Cell-cycle dependent tyrosine phosphorylation on mortalin regulates its interaction with fibroblast growth factor-1.

We previously reported that endogenously expressed, intracellularly localized fibroblast growth factor (FGF)-1 interacts with mortalin. Here we report that FGF-1 added to the culture medium of quiescent BALB/c3T3 cells is taken up by the cells and interacts with mortalin in the cells in a regulated manner. Although both the internalized FGF-1 and mortalin were present at high levels throughout the FGF-1-initiated cell cycle, their interaction became apparent only in late G1 phase. Interestingly, mortalin was preferentially tyrosine phosphorylated at the same time, and when its normally weak phosphorylation in early G1 phase was augmented by treating the cells with vanadate, a strong interaction between mortalin and FGF-1 was established. Conversely, when phosphorylated mortalin was treated with tyrosine phosphatase, its interaction with FGF-1 was abrogated. These results indicate that FGF-1 taken up by cells preferentially interacts with mortalin in late G1 phase of the cell cycle, and that tyrosine phosphorylation of mortalin regulates this interaction.

Multiple duodeno-jejunal diverticula causing massive intestinal bleeding.

A case of massive intestinal blood loss from multiple duodeno-jejunal diverticula is described. A 39-year-old man was referred to our hospital because of recurrent bloody stool and worsening anemia. Upper and lower endoscopy, selective abdominal angiography, and radionuclide scanning were performed to seek the cause of the intestinal bleeding, but none of these studies revealed the source of bleeding. Small-bowel barium follow-through examination showed numerous diverticula in the distal duodenum and proximal jejunum. Excision of the duodenal diverticulum and resection of the involved portion of the jejunum cured the patient. On histopathological examination, an ulcerative lesion with an exposed vessel suggestive of the source of bleeding was seen in the resected duodenal diverticulum. Although duodeno-jejunal diverticula are rare, the importance of a careful search for this malformation in a patient with intestinal blood loss is stressed.

Fibroblast growth factor-1 interacts with the glucose-regulated protein GRP75/mortalin.

Fibroblast growth factor-1 (FGF-1), which lacks a signal peptide and is intracellularly localized as a result of endogenous expression or endocytosis, is thought to be involved in regulating cell growth and differentiation. In the study reported here, we purified proteins that bind intracellular FGF-1. Affinity adsorption was used to purify FGF-1-binding proteins from rat L6 cells expressing FGF-1. One of the isolated proteins was identified as the glucose-regulated protein GRP75/mortalin/PBP-74/mthsp70, a member of the hsp70 family of heat-shock proteins known to be involved in regulating glucose responses, antigen processing and cell mortality. The interaction of FGF-1 and GRP75/mortalin in vivo was confirmed by co-immunoprecipitation, immunohistochemical co-localization in Rat-1 fibroblasts and by using the yeast two-hybrid system. Moreover, a binding assay in vitro with the use of recombinant FGF-1 and mortalin demonstrated a direct physical interaction between the two proteins. These results reveal that GRP75/mortalin is an intracellular FGF-1-binding protein in cells and suggest that GRP75/mortalin is involved in the trafficking of and/or signalling by FGF-1.

[A case of advanced gastric cancer surviving 3 years and 6 months after resection of Krukenberg's tumor].

Total gastrectomy was performed in a patient with an advanced gastric cancer (stage III). One year and eleven months postoperatively, Krukenberg's tumor was recognized and the prognosis was considered to be poor. A recurrence of ascites was identified. After resection of tumor, CDDP was administered intraperitoneally, and 5-FU tablets were administered orally as a maintenance therapy for a long term. The patient has continued to be in a good condition without any sign of recurrence for three years and six months (ie, five years and five months after previous gastrectomy).

[Macroscopic and histological studies on the gastric carcinoma having arisen from the cardiac gland mucosa--concerning to the esophageal invasion and the reliable surgical cut-line].

Cardiac carcinoma is defined as the carcinoma whose center of the mucosal lesion is located at the area of the stomach within 2.0cm from the esophago-gastric junction. Histological and macroscopical examination was performed concerning to the frequency of macroscopic type, the direction of the mucosal invasion, the tendency of the submucosal invasion and the esophageal invasion by using these cardiac carcinomas. The objects of this study are a hundred and thirty-nine cases of cardiac carcinomas. The conclusions are as follows: 1) Depressed type (Type II c) in early carcinoma, Type Borrmann 2 and Borrmann 3 in advanced carcinoma are the most frequent form of macroscopic types. 2) The majority (87.7%) of the early carcinomas was situated at the lesser curvature and the posterior wall of the cardiac mucosa (Figure 1). 3) The early cardiac carcinoma had a tendency to invade in the mucosal layer along the esophago-gastric junction (Table 2). 4) The cardiac carcinoma was thought to invade into the submucosa in its early phase, comparing to the carcinoma on the other area of the stomach (Table 3). Twenty-four out of thirty-five (68.6%) cases of cardiac carcinoma ranged from 11 to 20mm in diameter invaded into the submucosa (Table 3). 5) Twelve out of seventy-three (16.4%) of early cases and fifty-seven out of sixty-six (86.4%) of advanced cases showed the infiltration into the esophagus (Table 4, Figure 6). The reliable and surgical cut-line of the oral site can be established at the area over 11 mm in the distance from the oral margin of the mucosal invasion in the cases of early cardiac carcinoma, over 25mm in the cases of advanced differentiated type, and over 30mm in the cases of advanced undifferentiated type (Figure 6).