Immunopathology of the implantation site utilizing monoclonal antibodies to natural killer cells in women with recurrent pregnancy losses

PROBLEM: Placental lesions of 71 women with documented recurrent spontaneous abortions of unknown etiology were evaluated using immunohistochemical staining. METHOD OF STUDY: Placental tissue blocks (less than 12 weeks gestation) from prior pregnancy losses were obtained, recut, and analyzed utilizing monoclonal antibody to identify the trophoblast (cytokeratin 8/18) and natural killer (NK) cells (CD57) at the implantation site. The following features were evaluated: trophoblast invasion pattern; syncytium formation; vasculitis and thromboembolism of decidual vessels; decidual inflammation; decidual necrosis; fibrin deposition at the decidual necrosis site; mononuclear-cell infiltration in villi and intervillous space; perivillous fibrin deposition; trophoblast morphology; and quantitation of CD57+ NK cells within the decidual tissue near the implantation site. Controls consisted of 20 healthy women with no history of recurrent pregnancy losses, who had their pregnancies electively terminated. RESULTS: Of the women studied, 29.6% demonstrated elevated CD57+ NK cells at the implantation site (P = 0.030), 54.1% had inadequate cytotrophoblast invasion depth (P = 0.000), 44.1% demonstrated inadequate syncytium formation (P = 0.004), and 33.9% presented thromboembolism in decidual vessels (P = 0.025). CONCLUSION: Some women with recurrent spontaneous abortions demonstrate abnormal placental lesions at the implantation site. Immunopathologic evaluation of the placental implantation site that terminated in a spontaneous abortion may reveal the immunopathogenesis of previous pregnancy losses.     

Production and characterization of monoclonal antibodies against human airway mucins

The objective of this study was to generate and characterize monoclonal antibodies (MAbs) against human airway mucins, and therefore, should serve as a useful tool in studying the regulation of airway mucins in various physiological or pathological situations of human airway. As an antigen, we used a high molecular mass mucin preparation purified from the sputum of normal human subjects. Two monoclonal hybridomas, namely MAbs HM02 and HM03 were obtained and they showed strong immunoreactivity against purified or crude mucin in sputum or bronchial washing of normal human subject. With the high immunoreactivity of these MAbs, mucin contents could be analyzed with more than 100-fold dilution of human airway secretion. The antibodies recognized carbohydrate epitopes because their immunoreactivity was completely abolished by treatment of the mucin with 5 mM periodate. Further characterization of MAbs HM02 and HM03 showed that: (1) they belong to the IgM type; (2) they bind to high molecular mass mucins based on Western blot; (3) they could indirectly immunoprecipitate human airway mucin and as we know, this is the first to demonstrate immunoprecipitation of human airway mucin with anti-human mucin antibodies; and (4) they bind to the goblet cell in airway epithelium as well as some submucosal glands based on immunohistochemistry. Therefore, MAbs HM02 and HM03 should be able to serve as an invaluable tool in studying the regulation of airway mucins in various physiological and pathological situations of human airway.     

Myelin glycosphingolipid/cholesterol-enriched microdomains selectively sequester the non-compact myelin proteins CNP and MOG

Plasma membranes are complex arrays of protein and lipid subdomains. Detergent-insoluble, glycosphingolipid/cholesterol-enriched micro-domains (DIGCEMs) have been implicated in protein sorting and/or as sites for signaling cascades in the plasma membrane. We previously identified the presence of DIGCEMs in oligodendrocytes in culture and purified myelin and characterized a novel DIGCEM-associated tetraspan protein, MVP17/rMAL (Kim et al. (1995) Journal of Neuroscience Research 42, 413–422). We have now analyzed the association of known myelin proteins with DIGCEMs in order to provide a better understanding of their roles during myelin biogenesis. We used four well-established criteria to identify myelin DIGCEM-associated proteins: insolubility in a non-ionic detergent Triton X-100 at low temperature (4°C), flotation of the insoluble complexes to low density fractions in sucrose gradients, and TX-100 solubilization at 37°C, or at 4°C following treatment with the cholesterol-binding detergent saponin. We demonstrate that these proteins fall into four distinct groups. Although all tested proteins could be floated to a low-density fraction, proteolipid protein (PLP), myelin basic protein (MBP) and myelin associated glycoprotein (MAG) were solubilized by the detergent extraction, and connexin32 (Cx32) and oligodendrocyte-specific protein (OSP) met only some of the criteria for DIGCEMs. Only the non-compact myelin proteins 2,3-cyclic nucleotide 3-phosphodiesterase (CNP) and myelin/oligodendrocyte glycoprotein (MOG) satisfied all four criteria for DIGCEM-associated proteins. Significantly, only 40% of CNP and MOG were selectively associated with DIGCEMs. This suggests that they may have both non-active soluble, and functionally active DIGCEM-associated, forms in the membrane, consistent with current views that DIGCEMs provide platforms for bringing together and activating components of the signal transduction apparatus. We therefore propose that CNP and MOG may have unique roles among the major myelin proteins in signaling pathways mediated by lipid-protein microdomains formed in myelin.     

Short-term effects of a new intravascular nitinol stent in canine arteries

RATIONALE AND OBJECTIVES: To evaluate the short-term effects of a new nitinol stent on canine arteries. METHODS: Eighteen nitinol mesh stents were placed in abdominal aortas, common iliac arteries, and renal arteries of six dogs. Angiography was performed to evaluate the patency rates and structural changes of arteries at 1 day, 3 weeks, 4 weeks, and 10 weeks after stent insertion. Gross and light microscopic examinations were performed after angiography. RESULTS: On angiography, the patency rate was 100%, and no thrombosis was observed. All side branches from stented segments were patent. The mean neointimal thickness over and between stent wires was 94 and 167 microns. No difference was found between the aorta and the small vessels. Histologically, the neointima was covered with endothelium and was composed of subintimal fibrosis with mild inflammation. CONCLUSIONS: The new type of nitinol mesh stent showed a high patency rate, with no thrombosis and relatively thin neointimal proliferation.     

Intracranial germinomas: correlation of imaging findings with tumor response to radiation therapy

OBJECTIVE: The purpose of this study was to correlate imaging characteristics of intracranial germinomas with response to radiation therapy. MATERIALS AND METHODS: Using tumor size at the completion of irradiation, we classified 23 patients with histologically proven germinomas in the pineal gland (n = 6), the suprasellar region (n = 7), and the basal ganglia (n = 10) into two groups: excellent response group (n = 14) and good response group (n = 9). Excellent response was defined as complete resolution or residual tumor less than 1.0 cm in diameter, and good response was defined as residual tumor of 1.0-3.0 cm in diameter. CT (n = 53) and MR (n = 32) images obtained before, during, and after radiation therapy were retrospectively analyzed with particular attention to the location, size, presence of cystic change, and CSF seeding of the tumors. RESULTS: In all 23 patients, the tumors decreased 85-100% in size at the completion of irradiation with 40-56 Gy. A significant factor in the different responses to irradiation between patients in the excellent and good response groups was cystic change of the tumor. Tumors with cystic components responded more slowly and had larger residual lesions than did tumors without cystic components (p < .01). In eight of 12 cystic tumors, the cystic portion of the tumor responded more slowly than did the solid portion and remained visible on imaging 6-12 months after irradiation. We found no significant differences between the two groups in location, size, and CSF seeding of tumors. In 12 patients with residual lesions at the completion of irradiation, the tumors proceeded to resolve after completion of treatment. CONCLUSION: In our study, tumor response to radiation therapy correlated negatively with the presence of a cystic region.     

Pancreatitis in association with Clonorchis sinensis infestation: CT evaluation

OBJECTIVE: The purpose of this study was to describe the CT characteristics in patients with Clonorchis sinensis pancreatitis. CONCLUSION: CT showed that in the presence of diffuse mild intrahepatic bile duct dilatation, the enlargement of the body or tail (or both) of the pancreas, with a cluster of small cystic changes within the pancreatic parenchyma, was strong evidence for the possibility of C. sinensis pancreatitis.     

Collision tumors of the ovary associated with teratoma: clues to the correct preoperative diagnosis

PURPOSE: Collision tumors represent a coexistence of two adjacent but histologically distinct tumors without histologic admixture in an organ. The purpose of this study was to describe the imaging findings of collision tumors of the ovary associated with teratoma and to look for clues that might lead to the correct preoperative diagnosis. METHOD: Seven pathologically proven cases of collision tumor of the ovary associated with teratoma were retrospectively reviewed. Ovarian teratomas were coexistent with mucinous cystadenoma (n = 4), borderline mucinous tumor (n = 1), mucinous cystadenocarcinoma (n = 1), and dysgerminoma (n = 1). US (n = 5), CT (n = 3), and/or MRI (n = 4) findings were evaluated. RESULTS: In addition to the typical findings of teratoma, the mass contained a multiloculated cystic portion filled with nonfatty fluid, suggesting the coexistent epithelial tumor in five cases. In one case, the mass contained a large solid component, suggesting the possibility of collision tumor. In the remaining one case, coexistent small mucinous cystadenoma could not be identified. CONCLUSION: Preoperative imaging for ovarian teratoma revealed a collision tumor in six of seven cases. The possibility of a collision tumor should be considered when an ovarian teratoma has imaging findings that cannot be explained solely by an ovarian teratoma.     

Postoperative adjuvant therapy for stage II non-small-cell lung cancer

BACKGROUND: Stage II non-small-cell lung cancer is regarded as one of the early lung cancers. Although resection, including the mediastinal lymph nodes, is currently regarded as the standard treatment, the survival rate of this disease is not encouraging. It is well known that the most common causes of death are locoregional recurrences or distant metastases, or both. However, the best adjuvant treatment to improve survival is as controversial an issue as ever. METHODS: This study was designed as a randomized, blinded, two-armed study with operation and adjuvant radiotherapy in one arm, versus operation and adjuvant mitomycin C (10 mg/m2), vinblastine (6 mg/m2), and cisplatin (100 mg/m2) (MVP) chemotherapy in the other arm. We assigned 57 resected patients with pathologic proven stage II non-small cell lung cancer to the groups according to our eligibility criteria. RESULTS: The most common pattern of recurrence was distant metastases, and nearly all the recurrences (17 of 18 patients) in both groups were found within 2 years after operation. The rates of the locoregional and distant metastases were 3.6% and 46.4% in the adjuvant radiotherapy group and 6.9% and 10.3% in the adjuvant chemotherapy group (p = 0.018). The 5-year disease-free survival rates were 52.0% in the adjuvant radiotherapy group and 74.0% in the adjuvant chemotherapy group (p = 0.16, log-rank test). The 2-year, 5-year, and 6-year survival portions were 60.3%, 56.5%, and 28.3% in the adjuvant radiotherapy group, and 82.8%, 70.1%, and 60.1% in the adjuvant chemotherapy group (p = 0.01, p = 0.17, and p = 0.03, Z-test). The difference of the actuarial survival between these two groups was somewhat significant (p = 0.09, log-rank test). CONCLUSIONS: Our results suggest that the addition of adjuvant MVP chemotherapy may reduce the distant metastasis rates and prolong the survival of the surgically resected stage II non-small-cell lung cancer patients.