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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.

The effects of electrical stimulation of the satiety and feeding centers (SC, FC) on gastric, cecal and rectal motility were studied in rats anesthetized with urethane. Each center produced excitatory, inhibitory and biphasic responses in these organs. Cecal and rectal responses to stimulation of SC or FC were usually the opposite of the gastric response; for example, the gastric response was excitatory, whereas cecal and rectal responses were inhibitory. Gastric and cecal excitatory responses were abolished by vagotomy and the rectal response by severance of parasympathetic branches of the pudendal plexus (PSB). Gastric and ceca inhibitory responses were fairly depressed by vagotomy and abolished by successive splanchnicotomy, while the rectal inhibitory response was abolished by severance of inferior mesenteric nerves (IMN) and PSB. It was concluded that the satiety and feeding centers modulate not only gastric motility but also cecal and rectal motility, and that the excitatory response is conveyed through vagus nerves to the stomach and cecum and through PSB to the rectum. The inhibitory response is mediated mainly through vagus nerves, partially through splanchnic nerves to the stomach and cecum, and through IMN and PSB to the rectum. The characteristics of efferent terminal neurons eliciting excitatory and inhibitory responses were studied pharmacologically.

Human and bovine glomerular basement membranes (GBM) were previously shown to be a three-dimensional molecular sieve composed of pores and strands by negative staining and electron microscopy. In this study, rat GBM were isolated under several different conditions to rule out morphological changes due to isolation procedures. Rat GBM isolated under different conditions all showed the same morphological features as bovine and human GBM. The strands forming the molecular sieve were almost equal in width, measuring approximately 3.1 +/- 0.8 nm. Pores were oval or polygonal. The size of pores varied a little averaging 4.4 +/- 1.0 nm in the long dimension and 3.0 +/- 0.6 nm in the short dimension. The average density of the pores was 16 +/- 2/1,000 nm2. Negative staining demonstrated pores in isolated and unfixed GBM, indicating that the function of GBM is mechanical filtration of macromolecules on the basis of size.

This study investigated the optimal conditions for detection of nucleotides in blood using an IP-1B capillary isotachophoretic apparatus. The system used 10 mM HCl-beta-alanine (pH 4.2) as the leading electrolyte and n-caproic acid as the terminal electrolyte. Direct application of lysed red blood cells was shown to be inaccurate, and a method of deproteinization based on heat in a microwave oven was developed. The zones for 2,3-diphosphoglycerate, ATP, inorganic phosphate, and lactate were identified enzymatically by withdrawal of pure samples of each zone via a special withdrawal cell. The quantitative values obtained by isotachophoresis were also confirmed enzymatically. The technique is now available for convenient and accurate identification of these metabolites simultaneously.

Antiserum was produced in white rabbit by intravenously injecting living cells of a B cell acute lymphoblastic leukemia (ALL) line (BALL-1). The reactivity of the antiserum against various lymphoid cell lines was examined by membrane immunofluorescence after appropriate absorption. Serum absorbed with non-T, non-B (NALL-1) and T-ALL (TALL-1) cells recognized B cell antigens distinct from Ia-like antigens on both normal and neoplastic B cells. After further absorption with tonsillar cells or normal B cell line (KO-HL-3), it reacted only with BALL-1 cells and did not react with other leukemia/lymphoma and normal B cell lines. The serum absorbed with tonsillar cells reacted only with BALL-1 and some B cell lines. Thus we were able to obtain antisera with specificity to B cell antigen, B-ALL antigen, and B cell line antigen.

To study autoantibodies against liver cell surface membrane clinically, anti-LP-1 and anti-Tamm-Horsfall glycoprotein (THGP) were determined in the sera of patients with various liver diseases. They were detected by ADCC assay using antigen-coated cells as the target. A high incidence of anti-LP-1 was seen in chronic hepatitis (CH), liver cirrhosis (LC), primary hepatic cancer with cirrhosis (PHC), and primary biliary cirrhosis. The incidence of anti-THGP was also high in CH, LC, and PHC. Both anti-LP-1 and anti-THGP were detected in 2 of 3 patients with lupoid hepatitis. The patients studied here had no obvious evidence of renal tubular acidosis or pyelonephritis. Serum alanine transaminase activity, serum gamma-globulin content, and the presence of rheumatoid factors were not associated significantly with the presence of anti-LP-1 or anti-THGP in chronic liver disease. In 7 cases of CH tested serially during their clinical course, anti-LP-1 and/or anti-THGP tended to appear during acute exacerbations. The demonstration of anti-LP-1 and anti-THGP suggested that their appearance was related to the development of chronic liver disease.

Numerical changes in peripheral blood monocytes were examined in 125 patients with bronchial asthma using a new direct method of counting blood monocytes. The number of monocytes in non-attack stages of bronchial asthma was similar to that of healthy controls. The monocyte count observed in overall cases showed a significantly higher value both in pre-attack and attack stages than in non-attack stages. Changes in the number of monocytes in an individual spontaneous asthmatic cycle tended to increase in pre-attack stages, increase more markedly during asthma attacks, then to decrease after the attack was alleviated. Monocytes in cases with a positive test for bronchial challenge to house dust extract changed in almost the same manner as for spontaneous asthma attacks. The number of monocytes did not change during bronchospasm provoked by inhalation of acetylcholine. Exercise-induced asthma patients exhibited indefinite changes of monocytes; that is, some cases showed a significant increase in the number of monocytes related to the asthma cycle, but other cases did not show any appreciable change. These findings suggest that the number of monocytes in the peripheral blood may change in close relation to asthma attacks elicited by allergic reactions.

Urinary excretion of cyclic GMP (cGMP) and the plasma level of cyclic AMP (cAMP) were determined in patients with liver diseases. The urinary excretion of cGMP, expressed on the basis of creatinine excreted per day, was at significantly higher levels not only in primary hepatoma but also in liver cirrhosis, while the plasma level of cAMP was higher only in liver cirrhosis. Thus, the ratio of urinary cGMP excretion to plasma cAMP level in primary hepatoma was significantly higher than that in liver cirrhosis. In cirrhotic patients studied by catheterization, the level of cGMP in the hepatic vein was significantly lower than that in the superior mesenteric or portal vein, indicating the uptake of cGMP by the liver. Since cGMP excretion correlated with KICG both in liver cirrhosis and primary hepatoma, the increased cGMP excretion appeared to be explained by a reduced uptake of cGMP by the liver.