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The influence of surgical stress on the local graft-versus-host reaction (GVHR) in F1 mice was studied. Skin incision 1 day prior to injection of parental spleen cells produced impairment of popliteal lymph node enlargement; however, this effect was not observed when GVHR was induced 3 and 5 days after operation. Strong GVHR suppressive activity of spleen cells was observed three hours after leg amputation before a decrease in thymus weight became evident. The GVHR suppressive activity declined by six hours later, but a second peak of 60% inhibition was observed after 24 h. This suppressive activity completely disappeared by treatment with anti-Thy 1.2 and complement. This shows that the GVHR is suppressed by surgical stress, and that this suppression is due to suppressor T lymphocytes.

Using the technique of somatic cell fusion, we produced monoclonal antibodies to collagenase-digested human glomerular basement membrane (GBM). Fourteen monoclonal antibodies which reacted with normal human kidney in indirect immunofluorescence (IIF) studies were produced. An analysis of the binding patterns indicated that the antigens recognized could be divided into six broad groups. Monoclonal antibody B3-H10 (Group 1) reacted with only GBM in a fine granular pattern. A5-B12 and B5-C2 (Group 2) reacted with GBM and peritubular capillary in a linear pattern. B2-A12 (Group 3) reacted with only epithelial cells. Al-C9 and A4-E2 (Group 4) showed a mesangial pattern in glomerulus and a lineal pattern in tubular basement membrane (TBM), Bowman's capsule and peritubular capillary. A1-E1, A1-E11, A2-E6, A3-B6, A4-F8 and B5-H2 (Group 5) recognized determinants common to GBM, TBM, Bowman's capsule and/or peritubular capillary. A3-F1 and B5-E10 (Group 6) reacted with TBM and Bowman's capsule. The staining pattern of B3-H10 (Group 1) was characteristic because it was not linear, but finely granular along the GBM. The staining pattern of B2-A12 (Group 3) was also characteristic because only epithelial cells were stained, and processes of epithelial cells were observed as fine fibrils. To the best of our knowledge, these two types of monoclonal antibodies have not been reported previously.

A single injection of ferric nitrilotriacetate (Fe3+-NTA) caused a transitory increase in plasma immunoreactive insulin (IRI) and plasma immunoreactive glucagon (IRG) in rats. They reached maximum levels at 2 days after injection and returned to the normal range at 10 days. At 2 days after Fe3+-NTA injection, blood glucose level was normal but the glucose tolerance test (GTT) was impaired. There was a further increase in plasma IRI level and IRG level was suppressed after glucose loading. At 10 days after Fe3+-NTA injection, glucose tolerance was normal and IRI also returned to the normal range. No degenerative changes were found on H.E.-stained rat pancreatic tissue sections after Fe3+-NTA injection. Histochemical staining, however, showed a reduction in beta-granules and heavy metals (Timm's granules) from islet cells in the central area of the rat pancreatic islet 1 to 3 days after injection of Fe3+-NTA. The fading remained in some islets even at 10 days after injection, but by then the beta-granule distribution was restored in most islet cells. The results indicate a single Fe3+-NTA injection induced transitory instability of the pancreatic islet beta-cell granules and the glucose intolerance with a hyperresponse of IRI.

Seventy-one cases of bronchial asthma were classified into three types: bronchospasm, bronchospasm-hypersecretion and bronchiolar obstruction types. The characteristics of each type were studied in relation to patient age and age at onset of the disease. In the 71 subjects studied, the most frequent type was the bronchospasm type followed by the bronchospasm-hypersecretion type and bronchiolar obstruction type. Intractable asthma was most frequently observed in the bronchiolar obstruction type and least in the bronchospasm type. Most of the patients under 50 years of age showed the bronchospasm type. The bronchospasm-hypersecretion type was characteristically accompanied by blood eosinophilia when the patient age was under 50 years. In the bronchospasm-hypersecretion type, the incidence of intractable asthma was high in patients under 50 years of age, but not remarkable in those over 50. A large proportion of the patients over 50 years of age were of the bronchiolar obstruction type. There was no difference in the incidence of intractable asthma between the two groups classified by age at onset.

A modified method of passive immune hemolysis (PIH) was applied to the quantitative assay of heat-labile enterotoxin (LT) produced by enterotoxigenic Escherichia coli. The method enabled the measurement of 0.2 to 1.2 ng LT. The production of LT by enterotoxigenic E. coli under various conditions was analyzed using the modified method. LT production was intense during the logarithmic growth phase and decreased during the stationary growth phase. Lincomycin (50 to 100 micrograms/ml) affected cell growth slightly, but enhanced production of LT until the late-stationary growth phase. About 90% of the LT produced was retained in the cell, and the rest was excreted into the culture medium. The initial pH of the culture medium affected LT production. Alkaline pH enhanced LT production, though growth was depressed. Aeration enhanced both growth and LT production.

Ten adult cats were anesthetized and ventilated by respirator. After the basilar artery was exposed transclivally and visualized with an operative microscope, mean arterial blood pressure (MABP) was raised gradually by intravenous drip infusion of norepinephrine (5-20 micrograms/kg) or angiotensin-II-amide (0.3-1.0 micrograms/kg). At various blood pressures, microphotographs were taken. There was no appreciable change in vessel diameter at a MABP ranging from 78 to 191 mmHg. The blood pressure was allowed to return to the initial baseline level. Arterial spasm was produced by the topical application of 0.2 M calcium gluconate, which decreased the arterial diameter by 13 to 58 percent for more than 60 min. Blood pressure was increased again after the production of the arterial spasm. Significant increases in the diameter of the arteries were produced by the drug-induced hypertension at levels of MABP ranging from 82 to 192 mmHg. The maximum arterial dilations ranged from 123 to 208 percent of the untreated control. The degree of dilation of the arteries almost paralleled the rise in MABP. Norepinephrine and angiotensin-II had a similar effect on both the blood pressure and the arterial diameter. Induced hypertension would be expected to improve blood flow parameters in the case of spastic cerebral arteries.

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.