Biomedical subjects
Publications and source records attributed to Y Kikuchi.
1. Of all the cations tested only manganese ion inhibited the benzoyl peroxide/Cu2+-dependent formation of thiobarbituric acid (TBA)-reactive substance. 2. Ki of Mn2+ for the formation of TBA-reactive substance was 5.0 microM. 3. The inhibitory manner of manganese was non competitive against copper.
The effects of PSK on OKT 4/OKT 8 cell ratio, interleukin-2 (IL-2) production and expression of IL-2 receptor were examined in peripheral blood lymphocytes (PBL) from patients with advanced ovarian cancer during the course of chemotherapy. Preoperative levels of OKT 4/OKT 8 cell ratio and IL-2 production in PBL from patients with advanced ovarian cancer were significantly lower than those in cases of benign ovarian tumor. However, the expression of IL-2 receptor did not show any significant difference between ovarian cancer and benign ovarian tumor patients. When a combination chemotherapy of cisplatin, adriamycin and cyclophosphamide was given, the OKT 4/OKT 8 cell ratio was significantly increased with a significant decrease of the absolute number of the OKT 8 cell subset, while the expression of IL-2 receptor and the absolute number of the OKT 4 cell subset remained unchanged. In contrast, the IL-2 production was markedly depressed after the first course of chemotherapy. When PSK was combined with combination chemotherapy, the degree of inhibition of IL-2 production was reduced (though the effect was not statistically significant). If treatment with PSK was initiated after completion of combination chemotherapy, in addition to a significant elevation of OKT 4/OKT 8 cell ratio the depressed IL-2 production was restored to benign control levels. On the other hand, the expression of IL-2 receptor remained unchanged even if PSK was given after completion of chemotherapy.
The present study was designed to elucidate the mechanism of resistance to cisplatin. A cisplatin-resistant cell line (KFr) was established from KF cells derived from human serous cystadenocarcinoma of the ovary. The DNA histogram revealed an increase of S-phase cells and a decrease of G1-phase cells in cultured KFr cells, compared to that in cultured KF cells. Although the cisplatin content in the KF cells incubated with cisplatin at 10 micrograms/ml increased in a time-dependent manner, that in the KFr cells remained unchanged during the experimental period. When 0.5 mg of cisplatin was administered ip to nude mice with KF or KFr tumor, the cisplatin content in the KFr tumor was significantly lower than that in the KF tumor. The KFr cells showed a cross-resistance to L-phenylalanine mustard, while no cross-resistance to vincristine or 5-fluorouracil was observed. These findings suggest that the mechanism of cisplatin resistance in the KFr cells involves a decrease of cisplatin accumulation in the tumor cells.
An autopsy case of primary esophageal choriocarcinoma in a 42-year-old Japanese male is reported. The tumor was pure choriocarcinoma typical hemorrhagic and necrotic nature occupying almost the entire circumference of the mid-esophagus. The choriocarcinoma had metastasized to the liver, lung and lymph nodes. In the esophageal tumor, immunohistochemical staining showed the presence of mainly human chorionic gonadotropin (HCG), with human placental lactogen (HPL) in a few syncytiotrophoblastic cells. Only 3 cases of extragonadal choriocarcinoma originating in the esophagus have been reported up to now. The possible pathogenesis and pathological characteristics of primary esophageal choriocarcinoma are discussed.
TRF has originally been defined as a T-cell-derived lymphokine that triggers activated B cells for a terminal differentiation into Ig-secreting cells. HPLC-purified TRF from Sup of a murine TRF-producing B151 cell is an acidic glycoprotein, exerts BCGF II activity and induces expression of IL-2 receptors. It does not show IL-1, IL-2, IL-3, BSF-1/IL-4, or IFN gamma activity. We prepared monoclonal TB13 and NC17 antibodies against HPLC-purified B151-TRF which are specific for and can inhibit TRF as well as BCFG II activity of B151-TRF. Moreover, TB13 as well as NC17 antibody can immunoprecipitate the 46 Kd molecule from B151 Sup which exerts TRF as well as BCGF II activity. Complementary DNA (pSP6K-mTRF23) encoding for murine TRF/IL-5 was cloned and its entire nucleotide sequences were determined. The murine TRF/IL-5 cDNA encodes 133 amino acids including N-terminal strongly hydrophobic regions. Secreted recombinant TRF/IL-5 (apparent m.w. of 46 Kd) has 113 amino acid residues and also comprises homodimers of a molecule with an apparent m.w. of 25 to 30 Kd. TRF/IL-5 mRNA is constitutively expressed in constitutively TRF-producing B151 and is inducible in some T cell lines upon stimulation with PMA or Con A. TRF/IL-5 mRNA is also expressed in Tbc-primed T cells upon the stimulation with PPD, whereas its expression is not effectively induced in non-primed spleen cells by stimulation with Con A or PMA plus calcium ionophore. The translation product of murine TRF/IL-5 cDNA triggers resting as well as activated (DNP-primed or LPS-stimulated) murine B cells for terminal differentiation into Ig-secreting cells (IgM, IgG1, or IgA) accompanied by increased mRNA expression for secreted forms of relevant Ig heavy chain (mu, gamma, or alpha). Among these, increases in the level of mu, and alpha-specific mRNA for the secreted form of IgM and IgA, respectively, are prominent. Moreover, TRF/IL-5 induces maturation of resting B cells into IgM-secreting cells. TRF/IL-5 promotes growth of activated B cells as well as BCL1 cells. TRF/IL-5 is, therefore, a growth as well as a differentiation inducing factor for B cells. Moreover, it induces functional IL-2 receptors on resting as well as activated B cells, besides TRF and BCGF II activities.(ABSTRACT TRUNCATED AT 400 WORDS)
Ventilatory response to graded external dead space (0.5, 1.0, 2.0, and 2.5 liters) with hyperoxia and CO2 steady-state inhalation (3, 5, 7, and 8% CO2 in O2) was studied before and after 4% lidocaine aerosol inhalation in nine healthy males. The mean ventilatory response (delta VE/delta PETCO2, where VE is minute ventilation and PETCO2 is end-tidal PCO2) to graded dead space before airway anesthesia was 10.2 +/- 4.6 (SD) l.min-1.Torr-1, which was significantly greater than the steady-state CO2 response (1.4 +/- 0.6 l.min-1.Torr-1, P less than 0.001). Dead-space loading produced greater oscillation in airway PCO2 than did CO2 gas loading. After airway anesthesia, ventilatory response to graded dead space decreased significantly, to 2.1 +/- 0.6 l.min-1.Torr-1 (P less than 0.01) but was still greater than that to CO2. The response to CO2 did not significantly differ (1.3 +/- 0.5 l.min-1.Torr-1). Tidal volume, mean inspiratory flow, respiratory frequency, inspiratory time, and expiratory time during dead-space breathing were also depressed after airway anesthesia, particularly during large dead-space loading. On the other hand, during CO2 inhalation, these respiratory variables did not significantly differ before and after airway anesthesia. These results suggest that in conscious humans vagal airway receptors play a role in the ventilatory response to graded dead space and control of the breathing pattern during dead-space loading by detecting the oscillation in airway PCO2. These receptors do not appear to contribute to the ventilatory response to inhaled CO2.
We hypothesized that during maximal respiratory efforts involving the simultaneous activation of two or more chest wall muscles (or muscle groups), differences in muscle strength require that the activity of the stronger muscle be submaximal to prevent changes in thoracoabdominal configuration. Furthermore we predicted that maximal respiratory pressures are limited by the strength of the weaker muscle involved. To test these hypotheses, we measured the pleural pressure, abdominal pressure (Pab), and transdiaphragmatic pressure (Pdi) generated during maximal inspiratory, open-glottis and closed-glottis expulsive, and combined inspiratory and expulsive maneuvers in four adults. We then determined the activation of the diaphragm and abdominal muscles during selected maximal respiratory maneuvers, using electromyography and phrenic nerve stimulation. In all subjects, the Pdi generated during maximal inspiratory efforts was significantly lower than the Pdi generated during open-glottis expulsive or combined efforts, suggesting that rib cage, not diaphragm, strength limits maximal inspiratory pressure. Similarly, at high lung volumes, the Pab generated during closed-glottis expulsive efforts was significantly greater than that generated during open-glottis efforts, suggesting that the latter pressure is limited by diaphragm, not abdominal muscle, strength. As predicted, diaphragm activation was submaximal during maximal inspiratory efforts, and abdominal muscle activation was submaximal during open-glottis expulsive efforts at midlung volume. Additionally, assisting the inspiratory muscles of the rib cage with negative body-surface pressure significantly increased maximal inspiratory pressure, whereas loading the rib cage muscles with rib cage compression decreased maximal inspiratory pressure. We conclude that activation of the chest wall muscles during static respiratory efforts is determined by the relative strengths and mechanical advantage of the muscles involved.
We examined the role of CO2 responsiveness and breathing efficiency in limiting exercise capacity in 15 patients with chronic airway obstruction (FEV1 = 0.88 +/- 0.25 L, mean +/- SD). Responses of minute ventilation and P0.1 (mouth pressure 0.1 s after the onset of occluded inspiration) to hypercapnia (delta VE/delta PCO2, delta P0.1/delta PCO2) were measured by rebreathing, and the ratio of the two (delta VE/delta P0.1) was defined as an index of breathing efficiency during hyperventilation. Exercise capacity was measured as symptom-limited, maximal oxygen consumption (VO2max/BW) in an incremental treadmill test and also as the 12-min walking distance (TMD). All patients discontinued the treadmill test because of dyspnea, and the exercise capacity correlated with the degree of airway obstruction, although there was a wide variability among patients with comparable FEV1. There were no significant correlations between the responses to CO2 and exercise capacity. However, there was a significant correlation between delta VE/delta P0.1 and VO2max/BW (r = 0.87, p less than 0.001) or TMD (r = 0.78, p less than 0.001), and these correlations remained significant even when the relational effects of FEV1 were taken out. These results support the hypothesis that airway obstruction and breathing efficiency are important, but that CO2 responsiveness is not a major factor in determining the exercise capacity of patients with chronic airway obstruction.
The protective efficacy of immunization against Bacteroides gingivalis infection was examined in hamsters. Whole cells or extracted hemagglutinin of B. gingivalis 381 was injected with incomplete Freund adjuvant into the inguinal regions of hamsters. Two weeks after the rats received a booster injection, cotton threads were tied coronally to the gingival margins of the mandibular first molars, and then a streptomycin-resistant B. gingivalis 381R' strain was inoculated into the rats' oral cavities. The subcutaneous immunizations resulted in slight reductions in the numbers of B. gingivalis on the ligature threads compared with the sham-immunized group. Peroral administration of whole cells of B. gingivalis to hamsters elicited salivary immunoglobulin responses, but no reduction of B. gingivalis 381R' colonization was found in this group. Repeated passive immunizations with rabbit antiserum to B. gingivalis into the oral cavities of the hamsters resulted in a reduction in the number of organisms in the periodontal region.
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We have developed a portable home sleep monitoring system using nasal airflow (NA), tracheal sound recordings (TSR), and electrocardiogram (ECG). NA was recorded by two thermisters. TSR was recorded by a microphone attached to the skin overlying the cervical trachea. Three kinds of signals were recorded with a cassette recorder. Thirty-seven outpatients who had sleep complaints were monitored during sleep at home using this recorder. Attachment of the pickups was performed by the patients themselves. Recordings were played back and analyzed by a personal computer to evaluate apnea episodes from TSR and R-R intervals beat by beat. This home monitoring system had labor-saving and cost-saving benefits and seemed to be a satisfactory technique for screening.
In order to examine the effect of sleep position on sleep apnea episodes, seven male patients diagnosed as having obstructive sleep apnea syndrome without any organic complication of the upper airway were studied while lying in a supine or lateral position during an all-night polysomnographic study. Apnea index, apnea time/total sleep time (%) and the number of episodes per hour in which oxyhemoglobin saturation dropped below 85% decreased significantly from 51.0 +/- 8.6 (mean +/- S.D.) events/hr, 40.4 +/- 5.8% and 36.2 +/- 9.8 episodes/hr during sleep in supine position to 27.6 +/- 9.1 events/hr, 19.4 +/- 6.0% and 12.9 +/- 5.3 episodes/hr during sleep in lateral position, respectively. Lowest oxyhemoglobin saturation increased significantly from 70.7 +/- 2.6% to 78.0 +/- 2.4%. Thus, sleep in the lateral position may be a simple treatment before essential treatment for patients with obstructive sleep apnea syndrome.
The MR images, CT scans, and angiograms of 15 consecutive patients with intracranial, supratentorial arteriovenous malformations (AVMs) were studied retrospectively. The three imaging techniques were evaluated separately to assess their utility in defining the size, characteristics, and location of the AVM nidus, its arterial supply, and venous drainage. The studies were also evaluated for their ability to show associated parenchymal abnormalities, the presence of mass effect, and changes occurring after embolization. MR was superior to both CT and angiography in showing the exact anatomic relationships of the nidus, feeding arteries, and draining veins, as well as in demonstrating the extent of AVM nidus obliteration after embolization. MR was more sensitive than CT in revealing associated parenchymal abnormalities and subacute hemorrhage. Because of flow-related artifacts and low sensitivity in distinguishing calcification from rapid flow and/or hemosiderin, MR seemed to have a low sensitivity for detecting old hemorrhage within an AVM nidus. Angiography is still needed in the planning of either surgical or endovascular treatment of AVMs.
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We applied MFD to the treatment of forty-nine patients with lung and esophageal cancer. In lung cancer tumor response, tumor regression rate and local recurrence-free survival rate were higher in the MFD group. Although the actuarial survival rates in the two group were similar, the frequency of radiation pneumonitis was much lower in the MFD group. In esophageal cancer, the actuarial survival rate in the MFD group (49.8%) was significantly higher than that in the control group. (14.6%). However, the late effects of radiation were stricture in the 3.2 Gy/2f/day group. Further studies are needed to establish the optimal dose fractionation and indications for MFD therapy.
The 5' and 3' terminal sequences of the replicative form (RF) of RNA of a flavivirus, the Japanese encephalitis (JE) virus, strain Ja0ArS982, have been determined by in vitro labelling and mobility shift analysis. The plus strand sequence was 5'AGAAGUUUAUCUGUGUGAA...UCUOH3', while the minus strand sequence was 5'AGAUCCUGUGUUCUUCCUCA...UCUOH3'. These sequences were similar to those of West Nile (WN) virus being identical in 12 nucleotides at the 5'terminal of the minus strand, and in the 5'terminal dinucleotides, 5'AG3'. Somewhat more internal hexanucleotides 5'CUGUGU3' are conserved among 3 flaviviruses, the JE, WN, and yellow fever viruses.
The effect of calmodulin antagonists (W-5 and W-7) on antitumor activity of 1-(2-Tetrahydrofuryl)-5-fluorouracil (Tegafur; FT) and FT plus uracil (UFT) was examined by using nude mice bearing human ovarian carcinoma (KF cells). All nude mice developed a palpable tumor 17 days after KF cell inoculation unless treatment was done. A combination of UFT and calmodulin antagonists (W-5 or 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 volume in the treatment groups combined with calmodulin antagonists was significantly less than in those in the untreated group after 31 days of tumor inoculation. In addition, tumor volume in a UFT plus W-7 treated group was significantly less than those not only in the untreated group but also in the UFT alone, FT alone, W-5 alone and W-7 alone treated groups, suggesting a synergistic inhibitory effect on tumor growth. The longest median survival time was also observed in a UFT plus W-7 treated group. 5-Fluorouracil (5-FU) content in the tumor of groups treated with FT plus W-5 or W-7 was similar to that in a group treated with FT alone. On the other hand, that of a group treated with UFT plus W-7 was about 2-fold higher than that of a UFT -only treated group.(ABSTRACT TRUNCATED AT 250 WORDS)
We have developed a human ovarian carcinoma cell line (KFr) which is relatively stable and resistant to cis-diamminedichloroplatinum (cisplatin) after repeated exposure to escalating doses of the drug. This resistant cell line (KFr) was 9.7-fold resistant to carboplatin (JM-8), 8.8-fold resistant to (glycolato-O, O') diammineplatinum (II) (254S), and 7.1-fold resistant to Cis-1, 1-cyclobutanedicarboxylato (2R)-2-methyl-1, 4-butanediammineplatinum (II) (NK121), respectively. The KFr cell line proved to be 3.1-fold resistant to L-phenylalanine mustard (L-PAM). On the other hand, no cross-resistance to vincristine (VCR), 5-fluorouracil (5-FU) and daunomycin (DM) was observed. In addition, we examined the level of platinum in whole cells after 1-16 h exposure to 20 micrograms cisplatin. The parent cell line (KF) took up cisplatin in a time-dependent manner until 4 h. The uptake reached the plateau level after 4 h. On the other hand, the uptake by the KFr cell line reached the plateau level at 1 h-exposure time; after 4 h the uptake was about 1/3 of that by the KF cell line. The release of cisplatin from both cell lines showed a similar pattern, reaching the plateau within the first 30 min. Based upon these results, we assumed that the impairment of transport of influx systems of cisplatin into cells was the mechanism of resistance.