Ability of myeloma cells to secrete macrophage inflammatory protein (MIP)-1alpha and MIP-1beta correlates with lytic bone lesions in patients with multiple myeloma

Macrophage inflammatory protein (MIP)-1alpha and MIP-1beta have been identified as candidates for multiple myeloma (MM)-derived bone-resorbing factors. To validate the clinical relevance of these observations, we investigated correlations between the ability of MM cells to secrete these chemokines and the extent of MM bone lesions as well as levels of biochemical bone markers in patients with MM. Patients with multiple bone lesions exhibited higher MIP-1alpha and MIP-1beta secretion from MM cells along with elevated urinary deoxypyridinoline (Dpd), without significant elevation of serum bone-specific alkaline phosphatase (BALP) or osteocalcin compared with those with minimal bone lesions. MIP-1alpha and MIP-1beta levels correlated positively with urinary Dpd and serum BALP but not with serum osteocalcin. These results provide further evidence for a causal role of MIP-1alpha and MIP-1beta in the development of lytic bone lesions, and suggest that MM cells suppress osteoblastic bone formation to cause an imbalance of bone turnover and development of destructive bone lesions.     

Chronic salt loading upregulates expression of adrenomedullin and its receptors in adrenal glands and kidneys of the rat

The vasodilator peptide adrenomedullin (AM) elicits diuresis and natriuresis and inhibits aldosterone secretion. The aim of this study was to better understand the role of AM in maintaining water and electrolyte balance during chronic salt loading. Male Wistar rats were divided into a high salt (HS) group that received a diet containing 8% sodium chloride (NaCl) and a normal salt group that received a diet containing 0.4% NaCl. Plasma AM concentrations as well as expression of AM mRNA in the adrenal gland and kidney were then measured after 3, 7, 14, and 28 days. After 28 days, sodium and water excretion were significantly higher in HS rats than in control, although blood pressure and fluid volume were not significantly affected. Moreover, although plasma AM remained unchanged for up to 14 days, it was increased 2.5-fold in HS rats after 28 days on a high salt diet, and there were corresponding 3-fold and 1.5-fold increases in the levels of AM mRNA in the adrenal gland and kidney, respectively. At the same time, expression of calcitonin receptor-like receptor mRNA was significantly upregulated in both kidney and adrenal gland, as was expression of receptor activity-modify protein 1 (RAMP1) and RAMP2 mRNA in the adrenals and expression of RAMP3 in kidneys. Taken together, these results suggest that AM plays a role in the regulation of water and electrolyte balance in animals chronically ingesting high levels of salt.     

Protein-losing gastropathy associated with autoimmune disease: successful treatment with prednisolone

99m Tc-labeled human serum albumin scintigram showing abnormal radioactivity in the stomach. Endoscopic gastric biopsies revealed nonspecific inflammation, but marked intramural edema. Based on a slight elevation of antinuclear antibody level, autoimmune disease was suspected to be involved in this patient. Administration of prednisolone, as a diagnostic therapy, alleviated the hypoproteinemia, hypoalbuminemia, and hypercholesteremia. These findings suggest that an autoimmune mechanism could have been involved in this case of protein-losing gastropathy. Received: September 4, 2000 / Accepted: February 23, 2001     

Surgical resection of malignant lymphoma in the right atrium after systemic chemotherapy

A 74-year-old man was referred to us for evaluation of a tumor in the right atrium (RA). Transesophageal echocardiography (TEE) showed an unmovable 50x60 mm mass in the RA. Based on histological findings of subcutaneous tumors in the right abdominal wall, he was diagnosed as malignant lymphoma (ML), and treated with a THP-COP regimen. Upon completion of first THO-COP therapy, TEE showed marked regression of the mass and division into 3 masses, one of which showed marked floating movement with a small stalk. To prevent the risk of embolic events, surgical resection was performed. Resected tumors were necrotic tissues. Serial imaging of cardiac tumor and surgical resection is desirable to decrease the possibility of embolic complication.     

Clinical characteristics of COVID-19 patients with underlying rheumatic diseases in Japan: data from a multicenter observational study using the COVID-19 Global Rheumatology Alliance physician-reported registry

Clinical Rheumatology - To describe clinical characteristics of patients in Japan with coronavirus disease 19 (COVID-19) and pre-existing rheumatic disease and examine the possible risk factors...     

Helicobacter pylori and gut hormones

Helicobacter pylori infection has been found to decrease the expression of antral somatostatin and to increase the release of the acid-stimulating hormone gastrin. The reversal of these changes in gut hormones by the eradication of H. pylori, and in-vivo and in-vitro studies in animals either infected with H. pylori or exposed to H. pylori-related materials may support the somatostatin-gastrin link theory in the pathophysiology of H. pylori infection. The following mechanisms have been proposed to explain the H. pylori infection-associated changes in gut hormones; (1) ammonia produced by H. pylori and monochloramine, (2) effect on somatostatin receptor subtype-2, (3) action of lipopolysaccharide from H. pylori on somatostatin receptor, (4) inflammatory cells and mediators, and (5) bacterial strain diversity. H. pylori infection can alter gastric acid secretion in both directions. The elevated acid secretion in patients with duodenal ulcer is decreased by H. pylori eradication, and is accompanied by the normalization of gut hormones in patients whose H. pylori-induced gastritis is limited to the antrum with hyperacidity. Corpus gastritis and the subsequent development of mucosal atrophy induced by H. pylori result in decreased acid secretion, although the mechanism underlying H. pylori-induced atrophy in some subjects remains unclear. Hypoacidity enhances corpus atrophy and increases gastrin secretion, mediated via a physiological suppression of somatostatin release, features that are also observed in H. pylori infection. Therefore, the capacity of acid secretion and distribution of gastritis or atrophy should be taken into consideration when we discuss the affect of H. pylori on gut hormones. Received: October 1, 2001 / Accepted: November 30, 2001     

Near-infrared spectrometry analysis of fat, neutral sterols, bile acids, and short-chain fatty acids in the feces of patients with pancreatic maldigestion and malabsorption

Summary Conclusion. Near-infrared spectrometry is a new, rapid, and accurate method for measuring fecal fat that does not require a great deal of chemical knowledge and that can be used by anyone. This method is considered indispensable for the diagnosis of pancreatic steatorrhea and treatment follow-up. Methods. Fecal fats (GLC method, van de Kamer method), neutral sterols (GLC method), bile acids (GLC method) and short-chain fatty acids (HPLC method) were assayed by the respective conventional methods in 120 subjects, including patients with pancreatic dysfunction, and the results were compared with the those obtained by near-infrared spectrometry. The correlations between fecal fat excretion measured by the GLC method (x) and van de Kamer method (x) and by near-infrared spectrometry (y) were expressed by y=1.10 x-0.16 (r=0.949, P<0.01) and y=0.750x+1.654 (r=0.930, p<0.01), respectively. Results. The sensitivity and specificity of near-infrared spectrometry for fecal fats were 94.9 and 98.2%, respectively, when compared with the GLC method, and 87.5 and 90.0%, respectively, when compared with the van de Kamer method. In contrast, near-infrared spectrometry was not nearly as accurate as the conventional methods for determining neutral sterols, bile acids, and short-chain fatty acids.     

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