Gastroduodenal intussusception caused by a gastric collision tumor consisting of adenocarcinoma and neuroendocrine carcinoma.

Adenocarcinoma is the most common histological type of gastric tumor. Gastric tumor arising from collision of an adenocarcinoma with a neuroendocrine carcinoma is extremely rare. Moreover, this uncommon gastric collision tumor in our case had prolapsed into the duodenum. A 77-year-old woman was admitted to our hospital complaining of vomiting and severe weight loss. Abdominal X-ray showed gastric distension, and computed tomography revealed a duodenal giant mass spreading from the bulb to the horizontal part of the duodenum. Upper gastrointestinal endoscopy was not helpful in confirming the diagnosis of the tumor. We suspected duodenal malignant tumor and performed laparotomy. The operative findings indicated that the gastric antrum was deeply invaginated into the duodenum because of the gastric tumor. Partial resection of the stomach and duodenum was performed because the tumor was irreducible. Intraoperative diagnosis of the frozen section was well-differentiated adenocarcinoma and undifferentiated carcinoma. Additional distal gastrectomy with lymphadenectomy was performed. We herein report the first case of gastroduodenal intussusception caused by a gastric collision tumor consisting of well-differentiated adenocarcinoma and poorly differentiated neuroendocrine carcinoma.

Up-regulation of NaV1.7 sodium channels expression by tumor necrosis factor-α in cultured bovine adrenal chromaffin cells and rat dorsal root ganglion neurons.

BACKGROUND: Tumor necrosis factor-α (TNF-α) is not only a key regulator of inflammatory response but also an important pain modulator. TNF-α enhances both tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant Na channel currents in dorsal root ganglion (DRG) neurons. However, it remains unknown whether TNF-α affects the function and expression of the TTX-S NaV1.7 Na channel, which plays crucial roles in pain generation. METHODS: We used cultured bovine adrenal chromaffin cells expressing the NaV1.7 Na channel isoform and compared them with cultured rat DRG neurons. The expression of TNF receptor 1 and 2 (TNFR1 and TNFR2) in adrenal chromaffin cells was studied by Semiquantitative reverse transcription-polymerase chain reaction. The effects of TNF-α on the expression of NaV1.7 were examined with reverse transcription-polymerase chain reaction and Western blot analysis. Results were expressed as mean ± SEM. RESULTS: TNFR1 and TNFR2 were expressed in adrenal chromaffin cells, as well as reported in DRG neurons. TNF-α up-regulated NaV1.7 mRNA by 132% ± 9% (N = 5, P = 0.004) in adrenal chromaffin cells, as well as 117% ± 2% (N = 5, P < 0.0001) in DRG neurons. Western blot analysis showed that TNF-α increased NaV1.7 protein up to 166% ± 24% (N = 5, corrected P < 0.0001) in adrenal chromaffin cells, concentration- and time-dependently. CONCLUSIONS: TNF-α up-regulated NaV1.7 mRNA in both adrenal chromaffin cells and DRG neurons. In addition, TNF-α up-regulated the protein expression of the TTX-S NaV1.7 channel in adrenal chromaffin cells. Our findings may contribute to understanding the peripheral nociceptive mechanism of TNF-α.

Lap-Protector and Circular Stapler Are Useful in Cystogastrostomy for Large Pancreatic Pseudocyst with Severe Infection.

Lap-Protector, which is an abdominal wall sealing device, is usually used for wound protection from implantation of malignant cells or pyogenic fluid. A circular stapler is a common easy-to-use device for anastomosis of the digestive tract. We report the case of an infected pancreatic pseudocyst which was treated by surgical procedure using these useful devices. A 69-year-old man was followed up in our hospital after severe acute pancreatitis. He had undergone drainage surgeries twice for intractable pancreatic abscess followed by severe acute pancreatitis. He was admitted to our hospital complaining of loss of appetite, hiccups, and high fever. Computed tomography of the abdomen revealed an infected pancreatic pseudocyst which compressed the gastric wall. Internal drainage into the stomach was performed using Lap-Protector and circular stapler. The patient recovered uneventfully. Recently many endoscopic or laparoscopic procedures in cystogastrostomy are reported; however, a conventional open surgical approach is also important. This easy method may be useful for operative cystogastrostomy.

[Establishment of an economic foundation for neurologists in Japan].

Establishment of an economic foundation for clinical neurologists is essential for the advancement of neurology in Japan. However, this concept sometimes seems to slip easily from the minds of neurologists in academia. This has been true in the history of the Japanese Society of Neurology for half a century. Japan has a system of public health insurance for all people, but there are many problems related to medical pay that need to be discussed, especially for doctors seeing patients. Almost all Japanese doctors have been worried about the low medical pay in the Japanese health insurance system. We have made various approaches to the Ministry of Health, Labor and Welfare to solve these economic problems, but our hard work for the improvement of our economic situation has often been unsuccessful. The Japanese Society of Neurotherapeutics took a step toward dealing with this problem with a symposium to discuss medical payments in 2002, and it has contributed to progress in the economic and financial systems for health insurance from the standpoint of clinical neurology. We Japanese neurologists need to make greater efforts to improve our poor economic situation, following the success of Japanese surgeons in their diligent work with the Ministry of Health, Labor and Welfare to improve critical conditions in the field of surgery.

Ruptured hepatic abscess caused by fish bone penetration of the duodenal wall: report of a case.

The accidental ingestion of a foreign body into the gastrointestinal tract is not uncommon; however, the development of a hepatic abscess secondary to foreign body perforation is extremely rare. We report the case of a ruptured hepatic abscess caused by fish bone penetration of the duodenal bulb, resulting in generalized peritonitis. A 73-year-old man was admitted to our hospital with generalized abdominal pain and high fever. Computed tomography of the abdomen showed ascites and a heterogeneously enhanced mass with a less-dense center and a linear dense object. We diagnosed a ruptured hepatic abscess caused by a calcified foreign body, which was managed by peritoneal lavage, drainage of the hepatic abscess, and removal of the fish bone, followed by simple closure of the hepatoduodenal fistula. The patient's postoperative course was complicated by systemic inflammatory response syndrome, but he recovered eventually.

Prostaglandin E1-initiated immune regulation during human mixed lymphocyte reaction.

Prostaglandin E1 (PGE1) has therapeutic value for transplantations due to its microvascular activity. Interleukin (IL)-18, which is elevated in plasma during the acute rejection after organ transplantation, elicits the expression of intercellular adhesion molecule (ICAM)-1, B7.1, B7.2, CD40, and CD40 ligand (CD40L) on monocytes as well as the production of interferon (IFN)-gamma and IL-12 and proliferation of T-cells during the human mixed lymphocyte reaction (MLR) in an in vitro model of acute rejection. In contrast, PGE1 inhibits all the adhesion molecule expression, cytokine production and T-cell proliferation in the presence of IL-18. The effects of PGE1 depend on stimulation of the IP/EP2/EP4-receptor, and thus, PGE1 might have therapeutic potential for treating acute rejection due to its immune regulatory effect.

Differential effect of prostaglandins E1 and E2 on lipopolysaccharide-induced adhesion molecule expression on human monocytes.

The effect of prostaglandins E1 and E2 on the 1 ng/ml lipopolysaccharide-induced expression of intercellular adhesion molecule (ICAM)-1, B7.1, B7.2, CD40 and CD40 ligand (CD40L) on monocytes was examined. Prostaglandin E1 suppressed B7.1 and CD40 expression, but prostaglandin E2 did not effect on any type of adhesion molecule expression. Both prostaglandins inhibited tumor necrosis factor (TNF)-alpha production and T-cell proliferation of lipopolysaccharide-treated human peripheral blood mononuclear cells (PBMC). Among prostaglandin E1 receptors (IP/EP1/EP2/EP3/EP4) agonists, ONO-1301, a prostanoid IP-receptor agonist, prevented B7.1 and CD40 expression. ONO-AE1-259-01 a prostanoid EP2-receptor agonist, ONO-AE1-329, a prostanoid EP4-receptor agonist, and ONO-1301 inhibited TNF-alpha production and T-cell proliferation. Moreover, anti-B7.1 and anti-CD40 Abs prevented lipopolysaccharide-induced TNF-alpha production and T-cell proliferation. Therefore, the effect of prostaglandin E1 on TNF-alpha production and T-cell proliferation might depend on the inhibition of B7.1 and CD40 expression, but that of prostaglandin E2 might be independent of adhesion molecules expression. In conclusion, the mechanism responsible for the effect of prostaglandin E1 on lipopolysaccharide-induced responses is distinct from that of prostaglandin E2.

Effect of antibodies against intercellular adhesion molecule-1, B7, and CD40 on interleukin-18-treated human mixed lymphocyte reaction.

The interleukin (IL)-18 level in plasma is elevated during the acute rejection after organ transplantation. IL-18 elicits adhesion molecule expression as well as interferon-gamma/IL-12 production and T-cell proliferation in the human mixed lymphocyte reaction, an in vitro model of acute rejection. We examined whether antibodies (Abs) against intercellular adhesion molecule (ICAM)-1, B7, CD40, and CD40, ligand (CD40L) affect the cytokine production and T-cell proliferation. Anti-ICAM-1 and B7 Abs suppressed the cytokine production, while all Abs inhibited T-cell proliferation. ICAM-1 and B7 as well as CD40 may play different roles in the acute rejection.

alpha1-Adrenergic receptor antagonists induce production of IL-18 and expression of ICAM-1 and CD40 in human monocytes.

The activation of T cells plays a role in antitumor response. Monocytes activate T cells by inducing the cell-to-cell interaction that involves the engagement of adhesion molecules with their ligands, and the production of IL-18. The authors examined the effect of the quinazoline-based alpha1-adrenergic receptor antagonists bunazosin, doxazosin, prazosin, and terazosin on the expression of adhesion molecules such as ICAM-1, B7.1, B7.2, CD40, and CD40L on monocytes isolated from human peripheral blood mononuclear cells. Doxazosin, prazosin, and terazosin induced the expression of ICAM-1 and CD40 but had no effect on the expression of B7.1, B7.2, and CD40L. Moreover, IL-18 was detected in the medium of incubated monocytes treated with doxazosin, prazosin, and terazosin. Bunazosin did not affect adhesion molecule expression and IL-18 production, suggesting that the chemical structure of quinazoline might not be related to the effect of doxazosin, prazosin, and terazosin. Although caspase-1 inhibitor completely abolished the production of IL-18, anti-IL-18 mAb and caspase-1 inhibitor partially inhibited the increase in ICAM-1 and CD40 expression induced by doxazosin, prazosin, and terazosin. Doxazosin, prazosin, and terazosin can induce monocyte activation with a specific pattern of expression of adhesion molecules and IL-18 production, and this may lead to T-cell activation through the cell-to-cell interaction. The activation of T cells induced by the increase of the expression of ICAM-1 and CD40 and the production of IL-18 may be involved in the anti-cancer effects of doxazosin, prazosin, and terazosin.

Effect of beta2-adrenergic receptor agonists on intercellular adhesion molecule (ICAM)-1, B7, and CD40 expression in mixed lymphocyte reaction.

BACKGROUND: The plasma interleukin (IL)-18 level is elevated in acute rejection after organ transplantation. Although beta2-adrenergic receptor (AR) agonists suppress the rejection of organ and tissue transplants, little is known about their action mechanisms. We examined the effects of endogenous catecholamines and beta2-AR agonists on the expression of intercellular adhesion molecule (ICAM)-1, B7.1, B7.2, CD40, and CD40 ligand (CD40L) in human mixed lymphocyte reaction (MLR) and in an in vitro model of acute rejection in the presence or absence of IL-18. METHODS: ICAM-1, B7.1 B7.2, CD40, and CD40L expression on monocytes was measured by flow cytometry, and the production of interferon (IFN)-gamma and IL-12 was determined by enzyme-linked immunosorbent assay. Lymphocytes proliferation in MLR was measured by [3H]-thymidine uptake. The relevant AR subtypes were characterized using subtype-selective agonists and antagonists. RESULTS: beta2-AR agonists inhibited the expression of ICAM-1 and CD40 during MLR in the absence of IL-18. Among IL-18-induced expression of ICAM-1, B7.1, B7.2, CD40, and CD40L, beta2-AR agonists inhibited ICAM-1 and CD40 expression. beta2-AR agonists prevented the production of IFN-gamma and IL-12 in the presence of IL-18 but had no effect in the absence of IL-18. beta2-AR agonists inhibited lymphocyte proliferation in IL-18-treated MLR. CONCLUSIONS: We found that beta2-AR agonists strongly inhibited the expression of ICAM-1 and CD40, irrespective of the presence or absence of IL-18, which is different from that of histamine and prostaglandin E2.

Histamine downregulates CD14 expression via H2 receptors on human monocytes.

Lipopolysaccharide (LPS) binds to LPS-binding protein (LBP) in plasma and is delivered to the cell surface receptor CD14 on human monocyte. LPS is transferred to the transmembrane signaling receptor toll-like receptor (TLR) 4. In the present study, the effect of histamine on the expression of CD14 on human monocytes was investigated. Histamine concentration- and time-dependently decreased the expression of cell surface CD14, whereas histamine did not decrease mRNA for CD14 nor increase soluble CD14 (sCD14). The inhibitory effects of histamine on CD14 expression were antagonized by H2-receptor antagonist, but not by H1 and H3/H4 antagonist. The effects of selective H2-receptor agonists, 4-methylhistamine and dimaprit, on CD14 expression mimicked that of histamine indicating that histamine regulated CD14 expression through the stimulation of H2-receptors. The pretreatment with histamine partially inhibited the LPS-induced TNF-alpha production in human peripheral blood mononuclear cells (PBMC). Such inhibition might be due to the down-regulation of CD14 expression on monocytes by histamine.

Histamine inhibits lipopolysaccharide-induced tumor necrosis factor-alpha production in an intercellular adhesion molecule-1- and B7.1-dependent manner.

Lipopolysaccharide (LPS) is recognized as a key molecule in the pathogenesis of Gram negative sepsis and septic shock. In the present study, we demonstrate that LPS (1-1000 pg/ml) concentration dependently up-regulated the expression of intercellular adhesion molecule (ICAM)-1, B7.1, and B7.2 on human monocytes using fluorescence-activated cell sorting analysis, and that tumor necrosis factor (TNF)-alpha production induced by LPS in peripheral blood mononuclear cells (PBMCs) was inhibited by the addition of antibodies against these adhesion molecules, suggesting the dependence of TNF-alpha production on cell-cell interaction through these adhesion molecules. Moreover, we found that histamine (10(-7)-10(-4) M) concentration dependently inhibited the expression of ICAM-1 and B7.1, but not B7.2 on monocytes induced by LPS. Histamine also inhibited the responses of TNF-alpha production induced by LPS. The modulatory effects of histamine on ICAM-1 and B7.1 expression and TNF-alpha production were all concentration dependently antagonized by famotidine but not by d-chlorpheniramine and thioperamide, and were mimicked by selective H2-receptor agonists but not by H1-, H3-, and H4-receptor agonists, indicating the involvement of H2-receptors in the histamine action. Dibutyryl cAMP down-regulated ICAM-1 and B7.1 expression on monocytes stimulated by LPS, suggesting the mediation by the cyclic adenosine monophosphate-protein kinase A pathway of H2-receptor activation. These results as a whole indicated that histamine via H2-receptor inhibited the LPS-induced TNF-alpha production through the regulation of ICAM-1 and B7.1 expression, leading to the reduction of innate immune response stimulated by LPS.

Effect of beta 2-adrenergic receptor stimulation on interleukin-18-induced intercellular adhesion molecule-1 expression and cytokine production.

beta-Adrenergic receptor (AR) agonists have been demonstrated to modulate the production of inflammatory mediators. Recent studies implied that beta 2-AR agonists might be useful for chronic inflammatory diseases caused by interleukin (IL)-18. In the present study, we found that norepinephrine, epinephrine, or isoproterenol down-regulated IL-18 (100 ng/ml)-induced intercellular adhesion molecule (ICAM)-1 expression on monocytes in a dose-dependent manner (10(-8)-10(-4) M), but did not effect B7.1 and B7.2 expression after 24-h incubation. The modulatory effect of these catecholamines on ICAM-1 expression was antagonized by beta 2-AR antagonist, but not by alpha 1-, alpha 2-, or beta 1-AR antagonist. beta 2-AR-selective agonists salbutanol and terbutaline down-regulated IL-18-induced ICAM-1 expression on monocytes, but alpha 1-, alpha 2-, or beta1-AR agonist had no effect. In the same manner, salbutanol and terbutaline as well as norepinephrine, epinephrine, and isoproterenol regulated the IL-18-induced cytokine production, including IL-12, tumor necrosis factor-alpha or interferon-gamma through the stimulation of beta 2-AR. Together with the previous finding that ICAM-1/lymphocyte function-associated antigen-1 interaction plays a crucial role in the IL-18-initiated cytokine network, the present study strongly suggested that the stimulation of beta 2-AR inhibited the IL-18-activated cytokine cascade through the inhibitory effect on ICAM-1 expression, contributing to finding a new method for clinical treatment.

Enteropathy-type T-cell lymphoma showing repeated small bowel rupture and refractoriness to chemotherapy: a case report.

The majority of gastrointestinal lymphomas arise in the stomach, whereas lymphomas occurring in the intestine are relatively rare and a limited fraction of them show the T-cell phenotype with clinical manifestations similar to de novo celiac disease. Enteropathy-type T-cell lymphoma is extremely rare in Japan, presumably owing to the very low incidence of celiac disease among the Japanese population. Here, we report a 66-year-old Japanese male who was diagnosed as having enteropathy-type T-cell lymphoma preceded by diarrhea and intermittent bloody stool for over 1 year. He was admitted to our hospital as an emergency case because of panperitonitis due to intestinal perforation. After immediate partial small-bowel resection, cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy was started. However, the disease was highly refractory and was exacerbated with leukemic transformation. Subsequent salvage chemotherapy could not be completed because of the formation of spontaneous jejuno-abdominal fistula, followed by fatal septic shock. Particular attention should be paid to the peculiar clinical manifestations of enteropathy-type T-cell lymphoma such as malnutrition, frequent intestinal perforation and refractoriness to chemotherapy.