Biomedical subjects

K Nakazawa

Publications and source records attributed to K Nakazawa.

At least 19 recordsLinked to original sources

PubMed2006

Effects of electrical stimulation of the raphe area on the micturition reflex in cats.

The raphe nucleus has a variety of physiological functions, including emotion, regulation of skeletal muscle motoneurons, spinal transmission of nociceptive signals, sleep, respiration, gastric motility, and cardiovascular function. Recent evidence has shown that centrally administered serotonin has modulatory effects on micturition function, and that decreased brain serotonin might underlie depression and an overactive bladder. We applied high-frequency stimulation (HFS; 0.2-ms duration, 100 Hz) in the raphe nucleus and the adjacent midline area in 20 supracollicular decerebrate cats, which mostly elicited inhibition of the micturition reflex. The effective amplitude of the electrical stimulation for evoking inhibitory responses was less than 50 muA. We also examined single neuronal activities in the raphe nucleus in response to isovolumetric spontaneous micturition reflexes. In total, 79 neurons were recorded in the raphe nucleus that were related to urinary storage/micturition cycles. Of the neurons recorded, the most common were tonic storage neurons (48%), followed by tonic micturition neurons (28%), phasic storage neurons (18%), and phasic micturition neurons (6%). In addition to the tonic/phasic as well as storage/micturition classification, the neurons showed diverse discharge patterns: augmenting, constant and decrementing, with the constant discharge pattern being most common. Among neurons in the raphe nucleus, the neurons with a decrementing discharge pattern were concentrated in the rostral portion, whereas the augmenting and constant neurons existed diffusely. The storage and micturition neurons were intermingled in the rostral portion, whereas they were separate in the caudal portion. In conclusion, the results of the present study indicate that HFS of the raphe area inhibits the micturition reflex and that there are micturition-related neuronal firings in the raphe area in cats, suggesting that the raphe nucleus is involved in neural control of micturition.

Action Potentials↗

PubMed2006

Synaptic origin of the respiratory-modulated activity of laryngeal motoneurons.

To determine the synaptic source of the respiratory-related activity of laryngeal motoneurons, spike-triggered averaging of the membrane potentials of laryngeal motoneurons was conducted using spikes of respiratory neurons located between the Bötzinger complex and the rostral ventral respiratory group as triggers in decerebrate, paralyzed cats. We identified one excitatory and two inhibitory sources for inspiratory laryngeal motoneurons, and two inhibitory sources for expiratory laryngeal motoneurons. In inspiratory laryngeal motoneurons, monosynaptic excitatory postsynaptic potentials were evoked by spikes of inspiratory neurons with augmenting firing patterns, and monosynaptic inhibitory postsynaptic potentials (IPSPs) were evoked by spikes of expiratory neurons with decrementing firing patterns and by spikes of inspiratory neurons with decrementing firing patterns. In expiratory laryngeal motoneurons, monosynaptic IPSPs were evoked by spikes of inspiratory neurons with decrementing firing patterns and by spikes of expiratory neurons with augmenting firing patterns. We conclude that various synaptic inputs from respiratory neurons contribute to shaping the respiratory-related trajectory of membrane potential of laryngeal motoneurons.

Action Potentials↗

PubMed2006

Effect of lesion level on the orthotic gait performance in individuals with complete paraplegia.

STUDY DESIGN: Cross-sectional, experimental research. OBJECTIVES: To clarify the effect of lesion level on cardio-respiratory responses and biomechanical characteristics of walking with a reciprocating gait orthosis in complete paraplegia with spinal cord injury (SCI). SETTING: National Rehabilitation Center for Persons with Disabilities, Japan. METHODS: Ten SCI individuals (age: 20-34 years, injured level: Th5-12) who experienced orthotic gait training at least for 10 weeks participated in two experiments: (1) measurement of the cardiorespiratory responses during 20 min of orthotic gait exercise; and (2) three-dimensional motion analysis and ground reaction force measurement using the VICON system. We calculated the following parameters: pulmonary ventilation, oxygen consumption (VO(2)), heart rate (HR), gait speed, cadence, stride length, crutch force (CF), hip range of motion (ROM), and hip angular velocity (VEL). Further, energy consumption and energy cost were calculated using the steady-state value of VO(2) and gait speed. RESULTS: The steady-state value of the VO(2) (18.2 +/- 3.80 ml/kg) and HR (133.0 +/- 21.63 b/min) tended to be larger in higher thoracic SCI subjects. There were strong positive correlations between the lesion level and walking speed (r = 0.74), energy cost (r = 0.85), and hip ROM (r = 0.78). On the other hand, negative correlation between the lesion level and peak CF (r = -0.78) was clarified. CONCLUSIONS: The physiological intensity of the orthotic gait strongly depended on the level of lesion. It seems likely that a limited hip range of motion and excess upper limb load result in the low energy cost of orthotic gait for the higher thoracic level of paraplegic patients.

Adult↗

PubMed2006

Hepatocyte spheroid formation on a titanium dioxide gel surface and hepatocyte long-term culture.

The cell morphology and expression of differentiated functions of primary rat hepatocytes on a titanium dioxide (TiO(2)) gel surface were investigated. Polystyrene culture dishes were coated with TiO(2) gel by spin-coating an ethanol solution of titanium n-butoxide, hydrolyzing in a humidity chamber and drying with nitrogen gas. The TiO(2) gel layer formed on the polystyrene dishes was transparent and robust, and its surface was quite flat. Rat hepatocytes inoculated on the TiO(2) gel-coated polystyrene dishes gradually accumulated with increasing culture time, and then spontaneously formed many hepatocyte spheroids at 90 +/- 21 microm diameter from about 3 days of culture. The diameter of the spheroids increased during the culture, and was 151 +/- 43 microm at 14 days of culture. Ammonia removal and albumin secretion by hepatocytes on the TiO(2) gel-coated polystyrene dishes were maintained at a high level for at least 14 days of culture compared with on a type I collagen-coated dish and a non-coated polystyrene dish. These results indicate that TiO(2) gel is an adequate material for hepatocyte spheroid formation and long-term culture of spheroids.

Animals↗

PubMed2006

Formation of a sheet-shaped organoid using rat primary hepatocytes for long-term maintenance of liver-specific functions.

In recent years, use of hepatocyte aggregates has led to development of a hybrid artificial liver support system (HALSS) that has high performance. However, in general, their thickness is 100 microm or more, and generation of a dead cell layer due to oxygen exhaustion inside the aggregates has been a universal problem. The present study proposes a novel organoid culture method with better performance than previous organoid culture methods by forming a sheet-shaped organoid (organoid-sheet) with a thickness of approximately 100 microm. The cell number of the organoid-sheet was maintained at approximately 75% of the initial number at 4 days of culture. On the other hand, that of a cylindrical organoid (cylindroid), which formed inside of a plasma separation hollow fiber with 285 microm inner diameter in our previous study, decreased to approximately 50% within 2 days. The ammonia removal rate of the cells in the organoid-sheet was higher than that of the cells in the cylindroid on the first day, but it decreased during the culture time. At day 15, the rate was reduced by almost 50% with respect to the value on the first day. The cells in the cylindroid displayed a lower ammonia removal rate. A significant difference was not observed between the albumin synthesis rates of the two cultures on the first day. However, over a period of time the cells in the organoid-sheet showed a higher albumin synthesis rate than cells in the cylindroid. As this novel organoid maintains these functions for at least 1 month, it is expected to be applied for the development of a HALSS with higher performance.

Animals↗

PubMed2005

Cardiorespiratory responses during passive walking-like exercise in quadriplegics.

STUDY DESIGN: Cross-sectional and comparative investigation using quadriplegics (QP) and nondisabled subjects (ND). OBJECTIVE: To evaluate cardiorespiratory responses during passive walking-like exercise (PWE) in QP. SETTING: National Rehabilitation Center for Persons with Disabilities in Japan. METHOD: The subjects were seven male QP with complete lesion (age: 27.0 +/- 5.4, injured level: C6-C7) and six male ND (age: 26.3 +/- 4.5). Cardiorespiratory responses were measured until voluntary fatigue during PWE, the rhythmical activity of paralyzed lower limbs synchronized with arm movements. RESULTS: There were no significant differences in oxygen consumption (VO(2)), pulmonary ventilation (VE), heart rate (HR) and oxygen pulse (O(2) pulse) between QP and ND during PWE. ND showed increased ventilatory equivalent for oxygen (VE/VO(2) ratio) during exercise, while QP showed a significantly greater respiratory rate (RR) during exercise than ND (P < 0.05). CONCLUSION: PWE elicited an increase in VO(2) with workload increment in QP similar to ND. However, higher RR suggested the intrinsic dysfunction of RR control during submaximal exercise in QP. From these results, it was thought that respiratory response would be the restriction factor of efficient oxygen transportation during PWE in QP.

Adult↗

PubMed2005

A short gamma-ray burst apparently associated with an elliptical galaxy at redshift z = 0.225.

Gamma-ray bursts (GRBs) come in two classes: long (> 2 s), soft-spectrum bursts and short, hard events. Most progress has been made on understanding the long GRBs, which are typically observed at high redshift (z approximately 1) and found in subluminous star-forming host galaxies. They are likely to be produced in core-collapse explosions of massive stars. In contrast, no short GRB had been accurately (< 10'') and rapidly (minutes) located. Here we report the detection of the X-ray afterglow from--and the localization of--the short burst GRB 050509B. Its position on the sky is near a luminous, non-star-forming elliptical galaxy at a redshift of 0.225, which is the location one would expect if the origin of this GRB is through the merger of neutron-star or black-hole binaries. The X-ray afterglow was weak and faded below the detection limit within a few hours; no optical afterglow was detected to stringent limits, explaining the past difficulty in localizing short GRBs.

Journal Article↗

PubMed2005

Striatal dopamine level increases in the urinary storage phase in cats: an in vivo microdialysis study.

Parkinson's disease is a common neurodegenerative disease that shows not only movement disorder, but also profound urinary dysfunction. Bladder hyperactivity is the major urodynamic abnormality. Therefore, the basal ganglia have been thought to modulate the micturition reflex. In six male adult cats under ketamine anesthesia, in which spontaneous isovolumetric micturition reflexes had been generated, we measured levels of striatal dopamine, in micturition and storage phases, using in vivo microdialysis. The striatal dopamine level significantly increased in the storage phase as compared with that in the micturition phase. It is suggested that striatal dopamine may inhibit the micturition reflex via the dopamine D1 receptor-GABAergic direct striatal output pathway, and that disruption of this pathway may be what leads to bladder hyperactivity in patients with Parkinson's disease.

Animals↗

PubMed2005

Unilateral recurrent laryngeal nerve neuropraxia following placement of a ProSeal laryngeal mask airway in a patient with CREST syndrome.

We report a severe unilateral recurrent laryngeal nerve neuropraxia following use of the ProSeal laryngeal mask airway (PLMA) in a 71-year-old female patient with CREST syndrome. She required amputation of the 5th phalanx of foot because of gangrene due to Raynaud's syndrome. Anesthesia was induced with propofol, and a size 3 PLMA was inserted. Anesthesia was maintained with sevoflurane and nitrous oxide for 2 h and the operation was performed uneventfully. On removal of PLMA, the cuff volume was measured to 40 ml. The patient did not complain of respiratory discomfort shortly after PLMA removal. However, the next day she developed dysphagia and hoarseness. Laryngoscopic examination revealed unilateral vocal cord paralysis. Cricothyrotomy was required because of suspected silent aspiration pneumonia. The pharyngolaryngeal complications improved with a mobile vocal cord but slight hoarseness after 2 months. We considered the patient's CREST syndrome with a potential of tissue ischemia, and the high intracuff pressure of the PLMA due to nitrous oxide influx, to be the cause of severe recurrent laryngeal nerve neuropraxia in this case.

Aged↗

PubMed2005

CYP1A1 is a major enzyme responsible for the metabolism of granisetron in human liver microsomes.

Granisetron, a potent 5-HT3 receptor antagonist, has been reported to be mainly metabolized to 7-hydroxygranisetron and a lesser extent to 9'-desmethylgranisetron in humans. A previous study indicated that cytochrome P450 (CYP)3A4 is a major catalyst of 9'-demethylation, although the major CYP isoform(s) responsible for 7-hydroxylation are unknown. To clarify granisetron 7-hydroxylase, the in vitro metabolism of granisetron using expressed human CYPs and human liver microsomes was investigated. 7-Hydroxygranisetron was produced almost exclusively by CYP1A1, while, apparently, 9'-desmethylgranisetron was preferentially produced by CYP3A4. Marked inter-individual differences in the ratio of the formation of 7-hydroxygranisetron and 9'-desmethylgranisetron in human liver microsomes was observed. Granisetron 7-hydroxylase activity was strongly correlated with benzo[a]pyrene 3-hydroxylase activity (p<0.0001), but not with testosterone 6beta-hydroxylase activity in human liver microsomes. Furthermore, an anti-human CYP1A1 antibody completely inhibited 7-hydroxylation in human liver microsomes, however, the reaction was not inhibited at all by an anti-CYP3A4 antibody. On the other hand, granisetron 9'-demethylase activity correlated significantly not only with testosterone 6beta-hydroxylase activity (p<0.0001) but also with benzo[a]pyrene 3-hydroxylase activity (p<0.01). Consistent with this, both the anti-CYP1A1 and anti-human CYP3A4 antibodies inhibited the 9'-demethylase activity. These data indicate that CYP1A1 is a major enzyme responsible for the metabolism of granisetron via a main 7-hydroxylation pathway and an alternative 9'-demethylation route. This is the first report demonstrating the substantial contribution of CYP1A1 to the metabolism of a drug, although its role in the metabolism of environmental compounds is well established.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed2005

Differentiation effects by the combination of spheroid formation and sodium butyrate treatment in human hepatoblastoma cell line (Hep G2): a possible cell source for hybrid artificial liver.

The aim of this study was to investigate the feasibility of human hepatoblastoma cell line (Hep G2), which differentiates by spheroid formation, and treatment with sodium butyrate (SB) as a cell source for hybrid artificial liver (HAL). Hep G2 spontaneously formed spheroids in polyurethane foam (PUF) within 3 days of culture and restored weak ammonia removal activity. Treatment with SB, which is a histone deacetylase inhibitor, further increased the ammonia removal activity of Hep G2 spheroids in a concentration-dependent manner. The activation of ornithine transcarbamylase--a urea cycle enzyme--was significantly related to the upregulation of ammonia removal by spheroid formation, but scarcely contributed to the further upregulation following SB treatment. In contrast with ammonia removal, treatment with SB reduced the albumin secretion of Hep G2 spheroids in a concentration-dependent manner. In the PUF-HAL module in a circulation culture, the ammonia removal rate and albumin secretion rate (per unit volume of the module) of Hep G2 spheroids treated with 5 mM SB were almost the same as those of primary porcine hepatocyte spheroids. These results suggest that simultaneous use of spheroid formation and SB treatment in Hep G2 is beneficial in enhancing the functions of human hepatocytes with potential applications in regenerative medicine and drug screening.

Albumins↗

PubMed2004

Hypernuclear fine structure in (16)(Lambda)O and the LambdaN tensor interaction.

We have observed two gamma-ray transitions in (16)(Lambda)O from the 6.6 MeV excited 1(-)(2) state to both ground-state spin-doublet members (1(-)(1),0(-)) by the (K-,pi(-)gamma) reaction. We have obtained the ground-state doublet spacing to be 26.4+/-1.6(stat)+/-0.5(syst) keV and the excitation energy of the 1(-)(2) state to be 6561.7+/-1.1(stat)+/-1.7(syst) keV. The ground-state doublet spacing provides a small but nonzero strength of the tensor interaction between a Lambda and a nucleon. This is the first experimental result on the LambdaN tensor interaction.

Journal Article↗

PubMed2004

Effect of prostaglandin E1 on inflammatory responses and gas exchange in patients undergoing surgery for oesophageal cancer.

BACKGROUND: Oesophageal surgery causes morbidity and mortality from respiratory complications. We tested the possibility that prostaglandin E1 (PGE1) could reduce inflammatory cytokine responses and improve gas exchange after oesophagectomy. METHODS: We randomized 14 patients into two groups. One group received PGE1 20 ng kg(-1) min(-1) i.v. during anaesthesia (PGE1 group) and the other group did not (control group). Anaesthesia was maintained with sevoflurane and epidural anaesthesia. During oesophagectomy, ventilation of one lung was carried out with a double-lumen bronchial tube. The patients were extubated on or after the first postoperative day. Blood samples were taken at induction of anaesthesia, at the end of thoracotomy, at the end of the operation, 2 h after surgery and on the first day after surgery. RESULTS: The groups were similar for ASA physical status, age, FEV1%, operation time, duration of thoracotomy, intraoperative fluid volume and blood loss. The arterial blood gas and arterial pressure during surgery were also similar in the PGE1 and control groups. However, the PaO2/FiO2 ratio on the first day after surgery was significantly greater in the PGE1 group compared with the control group. Serum concentrations of IL-6 and IL-8 increased after surgery in both groups. IL-6 was significantly less in the PGE1 group at the end of the operation and 2 h after the operation. CONCLUSIONS: Intraoperative PGE1 reduced IL-6 production in patients undergoing oesophagectomy and oxygenation was better in the postoperative period.

Aged↗

PubMed2004

Micturition-related neuronal firing in the periaqueductal gray area in cats.

The midbrain periaqueductal gray (PAG) is the area promoting emotional motor responses, reproductive behaviors and analgesia. Recent studies suggest that neurons in the PAG may be crucial for regulating the micturition reflex in both experimental animals and humans. We examined single neuronal activities in the PAG and the adjacent area in response to isovolumetric spontaneous micturition reflexes in 20 supracollicular decerebrated cats. In total, 84 neurons were recorded in the PAG that were related to urinary storage/micturition cycles. Of the neurons recorded, the most common were tonic storage neurons (43%), followed by tonic micturition neurons (29%), phasic storage neurons (15%) and phasic micturition neurons (13%). In addition to the tonic/phasic as well as storage/micturition classification, the neurons showed diverse discharge patterns: augmenting, constant and decrementing, with the constant discharge pattern being most common. Of the 16 neurons located within the PAG that had similar discharge patterns to those just ventral to the PAG, the micturition neurons were distributed in a broader area, whereas the storage neurons seemed to be concentrated in the middle part of the PAG (P0-1, Horsley-Clarke coordinate). High-frequency stimulation (HFS; 0.2-ms duration, 100 Hz) applied in the PAG elicited inhibition of the micturition reflex. Effective amplitude of the electrical stimulation for evoking inhibitory responses was less than 50 microA. In conclusion, the results of the present study showed that HFS of the PAG inhibited the micturition reflex and there were micturition-related neuronal firings in the PAG in cats, suggesting that the PAG is involved in neural control of micturition.

Action Potentials↗

PubMed2004

Human normal hepatocytes are susceptible to apoptosis signal mediated by both TRAIL-R1 and TRAIL-R2.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in tumor cells without toxicity to normal cells, but some recombinant versions of TRAIL caused hepatocyte death. We generated fully human monoclonal antibodies (mAbs) that bind specifically to TRAIL receptor 1 (TRAIL-R1) and TRAIL receptor 2 (TRAIL-R2), which mediate apoptosis signal when they ligate with TRAIL, to investigate the contribution of each receptor to induce tumor cell apoptosis and hepatocyte toxicity. All of mAbs to TRAIL-R1 and TRAIL-R2 induced cell death in several cancer cell lines susceptible to TRAIL but not in human umbilical vein endothelial cells in vitro. Both anti-TRAIL-R1 mAbs and anti-TRAIL-R2mAbs also caused cell death in hepatocytes. However, a subset of mAbs to TRAIL-R2, which was characterized by the TRAIL blocking activity, did not show strong hepatocyte toxicity. These results indicate that human normal hepatocytes are susceptible to both TRAIL-R1- and TRAIL-R2-mediated apoptosis signal. Cell Death and Differentiation (2004) 11, 203-207. doi:10.1038/sj.cdd.4401331 Published online 24 October 2003

Animals↗

PubMed2004

Potential impact of orthotic gait exercise on natural killer cell activities in thoracic level of spinal cord-injured patients.

STUDY DESIGN: Prospective before-after trial. OBJECTIVE: To examine the changes of natural killer (NK) cell activity in response to orthotic gait exercise in thoracic level of spinal cord-injured (SCI) patients. SETTING: National Rehabilitation Center for Persons with Disabilities, Japan. METHODS: In all, 10 thoracic level of SCI patients (ranging Th5-Th12), who experienced orthotic gait training, participated in this study. NK cell activity at an effector:target (E/T) ratio (20:1) was examined in a sample of peripheral blood taken before and just after orthotic gait exercise for 20 min. On a separate day, to evaluate the physical intensity of the orthotic gait exercise, cardiorespiratory responses at rest and during exercise were measured. RESULTS: The resting value of the NK cell activity in our SCI patients was remarkably lower than that in normal subjects reported in previous studies. The NK cell activity was significantly increased through a 20 min orthotic gait exercise (pre versus post; 12.7+/-5.28 versus 17.76+/-6.71, P<0.05). The steady-state value of oxygen (VO2) and heart rate (HR) were 18.13+/-3.92 ml/kg and 142.53+/-19.84 b/min, respectively. It was noteworthy that a patient who showed decrement of NK cell activity in response to exercise had the highest level of injury (Th5), and showed the higher energy cost of orthotic gait. CONCLUSION: These findings suggested that the orthotic gait exercise has the potential to enhance the immune function for SCI persons, although patients with a higher level of SCI may have some difficulties. SPONSORSHIP: Mitsui Sumitomo Insurance Welfare Foundation

Adult↗

PubMed2004

Stretch reflex excitability of the anti-gravity ankle extensor muscle in elderly humans.

AIM: To examine whether the stretch reflex excitability of the soleus muscle changes with age, stretch reflexes at rest (REST) and during weak voluntary contractions (ACT) were elicited in 18 older and 14 younger subjects. METHOD: The amplitude of the stretch reflex responses and gain, defined as the gradient of the regression line for the relation between stretch reflex responses against the angular velocity of the applied perturbation, were evaluated in each short-latency (M1) and two long-latency components (M2 and M3). RESULTS: It was found that in the older group, both the amplitude and gain of the M1 component did not change from the REST to the ACT conditions, whereas in the younger group both variables significantly increased from the REST to ACT conditions. The latency of the M1 component was significantly shorter under the REST condition (older vs. younger: 51.8 +/- 7.37 vs. 55.1 +/- 8.69 ms), while no group differences were found in those variables under the ACT condition, suggesting that the muscle-tendon complexes of SOL muscles of the older subjects were less elastic and had less slack, probably due to age-related histochemical alterations. Further, the Hoffman reflex (H-reflex), elicited during the REST condition in 10 older and 11 younger subjects showed no significant differences, suggesting that the soleus motoneuron response to the Ia input was comparable between the two subject groups. CONCLUSION: The histochemical alterations occurring with the ageing process might augment the short-latency stretch reflex in the SOL muscle without enhancement of motoneuronal excitability, and this effect might be masked when the muscle is voluntarily activated.

Adult↗

PubMed2004

Plasma brain natriuretic peptide in takotsubo cardiomyopathy.

BACKGROUND: Takotsubo cardiomyopathy is a reversible left ventricular dysfunction with symptoms resembling acute myocardial infarction, but without coronary lesions. Patients have wall motion abnormalities (apical akinesis and basal hyperkinesis), and characteristic left ventricular morphology. AIM: To investigate plasma brain natriuretic peptide (BNP) concentrations in takotsubo cardiomyopathy. METHODS: Ten consecutive patients with takotsubo cardiomyopathy underwent cardiac catheterization on their first hospital day, and blood was collected to measure BNP. To evaluate acute basal hyperkinesis, the difference in diameter between systole and diastole was measured at 10 mm below the aortic valve (the deltaBase value). RESULTS: Coronary angiography revealed no significant stenosis in any patient. Initial ejection fraction was 42.2 +/- 7.3%, cardiac index was 1.90 +/- 0.39 l/min/m(2), and plasma BNP was 522.5 +/- 632.9 pg/ml. Ventricular contraction and the ejection fraction were normalized on echocardiography after 17.9 +/- 6.3 days. BNP was significantly correlated with deltaBase, but not with other cardiac parameters. DISCUSSION: Initial deltaBase value seems to be a good indicator of the severity of basal hyperkinesis in patients with takotsubo cardiomyopathy. In contrast to other diagnoses, a high BNP concentration is not associated with a poor prognosis in this condition.

Aged↗