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Biomedical subjects

Hiroyuki Shimizu

Publications and source records attributed to Hiroyuki Shimizu.

At least 37 records · Page 2Linked to original sources

Effectiveness of cerebral hemispherotomy for improving behavioral disorders associated with intractable post-traumatic seizures.

A 25-year-old man presented with intractable post-traumatic seizures after suffering cerebral contusion in a traffic accident at age 5 years. Cerebral hemispherotomy was performed to transect the neuronal fibers to interrupt connections between seizure foci in wide areas of the brain, and to minimize the resected brain parenchyma. His seizures resolved and behavioral disorders improved, which had been impaired since age 8 years. Increased glucose metabolism in the normal frontal lobe detected by interictal fluorodeoxyglucose-positron emission tomography was correlated with the improvements in behavioral disorders. These findings suggest that the effects of seizures may be reversible in brain areas connected with, but remote from, the epileptogenic cortex.

Adult↗

Temporal lobe epilepsy caused by dermoid cyst.

A 15-year-old boy presented with a dermoid cyst in the left temporal lobe manifesting as complex partial seizures. Magnetic resonance imaging demonstrated a tumor with mixed signal intensity in the left anterior temporal subdural area, but no evidence of rupture. Intraoperatively, the tumor was located mainly in the deep sylvian fissure, adjacent to the amygdala, and had compressed the hippocampus. Intraoperative electrocorticography (ECoG) showed sporadic interictal spikes in both the adjacent areas of the tumor and over the anterior segment of the hippocampus. Total removal of the tumor and gliotic area of the surrounding tissue including the amygdala was performed. The hippocampal epileptic region was treated by transection of the pyramidal layer to preserve verbal memory function. Histological examination showed the dermoid tumor was closely attached to the brain parenchyma. The complex partial seizures ceased completely after surgery. Intraoperative recording of ECoG from the hippocampus and other limbic structures was very important to determine the epileptogenic area even if the tumor did not directly invade the hippocampus.

Adolescent↗

[A case of Sturge-Weber syndrome with severe temper tantrum].

We report a case of Sturge-Weber syndrome with intractable epilepsy presenting complex partial seizures(CPSs) and severe temper tantrum successfully treated with anterior temporal lobectomy. A 23-month-old girl without facial angioma presented with seizures from 8 months after birth. Neuroradiological examination demonstrated angioma in the left temporooccipital lobes and calcification in the left occipital lobe. Thus she was diagnosed as having Sturge-Weber syndrome. Her parents sought medical advice because of intractable and more frequent CPSs and a change in temperament manifesting as severe temper tantrums. Interictal electroencephalogram (EEG) showed relatively mild abnormal slow wave discharges in the left temporal region. The patient underwent left anterior temporal lobectomy based on intraoperative electrocorticography (ECoG) findings. Histopathological examination demonstrated gliotic change in the amygdala. After the surgery, she has remained seizure-free for 14 months while taking anticonvulsants and temper tantrums ultimately showed remission 10 months following surgery. This case may indicate that severe temper tantrum was associated with a change in amygdala structures.

Amygdala↗

[Bone and joint infection].

Older adults are at risk for the immune dysfunction associated with advanced age, which contribute to their increased risk of infection. Hematogenous osteomyelitis occurs not only in children, but also in older adults. Iatrogenic septic arthritis can be occured after the intraarticular injection for the osteoarthritis in aging society. Tuberculous spondylitis occurs in older adults and the differential diagnosis with pyogenic spondylitis and vertebral metastasis is important.

Aged↗

Akt2 phosphorylates Synip to regulate docking and fusion of GLUT4-containing vesicles.

We have identified an unusual potential dual Akt/protein kinase B consensus phosphorylation motif in the protein Synip (RxKxRS(97)xS(99)). Surprisingly, serine 97 is not appreciably phosphorylated, whereas serine 99 is only a specific substrate for Akt2 but not Akt1 or Akt3. Although wild-type Synip (WT-Synip) undergoes an insulin-stimulated dissociation from Syntaxin4, the Synip serine 99 to phenylalanine mutant (S99F-Synip) is resistant to Akt2 phosphorylation and fails to display insulin-stimulated Syntaxin4 dissociation. Furthermore, overexpression of WT-Synip in 3T3L1 adipocytes had no effect on insulin-stimulated recruitment of glucose transporter 4 (GLUT4) to the plasma membrane, whereas overexpression of S99F-Synip functioned in a dominant-interfering manner by preventing insulin-stimulated GLUT4 recruitment and plasma membrane fusion. These data demonstrate that insulin activation of Akt2 specifically regulates the docking/fusion step of GLUT4-containing vesicles at the plasma membrane through the regulation of Synip phosphorylation and Synip-Syntaxin4 interaction.

3T3 Cells↗

High frequency activities in the human orbitofrontal cortex in sleep-wake cycle.

We recorded human orbitofrontal electrocorticogram during wakefulness and sleep in epileptic patients using subdural electrodes. During wakefulness and rapid eye movement (REM) sleep, we observed beta activity in the raw orbitofrontal signals. Power spectral analysis demonstrated beta enhancement during wakefulness and REM sleep when compared to slow wave sleep (SWS). During the phasic REM periods, the beta power was significantly lower than during the tonic REM periods. Gamma enhancement manifested itself in four out of six subjects during the phasic periods. This study is the first that has focused on electrical activity in the human orbitofrontal cortex. Although the role of the orbitofrontal cortex during sleep still remains unclear, high frequency activities give us important suggestions in elucidating the human sleep mechanism.

Adult↗

Molecular mechanisms associated with leptin resistance: n-3 polyunsaturated fatty acids induce alterations in the tight junction of the brain.

High-fat diets cause peripheral leptin resistance, and dietary lipid composition affects sensitivity to leptin. We examined the role of n-3 polyunsaturated fatty acid (PUFA) in peripheral leptin resistance. Dietary PUFAs (0.4% wt/wt) caused insensitivity to peripherally but not intracerebroventricularly administered leptin. n-3 PUFA increased body weight, associated with a significant reduction of leptin concentration in the cerebrospinal fluid. Dietary n-3 PUFA reduced transport of endogenous or exogenously administered leptin into the brain, associated with increased expression of hypothalamic occludin, but caused no change in expression of leptin receptors, proteins associated with leptin signaling or other tight junction proteins. Continuous intracerebroventricular infusion of an antisense morpholino oligonucleotide targeted to occludin mRNA reversed n-3 PUFA-induced insensitivity to peripherally administered leptin. We conclude that n-3 PUFA induces peripheral leptin resistance via an increase in the expression of hypothalamic occludin, reducing paracellular transport of leptin into the brain.

Animals↗

The Tajimi Study report 2: prevalence of primary angle closure and secondary glaucoma in a Japanese population.

PURPOSE: To determine the prevalence of primary angle-closure glaucoma (PACG), secondary glaucoma (SG), and all glaucoma in a Japanese population as a part of the Tajimi Study. DESIGN: Population-based epidemiological survey. PARTICIPANTS: A random sample of residents 40 years or older from Tajimi, Japan. INTERVENTION: Each subject underwent a screening program comprising an interview and an ophthalmic examination, including Goldmann applanation tonometry, slit-lamp examination, a van Herick test, fundus photography, and a screening visual field (VF) test using frequency-doubling technology. If glaucoma was suspected, the subject was referred for a definitive examination that included slit-lamp examination, gonioscopy, intraocular pressure measurement, a VF test, and optic disc and fundus examination. A diagnosis of PACG or SG was made based on slit-lamp examination, gonioscopy, optic disc appearance, and perimetric results. MAIN OUTCOME MEASURES: Prevalences of PACG, SG, and all cases of glaucoma. RESULTS: Of 3870 eligible people, 3021 (78.1%) participated in the study. Estimated prevalences of PACG and SG in those over 40 years were 0.6% (95% confidence interval [CI], 0.4%-0.9%) and 0.5% (95% CI, 0.2%-0.7%), respectively. Prevalences of all glaucoma and glaucoma/suspected glaucoma were estimated to be 5.0% (95% CI, 4.2%-5.8%) and 7.5% (95% CI, 6.5%-8.4%), respectively. CONCLUSIONS: Prevalences were 0.6%, 0.5%, and 5.0%, respectively, for PACG, SG, and all glaucoma in subjects over 40 years from Tajimi, Japan.

Adult↗

Identification of the layers of the bladder wall on high-frequency endoluminal ultrasonography by a needle puncture experiment.

The purpose of this study was to identify the layers of the bladder wall on high-frequency endoluminal ultrasonography (ELUS). We performed a needle puncture experiment using five normal pig bladders. The histologic layer structure was compared with the ELUS images obtained using a 30-MHz miniature transducer. The bladder wall was depicted as five layers by ELUS and these corresponded to the histologic layers. The first layer (hyperechoic) was a margin echo that included the epithelium and the upper part of the lamina propria. The second layer (hypoechoic) corresponded to the lamina propria and the third layer (hyperechoic) was a margin echo that included the upper part of the muscle layer. The fourth layer (hypoechoic) corresponded to the muscle layer, and the fifth layer (hyperechoic) was a margin echo that included the upper part of the adventitia.

Animals↗

The brain-adipose axis: a review of involvement of molecules.

Many molecules are involved in the regulation of feeding behavior, and they and their receptors are located in the brain hypothalamus and adipocytes. On the basis of evidence suggesting an association between the brain and adipose tissue, we propose the concept of the brain-adipose axis. This model consists of (l) the expression of endogenous molecules and/or their receptors in the hypothalamus and peripheral adipose tissue, (2) the function of these molecules as appetite regulators in the brain, (3) their existence in the general circulation as secreted proteins and (4) the physiological affects of these molecules on fat cell size and number. These molecules can be divided into two anorexigenic and orexigenic classes. In adipose tissue, all orexigenic molecules possess adipogenic activity, and almost all anorexigenic molecules suppress fat cell proliferation. Although the manner, in which they present in the circulating blood connect the brain and peripheral adipocytes, remains to be well-organized, these observations suggest the positive feedback axis affecting molecules in the hypothalamus and adipose tissue. Analysis of the disturbance and dysregulation of this axis might promote the development of new anti-obesity drugs useful in treating the metabolic syndrome.

Adipose Tissue↗

New ultrasonic cystofiberscope for staging bladder tumors.

We report on a new ultrasonic cystofiberscope for staging bladder tumors. The endoscope makes it possible to view endoscopic and ultrasound images of bladder tumors at any location, either alternately in full screen or simultaneously on the same monitor, with higher resolution. The cystofiberscope is useful for assessing the depth of bladder tumor invasion accurately.

Cystoscopes↗

Fat intake is associated with serum estrogen and androgen concentrations in postmenopausal Japanese women.

A reduction in fat intake has been associated with decreased estrogen levels in dietary intervention studies. However, previous cross-sectional studies conducted mainly among Western populations did not find a positive association between fat intake and postmenopausal estrogen levels. This study examined the cross-sectional association of fat intake with serum levels of estrone, estradiol, testosterone, and dehydroepiandrosterone sulfate (DHEAS) in women. Study subjects were 324 healthy postmenopausal Japanese women. Diet including fat intake was assessed by a validated semiquantitative FFQ. After controlling for age and other potential breast cancer risk factors, serum estrone was positively associated with the percentage of energy from total fat (P = 0.04). The associations of serum estrone with monounsaturated fat and polyunsaturated fat were of borderline significance (P = 0.05). Serum DHEAS was positively associated with the percentage of energy from total fat (P = 0.007), saturated fat (P = 0.009), monounsaturated fat (P = 0.006), and polyunsaturated fat (P = 0.04). Serum estrone and DHEAS concentrations increased 11.8 and 9.3%, respectively, with a 5% increase in the percentage of energy from total fat. These data suggest that a high intake of fat is associated with higher serum levels of estrone and DHEAS in postmenopausal women.

Adult↗

Temperature-sensitive mutants of enterovirus 71 show attenuation in cynomolgus monkeys.

Enterovirus 71 (EV71) is one of the major causative agents of hand, foot and mouth disease and is sometimes associated with serious neurological disorders. In this study, an attempt was made to identify molecular determinants of EV71 attenuation of neurovirulence in a monkey infection model. An infectious cDNA clone of the virulent strain of EV71 prototype BrCr was constructed; temperature-sensitive (ts) mutations of an attenuated strain of EV71 or of poliovirus (PV) Sabin vaccine strains were then introduced into the infectious clone. In vitro and in vivo phenotypes of the parental and mutant viruses were analysed in cultured cells and in cynomolgus monkeys, respectively. Mutations in 3D polymerase (3D(pol)) and in the 3' non-translated region (NTR), corresponding to ts determinants of Sabin 1, conferred distinct temperature sensitivity to EV71. An EV71 mutant [EV71(S1-3')] carrying mutations in the 5' NTR, 3D(pol) and in the 3' NTR showed attenuated neurovirulence, resulting in limited spread of virus in the central nervous system of monkeys. These results indicate that EV71 and PV1 share common genetic determinants of neurovirulence in monkeys, despite the distinct properties in their original pathogenesis.

3' Untranslated Regions↗

Our experience with pediatric epilepsy surgery focusing on corpus callosotomy and hemispherotomy.

PURPOSE: In pediatric patients with intractable epilepsy, surgical intervention should be considered in terms of seizure control and prevention of neuronal deterioration. We present our experience with pediatric epilepsy surgery, focusing on corpus callosotomy and hemispherotomy. METHODS: A total of 257 pediatric patients underwent epilepsy surgeries during the last decade in our clinic. The two most common surgical procedures were corpus callosotomy and hemispherotomy. The surgical outcomes of the patients undergoing these operations were analyzed with regard to seizure outcomes and surgical complications. RESULTS: Corpus callosotomy proved to be extremely effective in controlling drop attacks, especially when the callosum was totally sectioned. Postoperative improvement of psychomotor function also was noticeable in >70% of the cases. In patients who underwent hemispherotomy, the etiology of unilateral hemispheric lesions was closely related to surgical results, with cases of hemimegalencephaly having the worst seizure outcome and most frequent surgical complications. Incomplete section of the callosum, one of the most important causes of residual seizures, was found in three cases. CONCLUSIONS: In pediatric epilepsy surgery, corpus callosotomy is very effective in abolishing drop attacks and improving postoperative psychomotor function. For hemispherotomy, cases of hemimegalencephaly had the worst seizure control and surgical complications. Incomplete section of the corpus callosum should be carefully evaluated as a cause of surgical failure.

Adolescent↗

Intratypic recombination among lineages of type 1 vaccine-derived poliovirus emerging during chronic infection of an immunodeficient patient.

We determined the complete genomic sequences of nine type 1 immunodeficient vaccine-derived poliovirus (iVDPV) isolates obtained over a 337-day period from a poliomyelitis patient from Taiwan with common variable immunodeficiency. The iVDPV isolates differed from the Sabin type 1 oral poliovirus vaccine (OPV) strain at 1.84% to 3.15% of total open reading frame positions and had diverged into at least five distinct lineages. Phylogenetic analysis suggested that the chronic infection was initiated by the fifth and last OPV dose, given 567 days before onset of paralysis, and that divergence of major lineages began very early in the chronic infection. Key determinants of attenuation in Sabin 1 had reverted in the iVDPV isolates, and representative isolates of each lineage showed increased neurovirulence for PVR-Tg21 transgenic mice. None of the isolates had retained the temperature-sensitive phenotype of Sabin 1. All isolates were antigenic variants of Sabin 1, having multiple amino acid substitutions within or near neutralizing antigenic sites 1, 2, and 3a. Antigenic divergence of the iVDPV variants from Sabin 1 followed two major independent evolutionary pathways. The emergence of distinct coreplicating lineages suggests that iVDPVs can replicate for many months at separate sites in the gastrointestinal tract. Some isolates had mosaic genome structures indicative of recombination across and within lineages. iVDPV excretion apparently ceased after 30 to 35 months of chronic infection. The appearance of a chronic VDPV excretor in a tropical, developing country has important implications for the strategy to stop OPV immunization after eradication of wild polioviruses.

Amino Acid Substitution↗