Impact of lymph node metastasis on survival in patients with pathological T1 carcinoma of the ampulla of vater

To determine the prognostic factors for patients with pathological T1 (pT1) carcinoma of the ampulla of Vater, 36 consecutive patients with carcinoma of the ampulla of Vater who underwent surgery were retrospectively analyzed in terms of clinicopathological features. The overall 5-year Kaplan-Meier survival in all patients was 50.2%, and the median survival of all patients was 64.0 months. Factors favorably influencing a long-term outcome were the absence of lymph node metastasis (P<0.0001), the absence of ulcer formation of the tumor (P=0.0062), and the absence of tumor invasion into the duodenum (P = 0.0025) and the pancreas (P=0.0098). In a multivariate analysis, lymph node metastasis was the only predictor of survival (P=0.0023). In the pT1 stage patients, 20% of the patients had lymph node metastasis, and their survival was statistically poor compared to the pT1 patients without lymph node metastasis (P=0.017). As for survival after the operation, there was no significant difference between pancreatoduodenectomy and pylorus-preserving pancreatoduodenectomy.     

Preoperative diagnosis of internal mammary node metastases in patients with breast cancer by using ultrasonography]

US findings of 81 patients with breast cancer were analyzed respectively to evaluate the usefulness of US in the preoperative diagnosis of internal mammary mode metastases. The internal mammary area (I.M.A.) in which internal mammary nodes lie was shown as a hypoechoic stripe in a sagittal scan along the sternum and as a triangular or spindle-shaped hypoechoic area in a transverse scan in the intercostal space. The US features of each I.M.A. in the first three intercostal spaces were divided into three patterns: Pattern-A wad defined as widening of the ipsilateral side of the I.M.A. compared with the contralateral side; Pattern-C was defined as normal at both sides of the I.M.A. Pathological examination confirmed the node metastases in 85.7% of intercostal scans showing Pattern-A and in 35% of intercostal scans showing Pattern-B. Only one of 189 intercostal scans showing Pattern-C had nodal metastases. The overall accuracy was 88.1% in 243 intercostal scans and 90.1% in 81 patients. We conclude that US is useful in the detection of internal mammary node metastases in patients with breast cancer.     

Acquisition of interleukin-3 independence in FDC-P2 cells after transfection with the activated c-H-ras gene using a bovine papillomavirus-based plasmid vector.

Since the ras family of proto-oncogenes is supposed to be involved in leukemogenesis by point-mutational activation, we studied the effect of the activated ras gene on the growth of a murine interleukin-3 (IL-3)-dependent cell line, FDC-P2. The human activated c-H-ras gene was transfected into FDC-P2 cells by electroporation using a high-level expression vector, BMGhph, which contains a partial DNA sequence from bovine papillomavirus (BPV) and a hygromycin B (hmB)-resistant gene as a selectable marker. The transformed FDC-P2 cells showed a high incidence of IL-3-independent growth and tumorigenicity in nude mice. These clones did not express or secrete IL-3, suggesting the acquisition of IL-3 independence by a nonautocrine mechanism. The high incidence of autonomous growth may be due to the use of the BMG vector, because (1) the activated ras gene in pBR322 vector (pHs-49) was not so efficient in the induction of IL-3 independence, (2) the c-H-ras genome copies per cell increased in number up to about 50 copies by using the BMG vector, and (3) cotransfection with the activated ras gene and the BPV gene in separate plasmids partly enhanced the incidence of autonomous growth without increasing the copy number of the ras gene compared with transfection with the activated ras gene alone. The present study supports the idea that the activation of ras gene is an important step in malignant transformation of hematopoietic cells and suggests that the BPV gene products may cooperate with ras gene activation probably by affecting the cellular genes that may be involved in multistep leukemogenesis. The BMG vector may be useful to test the transforming ability of oncogenes whose oncogenic potential is relatively low.     

Perceptual dysfunction in hemiplegia and automobile driving.

Sixteen post-stroke, hemiplegic patients, who requested that they be allowed to return to driving, were extensively evaluated by a physiatrist, psychologist, occupational therapist, and driver training specialist. After they completed a driver training program, the patients were divided into three groups based on their driving program success and follow-ups. Significant differences in the psychological test results were found between Group I (those who drove without any difficulty) and Groups II and III (those who drove limited distance or who failed driver training). Results suggest that patients with significant cognitive and perceptual problems who take training and limit their driving can be safe drivers when they return to driving.     

Menaquinone (vitamin K2)-6 production by mutants of Flavobacterium meningosepticum

Flavobacterium meningosepticum IFO 12535, a menaquinone (MK) producer, was mutagenized to improve productivity. A mutant, which was resistant to 1-hydroxy-2-naphthoate (HNA), was found to produce MK more abundantly: 34 mg/liter of culture broth and 5.5 mg/g of dry cells. The mutant was less sensitive to inhibition by HNA on MK biosynthesis than the wild-type strain. MK was isolated from cells of the mutant and identified as MK-6 based on its physicochemical characteristics. Mutants, which were given each KCN resistance, aromatic amino acid auxotrophy and no carotenoid productivity, did not show further increase of productivity.     

Pivotal function for cytoplasmic protein FROUNT in CCR2-mediated monocyte chemotaxis

Ligation of the chemokine receptor CCR2 on monocytes and macrophages with its ligand CCL2 results in activation of the cascade consisting of phosphatidylinositol-3-OH kinase (PI(3)K), the small G protein Rac and lamellipodium protrusion. We show here that a unique clathrin heavy-chain repeat homology protein, FROUNT, directly bound activated CCR2 and formed clusters at the cell front during chemotaxis. Overexpression of FROUNT amplified the chemokine-elicited PI(3)K-Rac-lamellipodium protrusion cascade and subsequent chemotaxis. Blocking FROUNT function by using a truncated mutant or antisense strategy substantially diminished signaling via CCR2. In a mouse peritonitis model, suppression of endogenous FROUNT markedly prevented macrophage infiltration. Thus, FROUNT links activated CCR2 to the PI(3)K-Rac-lamellipodium protrusion cascade and could be a therapeutic target in chronic inflammatory immune diseases associated with macrophage infiltration.     

SOLITARY GASTRIC POLYPS IN THE FUNDIC GLAND AREA A Histochemical Study

Six solitary gastric polyps in the acid-secreting fundic mucosa were histo-chemically investigated using the mucin histochemistry, immunoperoxidase method, and silver methods for endocrine cells. Histologically, the polyps were grouped into three types : they largely consisted of either hyperplastic foveolar cells (group 1), normal-appearing fundic gland cells with mild cystic changes (group 2) or hyperplastic fundic gland cells with cystic dilatation (group 3). The presence of parietal cells and mucous neck cells was confirmed in all polyps by the immunoperoxidase method using parietal cell autoantibody and the paradoxical Concanavalin A staining, respectively. Regarding the endocrine component, somatostatin-containing cells, Grimelius-positive argyrophil cells, and Fontana-Masson-positive enterochromaffin cells were scattered in the fundic gland area of the polyps as well as in the surrounding normal-appearing fundic mucosa. Gastrin-containing cells were absent. In one of the group 2 polyps and both group 3 polyps, a varying number of glicentin-containing cells were found among the fundic gland components : In one polyp in group 3, glucagon immunoreactivity was detected in the glicentin-containing cells. These findings suggest that some of the polyps express characteristics of the fetal fundic mucosa, since glicentin and glucagon immunoreactivities in normal human stomach have been detected exclusively in the fetal fundus. ACTA PATHOL. JPN. 35: 831–840, 1985.     

Follicular epithelial cell hypertrophy induced by chronic oral administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin in female Harlan Sprague-Dawley rats

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) affects the thyroid morphologically and/or functionally in adult animals. Recently, the National Toxicology Program conducted a 2-year gavage study of TCDD in female Harlan Sprague-Dawley rats. The only treatment-related alterations found in thyroid follicles were decreased luminal size and increased height of the follicular epithelial cells, without prominent protrusion into the lumen. The present study elucidated the nature of these follicular lesions. Thyroid glands of 10 rats each from the control, high (100 ng/kg/day)-dose, and stop-study (100 ng/kg/day, 30 weeks; vehicle to study termination) groups in the 2-year study were evaluated microscopically. Twenty randomly selected follicles were measured morphometrically in each animal. TCDD treatment significantly decreased the mean ratio of luminal/epithelial areas and increased the mean sectional epithelial height of the high-dose group compared to controls. Thyroid sections were immunostained with antibody against minichromosome maintenance (MCM) proteins, a novel cell-cycle biomarker. The MCM labeling index of the high-dose group was significantly higher than that of the control; however, the TUNEL labeling index was also higher in the high-dose group than the control. All data from the stop group were comparable to those from controls. These results indicate that the follicular cell response was hypertrophic and reversible. This information should contribute to diagnosis of nonneoplastic thyroid follicular lesions in rats.