PubMed Health⌕ Search

Biomedical subjects

Kenichi Ishibashi

Publications and source records attributed to Kenichi Ishibashi.

At least 19 recordsLinked to original sources

Aquaporin-11 containing a divergent NPA motif has normal water channel activity.

Recently, two novel mammalian aquaporins (AQPs), AQPs 11 and 12, have been identified and classified as members of a new AQP subfamily, the "subcellular AQPs". In members of this subfamily one of the two asparagine-proline-alanine (NPA) motifs, which play a crucial role in selective water conduction, are not completely conserved. Mouse AQP11 (mAQP11) was expressed in Sf9 cells and purified using the detergent Fos-choline 10. The protein was reconstituted into liposomes, which were used for water conduction studies with a stopped-flow device. Single water permeability (pf) of AQP11 was measured to be 1.72+/-0.03x10(-13) cm(3)/s, suggesting that other members of the subfamily with incompletely conserved NPA motifs may also function as water channels.

Alanine↗

Comparison of neuropsychological outcomes after selective amygdalohippocampectomy versus anterior temporal lobectomy.

Transsylvian selective amygdalohippocampectomy (TSA) is an operative technique designed to spare unaffected brain tissue during surgical treatment for mesial temporal lobe epilepsy. In contrast to standard anterior temporal lobectomy (ATL), the advantages of TSA with respect to postoperative cognitive outcome are equivocal. We compared cognitive function before and after surgery in 49 patients with unilateral mesial temporal lobe seizures who underwent either ATL (n=17) or TSA (n=32). All patients received neuropsychological testing before and 1 year after surgery. The intelligence quotient (IQ) increased postoperatively in both surgical groups. Memory evaluation in the ATL group revealed a postoperative decline in nonverbal memory after right-sided resection and a postoperative decline in verbal memory after left-sided resection. In the TSA group, there was a slight postoperative decline only in verbal memory after left-sided resection, but other memory function was well preserved. In particular, there was significant postoperative improvement in verbal memory after right-sided resection. Overall, memory function was better preserved in the TSA group than in the ATL group.

Adult↗

Aquaporin subfamily with unusual NPA boxes.

Aquaporins have been identified based on highly conserved two asparagine-proline-alanine (NPA) boxes that are important for the formation of a water-permeating pore. Some aquaporin-like sequences, however, have less conserved NPA boxes. Although they have lower homology with conventional aquaporins, they should be included in aquaporin family based on their conserved six transmembrane domains and hydrophobic NPA box-like repeats. They are widely distributed in multicellular organisms. Only SIPs from plants and AQP11/12 from mammals were examined previously and found to be localized inside the cell. Intracellular localization will be a common feature of these aquaporin-like proteins since most of them have positively charged amino acid clusters at the carboxy-termini similar to di-lysine motif (-KKXX) for an endoplasmic reticulum retention signal. Accordingly, they are tentatively named subcellular-aquaporins in this review. Currently, studies on their functions and biological roles are limited. SIPs were shown to function as water channels and the disruption of AQP11 produced neonatally fatal polycystic kidneys. Further works on subcellular-aquaporins will reveal new insights into the roles of aquaporins.

Alanine↗

Small artery dementia in Japan: radiological differences between CADASIL, leukoaraiosis and Binswanger's disease.

CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is a hereditary small artery disease which is phenotypically similar to Binswanger's disease (BD), a nonhereditary form of small artery disease. Recent studies have indicated that lesions in the temporopolar, medial frontopolar areas and external capsule are frequently seen in Caucasian patients with CADASIL. However, it remains unclear whether magnetic resonance (MR) imaging findings are helpful in diagnosing small artery disease outside countries with Caucasian populations, since CADASIL is rare despite the high prevalence of small artery disease in Japan. We examined 58 patients with small artery disease, all of whom were devoid of major vessel occlusion or severe stenosis. These patients included 7 patients from 3 families with CADASIL, 27 nondemented patients with extensive leukoaraiosis (LA) and 24 patients with BD. On T(2)-weighted MR images, hyperintensities in the temporopolar areas were observed in all 7 patients with CADASIL, whereas these lesions were observed in only 1 subject from each of the nondemented LA and BD groups. Hyperintensities in the medial frontopolar areas were seen in 4 of the 7 patients with CADASIL (57%) and in 14 of the 24 patients with BD (58%), and were more frequent than in the nondemented LA group (4 of the 27 patients; 15%). In contrast, hyperintensities in the external capsule were frequently observed in all groups. Therefore, temporopolar lesions can also serve as diagnostic markers for CADASIL in non-Caucasian patients.

Adult↗

Identification of a keratinocarcinoma cell line expressing AQP3.

BACKGROUND INFORMATION: AQP3 (aquaporin 3) in the skin is important for skin moisture as demonstrated by the studies of AQP3-null mice, which have accelerated skin drying. Prevention of dry skin is important not only from a cosmetic but also from a clinical point of view. Primary keratinocyte cultures are cumbersome for screening substances that modulate AQP3 expression. RESULTS: A human keratocarcinoma cell line was found to express AQP3 mRNA and protein, which responded to hypertonic stimulation with sorbitol, suggesting that the AQP3 expression is normally regulated in this cell line. This cell line also expressed the type 1 keratinocyte transglutaminase gene. The AQP3 expression was unaffected by all-trans-retinoic acid up to 10(-6) M. Similarly, the retinoic acid did not increase the AQP3 expression up to 1% concentration in rat skin. CONCLUSION: This cell line is useful for the screening of candidate substances that modulate AQP3 expression.

Animals↗

The anterolateral partial vertebrectomy approach for ventrally located cervical intramedullary cavernous angiomas.

OBJECTIVE: We report three cases with ventral cervical intramedullary cavernous angiomas. An anterolateral partial vertebrectomy was performed to surgically approach and successfully resect these lesions. MATERIALS AND METHODS: All three patients presented with numbness in the upper extremities and investigation revealed a cavernous angioma on the ventral aspect of the spinal cord in each case. The lesion was exposed by an anterolateral partial vertebrectomy in all cases. Postoperative stabilization was achieved by using autografted iliac bone in all patients. In two patients, locking screws and plates were also used. RESULTS: Complete resection of the cavernous angioma was performed in all patients. There was symptomatic relief in all cases, and there was no postoperative morbidity. CONCLUSION: Anterolateral partial vertebrectomy provides direct exposure and is probably an ideal approach for selected cases with ventrally located intramedullary cavernous angiomas.

Adult↗

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↗

Schwannoma of the oculomotor nerve.

A 63-year-old woman presented with an extremely rare oculomotor schwannoma not associated with neurofibromatosis, manifesting as a transient diplopia and ptosis. Magnetic resonance images showed a well-enhanced mass extending from the cavernous sinus to the intraorbital region. Surgical exposure confirmed the tumor originating from the oculomotor nerve in the cavernous sinus. The intraorbital cystic part of the tumor was partially resected to preserve the oculomotor function. This is the first case of oculomotor schwannoma in the cavernous sinus with intraorbital component.

Blepharoptosis↗

Radioiodinated flavones for in vivo imaging of beta-amyloid plaques in the brain.

In vivo imaging of beta-amyloid (A beta) peptide aggregates in the brain may lead to early detection of Alzheimer's disease (AD) and monitoring of the progression and effectiveness of AD treatment. The purpose of this study was to develop novel amyloid imaging agents based on flavone as a core structure. Radioiodinated flavone derivatives were designed and synthesized. The binding affinities of flavone derivatives for A beta aggregates varied from 13 to 77 nM. When in vitro plaque labeling was carried out using post-mortem AD brain sections, all flavones intensely stained not only amyloid plaques but also cerebrovascular amyloids. In biodistribution studies using normal mice, they displayed high brain uptakes ranging from 3.2 to 4.1% ID/g at 2 min postinjection. The radioactivity washed out from the brain rapidly (0.5-1.9% ID/g at 30 min), which is highly desirable for amyloid imaging agents. The results in the study suggest that these classes of radioiodinated flavones may be useful candidates as potential imaging agents for amyloid plaques.

Aged↗

Identification of a novel aquaporin, AQP12, expressed in pancreatic acinar cells.

Members of the aquaporin (AQP) water channel family are widely distributed in various tissues and contribute to the water permeability of epithelial and endothelial cells. Currently 11 members of the AQP family (AQP0-10) have been reported in mammals. Here we report the identification of AQP12, which we found by performing a BLAST program search. Northern blot analysis revealed that AQP12 was specifically expressed in the pancreas. Further analysis by in situ hybridization and RT-PCR studies showed that AQP12 was selectively localized in the acinar cells of the pancreas. To analyze the cellular localization and function of AQP12, we expressed AQP12 in Xenopus oocytes and cultured mammalian cells. Immunocytochemistry revealed that AQP12 was not targeted to the plasma membrane. The selective localization of AQP12 in pancreatic acinar cells and possibly in the intracellular organelles suggests a role of AQP12 in digestive enzyme secretion such as maturation and exocytosis of secretory granules.

Amino Acid Sequence↗

Expression and localization of two isoforms of AQP10 in human small intestine.

BACKGROUND INFORMATION: AQP10 (aquaporin 10) is a new member of water channels and two different transcripts have been reported. The difference between these transcripts is in the presence or the absence of an insertion of 475 nt, which leads to a translation frame shift resulting in a different termination of amino acid translation and synthesis of a shorter form of AQP10. Thus an AQP10 molecule deduced from the transcript with an insertion has a distinct C-terminus, different from that translated from the transcript without the insertion. In the present study, we investigated the expression and localization of these AQP10 isoforms. RESULTS: Two transcripts were expressed in human duodenum and jejunum. Western-blot analysis using antibodies for these AQP10 isoforms immunoblotted two bands of approx. 35 and 30 kDa respectively. Immunohistochemistry and immunoelectron microscopy demonstrated localization of the AQP10 with an insertion in the capillary endothelium in villi of the small intestine and the isoform without the insertion in the gastro-entero-pancrestic endocrine cells. CONCLUSION: The different forms of localization of the AQP10 isoforms indicate that they may play different roles in the proximal portion of human small intestine.

Amino Acid Sequence↗

Acute digoxin loading reduces ABCA8A mRNA expression in the mouse liver.

Human ABCA8, a new member of the ATP binding cassette (ABC) transporter family, transports certain lipophilic drugs, such as digoxin. To investigate the roles of this transporter, we cloned a mouse homologue of ABCA8, from a mouse heart cDNA library, named ABCA8a. The deduced mouse ABCA8a protein is 66% identical with that of human ABCA8 and possesses features common to the ABC superfamily. It was found that ABCA8a was mainly expressed in the liver and heart, similar to human ABCA8. We further evaluated the effect of acute digoxin (a substrate for ABCA8) intoxication on the mRNA expression of ABCA8 using northern blotting with a 3' non-coding region as a probe to avoid cross-hybridization with other ABCA genes. Following acute digoxin infusion, the mRNA expression of ABCA8 was significantly reduced in the liver 12-24 h after injection (14.7% of vehicle treatment), but not in the heart and kidney. Real-time quantitative polymerase chain reaction analysis confirmed the reduction in ABCA8a mRNA. Similar reductions in ABCA5, ABCA7, ABCA8b and ABCA9 mRNA were also observed. A comparable amount of digitoxin did not affect ABCA8a mRNA expression in the liver. The results suggest that ABCA8 may play a role in digoxin metabolism in the liver.

ATP-Binding Cassette Transporters↗

Disruption of aquaporin-11 produces polycystic kidneys following vacuolization of the proximal tubule.

Aquaporin-11 (AQP11) has been identified with unusual pore-forming NPA (asparagine-proline-alanine) boxes, but its function is unknown. We investigated its potential contribution to the kidney. Immunohistochemistry revealed that AQP11 was localized intracellularly in the proximal tubule. When AQP11 was transfected in CHO-K1 cells, it was localized in intracellular organelles. AQP11-null mice were generated; these mice exhibited vacuolization and cyst formation of the proximal tubule. AQP11-null mice were born normally but died before weaning due to advanced renal failure with polycystic kidneys, in which cysts occupied the whole cortex. Remarkably, cyst epithelia contained vacuoles. These vacuoles were present in the proximal tubules of newborn mice. In 3-week-old mice, these tubules contained multiple cysts. Primary cultured cells of the proximal tubule revealed an endosomal acidification defect in AQP11-null mice. These data demonstrate that AQP11 is essential for the proximal tubular function. AQP11-null mice are a novel model for polycystic kidney diseases and will provide a new mechanism for cystogenesis.

Animals↗

[Japanese CADASIL case with limited dementia who had the Notch 3 R141C mutation].

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary disease characterized by recurrent transient ischemic attacks (TIA) and strokes, and vascular dementia caused by point mutations of the Notch 3 gene. Here, we report a Japanese CADASIL case who displayed limited dementia and had the Notch 3 R141C mutation. The relationship between pathogenesis and the mutation site in Notch 3 is discussed based on the case presented here.

CADASIL↗

Molecular mechanisms and drug development in aquaporin water channel diseases: aquaporin superfamily (superaquaporins): expansion of aquaporins restricted to multicellular organisms.

Eleven aquaporins are identified in mammals. They all have highly conserved two asparagine-proline-alanine (NPA) boxes that are important for the formation of the water permeating pore. Recently we identified two new proteins in mammals distantly related to aquaporins (AQPs) with poorly conserved NPA boxes. Similarly poorly conserved AQP-like proteins were found in several genome projects of multicellular organisms. They may be subgrouped as the AQP superfamily or superaquaporins. Their function is still unknown. AQP11 knockout mice suffer from polycystic kidneys and neonatal fatality. The identification of superaquaporins will provide new insights into the role of AQPs in organogenesis.

Animals↗

Surgical treatment of temporal lobe epilepsy associated with subcortical ectopic gray matter under the guidance of intraoperative electrocorticography.

We describe a dual pathology presenting as intractable temporal lobe epilepsy associated with subcortical ectopic gray matter. The patient was a 28-year-old male with a 12-year history of refractory temporal lobe epilepsy. Preoperative diagnostic imaging revealed right hippocampal sclerosis, in addition to subcortical ectopic gray matter extending from the posterior end of the inferior horn of the right lateral ventricle to the cerebral parenchyma in the temporoparietal lobe. As surgical therapy for epilepsy, right anterior temporal lobectomy with amygdalohippocampectomy was initially performed. Intraoperative electrocorticography (ECoG) was extremely useful at this point in determining the range of excision of ectopic gray matter after resection of mesial temporal lobe structures. Based on ECoG findings, about 50% of the ectopic gray matter was excised. As of 2 years postoperatively, the patient has remained seizure free with no medication. In cases concomitantly manifesting hippocampal sclerosis and subcortical ectopic gray matter, epilepsy may be associated with dual pathology. This case report raises the potentially important issue of the possible presence of areas of structural abnormality that are non-epileptogenic.

Adult↗

Localization of aquaporin-7 in human testis and ejaculated sperm: possible involvement in maintenance of sperm quality.

PURPOSE: We have previously reported the expression of aquaporin-7 (AQP7) in the rat testis and cloned human AQP7 from the testicular cDNA library. However, to our knowledge the spatial expression pattern and biological roles of AQP7 remain to be elucidated in humans. MATERIALS AND METHODS: We investigated AQP7 expression in the human testis and ejaculated sperm from fertile men and from infertile patients. RESULTS: AQP7 was expressed at the tail of spermatids and spermatozoa in the human testis. AQP7 protein was also detected at the middle piece and the anterior tale portion of ejaculated sperm. However, some infertile patients lacked AQP7 expression in ejaculated sperm, although all fertile men expressed AQP7 protein. The motility rate of AQP7 negative sperm was significantly lower than that of AQP7 positive sperm, while the sperm concentration was not different between AQP7 positive and negative subjects. CONCLUSIONS: AQP7 shows a spatial expression pattern in the human testis. AQP7 may be involved in the maintenance of sperm motility. Furthermore, a lack of AQP7 expression in sperm may be an underlying mechanism of male infertility.

Aquaporins↗