selected by homecare stations in which the management was going from bad to worse, it would be difficult to maintain a nationwide quality of homecare system. By presenting such an extreme case in the homecare services, we propose a homecare scoring system, in consideration of homecare service limitations, which will be helpful assessing a difficult case of a patient taken care of at home.

Coexistence of nodular regenerative hyperplasia of the liver and pulmonary arterial hypertension in patients with connective tissue diseases: report of three cases and review of the literature.

Nodular regenerative hyperplasia of the liver (NRH) is known to be a rare condition in patients with connective tissue diseases (CTD). In this report, we document three patients with CTD who had both NRH and pulmonary hypertension (PH). All three patients developed PH during their course and thereafter developed NRH. The clinical course of these patients suggests that circulatory disturbance caused by PH might be a trigger for NRH.

Two novel kickxellalean fungi, Mycoëmilia scoparia gen. sp. nov. and Ramicandelaber brevisporus sp. nov.

Mycoëmilia scoparia gen. sp. nov. is described as a new member of Kickxellales. It is characterized by lageniform sporocladia produced acrogenously in mass and bears wet and fusiform spores on the sporocladia. Ramicandelaber brevisporus sp. nov. is distinguished from the type species of the genus, R. longisporus, by producing much shorter asexual spores, (3-)8(-13) long fertile branches arising from a globose body, and lateral branches.

Arborcandins A, B, C, D, E and F, novel 1,3-beta-glucan synthase inhibitors: physico-chemical properties and structure elucidation.

Arborcandins A, B, C, D, E and F, which possess potent 1,3-beta-glucan synthase inhibitory activity, were isolated from the cultured broth of a filamentous fungus, strain SANK 17397. The structures of arborcandins A, B, C, D, E and F were elucidated by a combination of NMR and mass spectrometry, and established to be novel cyclic peptides containing uncommon amino acid residues.