The time course of fibrinogen mRNA expression in liver and plasma coagulative and fibrinolytic activities were examined in rats in which hyperlipidemia had been induced by Triton WR-1339. After injection of Triton WR-1339 (300 mg/ kg) into the tail vein of Sprague-Dawley rats, plasma lipid levels, especially of triglyceride (TG) and VLDL-TG, increased from 1 hr to 48 hr. Plasma fibrinogen, a major coagulative factor, tended to accumulate at 1 hr, significantly decreased at 3 hr and increased again at 24 hr after Triton WR-1339 treatment. The levels of β-chain fibrinogen mRNA increased quickly to 3 hr to markedly higher levels than those of α- and γ-chain fibrinogen, and then decreased from 12 to 24 hr. Moreover, Triton WR-1339 caused a significant decrease in plasma levels of α2-plasmin inhibitor, plasminogen and antithrombin III, a slight increase in the plasma tissue-type plasminogen activator level at 24 hr, and a significant increase in the plasma interleukin-6 level at 3 hr and 6 hr. Triton WR-1339-induced hypertriglyceridemia and hyperfibrinogenemia were therefore associated with changes in a-chain fibrinogen mRNA levels that were negatively correlated with the plasma fibrinogen levels.Accordingly, β-chain synthesis appears to be the rate-limiting step in the synthesis of fibrinogen in liver cells and IL-6 might be involved in the regulation of plasma fibrinogen levels in Triton WR-1339-treated rats. Therefore, Triton WR-1339-treated rats with hyper-triglyceridemia and hyperfibrinogenemia may be a suitable model for studying vascular disease that is characterized by these changes.

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Clinical reports suggest that women may be more prone to develop drug-related QT prolongation and torsades de pointes (TdP) . Lengthening of the QT interval reflects prolonged cardiac repolarization, in which the delayed outward K+ current (Ik) plays a major role. The aim of this study was to investigate the effect of 17 β-estradiol (Es) on Ik using a whole-cell voltage clamp. In isolated guinea pig ventricular myocytes, 10μ mol/L Es decreased Ik.tail elicited by a 5000-msec depolarization, where a slowly activating component of Ik (Iks) dominates (current density using + 50 mV depolariza-tion: control 7.1±2.8vs. Es 5.1±2.0 pA/pF, P<0.05, n=10) . In contrast, 1μ mol/L Es significantly increased Ik.tail elicited by a 250-msec depolariza-tion from -10 to +10 mV (at 0 mV: control 0.68±0.24 vs. Es 0.92±0.24 pA/pF, P<0.05, n=8) . This increase was eliminated by E-4031, suggesting that this increase specifically represents the rapidly activating component of Ik (Ikr) . Es has an acute dose-dependent effect on Ik, and has an opposite effect on Iks and Ikr. These effects may contribute to drug-related QT prolongation and the susceptibility to TdP in women.

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The prognosis of patients with colorectal cancer involving adjacent organs is still poor. In this study, we assessed the therapeutic benefit of surgery and factors that might help the surgeon to decide whether more extensive surgery would be beneficial or not. Between January 1989 and December 1998, 473 consecutive patients with colorectal cancer were retrospectively studied. Colorectal carcinoma involving adjacent organs was seen in 43 (9.1 %) of the 473 cases. Histological invasion was seen in 22 (51 %) of 43 patients. The maximal diameter in patients with the carcinoma involving adjacent organs was larger than that in patients without. The five-year survival time was significantly different between the patients with colorectal cancer involving adjacent organs and without. Curative operation improved the five-year survival rate of the patients with pathological invasion into other organs. Even with histological invasion into other organs, the five-year survival time of the patients without lymph node metastasis was better than that of the patients with metastasis. Our data indicated that aggressive combined resection should lead to better prognosis in selected patients.

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Coagulation factors play an important role in macrovascular and macrovascular disease in diabetes. We studied the time-course of coagulation and fibrinolysis factors in plasma and hepatic levels of fibrinogen and prothrombin mRNA in streptozotocin (STZ) -induced diabetic rats. The hepatic mRNA levels for fibrinogen subunit polypeptides (α-, β- and γ-chains) and prothrombin were determined by quantitative reverse transcription-polymerase chain reaction at 24, 48, 72 hours, 1 and 8 weeks after injection of 50 mg/kg STZ. The plasma fibrinogen contents were increased at 24 and 72 hours in STZ-treated rats and returned to the control level at 1 week. At 8 weeks, plasma fibrinogen levels in control and STZ-treated rats were increased with no significant difference between the two groups of rats. However, the plasma thrombin-ATIII complex level significantly increased with a decrease in plasminogen level at 8 weeks after STZ treatment. The levels of β-chain fibrinogen mRNA increased at 24, 48 and 72 hours and returned to nearly control levels at 1 and 8 weeks. The a-chain fibrinogen mRNA levels decreased significantly to 71% and 84% at 1 and 8 weeks, respectively, whereas the y-chain fibrinogen mRNA levels decreased slightly at 24 hours and increased again at 48 and 72 hours. There were no significant changes in prothrombin mRNA levels at 24, 48, 72 hours or 1 week but levels were slightly decreased at 8 weeks. These results suggest that a moderate decrease in fibrinogen and prothrombin mRNA levels at 8 weeks may be sufficient to induce the hypercoagulation due to the long-term hyperglycemia observed in STZ-induced diabetic rats.

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After right upper (RU) lobectomy, a deformity of the orifice of the right middle lobe bronchus (RMLB) may be observed in some cases. In this study, we examined the relationship between the postoperative deformity of the orifice of the RMLB (ORMLB) and the pre-and post-operative right lung lobar volume ratio. Before and after RU lobectomy, the lobar volume ratio was calculated using computed tomography and the ORMLB was measured using bronchofiberscopy (n=19) . A preoperative ratio of the volume of the right upper lobe (RUL) to the volume of the right lung was not correlated with the postoperative deformity of the ORMLB. When a postoperative ratio of the volume of the right middle lobe (RML) to the volume of the right middle and lower lobes (RMLL) was less than 30%, postoperative deformity of the ORMLB was observed in a case who had preoperative semicircular ORMLB, but not in a case who had a round-shaped ORMLB preoperatively. To study the postoperative change in the RML to RMLL ratio, the preoperative RML to RMLL volume ratio was divided by the postoperative volume ratio. The ORMLB was deformed when the ratio was less than 60%, however, there was no deformity if the ratio was greater than 60%, regardless of the preoperative shape of the ORMLB. In conclusion, the preoperative volume ratio of the RUL to the right lung is not useful to predict the postoperative deformity of the ORMLB. Deformation of the ORMLB is not observed when the preoperative ratio of the volume of the RML to the volume of the RMLL is preserved after surgery.

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The putative HLA-DR associated protein I (PHAPI) is a nuclear protein with a molecular mass of 32 kDa, which consists of about 250 amino acids. The cDNAs encoding the wild-type and mutated PHAPI were ligated into a eukaryotic expression vector, which produces the GFP fusion protein, and were expressed in the mouse fibroblast BALB3T3 cell line. The wild-type PHAPI and a series of mutated PHAPIs which lacked each 20-amino acid segment within the leucine-rich N-terminal region were localized to nuclei, whereas a mutant protein which lacked the acidic C-terminal tail including the potential nuclear localization signal was diffusely spread throughout the whole cell. We have shown previously that PHAPI is phosphorylated in vitro by unknown protein kinases, at Ser-204 in human PHAPI. To investigate the phosphorylation of PHAPI in vivo, mutant PHAPI in which Ser-204 was changed to Ala was also expressed in the cells and was metabolically labeled with a radioactive orthophosphate. The mutant PHAPI was localized to nuclei in the same manner as wild-type PHAPI and was still phosphorylated at Ser residues although the phosphorylation level was slightly reduced compared to that of the wild-type PHAPI. These results suggest that PHAPI might be phosphorylated in vivo at several Ser residues including Ser-204, and that the phosphorylation of Ser-204 is not essential for the nuclear localization of PHAPI.

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Six cDNA sequences encoding the putative HLA-DR associated protein II ( PHAPII), which binds the intracellular domain of HLA class II molecules, were isolated from a mouse embryo cDNA library using a PCR technique. Based on the N-terminal structure of the predicted proteins, these cDNA clones were divided into two groups, PHAPII a and PHAPII β based on sequence similarity to the known PHAPII homologue template activating factors (TAF) -Iα and TAF-I β. Four PHAPIIα cDNA clones (1015, 925 819 and 409 bp) were amplified with the same oligonucleotide primers and two cDNA clones (920 and 869 bp) were amplified with other primers. The 925-bp cDNA, designated PHAPII a, and the 820-bp cDNA, designated PHAPII β, encoded the 289-amino acid TAF-Iα and 177-amino acid TAF-I β, respectively. Although the other four clones were almost identical to PHAPIIα except for small insertions or deletions, the predicted proteins were markedly smaller than the authentic PHAPII due to premature termination of translation or deletion of some of the coding region. Sequence comparison and the fact that the inserted nucleotide sequence included consensus sequences for intron 5'-donor and 3'-acceptor sites suggested that these isoforms are generated by alternative splicing of a single gene. The developmental expression and tissue distributions revealed that both proteins are ubiquitously expressed in different tissues and throughout embryonic development of mouse.

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To improve the quality of trauma care, we adopted the TRISS methodology in Japan from 1995, but have faced difficulties judging the preventability with reliability and objectivity by peer review. In this study, the authors designed and verified a new objective scale based on CT classification and the Glasgow Coma Scale to extract non-preventable death. All trauma patients admitted to 10 designated trauma and emergency medical centers around the Tokyo metropolitan area from April 1, 1994, until March 31, 1996, were reviewed. During the period, 3, 476 trauma patients were admitted, and 351 out-of-hospital cardiac arrests were excluded. Of the remaining 3125 patients, 747 patients were dead, and 189 (25.3%) of them had a Ps value of more than 0.5 and were defined as unexpected death. By peer review, we judged 84 cases as preventable trauma death (PTD) and the other 105 (55.6%) as non-preventable trauma death. There were 346 severe head injury patients without other severe fatal traumas. The mean GCS was compared to mortality for each CT classification. They are statistically significant difference for GCS and mortality. Patients whose mortality exceeds 50% significantly might be decided as non-preventable trauma death without further discussion by peer review. These subgroups include GCS 3 to 5 of D₃, GCS 3 to 5 of D₄, and GCS 3 of SDH. Patients whose mortality exceeds 50%, but not significantly because of a small number might be considered as candidates of non-preventable trauma death at the peer review discussion. These subgroups include GCS 6 to 8 of D₃, GCS 4 to 5 of SDH and GCS 3 to 5 of MIX. This new objective scale will contribute to future trauma analysis and improvement of trauma care quality.

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We report a 43-year-old woman with advanced gastric cancer. Upper GI series and endoscopy revealed Type 3 gastric cancer and abdominal computed tomography showed marked para-aortic lymph node metastases suggesting curative resection was impossible. Neoadjuvant chemotherapy of cisplatinum, mitomycin C and etoposide markedly reduced the tumor, lymph nodes and para-aortic nodes. A total gastrectomy with D4 lymph node dissection, cholecystectomy and distal pancreaticosplenectomy was performed. The resected primary tumor had Grade 2 histology; some lymph nodes were Grade 3. Seven years after surgery the patient has no evidence of recurrence. In conclusion, D4 dissection after effective neoadjuvant chemotherapy may be useful in advanced gastric cancer with marked lymph node metastases.

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A case of endometrial stromal nodule showing immunoreactivity for α-SMA in a majority of the tumor cells, with smooth muscle as a minor component, is reported. This tumor was mainly composed of diffuse proliferation of uniform cells resembling those of endometrial stroma, and included blood vessels resembling arteria spiralis and prominent perivascular whorl arrangement of the tumor cells. In addition, the smooth muscle component was detected by light microscopy. Immunohistochemically, many tumor cells showed α-SMA positivity. In previous studies of endometrial stromal tumor, we showed a variety of combinations and proportions of positivity for several myogenic antibodies, and suggested that endometrial stromal tumor is heterogeneous based on immunoreactivity for several myogenic antibodies. In the present case, a distinction between endometrial stromal nodule and cellular leiomyoma was necessary. We concluded that light microscopic findings, including staining with hematoxylin and eosin, are the most important means for differential diagnosis of this tumor.

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