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To elucidate the clinical significance of perineural invasion on bile duct cancer, a clinicopathologic study was performed on 70 resected patients with bile duct carcinoma. The overall incidence of perineural invasion in the resected specimen was 81.4%. There seemed to be no correlation between perineural invasion and site, size of the tumor, and lymph node metastasis. A significant correlation was observed, however, between macroscopic type, microscopic type, depth of invasion, and perineural invasion. Perineural invasion index (PNI) was defined as the ratio between the number of nerve fibers invaded by cancer and the total number of nerve fibers with and without cancer invasion. Perineural invasion index was significantly higher at the center compared with the proximal and distal part of the tumor (p less than 0.001). The 5-year survival rate for patients with perineural invasion was significantly lower (p less than 0.05) than that for those without perineural invasion (67% versus 32%).

Although Buerger's disease is known to be closely related to smoking, no objective analysis of the smoke-associated problems has been performed. In this study, cotinine, the major metabolite of nicotine, was used as a sensitive marker to measure levels of active smoking and the exposure of nonsmokers to tobacco smoke because it has a relatively long half-life and because cotinine levels can be determined by noninvasive means in urine. According to urinary cotinine levels, 40 patients with Buerger's disease were classified as (1) smokers: those with urinary cotinine levels above 50 ng/mg creatinine; (2) passive smokers: those with levels between 10 and 50 ng/mg creatinine; and (3) nonsmokers who did not experience noticeable passive smoking: those with levels below 10 ng/mg creatinine. There were 10 smokers, 9 passive smokers, and 21 nonsmokers. The course of the disease, after the initial treatment at our hospital, was studied retrospectively. Seven of the 10 smokers, none of the 9 passive smokers, and 4 of the 21 nonsmokers experienced aggravation of the disease. Of the four nonsmokers who experienced aggravation, three had still been smokers and one had been exposed to tobacco smoke in the workplace at the time of relapse. There was a significant difference in the aggravation rate between the smokers' group and the other two groups. Among the smokers, the seven patients whose conditions worsened showed significantly higher cotinine levels than the three remaining patients who were in the stage of remission.(ABSTRACT TRUNCATED AT 250 WORDS)

Obstructive jaundice, produced by ligating the common bile duct, induced a transient DNA replication followed by cell proliferation in rat liver. At 48 h after the operation, DNA polymerase alpha activity started to increase and reached its maximum level (more than twice the control) at day 4. At day 7, the enzyme level had decreased to the control level. Pulse-labeling experiment using radioactive thymidine showed that the rate of DNA synthesis increased approximately 2.5-fold in the same pattern as that of DNA polymerase alpha. The mitotic index in hepatocytes also increased 10-fold at day 4 and then decreased. The proliferation of liver cells induced by obstructive jaundice mimics the regeneration of partially hepatectomized liver, although the response was slightly delayed and the proliferation was transient.

This article reports a case of an infrarenal abdominal aortic aneurysm complicated with chronic disseminated intravascular coagulopathy (DIC). The patient was a 68-year-old man; bleeding of 20 months' duration was reported. Physical examination indicated a pulsating mass in the abdomen. The diagnosis of DIC was made on the basis of standard coagulation studies. Indium 111-labeled platelet scintigraphy demonstrated an increased accumulation of radioactivity over the aneurysm. After preoperative control of the bleeding tendency was obtained by continuous intravenous infusion of gabexate mesilate (FOY), the aneurysm was successfully replaced with a prosthetic graft. Gabexate mesilate therapy is useful for DIC as is heparin therapy. If surgical intervention is required for an abdominal aortic aneurysm with concomitant DIC, preoperative control of bleeding with gabexate mesilate or heparin is recommended to lessen operative bleeding.

When K562 cells were made resistant to cisplatin their neutral amino acid transport systems changed. K562 cells cloned in cisplatin developed a 6.7-fold resistance to the drug. The generation times for K562 cells sensitive (S) and resistant (DDP) to cisplatin were similar. The initial uptake and rapid efflux of cisplatin were similar in both cell lines. However, they differed in their sodium dependent neutral amino acid transport properties. In K562S cells the sodium-dependent uptake for methylaminoisobutyric acid was significantly inhibited by threonine (Ki = 10.3 mM), but in K562DDP the uptake of neutral amino acids was significantly lower, and methylaminoisobutyric acid uptake was minimally inhibited by threonine. When K562DDP cells were grown in the absence of cisplatin for 8 weeks, their amino acid transport properties reverted to those of K562S cells. In K562 cells, changes in plasma membrane essential amino acid transport systems were concomitant to both the development of resistance and the redevelopment of sensitivity to cisplatin. Therefore, human malignant cell sensitivity and resistance to cisplatin may be related to membrane nutrient transport systems.

The effects of bone marrow-conditioned medium obtained from colony-stimulating factor-producing tumor-bearing nude mice (G-BM-CM) on mouse and human granulocyte-macrophage colony formation and mouse erythroid colony and burst formation were studied. Addition of G-BM-CM into the mouse granulocyte-macrophage colony-forming system containing colony-stimulating activity more strongly inhibited granulocyte colony formation than did mixed granulocyte-macrophage and macrophage colony formation, while it did not change the number of granulocyte colonies formed by human bone marrow cells stimulated by human granulocyte colony-stimulating activity. Addition of G-BM-CM slightly increased mouse erythroid colony and burst numbers when it was added into an erythroid colony-forming system stimulated by erythropoietin (1 unit/ml), and into the erythroid burst-forming system stimulated by erythropoietin (1 unit/ml) and 7% spleen cell-conditioned medium. These results might indicate that G-BM-CM mainly blocked commitment of mouse granulocyte-macrophage colony-forming cells to granulocytic progeny.

The purpose of this study is to quantify leg muscle perfusion with 201Tl single photon emission computed tomography (SPECT). Six normal controls and 21 patients with peripheral arterial disease underwent this examination. Thallium-201 leg SPECT of both stress and redistribution was performed using a dual-headed digital gamma camera. Each slice of transverse images was normalized with pixels and whole-body counts. In normal controls, the activity of posterior tibial muscle components was significantly higher than that of anterior tibial muscle components (p less than 0.001). In 14 components, where patients had insignificant lesions, profile curves were normal in 10 (71%). In 62 components, where patients had arteriographically significant lesions, stress profile curves were abnormal in 57 (92%) compared with normal controls. Approximately, in half (28/62) components which had significant lesions, profile curves showed redistribution after 3 hr compared with normal redistribution curves. In three patients who underwent successful bypass graftings, the activity of each muscle component returned to a normal range.

Human acute myeloid leukemia (ML-1 and HL-60) cells grew continuously in the serum-free liquid medium supplemented with human transferrin and bovine insulin. Both ML-1 and HL-60 cells formed clusters and colonies in the serum-free agar medium supplemented with bovine serum albumin, human transferrin, cholesterol, and L-alpha-phosphatidylcholine. Medium conditioned by phytohemagglutinin-stimulated leukocytes prepared in the absence of serum had three types of colony-stimulating factors on normal human bone marrow cells. When fetal calf serum was present, medium conditioned by phytohemagglutinin-stimulated leukocytes stimulated the clonal growth of HL-60 cells at the lower concentration. However, it inhibited that of ML-1 cells. In contrast, under serum-free conditions, medium conditioned by phytohemagglutinin-stimulated leukocytes promoted the clonal growth of both ML-1 and HL-60 cells at the lower concentrations. The study using a Sephadex G-200 column revealed that, in the serum-supplemented cultures, HL-60 cells responded to one of the three colony-stimulating factors and an activity with molecular weight of around 12,000, while ML-1 cells responded only to an activity with molecular weight of around 12,000. In the serum-free cultures, both ML-1 and HL-60 cells were stimulated by activities with molecular weights of 62,000 and 54,000, respectively. These studies demonstrate that the determination of growth factors for cell lines is dependent on culture conditions, particularly on serum component; that there is a heterogeneity of ML-1 and HL-60 cells in response to the growth factors; and that there is potential importance of demonstration of heterogeneity among different cell lines in establishing requirements for different stages of differentiation.