Prognostic significance of echogenic lesion within small hepatocellular carcinoma]

To evaluate prognostic significance of echogenic lesion within small hepatocellular carcinoma (SHCC, less than or equal to 2 cm in diameter), clinical and pathological findings of 32 cases with SHCC containing echogenic lesion (echogenic SHCC) were compared with those of 55 cases with non-echogenic SHCC. Compared with the non-echogenic SHCC group, the frequency of clinical stage I was significantly higher, and there were significantly more cases with solitary tumor relative to cases with multiple tumors in the echogenic SHCC group. Histologically, the incidence of the HCC composed of well-differentiated tumor cells corresponding to Edmondson's grade I was significantly higher in the echogenic SHCC group than in the non-echogenic SHCC group. Although HCCs tended to become progressively less differentiated with increasing tumor sizes in the both groups, the process of cellular change appeared to proceed more slowly in the echogenic SHCC group. Survival rate after tumor detection was 73% at three years, 56% at five years and 48% at seven years and nine years in the echogenic SHCC group, while it was 46% at three years, 42% at five years and 0% at seven years in the non-echogenic SHCC group. The present results showed that the presence of echogenic lesion within SHCC could be useful prognostic indicator.     

Apolipoprotein levels in preeclamptic pregnancies]

Lipoprotein is known to increase during pregnancy but the factors responsible for the change have not been established. In addition, the lipoprotein concentration in preeclamptic pregnancy is significantly higher than in normal pregnancy. The apolipoproteins are an important determinant of metabolism and the structure of plasma lipoproteins. In normal pregnancies, non pregnancies and preeclamptic pregnancies the levels of blood apolipoproteins AI, AII, B and E were determined by TIA methods. (1) In normal pregnancies, the concentrations of apolipoproteins AI, AII, B and E were 182.6 +/- 20.9 mg/dl (n = 12, mean +/- S.D.), 33.3 +/- 5.7 mg/dl, 128.6 +/- 20.8 mg/dl, and 6.8 +/- 1.9 mg/dl, respectively. (2) In the pregnancies, the concentrations of apolipoproteins AI, AII, B and E were 135.6 +/- 9.3 mg/dl (n = 5), 30.8 +/- 1.9 mg/dl, 76.0 +/- 19.7 mg/dl, and 4.4 +/- 0.7 mg/dl, respectively. (3) In the preeclamptic pregnancy, the concentrations of apolipoproteins AI, AII, B and E were 181.0 +/- 27.6 mg/dl (n = 22), 33.2 +/- 4.8 mg/dl, 145.7 +/- 41.6 mg/dl and 5.8 +/- 1.4 mg/dl, respectively. The concentration of apolipoprotein B in preeclamptic pregnancy was significantly higher (p less than 0.001) and apolipoprotein E was significantly lower (p less than 0.01) than in normal pregnancies. These data suggest that the measurement of apolipoprotein is useful for the evaluation of preeclamptic pregnancy.     

Effect of verapamil on ventilatory and circulatory responses to hypoxia and hypercapnia in normal subjects.

Recent investigations have shown that the calcium channel blocker verapamil attenuated the hypoxic ventilatory chemosensitivity of carotid body in animals. To determine whether this is also the case in humans, transient physiological chemodenervation by O2 breaths (withdrawal test) during sustained hypoxia (N = 7), and ventilatory and circulatory responses to progressive hypoxia and hypercapnia (N = 8) were examined after oral administration of verapamil. During sustained hypoxia after verpamil, there was a significant reduction of withdrawal response from 5th to 25th min value (p < 0.01), but not after placebo. On the other hand, no significant difference in ventilatory responses to progressive hypoxia and hypercapnia was observed after verapamil. Verapamil run reveals similar features with placebo run in circulatory parameters except blood pressure response, which tended to be suppressed by verapamil. We conclude that verapamil attenuates peripheral chemoreceptor activity with time during sustained mild hypoxia in normal adult humans and this may be explained by delayed depletion in intracellular Ca2+ for chemotransduction of the peripheral chemoreceptors.     

Anatomy and pathophysiology of the popliteal tendon area in the lateral meniscus: 1. Arthroscopic and anatomical investigation

An arthroscopic and anatomical investigation was performed to define the abnormal conditions of the popliteal tendon area in a lateral meniscus. Arthroscopic findings for 100 patients and anatomical observations of 10 amputated knees were analyzed. Five of the 10 dissected menisci were also examined histologically. Menisco-tibial coronary ligaments were classified into two types, as follows: type I--a coronary ligament covering an entire popliteal tendon beneath the meniscus; type II--a popliteal tendon visible beneath the meniscus through defects of the coronary ligament. Twenty-one of 100 cases were classified as type I, and 79 were classified as type II. Three of the 10 anatomical dissections were type I, and the remaining 7 were type II. Menisci in which the type I coronary ligaments were thought to be torn and menisci with type II coronary ligaments showed a rather marked mobility, but no conclusion could be reached.     

Preferential consumption of heparin cofactor II in disseminated intravascular coagulation associated with acute promyelocytic leukemia.

We measured plasma heparin cofactor II (HC II) activity in patients with disseminated intravascular coagulation (DIC) due to various underlying diseases together with the levels of antithrombin III (AT III), pseudocholinesterase (a marker of hepatic synthesis), and various haemostatic molecular markers. Both HC II and AT III were decreased in DIC secondary to all the underlying diseases studied, except acute promyelocytic leukemia (APL), when compared with healthy subjects. The lowest HC II and AT III levels was observed in coagulopathy secondary to liver disease, the HC II level in sepsis was the second lowest. In DIC due to APL, the decrease in HC II was not accompanied by a decrease in AT III. Thus, we divided all 124 samples tested into APL and non-APL groups. The HC II level correlated positively with fibrinogen and plasminogen in both the APL and non-APL groups. In the APL group, the HC II level had a significant negative correlation with the thrombin-AT III complex (TAT), fibrinogen/fibrin degradation products, and D-dimer levels as well as the prothrombin time, while AT III showed no correlations with any of the haemostatic parameters. These results suggest that HC II may be consumed preferentially by thrombin in APL patients with DIC, and thus may spare the consumption of AT III. Accordingly, HC II seems to be a superior indicator of DIC than AT III in APL patients. Moreover, replacement therapy with HC II instead of AT III may be useful to treat DIC associated with APL. In the non-APL group, the HC II levels were positively correlated with the levels of AT III and pseudocholinesterase activity. This indicates that plasma HC II levels are closely related not only to consumption coagulopathy but also to hepatic synthetic activity, as is the case for plasma AT III.     

Influence of fibroblasts on the invasion and migration of highly or weakly metastatic b16 melanoma cells

We have examined the influence of fibroblasts on the invasive and migratory potential of highly metastatic melanoma B16-BL6 and weakly metastatic B16-FI cells in vitro. Co-culture of B16-BL6 cells with a fibroblast monolayer without cellular contact in a Transwell chamber more effectively induced tumor-cell invasion into Matrigel basement membrane than co-culture of B16-FI cells with a fibroblast monolayer. The activity was closely correlated with the chemotactic migration of tumor cells toward the fibroblast monolayer. We also found that the conditioned medium (CM) from the co-culture of fibroblasts with B16-BL6 cells without cellular contact, i.e., CM (B16-BL6/fibroblast), rather than from co-culture with B16-FI cells, could potentially promote the migration of tumor cells of both types. Tumor cells did not chemotactically migrate to the CM (B16-BL6), CM (B16-FI) or CM (fibroblast). Antibodies against TGF-β1 or FN almost completely abolished the chemotactic migration of B16-BL6 cells to the CM (B16-BL6/fibroblast) or CM (TGF-β1 -treated fibroblast) when these antibodies were c-incubated with fibroblasts and either B16-BL6 or TGF-β1. In contrast, the anti-EGF antibody did not show any inhibitory effects. Analysis of amounts of TGF-β1 or FN in various CM using ELISA plates, and using their specific antibodies, revealed that the concentration of TGF-β1 in the CM (B16-BL6) was slightly higher than in the CM (B16-FI), and the amount of FN in the CM (B16-BL6/fibroblast) was twice as high as in the CM (B16-FI /fibroblast). These results suggest that TGF-β1 released from B16-BL6 cells can stimulate fibroblasts to produce FN; consequently, the tumor cells were able to chemotactically migrate toward the released FN, and the differences in invasive and migratory activities towards fibroblasts in B16-BL6 and B16-FI cells may in part be due to the amounts of TGF-β1 from tumor cells and of FN from TGF-β1 -stimulated fibroblasts.     

Serum sialyl Tn antigen as a prognostic marker in patients with epithelial ovarian cancer]

Circulating serum sialyl Tn (STN) antigen levels were measured in 89 patients with epithelial ovarian cancer, 157 benign disease, and in 126 healthy controls. Serum antigen levels were increased in 48.3% of patients with ovarian cancer. The false positive rate is significantly low (4.0% in healthy controls and 9.6% in benign disease). The levels of STN antigen were significantly higher in sera of patients with cancer than in those in benign and healthy controls (p less than 0.05). The rise in serum STN antigen levels correlated to the size of the primary tumors. Of the histological type, it is interesting to note the high sensitivity in mucinous-type ovarian cancer. Survival at 1, 2, 3, 4 and 5 years for patients with STN-negative (serum STN levels less than 50 U/ml) versus STN-positive (serum STN levels greater than or equal to 50 U/mol) was 96.2, 92.3, 86.5, 82.7, and 76.9% versus 59.5, 29.7, 18.9, 10.8, and 10.8%, respectively (p less than 0.05). The overall survival probability was worse in patients with STN-positive sera. Percent progression-free survival at 1, 2, 3, 4 and 5 years for patients with STN-negative versus STN-positive was 90.4, 86.5, 76.9, 59.6, and 51.9% versus 35.1, 16.2, 8.1, 8.1, and 5.4%, respectively (p less than 0.05). The overall progression-free period of survival was shorter in patients with STN-positive sera. Multivariate regression analysis revealed that positive STN, stage, PS and histologic grade were the four variables of most importance in predicting survival. These results indicate that a positive STN antigen level in sera is an independent predictor of poor prognosis in ovarian cancer.     

Pulmonary Mycobacterium avium complex infection: association with NRAMP1 polymorphisms.

The present study aimed to elucidate risk factors for nonimmunocompromised pulmonary Mycobacterium avium complex (MAC) infection. Epidemiological data and variations of candidate genes for mycobacterial diseases were analysed in 111 patients with pulmonary MAC infection. Four polymorphisms of the human natural resistance-associated macrophage protein (NRAMP)1 gene, the 5'(GT)n, 469+14 G/C, D543N and the 3'untranslated region (3'TGTG) insertion/deletion, were genotyped using PCR-based methods. Fok I and Taq I polymorphisms of the vitamin D receptor gene and -221 X/Y and codon 54 A/B polymorphisms of the mannose binding lectin gene were also evaluated. Females were more susceptible to MAC infection mainly affecting the right middle lobe or lingular segment of the lung. Patients' residence at the onset of the disease was distributed evenly irrespective of a waterfront or city water supply system. As compared with homozygotes for major alleles of the D543N and TGTG insertion/deletion polymorphism of the NRAMP1 gene, heterozygotes containing minor alleles were less often observed in MAC cases than in controls. This genetic effect was more significant in patients without comorbidity but not in patients with comorbidity. Other polymorphisms did not show any association with the MAC infection. The human natural resistance-associated macrophage protein 1 gene might be involved in susceptibility to pulmonary Mycobacterium avium complex infection.     

Localized wall thickening of the gallbladder mimicking a neoplasm

Clinical diagnosis of chronic cholecystitis is made based on diffuse hyperechoic thickening of the gallbladder wall as shown by ultrasonographic examination. We herein report three cases of chronic cholecystitis showing localized hypoechoic thickening of the gallbladder wall that mimicked gallbladder cancer by ultrasonography. Histologically, hypertrophy of the muscularis propria was a common characteristic finding in these three patients. A smooth surface of the inner hypoechoic layer of the thickened wall was considered to be a reliable finding in the differential diagnosis between this type of chronic cholecystitis and gallbladder cancer.