Correlations among blood levels of renin-angiotensin-aldosterone, bradykinin, and catecholamines in healthy subjects.
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Adult↗
Biomedical subjects
Y Kikuchi
Publications and source records attributed to Y Kikuchi.
Gas chromatographic determination of nicotinamide in meats and meat products as 3-cyanopyridine.
The determination of nicotinamide as 3-cyanopyridine after dehydration by heptafluorobutyric anhydride (HFB) was performed by gas-liquid chromatography (GLC) with flame ionization detection (GLC-FID) and a column of 5% OV-17 on Chromosorb W AW DMCS at 130 degrees C. Determination was possible with 3-100 micrograms of the dehydrated reaction mixture. The procedure for determining nicotinamide in various meats and meat products involves direct analysis by GLC-FID without a clean-up stage; the detection limit is 5 ppm and the recovery ranged from 93.4 to 104.6% (average 98.0%). Various possible interferents in the samples did not interfere in the production or determination of 3-cyanopyridine. The procedure is suitable for routine use. The dehydrated derivative of nicotinamide was confirmed as 3-cyanopyridine by combined gas chromatography-mass spectrometry and infrared spectrometry.
Chromatography, Gas↗
[Analysis of therapeutic efficacy of combined radio-chemotherapy, pre-radio-therapy in 61 cases of non-Hodgkin's lymphoma].
Treatment results were retrospectively analyzed in 61 cases of non-Hodgkin's lymphoma (stage I: 21 cases, stage II: 40 cases) that were diagnosed between July, 1977 and Oct., 1987. The actuarial five-year survival rates for stages I and II were 84.4% and 50.7% respectively, whereas those were 47.5% and 75.3% respectively for those treated by radiotherapy (XRT) alone and combined radio-chemotherapy including all cases of stage I and II. Also the results of combined radio-chemotherapy were significantly better than those of XRT alone. Particularly, the pre-radio-chemotherapy group had a 5-year survival rate of 85.7%. In conclusion, the results of combined radio-chemotherapy, particularly pre-radio-chemotherapy, was significant between those of XRT alone.
Adolescent↗
Effects of lymphokine-activated killer cells and interleukin-2 on the ascites formation and the survival time of nude mice bearing human ovarian cancer cells.
The effect of intraperitoneal instillations of interleukin-2 (IL-2) and/or lymphokine-activated killer (LAK) cells on the ascites formation and the survival time was examined using nude mice as a model, with malignant ascites produced by intraperitoneal inoculation of human ovarian cancer cells derived from ascites of a patient with serous cystadenocarcinoma of the ovary. Twenty-eight days after tumor inoculation, all nude mice in the untreated group and in the group treated with spleen cells alone formed ascites. Two of ten nude mice treated with IL-2 alone after tumor inoculation survived without forming ascites during the experimental period. On the other hand, all nude mice treated with LAK cells alone had formed ascites 14 days after tumor inoculation. When LAK cells and IL-2 were combined, five of ten mice survived without forming ascites during the experimental period. The survival time of the group treated with IL-2 alone was significantly prolonged compared to the groups that received medium alone, spleen cells alone and LAK cells alone. When administration of LAK cells was followed by IL-2, the survival time was further prolonged.
Animals↗
Inhibition of human ovarian cancer cell proliferation by calmodulin inhibitors and the possible mechanism.
Direct inhibitory effects of calmodulin inhibitors on human ovarian cancer cell proliferation in vitro were examined. All calmodulin inhibitors used in this study inhibited proliferation of HR cells derived from human serous cystadenocarcinoma of the ovary in a dose-dependent manner. The degree of inhibition by melittin and W-5 was most marked and was followed by that of W-7, R24571, and bepridil. HR cell proliferation was dose-dependently stimulated by epidermal growth factor (EGF). The stimulatory effects seemed to be a result of the binding of EGF to HR cells. Binding of EGF was significantly inhibited by W-5, R24571, and melittin. These results suggest that inhibition by calmodulin inhibitors of cancer cell proliferation may result in part from the interference in the binding of EGF to the cells.
Biomechanical Phenomena↗
Adjuvant effects of calmodulin antagonists on antitumor activity of 1-(2-tetrahydrofuryl)-5-fluorouracil (ftorafur) and a mixture of ftorafur and uracil (UFT) in nude mice bearing human ovarian carcinomas.
Effects of N-(6-aminohexyl)-1-naphthalenesulfonamide (W-5) and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) on antitumor activity of 1-(2-tetrahydrofuryl)-5-fluorouracil (ftorafur, FT) and a mixture of FT and uracil (UFT) were determined in nude mice bearing human ovarian carcinoma (KF cells). All nude mice developed palpable tumor 17 days after KF cell inoculation unless treated. A combination of UFT and calmodulin antagonists (W-5 and W-7) resulted in a delay in tumor formation in nude mice. One of 10 nude mice treated with a combination of UFT and W-5 and 3 of 10 nude mice treated with UFT and W-7 did not develop tumors during the experimental period. Tumor volumes in groups treated with the combinations of UFT and calmodulin antagonists were significantly smaller than those in the untreated group after 31 days of tumor inoculation. In addition, tumor volumes in a group treated with UFT plus W-7 were significantly smaller than not only those in the untreated group but also those in groups treated with UFT alone, FT alone, W-5 alone, or W-7 alone. The longest median survival time was also observed in the group treated with UFT plus W-7. 5-Fluorouracil (5-FU) content of the tumors of groups treated with FT plus W-5 or W-7 was similar to that of the group treated with FT alone. On the other hand, 5-FU content of a group treated with UFT plus W-7 was about twofold higher than that of a group treated with UFT alone. These results suggest that a synergistic effect of W-7 and UFT on inhibition of tumor growth and prolongation of survival time may result from accumulation of 5-FU in the tumor.
Animals↗
Inhibition of human ovarian cancer cell proliferation in vitro by neuroendocrine hormones.
Direct inhibitory effects of neuroendocrine hormones on human ovarian cancer cell proliferation in vitro were examined. Except for melatonin, all neuroendocrine hormones used in this study inhibited proliferation of KF cells derived from human serous cystadenocarcinoma of the ovary in a dose-dependent manner. The degree of inhibition of prostaglandin D2 was most marked being comparable to that of 5-fluorouracil and followed by beta-endorphin, alpha-endorphin, and Met-enkephalin. More than 200 microM melatonin stimulated the cell proliferation. The inhibitory effects by endorphins were partially reversible by 20 microM naloxone. From analyses of uptakes of radiolabeled precursors by the KF cell, endorphins were considered to inhibit protein and RNA syntheses but not DNA synthesis. These results suggest that neuroendocrine hormones may play an important role in regulation of tumor growth.
Cell Division↗
Intracavernous injection of prostaglandin E1 for the treatment of erectile impotence.
We administered intracavernous injections of 20 micrograms. prostaglandin E1 to 135 patients with impotence, and evaluated the effects and side effects. Among 135 patients who underwent intracavernous injection of prostaglandin E1 complete erection was observed in 83 (62 per cent), while incomplete erection was noted in 33 (24 per cent). In both groups the erection was sufficient for sexual intercourse. Tumescence without rigidity was noted in 12 patients and no response was obtained in 7. Poor response was seen frequently in patients with disorders of the vascular system and/or damage to the cavernous body of the penis. Priapism after the injection was not observed. Moreover, we never observed any other severe side effects. Intracavernous injection of prostaglandin E1 could be applicable to the therapy of impotence, especially that due to neurogenic disturbance. Since prostaglandin E1 acts quickly and loses its validity rapidly it is considered to be a more suitable agent than other vasoactive drugs.
Adult↗
Characterization of high-affinity receptors for interleukin 5 on interleukin 5-dependent cell lines.
Interleukin 5 (IL-5) is a glycosylated polypeptide that acts as a key factor for B-cell growth and differentiation. We demonstrated previously that there are two classes (high and low affinity) of IL-5 receptors on murine chronic B-cell leukemic cells (BCL1-B20). Treatment of surface-bound radiolabeled IL-5 with bivalent crosslinkers identified a polypeptide of Mr 92,500. In this study, we analyzed characteristics of high-affinity IL-5 receptors on IL-5-dependent early B-cell lines (T-88 and T88-M), mouse myeloma cells (MOPC-104E), and BCL1-B20 cells. All cell lines had two classes of IL-5 binding sites, but T88-M cells bore the highest number of high-affinity receptors. The number of high-affinity IL-5 receptors on BCL1-B20 cells could be up-regulated 3-fold by lipopolysaccharide and down-regulated by IL-5. Disuccinimidyl tartarate crosslinking of 35S-labeled IL-5 to the receptors on the T88-M and lipopolysaccharide-stimulated BCL1-B20 cells revealed two major 35S-labeled components of Mr 92,500 and Mr 160,000, even when the binding of 35S-labeled IL-5 was carried out under high-affinity conditions (100 pM 35S-labeled IL-5). The Mr 92,500 component, but not the Mr 160,000 component, was detected in the lysates of MOPC-104E and T-88 cells, both of which bore a large number of low-affinity receptors and a limited number of high-affinity receptors. The results suggest that the Mr 92,500 component represents the complex of IL-5 with the low-affinity Mr 46,500 receptor, whereas the high-affinity receptor consists of the Mr 46,500 peptide and an additional peptide.
Adjuvants, Immunologic↗
Interferon-gamma inhibits the proliferation but not the differentiation of murine B cells in response to IL-5.
Interferon-gamma (IFN-gamma) is supposed to be produced by type 1 helper T cells (TH1) and inhibits IL-4-dependent B cell growth and differentiation. IL-5 (T cell-replacing factor, TRF), is a T cell-derived lymphokine which is predominantly produced by type 2 helper T cells (TH2) and regulates proliferation and differentiation of activated B cells. In this study, the effect of IFN-gamma on IL-5-dependent B cell growth and differentiation has been studied using murine chronic B cell leukemic cells (BCL1), normal splenic B cells, and cloned early B cell line. IFN-gamma selectively inhibits the IL-5-mediated proliferation of activated B cells as well as cloned early B cell lines at a low concentration (2 U/ml) in which polyclonal IgM production was not affected. This inhibitory effect of IFN-gamma occurs within 24 h after the onset of culture, as demonstrated by the inability of antibody to IFN-gamma to reverse totally the IFN-gamma-mediated suppressive effects if it was added later than 24 h after the onset of the culture. On the contrary, IL-5-mediated IgM secretion of BCL1 and IgA formation of LPS-stimulated normal B cells were relatively resistant to the suppressive effect of IFN-gamma. IFN-gamma does not affect the receptor expression for IL-5. Interestingly, IL-4-mediated IgG1 formation of LPS-stimulated B cells was markedly suppressed by IFN-gamma at 10 U/ml. These results strongly suggest that IFN-gamma may have differential effects on IL-5-mediated B cell triggering.
Animals↗
Exoribonuclease activity of purified reverse transcriptase preparations from retroviruses.
Highly purified and commercially available preparations of reverse transcriptases from retroviruses contain a 3' to 5' exoribonuclease activity capable of hydrolyzing synthetic homopolyribonucleotides having a 3'-OH end. The exoribonuclease activity of reverse transcriptase preparations from Rous associated virus-2 was further characterized. This exoribonuclease activity cleaves poly(C) and poly(U) exonucleolytically from the 3'-OH end to produce nucleoside 5'-phosphates. Poly(A), poly(G), circular polyribonucleotide, and double-stranded polyribonucleotide were not hydrolyzed by the activity. This is a novel type of exoribonuclease activity.
Buffers↗
Lectin- and immunohistochemical studies on acquired cystic kidney and associated renal cell carcinoma.
Nine specimens of acquired cystic kidney were studied by means of lectin- and immunohistochemistry. The cysts appeared to originate from any part of the nephron, but mostly from the proximal tubule. The cause of multicyst formation is still unclear, but the results of this study suggested that obstruction of the lower nephron might play an important role. Many microscopic carcinomas or dysplastic epithelial cells were observed in the cyst wall. All these carcinomas originated from the proximal tubule, except for one which was of Bellini duct origin and showed papillary growth. The reasons why almost all of the carcinomas originated from the proximal tubule were: 1) the majority of the cysts originated from the proximal tubule, and 2) dysplastic epithelial cells in the cysts originating from the proximal tubules were more frequent in number than those in cysts originating from other parts of the nephron. Histological observation showed that stimulation due to oxalate crystals in the proximal cysts was one of the causes of dysplastic epithelial cell hyperplasia.
Adult↗
Preparation of drug-diluent hybrid powders by dry processing.
New hybrid powders have been produced by the dry processing of six drugs (oxyphenbutazone, prednisolone, theophylline, indomethacin, phenacetin and aspirin), with potato starch used as a core material, by means of an electric mortar and a powder surface reforming system designed to produce hybrid powders. The hybrid powders obtained immediately after production differed in their structure from interactive mixtures. With the hybrid powders the drug was spread on the surface of the core particle by friction and collision that occurred in the dry process, but with interactive mixtures the drug simply adhered as intact particles to the surface of diluent particles. Scanning electron microscopy and powder X-ray diffractometry indicated that the mechanochemical phenomenon was essential for the production of the hybrid powders. With time, a shape change in the adhering drug was observed as a relaxation process took place, with recrystallization resulting from the release of accumulated energy. The change with time might depend upon the method of producing powders and the physical properties of the drug used, e.g. the smooth layer of indomethacin produced by the powder surface reforming system reverted to fine particles tightly adhering to the starch surface, though no change was observed with prednisolone.
Chemistry, Pharmaceutical↗
Chest wall impedance partitioned into rib cage and diaphragm-abdominal pathways.
We measured chest wall "pathway impedances" (ratios of pressure changes to rates of volume displacement at the surface) with esophageal and gastric balloons and inductance plethysmographic belts around the rib cage and abdomen during forced volume oscillations (5% vital capacity, 0.5-4 Hz) at the mouth of five relaxed, seated subjects. Volume displacements of the total chest wall surface, measured by summing the rib cage and abdominal signals, approximated measurements using volume-displacement, body plethysmography over the entire frequency range. Resistance (R) and elastance (E) of the diaphragm-abdomen pathway were several times greater than those of the rib cage pathway, except at the highest frequencies where diaphragm-abdominal E was small. R and E of the diaphragm-abdomen pathway and of the rib cage pathway showed the same frequency dependencies as that of the total chest wall: R decreased markedly as frequency increased, and E (especially in the diaphragm-abdomen) decreased at the highest frequencies. These results suggest that the chest wall can be reasonably modeled, over the frequency range studied, as a system with two major pathways for displacement. Each pathway seems to exhibit behavior that reflects nonlinear, rate-independent dissipation as well as viscoelastic properties. Impedances of these pathways are useful indexes of changes in chest wall mechanical behavior in different situations.
Abdomen↗
Preferential fatigue of the rib cage muscles during inspiratory resistive loaded ventilation.
Because the inspiratory rib cage muscles are recruited during inspiratory resistive loaded breathing, we hypothesized that such loading would preferentially fatigue the rib cage muscles. We measured the pressure developed by the inspiratory rib cage muscles during maximal static inspiratory maneuvers (Pinsp) and the pressure developed by the diaphragm during maximal static open-glottis expulsive maneuvers (Pdimax) in four human subjects, both before and after fatigue induced by an inspiratory resistive loaded breathing task. Tasks consisted of maintaining a target esophageal pressure, breathing frequency, and duty cycle for 3-5 min, after which the subjects maintained the highest esophageal pressure possible for an additional 5 min. After loading, Pinsp decreased in all subjects [control, -128 +/- 14 (SD) cmH2O; with fatigue, -102 +/- 18 cmH2O; P less than 0.001, paired t test]. Pdimax was unchanged (control, -192 +/- 23 cmH2O; fatigue, -195 +/- 27 cmH2O). These data suggest that 1) inability to sustain the target during loading resulted from fatigue of the inspiratory rib cage muscles, not diaphragm, and 2) simultaneous measurement of Pinsp and Pdimax may be useful in partitioning muscle fatigue into rib cage and diaphragmatic components.
Adult↗
Effects of electrical stimulation of the genioglossus on upper airway resistance in anesthetized dogs.
We examined the relationship between the frequency of stimulation of the genioglossus and upper airway resistance in six anesthetized dogs in the supine position. The upper airway was isolated from the lower airway by transecting the cervical trachea, and the pressure flow relationship of the upper airway was obtained by applying constant negative pressure (5, 10, and 20 cm H2O) to the proximal cut end of the trachea. Electrical stimulation of the genioglossus was performed at a constant voltage (10 to 20 V) and at various frequencies (as high as 100 Hz). Upper airway resistance (Rua) during both inspiration and expiration increased with an increase in tracheal negative pressure, and at each tracheal negative pressure Rua was significantly reduced by stimulation of the genioglossus. The effects of genioglossal muscle stimulation were nonlinearly dependent on the stimulating frequency. Below 50 Hz, Rua decreased markedly as the stimulating frequency was increased, but above 50 Hz, Rua plateaued at a minimum value. These findings suggest that at a stimulating frequency of more than 50 Hz, upper airway patency is stably maintained in anesthetized dogs.
Airway Resistance↗
Effects of submental electrical stimulation during sleep on upper airway patency in patients with obstructive sleep apnea.
We examined the effects of percutaneous electrical stimulation of the genioglossus in six patients with obstructive sleep apnea syndrome (OSAS) during sleep and investigated the possible applicability of this procedure as a treatment of OSAS. Six patients with OSAS were polysomnographically studied in the supine position during all-night sessions with and without electrical stimulation of the genioglossus. Using an apnea demand-type stimulator that we developed, electrical pulses of 0.5 ms (repetition rate, 50 Hz) and 15 to 40 V were delivered through bipolar electrodes (10 mm in diameter) attached to the skin of the submental region when apnea lasted more than 5 s, and was stopped immediately after breathing resumed or after 10 s at the longest. With submental stimulation, the apnea index, apnea time/total sleep time, longest apnea duration, and the number of times per hour that oxygen saturation dropped below 85% decreased significantly compared with those on control nights. The lowest arterial oxygen saturation and the duration of sleep stages III and IV increased significantly. The stimulation employed did not cause arousal, and it did not affect blood pressure or heart rate significantly. These findings show that submental stimulation decreases the incidence of apnea episodes and promotes deeper sleep without accompanying serious side effects, suggesting that the apnea demand-type stimulator may be a noninvasive and effective treatment for OSAS.
Electric Stimulation↗
Change in P wave height during progressive exercise in patients with chronic obstructive pulmonary disease.
We examined changes in P wave height in lead II of electrocardiogram during progressive exercise in patients with chronic obstructive pulmonary disease (COPD), and obtained the slope (delta P/delta VO2, %/ml/min) of the regression line calculated from the relationship between percent change of P wave height and oxygen consumption (VO2). Four COPD patients, who had a decrease over 5 mmHg in arterial oxygen tension (PaO2) at maximal exercise (group A), had significantly greater slope (0.45 +/- 0.14%/ml/min, mean +/- S.E.) than in five COPD patients (group B, 0.14 +/- 0.05), who did not have a decrease over 5 mmHg in PaO2 at maximal exercise. The increase in P wave height during exercise was inhibited by oxygen inhalation at the given VO2 in group A. These findings suggest that increase in P wave height during exercise in COPD patients may be correlated with hypoxemia during exercise.
Adult↗