Extensive ischaemic colitis-like colonic lesions in eosinophilic granulomatosis with polyangiitis.

Eosinophilic granulomatosis with polyangiitis is a rare, immune-mediated, multisystemic disorder belonging to the group of antineutrophil cytoplasmic antibody-associated vasculitides. Gastrointestinal symptoms are relatively common in patients with eosinophilic granulomatosis with polyangiitis, reportedly occurring in ∼22.3% of cases. Vasculitic necrotising lesions normally occur in the intestinal tract, and in the present case, the colonic lesions were remarkably severe and extensive. Pulse steroid therapy combined with cyclophosphamide improved the patient's condition without any serious complications, such as intestinal perforation.

Non-bacterial vertebral osteitis as the first manifestation of pustulotic arthro-osteitis.

Pustulotic arthro-osteitis (PAO) is an osteoarticular comorbidity of palmoplantar pustulosis, a chronic, recurrent, inflammatory skin disease presenting with erythema, scales, and pustules on the palms and soles. Palmoplantar pustulosis is one of the most common skin diseases in Japan and is accompanied by PAO in 10-30% of patients. PAO often involves anterior chest wall lesions, but vertebral involvement is uncommon. The present report describes a case of PAO in which the initial manifestation was only non-bacterial vertebral osteitis, with palmoplantar pustulosis developing 8 months after its onset. A patient with vertebral osteitis of unknown aetiology should be followed up and examined periodically for skin problems, which may provide a clue to the presence of PAO.

C-reactive protein and the neutrophil-to-lymphocyte ratio on admission predicting bacteraemia with COVID-19.

BACKGROUND: Bacteraemia can co-occur with COVID-19. The present study aimed to determine the cut-off value for C-reactive protein (CRP) and the neutrophil-to-lymphocyte ratio (NLR) for predicting bacteraemia in patients with COVID-19. METHODS: Patients admitted to Tokyo Metropolitan Tama Medical Centre for COVID-19 treatment between 1 April 2020 and 30 October 2022 were included. Patients transferred from other hospitals and those whose CRP and/or neutrophil count was not measured at admission were excluded. Community-acquired bacteraemia was diagnosed if true bacteraemia was diagnosed in patients via a blood culture performed within 72 h of admission. The cut-off value for CRP and the NLR for community-acquired bacteraemia were determined using receiver operating characteristic analysis. RESULTS: Among 2989 patients hospitalized for COVID-19 treatment, 19 received the diagnosis of community-acquired bacteraemia, for which CRP ≥ 6.3 was determined to be the cut-off value. The sensitivity and specificity of the cut-off was 89.5% and 73.3%, respectively. The NLR cut-off value was ≥ 7.7, which had a sensitivity and specificity of 84.2% and 84.0%, respectively. CONCLUSIONS: Considering the possibility of the co-occurrence of bacteraemia with COVID-19, a blood culture should be performed when CRP is ≥ 6.3 or the NLR is ≥ 7.7.

The comb sign in a patient with Crohn's disease.

There are many CT findings suggestive of Crohn's disease. The comb sign is one of them, and the sign helps us to diagnose it.

Discovery of α-l-Glucosidase Raises the Possibility of α-l-Glucosides in Nature.

Glucose, a common monosaccharide in nature, is dominated by the d-enantiomer. Meanwhile, the discovery of l-glucose-utilizing bacteria and the elucidation of their metabolic pathways 10 years ago suggests that l-glucose exists naturally. Most carbohydrates exist as glycosides rather than monosaccharides; therefore, we expected that nature also contains l-glucosides. Sequence analysis within glycoside hydrolase family 29 led us to identify two α-l-glucosidases, ClAgl29A and ClAgl29B, derived from Cecembia lonarensis LW9. ClAgl29A and ClAgl29B exhibited higher K m, k cat, and k cat/K m values for p-nitrophenyl α-l-glucoside than that for p-nitrophenyl α-l-fucoside. Structural analysis of ClAgl29B in complex with l-glucose showed that these enzymes have an active-site pocket that preferentially binds α-l-glucoside, but excludes α-l-fucoside. These results suggest that ClAgl29A and ClAgl29B evolved to hydrolyze α-l-glucoside, implying the existence of α-l-glucoside in nature. Furthermore, α-l-glucosidic linkages (α-l-Glc-(1 → 3)-l-Glc, α-l-Glc-(1 → 2)-l-Glc, and α-l-Glc-(1 → 6)-l-Glc) were synthesized by the transglucosylation activity of ClAgl29A and ClAgl29B. We believe that this study will lead to new research on α-l-glucosides, including determining the physiological effects on humans, and the discovery of novel α-l-glucoside-related enzymes.

Negligible contribution of bone marrow-derived cells to collagen production during hepatic fibrogenesis in mice.

BACKGROUND & AIMS: Recent studies have reported that bone marrow (BM)-derived cells migrating into fibrotic liver tissue exhibit a myofibroblast-like phenotype and may participate in the progression of liver fibrosis. However, their contribution to collagen production has not been fully verified yet. We revisited this issue by using 2 mechanistically distinct liver fibrosis models introduced into transgenic collagen reporter mice and their BM recipients. METHODS: BM of wild-type mice was replaced by cells obtained from transgenic animals harboring tissue-specific enhancer/promoter sequences of alpha2(I) collagen gene (COL1A2) linked to enhanced green fluorescent protein (EGFP) or firefly luciferase (LUC) gene. Liver fibrosis was introduced into those mice by repeated carbon tetrachloride injections or ligation of the common bile duct. Activation of COL1A2 promoter was assessed by confocal microscopic examination detecting EGFP signals and luciferase assays of liver homogenates. RESULTS: The tissue-specific COL1A2 enhancer/promoter was activated in hepatic stellate cells following a single carbon tetrachloride injection or during primary culture on plastic. A large number of EGFP-positive collagen-expressing cells were observed in liver tissue of transgenic COL1A2/EGFP mice in both liver fibrosis models. In contrast, there were few EGFP-positive BM-derived collagen-producing cells detected in fibrotic liver tissue of COL1A2/EGFP recipients. Luciferase assays of liver tissues from COL1A2/LUC-recipient mice further indicated that BM-derived cells produced little collagen in response to fibrogenic stimuli. CONCLUSIONS: By using a specific and sensitive experimental system, which detects exclusively BM-derived collagen-producing cells, we conclude an unexpectedly limited role of BM-derived cells in collagen production during hepatic fibrogenesis.

Reactive nonsexually related acute genital ulcers.

The case of a 19-year-old Japanese woman with reactive nonsexually related acute genital ulcers.

Generalized pustular psoriasis in a 92-year-old man with a homozygous nonsense mutation in IL36RN.

A 92-year-old man developed an erythematous eruption on the trunk and extremities with numerous pustules accompanied by fever. He had never experienced pustular eruption or been diagnosed with psoriasis previously. Skin biopsy revealed Kogoj's spongiform pustule, and he was diagnosed with generalized pustular psoriasis (GPP). Genomic DNA was extracted from his peripheral blood and the sequence of IL36RN gene was analyzed, which revealed a p.Arg10X homozygous mutation. Several cases of elderly-onset GPP have been reported, however, this is the oldest case of GPP. The existence of splice variants of IL36RN was suspected, but we could not detect any splice variants of IL36RN in this case or in a healthy control from peripheral blood samples.

5-fluorouracil arterial infusion + interferon therapy for highly advanced hepatocellular carcinoma: A multicenter, randomized, phase II study.

AIM: The efficacy and safety of 5-fluorouracil arterial infusion + interferon therapy (FAIT) was evaluated in patients with hepatocellular carcinoma (HCC) with a high degree of vascular invasion associated with poor prognosis, using best salvage therapy (BST) as a reference group. METHODS: Sixty-nine patients with advanced HCC with a high degree of vascular invasion (Vp3, Vp4, Vv3) were randomly assigned to a FAIT group or a BST group. The FAIT group received interferon-α and 5-fluorouracil combination therapy; the BST group received either combination therapy of cisplatin and 5-fluorouracil (low-dose FP therapy) or cisplatin for arterial infusion. RESULTS: Thirty patients in the FAIT group and 31 patients in the BST group were included in the efficacy analysis. The response rate (primary endpoint) was 26.7% (eight out of 30 patients) for the FAIT group and 25.8% (eight out of 31) for the BST group. The number of occurrences of adverse events of grade 3 or higher was 115 in 30 patients in the FAIT group and 113 in 29 patients in the BST group. None of the deaths were related to the study therapy. CONCLUSIONS: FAIT exerts modest antitumor effects and poses no particular safety concerns. FAIT may be a strategy of choice worth trying for advanced HCC with high degree of vascular invasion, which is associated with poor prognosis.

Differential contribution of dermal resident and bone marrow-derived cells to collagen production during wound healing and fibrogenesis in mice.

Recent studies show that bone marrow (BM)-derived cells migrating into a dermal wound promote healing by producing collagen type I. However, their contribution to the repair process has not been fully verified yet. It is also unclear whether BM-derived cells participate in dermal fibrogenesis. We have addressed these issues using transgenic mice that harbor tissue-specific enhancer/promoter sequences of α2(I) collagen gene linked to either enhanced green fluorescent protein (COL/EGFP) or the luciferase (COL/LUC) reporter gene. Following dermal excision or subcutaneous bleomycin administration, a large number of EGFP-positive collagen-producing cells appeared in the dermis of COL/EGFP reporter mice. When wild-type mice were transplanted with BM cells from transgenic COL/EGFP animals and subjected to dermal excision, no EGFP-positive BM-derived collagen-producing cells were detected throughout the repair process. Luciferase assays of dermal tissues from COL/LUC recipient mice also excluded collagen production by BM-derived cells during dermal excision healing. In contrast, a limited but significant number of CD45-positive collagen-producing cells migrated from BM following bleomycin injection. These results indicate that resident cells in the skin are the major source of de novo collagen deposition in both physiological and pathological conditions, whereas BM-derived cells participate, in part, in collagen production during dermal fibrogenesis.

Lysophosphatidylcholine enhances glucose-dependent insulin secretion via an orphan G-protein-coupled receptor.

A lysophospholipid series, such as lysophosphatidic acid, lysophosphatidylserine, and lysophosphatidylcholine (LPC), is a bioactive lipid mediator with diverse physiological and pathological functions. LPC has been reported to induce insulin secretion from pancreatic beta-cells, however, the precise mechanism has remained elusive to date. Here we show that an orphan G-protein-coupled receptor GPR119 plays a pivotal role in this event. LPC potently enhances insulin secretion in response to high concentrations of glucose in the perfused rat pancreas via stimulation of adenylate cyclase, and dose-dependently induces intracellular cAMP accumulation and insulin secretion in a mouse pancreatic beta-cell line, NIT-1 cells. The Gs-protein-coupled receptor for LPC was identified as GPR119, which is predominantly expressed in the pancreas. GPR119-specific siRNA significantly blocked LPC-induced insulin secretion from NIT-1 cells. Our findings suggest that GPR119, which is a novel endogenous receptor for LPC, is involved in insulin secretion from beta-cells, and is a potential target for anti-diabetic drug development.