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Biomedical subjects

N Otsuka

Publications and source records attributed to N Otsuka.

At least 19 recordsLinked to original sources

[Nuclear medicine of bone].

Bone scintigraphy using 99mTc-labeled phosphorous compounds was found to be the most frequently ordered nuclear medicine examination in a nationwide survey in Japan, and has been used for the detection of lesions and the evaluation of disease progression and response to therapy in various skeletal diseases. In this article, we review improvement of the diagnostic sensitivity and specificity for bone metastasis of not only nuclear medicine techniques, such as planar imaging, SPECT, early flow phase imaging and quantification of bone scintigraphy, and bone marrow scintigraphy but also such recently developed methods as bone mineral measurement, and bone metabolic marker assays. In addition, radionuclide therapy of intractable bone pain due to bone metastasis is also addressed.

Bone Density

[Development of a simple method for the washout correction of 123I-IMP SPECT and its application to a quantitative rCBF method].

We have developed a simple method to correct the washout of tracer from the brain based on the two-compartment model in brain early SPECT using N-isopropyl-p-[123I]iodoamphetamine (123I-IMP). This correction was applied to a new quantitative method of regional cerebral blood flow (rCBF) in combination with the microsphere method by continuous arterial sampling previously reported. Data acquisition of 123I-IMP early SPECT was started from 35 min after 123I-IMP i.v. injection, and the time activity curve of whole brain on anterior head planar images was monitored immediately after 123I-IMP i.v. injection for the correction of washout of tracer from the brain. The usefulness of this method was evaluated in 12 patients with various brain diseases by comparison with the results obtained from the super-early SPECT at 7-10 min after 123I-IMP i.v. injection. The washout rates in cases of early SPECT corrected by this method ranged from 16.91% to 39.34% with a mean +/- SD of 27.72 +/- 5.44%. The contrast of hypo- to hyperperfusion regions on early SPECT was improved by the correction of the washout, and its intracerebral distribution was similar to the simultaneously obtained super-early SPECT images. These results indicated that the present correction method for the washout was useful for more correct quantification of rCBF.

Brain

Phosphorylation of CrkII adaptor protein at tyrosine 221 by epidermal growth factor receptor.

CrkII adaptor protein becomes tyrosine-phosphorylated upon various types of stimulation. We examined whether tyrosine 221, which has been shown to be phosphorylated by c-Abl, was phosphorylated also by other tyrosine kinases, such as epidermal growth factor (EGF) receptor. For this purpose, we developed an antibody that specifically recognizes Tyr221-phosphorylated CrkII, and we demonstrated that CrkII was phosphorylated on Tyr221 upon EGF stimulation. When NRK cells were stimulated with EGF, the tyrosine-phosphorylated CrkII was detected at the periphery of the cells, where ruffling is prominent, suggesting that signaling to CrkII may be involved in EGF-dependent cytoskeletal reorganization. The EGF-dependent phosphorylation of CrkII was also detected in a c-Abl-deficient cell line. Moreover, recombinant CrkII protein was phosphorylated in vitro by EGF receptor. These results strongly suggest that EGF receptor directly phosphorylates CrkII. Mutational analysis revealed that the src homology 2 domain was essential for the phosphorylation of CrkII by EGF receptor but not by c-Abl, arguing that these kinases phosphorylate CrkII by different phosphorylation mechanisms. Finally, we found that the CrkII protein phosphorylated upon EGF stimulation did not bind to the phosphotyrosine-containing peptide and that CrkII initiated dissociation from EGF receptor within 3 min even with the sustained tyrosine phosphorylation of EGF receptor. This result implicated phosphorylation of Tyr221 in the negative regulation of the src homology 2-mediated binding of CrkII to EGF receptor.

Animals

The nocturnal secretion of cardiac natriuretic peptides during obstructive sleep apnoea and its response to therapy with nasal continuous positive airway pressure.

The nocturnal secretion profile of the newly identified natriuretic peptide (NP), brain natriuretic peptide (BNP), was studied in 14 patients with obstructive sleep apnoea syndrome (OSAS) (apnoea hypopnoea index: 60.5 +/- 3.4, mean +/- SE) during two separate nights before and during nasal continuous positive airway pressure (NCPAP) therapy. Plasma levels of NPs (atrial natriuretic peptides; ANP and BNP) were measured at 2-h intervals during sleep. Simultaneously, blood pressure was measured by a non-invasive method (Finapres, Ohmeda, Englewood, CO, USA) and urine was collected for determining volume and catecholamine levels. Urinary and serum sodium concentration were determined before and after the study. Eight non-snoring subjects were also studied for the investigation of normal nocturnal profiles of BNP levels. To understand the discrete secretion profiles of the two NPs during sleep, blood was sampled from an additional seven patients every 5 min over a 30-min period around 00.00 and 04.00 hours before NCPAP. In patients with OSAS, plasma BNP levels increased from the beginning of sleep (22:00 h) to the morning (06:00 h) before NCPAP therapy (P < 0.01, ANOVA). Baseline BNP levels were not significantly correlated with patient's clinical and polysomnographic parameters. However, in the latter half of the sleep period (02:00-06:00 h), increases in BNP levels during the night before NCPAP therapy were significantly correlated with blood pressure elevations (systolic: r = 0.784 P < 0.01, diastolic: r = 0.587 P < 0.01) and with apnoea duration (r = 0.582 P < 0.01). In normal subjects BP and BNP levels were not changed significantly during sleep. Plasma BNP levels were well correlated with concomitant ANP levels (P < 0.001). NCPAP therapy reduced ANP and BNP levels during sleep and in the morning (P < 0.01). Plasma levels of BNP at 5 min intervals before NCPAP therapy revealed few variations. On the other hand, ANP levels fluctuated over the 30-min period. Changes in BNP levels during sleep in the patients with OSAS may be related to blood pressure variations, but may be too small to play a significant physiological role in regulating diuresis in OSAS. Further work is required to determine the precise role of dual natriuretic system in cardiovascular load and natriuresis in OSAS.

Atrial Natriuretic Factor

Interrater reliability of the Japanese version of the Positive and Negative Syndrome Scale and the appraisal of its training effect.

The purpose of the present study is to test interrater reliability of the Japanese version of the Positive and Negative Syndrome Scale (PANSS) and to examine factors possibly affecting the reliability. The study group conducted the PANSS rating on 20 patients with DSM-IV schizophrenia. For the analysis of interrater reliability, intraclass correlation coefficient (ICC) was calculated. The ICC for individual items of the PANSS ranged from 0.26 to 0.92, and those for the positive, negative, and general psychopathology subscales were 0.85, 0.83 and 0.75, respectively. The Cronbach's alpha coefficient for the subscales were 0.84, 0.87 and 0.76, respectively. The interrater reliability and the internal consistency were satisfactory and similar to those obtained in the antecedent studies. No salient training effect was found in a sequential analysis of the concordance rate. It is concluded that the Japanese version of the PANSS is a reliable and efficient tool for comprehensive assessment of the schizophrenic syndrome.

Adult

Improvement of factor VII clotting activity following long-term NCPAP treatment in obstructive sleep apnoea syndrome.

Obstructive sleep apnoea syndrome (OSAS) is a very common disorder. Patients with OSAS are at an increased risk for cardiovascular events. It has also been reported that a 25% rise in factor VII clotting activity (FVIIc) is associated with a 55% increase in ischaemic heart disease death during the first 5 years. We examined the effects of nasal continuous positive airway pressure (NCPAP) treatment on FVIIc in patients with OSAS. FVIIc was investigated prospectively in 15 patients with OSAS before (mean +/- SEM apnoea and hypopnoea index (AHI) 61.5 +/- 4.2 and after (AHI 3.0 +/- 0.9) NCPAP treatment for immediate relief, at 1 month after treatment and at over 6 months. FVIIc levels gradually decreased after NCPAP treatment. After 6 months of NCPAP treatment, FVIIc levels had decreased significantly (before 141.1 +/- 11.7% vs. after 6 months 110.7 +/- 6.2%; p < 0.01). Six of the seven patients whose FVIIc levels were over 140% before the NCPAP treatment had FVIIc levels below 130% after 6 months or 1 year of NCPAP treatment. This decrease in FVIIc after long-term NCPAP treatment could improve mortality in OSAS patients. If patients, especially obese ones, present with high FVIIc of unknown origin, it would be prudent to check for OSAS.

Adult

Inhibition of human immunodeficiency virus type 1 virion entry by dominant-negative Hck.

To study the role of Src family tyrosine kinases in infection with human immunodeficiency virus type 1 (HIV-1), we constructed an Hck mutant, HckN, that hinders signaling from wild-type Hck. HIV-1 produced in HckN-expressing cells was significantly less infectious to HeLa-CD4-LTR-beta-gal (MAGI) cells than HIV-1 produced in mock-transfected cells. The inhibitory effect of HckN was compensated for by the expression of vesicular stomatitis virus G protein. Finally, we found that the HIV-1 produced in the HckN-expressing cells entered into the cells less efficiently than did the control HIV-1. These results suggest that the Src family tyrosine kinases regulate entry of HIV-1 into target cells.

Gene Products, nef

Effects of nasal continuous positive airway pressure therapy on respiratory parameters of upper airway patency in patients with obstructive sleep apnea syndrome.

OBJECTIVES: To assess whether an initial treatment with nasal continuous positive airway pressure (NCPAP) therapy, applied for one night, had any effect on airway patency. METHODS: In 18 patients with obstructive sleep apnea syndrome (OSAS), we measured the total resistance of the respiratory system (Rrs) and their relevant lung functions before and after polysomnography, with and without NCPAP therapy. The Rrs was measured at 3 Hz with the forced oscillation technique. The overnight changes in the specific respiratory conductance (SGrs=reciprocal of the Rrs per unit lung volume) was also calculated in the sitting position. Since many reports have suggested that obesity, through fat deposits around the pharynx, can affect the mechanical and neuromuscular properties of the upper airway, we also investigated if the degree of obesity was related to the magnitude of improvement in these parameters. RESULTS: After the first night of NCPAP therapy, the Rrs decreased (sitting: 4.8+/-0.4 vs 4.3+/-0.4 cm H20/L/s, p < 0.05; lying: 6.5+/-0.4 vs 5.6+/-0.4 cm H20/L/s, p < 0.05) and the maximal voluntary ventilation increased in the morning (sitting: 101.6+/-5.8% vs 106.4+/-4.5%, p < 0.05; lying: 91.2+/-5.4% vs 97.9+/-4.7%, p < 0.05). The overnight difference in the SGrs showed a significant improvement after the initial treatment with NCPAP therapy (p < 0.05). However, the lung volume, flow volume loop, and closing volume in the morning did not change significantly after the therapy. An overnight decrease in the Rrs following NCPAP therapy is significantly correlated with the body mass index (sitting: r=0.54, p < 0.05; lying: r=0.61, p < 0.01). CONCLUSION: The improvements in Rrs without changes in spirometry may reflect improved upper airway patency after NCPAP therapy. The degree of obesity is suggested to be associated with the treatment effect on upper airway in patients with OSAS.

Adult

Unmyelinated nerve fiber analysis of the human abducent nerve.

Unmyelinated nerve fibers of the abducent nerve have occasionally been observed with electron microscopes, but, to our knowledge, they have never been evaluated from the morphometric point of view. We analyzed the aging process of the unmyelinated nerve fibers in the human abducent nerve with the help of a new staining method suitable for morphometric research on the nervous system. We studied numbers and transverse areas of unmyelinated fibers of the abducent nerve in 10 cadavers. Our findings were that (1) these fibers were distributed diffusely, (2) their number decreased with age, and (3) the mean transverse area did not change with age. Most of the unmyelinated axons were thinner than the myelinated axons. These results may be important for analysis of clinical signs in relation to aging and ophthalmologic functions.

Abducens Nerve

Morphometric nerve fiber analysis and aging process of the human abducent nerve.

Myelinated nerve fibers of the human abducent nerve were analyzed with a new staining method that permits simultaneous observation of the axon and surrounding myelin sheath. The following equipment was employed for the measurements: an image-analyzing digitizer, a microscope equipped with a drawing tube (or camera lucida), and a computer for data storage and statistical analysis. The numbers, transverse areas, and circularity ratios of axons were measured in 10 human abducent nerves. The average number was 1,997 with a definite decrease with age, and the average area was 3.90 micron 2.

Abducens Nerve

Ultrastructural localization of CD38 immunoreactivity in rat brain.

The subcellular localization of CD38 in the rat cerebral and cerebellar cortices was studied using immunoelectron microscopy. In the cerebral cortex, immunoreactivity was present in a subset of pyramidal neurons, and was distributed predominantly in the perikarya and dendrites. It was found in association with rough endoplasmic reticulum, ribosomes, small vesicles, mitochondria and the plasma membrane including the postsynaptic densities. In the cerebellum, labeling was observed in several types of neuron such as granule, Golgi, basket and Purkinje cells. In contrast to the cerebrum, immunoreactivity was accentuated in the perikarya or axon terminals, and the synaptic vesicles represented another organelle that was immunopositive for CD38. In both of these CNS regions, the nuclear envelope, particularly the outer membrane, showed constant labeling. Diffuse immunoreactivity was also present in the astrocytes from the perikarya to the processes including the perivascular glia limitans. Oligodendrocytes and microglia were immunonegative for CD38. The pattern of distribution of CD38 in the CNS is suggestive of multiple roles for this molecule at various functional sites in both neurons and astrocytes.

ADP-ribosyl Cyclase

Bone mineral measurement in Japan.

Various methods for evaluating bone mineral in appendicular, and axial bone or in the whole skeleton have recently become available. As bone mineral is one of the major determinants of bone strength, its exact measurement should be useful for the diagnosis of osteoporosis, as well as for the prediction of fracture risk and monitoring of therapeutical response. The aims of this paper are to review the fundamental performance of bone mineral measurements, the improvements in DXA systems, and the progress in site-specific bone mineral instruments for the radius and calcaneus used in Japan, and to introduce diagnostic criteria for primary osteoporosis, and report on annual rates of bone loss in Japanese females.

Absorptiometry, Photon

Heat shock protein 72 level decreases during sleep in patients with obstructive sleep apnea syndrome.

Patients with obstructive sleep apnea syndrome (OSAS) suffer from stresses related to repetitive apneas during sleep. To examine whether the level of 72 kDa heat shock protein (HSP72) increases during sleep, 11 OSAS patients (apnea-hypopnea index: 63.5 +/- 36.1, mean +/- SD) underwent polysomnography and their peripheral blood mononuclear cells (PBMC) were isolated before, during, and after sleep. HSP72 level was determined by Western blotting and hsp72 mRNA level was quantified by Northern blotting. Nine normal subjects without OSAS were examined as normal controls. HSP72 level decreased progressively during sleep and its level at 8:00 A.M. was 78.0 +/- 17.5% of that at 8:00 P.M. (p < 0.01). No such decrease was seen in normal subjects. When OSAS patients received nasal continuous positive airway pressure (NCPAP) therapy, HSP72 level did not decrease significantly. In untreated OSAS patients, hsp72 mRNA level decreased during sleep (p < 0.01). When OSAS patients were treated with NCPAP therapy, the decrease in hsp72 mRNA level was not observed. HSP72 level before sleep in OSAS patients was higher than that in normal subjects (p < 0.01). We concluded that repetitive apneas caused high HSP72 level before sleep in OSAS patients and that NCPAP therapy had significant effect on HSP72 levels during sleep.

Blotting, Northern

Hypoxic ventilatory response and breathlessness following hypocapnic and isocapnic hyperventilation.

STUDY OBJECTIVES: To investigate the etiology of posthyperventilation (post-HV) hypoxemia following voluntary hyperventilation (VHV), we examined the effects of hypocapnic (hypo-CO2) and isocapnic (iso-CO2) VHV on the hypoxic ventilatory response (O2-response) and on the sensation of breathlessness during the O2-response. METHODS: O2-responses and visual analog scale (VAS) scores for estimating breathlessness in 10 normal subjects during the O2-response under iso-CO2 conditions and under hypo-CO2 conditions immediately following voluntary maximal HV of 3 min duration were examined. RESULTS: Although there was no significant difference in the post-HV ventilation levels following hypo-CO2 vs iso-CO2 VHV, the VAS scores at the start of the O2-response following hypo-CO2 VHV (30.2+/-24.2 mm) were significantly higher (p<0.05) than the VAS scores at the start of the O2-response following iso-CO2 VHV (13.7+/-8.4 mm). However, VHV did not have a significant effect on the O2-response at 2 min after the VHV when the arterial O2 saturation (SaO2) was below 90%. The nonsteady-state hypo-CO2 induced by VHV greatly attenuated the O2-response below 90% SaO2 and VAS scores at 70% SaO2. CONCLUSIONS: Elevated VAS scores immediately following the hypo-CO2 VHV, which might be independent of actual breathing levels, and the attenuation of the O2-response following the hypo-CO2 VHV were not due to input from lung and chest wall mechanoreceptors induced by the hyperpnea itself, but rather to the hypo-CO2 induced by hyperpnea.

Adult

Ventilatory support during exercise in patients with pulmonary tuberculosis sequelae.

STUDY OBJECTIVE: The aim of this study was to determine whether intermittent positive pressure ventilation through a nasal mask (NIPPV) applied during exercise in patients with pulmonary tuberculosis sequelae (PTS) could improve arterial blood gas measurements, ameliorate breathlessness, and increase exercise endurance. PATIENTS: Seven PTS patients with a severe restrictive ventilatory defect (mean [SD] vital capacity, 1.02 [0.25] I) enrolled in this study had experienced NIPPV previously, and were familiar with the procedure. DESIGN: The patients underwent four constant-load cycle ergometer tests in the supine position to tolerance. The tests were performed with and without NIPPV, while breathing normoxic air (Air) or supplemental oxygen (O2; 35%). NIPPV was delivered during exercise in a controlled, volume-cycled mechanical ventilation mode, and the ventilator settings were modulated manually to meet patients' respiratory demands as estimated from the airway pressure waveform and the patient's breathlessness. RESULTS: All patients matched their breathing to the ventilator cycle during most of the exercise while receiving NIPPV. NIPPV significantly prolonged their exercise endurance time, from a mean (SD) of 180 (58) s to 310 (96) s in Air, and from 227 (64) s to 465 (201) s in O2. During exercise, NIPPV effectively decreased their breathlessness and significantly improved arterial blood gas measurements. CONCLUSIONS: NIPPV applied during exercise can effectively support ventilation, significantly ameliorate breathlessness, and consequently improve exercise endurance in patients with PTS.

Aged

Myelinated nerve fibre analysis of the human small splanchnic nerve.

The aim of the present study is to analyse nerve fibres of the human small splanchnic nerve in relation to the ageing process. The analysis was conducted with the use of a new staining method that makes it possible to discriminate various structures of the nervous tissue. An image-analysing digitiser, a microscope with a drawing tube and a personal computer for storing data and performing statistical analyses were employed in this study. We examined 30 human small splanchnic nerves which were taken from cadaver specimens (20 males and 10 females) aged from 44 to 96 years. Our report may provide a first information concerning the ageing process of the human small splanchnic nerve. The results indicate that a decrease in transverse area and perimeter of myelinated axons in one of the important changes occurring in the human small splanchnic nerve with the ageing process.

Adult

Morphometric analyses of axons in the lateral corticospinal tract with ageing process.

Morphometric analyses were carried out to reveal a relation between age and axonal changes in the lateral corticospinal tract (LCST) at the L1 level of the human spinal cord. Histological preparations of the spinal cord were made after embedding in celloidin to stain with Luxol fast blue-periodic acid-Schiff-hematoxylin or Klüver-Barrera methods. The number, average transverse area, total area and diameter of axons of the LCST were counted and measured using an image-analyser combined with a computer. The morphometric analyses revealed that (1) there was a significant decrease in the axonal number of the LCST with age (p < 0.001); (2) the axons were not partially nor completely accompanied by surrounding myelin sheaths, and increased in number with age; (3) the diameter and average area of axons in the LCST became significantly reduced with age (p < 0.01); (4) the total area decreased significantly with age in a unit area of 2,700 microns2; and (5) the circularity ratio showed no significant change with age.

Adult

Assessment of cardiac sympathetic function with iodine-123-MIBG imaging in obstructive sleep apnea syndrome.

UNLABELLED: Iodine-123-MIBG imaging has been used to evaluate myocardial sympathetic function in various cardiac diseases. In patients with obstructive sleep apnea syndrome (OSAS), increased sympathetic activity has been widely recognized, as assessed by measuring the plasma concentration and urinary excretion of catecholamines and by measuring muscle sympathetic nerve activity. However, these measurements are not specific indices of cardiac sympathetic function. Therefore, this study was undertaken to assess cardiac sympathetic function in patients with OSAS using MIBG cardiac scintigraphy. METHODS: This study consisted of 11 patients (10 men, 1 woman; mean age 43 +/- 16 yr) with a diagnosis of OSAS established by polysomnography, and 8 age-matched normal control subjects (7 men, 1 woman; mean age 45 +/- 18 yr). Early (15 min) and delayed (3 hr) planar images were taken after the injection of 111 MBq of [123I]MIBG. The mean counts of the whole heart and the mediastinum were obtained to calculate heart-to-mediastinum count ratios from the early images (H/Me) and from the delayed images (H/Md) and the myocardial washout rate (WR). Eight patients were restudied after 1 mo of nasal continuous positive airway pressure treatment. RESULTS: The H/Me and H/Md ratios were significantly lower in the patients than in the control subjects (H/Me, 2.49 +/- 0.32 versus 2.84 +/- 0.34, p = 0.0207; and H/Md, 2.33 +/- 0.30 versus 3.02 +/- 0.36, p = 0.0013). The WR was higher in the patients than in the control subjects (36.2 +/- 9.0% versus 23.6 +/- 4.9%, p = 0.0022). The H/Me and H/Md ratios in the patients were significantly correlated with the apnea-hypopnea index and the degree of hypoxemia during sleep. After treatment, H/Me and H/Md remained unchanged, but WR significantly recovered (from 34.9 +/- 10.4% to 26.3 +/- 7.7%, p = 0.0357). CONCLUSION: Cardiac sympathetic function and integrity are impaired in subjects with OSAS when compared with age-matched control subjects. MIBG cardiac imaging can be helpful in evaluating cardiac involvement and efficacy of therapy in OSAS.

3-Iodobenzylguanidine