Biomedical subjects

K Kuno

Publications and source records attributed to K Kuno.

At least 55 records · Page 3Linked to original sources

PubMed1997

Stimulation of interleukin-8 production by okadaic acid and vanadate in a human promyelocyte cell line, an HL-60 subline. Possible role of mitogen-activated protein kinase on the okadaic acid-induced NF-kappaB activation.

Most types of cells can produce interleukin (IL)-8 in response to various inflammatory stimuli. To study the role of protein phosphatases in the signal transduction leading to IL-8 production, a subline of HL-60 (C-15) was treated with okadaic acid (OA) and sodium orthovanadate (VA), inhibitors of phosphoserine/phosphothreonine phosphatase and phosphotyrosine phosphatase, respectively. Both OA and VA dramatically increased IL-8 secretion up to 200-fold in the HL-60 cells. OA and VA stimulation was accompanied by a marked increase in IL-8 mRNA expression and also by activation of a transcription factor, NF-kappaB. In addition, an essential role of the NF-kappaB site in the IL-8 gene activation was confirmed by the chloramphenicol acetyltransferase assay. IL-8 production by OA or VA was inhibited by protein kinase inhibitors, including staurosporine, H-7, K252a, herbimycin A, and genistein. Both OA and VA induced significant tyrosine phosphorylation of p44, which was presumed to be Erk1, a member of the mitogen-activated protein kinase family, with concomitant activation of the mitogen-activated protein kinase activity. In parallel, rapid degradation of IkappaB-alpha, an inhibitory component of NF-kappaB, was observed. Since OA-activated Erk1 phosphorylated recombinant IkappaB-alpha in vitro, we assumed that Erk1 is involved in the phosphorylation and subsequent degradation of IkappaB-alpha, thus leading to the activation of IL-8 gene transcription.

Base Sequence↗

PubMed1997

Molecular cloning of a gene encoding a new type of metalloproteinase-disintegrin family protein with thrombospondin motifs as an inflammation associated gene.

A cellular disintegrin and metalloproteinase (ADAM) is a new family of genes with structural homology to the snake venom metalloproteinases and disintegrins. We screened genes which were selectively expressed in the cachexigenic colon 26 adenocarcinoma subline in vivo. It was found that one novel cDNA clone, identified as a cachexigenic tumor selective gene, encodes a cysteine-rich protein which shows a sequence similarity to that of both the snake venom metalloproteinases and thrombospondins. We named this cDNA clone A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-1). ADAMTS1 consists of six domains, 1) a pro- and 2) a metalloproteinase, 3) a disintegrin-like, 4) a thrombospondin (TSP) homologous domain containing TSP type I motif, 5) a spacer region, and 6) COOH-terminal TSP submotifs. Unlike other ADAMs, ADAMTS-1 does not possess a transmembrane domain and is a putative secretory protein. Therefore, ADAMTS-1 is a new type of ADAM family protein with TSP type I motifs. We demonstrated that the TSP homologous domain containing the TSP type I motif of ADAMTS-1 is functional for binding to heparin. ADAMTS-1 mRNA could be induced by stimulating colon 26 cells with an inflammatory cytokine, interleukin-1, in vitro. Moreover, intravenous administration of lipopolysaccharide in mice selectively induced ADAMTS-1 mRNA in kidney and heart. These data suggest that ADAM-TS-1 may be a gene whose expression is associated with various inflammatory processes as well as development of cancer cachexia.

ADAM Proteins↗

PubMed1997

The effect of the level of ventilatory assist on the level of respiratory drive in decerebrate cats.

The present study was undertaken to investigate whether, independent of changes in PaCO2, ventilatory assist influences not only the pattern but also the level of the respiratory drive. The experiments were performed on decerebrate and paralyzed cats ventilated by a phrenic-driven servo respirator at three different FICO2 levels (0, 0.30, 0.05). The level of ventilatory assist was altered within the range where PaCO2 did not exceed 80 Torr. A higher FICO2 accompanied a higher level of ventilatory assist. The relationship between the minute phrenic activity and log10 PaCO2 at a given FICO2 was linear. No significant difference was found in the regression lines at different levels of FICO2. We conclude that ventilatory assist has little effect on the respiratory drive at a constant level of chemical feedback during hypercapnia.

Animals↗

PubMed1997

Sclerosing inflammatory pseudotumor arising from the carotid artery region.

We report a 42-year-old female patient with sclerosing inflammatory pseudotumor. She had found a mass in her left neck after she caught a cold. An elastic hard mass (25 x 15 mm), unaccompanied by any other symptoms, was palpated adjacent to the left carotid bifurcation. The mass extended vertically along the common carotid artery, partially adhering to the pulsating artery. Under ultrasonography, the mass was characterized by a homogenized low echoic shadow surrounding the left common carotid artery. Angiography revealed a slight narrowing of the common carotid artery with a surrounding hypovascular mass. Computerized tomography (CT) and magnetic resonance imaging (MRI) both showed a mass enclosing the carotid artery; a Ga scintigram also showed a highly concentrated mass. Surgical removal of the mass included removing part of the carotid artery, internal and external carotid arteries and sympathetic trunk. The left internal jugular vein was transplanted to connect the common carotid artery to the internal carotid artery. Although the hypoglossal and vagus nerves adhered to the mass, they were preserved by sharp dissection with the scalpel. Although hypoglossal and vagus nerve dysfunction were observed temporarily after the surgery, Horner's syndrome appeared and persisted. Histological examination revealed markedly fibrotic tissues surrounding the carotid artery with extensive lymphocyte and plasmacyte infiltration and a diagnosis of sclerosing inflammatory pseudotumor was made.

Adult↗

PubMed1997

Dysmature EEG pattern in EEGs of preterm infants with cognitive impairment: maturation arrest caused by prolonged mild CNS depression.

The significance of mild sustained brain injury in the pathogenesis of perinatal brain damage was investigated using serial EEG recordings performed on 102 early preterm infants surviving beyond 2 years of age. Sixteen infants (16%) elicited mild depression of background EEG activities in the neonatal period. Of nine infants with mild depression of prolonged duration (more than 3 weeks), five (56%) were diagnosed as having cognitive impairment in the follow up study. Four showed no signs of cerebral palsy, while one had cerebral palsy. The infants with cognitive impairment showed mild prolonged depressions in background EEG activities in the early neonatal period and dysmature EEG patterns in the late neonatal period. They also showed maturation arrest in EEG patterns during prolonged mild depression of background EEG activities. In addition to strong sudden depression of CNS causing deep white matter injury and motor impairment, prolonged mild depression is another mode of brain injury in early preterm infants which can induce future cognitive impairment.

Brain Ischemia↗

PubMed1997

Disorganized patterns: chronic-stage EEG abnormality of the late neonatal period following severely depressed EEG activities in early preterm infants.

EEG recordings were performed within 72 hours following the birth of 55 preterm infants with a gestational age of less than 29 weeks. Seventeen infants (31%) manifested moderately to severely depressed EEG activities during this period. Eight of the infants died within a few days after birth, and 9 survived. We recorded EEGs from the surviving infants serially throughout the neonatal period, and evaluated EEG findings in the recovery phase following depressed EEG activities. At 1 to 3 weeks after birth, EEGs revealed an abnormal morphology of background activities in 8 of 9 cases; this was also true of the EEGs of 6 cases at 4 weeks or more of postnatal age. The latter 6 cases demonstrated deep white matter injury on cranial ultrasonography, and all of them later developed cerebral palsy. Based on the foregoing, EEG findings of early preterm infants in the late neonatal period are considered a useful means to detect deep white-matter injury and to allow neurological prognosis.

Brain Damage, Chronic↗

PubMed1997

Hypoxaemia in patients with hyperventilation syndrome.

We assessed 12 patients with hyperventilation syndrome (HVS) who had experienced hypoxaemia (PaO2 < 60 Torr or SaO2 < 90%) despite the lack of any other organic disease and variability in their blood gas data. Hypoxic and hypercapnic ventilatory responses were measured in nine. Eight of the 12 patients had been referred from other hospitals to our institution for hypoxaemia of unknown origin. Mean PaO2 (n = 12) at rest (non-attack stage) was 87.3 +/- 7.5 Torr (mean +/- SD). Their (n = 9) hypoxic (-0.53 +/- 0.32 l/min/%; range 0.12-0.99) and hypercapnic (2.01 +/- 0.76 l/min/Torr; range 0.69-3.17) ventilatory responses were both within the normal range in our laboratory. The patients with HVS had variable blood gas data, and some of them also exhibited hypercapnia (PaCO2 > 45 Torr). Clinicians who treat patients with HVS should be aware of the possibility of hypoxaemia, even when ventilatory responses are normal. Physicians should also consider HVS as a diagnosis when treating patients with hypoxaemia of unknown origin.

Adult↗

PubMed1997

MRI findings in patients with spastic cerebral palsy. I: Correlation with gestational age at birth.

The authors studied MR images of the brain in 152 patients, aged 1 to 19 years (mean 3.3), who had spastic cerebral palsy (CP) and were attending two hospitals in Japan in 1993 and 1994. The relation was studied between the patients' gestational age at birth and their MRI findings, including the severity of periventricular leukomalacia (PVL) seen on MRI. In 119 of these patients, the CP was thought to be due to acquired, destructive brain injury. PVL was seen in 90 and posthemorrhagic porencephaly in 11. These preterm-type brain injuries were observed often in patients who had been born preterm but were also seen in those born at term. Fullterm-type border-zone infarct, bilateral basal ganglia-thalamic lesion, subcortical leukomalacia, and multicystic encephalomalacia were seen in 9, 14, 7, and 3 patients, respectively; these term-type brain injuries were observed only in patients born at or near term. Of the patients with PVL, 90% had been born preterm. Severe PVL was common in the patients whose gestational ages at birth were between 25 and 32 weeks; all patients with PVL who had been born at term had only mild PVL. The authors concluded that MRI findings for patients with spastic CP are closely correlated with gestational age.

Adolescent↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

Changes in the arterial PCO2 during a single night's sleep in patients with obstructive sleep apnea.

To investigate the relationship between hypercapnia during sleep and its influence on the PaCO2 during the morning after sleep in patients with obstructive sleep apnea syndrome (OSAS), the transcutaneous PCO2 (PtcCO2) was measured throughout the night, and the arterial blood gases (ABG) were also measured while awake before and after polysomnography in 30 OSAS patients with (n=13, hypercapnic group: HC) and without (n=17, normocapnic group: NC) hypercapnia. Significant differences were observed in the body mass index (p=0.03), the difference between the highest PtcCO2 during sleep and the PtcCO2 during awake before sleep (D-PtcCO2), (HC: 11.l+/-1.7 mmHg; NC: 6.3+/-0.5 mmHg; p=0.0057) and the lowest SaO2 during sleep (p=0.0007). In the HC, the PaCO2 on the morning after sleep (50.0+/-0.14 mmHg) was significantly increased (p=0.0029) compared with the PaCO2 on the night before sleep (47.4+/-1.1 mmHg). In the NC, this phenomenon was not observed. Severe hypercapnia (high D-PtcCO2) during a single night's sleep has a significant effect on the waking PaCO2 immediately following sleep in the HC.

Body Mass Index↗

PubMed1997

Ventilatory responses and subjective sensations during arm exercise and hypercapnia in patients with lower-cervical and upper-thoracic spinal cord injuries.

We measured the ventilatory responses and subjective sensations during arm exercise in patients with lower cervical and upper thoracic spinal cord injuries in order to evaluate the effects of chest wall deafferentation on these responses. Visual analog scales with verbal descriptors were used to quantify respiratory sensations of different affectional qualities. Patients as well as normal subjects reported stronger respiratory sensations upon CO2 rebreathing as compared to during arm exercise with an equivalent minute ventilation (p<0.05). There were no qualitative nor quantitative differences in the respiratory sensations during CO2 rebreathing between the patients and normal subjects. However, patients with spinal cord injuries showed a higher minute ventilation and a lower end-tidal PCO2 during incremental arm exercises (p<0.01), and thus tended to hyperventilate. We conclude that chest wall afferent denervation does not contribute significantly to the perception of breathlessness in patients with spinal cord injuries.

Adult↗

PubMed1997

Effects of resistive load on the phase difference between chest and mouth flow in patients with chronic obstructive pulmonary disease.

The influence of the resistive load on the phase difference (PD) between chest wall and mouth flow in patients with chronic obstructive pulmonary disease (COPD) was investigated, and the factors that induce an enlargement of the PD were assessed. After a resistance tube (R = 2.8 hPa/l/s) was applied to the mouth of the subjects, the PDs increased significantly both in normal (pre: 2.20 +/- 0.89, post: 5.60 +/- 2.04, P < 0.01) and in COPD (pre: 10.86 +/- 3.81; post: 13.12 +/- 3.64, P < 0.01). A significant correlation between the airway resistance and PD was noted (r = 0.730, P < 0.001). These results suggest that airway resistance is an important determinant for the PD. The predicted phase difference (PD') was then calculated by the Runge-Kutta method, using the measured chest flow, the time domain functions of airway resistance and the thoracic gas volume during a respiratory cycle, assuming that the respiratory system was a single compartment. The PD/PD' at pre-resistive load was significantly larger in COPD than in normal subjects (normal: 1.03 +/- 0.11; COPD, 1.45 +/- 0.19, P < 0.01), whereas the PD/PD' at a post-resistive load was significantly smaller than at the pre-resistive load in COPD patients. These results agree well with the two parallel or serial compartment model with inhomogeneous airway resistance, where the mechanical property of the partitioning tissue between the two compartments was taken into account. The pattern of the increase in the work energy consumed within the airway lumen calculated from this model was almost the same as for PD. Thus, we conclude that the PD may be a good index of the overload of the respiratory movement and available to predict muscle fatigue in COPD patients.

Adult↗

PubMed1997

Quantitative assessment of the spatial distribution of low attenuation areas on X-ray CT using texture analysis in patients with chronic pulmonary emphysema.

An automated and quantitative assessment of the spatial distribution of low attenuation areas (LAA) on X-ray CT was performed using texture analysis in chronic pulmonary emphysema (CPE) patients. LAA was defined as those areas having a density less than the mean minus one SD of the control (-960 HU). The probability of change from non-LAA to LAA between a given pair of pixels with horizontal intervals of i pixels (RNi) was evaluated, because this reflects the interaction between LAA and non-LAA regions with different resolutions. The relationship between the percentage area of the LAA over the total area of the entire lung field (LAA%) was subsequently estimated. The RNi increased sharply as the i value increased from 1 to 5, but then almost became a plateau for i values larger than 5. This suggests that the fundamental structures in the LAA areas ranged from 1 x 1 to 5 x 5 pixels in size. RN1-LAA% and RN5-LAA% plots produced curves which were convex, with peak values at approximately 50 LAA% of 0.09 and 0.18, respectively. In the RN5/RN1-LAA% plot, the RN5/RN1 ratio remained constant at 2.0 regardless of the LAA%. A random process simulation was performed to determine the patterns of LAA proliferation if the spatial distribution of the LAA units was random. When the unit size was kept constant, the results of the simulation did not fit the empirical relationship between the LAA% and the three parameters (RN1, RN5 and RN5/RN1). The simulation provided the best-fitting curves when the unit size of the LAA increased in proportion with the LAA%, starting from a 1 x 1 pixel size increasing at a ratio 1 x 1/(5 LAA%). This suggested that the LAA units do not proliferate randomly in spatial orientation at a fixed unit size, but rather spread throughout the whole lung field in a congregated form whilst increasing their unit size. Thus, it may be concluded that healthy lung tissues near emphysematous lesions have a high probability of suffering from emphysema in the future. This may be due to a direct effect of the neighboring emphysematous lesion or due to a pathologic change in the larger bronchii which dominate both the healthy tissues and the emphysematous lesions.

Aged↗

PubMed1997

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↗

PubMed1997

MRI findings in patients with spastic cerebral palsy. II: Correlation with type of cerebral palsy.

The authors studied MR images of the brain in 152 patients, aged 1 to 19 years (mean 3.3), who had spastic cerebral palsy (CP) and were attending two hospitals in Japan in 1993 and 1994. Eighty-one patients had diplegia, 45 had quadriplegia, and 26 had hemiplegia. Of patients with diplegia, 72 had periventricular leukomalacia (PVL) and very few had other types of lesions. In patients with quadriplegia, three main types of brain lesions were observed: PVL in 12 patients, term-type brain injury in 22, and brain anomaly in 10. In the 26 patients with hemiplegia, 17 had a unilateral lesion (rare in patients with diplegia and quadriplegia), and bilateral lesions were seen in seven others.

Adolescent↗

PubMed1997

Standardization of low attenuation area versus total lung area in chest X-ray CT as an indicator of chronic pulmonary emphysema.

We examined the methods for measuring the LAA% (100 x low attenuation area/total lung area) on thoracic X-ray CT scans in order to develop a useful indicator of chronic pulmonary emphysema (CPE). First, we modified the method for calculating the LAA% to be applicable by the programming tool installed in a commercially available CT machine in order to minimize manual procedures. This new method proved to be applicable in all CT machines produced after 1987. Second, we examined the difference in the Hounsfield Unit (HU) between different CT machines using two kinds of phantoms. One phantom was composed of Styrofoam, which has a density similar to the low attenuation areas. The other phantom was composed of Styrofoam and water, which has a density similar to the lung. We proved that the difference of LAA% with the correct value was 5% at maximum among four different CT machines. Thus, the phantom developed in the present study may play an important role in the standardization of HU. Finally, the possibility of decreasing the X-ray levels was examined. Twenty-five percent of the standard electrical current provided the same LAA% in cases where the subject was an established CPE patient, whereas the LAA% was overestimated in subjects with a normal LAA% value. However, a correction using a linear regression equation may be possible in the latter cases. It may be concluded that LAA% analysis can easily be performed in many city hospital, without much investment of manual procedures or any corrections to the HU levels between different CT machines. This method may be useful as a routine follow up for CPE patients because of the smaller irradiated dose given when using a CT machine.

Algorithms↗