Ocular albinism with unilateral sectorial pigmentation in the fundus.
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Albinism, Ocular↗
Biomedical subjects
T Mutoh
Publications and source records attributed to T Mutoh.
Gene expression of high- (p140trk) and low-affinity nerve growth factor receptor (LNGFR) in the adult and aged human peripheral nervous system.
Steady-state mRNA levels and immunoreactive proteins for high- (p140trk) and low-affinity nerve growth factor receptor (LNGFR) in the adult and aged human peripheral nervous system (PNS) were examined in autopsied material. trk mRNA expression was observed only in the sympathetic and dorsal root ganglia, while LNGFR mRNA was expressed widely through the PNS as well as non-neural tissues. Immunoreactive trk proto-oncogene product (p140trk) and LNGFR occurred in the perikarya of the subset of the sympathetic and dorsal root ganglion neurons, but only LNGFR immunoreactivity also occurred in the perineurium and the outer layer of the vessels. The spatial patterns of the trk and LNGFR gene expression in the adult human PNS were similar to those observed in the rat, mouse and chick, and their expression was well preserved in the aged.
Aged↗
Functional analysis of TCR gamma delta+ T cells in tumour-infiltrating lymphocytes (TIL) of human pancreatic cancer.
In six patients with advanced pancreatic carcinoma, TIL and tumour-draining lymphocytes (TDL) were isolated from primary pancreatic tumour and regional lymph nodes. In comparison with TDL and peripheral blood lymphocytes (PBL), TIL contained a comparatively higher percentage of TCR gamma delta+ cells, although they were still a small fraction. By 2 weeks culture with rIL-2 and immobilized OKT-3 antibody, the TCR gamma delta+ cells in TIL were preferentially expanded at the early culture periods, although it was temporary. In four cases, the TCR gamma delta+ and CD8+ TCR alpha beta+ TIL were separated by negative sorting using flowcytometry. All the TCR gamma delta+ TIL were CD4-, CD8- (double negative), and one of the TIL lines was mostly composed of delta TCS1+ cells, while the others were delta TCS1-. In comparison with CD8+ TCR alpha beta+ TIL, all the TCR gamma delta+ TIL exhibited much stronger lytic activity against freshly isolated autologous pancreatic cancer cells. However, all the gamma delta+ TIL also exhibited a strong non-MHC-restricted cytotoxicity, and there was no correlation between the lytic pattern and the percentage of delta TCS1+ cells. These data suggest that the TCR gamma delta+ T cells can proliferate vigorously in a certain condition, and if successfully expanded in vitro they might be helpful material for effective adoptive immunotherapy.
Aged↗
The effect of the B subunit of cholera toxin on the action of nerve growth factor on PC12 cells.
Exogenous gangliosides, especially ganglioside GM1 (GM1), seem to potentiate the action of nerve growth factor (NGF). We have examined the possible regulation of the NGF signaling pathway in PC12 cells by the B subunit of cholera toxin (CTB), which binds to endogenous GM1 specifically and with a high affinity. CTB treatment (1 micrograms/ml) enhanced NGF-induced neurite outgrowth from PC12 cells, NGF-induced activation of ribosomal protein S6 kinase, and NGF-induced stimulation of trk phosphorylation. CTB plus NGF also caused a greater inhibition of [3H]thymidine incorporation into DNA than did NGF alone. These enhancing effects of CTB were blocked by the presence of cytochalasin B in the culture medium but were not affected by the presence of colchicine or by the depletion of Ca2+ in the medium. 125I-NGF binding experiments revealed that CTB treatment did not affect the specific binding of NGF to the cells. These results strongly suggest that the binding of cell surface GM1 by CTB modulates the pathway of intracellular signaling initiated by NGF and that the association of CTB with a cytoskeletal component is essential for these effects.
Animals↗
[Volatile anesthetics suppress cardiac function in man; an investigation based on systolic time intervals].
Hemodynamic changes and left ventricular performance were investigated by simplified mechanocardiography using finger plethysmography instead of carotid artery pulse tracing in patients who received 4 volatile anesthetics with or without nitrous oxide. Systolic blood pressure (Ps), diastolic blood pressure (Pd), heart rate (HR), pre-ejection period (PEP), left ventricular ejection time (LVET), isovolemic contraction time (ICP), PEP/LVET, Pd/ICT, and 1/PEP2 were selected as indices which represent hemodynamics and systolic time intervals. Enflurane 0.6 and 1.2MAC prolonged PEP, and shortened 1/PEP2 and Pd/ICT significantly. Addition of nitrous oxide caused more depression. Halothane 0.6MAC prolonged PEP, and shortened 1/PEP2 and Pd/ICT. Sevoflurane 1.2MAC shortened only 1/PEP2. Addition of nitrous oxide prolonged PEP and PEP/LVET, and shortened Pd/ICT. Isoflurane 1.2MAC lowered Ps and increased HR. The results indicate that cardiac performance was depressed by volatile anesthetics in the order of enflurane, halothane, sevoflurane and isoflurane.
Adult↗
[A case of hematological metastatic tumor of the liver from sigmoid colon cancer].
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Adenocarcinoma↗
Cytohistologic assessment of antitumor effects of intraperitoneal hyperthermic perfusion with mitomycin C for patients with gastric cancer with peritoneal metastasis.
For 15 patients with refractory gastric cancer and peritoneal metastasis, intraperitoneal hyperthermic perfusion (IPHP) using mitomycin C combined with extensive surgery was prescribed. The antitumor effects were assessed cytohistologically in pre-IPHP and post-IPHP specimens of the abdominal effusion and peritoneal tissue. Gastric cancer cells in the abdominal effusion and/or lavage vanished from post-IPHP peritoneal exudate obtained from the pouch of Douglas. Peritoneal tissues from nine patients were harvested just after the IPHP treatment. All the nuclei of cancer cells were pyknotic in three of nine patients, and two of these three patients are alive with no local recurrence; one patient died of hepatic metastasis. In the remaining six patients, four with preoperative ascitic effusion and positive post-IPHP histologic findings died of peritoneal, intraabdominal, and pericardial metastases. The other two had some residual microscopic foci in the subperitoneal deep layer; one patient died of pleural recurrence, and the other is alive with no evidence of recurrence 42 months after the IPHP. Among the other six patients, whose post-IPHP peritoneal tissues were not available because of disappearance of disseminating foci as a result of the IPHP, two are living with no recurrence and, of the remaining four patients, three died of hepatic and intraabdominal metastases and the other one died of other causes. The histologic findings are suggestive of the following: (1) uniform heat and drug distribution in the abdominal cavity with IPHP treatment, except for an area adjacent to the inflow point of the perfusate; and (2) limited penetration of heat and drug through the subperitoneal layer. Thus, IPHP treatment results in complete destruction of cancer cells in the abdominal effusion and on and just beneath the peritoneum.
Adult↗
Abnormal sclerocytes in nanophthalmos.
Scleral tissue from a nanophthalmic patient was examined morphologically and by a tissue culture method. Collagen in the unusually thickened scleral tissue was arranged in irregularly interlacing bundles. Results of tissue culture studies showed sclerocytes that seemed to secrete many granules that stained positively with Alcian blue and periodic acid-Schiff (PAS). No granules were seen in cells of scleral tissue cultured from two control eyes. These findings may be the result of the modified glycosaminoglycan metabolism, which in turn contributes to the abnormal packing of collagen bundles and thickening of sclera in nanophthalmos.
Adult↗
Differential responses of the phosphorylation of ribosomal protein S6 to nerve growth factor and epidermal growth factor in PC12 cells.
Previous studies from this laboratory have shown that the phosphorylation of the S6 protein of the ribosomes is catalyzed by at least two different and separable kinase activities in PC12 cells. One of these activities is increased by treatment of the cells with nerve growth factor, the other by treatment of the cells with epidermal growth factor. The present work shows that these two factors stimulate the phosphorylation of S6 with quite different kinetics, and that both the number of phosphates incorporated into S6 and the phosphopeptide pattern of S6 are different in cells treated with nerve growth factor than in cells treated with epidermal growth factor. The characteristics of the nerve growth factor-sensitive S6 kinase and of the epidermal growth factor-sensitive kinase were also clearly different. Substrate specificity and inhibitor studies indicated that neither was identical to cyclic AMP-dependent kinase, kinase C, or the calcium/calmodulin-dependent kinases. However, two major phosphopeptides produced by S6 phosphorylation in nerve growth factor-treated cells were also seen on phosphorylation of S6 by cyclic AMP-dependent kinase in vitro. In addition, when rat liver 40S ribosomal subunits were pretreated with cyclic AMP-dependent kinase in vitro, the action of the nerve growth factor-sensitive S6 kinase was increased about twofold.
Amino Acids↗
Volume infusion produces abdominal distension, lung compression, and chest wall stiffening in pigs.
The effect of severe generalized edema on respiratory system mechanics is not well described. We measured airway pressure, gastric pressure, and four vertical pleural pressures in 13 anesthetized paralyzed pigs ventilated in the upright position. Pressure-volume relationships of the respiratory system, chest wall, and lung were measured on deflation from total lung capacity to residual volume and during tidal breathing both before (control) and 50 min after one of two interventions. In one series of experiments, a volume equal to 15-20% of the pig's body weight was infused intravenously. In a second series, a balloon was placed in the peritoneal space to distend the abdomen to the same gastric pressures as achieved in the first series. Measurements were compared before and after either abdominal balloon inflation or volume infusion. Volume infusion increased the pleural pressure in dependent lung regions, decreased both total lung capacity (34%) and functional residual capacity (62%) (both P less than 0.05), and markedly shifted the respiratory system and chest wall pressure-volume curves to the right, but it only moderately affected the lung deflation curve. Tidal compliances of the respiratory system, chest wall, and lung decreased 36, 31, and 49%, respectively (all P less than 0.05). The effect of abdominal balloon inflation on respiratory system mechanics was similar to that of volume infusion. We conclude that infusing large volumes of fluid markedly alters chest wall mechanics, mainly by causing abdominal distension that prohibits descent of the diaphragm.
Abdomen↗
Prone position alters the effect of volume overload on regional pleural pressures and improves hypoxemia in pigs in vivo.
Oxygenation improves in patients with adult respiratory distress syndrome and in animals with oleic acid-induced lung injury when they are turned from the supine to the prone position. Dependent and nondependent pleural pressures (Ppl) were measured in six pigs ventilated in the supine and prone positions before and after volume infusion (VI). Before VI the mean +/- SEM AaPO2 difference was 26 +/- 8 mm Hg when the animals were supine and 10 +/- 2 mm Hg when they were prone (p > 0.05). After VI the AaPO2 was 64 +/- 6 mm Hg when the animals were supine (p < 0.05) and 43 +/- 7 mm Hg when they were prone (p < 0.05). VI increased the Ppl gradient from 0.53 +/- 0.1 to 0.71 +/- 0.1 cm H2O/cm when the animals were supine (p < 0.05) and from 0.17 +/- 0.1 to 0.27 +/- 0.1 cm H2O/cm when they were prone (p < 0.05). Dependent Ppl at FRC was much less positive when the animals were prone versus supine (0.9 +/- 0.3 versus 3.0 +/- 0.5 cm H2O, p < 0.05), suggesting that the airways in these dependent regions would narrow and/or close and that ventilation to these regions would diminish as a result of VI.
Abdomen↗
[Effects of theophylline on the respiratory system].
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Animals↗
[Adult GM1 gangliosidosis--biochemical studies--1].
To address the pathogenesis of GM1 gangliosidosis, especially adult form, intracellular signal transduction pathway of EGF in skin fibroblasts from patients with this disorder was examined. For this purpose, skin fibroblasts from 2 different patients with adult form of the disorder and from 4 different normal controls were used. The results showed that 1) EGF-receptor autophosphorylation was diminished in skin fibroblasts from patients with altered time course of phosphorylation-dephosphorylation reaction. 2) The amount of EGF-receptor protein was decreased in cells from patients compared with that of controls. 3) 125I-EGF binding + internalization studies revealed decreased rate of EGF binding and internalization in patient cells. 4) Ribosomal S6 protein phosphorylation was strongly enhanced in naive cells from patients, but the reactivity to EGF was diminished compared with control cells. These data strongly suggest that patient fibroblasts have abnormalities in the intracellular signal transduction pathway of EGF. This paper is considered to be the first report demonstrating abnormalities in EGF-signal transducing system in human disorders.
Adult↗
Genetic disease patterns in Japan: a review.
Comprehensive genetic studies in which the genetic structure of a population is considered against the background of ecological factors, including environmental and social variables, often supply valuable information for the solution of a number of problems in human biology, including reproductive compensation and inbreeding depression. In the first section of this paper we consider the incidence of genetic diseases in Japan in reference to other populations. Some of the genetic disorders found elsewhere do not occur or are of lower frequencies in Japan. On the other hand, a number of genetic diseases occur at higher than usual frequencies, leading to an incidence of genetic disease of the order of about 1 per 100 in newborn Japanese. We next review the studies of consanguinity in Japan and report evidence of very high levels, ranging from 8.6% to 58.0%, for villages during the early part of the twentieth century. The rates are declining rapidly for the country but, because of traditional social values, inbreeding rates remain significant in many small villages. In the final section we consider the probable trends in the frequency of inbreeding on a worldwide basis and point out that frequencies of certain genetic diseases are likely to remain high and even increase in some societies because of various socially prescribed mating patterns.
Consanguinity↗
[Peripheral airway obstruction and treatment].
The effect of medication on peripheral airway obstruction was examined in cases of bronchial asthma. Subjects were 1) patients with exercise-induced asthma, 2) an animal model of hyperventilation-induced asthma and 3) patients with chronic asthma. Peripheral airway obstruction was induced in 30 of 51 patients with exercise-induced asthma. Induction of peripheral airway obstruction was protected significantly by procaterol. Cromoglycate was effective in 12 of 17 patients but ipratropium was not effective against induction of peripheral airway obstruction. In the animal model, humid air inhalation, procaterol and ipratropium completely prevented hyperventilation-induced bronchoconstriction, but cromoglycate caused only partial prevention. In cases of chronic asthma with peripheral airway obstruction, beclomethasone inhalation reduced the symptom rating rapidly, but no changes were observed in pulmonary function and threshold of airway responsiveness. Cromoglycate was started in patients with chronic asthma who had been treated with beclomethasone. After cromoglycate administration, therapeutic rating decreased, but increased again after 8 weeks of cromoglycate therapy. Peripheral airway obstruction induced by exercise or hyperventilation could be prevented by adequate premedication, but chronic peripheral airway obstruction was difficult to treat.
Administration, Inhalation↗
Abdominal distension alters regional pleural pressures and chest wall mechanics in pigs in vivo.
Abdominal distension (AD) occurs in pregnancy and is also commonly seen in patients with ascites from various causes. Because the abdomen forms part of the "chest wall," the purpose of this study was to clarify the effects of AD on ventilatory mechanics. Airway pressure, four (vertical) regional pleural pressures, and abdominal pressure were measured in five anesthetized, paralyzed, and ventilated upright pigs. The effects of AD on the lung and chest wall were studied by inflating a liquid-filled balloon placed in the abdominal cavity. Respiratory system, chest wall, and lung pressure-volume (PV) relationships were measured on deflation from total lung capacity to residual volume, as well as in the tidal breathing range, before and 15 min after abdominal pressure was raised. Increasing abdominal pressure from 3 to 15 cmH2O decreased total lung capacity and functional residual capacity by approximately 40% and shifted the respiratory system and chest wall PV curves downward and to the right. Much smaller downward shifts in lung deflation curves were seen, with no change in the transdiaphragmatic PV relationship. All regional pleural pressures increased (became less negative) and, in the dependent region, approached 0 cmH2O at functional residual capacity. Tidal compliances of the respiratory system, chest wall, and lung were decreased 43, 42, and 48%, respectively. AD markedly alters respiratory system mechanics primarily by "stiffening" the diaphragm/abdomen part of the chest wall and secondarily by restricting lung expansion, thus shifting the lung PV curve as seen after chest strapping. The less negative pleural pressures in the dependent lung regions suggest that nonuniformities of ventilation could also be accentuated and gas exchange impaired by AD.
Abdomen↗
[A case of neoplastic angioendotheliosis--possible mechanism of JC virus infection for the selective growth of tumor cells in the blood vessel].
A case of 55-year-old man pathologically proven as neoplastic angioendotheliosis was reported. He initially developed sensory disturbance and motor weakness in the lower extremities. After admission, he showed progressive deterioration of higher brain functions with moderate fever. Routine laboratory examinations revealed elevated serum LDH level and erythrocyte sedimentation rate without leukocytosis or increased serum globulin level. Immunological tests were normal, except positive RA. Immunocytochemical investigation of tumor cells in the blood vessel gave the results that these cells appeared to be derived from B cells. Southern blot analyses of the brain samples revealed clear positive bands corresponding to JC virus DNA in the blot. JC virus has been known to infect the endothelial cells of the blood vessel as well as urethral epithelial cells. We discussed the possible mechanism of the selective growth of tumor cells in the blood vessel in terms of possible JC virus infection to the endothelial cells of the blood vessel and abnormal recognition between tumor cells and endothelial cells.
B-Lymphocytes↗
[Development of image processing system for fundus video-angiography with non-stroboscopic illumination].
A new recording system for fluorescein video-angiography using a highly sensitive color charge coupled device (CCD) camera was developed. An image processing unit installed in a personal computer made it possible to process video signals from the camera and/or a video tape recorder. Functions of the unit are on-line and/or off-line operations on image data such as smoothing, digital subtraction, differentiation etc. Application of the unit improved the quality of images observed on a monitor screen. This system enabled observation of the ocular fundus with illumination of low intensity, which reduced physical and psychological suffering of patients. In addition continuous and whole sequences of fundus fluorographs were recorded, without using strong stroboscopic lights. Extraction of a clear image from ambiguous records at any moment was possible through off-line processing on the stored data. Furthermore quantification of the blood flow in any blood vessels was possible by subtracting two successive images. With this system, quantitative expression of a slight difference in the color of the fundus could be made through calculation of the ratios among R-, G-, and B-components of signals at any place. Finally, comparative study of images of the fundus with natural color could be made with those of fluorography. These features may provide further information on the physiology and pathology of the fundus.
Animals↗