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Biomedical subjects

N Takano

Publications and source records attributed to N Takano.

At least 19 recordsLinked to original sources

Stem cell factor and/or endothelin-3 dependent immortal melanoblast and melanocyte populations derived from mouse neural crest cells.

Stem cell factor (SCF) and endothelin-3 (ET3) are both necessary for melanocyte development. In order to obtain immortal cell populations of melanoblasts that can survive without feeder cells, we first obtained an immortal cell population of neural crest cells (NCCs) from Sl/+ and +/+ mice of strain WB by incubating with a culture medium supplemented with SCF and ET3, and then we designated them as NCC-SE3 cells. NCC-SE3 cells were bipolar, polygonal, or round in shape and possessed melanosomes of stages I-III (mainly stage I). They were positive to dihydroxyphenylalanine (DOPA) reaction and expressed KIT (a receptor tyrosine kinase), tyrosinase, tyrosinase-related protein-1 (TRP1), tyrosinase-related protein-2 (TRP2), and endothelin-B receptor (ETRB) as determined by immunostaining. We next cultured NCC-SE3 cells by changing culture medium from the one supplemented with SCF + ET3 to the one supplemented with SCF or ET3. NCC-SE3 cells cultured with ET3 alone, designated as NCC-E3 cells, were bipolar in shape and had mainly stage II melanosomes and expressed the same proteins as did NCC-SE3 cells. However, NCC-SE3 cells cultured with SCF alone, designated as NCC-S4.1 cells, were polygonal in shape and had mainly stage I melanosomes. They are thought to be more immature because they were positive to KIT, TRP1, and TRP2, but not to ETR(B), tyrosinase, and DOPA reaction. When 12-O-tetradecanoylphorbol 13-acetate and cholera toxin were added to the culture medium, NCC-S4.1 cells changed shape from polygonal to bipolar and became DOPA-positive. This suggests that NCC-S4.1 cells are melanoblasts that have the potential to differentiate into melanocytes. These cell populations will be extremely useful to study factors that affect melanocyte development and melanogenesis.

Animals↗

Respiratory compensation point during incremental exercise as related to hypoxic ventilatory chemosensitivity and lactate increase in man.

The pulmonary ventilation-O2 uptake (VE-VO2) relationship during incremental exercise has two inflection points: one at a lower VO2, termed the ventilatory threshold (VT); and another at a higher VO2, the respiratory compensation point (RCP). The individuality of RCP was studied in relation to those of the chemosensitivities of the central and peripheral chemoreceptors, which were assessed by resting estimates of hypercapnic ventilatory response (HCVR) and hypoxic ventilatory response (HVR), respectively, and the rate of lactic acid increase during exercise, which was estimated as a slope difference (delta slope) between a lower slope of VCO2-VO2 relationship (VCO2:CO2 output) obtained at work rates below VT and a higher slope at work rates between VT and RCP. Twenty-two male and sixteen female subjects underwent a 1 min incremental exercise test until exhaustion, in which VT, RCP and delta slope were determined. All measures were normalized for body surface area. In the males, the individual difference in RCP was inversely correlated with those of HVR and delta slope (p < 0.05), and in the females, similar tendencies persisted, while the correlation did not reach statistically significant levels (0.05 < p < 0.1). There was no significant correlation between RCP and HCVR in either sex. A multiple linear regression analysis showed that 40 to 50% of the variance of RCP was accounted for by those of HVR and delta slope, both of which were related linearly and additively to RCP, this relation being manifested in the males but not in the females without consideration of the menstrual cycle. These results suggest that the individuality of RCP depends partly on the chemosensitivity of the carotid bodies and the rate of lactic acid increase during incremental exercise.

Acidosis, Lactic↗

Individual differences in breathlessness during exercise, as related to ventilatory chemosensitivities in humans.

1. The present study attempted to test the hypothesis that breathlessness associated with exercise hyperpnoea is greater in subjects with greater activities of the central and peripheral chemoreceptors during exercise. The chemoreceptor activities were assessed by resting estimates of hypercapnic ventilatory response (delta VE/delta PCO2, HCVR) and hypoxic ventilatory response (delta VE/-delta SO2, HVR), respectively, where VE is minute ventilation and SO2 is oxygen saturation. 2. Nine female and nine male subjects performed a 1 min incremental exercise test until exhaustion, during which breathlessness intensity (BS), assessed by a Borg category scale, and VE were measured every minute. The maximum O2 uptake (VO2,max) was also determined. 3. Using a stepwise multiple linear regression analysis, the relative contributions of not only VE, HCVR and HVR, but also VO2,max and a predicted maximum voluntary ventilation (MVVp) of the individuals to BS, were examined. 4. The analysis showed that BS = 0.1VE + 4.9HVR - 0.03MVVp + 0.55 (r2 = 0.71), indicating that VE accounted for 44% of the variance of BS, HVR for 12% and MVVp for 15%. No significant relation of HCVR and VO2,max to BS was found. 5. These results suggest a contribution of peripheral chemoreceptors to the generation of exertional breathlessness.

Adult↗

Sensation of breathlessness and respiratory oxygen cost during cycle exercise with and without conscious entrainment of the breathing rhythm.

The conscious entrainment of respiratory rhythm to exercise rhythm (ENT) has been hypothesized to alleviate breathing discomfort and reduce the oxygen (O2) cost of ventilation with a resulting decrease in total O2 uptake (VO2) during rhythmic exercise. This hypothesis has been tested in the study reported here. Eight female subjects performed cycle exercise at 50 rpm under two work load conditions of 40% and 60% of maximal VO2. During a 30-min exercise period at each work load, each subject was asked to breathe under two conditions for 15 min each: (1) spontaneously (non-ENT run), and (2) deliberately entraining the breathing rhythm to the cycling rhythm at preferred coupling ratios of the two rhythms (ENT run). In the ENT run, most subjects chose a ratio of 1:2. In each run, pulmonary ventilation (VE), total VO2 and the breathlessness sensation (BS) were measured at 4-5 min. BS was assessed according to a Borg category scale. The remaining 10 min of each 15-min run were allotted for measurement of the O2 cost of ventilation (delta VO2/delta VE), assessed by a hypercapnia-induced hyperventilation method in which the VO2 of the respiratory muscles (VO2RM) was calculated by multiplying delta VO2/delta VE by the prevailing VE. On average, there were no significant differences in any of the variables, VO2, delta VO2/delta VE, VO2RM and BS, between the non-ENT and ENT runs performed at any work load. However, there were wide variations among the subjects in the differences (delta) between the two runs, and significant correlations were found between delta VO2 vs delta VE, delta VO2 vs delta VO2RM, and delta BS vs delta VO2RM of individual subjects. These results indicate that reductions of the total VO2 and BS with ENT could occur in subjects in whom the VO2RM decreased during ENT.

Adult↗

Merkel cell carcinoma of palatal mucosa in a young adult: immunohistochemical and ultrastructural features.

The first case report of a merkel cell carcinoma arising from the palatal mucosa in a young adult is presented. The histopathological similarities of this tumour in skin and oral mucosa are also discussed. The patient was a 14-year-old female with a non-symptomatic painful swelling in the left molar region of the maxilla. Under the diagnosis of a malignant tumour, a partial maxillary resection was performed, but there was a recurrence, and finally the patient died of cerebral metastasis. The tumor was composed mainly of uniform small cells. Immunohistologically, a large number of the cells were reactive to neuron specific enolase (NSE) and cytokeratin CK19, and some of the cells were positive to CK8, CK13, CK20, PGP9.5 and CEA focally and slightly. Pseudo-rosette formation and squamous differentiation were frequently detected. The ultrastructure of the tumour cells showed abundant Golgi bodies associated with neurosecretory granules. We conclude that it is the first case of a Merkel cell tumour arising from palatal mucosa and invading underlying bone with reactive hyperplasia. These findings closely resemble those of the same tumour occurring in the skin

Adolescent↗

Decrease in Thy-1 expression on peripheral CD34 positive cells induced by G-CSF mobilization. The Tohoku Children Leukemia Study Group.

In order to ascertain the cytological features of peripheral hematopoietic progenitor cells (PHPC) mobilized after administration of chemotherapeutic agents and G-CSF, lineage- and progenitor cell-specific surface markers on CD34 positive (+) cells were sequentially examined. Nineteen evaluable samples were obtained from a malignant lymphoma, an acute lymphoblastic leukemia and 5 neuroblastoma patients. CD38 and HLA-DR were respectively expressed on more than 95% and approximately 85% of CD34+ PHPC cells. CD19 was also expressed on the majority and CD117 on 10 to 20% of the CD34+ cells. The most striking finding was that the Thy-1(CDw90)+/CD34+ population was decreased at the peak of mobilization of CD34+ cells as compared to the early phase after G-CSF administration (approximately 20% vs. 60%). These results suggest that decrease in Thy-1 expression on CD34+ cells is related to mechanisms easing CD34+ cell mobilization to the peripheral blood.

Antigens, CD34↗

[Abnormal metabolism of fatty acids and ketone bodies in Duchenne muscular dystrophy, and the effect of biotin on these abnormalities].

It has been reported that serum levels of ketone bodies often elevate in patients with Duchenne muscular dystrophy (DMD). The cause of this abnormal metabolism, however, has not been elucidated. In this study, serum levels of ketone bodies were measured in the early morning in patients with DMD, congenital muscular dystrophy and cerebral palsy. Serum free fatty acids (FFA), glucose, and thickness of subcutaneous fat were also measured. Ketone bodies elevated in most DMD patients, but not elevated in patients with the other disorders. Hyperketonemia in the DMD patients was accompanied by elevation of the FFA level, but no correlation was seen between hyperketonemia and the creatine kinase level or the severity of muscle involvement. No differences were found between DMD patients and others in the levels of FFA, glucose and thickness of subcutaneous fat. These results indicate that DMD patients are more prone to ketosis than the others. The effect of biotin administration (2 mg/day) on hyperketonemia also was investigated in 11 patients with DMD. The levels of total ketone bodies decreased by biotin administration for 2 weeks. These data suggest that the utilization of FFA and ketone bodies may be impaired in DMD patients. Biotin treatment will be useful for improving the abnormal metabolism of ketone bodies in DMD patients.

Adolescent↗

[Prevalence of serum anti-Helicobacter pylori IgG antibody in persons with severe motor and intellectual disabilities--comparison between institutionalized persons and persons living at home].

The seroprevalence of an anti-Helicobacter pylori antibody (ELISA) was investigated in institutionalized persons with severe motor and intellectual disabilities (SMID). The rate of seropositivity was significantly higher in persons with SMID under 29 years of age than in age-matched controls and in institutionalized patients with muscular dystrophy. No difference in seropositivity among SMID patients was found between those in our and other institutions. Therefore, it is speculated that Helicobacter pylori infection occurs soon after the institutionalization of SMID patients. Persons with SMID living at home, in their teens and twenties, had lower seropositivity than that of institutionalized patients but higher than controls. These data implicate the life style of persons with SMID and long-term institutionalization as one of important risk factors of Helicobacter pylori infection.

Adolescent↗

[A case of pacemaker implantation for complete atrioventricular block associated with Duchenne muscular dystrophy].

We report here a case of Duchenne muscular dystrophy (DMD) who underwent pacemaker implantation for complete atrioventricular block. This 30 year-old male had the deletion of exon 45-52 in the dystrophin gene and complained of palpitation and precordial oppression. Because his electrocardiogram showed complete atrioventricular block, a permanent pacemaker was implanted. He has been doing well for 15 months after implantation. There have been few reports about pacemaker implantation for patients with DMD. As these patients survive longer by mechanical ventilation with chest respirators or nasal intermittent positive pressure ventilators, an increasing number of cases may require pacemaker implantation.

Adult↗

Cell surface c-kit receptors in human leukemia cell lines and pediatric leukemia: selective preservation of c-kit expression on megakaryoblastic cell lines during adaptation to in vitro culture.

We produced a monoclonal antibody MTK1 which recognized c-kit protein. Using MTK1, 31 leukemia cell lines and 76 leukemia blasts from pediatric patients were analyzed for expression of the c-kit receptor by flow cytometry. The c-kit receptor was detectable on four of four cell lines assigned to the megakaryo/erythromegakaryoblastic lineage and on one of seven cell lines of myeloid lineage. C-kit expression was not seen on any of 20 cell lines of erythroid and lymphoid lineages. Furthermore, c-kit was expressed on 16 of 24 nonlymphoid blasts without platelet surface antigens (67%) and on six of eight non-lymphoid blasts with platelet surface antigens (75%), but was not detectable on 44 lymphoid blasts from pediatric leukemia patients. In these cases CD34 was expressed on 26 of 32 myeloid blasts (81%) and on 27 of 44 lymphoid blasts (61%). The findings indicate a dominant expression of the c-kit receptor on established cell lines assigned to the megakaryo/erythromegakaryoblastic lineage, though a high percentage of leukemic myeloblasts also expressed the c-kit receptor on their surface.

Antibodies, Monoclonal↗

The importance of mental support to the patients with adult atopic dermatitis.

To study mental condition of the patients with severe adult atopic dermatitis, the General Health Questionnaire of 60 symptoms proposed by Goldberg was completed by 64 patients composed of 22 males and 42 females twice (before the start of the treatment and following improvement or reduction of their skin symptoms), and also 65 healthy persons as a matched healthy control. The patients were much more markedly disturbed in the sum of all morbid ratings and all four scales for somatic symptoms, anxiety and worry, social dysfunction and despondency and depressed mood before the start of the treatment than the healthy control. However, the patients showed remarkably reduced scores in all measured scales with improvement of their skin symptoms lower than healthy control. These depressed mental conditions reflected on their daily and social activities. The results obtained indicated that atopic dermatitis could be not only a disease of dermatology but also a disease of mental and even social disease. The results endorsed importance and necessity to provide for dermatologists, the patients family and even nurses concerned mental support to those patients with adult atopic dermatitis.

Adolescent↗

Phase relation and breathing pattern during locomotor/respiratory coupling in uphill and downhill running.

Differential effects of uphill and downhill running on phase relation between locomotor and respiratory cycles were studies in nine experienced runners who were instructed to run uphill and downhill on a sloped surface at comfortable and constant speeds (actually 1.7-4.4 m s-1). Timings of footstrike and onsets of inspiration and expiration were measured to compute respiratory cycle duration (Ttot), inspiratory time (Ti), duty cycle (Ti/Ttot), and stride time (Ts). Incidence of locomotor/respiratory coupling (LRC) was determined based on steadiness of Ttot and Ts (within +/- 0.1 s in SD) and Ttot/Ts (LRC ratio, integer or a half-integer multiples). Both in the uphill and downhill running, LRC ratio observed was 1:1, 2:1, and 2.5:1. Ti/Ttot during LRC was 0.41-0.49, which depended on the combinations of Ts and LRC ratio but not on the running conditions. In the uphill running, the onset of inspiration subsequent to footstrike was seen during the first half period (corresponding to the support phase) of the step interval (Ts/2, the time interval between the right and left footstrikes) in 7 of the 9 subjects, while in the downhill running it occurred during the last half period of the step interval (the floating phase) in all subjects. For onset of expiration, no consistent relation to footstrike was observed. These results suggest that the mechanical constraints of running on the respiratory system affect the phase relation between locomotor and respiratory cycles but not Ti/Ttot during LRC.

Adult↗

[Increased gamma delta T cells in peripheral blood of patients with severe neurologic impairment].

We examined peripheral gamma delta T cells in patients with severe neurologic impairment. The gamma delta T cells in these patients significantly increased as compared with those in healthy adults (P < 0.0001). These cells expressed the V gamma 9/V delta 2 phenotype which was reported to proliferate by infections. When patients with severe neurologic impairment and patients with Duchenne muscular dystrophy (DMD) were divided into frequent and non-frequent infectious groups, the gamma delta T cells increased significantly in the frequent infectious group of DMD (P < 0.005), but not significantly in the frequent infectious group of patients with severe neurologic impairment. These results indicated that the gamma delta T cells of patients with severe neurologic impairment increased in frequent infections and other factor(s).

Adolescent↗

Differential role in lipid peroxidation between rat P450 1A1 and P450 1A2.

The role of cytochrome P450 (P450) in lipid peroxidation induced by NADPH or peroxide was investigated in a reconstituted system. When cumene hydroperoxide, t-butyl hydroperoxide and hydrogen peroxide were used as initiators, the rates of malondialdehyde (MDA) formation were much higher in a reconstituted system containing P450 1A1 than those observed in a reconstituted system containing P450 1A2. In contrast to peroxide-induced lipid peroxidation, P450 1A2 catalysed NADPH-induced lipid peroxidation more effectively than did P450 1A1 regardless of the presence of ADP-Fe(NO3)3. Carbon monoxide inhibited NADPH-induced formation of MDA in a reconstituted system containing P450 1A2, but not P450 1A1. In addition, superoxide dismutase (SOD) was an effective inhibitor in a NADPH-induced lipid peroxidation system catalysed by P450 1A2 but not by P450 1A1. These results suggest that a peroxide-induced reaction might proceed readily with P450 1A1, whereas P450 1A2 mainly functions in NADPH-induced lipid peroxidation via generation of an active oxygen species. It is furthermore indicated that the difference in the effect of SOD in NADPH-induced lipid peroxidation depends on the P450 used.

Animals↗

Ventilatory responses during arm and leg exercise at varying speeds and forces in untrained female humans.

1. Involvement of neural stimuli, central and/or peripheral in origin, in exercise ventilatory control was ascertained by examining the ventilatory responses to varying mechanical conditions of arm and leg cycle ergometries. Twelve untrained women underwent each of two modes of exercise at three levels of loading (0, 5 and 10 N), each at three levels of speed (30, 50 and 72 r.p.m.), during which steady-state values of minute ventilation (VE), tidal volume (VT), respiratory frequency (f) and CO2 excretion (VCO2) were measured. 2. Using the data obtained at the aerobic work intensities, the relationship of ventilatory responses (VE, VT and f) to the metabolic (VCO2) and mechanical (speed and load) variables were studied by multiple linear regression analysis. Coefficient of determination (r2) of the regression model was lowest (0.84) for f in the arm exercise and highest (0.99) for VE in the leg exercise. 3. Standardized partial regression coefficients of the model indicated that VE response is related to VCO2 at the rate of 94 +/- 3% (mean +/- S.E.M.) and to the pedal rate at 8 +/- 3% during the leg exercise, while it is closely related to VCO2 in the arm exercise. For f response, influence of the rate of limb movement was seen in the leg exercise but not in the arm exercise. The different effects of the rate of limb movement between the two exercise modes may be related to familiarity with the exercise modes, suggesting that a familiarity-related mechanism is involved in exercise ventilatory control. 4. A heavier load imposed on the limb muscles elicited a greater VT both in the arm and leg exercise and a lower f in the arm exercise. Postural control in the upper torso during increased limb muscle tension seems to affect VT and f.

Adult↗

Defective production of interleukin-6 in very small premature infants in response to bacterial pathogens.

In the present study, a whole-blood culture was employed to examine the ability of preterm and term newborn infants to produce interleukin-6 (IL-6) in response to major bacterial pathogens such as group B streptococci, Escherichia coli, Listeria monocytogenes, and Streptococcus pneumoniae. Similarly, in response to stimulation with lipopolysaccharide, a potent stimulant for monocyte cytokine production, appreciable levels of IL-6 activity in the stimulated whole blood from term newborns as well as adults was effectively induced by all of these pathogens. In contrast to that of term infants, the bacteria-induced IL-6 production of preterm infants, especially those born before 30 weeks of gestation, was somewhat decreased (P less than 0.01 for each pathogen). It was also demonstrated that IL-6 responses to lipopolysaccharide stimulation were reduced in preterm newborns (for term versus preterm newborns less than 30 weeks of gestation, P was less than 0.01). These findings imply some inherent abnormality of monocytes in preterm babies. The diminished IL-6 production may be partly responsible for the susceptibility of preterm newborn infants to bacterial infections.

Adult↗

Detection and clinical usefulness of urinary interleukin-6 in the diseases of the kidney and the urinary tract.

Interleukin-6 (IL-6) plays a key role in inflammatory and immune responses in the host. In the present study, the IL-6 activity in urine from patients with various renal diseases was examined to elucidate the pathological and clinical significance of urinary IL-6. In patients with mesangial proliferative glomerulonephritis (mes-PGN) including, IgA nephropathy, the urinary IL-6 activity tended to increase with the progression of mesangial hypercellularity. In four patients with IgA nephropathy, urinary IL-6 activity increased markedly but transiently during episodes of acute exacerbation associated with upper respiratory tract infection. In addition, it was demonstrated that urine from patients with other types of PGN such as poststreptococcal acute glomerulonephritis and membrano-proliferative glomerulonephritis contained large quantities of IL-6. However, the levels of urinary IL-6 activity were almost within the normal range in non-proliferative glomerular diseases such as membranous nephropathy, minimal change nephrotic syndrome and lupus nephritis (WHO class I and V), non-glomerular bleeding and orthostatic proteinuria. It should be noted that a marked increase in urinary IL-6 was often observed in the patients with urinary tract infection. These results indicated that IL-6 in urine might be derived from various types of cells participating in inflammatory reactions not only in the renal parenchyma but also in the urinary tract.

Adult↗