Selective transcatheter hepatic arterial chemoembolization for hemobilia from hepatocellular carcinoma: report of three cases.
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Aged↗
Biomedical subjects
K Takeda
Publications and source records attributed to K Takeda.
Nicotinic acetylcholine receptor labeled with a tritiated, photoactivatable agonist: a new tool for investigating the functional, activated state.
Upon agonist activation, the nicotinic acetylcholine receptor undergoes allosteric transitions leading to channel opening and sodium ion influx. The molecular structure of the agonist binding site has been mapped previously by photoaffinity labeling, but most photosensitive probes used for this purpose interact only with closed receptor states (resting or desensitized). We have synthesized two novel photoactivatable 4-diazocyclohexa-2,5-dienone derivatives as cholinergic agonist candidates, with the objective of identifying structural changes at the acetylcholine binding site associated with receptor activation. One of these ligands, 9b, is a functional agonist at muscle acetylcholine receptors in human TE 671 cells. In photolabeling experiments with 9b, up to 35% inactivation of agonist binding sites was observed at Torpedo acetylcholine receptors. Tritiated 9b was synthesized, and photolabeling was found to occur mainly on the alpha-subunit in a partially protectable manner. This novel radiolabeled photoprobe appears to be suitable for future investigation of the molecular dynamics of allosteric transitions occurring at the active acetylcholine receptor binding site.
Animals↗
Phase I and pharmacologic study of oral (E)-2'-deoxy-2'-(fluoromethylene) cytidine: on a daily x 5-day schedule.
(E)-2'-deoxy-2'-(fluoromethylene)cytidine (FMdC), one of the most potent inhibitors of ribonucleoside diphosphate reductase, was selected for clinical development because of its novel mechanisms of action, and strong antitumor activity against experimental tumor models. This study was designed to determine the toxicities, maximum-tolerated dose (MTD), and pharmacokinetic profile of FMdC. FMdC was given orally for 5 consecutive days every 3 or 4 weeks in patients with advanced solid tumors. The starting dose was 8 mg/m2/day. Pharmacokinetic studies were carried out on days 1 through 5 of the first cycle. Ten patients with non-small cell lung cancer received 15 courses of FMdC at doses which were de-escalated from 8 mg/m2/day to 2 mg/m2/day because of unexpected severe toxicities at the starting dose level. Neutropenia was the dose-limiting toxicity. Thrombocytopenia and anemia were mild. Flu-like symptoms and fever were the common non-hematologic toxicities. The MTD was 4 mg/m2/day, since four of six patients developed grade 3-4 neutropenia. At the 4 mg/m2/day dose level, the mean terminal half-life, maximum plasma concentration (Cmax), plasma clearance, and mean residence time on day 1 were 3.20 h, 15.8 ng/ml, 2.91 l/h/kg, and 4.03 h, respectively. The recommended dose for phase II studies with this schedule is also 4 mg/m2/day for 5 days. Further investigations are necessary to establish optimal dosing schedules and routes for the administration of FMdC.
Administration, Oral↗
Identity of differentiation inducing factor and tumour necrosis factor.
Human myelogenous leukaemic cells can be induced to differentiate into the monocyte/macrophage pathway by protein inducers called differentiation inducing factors (DIF) in conditioned media of mitogen-stimulated human peripheral blood leukocytes. However, human DIF has not yet been well characterized. DIF is known to be a T-cell lymphokine, as it can be obtained from the T-cell line HUT-102 and can be partially purified from medium conditioned by phytohaemagglutinin (PHA)-stimulated lymphocytes. We found that monocytes also produce factor(s) that induce differentiation of human myelogenous leukaemia cell lines to cells with macrophage-like characteristics. This factor(s) has activity different from that of colony-stimulating factor(s) or interferons. We have now purified a DIF to homogeneity from medium conditioned by PHA-stimulated leukocytes using a human myeloblastic leukemia cell line, ML-1, as target cells. The purified DIF has a relative molecular mass (Mr) of approximately 17,000, with an NH2-terminal sequence the same as that of human tumour necrosis factor (TNF). Recombinant human TNF (rHuTNF) induces differentiation of ML-1 cells and an anti-pDIF monoclonal antibody can neutralize both differentiation inducing activity and cytotoxic activity of DIF and rHuTNF. The findings indicate that one of the DIF(s) produced by leukocytes is probably TNF.
Amino Acid Sequence↗
Activation of a calcium-dependent photoprotein by chemical signalling through gap junctions.
In the hydrozoan coelenterate Obelia geniculata, epithelial cell action potentials trigger light emission from photocyte effector cells containing obelin, an endogenous calcium-activated photoprotein. As this luminescence is blocked by the removal of extracellular calcium it seemed likely that calcium entry via voltage-gated channels in the photocyte membrane would account for the light emission. However, no inward calcium current was detected in whole cell recordings from dissociated photocytes and depolarization of isolated photocytes produced no luminescence. In contrast, a voltage-dependent calcium current was recorded from non-luminescent support cells, and activation of this current triggered luminescence in an adjacent photocyte. Surprisingly, light emission was abolished when the gap junctions between the photocyte and support cell were blocked. We conclude that calcium entry into support cells leads to light emission from neighbouring photocytes via chemical signalling through intercellular gap junctions.
Action Potentials↗
Detection of doxorubicin cardiotoxicity by using iodine-123 BMIPP early dynamic SPECT: quantitative evaluation of early abnormality of fatty acid metabolism with the Rutland method.
BACKGROUND: To evaluate the possibility of predicting the development of doxorubicin-induced cardiomyopathy, we performed quantitative assessment of the early kinetics of iodine-123 beta-methyl-iodophenyl-pentadecanoic acid (I-123 BMIPP) by means of dynamic myocardial SPECT. METHODS: Thirty-six patients with various malignancies were examined. I-123 BMIPP dynamic myocardial SPECT was performed before chemotherapy, after chemotherapy, or both. Immediately after the injection of I-123 BMIPP (111 MBq), 30-second dynamic SPECT data were acquired successively for 15 minutes. The left ventricular (LV) myocardium was divided into 8 segments in short-axial and vertical slices. By using the time-activity curve (TAC) of each myocardial segment [Mo(t)] as an output function and the TAC of the LV cavity [B(t)] as an input function, the Rutland equation, Mo(t)/B(t)= F + K Integral of(B(t)dt/B(t)), was used as a means of assessing all segments. RESULTS: Mo(t)/B(t) showed a good linear correlation with Integral of(B(t)dt/B(t)) from 30 seconds to 4 minutes in all 456 segments. The mean K value of 8 LV segments was significantly lower after chemotherapy than before chemotherapy (0.071+/-0.019 [n = 21] vs. 0.095+/-0.025 [n = 36], P<.001). In 21 patients in whom dynamic SPECT was performed both before and after chemotherapy, the mean K values of left ventricle showed a significant decrease, from 0.101+/-0.024 to 0.071 +/-0.019 (P<.0001). The fractional change in the value of K after chemotherapy showed a significant linear correlation with the administered dose of doxorubicin (r = 0.648, P<.002). CONCLUSION: I-123 BMIPP dynamic myocardial SPECT may be clinically useful, because it permits the early detection of doxorubicin-induced cardiomyopathy.
Adult↗
Individual variation in semen parameters of healthy young volunteers.
Individual variation in semen parameters was investigated in healthy young volunteers. Semen samples were collected approximately once a month over a one-year period for a total of 93 samples (5 to 10 samples per subject) from 12 volunteers in their twenties. Semen analysis was carried out according to the WHO Manual. The amount of variation in each semen variable was calculated for each subject by dividing the maximum value by the minimum value. The results showed that the semen volume varied by 1.9+/-0.8 fold (1.3 to 4.2 fold), the sperm concentration by 4.8+/-4.3 fold (1.5 to 17.2 fold), the percentage of sperm with forward progression by 2.8+/-1.4 fold (1.6 to 6.4 fold), the percentage of sperm with rapid linear progression by 3.4+/-2.6 fold (1.7 to 10.9 fold), the percentage of sperm with normal morphology by 1.9+/-0.4 fold (1.3 to 2.4 fold), and the percentage of live sperm by 1.5+/-0.4 fold (1.1 to 2.6 fold). A between-group comparison showed significant differences in all of the variables except the percentage of sperm with normal morphology. These results suggest multiple and considerable semen analyses are needed when evaluating semen parameters.
Adult↗
Atlas of dopamine receptor images (PET) of the human brain.
An atlas of positron emission tomographic images of dopamine and serotonin receptor distribution in the normal and abnormal human brain has been generated using 3-N-[11C]methylspiperone as the tracer.
Aged↗
Mesenteric panniculitis: MR findings.
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Female↗
MR assessment of normal brain development in neonates and infants: comparative study of T1- and diffusion-weighted images.
PURPOSE: This study was designed to compare the sensitivity of T1- and diffusion-weighted images for the assessment of brain maturation in human brains. METHODS: T1- and diffusion-weighted images were obtained in 32 children without neurological abnormalities or growth retardation. The ages at which signal intensity changes of white matter on T1-weighted images and diffusional anisotropy appeared were compared. RESULTS: In the optic radiation, diffusional anisotropy was observed in neonates < 1 month old, whereas signal intensity became high after 1 month old. In the frontal lobe, diffusional anisotropy began to appear after 1 month of age, but signal intensity became high after 6 months of age. These visual findings were confirmed statistically by quantitative analysis using signal intensity ratios and anisotropic ratios. Similar findings were observed in the external capsule and the genu of the corpus callosum. CONCLUSION: In conclusion, diffusional anisotropy is a sensitive indicator of brain maturation in neonates and infants and precedes signal intensity change on T1-weighted images.
Brain↗
Pressor responses to intracisternal injection of hypertonic NaCl in rats.
Hypertonic NaCl solution injected into the cisterna magna of anesthetized rats produced dose-dependent pressor responses accompanied by slight tachycardia. Similar injections of hypertonic urea solution were ineffective. Because the early phase of the pressor response to hypertonic NaCl was always accompanied by increased sympathetic nerve firing and was inhibited following alpha-adrenergic blockade with phentolamine, initial pressor response was attributed to sympathetic hyperactivity. On the other hand, because the later phase of the pressor response was unaffected either by adrenalectomy or by alpha-adrenergic blockade, but was significantly inhibited by hypophysectomy or by pretreatment with a vasopressin antagonist, the later pressor response was ascribed to an increased release of endogenous vasopressin. Thus, our findings indicate that central pressor responses to hypertonic NaCl solution involve two different mechanisms: sympathetic hyperactivity in the early phase and vasopressin release during the later phase. In spontaneously hypertensive rats (SHR), both pressor and sympathetic responses to intracisternally injected NaCl were greater than in Wistar-Kyoto rats (WKY). Our results further indicate hypersensitivity to NaCl around the brain stem in SHR, which could account for the increased sympathetic activity and cause SHR to develop hypertension.
Adrenalectomy↗
In vivo and in vitro assessment of the cardiovascular effects of 8-(benzylthio)-N6-n-butyl-cyclic AMP.
In the canine heart-lung preparation (HLP) and the anesthetized open-chest dog, both 8-(Benzylthio)-N6-n-butyl-cyclic AMP (BTB-cyclic AMP) (10 times more potent) and dibutyryl-cyclic AMP (DB-cyclic AMP) produced a definite positive inotropic effect (PIE) and an increase in the coronary blood flow with either no change (HLP) or a slight increase (anesthetized animal) (BTB-cyclic AMP) and a definite increase in the heart rate (DB-cyclic AMP). In the isolated atrial preparations of the guinea pig (AG), BTB-cyclic AMP produced a slight PIE at 3 X 10(-5) M and a negative chronotropic effect at 3 X 10(-4) M. Aminophylline reversed the latter to the positive one, while potentiating the former. At 10(-3) M marked positive inotropic and chronotropic effects were observed. DB-cyclic AMP was without effects. In the right ventricular papillary muscle preparations of the guinea pig (PMG), both compounds produced PIE. BTB-cyclic AMP initiated a contraction (AG) and a "slow" action potential (PMG) in partially depolarized preparations. Both of these effects were abolished by diltiazem. BTB-cyclic AMP (10(-3) M) suppressed the heart rate increase induced by isoproterenol in right AG. It was concluded that BTB-cyclic AMP was a cardiotonic agent with a relatively weak positive chronotropic effect and that the cardiotonic effect was ascribable to the initiation of slow action potentials and related contractions.
Anesthesia↗
Antihypertensive and hypothalamic depressant effects of tripamide in spontaneously hypertensive rats.
When tripamide was added to the food of spontaneously hypertensive rats (SHR), there were no appreciable effects on heart rate, body weight, or food intake. Tail-cuff systolic pressures measured weekly were also unaffected in normotensive control rats (WKY), but the elevation expected in SHR was significantly reduced. Pressor responses to hypothalamic stimulation were also reduced selectively only in SHR. A peripheral inhibition of cardiovascular reactivity was considered unlikely, since pressor responses to injected norepinephrine, tyramine, or vasopressin were unaltered. Diminished pressor responsiveness was considered to be due to concurrent reduction of central sympathetic vasomotor activity, because sympathetic nerve responses to hypothalamic stimulation were appreciably lessened in tripamide-treated SHR. Although neither the site nor the mechanism causing sympathetic inhibition was determined exactly, our results are in accord with the interpretation that antihypertensive effects of tripamide in SHR depend, at least partly, on sympathetic inhibition.
Animals↗
Irradiated pancreatic cancer cells undergo both apoptosis and necrosis, and could be phagocytized by dendritic cells.
The interaction of immature dendritic cells (DC) with irradiated pancreatic cancer cells was examined. Flow cytometric analysis using annexin V and propidium iodide revealed that ionizing radiation (25-35 Gy X-ray) induced both apoptosis and necrosis in pancreatic cancer cell lines. After irradiation, PK-1 and Panc-1 cells were likely to undergo necrosis, whereas MIAPaCa-2 cells underwent apoptosis. When DiO-stained immature DCs were co-incubated with DiI-stained irradiated MIAPaCa-2, it was observed under fluorescent microscopy that DCs phagocytized dead tumor cells as early as 4 h after co-incubation. The DCs' phagocytosis of irradiated tumor cells was also confirmed by flow cytometry. These results suggest that irradiated pancreatic cancer cells, which undergo both apoptosis and necrosis, could be a good source of tumor-associated antigens for cross-presentation by DCs.
Apoptosis↗
Augmented sympathetic nerve activity and pressor responsiveness in DOCA hypertensive rats.
Spike potentials in abdominal sympathetic nerves were recorded together with aortic blood pressure before and during electrical stimulation of the posterior hypothalamus in urethane-anesthetized rats. Both the initial rate of sympathetic nerve firing and the subsequent acceleration produced by hypothalamic stimulation were higher in deoxycorticosterone acetate (DOCA) hypertensive than in normotensive rats. Pressor responsiveness was generally augmented, but responses to hypothalamic stimulation, were increased far more than those to injected norepinephrine. Vasodepression produced by blocking autonomic ganglia pharmacologically with pentolinium was also more pronounced in DOCA hypertensive rats than in normotensive controls. These results support the conclusion that a centrally induced sympathetic hyperactivity is important for maintaining the blood pressure elevation in rats with established DOCA hypertension.
Animals↗
Chronic propranolol treatment inhibits sympathetic nerve activity and keeps blood pressure from rising in spontaneously hypertensive rats.
When D,L-propranolol, 100 mg/kg/day, was added to the drinking water of spontaneously hypertensive rats (SHR), systolic pressures measured with the tail-cuff method fell significantly within 1 month and were almost the same as those in normotensive controls (KNR) by the end of 3 months. This antihypertensive effect was later confirmed by direct recording of phasic aortic pressures from indwelling catheters. Blood pressure was lowered selectively only in SHR and not in KNR; by contrast, body weight, fluid intake, and heart rate always decreased whether the rats were hypertensive or not. Because pressor responses to hypothalamic stimulation in SHR treated with propranolol were reduced while those to injected norepinephrine were unaltered, a peripheral inhibition of cardiovascular reactivity was considered unlikely. Supporting the interpretation that diminished pressor responsiveness was caused by concurrent reduction of sympathetic vasomotor activity, frequency of spike potentials recorded from abdominal sympathetic nerves was appreciably lessened in propranolol-treated SHR, as was the vasodepression resulting when autonomic ganglia were pharmacologically blocked with pentolinium. These findings are consistent with the conclusion that prolonged oral administration of propranolol prevents development of spontaneous hypertension in rats by reducing sympathetic vasomotor tons.
Animals↗
Spontaneous remission of hypertension in awake rats chronically exposed to shaker stress.
Hypertension was induced experimentally by subjecting rats to vigorous shaking, 4 hours (at random) daily for 14 weeks. Systolic pressures measured with the tail-cuff method began to rise after the first week and were significantly elevated on Weeks 3, 4, 6, 7, and 8, but reverted to normotensive levels thereafter despite continued shaking. A similar hypertension was then induced in another group of rats and when spontaneous remission occurred, pressor responsiveness was tested on the eleventh week by recording aortic pressures from indwelling catheters. Pressor responses to further shaking or electrical stimulation of the anterior hypothalamus were smaller in shaker-stressed than in control rats, while those to injected norepinephrine were almost the same in both groups. Spike potentials recorded from postganglionic sympathetic (splanchnic) nerves showed higher baselines but smaller increases in neural firing during hypothalamic stimulation in shaker-stressed than in control rats. These results suggest that while shaker stress alone can induce hypertension, the resulting blood pressure elevation is not sustained, perhaps because adaptation within the central nervous system concurrently reduces pressor responsiveness.
Animals↗
Immunopathological study of the larynx. IgA distribution and secretory activity.
Using immunofluorescent and histopathological techniques, we studied the distribution and secretory activity of the glands of the larynx from 55 humans. The cavity of the larynx was covered with secretory glandular cells with the exception of the true vocal cords, aryepiglottic folds and upper part of the laryngeal surface of the epiglottis. Immunofluorescent study revealed the presence of IgG and other immunoglobulins throughout the connective tissue ground in each laryngeal mucosa. The most striking was seen in the staining pattern of IgA. Diffuse fluorescence for IgA was observed not only in the submucosal or periglandular connective tissue area but also in the intraeptithelial or submucosa glands. Secretory component synthesis was found mainly in each serous-type glandular epithelium or acinus. In the submucosa or periglandular area, IgA producing plasma cells were numerous. Our observations suggest that IgA, produced locally, is secreted via the glandular cells as secretory component--SIgA. Secretory activity of SIgA in these glandular tissues indicates that the larynx is possibly an immunologically active organ in the upper respiratory tract.
Adolescent↗