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Biomedical subjects

F Hayakawa

Publications and source records attributed to F Hayakawa.

At least 19 recordsLinked to original sources
PubMed2007

Lyn is an important component of the signal transduction pathway specific to FLT3/ITD and can be a therapeutic target in the treatment of AML with FLT3/ITD.

Fms-like tyrosine kinase 3 (FLT3) is expressed in hematopoietic progenitor cells. An internal tandem duplication (ITD) of FLT3 (FLT3/ITD) is the most frequent mutation in human adult acute myeloid leukemia (AML). FLT3/ITD contributes to the constitutive activation of FLT3 itself and its downstream signal components, mitogen-activated protein kinase and signal transducers and activators of transcription 5 (STAT5), and enables interleukin (IL)-3-dependent cell lines to grow autonomously. In the present study, we showed the specific association of FLT3/ITD with Lyn, which led to the phosphorylation of Lyn in vivo. We also demonstrated that FLT3/ITD receptors displayed a higher affinity to bind to Lyn than wild-type FLT3 receptors in vitro and that this affinity was relative to the intensity of tyrosil phosphorylation of the receptor. Both treatment with small interfering RNA (siRNA) targeting Lyn and the Src family kinase inhibitor PP2 suppressed the IL-3-independent growth of FLT3/ITD-expressing 32D cells (FLT3/ITD-32D), reducing the constitutive phosphorylation of Lyn and STAT5. PP2 treatment of mice transplanted with FLT3/ITD-32D cells blocked the onset of tumors and decreased the size of established tumors. These results demonstrate that Lyn is an important component of the signal transduction pathway specific to FLT3/ITD and can be a therapeutic target in the treatment of AML with FLT3/ITD.

Acute Disease↗
PubMed2006

Irradiation inactivation of Listeria monocytogenes in low-fat ground pork at freezing and refrigeration temperatures.

Gamma radiation effectively controls Listeria monocytogenes in uncooked and in ready-to-eat foods. This study was conducted to determine if gamma radiation could be used to control L. monocytogenes in ground pork. Ground pork was contaminated with L. monocytogenes, kept at refrigeration (4 degrees C), chilling (0 degrees C), and freezing (-18 degrees C) temperatures overnight, exposed to gamma radiation and stored at 4 degrees C for 7 days, and at 0 and -18 degrees C for 60 days. Following irradiation, the meat was assayed for L. monocytogenes viable counts and lipid oxidation. A triangle test was performed to determine if sausage made from the irradiated and nonirradiated ground pork differed in sensory quality. It was observed that a 5-log reduction of L. monocytogenes viable counts would require a 3.0-kGy radiation dose. The results of a 60-day storage study of ground pork inoculated with 10(5) to 10(6) CFU of L. monocytogenes per gram indicated that counts for nonirradiated meat remained fairly constant at refrigeration, chilling, and freezing temperatures. However, irradiation of ground pork at 3.0 kGy could inactivate L. monocytogenes totally in ground pork subsequently held at all the temperatures used in this study. Lipid oxidation measurements, as determined by the thiobarbituric acid-reactive substance assay, ranged from 0.16 nmol/g for nonirradiated ground pork and 0.20 nmol/g for meat irradiated at 3.0 kGy. Sensory panelists could distinguish between irradiated and nonirradiated sausage but were divided on whether irradiation adversely affected the sausage quality. Our results suggest that gamma radiation could be useful to control L. monocytogenes in ground pork and improve the safety of ground pork products.

Animals↗
PubMed2004

Electroencephalographic aspects of periventricular hemorrhagic infarction in preterm infants.

The aim of this study was to investigate electroencephalographic aspects of periventricular hemorrhagic infarction (PVHI) in preterm infants. The subjects were 11 preterm infants with PVHI, who were admitted to the Neonatal Intensive Care Unit of Anjo Kosei Hospital from April 1985 through December 1997. The patients underwent serial cranial ultrasonography and were diagnosed as having PVHI. An EEG was recorded at least once within 1 week after PVHI and then recorded at 1- to 4-week intervals until 40 weeks of postconceptional age. The EEG findings were classified into acute and chronic stage abnormalities. Acute stage EEG abnormalities were seen in 5 infants after PVHI, which were symmetrical in all infants. Among them, 3 infants died during the early neonatal period. The infants who had a higher grade of acute stage EEG abnormalities showed significantly higher mortality. Among the surviving 8 infants, chronic stage EEG abnormalities were seen in 3 predominantly in the ipsilateral side of PVHI, and all of them developed hemiplegia. The sensitivity and specificity of chronic stage EEG abnormalities to predict outcome were 0.75 and 1.0, respectively. Acute and chronic stage EEG abnormalities give valuable information for short-term and long-term outcome in preterm infants with PVHI.

Brain Infarction↗
PubMed2002

Prognostic value of EEG depression in preterm infants for later development of cerebral palsy.

The aim of this study is to examine the most appropriate timing for EEG recordings in order to predict the risk of cerebral palsy (CP) on the basis of the degree of acute stage abnormalities (ASA) in preterm infants. We retrospectively investigated the correlation between the degree of ASA and psychomotor outcome of 295 infants born between 27 and 32 weeks of gestational age whose initial EEG recording was performed within 7 days of life. Forty-six infants were diagnosed as having CP at 18 months of corrected age, and most of them suffered from diplegia due to periventricular leukomalacia (PVL). The maximum degree of ASA correlated with a later development of CP and its severity. Correlation between the degree of ASA and the severity of CP was highest on day 1 - 2, but this tendency was less clear after day 3. Specificity and negative predictive value were generally high within the first 7 days of life. But sensitivity was markedly decreased after day 3, and positive predictive value was highest on day 2. An EEG on day 1 or 2 will be useful in order to predict developmental outcome of preterm infants on the basis of the grade of ASA.

Acute-Phase Reaction↗
PubMed2001

Histone deacetylase 3 associates with and represses the transcription factor GATA-2.

The zinc finger transcription factor GATA-2 plays a critical role in the survival and proliferation of hematopoietic stem cells. This study examined the interaction of GATA-2 with histone deacetylases (HDACs) to define the involvement of HDACs in the regulation of GATA-2 function. GATA-2 directly associates with HDAC3 but not with HDAC1. Consistent with this, HDAC3 suppressed the transcriptional potential of GATA-2, whereas HDAC1 did not affect GATA-2-dependent transcription. Results further demonstrated that GATA-2 and HDAC3 colocalized in the nucleus. These results identify GATA-2 as a nuclear target for HDAC3-mediated repression. Furthermore, GATA-2 also directly associated with HDAC5 but not with other class II HDACs examined, that is, HDAC4 and HDAC6. This is the first demonstration that a tissue-specific transcription factor directly and selectively interacts with HDAC3 and HDAC5 among HDAC family members.

Animals↗
PubMed2001

Relation between the date of cyst formation observable on ultrasonography and the timing of injury determined by serial electroencephalography in preterm infants with periventricular leukomalacia.

The aim of this study was to clarify the relation between the date of cyst formation and the timing of injury in preterm infants with periventricular leukomalacia in order to address the issue of whether or not we can determine the timing of injury on the basis of ultrasonographic findings. We studied 33 preterm infants with cystic periventricular leukomalacia, the gestational ages being 32 weeks or less. As 27 of them exhibited either acute or chronic stage abnormalities in the initial electroencephalogram, the timing of injury was presumed to be before or around birth. For the remaining six infants, the timing of injury was considered to be postnatal in two infants, and was not determined in another four. The median date of cyst formation was 18 days of age (range, 10-39 days) in the 27 infants with abnormal initial electroencephalograms. For these 27 infants, the gestational age did not influence the date of cyst formation. In contrast, the date of cyst formation was significantly earlier in infants with widespread cysts than in those with localized cysts. In conclusion, it is difficult to determine the timing of injury from ultrasonographic findings, because the range of the date of cyst formation on ultrasonography was very wide among infants whose timing of injury was not greatly different.

Adult↗
PubMed2001

Physical condition of preterm infants with periventricular leukomalacia.

The aim of this study is to determine the general condition of preterm infants with severe brain lesions and to compare it with that of normal preterm infants. The Score for Neonatal Acute Physiology (SNAP) was calculated in nine preterm infants with periventricular leukomalacia (PVL) whose initial electroencephalograms showed grade IV depression (PVL group), 18 preterm infants who did not require mechanical ventilation during the neonatal period, Spontaneous respiration (SR group), and 18 preterm infants who required mechanical ventilation (MV group). The sum of the following four items in SNAP was separately calculated and called the 'lung score': PaO(2), PaO(2)/FiO(2) ratio, PaCO(2), and oxygenation index. In addition to SNAP, we evaluated some neonatal variables. SNAP is lower in the SR group than in the PVL (P<0.05) or MV (P<0.01) groups. The lung score was also lower in the SR group than in the PVL (P<0.05) or MV (P<0.01) groups. On the other hand, the residual score (SNAP minus lung score) was not significantly different among the three groups. The physical condition of infants with PVL was not poor, although respiratory distress was often observed.

Apgar Score↗
PubMed2001

Five-year follow-up of patients with partial epilepsies in infancy.

The aim of this study is to clarify the long-term outcome of patients with partial epilepsies that begin in the first 2 years of age. Thirty-nine infants who experienced partial epilepsies with onset by 2 years of age were followed until they were at least 5 years of age. Seizure and developmental outcome were investigated in relation to the following items: delayed psychomotor development before onset of seizures; interictal electroencephalogram (EEG) abnormalities; abnormal neuroimaging; family history of epilepsy; and history of neonatal seizures. Thirty-three infants achieved freedom from seizures and 27 achieved normal development. Delayed development before the onset and abnormal interictal EEG correlated with both poor seizure and developmental outcome. Abnormal neuroimaging findings correlated with a poor seizure outcome. A history of neonatal seizures and lack of a family history of epilepsy correlated with poor developmental outcome. The combination of the first four factors predicted a normal outcome with a sensitivity of 0.79 and a specificity of 0.87. The seizure and developmental outcomes were better in this study than those in previous studies. The combination of the four factors will be useful for predicting the outcomes in patients with partial epilepsies in infancy.

Brain↗
PubMed2001

Quantitative evaluation of thalami and basal ganglia in infants with periventricular leukomalacia.

Quantitative analyses of cross-sectional areas of the thalami, caudate nuclei, and lentiform nuclei were performed in 29 preterm infants (16 males, 13 females; mean age 29.6 weeks, age range 27 to 24 weeks,) with periventricular leukomalacia (PVL). MRI was carried out in the infants between 9 and 18 months of corrected age and in 16 control infants. Bilateral thalami, caudate nuclei, lentiform nuclei, cerebral hemispheres, and cerebellum were measured by computer. Ratios of the areas of the thalami (Th), caudate nuclei (Ca), lentiform nuclei (Le), and cerebral hemispheres (CH) to that of the cerebellum (Ce) were calculated in each infant. The ratio of Th:Ce was significantly smaller in infants with moderate and severe PVL than in the control group bilaterally. Abnormal intensity areas were not observed in the thalami in any infants with PVL. CH:Ce was also smaller in infants with severe PVL than in the control group. No significant difference was observed between the groups in ratios Le:Ce or Ca:Ce. Results of our study suggest that the volume of the thalami is reduced and that thalamic involvement is present in infants with white matter lesions who have moderate to severe PVL.

Basal Ganglia↗
PubMed2001

The timing of brain insults in preterm infants who later developed West syndrome.

Abstract. The aim of this study is to clarify the timing of brain injuries in preterm infants who later developed West syndrome. We assessed the timing of brain insults with serial EEG recordings beginning immediately after birth in preterm infants less than 33 weeks of gestational age. The timing of brain insult was assessed by considering EEG findings in relation to the time of birth. The timing was considered prenatal if an EEG immediately after birth already showed chronic stage abnormalities, perinatal if it showed acute stage abnormalities, and postnatal if it was normal and a later EEG showed acute stage abnormalities. Eleven infants had periventricular leukomalacia and developed West syndrome. The timing of the brain insult was considered prenatal in 5 infants, perinatal in 2, postnatal in 2, prenatal plus postnatal in one, perinatal plus postnatal in one. The infants of less than 29 weeks of gestation were more likely to suffer brain damage postnatally, whereas those of more than 28 weeks tended to have brain injury prenatally. The timing of brain injury of preterm infants who later developed West syndrome is more often prenatal than generally considered.

Brain Damage, Chronic↗
PubMed2001

Background electroencephalographic (EEG) activities of very preterm infants born at less than 27 weeks gestation: a study on the degree of continuity.

AIMS: To clarify the features of the background electroencephalographic (EEG) activities in clinically well preterm infants born at less than 27 weeks gestation and to outline their chronological changes with increasing postconceptional age (PCA). METHODS: EEGs of clinically well premature infants born at less than 27 weeks gestation were recorded during the early postnatal period. The infants were separated into three groups according to their PCA at the time of EEG recording (21-22 weeks PCA, 23-24 weeks PCA, and 25-26 weeks PCA). The mean and maximum duration of interburst intervals (IBIs), the mean duration of bursts, and the percentage of continuous and discontinuous patterns in each PCA group were evaluated. RESULTS: There were three infants at 21-22 weeks PCA, seven at 23-24 weeks PCA, and five at 25-26 weeks PCA. Eighteen EEG recordings were obtained. The mean and maximum IBI duration decreased with increasing PCA. The percentage of continuous patterns increased with increasing PCA. Conversely, the percentage of discontinuous patterns decreased with increasing PCA. CONCLUSIONS: In premature infants born at less than 27 weeks gestation, the characteristics of the background EEG activities were similar to those of older premature infants. These changes reflect the development of the central nervous system in this period.

Analysis of Variance↗
PubMed2001

Spin-trapping study on the hydroxyl radical formed from a tea catechin-Cu(II) system.

A spin-trapping method was applied to examine the formation of the hydroxyl (OH) radical from a tea catechin-Cu(II) system to elucidate a previous result that some tea catechin-Cu(II) systems induced DNA scission. Three tea catechins, (-)-epigallocatechin (EGC), (-)-epigallocatechin gallate (EGCg) and (-)-epicatechin (EC), were used. The spin-trapping agent, 5,5'-dimethyl-pyrroline-1-oxide (DMPO), was dissolved in a pH 9 phosphate buffer solution, then a catechin and Cu(II) were added in that order, and the ESR spectral change was monitored for one hour. The order of adding the catechin and Cu(II) was then reversed, and the ESR spectral change was again monitored to examine the coordinating activity of each catechin toward the Cu(II) ion and the effect on OH radical generation. The intensity changes of the spin adducts, DMPO-OH, DMPO-CH3 and DMPO-H, were analyzed, the results suggesting that the OH radical generated in the system decomposed DMPO, resulting in the formation of DMPO-CH3 and DMPO-H. The results show that EGC formed a stable complex with Cu(II) and generated the OH radical. EGCg seemed to have this activity, but the OH radical that was generated was scavenged by the gallate group existing in the complex. EC did not show strong coordinating and OH-generating activities. These characteristics of the three catechins are consistent with the results shown for DNA scission.

Catechin↗
PubMed2001

Influence of adenine-induced renal failure on tryptophan-niacin metabolism in rats.

To discover the role of the kidney in tryptophan degradation, especially tryptophan to niacin, rat kidneys were injured by feeding a diet containing a large amount of adenine. The kidney contains very high activity of aminocarboxymuconate-semialdehyde decarboxylase (ACMSD), which leads tryptophan into the glutaric acid pathway and then the TCA cycle, but not to the niacin pathway. On the other hand, kidneys contain significant activity of quinolinate phosphoribosyltransferase (QPRT), which leads tryptophan into the niacin pathway. The ACMSD activity in kidneys were significantly lower in the adenine group than in the control group, while the QPRT activity was almost the same, however, the formations of niacin and its compounds such as N1-methylnicotinamide and its pyridones did not increase, and therefore, the conversion ratio of tryptophan to niacin was lower in the adenine group than in the control group. The contents of NAD and NADP in liver, kidney, and blood were also lower in the adenine group. The decreased levels of niacin and the related compounds were consistent with the changes in the enzyme activities involved in the tryptophan-niacin metabolism in liver. It was concluded from these results that the conversion of tryptophan to niacin is due to only the liver enzymes and that the role of the kidney would be extremely low.

3-Hydroxyanthranilic Acid↗
PubMed2001

Hypocarbia in preterm infants with periventricular leukomalacia: the relation between hypocarbia and mechanical ventilation.

OBJECTIVE: The aim of this study was to elucidate the relationship between mechanical ventilation and hypocarbia in infants with periventricular leukomalacia (PVL). STUDY DESIGN: Matched pair analysis was conducted for 26 infants with PVL and 26 with normal development, who were born between 27 and 32 weeks' gestational age and required mechanical ventilation. The time-averaged carbon dioxide (CO(2)) index, PaCO(2), and pH were calculated every 24 hours for samples obtained from indwelling arterial catheters within the first 72 hours of life. The time-averaged respiratory rate of the ventilator (RR), peak inspiratory pressure (PIP), mean airway pressure (MAP), and ventilator index (VI) were also determined. The time-averaged total respiratory rate (TRR) was determined by observing the movement of the chest wall. The patients' characteristics, antenatal and neonatal variables, and electroencephalographic findings were also compared. RESULTS: The time-averaged CO(2) index was larger, the time-averaged CO(2) lower and the time-averaged pH higher in infants with PVL than in those with normal development on the third day of life. There was no significant difference in the time-averaged RR, PIP, MAP, or VI on any day. TRR was larger in the PVL group than in the control group on each day, but there was no significant difference. No significant difference was observed in the clinical characteristics or neonatal variables. Electroencephalographic abnormalities within 48 hours of life were more frequent in infants with PVL than in those with normal development. CONCLUSION: Hypocarbia was associated with PVL because the time-averaged CO(2) index was larger and the time-averaged PaCO(2) lower in infants with PVL than in those with normal development. However, the ventilator settings were similar among the infants with and without PVL.

Blood Gas Analysis↗
PubMed2000

Tandem-duplicated Flt3 constitutively activates STAT5 and MAP kinase and introduces autonomous cell growth in IL-3-dependent cell lines.

We have recently identified an internal tandem duplication of the human Flt3 gene in approximately 20% of acute myeloid leukemia (AML) cases. In the present study, the wild-type and the mutant Flt3 genes were transfected into two IL-3-dependent cell lines, 32D and BA/F3 cells. Mutant Flt3-transfected cells exhibited autonomous growth while wild-type Flt3-transfected cells with the continuous stimulation of Flt3 ligand exhibited a minimal proliferation. Cells expressing mutant Flt3 showed constitutive activation of STAT5 and MAP kinase. In contrast, Flt3 ligand stimulation caused rapid activation of MAP kinase but not STAT5 in cells expressing wild-type Flt3. Finally, we found constitutive activation of MAP kinase and STAT5 in all clinical samples of AML patients with mutant Flt3. Our study shows the significance of internal tandem duplication of Flt3 receptors for leukemia cell expansion.

Amino Acid Sequence↗
PubMed2000

c-Myb acetylation at the carboxyl-terminal conserved domain by transcriptional co-activator p300.

Transcription factor c-Myb plays important roles in cell survival and differentiation in immature hematopoietic cells. Here we demonstrate that c-Myb is acetylated at the carboxyl-terminal conserved domain by histone acetyltransferase p300 both in vitro and in vivo. The acetylation sites in vivo have been located at the lysine residues of the conserved domain (K471, K480, K485) by the use of the mutant Myb (Myb-KAmut), in which all three lysine residues are substituted into alanine. Electrophoretic mobility shift assay reveals that Myb-KAmut shows higher DNA binding activity than wild type c-Myb and that acetylation of c-Myb in vitro by p300 causes dramatic increase in DNA binding activity. Accordingly, transactivation activity of both mim-1 and CD34 promoters by Myb-KAmut is higher than that driven by wild type c-Myb. Furthermore, the bromodomain of p300, in addition to the histone acetyltransferase (HAT) domain, is required for effective acetylation of c-Myb, and hGCN5 is revealed to be a factor acetyl-transferase for c-Myb in vitro. We present a new manner of post-translational modification of the c-Myb protein and the potential significance of the acetylation in c-Myb.

Acetylation↗
PubMed2000

Bilateral basal ganglia-thalamic lesions subsequent to prolonged fetal bradycardia.

We report two infants with bilateral basal ganglia-thalamic lesions subsequent to prolonged fetal bradycardia. Cardiotocogram revealed severe bradycardia lasting for more than 20 min in both. They demonstrated a significant encephalopathy, abnormal muscle tones and signs of brainstem injury. Clinical or electrical seizures were not observed in either of them. CT during early neonatal period demonstrated decreased tissue attenuation in basal ganglia and thalami in the absence of extensive cortical changes. Both of them developed severe mental retardation and quadriplegia. MRI in late infancy demonstrated abnormal high intensity areas in bilateral basal ganglia, thalami and around central sulci on T2-weighted image. Close correlation between prolonged fetal bradycardia and basal ganglia-thalamic lesion was suggested.

Adult↗