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Biomedical subjects

F Hayakawa

Publications and source records attributed to F Hayakawa.

At least 37 records · Page 2Linked to original sources

Predictive value of acetylcholine stimulation testing for oligohidrosis caused by zonisamide.

We studied 16 patients for whom zonisamide was newly prescribed. Acetylcholine stimulation testing was performed about 1 month after zonisamide was initiated. Oligohidrosis occurred in none of the four with a normal response and in four of the 12 with a decreased response. Acetylcholine stimulation testing predicted oligohidrosis with a sensitivity of 1 and a false-positive rate of 0.67. The acetylcholine stimulation test was sensitive in detecting oligohidrosis caused by zonisamide, although the false-positive rate was high.

Acetylcholine↗

Bactericidal activity of catechin-copper (II) complexes against Staphylococcus aureus compared with Escherichia coli.

The bactericidal activity of catechin-copper (II) complexes against Staphylococcus aureus compared with Escherichia coli was investigated in relation to the generation of hydrogen peroxide and the binding of Cu(II) ion onto the bacteria. The bactericidal activity of catechin-Cu(II) complexes against Staph. aureus (Gram-positive) was much lower than that against E. coli (Gram-negative), suggesting that the binding of copper ions to the surface of bacterial cells plays an important role in the bactericidal activity of catechin-Cu(II) complexes.

Anti-Bacterial Agents↗

MRI findings in patients with symptomatic localization-related epilepsies beginning in infancy and early childhood.

We studied MRI findings in patients with symptomatic localization-related epilepsy (S-LRE) beginning in infancy and early childhood and their relation to some clinical features. MRI findings were investigated in 183 patients with S-LRE beginning before 6 years of age. S-LRE was defined as an epileptic syndrome manifesting with only partial seizures at least for a certain period during the clinical course, having specific neuroimaging abnormalities considered to be related to epileptic seizures, moderate or severe mental retardation, or cerebral palsy. The timing of injury was divided into the following four groups; prenatal, perinatal, postnatal and unknown. It was presumed prenatal in 56 patients (31%), perinatal in 25 (14%), postnatal in 32 (18%) and unknown in 70 (38%). The median age at the onset of partial seizures was 24 months in the congenital (prenatal and unknown) group, 39 months in the perinatal group and 25 months in the postnatal group. The onset of partial seizures was later in the perinatal group than in the congenital group. There were no significant differences in the other clinical characteristics among groups except for more frequent association of cerebral palsy in the perinatal group than in the congenital group. Our study suggests that congenital (prenatal and unknown group) disorders may be most common in patients with S-LRE beginning in infancy and early childhood. The onset of partial seizures occurred later in the perinatal group.

Brain↗

Early recognition of benign partial epilepsy in infancy.

PURPOSE: The aim of this study is to determine how precisely we can recognize the outcome in infants with epilepsy beginning in the first year of life. METHODS: We performed a prospective 5-year follow-up study on 63 patients who developed epilepsy in the first year of life. We first judged that patients met the criteria of "possible benign partial epilepsy in infancy (BPEI)" on enrollment in this study. At 2 years of age, we reevaluated the seizure and developmental outcome in the patients who were diagnosed as having "possible BPEI." We finally judged that patients met the criteria of "definite BPEI" at age 5 years. "Possible BPEI" was defined as epilepsy meeting all the following conditions: (a) complex partial seizures and/or secondarily generalized seizures; (b) normal psychomotor development and neurologic findings before onset; (c) normal interictal electroencephalograms; (d) normal cranial computed tomography (CT) and magnetic resonance imaging (MRI) findings; and (e) no seizures during the first 4 weeks of life. "Definite BPEI" was defined as epilepsy meeting all the following criteria in addition to those of "possible BPEI": (a) normal psychomotor development beyond age 5 years, and (b) no seizures beyond age 2 years. RESULTS: Thirty-two of the 63 patients met the inclusion criteria completely and were included in the "possible BPEI" group. Twenty-five of the 32 patients completed the 5-year follow-up. At age 2 years, four patients were excluded from the "possible BPEI" group because of seizure recurrence and/or delayed development. By age 5 years, one had a recurrence of seizures, and another exhibited mildly delayed psychomotor development. We finally diagnosed 19 patients as having "definite BPEI." "Definite BPEI" accounted for 76% of the patients diagnosed as having "possible BPEI" at the first presentation and 90% of those who met the conditions on reevaluation at age 2 years. CONCLUSIONS: Recognition of BPEI is possible, to some extent, at the first presentation, and reevaluation at age 2 years is useful for a more precise diagnosis.

Age Factors↗

Constitutively active STAT5A and STAT5B in vitro and in vivo: mutation of STAT5 is not a frequent cause of leukemogenesis.

We recently identified several constitutively active forms of signal transducers and activators of transcription 5 (STAT5) using polymerase chain reaction-driven random mutagenesis followed by retrovirus-mediated expression screening. All constitutively active STAT5 showed constitutive phosphorylation on their tyrosine residues and induced factor-independent growth in a mouse interleukin-3-dependent cell line, Ba/F3. Sequence analysis of these active STAT5 revealed two important mutations: S710F and N642H. The N642H mutation localized in the SH2 domain was able to induce autonomous growth of Ba/F3 cells by itself, whereas S710F in the effector domain was able to induce autonomous growth of Ba/F3 cells in concert with a second mutation including H298R and E150G. Recently, constitutive activation of STAT5 has been reported in patients' leukemic cells and is implicated in leukemogenesis. We attempted to clarify whether leukemic cells harbored activating mutations primarily in STAT5 proteins, and analyzed the sequence of STAT5 derived from 49 leukemic patients. No mutations were found, however, in the regions surrounding S710 and N642 of STAT5A and corresponding residues of STAT5B. We also cloned full-length cDNAs for STAT5s from three patients whose leukemic cells exhibited constitutive tyrosine phosphorylation of the STAT5 protein and expressed the derived STAT5 proteins in Ba/F3 cells. However, none of these clones exhibited constitutive tyrosine phosphorylation or gave rise to FI proliferation of Ba/F3 cells. These results indicate that constitutive activation of STAT5 is a secondary event in most leukemias.

Animals↗

Neonatal EEG: a powerful tool in the assessment of brain damage in preterm infants.

Serial EEG recordings beginning immediately after birth are not only of great diagnostic and prognostic value but also useful to elucidate the timing and the mode of brain injuries in the preterm newborn. It is extremely useful to distinguish between acute stage and chronic stage EEG abnormalities. The former is characterized by findings of acute depression such as increased discontinuity, decreased faster frequency activities, and lowered amplitudes. The latter mainly includes dysmature patterns and disorganized patterns. The timing of brain insult can be assessed by considering EEG findings in relation to the time of birth. Different modes of brain injury are associated with different types of EEG abnormalities and different types of neurological outcome. Sudden strong brain insults are usually associated with findings of severe depression followed by disorganized pattern and later cerebral palsy, while persistent mild insults are usually associated with prolonged mild depression followed by dysmature pattern and later mental retardation. Routine serial EEG studies in preterm infants demonstrated that one fourth of cerebral palsies in these infants were of antenatal origin, two thirds of perinatal origin and postnatal injuries played the least role. Periventricular leucomalacia (PVL) manifesting itself on the ultrasound in the late neonatal period and suggesting postnatal origin was often found to be of antenatal origin with an EEG soon after birth. PVL without apparent causes was often associated with abnormal fetal heart rate patterns and early neonatal EEG abnormalities, and considered to have originated in the antepartum period.

Brain Damage, Chronic↗

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↗

Epilepsies of neonatal onset: seizure type and evolution.

Most neonatal seizures are occasional seizures and not true epilepsy. This study investigates seizure types of true neonatal epilepsies and their evolution with development. Seventy-five children with epilepsies of onset within 1 month of life, who were examined between 1970 and 1995, and whose seizure types could be confirmed with ictal EEG recordings, were studied. The patients were followed up for a minimum of 3 years and the evolution of epileptic syndromes was investigated. Sixty-three (84%) of 75 patients had partial seizures, while nine had generalized seizures, and only three had both generalized and partial seizures. Twenty-three of 24 neonates with benign familial or non-familial neonatal convulsions presented with partial seizures; these syndromes should not necessarily be categorized into generalized epilepsy as they are in the present International Classification. Age-dependent changes were a common feature of symptomatic neonatal epilepsies. Eighteen (41%) of 44 patients with symptomatic epilepsies of neonatal onset developed West syndrome in infancy. Fifteen (83%) of these 18 patients presented with symptomatic localization-related epilepsy in the neonatal period. In seven of these 15 patients, West syndrome was followed by localization-related epilepsy. Symptomatic localization-related epilepsy with transient West syndrome in infancy is another type of age-dependent epileptic syndrome.

Epilepsy↗

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↗

DNA cleavage activities of (-)-epigallocatechin, (-)-epicatechin, (+)-catechin, and (-)-epigallocatechin gallate with various kinds of metal ions.

The DNA cleavage activities of (+)-catechin (C), (-)-epicatechin (EC), (-)-epigallocatechin (EGC), and (-)-epigallocatechin gallate (EGCg) were examined with 16 different metal ions. Cu(2+) with all the catechins facilitated DNA cleavage, while Ag+ with EGC and EC showed a strong repressive effect. The other metal ions examined showed little effect.

Animals↗

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↗

Differential constitutive activation between STAT-related proteins and MAP kinase in primary acute myelogenous leukaemia.

Many cytokines and growth factors stimulate multiple signal transduction pathways essential for proliferation in human acute leukaemia cells, including a mitogen-activated protein (MAP) kinase pathway and a Janus kinase (JAK)-STAT (signal transducers and activators of transcription) pathway. We have previously shown constitutive activation of MAP kinase in approximately 50% of acute myelogenous leukaemia (AML) samples. Recently, STAT proteins have been reported to be constitutively activated in 10-20% of AML cases. STAT3 and STAT5 are the main STAT proteins activated in haemopoietic progenitors in response to cytokines such as IL-3, GM-CSF, erythropoietin and thrombopoietin. Although the possibility of STAT1 protein as a substrate for MAP kinase at a serine residue has been suggested, the cross-talk between STATs and MAP kinase pathways in vivo, especially in leukaemia cells, remains unknown. We examined the phosphorylation of STAT 3 and STAT 5 at the tyrosine residues in AML samples in which MAP kinase activity had already been found. 40/50 primary AML cases (80%) exhibited constitutive tyrosine phosphorylation of STAT5. Electrophoretic mobility shift assay showed DNA binding activity of STAT5 correlated with tyrosine phosphorylation of STAT5. Similarly, with respect to STAT3, 17/23 cases examined (74%) showed constitutive tyrosine phosphorylation of STAT3. In addition, we examined the tyrosyl-phosphorylation of STAT5 isoforms, STAT5A and STAT5B, in 20 AML cases, and found selective STAT5B phosphorylation in the absence of STAT5A phosphorylation in three cases. Furthermore, in certain AML cases, constitutive activation of MAP kinase and STAT proteins occurred independently. No significant correlation of MAP kinase activation was observed with either tyrosine phosphorylation of STAT3/STAT5 or positive DNA binding of STAT proteins. These results suggest that constitutive activation of STAT proteins occurs commonly and that the causes of constitutive activation of these two major cascades are heterogeneous in AML.

Acute Disease↗

Bactericidal activity of catechin-copper (II) complexes on Escherichia coli ATCC11775 in the absence of hydrogen peroxide.

Washed Escherichia coli ATCC11775 cells were killed by (-)-epigallocatechin (EGC) in the presence of a non-lethal concentration of Cu2+ (1 mumol l-1) without additional H2O2, but not by (-)-epicatechin (EC). EGC alone (< 0.1 mmol l-1) did not reduce the viability of the cells. The survival curve obtained in the presence of EGC and Cu2+ was similar to that obtained in the presence of (-)-adrenaline (EN) and Cu2+.

Catechin↗

Evolutional changes and outcome of West syndrome: correlation with magnetic resonance imaging findings.

The prognosis and evolutional changes of 77 patients with West syndrome (WS) were studied after patients were classified into four groups on the basis of their magnetic resonance imaging (MRI) findings: anomaly, perinatal injury, normal, and the other groups. The average age at onset of spasms was earliest in the patients with anomalies and latest in patients with normal MRI findings. Patients with normal MRI findings had the shortest duration of spasms, and patients with anomalies had the longest duration of spasms. Antecedent seizures were observed in 6 patients (3 patients with anomalies, 1 patient with normal MRI findings, and 2 patients with other abnormalities). Thirty-five patients had subsequent seizures. Patients with anomalies often had partial seizures and patients with perinatal injuries often had generalized seizures. Seizures were infrequent in patients with normal MRI findings. Developmental outcome was best in the patients with normal MRI findings and worst in patients with perinatal injuries. Various types of epileptic syndromes occurred subsequent to WS in patients with anomalies, although nonspecific symptomatic generalized epilepsy was common in patients with perinatal injuries. These results suggest that seizure prognosis, evolutional changes in seizures, and developmental outcome are different among the types of brain lesions.

Adolescent↗