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Biomedical subjects

Y Takeuchi

Publications and source records attributed to Y Takeuchi.

At least 55 records · Page 3Linked to original sources

Elevated circulating levels of tumor necrosis factor in patients with mitral valve disease and ventricular septum defect.

Elevated levels of circulating tumor necrosis factor (TNF)-alpha have been reported in patients with decreased left ventricular ejection fraction. Also, TNF has been reported to depress myocardial contractility. In our previous study, no correlation was found between the plasma level of TNF and clinical parameters in patients with cardiomyopathy. In the present study, we detected elevated levels of circulating TNF-alpha in 5 out of 15 patients with mitral valve disease and in 1 patient with ventricular septal defect whose left ventricular ejection fraction was within the normal range. The levels of TNF-alpha were not correlated with any hemodynamic parameters. Further studies are necessary to clarify the mechanisms of the regulation and effects of TNF-alpha in patients with chronic heart failure.

Adult

A mathematical model for drug administration by using the phagocytosis of red blood cells.

A mathematical model for the delivery of drug directly to the macrophages by using the phagocytosis of senescent red blood cells is proposed. The model is based on the following assumption: At time t = 0 a preassigned red blood cell population n(0,a) = phi (a), a > 0, loaded by the drug, is injected in the blood circulation. Among the cells of that population only those with an age a > or = a (a = 120 days) will be phagocytosed by macrophages. Of course, the lifetime of the drug must be higher than a. Within the red blood cells it cannot be metabolized, neither can it diffuse through their membranes. The emphasis of the paper is on the mathematical properties and on the formulation of the control problem.

Drug Therapy

Efficacy of short-term treatment of pertussis with clarithromycin and azithromycin.

The recommended treatment for pertussis is erythromycin, 40 to 50 mg/kg per day for 2 weeks. The newly developed macrolides, clarithromycin and azithromycin, have been demonstrated to be superior to erythromycin because of improved absorption and a longer half-life. As a result, we conducted two separate comparison studies to evaluate the efficacies of clarithromycin, 10 mg/kg per day, twice a day for 7 days, and azithromycin, 10 mg/kg per day, once a day for 5 days, compared with the standard erythromycin regimen. A total of 17 patients, including 10 infants 1 year of age or less, for whom pertussis had been confirmed by culture, were allocated to receive either clarithromycin or azithromycin treatment, and each patient was matched (age, sex, and immunization status) with historical control subjects who had been treated with erythromycin. Eradication rates examined at 1 week after treatment were as follows: 9 of 9 with clarithromycin versus 16 of 18 with erythromycin (psi M-H = 1.13), and 8 of 8 with azithromycin versus 13 of 16 with erythromycin (psi M-H = 1.23). No bacterial relapse after treatment was detected in either group. All isolated strains of Bordetella pertussis were susceptible to clarithromycin, azithromycin, and erythromycin, and no change in drug susceptibility has been confirmed for the past 20 years in Japan. Because of the very low incidence of pertussis resulting from widespread use of acellular pertussis vaccination, this study did not enroll a large number of patients; however we conclude that short-term treatment with clarithromycin or azithromycin is expected to be equal or superior to the standard long-term erythromycin regimen for pertussis.

Adolescent

Distribution and morphology of valves in the human external jugular vein: indications for utilization in microvascular anastomosis.

PURPOSE: This study examined the valves in the external jugular vein (EJV) that could affect microvascular anastomosis and increase the risk of thrombogenesis. MATERIALS AND METHODS: The EJVs of 57 sides from 36 cadavers aged 40 to 95 years (20 males and 16 females) were dissected. After opening the veins, the distribution and morphology of the valves were investigated using a stereoscopic microscope. The length of the valves and inner diameter of the vessels were measured and related to the location of the valves. RESULTS: Forty-nine (86%) of 57 EJVs were confluent with the subclavian vein. The EJV possessed bicuspid valves, and in 46 (93.9%) of the 49 specimens there were valves at the junction with the subclavian vein, whereas 44 (89.8%) contained valves in the middle portion of the specimen. The length of the valves was less than twice the inner diameter, and some were occasionally only rudimentary. CONCLUSION: Numerous valves exist in the middle portion of the EJV where microvascular anastomoses are performed. When valves are observed in the site of anastomosis, they can be avoided by resecting a length equal to approximately twice the inner diameter.

Adult

Effects of asymmetric dynamic and isometric liftings on strength/force and rating of perceived exertion.

A laboratory study was undertaken to determine the postural and physical characteristics and subjective stress during dynamic lifting of a usual load (10 kg) compared with during isometric lifting. The authors also aimed to clarify the effects of asymmetric lifting on these parameters. The subjects were thirteen male college students. They were asked to lift a box weighing 10 kg. They performed sixteen different lifting tasks from the floor to a height of 71 cm, involving a combination of three independent factors: two lifting modes (isometric lifting and dynamic lifting), four lifting angles in relation to the sagittal plane (sagittal plane, right 45 degree, right 90 degree and left 90 degree planes) and two lifting postures (squat and stoop). For each lifting task, strengths or forces and ground reaction forces were measured. At the end of each task, the authors asked the subjects to rate their perceived exertion (RPE) during lifting at ten sites of the body. Angle factor had a significant effect on isometric strengths and dynamic peak forces. Isometric strengths during the maximum 3 s were highest in lifting in the right 45 degree plane, followed by that in the sagittal plane, while those in the right 90 degree and left 90 degree planes were the lowest. However, peak forces in dynamic lifting were the highest in the lifting in the sagittal plane, followed by that in the right 45 degree plane, while those in the right 90 degree and left 90 degree planes were the lowest. Postural factor had a significant effect on height at peak force, which is higher in squat lifting than in stoop lifting. RPEs for the left arm, the backs and the right whole body in isometric lifting were significantly higher than in dynamic lifting of 10 kg. There were remarkably high RPEs for the ipsilateral thigh to the box in right 90 degree and left 90 degree planes during both isometric and dynamic liftings. Locations of the resultant force consisting of three component forces on the force plate were closer to the foot on the same side as the box in asymmetric lifting. Thus, some similarities and differences were found between isometric lifting and dynamic liftings regarding the indexes of strength used in this experiment. The authors consider that the subjects used the foot nearer to the box as a fulcrum during asymmetric lifting. Dynamic measurement using the 10 kg weight is less stressful than the conventional isometric measurement. It was possible to obtain the height data at peak force and time-based changes in the force and the box location during lifting only through dynamic lifting measurement. The results provide new knowledge about the biomechanical features of dynamic lifting tasks.

Adolescent

Adjustments of posture and viewing parameters of the eye to changes in the screen height of the visual display terminal.

To understand the motions caused by the interaction among the different body parts, adjustments of both eye position and body posture to screen height settings of 80, 90, 100, 110 and 120 cm were determined in 10 subjects. The subjects engaged in a non-keyboard, interactive computer game requiring constant visual monitoring. Changes in body positions were determined by video image analysis for the posture parameters and by video frame analysis for the eye parameters. Analysis of variance and correlation analysis showed that neck angle, thoracic bending and vertical eye position were significantly affected by changes in the screen height of the VDT. The study of the interrelationship of eye position and body posture suggested that changes in body positions served to complement the eye position in attaining a better view of the visual target. Viewing angle was observed to be decided mainly by inclination of the neck and the eye. Thoracic bending was also noted to contribute in setting the viewing angle, although to a lesser extent. On the other hand, viewing distance and trunk inclination showed significant correlation.

Adult

Detection of protein kinase activity specifically activated at metaphase-anaphase transition.

We have previously reported that Ser13 and Ser34 on glial fibrillary acidic protein (GFAP) in the cleavage furrow of glioma cells are phosphorylated during late mitotic phase (Matsuoka, Y., K. Nishizawa, T. Yano, M. Shibata, S. Ando, T. Takahashi, and M. Inagaki. 1992, EMBO (Eur. Mol. Biol. Organ.) J. 11:2895-2902). This observation implies a possibility that there is a protein kinase specifically activated at metaphase-anaphase transition. To further analyze the cell cycle-dependent GFAP phosphorylation, we prepared monoclonal antibodies KT13 and KT34 which recognize the phosphorylation of GFAP at Ser13 and Ser34, respectively. Immunocytochemical studies with KT13 and KT34 revealed that the GFAP phosphorylation in the cleavage furrow during late mitotic phase occurred not only in glioma cells but also in human SW-13 and mouse Ltk- cells in which GFAP was ectopically expressed, thus the phosphorylation can be monitored in a wide range of cell types. Furthermore, we detected kinase activity which phosphorylates GFAP at Ser13 and Ser34 in the lysates of late mitotic cells but not in those of interphase cells or early mitotic cells. These results suggest that there exists a protein kinase which is specifically activated at the transition of metaphase to anaphase not only in GFAP-expressing cells but also in cells without GFAP.

Anaphase

Motor nerve conduction studies on children with spinal muscular atrophy.

Median and posterior tibial motor nerve conduction studies were performed on 10 children with spinal muscular atrophy (SMA). Three patients with SMA type I, in whom rapid deterioration occurred, showed reduced motor nerve conduction velocity and a remarkably low M-wave amplitude in both nerves. In type II and III patients, the motor nerve conduction velocity was normal in the median nerve, although the M-wave amplitude was small in the tibial nerve. In four patients, a reduction of the M-wave amplitude was observed as clinical symptoms advanced. These findings may suggest that motor conduction studies in spinal muscular atrophy provide complementary information for understanding the pathogenesis and are also useful to clarify the heterogeneity of this disease.

Child

Improvement of retroviral retargeting by using amino acid spacers between an additional binding domain and the N terminus of Moloney murine leukemia virus SU.

We previously reported a strategy to redirect the retroviral host range by expressing single-chain antibodies (S. J. Russell, R. E. Hawkins, and G. Winter, Nucleic Acids Res. 21:1081-1085, 1993) or ligands (F.-L. Cosset, F. J Morling, Y. Takeuchi, R. A. Weiss, M. K. L. Collins, and S. J. Russell, J. Virol. 69:6314-6322, 1995) at the N terminus of Moloney murine leukemia virus (MoMLV) surface proteins (SU). Although such chimeric envelopes were able to bind the new receptors, the transduction efficiency of retargeted viruses was generally low. We hypothesized that conformational rearrangements of envelope glycoproteins were not optimally triggered following binding, and to overcome these postbinding blocks, we have generated here a set of chimeric MoMLV-derived envelopes targeted to the Ram-1 phosphate transporter in which we have varied the spacing between the Ram-1-binding domain and the MoMLV SU. All of the recombinant envelopes were correctly expressed on virions, and all bound efficiently to Ram-1. However, the interdomain spacing greatly affected the efficiency of gene transfer by retroviral vectors that had bound to Ram-1 via their chimeric envelopes. Optimal interdomain spacing allowed a 100-fold-increased viral transduction via Ram-1 compared to our previous results.

3T3 Cells

TM domain swapping of murine leukemia virus and human T-cell leukemia virus envelopes confers different infectious abilities despite similar incorporation into virions.

We investigated the influence of transmembrane protein (TM) domains on incorporation of retroviral envelopes into virions and on infectivity. We introduced complete, truncated, or chimeric Friend murine leukemia virus (F-MuLV) and human T-cell leukemia virus type 1 (HTLV-1) envelopes into an MuLV particle-producing complementation cell line. As shown previously for HTLV-1 envelopes containing extracellular domains of F-MuLV TM (C. Denesvre, P. Sonigo, A. Corbin, H. Ellerbrok, and M. Sitbon, J. Virol. 69:4149-4157, 1995), reverse chimeric F-MuLV envelopes containing the extracellular domain of HTLV-1 TM were not processed. In contrast, a chimeric MuLV envelope containing the entire HTLV membrane-spanning and cytoplasmic domains (FHTMi) was efficiently processed, fusogenic as tested in a cell-to-cell assay, and efficiently incorporated into MuLV particles. However, these MuLV particles bearing FHTMi envelope proteins could not infect mouse or rat cells which are susceptible to wild-type F-MuLV. Therefore, envelopes which are readily fusogenic in cell-to-cell assays and also efficiently incorporated into virions may not necessarily confer virus-to-cell fusogenicity. HTLV envelopes, whether parental, chimeric (containing the MuLV cytoplasmic tail) or with a truncated cytoplasmic domain, were incorporated into MuLV particles with equal efficiencies, indicating that the cytoplasmic tails of these envelopes did not determine their incorporation into virions. In contrast to FHTMi envelope, HTLV-1 envelopes with F-MuLV membrane-spanning and cytoplasmic domains, as well as wild-type HTLV-1 envelopes, conferred virion infectivity. These results help to define requirements for envelope incorporation into retroviral particles and their cell-free infectivity.

3T3 Cells

Pheromone-induced stimulation of hypothalamic gonadotropin-releasing hormone pulse generator in ovariectomized, estrogen-primed goats.

As an example of pheromone-induced activation of reproductive function, the 'male effect' is well known in seasonally anestrous goats. The effect of this male pheromone on the hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator activity was examined by monitoring the characteristic increases in the multiple-unit activity (MUA volleys) of the medial basal hypothalamus which had been associated with the pulsatile secretion of luteinizing hormone in ovariectomized goats carrying estradiol implants under 16L/8D condition. Male goat hair was used as the source of male pheromones, and the exposure to the hair was accurately timed to be midway between succeeding MUA volleys. The interval from the pheromone exposure to the subsequent volley was measured, so that the primer pheromone effect was assessed in terms of the stimulation of the GnRH pulse generator activity. Exposure to hair from an intact male goat resulted in occurrence of a MUA volley within a few minutes (1.7 +/- 0.2 min, n = 15) with the intervolley interval being apparently shortened as compared with the preexposure period. Hair from castrated male goats, on the other hand, had no such stimulatory effect at all on the hypothalamic GnRH pulse generator activity, but treatment of the castrated goats with testosterone for 2 months resumed the pheromone activity. The present results provide first direct evidence for the central action of the primer pheromone in a mammalian species, and pheromonal stimulation of the reproductive neuroendocrine system is shown to be exerted by instantaneously stimulating the hypothalamic GnRH pulse generator activity.

Animals

Differences in bone and vitamin D metabolism between primary hyperparathyroidism and malignancy-associated hypercalcemia.

Bone and vitamin D metabolism are examined in patients with primary hyperparathyroidism (1 degree HPT), humoral hypercalcemia of malignancy (HHM), and local osteolytic hypercalcemia (LOH) with normal renal function. Among the bone resorption markers, T scores of total deoxypyridinoline (Dpyd) were highest in HHM and were significantly higher than those in 1 degree HPT. Among the formation markers, T scores of osteocalcin (OC) were highest in 1 degree HPT but were negative in HHM. The elevation in total Dpyd was associated with an increase in OC in 1 degree HPT, and the ratios of total Dpyd/OC were similar to those in controls. In contrast, many patients with HHM and LOH exhibited elevated total Dpyd and suppressed OC with increased total Dpyd/OC ratios, but the ratios varied widely. Serum 1,25-dihydroxyvitamin D [1,25(OH)2D] was elevated in 1 degrees HPT but was suppressed in HHM and LOH at any serum Ca levels. These results demonstrate that increased bone resorption is associated with enhanced bone formation in 1 degrees HPT but are uncoupled in many of the HHM and LOH patients, and that total Dpyd/OC ratio can be a useful index to estimate the coupling state of bone. It is suggested that the reduction in serum 1,25(OH)2D cannot be explained by an elevation in serum Ca in HHM and LOH, and that the differences in bone and vitamin D metabolism in HHM and LOH from those in 1 degree HPT may be caused by a common mechanism such as the secretion of some cytokines from tumors.

Adult

Absence of mutations in parathyroid hormone (PTH)/PTH-related protein receptor complementary deoxyribonucleic acid in patients with pseudohypoparathyroidism type Ib.

To clarify the mechanism of resistance to PTH in patients with pseudohypoparathyroidism (PHP) type Ib, the complementary DNA (cDNA) for PTH/PTH-related protein (PTHrP) receptor was analyzed in skin fibroblasts from three patients with PHP Ib and compared with those from a patient with PHP Ia and a normal subject. We have divided the full coding region of PTH/PTHrP receptor cDNA into five parts and amplified the cDNA by reverse transcription-coupled PCR. There was no difference in the size of PCR products among these patients and the normal control. Single strand conformation polymorphism analysis of the PCR products also showed no aberrant bands in PHP Ib patients. Furthermore, no mutation in PTH/PTHrP receptor cDNA was found by direct sequencing of the PCR products from these patients. These results demonstrate that there is no mutation in PTH/PTHrP receptor cDNA from skin fibroblasts at least in the examined patients with PHP Ib. In addition, the expression of PTH/PTHrP receptor messenger ribonucleic acid was reduced in two patients but was increased in one patient with PHP Ib, suggesting that a reduction in PTH/PTHrP receptor expression cannot explain the resistance to PTH in all patients with PHP Ib. Elucidation of the pathogenesis of PHP Ib may require examination of tissue-specific abnormality in the PTH signal transduction system in the kidney.

Adolescent

Timing of proceptive and receptive behavior of female goats in relation to the preovulatory LH surge.

The temporal relation between the luteinizing hormone (LH) surge and the occurrence of two components of sexual behavior was investigated in female goats. Behavior observation and blood sampling were carried out every 2-6 hr from 26 hr before through 116 hr after prostaglandin (PG) administration which was given to induce luteolysis during the mid-luteal phase. The preovulatory LH surge appeared 30-100 hr after PG injection, and it continued for 6.5 +/- 0.4 hr. Although the interval from PG injection to the onset of the LH surge differed considerably among individuals, the proceptivity (defined as an approach to a male with vigorous tail-swishing) and the receptivity (defined as an acceptance of male's mounting or copulation) occurred well synchronized with the LH surge in each female. The proceptivity and receptivity were observed from -7.4 +/- 1.7 hr to 16.8 +/- 1.5 hr and from -2.6 +/- 1.6 hr to 13.0 +/- 2.0 hr, respectively, with regard to the LH surge onset (0 hr). Thus the proceptivity appeared first and lasted longest, and the receptivity was always seen around the time of the LH surge suggesting an existence of causal relationship between these two preovulatory events. The present results support the view that the female goat has evolved an efficient behavioral strategy such that it actively attracts males before it becomes fully receptive of male's approach to mate, when the LH surge occurs simultaneously to ensure a high conception rate at the subsequent ovulation.

Animals

Expression sites of two byssal protein genes of Mytilus galloprovincialis.

Mussels form byssal threads that can attach tenaciously to wet and irregular surfaces. The byssus consists of a fibrous collagenous core, and at least two types of polyphenolic proteins surround it. One of these proteins, designated Mgfp-1, coats the collagenous core; the other, designated Mgfp-2, is the major component of the terminal adhesive plaque of byssal threads. Both proteins contain 3,4-dihydroxyphenylalanine (DOPA) in their primary sequences. In this study, the sites of expression of the genes encoding the polyphenolic proteins were investigated in Mytilus galloprovincialis. By northern blot analysis, we found that the expression of both genes is foot-specific. Northern blot analysis of RNA isolated from the distal end and the remaining proximal portion of the foot indicated that the Mgfp-2 gene is expressed primarily in the distal part, whereas Mgfp-1 expression occurs in both parts. In situ hybridization indicated that the Mgfp-1 gene transcript is localized in the accessory gland along the ventral groove of the foot, and the Mgfp-2 gene transcript is localized in the phenol gland near the foot apex. Thus, it was shown that tissues expressing Mgfp-1 and Mgfp-2 are located around the ventral groove in an arrangement appropriate for byssus formation.

Amino Acid Sequence