Evaluation of community-acquired pneumonia guidelines of Japanese Respiratory Society: differentiation of atypical pneumonia and bacterial pneumonia]

To evaluate the usefulness of differentiation of atypical pneumonia and bacterial pneumonia in the community-acquired pneumonia guidelines of the Japanese Respiratory Society, we investigated 124 cases of three atypical pneumonias (Mycoplasma pneumonia, 62 cases; Chlamydia pneumoniae pneumonia, 46 cases; Chlamydia psittaci pneumonia, 13 cases) and 403 cases of bacterial pneumonia at our hospital over seven years. Overall, the sensitivity and specificity of the criteria in the guideline were 70.4% and 91.8%, respectively. High accordance was recognized in patients under 60 years old with atypical pneumonia. Items in the criteria that included subjective factors were considered inassessable. We found that the differentiation of pneumonias in the guideline is useful for the diagnosis of atypical pneumonia among younger patients, but it should be concise and objective. We therefore propose that the criteria would be more effective if they consisted of only 4 items: age under 60 years, no underlying disorders, presence of stubborn dry cough, and normal peripheral white blood cell count.     

Increased bone resorption may play a crucial role in the occurrence of osteopenia in patients with type 2 diabetes: Possible involvement of accelerated polyol pathway in its pathogenesis

In order to investigate the underlying mechanism of alterations in bone mineral metabolism in patients with type 2 diabetes, we determined circulating levels of bone functional markers along with urinary excretion of sorbitol (SOR) and bone mineral density (BMD), and also examined their mutual interrelationship. A total of 151 male type 2 diabetic patients were examined in this study. Forty-eight age-matched male healthy subjects were also studied as the controls. A significant reduction of serum intact osteocalcin (i-OC) was found in the diabetic groups (p<0.01). On the other hand, circulating levels of tartrate resistant acid phosphatase (TRAP) in the diabetic patients were significantly higher than those in the controls (p<0.01). Interestingly, a significantly negative relationship was observed between BMD and serum TRAP (p<0.01), although no significant relationship was noted between BMD and serum i-OC in diabetic patients. Urinary excretion of SOR was significantly elevated in the diabetic patients when compared with the controls (p<0.01). In addition, a significantly positive correlation was observed between serum TRAP and urinary SOR (p<0.01), but not between serum i-OC and urinary SOR. Elevated serum TRAP in diabetes was reduced after the administration of aldose reductase inhibitor (p<0.05). It seems most likely that the increase in osteoclastic function probably due to accelerated polyol pathway plays a crucial role in the pathogenesis of decreased bone mineral content in male patients with type 2 diabetes.     

Blockade of Rho/Rho-associated coiled coil-forming kinase signaling can prevent progression of hepatocellular carcinoma in matrix metalloproteinase-dependent manner

Aim:  There is growing evidence that the Rho/Rho-associated coiled coil-forming kinase (ROCK) signaling pathway is upregulated in tumors and plays a key role in cancer invasion and metastasis. Our aim was to test the anticancer effects of Rho/ROCK inhibitor, Y-27632, including possible mechanisms in a highly-metastasizing hepatocellular carcinoma (HCC) mouse model on its secretion of matrix metalloproteinase (MMP) and tumor progression.
Methods:  Following orthotopic implantation of CBO140C12 HCC tumor fragments into the liver of mice, the mice were randomly assigned to a Y-27632-treated group or control group. After treatment for 4 weeks, specimens were obtained to evaluate tumor size, metastases, and immunohistochemical findings. In vitro , we examined the effects of Y-27632 and RhoC siRNA on MMP-2 and -9 expressions, invasiveness, and apoptosis in cultured tumor cells.
Results:  Both RhoA and RhoC were upregulated in HCC-bearing livers, and Y-27632 significantly inhibited not only tumor growth and intrahepatic metastasis ( P  < 0.05), but also tumoral MMP-9 expression. Moreover, Y-27632 treatment resulted in large necrotic areas in tumors. In vitro , Y-27632 and RhoC siRNA reduced MMP-2 and -9 expressions, as well as the chemotactic migration of tumor cells dose-dependently, and increased apoptosis eight times.
Conclusion:  Y-27632 suppresses progression and limits the intrahepatic metastasis of established HCC. This could be linked to the decreased MMP expression and induction of apoptosis in tumor cells. Rho signaling may prove to be a productive target in anticancer therapy.     

Expression of hepatitis B surface antigen subtypes in liver of patients with hepatocellular carcinoma; comparison of subtypes in serum and liver

ABSTRACT— To clarify the discrepancy in hepatitis B surface antigen (HBsAg) subtypes present in the serum and liver, as well as among hepatocytes, liver specimens which were resected from 37 HBsAg-positive patients with hepatocellular carcinoma (HCC) were examined. We evaluated HBsAg and the subtypic determinants of HBsAg and hepatitis B core antigen (HBcAg) using the peroxidase-antiperoxidase (PAP) staining method. Hepatitis B antigens were more frequently detected in small tumors (HBsAg in 67%, HBcAg in 40%) than in large ones (HBsAg in 36%, HBcAg in 14%). The prevalence of each subtypic determinant in the HBsAg positive non-tumorous vs. tumorous areas was 100% vs. 67% in a, 100% vs. 57% in d, 100% vs. not tested in y, 100% vs. 53% in r and 25% vs. 0% in w (a, d, y, r and w represent subtypic determinants). There was virtually no difference in a set of subtypic determinants between the serum and liver. However, there were some variations in a set of subtypic determinants among the hepatocytes. On the other hand, liver tissue of compound subtype adyr in serum contained both cells with a,d,r and with a,y,r as well as a few cells with a,d,y,r. These findings suggest that HBV genomes in hepatocytes of type B chronic liver disease may differ genetically among cells even in the same liver tissue.     

Altered relationship between body fat and plasma adiponectin in end-stage renal disease

Patients with end-stage renal disease (ESRD) show an inverse association between body mass index and risk of death from cardiovascular disease. Paradoxical epidemiology may suggest some beneficial effects of body fat in ESRD. Because an antiatherogenic adipocytokine adiponectin is increased in uremic plasma, we tested a hypothesis that, in ESRD, plasma adipocytokine profile may be less atherogenic or that the relationship between body fat and adipocytokines may be altered. The subjects were 103 patients with ESRD undergoing hemodialysis and 166 healthy subjects comparable in age and sex. We measured body fat mass by dual-energy x-ray absorptiometry and plasma levels of adiponectin and leptin by enzyme-linked immunosorbent assay. The ESRD group showed a significant increase in plasma adiponectin, leptin, and adiponectin/leptin ratio than the healthy subjects. Although sex and fat mass were significant factors correlating with plasma adiponectin level in the healthy group, none of these were significantly associated with plasma adiponectin in the patients with ESRD. In contrast, leptin showed significant relationships with sex and fat mass regardless of the presence of ESRD. Plasma adiponectin correlated negatively with plasma triglycerides and positively with high-density lipoprotein cholesterol in both healthy and ESRD groups, suggesting that uremic adiponectin retains its actions in favor of its antiatherogenicity. Thus, plasma adipocytokine profile was altered in ESRD, and the effects of body fat and sex on adiponectin were less significant in the patients with ESRD.     

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.     

Effects of angiotensin-converting enzyme inhibition on changes in left ventricular myocardial creatine kinase system after myocardial infarction: their relation to ventricular remodeling and function

We assessed the effects of angiotensin-converting enzyme (ACE) inhibition on changes in the myocardial intracellular creatine kinase (CK) system in relation to left ventricular (LV) remodeling and function in heart failure after myocardial infarction (MI) in rats. We compared the findings at 4 weeks after MI to those at 12 weeks after MI. LV weight and chamber size were significantly increased and percent fractional shortening (%FS) was decreased in untreated MI rats compared with normal control animals both at 4 and 12 weeks after MI. Animals with MI and treated with the ACE inhibitor temocapril showed significantly reduced LV weight and chamber size and increased %FS compared with untreated MI rats at 12 weeks after MI, but not at 4 weeks after MI. At 4 weeks after MI, no significant changes were found in the total creatine and relative distribution of each CK isoenzyme in either the temocapril-treated or untreated animals with MI compared with the normal controls. In contrast, at 12 weeks after MI, untreated MI rats showed significant reductions in the total creatine and mitochondrial and MM-CK fractions and increases in the MB- and BB-CK fractions compared with the controls. The alterations in the mitochondrial and MB-CK fractions were significantly attenuated after 12 weeks of ACE inhibition. Thus, LV myocardial energy metabolism is progressively impaired and its alteration is not related to the magnitude of geometric changes and LV dysfunction after MI. Most of the beneficial effects of ACE inhibition were observed at 12 weeks after MI. Our results may provide an insight into the therapeutic strategy of ACE inhibition in chronic heart failure after MI.     

Clinicopathology of pancreaticobiliary maljunction: relationship between alterations in background biliary epithelium and neoplastic development

Background/Purpose

Between 1988 and 2003, 38 patients underwent biliary resection for pancreaticobiliary maljunction (PBM). We reviewed the histopathologic findings for the surgically resected specimens to compare the clinical and pathologic features and assess the relationship between changes in the background biliary epithelium and the development of neoplasms.

Methods

Papillary hyperplasia (PHP) seen in the biliary epithelium of patients with PBM, was classified into grades 0–III in the gallbladder and grades 0–II in the extrahepatic bile duct, according to the extent, and was assessed for links with tumors in the same specimens.

Results

The incidence of gallbladder carcinoma was 13/21 in grades I–II, versus 0/16 in grade III, while the incidence of bile duct carcinoma was 4/20 in grade I versus 0/5 in grade II. Furthermore, these incidences for patients below age 50 years and age 50 or older were 1/18 versus 12/20, and 0/14 versus 6/17, respectively.

Conclusions

PHP of the biliary epithelium in PBM patients is an important precursor lesion, especially for gallbladder cancer, and the risk becomes greater with age, regardless of the type of pancreatobiliary junction (PBJ) and its location in the biliary tract.     

A case of thymic cyst with thymic hyperplasia]

A 70-year-old man was admitted to our hospital for treatment of an anterior mediastinal tumor. Although he was asymptomatic, an abnormal shadow was visible on chest radiography. CT revealed a heterogeneous tumor located in the anterior mediastinum. On MRI, the tumor demonstrated low signal intensity in T1-weighted images and high signal intensity in T2-weighted images. Laboratory data, including tumor markers, were mostly within the reference ranges. Although a CT-guided needle biopsy was performed, histologic diagnosis could not be confirmed. We resected the tumor with the thymus by median sternotomy. Histopathological examination demonstrated that the tumor was a multilocular thymic cyst with thymic hyperplasia and numerous lymphocytes. The lining epithelial cells gave positive reactions to immunohistochemical staining for carbohydrate antigen 19-9. Carcinoembryonic antigen and squamous cell carcinoma antigen levels in the cystic fluid were elevated. This case appeared to be an acquired thymic cyst with thymic hyperplasia. There are few reports of such cysts.     

Phenotyping of malignant hematopoietic cells

Summary 1255 cases of leukemia-lymphoma were tested between 1972 and 1984 by multiple marker analysis. Routine leukemia phenotyping was performed using standard morphological and cytochemical techniques in combination with clinical and histo-pathological information; the main emphasis was put on immunological surface marker analysis using erythrocyte rosette assays, TdT and a large panel of poly- and monoclonal antibody tests. The 1255 cases were divided into these major types and subtypes: 349 cases of ALL and related immature T- and Burkitt-lymphomas (cALL, pre B-ALL, B-ALL and Burkitt-lymphomas, T-ALL and immature, mostly leukemic T-lymphomas, Null-ALL), 454 cases of mature T- and B-cell malignancies (T-CLL, mycosis fungoides, Sezary-syndrome, T-lymphomas, B-CLL, hairy cell leukemia, multiple myeloma, B-lymphomas), 263 cases of acute myeloid leukemias (AML, AMMoL/AMoL), 182 cases of chronic myeloid leukemias (CML in chronic phase, CMoL, CML in blast crisis), 6 cases of erythroleukemia and 1 case of megakaryoblastic leukemia. A simplified classification scheme which has been used in our laboratories is presented. Phenotyping is of diagnostic, prognostic and therapeutic relevance, most evidently for patients with ALL. Routine leukemia phenotyping should be performed with highly standardized techniques and reagents and by combining information from several fields in the multiple marker analysis. New areas of leukemia research might become very useful for the routine procedure of phenotyping.Abbreviations ALL acute lymphoblastic leukemia - AML acute myeloblastic leukemia - AMMoL acute myelomonoblastic leukemia - AMoL acute monoblastic leukemia - cALL common ALL - CLL chronic lymphocytic leukemia - CML chronic myelocytic leukemia - CML-BC CML in blastic crisis - CMoL chronic monocytic leukemia