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Biomedical subjects

M Iizuka

Publications and source records attributed to M Iizuka.

At least 19 recordsLinked to original sources

Development in neonatal rats of the sensory resetting of the locomotor rhythm induced by NMDA and 5-HT.

Developmental changes in the effects of quadriceps (Q) nerve stimulation on the locomotor rhythm induced by a mixture of N-methyl-D-aspartic acid and 5-hydroxytryptamine were examined using in vitro preparations from neonatal rats at postnatal days (P) 1-6. The effects of such stimulation on the rhythm were dependent both on stimulus strength and on the age of the animal. Low-intensity stimulation (< or =3.0 x T, where T=threshold for the monosynaptic reflex) during the flexor phase reset the rhythm via a prolongation of the flexor burst in most rats at P1-3, but via flexor burst truncation at P4-6. At any age, low-intensity stimulation during the extensor phase had no consistent effect on the ongoing rhythm. Activation of muscle afferents evoked via isometric contraction of the Q muscle caused effects similar to those obtained on low-intensity electrical stimulation in all age groups. In all age groups, high-intensity stimulation (> or =5.0 x T) caused resetting when delivered during the flexor phase via a prolongation of the flexor burst and during the extensor phase via a truncation of the extensor burst. These results suggest that the type of resetting evoked from low-threshold muscle afferents changes drastically during postnatal weekl, while effects evoked from high-threshold afferents remain unchanged.

Aging

Localization of a G-protein-coupled inwardly rectifying K+ channel, CIR, in the rat brain.

The cellular localization of a G-protein-coupled K+ channel, CIR, in the rat brain has been demonstrated using a CIR-specific antibody, in combination with in situ hybridization. The CIR protein and messenger RNA were found in the cerebellar cortex, hippocampal formation, olfactory system, cerebral cortex, basal ganglia, several nuclei of the lower brain stem and the choroid plexus. In contrast to the messenger RNA, which was concentrated in the cell soma, the CIR protein was found in a subset of nerve fibers and, in other cases, in axon terminals. In the cerebellar cortex and hippocampus, the CIR protein was concentrated in the axon terminals of basket cells which are known to be GABAergic interneurons. This discrepancy between the distribution of protein and messenger RNA was observed in the substantia nigra, the interpeduncular, trigeminal, hypoglossal, oculomotor and red nuclei of the lower brain stem, and the tufted and mitral cells of the olfactory bulb. These observations suggested the translocation of the CIR protein into the nerve fibers following synthesis in the cell soma. Furthermore, its specific neuronal localization, especially in GABAergic interneurons, suggested the importance of CIR in synaptic transmission in neuronal systems.

Animals

Decreased sulfhydryl groups in the reperfused myocardial tissue of a rat model of myocardial infarction.

The aim of this study was to determine whether myocardial injury resulting from temporary ischemia followed by reperfusion can be measured by assaying sulfhydryl groups in the affected tissue of a rat model of myocardial infarction. We studied 3 groups: a control group (n = 6), which underwent surgery without left coronary artery (LCA) ligation; group NoR (n = 9), in which the LCA was ligated for 3 h; and group I + R (n = 7), in which 30 min LCA ligation was followed by 3 h reperfusion. The sulfhydryl group content of myocardial tissue was assayed by measuring the fluorescence produced by incubating heart sections with N-(7-dimethylamino-4-methyl-3-coumarinyl) maleimide (DACM), which binds sulfhydryl groups. The fluorescence intensity (FI) of normal and infarcted myocardium was quantified by our computerized system of microscopic fluorophotometry. Indices such as sulfhydryl group content, the size of the low-FI area [% AREA(lower FI)] and the relative decrease in FI [%FI(decrease)]) in the infarct zone were calculated. Both %AREA(lower FI) and %FI(decrease) were significantly higher in the infarcted zone of animals in NoR and I + R groups than in control animals. Both indices were higher in infarct tissue from animals in the I + R group than in the NoR group. These changes suggest that sulfhydryl group content is significantly reduced in tissue that has been subjected to ischemia-reperfusion. Microscopic fluorophotometry, as defined by DACM staining of myocardial tissue, may help to delineate areas of myocardial reperfusion injury.

Animals

Effects of reoxygenation on repair of potentially lethal radiation damage in cultured MG-63 osteosarcoma cells.

The effects of reoxygenation on repair of potentially lethal radiation damage were investigated using MG-63 human osteosarcoma cells in vitro. When exponentially growing MG-63 cells were cultured under hypoxic conditions for 24 h, cells stopped growing and remained at a low density. The hypoxic cells were then reoxygenated by exposure to air and irradiated with a single dose of 3 Gy X rays. The fraction of the reoxygenated cells surviving after 3 Gy increased by a factor of 20.6 when the colony assay was delayed for 24 h. In control cells which were cultured under aerobic conditions before receiving a single dose of 3 Gy, the surviving fraction increased by a factor of 2.5 when the assay was delayed for 24 h. The difference in the magnitude of the repair observed between reoxygenated and aerobic cells was less prominent in confluent cells plated at high density. The enhanced repair after reoxygenation was due mainly to a decrease in the alpha coefficient when the dose-survival curve was fitted to the linear-quadratic model, whereas the most significant change in the fit of the dose-survival curve for the aerobic cells was a decrease in the beta coefficient. The control aerobic cells accumulated at G2/M phase after irradiation, whereas the reoxygenated cells did not show such an accumulation. When the hypoxic cells were irradiated and then reoxygenated, repair of these cells irradiated under hypoxic conditions was also enhanced. This is the first report to show that reoxygenation could increase cell survival after tumor irradiation.

Aerobiosis

[Long-term effects of a selective alpha 1-adrenergic inhibitor on right and left ventricular masses in patients with chronic pulmonary disease].

We examined the effect of one year of treatment with the selective alpha 1-adrenergic inhibitor doxazosin on right ventricular mass (RV mass), left ventricular mass (LV mass), and arterial blood gases. The subjects were 24 outpatients (18 men and 6 women, mean age 68.3 +/- 9.4 years) with chronic pulmonary disease complicated by hypertension who were clinically stable. One year of drug therapy was associated with significant decreases both in systolic pressure (159 +/- 15.2 vs 125.8 +/- 14.1 mmHg, p < 0.05, n = 24), and in LV mass index (101.0 +/- 13.4 vs 97.6 +/- 11.8 gm-2, p < 0.05), n = 24). We obtained the RV mass index by multiplying the thallium score RV/LV count and the LV mass index obtained by echocardiography. One year of drug therapy was associated with a significant increase in RV mass index (42.9 +/- 31.2 vs 53.6 +/- 30.5 gm-2, p < 0.05, n = 8). Vital capacity decreased (2.18 +/- 1.95 vs 1.95 +/- 0.57 l, p < 0.05, n = 24), but PaO2 improved (77.3 +/- 17.2 vs 82.2 +/- 2.4 mmHg, p < 0.05, n = 24). These data indicate that doxazosin can decrease blood pressure and can depress the left ventricle with no adverse effect on oxygenation in patients with chronic pulmonary disease complicated by hypertension. The worsening of RV hypertrophy may have been caused by a mechanism different from the one that caused LV hypertrophy, and by an increase in the work load on the right ventricles secondary to lung deterioration.

Adrenergic alpha-Antagonists

[Simultaneous ambulatory electrocardiography and pulse oximetry].

We developed a system for 24-hour ambulatory recording of blood oxygenation (SpO2) and electrocardiography (ECG). Using this system, we studied 10 healthy volunteers and 7 patients with chronic pulmonary diseases. The system incorporated a portable pulse oximeter (SM50) manufactured by Fukuda Denshi KK; the first and second channels were used to record ECG data and the third was used to record SpO2 data. An SpO2 sensor (Dispo-sensor D-25; Nellcor Inc.) was applied to the fourth of fifth finger. The SpO2 data (MicrO2; Siemens AG) were digitized and stored in the ambulatory recording device; the ECG was recorded simultaneously. The data were analyzed with a model DMW-9000H analyzer (Fukuda Denshi KK). A custom-designed program was also used, to remove noise errors. In the healty volunteers, SpO2 was at least 90% for the entire 24 hours. In all the patients, SpO2 fell below 90% at rest during the night or after a 15-minute walk. Transient atrial tachycardia was observed in 3 patients, and during the tachycardia the SpO2 was low. The number of extra ventricular beats divided by the total number of beats increased more in the patients than in the healthy volunteers (1.21 +/- 0.89 vs 0.6 +/- 0.3%, p < 0.05). SpO2 did not change significantly in the patients. In outpatients and in patients receiving home health care, the present system facilitates simultaneous diagnosis of respiratory failure an arrhythmias. In patients with chronic pulmonary diseases desaturation may cause transient atrial tachycardia.

Adult

[Effect of percutaneous transluminal mitral commissurotomy on pulmonary function and on the pulmonary vasculature].

We evaluated the therapeutic effect of percutaneous transluminal mitral commissurotomy (PTMC) on pulmonary function, and the damage caused to pulmonary vasculature by transient occlusion of the mitral valve during PTMC in patients with mild mitral stenosis. Pulmonary function tests were done and serum thrombomodulin was measured in 6 patients before and after PTMC. The mean pulmonary arterial pressure and mean pulmonary arterial wedge pressure decreased significantly from the control values, and the decreases were proportional to the increase in the area of the mitral valve. VC, %VC, and DLco were in the normal range before and after PTMC but PEFR, FEV1%, FEV1, V50, V25, and V50/V25 were significantly higher after PTMC. Change in the area of the mitral valve correlated with the changes in FEV1% (r = 0.841), in V50 (r = 0.624), and in V25 (r = 0.697). The serum thrombomodulin levels before and after PTMC did not differ. We conclude that pulmonary dysfunction in patients with mild mitral stenosis MS is mainly due to an obstructive ventilatory defect, and that PTMC can correct this dysfunction without damaging the pulmonary vasculature.

Aged

Development of locomotor activity induced by NMDA receptor activation in the lumbar spinal cord of the rat fetus studied in vitro.

The development of neuronal circuits generating locomotor activity was characterized in an isolated lumbar spinal cord preparation from of fetal and neonatal rats. Locomotor activity induced by bath application of the NMDA receptor agonists, NMA and NMDA, was monitored from both sides of the corresponding lumbar ventral roots. Activation of NMDA receptors first evoked rhythmic motor activity at E15.5. NMA-induced rhythmic motor activity was not observed under synaptic blockade by TTX or cadmium ions, suggesting that this activity was evoked by synaptic drive from the interneuronal circuits in the spinal cord. At E15.5-E16.5, the rhythmic motor activity on both sides was synchronized. Phase relationship of the rhythmic motor activity between both sides was variable at E17.5-E19.5. The rhythmic motor activity was alternating on both sides at E20.5. Mid-sagittal splitting of the spinal cord did not affect the rhythm generation at all stages examined, suggesting the existence of independent rhythm-generating circuits on each side. The rhythmic motor activity in the presence of strychnine was synchronized on both sides at all stages examined. These results indicate that the changes in rhythm pattern are mediated by development of glycinergic inhibitory pathways, while the basic rhythm can be generated without the glycinergic inhibitory pathways.

Animals

Spontaneous motoneuronal activity mediated by glycine and GABA in the spinal cord of rat fetuses in vitro.

1. Spontaneous motoneuronal activity was monitored from the lumbar ventral roots in an isolated spinal cord preparation from rat fetuses at embryonic days (E) 13.5-18.5. 2. Spontaneous bursts that were synchronized in both left and right ventral roots were observed periodically (mean interval, 1.5-2.6 min) from E14.5 to 17.5. This activity was abolished in Ca(2+)-free saline or by application of tetrodotoxin (1 microM), indicating that it was synaptically mediated. 3. The glutamate receptor blocker kynurenate (4 mM) failed to block spontaneous bursts at E14.5-15.5, though it completely abolished them at E17.5. The glycine receptor antagonist strychnine (10 microM) completely blocked spontaneous bursts at E14.5-15.5. Bicuculline, a GABAA receptor antagonist, reduced the amplitude of the spontaneous bursts. 4. At E15.5, a brief application of glycine (250 microM to 2 mM) evoked excitatory responses resembling the spontaneous bursts in both time course and amplitude. Such glycine-induced responses were not observed under Ca(2+)-free conditions, suggesting that they were synaptically evoked. These synaptic responses were not blocked by kynurenate (4 mM), but they were abolished by strychnine (10 microM). 5. It is concluded that glycine and GABA generate the earliest spontaneous motor activity of the fetus and function transiently as excitatory transmitters in the embryonic spinal cord.

Animals

Identification of domains of the cardiac inward rectifying K+ channel, CIR, involved in the heteromultimer formation and in the G-protein gating.

The cardiac inward rectifying K+ channel, CIR, and the strongly inward rectifying K+ channel, IRK1, exhibited clearly different electrophysiological properties. CIR formed a heteromultimer with the G-protein coupled inward rectifying K+ channel, GIRK1, whereas IRK1 did not, and CTR homo- and heteromultimeric channels were activated by G-protein beta 1 gamma 2 subunits (G beta 1 gamma 2), whereas IRK1 channels were not. To identify the domains of CIR involved in the heteromultimer formation with GIRK1 and in the G beta 1 gamma 2 gating, we constructed chimeras of CIR and IRK1 and examined their electrophysiological properties. The channels were divided into three domains; the N-terminal cytoplasmic domain, the C-terminal cytoplasmic domain and the residual core domain. By the analysis, it was concluded that (i) the core region of CIR, but not the N and C cytoplasmic domains, is critical for the heteromultimer formation with GIRK1; and (ii) the N and C terminal cytoplasmic regions of CIR are sufficient for the G beta 1 gamma 2 gating. We also showed that the N terminal cytoplasmic region is involved in the determination of the rate of activation upon hyperpolarization.

Animals

Angiographic and coronary risk factor analyses of Japanese patients with ischemic heart disease before age 40--a multicenter cooperative study.

Coronary angiographic and risk factor (RF) characteristics were analyzed in 133 Japanese patients with ischemic heart disease (IHD) who were less than 40 years old and who had undergone coronary angiography (CAG) during the past 10 years at six university hospitals in the Tokyo area. We compared the coronary angiographic characteristics of the subject group with those of 216 controls with coronary sclerosis detected by CAG who were more than 40 years old (older control group) and the RF characteristics with those of 133 sex- and age-matched volunteers (younger control group). Sixty seven percent of the subjects (89 cases) were diagnosed as having myocardial infarction (MI) and 33% (44 cases) had angina pectoris (AP). Coronary artery disorders in this group consisted of 103 (77%) cases of coronary sclerosis, 20 (15%) cases of coronary spasm and 10 (8%) cases of miscellaneous diseases, eg, possible vasculitis with connective tissue disease, congenital anomalies, etc. The incidences of significant (> or = 75%) sclerotic narrowing in 0 vessels (31%) and 1 vessel (49%) in the subject group were significantly (p < 0.01) higher than those in the older control group, while the incidence of multivessel disease was significantly (p < 0.05) less in the subject group than in the older control group. The incidences of the following coronary risk factors were significantly (p < 0.05) higher in the subjects than in the younger controls: smoking (83% vs 35%), hypercholesteremia (44% vs 10%), obesity (31% vs 9%), hypertension (29% vs 3%), familial IHD (28% vs 7%) and diabetes mellitus (19% vs 2%). Thus, zero- or single-vessel disease predominated in the younger subject group and the prevalence of coronary risk factors was significantly higher in the subject.

Adult

Early diagnosis and estimation of pulmonary congestion and edema in patients with left-sided heart diseases from histogram of pulmonary CT number.

To establish an early diagnosis and have a quantitative estimation of congestion or edema, pulmonary CT scans were performed to detect the increase of regional lung water volume of patients with congestive heart failure. CT scanning of the upper, middle, and lower lung fields at maximum inspiration and hemodynamic analysis to ensure a hemodynamically chronic stable condition after the heart failure therapy for 5 weeks by cardiac catheterization within 2 weeks before CT scanning were performed in 10 normal subjects and 25 patients with left-sided heart failure. Patients were divided into two groups according to the presence or absence of pulmonary congestion or edema on chest radiographs, and the mean pulmonary wedge pressure (mPWP). The pulmonary congestion group (14 patients) had pulmonary congestion or edema, and mPWP was greater than 13 mm Hg despite the heart failure therapy. The nonpulmonary congestion group (11 patients) had no pulmonary congestion or edema, and mPWP was lower than 10 mm Hg. Histograms of pulmonary CT numbers were graphed to a set region of interest (ROI) on transverse CT images in all subjects; then changes of pulmonary CT numbers when pulmonary congestion or edema occurred were estimated from those histograms. We found that when severe pulmonary congestion or edema occurred in 6 patients with severe left heart failure, the pulmonary CT numbers within the ROI rapidly increased from -650 to -750 Hounsfield units (HU). We defined the amount ratio between the pixels (pixel counts between -650 and -750 HU within these R0Is) and the pixels (pixel counts between -300 and -950 HU) of the CT number (which were all pixels composing these R0Is) x100(%) as "%PXL." %PXL showed a linear correlation with mPWP. Compared with the %PXL in the normal group, the %PXL in the pulmonary congestion group was significantly higher than that in the normal group (p<0.05, p<0.01, p<0.001) in all lung fields. Similarly, compared with the %PXL in the normal group, %PXL in the nonpulmonary congestion group was significantly higher than that in the normal group in the middle and lower lung fields (p<0.05, p<0.01) in the posterior field. From these results, we concluded that %PXL was a good index to identify abnormal water content usually not recognizable by routine chest radiograph in the lungs.

Adult

[A clinical evaluation of chest wall reconstruction].

From April 1987 to June 1995, we performed the chest wall reconstruction in 13 cases of 25 ones who had chest wall resection. The clinical records of these 13 patients were reviewed as follows. The histological diagnosis of these cases were direct invasion by primary lung cancer in 13 cases, malignant tumor of the chest wall in 5 cases, benign tumor or inflammation of the chest wall in 4 cases, local recurrence of the breast cancer and post operative radiation ulcer in each 1 case respectively, and mediastinal peripheral nerve sheath tumor in 1 case. Full diagnosis of the mediastinal malignant tumors were Ewing' sarcoma, chondrosarcoma, malignant lymphoma, malignant fibrous histiocytoma and eosinophilic granuloma in each 1 case respectively. The total number of resected ribs was 10 (bilateral 5 ribs with sternal body) in 1 case, 4 in 1 case, 3 in 6 cases, 2 in 2 cases and 1 in 4 cases. The following statement shows our methods of chest wall reconstructions. We treated one case with wide anterior chest wall resection, we treated by the Marlex-resin sandwich, 4 cases with 4 or 3 ribs of anterior or lateral chest wall, by sheets of Marlex mesh in layers, 3 cases with 3 ribs of posterior site, 1 case with 2 ribs and 4 cases with one rib, these 7 cases treated by cross sutures. And, we treated another 2 cases by pedicle omental flap and major pectoral muscle in each case respectively. The Marlex-resin sandwich has easy fixation and excellent stability, but it has also foreign body reaction. Therefore our case needed to remove of sandwich 10 months later for cellulitis and infection after the operation. Recently we use mostly sheets of Marlex mesh in layers, for the reconstruction of the chest wall with 3 or more rib's defect, but if it is more small defect, we use the cross suture method. The cross suture is very easy and effective method to maintain the stability of small chest wall defect.

Adolescent

[Pulmonary typical carcinoid with metastases to pulmonary hilar, and mediastinal lymph nodes].

A 50-year-old woman was admitted to our hospital complaining of recurrent bloody sputum and hemoptysis. Chest X-ray films showed an infiltrative shadow in the left lower lung field. Chest computed tomograms showed a nodular tumor shadow near the left B8 and this tumor shadow was found between A8 and A9 by pulmonary arteriography. Bronchoscopic examination revealed a red coagulum in the left B8 and cytologic examination of broncho alveolar lavage fluid revealed atypical squamous cells. With a clinical diagnosis of squamous cell carcinoma of the lung, a left lower lobectomy with hilar and mediastinal lymph node dissection was done. A milk-white tumor was found in the lower lobe of the resected lung. The pathological diagnosis of the resected tissue specimen was carcinoid, accompanied by pulmonary, hilar, and mediastinal lymph node metastases. Reduced immunofluorescence by Chromogranin A and serotonin staining were further evidence that the tumor was atypical. This case is very interesting in that the tumor metastasized to the lung and lymph nodes, even-though it was pathologically typical.

Carcinoid Tumor

[Deletion map of human chromosome 11 in lung cancers].

The relatively frequent loss of heterozygosity at loci on the short arm of chromosome 11 in lung cancers has suggested the presence of a putative tumor suppressor gene. For location of the gene, a fine deletion map of human chromosome 11 was constructed by analysis of 79 lung cancers with 31 sequence-tagged-site markers that dotted chromosome 11 and detected polymorphic changes in nucleotide sequences. The results showed that three regions, 11p12-p15, 11q12, and 11q14-q24, were commonly deleted in a considerable number of cancers, indicating the possible presence of more than one tumor suppressor gene.

Chromosome Deletion

[Abnormal branching of left pulmonary artery to the lateral and posterior basal segments].

A 70-year-old male, underwent left lower lobectomy due to lung cancer, had an extremely rare form of left pulmonary artery branching. His pulmonary artery supplying to lateral and posterior basal segments (A9 + 10) was arisen anteriorly from the root of the left pulmonary artery in the mediastinum and ran below in the anterior portion of the upper lobe stem bronchus. Embriologically, this abnormality might be due to a derangement of anastomosis between the pulmonary arch system and splanic plexus in primitive lung, and was interpreted as one of the pulmonary sequestration. Clinically, particularly at thoracotomy, the presence of a large vessel in an unexpected location is very hazardous, so that preoperative pulmonary angiography is useful to detect the abnormal branching.

Aged