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Biomedical subjects

K Iida

Publications and source records attributed to K Iida.

At least 253 records · Page 14Linked to original sources

Membrane vesiculation protects erythrocytes from destruction by complement.

Nucleated cells can resist attack by C by exocytosis or endocytosis of the terminal C components C5b-9 (membrane attack complex) (MAC), but it is generally accepted that formation of a single MAC channel on E leads to lysis (one-hit theory). We find that human and guinea pig E, but not SRBC, can eliminate the MAC from the membrane in the form of microvesicles and escape destruction. When guinea pig or human E are incubated with C5b-9, vesiculation proceeds without a lag and is detected at nonlytic doses of C9. Continuous Ca2+ influx is required for vesiculation. The amount of released vesicles is in direct relation to Ca2+ concentration, and the increase in vesiculation is associated with a parallel decrease in lysis. SRBC, which do not vesiculate when Ca2+ loaded, are lysed by C5b-9 with the same efficiency in the presence or absence of Ca2+. Vesicles released from guinea pig RBC under C5b-9 attack are enriched in C9 by a factor of 10, compared with the unlysed cells, and by a factor of 3 to 4, compared with ghosts. We conclude that E are protected from lysis not only by CD59 and C8bp/HRF, which prevent MAC assembly, but also by selective elimination of the MAC.

Animals↗

Inhibition of actin polymerization by a synthetic dodecapeptide patterned on the sequence around the actin-binding site of cofilin.

Cofilin is an F-actin side-binding and -depolymerizing protein with an apparent molecular mass of 21 kDa. By means of the end label fingerprinting method, the amino acid residue on cofilin sequence cross-linked to actin by zero length cross-linker, 1-ethyl-3-(3-dimethylamino propyl)carbodiimide, was identified as Lys112 and/or Lys114. A synthetic dodecapeptide patterned on the sequence around the actin-cross-linking site of cofilin (Trp104-Met115) inhibited the binding of cofilin to actin. Moreover, the dodecapeptide was found to be a potent inhibitor of actin polymerization. Thus, we conclude that the dodecapeptide sequence constitutes the region essential for the actin-binding and -depolymerizing activity of cofilin. A sequence similar to the dodecapeptide is found in other actin-depolymerizing proteins, destrin, actin-depolymerizing factor, and depactin. Therefore, the dodecapeptide sequence may be a consensus sequence essential for actin-binding and -depolymerizing activity in actin-depolymerizing proteins.

Actin Depolymerizing Factors↗

Direct action of gonadotropin-releasing hormone (LH-RH) analogue on ovary: an alternative acting mechanism of buserelin.

The mechanisms by which gonadotropin-releasing hormone (LH-RH) analogue buserelin exerts direct action on the ovary was investigated. The analogue inhibited the luteinizing hormone (LH)-induced increase of steroidogenesis by rat ovarian granulosa cells in a dose-dependent manner. The LH-RH analogue did not alter binding capacity and affinity of 125I-LH to granulosa cells, suggesting the involvement of post-receptor mechanism. Likewise, the analogue caused inositol trisphosphate (IP3) formation as a result of stimulated inositol-phospholipid turnover. Half maximal effects of both steroidogenesis suppression and IP3 production occurred at 10 nM buserelin. These findings indicate that the inhibitory action of buserelin on granulosa cell function is mediated by IP3 (or calcium)-dependent mechanisms. Buserelin, in addition to its well-known action at pituitary level, exerts a direct inhibition of ovarian steroidogenesis at gonadal level without changes in gonadotropin receptors.

Animals↗

Treatment of an antenatally diagnosed fetal ovarian cyst by needle aspiration during the neonatal period.

An ultrasound scan revealed an ovarian cyst in the fetal lower abdomen at 29 weeks of gestation. Repeated examinations demonstrated that the cyst increased in size to 6.5 cm x 6.1 cm x 5.0 cm at 33 weeks of gestation, and the cyst showed no complications between 29 weeks of gestation and early infancy. The female infant was vaginally delivered at 41 weeks of gestation without any complications. Transabdominal needle aspiration of the cyst fluid was performed on the 14th day after birth. The concentrations of estrone, estradiol, estriol, and progesterone in the cyst fluid were almost the same as those in the infant's serum, while the concentration of pregnenolone was six times that in the infant's serum. Cytology of the cyst fluid was negative. The cyst thus seems to have been a non-functioning simple cyst of ovarian origin. Follow-up until the baby was one year old showed no recurrence of the cyst.

Adult↗

A study of ventricular contraction sequence in complete right bundle branch block by phase analysis.

Twenty-four patients with complete right bundle branch block (CRBBB) combined with and without left axis deviation (LAD) on ECG, were compared with 17 normal subjects to evaluate the right ventricular contraction sequence and pattern in detail. Blood pool scintigrams were obtained in the left anterior oblique projection, and these images were analyzed by first component Fourier harmonics. In the normal subjects, the phase value distribution representing the pattern of ventricular contraction was almost homogeneous in both the right and left ventricles (RV & LV). In the CRBBB patients without LAD, the phase images showed apparent phase delay in the right ventricle. In the CRBBB patients with LAD, the phase images showed many different contraction patterns varying from normal to RV phase delay, owing to the effects of the hemi-block. Quantitative analysis of the absolute values, showed that the mean (RV-LV) value was 6.6 +/- 8.4 msec in the normal subjects. In the CRBBB patients without LAD, the duration of the QRS complex correlated with the mean (RV-LV) value, whereas no difference was observed between the duration of the QRS complex and the standard deviation of the right ventricle. Using phase analysis the degree of the RBBB can be determined from the phase images, and can be quantitatively analyzed as in electrical studies.

Adult↗

Estriol binding in uterine corpus cancer and in normal uterine tissues.

1. The specific bindings of estriol (E3) and estradiol-17 beta (E2) to their specific receptors were investigated in endometrial carcinoma from 7 patients and normal tissues from their respective organs or from other patients. 2. In both cytosolic and KCl-extracted fractions from them, specific binding sites for E3 and E2 were detected, demonstrating the presence of their separate receptors in human uterus-associated tissues. 3. In certain cases (6 cases) of well-differentiated adenocarcinoma, the ratio of concentration of E3 receptor to that of E2 receptor was almost equal to or higher than in other normal tissues. 4. These findings of unique localization of E3 receptor distribution may offer new insight into identification of endometrial carcinoma more likely to respond to hormonal influence or therapy.

Adenocarcinoma↗

Stimulatory effects of estrogen on gonadotropin-releasing hormone-induced phosphoinositide turnover in granulosa cells.

Gonadotropin-releasing hormone (Gn-RH) stimulates phosphoinositide metabolism in granulosa cells by binding to its specific receptor, and suppresses gonadotropin-induced steroidogenesis. Incubation of immature rat granulosa cells with Gn-RH stimulated time-sequential [32P]phosphate incorporation into phosphatidic acid (PA) and phosphatidylinositol (PI) in a dose-dependent manner; EC50 was at 10 nM. Concurrent exposure to estradiol-17 beta (E2) (100 nM) and Gn-RH (1 microM) augmented 32P-labeling of PI by 5-fold, while Gn-RH alone induced 3.5-fold increase in PI-labeling. In cells preincubated with E2 for 48 h, Gn-RH provoked a 7-fold [32P]phosphate incorporation into PI, suggesting the induction by E2 of Gn-RH-responsible phosphoinositide turnover. E2 alone provoked a low but significant increase in basal labeling rate of PA and PI. Progesterone failed to mimic the action of E2. Essentially similar results were also obtained in mature rat granulosa cells. These results indicate that E2 augments Gn-RH-stimulated phospholipid turnover in granulosa cells, and suggest that estrogens within the microenvironment of the ovary may exert a local autoregulatory effect on their own production pathway through accelerating Gn-RH action to attenuate steroidogenesis.

Animals↗

Direct monitoring by carbon-13 nuclear magnetic resonance spectroscopy of the metabolism and metabolic rate of 13C-labeled compounds in vivo.

Carbon-13 nuclear magnetic resonance spectroscopy has been used to observe the transformations of [1-13C]-D-glucose to [1,1'-13C2]-D-trehalose, and [3-13C]-L-alanine to [2-13C]-L-glutamic acid in the living body of Gryllodes sigillatus. [3-13C]-D-Alanine was not metabolized. The metabolic rate of [1-13C]-D-glucose was found to be altered by prior injection of boric acid.

Alanine↗

Isolation of a new antitumor substance from Bacillus stearothermophilus.

A new antitumor substance, BS-1, was isolated from the autolysate and culture filtrate of Bacillus stearothermophilus UK563 by ethylacetate extraction and HPLC. BS-1 inhibited the proliferation of mouse macrophage-like cells, P388-D1 (IC50: 4 micrograms/ml) and mouse mastocytoma, P-815 (IC50: 0.6 microgram/ml), but not that of Balb/c 3T3.

Animals↗

Isolation and characterization of a 92-KD surface molecule of Trypanosoma cruzi amastigotes recognized by a monoclonal antibody that induces complement-mediated killing.

The presence of lytic antibodies in the circulation of patients with chronic Chagas' disease might lead to their cure. It has been shown that amastigotes of Trypanosoma cruzi activate complement and accumulate large amounts of the terminal complement components, but without killing the parasites. One plausible explanation for this observation is that the insertion of the membrane attack complex of complement is prevented by inhibitors present in the parasite membrane. To explore this possibility, we raised a panel of monoclonal antibodies (MAbs) against the surface molecules of T. cruzi amastigotes. One of these, MAb M4C12, induced complement-mediated lysis of amastigotes as detected with a 86Rb-release assay. The antigen molecule from the membrane lysate of amastigotes that was recognized by MAb M4C12 was purified, characterized, and designated M4C12Ag. It is a 92-kD molecule structurally related to Ssp4, a previously characterized amastigote surface molecule. However, M4C12Ag is more basic (pI 6.9-7.1) than Ssp4 (pI 5.2-6.0), and is larger (92 kD) than Ssp4 (70 kD and 84 kD). Purified M4C12Ag did not inhibit the terminal components of complement when tested in hemolytic assays. This molecule may not be an inhibitor of complement, yet it is certainly an amastigote-specific surface molecule with immunologic importance because it is the only molecule that could induce formation of a lytic antibody.

Animals↗

[Effects of aging on right and left ventricular function in patients with right bundle branch block].

The effect of aging on cardiac function in patients with right bundle branch block (RBBB) was commonly unknown, so left ventricular function and right ventricular function were investigated, using first-pass radionuclide angiography. Twenty-six patients with RBBB and 28 normal subjects were studied at rest and during bicycle exercise. Patients with RBBB but normal cardiovascular systems aged 33 to 75 years were divided into those within 60 years (n = 17) and those over 65 years (n = 9). Using the same method, normal subjects aged 38 to 83 years were divided into those within 60 years (n = 18) and those over 65 years (n = 10). Mean age between normal subjects and patients with RBBB didn't differ significantly. The response of left ventricular ejection fraction in normal groups rose during exercise, but its exercise tolerance function declined with aging. Left ventricular diastolic filling in normal groups declined at rest and during exercise with aging. Left ventricular function in RBBB groups showed the same results as those of normal groups. The response of right ventricular ejection fraction and its exercise tolerance function in normal groups was not influenced by aging. However, in contrast, right ventricular function in RBBB groups decreased with aging. We suggest that the mechanism of decrease of right ventricular function in aging patients with RBBB may be caused by the change of right ventricular contraction which is affected by the aging process.

Adult↗

[Cervical lung hernia in a case of severe chronic asthma and bronchitis].

A case of a bilateral pulmonary hernia of the lungs into the supraclavicular fossae is described. A man, aged 79, with severe chronic asthma and chronic bronchitis due to air pollution, complained of a cervical mass off and on for several years. The herniation was greater on the right side. It could be identified on physical examination by the presence of a soft painless supraclavicular bulge which was exaggerated by strain or cough. Radiologically this herniation could best be identified on lateral cervical roentgenogram. It is said that cervical lung hernia is a rare condition, but in our experience supraclavicular herniation of the lung is not unusual in cases of severe chronic obstructive lung disease.

Aged↗

Inhibition of the interactions of cofilin, destrin, and deoxyribonuclease I with actin by phosphoinositides.

Cofilin is a widely distributed actin-modulating protein that has the ability to bind along the side of F-actin and to depolymerize F-actin in a pH-dependent manner. We found that phosphatidylinositol (PI), phosphatidylinositol 4-monophosphate (PIP), and phosphatidylinositol 4,5-bisphosphate (PIP2) inhibited both actions of cofilin in a dose-dependent manner, while inositol 1,4,5-triphosphate (IP3), 1-oleoyl-2-acetylglycerol (OAG), phosphatidylserine (PS), or phosphatidylcholine (PC) had little or no effect on them. Gel filtration analyses showed that PIP2 bound to cofilin and thereby inhibited the binding of cofilin to G-actin. Destrin is a mammalian, pH-independent actin-depolymerizing protein. The actin-depolymerizing activity of destrin was also inhibited by PI, PIP, and PIP2, but not by IP3, OAG, PS, or PC. In addition, we found further that an actin-depolymerizing activity of bovine pancreas deoxyribonuclease I, a G-actin-sequestering protein, was inhibited by PIP and PIP2, but not by PI, IP3, OAG, PS, or PC. These results together with previous findings (Lassing, I., and Lindberg, U. (1985) Nature 314, 472-474; Janmey, P. A., and Stossel, T. P. (1987) Nature 325, 362-364) suggest that the sensitivity to polyphosphoinositides may be a common feature in vitro among actin-binding proteins that can bind to G-actin and regulate the state of actin polymerization.

Actin Depolymerizing Factors↗

Mechanisms of stress-induced ST elevation and negative T-wave normalization studied by serial cardiokymogram in patients with a previous myocardial infarction.

Seventeen patients with a previous myocardial infarction were studied during pacing to characterize the clinical correlates of ST elevation, to analyze the relation between ST elevation and negative T-wave normalization and to investigate the mechanism of these electrocardiographic changes. Myocardial ischemia was evaluated by measurement of blood lactate, and wall motion was analyzed using cardiokymographs concurrently and serially. Results show that ST elevation and negative T-wave normalization were most marked in leads containing abnormal Q waves, that ST elevation greater than or equal to 1 mm during pacing was associated with a significant increase in left ventricular end-diastolic pressure and deterioration of left ventricular wall motion and that the magnitude of ST elevation and negative T-wave normalization was significantly correlated, but the latter appeared earlier and more markedly. In addition, there was no significant correlation between the extent of either ST elevation or negative T-wave normalization and myocardial lactate production. Thus, ST elevation and negative T-wave normalization are caused by abnormal left ventricular wall motion rather than myocardial ischemia. Negative T-wave normalization is a more sensitive marker of abnormal wall motion than ST elevation in patients with a previous myocardial infarction.

Cardiac Pacing, Artificial↗

Destrin, a mammalian actin-depolymerizing protein, is closely related to cofilin. Cloning and expression of porcine brain destrin cDNA.

Destrin is a mammalian 19-kDa protein that rapidly depolymerizes F-actin in a stoichiometric manner. In this study, we isolated cDNA clones coding for destrin from a porcine brain cDNA library. The deduced amino acid sequence of destrin is 165 residues long and is very similar (71% identical) to that of cofilin, a widely distributed, pH-sensitive actin-modulating protein. Destrin contains a sequence nearly identical with the putative nuclear transport signal sequence of cofilin and a hexapeptide sequence identical with the amino-terminal sequence (residues 2-7) of tropomyosin, which is shown to be involved in cofilin binding to actin. Destrin, like cofilin, also has in its carboxyl-terminal portion a region homologous to the sequence shared by gelsolin, fragmin, and Acanthamoeba profilin. We have expressed destrin as well as cofilin in Escherichia coli, purified them, and examined their function in vitro. The two proteins were found to differ in their interaction with actin, like destrin and cofilin isolated from porcine brain. This suggests that the difference in the function of the two proteins results from the subtle difference in their amino acid sequence rather than possible differences in post-translational modifications. Northern blot analyses indicated that both destrin mRNA and cofilin mRNA are widely distributed in various tissues, but both mRNAs differ in their relative abundance among tissues.

Acanthamoeba↗

Cardiac determinants of regression of left ventricular hypertrophy in essential hypertension with antihypertensive treatment.

To study the cardiac determinants of regression of left ventricular hypertrophy in hypertension, left ventricular mass, fractional shortening and end-systolic wall stress were measured echocardiographically in 36 patients with essential hypertension and left ventricular hypertrophy. The patients were classified into two groups. Group I consisted of 15 patients with subnormal end-systolic wall stress, and Group II consisted of 21 patients with normal end-systolic wall stress. There were no significant differences between groups in systolic or diastolic blood pressure. After treatment for 4.4 +/- 1.7 years, echocardiographic studies were repeated. There were no significant differences between groups in the duration of the follow-up period and the kinds of antihypertensive drugs. After treatment, blood pressure decreased significantly in both groups (p less than 0.001 for both), with no significant difference between groups. Left ventricular mass increased significantly in Group I (from 331 +/- 7 to 363 +/- 24 g, mean +/- SEM, p less than 0.05), whereas it decreased significantly in Group II (from 318 +/- 16 to 268 +/- 17 g, p less than 0.001). Myocardial contractility (the relation between end-systolic wall stress and fractional shortening) remained almost the same as before treatment. In conclusion, in patients with hypertensive ventricular hypertrophy with subnormal end-systolic wall stress (inappropriate hypertrophy, probably induced by a neurohumoral factor), a decrease in blood pressure with antihypertensive treatment does not lead to regression of left ventricular hypertrophy, but rather to an increase in left ventricular mass.(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive Agents↗

Diurnal change of giant negative T wave in patients with hypertrophic cardiomyopathy.

To examine the diurnal change of negative T wave (deeper than 10 mm in precordial leads) in apical hypertrophic cardiomyopathy and the mechanism of giant negative T wave, 24-h ambulatory electrocardiographic monitoring was performed in 8 patients with apical hypertrophic cardiomyopathy, and effect of atropine on electrocardiogram was studied. The mean depth of negative T wave at 1, 2, and 3 P.M. was 9.3 +/- 3.0 mm, and that at 1, 2, and 3 A.M. was 12.6 +/- 4.8 mm. The mean R-R interval at 1, 2, and 3 P.M. was 792 +/- 113 ms and that at 1, 2, and 3 A.M. was 1055 +/- 94 ms. In seven patients (88%), negative T wave was deeper during the night than during the daytime. There was a positive correlation between R-R interval and depth of negative T wave in 6 patients (75%). Despite significant shortening of R-R interval (879 +/- 116 to 804 +/- 110 ms, p less than 0.05), atropine did not significantly change the depth of negative T wave (14 +/- 5 to 14 +/- 5 mm). In conclusion, negative T wave is not fixed, but is variable, diurnally, probably due to the change of sympathetic tone.

Aged↗