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Biomedical subjects

Y Yokota

Publications and source records attributed to Y Yokota.

At least 19 recordsLinked to original sources

Properties of plasma membrane-induced amylase release from rat parotid secretory granules: effects of Ca2+ and Mg-ATP.

A secretory granular fraction (SG) and a plasma membrane rich fraction (PM) have been isolated from rat parotid gland by differential and Percoll gradient centrifugation. With these two fractions, a cell-free interaction system has been reconstituted to clarify the exocytotic interaction between the secretory granules and plasma membranes, and the conditions of amylase release from SG have been characterized in vitro. The addition of PM into this assay system induced a rapid and transient release of amylase from SG. Some other membranes such as erythrocyte ghosts also mimicked the effect of PM. This release was increased by Ca2+, but was not completely blocked by EGTA. Simultaneous addition of 1 mM ATP with 1 mM MgCl2 (Mg-ATP) in the presence of Ca2+ reduced this release. However, in spite of the existence of Mg-ATP, the stimulation of PM-induced amylase release was caused by Ca2+ in a concentration-dependent manner (10(-7)-10(-3) M). These results suggest that Ca2+ and Mg-ATP should participate as important regulators in the exocytotic interaction between secretory granules and plasma membranes in this system. Furthermore, the differences between our system and intact cells are also discussed.

Adenosine Triphosphate

Delineation of structural domains involved in the subtype specificity of tachykinin receptors through chimeric formation of substance P/substance K receptors.

The mammalian tachykinin receptors belong to the family of G protein-coupled receptors and consist of the substance P, substance K and neuromedin K receptors (SPR, SKR and NKR). We constructed 14 chimeric receptors in which seven transmembrane segments were sequentially exchanged between the rat SPR and SKR and examined the subtype specificity of the chimeric receptors by radioligand binding and inositol phosphate measurements after transfection into COS cells. All chimeric receptors showed maximum responses in agonist-induced inositol phosphate stimulation. Detailed analysis of five receptors with agonist selectivity similar to SPR indicated that the selectivity is mainly determined by the region extending from transmembrane segment II to the second extracellular loop together with a minor contribution of the extracellular N-terminal portion. This conclusion was more directly confirmed by an additional chimeric formation in which the introduction of the above middle portion of SPR into the corresponding region of SKR conferred a high affinity binding to substance P. The tachykinin receptors can thus be divided into two functional domains: the region covering transmembrane segments V-VII and responsible for fundamental recognition of the common tachykinin sequence; and its preceding portion involved in evoking subtype specificity by interacting with the divergent sequences of the peptides.

Animals

T-independent polyclonal activation of B cells in vitro by immunoglobulin binding substance (IBS) from the granary weevil.

Experiments are described for T-independent polyclonal activation of B cells in vitro by the immunoglobulin binding substance (IBS) from the granary weevil. The affinity-chromatographically purified IBS was used. IBS is a heat-, alkali- and acid-stable glucopeptide which is characterized by non-specific immunoglobulin binding to the Fab fragment. The purified IBS consists of three polymer homologues whose molecular weights are 12-14,000, 25-30,000 and more than 150,000 Da. IBS did not stimulate DNA synthesis by murine T cells, macrophages or plasma cells whereas it did stimulate that by mature B cells without any help from T cells or macrophages. IBS also stimulated both in vitro IgG production by spleen cells and in vitro sensitization of spleen cells by sheep red cells (SRBC). IBS was found to stimulate DNA synthesis by B cells mediated by binding to surface immunoglobulins of B cells. IBS is thought to be a useful amplifier for inducing human hybridomas and a valuable tool for examining mature B cells, both diagnostically and experimentally.

Animals

Ontogenic expression of somatostatin-messenger RNA in the intestinal tract of neonatal rats.

Ontogenic expression of somatostatin (SRIF) -messenger RNA (mRNA) in the gastrointestinal tract was examined in neonatal rats aged from 1 day preterm to 60 days postpartum in comparison with that in the hypothalamus. SRIF-mRNA in the hypothalamus was already expressed in prenatal rats and its developmental change was relatively small. In contrast, a unique pattern of SRIF-mRNA expression was seen in the different intestinal regions, gastric antrum, duodenum, jejunum and colon. In the duodenum, SRIF-mRNA level was low at birth, markedly increased during the postnatal 3 days and declined to the previous level by day 21. Jejunal SRIF-mRNA was found in neonates but progressively decreased in a similar way to duodenum. On the contrary, gastric SRIF-mRNA level, which was low during early development, rose rapidly to a peak on day 21 and gradually declined to an adult level. In the colon age-related change was not conspicuous, remaining at a low level. These results indicate that (1) expression of SRIF gene in the intestinal tract is regulated by local factor(s) as well as developmental stage, and (2) shift of SRIF-mRNA pattern occurs during weaning from the duodenum-dominant infantile pattern to the gastric-dominant adult pattern.

Age Factors

Antibacterial activity of cefixime against Streptococcus pneumoniae, Streptococcus pyogenes, and Haemophilus influenzae in the presence of Moraxella (Branhamella) catarrhalis.

We measured the sizes of the inhibition zones of oral beta-lactam antibiotics for Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae in the presence of beta-lactamase-producing-Moraxella (Branhamella) catarrhalis by the agar double-layer method. The sizes of the zones of amoxicillin for S. pneumoniae alone were the largest, followed in a descending order by those of cefixime and cefaclor. In the presence of 10(7) CFU/ml of M.(B.) catarrhalis, however, significant reduction of the sizes of the zones was seen with amoxicillin and cefaclor; inhibition with cefixime was nearly unchanged. Similar results were observed in those for S. pyogenes. These variable findings were attributed to the difference in stability of these drugs to the beta-lactamase produced by M.(B.) catarrhalis. When the susceptibility of H. influenzae in the presence of 10(8) CFU/ml of M.(B.) catarrhalis to cefixime, cefoteram, cefpodoxime, cefotiam and cefuroxime was examined, the sizes of the inhibition zones of all the drugs were reduced by the presence of 10(8) CFU/ml of M.(B.) catarrhalis, but those of cefixime were the largest of all the drugs tested. Our agar double-layer method is simple and useful for evaluating the influence of beta-lactamase-producing organism, as M.(B.) catarrhalis, on the disk susceptibility of other pathogens to antibiotics.

Cefixime

Effects of long-term beta-blockade therapy in patients with dilated cardiomyopathy--serial clinical and echocardiographic observations.

Twenty-three patients with dilated cardiomyopathy (DCM) were treated with metoprolol and their clinical courses compared with those of 26 patients untreated with beta-blocking agents (non beta group). Of the 23 patients treated with metoprolol, 20 (beta group) were treated for 6 months or longer, while the remaining 3 patients were intolerant of the drug and suffered aggravation of heart failure. In the beta group, 2 deaths occurred, while of the remaining 18 patients 4 were considered clinically improved in NYHA class 6 or 12 months later, and none suffered clinical deterioration during the follow-up period. In the non-beta group, clinical improvement was found in 2 patients and deterioration of functional class in 10. Heart rate and pressure rate product were significantly decreased by 1 month after the treatment with metoprolol. At that time, blood pressures, systolic and diastolic left ventricular dimensions, indices of systolic function (% FS, mVcf) and exercise capacity had not changed, while cardiac output was decreased and systemic peripheral vascular resistance was significantly increased. In the beta group, significant improvements in left ventricular dimensions, systolic function and exercise tolerance were delayed and observed within 3 to 6 months during the follow-up period, while no such improvements occurred in patients of the non-beta group. During the follow-up period, 2 patients of the beta group and 10 patients of the non-beta group died. The survival curve for patients of the beta group, prepared using the Kaplan Meier's Method, was better than that for patients of the non-beta group. Metoprolol was therefore found to be useful for treatment of DCM.

Adult

Protective effects of immunoactive peptide, FK565 against systemic and local infections with herpes simplex virus and murine cytomegalovirus and respiratory tract infection with influenza virus in mice.

The protective effects of FK565 against systemic infections with herpes simplex virus (HSV) and murine cytomegalovirus (MCMV), respiratory tract infection with influenza virus and zosteriform rash with HSV investigated in mice. FK565 showed excellent protective activities against systemic infections with both acyclovir (ACV)-sensitive and -resistant HSV at intravenous and subcutaneous doses of 0.1 and 1 mg/kg and oral dose of 1 mg/kg. FK565 showed superior protective activities at subcutaneous doses of 0.01 and 0.1 mg/kg compared to ACV at subcutaneous dose of 15 mg/kg against MCMV infection. In respiratory tract infection with influenza virus, FK565 showed potent protective effects at intravenous, subcutaneous and oral doses of 0.001 to 1 mg/kg. FK565 markedly inhibited zosteriform spread of HSV on the flank skin at an intravenous dose of 0.1 mg/kg and the mice given FK565 survived longer than the control mice. The peritoneal exudate cells from FK565-treated mice suppressed the growth of HSV in mouse embryo fibroblast more strongly than those from the control mice, although FK565 had no direct antiviral activity against HSV. These findings suggest that FK565 enhanced the host defense ability against viral infections by nonspecific activation of macrophages.

Animals

[Left atrial ejection performance in heart failure as assessed by transesophageal Doppler echocardiography].

To investigate the left atrial ejection performance in heart failure, we observed both the transmitral (TMF) and pulmonary venous flow waves (PVF) by transesophageal Doppler echocardiography in 20 patients with heart failure (16 males, 4 females, 56 +/- 13 years old). In 7 of 20 patients, pulmonary capillary wedge pressures (PC) were also obtained within 72 hours after the transesophageal Doppler echocardiographic examinations. A reversal flow on PVF during atrial systole (atrial backward ejection flow) was observed in all of the 20 patients. Corrected atrial pre-ejection period correlated significantly with PC (r = -0.76, p < 0.05), indicating that the period was shortened in accordance with left atrial Starling's law. This period correlated significantly with both the duration and the time velocity integral of atrial backward flow (r = -0.72, p < 0.005; r = -0.55, p < 0.05, respectively), but not with the atrial ejection time nor with the time velocity integral of atrial systole. These results suggest that in some cases of heart failure, left atrial contractile function is preserved despite the marked augmentation of left atrial afterload, resulting in a decrease of the left atrial forward ejection and an increase of the left atrial backward ejection. Thus, the observations of TMF and PVF by transesophageal Doppler echocardiography are useful for assessing the left atrial ejection performance in patients with heart failure.

Adult

[Clinical features of latent dilated cardiomyopathy].

To identify the evidence of presymptomatic manifestations of dilated cardiomyopathy (DCM), we studied 30 patients with latent DCM (mean 37 +/- 14 years) who satisfied the following criteria: 1) left ventricular (LV) systolic function was slightly reduced; 2) LV end-diastolic dimension (< 54 mm) and coronary arteries were normal. The incidence of ECG abnormalities was relatively high; nonspecific ST-T changes were the most common (90%). The incidence of grade 3 or 4 ventricular premature contractions according to Lown's classification on 24 hour ambulatory ECGs was 50%. Perfusion defects were observed in 83% on the thallium-201 images. Right ventricular biopsy showed that the interstitial fibrosis was milder (9 +/- 9%) in the study subjects than in 32 patients with DCM (17 +/- 8%) who were treated in our hospital, but there were no significant differences in the diameters of the myofibers (15 +/- 4 vs 17 +/- 4 microns) between the 2 groups. During the follow-up study, deterioration of LV dysfunction was observed in 3 patients. One patient died suddenly. These findings proved the importance of the early detection and characterization of latent state of DCM.

Adult

[Clinical and echocardiographic evaluation of the effects of atrial defibrillation in patients with idiopathic cardiomyopathy].

To elucidate the effects of atrial defibrillation in patients with idiopathic cardiomyopathy, we clinically and echocardiographically assessed 6 patients with hypertrophic cardiomyopathy (HCM) and 7 patients with dilated cardiomyopathy (DCM). Their mean age was 57 +/- 14 years and the mean duration of their atrial fibrillation (Af) was 47 +/- 29 days. There were no differences in age and the duration of Af between the HCM and DCM groups. We assessed the effects of defibrillation on the NYHA functional classification, heart rate (HR), systolic blood pressure (S-BP), M-mode echocardiographic data (LVDd, LVDs, %FS, LAD) and transmitral pulsed Doppler echocardiographic findings (peak velocity, time-velocity integral of rapid and atrial filling waves). These indices were obtained before and 52 +/- 22 days after defibrillation, and were compared with each other. 1. HR decreased (HCM: 87 +/- 16-->58 +/- 7/min, DCM: 93 +/- 19-->70 +/- 14/min) and total left ventricular filling increased (HCM: 6 +/- 1-->11 +/- 4 cm, DCM: 6 +/- 1-->10 +/- 2 cm) after defibrillation, and the increment of %FS (HCM: 36 +/- 6-->41 +/- 6%, DCM: 16 +/- 6-->25 +/- 11%) was observed. Four of 6 HCM patients and 5 of 7 DCM patients also improved with regard to the NYHA classification. 2. After defibrillation, LVDd increased in HCM (42 +/- 4-->47 +/- 4 mm), but not in DCM. However, LVDs decreased in DCM (52 +/- 9-->44 +/- 12 mm), but not in HCM. We concluded that atrial defibrillation had a beneficial effect on the recovery of the left ventricular function both in HCM and DCM due to the reduction in HR and increase in left ventricular filling. The mode of LV functional improvement after defibrillation varied depending on the state of patient's basal pathophysiology .

Adult

[A successful two-staged Fontan procedure for tricuspid atresia with bilateral superior venae cavae and left pulmonary arterial stenosis].

A 10-year-old boy with tricuspid atresia (type I-b), bilateral superior venae cavae and left pulmonary arterial branch stenosis was treated successfully by a two-staged Fontan procedure. At 7 years of age, left Glenn shunt was performed after creation of a communicating vessel between the right and left superior vena cava, using a GORE-TEX graft of 10 mm of diameter. Three years later, after having confirmed graft patency, Fontan procedure was achieved without any problems. We think the innominate vein creation by an artificial material was a key design for the following successful two-staged Fontan procedure in this case.

Blood Vessel Prosthesis

[Long-term effect of medical treatment in patients with chronic aortic regurgitation].

We often experience patients with chronic severe aortic regurgitation (AR) whose cardiac function significantly improves by medications, especially by vasodilator therapy. To find the factors determining the response to pharmacologic treatment, we studied 20 patients with chronic AR with dilated left ventricle (end-diastolic dimension > or = 55 mm) using echocardiography; 9 patients with significant improvement (delta Ds < or = -3 mm: improved group) and 11 without improvement (unchanged group). In the initial evaluation, systolic blood pressure and left ventricular relative wall thickness (Thd/Dd) were greater and left ventricular end-diastolic dimension was smaller in the improved group than in the unchanged group. During the follow-up period, systolic blood pressure and end-systolic wall stress decreased significantly and absolute and relative wall thickness increased significantly in the improved group, however, they remained nearly the same in the unchanged group. Significant negative correlation was observed between Thd/Dd and delta Ds. In conclusion, cardiac function in some patients with chronic AR can be improved by pharmacologic treatment, and in such cases, the Thd/Dd ratio could be a parameter of the response to pharmacologic treatment.

Adult

[Augmentation of left ventricular slow filling in hypertrophic cardiomyopathy].

To investigate the significance of augmentation of left ventricular slow filling, trans-mitral flow (TMF) was echocardiographically observed through pulsed Doppler method in 116 patients with hypertrophic cardiomyopathy (HCM), 74 with dilated cardiomyopathy (DCM), 27 with mitral regurgitation (MR), 86 with old myocardial infarction (OMI) and 80 normal controls (C). The slow filling-wave (SFW) in TMF was defined as the filling wave with obvious peak velocity during slow filling phase. The peak velocities (E, A, S) of the early filling, the atrial contraction and the slow filling waves were measured. The SFW was divided into two patterns according to the S and E ratio: large SFW (S/E greater than or equal to 1/2) and small SFW (S/E less than 1/2). 1) The small SFW was more frequently, but not significantly, observed patients with MR (37%) than in normal subjects (18%), patients with HCM (10%), DCM (4%) and OMI (7%). However large SFW was observed in 16 patients (14%) with HCM, but not in normal subjects and patients with other cardiac diseases excluding one patient with DCM. 2) In normal subjects and patients with DCM, OMI and MR, those with small SFW had larger E and smaller A/E than those without small SFW. However in patients with HCM, there was no difference in these indices (E and A/E) according to whether the patients were with or without SFW. 3) In HCM, patients with large SFW had significantly smaller E and significantly larger isovolumic relaxation time than those without SFW. Thus, appearance of the large slow filling wave, which might be caused by abnormal relaxation of the left ventricle, was frequently observed in patients with HCM.

Adult

A comparison of the perceived and the ECG measured heart rate during cycle ergometer, treadmill and stairmill exercise before and after perceived heart rate training.

The ability to perceive exercise heart rate before and after training was tested in six young male university students, perceptions of heart rate being compared with ECG monitored heart rates during cycle ergometry, treadmill running and stairmill climbing. Between initial and final tests, subjects undertook 13 weeks of running training (2 h/day, 3-4 days/week), and during this period they compared their perceptions of heart rate with values observed on watch-type wrist-mounted pulse monitors. Individual initial perceptions showed only a moderate correlation with ECG values. This correspondence was improved as perceptions were compared with measured heart rates over the course of training, significantly so for the mode of exercise most similar to that adopted in the training sessions (treadmill running at a heart rate of 140 beats/min). The final accuracy of perceptions at a heart rate of 140 beats/min (error 8-9 beats/min during treadmill running) compared favourably with the accuracy of either pulse counting or the traditional rating of perceived exertion as commonly observed in the exercising public. This suggests that there may be an application for perceived heart rates in regulating the intensity of prescribed exercise.

Adult

In vitro closing behavior of the St. Jude Medical heart valve in the pulmonary position. Valve incompetence originating in the prosthesis itself.

We examined the in vitro closing behavior of the St. Jude Medical heart valve, simulating (1) a low-pressure system, (2) the anatomic peculiarity of the right ventricular outflow tract and the main pulmonary artery, and (3) disturbed diastolic compliance of the right ventricle. The variables in the experiment were the load impedance to the pump and the valve orientation. The results were as follows. The sequence of closure of the two semidiscs was based on the valve orientation; reduction in impedance caused the semidisc that closed last to remain open, while the other semidisc continued its open-close motion; further reduction in impedance prevented the semidisc, which continued its open-close motion, from closing completely. These results highlight the forces involved in semidisc closure and the existence of a threshold of force for completion of semidisc closure. Further, the results demonstrate that under certain circumstances the threshold cannot be exceeded via those forces. Therefore this incompetence must originate in the prosthesis itself. In this regard, we suggest an urgent need to reconsider the indications for St. Jude Medical heart valve pulmonic implantation. Finally, we advocate the necessity for an in vitro assessment of valve prostheses in a low-pressure system, to evaluate the safety of right-sided placement.

Evaluation Studies as Topic