Diabetic peripheral neuropathy and prevalence of erectile dysfunction in Japanese patients aged <65 years with type 2 diabetes mellitus: The Dogo Study.

Only limited epidemiological evidence exists regarding the relationship between diabetic neuropathy and erectile dysfunction (ED) among Japanese patients with type 2 diabetes mellitus. To investigate the relationship between diabetic neuropathy and ED among Japanese patients with type 2 diabetes mellitus, a multicenter cross-sectional study was conducted in 287 male Japanese patients with type 2 diabetes mellitus, age (19-65 years). Diabetic neuropathy was diagnosed if the patients showed two or more of the following three characteristics: neuropathic symptoms, decreased or disappeared Achilles tendon reflex and/or abnormal vibration perception. ED, moderate to severe ED, and severe ED were defined as present when a subject had a Sexual Health Inventory for Men score <22, <12 and <8, respectively. The prevalence values of diabetic neuropathy and severe ED were 47.0 and 39.0%, respectively. Diabetic neuropathy was independently positively associated with severe ED, but not ED and moderate ED: the adjusted odds ratio was 1.90 (95% confidence interval: 1.08-3.38). No relationships were found between diabetic retinopathy or diabetic nephropathy and ED. Diabetic neuropathy is positively associated with severe erectile dysfunction among Japanese type 2 diabetes mellitus patients aged <65 years.

Depressive symptoms and prevalence of erectile dysfunction in Japanese patients with type 2 diabetes mellitus: the Dogo Study.

In several studies of patients with type 2 diabetes mellitus, a positive association between depressive symptoms and erectile dysfunction (ED) has been reported. No evidence exists, however, regarding the association between depressive symptoms and ED among Japanese patients with type 2 diabetes mellitus. Thus, we examined this issue among Japanese patients with type 2 diabetes mellitus. Study subjects were 469 male Japanese patients with type 2 diabetes mellitus, aged 19 years or over. ED, moderate to severe ED and severe ED were defined as present when a subject had a Sexual Health Inventory for Men score <22, <12 and <8, respectively. Depressive symptoms were defined as present when a subject had a Self-Rating Depression Scale (SDS) score >49. Adjustment was made for age, body mass index, waist, duration of type 2 diabetes, current smoking, current drinking, hypertension, dyslipidemia, coronary artery disease, stroke, glycated hemoglobin and diabetic neuropathy. The prevalence values of depressive symptoms, moderate to severe ED and severe ED were 15.1%, 64.2% and 51.0%, respectively. Depressive symptoms were independently positively associated with moderate to severe ED and severe ED (adjusted odds ratios were 2.23 (95% confidence interval (CI): 1.17-4.43) and 1.86 (95% CI: 1.04-3.41), respectively). In Japanese patients with type 2 diabetes mellitus, depressive symptoms may be associated with ED.

Differential expression of metallothioneins in human prion diseases.

We herein report an immunohistochemical and a Western blot analysis on metal/free radical chelating proteins, metallothioneins (MTs; MT-I/II and MT-III), in the brains of human prion disease patients with or without prion protein gene mutation and polymorphism. Irrespective of the isoforms of MTs, the immunoreaction was detected in the cytoplasm and processes of the astrocytes in the cerebral cortex and white matter in normal controls and prion disease brains. Although the immunoreactivities for MTs in Creutzfeldt-Jakob disease (CJD) brains varied from case to case, they were generally dependent upon the disease duration. In CJD patients with a relatively long disease course, the immunoreaction for both MT-I/II and MT-III in the astrocytes was significantly reduced, and this finding was not modified by the genotypes of the patients. On the other hand, in patients with Gerstmann-Sträussler-Scheinker syndrome, MT-I/II immunoreactivity in the astrocytes was exclusively reduced, while the immunoreaction for MT-III was relatively well preserved. Especially the astrocytes in the vicinities of the kuru plaques exhibited a weak or no immunoreaction even for MTs but a strong immunoreaction for glial fibrillary acidic protein. A quantitative Western blot analysis also revealed that MT-I/II protein accumulated in CJD brain with a short disease duration, whereas MT-III in CJD brain with a long disease duration was statistically significantly reduced in comparison to the normal brains. These findings suggest that the protein expression of MTs in the astrocytes is thus regulated differentially among human prion diseases and modified locally by such abnormal prion protein depositions as kuru plaques.

Existence of TT virus DNA in extracellular body fluids from normal healthy Japanese subjects.

Although recent studies indicate a high prevalence (12-92%) of TT virus (TTV) DNA in sera of healthy Japanese individuals, there is a paucity of information regarding the route of transmission of this virus. Analyzing the nucleotide sequences of the existing polymerase chain reaction (PCR) primers of TTV DNA, we developed a set of noble primers (HM-1) and looked for the prevalence of TTV DNA in sera from 39 normal healthy Japanese individuals using PCR. The existence of TTV DNA was also checked in saliva, urine, sweat, stool, and tears from 11 and in semen from 10 serum TTV-positive normal subjects. TTV DNA was detected in sera from 23 of 39 (59.0%) normal subjects. TTV DNA was also detected in saliva, stool, semen and tears from all cases with TTV-DNA-positive serum, but not in body fluids from subjects with TTV-DNA-negative serum. TTV DNA remained undetected in urine and sweat from all cases. Data from these experiments showing the existence of TTV DNA in different body fluids suggest that the high rates of prevalence of TTV among normal healthy subjects might be due to a possible fecal-oral, droplet, or sexual route of transmission of TTV.

Vascular endothelial growth factor and malignant transformation of a meningioma: case report.

Although meningiomas are common benign intracranial tumors which grow slowly, we occasionally encountered aggressive or malignant ones. One of these cases showed an interesting relationship to vascular endothelial growth factor (VEGF). A 39-year-old woman underwent resection of a sphenoid ridge meningioma; the residual tumor showed evidence of malignant transformation 14 years later. We immunohistochemically examined six successive surgical specimens plus the autopsy specimen of this patient's tumor for proliferative potential, vascularity, and expression of various growth factors. In the latter stage of clinical courses, proliferative potential and vascularity was seen to increase year by year. Expression of VEGF was upregulated and correlated with vascularity. On the other hand, basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), and epidermal growth factor (EGF) were not overexpressed in this tumor. This case suggests that overexpression of VEGF and increased angiogenic potential might be involved in malignant transformation of meningiomas.

Phospholipase A2 mediates nitric oxide production by alveolar macrophages and acute lung injury in pancreatitis.

OBJECTIVE: Reportedly, nitric oxide (NO) derived from alveolar macrophages (AMs) and increased serum phospholipase A2 (PLA2) activity are associated with the pathogenesis of lung injury in acute pancreatitis. The authors examined the possibility that PLA2 causes, in part, the induction of NO production by AMs in pancreatitis. METHODS: Pancreatitis was induced in rats by selective pancreatic duct ligation (SPL). AMs were stimulated with PLA2 or SPL rat serum, with or without administration of the PLA2 inhibitor quinacrine. Then NO production from the AMs was measured by the Griess method, inducible NO synthase mRNA expression of AMs was analyzed by the reverse transcription-polymerase chain reaction, and cytotoxic effects of AMs on human umbilical vein endothelial cells was examined by a 51Cr release assay. In vivo, the effect of quinacrine on lung injury was determined by measuring the arterial blood oxygen pressure (PaO2), lung weight, and lung permeability using Evans blue dye concentration of SPL rat. RESULTS: In vitro, the serum with high PLA2 activity induced NO production by rat AMs. PLA2 (50 ng/ml) induced significant amounts of NO production, inducible NO synthase mRNA expression, and cytotoxicity toward the human umbilical vein endothelial cells in normal rat AMs, and these activities were significantly inhibited by quinacrine. In vivo, rats with pancreatitis that were given quinacrine showed decreased concentrations of NO2- and NO3- in the bronchoalveolar lavage fluid, and the PaO2, lung edema, and lung permeability were improved significantly. CONCLUSION: PLA2 induces AMs to release NO, which contributes to lung injury in acute pancreatitis. This lung injury was prevented by the administration of the PLA2 inhibitor quinacrine.

Expression of inducible nitric oxide synthase in circulating neutrophils of the systemic inflammatory response syndrome and septic patients.

There is increasing evidence that nitric oxide (NO) is an important factor in the pathogenesis of septic shock. It is known that polymorphonuclear neutrophils (PMNs) are activated during sepsis or after surgical stress, and they then release various toxic mediators including free radicals. It has not been clear whether NO synthesis can be induced in circulating PMNs. Blood samples were obtained from 11 patients with sepsis, 23 patients with systemic inflammatory response syndrome (SIRS), and 16 patients without SIRS (nonSIRS) who underwent operation. We examined mRNA expression of inducible NO synthase (iNOS) in circulating PMNs from those patients pre- and postoperatively using the reverse transcriptase polymerase chain reaction (RT-PCR) method and measured their serum nitrate (NO2-) + nitrate (NO3-) concentration, peripheral blood white cell (WBC) count, and serum C-reactive protein (CRP) level. The frequency of iNOS expression in PMNs increased in sepsis (100%) and SIRS (70%) patients compared to that in nonSIRS patients (18%) (p < 0.001). The peripheral WBC count and CRP level were significantly higher in iNOS-positive patients than in iNOS-negative patients (p < 0.05 and p < 0.01, respectively). Postoperatively, the serum NO2- + NO3- concentration increased in 87% of septic patients and in 56% of patients with SIRS (p < 0.05 for both). Our study indicated that iNOS mRNA expression is induced in human circulating PMNs of patients with postoperative sepsis and SIRS and may be involved in the pathogenesis of the sepsis syndrome.

Assessment of c-erbB2 and vascular endothelial growth factor mRNA expression in fine-needle aspirates from early breast carcinomas: pre-operative determination of malignant potential.

AIMS: Although axillary lymph nodes status, tumour size, hormonal-receptor status and histological grade at diagnosis are frequently used to orient the treatment of breast cancer patients, some tumours recur in patients with early stage disease. Pre-operative assessment of individual tumour characteristics, based on oncogenes and growth factors related to tumour growth, invasion or metastasis, may guide the treatment for patients with breast carcinomas. METHODS: We examine here the prognostic significance of cyclin D1, urokinase type plasminogen activator, vascular endothelial growth factor (VEGF), platelet-derived growth factor, and c-erbB2 expression in pre-operatively obtained fine-needle aspirates from breast carcinomas less than or equal to 3 cm in size. Correlation between mRNA expression of these factors and clinicopathological characteristics was analysed. RESULTS: The level of c-erbB2 mRNA expression was significantly higher in tumours with lymph node metastases than in those without lymph node metastases. VEGF mRNA expression positively correlated with the degree of angiogenesis as quantitated by immunohistological staining with a CD31 monoclonal antibody. CONCLUSIONS: Analysis of c-erbB2 and VEGF mRNA expression in fine-needle aspirates may be useful in assessing the malignant potential of individual breast carcinomas, leading to a pre-operative discrimination of a high-risk group.

Preoperative assessment of tumor angiogenesis by vascular endothelial growth factor mRNA expression in homogenate samples of breast carcinoma: fine-needle aspirates vs. resection samples.

BACKGROUND AND OBJECTIVES: Tumor angiogenesis is receiving increased attention as a prognostic factor and also as a possible target for new anticancer agents. We investigated whether extent of vascular endothelial growth factor (VEGF) mRNA expression correlated with degree of neovascularization, and whether this expression in fine-needle aspirates could be a marker for assessing angiogenic potential of breast tumors. METHODS: VEGF mRNA expression was semiquantitated by reverse transcriptase-polymerase chain reaction (RT-PCR) followed by Southern blotting. Tumor neovascularization was assessed by immunohistochemical staining with anti-CD31 (PECAM) antibody. RESULTS: There was a positive correlation between degree of neovascularization and semiquantitated VEGF mRNA expression in invasive ductal carcinomas (r2 = 0.346, n = 48, P < 0.05). Extent of VEGF mRNA expression in fine-needle aspirates was closely correlated with that in resected invasive ductal carcinomas equal to or less than 3 cm in size (r2 = 0.874, n = 14, P < 0.05). CONCLUSION: These data suggest that semiquantitation of VEGF mRNA expression in fine-needle aspirates is useful for assessing angiogenic potential of invasive ductal carcinomas.

Immunosuppressive cytokines (IL-10, TGF-beta) genes expression in human gastric carcinoma tissues.

BACKGROUND: Contribution of immunosuppressive cytokines to tumor progression in many types of cancers has been suggested. To characterize the in vivo expression of immunosuppressive cytokines in gastric cancer, we analyzed the messenger RNA (mRNA) expression of transforming growth factor-beta (TGF-beta) and interleukin-10 (IL-10) in human gastric carcinoma tissues. METHODS: Both tumor tissues and nontumor tissues from each resected specimen of 29 primary gastric carcinomas were tested for IL-10 and TGF-beta mRNA expression by the reverse transcriptase-polymerase chain reaction (RT-PCR), and the mRNA expression was correlated with various pathological parameters of the tumors. RESULTS: Among the 29 tumors, mRNAs of TGF-beta and IL-10 were detected in 79% and 62% of tumor samples, respectively. These cytokines were detected only in 31% for TGF-beta and 17% for IL-10 in nontumor samples. Both mRNAs were frequently expressed in the poorly differentiated adenocarcinomas and the tumor tissues with high degree of stage or lymph node metastasis. CONCLUSIONS: Local expression of immunosuppressive cytokines may contribute to the progression of primary gastric carcinomas possibly through immunosuppression.

Role of nitric oxide derived from alveolar macrophages in the early phase of acute pancreatitis.

BACKGROUND: Acute pancreatitis is known to be often complicated by lung injury; however, the pathogenesis of lung injury in the early phase of acute pancreatitis remains unclear. Alveolar macrophages (AMs) have been suggested to contribute to lung injury by releasing various cytotoxic products including nitric oxide (NO). We investigated the role of AM-derived NO in the pathogenesis of lung injury during the early phase of acute pancreatitis. MATERIALS AND METHODS: Pancreatitis was induced in rats by selective pancreatic duct ligation (SPL). The mRNA expression of inducible NO synthase (iNOS) in AMs from rats after SPL (at 1, 2, 4, 6, 8, 12, 18, and 24 hr) was examined by reverse-transcriptase polymerase chain reaction method. The in vitro production of NO and superoxide by AMs 24 hr after SPL was measured and the cytotoxic effect of AMs on human umbilical vein endothelial cells (HUVECs) was examined with or without the NO synthase inhibitor L-NG-monomethyl-L-arginine (L-NMMA). The in vivo effect of L-NMMA on lung injury was also examined. RESULTS: In this model, serum amylase level peaked 24 hr after SPL, whereas PaO2 bottomed 24 hr after SPL. (In vitro) AMs expressed iNOS mRNA 6 hr after SPL and generated large amounts of NO and superoxide and demonstrated strong cytotoxicity against HUVECs significantly. This cytotoxicity was reduced by the administration of L-NMMA. (In vivo) L-NMMA administrated to rats with pancreatitis apparently reduced lung edema histologically and improved the PaO2. CONCLUSION: Our results suggest that, during early phase of acute pancreatitis, AM-derived NO contributes to lung injury. Administration of the NOS inhibitor L-NMMA prevented lung injury in this model.

Vascular endothelial growth factor and platelet-derived growth factor are potential angiogenic and metastatic factors in human breast cancer.

BACKGROUND: Angiogenesis is a prerequisite for tumor growth and metastasis. Tumor angiogenesis may be mediated by several angiogenic factors such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), transforming growth factor-alpha, and basic fibroblast growth factor. METHODS: Differential mRNA expressions of VEGF, PDGF (A chain), transforming growth factor-alpha and basic fibroblast growth factor in 32 primary invasive breast tumors were examined by reverse transcriptase-polymerase chain reaction. We analyzed relationships between mRNA expressions of these angiogenic factors and the degree of angiogenesis, tumor size, and metastasis. Quantification of angiogenesis was achieved by the immunohistochemical staining of endothelial cells with antibody to CD31. RESULTS: VEGF and PDGF-A mRNAs were expressed more frequently in breast tumors than in nontumor breast tissues, whereas no difference was found in expression frequency of either transforming growth factor-alpha or basic fibroblast growth factor mRNA. Vascular counts in tumors correlated with each expression frequency of VEGF and PDGF-A mRNA. PDGF-A mRNA was expressed more frequently in tumors with lymph node metastasis than in those without metastasis. CONCLUSIONS: Expression of VEGF and PDGF mRNAs detected by reverse transcriptase-polymerase chain reaction in breast tumors correlates with tumor-related characteristics of angiogenesis and metastatic potential. Analysis of these mRNAs by reverse transcriptase-polymerase chain reaction may be useful for assessing the biologic behavior of a breast tumor before surgical treatment.

Induction of inflammatory cytokines in effusion cavity by OK-432 injection therapy for patients with malignant effusion: role of interferon-gamma in enhancement of surface expression of ICAM-1 on tumor cells in vivo.

The intracavitary injection of OK-432, a streptococcal preparation, has been shown to be an effective immunotherapy for patients with malignant effusion. We found that this therapy increases surface expression of intercellular adhesion molecule-1 (ICAM-1) on tumor cells, and that the degree of increased ICAM-1 was correlated with therapeutic effects. In the present study, we investigated the ability of OK-432-induced inflammatory cytokines, such as interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta), to enhance ICAM-1 expression. We treated 17 patients who had a malignant effusion with OK-432. At 24 hr after OK-432 injection, ICAM-1 levels on tumor cells were increased significantly in responders except in one case (n=9), whereas no change was evident in nonresponders except in two cases (n=8). Induced maximum levels of IFN-gamma in responders were significantly higher than those in nonresponders. In contrast, there was no significant difference in the induced TNF-alpha or IL-1 beta levels between the two groups. Two types of cultured tumor cells derived from responder patients were successfully established from the 17 different tumor cells in effusion. We performed an in vitro study using these cultured tumor cells. Treatment of the two cultured tumor cells with recombinant IFN-gamma, but not recombinant TNF-alpha or IL-1 beta, significantly increased their ICAM-1 expression to a clinically detectable level. Direct treatment of the tumor cells with cell-free effusion samples obtained from the same patients 24 hr after the therapy successfully increased ICAM-1 expression and this action was blocked completely only by a pretreatment with anti-IFN-gamma mAb. Our results suggests that in this therapy IFN-gamma plays a crucial role in enhancing ICAM-1 expression by tumor cells and that induced IFN-gamma levels may be a useful marker for evaluation of the therapeutic effect.

Evaluation of the effects of steroids on experimental septic lung injury.

To evaluate the clinical usefulness of steroids for septic lung injury, we investigated the effects of methylprednisolone (MP) on this disorder using an experimental rat model of cecal ligation and puncture (CLP). While 92% of the rats that underwent CLP (CLP rats) died within 30 h, those given high-dose MP (30 mg/kg) just after the operation (CLP + MP rats) survived for a significantly longer period (p < 0.01). Concentrations of endotoxin (ET) in arterial blood were significantly higher in the CLP + MP rats than in the CLP rats, while those in the bronchoalveolar lavage fluid (BALF) were significantly lower. Alveolar macrophages (AM) obtained from the CLP rats (CLP-AM) generated more O2-than did AM from sham-operated rats (sham-AM) following stimulation. However, the administration of MP did not reduce the upregulated generation of O2-by CLP-AM. While CLP-AM produced less leukotriene (LT)B4 than did sham-AM following stimulation with A23187, the administration of MP further reduced LTB4 production. When AM were cultured with [3H]arachidonic acid (3H-AA), the uptake of the isotope and the 3H release were significantly less in CLP-AM than in sham-AM. The administration of MP did not cause recoveries in the uptake and release of 3H-AA by CLP-AM. Although the survival time of CLP rats was significantly prolonged and the translocation of ET into BALF was reduced by steroid administration, the steroid effects were not explained by those on altered AM function. The upregulated generation of O2- and reduced LTB4 production from CLP-AM were not reversed by the treatment of this drug.

In vitro analysis of peritoneal adhesions in peritonitis.

Peritoneal adhesions due to peritonitis make surgery more difficult and may cause complications. Clarifying the formation mechanism of peritoneal adhesions could help identify methods useful for their prevention. We cultured mesothelial monolayers on plates and microcarriers to simulate the parietal and visceral peritoneum, respectively. We then investigated the effects of lipopolysacchride (LPS) and tumor necrosis factor (TNF) on the homologous adhesion of these mesothelial monolayers. There was no adhesion of mesothelial monolayers in the control medium. When monolayers were cultured with endotoxin (LPS), approximately 90% of the microcarriers adhered to the mesothelial microplate. Adhesions occurred at LPS concentrations of 10 ng/ml and increased linearly in a dose-dependent manner. Kinetic studies revealed that the mesothelial adhesion appeared at 12 hr, and that 90% of the microcarriers were adherent after 24 hr. Open intercellular spaces were observed after a 24-hr treatment with LPS. Scanning electron microscopy revealed that the mesothelial cells adhered to the naked glass. LPS also caused increased permeability of the mesothelial monolayer. TNF did not cause any significant adhesion. Through our experiments we were able to develop an in vitro model of peritoneal adhesion using peritoneal mesothelial cell culture. Endotoxin caused an increase in homologous adhesion of peritoneal mesothelial monolayers, which may correspond to the initial stage of peritoneal adhesion formation in peritonitis.

Inferior vena caval thrombus associated with double neoplasms of the retroperitoneum and kidney: report of a case.

We report herein the case of a patient we recently encountered who was found to have a giant retroperitoneal tumor coincident with tumor thrombus in the inferior vena cava (IVC). On the assumption that the origin was retroperitoneal, the two lesions were resected using an intracaval filter. However, histopathological examination of the specimens revealed neurilemoma for the retroperitoneal tumor and adenocarcinoma for the tumor thrombus. A right renal tumor was subsequently detected, which led to right nephrectomy being performed en bloc with part of the IVC using a venoarterial bypass. Microscopy revealed carcinoma of the Bellini duct, or collecting duct, which is an extremely rare tumor. Retrospectively, a lesion with soft tissue density was noted in the renal vein. Surgical management focused on the prevention of pulmonary embolism. We describe this case because of its extreme rarity and its significance from the viewpoint of diagnosis and therapeutic strategies.

The order of ward rounds influences nosocomial infection. A 2-year study in gastroenterologic surgery patients.

We studied the effect of the order of ward rounds on nosocomial infection in gastroenterologic surgery patients. The subjects were patients with gastrointestinal diseases admitted between September 1992 and August 1994. During the 1st year, the round proceeded indiscriminately among recovery rooms and rooms with stable patients and isolated patients with methicillin-resistant Staphylococcus aureus (MRSA). In the subsequent year, the round started in the recovery rooms and moved into the general rooms with stable patients and finally into the isolation rooms. Against the time course, piecewise linear regression analyses were made with the number of culture-positive patients and the quantities of antibiotics and disinfectants used. Of a total of 1894 strains from 264 patients, isolates of MRSA (n = 200) decreased from 150 in the 1st year to 50 in the 2nd year. The number of MRSA-positive patients showed the point of inflexion in the analysis at the change of round order, with a later decrease. The trend was similar for Candida (n = 99) and Enterococcal (n = 225) species. The amount of antibiotics was unchanged while the amount of disinfectants used decreased in the 2nd year. Thus, the round re-ordering appeared to help prevent nosocomial infection. Ward rounds for patients who have had gastroenterologic surgery should proceed from compromised hosts to stable patients, and then isolated patients.

A possible role of TGF-beta in the formation of malignant effusions.

The detailed mechanisms underlying the formation of malignant effusions are incompletely defined. In order to determine whether transforming growth factor-beta (TGF-beta) would contribute to the formation of malignant effusions, we investigated the effect of TGF-beta on the morphology, growth, and permeability of human mesothelial cells, which are thought to serve as a permeability barrier in the pleuroperitoneal cavities. Treatment of the mesothelial cells with a TGF-beta dose ranging from 0.1 to 10 ng/ml for 96 hr induced distinct morphologic changes in the cells. Each cell increased in size as did the volume of the intercellular spaces. TGF-beta also significantly inhibited the growth of mesothelial cells at a concentration ranging from 0.1 to 10 ng/ml. This growth inhibition was blocked completely by the addition of anti-TGF-beta antibody. Treatment of the mesothelial cells with 2.0 ng/ml TGF-beta significantly increased the permeability of a mesothelial cell monolayer as assessed by a FITC-albumin permeability assay. In our clinical analysis using 10 effusion samples obtained from patients with various types of carcinoma cells, considerable level of TGF-beta could be detected by ELISA, ranged from 0.90 to 8.75 ng/ml. Our data suggest that TGF-beta plays an important role in the formation of malignant effusions through structural and functional damage to the mesothelial cells. Malignant effusions may accumulate in the pleuroperitoneal cavity as a result of the mesothelial cell damage caused by this cytokine which is released from disseminated cancer cells.

CEA-mediated homotypic aggregation of human colorectal carcinoma cells in a malignant effusion.

This study was performed to clarify the role of carcinoembryonic antigen (CEA) in the aggregation of colorectal carcinoma (CRC) cells in malignant effusions. We analysed freshly purified CRC cells from one patient, which expressed CEA (98% positive cells) on the surface and formed huge cell aggregates in the patient's ascites. The carcinoma cells expressed Sialyl Lewis A (82%), Sialyl Lewis X (92%) and the beta 1 integrin subunit (78%) but did not express the pair-ligands for these molecules. Cell aggregation was completely inhibited by anti-CEA mAb. The decreased CEA expression induced by phosphatidylinositol-specific phospholipase C (PI-PLC) treatment led to decreased cell aggregation. We also examined the correlation between the degree of cell aggregation and CEA expression using smears of ascites fluid from 27 patients with colorectal cancer. There was a significant correlation between the degree of cell aggregation and CEA expression by CRC cells. The present study provided the first evidence that CEA molecules mediate the homotypic aggregation of CRC cells in malignant effusions.