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Lentinan inhibited the proliferation of MH-134 ascites hepatoma transplanted subcutaneously. The best result occurred when 1 mg-2 mg/kg of lentinan was administered for 10 consecutive days from the eighth day after tumor transplantation. Tumor proliferation was 33% inhibited as measured by the average tumor diameter. The average survival (days) when chemotherapy with mitomycin-C (MMC), 5-FU and Ara-C in combination with lentinan, was administered concurrently in the second week of the tumor transplantation was 29.2 days as compared to 20.5 days in the untreated group, 25.1 days in the group given lentinan alone, and 22.0 days in the group receiving chemotherapy alone. When lentinan was administered in combination with bacterial lipopolysaccharide (LPS), the group given lentinan for 5 consecutive days from the third day after tumor transplantation and 30 micrograms LPS i.p. on the thirteenth day, had 70% inhibition of tumor as measured by the average tumor weight. The antitumor activity of lentinan was studied by following changes in macrophage migration inhibition activity (MI). In the untreated group, MI activity disappeared on the 14th day after tumor transplantation. In the group treated with lentinan, spleen cells had positive activity suggesting a restorative action of lentinan on the immune suppression accompanying tumor growth.

Erythrocyte catalase in normal and Japanese type acatalasemia hemolysates was separated by chromatofocusing into several fractions in the pH range of 6.1 to 5.7. Normal hemolysate gave a major peak of catalase activity with a pH of 6.1 to 5.5, while acatalasemia hemolysate gave several small peaks in this pH range and a main peak with a pH of 6.6 to 6.2. The main protein band in catalase active fractions separated from normal erythrocytes had a molecular weight of 60,000 by SDS polyacrylamide gel electrophoresis. A similar faint protein band having a molecular weight of 60,000 was also found in acatalasemia hemolysate in addition to a fairly intense band with a molecular weight of about 30,000. Catalase active fractions from normal erythrocytes reacted with antihuman erythrocyte catalase rabbit serum by double immunodiffusion.

The patient was a 37-year-old female teacher with hyperemesis diabeticorum and juvenile Type-I diabetes. At the age of 29 years, nausea and vomiting developed and secured at nearly weekly intervals. She was started on clotiazepam (15 mg/day). The vomiting was cured and psychological improvement was evident; her anxiety about diabetes was markedly reduced. An X-ray examination after the administration of clotiazepam showed that she was entirely free from marked hypoperistalsis and the severe retention of gastric contents which had been present before this treatment. The present case is a clear example of stress closely related to the pathogenesis of hyperemesis diabeticorum.

Two factors from normal rat liver cytoplasm inhibited the proliferation of cultured L-929 fibroblasts. One was arginase, the other was a small molecular weight inhibitor stable to trypsin and heat treatment. The small molecular weight inhibitor inhibited the protein and DNA synthesis of L-cells. Inhibition of DNA synthesis was thought to be secondary to the inhibition of protein synthesis.

Response rates and survival times were studied in 47 patients who had multiple myeloma and who were being treated with Prednisolone and sequential Melphalan and Ifosfamide (MIP therapy). The clinical response was determined by objective parameters such as the reduction of M-protein level, tumor volume and healing of bone destruction. Twenty-eight of the patients (59.6%) responded to the MIP therapy. The 50% survival time as followed from the initiation of treatment to death was 19 months. Of the prognostic factors, the age (greater than or equal to 70 years), clinical stage III of Durie and Salmon, hypercalcemia, extensive bone lesions, and the patho-morphological type IV of Brucher were associated with a decreased life-span. Therefore, MIP therapy was more effective in poor risk (high tumor mass group) than in good risk (low or intermediate tumor mass group) patients, but the survival of patients on MIP therapy was shorter in the poor risk group than in the good risk one. In addition, the group which responded rapidly (i.e. within 2-5 weeks) had longer remission and longer survival than the group which improved slowly (i.e. after 6-16 weeks).

Six established Japanese Burkitt lymphoma (BL) cell lines including one case with null cell type were studied by chromosomal banding techniques. The modal chromosome number was diploid or nearly diploid in five cases and hyperdiploid in one case. The marker chromosome 14q+ was observed in four of the six cases; the origin of the extra band was a chromosome 8 in three including the null cell case but could not be identified in the other. The two cases lacking the 14q+ marker had variant translocations involving the long arm of chromosome 8, one of which carried a translocation, t(8;22) (q24;q13) and the other a translocation, t(2;8) (p12;q24). Although structural and/or numerical aberrations were found in all six cell lines, chromosome 8 was the one most consistently involved. This frequent involvement of chromosome 8 in aberrations; therefore, may be an important event in the development of BL rather than the presence of a 14q+ marker chromosome.

Relapses in nine patients with acute myelocytic leukemia were treated with a combination of aclarubicin (ACR) and cytosine arabinoside (ara-C). ACR, 40 mg/m2/day, was administered daily by intravenous injection from day 1 to day 3 and ara-C, 60-80 mg/m2/day, divided into 2 doses, was given every 12 h by intravenous infusion from day 1 to day 7. Depending on the state of the bone marrow, ACR-ara-C regimen was modified in administration period and repeated after the resting periods of at least 7 days. Complete remission was obtained in 7 of 9 patients (77.8%). The time required for achieving the complete remission varied from 20 to 55 days with a median of 39 days. The duration of complete remission was from 8 to 52 weeks with a median of 22 weeks. Side effects on digestive system such as nausea, vomiting and anorexia, were seen in all patients, although they were managed by symptomatic treatment. The results indicate the effectiveness of this ACR-ara-C regimen in the clinical management of acute nonlymphocytic leukemia.

Nine eyeballs were enucleated from nine patients with excessive myopia, secondary retinochoroidal atrophy, absolute glaucoma, uveal malignant melanoma, Behcet's disease and sympathetic ophthalmia. The retina and choroid were studied with light and electron microscopes. The results were: In excessive myopia, marked blockade of choriocapillaries was accompanied by progressive retinal degeneration. In secondary retinochoroidal atrophy induced by retrobulbar fibrosis, the choriocapillaries were partially blocked and the retina had markedly degenerated. In Behcet's disease, exudative inflammation was recognized in the choroid extending to the retina and causing retinal detachment, though the choriocapillaries remained morphologically normal. In sympathetic ophthalmia, both the choriocapillaries and the retina remained normal, though marked inflammation was recognized in the outer layer of the choroid. In absolute glaucoma, the fine structures of the choriocapillary were well preserved in spite of bulbar hypertonia. In uveal malignant melanoma, the ultra structure of the choriocapillary near the tumor was well preserved. The choriocapillaries were normal even when the retina had degenerated. Retinal degeneration was recognized when changes such as blockage, disappearance, dilatation and increased permeability were found in the choriocapillaries. Damage to the choriocapillaries might play an important role in inducing and developing retinochoroidal atrophy.

Eighteen patients with advanced non-Hodgkin's lymphoma other than the diffuse histiocytic type were treated with a combination of adriamycin, vincristine, ifosfamide and prednisolone (AVIP). The objective response rate was 83% (15/18); 61% (11/18) achieved complete remission. The median duration of complete remission was 11 months ranging from 2 to 39+ months. Eleven of the 18 patients are still alive during the median follow-up time of 13 months. The median survival was 14+ months for complete responders, and 9.5 months for partial and nonresponders. A myelosuppressive toxicity was well tolerated. AVIP offers some hope as treatment of advanced non-Hodgkin's lymphoma.

The effects of steroid sex hormones on the established cell lines derived from human urinary bladder cancer, T24, and from human transitional cell cancer of the urinary tract, 253J, were examined using the colony formation method. Of the seven kinds of steroid hormones tested, estradiol-17 beta was intensively cytotoxic for both cells. The cytotoxic effect was depended on the dose and time of treatment. The combined effect of Adriamycin and estradiol-17 beta on T24 cells could be recognized at low concentrations of Adriamycin (less than or equal to 10(-3) micrograms/ml) after exposure for 24 h.

The cholinesterase activity of skeletal muscle and its subcellular components, including motor endplates, was compared chemically in human, mouse and rat. The total cholinesterase activity of muscle per unit protein was in the descending order of human, mouse and rat. Cholinesterase was present in all subcellular components fractionated by differential centrifugation, and was greatest in the microsome fraction followed, in descending order, by the mitochondria, myofibril, and supernatant fractions. Each of these fractions had greater cholinesterase activity in human muscle than in mouse muscle, and in mouse muscle than in rat muscle. The ratio of the activity of the microsome fraction to the activity of muscle homogenate was 11.1 in human, 4.6 in mouse and 3.4 in rat. Because of its relatively greater proportion, the myofibril fraction seems to contribute most to the total cholinesterase activity of muscle. Muscle membrane contained high cholinesterase activity of motor endplates, and the activity was greater than the activity of the microsome fraction in rat. Cholinesterase activity per motor endplate was in the descending order of rat, human and mouse, and the variation was less than the variation in the total muscle cholinesterase activity among these species.

Under barbiturate anesthesia, male Wistar rats weighing 250-300 g were injected with 2.5 microliters of 0.2 M FeCl3 solution into the left sensori-motor cortex to induce an epileptic focus with minimal abnormal activities. Polygraphy started 1 week after the surgery, showed a spindle-like hypersynchronous activity that appeared not only in the slow wave sleep period but also during paradoxical sleep (PS). This activity had a frequency of 8-14 Hz. The amplitude was more than 200 mu v in the right (non-injected side) cortex but very small in the left cortex (injected side). Isolated spike discharges were observed in an ECoG of slow wave sleep. Apart from this activity there was nothing resembling the usual sleep spindles.

Measurement of lipid peroxides and alpha-tocopherol was undertaken in rats with streptozotocin-induced diabetes. In sera and livers in diabetic rats, the lipid peroxides increased but alpha-tocopherol decreased. To study the effect of vitamin E deficiency in the diabetic state, diabetes was induced in rats maintained on a vitamin E deficient diet. Serum lipid peroxides increased greatly but alpha-tocopherol decreased. Lipid peroxides and alpha-tocopherol increased in the liver of vitamin E deficient states. In the liver, vitamin E deficient diabetic rats had lower lipid peroxides levels but higher alpha-tocopherol levels than vitamin E deficient non-diabetic rats. On the basis of the present experiments, it was considered that the decrease of alpha-tocopherol might be due to consumption as an antioxidant as lipid peroxides increased in sera and livers. The decrease of lipid peroxides in the liver was thought to play an important part of the increase in serum lipid peroxides.

Changes in the stenotic resistance of a coronary artery following brief coronary occlusion were studied in the anesthetized open-chest dog. A critical coronary stenosis was constructed by tying a thick string around the circumflex coronary artery (LCx) near its origin. The LCx was occluded for 5, 10, 15, 20 and 30 seconds with and without coronary stenosis then the reactive hyperemia was observed. In the absence of the stenosis, resistance of the segment of the large coronary artery remained unchanged during the reactive hyperemia independent of the duration of occlusion. In the presence of the stenosis, however, stenotic resistance increased for a certain time after the release of occlusion. This increased resistance lasted longer with more severe stenosis and with longer duration of coronary occlusion. These results suggest that stenotic resistance can increase dynamically, and that the duration of increased resistance may reflect the severity of the stenosis.

Cysteine aminotransferase (L-cysteine: 2-oxoglutarate aminotransferase, EC 2.6.1.3) was purified over 400-fold from the high-speed supernatant fraction of rat liver. The purified enzyme was homogeneous as judged by gel filtration, isoelectric focusing and disc electrophoresis. The molecular weight of the enzyme was about 74,000 by gel filtration and the isoelectric point was 6.2 (4 degrees C). The enzyme catalyzed transamination between L-cysteine and 2-oxoglutarate and the reverse reaction. The optimum pH was 9.7. The Km value for L-cysteine was 22.2 mM, and that for 2-oxoglutaric acid was 0.06 mM. L-Aspartate was a potent inhibitor of the cysteine aminotransferase reaction. The enzyme was very active toward L-alanine 3-sulfinic acid at pH 8.0, and was also very active toward L-aspartic acid (Km = 1.6 mM). Ratios of activities for L-aspartic acid and L-cysteine were essentially constant during the purification of the enzyme. Evidence based on substrate specificity, enzyme inhibition, and physicochemical properties indicates that cytosolic cysteine aminotransferase is identical with cytosolic aspartate aminotransferase (L-aspartate: 2-oxoglutarate aminotransferase, EC 2.6.1.1).

Cholinesterase activity was localized solely in the motor endplate of the membrane in rate intercostal muscle. The diameter of rat motor endplates in the gradient dimension was 31.9 micrometers. The cholinesterase activity per unit protein of the soluble fraction of rat muscle membrane was 35.6% higher than the original membrane. From studies with specific substrates and cholinesterase inhibitors, the cholinesterase activity of rat muscle membrane and its soluble fraction consists of more than 90% acetylcholinesterase and less than 10% pseudocholinesterase.

A single withdrawal of blood (about 0.6 ml) from a splenectomized mouse induced extramedullary hemopoiesis in the liver. Twenty days after splenectomy, blood was taken from the retroorbital sinus. Hemopoietic foci in the liver increased in number daily reaching maximum value 6 days after blood withdrawal, then decreased gradually to the initial level with recovery of the hematocrit value and disappearance of reticulocytosis 25 days after blood withdrawal. Hemopoietic foci were pure erythrocytic, granulocytic, megakaryocytic or unclassified, but not mixed. Small unclassified cell foci appeared first, increased in number, followed by the development of erythrocytic, granulocytic and megakaryocytic foci. This suggests that small unclassified cell foci grow to erythrocytic and large granulocytic ones. Most of the liver hemopoietic foci were in the intralobular area. Some were in the portal area; none of these were megakaryocytic. Electron microscopic observation revealed that lymphoid cells having distinct nucleoli migrate into Disse's space through the sinusoidal walls. There they proliferate by cell division to form large foci in the perisinusoidal area. The morphologic characteristics of the lymphoid cell are discussed.

The inhibition of human motor endplate cholinesterase by anticholinesterase compounds was studied using isolated muscle membrane preparation. Ambenonium was most potent, and edrophonium was least potent in inhibiting motor endplate cholinesterase. The slope of the regression line for inhibition of motor endplate cholinesterase was greatest for ambenonium, and smallest for neostigmine and edrophonium. These compounds were less potent inhibitors of plasma cholinesterase. Ambenonium was more specific, and other compounds were less specific inhibitors of motor endplate cholinesterase. In myasthenic patients, these compounds produced adequate inhibition of motor endplate cholinesterase even in the presence of relatively mild plasma cholinesterase inhibition.