[Discussion: changes in women's status over the past 10 years].
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Biomedical subjects
Publications and source records attributed to M Fujiwara.
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The patient was a 69-year-old woman who complained of bloody stools and abdominal pain. A tumor was removed with abdominoperineal excision, and histologic examination revealed malignant lymphoma associated with reactive lymphoreticular hyperplasia. The lesion was of the diffuse, medium-sized cell type according to the classification of the Japan Lymphoma Study Group.
We review the technical problems and examine the different parameters concerning the culture of human bone marrow over a long period of time (10-20 weeks). The main points of interest for the study of normal hematopoiesis and its impairment in blood diseases are indicated. The aim of this review is practical as well as theoretical.
Cyclopentenone prostaglandins (PGs) such as PGA2 and 9-deoxy-delta 9,12-13,14-dihydro-PGD2 (delta 12-PGJ2) are transported actively into the cytoplasm and exert growth inhibition in cultured cells. We examined effect of temperature on the uptake of delta 12-PGJ2 and its subsequent translocations within and out of the cells. When L-1210 murine leukemia cells were incubated with the PG at 4, 20 and 37 degrees C, the initial rate of uptake increased with temperature. However, the uptake at 37 degrees C declined rapidly after 5 min, whereas that at 4 and 20 degrees C increased linearly and reached plateau. Subcellular distribution study revealed that about 90% of the radioactivity taken up at 4 and 20 degrees C was present in the cytoplasm, whereas more than 50% of the radioactivity transported at 37 degrees C accumulated in the nuclei. When incubation temperature was shifted from 4 to 37 degrees C during incubation, significant accumulation of the radioactivity in the nuclei occurred at 37 degrees C. In contrast, when the cells were first incubated with delta 12-PGJ2, then washed and incubated without the PG at either 20 or 37 degrees C, most of the radioactivity found in the cytoplasm was effluxed to the medium during the second incubation. The rate of this efflux was negligible at 4 degrees C but increased with temperature above 20 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)
[14C]-Carbon tetrachloride (CCl4) entered extensively into the liver and, to the small extent, into the brain 3 hr following the intragastric administration of the hepatotoxic dose. Although thiobarbituric acid (TBA) in the liver homogenates increased 12 hr after CCl4 administration, the brain showed little TBA values probably due to very low levels of chytochromes P-450 and b5 in the brain. These results suggest that CCl4 have no direct toxic effect upon the brain.
The present study was designed to examine the influence of delta 9-tetrahydrocannabinol (THC) on the central dopaminergic system using circling behavior. THC 5 mg/kg i.p. produced ipsilateral circling in rats with unilateral nigral lesion by 6-hydroxy-dopamine. THC-induced ipsilateral circling was completely antagonized by 0.2 mg/kg of haloperidol. These findings suggest that THC may cause a presynaptic stimulation of nigrostriatal dopaminergic neurons.
Cholinergic receptor sites in bovine cerebral arteries were analyzed using radioligand binding techniques with the cholinergic agonist, 3H-acetylcholine (ACh), as the ligand. Specific binding of 3H-ACh to membrane preparations of bovine cerebral arteries was saturable, of two binding sites, with dissociation constant (KD) values of 0.32 and 23.7 nM, and maximum binding capacity (Bmax) values of 67 and 252 fmol/mg protein, respectively. Specific binding of 3H-ACh was displaced effectively by muscarinic cholinergic agents and less effectively by nicotinic cholinergic agents. IC50 values of cholinergic drugs for 3H-ACh binding were as follows: atropine, 38.5 nM; ACh, 59.8 nM; oxotremorine, 293 nM; scopolamine 474 nM; carbamylcholine, 990 nM. IC50 values of nicotinic cholinergic agents such as nicotine, cytisine and alpha-bungarotoxin exceeded 50 microM. Choline acetyltransferase activity was 1.09 nmol/mg protein/hour in the cerebral arteries. These findings suggest that the cholinergic nerves innervate the bovine cerebral arteries and that there are at least two classes of ACh binding sites of different affinities on muscarinic receptors in these arteries.
To investigate the role of the amygdala in central regulation of pancreatic exocrine secretion, the effects of electrolytic lesions on pancreatic secretion were studied in rats. Small bilateral electrolytic lesions in amygdaloid body restricted to basolateral, medial and central nuclei were produced. Eight days after the lesions, bile-pancreatic juice was collected following anesthetization with urethane and chloralose. Basal secretion and secretion stimulated by exogenous pancreozymin and secretin were evaluated in terms of amylase output. In the group with basolateral nucleus lesions, both basal and stimulated secretion were significantly increased. After medial nucleus lesions, mean body weight was reduced to 59% of initial, and basal and stimulated secretion were significantly lower than in the control group and also significantly lower than in an unoperated group, whose mean body weight was reduced to the same level as that of the medially lesioned group by restricting daily food intake. After lesions of the central nucleus, basal secretion was significantly increased, while stimulated secretion was not affected. These results indicated that the amygdala is involved in regulating pancreatic exocrine secretion and that its various nuclei exert different effects.
Contractile responses due to substance P released from the trigeminal nerve were observed after electrical transmural stimulation or exogenous application of bradykinin in the isolated rabbit iris sphincter muscle. Prostaglandins, particulary prostaglandin E1, enhanced and indomethacin inhibited these substance P-ergic responses. Since the responses to exogenously applied substance P were neither affected by prostaglandins nor indomethacin, it was suggested that prostaglandins acted presynaptically to enhance the release of substance P from the trigeminal nerve terminals.
Effects of various calmodulin antagonists and calmodulin on the incorporation of serine, ethanolamine and choline into the corresponding phospholipids, such as phosphatidylserine, phosphatidylethanolamine and phosphatidylcholine by Ca2+-stimulated base-exchange reactions in rabbit platelet membranes were studied. Under a Ca2+-EGTA buffer system, the incorporation of three bases were stimulated by Ca2+ in a biphasic manner. Minimum requirement of free Ca2+ for the reactions was found to be around 0.5 microM and maximal incorporation took place at high Ca2+ concentrations (3-5 mM). Various calmodulin antagonists such as chlorpromazine, trifluoperazine and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, not only activated the three reactions but also greatly enhanced their sensitivity to Ca2+ (K0.5, 0.1-0.3 microM). In the absence of Ca2+, however, the drugs did not show any effect on the reactions. The concentrations of the drugs required for half maximal stimulation were approx. 30-40 microM. Although platelet membranes contained endogenous calmodulin (0.3-0.6 microgram/mg of membrane protein), the addition of exogenous calmodulin inhibited choline exchange activity but had no or little effect on serine or ethanolamine exchange activity. The results suggest that in the presence of low Ca2+ concentrations, these drugs markedly stimulate base-exchange activities, and choline exchange activity may be regulated by calmodulin.
Due to an increase in mature neutrophils, a 72-year-old female with gall bladder cancer showed leukocytosis of up to 1.32 X 10(11)/l; hypercalcemia was up to 7.7 mEq/l in her terminal stage. Leukocyte counts and calcium values increased as the tumor progressed. There was no sign of infection or bone marrow metastasis. Cultured cells from the tumor tissue produced high colony-stimulating factor (CSF) activity into the supernatant. The tumor cell-conditioned medium stimulated exclusively granulocytic colonies. The study of this patient shows that leukocytosis was caused by the CSF produced by tumor cells. Approximately 90% of CSF activity was lost by heat treatment at 60 degrees C for 30 min. The CSF was stable over a pH range of 3-11 and was inactivated by treatment with proteolytic enzymes, but was not affected by treatment with DNase or neuraminidase. Molecular weight of the CSF, demonstrated by fractionation using Sephacryl S-200, was approximately 27,000 to 30,000.
The relationship between the accumulation of isoprenaline and the incidence and duration of ventricular fibrillation was investigated in the perfused rat heart. Isolated rat hearts were perfused with 3H-isoprenaline (1 mumol/l) for 30 min at a constant flow rate of 6.5 ml/min at a temperature between 40 and 41 degrees C. Electrocardiograms were recorded during the perfusion period and the isoprenaline content of the tissue was measured after the perfusion. The accumulation of isoprenaline was significantly increased and the duration of ventricular fibrillation was significantly prolonged by the presence of tropolone (100 mumol/l). When extraneuronal uptake inhibitors such as normetanephrine (100 mumol/l), 3-O-methylisoprenaline (100 mumol/l) or phenoxybenzamine (1 mumol/l) were added to the perfusion fluid containing 3H-isoprenaline (1 mumol/l) and tropolone (100 mumol/l), the accumulation of isoprenaline was significantly decreased, the incidence of ventricular fibrillation was significantly reduced and the duration of ventricular fibrillation was significantly shortened. There was a significant correlation for dependence of duration of ventricular fibrillation on the isoprenaline content of rat hearts perfused with various extraneuronal uptake inhibitors in the presence of tropolone (correlation coefficient [r] = 0.62, P less than 0.001). These results indicate that the accumulation of isoprenaline in perfused rat hearts relates to the occurrence and duration of ventricular fibrillation.
When goniopora toxin (GPT), a marine toxin isolated from coral, was applied to the bullfrog atrial muscle, the duration of action potential (APD) was prolonged, and a positive inotropic effect was produced. Such effects of GPT were influenced by stimulus frequency. At lower frequencies of 0.1 Hz, GPT (10 to 100 nmol/l) produced a moderate prolongation of APD and positive inotropic effect. At higher frequencies (1.0 Hz), however, the effects of GPT on both APD and contraction were suppressed. In contrast, APD and duration of contraction were prolonged with long intervals of stimulation (1-3 min), in the presence of GPT. The rested-state contraction was also markedly increased and prolonged by GPT. When the membrane potential was conditioned by voltage clamp pulses, the prolonged action potential in GPT-treated muscle was shortened in proportion to the increase in conditioning depolarization. However, the shortening effect of conditioning depolarization was attenuated by lengthening the resting period after the conditioning depolarization. These results, in conjunction with our previous results, suggest that the frequency-dependent effects of GPT on APD and contraction reflect time- and and membrane potential-dependent changes of the toxin-modified sodium channels.
Infusion of an ammonium acetate solution into dogs during mannitol-induced reversible opening of the blood-brain barrier (BBB) resulted in a marked rise in intracranial pressure with exclusion of Evans blue dye. This indicated cytotoxic brain edema. These findings suggest a role for hyperammonemia in cerebral edema during acute liver failure.
Extremely high concentrations of hepatic acetaldehyde were induced in rats by the intragastric administration of ethanol and cyanamide, an aldehyde dehydrogenase inhibitor; and these high levels were maintained for 4 weeks. Liver function tests, including mitochondrial ornithine carbamoyltransferase (OCT) and GOT activities, were within normal limits, and no increase in either hepatic triglyceride or collagen contents was observed. These results suggest that hepatotoxic effects of ethanol are not derived from the high acetaldehyde levels in the liver.
Sake, a rice wine, induced hepatic collagen accumulation in rats. This was noted after 16 weeks of a liquid diet containing 35% ethanol by caloric content. However, under similar experimental conditions, whiskey and ethanol did not produce any changes. Hepatic collagenase activities in sake-fed rats were slightly, but significantly, higher than in the whiskey group. The central and pericellular liver fibrosis in sake-fed rats was caused possibly by either accelerated collagen synthesis or maturation, exceeding the increased collagen degradation. Mechanisms of enhanced fibrogenesis in sake-fed rats were discussed.
From the spleen cells of C57BL/6 (B6) mice, T-cell clones were established which responded to mutant H-2K antigen of B6. B-H-2bml (Hz1) mice. One clone and its subclones were maintained in culture medium containing lower concentration (2.5%) of IL-2 (culture supernatant of rat spleen cells stimulated with concanavalin A). They were shown to have a capability to induce graft-versus-host reaction in (B6 X Hz1)F1 recipients as well as to exert cytotoxicity against concanavalin-A-activated spleen cells of Hz1 mice and also their kidney fibroblasts. They lacked cytotoxicity against syngeneic and also third-party Con-A-stimulated spleen cells. These reactive clones were Thy-1.2 and Lyt-2 positive and Lyt-1 negative. On the other hand, clones which were maintained in culture medium containing higher concentration (20%) of IL-2 were devoid of activities in vivo as well as in vitro. These clones were Thy-1.2 positive but Lyt-1.2 and Lyt-2.2 negative.