Hypercoagulability is known to occur in the early phase of hemorrhagic shock. The prolongation of excessive clot formation after recovery from a shock state leads to the formation of microthrombi or disseminated intravascular coagulation which disturbs microcirculation, damaging organ function. The aim of the present study is to investigate the beneficial effect of a synthetic protease inhibitor, 6-amidino-2-naphthyl p-guanidinobenzoate dimethanesulfonate (nafamostat mesilate), in the attenuation of hypercoagulability in hemorrhagic shock. A model of hemorrhagic shock that simulates the clinical course of injured patients was created in anesthetized dogs. The animals were divided into two groups: a control group (group-C, n=9) and an experimental group (group-E, n=9). Animals received saline or 0.2 mg/kg of nafamostat mesilate respectively when their mean arterial pressure declined to 50 mmHg. The serum concentration of hydroxytryptamine (5-HT), prothrombin time (PT), and activated partial thromboplastin time (APTT) were determined as indicators of platelet activity and blood coagulation.
In group-C, serum 5-HT was elevated significantly at 60 min after hemorrhagic shock but not so in group-E. The APTT at 30 and 60 min was shorter in group-C than in group-E. The PT at 30 min was also shorter in group-C. Plasma fibrin degradation products (FDP) increased at 60 min after the induction of shock in group-C. The results indicate that inadequate tissue perfusion in shock stimulates blood coagulation and that nafamostat mesilate might be beneficial in decreasing excessive blood coagulation. (J Nippon Med Sch 1997 ; 64: 9-15)

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To determine the appropriate timing for surgical intervention in infective endocarditis (IE), we evaluated 24 patients (17 males, 6 females, with one included twice) who underwent surgical intervention for IE of native valves (NVE, n=21) and prosthetic valves (PVE, n=3) between January 1989 and September 1994. The mean age was 41 ± 13 years (range 6 to 64 years). The most common infective organisms were Staphylococcus (33% of NVE) and Streptococcus (19% of NVE), with five NVE patients (24%) negative for blood culture. The PVE patients showed a different pattern of infecting organisms, with Enterococcus in one and Pseudomonas in another. From the resected valve culture and pathological findings, 12 patients were in the active stage at operation.
Two in-hospital deaths occurred for a mortality rate of 8.7% (2/23). Further, surgical interventions were performed earlier with Staphylococcal infections than with Streptococcal infections, because hemodynamic compromise presented more progressively in the former. Also resected valve cultures and the pathological findings showed that a persistent infectious process existed in many cases of Staphylococcal infection in spite of intensive antibiotic therapy.
In conclusion, we suggest that internists make referrals for surgical intervention for patients with NVE or PVE as early as possible in the active stage of infection. (J Nippon Med Sch 1997; 64: 16-21)

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Tumor tissue samples were obtained from each of ten patients with stomach cancer who had undergone surgery. The simultaneous detection of signals from 17 alpha pericentromeric and 17 p 13.1 loci after hybridization with the appropriate probes was carried out on 100-200 tumor cells in each case. The copy number category (i.e., monosomy, disomy, trisomy, and so on) was defined as described by Waldman et al., and the deletion of a gene of interest was defined as described by Matsumura et al.
The copy number category was monosomic in seven and disomic in three out of ten cases. The frequency of the copy number 2 (two centromeric signals per nucleus) was lower in tumor cells than in control cells that comprise normal gastric epithelium cells and cells from a normal fibroblast cell line. The copy numbers 3, 4, 5, and above (polysomy) were more frequent in tumor cells, whereas no normal cells having three or more centromeric signals per nucleus was present in the control. Incidence of p 53 gene deletion in ten patients ranged from 55.4% to 90.0%, and from 1.5% to 30.7% if nuclei having three or more copy numbers were taken into consideration. The mean incidence of the p 53 deletion was significantly higher in the differentiated type than in the undifferentiated type of carcinoma (p<0.02). Various types in the combination pattern of 17 alpha centromere/17 p 13.1 signals were observed, and the most frequent pattern in the ten cases was a combination of 1/1. The deletion of chromosome 17 p may play an important role in carcinogenesis of the stomach. (J Nippon Med Sch 1997; 64: 22-29)

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The relationship between blood group-related antigen A and cell proliferation was studied in a pancreatic carcinoma cell line (PGHAM-1) induced by N-nitrosobis (2-oxopropyl) amine (BOP) in hamsters. In vitro, the cell proliferation of PGHAM-1 was inhibited in a culture medium with an added monoclonal antibody (MoAb) against blood group-related antigen A depending on its concentration. In in vivo experiments, immunohistochemical double staining was performed using MoAb against blood group-related antigen A and bromodeoxyuridine (BrdU) in pancreatic carcinomas by intrapancreatic transplantation of PGHAM-1.
Antigen A was expressed in the cell membrane and cytoplasm of PGHAM-1 cells. The BrdU labeling index (LI) in lesions with strong expression of MoAb A (≥50%) was 27.4±5.00, whereas the BrdU LI in lesions with weak expression of MoAb A (≤10%) was 11.9±2.10.
The mean LIs in strongly expressed lesions of MoAb A were higher than those in weakly expressed lesions of MoAb A (p<0.01). These results indicated that antigen A might be associated with cell proliferation in pancreatic carcinomas induced in hamsters. (J Nippon Med Sch 1997; 64: 30-38)

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A method was established for detecting mutations in the mouse p53 gene by cDNA-PCR-SSCP, using four cell lines which were derived from forestomach tumors induced in CDF¹ mice by 2-amino-3, 4-dimethylimidazo [4, 5-f] quinoline (MeIQ). All the cell lines were demonstrated to have mutations in exons 4, 5, 7 and 10, respectively, and the method was confirmed to be efficient and reliable. It was therefore used to analyse the role of p53 gene mutations in forestomach carcinogenesis induced by MeIQ, by examining four original tumors, one papilloma, two primary carcinomas and one lymph node metastasis. The papilloma (F 14) and the carcinoma (F 12) had mutations, but the lymph node metastasis of F 12 mouse (F 12 LN) did not. These results thus indicate that p53 mutations may occur relatively early but do not confer any predisposition for lymph node metastasis. (J Nippon Med Sch 1977; 64: 39-44)

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Allergic rhinitis and nasal polyposis are upper airway inflammatory conditions char-acterized by increased numbers of eosinophils and metachromatic cells in the epithelial layer of the nasal mucosa. However, the mechanism by which these cells accumulate still remains obscure in many respects. It is suggested that the granulocyte-macrophage colony stimulating factor (GM-CSF) plays an important role in the nasal mucosa, since the supernatant of cultured epithelial cells induce differentiation of peripheral mononuclear cells into metachromatic cells and eosinophils, and this activity was inhibited by the anti-GM-CSF antibody. In addition, the presence of several cytokines in the supernatant of nasal epithelial cell cultures has been reported. These observations suggest the possibility that GM-CSF and cytokines play an important role in the allergic and inflammatory reactions of the nasal mucosa. In the present study epithelial cells of nasal mucosa were cultured under different conditions to find out the optimal conditions of production for GM-CSF and interleukin-6 (IL-6). When the concentration of fetal calf serum (FCS) in the culture medium was varied, the number of cultured epithelial cells and the concentration of GM-CSF and IL-6 in the super-natant showed an FCS concentration-dependent increase. When nasal mucosal epithelial cells were cultured in 15% FCS, production of both GM-CSF and IL-6 was increased with increas-ing duration of incubation. There was no significant difference in production of GM-CSF or IL-6 between the patients with allergic rhinitis and those with nasal polyps. These results suggest that neither allergic rhinitis nor nasal polyposis are associated with the ability of epithelial cells to produce cytokines, but the interplay of various factors in the epithelial layer, as well as of diseases, affects their ability to produce cytokines. When the condition of epithelial cell propagation was rendered favorable or unfavorable by varying the concentra-tion of FCS in the culture medium, using the same culture system, production of GM-CSF and IL-6 was increased in a dose-dependant manner (%) favoring epithelial cell growth. These observations indicate that epithelial cells produce GM-CSF and IL-6 only when conditions are favorable for their proliferation is required. (J Nippon Med Sch 1997; 64: 45-52)

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We experienced a 49 years old female SAD patient who showed a good response the next day after alprazolam 1.2 mg administration. The back ground EEG of the patient showed a abnormal EEG with slow waves. The personality was colored with histerical features. The nadir of body core temperature from rectum slightly delayed in remission phase compared with depressive phase. The patient became hypomania and calmed down gradually. Alprazolam tratment is seemed to be available for SAD patients. (J Nippon Med Sch 1997; 64: 53-56)

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