[Clinical evaluation of serum CEA levels in uterine cervix cancer patients with radiotherapy].
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Biomedical subjects
Publications and source records attributed to Y Kikuchi.
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Examined were effects of calmodulin antagonists (W-5 and W-7) on proliferation of two kinds of human cell lines, designated HR and KF, derived from serous cystadecarcinoma of the ovary. Although both W-5 and W-7 inhibited their cell proliferation in vitro, the degree of inhibition was more marked with W-5 rather than with W-7. HR cells had higher sensitivity to cisplatinum than KF cells, while KF cells had higher sensitivity to adriamycin. Combinations of calmodulin antagonists and anti-cancer drugs resulted in adjuvant effects with regard to the inhibition of their cell proliferation in vitro.
The terminal structures of linear DNA killer plasmids from yeast, pGKL1 and pGKL2, were analyzed. Results obtained by exonuclease treatments of these plasmids show that both pGKL plasmids have free hydroxyl 3'-ends and blocked 5'-ends. Electrophoretic analysis of the terminal restriction fragments treated with proteases revealed that pGKL1 and pGKL2 have proteins bound at 5'termini and that the terminal protein of pGKL1 is distinct from that of pGKL2. This is the first linear DNA-terminal protein association found in yeast.
A small test area of the pulmonary capillary bed of frog's lung was exposed to carbon dioxide. The capillary bed was observed by means of a dark field episcopal microscope and recorded on video tapes via a TV-camera. Swollen capillaries forming a hexagonal network surrounded concave alveolar cells. The flow velocity of red blood cells through capillaries was reduced to 17.5% of the flow velocity during the control condition by the application of the moistened gas mixture containing 30% CO2. The blood flow in capillaries ceased when wet 100% CO2 was applied to the test area. Red blood cells were packed in capillaries. They disaggregated by the introduction of air in five seconds and were quickly flowing in an elongated leaflet shape in 30 seconds after the introduction of air.
A small ring chamber (I.D. = 6 mm) was placed on the exposed lung of anaesthetized bullfrogs. A localized hypoxia was induced in the ring chamber by introducing nitrogen in it. Blood flow velocity in pulmonary microvessels was measured by means of a laser Doppler microscope. The mean blood flow velocity was 1.98 +/- 0.45 and 1.52 +/- 0.10 mm/sec during the control condition in arterioles and capillaries, respectively. It was then reduced by the localized hypoxia to 1.63 +/- 0.32 and 1.33 +/- 0.08 mm/sec in arterioles and capillaries, respectively. The reduction, when expressed in the percentage ratio to the control flow velocity in each blood vessel group, was significantly larger in arterioles than in capillaries. A phase delay in the pulsation of the flow velocity contour was detected only in arterioles. These differences between pulmonary arterioles and capillaries in response to the localized hypoxia may be attributed to the dense interconnection of capillary network extending beyond the localized hypoxic area to the normoxic area.
In a previous study, we showed that the three hitherto serologically indistinguishable HLA-D specificities associated with HLA-DR4, HLA- DYT , HLA- DKT2 , and HLA-Dw4 can be distinguished on the basis of their reactivity with two distinct Ia-like-specific monoclonal antibodies, HU-18 and HU-23. In this study, we attempted to identify and characterize Ia-like molecules recognized by HU-18 and HU-23 on a molecular level because Ia subsets (HLA-DR, MB, MT, or SB) identified by them remained unknown. The results of sequential coprecipitation assays and two-dimensional gel analyses showed that both HU-18 and HU-23 recognize antigenic determinants borne on MB3 but not on HLA-DRw6.2 molecules. Because the two monoclonal antibodies, specific for determinants carried on MB3 molecules, show distinct reactivity against homozygous typing cells defining HLA- DYT , HLA- DKT2 , and HLA-Dw4, all of which share DR4- MB3 , the data indicate that these three HLA-D clusters associated with HLA-DR4 possess distinct MB3 molecules, suggesting the existence of polymorphism in MB3 antigens.
Two- and three-dimensional electron microscopic observations by a serial sectioning method revealed endothelial sprouts with intracytoplasmic vacuolization in rapidly growing human juvenile hemangioma. A large vacuole bounded by a single unit membrane was enclosed in the cytoplasm and on the inner aspect of the vacuolar membrane several short microvilli were demonstrated. These appearances have not been reported before. The presence of microvilli in the vacuole indicates that the endothelium has reached the point of differentiation when a vascular lumen forms. In the cytoplasm adjacent to the vacuolar membrane, a significant number of 7 to 10 nm microfilaments were identified. These intracytoplasmic microfilaments are assumed to play a mechanical role in the development of the cytoplasmic vacuole and/or the sprout. The formation of a vacuole observed in the endothelial sprout is similar to the findings of Sabin (1920) by light microscopy in endothelial sprouts in the blood island of the chick embryo. The active endothelial sprout in juvenile hemangiomas is considered to be at least partially responsible for the capillary proliferation and enlargement of the tumor.
The effects of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) on the induction of micronuclei were examined in mouse fetuses exposed in utero. By this study, MNNG was proved to be mutagenic in vivo. The frequency of micronucleated erythrocytes (MNEs) in fetal liver peaked at 18 h after a single intraperitoneal injection into pregnant mice on day 13 of gestation. Then, to examine the effects of administration routes on the induction of micronuclei, the chemical was given by various routes, and the percentage of MNEs (%MNEs) in fetuses were examined 18 h after treatment. The %MNEs after administration of MNNG intraperitoneally, subcutaneously, intravenously, and orally was 4.7, 1.9, 0.8 and 0.3, respectively. The control value was 0.3. In the intraperitoneally treated mice, %MNEs for fetuses in the uterine horn located nearer the injection site was higher than that in the other. In addition, in the intraperitoneally treated mice, there was a tendency for the higher %MNEs to occur in the fetuses located near the injection site. Together with the results on the distribution of MNNG in mice (Frei and Lawley, 1976), these findings suggest that MNNG might be inactivated in the maternal systemic circulation and that the agent which induces micronuclei might be distributed to the fetuses by diffusion.
The relevance of the micronucleus test to human studies was investigated by using bone marrow from leukemic patients treated with antileukemic drugs. The median incidence of micronucleated erythrocytes and erythroblasts, respectively, increased from control values of 0.04 and 0.72% to 0.29 and 25.3% in leukemic cases; and the frequency of micronucleated erythroblasts was inevitably higher than the control value in cases that showed a higher frequency of micronucleated erythrocytes, but the reverse was not true. These results indicate that almost the same changes of micronucleus formation that are observed in the mouse micronucleus test are produced in human bone marrow by antileukemic drugs--mutagenic compounds--and, if the micronuclei were scored restrictively in erythroblasts, the application of the micronucleus test to human bone marrow would be reasonable.
This paper concerns with two autopsied cases of siblings who died from cerebral disturbances. In these patients hyperammonemia developed in the neonatal phase due to carbamyl phosphate synthetase I (CPS I) deficiency. The patient in Case 1 was admitted 2 days after birth because of oliguria and vomiting. Hyperammonemia developed and she died on the 43rd day. In Case 2 hyperammonemia developed from the 2nd day after birth and she expired on the 42nd day. In both cases the diagnosis of CPS I deficiency was established from autopsy findings of the liver.
Thirty-seven patients with peripheral vascular disease involving the legs were studied with first-pass peripheral radionuclide arteriography (RNA) and contrast arteriography to determine whether RNA could be used to evaluate perfusion of the toes. Data were acquired for 100 seconds using a multicrystal gamma camera following bolus injection of 30-35 mCi (1,110-1,295 MBq) of Tc-99m-labeled albumin during reactive hyperemia. Peripheral time-activity curves were examined and the time required for activity to decline to 75% of peak activity ( T75 ) was recorded. When an abnormal RNA was defined as T75 greater than or equal to 50 seconds, sensitivity was 92%, positive predictive accuracy 100%, and negative predictive accuracy 75%. These data suggest that peripheral RNA of the toes is a reliable, noninvasive procedure for evaluation of peripheral arterial disease; it can be valuable as a screening test prior to contrast arteriography as well as for follow-up.
Effects of protein and NaCl concentrations in plasma on red blood cell (RBC) deformability were studied using fresh human blood and a 5-microns Nuclepore filtration test. The protein and salt concentrations were varied by diluting the plasma with saline and adding crystalline NaCl to the fluids, respectively. The mean pore passage time of the RBCs, which was measured as an index of the deformability, increased with increasing plasma protein and NaCl concentrations. A marked interdependence was observed; the relation of RBC deformability with plasma protein was accentuated by an increase in plasma NaCl, whereas the effect of increasing plasma NaCl was diminished by a decrease in plasma protein. It is suggested that the RBC-protein interaction which is modified by the fluid ionic strength plays a dominant role in producing these characteristic changes in RBC deformability with protein and salt contents in the plasma. An analysis is made of the cell-protein interaction; the electric repulsive and van der Waals attractive forces are calculated with a result that the protein adsorption on a RBC increases with increasing fluid ionic strength above normal. This analysis, furthermore, provides information on the surface charge distribution on a RBC.
Effects of Na+ and K+ in plasma on the protein adsorption on red blood cells (RBCs) were studied using fresh human blood and human plasma albumin labeled with a radioactive isotope. Crystalline NaCl and/or KCl were added to blood samples containing labeled albumin so that the plasma osmolarity was increased to final values of 350, 400, and 450 mosmol. The number of albumin molecules adsorbed on the RBCs increased markedly with increases in Na+ but remained unaltered or increased only slightly with increases in K+. The distribution of Na+ and K+ around the RBC membrane was considered to contribute to increasing the adsorption of albumin on the outer surface and to restricting the deposition of hemoglobin on the inner surface with a consequent positive effect on maintaining the stiffness and flexibility of the membrane. In support of this hypothesis the ouabain treatment of RBCs resulted in a decrease in the cellular deformability.
We examined the interaction between histamine and vagal efferent activity on airway smooth muscle reactivity in 11 anesthetized vagotomized dogs using an isolated closed segment of the intrathoracic trachea filled with Tyrode solution under an isovolumetric condition. Intratracheal pressure change was measured as an index of tracheal smooth muscle tone. The administration into the tracheal segment of histamine (0.1 or 1.0 mg/ml) in six dogs and methacholine chloride (0.001 or 0.01 mg/ml) in the other five dogs elevated intratracheal pressure by about 5 cmH2O. The electrical stimulation of the peripheral ends of both of the cut cervical vagus nerves in the presence of histamine produced significantly greater responses than the additive responses of these two stimuli applied individually (two-way analysis of variance, P less than 0.025). However, the combined effects of vagal stimulation and methacholine were not significantly different from the additive responses of these two stimuli applied individually. The average values of intratracheal pressure elevated by the combined effects of vagal stimulation and histamine were significantly higher than those obtained by the combination of vagal stimulation and methacholine (two-way analysis of variance, P less than 0.01). This suggests that histamine potentiates tracheal smooth muscle reactivity to electrical vagal stimulation, which may contribute to the hyperreactivity observed in patients with asthma.
We examined the relationship between response to hypercapnia and ventilatory response to exercise under graded anesthesia in eight dogs. The response to hypercapnia was measured by the CO2 rebreathing method under three grades of chloralose-urethan anesthesia. The degrees of response to hypercapnia (delta VE/delta PETCO2, 1 X min-1 X Torr-1) in light (L), moderate (M), and deep (D) anesthesia were 0.40 +/- 0.05 (mean +/- SE), 0.24 +/- 0.03, and 0.10 +/- 0.02, respectively, and were significantly different from each other. Under each grade of anesthesia, exercise was performed by electrically stimulating the bilateral femoral and sciatic nerves for 4 min. The time to reach 63% of full response of the increase in ventilation (tauVE) after beginning of exercise was 28.3 +/- 1.5, 38.1 +/- 5.2, and 56.0 +/- 6.1 s in L, M, and D, respectively. During steady-state exercise, minute ventilation (VE) in L, M, and D significantly increased to 6.17 +/- 0.39, 5.14 +/- 0.30, and 3.41 +/- 0.16 1 X min-1, from resting values of 3.93 +/- 0.34, 2.97 +/- 0.17, and 1.69 +/- 0.14 1 X min-1, respectively, while end-tidal CO2 tension (PETCO2) in L decreased significantly to 34.8 +/- 0.9 from 35.7 +/- 0.9, did not change in M (38.9 +/- 1.1 from 38.9 +/- 0.8), and increased significantly in D to 47.3 +/- 1.9 from 45.1 +/- 1.7 Torr.(ABSTRACT TRUNCATED AT 250 WORDS)
The relationship between the hypercontractile response of the regional coronary artery to ergonovine and induced vascular change after endothelial denudation and a high-cholesterol diet was examined in dogs by arteriographic (in situ) and mechanographic (in vitro) methods. In 15 mongrel dogs, selective endothelial denudation of either the left circumflex coronary artery (LCX) or left anterior descending coronary artery (LAD) was repeated twice 1 month apart by means of coronary arterial catheterization. A high-cholesterol diet (20 g/day) was given thereafter for 3 (n = 15) and 6 (n = 8) months. Although there was no difference in the extent of coronary vasoconstriction between the LAD and LCX before or immediately after endothelial denudation, after intravenous administration of ergonovine a significant augmentation of coronary constriction along the denuded portion was noted arteriographically in the long-term phase (1 to 6 months). At the end of the study in vivo, isometric tension of the strips of the denuded and contralateral intact coronary arteries was measured during the cumulative addition of ergonovine, serotonin, or phenylephrine to the organ bath; agonist responses were standardized by the response to 35 mM KCl. Although the concentration-response relations for phenylephrine (10(-9) M to 10(-5) M) were not significantly different between intact and denuded arteries, responses of the denuded portion to cumulative addition of ergonovine (10(-10) M) or serotonin 10(-9) M to 10(-5) M) exhibited markedly depressed threshold concentrations along with a significantly lowered negative logarithm (pD2) of the dose producing 50% of the maximum effect. The tension developed in the denuded portion was also enhanced over that noted in the contralateral coronary artery during the cumulative addition of ergonovine but not during application of phenylephrine. Thus enhanced constriction documented arteriographically may be derived from the localized hypersensitivity to ergonovine. Microscopically, the endothelial denudation and a long-term high-cholesterol diet resulted in a regional intimal thickening with fibrous proliferation but little lipid deposition. Therefore smooth muscle in atherosclerotic arteries may be hypersensitive to specific agonists such as ergonovine and serotonin in a canine preparation. These results suggest that coronary spasm induced by ergonovine in humans is relevant to the presence of atherosclerotic changes in the vascular wall.
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