Addition formulae for Abelian functions associated with specialized curves.

We discuss a family of multi-term addition formulae for Weierstrass functions on specialized curves of low genus with many automorphisms, concentrating mostly on the case of genus 1 and 2. In the genus 1 case, we give addition formulae for the equianharmonic and lemniscate cases, and in genus 2 we find some new addition formulae for a number of curves.

Trajectory and terminal distribution of single centrifugal axons from olfactory cortical areas in the rat olfactory bulb.

The olfactory bulb receives a large number of centrifugal fibers whose functions remain unclear. To gain insight into the function of the bulbar centrifugal system, the morphology of individual centrifugal axons from olfactory cortical areas was examined in detail. An anterograde tracer, Phaseolus vulgaris leucoagglutinin, was injected into rat olfactory cortical areas, including the pars lateralis of the anterior olfactory nucleus (lAON) and the anterior part of the piriform cortex (aPC). Reconstruction from serial sections revealed that the extrabulbar segments of centrifugal axons from the lAON and those from the aPC had distinct trajectories: the former tended to innervate the pars externa of the AON before entering the olfactory bulb, while the latter had extrabulbar collaterals that extended to a variety of targets. In contrast to the extrabulbar segments, no clear differences were found between the intrabulbar segments of axons from the lAON and from the aPC. The intrabulbar segments of centrifugal axons were mainly found in the granule cell layer but a few axons extended into the external plexiform and glomerular layer. Approximately 40% of centrifugal axons innervated both the medial and lateral aspects of the olfactory bulb. The number of boutons found on single intrabulbar segments was typically less than 1000. Boutons tended to aggregate and form complex terminal tufts with short axonal branches. Terminal tufts, no more than 10 in single axons from ipsilateral cortical areas, were localized to the granule cell layer with varying intervals; some tufts formed patchy clusters and others were scattered over areas that extended for a few millimeters. The patchy, widespread distribution of terminals suggests that the centrifugal axons are able to couple the activity of specific subsets of bulbar neurons even when the subsets are spatially separated.

Therapeutic effect of balloon-occluded retrograde transvenous obliteration for gastric varices in relation to haemodynamics in the short gastric vein.

The aim of this study was to elucidate the relationship between the therapeutic effect of balloon-occluded retrograde transvenous obliteration (B-RTO) and haemodynamic features in the short gastric vein (SGV) in patients with gastric fundal varices (GV). The subjects in this retrospective cohort study comprised 34 patients who had moderate- or large-grade GV with the SGV both on retrograde venography and Doppler ultrasound. The diameter, flow velocity and flow volume in the SGV measured by Doppler ultrasound before B-RTO with 1 h balloon occlusion were compared with the therapeutic effect. Embolisation of GV was achieved in 30/34 patients (88.2%): 27 by initial B-RTO and 3 by second B-RTO. Flow velocity and flow volume in the SGV before B-RTO were significantly lower in the 27 patients with a complete effect on initial B-RTO (7.19+/-2.44 cm s(-1), p = 0.0246; 189.52+/-167.66 ml min(-1), p = 0.002) than in the 7 patients with an incomplete effect (10.41+/-5.44 cm s(-1), 492.14+/-344.94 ml min(-1)). Neither endoscopy nor contrast-enhanced CT had recurrent findings of GV in the subject during the follow-up period (94-1440 days; mean, 487.2+/-480.5 days). In conclusion, haemodynamic evaluation of the SGV using Doppler ultrasound may be useful for the prediction of the therapeutic effect of B-RTO.

Application of percutaneous ultrasound-guided treatment for ultrasonically invisible hypervascular hepatocellular carcinoma using microbubble contrast agent.

AIM: To evaluate the efficacy of contrast-enhanced ultrasound for the localization of ultrasonically invisible hypervascular lesions in the liver to facilitate percutaneous ultrasound-guided treatment. MATERIALS AND METHODS: Forty patients with 47 ultrasonically invisible hypervascular lesions (5-20mm) diagnosed on contrast-enhanced computed tomography were enrolled in the retrospective study. Contrast-enhanced ultrasound (CEUS) with Levovist was performed to localize the lesions both in the early phase and liver-specific phase. Diagnosis of was confirmed by percutaneous needle biopsy where feasible, and on the basis of on treatment outcomes or changes in computed tomography findings in those not amenable to biopsy. RESULTS: Thirty-two lesions were diagnosed as hepatocellular carcinoma (HCC). Contrast-enhanced ultrasound localized hepatocellular carcinoma in 24/32 (75%) lesions, the mean diameter (15.1+/-4.9mm), as measured using computed tomography, being significantly larger than that of the remaining eight lesions (10.5+/-2.1mm). Ultrasound-guided treatment was performed in 19 of the 24 lesions, and transarterial chemoembolization (TACE) was applied for the other five lesions because of difficult percutaneous access. Five of the eight non-visualised lesions were treated by transarterial chemoembolization, and the other three by surgical resection. The beneficial effect of CEUS was significantly greater when the reason for poor initial visualisation was the coarse liver architecture (17/17) than when it was due to adverse location (seven of 15, p<0.005). Fifteen of the CT-detected hypervascular lesions were considered to represent false positives for HCC, based on their behaviour during follow-up. CONCLUSION: Contrast-enhanced ultrasound with Levovist facilitates the application of percutaneous ultrasound-guided treatment by improving localization of ultrasonically invisible hypervascular hepatocellular carcinomas in the liver.

Tonsillectomy in the treatment of pediatric Henoch-Schönlein nephritis.

The exact pathophysiology of HSN remains to be elucidated. Hence, a therapeutic strategy that enables curative treatments for all the various grades of HSN patients has yet to be established. We report our experience performing tonsillectomy combined with steroid therapy for 16 pediatric proteinuric Henoch-Schönlein nephritis (HSN) patients. All patients exhibited hematuria and proteinuria in their first HSN attack with the mean age of onset 7.7 years (range 4.75 - 13.9 years). Nine patients were diagnosed with clinically severe HSN presenting with massive proteinuria (> 1 g/m(2)/day). Renal biopsy findings performed in 6 patients were Grade II (3), Grade III (2) and Grade IV (1) according to the International Study of Kidney Diseases in childhood classification. Tonsillectomy was performed after 1-4 cycles of methylprednisolone pulses during oral prednisolone (0.5 - 1.5 mg/kg/day) therapy. In 2 patients, oral cyclophosphamide therapy was added before the tonsillectomy. The interval between the onset of HSN and tonsillectomy was 97.4 +/- 24.5 days (range 27 424 days). In all patients, proteinuria had disappeared by 6 months after the tonsillectomy and the urine findings had normalized. The interval between therapy initiation and complete remission was 9.6 +/- 2.0 months (range 2 - 26 months). Over follow-up periods of 4.9 +/- 0.6 years (range 2.2 - 9.3 years), no recurrences of Henoch-Schonlein purpura or HSN were observed. There was a significant correlation between early tonsillectomy performance and decreased time until normalization of the urine findings, indicating that the tonsils may have pivotal roles in the initiation and progression of HSN. Their elimination might promote the reversal of nephritis. Although this study is retrospective, we suggested that tonsillectomy at an early stage of HSN may be beneficial by shortening the period of illness and contributing to clinical recovery. Randomized controlled trials will be needed to confirm this supposition.

Real-time blood-pool images of contrast enhanced ultrasound with Definity in the detection of tumour nodules in the liver.

Lower mechanical index (MI) technique with newer microbubble agents has been introduced into clinical practice as a newer ultrasound (US) imaging. However, the efficacy in detecting tumour nodules has not been proven scientifically. The aim of this study was to elucidate the efficacy of a blood-pool image of real-time contrast-enhanced US under low MI in detecting liver tumours. 15 rabbits with VX-2 tumour were used; the number of implantations was none in two rabbits, one in four, two in five and three in four. US equipment was APLIO (Toshiba) with linear probe (3.5/7.0 MHz). The number, location and size of tumour nodules were examined by non-contrast tissue harmonic imaging (NC-US) or contrast-enhanced pulse subtraction harmonic imaging (C-US) under extra-low MI (MI 0.065) with the injection of Definity (30 microl kg(-1)). The number of tumour nodules detected by both NC-US and C-US were consistent with the histopathological results in five rabbits - two with none, two with one nodule and one with two nodules. In the other 10 rabbits, C-US showed all the implanted tumours and small daughter nodules around them that were confirmed by histopathology. However, NC-US failed to demonstrate two implanted nodules and all the daughter nodules. On the basis of the histopathological results, detectability of implanted tumour was not significantly different between NC-US (24/26, 92.3%) and C-US (26/26, 100%). However C-US was superior to NC-US in delineating the nodules and in detecting small daughter nodules. The sizes of the implanted tumour nodules measured by histopathology correlated closely with those measured by C-US. Real-time blood-pool images by pulse subtraction harmonic imaging under extra-low MI with Definity will contribute to the improvement of the ultrasound delineation and detection of liver tumours.

Brain-derived neurotrophic factor induces rapid morphological changes in dendritic spines of olfactory bulb granule cells in cultured slices through the modulation of glutamatergic signaling.

While the acute physiological effects of brain-derived neurotrophic factor (BDNF) have been well demonstrated, little is known regarding possible morphological effects that occur within a short period of time. The acute effects of BDNF on dendritic spine morphology were examined in granule cells in cultured main olfactory bulb slices. Organotypic slices prepared from 7-day-old rats were cultured for 1 day, and BDNF was applied at varying time points prior to fixation. Granule cell dendrites were labeled with a membrane dye and observed with a confocal laser scanning microscope. The addition of BDNF into the culture medium 6 h before fixation decreased the mean diameter of the dendritic processes (filopodia/spines), but the length and density of the processes were not affected. Both filopodia/spines in the external plexiform layer and those in the granule cell layer exhibited similar changes. Considering the slow penetration into the slices, BDNF was then applied to the top of each slice. When applied 1 h before fixation, 5 ng and 0.5 ng of BDNF induced the same changes in the external plexiform layer and the granule cell layer, respectively. The changes became detectable as early as 30 min when 50 ng of BDNF was applied. The pretreatment with tetanus toxin or an N-methyl-D-aspartate receptor antagonist abolished the acute effects of BDNF on spine morphology. These results indicate that BDNF can alter spine morphology within a shorter period of time than previously observed and that the effects are mediated by enhanced glutamatergic signaling.

Eosinophils are activated in middle ear mucosa and middle ear effusion of patients with intractable otitis media associated with bronchial asthma.

BACKGROUND: Although patients with intractable otitis media associated with bronchial asthma have extensive accumulation of eosinophils in the middle ear mucosa and middle ear effusion, systematic histological and immunohistochemical studies have not been performed. OBJECTIVES: To clarify the pathogenesis of middle ear diseases, we carried out immunohistochemical studies on middle ear specimens, particularly focusing on the characteristics of accumulated eosinophils. METHODS: Middle ear specimens obtained from eight adult patients and from 17 controls were immunohistochemically stained using monoclonal antibodies against EG1, EG2, mast cell tryptase, IgA and IgE. The concentration of eosinophil cationic protein (ECP) in middle ear effusion samples was also measured. RESULTS: In the asthmatic patients, severe round-cell infiltration was observed in the submucosa and most of the EG1-positive cells were also EG2-positive. In the control patients, the mucosa showed a fibrotic change with a few inflammatory cells, and EG1- or EG2-positive cells were quite few. The expression of IgE was found not only on the surface of mast cells but also within the plasma cells in the asthmatic patients, and the number of IgE-positive cells was about twice as high as that of mast cells. A significantly higher concentration of ECP was noted in middle ear effusion obtained from the asthmatic patients than that from the control patients. CONCLUSION: Most of the eosinophils in the middle ear mucosa and middle ear effusion were activated, resulting in degranulation and release of ECP, and local IgE production occurs in the middle ear mucosa, indicating that the intractable inflammation is closely associated with IgE-mediated late phase response with eosinophil accumulation.

Hemodynamics in the left gastric vein after endoscopic ligation of esophageal varices combined with sclerotherapy.

BACKGROUND AND METHODS: We examined the changes in portal hemodynamics after endoscopic variceal ligation (EVL) combined with endoscopic injection sclerotherapy (EIS) in relation to post-treatment relapse. The present study included 93 patients who underwent EVL-EIS combination therapy. Portal hemodynamics were examined by Doppler ultrasonography and percutaneous transhepatic portography (PTP). RESULTS: Therapy with EVL-EIS resulted in the complete disappearance of varices in 89 of 93 patients. Cumulative relapse-free rates (Kaplan-Meier method) were 75.8 and 50.2%, respectively, 1 and 3-5 years after treatment. At the end of treatment, the flow in the left gastric vein was examined by Doppler ultrasonography. In 50 of 63 patients, the flow remained hepatofugal. In 23 of these patients, PTP was performed at the end of treatment; selective left gastric venography did not reveal any palisade zone vessels or varices. However, fine blood vessels were seen around the lower esophagus in nine patients, only the paraesophageal vein was found in 10 patients and these two findings were present in four patients, indicating that collateral blood flow remained in the lower esophagus in 13 of 23 patients. These findings suggest that frequent relapse of varices results from insufficient blockage of blood flow from the left gastric vein to the lower esophagus. However, in patients with a patent paraesophageal vein, long-term effects obtained by EVL-EIS combination therapy were satisfactory. CONCLUSIONS: The pattern of the development of collateral left gastric veins represents important hemodynamic changes that predict the long-term prognosis of patients after treatment.

Arterio-portal shunt in liver rescued by hepatectomy after arterial embolization.

Arterio-portal shunts are generally treated with transcatheter arterial embolization, as a therapeutic measure for bleeding of esophageal varices. However, transcatheter arterial embolization is frequently associated with reestablishment of arterio-portal shunts. We now report our experience with partial hepatectomy to remove the arterio-portal shunt associated with esophageal varices, which recurred after transcatheter arterial embolization. The patient was a 60-year-old female, who had massive hematemesis caused by rupture of esophageal varices. Doppler sonography and arteriography demonstrated an arterio-portal shunt in the right anterior superior segment of the liver. Temporary hemostasis was achieved with transcatheter arterial embolization, however, hemorrhage recurred one month later. The second transcatheter arterial embolization failed to manage the shunt and varices. The patient developed hepatic coma. After recovery from coma, she was referred to our hospital. We carried out partial hepatectomy, which provided remarkable hemodynamic improvement; the portal vein flow changed from hepatofugal to hepatopetal. Esophageal varices and hepatic coma have totally disappeared. This patient has had no complaint and has remained free of esophageal varices, for 3 years postoperatively. She is having a normal life. The partial hepatectomy to remove the arterio-portal shunt induced complete resolution of the arterio-portal shunt, as well as dramatic improvement in portal flow and hepatic coma. Our experience in the present case suggests that partial hepatectomy should be considered as a radical therapy for arterio-portal shunt, without insistence on transcatheter arterial embolization.

EUS changes predictive for recurrence of esophageal varices in patients treated by combined endoscopic ligation and sclerotherapy.

BACKGROUND: Recurrence of varices is still common after endoscopic treatment of esophageal varices. In this study, predictive signs of variceal recurrence were investigated by ultrasonic (US) miniature probe in patients treated by combined endoscopic ligation and sclerotherapy. METHODS: Detectability of vessels by US miniature probe was evaluated first in rats. In 41 patients treated by combined therapy, the esophagus and the cardia region were examined by US miniature probe. In 25 patients examined by percutaneous transhepatic portography, the relationship between US miniature probe and percutaneous transhepatic portography findings was evaluated. RESULTS: The smallest vessel detected by US miniature probe was 0.3 mm in diameter in the study using intra-abdominal vessels of rat. After variceal eradication, US miniature probe showed intramural vessels in the cardia that were classified as follows: grade I, a few vessels (19 patients, 46%); grade II, uniformly scattered vessels (11, 27%); grade III, abundant vessels resembling a honeycomb (11, 27%). As the sonographic grade increased, the rate of variceal recurrence increased. As the venographic grade of staining in the distal esophagus increased, the esophageal wall became thicker and the sonographic grade at the cardia increased. CONCLUSIONS: Endosonographic evaluation of the distal esophagus and cardia is predictive of variceal recurrence.

Inactivation of a hepadnavirus by electrolysed acid water.

Glutaraldehyde is used as a disinfectant for endoscopes, but is an irritant and so should be replaced by an alternative. Electrolysed acid water (EAW) has a bactericidal effect, and an endoscopic washing device using EAW has been developed in Japan. To investigate the effect of EAW on the infectivity of viruses, we treated duck hepatitis B virus (DHBV), which has similar properties to hepatitis B virus, with EAW, and determined the number of remaining infectious virus particles in a bioassay system. One-day-old Pekin ducks were inoculated with duck serum containing 10(5.5) ID(50) DHBV; the serum had previously been incubated with 100 volumes of EAW or ion-exchanged water at room temperature for 7 min. DHBV infection was indicated by detection of viral DNA in duck serum samples 1-8 weeks after inoculation. Treatment of serum with EAW diminished DHBV infectivity whereas treatment with ion-exchanged water did not. The virus load was estimated to have been reduced to 10(1)-10(3) ID(50) during the first 1 min and to <10(0.5) ID(50) in the next 6 min of incubation when compared with the control. Thus, EAW directly inactivates DHBV and its clinical application is recommended.

Differentiation of mitral cell dendrites in the developing main olfactory bulbs of normal and naris-occluded rats.

The morphological differentiation of mitral cell dendrites during embryonic and early postnatal development was examined in the main olfactory bulb of rats to determine a possible role of afferent activity in the development of the dendrites. Mitral cells and olfactory nerve fibers were labeled with 1,1'-dioctadecyl-3,3,3', 3'-tetramethylindocarbocyanine perchlorate (DiI) and fluorescein-conjugated lectin (Ulex europeus agglutinin-I), respectively. Morphogenesis of mitral cell dendrites proceeded as previously described (Malun and Brunjes [1996] J. Comp. Neurol. 368:1-16); that is, undifferentiated dendrites with radial orientation were transformed into a single primary dendrite having a glomerular tuft and secondary dendrites extending tangentially into the external plexiform layer. Quantitative examinations in both pre- and postnatal rats revealed that the differentiation of primary dendrites, including tuft formation, increases in diameter and decreases in branching, started before birth, whereas differentiated secondary dendrites were only observed in postnatal animals. Mitral cells with more than two primary dendrites were found after embryonic day 21. The proportion of the mitral cells with differentiated dendrites increased postnatally. At postnatal day 10, almost all mitral cells had fully differentiated dendrites, and mitral cells with multiple primary dendrites were no longer seen. No significant change was found during development in the number of stem dendrites that arose directly from the cell body. Unilateral naris occlusion started on postnatal day 1 retarded differentiation of primary and secondary dendrites, and increased the proportion of mitral cells with multiple primary dendrites. These finding revealed that differentiation of mitral cell primary dendrites precedes that of secondary dendrites, and suggested that the differentiation of secondary dendrites proceeds in an activity-dependent manner.

Enhanced color flow images in small hepatocellular carcinoma.

BACKGROUND: Features of enhanced color flow images in small hepatocellular carcinoma (HCC) are not fully elucidated. The purpose of this study was to clarify the characteristic vascular images in small HCC observed by enhanced color Doppler. METHODS: Enhanced color Doppler using the contrast agent Levovist was performed on 13 patients with HCC smaller than 30 mm. Enhanced color flow appearance was compared with angiographic findings. Time-intensity changes after injection of the contrast agent were analyzed in HCC nodules. RESULTS: Significant improvement in the detection of color flow signals was obtained in small HCC using Levovist, from 33% in precontrast to 92% in postcontrast (p < 0.005). Three patterns of enhanced color flow images, which were related to the angiographic findings, were observed. The time-intensity curve was classified into two types by "time to peak" and "time on plateau" and was associated with the patterns of enhanced images. CONCLUSION: Enhanced color flow imaging promises to be a useful method for evaluating tumor vascularity noninvasively and to contribute to the elucidation of the hemodynamics in small HCC.

Grey-scale contrast enhancement in rabbit liver with DMP115 at different acoustic power levels.

The contrast enhancement effect of ultrasound (US) contrast agent DMP-115 (YM454, Definity) in rabbit liver at two acoustic transmit power levels was studied. A total of 12 rabbits with healthy livers and 7 rabbits with VX-2 tumors were used. Grey-scale ultrasonograms in both fundamental (3.75 MHz) and harmonic (2.5/5.0 MHz) imaging modes were performed at a frame rate of 26 Hz under baseline acoustic power (MI = 0.6) or lower acoustic power (MI = 0.2). The contrast enhancement depended on the contrast agent dose and the acoustic power. The video intensity change was higher in the portal vein under the baseline acoustic power and higher in the liver parenchyma under the lower acoustic power. The contrast-enhanced US observation of the VX-2 tumor in the arterial phase correlated well with the angiographic and histopathological appearance of the tumor. In the parenchymal phase, the borderline of the tumor could be clearly delineated from the surrounding liver parenchyma. Continuous fundamental and harmonic grey-scale imaging with DMP115 has the capability of making peripheral circulation images of liver parenchyma and tumors.

GABAergic neuron-to-astrocyte signaling regulates dendritic branching in coculture.

Effects of neurotransmitters on dendritic morphology were analyzed in cocultures of neurons and astrocytes from the neonatal rat olfactory bulb by means of immunocytochemical staining and morphometry. About 70% of the neurons gamma-aminobutyric acid (GABA)-immunoreactive on day 7 of the coculture. Morphometric analysis of neurons having no contact with other neurons revealed that incubation of the coculture with either a sodium channel blocker, tetrodotoxin, or GABAA receptor antagonists such as bicuculline or picrotoxin resulted in a decreased number of dendritic branch points as compared to neurons in control cultures, while the same treatment did not affect radial dendritic outgrowth or the number of primary dendrites. Application of a GABAB receptor antagonist, phaclofen, or an AMPA-type glutamate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione, had no detectable effect on dendritic morphology. Incubation of the coculture with a GABAA receptor agonist, muscimol, enhanced branching and reversed the inhibitory effect of tetrodotoxin. Branching was also enhanced by increasing extracellular K+. The inhibitory effect of tetrodotoxin or bicuculline and the stimulatory effect of muscimol or elevated K+ were abolished when neurons were grown on a monolayer of dead astrocytes, indicating that the morphoregulatory action of GABA requires living astrocytes to operate. Astrocytes pretreated with muscimol before the addition of neurons supported branching better than those without pretreatment. These results suggest that various aspects of dendritic growth are regulated by distinct mechanisms, and that neuron-to-astrocyte signaling mediated by GABA promotes dendritic branching.