Acid and thermal unfolding of Escherichia coli dihydrofolate reductase.

The acid and thermal unfolding of Escherichia coli dihydrofolate reductase (DHFR) were studied by means of circular dichroism (CD) and fluorescence spectroscopy. There existed at least one intermediate around pH 4 in the acid unfolding process at 15 degrees C, in which the tertiary structure was disrupted before unfolding of the secondary structure. The fluorescence energy transfer from intrinsic tryptophan residues to 1-anilinonaphthalene-8-sulfonate suggested the disruption of the tertiary structure around some tryptophan residues of the intermediate. The thermal unfolding process at pH 7.0 also involved at least one intermediate having a disrupted tertiary structure and a folded secondary structure. The three-state thermodynamic analysis showed that the intermediate in thermal unfolding was less stable by 1.8 kcal/mol than the native state. The similarity of the far-ultraviolet CD spectra of acid and thermally unfolded forms suggests that both types of unfolding produce the same structure, which may be a molten globule intermediate such as that in the folding kinetics of DHFR. The acid and thermal unfolding were depressed in the presence of KCl due to stabilization of the native form.

[Strategy for the treatment of hepatocellular carcinoma].

Hepatocellular carcinoma is a refractory cancer for the following two reasons: the tumor characteristics, including formation of tumor thrombus in the portal vein, metastasis within the liver and multicentricity of growth; and liver function disturbance due to cirrhotic change by B- or C-type viral infection. The most desirable treatment is hepatic resection, the only method producing a disease-free condition. However, there are not many cases that meet the indications for hepatic resection, since they have advanced lesions and/or liver dysfunction. If one cannot perform a hepatic resection, other suitable therapies should be selected, including transcatheter arterial embolization, percutaneous ethanol injection therapy, ligation of hepatic artery, irradiation, chemotherapy from hepatic artery via reservoir and so on. Combined therapy may sometimes be necessary for satisfactory efficacy. For long-term survival it is very important to do a close follow-up study over a long period. This encourages us to detect new lesions earlier and then perform suitable therapy again. Notifying patients of the disease and obtaining informed consent are needed for this long-term follow-up and treatment. When patients were examined who had first undergone hepatic resection and then hepatic re-resection for recurrence, we found that their survival rate was not different from that in the non-recurrent cases. This result indicates that overcoming refractory hepatocellular carcinoma requires a multidisciplinary treatment in which hepatic resection is the main means.

Repeated hepatic resection for recurrent hepatocellular carcinoma in eighteen cases.

BACKGROUND: Although intrahepatic recurrence after hepatic resection for hepatocellular carcinoma is the most significant cause of death, very few reports are available for hepatic re-resection as a radical treatment for recurrence. METHODS: Eighteen patients who underwent repeated hepatic resections for hepatocellular carcinoma were evaluated. Most of the patients regularly received measurement of alpha-fetoprotein level once a month and examination by ultrasonography and/or computed tomography scanning once every 3 to 4 months. RESULTS: No operative deaths occurred. The alpha-fetoprotein levels of 9 of the 18 patients were within the normal range. Most patients underwent limited hepatic resection to maintain the remaining hepatic function. The 1-, 3-, and 5-year cumulative survival rates after repeated resection were 88%, 37%, and 37%, respectively. The 3-, 5-, and 7-year survival rates after the first resection were 88%, 68%, and 45%, respectively. These showed no significant difference from the survival rates of patients with no recurrences after hepatic resection. CONCLUSIONS: Careful follow-up examinations after hepatic resection are needed for early detection of recurrences, and efforts should be made for repeated hepatic resection, which leads to satisfactory outcome.

[A case report of adenolipoma of the breast].

A rare case of breast adenolipoma is presented. A 49-year-old, otherwise healthy woman had a tumor of the left breast for approximately 25 years. Ultrasound mammography demonstrated a well-demarcated, high echoic mass with islands of a low echoic area in the center of the tumor. The well-defined, oval, soft tumor, measuring 7 x 5 x 3.5 cm in size, was surrounded by a thin capsule which was removed, and its yellow cut surface was found to be mottled by greyish-white areas. Microscopically, the tumor was diagnosed as a breast adenolipoma consisting of fatty tissue interspersed with islands of glandular tissue. The findings of ultrasound examination on adenolipoma of the breast are described and its histogenesis was discussed.

[Significance of CA19-9 values in the feces of patients with colorectal carcinoma].

We measured CA19-9 value in feces of 119 cases with malignant disease, 78 cases with benign diseases and 36 healthy volunteers, and studied its usefulness for the diagnosis of digestive tract cancer. Mean value of CA19-9 in feces of healthy volunteer was 276.4 +/- 643.3 U/ml (mean +/- 2S.D.) and cut off value was defined as 1000 U/ml. The positive ratio of CA19-9 in feces of patients with malignant diseases as 44.5%. On the other hand, the mean of the false positive ratio was only 1.4% in benign diseases. Regarding to its breakdown, CA19-9 in feces revealed the highest positive ratio as 68% in colonic cancer. In colonic cancer, CA19-9 in feces showed a high positive ratio of 83% at advanced stage. Histologically, the positive ratios of CA19-9 in feces were higher, such as in more than 80% of the reaching degree of depth ss, a1, more than 82% of the disease due to higher parasites of lymph vessel ly1 and more than 95% of the metastasis of lymph node n1. Moreover, all CA19-9 in feces were positive in positive cases of CEA in serum.