Clinical significance of faecal calprotectin levels in patients with ulcerative colitis]

AIMS: To assess the clinical significance of faecal calprotectin levels (a neutrophil protein) in patients with ulcerative colitis (UC). METHODS: 25 patients with UC provided stool samples for calprotectin assay and the amount of calprotectin was related to UC disease activity index in each patient. Of 25 patients 4 with prednisolone refractory UC received 10 granulocyte and monocyte adsorption apheresis (GMCAP) sessions of 60 minutes duration, flow rate 30 mL per minute for 10 consecutive weeks. RESULTS: Calprotectin level in consecutive faecal samples from three patients was stable. However, increased calprotectin levels were significantly (p < 0.005) associated with Matts's endoscopic index, reflecting the level of colorectal inflammation. The 4 patients who received GMCAP therapy had a clinical activity index < 2 at week 7, the calprotectin level declined with improving Matts' index. CONCLUSIONS: Assay of faecal calprotectin holds promise as a sensitive biomarker to identify colorectal inflammation.     

Abnormal cerebrospinal fluid plasma cells in a case of myeloma

Cerebrospinal fluid (CSF) involvement in myeloma is rarely seen. Recently we experienced a case with this lesion. A 70-year-old man developed consciousness level disorder during the course of bronchopneumonia. Neurological examination revealed stuporous consciousness, neck stiffness and Kernig's sign. Immunoelectrophoresis showed monoclonal IgG in serum. CSF which was obtained through lumbar puncture was clear and its pressure was 155 mm H2O. It contained 207 white cells/3 mm3; glucose, 54 mg/dl; and protein, 33 mg/dl. The differential count of the CSF was (in %) monocytes, 48.0; plasma cells, 25.5; neutrocytes, 15.5; and lymphocytes, 11.0. Cytoplasm and nucleus of the plasma cells were in various sizes. Some irregular multiple nuclei, flaming cells and grape cells were also observed in them. The cytoplasm of the plasma cells fluoresced with antisera against lambda chains IgG. The value of immunofluorescent technique in identifying plasma cells in the CSF is emphasized.     

Peripheral small-sized (2 cm or less) non-small cell lung cancer with mediastinal lymph node metastasis; clinicopathologic features and patterns of nodal spread

Objective: The diagnosis of small-sized (2 cm or less) non-small cell lung cancer (NSCLC) has increased with the development of computed tomography (CT), whereas unexpected extensive multiple-level mediastinal involvement has been occasionally detected in this small-sized lung cancer. To establish the optimal surgical strategy, we retrospectively analyzed the clinicopathologic features, efficacy of preoperative investigations and lobe specific patterns of nodal spread in small-sized NSCLC with mediastinal involvement. Methods: Among 1550 resected lung cancer cases between 1981 and 2000, 267 (17.2%) had peripheral small-sized NSCLC. Of these, 29 patients (10.8%) with mediastinal lymph node involvement who underwent pulmonary resection and systematic nodal dissection were reviewed. Results: Among 29 patients, 27 patients (93.1%) were adenocarcinoma, and 51.7% (15/29) showed no lymph node enlargement on CT (cN0). Surgical pathology revealed multiple-level mediastinal involvement in 65.5% (19/29) of all patients and 60.0% (9/15) of cN0 patients. All of right upper lobe tumors (n=11) showed multiple-level involvement. Thallium-201 single photon emission computed tomography (201Tl-SPECT) was positive for increased focal uptake in the mediastinum in 72.7% (8/11) of patients. Conclusions: The vast majority of cases were adenocarcinoma, and two thirds of them showed multiple-level mediastinal involvement, even in cN0 patients. We thus recommend to perform systematic nodal dissection or meticulous sampling for accurate intrathoracic staging, especially for right upper lobe tumor. 201Tl-SPECT appears to be more sensitive preoperative investigation for mediastinal metastasis compared with CT scan.     

Structure-function relationships of microcystins, liver tumor promoters, in interaction with protein phosphatase.

Microcystins, isolated from toxic blue-green algae, are potent inhibitors of protein phosphatases 1 and 2A. Recently, we have reported that microcystin LR has a potent tumor-promoting activity on rat liver initiated with diethylnitrosamine. The structure of microcystins is unique in having an unusual amino acid, 3-amino-9-methoxy-10-phenyl-2,6,8-trimethyl-deca-4(E),6(E)-dienoic acid (Adda), which is thought to be significant for the activity. Geometrical isomers at C-7 in the Adda portion of microcystins, 6(Z)-Adda microcystins LR and RR, have been isolated from cyanobacteria. To estimate their tumor-promoting activities and to understand the importance of the Adda portion for activity, the maternal microcystins LR and RR and their isomers were subjected to examination of their interaction with protein phosphatases 1 and 2A and the release of glutamic pyruvic transaminase from rat liver. 6(Z)-Adda microcystins LR and RR bound to protein phosphatases 1 and 2A, inhibited their activities and released glutamic pyruvic transaminase from rat liver into serum, ten to one hundred times more weakly than the maternal microcystins LR and RR. These results indicated that the conjugated diene with 4(E),6(E) geometry in the Adda portion is important in the interaction with protein phosphatases.     

Antibody-Dependent Cellular Cytotoxicity and Natural Killer Activity Against HTLV-1 Infected Cells

Antibody-dependent cellular cytotoxicity (ADCC) and natural killer (NK) ativity were examined using MT-2 cells persistently infected by HTLV-1 as target cells, and mononuclear cells as effector cells, from helathy one-week-old newborn babies, infants, children and adults. More than 10% of ADCC was observed in 17 newborn babies out of 22 (77.3%) and in all 67 healthy one-month-old babies to adults, by adding serum from anti-HTLV-1 positive carriers. When anti-HTLV-1 negative serum was added, less than 10% of ADCC was observed. If infants without anti-HTLV-1 antibodies were breast-fed they had the possibility of HTLV-1 vertical transmission. There was no significant decrease in NK activity between 90 healthy newborn babies, infants, children, or adults. These results suggest that ADCC and NK activity protect against the transmission of HTLV-1 from mother to child.     

Lymphoid tumor in the orbit: malignant or benign? MRI, histomorphological and molecular genetic analysis of eight cases

Differentiation between benign and malignant lymphoid infiltrates of the conjunctiva and the orbit is difficult even on the basis of histopathological appearance. We describe eight cases with low-grade malignant lymphoma, mucosa-associated lesion tissue (MALT) lymphoma. Laboratory analysis was done using microscopy, immunophenotyping and gene rearrangement using the Southern blot technique. DNA-rearrangement analysis allows a very precise determination of the benign and malignant lymphoid infiltrates of the ocular region. Our MRI findings show that these tumors can also generally be distinguished by their signal intensity on T2-weighted images. These findings might explain the favorable prognosis for MALT lymphoma of the conjunctiva and the orbit, and the absence of any recurrence in follow-ups ranging from 6 months to 9 years.     

Activated protein C attenuates coagulation-associated over-expression of fibrinolytic activity by suppressing the thrombin-dependent inactivation of PAI-1

Summary.  Several activated coagulation factors have been reported to enhance fibrinolysis by neutralizing plasminogen activator inhibitor type 1 (PAI-1) activity. We evaluated the physiological relevance of this mechanism using the euglobulin clot lysis time (ECLT) assay in the presence and absence of Ca²⁺, which is controlled by PAI-1 and mimics physiological thrombolysis. We found that the ECLT (18.5 ± 0.6 h) was shortened by Ca²⁺ (5 m m ) (6.6 ± 0.1 h). A significant difference was observed in thrombin generation by the presence of Ca²⁺ in the euglobulin fraction. Prothrombin was almost fully converted to thrombin within 15 min in the presence of Ca²⁺, whereas essentially no conversion was observed without Ca²⁺. The presence of activated protein C (aPC) suppressed thrombin generation, and attenuated the shortening of ECLT in a dose-dependent manner, an effect enhanced by phospholipid and protein S. In the absence of Ca²⁺, aPC did not prolong the ECLT. After addition of biotin-labeled recombinant PAI-1 to the euglobulin fraction, PAI-1 was cleaved to lower molecular weight forms only in the presence of Ca²⁺. This cleavage did not occur in the presence of aPC, suggesting that thrombin was the catalyst for PAI-1 cleavage. The cleavage and inactivation of PAI-1 by generated thrombin is proposed to be responsible for the shortening of ECLT by Ca²⁺ and for coagulation-associated over-expression of fibrinolysis. Under such conditions, aPC appeared to suppress thrombin generation and to normalize highly activated fibrinolysis.     

Peripherally located occult lung cancer with AMFR expression.

A 67-year-old man was referred to our hospital because of positive sputum cytology. Despite detailed examination, the malignant cell source remained elusive. Twenty months later, CT revealed two nodules in the right S1 and S10 regions which were resected. A year following the operation, gastoendoscopy showed a stomach tumor. Total gastrectomy with lymph node dissection was performed. Histologically, this patient was diagnosed with double primary lung cancer with metastasis to the stomach. The tumors of the lung, stomach and tumor cells in the sputum showed the same immunoreactivities of autocrine motility factor receptor (AMFR). In our institution, of 38 occult lung cancers encountered during the past 10 years, four (10.5%) occurred in the peripheral region. The presented four cases of radiologically occult lung cancer in the peripheral resion revealed bad prognosis, as three out of four patients were dead within 24 months after surgery. All of the four cases showed venous invasion, though the size of the primary tumor was small. Careful follow-up, including monitoring for distant metastasis, is necessary in radiologically occult peripheral lung cancer.