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Numerous empirical studies, largely conducted in Western societies, have linked social capital to health outcomes. However, few studies thus far have been conducted in northeastern Asian countries, particularly Japan. Therefore, whether social capital is a determinant of health in Japanese society remains unclear. This study attempted to provide new evidence for the impact of social capital on health in Japan by analyzing original survey data with two different statistical models. In total, 1910 subjects were randomly selected from 210 enumeration districts (EDs) considered in the 2000 population census. In the present study, after excluding missing data on the outcome and predictor variables, we conducted an analysis of 1157 individuals nested within 206 EDs. Ecological and multilevel regression analyses were performed to examine the association between social capital and health, measured by the General Health (GH) perception item (a subcategory of Short Form 36 (SF-36)), and to estimate the impact of aggregated indicators of social capital on health. We developed an original Japanese version of three social capital items (perceived helpfulness, kindness, and greeting) based on previous studies and expert opinions and prepared a social cohesion index that integrated these three social capital items. The ecological model, after adjusting for sociodemographic factors, revealed that perceived helpfulness and greeting, along with the social cohesion index, were observed to have statistically significant associations with GH. The multilevel model, after adjusting for individual social capital perceptions, indicated that the two aggregated indicators of community social capital (kindness and greeting), along with the social cohesion index, showed a statistically significant association with GH. These results showed the existence of a contextual effect of social capital on health outcomes, although individual differences in social capital perceptions in Japan were considered.

Background: The chemokine family plays important roles in cell migration and activation. In humans, at least 44 members are known. Based on the arrangement of the four conserved cysteine residues, chemokines are now classified into four subfamilies, CXC, CC, XC and CX3C. Given that zebrafish is an important experimental model and teleost fishes constitute an evolutionarily diverse group that forms half the vertebrate species, it would be useful to compare the zebrafish chemokine system with those of mammals. Prior to this study, however, only incomplete lists of the zebrafish chemokine genes were reported., Results: We systematically searched chemokine genes in the zebrafish genome and EST databases, and identified more than 100 chemokine genes. These genes were CXC, CC and XC subfamily members, while no CX3C gene was identified. We also searched chemokine genes in pufferfish fugu and Tetraodon, and found only 18 chemokine genes in each species. The majority of the identified chemokine genes are unique to zebrafish or teleost fishes. However, several groups of chemokines are moderately similar to human chemokines, and some chemokines are orthologous to human homeostatic chemokines CXCL12 and CXCL14. Zebrafish also possesses a novel species-specific subfamily consisting of five members, which we term the CX subfamily. The CX chemokines lack one of the two N-terminus conserved cysteine residues but retain the third and the fourth ones. (Note that the XC subfamily only retains the second and fourth of the signature cysteines residues.) Phylogenetic analysis and genome organization of the chemokine genes showed that successive tandem duplication events generated the CX genes from the CC subfamily. Recombinant CXL-chr24a, one of the CX subfamily members on chromosome 24, showed marked chemotactic activity for carp leukocytes. The mRNA was expressed mainly during a certain period of the embryogenesis, suggesting its role in the zebrafish development., Conclusion: The phylogenic and genomic organization analyses suggest that a substantial number of chemokine genes in zebrafish were generated by zebrafish-specific tandem duplication events. During such duplications, a novel chemokine subfamily termed CX was generated in zebrafish. Only two human chemokines CXCL12 and CXCL14 have the orthologous chemokines in zebrafish. The diversification observed in the numbers and sequences of chemokines in the fish may reflect the adaptation of the individual species to their respective biological environment.

Age-related Epstein-Barr virus-positive (EBV(+)) B-cell lymphoproliferative disorder (ALPD) is a disease entity identified from a large-scale re-survey of cases diagnosed as diffuse large B-cell lymphoma. ALPD is a group of EBV(+) polymorphic B-cell lymphoma typically seen in elderly patients. An age-associated decline in host immunity against EBV might be partly responsible for the pathogenesis of ALPD. Histologically, ALPD is often characterized by a minor proportion of EBV-encoded RNA-positive tumor cells in a background of extensive cellular infiltration, similar to that of classical Hodgkin's lymphoma. In contrast to Hodgkin and Reed-Sternberg cells, ALPD tumor cells are clearly positive for B cell markers CD20 and/or CD79a. Hodgkin and Reed-Sternberg cells produce various chemokines, including CCL17 and CCL22, that attract chemokine receptor CCR4-expressing Th2 cells and regulatory T cells. Previously, we have shown that EBV-immortalized B cells also produce CCL17 and CCL22 through latent membrane protein 1 (LMP1)-mediated activation of nuclear factor kappaB. Here we examined expression of CCL17 and CCL22 in ALPD. ALPD tumor cells were often heterogeneous in size in accordance with the differential expression of EBV latent genes at the single cell level. LMP1-expressing tumor cells were typically large in size and selectively positive for CCL17 and CCL22. CCR4(+) cells and forkhead box protein 3(+) regulatory T cells were abundantly present, and the majority of forkhead box protein 3(+) cells were CCR4(+). Collectively, our data show production of CCL17 and CCL22 by LMP1(+) large-sized tumor cells and accumulation of CCR4-expressing cells including regulatory T cells in ALPD.

The present study sought to identify the therapeutic efficacy of adjuvant external beam radiotherapy (EBRT) for carcinomas of the extrahepatic bile duct (EHBD) and gallbladder. Twenty-one patients with pathologically verified EHBD carcinoma and 18 patients with gallbladder carcinoma were analyzed retrospectively by Cox regression analysis for predictors of survival. The overall 5-year survival rates after resection were 33% for EHBD carcinoma and 56% for gallbladder carcinoma. The overall 5-year survival rate for EHBD carcinoma was 60% in 8 patients without microscopic residual disease (R0), 15% in 9 patients with microscopic residual tumor (R1), and 0% in 4 patients with macroscopic residual tumor (R2). The overall 5-year survival rate of gallbladder carcinoma patients was also decreased with R status equal to 73%, 40%, and 0% for R0, R1 and R2, respectively. Adjuvant radiotherapy significantly improved the 5-year survival rate in 7 patients with R1 disease of EHBD carcinoma (P = .035), compared with survival in 2 patients who underwent resection alone. However, no significant difference was noted in the 5-year survival rate between the resection plus EBRT group and the resection alone group for gallbladder carcinoma. Multivariate analysis revealed that histopathologic grade (G) was an independent predictor of survival for EHBD carcinoma and that direct invasion of liver parenchyma was a predictor of survival for gallbladder carcinoma. This study suggests that curative resection provides the best survival for patients with EHBD and gallbladder carcinoma, and that radiotherapy may play a beneficial role in controlling local-regional residual EHBD carcinoma tumors. However, new strategies for adjuvant therapy are needed to improve survival in patients with gallbladder carcinoma.

Effects of radiation therapy for lymph node metastases from gastric cancer were retrospectively analyzed. The radiation sites were residual paraaortic lymph node involvement and postoperative recurrent lymph node metastases in 10 patients. The size of lymph node swelling was decreased in 6 (60%) patients after radiation therapy using liniac. Complaints due to lymph node metastases such as pain and edema of extremities were voiced by 7 patients. These complaints were eventually relieved or disappeared in all 7 patients. There were no severe adverse effects during radiation therapy, and 7 patients (70%) could shift to home care. One-year and 3-year survival rates were 20 and 10%, respectively. Radiation therapy for lymph node metastases from gastric cancer was chiefly effective in relieving complaints. Although it is unclear whether radiation therapy can improve the survival rate, these results suggest that radiation therapy could be one of the most useful locoregional therapies for paraaortic lymph node involvement and recurrent lymph node metastases from gastric cancer.

Classical Hodgkin's disease (HD) is characterized by rare neoplastic Hodgkin and Reed-Sternberg (H-RS) cells within abundant reactive cellular backgrounds. In most cases, H-RS cells originate from the B-cell lineage, but their immunophenotypes are unusual. Here we newly found frequent expression of chemokine receptors CXCR6 and CCR10 and their respective ligands CXCL16 and CCL28 in HD-derived cell lines. CCR10 is known to be selectively expressed by plasma cells, whereas CCL28 attracts eosinophils via CCR3 and plasma cells via CCR10 and CCR3. Therefore, we examined their expression in HD tissues by immunohistochemistry. We found that H-RS cells in 15 of 19 cases were positive for CCL28. Among them, seven cases were also positive for CCR10, suggesting a potential autocrine effect. In situ hybridization confirmed the expression of CCL28 mRNA in H-RS cells. The CCL28 positivity in H-RS cells did not significantly correlate with that of LMP-1, CCL17, CCL22, or CCL11. However, it significantly correlated with the background accumulation of eosinophils, plasma cells, and CCR10+ cells. Thus, the production of CCL28 by H-RS cells may play a major role in tissue accumulation of eosinophils and/or plasma cells in classical HD. The frequent expression of CCR10 in H-RS cells themselves also supports their close relationship to plasma cells.

Compounds which interfere with steroid sulfatase (STS) are expected as important novel therapeutic drugs for postmenopausal breast tumor. Therefore, a number of strategies have been adopted to design and synthesize potent, nonestrogenic STS inhibitors. We chose biphenyl as a scaffold for STS inhibitors and synthesized some biphenyl-4-O-sulfamate derivatives (29-43). Their inhibitory activity on STS and estrogenicity were evaluated. Substitution of electron-withdrawing groups (e.g., cyano, nitro) at the 2'- or 4'-position of biphenyl-4-O-sulfamate remarkably increased STS-inhibitory activity. Especially, 2',4'-dicyanobiphenyl-4-O-sulfamate (35, TZS-8478) showed very potent STS-inhibitory activity in vitro. The administration of TZS-8478 (0.5 mg/kg per day, p.o., for 5 days) completely inhibited rat liver and uterine STS similarly to EMATE (1). Furthermore, TZS-8478 (10 mg/kg per day, p.o., for 5 days) had no stimulative effect on uterine growth in ovariectomized rats, and its desulfamoylated compound (20) was little bound to the human estrogen receptor alpha. The identification of a potent steroid sulfatase inhibitor without estrogenicity, such as TZS-8478, should be of considerable value in evaluating the potential of steroid sulfatase inhibition for breast tumor therapy.

A 69-year-old male was admitted to the hospital for further examination of an abnormal shadow in the right lower lung fields. He was previously under medical treatment for right thoracic empyema. Chest computed tomography (CT) showed a solitary mass, 4.5 cm in diameter and broncofiberscopy evidenced a tumor in the right lower bronchus. The biopsy was performed and the tumor was diagnosed as a pleomorphic adenoma. Intraoperativefinding showed the tumor was 6 cm in gross, extended to the left atrium, and a daughter tumor was palpable in the middle lobe. The middle and lower lobe were resected. The tumor was located in S9, S10, 6 x 4 x 3.5 cm in size, 2 daughter tumor was found in the middle lobe, the pulmonary vein was thickened by tumor invasion. Pathohistologically, main tumor and daughter tumor showed malignant feature, were compatible with adenoid cystic cancer. Four years after operation, he is still now alive with home oxygen therapy.

A 64-year-old man had undergone subtotal gastrectomy with a D2 lymphadenectomy for advanced carcinoma of the stomach with paraaortic lymph nodes metastases 12 months earlier. The histopathological findings revealed a well differentiated adenocarcinoma [type 2 macroscopic findings, SE, INF beta, ly2, v1, N2, M1 (LYM)]. On admission, biochemical investigations showed an elevation of CEA, CA19-9, and CA 125. An abdominal ultrasonography and a computed tomography (CT) revealed lymph node swelling of the paraaorta. After non-curative operation, he has received adjuvant chemotherapy with TS-1 plus CDDP. At first, 100 mg/day of TS-1 was orally administered for three weeks followed by two drug-free weeks, with CDDP (60 mg/m2/day) infused on day 8. Next, the treatment course consisted of four-week consecutive administration of TS-1 (80 mg/day) followed by two drug-free weeks, with biweekly infusion of CDDP at a dose of 15 mg/m2. The CT findings revealed that an almost complete reduction of the metastatic paraaortic lymphnodes was obtained after completion of course 1, and was maintained thereafter. No noteworthy adverse reactions were observed and the patient has a good QOL. The patient is now in a good health and continues to undergo low dose TS-1 plus CDDP chemotherapy as an outpatient.

Major gastrointestinal bleeding is a rare manifestation of intestinal Behçet's disease. We report herein the case of a 64-year-old man with intestinal Beh,et's disease complicated by myelodysplastic syndrome who suffered massive hemorrhage. Colonoscopy demonstrated ulceration of the entire colon from the cecum to the rectum, characterized by punched-out ulcers. Angiography demonstrated apparent extravasation of contrast material in the terminal ileum, and embolization was not successful. Continued and massive bleeding necessitated surgical resection of the involved segment of ileum; however, massive bleeding recurred. Re-endoscopy showed oozing hemorrhage from the multiple colon ulcerations. Intra-arterial prednisolone injection therapy was given, following which the melena gradually subsided and completely stopped within a few days.

In contrast to malignant lymphomas or skin cancer, smooth muscle tumors including leiomyosarcoma are rarely associated with transplant recipients. We herein present a 33-year-old woman with end-stage renal disease who received a transplant at 27 years of age. Four years after the transplantation, at age 31, she underwent a mastectomy because of primary right breast cancer, which was found to be a 5-mm-sized mucinous carcinoma with no regional lymph node metastasis. Six years after the transplantation, a liver tumor was unexpectedly discovered. An explorative laparotomy revealed a well-encapsulated tumor occupying the posterior portion of the right lobe of the liver. The patient underwent a posterior segmentectomy. Histologically, the tumor possessed intermingling fascicles of spindle cells with eosinophilic cytoplasm and elongated nuclei. Based on an immunohistochemical examination, the tumor cells were positive for the muscle-associated antibody. In addition, RNA probes for Epstein-Barr virus were negative based on in situ hybridization. The histologic, immunohistochemical findings were considered to be diagnostic for leiomyosarcoma, which is a low-grade malignancy. Two years after surgery, the patient is doing well with no recurrence of liver tumors or breast cancer.

A 72-year-old woman was admitted to our hospital for further evaluation of a abnormal shadow in left middle lung field. The patient had undergone right mastectomy for infiltrating ductal carcinoma 19 years ago. She had no symptom, but had a time of mass X-ray screening this year. Chest CT finding showed a nodule 2 cm in diameter with slight irregular margin in S6 of left lung. We couldn't determine preoperatively that this tumor was a metastatic lesion or a primary lung cancer. And first, tumor was taken out for intraoperative frozen section diagnosis. Pathologist didn't diagnose whether this tumor was a metastatic or primary. So, we performed left lower lobectomy and mediastinal lymphadenectomy. On postoperative histopathologic finding lung cancer resembled well previous breast cancer. In immunohistochemical study cancer cells from lung and breast of the patient were respectively positive for anti Estrogen Receptor (ER) and anti Gross Cystic Disease Fluid Protein-15 (GCDFP-15). In conclusion lung cancer was diagnosed as a metastatic lesion from breast cancer 19 years ago. The patient has been well 2 years postoperatively without recurrence. In this case immunohistochemical examination was very useful for differentiation metastatic lesion and primary one.

A 58-year-old man was admitted to our hospital for detailed examination of continuous cough. On a chest X-ray film, abnormal shadow was detected in the right lower lung field. Preoperative examination findings didn't lead to a definitive diagnosis. Under thoracoscopy partial resection of the lung was performed to rule out a malignant lesion. Intraoperative pathologic finding revealed a granulomatous lesion. And, final pathological diagnosis showed to be a pulmonary dirofilariasis. His postoperative course was not eventful. On 20 th day he discharged postoperatively. Now, under the Pet-boom the disease has been reported increasingly. But it is difficult to find the disease preoperatively. So, it is real to be operated for differentiate from a malignant lesion. Recently in many cases open lung biopsy, has been undergone with less invasive procedure such as thoracoscopy and VATS. It will be mainstream in future.

A 67-year-old man was admitted to our hospital with blood sputum. Adenocarcinoma was diagnosed by sputum cytological examination. A chest X-ray film showed a tumor shadow in the lower field of the right lung. The middle and lower lobes were resected and lymph node dissection was performed. Tumor was composed of well differentiated adenocarcinoma and spindle cell sarcomatous element, and diagnosed as so-called carcinosarcoma. Pathological staging was IIIA by pT1N2M0. Postoperative chemotherapy was not performed for side effect, so radiotherapy only was done. He died of recurrence and metastasis after about 1 postoperative year.

A 78-year-old female was pointed out an abnormal shadow in left lung field. For 4 years this shadow was followed up as benign tumor. Chest CT scan revealed growing tumor and new tumor in right lung. Tumor resection was performed. Until operation time carcinoid syndrome was not found. This case was diagnosed histopathologically typical carcinoid of peripheral lung.

The preparation of 6- and/or 7-substituted 3-oxo-2-oxasteroids having a spirotetrahydrofuran ring at the 17-position is described. These compounds showed high antiandrogenic potency in the castrated male rat.

We present a case of portal-systemic encephalopathy due to a congenital splenorenal shunt. A 69 year old woman was admitted to hospital because of recurrent episodes of disturbed consciousness. The present episode had begun 3 months prior to admission. Although the patient demonstrated mildly slurred speech, the remainder of her neurological examination was unremarkable. She showed no clinical signs of portal hypertension and her liver function, except for a serum hepaplastin test of 58% and an ICG retention rate of 28% at 15 min, was normal. Her serum ammonium level was 210 micrograms/dL. The venous phase of a superior mesenteric arteriogram revealed a splenorenal shunt and narrowing of the portal vein, which was 4 mm in diameter. The histological findings, demonstrated by a needle liver biopsy specimen, were consistent with mild fibrosis and lymphocytic infiltration. Following the diagnosis of a splenorenal shunt in the absence of liver cirrhosis, ligature of the shunt was performed with a splenectomy. The portal vein pressure after ligature of the shunt rose from 12.5 to 18.8 mmHg. This shunt was thought to be of congenital origin. The high preoperative serum ammonia concentration decreased to the normal range postoperatively and the serum hepaplastin test and ICG retention rate similarly improved postoperatively. A follow-up superior mesenteric arteriogram was performed during the venous phase, demonstrating resolution of the shunt and decreased portal vein narrowing. The patient has suffered no further episodes of disturbed consciousness postoperatively.

11-Oxachlormadinone acetate (17-acetoxy-6-chloro-11-oxapregna-4,6-diene-3,20-dione) and 2,11-dioxachlormadinone acetate (17-acetoxy-6-chloro-2,11-dioxapregna-4,6-diene-3,20-dione) were prepared as potential antiandrogenic agents. The effect of the latter compound on antiandrogenic activity when tested in the castrated rat was shown to be more potent than that of the parent compound, chlormadinone acetate.

We report herein what to our knowledge is the first documented case of a malignant granular cell tumor of the stomach. A 64-year-old woman was admitted to our hospital for investigation of gastric submucosal tumor. Endoscopy disclosed a large hemispherical mass located on the lesser curvature at the gastric antrum with a normal mucosal surface, and computed tomography (CT) revealed a solid tumor about 7 cm in diameter with clear margins. A laparotomy was carried out under the preoperative diagnosis of leiomyosarcoma of the stomach. A tumor was found in the gastric antrum, with extragastric extension to the hepatic hilum, and a distal partial gastrectomy was performed. However, a follow-up CT scan performed 21 months postoperatively revealed a solid tumor of about 10 cm in diameter with clear margins, situated between the liver and the transverse colon. This was subsequently diagnosed as local recurrence and a resection was carried out. Microscopic examination of both the first and second specimens showed that the tumor cells were large and polygonal, with medullary proliferation and finely granular eosinophilic cytoplasm. Mitotic figures were also present. Thus, the lesion was diagnosed as a malignant granular cell tumor of the stomach from the clinical and pathological findings.

The metabolism of levonorgestrel (LNG) in the bile following oral administration of the drug was examined in female rat. 1) Within 48 h after administration of 14C-labelled LNG (LNG-14C), 67-82% of the radioactivity was excreted into the bile. 2) Almost all the metabolites in the bile were conjugated with glucuronic acid or sulfuric acid and only a small amount of the unchanged compound was found. 3) After treatment of these metabolites in the bile with beta-glucuronidase and arylsulfatase, more than ten aglycones were detected on TLC. Three main aglycones, M1, M2 and M3, were isolated. They accounted for 68.0, 0.8 and 11.5% of the radioactivity excreted into the bile, respectively. 4) The structures of M1 and M2 were assumed to be 13-ethyl-18,19-dinor-5 alpha,17 beta-pregn-20-yne-3 alpha,17- diol and 13-ethyl-18,19-dinor-5 beta,17 beta-pregn-20-yne-3 alpha,17-diol, respectively, by NMR and LC/MS analyses, and confirmed by direct comparison with respective authentic samples. M3 was assigned to be 13-ethyl-18,19-dinor-5 alpha,17 beta-pregn-20-yne-3 alpha,16 beta,17-triol by NMR, LC/MS and GC/MS analyses and acetonide derivation. 5) Isolation of the glucuronide metabolite, M4, from the bile, was achieved by column chromatography using Amberlite XAD-2 and Sephadex LH-20. Hydrolysis of this compound with beta-glucuronidase released M1 and glucuronic acid. After M4 was converted to an acetylated-methyl ester derivative, the definite structural assignment of M4 was established to be M1-3-O-yl glucuronic acid by NMR analysis. The NOE effect and the value of the corresponding coupling constant of the anomeric proton showed that the glucoside moiety was in the beta configuration. These findings suggested that LNG was predominantly converted to 5 alpha-reduced metabolites and that the 5 beta-metabolite accounted for less than 1% of the total metabolites in female rats. These metabolites were excreted as glucuronides into the bile.

Oxygenated derivatives of 2-oxachlormadinone acetate (17-acetoxy-6-chloro-2-oxapregna-4,6-diene-3,20-dione) at C11, C15, and C16 were prepared as potential antiandrogenic agents. Biological evaluation showed the 15 beta-hydroxyl compound to have a high potent antiandrogenic activity when tested in the castrated male rat.

This study was undertaken in order to evaluate the effect of intraoperative intraperitoneal (IP) administration of cisplatin (CDDP) and/or mitomycin C (MMC) on patients who underwent an operation for gastric cancer, compared with an untreated group. There were no differences between the effect of CDDP and that of MMC. No differences were found between the survival rate of IP and untreated group in no liver and no peritoneal metastasis cases, nor in non-resection cases. However, the median survival time was longer at 377 days in IP group than at 213 days in the untreated group (p less than 0.1). The free CDDP levels in the serum after 50 mg IP injection remained effective for 15-30 min. On the other hand, the MMC levels in the serum after 20 mg IP proved in effective.

We studied the usefulness of the DNA index (DI) and bromodeoxyuridine (BrdU) labeling index (BLI) using fresh material from 71 patients with colorectal carcinoma. We compared the DI and BLI of the biopsy specimens with those of the resected specimens from 17 patients. These DI and BLI values were evaluated by flow cytometry. Neither DNA ploidy nor DI was correlated with other clinicopathologic factors. Intratumoral DI heterogeneity (DIH) was found in 33.8% (24/71) of tumors. Lymph node metastases were observed more often in cases with DIH than without DIH. The incidence of DIH was correlated with histologic stage. BLIs were higher in well-differentiated adenocarcinoma than in moderately and poorly differentiated adenocarcinoma. BLIs were not correlated with histologic stage. A significant correlation was observed between DI and BLI (r = 0.47, p less than 0.001). In cases without DIH, there was a good correlation between the DI values of the biopsy and resected specimens (r = 0.99, p less than 0.001). A significant correlation was also found between the BLI values of the two types of specimens (r = 0.69, p = 0.002). These results suggested that 4 biopsy specimens were adequate to estimate DI and BLI by FCM, and that DI and BLI values determined by FCM could facilitate the design of treatment regimens for preoperative patients.

2-Azachlormadinone acetate (5a, 17-acetoxy-6-chloro-2-azapregna-4,6-diene- 3,20-dione), 2-oxachlormadinone acetate (6, 17-acetoxy-6-chloro-2-oxapregna-4,6-diene-3,20-dione) and the derivatives were prepared as potential antiandrogenic agents. Biological evaluation showed that 5a and 6 had a potent antiandrogenic activity when tested in the castrated male rat.

The results of surgical treatment of patients with gastric carcinoma infiltrating into the duodenum and the pancreas head and with N3 metastases are very poor. We have employed pancreaticoduodenectomy in combination with right hemicolectomy (PD + LH) with the aim of leaving no remnant of cancer cells in the vicinity of the primary lesion, in patients with carcinomas of the distal third of the stomach, associated with duodenal invasion, presence of fixity to the pancreas head or N3 metastases, in the last ten years. Twenty-six cases were treated with this technique (Group A). These cases were compared with 63 patients who underwent subtotal gastrectomy (Group B) in the same period. The operation time, amount of blood loss and numbers of operative complications were greater in Group A than in Group B. Operating mortality was found in 2 cases in Group B but was 0 for Group A. When the survival rates were compared, PD + LH can provide better long-term results than subtotal gastrectomy, especially in the patients with tumors infiltrating into the pancreas head or metastasizing to N3. The PD + LH is a rational and safe method for the treatment of gastric carcinoma infiltrating into the pancreas head or metastasizing to N3.

With colorectal cancer, the therapeutic outcome for multiple hepatic metastasis extending to the bilateral lobe, even when various chemotherapies are administered, is extremely poor. For multiple hepatic metastases at our clinic, from November, 1985, through February, 1991, we used an implantable reservoir to administer intra-arterial infusion chemotherapy and reviewed the results. We treated 16 patients with hepatic metastases of colorectal cancer, H2 in 3 cases and H3 in 13 cases. When we used the reduction rate of the tumor diameter as seen by CT scan as a criteria for antitumor effectiveness, 1 case was CR and 3 cases were PR, for an efficacy rate of 25.0%. Changes in the serum CEA level were related to antitumor effectiveness. Among the evaluable cases, the 1-year survival rate was 60.0%, which was significantly more favorable than the 20.0% obtained in the systemic chemotherapy group (p less than 0.05). Given the above, although there are a few problems such as the kind and dose of drugs, the use of intra-arterial infusion chemotherapy with an implantable reservoir to treat hepatic metastases of colorectal cancer permits a form of chemotherapy providing a better QOL out of hospital.

Continuous hyperthermic peritoneal perfusion (CHPP) with anticancer agents (mitomycin C and cisplatin) in warm saline was performed in patients with peritoneal dissemination of gastric cancer following resection of the primary lesion. The effect of CHPP was examined by a second-look operation. This study includes 41 cases of gastric cancer with peritoneal dissemination but without liver metastasis treated during the past 6 years. The overall median survival was 14.6 months to 64.2 months from CHPP to death and the 3-year survival rate was 28.5%. Second look surgery revealed a remarkable diminution in the degree of peritoneal dissemination in 7 (50%) of 14 patients with disappearance of ascites after only one course of CHPP in 7 (77.8%) of 9 patients. Long-term 3 year-survival was noted in 4 (9.8%) patients on CHPP. Side effects were renal insufficiency in 2 (5%) patients, leukopenia in 2 (5%) patients, and perforation of the small intestine in 1 (2%) patient. These results suggest the effectiveness of CHPP in the treatment of gastric cancer with peritoneal dissemination.

Thermochemotherapy was performed on gastric cancer cases of hepato-metastasis. The subjects were 12 gastric cancer cases having hepato-metastatic lesions (10 synchronous, 2 heterochronous). Using 8 or 13.58 MHz-dielectric heating apparatus, thermotherapy was carried out for 40-60 min (twice a week, 5-35 times, averaging 12.8 per case) at an intra-tumoral temperature greater than 42 degrees C. Chemotherapy consisted of hepato-arterial infusion of MMC 10 mg/BW, CDDP 75 mg/m2 once per 3-4 weeks and consecutive daily administration p.o. of UFT 800 mg/BW. Effect greater than PR was noted in 75% (9/12) on the whole and in 100% (5/5) and 57% (4/7) for H1-2 and H3, respectively. Mean and 50% survival periods were 9.3 and 7.2 months, respectively, with a one-year survival rate of 38%. Chemotherapy-induced side effects were nausea and vomiting in 83% and leukopenia and thrombopenia in 67%, while the only thermotherapy-induced side effect was subcutaneous fatty tissue necrosis in 3 cases. The above results suggested the effectiveness of the present thermochemotherapy in the treatment of hepato-metastasis of gastric cancer.

The difference of the cell kinetics between primary tumor and its metastasis was studied on six cases of human colorectal cancers (four cases at synchronous liver metastases and two metachronous) with migration chase method using flow cytometry in vivo. The bromodeoxyuridine labeling indices (LI), DNA synthesis time (Ts), and generation time (Tg) were measured in normal colonic mucosae, primary tumors, lymph node metastases, and liver metastases. The LI, Ts, and Tg were 4.9 +/- 2.2%, 11.6 +/- 1.4 hours, and 11.3 +/- 3.7 days, respectively, in normal mucosa. In cancer, they were 13.9 +/- 7.1%, 16.9 +/- 4.8 hours, and 6.0 +/- 2.5 days, respectively. LI was higher and Ts was longer in cancer than in normal mucosa. Tg was shorter in cancer than in normal mucosa. In lymph node metastases, LI, Ts, and Tg were 12.0 +/- 4.5%, 14.4 +/- 6.0 hours and 5.0 +/- 0.5 days, respectively. Ts was faster in lymph node metastases than in primary tumors. In liver metastases, they were 30.1 +/- 18.1%, 28.0 +/- 10.2 hours, and 4.8 +/- 2.1 days, respectively. LI was higher and Ts was longer in liver metastases than in primary tumors. In both metastatic lesions, Tg was shorter than in primary tumors. The proliferation rate correlated with LI/DNA index significantly (r = 0.7868, p less than 0.00001). From the results, it was revealed that the proliferation rate was higher in metastatic lesions than primary tumors in vivo. The application of this method for clinical and experimental use would be expected.

Studying the DNA ploidy patterns of 52 primary tumors, diploid tumors accounted for 48.1% and aneuploid tumors for 51.9%. Out of 31 patients with liver metastases, 35.5% had diploid tumors and 64.5%, aneuploid tumors. Heterogeneity (difference in DNA ploidy pattern between the primary lesion and liver metastases) was found in 20% of the patients examined. In 28 of the patients, the liver metastases were unresectable, and their prognoses were such that the 1- and 2-year survival rates from the diploid tumors were 42.9 and 14.3%, respectively, while 1-year survivors from aneuploid tumors died within 2 years. In resected cases of hepatic metastases, the DNA ploidy pattern of the metastatic lesions did not correlate with the metastasis period, extent of spread or number of lesions. The recurrence rate of aneuploid tumors in the residual livers was 50%, which was slightly higher than the rate of 36.4% for diploid tumors. The prognoses in patients with diploid tumors were significantly better than those in patients with aneuploid tumors: 5-year survival was 71.1% in diploid tumor patients, compared with 21% in aneuploid tumor patients.

Two kindreds of phosphofructokinase (PFK) deficiency associated with congenital nonspherocytic hemolytic anemia and mild myopathy were found in Japan. Both probands had jaundice, gallstones, and slight to moderate degree of exercise intolerance. They showed decreased level of red cell PFK activity and no increase of blood lactate in forearm ischemic exercise test. We studied these probands' red cell PFKs by partial purification and condensation. Muscle type isozyme of PFK in both cases was not demonstrable in starch gel electrophoresis and DEAE-Sephadex chromatography. The clinical symptoms are considered to be due to a defect of muscle type isozyme.

We have analyzed the chromatin structure of the human beta-globin locus in somatic cell hybrids resulting from the fusion of human non-erythroid cells and mouse erythroleukemia (MEL) cells. In these hybrids, the human adult beta-globin gene, but neither the embryonic nor fetal globin genes, is activated transcriptionally. In addition, the DNase I-resistant beta-like globin locus characteristic of the parental non-erythroid human cells (1,2) is reorganized over an approximately 80 kb region, including the formation of the developmentally stable hypersensitive sites 50 kb 5' and 20 kg 3' of the activated adult beta-globin gene (2,3). These results are consistent with the hypothesis that events occurring at the 5' and/or 3' developmentally stable hypersensitive sites are important, if not necessary, for the activation of the beta-globin locus.

A 60-year-old woman was diagnosed as having liver metastasis from gastric cancer 14 months after total gastrectomy and total pancreatectomy. The liver tumor was so huge and the complication, diabetes mellitus, was so severe that she was palliatively treated by hyperthermo-chemo-radiotherapy (HCR therapy) with 8-MHz capacitive heating system. Because hyperthermia for deep seated tumor is very difficult, irradiation (10 MV X-ray, 36 Gy) and systemic chemotherapy (CDDP, MMC) were combinedly used. After 10 session of hyperthermia, the tumor showed a remarkable regression in size, followed by S8 subsegmentectomy of the liver. Histologically, cancer cells were still viable in the midst of fibrosis around coagulation necrosis, while normal liver cells remained intact. Multidisciplinary HCR therapy is quite a useful modality for liver tumors and may serve to expand the indication for surgical operation.

A 23-year-old Japanese male with severe lead intoxication accompanied by hemolytic anemia was studied. The patient had taken 12 g to lead in about a month. He had moderate hemolytic anemia (Hb 8.9 g/100 ml) with reticulocytosis ranging from 2.5 to 11.7%. Peripheral blood smear showed nucleated red cells (42/200 white blood cells) and marked basophilic stippling in the red cells. Activities of erythrocyte enzymes were either normal or increased except for pyrimidine 5'-nucleotidase (P5N) and delta-aminolevulinic acid dehydratase (ALA-D) both of which were found to be decreased, being 48.8% and 4.1% of the normal controls respectively. Erythrocyte reduced glutathione (GSH) was high (145.6 mg/100 ml RBC). Erythrocyte pyrimidine nucleotides were accumulated up to 10.2% of total nucleotides. The level of lead in peripheral blood was 112 microgram per 100 ml blood. Ca2+-Na2-EDTA was given to the patient as treatment. The level of lead in the blood decreased gradually and hemolytic anemia improved. Basophilic stippling in the red cells disappeared. These results confirmed the findings of Valentine et al [1] that lead-induced deficiency of P5N resulted in basophilic stippling and hemolytic anemia just like hereditary hemolytic anemia due to P5N deficiency.

Thirteen cases of pyruvate kinase (PK) deficiency, considered to be heterozygous for different PK mutants because of no consanguinities in their parents, were characterized by the International Committee for Standardization in Haematology (ICSH) recommended methods. These deficiency cases are named PK "Kagoshima," PK "Kyoto," PK "Takamatsu," PK "Abeno," PK "Kobe," PK "Marugame," PK "Hoenzaka," PK "Osaka," PK "Motomachi," PK "Gifu," PK "Hiroshima" PK "Matsumoto," and PK "Tama." The characteristics of mutant PK enzymes suggest that the cause of chronic hemolysis depends mainly on decreased affinity for phosphoenolpyruvate, thermolability, increased inhibition by adenosine triphosphate, and low activation by fructose-1, 6-diphosphate.

Two cases of red cell aldolase deficiency associated with congenital nonspherocytic hemolytic anemia are reported. The proband is a fourteen-month-old Japanese boy. Consanguineous marriage was not proven but probable in this family, as the parents were born in the same small island. The proband had moderate to mild anemia aggravated by upper respiratory infections, 1 cm hepatomegaly and 2.5 cm splenomegaly, but was unremarkable in other respects and has thus far not shown mental or growth retardation. He did not have dysmorphic features. The red cell aldolase activity was 6% of the normal mean. The enzyme was unstable with respect to heat, and Km for fructose 1,6-diphosphate (F-1,6-DP) was high. The parents and other heterozygotes showed intermediate activity between that of the proband and that of normal subjects. Red cell F-1,6-DP concentration in this case was remarkably increased. Red cell glucose consumption, and lactate formation, as well as hexose monophosphate shunt activity, were decreased as compared with a comparable reticulocyte-rich hereditary spherocytosis patient. Hexose monophosphate dehydrogenase by a high concentration of F-1,6-DP in his red cells. As a result of family study, another homozygous aldolase deficiency case associated with hemolytic anemia was found. He is 13 years old and a nephew of the proband's paternal grandmother. His hemolytic anemia also is moderate to mild and aggravated by upper respiratory infections. He does not seem to have mental or growth retardation, nor does he possess dysmorphic features.

Red cells from 5 healthy adults and an unstable mutant pyruvate kinase (PK), PK Maebashi, were stored for 12 months in a -80 degrees C freezer. With an exception of triosephosphate isomerase and phosphoglycerate kinase activities, normal red-cell enzyme activities remained essentially unchanged. Mutant PK was characterized by the methods recommended by the International Committee for Standardization in Haematology (ICSH). Normal control and PK Maebashi remained essentially unchanged in their characteristics after storage in a -80 degrees C freezer for 12 months. These results indicate that the red cells stored over a long term in a -80 degrees C freezer can be used for the study of unstable mutant PK.

Using immunofluorescent antibody techniques, conversion of pyruvate kinase (PK) isozymes during the maturation of erythroblasts was studied. In normal subjects, M2-type PK was clearly seen at the proerythroblast stage, then markedly declined with cell maturation, whereas L-type PK continued to increase. In classical type PK deficiency, M2-type PK was still clearly seen in orthochromatic erythroblasts, whereas L-type PK was scarcely detected during maturation. In other PK deficiency cases, change of L-type PK showed a similar pattern to that of normal while M2-type PK was still clearly seen at the later stage of maturation as in the classical type. In K-562 human leukemia cell line, M2-type PK declined and L-type PK increased in parallel with hemoglobin synthesis by addition of hemin, an inducer for differentiation into erythroblasts. Hemoglobin synthesis and L-type PK production appear to have interrelation during the differentiation and maturation of erythroblasts.

A 72-year-old woman developed adenocarcinoma of the left parotid gland. Because of the excessive size of her tumor and the fact that she suffered from severe liver dysfunction, she was treated by hyperthermo-chemo-radiotherapy (HCR therapy). After ten sessions of radiofrequency hyperthermia with HEH 500 (13.56 MHz radiofrequency wave), 50-Gy irradiation from a linac and administration of 33.0g of tegafur in suppository form, the tumor mass showed remarkable regression decreasing in size by as much as 84% on computed tomography. Histologically the tumor which was resected under local anesthesia, showed almost total necrosis. The multidisciplinary HCR therapy was well tolerated and effective as a therapy for cancer in this case.

Human fetal globin genes are not expressed in hybrid cells produced by the fusion of normal human lymphocytes with mouse erythroleukemia cells. In contrast, when lymphocytes from persons with globin gene developmental mutations (hereditary persistence of fetal hemoglobin) are used for these fusions, fetal globin is expressed in the hybrid cells. Thus, mutations of developmental origin can be reconstituted in vitro by fusing mutant lymphoid cells with differentiated cell lines of the proper lineage. This system can readily be used for analyses, such as globin gene methylation, that normally require large numbers of pure nucleated erythroid cells, which are difficult to obtain.

A 56-year-old woman was diagnosed as having gastric cancer with lymph node metastasis and invasion to the pancreas head and was admitted to our hospital in September, 1984. She was treated with hyperthermo-chemo-radiotherapy, using radiofrequency-induced hyperthermia (8 MHz) with a daily dose of fractionations at 42-43 degrees C for 60 minutes, 5 fractions per week of irradiation at 180 cGy and systemic chemotherapy. After the total doses of hyperthermia and radiation had reached 11.8 hours and 2500 cGy, the primary tumor and lymph node metastasis measured by X-ray examination were reduced in size. On October 8th, laparotomy was done, and total gastrectomy combined with total pancreatectomy, left hepatic lobectomy and right hemicolectomy was performed. Histologically, almost all of the cancer cells in the primary tumor and lymph node metastasis had disappeared. These results show that this multimodal therapy is effective for local control of gastric cancer, when used preoperatively.