守瀬 善一

46歳男.ときどき背部痛が出現し,肝機能障害と胆嚢結石を指摘され,入院となった.ERCP検査で総肝管が本来の位置に造影されず,右肝管系の合流部付近から起始して胆嚢管に合流する胆管を認めた.胆嚢摘出を目的に手術を行ったところ,総肝管は本来の位置に認められたが内腔が閉鎖し,ERCPで造影された右肝管と胆嚢管との間の胆管は交通枝で,これが唯一の胆汁流路となっていた

Yamafuji K, Tsuji T, Morise Z, Hayashi N, Kogiso T, Kato H, Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology, 2002, vol. 99, no. 7, pp. 833-837, 2002

We describe a rare case of pancreas divisum associated with a giant retention cyst (cystic dilatation of the dorsal pancreatic duct), presumably formed following obstruction of the minor papilla. The patient was treated by pancreatico(cysto)jejunostomy. A 50-year-old man was admitted with complaints of increasing upper abdominal distension and body weight loss. There was no previous history of pancreatitis, gallstones, drinking, or abdominal injury. An elastic-hard tumor-like resistance was palpable in the upper abdomen. Computed tomography and ultrasound (US) examinations revealed a giant cystic lesion expanding from the pancreas head to the tail. Endoscopic retrograde cholangiopancreatography findings showed a looping pancreatic duct which drained only the head and uncinate process of the pancreas to the main papilla. A US-guided puncture to the cystic lesion revealed that the lesion continued to the main pancreatic duct in the tail of pancreas. The lesion was connected to a small cystic lesion, which was located inside the minor papilla, and ended there. The amylase level in liquid aspirated from the cyst was 37869IU/l, and the result of cytological examination of the liquid showed class II. A pancreatico(cysto) jejunostomy was performed, with the diagnosis being pancreas divisum associated with a retention cyst following obstruction of the minor papilla. The histological findings of a specimen from the cyst wall revealed that the wall was a pancreatic duct covered with mildly inflammatory duct epithelium; there was no evidence of neoplasm. The patient is currently well, and a CT examination 2 years after the operation showed disappearance of the cyst and normal appearance of the whole pancreas.

Objectives: 1) To determine if endothelial expression of adhesion molecules involved in leukocyte recruitment is increased in the brain and other organs in four different models of experimental colitis, and 2) to investigate whether leukocyte infiltration occurs in the brain of colitic animals. Methods: Endothelial vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) expression was quantified using the dual radiolabeled antibody technique in rats with trinitrobenzenesulfonic acid (TNBS)-induced colitis, in mice with dextran sulfate sodium (DSS)-induced colitis, in SGID mice reconstituted with CD43RB(high) T-cells, and in IL-10(-/-) mice. Leukocyte infiltration in the brain of TNBS-induced colitic rats was assessed by myeloperoxidase activity and immunohistochemical staining with anti-CD43 monoclonal antibody. Results: Marked upregulation of brain endothelial VCAM-1 (2- to 5.5-fold) was consistently found in colitic animals in the four models studied. Brain VCAM-1 strongly correlated with colon VCAM-1 and colon weight. By contrast, upregulation of brain ICAM-1 in colitic animals was only observed in the CD45RB(high) transfer (3-fold) and the TNBS-induced (1.5-fold models). Heart and muscle VCAM-1 and ICAM-1 were not upregulated in colitic animals in the majority of models studied. There was no leukocyte infiltration into the brain of TNBS-induced colitic rats. Conclusions: Our study demonstrates a marked and specific upregulation of endothelial VCAM-1 in the brain of colitic animals. This activation of cerebral endothelial cells was not assisted with an infiltration of leukocytes into brain tissue.

Objectives: 1) To determine if endothelial expression of adhesion molecules involved in leukocyte recruitment is increased in the brain and other organs in four different models of experimental colitis, and 2) to investigate whether leukocyte infiltration occurs in the brain of colitic animals. Methods: Endothelial vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) expression was quantified using the dual radiolabeled antibody technique in rats with trinitrobenzenesulfonic acid (TNBS)-induced colitis, in mice with dextran sulfate sodium (DSS)-induced colitis, in SGID mice reconstituted with CD43RB(high) T-cells, and in IL-10(-/-) mice. Leukocyte infiltration in the brain of TNBS-induced colitic rats was assessed by myeloperoxidase activity and immunohistochemical staining with anti-CD43 monoclonal antibody. Results: Marked upregulation of brain endothelial VCAM-1 (2- to 5.5-fold) was consistently found in colitic animals in the four models studied. Brain VCAM-1 strongly correlated with colon VCAM-1 and colon weight. By contrast, upregulation of brain ICAM-1 in colitic animals was only observed in the CD45RB(high) transfer (3-fold) and the TNBS-induced (1.5-fold models). Heart and muscle VCAM-1 and ICAM-1 were not upregulated in colitic animals in the majority of models studied. There was no leukocyte infiltration into the brain of TNBS-induced colitic rats. Conclusions: Our study demonstrates a marked and specific upregulation of endothelial VCAM-1 in the brain of colitic animals. This activation of cerebral endothelial cells was not assisted with an infiltration of leukocytes into brain tissue.

Objectives: 1) To determine if endothelial expression of adhesion molecules involved in leukocyte recruitment is increased in the brain and other organs in four different models of experimental colitis, and 2) to investigate whether leukocyte infiltration occurs in the brain of colitic animals. Methods: Endothelial vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) expression was quantified using the dual radiolabeled antibody technique in rats with trinitrobenzenesulfonic acid (TNBS)-induced colitis, in mice with dextran sulfate sodium (DSS)-induced colitis, in SGID mice reconstituted with CD43RB(high) T-cells, and in IL-10(-/-) mice. Leukocyte infiltration in the brain of TNBS-induced colitic rats was assessed by myeloperoxidase activity and immunohistochemical staining with anti-CD43 monoclonal antibody. Results: Marked upregulation of brain endothelial VCAM-1 (2- to 5.5-fold) was consistently found in colitic animals in the four models studied. Brain VCAM-1 strongly correlated with colon VCAM-1 and colon weight. By contrast, upregulation of brain ICAM-1 in colitic animals was only observed in the CD45RB(high) transfer (3-fold) and the TNBS-induced (1.5-fold models). Heart and muscle VCAM-1 and ICAM-1 were not upregulated in colitic animals in the majority of models studied. There was no leukocyte infiltration into the brain of TNBS-induced colitic rats. Conclusions: Our study demonstrates a marked and specific upregulation of endothelial VCAM-1 in the brain of colitic animals. This activation of cerebral endothelial cells was not assisted with an infiltration of leukocytes into brain tissue.

本法は,膵液漏が発生しても漏出した膵液を膵腸吻合部より腹側に限局させ,背側に位置する剥離露出された血管系へ及ぶのを防ぎ,膵液漏に続発する腹腔内出血を予防する有用な方法であった.膵頭十二指腸切除の安全性の向上に寄与するものと思われた

Inflammatory bowel disease (IBD) is associated with Th1/th2 cytokine dysregulation, leukocyte extravasation, and tissue edema, but the mechanisms for cytokine-mediated vascular dysfunction are not understood. To investigate how cytokines might control edema in IBD, we determined vascular permeability and IFN-gamma expression in two models of murine colitis: SCID mice reconstituted with CD45RB(high) T-lymphocytes (CD45RB(high)/ SCID mice), and interleukin-10 gene deficient (IL-10(-/-)) mice. We also investigated the in vitro effects of IFN-gamma and IL-10 on human endothelial solute barrier and junction protein expression. Vascular permeability in CD45RB(high)/SCID and IL-10(-/-) mice was quantified using tissue I-131-IgG accumulation. The IFN-gamma message was quantified using the ribonuclease protection assay. Endothelial barrier integrity in vitro was measured by transmonolayer electrical resistance, and junctional proteins were examined by immunoblotting and fluorescence microscopy. Both CD45RB(high)/SCID and IL-10(-/-) mice exhibit enhanced colonic microvascular leakage and IFN-gamma message levels compared to their respective controls. In vitro, IFN-gamma also reduced endothelial barrier (monolayer electrical resistance, increased albumin permeability) and reduced tight junction (occludin) expression and staining. These effects were reversed by pretreatment of monolayers with IL-10. Therefore, in vivo IFN-gamma and IL-10 may modulate microvascular leakage in IBD partly by controlling the expression of intestinal endothelial tight junctional proteins, (C) 2001 Academic Press.

The objectives of this study were to quantify colonic cytokine and endothelial cell adhesion molecule (ECAM) expression in the colons of severe combined immunodeficient (SCID) mice reconstituted with different subsets of CD4+ T lymphocytes. We found that animals injected with CD45RB(high) but not CD45RB(low) T cells or phosphate-buffered saline (PBS) developed clinical evidence of colitis at 6-8 weeks following reconstitution, as assessed by loss of body weight, development of loose stools and/or diarrhea, and histopathology. Concurrent with the onset of distal bowel inflammation was enhanced expression of a variety of Th1 and macrophage-derived cytokines including interferon gamma, tumor necrosis factor-alpha, interleukin (IL)-1 beta, IL-6, IL-12, and IL-18 lymphotoxin-beta. In addition, message levels and vascular surface expression of ICAM-1, VCAM-1, and MAdCAM-1 were all significantly enhanced in the colitic SCID mice reconstituted with CD45RB(high) T cells compared with SCID mice reconstituted with PBS or CD45RB(low) T cells that did not develop disease. Significant increases in some of these ECAMs were also noted in the cecum and stomach and to a lesser degree in the small bowel. Our data confirm that reconstitution of SCID mice with CD45RB(high) but not CD45RB(low) T cells induces chronic colitis, and that the colonic inflammation is associated with enhanced expression of proinflammatory cytokines and different ECAMs in the colon. Furthermore, our studies demonstrate that reconstitution of SCID mice with CD45RB(high) T cells enhances ECAM expression in tissues distant from the site of active inflammation.

The objective of this study was to quantify E-selectin surface expression in the colon as well as other tissues in a CD4+ T-cell model of chronic colitis in mice using the newly developed dual radiolabel monoclonal antibody technique. Male SCID mice were reconstituted with either 5 x 10(5) CD4+ CD45RB(low) or CD45RB(high) T-cells isolated from normal CB-17 donor mouse spleens and subsequently monitored for clinical signs of colitis. We found that animals injected with CD45RB(high) but not CD45RB(low) T-cells nor PBS developed colitis at 6-8 weeks following reconstitution as assessed by loss of body weight, development of loose stools and/or diarrhea, and histopathology. Concurrent with the onset of distal bowel inflammation was enhanced expression of E-selectin compared to SCID mice injected with PBS or reconstituted with CD45RB(low) T-cells, both of which did not develop colitis. We also observed significant increases in E-selectin expression in cecum, small intestine, mesentery, and liver of colitic mice. Our data confirm that reconstitution of SCID mice with CD45RB(high) but not CD45RB(low) T-cells induces chronic colitis and demonstrate that this chronic colitis is associated with enhanced expression of an endothelial cell-specific adhesion molecule. Furthermore, our studies demonstrate that reconstitution of SCID mice with CD45RB(high) T-cells enhances E-selectin expression in a variety of tissues distant from the site of active inflammation. (C) 2000 Academic Press.

肝外胆道走向変異例について857例を対象として検討した.1)胆嚢管が低位合流肝管に合流する変異の頻度は1.5%であり,低位合流肝管が胆嚢管に合流する変異の頻度は0.6%であった.2)関与する低位合流肝管の肝支配域は亜区域から肝葉まで様々であったが,全て右葉系であった

We describe herein the case of a patient in whom recurrent liver metastases from gastric cancer were successfully treated by performing repeated hepatic resections. A 63-year-old man underwent a total gastrectomy with regional lymph node dissection for an advanced gastric cancer on November 17, 1992, the pathological findings of which confirmed a diagnosis of well-differentiated tubular adenocarcinoma, ss, INF alpha, ly1, v0, n1(+). Follow-up computer tomography (CT) and ultrasonography scans done 7 months after the gastrectomy revealed a metastasis in the liver S5, and a partial resection of S5 was performed on July 5, 1993. Subsequently, on November 17, 1994, an anterior segmentectomy of the liver was performed for a liver metastasis in the liver S8, then on August 11, 1998, a partial resection of the liver S6 was performed for a metastasis in the liver SG. The pathological findings of each liver specimen resected were compatible with metastatic adenocarcinoma from the primary gastric cancer. The liver tumors were expansive-growing tumors with capsules and massive necrosis. The patient is currently well with no evidence of recurrence on repeat CT scans, 6 years 6 months since-the initial gastrectomy, and 5 years 10 months since the first hepatic resection.

Background-Neutrophil-endothelial cell interactions are thought to play a critical role in the pathophysiology of nonsteroidal anti-inflammatory drug (NSAID) induced gastropathy. Aims-To optimise a mouse model of NSAID induced gastropathy and to evaluate the importance of adhesion molecules using adhesion molecule deficient mice. Methods-Gastropathy was induced in C57BL/6 mice or their adhesion molecule deficient counterparts via oral administration of indomethacin (20 mg/kg). Lesion scores, mucosal permeability, and histopathology were used to assess gastric mucosal injury. Results-Intragastric administration of indomethacin induced linear haemorrhagic mucosal lesions, primarily in the corpus of the stomach that were first observed at six hours. These lesions continued to develop over the next six hours with maximal lesion scores and mucosal permeabilities at 12 hours. When indomethacin was administered to mice deficient in CD18, intercellular adhesion molecule 1 (ICAM-1), or P-selectin, there were significant decreases in lesion scores compared with their C57BL/6 controls. In addition, mucosal permeabilities were found to be significantly lower in CD18 or ICAM-1 deficient mice observed at 12 hours. Conclusion-Certain leucocyte and endothelial cell adhesion molecules are important determinants for full expression of indomethacin induced gastropathy. It is proposed that this modification of the mouse model may be useful for the investigation of other pathophysiological mechanisms of NSAID induced gastropathy.

Background & Aims: Intercellular adhesion molecule (ICAM)-dependent adhesion of circulating neutrophils to microvascular endothelial cells is thought to be critical in causing indomethacin (nonsteroidal antiinflammatory drug [NSAID])-induced gastropathy, Indomethacin stimulates tumor necrosis factor (TNF)-alpha expression, which may enhance adhesiveness of gastric capillaries for neutrophils by activating ICAM expression on endothelial cells. Stimulation of ICAM expression is mediated by activation of the transcription factor NF-kappa B, Because activation of NF-kappa B requires proteolytic degradation of I kappa B by the ubiquitin-proteasome pathway of intracellular proteolysis, treatment with proteasome inhibitors was evaluated for efficacy in preventing NSAID gastropathy, Methods: The effect of proteasome inhibitors on gastric injury caused by oral indomethacin was measured, along with their effects on gastric mucosal permeability measured by the blood to lumen EDTA clearance, Gastric ICAM expression was measured in vivo using infusion of a labeled rat ICAM antibody, Results: Proteasome inhibitors prevented NSAID gastropathy if administered from 0 to 12 hours before indomethacin. Equivalent efficacy was observed with intravenous and oral administration of proteasome inhibitors. There was a strong correlation between the potency of proteasome inhibitors in preventing NSAID gastropathy and their potency in inhibiting intracellular proteolysis or their anti-inflammatory potency. All three classes of proteasome inhibitors, peptide boronates, aldehydes, and the mechanistically different lactacystin, prevented NSAID gastropathy. Proteasome inhibitor treatment also abolished the increase in gastric mucosal permeability and the increase in gastric endothelial ICAM expression induced by indomethacin. Conclusions: Indomethacin-induced gastric injury and increased ICAM expression are inhibited by inhibition of the proteasome.

Interleukin (IL)-10 is known to inhibit the production of proinflammatory cytokines by macrophages suggesting that endogenous IL-10 may act as an anti; inflammatory agent. Because endothelial cell adhesion molecules (ECAMs) play a key role in the recruitment of leukocytes into tissue in response to an inflammatory stimulus (i.e., lipopolysaccharide (LPS)) and the following cytokine production, we wished to assess the importance of IL-IO as an endogenous modulator of ECAM expression using IL-10 deficient mice. Constitutive and LPS-stimulated expression of intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1 and E-selectin were measured in wild type C57BL/6 and IL-10 deficient mice with no signs of active enterocolitis, using the dual radiolabeled monoclonal antibody technique. We found that constitutive expression of these ECAMs did not differ between IL-10 deficient and WT mice for all organs tested. However, we demonstrated larger increments in LPS-induced expression of ICAM-1 and VCAM-1 in the vasculature of the small intestine in IL-IO deficient mice compared to WT mice. These findings suggest that endogenous IL-10 does not modulate constitutive or LPS-induced expression of ECAMs in most tissues, however it does appear to play an inhibitory role in LPS-stimulated expression of ICAM-1 and VCAM-1 in the intestinal vasculature.

The objective of this study was to quantify, in vivo, constitutive and tumor necrosis factor alpha (TNF-alpha)-enhanced expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in different tissues fi om healthy wild-type mice (C57BL/6) as well as interleukin-10 (IL-10)-deficient mice with and without active colitis. Using the dual radiolabel monoclonal antibody technique, we found substantial constitutive expression of MAdCAM-1 in the intestine, colon, and mesenteric lymph nodes. MAdCAM-1 expression in these tissues was significantly enhanced, in a time-dependent manner, by systemic administration of TNF-alpha. Maximum surface expression was observed at 18 h after TNF-alpha administration and remained significantly elevated at 48 h post-TNF-alpha injection. No significant constitutive nor TNF-alpha-induced expression of MAdCAM-1 was detected in skeletal muscle, brain, or heart. In IL-10-deficient (IL-10 k/o) mice with no clinical or histological evidence of colitis, constitutive and TNF-alpha-induced expression of MAdCAM-1 in the intestine, cecum, and colon was not different from those values obtained with healthy wild-type controls. IL-10-deficient mice with active colitis exhibited a four- to five-fold greater expression of MAdCAM-1 in the cecum and colon compared,with their healthy controls or to IL-10 k/o mice with no evidence of colitis. Taken together, these data demonstrate that TNF-alpha enhances surface expression of MAdCAM-1 in intestinal and colonic tissues to the same extent in both wild-type and IL-10 k/o mice with no colonic inflammation, whereas IL-10 k/o mice with active colitis exhibited a profound up-regulation of MAdCAM-1 in the colon.

Interleukin (IL)-10 is known to inhibit the production of proinflammatory cytokines by macrophages suggesting that endogenous IL-10 may act as an anti-inflammatory agent. Because endothelial cell adhesion molecules (ECAMs) play a key role in the recruitment of leukocytes into tissue in response to an inflammatory stimulus (i.e., lipopolysaccharide (LPS)) and the following cytokine production, we wished to assess the importance of IL-10 as an endogenous modulator of ECAM expression using IL-10 deficient mice. Constitutive and LPS-stimulated expression of intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1 and E-selectin were measured in wild type C57BL/6 and IL-10 deficient mice with no signs of active enterocolitis, using the dual radiolabeled monoclonal antibody technique. We found that constitutive expression of these ECAMs did not differ between IL-10 deficient and WT mice for all organs tested. However,we demonstrated larger increments in LPS-induced expression of ICAM-1 and VCAM-1 in the vasculature of the small intestine in IL-10 deficient mice compared to WT mice. These findings suggest that endogenous IL-10 does not modulate constitutive or LPS-induced expression of ECAMs in most tissues, however it does appear to play an inhibitory role in LPS-stimulated expression of ICAM-1 and VCAM-1 in the intestinal vasculature.

1)肝転移切除例42例の予後は3年生存率51.3%,5年生存率41.4%. 2)予後因子を用いた単変量解析では転移個数のみが統計学的に有意な予後因子であった. 3)Coxハザードモデルを用いた多変量解析でも転移個数のみが独立した重みのある予後因子であった

A growing body of experimental evidence suggests that neutrophilic polymorphonuclear leukocyte (PMN)-endothelial cell interactions play a critical role in the pathophysiology of nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy. The objective of this study was to directly determine whether the expression of endothelial cell adhesion molecules is enhanced in a model of NSAID-induced gastropathy. Gastropathy was induced in male Sprague-Dawley rats via oral administration of indomethacin (Indo, 20 mg/kg). Lesion scores, blood-to-lumen clearance of Cr-51-EDTA (mucosal permeability), and histological analysis (epithelial necrosis) were used as indexes of gastric mucosal injury. Gastric mucosal vascular expression of intercellular adhesion molecule 1 (ICAM-1) or P-selectin were determined at 1 and 3 h after Indo administration using the dual radiolabeled monoclonal antibody (MAb) technique. For some experiments, a blocking MAb directed at either ICAM-1 (1A29) or P-selectin (RMP-1) or their isotype-matched controls was injected intravenously 10 min before Indo administration. We found that P-selectin expression was significantly increased at 1 h but not 3 h after Indo administration, whereas ICAM-1 expression was significantly increased at both 1 and 3 h after Indo treatment. The blocking ICAM-1 and P-selectin MAbs both inhibited Indo-induced increases in lesion score, mucosal permeability, and epithelial cell necrosis. However, the Indo-induced gastropathy was not associated with significant PMN infiltration into the gastric mucosal interstitium, nor did Indo reduce gastric mucosal blood flow. We propose that NSAID-induced gastric mucosal injury may be related to the expression of P-selectin and ICAM-1; however, this mucosal injury does not appear to be dependent on the extravasation of inflammatory cells or mucosal ischemia.

Morise Z, Komatsu S, Fuseler JW, Granger DN, Perry M, Issekutz AC, Grisham MB, The American journal of physiology, 1998, vol. 274, no. 2 Pt 1, pp. G246-52, 1998

A growing body of experimental evidence indicates that leukocyte-endothelial cell interactions may play an important role in the pathogenesis of NSAID-induced gastropathy. Using a newly described, dual radiolabeled monoclonal antibody technique to quantify adhesion molecule surface expression in vivo, we have demonstrated increases in surface expression of ICAM-1 and P-selectin in the gastric mucosa after oral administration of indomethacin. We have also found that CD18-, ICAM-1-, or P-selectin-deficient mice are less sensitive to the ulcerogenic effects of orally administered indomethacin. Although there is virtually no information regarding the regulation of expression of endothelial cell adhesion molecules (ECAMs) in experimental NSAID-induced gastropathy, the nuclear transcription factor kappa B (NF kappa B) may represent a potential modulator of transcriptional activation of ECAM expression. We have demonstrated that two structurally distinct yet highly selective proteasome inhibitors (MG341, lactacystin) inhibit tumor necrosis factor (TNF)-induced NF kappa B activation as well as ECAM expression in human endothelial cells in vitro. In addition, we found that these proteasome inhibitors significantly reduced indomethacin-induced gastric mucosal injury as well as gastric mucosal ICAM-1 expression in the rat in vivo. We conclude from these studies that indomethacin activates NF kappa B (possibly via TNF synthesis) in gastric microvascular endothelial cells, thereby enhancing surface expression of ICAM-1 which binds the CD18 on polymorphonuclear leukocytes (PMNs). These adherent PMNs are then believed to mediate endothelial and/or epithelial cell injury either directly or indirectly.

Jourd'heuil D, Morise Z, Conner EM, Kurose I, Grisham MB, The Keio journal of medicine, 1997, vol. 46, no. 1, pp. 10-15, 1997

Oxidant regulation of gene expression is fast becoming one of the most active areas of investigation in inflammation research. Although oxidants and free radicals have been thought to promote inflammation and tissue injury directly via their ability to oxidize, inactivate and/or degrade important cellular constituents, it is now becoming increasingly apparent that non-toxic concentrations of these same oxidizing agents may initiate and/or perpetuate inflammation by activating certain transcription factors known to be critical in the inflammatory response. One such pleiotropic transcription factor is NF-(κ)B, whose activation includes multiple intracellular signaling pathways comprised of an overlaying network of oxidation, phosphorylation, ubiquitination and proteolytic reactions. There is also a growing body of both experimental and clinical data to suggest that certain antioxidants may be very effective in modulating a number of different human diseases including chronic inflammation. Thus, understanding how oxidants regulate basic cell function may prove helpful in the design of new therapeutic agents for the treatment of chronic inflammatory diseases.

It is now well appreciated that chronic gut inflammation is characterized by enhanced production of reactive metabolites of oxygen and nitrogen. Some of these oxidants are known to modulate the expression of a variety of genes that are involved in the immune and inflammatory responses. For example, certain oxidants are known to activate the nuclear transcription factor kappa B, which regulates the expression of a variety of different adhesion molecules, cytokines, and enzymes. Oxidants are also known to activate another transcription factor, activator protein-1. This transcription factor is composed of products from the fos and jun proto-oncogene family and is believed to be important in regulating cell growth and proliferation. Finally, oxidants are believed to promote intestinal epithelial cell apoptosis, and the B-cell lymphoma/leukemia-2 gene product is believed to inhibit this phenomenon in an antioxidant-dependent manner. Taken together, these observations suggest that nontoxic concentrations of reactive metabolites of oxygen and nitrogen play an important role in regulating the expression of genes involved in the inflammatory response and in modulating apoptosis.

Primary and secondary alpha-chlorophosphines 2a-g are prepared in ca. 70% yield by chemoselective reduction of the corresponding phosphonic and phosphinic esters with AlHCl(2) and are characterized by (31)P, (13)C, and (1)H NMR and by HMRS. They can be kept several weeks in the refrigerator after purification. They lead then to the corresponding phosphaalkenes 3a-g by HCl elimination. For the volatile alpha-chlorophosphines 2a-e HCl elimination occurs in the gas phase on solid potassium carbonate under VGSR conditions (vacuum gas-solid reactions); the corresponding phosphaalkenes 3a-e are characterized by real time HRMS analysis of the gaseous flow (VGSR/HRMS coupling) and by solid-phase IR spectroscopy after condensation of the gaseous flow on a KBr window cooled to 77 K. The decomposition of phosphaalkenes at this temperature is monitored by IR spectroscopy. The alpha-chlorophosphines 2a-g undergo a HCl elimination in the liquid phase in the presence of a Lewis base; the formation of the transient phosphaalkenes is monitored by (31)P FT-NMR. The temperature of HCl elimination is dependent both upon the P-H acidity of the phosphine precursors and the nature of the base. The (31)P NMR data of the simple phosphaalkenes 3a-g are for the first time reported. They are consistent with the proposed structure. The stereochemistry of the (Z)- and (E)-isomers is established according to the "cis-rule". Phosphaalkenes 3a-g are also characterized by chemical trapping in solution with various dienes, dipoles, or thiols. All of these experiments confirm the transient character of these species. The synthetic potential of this route is evaluated.

A case of extended necrotizing pancreatitis complicated with bacterial infection was treated successfully by our new surgical method, direct retroperitoneal open-drainage. A 69-year-old woman complaining of epigastralgia and severe back pain was hospitalized and treated for acute pancreatitis for about a month. Then she developed shock and underwent surgery. The CT findings just before the operation revealed a large amount of necrotic tissue complicated with bacterial infection spreading widely throughout the retroperitoneal space, from the peripancreatic space to the pelvic cacity. We made a long oblique incision from the root of the 12th rib to the anterior superior spina iliaca on the left side of her back to obtain a direct approach to the retroperitoneal space. The necrotic tissue was removed bluntly. The skin and muscle edge of the wound was turned over, and sutured to the skin around the wound. The wound was laid open. The same procedure was performed on her right back one week after that. Lavage and debridement were performed twice a day via these bilateral wounds. The infection in the retroperitoneal space was controlled completely after about one month. Although several surgical treatments for extended necrotizing pancreatitis has been advocated, they all involve trans-peritoneal approaches after laparotomy and may be frequently insufficient for drainage and removal of infectious necrotic tissue spreading throughout the retroperitoneal space. Our new method could achieve adequate drainage for the widespread infectious necrotic tissue in the retroperitoneal space under a minimally invasive operation. © 1995, The Japanese Society of Gastroenterological Surgery. All rights reserved.

Background. We hypothesized that endothelin-1 (ET-1) is an important mediator in renal dysfunction under septic conditions. This study clarified the pathophysiologic role of ET-1 in renal function under conditions of surgical stress, especially sepsis. Methods. We investigated the correlation between ET-1 levels and renal function and the effect of anti-ET-1 antibody (AwET-1N40) on renal function in a septic shock rat model. Results. The plasma ET-1 level increased significantly at 30 minutes and remained significantly elevated for 24 hours, reaching a peak (195 +/- 24.4 pg/ml) 3 hours after the endotoxin (lipopolysaccharide derived from Escherichia coli) injection. Increases in plasma creatinine concentration and blood urea nitrogen (BUN) level and decreases in urine volume and urinary sodium excretion were also observed in the early phase after endotoxin injection. The plasma creatinine concentration and the plasma ET-1 level increased significantly at 30 minutes, reached a peak at 3 hours, and then decreased. Anti-ET-1 antibody administration (5 nmol/kg body, four times intravenously) decreased plasma creatinine concentration and BUN level and increased urine volume and urinary sodium excretion 3 hours after endotoxin injection (creatinine, p = 0.07; BUN, p < 0.05; urine volume, p < 0.01; urinary sodium excretion, p < 0.01; anti-ET-1 vs shams). Conclusions. These results suggest that the increase in endogenous ET-1 induced by sepsis plays an important role in renal dysfunction in the septic state.

ET-1の上昇とそれによる腎機能障害の存在を証明したラット敗血症モデルを用い,1) bigET-1濃度の経時的変化,2)フォスフォラミドンの前投与が,血中ET-1,bigET-1の濃度上昇に与える効果,を検討した。エンドトキシン投与後の血中bigET-1濃度は,3時間をピークとしてET-1濃度と極めて相関した上昇を示した。フォスフォラミドンの前投与によって,血中ET-1濃度上昇は抑制され,bigET-1濃度上昇は促進された。フォスフォラミドンの前投与が,このモデルでの内因性bigET-1からET-1への変換を阻害したと考えられた