The diverse origin of bone-forming osteoblasts

Osteoblasts are the only cells that can give rise to bones in vertebrates. Thus, one of the most important functions of these metabolically active cells is mineralized matrix production. Because osteoblasts have a limited lifespan, they must be constantly replenished by preosteoblasts, their immediate precursors. Because disruption of the regulation of bone-forming osteoblasts results in a variety of bone diseases, a better understanding of the origin of these cells by defining the mechanisms of bone development, remodeling, and regeneration is central to the development of novel therapeutic approaches. In recent years, substantial new insights into the origin of osteoblasts—largely owing to rapid technological advances in murine lineage-tracing approaches and other single-cell technologies—have been obtained. Collectively, these findings indicate that osteoblasts involved in bone formation under various physiological, pathological, and therapeutic conditions can be obtained from numerous sources. The origins of osteoblasts include, but are not limited to, chondrocytes in the growth plate, stromal cells in the bone marrow, quiescent bone-lining cells on the bone surface, and specialized fibroblasts in the craniofacial structures, such as sutures and periodontal ligaments. Because osteoblasts can be generated from local cellular sources, bones can flexibly respond to regenerative and anabolic cues. However, whether osteoblasts derived from different cellular sources have distinct functions remains to be investigated. Currently, we are at the initial stage to aptly unravel the incredible diversity of the origins of bone-forming osteoblasts. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Evaluation of duodenal hypersensitivity induced by duodenal acidification using transnasal endoscopy

Background and Aim: Although duodenal hypersensitivity has been suggested as one of the causes of functional dyspepsia (FD), a practical method to clarify this has not yet been established. The aim of this study was to evaluate whether patients with FD have duodenal hypersensitivity to acid, using transnasal endoscopy. Methods: In all, 44 patients with FD and 16 healthy volunteers were enrolled, and all the subjects received transnasal endoscopy in the morning after overnight fasting. After ordinary transnasal endoscopy, an infusion tube was introduced into the duodenal bulb by transnasal endoscopy and acid (20 mL, 0.1 N HCl, 20 mL/min, 36.5°C) was injected via the infusion tube. The severity of 12 symptoms was assessed by each subject using a 100‐mm visual analogue scale. The maximum severity scale was defined as the maximum score of the symptom severity scale. The total score was defined as the aggregate score of the maximum severity scale of the 12 symptoms. The maximum severity scales and the total scores between patients with FD and healthy volunteers were evaluated. Results: The maximum severity scales of nine symptoms increased significantly more after acid infusion in patients with FD than in healthy volunteers (P < 0.05). There were significant differences in the total scores (patients with FD vs healthy volunteers 233.8 ± 37.8 vs 63.9 ± 14.6, mean ± standard error of the mean, P < 0.001). Conclusions: Duodenal acidification using transnasal endoscopy enabled the evaluation of duodenal hypersensitivity to acid in healthy volunteers and patients with FD.     

Comparison of endoscopic findings with symptom assessment systems (FSSG and QUEST) for gastroesophageal reflux disease in Japanese centres

Background and Aim: We compared endoscopic findings of the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG), a written questionnaire developed in Japan, to that for the questionnaire for the diagnosis of reflux esophagitis (QUEST) for the diagnosis of reflux esophagitis. Methods: We registered 475 patients with untreated symptoms of upper abdominal pain (male/female: 252/223, average age 52.4 ± 17.8 years). Subjects were assessed first with the FSSG and QUEST questionnaires, then by endoscopy, before allocation to a gastric ulcer (GU), duodenal ulcer (DU), gastroesophageal reflux disease (GERD) or functional dyspepsia (FD) group. Results: On the basis of the endoscopic findings the diagnoses for the 475 subjects were as follows: FD 52.2%, DU 7.6%, GU 7.8%, and GERD 32.4% (Grade M 10.1%, Grade A + B 20.2%, Grade C + D 2.3%). There was no difference between the FSSG and QUEST in sensitivity, specificity or accuracy for any condition. The FSSG score rose with increasing endoscopic severity of GERD, but there was no correlation between the QUEST score and endoscopic severity. The FSSG total score was inferior to QUEST in terms of distinguishing GERD from other conditions, but when only the questions relating to reflux symptoms were used, the FSSG was able to distinguish GERD from other conditions as well as QUEST. Conclusions: The FSSG score reflects the severity of the endoscopic findings of GERD.     

Concentrations of carcinoembryonic antigen in serum and bronchoalveolar lavage fluid of asthmatic patients with mucoid impaction]

BACKGROUND: Concentration of carcinoembryonic antigen (CEA) is known as a marker of malignant transformation and chronic inflammation. We recently observed increased levels of serum CEA in a patient with asthma accompanied by mucoid impactions, which dramatically decreased after a sequence of bronchial washings. The present study evaluated relationships between levels of CEA, bronchial asthma and mucoid impactions. METHODS: Serum CEA concentrations were determined by chemiluminescent immunoassay (CLIA) or enzyme immunoassay in 44 subjects, comprising 9 asthmatic patients with mucoid impactions, 13 asthmatic patients without mucoid impactions, 12 patients with bronchiectasis, and 10 healthy volunteers. CEA concentrations in bronchoalveolar lavage fluid (BALF) were determined in 5 asthmatic patients with mucoid impactions and 10 healthy volunteers. RESULTS: Serum concentrations of CEA were significantly increased in asthmatic patients with mucoid impactions compared with patients without mucoid impactions, patients with bronchiectasis, or healthy volunteers (median [range], 17.3 ng/ml [2.8-28.8 ng/ml]; 3.0 ng/ml [1.5-7.1 ng/ml], 2.2 ng/ml [0.9-17.9 ng/ml], and 1.9 ng/ml [0.6-2.9 ng/ml], respectively). Concentrations of CEA in BALF were also significantly increased in asthmatic patients with mucoid impactions compared to healthy volunteers (3.2 ng/ml albumin [1.2-12.4 ng/ml albumin] vs. 0.4 ng/ml albumin [0.2-1.9 ng/ml albumin]). CONCLUSION: These findings suggest that bronchial asthma with mucoid impactions is among several pathogeneses that cause increased levels of CEA in serum and BALF.     

Effects of cyclosporin A on water-immersion stress-induced gastric lesion and gastric secretion in rats

Cyclosporin A is an immunosuppressive agent which is well known as a specific inhibitor of calcineurin (protein phosphatase 2B). In this study, we investigated the effects of cyclosporin A on water-immersion stress-induced gastric ulcer formation and gastric acid secretion in rats. We also examined the localization of calcineurin immunohistochemically. Calcineurin was specifically expressed in gastric parietal cells and chief cells of the gastric mucosa. The intraperitoneal administration of cyclosporin A dose-dependently suppressed the development of gastric mucosal lesions induced by water-immersion stress and inhibited gastric acid secretion, as assessed by pylorus ligation. These results indicated that calcineurin may play an important role in gastric acid secretion. Received: October 14, 1999 / Accepted: January 28, 2000     

Amyloidosis associated with chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL), the most common form of leukemia in Western countries, rarely induces glomerular disease, but membranoproliferative glomerulonephritis or immunotactoid glomerulopathy has been reported. The proliferating cells in CLL are of mature B-cell origin and produce monoclonal immunoglobulin (Ig), thus leading to various kinds of autoimmune disorders or immunotactoid glomerulopathy. Although there have been a few reported cases of amyloidosis accompanying CLL, the type of amyloid fibrils has not been demonstrated nor described in detail, particularly regarding monoclonal Ig productivity. We report a rare case of amyloidosis associated with CLL, in which we detected ?-light chain type monoclonal Ig in the sera, urine, and on the surface membrane of lymphocytes, and discuss an association between monoclonal Ig-related disease and non-Hodgkin's lymphoma.     

A case of pulmonary hypertrophic osteoarthropathy associated with primary lung cancer in a young adult successfully treated with gefitinib]

The patient was a 39-year-old woman admitted with complaints of fever, clubbed fingers and arthralgia. A chest roentgenogram and chest computed tomographic scan revealed a mass in the left lower lobe. Transbronchial lung biopsy was performed, and a diagnosis of moderately differentiated adenocarcinoma was made. Physical examination confirmed finger clubbing in both hands. Bone scintigram showed marked accumulation of 99mTc-MDP in the long bones, bones of the elbows, and patellae. These findings yielded a diagnosis of pulmonary hypertrophic osteoarthropathy associated with primary lung cancer in young adult. The patient had fever and disturbance of gait of arthralgia on admission, and was treated with an oral non-steroidal anti-inflammation drug (NSAID). Advanced non small cell lung cancer (clinical stage T2 N3 M1, Stage IV) was then diagnosed. Gefitinib was administered after EGFR mutation was found in the tumor specimen. NSAID therapy alleviated the fever and arthralgia. After starting gefitinib and discontinuing the NSAID, She had kept a remission of rational symptom with cytoreductive effect. The abnormal findings of bone scintigrams subsequently disappeared and the patient's serum ICTP dropped.