Analyzing drilling noise in rotational atherectomy: Improving safety and effectiveness through visualization and anomaly detection using autoencoder-A preclinical study.

Background and Aims: As the population of aging societies continues to grow, the prevalence of complex coronary artery diseases, including calcification, is expected to increase. Rotational atherectomy (RA) is an essential technique for treating calcified lesions. This study aimed to assess the usefulness of the drilling noise produced during rotablation as a parameter for evaluating the safety and effectiveness of the procedure. Methods: A human body model mimicking calcified stenotic coronary lesions was constructed using plastic resin, and burrs of sizes 1.25 and 1.5 mm were utilized. To identify the noise source during rotablation, we activated the ROTAPRO™ rotablator at a rotational speed of 180,000 rpm, recording the noise near the burr (inside the mock model) and advancer (outside). In addition to regular operation, we simulated two major complications: burr entrapment and guidewire transection. The drilling noise recorded in Waveform Audio File Format files was converted into spectrograms for analysis and an autoencoder analyzed the image data for anomalies. Results: The drilling noise from both inside and outside the mock model was predominantly within the 3000 Hz frequency domain. During standard operation, intermittent noise within this range was observed. However, during simulated complications, there were noticeable changes: a drop to 2000 Hz during burr entrapment and a distinct squealing noise during guidewire transection. The autoencoder effectively reduced the spectrogram data into a two-dimensional representation suitable for anomaly detection in potential clinical applications. Conclusion: By analyzing drilling noise, the evaluation of procedural safety and efficacy during RA can be enhanced.

Predictors of In-Hospital Death in Patients With Acute Myocardial Infarction.

OBJECTIVE: Factors such as age, vital signs, renal function, Killip class, cardiac arrest, elevated cardiac biomarker levels, and ST deviation predict survival in patients with acute myocardial infarction (AMI). However, the existing risk assessment tools lack comprehensive consideration of catheter-related factors, and short-term prognostic predictors are unknown. This study aimed to clarify in-hospital prognostic predictors in hospitalized patients with AMI. METHODS: Five hundred and thirty-six patients who underwent percutaneous coronary intervention (PCI) for AMI were divided into non-survivor (n = 36) and survivor (n = 500) groups. Coronary risk factors, laboratory findings, angiographic findings, and clinical courses were compared between the two groups. Multiple logistic regression was used to analyze in-hospital death in pre- and post-PCI phases. RESULTS: In the pre-PCI phase, multiple logistic regression analysis revealed several predictors of in-hospital death, including systolic blood pressure [odds ratio (OR) = 0.985, p = 0.023)], Killip class ≥2 (OR = 14.051, p <0.001), and chronic kidney disease (OR = 4.859, p = 0.040). In the post-PCI phase, multiple logistic regression analysis revealed additional predictors of in-hospital death, including Killip class ≥2 (OR = 5.982, p = 0.039), presence of lesions in the left main trunk (OR = 51.381, p = 0.044), utilization of intra-aortic balloon pumps and percutaneous cardiopulmonary support (OR = 6.141, p = 0.016), and presence of multi-vessel disease (OR = 6.323, p = 0.022). CONCLUSION: Predictors of in-hospital death in AMI extend beyond conventional risk factors to include culprit lesions, mechanical support, and multi-vessel disease that manifest post-PCI.

Requirement of the Ca2+ channel ß2 subunit for sympathetic PKA phosphorylation.

Facilitation of cardiac function in response to signals from the sympathetic nervous system is initiated by the phosphorylation of L-type voltage-dependent Ca2+ channels (VDCCs) by protein kinase A (PKA), which in turn is activated by ß-adrenoceptors. Among the five subunits (α1, ß, α2/δ, and γ) of VDCCs, the α1 subunit and the family of ß subunits are substrates for PKA-catalyzed phosphorylation; however, the subunit responsible for ß-adrenergic augmentation of Ca2+ channel function has yet to be specifically identified. Here we show that the VDCC ß2 subunit is required for PKA phosphorylation upon sympathetic acceleration. In mice with ß2 subunit-null mutations, cardiac muscle contraction in response to isoproterenol was reduced and there was no significant increase in Ca2+ channel currents upon PKA-dependent phosphorylation. These findings indicate that within the sympathetic nervous system the ß2 subunit of VDCCs is required for physiological PKA-dependent channel phosphorylation.

Investigation of arterial-cardiac-pulmonary interaction.

Pulmonary function and arterial stiffness correlate significantly, attributing to the chronic inflammation of atherosclerosis. However, through the pulmonary or systemic circulation, pulmonary and vascular functions associate hemodynamically with cardiac morphology and function. In the present study, we investigated arterial-cardiac-pulmonary interaction by examining how the pulmonary and vascular functions correlate with the heart. This study investigated 55 consecutive subjects not suffering from pulmonary, vascular and cardiac disease who underwent health screening test at our medical center. First, the presence of atherosclerotic disease (hypertension, dyslipidemia and diabetes) and smoking status of the patients were determined. Next, pulmonary function test, vascular function test including cardio-ankle vascular index, and echocardiography were performed. Then, we examined the correlation among the pulmonary, vascular and the heart. Our results revealed many correlations among these three factors. Especially left atrial dimension (LAD) and E/A ratio (E/A) were important cardiac factors associated with both pulmonary and vascular functions independently. Conventionally, inflammatory responses are known to involve in the correlation between pulmonary and vascular functions. Our study demonstrated that cardiac function and morphology were also involved in this correlation, signifying that LAD and E/A plays important roles in the arterial-cardiac-pulmonary interaction.

Eicosapentaenoic Acid combined with optimal statin therapy improves endothelial dysfunction in patients with coronary artery disease.

PURPOSE: Eicosapentaenoic acid (EPA) has been reported to augment endothelial function and improve clinical outcomes in patients with coronary artery disease (CAD). The purpose of this study was to determine whether EPA could improve residual endothelial dysfunction despite adequate lipid-lowering with statin in CAD patients. METHODS: Eighty patients with established CAD, who had been on statin treatment and had serum low-density lipoprotein cholesterol (LDL-C) levels <100 mg/dl, were randomly assigned to receive either 1,800 mg of EPA daily plus statin (EPA group, n = 40) or statin alone (Control group, n = 40). Lipid profiles and flow-mediated dilation (FMD) were assessed just before and after more than 3 months of treatment in both groups. Only patients who had impaired FMD (<6 %) before randomization were enrolled. RESULTS: After treatment for 5.2 ± 1.7 months, the EPA group showed a significant increase in the serum concentration of EPA and EPA to arachidonic acid (AA) (EPA/AA) ratio (62.5 ± 38.1 to 159.8 ± 53.8 µg/ml, 0.45 ± 0.34 to 1.20 ± 0.55, p < 0.01 for both). In the EPA group, serum triglycerides significantly decreased (150.7 ± 92.9 to 119.3 ± 60.7 mg/dl, p = 0.02), whereas no significant change was seen in the Control group. FMD, the primary study endpoint, showed a significant improvement in the EPA group (2.6 ± 1.6 % to 3.2 ± 1.6%, p = 0.02), whereas no significant change was observed in the Control group (2.7 ± 1.6% to 2.4 ± 1.7 %, p = 0.29). CONCLUSIONS: EPA improved endothelial function and impaired FMD in patients with established CAD who were on optimal statin therapy.

Aortopulmonary artery fistula: ruptured aneurysm of the distal aortic arch into the pulmonary artery.

Aortopulmonary artery fistula is uncommon, but the clinical outcome is often lethal. A 76-year-old man with a history of acute thoracic aortic dissection 6 years previously was admitted with dyspnea. A chest x-ray showed pleural effusion and pulmonary congestion. Transthoracic echocardiography revealed preserved systolic function, but continuous and abnormal flow from the distal aortic arch into the pulmonary artery (PA). Transesophageal echocardiography (TEE) in the Doppler color-flow mode demonstrated a left-to-right shunt between a large distal aortic arch aneurysm and the left PA via an aortopulmonary fistula and a pressure gradient across the shunt of 56 mmHg. Contrast-enhanced computed tomography showed that the aneurysm compressed the PA. Aortography also revealed a large distal aortic arch aneurysm and almost simultaneous contrast enhancement of the aorta and the PA. Right-heart catheterization showed a significant increase in oxygen saturation between the right ventricle and the PA. A left-to-right shunt due to a distal aortic arch aneurysm rupturing into the left PA was diagnosed based on these findings. TEE was very helpful in confirming the presence and precise location of the fistula.

Longitudinal heterogeneity of coronary artery distensibility in plaques related to acute coronary syndrome.

BACKGROUND: How coronary distensibility contributes to stable or unstable clinical manifestations remains obscure. We postulated that the heterogeneous plaque distensibility is associated with unstable clinical presentations in patients with acute coronary syndrome (ACS). METHODS AND RESULTS: Seventeen and 19 ACS-related and -unrelated lesions, respectively, were visualized using intravascular ultrasound imaging with simultaneous intracoronary pressure recording. Systolic and diastolic lumen cross-sectional areas were measured at the lesion site and at five evenly spaced sites between the proximal and distal reference sites. The coronary distensibility index and stiffness index ß were calculated for each site and averaged for each coronary segment. Maximal distensibility index, standard deviation and the difference between maximal and minimal distensibility indices within each segment were significantly higher in the ACS-related than -unrelated plaques (5.6 ± 2.3 vs. 3.7 ± 1.8, p < 0.001, 2.1 ± 0.9 vs. 1.1 ± 0.6, p < 0.001 and 5.3 ± 2.3 vs. 2.8 ± 1.5, p < 0.001, respectively). Moreover, the difference in the distensibility index between the lesion site of ACS-related plaques and the immediate proximal site was significantly larger (2.88 ± 2.35 vs. 1.17 ± 1.44, p = 0.022) than that in ACS-unrelated plaques. CONCLUSIONS: Coronary artery distensibility is longitudinally more heterogeneous in ACS-related than-unrelated plaques, especially between the lesion and the immediate proximal site.

Developmental switching of perisomatic innervation from climbing fibers to basket cell fibers in cerebellar Purkinje cells.

In early postnatal development, perisomatic innervation of cerebellar Purkinje cells (PCs) switches from glutamatergic climbing fibers (CFs) to GABAergic basket cell fibers (BFs). Here we examined the switching process in C57BL/6 mice. At postnatal day 7 (P7), most perisomatic synapses were formed by CFs on to somatic spines. The density of CF-spine synapses peaked at P9, when pericellular nest around PCs by CFs was most developed, and CF-spine synapses constituted 88% of the total perisomatic synapses. Thereafter, CF-spine synapses dropped to 63% at P12, 6% at P15, and <1% at P20, whereas BF synapses increased reciprocally. During the switching period, a substantial number of BF synapses existed as BF-spine synapses (37% of the total perisomatic synapses at P15), and free spines surrounded by BFs or Bergmann glia also emerged. By P20, BF-spine synapses and free spines virtually disappeared, and BF-soma synapses became predominant (88%), thus attaining the adult pattern of perisomatic innervation. Parallel with the presynaptic switching, postsynaptic receptor phenotype also switched from glutamatergic to GABAergic. In the active switching period, particularly at P12, fragmental clusters of AMPA-type glutamate receptor were juxtaposed with those of GABA(A) receptor. When examined with serial ultrathin sections, immunogold labeling for glutamate and GABA(A) receptors was often clustered beneath single BF terminals. These results suggest that a considerable fraction of somatic spines is succeeded from CFs to BFs and Bergmann glia in the early postnatal period, and that the switching of postsynaptic receptor phenotypes mainly proceeds under the coverage of BF terminals.

Developmental localization of potassium chloride co-transporter 2 (KCC2), GABA and vesicular GABA transporter (VGAT) in the postnatal mouse somatosensory cortex.

Gamma-amino butyric acid (GABA) mediates the hyperpolarization of membrane potential, negatively regulating glutamatergic activity in the adult brain, whereas, mediates depolarization in the immature brain. This developmental shift in GABA actions is induced by the expression of potassium chloride co-transporter 2 (KCC2). In this study, we focused on the developing mouse somatosensory cortex, where the barrel structure in layer 4 is altered by the whisker-lesion during the critical period, before postnatal day 4 (P4). First, to clarify the time-course of postnatal changes in GABA actions, we investigated the developmental localization of KCC2. Second, to reveal its spatial and temporal relationship with GABA synapse formation, we examined the developmental localization of GABA and vesicular GABA transporter. KCC2 was localized within the pyramidal cells in layer 5 after P3, granule cells in layer 4 after P5 and neurons in layers 2 and 3 after P7, indicating that KCC2 was expressed in the chronological order of neuronal settling at the destination. The onset of KCC2 localization was almost concomitant with the formation of GABA synapses, suggesting that GABA was inhibitory after GABA synapse formation. Furthermore, extrasynaptically released GABA might be involved in the maintenance of activity-dependent plasticity as an excitatory transmitter during the critical period.

Cadmium and tubular dysfunction marker levels in urine of residents in non-polluted areas with natural abundance of cadmium in Japan.

OBJECTIVES: Literature survey has suggested that cadmium (Cd) in the general environment is more abundant in the northern part of the coast on the sea of Japan. The present survey was initiated to examine if the exposure to Cd in the area has been higher than other parts of Japan, and if so, the higher exposure has been associated with tubular dysfunction among the local residents. METHODS: In three prefectures of Akita, Yamagata and Ishikawa in the region, adult women (about 700 subjects per prefecture) were invited to participate in the survey. Each of the participants provided informed consents, offered spot urine samples and filled questionnaires (on age etc.). The urine samples were analyzed for Cd, alpha(1)-microglobulin (alpha(1)-MG), beta(2)-microglobulin (beta(2)-MG) and N-acetyl-beta-D: -glucosaminidase, together with creatinine and specific gravity. The results were combined with published data on two other prefectures of Niigata and Toyama (both in the area), as well as Japan as a whole (all Japan-A excluding Niigata prefecture, which was studied separately in the present study), and subjected to analysis for possible difference from all Japan-A in terms of the levels of internal Cd burden, and prevalence of beta(2)-MG-uria. RESULTS: Geometric means (GMs) for urinary Cd in the five prefectures were in a range from a low of 1.20 to a high of 2.65 microg/l, being higher than the GM (0.99 microg/l) for all Japan-A. GMs for alpha(1)-MG (2.15-2.80 mg/l) and beta(2)-MG (99-107 microg/l) were only slightly higher or even lower than all Japan-A values depending on the prefectures. Elevation in the prevalence of beta(2)-MG-uria was significant in Akita prefecture, but the elevation in beta(2)-MG was not associated with elevation in Cd in urine. Literature survey on general population Cd epidemiology showed that Cd, alpha(1)-MG and beta(2)-MG levels in urine of the residents in the five prefectures were within the levels reported for non-polluted areas, and such was also the case for prevalence of beta(2)-MG-uria. CONCLUSIONS: In an over-all evaluation, no clear-cut evidence was available for increased prevalence of Cd exposure-associated renal tubular dysfunction among general populations in the five prefectures in the northern part on the coast of Sea of Japan than in other prefectures in Japan, despite moderate elevation in urinary Cd levels.

N-acetyl-beta-D-glucosaminidase (NAG) as the most sensitive marker of tubular dysfunction for monitoring residents in non-polluted areas.

Alpha(1)-microglobulin (alpha(1)-MG), beta(2)-microglobulin (beta(2)-MG) and N-acetyl-beta-D-glucosaminidase (NAG) are tubular dysfunction markers often used in cadmium (Cd) epidemiology. The purpose of the present study was to identify the best maker among the above-referred three that correlates most closely with Cd in urine of residents with no known Cd pollution. Survey was conducted in 2007-2008 in three prefectures in Japan. Adult women, 2163 in total, participated in the survey; they provided informed consents, offered spot urine samples and filled questionnaires on possible confounders of Cd burden. Urine samples were analyzed for Cd, alpha(1)-MG, beta(2)-MG and NAG together with calcium (Ca), magnesium (Mg), creatinine (CR) and specific gravity (SG). The analyte levels, as observed (e.g., Cd(ob)) or after correction for CR (e.g., Cd(cr)) or SG (e.g., Cd(sg)) were subjected to simple and multiple regression analysis. Correlation matrix analysis with observed values for total cases showed that the coefficients of correlation with Cd were highest for NAG, followed by alpha(1)-MG, and lowest for beta(2)-MG. Multiple regression analysis by three prefectures either separately or in combination (thus four analyses) disclosed that Cd was the independent variable most influential to NAG (as the dependent variable) throughout the four analysis conditions with high R(2) values (>0.3), whereas the most influential variables were not the same depending on the analysis conditions in cases with alpha(1)-MG and beta(2)-MG. When coefficients of correlation for the three dysfunction markers with Cd were compared among the observed, CR- and SG-corrected values, the coefficients for the observed values were higher than the counterpart values for CR- or SG-corrected values. In conclusion, NAG rather than alpha(1)-MG or beta(2)-MG should be recommended for monitoring Cd exposure-related tubular effects among general populations. Observed (i.e., un-corrected) values rather than CR- or SG-corrected values should be used.

Developmental localization of potassium chloride co-transporter 2 (KCC2) in the Purkinje cells of embryonic mouse cerebellum.

Developmental shift in GABA actions from depolarization to hyperpolarization occurs as a result of decreasing the intracellular Cl(-) concentration regulated by K(+)-Cl(-) co-transporter 2 (KCC2). To clarify the time-course of the developmental shift on the Purkinje cells, we examined KCC2-localization in the embryonic mouse cerebellum. The KCC2 was first detected within the Purkinje cells in the Purkinje cell layer of the hemisphere at embryonic day 15 (E15) and the vermis at E17, but the ventricular and intermediate zones were negative. These results suggest that GABA might become inhibitory on the Purkinje cells after their settling in the Purkinje cell layer.

Developmental expression of GABA transporter-1 and 3 during formation of the GABAergic synapses in the mouse cerebellar cortex.

In the brain, gamma-amino butyric acid (GABA), released extrasynaptically and synaptically from GABAergic neurons, plays important roles in morphogenesis, expression of higher functions and so on. In the GABAergic transmission system, plasma membrane GABA transporters (GATs) mediate GABA-uptake from the synaptic cleft in the mature brain and are thought to mediate diacrine of cytosolic GABA in the immature brain. In the present study, we focused on two GATs (GAT-1 and GAT-3) in the mouse cerebellar cortex, which are widely localized in neural and glial cells. Firstly, we examined the localization of GATs in the dendrites and cell bodies of developing GABAergic neurons, where GABA is extrasynaptically distributed, to clarify the GABA-diacrine before synaptogenesis. Secondly, we examined the developmental changes in the localization of GATs to reveal the development of the GABA-uptake system. Neither transporter was detected within the dendrites and cell bodies of GABAergic neurons, including Purkinje, stellate, basket and Golgi cells, in the immature cerebellar cortex. GAT-1 was observed within the Golgi cell axon terminals after postnatal day 5 (P5) and presynaptic axons of stellate and basket cells after P7. GAT-3 was localized within the astrocyte processes, sealing the GABAergic synapses in the Purkinje cell and granular layers after P10. These results indicated that GABA-diacrine did not work in the mouse cerebellar cortex. The onset of GAT-1-expression was prior to that of GAT-3. GAT-1 started to be localized within the GABAergic axon terminals during synapse formation. GAT-3 started to be localized within astrocyte processes when they sealed the synapses.

Extrasynaptic localization of GABA in the developing mouse cerebellum.

In the adult brain, gamma-amino butyric acid (GABA) is synaptically released and mediates inhibitory transmission. Recent studies have revealed that GABA is a trophic factor for brain development. To reveal the distribution of GABA and its secretion mechanisms during brain development, we investigated the immunohistochemical localization of two molecules, GABA and vesicular GABA transporter (VGAT), which is a GABAergic vesicle protein, in the developing mouse cerebellum by means of newly developed antibodies. Furthermore, we tested the relationship between developmental changes in distribution of above two molecules in the presynapses and ontogeny of GABAergic synapses. GABAergic synapses were detected by immunohistochemistry for the GABA(A) receptor alpha1 subunit, which is an essential subunit for inhibitory synaptic transmission in the mature cerebellar cortex. Until postnatal day 7 (P7), GABA was localized throughout the GABAergic neurons, and VGAT accumulated at axon varicosities and growth cones, where the alpha1 subunit did not accumulate. After P10, both GABA and VGAT became confined to the terminal sites where the alpha1 subunit was localized. These results suggested that GABA was extrasynaptically released from axon varicosities and growth cones by vesicular secretion 'exocytosis' and from all parts of GABAergic neurons during the cerebellar development by non-vesicular secretion 'diacrine'.

GABAergic signaling in the developing cerebellum.

In the adult central nervous system (CNS), GABA is a predominant inhibitory neurotransmitter that regulates glutamatergic activity. Recent studies have revealed that GABA serves as an excitatory transmitter in the immature CNS and acts as a trophic factor for brain development. Furthermore, synaptic transmission by GABA is also involved in the expression of higher brain functions, such as memory, learning and anxiety. These results indicate that GABA plays various roles in the expression of brain functions and GABAergic roles change developmentally in accordance with alterations in GABAergic transmission and signaling. We have investigated morphologically the developmental changes in the GABAergic transmission system and the key factors important for the formation of GABAergic synapses and networks using the mouse cerebellum, which provides an ideal system for the investigation of brain development. Here, we focus on GABA and GABA(A) receptors in the developing cerebellum and address the processes of how GABA exerts its effect on developing neurons and the mechanisms underlying the formation of functional GABAergic synapses.

Morphological development and maturation of the GABAergic synapses in the mouse cerebellar granular layer.

In the adult central nervous system (CNS), gamma-amino butyric acid (GABA) is a predominant inhibitory neurotransmitter, which regulates glutamatergic activity. Recent studies have revealed that GABA serves as an excitatory transmitter in the immature CNS, and is involved in brain morphogenesis. To elucidate how GABA exerts its effect on immature neurons and how GABAergic synapses are formed, we examined both development of pre- and post-synaptic elements of the GABAergic synapses formed between granule and Golgi cells in the mouse cerebellar granular layer. Immunohistochemistry for glutamic acid decarboxylase (GAD) demonstrated that GABA was localized throughout the Golgi cells before postnatal day 7 (P7), and became confined to the axon terminals during the second postnatal week. Electron microscopic analysis demonstrated that GABAergic synapses were clearly detected at P10. In situ hybridization and immunohistochemistry for the GABA(A) receptor alpha1 and alpha6 subunits, which are mainly involved in inhibitory synaptic transmission, demonstrated that both subunits appeared at P7. Distribution of both subunits expanded in the granular layer with special reference to the development of GABAergic synapses. Furthermore, the majority of the subunits accumulated adjacent to the GABAergic terminals. These results suggested that in the granular layer, GABA might be non-synaptically secreted from Golgi cell axons and dendrites during the first postnatal week. From the second postnatal week, GABA is synaptically released and begins to mediate inhibitory transmission. Furthermore, it was suggested that GABAergic innervation could initiate expression and trafficking of the GABA(A) receptors containing the alpha1 and alpha6 subunits.

Transient expression of GABAA receptor alpha2 and alpha3 subunits in differentiating cerebellar neurons.

In the adult mammalian brain, synaptic transmission mediated by gamma-amino butyric acid (GABA) plays a role in inhibition of excitatory synaptic transmission. During brain development, GABA is involved in brain morphogenesis. To clarify how GABA exerts its effect on immature neurons, we examined the expression of the GABAA receptor alpha2 and alpha3 subunits, which are abundantly expressed before alpha1 and alpha6 subunits appear, in the developing mouse cerebellum using in situ hybridization. Proliferating neuronal precursors in the ventricular zone and external granular layer expressed neither alpha2 nor alpha3 subunits. Hybridization signals for the alpha2 and alpha3 subunit mRNAs first appeared in the differentiating zone at embryonic day 13 (E13). The alpha2 subunit was detected in the migrating and differentiating granule cells and cerebellar nucleus neurons until postnatal day 14 (P14). Hybridization signals for the alpha3 subunit mRNA, on the other hand, were localized in the developing Purkinje cells and cerebellar nucleus neurons, and disappeared from Purkinje cells by the end of first postnatal week. Taken together, this indicated that the alpha2 and alpha3 subunits were abundantly expressed in distinct types of cerebellar neurons after completing cell proliferation while forming the neural network. These results suggest that GABA might extrasynaptically activate the GABAA receptors containing alpha2 and/or alpha3 subunits on the differentiating neurons before finishing the formation of synapses and networks, and could be involved in neuronal differentiation and maturation in the cerebellum.

Tetraspanin protein CD9 is a novel paranodal component regulating paranodal junctional formation.

The axoglial paranodal junction is essential for the proper localization of ion channels around the node of Ranvier. The integrity of this junction is important for nerve conduction. Although recent studies have made significant progress in understanding the molecular composition of the paranodal junction, it is not known how these membrane components are distributed to the appropriate sites and interact with each other. Here we show that CD9, a member of the tetraspanin family, is present at the paranode. CD9 is concentrated in the paranode as myelination proceeds, but CD9 clusters become diffuse, associated with disruption of the paranode, in cerebroside sulfotransferase-deficient mice. Immunohistochemical and Western blot analysis showed that CD9 is distributed predominantly in the PNS. Ablation of CD9 in mutant mice disrupts junctional attachment at the paranode and alters the paranodal components contactin-associated protein (also known as Paranodin) and neurofascin 155, although the frequency of such abnormalities varies among individuals and individual axons even in the same mouse. Electron micrographs demonstrated that compact myelin sheaths were also affected in the PNS. Therefore, CD9 is a myelin protein important for the formation of paranodal junctions. CD9 also plays a role in the formation of compact myelin in the PNS.

Normal formation of the postsynaptic elements of GABAergic synapses in the reeler cerebellum.

Synaptic transmission mediated by gamma-amino butyric acid (GABA) plays an important role in inhibition of glutamatergic excitatory transmission and expression of higher brain functions, such as memory, learning and anxiety. To elucidate mechanisms underlying formation of the postsynaptic elements for GABAergic transmission, we employed the reeler mutant mice in this study. In the reeler cerebellum, abnormal cytoarchitecture and an aberrant environment affect the formation of neural networks and maturation of neurons. We examined the expression and localization of GABA(A) receptor alpha subunits in the reeler cerebellum and determined whether various abnormalities in the reeler mice affected formation of the postsynaptic elements. In situ hybridization analysis revealed that the specific expression of alpha subunit mRNAs in each neuronal type was preserved. Abnormal expression of alpha subunits was not detected, although GABAergic networks were altered and neuronal maturation was severely disturbed. Immunohistochemistry for the alpha1 and alpha6 subunits, which were expressed abundantly in the reeler cerebellum, revealed that both subunit proteins accumulated at positions adjacent to GABAergic terminals. These results, taken together, suggested that expression of the GABA(A) receptor subunits in postsynaptic neurons might be genetically determined, but trafficking and accumulation of the subunit proteins at the GABAergic synapse may be induced by GABAergic innervation.

Prospective endoscopic follow-up results of reconstructed gastric tube.

BACKGROUND/AIMS: Recent advances in the treatment of esophageal cancer have afforded better prognosis for patients. Despite the increased need to monitor the progress of patients with reconstructed digestive tracts over the long-term, no reliable prospective studies have yet been conducted. This prospective study determined secondary disease of the reconstructed gastric tube after esophagectomy for esophageal cancer. METHODOLOGY: One hundred and fourteen patients who underwent esophagectomy and reconstructed gastric tube via the posterior mediastinal route between April 1992 and March 1999 at Akita University Hospital, were followed up. Follow-up endoscopy was carried out once a year to determine the incidence and characteristics of secondary disease of the reconstructed gastric tube. RESULTS: Fifty-four (47%) patients were found to have secondary gastric abnormalities. Of these, 4 patients (3.5%) had carcinoma of the gastric tube, 12 patients (10.5%) had benign gastric tumor, 7 patients (6.1%) had gastric ulcers, and 40 patients (35.1%) had erosive or hemorrhagic gastritis. Three patients found to have early gastric cancer upon periodic follow-up endoscopy underwent successful complete resections. CONCLUSIONS: Annual follow-up endoscopy is vital to the detection of early, curative secondary gastric cancer and ulceration in patients following esophagectomy for esophageal cancer.