Ultrastructural localization of adhalin in normal murine skeletal myofiber

The ultrastructural localization of adhalin and its relations to dystrophin, β-dystroglycan, and β-spectrin were studied in normal murine skeletal myofibers. The C-terminal peptides of adhalin and β-dystroglycan were synthesized based on their cDNAs, and the affinity-purified antibodies against these peptides were produced. Single-immunolabeling electron microscopy showed that the adhalin was located just inside the muscle plasma membrane or inside the myofiber a short distance from the plasma membrane. The adhalin signal was also noted at the sarcoplasmic side of plasmalemmd invaginations or at vesicular structures in subsarcolemmal areas. Double-immunogold-labeling electron microscopy disclosed a similar localization of dystrophin, β-dystroglycan, and β-spectrin. The close association of adhalin with dystrophin or β-dystroglycan was demonstrated by formation of doublets by signals of antibodies of adhalin with those of dystrophin or β-dystroglycan and was confirmed by statistical analyses. This study demonstrated that the location of adhalin is close to that of dystrophin and β-dystroglycan at the muscle plasma membrane.     

Modifying Effects of Various Chemicals on Preneoplastic and Neoplastic Lesion Development in a Wide-spectrum Organ Carcinogenesis Model Using F344 Rats

Modifying potentials of various chemicals on tumor development were investigated in a wide-spectrum organ carcinogenesis model using male F344/DuCrj rats. The animals were treated with N-nitroso-diethylamine (100 mg/kg body weight, ip, single injection at the commencement of the study), N-methyl-N-nitrosourea (20 mg/kg body weight, ip, 4 times during weeks 1 and 2) and N-bis(2-hydroxypropyl)nitrosamine (0.1% in drinking water, during weeks 3 and 4) for multi-organ initiation and then were given one of 14 test chemicals including 6 hepatocarcinogens, 7 non-hepatocarcinogens and 1 non-carcinogen, or basal diet for 16 weeks. All rats were killed at the end of week 20, and the major organs were carefully examined for preneoplastic and neoplastic lesions. Immunohistochemical demonstration of glutathione S -transferase-positivc foci was also used for quantitative assessment of liver preneoplastic lesion development. Modifying effects were shown for 11 out of 14 test agents in the liver, forestomach, glandular stomach, lung, urinary bladder or thyroid, 7 of them targeting more than two organs. This was the first demonstration to our knowledge that cloflbrate possesses enhancing potential for urinary bladder carcinogenesis and an inhibiting effect on thyroid carcinogenesis. Caprolactam showed no effect in any organ, in agreement with its established inactivity. The results indicated that the system could be reliably applied as a medium-term multiple organ bioassay for assessment of the modification potential of test agents in unknown target sites.     

A case of chronic hepatitis C virus-related advanced hepatocelluar carcinoma surviving more than 8 years]

A 64-year-old man was admitted for further examinations of a liver tumor. The patient was diagnosed as chronic hepatitis C complicated with advanced hepatocelluar carcinoma (HCC) with left portal vein tumor thrombosis. As he refused surgical treatment, hepatic arterial infusion chemotherapy (HAIC) using cisplatin and 5-fluorouracil was performed initially. Administration of ursodesoxycholic acid (UDCA) was also started. Following HAIC, microwave coagulation therapy for residual tumor was added. Consequently, viable lesions of HCC disappeared completely. At present, after more than 8 years, neither signs of tumor recurrence, nor elevation of hepatic enzymes has been observed. Although the precise reason for long survival of this patient is not known, we speculate that suppression of levels of hepatic enzymes, as well as HAIC for subclinical intrahepatic metastasis, contributed to the good outcome. Therapeutic strategy for hepatic inflammation seems to be important for long-term prevention of hepatocarcinogenesis.     

Scintigraphic evaluation of myocardial uptake of thallium 201 and technetium 99m pyrophosphate utilizing a rat model of chronic doxorubicin cardiotoxicity

To evaluate the usefulness of myocardial scintigraphy as a monitoring tool for chronic doxorubicin (DXR) cardiotoxicity, a rat model was used to investigate the relationship between the myocardial uptake of thallium 201 (Tl) or rechnetium 99m pyrophosphate (^99mTc-PPi) and histological changes of the heart. Although there was no significant difference in myocardial Tl uptake between control and DXR-treated rats at an early phase after Tl injection, late-phase Tl uptake was significantly higher in the DXR-treated rats than in the control rats, indicating a slow wash-out of Tl from the myocardium. The wash-out rate calculated from scintigraphic examination of DXR-treated rats was significantly decreased with increasing degree of cardiomyopathy. Since the Tl wash-out rate was sharply decreased even in animals with minimal histological changes, it may be a possible monitoring tool for the early detection of chronic DXR cardiotoxicity. On the other hand, myocardial^99mTc-PPi images could be obtained only in rats with severe myocardial changes and hence would not useful for early detection.     

Intracellular free magnesium of red blood cells in patients with renal disease.

While serum magnesium (Mg) level is increased in patients with end-stage renal disease (ESRD), it is decreased in renal transplant recipients (TR) receiving ciclosporin. This study was performed to examine the cation metabolism of red blood cells (RBC) in these patients. Intracellular free Mg was measured with 31P-nuclear magnetic resonance spectrometry, and ouabain-sensitive sodium (Na) efflux rate (Eos) was measured from the increase in RBC-Na concentration when RBC were incubated in the presence of ouabain. The ouabain-sensitive Na efflux rate constant (ERCos) was obtained by dividing Eos by RBC-Na concentration. RBC free Mg and ERCos were significantly higher in the TR group than in the ESRD group. There was a significant correlation between RBC free Mg and ERCos (r = 0.474, p less than 0.01). These results support the views that the regulation mechanism for intracellular free Mg is different from that for extracellular Mg in patients with renal disease, and intracellular free Mg modulates Na pump activity of RBC.     

Thoracoscopic closure of a congenital partial pericardial defect

We describe our technique for performing direct thoracoscopic closure of a congenital partial pericardial defect, which was successfully employed in a 15-year-old boy. This is the first such report of a procedure that is noninvasive and may therefore become the treatment of choice for patients with a small congenital pericardial defect.     

The influence of reflux of bile and pancreatic juice on gastric carcinogenesis in rats

The effect of reflux of the duodenal contents on the development of gastric stump carcinoma without carcinogen in rats was studied. At the first experiment, seventy male Wistar rats were subjected to gastrojejunostomy for the diversion of duodenal contents into the resected stomach through the afferent and the efferent loops. The incidence of adenocarcinoma in the afferent anastomosis were 0/8 (0%) at the 10th week, 3/16 (18.8%) at the 20th week and 7/20 (35%) at the 40th week, so the incidence was apt to rise in parallel to the time. In the second experiment, ninety rats were divided into 4 groups: Group I received the same operation as the first experiment, group II received the operation with Braun's anastomosis, group III received the operation for reflux of bile alone to the remnant stomach, and group IV received the operation for reflux of pancreatic juice alone. Animals surviving after surgery were sacrificed at the 40th week. The incidence were 33.3% in group I, 0% in group II, 0% in group III, and 8.3% in group IV, respectively. These findings suggest that reflux of duodenal contents (both bile and pancreatic juice) is an important factor in the gastric stump carcinogenesis.