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A 56 years old male with chronic pancreatitis complained of intractable abdominal pain, anorexia, emaciation and peripheral edema. Medical treatment initiated only partial improvement in the general condition and hypoproteinemia. Endoscopic retrograde cholangiopancreatography revealed multiple filling defects in the dilated main pancreatic duct. Endoscopic aspiration of pure pancreatic juice yielded numerous protein plugs. The endoscopic removal of protein plugs from the pancreatic duct resulted in remarkable improvement in symptoms, laboratory findings and ERCP findings. We consider this procedure to be an important new treatment of chronic pancreatitis.

Six quantitative psychometric tests were performed on 51 healthy subjects, 19 cirrhotic patients with subclinical hepatic encephalopathy (SHE), 32 cirrhotic patients without SHE, and 26 patients with other diseases. Strong correlations between age and the results of all the psychometric tests were observed in the healthy subjects (p less than 0.005). Sex and etiology of liver cirrhosis did not affect the test results. SHE patients, compared with non-SHE and health subjects, presented impairment in the ability to perform the tests, even in the absence of obvious clinical and electroencephalogram findings. In SHE patients, trailmaking test A (TMT A) yielded the highest frequency of abnormal values, 63%. TMT A results were abnormal in 80% of SHE patients with abnormal scores in other tests, and thus it seemed to be the most sensitive test. Liver function tests did not correlate with psychometric testing in any of the groups. Blood ammonia levels in SHE patients with abnormal TMT A scores correlated with TMT A scores (r = 0.752, p less than 0.01); this was not the case in SHE nor non-SHE patients with normal TMT A results. These data demonstrate the usefulness of psychometric tests in detecting SHE.

The present study investigated the brain catecholamine metabolism of rats with liver injury induced either by malnutrition or with CCl4. In the malnutrition group, the plasma tyrosine concentration was low, while it showed a tendency to be high in the cerebral cortex. Dopamine concentrations were low in both the cerebral cortex and diencephalon. Norepinephrine concentrations were low in the cerebral cortex, striatum and diencephalon. Tyrosine hydroxylase activity was elevated while monoamine oxidase activity was decreased in the striatum. In the CCl4 group, tyrosine concentrations in the plasma and cerebral cortex did not change. The dopamine concentration in the cerebral cortex increased five days after, and the norepinephrine concentration in the diencephalon increased 24 h after the last administration of CCl4. These data suggest that catecholaminergic neurons in the brain may be substantially affected by liver injury. It may be considered that malnutrition disturbs brain development, particularly in young rats.

Using the peroxidase antiperoxidase (PAP) method, lysozyme (LZM) was shown to exist in normal, reactive and neoplastic cells belonging to the mononuclear phagocyte system (MPS), but was not detected in histiocytosis X cells. Immunostaining for cytoplasmic LZM by the PAP method is useful for identification of mononuclear phagocytes and for diagnosis of the diseases in which these cells participate.

Macromomycin (MCR), an unique membrane-reactive anticancer antibiotic, was incubated with murine monoclonal anti-HLA IgG1 antibody (H-1) in the presence of carbodiimide. The resulting mixture was fractionated with a Sephadex G-200 column. The first and second fractions were shown to contain MCR-(H-1) conjugate by the elution profile, as well as by the Sarcina lutea growth inhibition assay and Ouchterlony double-diffusion method. A membrane immunofluorescence test with anti-MCR and anti-mouse IgG antibodies demonstrated specific localization of MCR-(H-1) on the surface of HLA-bearing NALL -1 cells. MCR-(H-1) inhibited the growth of HLA-lacking NS-1 cells statistically less effectively than MCR alone (p less than 0.01). On the other hand, the conjugate and free MCR equally inhibited the growth and 3H-TdR incorporation of HLA-bearing NALL -1 cells. These results indicate that the antibody-bound MCR retained both MCR and antibody activities, and thus exerted antibody-targeting MCR cytotoxicity in vitro.

In 144 cases of hepatocellular carcinoma (HCC), 166 cases of cirrhosis without HCC and 142 cases of chronic hepatitis, we examined HBsAg, anti-HBs and anti-HBc in sera and compared the following factors between hepatitis B virus marker-negative and -positive patients: age, sex, alcohol consumption, family clustering of liver diseases, and histories of blood transfusion and post-transfusion hepatitis. Results of this study demonstrated several distinct differences in clinical backgrounds between non-B (negative for HBsAg, anti-HBs and anti-HBc) and B (positive for HBsAg) patients with HCC. Non-B patients were significantly older, had a lower frequency of familial tendencies for liver diseases, and more frequently had cancers other than HCC in their families. Some of these differences were also observed between non-B and B patients with cirrhosis and chronic hepatitis. Among patients with chronic hepatitis, the non-B patients had received blood transfusion or had post-transfusion hepatitis more frequently than the B patients. However, this difference was not apparent in patients with liver cirrhosis or HCC, suggesting that progression of non-A, non-B post-transfusion hepatitis to cirrhosis and HCC may not be as frequent as progression to chronic hepatitis.

Cepharanthine, a biscoclaurine alkaloids which interact with biomembranes, has been found to inhibit platelet aggregation. The effects of this drug on morphological and physiochemical phenomena following collagen-induced platelet stimulation were investigated. In the presence of cepharanthine, stimulated platelets became spherical, but did not form pseudopoda , nor did they become aggregated. Physiochemical reactions such as accelerated oxygen consumption, release of membrane-bound Ca2+, release of Ca2+ into the extracellular medium and deporalization of the membrane potential were all inhibited by cepharanthine. Using D,L-dipalmitoyl phosphatidylcholine liposomes as the substrate, cepharanthine was shown to inhibit phospholipase A2 activity. These results suggest that the changes in the membrane following the interaction of collagen with its receptor are important for platelet activation. Cepharanthine may inhibits these membrane state changes, thus blocking all subsequent reactions.

Spleen cells serially sampled from normal mice following partial hepatectomy were tested for antibody-dependent cellular cytotoxicity (ADCC) and natural killer (NK) activity. There was a marked augmentation of these activities of spleen cells from the hepatectomized animals, compared to cells from controls with a simple laparotomy. The augmentation of ADCC in the hepatectomized mice was largely attributable to the activity of T lymphocytes. When cultured with interleukin-2 (IL-2), the spleen cells from hepatectomized mice exhibited cytotoxicity to syngeneic lymphoblasts, which was found to be effected by T cells.

Sex, age and 21 routine liver function assays were analyzed by stepwise selection and the best-of-all-possible-combinations method to identify a small group of assays valuable in establishing which liver cirrhosis (LC) patients have a high risk of hepatocellular carcinoma (HCC), when alpha-fetoprotein (AFP) is not elevated. Data was obtained from 115 HCC and 122 LC patients on admission. Tumor size correlated with AFP (0.73), alkaline phosphatase (ALP, 0.47), leucine aminopeptidase (LAP, 0.42), lactic dehydrogenase (LDH, 0.42), and the glutamic oxaloacetic transaminase (GOT)/glutamic pyruvic transaminase (GPT) ratio (GOT/GPT, 0.41). The mean of the correct diagnosis rates (CDR) of HCC and LC utilizing AFP as the sole parameter (89%) was markedly higher than those of the other parameters. The best-of-all-possible-combinations method presented a more powerful combination than stepwise selection. The best combination of 7 parameters (LAP, GOT/GPT, choline esterase, one-hour erythrocyte sedimentation rate, age, albumin/globulin ratio, and total bilirubin) presented a mean CDR of 80%, HCC CDR of 77%, and false positive rate of 18%. LC patients statistically diagnosed as having HCC by these 7 parameters are proposed as high risk patients. Fourteen (78%) of 18 HCC patients who were AFP-negative were statistically diagnosed. This analysis can be applied to LC patients to distinguish those that should be followed closely by imaging diagnostic techniques.

The basilar artery was exposed transclivally , and a vascular spasm was produced by topical application of a lysed erythrocyte solution. The maximum fall in the mean arterial blood pressure (MABP) after administering of 2 micrograms/ kgBW and 15 micrograms/ kgBW of PGI2, ranged from 35 to 45 mmHg and from 65 to 85 mmHg, respectively. The drop in MABP after an injection of papaverine hydrochloride (1.5 mg/ kgBW ) was between 30 and 40 mmHg. If MABP did not fall, the vessel diameter did not change. Although papaverine elicited marked dilation of both normal and spastic basilar arteries, PGI2 did not dilate normal basilar arteries and produced only a slight dilation of spastic basilar arteries. Subarachnoid hemorrhage (SAH) was simulated by an intracisternal injection of fresh autologous arterial blood 3 days prior to experimentation. Changes in regional cerebral blood flow (rCBF) were measured by the heat clearance method, before and after an intravenous administration of either PGI2 or papaverine hydrochloride. Changes in rCBF fell into 3 categories: Type A, no change; Type B, a change which varied with the arterial blood pressure, and Type C, an increase rCBF despite systemic hypotension. Type A or B was observed in 17 out of 19 cats with SAH in which PGI2 was administered intravenously, and Type C was observed in only 2 cats. Thirteen untreated control cats produced a Type A or B response in 12, and Type C response in only one cat. There were no significant differences between the control and SAH groups. When 15-hydroperoxy-5, 8, 11, 13-eicosatetraenoic acid (15-HPETE) was infused, the same results prevailed. Papaverine hydrochloride increased rCBF either transiently or continuously in all cats. These results suggest that PGI2 dilates extracranial rather than intracranial vessels regardless of the presence or absence of cerebral vasospasm.

An enzyme-linked immunosorbent assay (ELISA) for the detection of serum blocking factors (BF), or antibodies to the albumin receptor on HBsAg particles, was developed, and its clinical usefulness was examined in healthy persons and patients with liver diseases. Thirteen of 80 anti-HBs-positive female (16.3%) had BF, but all 25 male anti-HBs-positive, 41 female and 32 male anti-HBs-negative subjects were negative for BF. The activity of BF in BF-positive cases was not associated with the positive reciprocal hemagglutination titer of anti-HBs. For a neutralization test of BF, the BFs from 5 cases were absorbed with IgG-immunobeads. It was determined that these IgG-BFs were antibodies to the albumin receptors on HBsAg particles. No significance between positive-BF and abnormal S-GPT levels was recognized. These results suggest that the present test for the detection of BF, or anti-albumin receptor antibody, different from anti-HBs, might be useful for diagnosis of hepatitis B and as a marker for HB virus.

The correlation between blood eosinophilia and anti-IgE-mediated histamine release was investigated in 22 bronchial asthma patients with peripheral eosinophilia (over 8%). In the cases (Group A-1 and Group A-2) in which house dust was the specific antigen, significant histamine release from basophils was induced by anti-IgE and house dust. The result indicates a relationship between eosinophilia and the IgE-mediated mechanism of disease onset. In the cases (Group A-3) with RAST scores of 0+ and 1+ to house dust, the anti-IgE-induced histamine release varied from low to high percentages, and the participation of the IgE-mediated pathway was indicated in some cases. In the cases (Group B) with negative skin reactions, few patients had a family history of allergic disease. Their ages at onset were higher, and they demonstrated lower total IgE levels. These cases showed an extremely low percent of histamine release from basophils, which indicated the absence of a correlation between eosinophilia and IgE-mediated mechanisms.

The Doppler-derived ankle pressure index (API) is a useful indicator of the necessity for peripheral vascular reconstruction of the lower extremities. But the API at rest dose not reflect the functional capacity of leg circulation, especially in the early stage of disease. Therefore, an asymptomatic but hemodynamically significant lesion in one leg is sometimes missed by pressure measurement at rest when there is a severe lesion with symptoms in the other leg. In this study, the API not only at rest but also after exercise was measured in twenty normal subjects and thirty-two patients with angiographically proven arteriosclerosis obliterans. About 60% of the patients had unilateral symptoms, although they had significant disease bilaterally. The API after exercise proved to be more sensitive than the API at rest and may be useful in assessing asymptomatic legs of such patients and determining their surgical indication.

Sake or bourbon (8g ethanol/kg body weight) was intragastrically administered to rats for 12 days. An equal dose of ethanol in water or an isocaloric glucose solution was administered to control groups. Food was withheld, but water freely provided. Neither mortality nor liver and body weights were different between the alcohol-treated groups. Glutamic oxaloacetic transaminase and glutamic pyruvic transaminase were more elevated in the sake group than in the other groups. Additionally, liver fibrosis was more pronounced, and vacuole formation or steatosis was less in this group. These results suggest that sake is more fibrogenic. Some components other than ethanol, such as long-alkyl chain alcohols, may have been responsible for the differential histopathology.

Effects of carbon tetrachloride (CCl4) and azathioprine (AZP) on the evolution of hyperplastic liver nodules and foci and hepatocellular carcinoma (HCC) were tested in short- and long-term in vivo experiments. In diethylnitrosamine (DEN)-treated rats, which were fed a N-2-fluorenylacetamide (FAA)-containing diet and additionally treated with repeated CCl4 injections, gamma-glutamyl transpeptidase (gamma-GTP)-positive hyperplastic nodules were markedly developed in the 8th week of the experiment. However, their number and area in liver sections were remarkably small in DEN-treated rats fed a diet containing both FAA and AZP. Increased area of gamma-GTP-positive foci was also observed in the 12th week in DEN-injected rats fed a choline-devoid died alone or treated with repeated doses of CCl4 alone. Hepatocellular carcinoma in DEN-injected rats treated with both FAA and CCl4 was first detected in the 21st week, and the incidence up to the 36th week was very high. However, no hepatocellular carcinoma developed in DEN-injected rats treated with both FAA and AZP. The increased activity of liver aniline hydroxylase observed 12 h after the administration of FAA, AZP or DEN alone was not observed when AZP was administered simultaneously with FAA to DEN-injected rats. The mechanisms of the effects of CCl4 and AZP on hepatocarcinogenesis are discussed with special reference to drug interaction.

To search for lymphocyte marker antigens on the surface of human T-cell leukemia virus (HTLV), an immunoelectron microscopic study was performed on a HTLV-producing human T-cell line, MT-2, using monoclonal antibodies, such as anti-Leu-1, -Leu-2b, -Leu-3a, -Leu-5, -Leu-10 and -HLA-DR and OKIal. The reactivity of each antibody with MT-2 cells was tested by the immunoperoxidase method at the light microscopic level. OKIal, anti-HLA-DR and -Leu-10 gave positive results. At the ultrastructural level, the surface of HTLV as well as the plasma membranes of MT-2 cells were labeled with ferritin by the monoclonal antibodies OKIal, anti-HLA-DR and -Leu-10, but not by anti-Leu-1 and -Leu-3a. These findings suggest that HLA-D region -associated antigens are common antigenic determinants shared by the surface of HTLV and the plasma membranes of MT-2 cells. These antigens on the virus surface are probably picked up selectively from the plasma membranes and may play an important role in the interaction of HTLV and target T-cells.

Two cases of chronic unconjugated hyperbilirubinemia and marked retention of indocyanine green (ICG) are described. Since bilirubin uridine diphosphate (UDP)-glucuronyl transferase activities were depressed in their liver, the patients seemed to have bilirubin metabolism similar to that in Gilbert's syndrome. However, the ICG fractional disappearance rates of the cases were rather low (0.018 and 0.019) compared to the rates reported for Gilbert's syndrome. These results suggest that the patients had a new metabolic disorder which results in constitutional unconjugated hyperbilirubinemia and ICG intolerance.

The combined effect of human lymphoblastoid interferon (HLBI) and anticancer agents on the growth of MOLT-4 was studied in vitro. The interferon showed a strikingly synergistic interaction in combination with aclarubicin, cytosine arabinoside or prednisolone. It was moderately synergistic in combination with adriamycin or 5-fluorouracil and tended to show additive effects with daunorubicin or vincristine. In vitro studies of combination chemotherapy with interferon and anticancer agents should yield valuable information as to the best combination for man.

We have studied the incidence pattern of childhood cancers in Korea. Although the incidence of many tumors in Korea is similar to that in other countries, the incidence of acute myelogenous leukemia, non-Hodgkin's lymphoma and hepatoma is greater in Korean children. Yonsei Cancer Center commenced a study of multi-modality treatment of childhood cancers in July 1974. The most striking improvement of survival rate was seen in patients with acute lymphocytic leukemia (50% at 5 years), Wilms' tumor (65% at 5 years), neuroblastoma (45% at 2 years), osteogenic sarcoma (55% at 2 years) and malignant histiocytosis (20% at 5 years). This study is an attempt to create a basic framework providing the best possible treatment of childhood cancer in Korea. The data obtained in Korea are briefly compared with those in Japan and the United States.

A 26-year-old male with renal allograft, who received immunosuppressive treatment with azathioprine, presented marked elevations of serum biliary tract enzymes, such as gamma-glutamyl transpeptidase (5,609 units/l) and alkaline phosphatase (60.5 Bessey-Lowry units), 14 months after transplantation. Two months later the patient became icteric; he died of respiratory failure 19 months after the renal allograft. Postmortem examination revealed intrahepatic cholestasis with minimal inflammatory cell infiltration, indicating drug hepatotoxicity.