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The aim of this study was to explain the role of monocyte chemoattractant protein-1 (MCP-1) in biliary atresia (BA).Concentrations of serum MCP-1 and collagen type IV were measured in 38 patients with BA by using commercially available kits. MCP-1 was also assessed in liver biopsy specimens by using immunohistochemistry. Subjects were classified into groups. Group 1 comprised BA patients with normal liver function (n = 13), group II comprised BA patients with moderate liver dysfunction (n = 18), group III comprised BA patients older than 20 years awaiting liver transplantation (n = 7), and the control group comprised age-matched patients without evidence of liver disease (n = 23).Serum MCP-1 levels were significantly increased in group II compared with group I (P.0001) and the control group (P.0001). Serum MCP-1 levels in group III were lower than in the control group (P.0001). There was a significant linear correlation between serum MCP-1 levels and type IV collagen levels in group II. Group II subjects with portal hypertension (PH) had higher MCP-1 levels than those without PH (P = .0009). Biopsy specimens showed MCP-1 was expressed mainly on biliary epithelial cells, vascular endothelial cells, and hepatocytes in group II.These findings suggest that MCP-1 probably plays a significant role in the development of progressive liver fibrosis in BA.

Aim We present a new approach to treating selected cases of Hirschsprung disease (HD) where suction rectal biopsy (SRBx) is performed in an operating room, and rapid acetylcholinesterase staining (RAST) is used to identify histopathology within 20 minutes, allowing primary laparoscopy-assisted transanal pull-through (PLTPT) to be commenced "immediately" (n = 7). Materials and Methods All subjects had an obvious caliber change in the rectum/sigmoid colon on barium enema and were strongly suspected of having HD. Results Rapid acetylcholinesterase staining clearly demonstrated acetylcholinesterase-positive hypertrophic nerve trunks and absence of ganglion cells in all SRBx specimens, indicating that all 7 patients had HD. All 7 proceeded to uneventful PLTPT. By taking this approach, SRBx results were available extremely quickly, and hospital stay was reduced by 2 to 4 days. Discussion Our approach enhanced the treatment of selected cases of HD by proceeding immediately to PLTPT after SRBx specimens were examined using RAST.

Recent years have seen dramatic growth in the real-time traffic generated by the emergence of various real-time applications on the Internet, which typically use the non-congestion-controlled UDP protocol as their transport protocol. This increasing growth of the non-congestion-controlled real-time traffic can easily cause critical issue, congestion collapse, or even prevent the traffic of well mannered congestion-controlled TCP flows. To solve these problems, the Datagram Congestion Control Protocol (DCCP) has been proposed. In order to successfully deploy DCCP on the Internet, it is vital to ensure that DCCP is fully compatible with the existing dominant TCP flows. In this paper, we evaluate and propose an algorithm to improve the TCP fairness of DCCP flow control for bursty real-time applications. Through numerous simulation results, we show that our proposed algorithm improves the fairness between TCP and DCCP flows without negative effect on real-time characteristics.

Aberrant activation of the Ras/Raf-1/extracellular-regulated kinase (ERK) pathway has been shown to be involved in the progression of human hepatocellular carcinoma (HCC). However, the mechanism of dysregulation of ERK activation is poorly understood. Recently, we identified Sprouty-related protein with Ena/vasodilator-stimulated phosphoprotein homology-1 domain (Spred) as a physiological inhibitor of the Ras/Raf-1/ERK pathway. In this study, we found that the expression levels of Spred-1 and -2 in human HCC tissue were frequently decreased, comparing with those in adjacent non-tumorous tissue. Moreover, Spred expression levels in HCC tissue were inversely correlated with the incidence of tumor invasion and metastasis. Forced expression of Spred-1 inhibited HCC cell proliferation in vitro and in vivo, which was associated with reduced ERK activation. Spred-1 overexpression also reduced the secretion of matrix metalloproteinase-9 (MMP-9) and MMP-2, which play important roles in tumor invasion and metastasis. In addition, Spred-1 inhibited growth factor-mediated HCC cell motility. These data indicate that the reduction of Spred expression in HCC is one of the causes of the acquisition of malignant features. Thus, Spred could be not only a novel prognostic factor but also a new therapeutic target for human HCC.

Aim To evaluate the efficacy of granulocytapheresis therapy in alcoholic hepatitis. Methods We attempted to trap leukocytes in the peripheral circulation using the granulocytapheresis (GCAP) technique in patients with severe alcoholic hepatitis who showed a marked elevation of peripheral leukocytes. Corticosteroids were co-administered. Results The Maddrey's indices for these patients varied between 42 and 117 and MELD scores for alcoholic hepatitis (Mayo) ranged from 20 to 44. Survival rate was 50% (3/6), which is better than the results reported recently for similar patients in a national survey (29%). The effect of GCAP was reflected in decreases in interleukin-6 and interleukin-8 levels as well as in serum concentrations of soluble intercellular adhesion molecule. White blood cell counts were not affected. In the surviving patients, the Maddrey's indices and MELD scores for alcoholic hepatitis varied between 49 and 67, and 20 and 22, respectively, showing that GCAP is effective in patients with disease of moderate severity. Hemolytic anemia occurred in one patient after GCAP therapy. Other events such as pancreatitis, pneumonia, and cerebral hemorrhage were considered to be related to the alcoholic hepatitis itself. Conclusion GCAP therapy deserves further evaluation as a new therapeutic modality for a moderately severe alcoholic hepatitis.

The aim of this study was to analyze the short- to mid-term outcome of primary modified Georgeson's laparoscopy-assisted endorectal pull-through (PMGLEPT) for Hirschsprung's disease (HD). HD patients treated by PMGLEPT were evaluated prospectively by a single surgeon using a standard structured questionnaire to assess complications, incidence of enterocolitis, and evaluate continence (CE). CE involved scoring five parameters (frequency of motions, severity of staining/soiling, severity of perianal erosions, anal shape, and requirement for medications) on a 3-point scale (0, 1, and 2 for each parameter). Thus, scores for CE were: 10 = normal, 8-9 = good, 6-7 = fair, and 0-5 = poor. Our modifications include transanal rectal dissection starting below or on the dentate line, near total excision of the posterior rectal cuff, and intraoperative acetylcholinesterase staining to accurately identify normal colon. Patients with total colon aganglionosis or trisomy-21 were excluded, leaving 33 cases of PMGLEPT performed between 1997 and 2004. Mean operative age was 11.0 months. Follow-up ranged from 8 months to 7 years (mean 4.0 years). There were no intraoperative complications. Post-PMGLEP, bowel obstruction occurred in 1 subject who required middle colic division for pull-through (PT), and enterocolitis occurred in 3 (9.1%) of 33 patients. In 20 subjects aged over 3 years with a follow-up period of more than 12 months, final CE was normal in 5, good in 10, fair in 4, and poor in 1, despite staining/soiling being present in 12 (60%) of 20 subjects. None of the 33 had constipation. Our results suggest that PMGLEPT is safe with acceptable outcome in the short- to mid-term. However, careful long-term follow-up is mandatory as there appears to be a relatively high incidence of staining/soiling on short- to mid-term follow-up.

The Datagram Congestion Control Protocol (DCCP) has been proposed as a transport protocol which supports real-time traffic using window-based flow control. We investigate the DCCP performance for various traffic flows, focusing on how DCCP flows affect TCP flows and vice versa. Through those simulations, we examine an unfair bandwidth distribution problem caused by the incompatibility of DCCP with the fast recovery algorithm of TCP.

Purpose The aim of this study was to describe a new technique for the surgical management of prenatally diagnosed small bowel atresia. Methods Under general anesthesia, a 5-mm trocar was inserted using an open technique through an intraumbilical incision. The proximal atretic bowel end was identified using laparoscopy and mobilized toward the umbilicus using an additional 3-mm trocar inserted in the left lower quadrant. The umbilical trocar then was removed, and a ring retractor was inserted into the trocar site and used to expand the wound to deliver both atretic bowel ends. The bowel was repaired and returned to the abdomen through the umbilical wound. The umbilical fascia and skin were closed conventionally. Results Three patients were reviewed. Two had minimal abdominal distension, and the atretic bowel ends could be identified easily; laparoscopy-assisted surgery was successful. The third case had significant dilatation, and laparotomy was required. Postoperatively, there was minimal abdominal scarring, and the umbilicus was normal in appearance. Conclusions Although this experience is limited to 3 patients, this technique is simple, safe, and virtually scar free and can be applied for the treatment of neonates with prenatally diagnosed small bowel atresia, especially if there is minimal abdominal distension at birth.

Purpose The authors investigated whether serum basic fibroblast growth factor (b-FGF) can be used as a noninvasive marker of renal parenchymal damage (scarring) in cases of vesicoureteric reflux (VUR). Methods Serum levels of b-FGF were measured in 120 children with known grade III to grade V VUR and 21 controls using a standard enzyme-linked immunosorbent assay technique. Results Sixty-five children had grade III VUR, 39 had grade IV, and 16 had grade V. Renal scarring was seen in 43 children on radionuclide scanning. There were no significant differences between serum b-FGF levels for different grades of VUR without scarring and controls. However, serum b-FGF levels were significantly higher in VUR patients with renal scarring than in patients with VUR without renal scarring ( P Conclusions This report is the first to document serum b-FGF profiles in children with VUR and renal scarring. The authors recommend measuring it as a simple, noninvasive marker of renal scarring in cases of VUR.

The mobile Internet is built upon a number of different wireless access networks with widely varying features in terms of coverage area, bandwidth, packet loss, and delay. To move across these different networks smoothly, issues associated with the changing features need to be addressed. In this paper, a path selection method for the coverage overlap area is proposed in which the mobile host actively measures the round trip time (RTT) and bottleneck bandwidth for each path and a path is selected based on four rules.

Purpose: The aim of this study was to assess the feasibility of allogenic penile transplantation (PTx) for creating a source of viable penile tissue for use in penile reconstruction. Methods: The entire penis from an adult Brown-Norway rat was transplanted into a pouch created in the omentum of an adult Lewis rat (fully allogenic PTx, n=23). Recipients were divided into 2 groups according to immunosuppressant (FK506) usage: in the FK+ group, FK506 (0.6mg/kg/d) was administered intraperitoneally until a predetermined day (day 3, 5, 7, 10, 14, or 21) after PTx, and then the grafts were harvested. No FK506 was used in the FK− group. Syngeneic PTx (n = 8) patients were used as controls. All grafts were stained with H&E for histologic examination. Results: At laparotomy, each successfully transplanted penis appeared as a cylindrical mass in the omentum. Grafts could be mobilized to the genital area because of a long omental pedicle. Graft survival in the control and FK+ groups was 100%. Rejection was minimal to moderate in FK+ grafts harvested on days 3 and 5 after PTx and minimal or absent in FK+ grafts harvested on days 7, 10, 14, and 21. Penile structure on H&E staining was normal in FK+ and control specimens. Rejection with massive cellular infiltration was observed in all FK− grafts. Conclusions: FK506 successfully prevented rejection in allogenic PTx, and the authors' technique has potential for creating viable penile tissue that could be used as an option for penile reconstruction.

Data transmission over wireless networks has attracted more attention with the growth of the Internet and wireless networks. However, TCP is tuned to perform well in wired networks where the error rates are very low and packet losses occur mostly because of congestion. Therefore, the performance of TCP can be severely affected by high bit error rate characterizing wireless links. We clarify the performance of TCP over wireless links of IMT-2000 in which selective-repeat ARQ is performed for recovering lost PDUs of Layer 2 on the links. ARQ can cause out-of-order delivery of SDUs, which will result in TCP performance degradation. In particular we examine the impact of the timeout timer employed to maintain sequence integrity.

The authors report on 2 neonates with irreducible inguinal hernia in whom a Pfannenstiel skin incision followed by lower abdominal midline fasciotomy were used to open the abdomen during emergency operation. By using this approach, the inguinal canal could also be opened and the hernia sac ligated. Bowel resection followed by anastomosis in one case and appendectomy in the other case could be performed safely intraabdominally because of the better exposure provided by using our approach compared with an inguinal incision alone. A Pfannenstiel incision followed by a midline fasciotomy decreases the risks associated with surgical intervention by enhancing exposure and contributing to good outcome by improving wound cosmesis.

In mobile networks, new technologies are needed to enable mobile hosts to move across various kinds of wireless access networks. In the past, many researchers have studied handover in IP networks. In almost all cases, special network devices are needed to maintain the host’s mobility. However, in these technologies, mobile hosts cannot move across different wireless access networks without closing the connection and degrading the goodput. To overcome these, we propose here a multi-path transmission algorithm for end-to-end seamless handover. The main purpose of this algorithm is to improve the goodput during handover by sending the same packets along multiple paths, reducing unnecessary consumption of network resources. We evaluate our algorithm through simulations and show that mobile hosts gain a better goodput.

IMT-2000 has attracted strong attention as the Next Generation Mobile Communication System. That can provide high-bit-rate data communication service, so that a great number of packets conveyed by TCP will be transmitted over a wireless link. W-CDMA standardized in 3GPP (standardizing IMT-2000) allows dynamic allocation of transmission rates to flows over a wireless link in response to changing link condition for each flow, which is thought to be essential for next generation mobile communication system. Therefore, in this paper, we study the characteristics of the dynamic allocation scheme when TCP flows share a wireless link, in particular by focusing on the throughput performance of those TCP flows. First, we examine the effectiveness of the dynamic allocation of down link transmission rate for TCP flows in response to changing FER by means of simulations. Through simulation results, we will show how it can improve the total throughput performance of TCP flows. Furthermore, we can obtain an effective way to allocate transmission rates to flows with different FERs in order to achieve high total throughput. Finally, we will deal with a case of multiple flows from a fixed host to a mobile host. In actual networks, it will very often happen. In this case, we will show that the total throughput of TCP flows less degrades than in the above single flow case even when FER becomes high.© (2002) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Mobile Networks have been expanding and IMT-2000 further increases their available bandwidth over wireless links. However, TCP, which is a reliable end-to-end transport protocol, is tuned to perform well in wired networks where bit error rates are very low and packet loss occurs mostly because of congestion. Although a TCP sender can execute flow control to utilize as much available bandwidth as possible in wired networks, it cannot work well in wireless networks characterized by high bit error rates. In the next generation mobile systems, sophisticated error recovery technologies of FEC and ARQ are indeed employed over wireless links, i.e., over Layer 2, to avoid performance degradation of upper layers. However, multiple retransmissions by Layer 2 ARQ can adversely increase transmission delay of TCP segments, which will further make TCP unnecessarily increase RTO (Retransmission TimeOut). Furthermore, a link bandwidth assigned to TCP flows can change in response to changing air conditions to use wireless links efficiently. TCP thus has to adapt its transmission rate according to the changing available bandwidth. The major goal of this study is to develop a receiver-based effective TCP flow control without any modification on TCP senders, which are probably connected with wired networks. For this end, we propose a TCP flow control employing some Layer 2 information on a wireless link at the mobile station. Our performance evaluation of the proposed TCP shows that the receiver-based TCP flow control can moderate the performance degradation very well even if FER on Layer 2 is high.

We analyzed the long-term outcome and late effects of treatment in 187 patients with childhood acute lymphoblastic leukemia (ALL) diagnosed between 1984 and 1990. Overall survival and event-free survival rates were 68.2% +/- 3.7% and 63.2% +/- 3.6% at 15 years, respectively. Of 55 patients who relapsed after achieving the first complete remission (CR), only 17.4% were rescued by salvage therapy. The advantage of stem cell transplantation over chemotherapy was observed only in those patients with bone marrow relapse during therapy. The SD for score height in patients maintaining the first CR significantly decreased at the time of final follow-up compared with that at diagnosis: 0.059 to -0.800 (P < .0001). The decrease was remarkable in patients younger than 5 years at diagnosis. Other late effects included mild liver dysfunction in 18% and hepatitis C virus infection in 9%. Congestive heart failure was observed in only 2.9% of patients despite the high cumulative dose of daunorubicin (450 mg/m2). Although the survival rates of patients on our protocols were comparable to those of other study groups, some modification, including reduction in dose of cranial irradiation and/or anticancer drugs, should be considered to reduce late adverse effects in survivors of childhood ALL.

A total of 62 patients with standard-risk acute lymphoblastic leukemia received three-drug induction consisting of vincristine, prednisolone, and L-asparaginase (l-Asp) followed by consolidation therapy with intermediate-dose methotrexate (MTX), intrathecal MTX, and 18 Gy of cranial irradiation. Maintenance therapy consisting of 6 drugs including daunorubicin (DNR, 450 mg/m2 in total) was continued for 3 years. Patients were randomized and half of them received weekly l-Asp during maintenance therapy as a late intensification. Complete remission (CR) was achieved in 61/62 (98.4%), and 11 of 61 patients relapsed. At 10 years, the event-free survival (EFS) was 80.6 +/- 5.0% and overall survival was 88.7 +/- 4.0%; median follow-up time was 9.3 years. The 10-year EFS of patients with additional l-Asp (84.8 +/- 6.2%) was superior to that without l-Asp (75.9 +/- 7.9%), although it was not statistically significant. No patients who received a full dose of DNR and maintained CR developed heart failure, although the shortening fraction decreased from 41.0% at diagnosis to 35.2% (median). The protocol AL841 provided good long-term disease control without severe late cardiac dysfunction.

The aortitis syndrome is a chronic inflammatory process that affects the aorta and its primary branches. Patients with aortitis syndrome exhibit various ocular changes. We present a patient in whom cataract was the initial objective finding. The serum concentration of vascular endothelial growth factor, a cytokine that affects neovascularization, and vasopermeability, was elevated before the initiation of prednisolone treatment. Cataract should be considered as a possible characteristic initial finding in patients with aortitis syndrome. Vascular endothelial growth factor may be involved in the progression of aortitis syndrome.

To determine the pathophysiology of the retinoic acid syndrome which occurs during all-trans-retinoic acid (ATRA) treatment of acute promyelocytic leukaemia patients, we investigated the direct effects of ATRA on the function of human neutrophils. We found that ATRA (10-200 microM) dose-dependently stimulated superoxide (O2-) generation in intact neutrophils. The maximal activity of ATRA-stimulated O2- generation was 3.0 nmol/min/10(6) cells. Adding EGTA to the assay mixture did not affect the activity nor was the intracellular free calcium concentration changed upon stimulation. The treatment of neutrophils with 0.1 microM staurosporine, an antagonist of protein kinase C, for 10 min, enhanced the activity of ATRA-stimulated O2- generation up to 186% of that for control samples. Wortmannin (1 microM), an inhibitor of phosphatidylinositol 3-kinase (PI 3-kinase), reduced this stimulatory activity by 67%. These results suggest that ATRA activates the signalling pathway related to PI 3-kinase rather than that utilizing calcium and protein kinase C. ATRA enhanced the O2- generated in a sodium-dodecyl-sulphate (SDS) cell-free system, resulting in rates up to 288% higher than that seen with SDS alone. This enhancement was not affected by pretreatment with staurosporine or wortmannin. ATRA may thus directly activate and/or enhance the function of neutrophils.

Congenital amegakaryocytic thrombocytopenia (CAMT) is an uncommon disorder in newborns and infants, characterized by isolated thrombocytopenia and megakaryocytopenia in the first year without physical anomalies. The defect of thrombopoiesis is not well understood. Recently, thrombopoietin (TPO), the ligand for the c-mpl receptor, was cloned. Accumulating evidence from in vitro and in vivo studies indicate that TPO plays a key role in the regulation of megakaryocytopoiesis. In this study we examined the effect of TPO on megakaryocyte colony formation from a patient with CAMT using a plasma-containing methylcellulose clonal culture. The in vitro results demonstrated a defective response to TPO in megakaryocyte colony formation from bone marrow mononuclear cells (MNC) of the patient. although interleukin-3 (IL-3) but not stem cell factor (SCF) induced only a small number of megakaryocyte colonies. These findings indicated that thrombocytopenia in CAMT could not be corrected by administration of TPO in vitro. Additionally, clonal cultures containing SCF, IL-3, IL-6 and erythropoietin showed decreased numbers of erythroid and myelocytic progenitors in the bone marrow of the patient. The serum TPO level measured by enzyme-linked immunosorbent assay was significantly higher than that in healthy controls. By PCR, marrow MNC from healthy children and from a patient with essential thrombocytosis expressed c-mpl mRNA, whereas no c-mpl mRNA was detected in marrow MNC from the patient with CAMT. There was no difference in the CD34 expression and c-kit mRNA between the CAMT patient and healthy children. The results of this study suggest that the pathophysiology in CAMT may be a defective response to TPO in haemopoietic cells through impaired expression of c-mpl mRNA.

In 1988, we reported a thrombasthenic patient whose platelets contained an abnormal molecular weight GPIIb ( Blood, 71 , 915,1988). Here we describe another patient whose platelets contain a variant GPIIb with properties similar to the previously reported abnormal GPIIb. This patient has a small amount of the abnormal GPIIb and was suggested to be a heterozygote characterized by deficient and abnormal GPIIb genes. The abnormal GPIIb was suggested to be related to the precursor form of GPIIb because the molecular weights of both proteins are the same. The abnormal GPIIb may lack a peptide region around the cleavage site of the two chains, as suggested from its lack of reactivity towards antibodies against these epitopes.

A 10-year-old boy with metastatic rhabdomyosarcoma had an HLA-identical sibling and received an allogeneic BMT. Recurrence was detected in the BM as the only site of treatment failure 12 months after BMT. Donor leukocyte infusion (DLI) was chosen as salvage therapy. Although sufficient cells (a total of 29.7 x 10(7)/kg) were infused, no signs of acute GVHD nor BM aplasia occurred and the patient died of disease progression 9 months after DLI.

Peroxisome proliferator-activated receptor-γ (PPAR-γ) regulates cell growth and differentiation. Recent evidence has suggested that PPAR-γ ligands have antitumor effects through inhibiting cell growth and inducing cell differentiation in several types of malignant neoplasm. In the present study, we investigated (a) the expression of PPAR-γ in both human hepatoma cell lines and five resected human hepatocellular carcinoma (HCC) tissues, (b) the growth inhibitory effect of troglitazone, a PPAR-γ ligand, on those hepatoma cells, and (c) the molecular mechanisms of troglitazone-induced cell cycle arrest. Five hepatoma cell lines, HLF, HuH-7, HAK-1A, HAK-1B, and HAK-5, were used. The mRNA expression levels of PPAR-γ, p21 WAF1/CIP1 and p27KIP1 were determined by real-time quantitative reverse transcription-polymerase chain reaction. The expression of cell cycle-regulating proteins, such as p21, p27, cyclin E, and pRb, was examined using Western blotting. PPAR-γ was constitutively expressed in all the cell lines and the HCC tissues used in this study. A cytostatic effect of troglitazone was found in those cell lines, and this inhibition of cell growth was dosage dependent. G0/G1 arrest was demonstrated in flow cytometric analysis in HLF, HAK-1A, HAK-1B, and HAK-5, all of which showed an increased expression of p21 protein. However, HuH-7, lacking p21 protein expression, did not demonstrate clear arrest in the cell cycle analysis. HLF, which is pRb deficient, responded most profoundly to troglitazone, showing an increased expression of not only p21 but also p27. These findings suggest that p21 and p27 might be involved in troglitazone-induced cell cycle arrest in human hepatoma cells.

Time-dependent thermal stress singularities at a semi-infinite crack tip associated with a transient temperature field have been analyzed on an infinite plate with a point heat source near the crack tip. As the heating begins, a mode I singularity increases gradually with time, but, after showing its maximum, decreases to be negative. This singularity variation causes a crack to start growing at some instance, but soon after to stop. That is, crack growth may be controlled, which is desirable for a cutting device for brittle materials. Deflection of a heating point from a crack line results in a mode II stress singularity, which also leads a crack to swerve from the original crack line. In an experiment using glass plates, a crack was successfully controlled to grow and also to branch in any angle toward the heat source as long as the heating location was kept appropriately apart from the crack tip.

Chronic neutrophilic leukemia (CNL) is a rare type of leukemia. We diagnosed a 81-year-old woman as CNL because she showed that sustained leukocytosis dominated by mature neutrophils, hepatosplenomegaly, high neutrophilic alkaline phosphatase (NAP) score, absence of the Ph1 chromosome and no evidence of leukemoid reaction. During the clinical course, she did not manifest hemorrhagic tendency or infection. We also examined neutrophilic function including chemotaxis, chemiluminescence, nitroblue tetrazolium (NBT) dye reduction, which all indicated normal neutrophil function. Using a reversed phase-high pressure liquid chromatography (HPLC), we detected the production of leukotriene B4 (LTB4) in neutrophils. We found that the LTB4 production was decreased in neutrophils whereas they showed normal chemotaxis. This discrepancy has never, to our knowledge, been reported before in case of CNL.