Quantitative insulin sensitivity check index is a useful indicator of insulin resistance in Japanese metabolically obese, normal-weight subjects with normal glucose tolerance

To clarify whether quantitative insulin sensitivity check index (QUICKI) is useful as an indicator of insulin resistance in Japanese metabolically obese, normal-weight (MONW, body mass index (BMI) <25 and visceral fat area (VFA) > or = 100 cm2 by abdominal computed tomography scanning) subjects with normal glucose tolerance (NGT). Insulin resistance was measured by QUICKI and euglycemic hyperinsulinemic clamp study (clamp IR) in 27 MONW and 27 normal subjects (BMI <25 and visceral fat area <100 cm2). QUICKI (P<0.01) and clamp IR (p<0.01) were significantly decreased in MONW subjects compared with normal subjects. QUICKI was significantly associated with VFA [MONW subjects: r = -0.459, p<0.02; all (MONW and normal) subjects: r = -0.506, p<0.0001] and with the serum levels of triglycerides (MONW subjects: r = -0.386, p<0.05; all subjects: r = -0.505, p<0.001) in MONW and all subjects. There were significant correlations between clamp IR and VFA (MONW subjects: r = -0.562, p<0.01; all subjects: r = -0.575, p<0.0001), fasting serum levels of insulin (MONW subjects: r = -0.673, p<0.001; all subjects: r = -0.619, p<0.0001) or serum levels of triglycerides (MONW subjects: r = -0.485, p<0.02; all subjects: r = -0.565, p<0.0001) in MONW and all subjects. QUICKI was significantly correlated with clamp IR in MONW (r = 0.754, p<0.0001) and in all subjects (r = 0.568, p<0.0001). QUICKI may be an useful method for assessing insulin resistance in Japanese MONW subjects with NGT.     

Role of the spleen in liver fibrosis in rats may be mediated by transforming growth factor beta-1

BACKGROUND: The effect of the spleen on the cirrhotic liver is unknown. Transforming growth factor-beta 1 (TGF-beta 1), which plays a crucial role in the matrix production during liver fibrosis, is an inhibitory factor regarding the regeneration of hepatocytes. In this study, we investigated the TGF-beta 1 production in the spleen of cirrhotic rats and the effects of a splenectomy on the healing process from liver fibrosis. METHODS: Thirty-six Wistar male rats were used. Thioacetamide (TAA) was administered intraperitoneally for 24 weeks. The rats underwent either a sham operation (TAA + Sham) or a splenectomy (TAA + SPL). The improvements in liver fibrosis and liver regeneration were investigated 10, 30 and 60 days after the operations in each group. The effect of a splenectomy on the plasma concentration of TGF-beta 1 in the portal vein was investigated by ELISA. The TGF-beta 1 expressions in the spleen were measured using immunohistochemical staining and the degree of such expression was measured using RT-PCR. The activity of TGF-beta 1 in the portal vein of TAA + Sham and TAA + SPL was assessed by the inhibiting effect of rat parenchymal hepatocyte proliferation in primary culture. RESULTS: Liver regeneration (PCNA-labeling index) in the TAA + SPL rats was stimulated more at 10 and 30 days after the operation (P < 0.05) than in the TAA + Sham rats, and the improvement of liver fibrosis (fibrosis rate) in the TAA + SPL rats was higher at 60 days (P < 0.05) than in the TAA + Sham rats. The plasma concentration of TGF-beta1 of the portal vein in TAA + SPL rats was significantly lower than in the TAA + Sham rats for each period. Immunohistochemically, TGF-beta1-positive stained cells were recognized in the spleen macrophages in the red pulp of cirrhotic rats. The plasma of the TAA + Sham rats at 10 and 30 days after the operation was significantly stronger than that of the TAA + SPL rats in inhibiting the proliferation of rat hepatocytes of primary culture. Inhibitory effects were then dose-dependently neutralized by monoclonal TGF-beta 1 antibody. CONCLUSION: Spleen-derived TGF-beta 1 may thus play an inhibitory role in the healing of liver cirrhosis by inhibiting the regeneration of the damaged liver.     

Biosynthesis and secretion of mucin-related products in Hs746T gastric cancer cells

We have previously studied the biosynthesis and secretion of mucin in the normal human stomach and reported that the tetramer of the 60-kDa subunit of mucin core protein was synthesized and highly glycosylated, and that only high molecular weight mucin was secreted. In this study, we investigated the mucin-related products of a gastric cancer cell line (Hs746T). Analysis of intracellular and extracellular products immunoprecipitated with an anti-apomucin monoclonal antibody revealed that a 110-kDa protein, the dimer of the 55-kDa subunit, was synthesized and secreted. Tunicamycin treatment inhibited the secretion of the 110-kDa protein. These findings suggest thatN-glycosylation may be involved in the secretory mechanism of the mucin-related product.     

Prevalence of gastroesophageal reflux symptoms in a large unselected general population in Japan

AIM：To examine the prevalence of gastroesophageal reflux disease （GERD） symptoms in a large unselected general population in Japan.
METHODS： In Japan, mature adults are offered regular check-ups for the prevention of gastric cancer. A notice was sent by mail to all inhabitants aged 〉 40 years. A total of 160 983 Japanese （60 774 male, 100 209 female; mean age 61.9 years） who underwent a stomach check up were enrolled in this study. In addition, from these 160 983 subjects, we randomly selected a total of 82 894 （34 275 male, 48 619 female; mean age 62.4 years） to evaluate the prevalence of abdominal pain. The respective subjects were prospectively asked to complete questionnaires concerning the symptoms of heartburn, dysphagia, and abdominal pain for a 1 mo period.
RESULTS： The respective prevalences of the symptoms in males and females were： heartburn, 15.8% vs 20.7%; dysphagia, 5.4% vs 7.8%; and abdominal pain, 6.6% vs 9.6%. Among these symptoms, heartburn was significantly high compared with the other symptoms, and the prevalence of heartburn was significantly more frequent in females than in males in the 60-89-year agegroup. Dysphagia was also significantly more frequent in female patients.
CONCLUSION： The prevalence of typical GERD symptoms （heartburn） was high, at about 20% of the Japan population, and the frequency was especially high in females in the 60-89 year age group.     

Demonstration of three distinct immunological disorders on erythropoiesis in a patient with pure red cell aplasia and autoimmune haemolytic anaemia associated with thymoma

A patient with pure red cell aplasia (PRCA) and autoimmune haemolytic anaemia (AIHA), associated with a thymoma which had already been removed, was studied in order to investigate the pathogenesis of PRCA and AIHA. The autoantibody eluted from the surface of the patient's red blood cells (RBC) reacted with the large E antigen of the Rh complex. Immunoglobulin-G (IgG) purified from the patient's serum suppressed CFU-E and BFU-E but not CFU-GM colony formation in the presence of complement. This antibody was not adsorbed with large E antigen. T-lymphocytes in the bone marrow suppressing autologous CFU-E and BFU-E colonies were demonstrated. Thus, three distinct immunological disorders on erythropoiesis were present in this patient with PRCA and AIHA associated with thymoma in a thymectomized state.     

Efficacy of plasma exchange therapy for Kawasaki disease intractable to intravenous gamma-globulin

Kawasaki disease (KD) causes coronary artery lesions (CALs) in 500 Japanese children each year. Intravenous gamma-globulin (IVGG) decreases the incidence of these lesions from 25% to 8% of the total KD cases. We examined whether plasma exchange is a safe and effective prophylaxis against CALs in children with KD intractable to IVGG therapy. Eighty-nine children with KD at high risk of CALs were selected on the basis of increases in fractional changes in inflammatory markers such as white blood cell count, neutrophil count, and C-reactive protein between the baseline and 1–2 days after IVGG treatment. Of 105 children who received a second course of IVGG therapy because the initial course was ineffective, plasma exchange (PE) was performed in 46 children who had not responded to the second IVGG treatment. The outcome was compared with the results when a third course of IVGG therapy was given to the other 59 children. No complications occurred with the plasma exchange therapy. CALs developed in only 8 of the 46 children (17.3%) who underwent plasma exchange, but they occurred in 24 of the 59 (40.7%) who had received a third course of IVGG therapy (P 0.0012). We concluded that PE was a safe, effective prophylactic measure against CALs in children with KD intractable to IVGG therapy. PE should be performed at an early stage, as soon as fractional increases in inflammatory markers are found after IVGG therapy.     

Cardiovascular risk factors associated with pulse pressure in a screened cohort in Okinawa, Japan.

We evaluated the association between pulse pressure (PP) and cardiovascular risk factors in a screened cohort. Individuals who were receiving medications for hypertension or heart disease, who had no ECG record, or who had a record of arrhythmia were excluded. In total, 8,508 subjects (5,299 men and 3,209 women; age range, 18 to 89 years) were studied. Subjects were divided into four PP classes: PP.1 (PP < or = 40 mmHg, n=2,127), PP.2 (40 < or = PP < or = 44 mmHg, n=2,127), PP.3 (44 < or = PP < or = 50 mmHg, n=2,127) and PP.4 (50 mmHg < or = PP, n=2,127). Multiple regression analysis was used for evaluating the association between PP and cardiovascular risk factor or lifestyle. In men, the regression coefficient was 0.27 for age, 2.50 for diabetes mellitus, 0.33 for uric acid, 0.20 for body mass index, 0.07 for heart rate, -0.83 for current smoking habit and 1.23 for habitual drinking. In women, the regression coefficient was 0.37 for age, 4.09 for diabetes mellitus, 0.42 for body mass index, 0.14 for heart rate, and 0.84 for habitual exercise. In both men and women, PP was significantly increased in association with an increase in the number of risk factors (diabetes mellitus, obesity, current drinking status, heart rate, and hyperuricemia). In conclusion, higher PP was associated with cardiovascular risk factors. These associations were similar in both men and women.     

Hormone replacement therapy causes a decrease in hepatocyte growth factor in hypertensive women

OBJECTIVE: Serum hepatocyte growth factor (HGF) is associated with blood pressure. We investigated whether the serum HGF level differs between hypertensive and normotensive postmenopausal women (PMW) and whether hormone replacement therapy (HRT) alters the serum HGF level and blood pressure in hypertensive and normotensive PMW. DESIGN: Prospective observational study. METHODS: A total of 33 PMW with mild to moderate essential hypertension controlled by antihypertensive treatment (mean age, 57 +/- 6 years) and 23 normotensive PMW (mean age, 57 +/- 7 years) received continuous HRT (0.625 mg of conjugated equine estrogen combined with 2.5 mg of medroxyprogesterone acetate) once a day orally for 12 months, and we measured serum HGF levels and blood pressure before and 12 months after the start of HRT. RESULTS: The baseline serum HGF level was significantly higher in hypertensive PMW than in normotensive PMW. HRT significantly decreased the serum HGF level in hypertensive subjects, from 2.85 +/- 0.64 pmol/l to 2.49 +/- 0.65 pmol/l (P < 0.001), but not in normotensive subjects. HRT did not change blood pressure in either group. CONCLUSIONS: Serum HGF level before the start of HRT was higher in the hypertensive PMW than in the normotensive PMW. Furthermore, HRT decreases serum HGF without decreasing blood pressure in hypertensive PMW. The HRT-induced decrease in serum HGF was greater in hypertensive PMW than in normotensive PMW, and the decrease was independent of blood pressure changes.     

Increased levels of serum osteoprotegerin in hypothyroid patients and its normalization with restoration of normal thyroid function

Hypothyroidism is associated with increased morbidity from cardiovascular disease, and an increase in serum osteoprotegerin (OPG) has recently been reported to be associated with the severity of coronary heart disease and cardiovascular mortality. The present study was designed to examine whether hypothyroidism causes an increase in serum OPG, and to determine whether levothyroxine (L-T4) replacement therapy might suppress serum OPG levels in hypothyroid patients. Fifty-three hypothyroid patients with chronic thyroiditis and age- and sex-matched normal control subjects were examined for the levels of serum OPG and plasma von Willebrand factor (vWF), a vascular injury marker. Thirty-seven of the hypothyroid patients were further monitored for changes in these markers during 1 year in a euthyroid state induced by L-T4 replacement therapy. Baseline OPG was significantly higher in hypothyroid patients than in normal controls (4.51 +/- 0.50 vs 3.72 +/- 0.23 pmol/l (mean +/- S.E.); P = 0.0182). In multivariate analysis, baseline OPG was significantly associated with baseline levels of TSH (r = 0.280, P = 0.0162) and vWF (r = 0.626, P < 0.0001). During one year of L-T4 replacement therapy, hypothyroid patients showed a significant decrease in OPG levels from 4.35 +/- 0.51 to 3.48 +/- 0.26 pmol/l (P = 0.0166), a level comparable to normal controls. The change in serum OPG levels during L-T4 replacement therapy was significantly and independently associated in a negative fashion with baseline vWF (r = -0.503, P = 0.0014). This study suggested that the severity of hypothyroidism and vascular injury might have important independent roles in increasing the serum OPG level in hypothyroid patients. Furthermore, it was demonstrated that a sustained euthyroid state might have the potential to decrease the serum OPG level in hypothyroid patients and that the degree of vascular injury in the hypothyroid state is independently associated with a decrease in serum OPG during a 1-year normalization of thyroid function.