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A 31-year-old female with chronic myelogenous leukemia, who developed myeloblastic involvement of the central nervous system during acute myeloblastic transformation of the disease, was treated with methotrexate intrathecally. The therapy produced prompt clinical response and complete reversal of abnormal cerebrospinal fluid findings. However, the patient expired 10 months following the acute blastic crisis.

Plasma immunoreactive CRF measured by radioimmunoassay decreased rapidly after intravenous injection of synthetic ovine corticotropin releasing factor (CRF) and showed a bi-exponential decay curve in five macaca fuscatas. Half lives of plasma immunoreactive CRF were 5.8 +/- 1.4 (Mean +/- SEM) min for the fast component and 38.3 +/- 2.4 min for the slow component. A bolus injection of 5 micrograms/kg CRF significantly increased the plasma cortisol level. CRF at 5 micrograms/kg induced a delayed response of ACTH and cortisol. Arginine vasopressin (AVP) at 0.5 micrograms/kg induced a slight increase in plasma ACTH and cortisol, but AVP at 0.1 micrograms/kg evoked no significant increase. When 0.5 micrograms/kg CRF and 0.1 micrograms/kg AVP were administered simultaneously, significant ACTH and cortisol responses occurred. The results indicate that CRF and AVP act synergistically to stimulate ACTH secretion in vivo.

Seventy patients with cervical carcinoma who underwent radical hysterectomy and pelvic lymphadenectomy were evaluated to assess spread to the vagina. The overall vaginal invasion rate was 34.2% (24/70), with 36% (21/58) by squamous cell carcinoma, 25% (2/8) by adenocarcinoma and 25% (1/4) by adenosquamous carcinoma. A high vaginal invasion rate (45.7%) was noted in cases in which the cervical lesion was greater than 21 mm (p less than 0.05). Combined parametrial extention (45%) and combined lymph node metastasis (33.3%) were significantly higher in the vaginal invasion cases. The diagnostic accuracy of colposcopy and the Schiller test was 80% and 67% respectively. Histologically, the course of vaginal invasion by squamous cell carcinoma could be divided into : a) continuous invasion (16/21), b) incontinuous invasion via vessel permeation (3/21) and c) combined invasion (2/21). Both cases of vaginal invasion by adenocarcinoma were noted to spread by vessel permeation. Of the 7 cases of vessel permeation, colposcopic examination was positive in only one case. A high percentage of parametrial involvement and lymph node metastasis was noted in the vessel permeation type.

Carbon tetrachloride (CCl4)-induced hepatotoxicity was potentiated by pretreatment with beta-phenethyl alcohol, abundantly present in sake. The injury was determined by serum GPT levels and histological examination. Similar results were observed in ethanol- and phenobarbital-pretreated rats. Acetaminophen-induced hepatotoxicity was not accentuated by beta-phenethyl alcohol or ethanol pretreatment. The activities of liver microsomal enzymes, such as cytochrome P-450, cytochrome b5 reductase, aniline hydroxylase and aminopyrine demethylase, were not altered in beta-phenethyl alcohol-pretreated rats. Thus, CCl4-induced hepatotoxicity potentiation by beta-phenethyl alcohol administration is postulated to be due to a mechanism other than increased free radical generation.

The prevention of hepatic encephalopathy by the intravenous infusion of a branched chain amino acid (BCAA)-enriched solution was investigated in methionine and ammonium acetate-treated rats whose liver was already injured with carbon tetrachloride. A BCAA-enriched solution protected the rats from entering a coma. The brain BCAA contents became higher, and the brain methionine and tyrosine levels and the ratio of glutamine to glutamic acid in the brain diminished after administering the BCAA-enriched solution.

Ferrous chloride solution was injected unilaterally into the sensorimotor cortex of rats to induce a chronic epileptic focus. Accumulation of cyclic AMP elicited by depolarizing agents was determined in slices from different cortical areas of rats 30-60 days after the injection. In anterior cortical areas which include the sensorimotor cortex, the cyclic AMP accumulation elicited by ouabain or a high concentration of potassium ion was greater in electrographic spike activity on the dominant side than on the other. In posterior cortical areas, no difference in cyclic AMP accumulation was detected. The regional difference in the depolarization-elicited accumulation of cyclic AMP is discussed with regard to the process of epileptic focus.

L-Cysteine (5.0 mmol per kg of body weight) was intraperitoneally injected into rats fed a 25% casein or 5% casein diet. Concentrations of acidic and neutral amino acids in various tissues were determined 2 h later. In the rats fed the 25% casein diet there was a tendency for tissue amino acid and glutathione levels to be slightly lower than controls. In the 5% casein diet group, however, concentrations of tissue amino acids and glutathione generally increased after L-cysteine administration. S-(2-Hydroxy-2-carboxyethylthio)cysteine (HCETC,3-mercaptolactate-cysteine disulfide), though in trace amounts, was detected in kidney and blood plasma in the 5% casein diet group. Increases in cysteine-glutathione disulfide in liver, kidney and erythrocytes in the 5% casein diet group were considerable. These results indicate that L-cysteine was rapidly metabolized in the 25% casein diet group through the oxidative pathway, while in the 5% casein diet group, in which liver cysteine dioxygenase activity is supposed to be quite low, the oxidative metabolism of L-cysteine decreased and part of the L-cysteine was metabolized through the transaminative pathway. Administration of 15.0 mmol L-cysteine per kg of body weight to rats fed the 25% casein diet resulted in an increase in cysteine-glutathione disulfide in liver, kidney and erythrocytes, and the appearance of HCETC in blood plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

<p>Murine sarcoma virus, CS-Moloney substrain, was inoculated intracranially into 2 litters of newborn Syrian hamsters within 24 h of birth. Seven of 12 hamsters which survived more than 30 days developed brain tumors in the cerebral cortex 104 to 153 days, 139 days on the average, after the virus inoculation. The tumors consisted of spindle-shaped, round or polygonal astrocytes which showed a positive reaction for glial fibrillary acidic protein by the immunoperoxidase method.</p>

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.

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.