Mechanism of thyroid stimulation by human chorionic gonadotropin in sera of normal pregnant women.

To elucidate the mechanism of thyrotropic activity of human chorionic gonadotropin in sera of normal pregnant women, we examined the effect of blockade of the TSH receptor on the serum-induced cAMP accumulation and the effect of hCG on the TSH binding to FRTL-5 cells. In the presence of crude immunoglobulin fractions in sera from patients with primary hypothyroidism, cAMP accumulation induced by both crude and purified hCG, and normal pregnant women serum were significantly inhibited compared with that in the presence of normal IgGs. The mode of inhibition of these IgGs on the cAMP accumulation was similar for TSH and hCG when analysed by Lineweaver-Burk plots. Moreover, binding of [125I]bTSH to the TSH receptor in porcine thyroid cell membrane was apparently inhibited by adding 4 x 10(6) IU/l of purified hCG. Binding studies of TSH in FRTL-5 cells also indicated the dose-dependent displacements of [125I]TSH by hCG. Although half-maximal inhibitory concentration of hCG was about 20 times as high as that of TSH on a molar basis, displacement of [125I]TSH was observed at a concentration of hCG of 10(5)IU/l or more, which could be a physiological concentration of hCG in sera of normal pregnant women. These results suggest that thyrotropic activity of hCG in sera of normal pregnant women is, at least in a part, mediated by TSH receptors.     

Comparison of the activities of multinucleated bone-resorbing giant cells derived from CD14-positive cells in the synovial fluids of rheumatoid arthritis and osteoarthritis patients

OBJECTIVE: To investigate the morphology and function of multinucleated bone-resorbing giant cells derived from CD14-positive cells in the synovial fluids (SF) of patients with rheumatoid arthritis (RA) or osteoarthritis (OA). METHODS: CD14-positive cells were obtained by magnetic-activated cell sorting of primary cultures of mononuclear cells from the SF. Multinucleated bone-resorbing giant cells were induced from the CD14-positive cells in the presence or absence of cytokines. We examined various characteristics, including osteoclast markers, fusion index and bone-resorption activities of the multinucleated giant cells. RESULTS: Multinucleated giant cells were induced from the CD14-positive cells in the SF of the RA and OA patients by the addition of interleukin (IL)-3, IL-5 and IL-7, or granulocyte-macrophage colony-stimulating factor (GM-CSF), respectively. These multinucleated giant cells were positive for tartrate-resistant acid phosphatase (TRAP), carbonic anhydrase II, actin, vitronectin receptor and the calcitonin receptor. However, the average values for the number of nuclei, fusion index and bone-resorption functions of the SF cells from the RA patients were significantly higher than those derived from the OA patients. CONCLUSION: These results suggest that the induction and activities of multinucleated bone-resorbing giant cells may play a pivotal role in bone destruction, and that these processes may be enhanced significantly in RA patients.     

Reverse redistribution of thallium-201 myocardial single photon emission tomography and contractile reserve

The present study investigated the contractile reserve of myocardium exhibiting reverse redistribution (RRD) of thallium-201 (201Tl) after acute myocardial infarction. Forty patients experiencing their first acute myocardial infarction underwent resting 201Tl single-photon emission computed tomography (SPECT) and low-dose (5-10 microgxkg(-1)xmin(-1)) dobutamine stress echocardiography (DSE) within 4 weeks after the onset of infarction. The left ventricle was divided into 13 segments for analysis. The severity of defects in 201Tl SPECT and the extent of wall motion abnormality in DSE were visually assessed and scored. The sum of each defect score and wall motion score of infarct-related segments were defined as total defect score (TDS) and total wall motion score (TWM), respectively. Quantitative analysis of 201Tl uptake was also performed. Resting 201Tl SPECT revealed RRD in 16 patients (group RRD), fixed defect (FIX) in 23 patients (group FIX), and redistribution in one. There was a significant difference in improvement of TWM between rest and stress in TWM in both the RRD and FIX groups (p<0.0001, each case). The improvement of TWM with dobutamine was significantly greater in RRD than in FIX (1.6+/-1.0 vs 0.6+/-0.7, p=0.001). There was a positive correlation between the magnitude of RRD and improvement of TWM with dobutamine (r=0.48, p=0.002). Myocardium exhibiting RRD on 201Tl SPECT in patients with acute myocardial infarction has greater contractile reserve than that exhibiting a fixed defect.     

The Change in Body Composition After Bilateral Lung Volume Reduction Surgery for Underweight Patients with Severe Emphysema

The aim of this study was to examine the short-term effect of lung volume reduction surgery (LVRS) on body composition and other nutritional indicators in 28 patients with emphysema underwent thoracoscopic LVRS. Functional tests, body weight (BW), and body composition were measured before and 6 months after surgery. Mean daily caloric intake (CI) was estimated by 3-day dietary record as well. Fat-free mass (FFM) and fat mass (FM) were assessed by bioelectrical impedance analysis (BIA). FEV_1.0 and Vo _2max have improved after LVRS by 35.2% and 23.8%, respectively. Preoperatively, 75% of patients were underweight (% ideal body weight (%IBW) <90) with the mean %IBW at 84.5%. BW, CI, and FFM increased significantly after LVRS, whereas FM was unchanged. The change in BW correlated significantly with the change in FEV_1.0, MVV, and Vo _2max (p < 0.01) but not with CI. Bilateral LVRS results in an increase in FFM and functional improvement for underweight patients with severe emphysema, and it may contribute to the improvement in maximal exercise capacity. Accepted for publication: 12 December 2000     

G‐cell hyperplasia of the stomach induces ECL‐cell proliferation in the pyloric glands in a paracrinal manner

An inhibitory mechanism toward gastrin hypersecretion is significantly different between G‐cell hyperplasia and gastrinoma despite the common clinical manifestations; hypergastrinemia and its related persistent gastric ulcers. We recenlty studied the G‐cell, d ‐cell and ECL‐cell density in a case of G‐cell hyperplasia. The 70‐year‐old patient has been treated for persistent gastric ulcers with a markedly increased plasma gastrin (5600 pg/mL). The stomach was surgically resected because of the obstruction associated with ulcer scars. The number of G‐cells in the pyloric glands was quantified on the surgical specimens and G‐cell hyperplasia was histolopathologically identified. Immunostainig of histidine decarboxylate revealed the presence of ECL‐cell hyperplasia in the pyloric glands and its density was significantly and positively correlated with G‐cell density. Somatostatin immunoreactive cells (d ‐cells) increased in their number in the oxyntic glands. These results all indicated that hypersecretion of gastrin in G‐cell hyperplasia could induce ECL‐cell proliferation in a paracrinal manner. In addition, relatively non‐prominent endocrinological features in the G‐cell hyperplasia compared to gastrinoma could be also related to the paracrinal somatostatin inhibitory effects upon ECL‐cells in the pyloric glands.     

Molecular diagnosis and characterization of a culture-negative mycotic aneurysm due to ST54 Haemophilus influenzae type b with PBP 3 alterations

Mycotic aneurysm is a rare but life-threatening disease that warrants an integrated therapeutic approach involving surgical intervention and prolonged antibiotic use. However, the causative organisms are often unidentified because antibiotics started empirically render blood and tissue cultures negative. Molecular diagnosis has been reported to be useful in such culture-negative cases. We report a case of a culture-negative mycotic aortic aneurysm due to Haemophilus influenzae, diagnosed by direct 16S rRNA polymerase chain reaction (PCR) and sequencing of the resected aneurysm tissue. PCR for serotype revealed type b, and PCR and sequencing of the ftsI gene revealed alterations in penicillin-binding protein 3, suggesting resistance to ampicillin. Multilocus sequence typing demonstrated that the isolate belonged to sequence type 54.     

Biomarkers in autoimmune pancreatitis and immunoglobulin G4-related disease

Solitary organ autoimmune disorders, formerly known as autoimmune pancreatitis (AIP), autoimmune sialadenitis, and autoimmune sclerosing cholangitis, are now considered organ-specific manifestations of systemic immunoglobulin G4-related disease (IgG4-RD). AIP and IgG4-RD are characterized by elevated serum concentration of IgG4 antibody (Ab), accumulation of IgG4-expressing plasmacytes in the affected organs, and involvement of multiple organs. It is well established that enhanced IgG4 Ab responses are a hallmark of AIP and IgG4-RD for diagnosis and monitoring disease activity. However, a significant fraction of patients with AIP and IgG4-RD who develop chronic fibroinflammatory responses have normal serum concentrations of this IgG subtype. In addition, disease flare-up is sometimes seen even in the presence of normalized serum concentrations of IgG4 Ab after successful induction of remission by prednisolone. Therefore, it is necessary to identify new biomarkers based on the understanding of the pathophysiology of AIP and IgG4-RD. Recently, we found that activation of plasmacytoid dendritic cells producing both interferon-α (IFN-α) and interleukin-33 (IL-33) mediate murine AIP and human IgG4-RD. More importantly, we provided evidence that serum concentrations of IFN-α and IL-33 could be useful biomarkers for the diagnosis and monitoring of AIP and IgG4-RD activity after induction of remission in these autoimmune disorders. In this Frontier article, we have summarized and discussed biomarkers of AIP and IgG4-RD, including Igs, autoAbs, and cytokines to provide useful information not only for clinicians but also for researchers.