Sero-epidemiologic study of hepatitis C virus infection in Fukuoka, Japan

We conducted an epidemiological study of 509 residents of H town, Fukuoka, Japan, to investigate the high mortality rate from liver disease. Antibodies to hepatitis C virus (HCV) (anti-HCV) were detected in 120 residents (23.6%); HCV RNA in 91 (17.9%), and hepatitis B surface antigen (HBsAg) in 13 (2.6%). Multivariate logistic regression analyses showed that presence of anti-HCV, male gender, and history of liver disease were associated with the presence of liver dysfunction, and that age of more than 40 years and a particular district were associated with the presence of anti-HCV. HCV RNA was more frequently detected in anti-HCV-positive men than women (41, or 85.4% versus 50, or 69.4%) (P < 0.05). The incidence of liver dysfunction was significantly higher in HCV RNA-positive men than women (32, or 66.7% versus 22, or 30.6%) (P < 0.05). These findings suggest that: (1) HCV was correlated with the high mortality rate from liver diseases, (2) there were district-related differences in the incidence of HCV, and (3) the lower frequency of elimination of HCV from men may explain why they showed a high mortality from liver disease. (Received Mar. 4, 1997; accepted Aug. 22, 1997)     

Cystic cavernous hemangioma of the liver

We report an unusual case of multilocular cystic cavernous hemangioma of the liver. The patient was a 61-year-old woman without liver disfunction but who had multicystic mass lesions in the liver. Although cavernous hemangiomas are usually accurately diagnosed by the various imaging modalities, our case showed atypical features.     

Serum vascular endothelial growth factor: a new predictive indicator for the occurrence of coronary artery lesions in Kawasaki disease

We investigated serum vascular endothelial growth factor (SVEGF) levels in Kawasaki disease and determined whether these levels had any association with the development of coronary artery lesions. We measured SVEGF levels in 66 patients with Kawasaki disease, 18 patients with active infections and 18 afebrile controls. SVEGF levels of patients in the acute phase of Kawasaki disease (0.0–2003.6 pg/ml, median 59.87 pg/ml) were significantly higher than those of patients with active infections (0.0–45.2 pg/ml, median 8.10 pg/ml; P < 0.05) or afebrile controls (0.0–49.8 pg/ml, median 7.75 pg/ml; P < 0.05) and decreased to undetectable or low levels in the recovery phase (n=31, acute phase: 0.0–2003.6 pg/ml, median 62.50 pg/ml versus recovery phase: 0.0–146.5 pg/ml, median 26.90 pg/ml; P=0.0007) of the disease. There existed a positive correlation between SVEGF levels and serum C-reactive protein concentrations in the acute phase of Kawasaki disease (r _s =0.347, P=0.0051). In addition, SVEGF level and duration of fever were found to be major risk factors for the occurrence of coronary artery lesions by univariate (P=0.012 and P=0.003, respectively) and multivariate (P=0.037, OR 6.16 and P=0.0059, OR 7.59, respectively) analyses. Conclusion Serum vascular endothelial growth factor level, in combination with persistence of fever, could be a powerful predictor for the development of coronary aneurysms. Received: 16 March 1999 / Accepted: 30 November 1999     

A case of invasive lobular carcinoma of the breast first manifesting with duodenal obstruction

Lobular carcinoma of the breast presents with various clinical manifestations. Lobular carcinoma comprises about one fifth of cases of ductal carcinoma. Intestinal metastasis is dominant in cases of lobular carcinoma. Without a prior diagnosis of lobular carcinoma of the breast, the diagnosis of intestinal metastasis from breast cancer is difficult. A 52-year-old women underwent duodenogastrectomy for duodenal cancer. About 18 months later, she underwent mastectomy for lobular carcinoma of the breast. The duodenal cancer consisted mainly of malignant cells invading the submucosa that were identical to those in the breast. Immunohistochemical assays for estrogen receptor also confirmed breast cancer metastasis. Duodenal obstruction was the first sign of isolated metastatic lobular carcinoma of the breast in this case. The characteristic metastatic pattern of lobular carcinoma, which differs from that of ductal carcinoma, should be kept in mind to ensue proper diagnosis. Preceding breast surgery for lobular carcinoma should prompt investigation based on the typical metastatic pattern.     

The kinetics of CD80 and CD86 expression on antigen-presenting cells in cedar pollinosis subjects

CD80 and CD86, which are costimulatory molecules in T-cell activation, play important roles in the differentiation of Th1- or Th2-phenotypes. The results of blocking studies using neutralizing antibodies have suggested that CD80 and CD86 also play important roles in sensitization to cedar pollen antigen, but very few studies have examined the kinetics of CD80 and CD86 expression on antigen-presenting cells (APC). We studied the kinetics of CD80 and CD86 expression on APC after allergen-stimulation in cedar pollinosis subjects. A skin-prick test was performed in nine subjects with pollinosis and seven control subjects. Peripheral blood mononuclear cells (PBMC) were isolated and stimulated with Japanese cedar pollen extract. Zero to 8 days following in vitro stimulation, the expression of CD80 and CD86 in either CD14+ or CD19+ cells was analyzed by two-color flow cytometry. The expression of CD28, CTLA-4 and CD40L on CD4+ cells was analyzed by two-color flow cytometry after eliminating either CD14+ or CD19+ cells. After in vitro stimulation, the expression of both CD80 and CD86 was significantly upregulated in pollinosis subjects compared to control subjects. However, the difference was observed in the kinetics of CD80 and CD86 expression following allergen stimulation. The expression of CD86 was upregulated earlier than that of CD80 after in vitro stimulation. In the absence of CD19+ cells, the expression of CD28, CTLA-4, and CD40L in CD4+ cells was significantly lower than that in the absence of CD14+ cells. These results indicate that CD19+ cells of pollinosis subjects expressed higher CD80 and CD86 than that of control subjects, and that the kinetics of CD80 and CD86 expression following stimulation differed. In pollinosis subjects, CD19+ cells may thus function as APC in allergen-induced activation of PBMC.     

Influence of acute progressive hypoxia on cardiovascular variability in conscious spontaneously hypertensive rats

The purpose of this study is to examine the influence of acute progressive hypoxia on cardiovascular variability and striatal dopamine (DA) levels in conscious, spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). After preparation for measurement, the inspired oxygen concentration of rats was decreased to 10% within 5 min (descent stage), maintained at 10% for 10 min (fixed stage), and then elevated back to 20% over 5 min (recovery stage). The systolic blood pressure (SBP) and heart rate (HR) variability at each stage was calculated to evaluate the autonomic nervous system response using the wavelet method. Striatal DA during each stage was measured using in vivo microdialysis. We found that SHR showed a more profound hemodynamic response to progressive hypoxia as compared to WKY. Cardiac parasympathetic activity in SHR was significantly inhibited by acute progressive hypoxia during all stages, as shown by the decrease in the high frequency band of HR variability (HR-HF), along with transient increase in sympathetic activity during the early hypoxic phase. This decrease in the HR-HF continued even when SBP was elevated. Striatal DA levels showed the transient similar elevation in both groups. These findings suggest that acute progressive hypoxic stress in SHR inhibits cardiac parasympathetic activity through reduction of baroreceptor reflex sensitivity, with potentially severe deleterious effects on circulation, in particular on HR and circulatory control. Furthermore, it is thought that the influence of acute progressive hypoxia on striatal DA levels is similar in SHR and WKY.     

Climbing exercise enhances osteoblast differentiation and inhibits adipogenic differentiation with high expression of PTH/PTHrP receptor in bone marrow cells

We developed previously a mouse voluntary climbing exercise model as a physiological mechanical loading model and reported that climbing exercise increased bone formation, but its effect on adipogenesis is unknown. We assessed the effects of loading and PTH/PTHrP receptor (PTHR1) on bone marrow adipocyte differentiation in relation with osteoblast differentiation. 8-week-old C57BL/6J male mice were divided into ground control (GC) and climbing exercise (EX) group. Mice were housed in 100-cm towers and climbed up toward a bottle placed at the top of the cage to drink water. The values of bone volume and osteoblast number were significantly higher while those of marrow adipocyte volume and number were significantly lower in the 28dayEX group than 28dayGC group. The mRNA expression levels of adipocyte differentiation genes CCAAT/enhancer-binding proteins (C/EBP) beta and delta were lower in 4dayEX mice, while the adipocyte specific genes fatty acid binding protein (aP2) and phosphoenolpyruvate carboxykinase (PEPCK) expressions were lower in 7dayEX mice. In primary bone marrow cell cultures, the number of alkaline phosphatase-positive colony forming units-fibroblastic (ALP+ CFU-f) and Oil-red-O-positive cells were both increased in the 4dayEX group. Climbing exercise transiently increases both osteogenic and adipogenic potential in bone marrow stromal cells, and inhibits terminal adipocyte differentiation and promotes osteoblast differentiation. Immunoreactivity for the PTHR1 was intense on osteoblastic cell lineage in the endosteal tibial metaphysis. PTHR1 mRNA expression was increased in 4dayEX mice and PTHR1-positive cells were increased after 7 days in the experimental group. Ex vivo addition of PTHR1 antibody decreased and that of PTHrP(1-34) increased the number of ALP+ CFU-f in bone marrow cell cultures obtained at 4 days after the exercise, while the addition of PTHR1 antibody increased and PTHrP(1-34) decreased the number of Oil-red-O-positive cells. Our results indicate that climbing exercise enhanced osteoblast differentiation and inhibited terminal differentiation of adipocyte progenitors with high expression of PTHR1 in bone marrow cells.