Cerebellopontine angle ganglioneuroblastoma.
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Biomedical subjects
Publications and source records attributed to T Takeda.
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We have previously reported that the antitumor effect of OK-432, a Streptococcal preparation, is markedly augmented when injected intratumorally together with fibrinogen (Cancer, 69: 636-642, 1992). In order to elucidate the mechanism of the antitumor effects, we established T cell clones from regional lymph nodes of colorectal cancer patients who received this local immunotherapy. By culture of lymph node lymphocytes, in the presence of IL-2 and OK-432, 4 clones of T cells were established from 4 patients treated by local immunotherapy. These clones had a helper T cell phenotype (CD3+, CD4+, CD8-, CD56-, WT31+) and were successfully maintained for several months. The cells strongly expressed CD25 when stimulated with OK-432 and exhibited a high level of cytotoxic activity in part explained by the increased expression of ICAM-1 and LFA-1, and the release of TNF beta. These results suggest that the CD4+ T cells play a role in the antitumor mechanism of local immunotherapy.
Regional wall thickening was assessed by ECG-gated SPECT using technetium-99m 2-methoxy-isobutyl-isonitrile (99mTc-MIBI). For myocardial segments with an optimal short axis, regional count changes from end-diastole to end-systole were used to calculate the regional wall thickening. Functional images displaying amplitude, % wall thickening (% WT), and phase were generated by a fundamental Fourier analysis. In the control subjects, % WT analysis showed heterogeneous contraction among the left ventricular wall segments. The amplitude values showed a similar pattern to the %WT values. Phase images demonstrated that the timing of ventricular contraction was almost homogenous between the various wall segments. In the CAD patients, regional decreases in amplitude and %WT corresponding to zones of reduced perfusion were shown in the ischemic segments. Phase images also indicated asynchronous contraction in these segments. Phase analysis of regional wall thickening in 99mTc-MIBI scintigraphy seems to be useful for understanding regional myocardial function in combination with perfusion scanning.
With technetium-99m 2-methoxy-isobutyl-isonitrile (99mTc-MIBI), regional wall thickening in a patient with dilated cardiomyopathy was analyzed by the first component Fourier method. The regional wall thickening was compared with thallium-201 and 99mTc-MIBI SPECT imaging. Thallium-201 SPECT images showed mildly reduced perfusion in the posterior wall and redistribution in the septum, whereas 99mTc-MIBI images showed heterogeneous accumulation around the left ventricular circumference. By means of phase analysis, diffusely decreased wall thickening and discontinuity of percent wall thickening in neighboring segments were observed throughout the left ventricle. Regional wall motion and wall thickening correlated roughly. However, discrepancies between the mechanical function and myocardial perfusion, and discrepancies in regional myocardial perfusion between thallium-201 and 99mTc-MIBI were observed.
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The minimal hepatic mass necessary to reverse the metabolic defect of unconjugated hyperbilirubinemia in the rat model of Crigler-Najjar type I deficiency was determined using heterotopic (auxiliary) partial liver transplantation (HLT) and orthotopic liver transplantation (OLT). In HLT, the donor graft consisted of the right upper and/or right lower hepatic lobe(s) depending on the final mass of liver tissue desired for transplantation. The mass of the donor graft ranged from 12% to 23% of the whole organ (n = 12). The serum unconjugated bilirubin levels decreased quickly after HLT from a preoperative value of 8.98 +/- 0.34 mg/dL to 0.63 +/- 0.11 mg/dL in 24 hours, which was similar to OLT in which the levels decreased from a preoperative value of 8.20 +/- 0.44 mg/dL to 0.24 +/- 0.07 mg/dL in 24 hours. Conjugated bilirubin was excreted from the graft liver shortly after OLT and also from both the host and graft livers after HLT. This study demonstrates that using as little as 12% of the whole liver mass in HLT reduces serum bilirubin significantly in 24 hours in a fashion similar to whole-organ OLT. The clinical application of alternative therapies to whole-organ OLT such as HLT or hepatocyte transplantation may provide sufficient replacement therapy in metabolic disease.
Brain natriuretic peptide (BNP) is secreted through the coronary sinus of the human heart. The purpose of this study was to determine whether BNP secretion from the heart is stimulated by exercise and to examine the relationship between pulmonary arterial BNP concentrations and hemodynamic measurements, especially cardiopulmonary hemodynamics, during exercise in patients with essential hypertension. The exercise protocol consisted of three fixed workloads (25, 50, 75 W) on a bicycle ergometer in the supine position. The mean pulmonary arterial BNP level at rest was 14.8 +/- 4.1 pg/mL, and BNP values gradually increased with higher stages of exercise. At the maximum exercise stage, the BNP value increased to 40.9 +/- 6.5 pg/mL. Close correlations of pulmonary arterial pressure (PAP) and pulmonary arterial wedge pressure (PAWP) with pulmonary arterial BNP level were observed at four points at rest and during each stage of exercise. In contrast, heart rate, mean blood pressure, cardiac index (CI), and stroke index (SI) were not correlated with BNP values. Results suggest that cardiac secretion of BNP was increased during exercise in essential hypertensive subjects, and the observed increase of BNP may be related to elevated PAP and PAWP. The enhancement of BNP secretion during exercise in these patients may reflect increased redistribution of blood to the cardiopulmonary compartment.
The cerebellar Purkinje cell has highly branched dendrites extending in a transverse plane to the cerebellar folium. Branching patterns of the dendrites were subjected to fractal analysis to obtain a quantitative measure of their intricacy. Using a square-covering method, we found that dendrites have a statistical self-similarity so that their fractal dimension can be evaluated. In postnatal mouse, dimensions of Golgi-stained Purkinje cells increased as dendrites developed. The time course of the dimension increase was correlated with development of the width and area of the dendritic fields. After the dimension reached the maximum value at postnatal day 20, the width and area further continued to grow until day 100. In human cerebellum, dimensions of Purkinje cell dendrites increased greatly during pregnancy and reached 97% of the adult value at birth. On the other hand, 41% of the adult dendritic field width and 11% of the adult area had been attained at birth. The physical size of dendrites increased in a more lagged phase than the dimensions, and growth proceeded mainly after birth. These observations indicate that after the maximum complexity and fundamental tree pattern have been attained, the overall tree size further increases. It is observed that phylogenetic development of dendritic trees of Purkinje cells in several species of vertebrates showed a correlation with the increase in dimensions. These studies demonstrated the potency of the fractal analysis in evaluating development of dendritic trees of neurons.
To discover whether hypoxia affects mediator responses and neurotransmission in tracheal smooth muscle, we studied in vitro tracheal segments from guinea-pigs under isometric conditions. Hypoxia itself did not alter the basal tone. The maximum response to acetylcholine and histamine under hypoxia was less than that under oxygenated conditions. The logarithm of 50% effective concentration (log EC50) of the response to acetylcholine under hypoxia was not altered, but the log EC50 of the response to histamine decreased significantly. In contrast to the response to exogenous acetylcholine, the maximum contractile response to electrical field stimulation (EFS) under hypoxia was not different from that under oxygenated conditions, but the logarithm of 50% effective frequency of contractions caused by EFS under hypoxia decreased significantly. On the other hand, non-adrenergic-non-cholinergic relaxation caused by EFS was unaffected by hypoxia. These observations suggest that hypoxia can modulate the responses of tracheal smooth muscle to acetylcholine, histamine and nerve stimulation.
The present study was designed to test two hypotheses: (1) that angiotensin II (Ang II) stimulates endothelin-1 secretion in cultured rat mesangial cells and (2) that atrial and brain natriuretic peptides (ANP and BNP) inhibit the above-mentioned secretion in these cells. Ang II stimulated immunoreactive (ir) endothelin-1 secretion in a concentration-dependent manner between 10(-8) M and 10(-7) M. The protein kinase C (PKC) inhibitors from two chemical classes, H7 and staurosporine, inhibited secretion following such stimulation. The stimulatory effect of Ang II was also abolished in the PKC-depleted cells. Rat ANP(1-28) and rat BNP-45, which are the respective major circulating forms of ANP and BNP in rats, potently inhibited Ang II-stimulated endothelin-1 secretion in a concentration-dependent manner. Inhibition by ANP and BNP of Ang II-stimulated endothelin-1 secretion was paralleled by an increase in the cellular level of cyclic guanosine 5'-monophosphate (GMP). The addition of a cyclic GMP analogue, 8-bromo cyclic GMP, reduced the stimulated endothelin-1 secretion. Rat ANP(5-25) was less effective that rat ANP(1-28) with respect to inhibiting ir-endothelin-1 secretion and increasing cellular cyclic GMP. These findings indicate that Ang II stimulates endothelin-1 secretion in cultured rat mesangial cells by a mechanism probably involving activation of PKC, and that rat ANP and BNP inhibit this stimulated secretion through a cyclic GMP-dependent process.
Structural transformation of arctiin and tracheloside, major components of seeds of Arctium lappa and Carthamus tinctorius, were investigated using rat gastric juice (pH 1.2-1.5) and rat large intestinal flora in vitro. Quantitative analysis of lignans and their metabolites was carried out by high performance liquid chromatography. Both lignans were stable in rat gastric juice and arctiin was rapidly transformed to arctigenin in rat large intestinal flora, followed by conversion to the major metabolite, 2-(3",4"-dihydroxybenzyl)-3-(3',4'-dimethoxybenzyl)-butyrolactone. On the other hand, tracheloside also decreased dependently with time and was converted to trachelogenin and its major metabolite, 2-(3",4"-dihydroxybenzyl)-3-(3',4'-dimethoxybenzyl)-2-hydroxybutyrola ctone. These experiments suggest that in the course of metabolism of lignans, firstly a cleavage of the glycosidic bond occurred and then demethylation of the phenolic methoxy group in the alimentary tract followed.
OBJECTIVE: The excessive release of adenosine has been reported to cause hyperaemia and to attenuate ischaemic injury in microembolised hearts. The direct effects of exogenous adenosine on cardiac performance were investigated in microembolised guinea pig hearts with the simultaneous measurement of phosphate compounds. METHODS: 21 male guinea pig hearts were perfused according to the Langendorff technique and microembolism was induced by injecting microspheres. Hearts were then treated as follows: group A, adenosine 20 microM and theophylline 60 microM; group B, theophylline 60 microM; group C, saline (control). Cardiac performance was monitored and phosphate compounds were measured by 31P magnetic resonance spectroscopy. RESULTS: Group A showed a significant increase in the left ventricular developed pressure and coronary flow, and a modest restoration of ATP content. Pi/(Pi+Pcr) remained virtually constant. There were no significant changes in left ventricular developed pressure or coronary flow in groups B and C. There was a gradual decrease in tissue ATP content and slight increase in Pi/(Pi+Pcr). CONCLUSIONS: Adenosine improved cardiac performance without adverse effect on energy metabolism in microembolised hearts. Adenosine also restored the ATP stores in microembolised hearts. (Pi = inorganic phosphate; Pcr = phosphocreatine.)
We developed a novel inbred strain of mouse with age-related brain atrophy and it was named "Senescence Accelerated Mouse (SAM)-P/10." Macroscopic morphometry indicated that the brains of SAM-P/10 showed age-dependent involutional changes mainly in the frontal portion of the cerebrum. The brain weight decreased by 8.6% throughout the life-span. There were no obvious defects in postnatal development. Semi-macroscopic morphometry revealed a prominent atrophy in the neocortex, olfactory cortex and amygdala. Microscopic morphometry showed that the neocortical neurons were lost with aging, with mostly the large neurons being affected which were lost by 35.6% throughout the life-span. Somata of the neocortical neurons shrank with advancing age. In a control SAM-R/1 strain with only a slight macroscopic involutional change in the brain without weight loss, neither loss of the neocortical large neurons nor shrinkage of the neocortical neurons was evident with aging. Learning and memory skills were evaluated using the one-trial passive avoidance task and conditional avoidance task. Young SAM-P/10 mice performed well in both tasks but older SAM-P/10 showed a poorer performance in both tasks, and this was even poorer than the performance of very old SAM-R/1 mice. Thus, SAM-P/10 can serve as a spontaneous animal model of brain atrophy for a variety of studies of aging of the brain. A better understanding of neurodegenerative diseases with dementia should be forthcoming.
A study was conducted with the purpose of examining the possible effects of vertical and horizontal eye movements upon accommodation. A special Badal stimulator was made which was vertically rotatable around the center of an eye. The stimulator was attached to the Three-Dimensional Optometer III (TDOIII), which could measure accommodation, eye movement, and pupil diameter simultaneously. The reliability of the TDOIII measurements of accommodation was checked by comparing with a stigmatoscope measurement. Three young males served as subjects. A small but definite near accommodation was measured dynamically in association with vertical eye movement. We believe this to be the first report of this finding. The amount of near accommodation with downgaze showed a tendency to decrease when the target was brought near.
Using food-deprived rabbits we investigated the effects of nutritional deficiency on the development of pressure sores. The body weight of these animals was decreased significantly from normal. Organ weights of liver, heart, spleen, kidney, and testis were significantly decreased from normal as well. Protein deficiency in these animals was indicated by serum tests, as well as by histologic features of liver and testis and ultrastructural findings on fibroblasts. We produced lesions in malnourished as well as normal rabbits by exposing their skin to a balloon-produced compressive force of 120 +/- 10 mmHg for 4 hours. Biopsies were taken 1, 2, and 3 days after the pressure application. Histologic findings at each time were as follows: At day one, the degree of ischemic skin destruction in the malnourished animals was more severe than that in the normal ones, and thrombi were occasionally seen in the malnourished cases. At day two, proliferation of fibroblasts and macrophage infiltration were evidenced in the normal animals, whereas signs of collagen fiber degeneration as well as microthrombi were seen in the malnourished ones. At three days, epidermal cells covered the lesions in the case of normal animals; however, massive necrosis of the epidermis was still recognized in the malnourished rabbits. Thus, the healing process of pressure sores was strongly suppressed in the malnourished animals. This suppression was attributed to the reduction in fibroblast proliferation, capillary formation, macrophage infiltration, and also to the low level of epidermal cell proliferation.
Human hybridomas were generated through the fusion of the human B-lymphoblastoid cell line HO-323 with the regional lymph node lymphocytes of colonic cancer patients who had received a local immunotherapy. A total of 353 hybridomas were obtained from 4 patients and 116 of these were found to secrete greater than or equal to 100 ng/ml human immunoglobulin. The efficiency was remarkably high as compared with that from patients without the local immunotherapy. Further immunohistological examination showed that 5 hybridomas secreted IgM which selectively reacted with colonic cancers. The results indicate that local immunotherapy could be an adjunctive tool for the generation of highly potent human hybridomas through augmenting the host's immunity.
1. Na+ influx into cultured vascular smooth muscle cells (VSMC) obtained from spontaneously hypertensive rats (SHR) and from Wistar-Kyoto rats (WKY) was measured. Na+ influx via the Na+/H+ exchange system was measured as the rate of 22Na+ influx into cultured VSMC sensitive to ethylisopropylamiloride (EIPA), a specific inhibitor of the exchange system. 2. The total 22Na+ influx rate in SHR was significantly higher than in WKY (6.08 +/- 0.16 vs 4.13 +/- 0.09 nmol/min per mg protein; P less than 0.001; n = 14). The EIPA (1 X 10(-4) mol/L)-sensitive 22Na+ influx rate in SHR was significantly higher than that in WKY (4.32 +/- 0.27 vs 2.17 +/- 0.14 nmol/min per mg protein; P less than 0.001; n = 14). There was no difference in EIPA-insensitive 22Na+ influx between SHR and WKY. The EIPA-sensitive 22Na+ influx rate into VSMC was significantly decreased in SHR but not in WKY by the addition of 1 X 10(-4) mol/L 1-(5-isoquinoline-sulfonyl)-methylpiperazine (H-7), an inhibitor of protein kinase C (PK-C). 3. These results suggest that the increase in Na+ influx in SHR may be due to elevation of the Na+/H+ exchange activity, and possible involvement of PK-C in the increased Na+/H+ exchange activity in VSMC from SHR.
1. This study examined whether brain and atrial natriuretic peptides (BNP, ANP) are secreted together through the coronary sinus from the heart, and whether plasma concentrations of BNP and ANP were affected by ergometric exercise in patients with essential hypertension. The effects of temocapril, a potent angiotensin-converting enzyme (ACE) inhibitor, on plasma concentrations of these peptides was also examined. 2. The plasma concentrations of immunoreactive (ir) BNP and ir-ANP in the coronary sinus in seven patients with ischaemic heart disease during cardiac catheterization were far greater than values with plasma obtained at the same time from the femoral artery. 3. The plasma concentrations of ir-BNP and ir-ANP increased with exercise and were correlated with each other. Temocapril reduced the blood pressure and slightly (but significantly) decreased the levels of both peptides at rest and during exercise. 4. The results suggest that BNP and ANP were secreted together through the coronary sinus from the heart. The secretion was increased by exercise and suppressed by acute ACE inhibition. The increase in these peptides during exercise may reflect a compensatory mechanism against further elevation of blood pressure.