Tricuspid valve annular tilt for assessment of pre- and post-intervention right ventricular volume in patients undergoing transcatheter pulmonary valve replacement.

INTRODUCTION: Transcatheter pulmonary valve replacement serves as a successful alternative to surgical replacement of a right ventricle to pulmonary artery conduit. Guidelines for recommending transcatheter pulmonary valve replacement depend on MRI right ventricular volumes, which have been correlated to the echocardiographic measure of right ventricular annular tilt. We aim to assess whether right ventricular annular tilt can be a clinically useful alternative tool in the acute and long-term periods after transcatheter pulmonary valve replacement to assess right ventricular health. METHODS: We reviewed 70 patients who underwent transcatheter pulmonary valve replacement at a single institution. Echocardiographic measurements were obtained prior to transcatheter pulmonary valve replacement, immediately after transcatheter pulmonary valve replacement, and within 6 months to 1 year after transcatheter pulmonary valve replacement. Right ventricular annular tilt measures the angle of the tricuspid valve plane relative to the mitral valve plane at end-diastole in the apical four-chamber view. Right ventricular fractional area change, right ventricular systolic strain, tissue Doppler velocity, and tricuspid annular plane systolic excursion Z-scores were obtained using published methods. RESULTS: Right ventricular annular tilt decreased significantly immediately after transcatheter pulmonary valve replacement (p = 0.0004), and this reduction in right ventricular volume persisted at the mid-term follow-up (p < 0.0001). Fractional area change did not change significantly after transcatheter pulmonary valve replacement while right ventricular global strain improved at mid-term follow-up despite no significant difference immediately after transcatheter pulmonary valve replacement. CONCLUSIONS: Right ventricular annular tilt decreases both immediately after transcatheter pulmonary valve replacement and at mid-term follow-up. Right ventricular strain also improved after transcatheter pulmonary valve replacement, corresponding to the improved volume load. Right ventricular annular tilt can be considered as an additional echocardiographic factor to assess right ventricular volume and remodeling after transcatheter pulmonary valve replacement.

Regularizing the fast multipole method for use in molecular simulation.

The parallel scaling of classical molecular dynamics simulations is limited by the communication of the 3D fast Fourier transform of the particle-mesh electrostatics methods, which are used by most molecular simulation packages. The Fast Multipole Method (FMM) has much lower communication requirements and would, therefore, be a promising alternative to mesh based approaches. However, the abrupt switch from direct particle-particle interactions to approximate multipole interactions causes a violation of energy conservation, which is required in molecular dynamics. To counteract this effect, higher accuracy must be requested from the FMM, leading to a substantially increased computational cost. Here, we present a regularization of the FMM that provides analytical energy conservation. This allows the use of a precision comparable to that used with particle-mesh methods, which significantly increases the efficiency. With an application to a 2D system of dipolar molecules representative of water, we show that the regularization not only provides energy conservation but also significantly improves the accuracy. The latter is possible due to the local charge neutrality in molecular systems. Additionally, we show that the regularization reduces the multipole coefficients for a 3D water model even more than in our 2D example.

Early developmental exposure to high fructose intake in rats with NaCl stimulation causes cardiac damage.

PURPOSE: Metabolic syndrome (MS) increases the risk of type 2 diabetes and cardiovascular disease. High consumption of fructose is a proposed cause of increased MS, manifested through hypertension, obesity, insulin resistance, and dyslipidemia. High NaCl also increases the risk of CD. The purpose of this study is to evaluate the influence of fructose and sodium on autonomic dysfunction and its relation with CD in MS. Fructose overload was started at weaning and continued through adulthood. METHODS: Male Wistar rats (21 days) were divided into four groups: Control (C), fructose consumption (10%, F), NaCl consumption (salt 1% for the 10 last days, S), and fructose and NaCl (FS), and monitored for 8 weeks. Metabolic evaluations consisted of Lee index, glycemia, insulin and glucose tolerance tests, triglycerides, and total cholesterol measurements. Cardiovascular parameters measured were arterial pressure (AP) and cardiac function performed by echocardiography. They also measured the influence of renin angiotensin (RAS) and autonomic nervous systems by drug blockage with losartan, atropine, and atenolol. RESULTS: Energy analysis showed no change between groups. Fructose overload induced a MS state, confirmed by insulin resistance, glucose intolerance, and dyslipidemia. Fasting glucose was increased in F and FS rat groups compared with C and S groups. AP was higher in F, S, and FS groups in comparison with the C group. The hypotensive response after sympathetic blockade was increased in F, S, and FS versus C. The cardiac vagal tonus was reduced in F and FS animal groups. The intrinsic heart rate was decreased in the FS group (372 ± 9 bpm) compared with the C group (410 ± 13 bpm). The morphometric measurements evaluated through left ventricular diameter during diastole and the left ventricular diameter during systole decreased in the FS group (16 and 26%, respectively). Diastolic function was reduced in F and FS. The depressor response induced by losartan was increased in the F group in comparison with other groups. However, there was a uniform increase in plasma ACE activity in all treated groups compared with the C group. CONCLUSIONS: Data suggest that early exposure to high fructose intake produced marked alterations in metabolic and cardiovascular function. When stimulated by NaCl, the fructose-fed subjects showed further impairment in cardiac function.

Intermittent pneumatic compression versus additional prophylaxis with enoxaparin for prevention of venous thromboembolism after laparoscopic surgery for gastric and colorectal malignancies: multicentre randomized clinical trial.

BACKGROUND: The role of antithrombotic chemoprophylaxis in prevention of venous thromboembolism (VTE) in laparoscopic surgery for gastric and colorectal malignancies is unknown. This study compared the addition of enoxaparin following intermittent pneumatic compression (IPC) with IPC alone in patients undergoing laparoscopic surgery for gastrointestinal malignancy. METHODS: In this multicentre RCT, eligible patients were older than 40 years and had a WHO performance status of 0 or 1. Exclusion criteria were prescription of antiplatelet or anticoagulant drugs and history of VTE. Patients were allocated to IPC or to ICP with enoxaparin in a 1 : 1 ratio. Stratification factors included sex, location of cancer, age 61 years and over, and institution. Enoxaparin was administered on days 1-7 after surgery. Primary outcome was VTE, evaluated by multidetector CT on day 7. RESULTS: Of 448 patients randomized, 208 in the IPC group and 182 in the IPC with enoxaparin group were evaluated. VTE occurred in ten patients (4·8 per cent) in the IPC group and six (3·3 per cent) in the IPC with enoxaparin group (P = 0·453). Proximal deep vein thrombosis and/or pulmonary embolism occurred in seven patients (3·4 per cent) in the IPC group and one patient (0·5 per cent) in the IPC with enoxaparin group (P = 0·050). All VTE events were asymptomatic and non-fatal. Bleeding occurred in 11 of 202 patients in the IPC with enoxaparin group, and one patient needed a transfusion. All bleeding events were managed by discontinuation of the drug. CONCLUSION: IPC with enoxaparin after laparoscopic surgery for gastric and colorectal malignancies did not reduce the rate of VTE. Registration number: UMIN000011667 ( https://www.umin.ac.jp/).

ANTECEDENTES: El papel de la quimioprofilaxis para la prevención del tromboembolismo venoso (venous thromboembolism, VTE) en la cirugía laparoscópica de los tumores malignos gástricos y colorrectales se desconoce. El objetivo de este estudio fue comparar la quimioprofilaxis antitrombótica (enoxaparina) y la compresión neumática intermitente (intermittent pneumatic compression, IPC) en pacientes sometidos a cirugía laparoscópica de tumores malignos abdominales. MÉTODOS: Se efectuó un ensayo aleatorizado, controlado y multicéntrico de pacientes sometidos a cirugía laparoscópica de tumores gástricos y colorrectales en Japón. Los criterios de inclusión eran pacientes mayores de 40 años de edad y con un estado funcional de WHO de 0-1. Los criterios de exclusión fueron la prescripción al paciente de fármacos antiagregantes o anticoagulantes y la historia de VTE. Los pacientes fueron asignados a IPC y ICP con la adición de enoxaparina en una relación 1:1. Los factores de estratificación incluyeron el sexo, la localización del cáncer, la edad mayor o menor de 61 años, y la institución. La enoxaparina fue administrada en los días postoperatorios (postoperative day, POD) 1-7. El resultado primario fue la VTE evaluada mediante tomografía computarizada multidetector en el POD7. Los cálculos de la potencia determinaron que se requerían 184 pacientes en cada grupo. RESULTADOS: De los 448 pacientes aleatorizados, se evaluaron finalmente 208 pacientes en el grupo IPC y 182 pacientes en el grupo IPC más enoxaparina. La VTE ocurrió en 10 de 208 pacientes en el grupo IPC (4,8%) y 6 de 182 pacientes en el grupo IPC más enoxaparina (3,3%) (P = 0,45). La trombosis venosa profunda proximal (proximal deep vein thrombosis, DVT) y/o el embolismo pulmonar (pulmonary embolism, PE) ocurrieron en 7 de 208 pacientes en el grupo IPC (3,4%) y 1 de 182 pacientes en el grupo IPC más enoxaparina (0,55%) (riesgo relativo 0,163, i.c. del 95% 0,020-1,314, P = 0,0503). Todos los eventos de VTE fueron asintomáticos y no mortales. Se produjo una hemorragia en 11 de 202 pacientes en el grupo IPC con enoxaparina (5,4%, i.c. del 95% 3,1%-9,5%, P < 0,001), y un paciente precisó transfusión. Todos los eventos hemorrágicos pudieron ser tratados con la interrupción del fármaco. CONCLUSIÓN: La IPC con la adición de enoxaparina tras cirugía laparoscópica de los tumores malignos gástricos y colorrectales no disminuye la VTE.

Impact of technically qualified surgeons on laparoscopic colorectal resection outcomes: results of a propensity score-matching analysis.

BACKGROUND: The Endoscopic Surgical Skill Qualification System (ESSQS) was introduced in Japan to improve the quality of laparoscopic surgery. This cohort study investigated the short- and long-term postoperative outcomes of colorectal cancer laparoscopic procedures performed by or with qualified surgeons compared with outcomes for unqualified surgeons. METHODS: All laparoscopic colorectal resections performed from 2010 to 2013 in 11 Japanese hospitals were reviewed retrospectively. The procedures were categorized as performed by surgeons with or without the ESSQS qualification and patients' clinical, pathological and surgical features were used to match subgroups using propensity scoring. Outcome measures included postoperative and long-term results. RESULTS: Overall, 1428 procedures were analysed; 586 procedures were performed with ESSQS-qualified surgeons and 842 were done by ESSQS-unqualified surgeons. Upon matching, two cohorts of 426 patients were selected for comparison of short-term results. A prevalence of rectal resection (50·3 versus 40·5 per cent; P < 0·001) and shorter duration of surgery (230 versus 238 min; P = 0·045) was reported for the ESSQS group. Intraoperative and postoperative complication and reoperation rates were significantly lower in the ESSQS group than in the non-ESSQS group (1·2 versus 3·6 per cent, P = 0·014; 4·6 versus 7·5 per cent, P = 0·025; 1·9 versus 3·9 per cent, P = 0·023, respectively). These findings were confirmed after propensity score matching. Cox regression analysis found that non-attendance of ESSQS-qualified surgeons (hazard ratio 12·30, 95 per cent c.i. 1·28 to 119·10; P = 0·038) was independently associated with local recurrence in patients with stage II disease. CONCLUSION: Laparoscopic colorectal procedures performed with ESSQS-qualified surgeons showed improved postoperative results. Further studies are needed to investigate the impact of the qualification on long-term oncological outcomes.

ANTECEDENTES: El Sistema de Certificación de Habilidades Quirúrgicas Endoscópicas (Endoscopic Surgical Skill Qualification System, ESSQS) fue introducido en Japón para mejorar la calidad de la cirugía laparoscópica. En este estudio de cohortes se investigaron los resultados postoperatorios a corto y a largo plazo de las intervenciones laparoscópicas de cáncer colorrectal realizadas por o con la asistencia de cirujanos con certificación en comparación con cirujanos no certificados. MÉTODOS: Todas las resecciones colorrectales laparoscópicas realizadas entre 2010 y 2013 en 11 hospitales japoneses fueron revisadas retrospectivamente. Los procedimientos se clasificaron en función de si habían sido realizados por cirujanos con o sin certificación del ESSQS, y las características clínicas, patológicas y quirúrgicas de los pacientes se utilizaron para emparejar los subgrupos mediante puntuaciones de propensión. Las variables de resultado incluyeron los resultados postoperatorios y a largo plazo RESULTADOS: En total se analizaron 1.428 procedimientos, incluyendo 586 y 842 procedimientos realizados con y sin cirujanos certificados por ESSQS, respectivamente. Tras el emparejamiento, se seleccionaron dos cohortes de 426 pacientes para la comparación de resultados a corto plazo. Se observó una mayor prevalencia de resecciones rectales (50,3% versus 40,1%, P = 0,0001) y un tiempo quirúrgico más corto (230 versus 238 min, P = 0,04) en el grupo ESSQS. Las tasas de complicaciones intra- y postoperatorias y de reoperaciones fueron significativamente más bajas en el grupo ESSQS que en el grupo no ESSQS (1,2%, 4,6% y 1,9% versus 3,6%, 7,5% y 3,9%, P = 0,01; 0,03, y 0,02, respectivamente). Estos hallazgos se confirmaron tras el análisis de emparejamiento por puntaje de propensión. El análisis de regresión de Cox mostró que la no participación de cirujanos certificados con ESSQS (razón de oportunidades, odds ratio, OR 12,3; i.c. del 95%, 1,28-119,1; P = 0,03) se asoció independientemente con la recidiva local en los casos en estadio II. CONCLUSIÓN: Los procedimientos colorrectales laparoscópicos realizados por cirujanos certificados por ESSQS presentaron mejores resultados postoperatorios. Son necesarios más estudios para determinar el impacto de la certificación en los resultados oncológicos a largo plazo.

Reversal of angiogenesis in vitro, induction of apoptosis, and inhibition of AKT phosphorylation in endothelial cells by thromboxane A(2).

Thromboxane A(2) (TxA(2)) causes platelet aggregation, vasoconstriction, and inhibition of endothelial cell (EC) migration and prevents vascular tube formation via its specific receptors (TP), of which there are two isoforms (TPalpha and TPbeta), both expressed in human ECs. In this study, we demonstrate that the TxA(2) mimetic IBOP increases apoptosis of human ECs and inhibits the phosphorylation of Akt kinase, an intracellular mediator required for cell survival. Treatment with IBOP destroyed EC networks formed on a basement membrane matrix in vitro. To distinguish the role of the TP isoforms, each isoform was expressed in TP-null ECs to create TPalpha and TPbeta ECs. IBOP induced apoptosis and inhibited phosphorylation of Akt kinase in both TPalpha and TPbeta. IBOP increased cAMP levels in TPalpha but not in TPbeta. Apoptosis induced by IBOP in TPalpha was not affected by either the adenylyl cyclase activator forskolin or the protein kinase A inhibitor 14-22 amide or H-89, whereas that in TPbeta was suppressed by forskolin and enhanced by the protein kinase A inhibitor 14-22 amide or H-89, suggesting that the TP isoforms differ in their signal pathways in mediating apoptosis. In conclusion, apoptosis may be the mechanism by which TxA(2)-mediated destruction of vascular structures in ECs occurs; although both TP isoforms induce apoptosis, possibly via inhibiting Akt phosphorylation, the signaling differs in each isoform, in that activation of the adenylyl cyclase pathway prevents apoptosis caused by TPbeta, but not by TPalpha, stimulation.

Downregulation of protein kinase cdelta activity enhances endothelial cell adaptation to hypoxia.

BACKGROUND: Although protein kinase C (PKC) has been implicated in ischemic cell death, the role of individual PKC isoenzymes in the response of endothelial cells (ECs) to hypoxia is unknown. METHODS AND RESULTS: To test the effect of hypoxia on the activity of individual PKC isoenzymes, human ECs were exposed to 95% N(2) with 5% CO(2) for 24 hours. This severe hypoxia reduced PKCdelta specific activity in both human umbilical vein ECs (HUVECs) and a HUVEC-derived EC line (ECVs) significantly (80.5+/-5.7% and 55.5+/-8. 6% of normoxia controls, respectively); the activities of PKCalpha and PKCepsilon were unchanged. The protein levels of PKCalpha, PKCdelta, and PKCepsilon were unchanged by hypoxia. To determine whether PKCdelta downregulation by hypoxia was linked to EC function, ECVs in which PKCdelta was stably overexpressed (PKCdelta-ECs) were exposed to hypoxia. A significant increase in cell death was observed in PKCdelta-ECs compared with controls (5.8+/-0.6% versus 2. 3+/-0.4% at 24 hours, 13.2+/-1.2% versus 4.1+/-0.4% at 48 hours, P<0. 05) during hypoxia. Neither the DNA laddering assay nor TUNEL staining revealed an increase in apoptosis of PKCdelta-ECs exposed to hypoxia, suggesting a hypoxia-induced increase in nonapoptotic cell death of PKCdelta-ECs. Inhibition of NO synthase with N(G)-monomethyl-L-arginine (L-NMMA) affected neither the decline in PKCdelta activity nor the EC death induced by hypoxia. CONCLUSIONS: PKCdelta activity is decreased by hypoxia by a mechanism that does not involve NO synthase; this downregulation appears to enhance EC survival during hypoxia by decreasing nonapoptotic cell death.

on the extracellular sheath of dermal melanocytes in nevus fusco-ceruleus acromiodeltoideus (Ito) and Mongolian spot. An ultrastructural study.

The dermal melanocytes in the lesions of nevus of Ito and Mongolian spot were shown to possess the extracellular sheath composed of both fine filaments and granules (2-5 nm in diameter). In the case of nevus of Ito, the granular component appeared to predominate in the shealth, which measured up to 3 micrometers in width and was estimated to cover about 97% of the total surface of dermal melanocytes. No ultrastructural changes were appreciable on the melanocyte shealth in nevus of Ito according to the difference in the age of patients (39 and 64 years), or in the lasting period of the dermal melanocytosis. By contrast, the melanocyte sheath in the case of Mongolian spot was much less developed than in nevus of Ito, predominantly filamentous in texture, and showed a marked decline with advance of the age of infants (from 2 mo to 6 yr). Many of the dermal melanocytes in Mongolian spot showed a partial disruption of their cytolemma, resulting in discharges of melanosomes free into the connective tissue matrix. Significance of these findings was discussed in relation to the differtial fate of melanocytes within the human dermis.

A novel hydroxyl radical scavenger, nicaraven, protects the liver from warm ischemia and reperfusion injury.

BACKGROUND: Reactive oxygen species have been considered to be involved in liver injury at the procurement, preservation, and transplantation from donors without beating hearts. A novel hydroxyl radical scavenger, nicaraven with hydrophilic and lipophilic properties, infiltrates both intracellular and extracellular spaces where it effectively scavenges reactive oxygen species. Protection by nicaraven against ischemia and reperfusion damage of the brain, heart, and kidneys has been shown. The effect of this agent on the liver remains unclear. METHODS: Two-hour total hepatic vascular exclusion was used. Eighteen beagle dogs were randomly assigned to 2 groups: 12 animals were not treated (group I) and 6 were treated with nicaraven (group II). Nicaraven was administered intravenously (2mg/kg/min) for 60 minutes before ischemia and for 3 hours, starting 30 minutes before reperfusion. RESULTS: Two-week survival rates were 25% in group I and 100% in group II (P <.01). Nicaraven inhibited lipid peroxidation in the liver, improved hepatic and systemic hemodynamics and energy metabolism, and suppressed liver enzyme release, endothelin-1 elevation in hepatic venous blood, histologic damage, and neutrophil infiltration into the liver. CONCLUSIONS: Nicaraven exerted hepatic protection against warm ischemia and reperfusion injury. This may indicate nicaraven as a potential candidate to attenuate liver injury from warm ischemia and preservation in transplantation from donors without beating hearts.

Schwann cell basal lamina and nerve regeneration.

Nerve segments approximately 7 mm long were excised from the predegenerated sciatic nerves of mice, and treated 5 times by repetitive freezing and thawing to kill the Schwann cells. Such treated nerve segments were grafted into the original places so as to be in contact with the proximal stumps. The animals were sacrificed 1, 2, 3, 5, 7 and 10 days after the grafting. The grafts were examined by electron microscopy in the middle part of the graft, i.e. 3-4 mm distal to the proximal end and/or near the proximal and distal ends of the graft. In other instances, the predegenerated nerve segments were minced with a razor blade after repetitive freezing and thawing. Such minced nerves were placed in contact with the proximal stumps of the same nerves. The animals were sacrificed 10 days after the grafting. Within 1-2 days after grafting, the dead Schwann cells had disintegrated into fragments. They were then gradually phagocytosed by macrophages. The basal laminae of Schwann cells, which were not attacked by macrophages, remained as empty tubes (basal lamina scaffolds). In the grafts we examined, no Schwann cells survived the freezing and thawing process. The regenerating axons always grew out through such basal lamina scaffolds, being in contact with the inner surface of the basal lamina (i.e. the side originally facing the Schwann cell plasma membrane). No axons were found outside of the scaffolds. One to two days after grafting, the regenerating axons were not associated with Schwann cells, but after 5-7 days they were accompanied by Schwann cells which were presumed to be migrating along axons from the proximal stumps. Ten days after grafting, proliferating Schwann cells observed in the middle part of the grafts had begun to sort out axons. In the grafts of minced nerves, the fragmented basal laminae of the Schwann cells re-arranged themselves into thicker strands or small aggregations of basal laminae. The regenerating axons, without exception, attached to one side of such modified basal laminae. Collagen fibrils were in contact with the other side, indicating that these modified basal laminae had the same polarity in terms of cell attachment as seen in the ordinary basal laminae of the scaffolds.(ABSTRACT TRUNCATED AT 400 WORDS)

Distribution of anionic sites on the basal lamina of Schwann cells.

Basal laminae (BL) were separated from Schwann cells of rat sciatic nerves by means of weak sonication, and the anionic sites of the BL were demonstrated by using cationized ferritin (CF) or ruthenium red (RR). CF particles were deposited in clusters at intervals of 100-150 nm on the interstitial side of the BL facing the connective tissue, while the cellular side facing the Schwann cell plasmalemma showed only an occasional deposition of CF particles. RR-positive sites were found only on the interstitial side with a pattern of distribution comparable to that of CF-binding sites. These results indicate that the patterns of anionic site distribution are different between the inner and outer surfaces of the Schwann cell BL.

Blockade of ATP-sensitive K+ channels attenuates preconditioning effect on myocardial metabolism in swine: myocardial metabolism and ATP-sensitive K+ channels.

OBJECTIVE: We investigated if blockade of ATP-sensitive K+ channels (KATP) abolishes the protective effect of ischemic preconditioning (IP) on myocardial metabolism and ischemia-induced reactive hyperemia (RH) in pigs. METHODS: IP was elicited by a single cycle of 5 min occlusion and 5 min reperfusion of coronary artery, followed by 15 min of test ischemia and 120 min of reperfusion. Vehicle or the ATP-sensitive K+ channels (KATP) blocker, glibenclamide (3 or 6 mg/kg; G3 or G6) was administered before IP (groups; IP, G3+IP, G6+IP). As respective controls, the same treatment was performed in groups without IP (groups; C, G3, G6). Tissue levels of ATP, creatine phosphate (CP) and intracellular pH (pHi) in the area at risk were measured by 31P-nuclear magnetic resonance spectroscopy. RH after 5 min of preconditioning ischemia was assessed by regional myocardial blood flow. RESULTS: ATP and pHi were preserved after 15 min of ischemia in the IP group [C/IP; ATP=57+/-4/76+/-10% of baseline, pHi=6.18+/-0.08/6.66+/-0.03, P<0.05, C vs. IP]. Both doses of glibenclamide completely abolished the ATP sparing effect of IP. The high dose completely abolished pHi preservation (G6+IP=6.33+/-0.06), while the low dose showed only a partial effect (G3+IP=6.48+/-0.03). Glibenclamide did not adversely affect myocardial metabolism in groups without IP. Glibenclamide attenuated RH after 5 min of ischemia by 30% in both subendocardium and subepicardium. CONCLUSIONS: Blockade of KATP abolished the preconditioning effect on myocardial metabolism, and partially attenuated post-ischemic reactive hyperemia in pigs. These results indicate that KATP activation might be involved in the mechanisms of these phenomena, reactive hyperemia is not sufficient to induce IP protection.

Localization of alkaline phosphatase activity of the small intestinal microvilli in various vertebrates from mammalia to fishes.

The localization of alkaline phosphatase activity in the small intestinal microvilli of the duodenum, jejunum, and ileum in various mammalia, birds, reptilia, amphibia and fishes has been investigated and compared both by light and by electron microscopes. When the incubating medium is intravitally perfused into the small intestine of living animals, deposition of azo-dye is found on the microvilli in the epithelium. Enzyme activity in the duodenal epithelium is strong in all 14 species. No appreciable differences in phosphatase activity are found among the species. In the birds and mammalia except rat, the microvilli of the jejunal and ileal epithelium shows strong alkaline phosphatase activity. In the amphibia and fishes, the jejunal epithelium of the striated border shows weak phosphatase activity. Ileal epithelium of the reptilia, amphibia and fishes shows weak or trace activity. In the glutaraldehyde-fixed material, the phosphatase activity of the duodenum in mammalia is similar in activity to that found in the intravitally perfused animal. But no azo-dye deposit can be seen on the microvilli in the jejunum of amphibia and fishes, nor the ileum of reptilia, amphibia and fishes. Furthermore, the effect of EDTA-inhibition for alkaline phosphatase in the small intestinal surface was also viewed in glutaraldehyde-fixed sections.

[Polycythemia vera with der(15) and der(20) associated with remarkable neutrophilia].

An autopsy case of polycythemia vera with der(15) and der(20) associated with remarkable neutrophilia was reported. A 87-year-old man was diagnosed as polycythemia vera in August 1987. The red blood cell count was 621 x 10(4)/microliters, Ht 58.5% and the white blood cell count 45,400/microliters with 92% neutrophils. The splenomegaly, increased red blood cell volume and the low erythropoietin level were present. The arterial SaO2 value was above 92%. The chromosome analysis of bone marrow cells revealed 46, XY, -15, -20, +der(15)t(15;?)(q13-15;?), +der(20)t(20;?)(q11;?). The breakpoint in No. 20 was in q11. The remarkable leukocytosis with relative and absolute neutrophilia were observed. Particularly late in the clinical course the white blood cell count was 92,900/microliters with 99% neutrophils. The Ph1 chromosome was negative and the bcr rearrangement was not detected. He died of bronchopneumonia in January 1989. At the autopsy findings neither the marrow fibrosis nor the extramedullary leukemic cell infiltration was noticed.

Tonotopic-column-dependent variability of neural encoding in the auditory cortex of rats.

Neural computation could benefit from the heterogeneity of neurons to achieve energy efficiency. Beyond a single neuron level, adaptation to biologically important signals should also make functional columns heterogeneous. In the present study, we test a hypothesis that variability of neural response depends on tonotopic columns in the primary auditory cortex (A1) of rats. Mutual information (MI) was estimated from multi-unit responses in A1 of anesthetized rats, to quantify how spike count (SC) and the first spike latency (FSL) carried information about frequency and intensity of test tones. Consequently, for both SC and FSL, we found best frequency (BF)-dependent MI distributions with wide variances in high BF regions. These MI distributions were caused by BF-dependence of the amount of information that neurons conveyed, i.e., total entropy, rather than the transmission efficiency. In addition, the relationship between the transmission efficiency and the total entropy differentiated SC encoding and FSL encoding, suggesting that SC encoding and FSL encoding are not redundant but each plays a different role in intensity encoding. These results provide compelling evidence that BF columns are heterogeneous. Such heterogeneity of columns may make the global computation in A1 more efficient. Thus, the efficient coding in the neural system could be achieved by multiple-scale heterogeneity.

Learning-stage-dependent, field-specific, map plasticity in the rat auditory cortex during appetitive operant conditioning.

Cortical reorganizations during acquisition of motor skills and experience-dependent recovery after deafferentation consist of several distinct phases, in which expansion of receptive fields is followed by the shrinkage and use-dependent refinement. In perceptual learning, however, such non-monotonic, stage-dependent plasticity remains elusive in the sensory cortex. In the present study, microelectrode mapping characterized plasticity in the rat auditory cortex, including primary, anterior, and ventral/suprarhinal auditory fields (A1, AAF, and VAF/SRAF), at the early and late stages of appetitive operant conditioning. We first demonstrate that most plasticity at the early stage was tentative, and that long-lasting plasticity after extended training was able to be categorized into either early- or late-stage-dominant plasticity. Second, training-induced plasticity occurred both locally and globally with a specific temporal order. Conditioned-stimulus (CS) frequency used in the task tended to be locally over-represented in AAF at the early stage and in VAF/SRAF at the late stage. The behavioral relevance of neural responses suggests that the local plasticity also occurred in A1 at the early stage. In parallel, the tone-responsive area globally shrank at the late stage independently of CS frequency, and this shrinkage was also correlated with the behavioral improvements. Thus, the stage-dependent plasticity may commonly underlie cortical reorganization in the perceptual learning, yet the interactions of local and global plasticity have led to more complicated reorganization than previously thought. Field-specific plasticity has important implications for how each field subserves in the learning; for example, consistent with recent notions, A1 should construct filters to better identify auditory objects at the early stage, while VAF/SRAF contribute to hierarchical computation and storage at the late stage.