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Biomedical subjects

K Kuno

Publications and source records attributed to K Kuno.

At least 37 records · Page 2Linked to original sources

Ischemia induces metallothionein III expression in neurons of rat brain.

Metallothionein III (MT-III) is a brain-specific member of the metallothionein family and binds zinc in vivo. In order to confirm the precise localization of MT-III in normal rat brain and the change of MT-III expression after transient whole brain ischemia, we raised a high affinity phagemid-antibody specific for rat MT-III. Immunohistochemical analysis revealed that MT-III in normal brain is localized abundantly in neuronal cell bodies in CA1-3 regions of hippocampus, dentate gyrus, cerebral cortex, olfactory bulb and Purkinje cells in cerebellum. This expression pattern of MT-III was similar to that of MT-III mRNA observed by in situ hybridization studies. ELISA and Northern blot analysis revealed that MT-III protein as well as mRNA levels were up-regulated in cerebrum soon after ischemic stress. Immunohistochemical analysis also demonstrated intense staining in neurons in injured brain after ischemia, which distributed in the same regions as in normal brain. These results suggest that MT-III plays an important role in protecting neurons from ischemic insult by reducing neurotoxic zinc levels and inhibits uncontrolled growth of neurites after ischemia.

Animals↗

Correlation between the serum level of endotoxin and periventricular leukomalacia in preterm infants.

The objective of our study was to determine the relation between the serum level of endotoxin at birth and the development of periventricular leukomalacia (PVL) in preterm infants. We studied 68 preterm infants whose gestational ages ranged between 27 and 33 weeks, and birthweights between 1000 and 2000 g. The serum endotoxin level was measured in the blood immediately after birth by means of a conventional chromogenic Limulus test. Serum endotoxin was taken as present when it was >5 pg/ml (indicated by ENDO(+)). Premature rupture of membranes (PROM), the mode of delivery, EEG findings and the development of PVL were investigated. Six infants were diagnosed as having cystic PVL on ultrasonography. Endotoxin was detected in 28 infants. PROM was observed in 18 ENDO(+) infants and 16 ENDO(-) infants (P = 0.085). Caesarean section was performed in nine ENDO(+) infants and 14 ENDO(-) infants (P = 0.29). PVL was observed in two ENDO(+) infants and four ENDO(-) infants (P > 0.99). EEG abnormalities were recognized in five ENDO(+) infants and six ENDO(-) infants (P > 0.99). Between ENDO(+) infants and ENDO(-) infants, no significant difference was observed in any of the four parameters. These results may indicate that endotoxin itself does not directly cause PVL.

Apgar Score↗

Epilepsy in patients with spastic cerebral palsy: correlation with MRI findings at 5 years of age.

The aim of this study was to determine the relationship between epilepsy and the magnetic resonance imaging (MRI) findings in patients with spastic cerebral palsy at five years of age. We studied 14 patients with congenital anomaly and 116 with perinatal injury. The patients with perinatal injury were subdivided into two groups; those with preterm type injury alone (group P), and those with term type injury with or without preterm type injury (group T). Epilepsy was found in 37 of the 130 patients. The initial type of seizures was partial in 12 patients. infantile spasms in 20 and generalized in five. Kaplan-Meier analysis demonstrated that patients with congenital anomaly had a higher incidence and an earlier onset of epilepsy than those with perinatal injury. Of the patients with perinatal injury, group T patients showed a higher incidence and a later onset of epilepsy than group P patients.

Adolescent↗

Positive rolandic sharp waves in preterm infants with periventricular leukomalacia: their relation to background electroencephalographic abnormalities.

The aim of this study was to clarify the significance of positive rolandic sharp waves (PRS) in preterm infants with periventricular leukomalacia (PVL) and their relation to background electroencephalographic (EEG) abnormalities. We retrospectively evaluated EEG findings of 93 preterm infants; 31 infants in the PVL group and 62 in the control group. PVL was diagnosed on the basis of ultrasonographic findings. We evaluated the EEG within 3 weeks of life in this study. PRS were defined as sharp transients of positive polarity appearing in the rolandic regions with an amplitude of more than 100 microV, sharply differentiated from the background activities. The number of PRS per minute was calculated over each record. PRS were defined as present when their frequency was beyond 0.1 per minute. PRS were observed in 14 (45%) and disorganized patterns in 27 (87%) of 31 infants in the PVL group, but both were not recognized in any infants in the control group. PRS were always associated with disorganized patterns. In the first EEG, PRS were absent in 8 of 11 infants with more than two recordings, although at least one of acute or chronic stage EEG abnormalities were already present. PRS were observed in 9 of 10 infants with severe diplegia, in 5 of 11 infants with moderate diplegia and none in 10 infants with mild diplegia. The average age of the first appearance of PRS was 7.6 days. The average age of the first appearance of periventricular echodensity and cyst was 4.2 days and 21.1 days, respectively. In conclusion, PRS are related to severe deep white matter injury and could be an early marker of severe PVL. PRS appeared in combination with disorganized patterns and were considered to be incorporated into chronic-stage EEG abnormalities. Detailed evaluation of background EEG activities can be helpful in detecting PVL with a high sensitivity from the early neonatal period.

Electroencephalography↗

The efficacy of a custom-fabricated nasal mask on gas exchange during nasal intermittent positive pressure ventilation.

Commercially available nasal masks have a large mask volume and give rise to considerable air leaks around the mask during nasal intermittent positive pressure ventilation (NIPPV) which may reduce alveolar ventilation (VA per breath). The effects of a custom-fabricated nasal mask (F-mask) versus a commercially available mask (C-mask) on arterial blood gas measurements, dead space including both physiological and apparatus dead space (VD), air leak and VA per breath were compared in patients with restrictive thoracic disease during short-term NIPPV sessions while using a volume cycled ventilator with equivalent settings for both masks. The mask volume of the C-mask was significantly larger than that of the F-mask (p<0.003). The arterial carbon dioxide tension (Pa,CO2) during NIPPV with either the F-mask (5.56+/-1.35 kPa) (mean+/-SD) or the C-mask (6.87+/-0.96 kPa) was significantly lower than during spontaneous breathing (7.75+/-0.81 kPa; p<0.003), but the Pa,CO2 decreased more during NIPPV with the F-mask than with the C-mask (p<0.003). The VD was significantly smaller (p<0.03), the air leak was significantly less (p<0.03), and the VA per breath was significantly larger (p<0.03) during NIPPV with the F-mask than with the C-mask. In conclusion, nasal intermittent positive pressure ventilation with the F-mask was more effective than nasal intermittent positive pressure ventilation with the commercially available mask due to its smaller dead space and less air leak. Further studies are needed to extend these results to all the commercially available-masks.

Blood Gas Analysis↗

Determination of timing of brain injury in preterm infants with periventricular leukomalacia with serial neonatal electroencephalography.

OBJECTIVE: The aim of this study was to determine the timing of brain injury in infants with periventricular leukomalacia (PVL) with serial electroencephalography (EEG) recordings during the neonatal period. PATIENTS AND METHODS: We evaluated 172 preterm infants having a gestational age <33 weeks and weighing <2000 g. Initial EEG was recorded within 72 hours of life and then recorded once every 1 to 4 weeks. Serial cranial ultrasonography was performed and cystic PVL was diagnosed when multiple cystic formations of >3 mm in diameter were observed. RESULTS: Of the 172 infants studied, 26 were diagnosed as having cystic PVL by ultrasonography. EEG abnormalities were observed in 25 of 26 infants with PVL, although EEG abnormalities were seen in 20 of 146 infants without PVL. The initial EEG recordings were normal in 7 infants, but EEG abnormalities were observed later in 6 of these infants. In these 6 infants, the timing of injury was presumed to be postpartum. Only acute stage abnormalities were observed on initial EEG recording in 14 infants, and the timing of injury was presumed to be just before or around birth. Chronic stage abnormalities were recognized already on initial EEG recordings in the other 5 infants, and the timing of injury was presumed to be some time before birth. CONCLUSIONS: Our study indicates that it may be possible to determine the timing of injury in infants with PVL by serial EEG recordings.

Cerebral Palsy↗

[Convulsion associated with mild gastroenteritis: occurrence in identical twins on the same day].

We reported identical twin cases having convulsion associated with mild gastroenteritis almost simultaneously. The patients were 14-month-old boys. They suffered from vomiting from one day before the onset of convulsion. Convulsions occurred firstly in the first twin, and then in the second one immediately after the convulsion of the first one. The twins experienced 6 and 4 convulsions respectively, although they were treated with diazepam and phenobarbital. An ictal EEG of the second twin revealed a focal paroxysmal discharge in the right occipital area spreading rapidly to all areas. During the follow-up period, no recurrence of seizures was observed and psychomotor development was normal in both of them.

Diseases in Twins↗

[A case of congenital plasminogen abnormality with recurrent cerebrovascular ischemic attacks].

We reported a 10-year-old boy with congenital plasminogen abnormality resulting in recurrent cerebrovascular ischemic attacks. He suddenly developed dystonia of the left upper limb at 9 years of age. MRI demonstrated small infarcts in the right thalamus and caudate nucleus. He then had a transient ischemic attack at 10 years. He complained of headache, vertigo, diplopia, and unsteady gait. DNA analysis revealed that he was heterozygotic for abnormal plasminogen. Thus, congenital plasminogen abnormality was suspected to be a cause of recurrent cerebrovascular ischemic attacks in this case.

Cerebral Infarction↗

ADAMTS-1 protein anchors at the extracellular matrix through the thrombospondin type I motifs and its spacing region.

Cellular disintegrin and metalloproteinases (ADAMs) are a family of genes with a sequence similar to those of snake venom metalloproteinases and disintegrins. The ADAMTS-1 gene encodes a new type of ADAM protein with respect to possessing the thrombospondin (TSP) type I motifs. Expression of the gene is induced in kidney and heart by in vivo administration of lipopolysaccharide, suggesting a possible role in the inflammatory reaction. In this study, we characterized the ADAMTS-1 gene product by using a transient expression system in COS-7 cells. We found that the precursor and processed forms of ADAMTS-1 were secreted from cells. Under normal growth conditions, little or none of both forms was detected in the cell culture medium, and instead the majority was found associated with the extracellular matrix (ECM). In addition, when cells were cultured in the presence of heparin, the mature form of ADAMTS-1 protein was detected in the cell culture medium, suggesting that binding of ADAMTS-1 to the ECM is mediated through sulfated glycosaminoglycans such as heparan sulfate. Analyses of deletion mutants of the ADAMTS-1 protein revealed that the spacer region as well as three TSP type I motifs in the carboxyl-terminal region of the ADAMTS-1 protein are important for a tight interaction with the ECM. These results suggest that the ADAMTS-1 is a unique ADAM family protein that anchors at the ECM.

ADAM Proteins↗

Prophylactic ureteral catheterization in gynecologic surgery.

OBJECTIVES: To examine the frequency of ureteral catheter usage, its efficacy in preventing injury, and related complications, because the preoperative routine placement of ureteral catheters as a prophylactic measure to prevent ureteral injury is controversial. METHODS: All major gynecologic operations performed between January 1992 and December 1994 were identified. All gynecologic procedures that were preceded by ureteral catheter placement were also identified. A data base maintained by the Department of Quality Management allowed identification of all urinary tract complications and ureteral injuries. Four categories of surgery were analyzed: exploratory laparotomy with catheters, exploratory laparotomy without catheters, operative laparoscopy with catheters, and operative laparoscopy without catheters. The medical records of all patients with urinary tract complications were reviewed. RESULTS: Bilateral prophylactic ureteral catheterization was performed in 469 (15.3%) of 3071 patients. A ureteral injury occurred in 4 (0.13%) of 3071 patients. All four ureteral injuries (0.17%) occurred among 2338 patients who underwent exploratory laparotomy. None of the 733 patients who underwent operative laparoscopy suffered ureteral injury. The incidence of ureteral injury in patients who had ureteral catheters placed before exploratory laparotomy was 2 (0.62%) of 322. Two (0.10%) of 2016 patients who did not have prophylactic ureteral catheters suffered a ureteral injury. There was no statistically significant difference in the incidence of ureteral injury between patients who did and patients who did not undergo ureteral catheterization (P=0.094). CONCLUSIONS: The use of prophylactic ureteral catheters did not affect the rate of ureteral injury in our patients. The very low incidence of ureteral injury among our patients is attributed mainly to meticulous surgical technique.

Female↗

Synergistic antitumor interaction of human monocyte chemotactant protein-1 gene transfer and modulator for tumor-infiltrating macrophages.

PURPOSE: In order to evaluate the possibility of synergistic antitumor gene therapy by the gene delivery of monocyte chemotactant protein-1 (MCP-1/MCAF/IE), the effect of a biological response modulater for macrophages on tumor progression of gene transfected tumor cells was studied. METHODS: Cachexia-inducing adenocarcinoma cells (cell line colon 26, clone 20) were transfected with either a control plasmid or MCP-1 cDNA. RESULTS: The production of MCP-1 reached 70-80 ng/ml in vitro when transfectant cells were cultured at a cell density of 1 x 10(5) cells/ml for 3 days. Transfection of MCP-1 cDNA did not affect the growth rate in vitro. Also, MCP-1-transfectants formed tumors after intra-footpad inoculation similar in size to the parental cells. The number of infiltrating macrophages in the primary tumor of the transfectant rapidly increased from the 3rd to 5th day after inoculation as revealed by immunohistochemical staining using an antibody against mouse macrophages. An earlier, greater, but no longer-lasting increase in tumor-infiltrating macrophages was induced in tumors by MCP-1 transfection was compared to that induced by the parent cells. On the 10th day after the inoculation, the tumor-infiltrating macrophages in mice inoculated MCP-1 transfectants were decreased to a level similar to that of the parent cells. Groups of mice were treated intraperitoneally with LPS at different times after the inoculation. Tumor cells producing high levels of MCP-1 were significantly lysed by macrophages treated with LPS, whereas parental or control transfected cells were not. Conclusions. Combination immunotherapy can provide a rationale for the application of MCP-1 treatment to increase immunological responses to cancer.

Adenocarcinoma↗

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↗

Induction of metallothionein isoforms in rat hepatoma cells by various anticancer drugs.

The induction of metallothionein (MT) isoforms (MT-1, -2) by anticancer drugs was investigated in cultured rat hepatoma H4 II E C3 cells. The steady-state expression of MT-1 mRNAs was higher than that of MT-2 mRNAs. During incubation of the cells with various anticancer drugs, namely, adriamycin, epirubicin, cis-diamminedichloroplatinum(II) (CDDP), and cis-diammine(1, 1-cyclobutyldicarboxylato)platinum(II), both MT-1 and MT-2 mRNAs were coordinately inducible: the levels of isoMT mRNA reached a maxim of approximate by 6-fold at 3 h. Immunofluorescent studies revealed that the cytosolic fluorescence in the cells exposed to 1 microM CDDP for 48 h was more intensified than that in the untreated cells. Transfer of antisense oligonucleotides resulted in marked reduction of isoMT mRNA, and upon exposure to 5 microM CDDP for 48 h, the viabilities of these cells dropped to 25.8% of the controls. These results indicate that anticancer drugs are potent inducers of MT isoforms in hepatoma cells and that a decrease in cellular MTs enhances the susceptibility of hepatoma cells to CDDP. Thus, we conclude that endogenous MTs play a role in determining the sensitivity or resistance of cancer cells to clinically important anticancer agents.

Animals↗

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↗

[Changes in the threshold values of lingua throughout aging].

The filter-paper-disk method was employed for measuring the threshold values of four basic taste on lingua-tip with 308 healthy females aged 20-79. Taste substance were sequentially diluted with distilluted water (30 stages from 80.0 g/dl for sucrose, 30 stages from 30.0 g/dl for NaCl, 30 stages from 8.0 g/dl for sodium tartrate, 30 stages from 4.0 g/dl for HCl quinine). The result was as follows. A sensibility of gustation decreased rapidly in accordance with aging. A decrease of bitterness sensibility was most remarkably with aging, succeeded sourness, sweetness, saltyness. Also, a decrease of a gustation sensibility is beginning in early twenties, especially the sensitivity to a sweetness and sour taste decreased conspicuously from twenties to thirties.

Adult↗

[Sleep apnea syndrome in Japan: analysis of pathophysiology and nasal continuous positive airway pressure effectiveness].

Forty eight Japanese sleep apnea syndrome (SAS) patients, whose apnea-hypopnea index (AHI) was more than 30 times/hr. from 5 university hospitals (46 males, 2 females) were enrolled in this study to analyze the characteristics of the disorder and the effectiveness of nasal continuous positive airway pressure (nCPAP) effectiveness. Although the severity of excessive daytime sleepiness (EDS), depressive state, and ventricular premature beats caused by SAS seemed milder in Japanese than reported Caucasian patients, the prevalences of hypertension and glucose intolerance were quite high: 50 and 30% respectively. Treatment with nCPAP for 3 months was completed in 41 of 48 enrollees, a compliance rate of 85.4%, which was substantially higher than studies from Western countries. nCPAP treatment normalized about 50% of hypertensive patients and more than half of glucose intolerant patients. Moreover, EDS, driving ability, the severity of arrhythmia, and so forth were all improved with nCPAP. We, therefore, conclude that 1) SAS could differ between Japanese Caucasians in terms of clinical features resulting from SAS and 2) treatment with nCPAP is effective and should be considered as first-line treatment for patients with moderate to severe SAS, as reported in Western countries.

Adult↗

[Laboratory and clinical studies on tazobactam/piperacillin in the field of pediatrics].

Laboratory and clinical studies on tazobactam/piperacillin (TAZ/PIPC), a combination drug of piperacillin (PIPC) with the new beta-lactamase inhibitor tazobactam (TAZ), were carried out in the field of pediatrics. 1. After intravenous administration of TAZ/PIPC at a dose of 25 mg/kg to one child, the peak plasma levels of TAZ and PIPC were 24.4 micrograms/ml and 119 micrograms/ml respectively after 5 min. The half-lives of TAZ and PIPC were 0.48 and 0.60 hours respectively. Same as 50 mg/kg to two children, the peak plasma levels of TAZ and PIPC were 17.5, 32.2 micrograms/ml and 92.8, 163 micrograms/ml after 5 min. The half-lives of TAZ and PIPC were 0.37, 0.50 hours and 0.51, 0.59 hours. A ratio of TAZ to PIPC was about 1 to 4 in plasma levels. The cumulative urinary recovery rates of TAZ and PIPC in the first 6 hours after intravenous administration were 15.8, 64.9% and 39.8, 53.4%. 2. The antibacterial activity of TAZ/PIPC against clinically isolated organisms was determined. The MICs of TAZ/PIPC were < or = 0.05 microgram/ml against Haemophilus influenzae and Streptococcus pneumoniae and > or = 1.56 micrograms/ml against Escherichia coli, Staphylococcus aureus and Haemophilus parainfluenzae. 3. The clinical efficacy of TAZ/PIPC could be evaluated in 14 patients with various bacterial infections, and was evaluated as "excellent" in 9 patients and as "good" in 5. The overall clinical efficacy rate in 14 cases was 100% and excellent was 64.3%. Bacteriological efficacy rate was 91.7% (10/11). 4. As a side effect, loose stool was observed in one case, no abnormal laboratory test values were observed. It has been concluded that TAZ/PIPC was a useful drug in the field of pediatrics.

Bacterial Infections↗

The exon/intron organization and chromosomal mapping of the mouse ADAMTS-1 gene encoding an ADAM family protein with TSP motifs.

ADAM is a recently discovered gene family that encodes proteins with a disintegrin and metalloproteinase. ADAMTS-1 is a gene encoding a new member protein of the ADAM family with the thrombospondin (TSP) type I motif, the expression of which is associated with inflammatory processes. In the present study, we have characterized the exon/intron organization of the mouse ADAMTS-1 gene. The ADAMTS-1 gene is composed of nine exons, all of which are present within the 9.2-kb genomic region. Among the nine exons, exons 1, 5, and 6 encode a proprotein domain, a disintegrin-like domain, and a TSP type I motif, respectively, of the ADAMTS-1 protein, suggesting that there is a correlation between exon/intron organization and functional domains. In addition, the exon/ intron organization of the ADAMTS-1 gene is very different from that of the metalloproteinase-like/disintegrin-like/ cysteine-rich protein gene (MDC) (ADAM11), suggesting that the genomic structure of ADAM family genes is not necessarily conserved. Furthermore, fluorescence in situ hybridization revealed that the ADAMTS-1 gene is located in region C3-C5 of chromosome 16, to which none of the previously identified ADAM genes have been mapped.

ADAM Proteins↗