Biomedical subjects
Publications and source records attributed to K Iida.
The rfb gene encoding the proteins responsible for the synthesis of the repeating units (O side-chain) of Escherichia coli 09 lipopolysaccharide was cloned into a conjugative plasmid RP4::miniMu and was expressed in E. coli K-12.
Extracts from uterine cervical and body cancers, but not from benign tumor or intact tissues tested, were found to contain a growth-promoting activity which induced the proliferation of human endometrial fibroblasts. Exposure of cultured fibroblasts to the cancer extracts increased the rate of [3H]thymidine incorporation in a dose-dependent manner. The activity was heat-labile, and not inactivated by removal of lipid-soluble material suggesting that the activity is associated with a protein. When the fibroblasts were preincubated with estradiol for 12 hours, but not for 1 hour, the extract-induced fibroblast proliferation was suppressed. The inhibitory effect of estradiol was dose related (EC50: 10nM) and non-competitive, suggesting that the steroid may reduce the sensitivity of fibroblasts to the extracts. This is the first report to provide direct evidence that estradiol may play an inhibitory role in the action of growth factor-like peptide produced from malignant tumors.
Syncytium formation in a rat tumor cell line (XC) induced by Suncus murinus mammary tumor virus (Sm-MTV) was studied. Multinucleate giant cells containing 20-30 nuclei were formed in a monolayer of XC cells by cocultivation with X-ray-irradiated Sm-MTV producing cells (Sm-MT-1). By fluorescent antibody staining. Sm-MTV antigens were demonstrated in the cytoplasm of syncytia, and budding particles and intracytoplasmic A particles were found in syncytial giant cells by electron microscopy. Cell-free supernatant of Sm-MT-1 was capable of inducing syncytia at a much lower incidence than cocultivation of Sm-MT-1 cells. Syncytium formation was completely inhibited when anti-Sm-MTV bovine serum was added to the coculture medium. Pretreatment of XC cells with actinomycin-D caused a partial reduction of Sm-MTV-induced cell fusion, but syncytium formation did occur at a reduced rate even when cellular RNA synthesis was completely inhibited. Dexamethasone increased virus production in Sm-MT-1 cells, resulting in the enhancement of Sm-MTV mediated syncytium formation. Sm-MTV was found to have a unique characteristic of cell fusion activity on XC cells with striking enhancement by dexamethasone.
Here we compare the properties of leukocyte antigens H19 and CD59 with those of the PI-linked 18,000-20,000 Mr molecules which inhibit lysis of human cells by the autologous terminal complement components C5b-9. H19, a 19,000 Mr protein found on human erythrocytes, monocytes, neutrophils, T-lymphocytes and other cells, is one of the ligands involved in the spontaneous rosette formation between human T-lymphocytes and erythrocytes. Recent evidence indicates that H19 also participates in T-cell activation. CD59 is a widely distributed 18,000-25,000 Mr protein anchored to the cell membrane by phosphatidylinositol (PI). The function of CD59 is unknown. Affinity-purified H19 incorporates into cell membranes and inhibits channel formation by human C5b-9 on guinea pig erythrocytes. Significant inhibition is achieved with picogram quantities of H19, corresponding to approximately 600 molecules per erythrocyte. H19 is most effective when C9 is limiting but quite active when C5b-7 or C8 are limiting, indicating that it may interact with several of the structurally related terminal complement components. The inhibitory activity is blocked by mAbs to either CD59 or to H19. H19 is PI-anchored: it is released from the cell membrane by treatment with PI-specific phospholipase C, and it is absent from cells from a patient with paroxysmal nocturnal hemoglobinuria (PNH). Analysis of PNH erythrocytes after treatment with terminal complement proteins shows that the H19-negative erythrocytes are more susceptible to C5b-9-mediated lysis. Treatment of normal human erythrocytes with either anti-H19 or anti-CD59 renders them more susceptible to lysis by human C5b-9. We conclude that H19 and CD59 are probably the same molecule and are identical or closely related to the recently described inhibitors of C5b-9 channel formation.
1. Phospholipases have been proposed to play a key role in sperm acrosome reaction. To examine the activation mechanism of phospholipases and subsequently sperm fertilizing capacity. Ca2+ fluxes and phospholipid turnover (breakdown and synthesis) were investigated in golden hamster spermatozoa during acrosome reaction. 2. Upon exposure of the spermatozoa to 1.7 mM Ca2+, a net uptake by the cells occurred in two distinguishable phases. 3. Depletion of extracellular Ca2+ by ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) at a time that an initial Ca2+ uptake was observed to reach almost steady-state, prevented the secondary Ca2+ uptake and acrosome reaction. 4. The time course of an initial Ca2+ uptake seemed to precede that of the acrosome reaction. 5. Incubation of the spermatozoa with Ca2+ in the presence of [3H]glycerol induced a rapid increase in labeling of phosphatidic acid, a key intermediate of phosphinositide turnover initiated by the action of phospholipase C, which appeared to parallel the time course of a first phase of Ca2+. 6. Phospholipase A2 activation, detected by lysophospholipid formation, slightly delayed the initial events of first Ca2+ uptake and phosphatidic acid production. 7. It is concluded that first Ca2+ entry into the cells, associated with phosphatidic acid production, activates a phospholipase A2, leading to the production of substances, like lysophospholipids and fatty acids, which may contribute to acrosome reaction.
1. Receptors for estradiol-17 beta (E2) and estriol (E3) were detected in the rabbit uterus. 2. Saturation analysis of estrogen binding sites in the cytosol showed that the dissociation constants of E2 and E3 for the high affinity binding sites were 1.8 +/- 0.5 nM and 2.3 +/- 0.3 nM, respectively, when dextran-coated charcoal was used to isolate free and bound ligands. 3. To eliminate non-specific (cross) bindings to their receptors, effects of unlabeled E2 and E3 on [3H]E3 and [3H]E2 bindings was examined. 4. [3H]E2 cytosol binding was observed to be specific for E2 and [3H]E3 cytosol binding was more specific for E3. 5. E2 priming to rabbits increased the binding sites for both E2 and E3, which was also more potent than E3 priming. 6. Moreover, the increase in E2 binding sites was greater than that in E3 binding sites. 7. These findings may suggest that there are separate binding sites for E2 and E3 in rabbit uterus and that synthesis of their binding sites is regulated by E2 but not E3.
1. Stimulated inositolphospholipid turnover has been proposed as a signal-transducing mechanism in many cell types. It appears to be initiated by stimulation of hydrolysis of inositolphospholipid by a phospholipase C. 2. In human endometrial fibroblasts, estradiol was observed to cause sequential enhancement of [32P]phosphate incorporation into phosphatidic acid (PA) and phosphatidylinositol (PI), indicating an accelerating effect of estradiol on inositolphospholipid turnover. Specific 32P-radioactivity in the gamma-phosphate of ATP was increased in response to estradiol. Estrone or estriol were without any effects. 3. To investigate possible mechanisms by which estradiol activates a phospholipase C enzyme in the fibroblasts, the plasma membrane fraction isolated from the fibroblasts was exposed to estradiol in the presence of guanosine triphosphate (GTP) to detect inositol trisphosphate (IP3) production. The IP3 production was Ca2+ dependent, a dependency not affected by estradiol. 4. However, ATP decreased the Ca2+ concentration required for IP3 production in a dose-dependent manner; adenosine diphosphate (ADP), cytidine triphosphate (CTP) showed no effects. 5. These findings from cell and cell-free systems might suggest that estradiol stimulates a phospholipase C, as a result of enhancement of intracellular ATP synthesis, but not as a result of a direct effect on the enzyme molecule or direct activation of receptor-phospholipase C unit. 6. This may give us new insight into estrogen-stimulated cellular phenomenon through some mechanisms other than that classically associated with the action of estrogen.
Healthy kangaroos are prone to sudden death. To investigate possible causes of this phenomenon, echocardiographic and electrocardiographic studies were conducted in seven healthy sedated (intramuscular ketamine 20 mg/kg, xylazine 2 mg/kg) kangaroos aged 1.5-5 years weighing 5.5-48 kg. As in human hypertrophic cardiomyopathy, kangaroos showed relative left ventricular hypertrophy measured as a ratio of (internal left ventricular end-diastolic diameter)/(septal + posterior wall thickness): 1.7 (SD 0.2) in kangaroos and 1.3 (SD 0.4) in hypertrophic cardiomyopathy cf 2.6 (SD 0.6) in normal man (p less than 0.001 respectively). Peak left ventricular diastolic filling velocity was smaller in kangaroos (2.6 (SD 0.3)/sec) and hypertrophic cardiomyopathy (3.3 (SD 0.7)/sec) than in normal man (4.1 (SD 1.0)/sec) (p less than 0.01, p less than 0.05). The end of T wave occurred earlier than the closing of aortic valve. Corrected QT interval (0.20 (SD 0.02) sec) was shorter than the normal value for man (0.34-0.40 sec). In conclusion, kangaroos have cardiac hypertrophy of unknown aetiology, with impaired diastolic function, as in non-obstructive hypertrophic cardiomyopathy patients. Corrected QT interval was short. These echocardiographic and electrocardiographic findings may explain the mechanism of sudden death in kangaroos, a species which may be used as an experimental model of non-obstructive hypertrophic cardiomyopathy in man.
The effects of ten 10-phenyl-[11]cytochalasins produced by Phomopsis sp. including novel compounds having 5,7- or 6,7-glycol structures and their derivatives, on the cell morphology and actin distribution in C3H-2K cells, as well as on lymphocyte capping and actin polymerization, were examined. The structure-activity relationship reported in the previous papers has been confirmed. The novel glycol type compounds showed little or no activity, suggesting the importance of the perhydroisoindol-1-one nucleus for the manifestation of the cytochalasin actions.
To investigate the clinical roles of mechanical and non-mechanical factors in hypertensive hypertrophy, 125 patients with essential hypertension, 20 with hypertrophic cardiomyopathy (HCM) and 20 with dilated cardiomyopathy (DCM), were studied using echocardiography. The hypertensive patients were separated into 3 groups: those with left ventricular (LV) hypertrophy (H), those without hypertrophy (H(-)) and those with dilatation (D). Group H patients were separated into 3 subgroups: those with subnormal LV end-systolic wall stress (ESS) (HI), those with normal ESS and mild hypertrophy (HIIA), and those with normal ESS and severe hypertrophy (HIIB). The inotropic response to isoproterenol infusion (0.02 microgram/kg/min for 5 min) was measured by the increase of fractional shortening (FS) corrected for the decrease of ESS (delta FS/delta ESS). After antihypertensive treatment for 4.4 +/- 1.7 years, echocardiography was repeated. delta FS/delta ESS was significantly larger in HI and HCM than in HIIA, was significantly larger in HIIA than in HIIB in which it was significantly larger than in D and DCM. After the treatment, LV mass decreased significantly except in HI. In conclusion, hypertensive hearts are regulated by mechanical and non-mechanical factors. Non-mechanical factors, for example the function of beta-adrenergic receptors in myocardium, have a variety of influences on myocardium, causing a broad spectrum of clinical features and courses.
To examine the effects of nipradilol on ischemic myocardium, experiments were performed on regional myocardial blood flow (MBF) and energy metabolism in anesthetized, open-chest dogs. Nipradilol at a dose of 0.3 mg/kg was i.v.-administered 10 min after coronary ligation. MBFs at various sites, including ischemic and non-ischemic areas, were determined by the hydrogen gas clearance method. The levels of ATP and creatine phosphate (CP) at the site of MBF determination were measured 60 min after ligation, and mitochondrial function (RCI, QO2) in the ischemic and non-ischemic areas was determined. Following nipradilol administration, aortic pressure and heart rate were significantly lowered. In ischemic areas with MBF below 40 ml/min/100 g, nipradilol had no influence on MBF. However, the tissue level of ATP in nipradilol treated hearts was significantly higher as compared with untreated hearts. In the area of mild ischemia with MBF of 40-60 ml/min/100 g, nipradilol preserved the tissue ATP and CP levels in spite of a decrease in MBF. Moreover, an inhibition of the decrease in mitochondrial respiratory function was observed in ischemic areas with MBF below 20 ml/min/100 g. Thus, nipradilol administered following ischemia preserved ATP content and mitochondrial function in the ischemic myocardium with reduction of heart rate and aortic pressure. This suggests that nipradilol exerts a cardioprotective effect in acute ischemia. It seems that the cardioprotective effect is due to a decrease in myocardial oxygen demand and preservation of mitochondrial function.
The purpose of this paper is to describe some fundamental physiological data in F 1 hybrids bred from a Mexican hairless dog and beagle cross. These F 1 hybrids numbered 5 hairless dogs and 12 haired dogs. The hematological profile of these offspring was assessed via an automated cell counter and compared with those of healthy beagles. In hairless dogs, red blood cell count, hemoglobin concentration and packed cell volume tended to be higher than in beagles. White cell distribution curves in hairless dogs and beagles yielded a single peak, while in haired dogs one or two peaks were present. Red blood cell and platelet distribution curves revealed few differences among the 3 kinds of dogs.
Explore the source record for details and available documents.
1. This study was designed to investigate the clomiphene or tamoxifen binding to receptor sites for estradiol-17 beta (E2R) and estriol (E3R) in the rabbit uterus. 2. Those so-called anti-estrogenic compounds tended to inhibit E2-E2R and E3-E3R bindings equally. 3. The inhibitor constant of clomiphene for E2R was approximately 3.8 x 10(-8) M at 4 degrees C and that for E3R approximately 1.8 x 10(-8) M at 4 degrees C in a given case, determined by charcoal assay. 4. It is suggested that the anti-estrogenic compounds demonstrate their effects after binding either to E2R or to E3R. 5. There were some tissue differences of the contents between E2R and E3R. For example, the uterus and the cortex contained E2R, and the pituitary E3R more than the other.
The clinical features of 20 patients with mildly dilated cardiomyopathy (MDCM) were investigated by electrocardiography and echocardiography. MDCM was defined as conditions with: 1) left ventricular end-diastolic dimension between 55 and 65 mm and 2) left ventricular fractional shortening between 10 and 25%. Nine patients (45%) had no histories of congestive heart failure. Eight patients had atrial fibrillation, and the other 12 patients were in regular sinus rhythm. Two patients had supraventricular premature contractions and five patients had ventricular premature contractions. One patient had paroxysmal atrial tachycardia. During the 40-months' span of this echocardiographic study, left ventricular end-diastolic dimension (60.8 +/- 3.8 mm to 57.3 +/- 4.6 mm) and left ventricular fractional shortening (17.2 +/- 4.6% to 22.7 +/- 7.1%) did not change significantly. One patient died suddenly. These results suggest that 1) some patients with MDCM have neither definite histories nor symptoms to suggest heart failure; 2) the hemodynamic conditions of patients with MDCM do not always deteriorate, but rather stabilize, and even improve during follow-up periods; 3) several types of arrhythmias can be observed, even in standard resting electrocardiograms; and 4) patients with MDCM may die suddenly.
Explore the source record for details and available documents.
Hypertensive cardiac hypertrophy of 20 patients was classified as inappropriate hypertrophy (HH-I) and appropriate hypertrophy (HH-II) according to their end-systolic wall stress, as measured by echocardiography. The differences in systolic and diastolic performances among the HH-I and HH-II subjects and 10 normal controls (NC) before and during isoproterenol infusion were investigated. Eight patients had subnormal end-systolic wall stress (inappropriate hypertrophy) and 12, normal end-systolic wall stress (appropriate hypertrophy). Before isoproterenol infusion, normalized peak rate of a change in left ventricular diameter during systole was significantly greater in HH-I (3.5 +/- 0.8/s) than in NC (2.3 +/- 0.5/s) and HH-II (2.6 +/- 0.6/s) (p less than 0.01 and p less than 0.005), but there was no significant difference between HH-II and NC. There was no significant difference in normalized peak rate of a change of left ventricular diameter during the rapid filling phase among the three groups (4.5 +/- 1.2/s in HH-I, 4.0 +/- 1.6/s in HH-II, and 4.2 +/- 0.8/s in NC). During isoproterenol infusion, normalized peak rate of a change of left ventricular diameter during systole was significantly greater in HH-I (7.0 +/- 1.9/s) than in HH-II (4.8 +/- 1.7/s) and NC (4.8 +/- 0.8/s) (p less than 0.05 and p less than 0.01, respectively), but there was no significant difference between HH-II and NC. Normalized peak rate of a change of left ventricular diameter during rapid filling was significantly less in HH-II (4.8 +/- 1.7/s) than in HH-I (7.3 +/- 1.3/s) and NC (6.5 +/- 0.8/s) (p less than 0.005 and p less than 0.005, respectively), but there was no significant difference between HH-I and NC. These results suggest that hypertensive patients with inappropriate hypertrophy have relatively diminished diastolic velocity (supernormal systolic velocity and normal diastolic velocity) before and during isoproterenol infusion, and that hypertensive patients with appropriate hypertrophy have absolutely diminished diastolic velocity during isoproterenol infusion, in spite of normal diastolic velocity before the infusion.
The clinical efficacy of LC9018, a biological response modifier prepared from heat-killed Lactobacillus casei YTT9018, used in combination with radiation was studied in a randomized controlled trial on 61 patients with carcinoma of the uterine cervix of Stage IIB or III. The combination therapy with LC9018 demonstrated a significant effect on tumor reduction, compared with radiation therapy alone, at the cumulative doses of 15-Gy and 30-Gy external irradiation (P less than 0.05). Histologic study confirmed that LC9018 also enhanced the therapeutic effect of the irradiation. Moreover, LC9018 seemed to be useful in protecting the patients from leukopenia during radiotherapy. This study suggests that LC9018, when used in combination with radiotherapy, will be an effective adjuvant immunotherapeutic agent. More studies in a large series of patients will, however, be needed to establish its long-term efficacy, safety, and effects on both prognosis and enhancing radiotherapy.