Nutritional status of people living in Dzong village, in the northern mountainous area of Nepal.

A nutritional survey was carried out among residents (39 males and 46 females) of Dzong village in the northern area of the Gandaki region of Nepal. The results were compared with our previous findings. The mean body mass index value was under 21 for both sexes, but the mean percentage of body fat of females (17-19 years old, 25.8 +/- 9.4%; 20-29 years old, 31.0 +/- 8.4%) was higher than that of males (17-19 years old, 12.0 +/- 1.0%; 50-59 years old, 24.4 +/- 7.6%). Most serum nutritional markers for both sexes were generally at normal levels although the iron levels were lower and packed red cell volume levels were higher than normal. As determined by results of the 24-hr dietary recall survey, the main food groups consumed by both sexes were cereals, potatoes, pulses, meats and vegetables. The mean daily intake of nutrients was similar for both sexes, with a few exceptions. The relatively high serum TG levels of the subjects may have been due to the high consumption of carbohydrate-laden cereals. The amounts of food consumed were not adequate, resulting in a latent and chronic deficiency of nutrients, especially calcium and iron. These results suggest that improvements in the nutritional status of this group of people are necessary.

Mosaicism in the expression of tumor-associated carbohydrate antigens in human colonic and gastric cancers.

Serial sequential sections from a single tumor were examined by immunohistological staining with several monoclonal antibodies directed, respectively, to different tumor-associated carbohydrate epitopes. Staining patterns were compared with those of conventional staining with hematoxylin-eosin or periodate/Schiff's reagent. Each tumor showed different areas of staining with different antibodies, and the combined staining map shows a clear mosaicism of antigen expression within the same tumor. For example, some areas of a given tumor were stained by FH4 (defining dimeric Le(x)), while other complementary areas were strongly stained, in a mutually exclusive manner, by SH1 (defining Le(x)), AH6 (defining Le(y)), FH6 (defining sialosyl dimeric (Le(x)), or TKH2 (defining sialosyl-Tn). Some areas were stained by two or three of these antibodies. Comparisons of the mosaic-staining patterns with cytohistological properties of tumor cells within specific areas suggested that the pattern of antigen expression is correlated with degree of differentiation; e.g., poorly-differentiated cells with severe dysplasia did not express high levels of Le(x) or Le(y) but did express sialyl-Le(x) or dimeric Le(x); on the other hand, moderately or well-differentiated tumor cells in some areas expressed high levels of Le(x) or Le(y) but lower levels of sialyl-Le(x). Areas showing strong expression of sialyl-Tn in their secretions were consistently correlated with presence of well-differentiated tumor cells, whereas secretions from normal mucosae were consistently characterized by lack of sialyl-Tn expression. It is postulated that the original in situ tumors (which had homogeneous glycosylation patterns) evolved into several spatially discrete cell populations displaying different degrees of glycosylation, reflecting stages of tumor cell differentiation and progression.

HLA antigens are candidate markers for prediction of lymph node metastasis in gastric cancer.

We investigated the association between human leucocyte antigen (HLA) antigens and lymph node metastasis in 724 gastric cancer patients. Among patients who had poorly differentiated adenocarcinoma with or without HLA-DR4 antigen, lymph node metastasis was detected in 80.8 and 54.9%, respectively (relative risk (RR) = 3.5, P = 0.0005, corrected P = 0.0285). It was more common in patients with a family history of cancer death (RR = 7.7). Among signet ring cell carcinoma patients with or without HLA-B52 antigen, lymph node metastasis was detected in 57.7 and 19.7%, respectively (RR = 5.6, P = 0.0001, corrected P = 0.0086). It was more common in patients who were smokers (RR= 8.3). Our findings suggest that HLA-DR4 and HLA-B52 antigens are associated with lymph node metastasis in gastric cancer.

Quantification of serum-soluble HLA class I antigens in patients with gastric cancer.

The amount of sHLA-I in serum was examined in 74 patients with gastric cancer and 15 normal healthy controls. For mAbs, W6/32 specific for HLA-A, -B, -C, and biotin IOT2 specific for HLA class I associated with beta 2 microglobulin, were used to determine the values of sHLA-I using an ELISA. The patients in stage-IV gastric cancer showed lower values of sHLA-I (445.4 +/- 247.1 ng/ml) than those in stage I (725.9 +/- 575.8 ng/ml), stage II (752.8 +/- 255.0 ng/ml), and normal controls (868.9 +/- 715.0 ng/ml) (P < 0.05). In analysis of the patients with HLA-A24, the allele that has been reported to secrete more sHLA-I than other alleles, the results were nearly the same. These results suggest that the secretion of sHLA-I is low in patients with very advanced cancer. However, there was no correlation between the sHLA-I level and the metastasis or prognosis in longitudinal studies in 11 patients.

The role of human leukocyte antigen and tumor necrosis factor D as a prognostic, preventive and therapeutic factor in gastric cancer.

In order to clarify the immunogenetical background, host factors in oncology, human leukocyte antigen (HLA) and tumor necrosis factor (TNF) beta alleles as prognostic, preventive and therapeutic indicators were investigated in 712 patients with a histologic diagnosis of adenocarcinoma of the stomach treated with gastrectomy. HLA and TNF beta alleles were tested serologically and by DNA-PCR typing. The absence of HLA Cw1 antigen may represent resistant and prognostic factors. HLA-B51, B61 and TNF beta 10.5 kb homozygote alleles are therapeutic, survival and prognostic factors. Considering the relation with lymph node metastasis, HLA-DR4 antigen and HLA-DRB 1*0405 allele were found to be risk factors for lymph node metastasis in poorly differentiated adenocarcinoma. TNF beta 10.5 kb homozygote allele also represented a risk factor for lymph node metastasis. TNF beta 5.5 kb homozygote allele was considered a resistant factor for lymph node metastasis in poorly differentiated adenocarcinoma. HLA and TNF beta alleles can play an important role as prognostic, preventive and therapeutic indicators in gastric cancer. Therefore, TNMH (TNM with host factor) should be proposed as a new approach.

Helicobacter pylori infection in two areas in Japan with different risks for gastric cancer.

BACKGROUND: We evaluated the relationship between Helicobacter pylori and various factors associated with gastric cancer in two areas in Japan with different risks for mortality due to gastric cancer. METHODS: A total of 250 sera from Niigata and 209 from Okinawa were used. H. pylori antibody and CagA antibody were measured by antigen-specific ELISAs. Serum gastrin and pepsinogen levels were determined by RIA. RESULTS: Although there was no significant difference in H. pylori prevalence among the persons in Niigata (50%) and Okinawa (42%), CagA prevalence in these populations was significantly different, at 41% and 26%, respectively (OR = 1.98, 95%CI: 1.33-2.95, P < 0.01). Serum gastrin levels in Niigata were significantly lower than those in Okinawa in H. pylori-negative persons (P < 0.01). The serum pepsinogen I/II ratio in Niigata was significantly lower than that in Okinawa in H. pylori positive persons (P < 0.01), whereas there was no significant difference in H. pylori-negative persons. Among those positive for H. pylori, serum pepsinogen I/II ratio in Niigata was significantly lower than that in Okinawa in CagA-negative persons (P < 0.01), whereas no significant difference was observed in CagA-positive persons. CONCLUSIONS: These results suggest that the difference in the mortality ratio of gastric cancer between Niigata and Okinawa is mainly associated with the difference between areas in the prevalence of cagA-positive strains rather than that of H. pylori itself.

Combination therapy of transcatheter chemoembolization and percutaneous ethanol injection therapy for unresectable hepatocellular carcinoma.

The therapeutic effectiveness of a combination therapy--pretreatment with transcatheter arterial chemoembolization (TACE) followed by percutaneous ethanol injection (PEI) therapy--for large (> 3 cm in diameter) unresectable hepatocellular carcinoma (HCC) was compared with that of TACE alone. PEI therapy was performed in 24 cases of unresectable HCC that had previously been treated with TACE using doxorubicin 30-60 mg or epirubicin 50-90 mg. In all, 2-10 ml of 90% ethanol mixed with carbocaine was repeatedly injected through a 21-gauge, closed-end needle (PEIT needle) for a median of 3.6 injections and 31.1 ml of ethanol. As adverse effects, transient localized pain and a burning sensation were observed in 75.0% of the cases; fever, in 66.7%; and transient hypotension, in two cases. A small unresectable tumor is a good indication for PEI therapy. In cases with a larger tumor, i.e., measuring more than 3 cm in diameter, or multiple tumors, the 1-year survival rate obtained with this combination therapy, i.e., TACE and PEI, was 87.0%, and the 2-year survival rate was 65.2%. These rates were greater than those obtained with TACE alone. Accordingly, additional PEI therapy was effective for larger tumors and multiple tumors previously treated with TACE.

Clinical evaluation of teprenone, a mucosal protective agent, in the treatment of patients with gastric ulcers: a nationwide, multicenter clinical study.

The recurrence rate of gastric ulcers healing to a white scar is low, whereas that of ulcers healing to a red scar is high. Teprenone is a mucosal protective agent that can promote epithelial regeneration by increasing the mucosal hexosamine content. It promotes white scar formation when administered as maintenance therapy for ulcers. A nationwide, multicenter study was performed to determine whether white scar formation was also promoted when teprenone was used during initial therapy. Analysis of the data from 1249 patients showed that teprenone significantly promoted white scar formation. The presence of severe ulcers (large size and active stage), ulcer location at the gastric angulus, and smoking retarded white scar formation irrespective of the use of teprenone.

Postoperative intravenous administration of lysine acetylsalicylate: effect on pain relief and platelet function.

The effects of lysine acetylsalicylate, a new injectable salicylate, on postoperative pain relief and platelet function were studied in ten men who had surgery for peptic ulcer. Four of five patients receiving lysine acetylsalicylate had satisfactory pain relief. One patient required an additional injection of 15 mg of pentazocine. Of the five patients in the control group, an average (+/- SD) dose of 90 +/- 23.7 mg of pentazocine was required to achieve adequate postoperative pain relief. Lysine acetylsalicylate decreased platelet aggregability but without resulting in hemorrhage. We concluded that this new salicylate administered intravenously to patients in the postoperative period provided adequate analgesia while allowing effective hemostasis despite its inhibitory effect on platelet aggregation.

Effects of oral lentinan on T-cell subsets in peripheral venous blood.

The effect of oral lentinan, a biological response modifier, on the control of systemic immune function was studied in six-week-old male Wistar-Imamichi specific-pathogen free rats. In the lentinan-treated group, 1 mg of lentinan dissolved in 1 ml of physiological saline was administered forcibly into the stomach twice weekly for four or eight weeks. Physiological saline alone was administered in a similar fashion to the control group. Leukocyte and lymphocyte counts were made and lymphocyte subsets measured using monoclonal antibodies W3/13, W3/25, and OX8, and a laser flow cytometry system. The T-cell level, the helper/inducer T-cell level, and the suppressor/cytotoxic T-cell level were measured. The peripheral leukocyte and lymphocyte counts did not change significantly in either group during treatment. After four weeks of treatment, however, the lentinan group had a significantly higher T-cell level, helper-cell level, and helper-suppressor ratio, and a significantly lower suppressor-cell level than did the control group. No significant between-group differences in the lymphocyte subsets or the helper-suppressor ratio were noted after eight weeks of treatment. Oral administration of lentinan appears to modulate the systemic immune function through stimulation of T cells, especially helper cells. Continued administration produced less effect, possibly due to a tolerance to the effect of lentinan.

Effect of Irsogladine on gap junctions in cerulein-induced acute pancreatitis in rats.

The capacity for intercellular communication (IC) via gap junctions is found in normal pancreatic acinar cells. The major role of IC is considered to be the maintenance of tissue homeostasis and the regulation of signal transmissions. Up to now, the participation of IC via gap junctions in acute pancreatitis has not been reported. We investigated the role of IC in cerulein (Cn)-induced acute pancreatitis in rats using irsogladine, an enhancer of IC via gap junction. Acute edematous pancreatitis was induced in rats by two intraperitoneal injections of 40 micrograms/kg Cn. Rats received various doses (25, 50, or 100 mg/kg body weight) of irsogladine orally, 15 and 2 h before the first Cn injection. The normal control group received only vehicle. The severity of pancreatitis was evaluated enzymatically and histologically 5 h after the first Cn injection. In Cn-induced acute pancreatitis, irsogladine significantly lowered the serum amylase level, the pancreatic wet weight, and the pancreatic amylase and DNA contents, in a dose-dependent manner. Particularly, the amylase content improved to the level of the normal controls. Histologically, the severity of pancreatitis was reduced significantly by treatment with irsogladine and no discernible vacuolization was seen in the group with 100 mg/kg irsogladine treatment. By immunofluorostaining pancreata with anti-connexin 32 (Cx32; a gap junction protein) antibody, we found that pancreatic acini were diffusely positive for Cx32 in the control group, but the number of Cx32-positive grains decreased markedly, to 19%, in the pancreatitis group. With 100 mg/kg irsogladine treatment, the number of Cx32 grains recovered to 70% of the normal control value. These findings indicate that IC via gap junction is disturbed in Cn-induced pancreatitis, which may result in the breakdown of tissue homeostasis and the progression of acute pancreatitis.

Small mucosal carcinoma of the stomach with para-aortic lymph node metastasis: a case report and review of the literature.

A 38-year-old woman presented with a mucosal gastric carcinoma measuring 0.7 x 0.5 cm and para-aortic lymph node metastasis. Radiographic and endoscopic studies showed a small depressed lesion on the anterior border of the gastric angle, which was classified as a type II c + III lesion. Histological examination of the biopsy specimen revealed a signet-ring cell carcinoma. Distal gastrectomy with wide lymph node excision was performed. Detailed study of the resected specimen revealed that the tumour was limited to the mucosa, but metastasized to both the perigastric and para-aortic lymph nodes. The patient received adjuvant immunochemotherapy postoperatively. However, multiple bone metastases developed at 3 years and she died 4 years after the operation.

Helicobacter pylori infection in gastric carcinoma.

PURPOSE: This study was undertaken to compare the pathoclinical findings in gastric adenocarcinoma with serum IgG antibody to Helicobacter pylori. MATERIALS AND METHODS: We examined 185 patients with histologically established gastric cancer. The presence of immunoglobulin (Ig)G antibody in the high molecular cell-associated antigen of H. pylori was determined by enzyme-linked immunosorbent assay. Pepsinogens I and II were measured by radioimmunoassay. The distribution of H. pylori on the gastric mucosa was assessed by the Campylobacter-like organism test and phenol red dye spraying. RESULTS: H. pylori IgG antibody was detected in 93.1% of patients with gastric cancer (mean age 61.7 years), 94.3% of patients with early gastric cancer and 91.2% with advanced gastric cancer. No statistical difference in serology was observed between type of gastric cancer, depth of cancer invasion, tumor size or histology. Only in patients with diffuse-type cancer of the cardia was there a lower percentage of positive results (80.0%). The ratio of pepsinogen I to pepsinogen II was higher in the patients who exhibited no H. pylori antibodies. CONCLUSIONS: H. pylori antibodies were common in patients with gastric cancer, and were not correlated with histological type nor stage of cancer. In the Niigata district, a higher percentage of patients with gastric carcinoma displayed H. pylori antibodies compared with other districts in Japan.

Determination of free fatty acids in human bile by high-performance liquid chromatography.

We developed a high-performance liquid chromatography (HPLC) method for free fatty acids (FFAs) analysis in bile. In this method, FFAs were extracted from bile in a single step using an Isolute ODS cartridge, derivatized with 9-anthryldiazomethane (ADAM). ADAM was chosen because of its high reactivity with carboxylic acid at room temperature. Then, HPLC was used for separating and quantifying FFAs. This method proved to be simple and time-saving. The mean recovery of FFA added to human gallbladder bile was 97.6%, and the detection limit was 100-250 pg. Using this method, we determined FFA concentrations in the gallbladder bile of 11 gallstone patients. The mean concentration of total FFA was 0.61 (SD = 0.41) mmol/L, and there was wide variation in the individual FFAs.

Co-mutagenicity of glyco- and tauro-deoxycholic acids in the Ames test.

Mutagenicity and co-mutagenicity of glyco- and tauro-deoxycholic acids (GDCA and TDCA), which are abundant in human bile, were examined by the Ames test. The two chemicals were not mutagenic for themselves to Salmonella typhimurium TA98 and TA100, with and without S9 mix. They enhanced, however, the mutagenic activities of the pro-mutagens, 2-aminoanthracene (2AA) and benzo[a]pyrene (BaP), for both TA98 and TA100 with S9 mix. They were more co-mutagenic for the pro-mutagens on TA98 than on TA100. On TA98, the mutagenic activities of 2AA with GDCA (5 mumol/plate) and with TDCA (5 mumol/plate) were 9.7-fold and 11.8-fold as high as that of the corresponding control (2AA only), respectively. BaP with GDCA (2.5 mumol/plate) and with TDCA (2.5 mumol/plate) showed 2.8-fold and 3.0-fold increases over the corresponding control level (BaP only), respectively. It is hence concluded that GDCA and TDCA may enhance the activity of some mutagens existing in bile.

Geographical variations in the concentration of biliary free fatty acids with anti-mutagenic action.

The concentrations and compositions of free fatty acids (FFAs) in human bile, especially of inhibitory free fatty acids (IFFAs), were analyzed in terms of anti-mutagenic effects in relation to the mutagenic activity of bile. Bile samples were collected from patients with cholelithiasis residing in either Niigata or Kochi prefectures of Japan, regions characterized as the highest and lowest risk areas for gallbladder cancer (GBC), respectively. Biliary FFAs and IFFAs were analyzed by high-performance liquid chromatography and mutagenicity was examined in by the Ames test (TA98+S9mix) after blue rayon treatment. There was a tendency for higher biliary FFA and IFFA concentrations in the Kochi subjects, but the proportion of IFFA to the total FFA concentration did not differ between the two areas. There was an inverse correlation between the concentrations of IFFAs and the numbers of revertant colonies in both Niigata and Kochi subjects. However, at a dose of 591 micromol/l, (calculated based on the average amount of IFFAs absorbed in blue rayon) IFFAs did not exhibit anti-mutagenic actions in the blue rayon extracts. Within this range, more positive samples were seen in Niigata than in Kochi, suggesting the presence of more active mutagen(s) in Niigata samples.

Immunotherapy for esophageal cancer. A randomized trial in combination with radiotherapy and radiochemotherapy. Cooperative Study Group for Esophageal Cancer in Japan.

We investigated the effect of multimodal therapy in 187 patients with esophageal cancer. All patients were followed up over a period of 5 years. Among the 187 patients, 174 (93.1%) eligible patients with biopsy-proved esophageal squamous cell carcinoma underwent esophagectomy and were randomly assigned to receive radiotherapy (RT) with or without protein-bound polysaccharide (PSK), or RT plus chemotherapy (CT) with or without PSK. The 5-year survival rates of patients with RT, RT+PSK, RT+CT and RT+CT+PSK were 40.0%, 42.3%, 29.1% and 37.2%, respectively. There was a tendency for longer survival on PSK, but statistical significance was not reached (RT+CT group versus RT+CT+PSK group: log-rank and generalized Wilcoxon tests, P = .1930, P = .1034). However, Cox multivariate regression analysis indicated that postoperative therapy with or without PSK was the most significant prognostic factor for patients receiving RT+CT and for the eligible patients. These results indicate that PSK may have a beneficial effect on esophageal carcinoma when given in combination with CT+RT.

Focus on the histologic diversity in primary and lymph node lesions and the outcome of gastric cancer.

According to the Japanese Classification of Gastric Carcinoma, one predominant type should be selected to represent the histology of the carcinoma. The authors investigated the relationship among the histologic variables of primary lesions, metastatic lesions and the outcome of patients. A total of 155 patients with node-positive gastric carcinoma were examined. According to the histologic diversity, histologic grades were assigned from 1 to 4 regardless of the predominant histologic type. A larger number of histologic types composing not the primary lesions, but metastatic lymph nodes, were associated with an increasing frequency of advanced stage tumors. On the prognosis by number of histologic types composing the primary tumor and the metastatic lymph nodes, there were significant differences except between the histologic type-2 and histologic type-3 groups in the only metastatic lymph nodes. In conclusion, patients with a greater number of histologic types composing lymph node metastases had poorer prognosis than with a small number of histologic types. Histologic diversity within metastatic lymph node was thought to be important for determining the prognosis of patients with gastric cancer.

Genetic polymorphisms of cytochrome P450 1A1 and risk of gallbladder cancer.

The relation between cytochrome P4501A1 (CYP1A1) gene polymorphisms and the risk of gallbladder cancer was examined. To clarify individual differences in susceptibility to gallbladder carcinogenesis, we investigated the frequency of the Mspl and Ile-Val polymorphisms of the CYP1A1 gene, in 52 patients with gallbladder cancer (32 females, 20 males) and 104 healthy controls (64 females, 40 males). We then examined the relationship between the CYP1A1 polymorphisms and the development of gallbladder cancer in members of both sexes. A statistical difference in the frequencies of the MspI and Ile-Val polymorphisms or their alleles (ml, m2 and Ile, Val) was not observed in the male patients and controls. Among females, however, the frequencies of genotypes C and Ile/Val were significantly higher (p < 0.05) in the patients than in their controls. Moreover, the frequency of the hetero genotype Ile/Val was statistically higher (p < 0.05) in the female patients than in the male patients. This study demonstrated a significant over-representation of genotypes C and Ile/Val in female patients with gallbladder cancer. Females with genotypes C and/or Ile/Val may have a high genetic susceptibility to the development of gallbladder cancer.

Correlation between erythropoietin and lactate in humans during altitude exposure.

The plasma concentrations of both immunoreactive erythropoietin (EPO) and lactate were determined in four healthy untrained subjects at sea level and on the 2nd or 3rd day at altitudes (1,300 and 3,500 m). The mean plasma EPO (18.8 +/- 1.6 mU/ml at sea level) increased significantly on the 3rd day at 1,300 m (25.5 +/- 2.0 mU/ml, p < 0. 05) and showed an almost three-fold increase on the 2nd day at 3,500 m (53.5 +/- 3.7 mU/ml, p < 0.001). Likewise, the mean plasma lactate at 3,500 m (3.98 +/- 0.27 mmol/l) was 3.6 times as high as that at sea level (1.11 +/- 0.05 mmol/l) (p < 0.001). The plasma EPO concentrations were found to correlate well with the lactate concentrations at sea level and altitudes (r = 0.86, p < 0.01). These results are consistent with the well-known EPO/lactate response to altitudes and suggest that the circulating EPO concentration as well as blood lactate concentration can be used as an index of anaerobic condition.