[Analysis of the questions of the national examination for nurses and a proposal for their improvement].
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Biomedical subjects
Publications and source records attributed to S Majima.
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Leucocytes from patients with gastric or colorectal cancer as well as from normal subjects were tested by the leucocyte migration-inhibition test against 3 M KCl extracts of three whole fetuses and eight fetal gastrointestinal tract tissues. The incidence of pathologic results in patients with gastric and colorectal cancer was 26% (25/77) and 34% (25/74), respectively. The values were significantly higher than those of normal subjects (3%, 1/30). No significant difference in the migration index was found between whole fetal and fetal gastrointestinal tract extracts. The migration index did not depend on CEA concentration in these fetal extracts. These results show that leucocytes from patients with gastric or colorectal cancer were sensitized to antigenic substance(s) in the fetal extracts, and suggest that gastrointestinal cancer and fetal tissue may share some common antigens.
The effect of a protein-bound polysaccharide preparation, PS-K, on the induction of intestinal tumors by dimethyl hydrazine (DMH) was assessed in Wistar rats. One hundred and fifty-one rats were randomly divided into two groups. Seventy-two rats were treated with DMH alone and 79 rats were treated with DMH and PS-K. All animals were subjected to a sequential autopsy and all lesions within the gastro-intestinal tract were examined macroscopically and histologically. Tumor incidence in the DMH plus PS-K-treated group was significantly lower than that in the group treated with DMH alone. The most interesting histological finding was marked lymphoid infiltration in and around the tumors of the rats in the PS-K-treated group. The number of circulating lymphocytes dropped below the control range in the 25th and 35th weeks for the group treated with DMH alone, but the drop in the PS-K-treated group was smaller. Delayed-type hypersensitivity reaction to purified protein derivative was well maintained in the PS-K-treated rats. The most interesting findings in these experiments were differences in the serum blocking activities and serum immunosuppressive substance in these two groups; they were markedly reduced in the PS-K-treated rats. The present results may be explained in terms of competitive action of PS-K against the immunosuppressive factor produced by a tumor-bearing host.
The distribution of vasoactive intestinal polypeptide (VIP) in the colon of patients with Hirschsprung's disease was investigated by the peroxidase-antiperoxidase (PAP) immunohistochemical method. Three colonic segments, ganglionic, oligoganglionic and aganglionic, were stained by the unlabeled antibody enzyme method. VIP immunoreactive nerve cell bodies, nerve fibers and nerve endings were distributed throughout the ganglionic and oligoganglionic segments. In contrast, the aganglionic segment contained no VIP nerve endings and the number of fibers was reduced. These differences are thought to be a cause of constriction of the colon in Hirschsprung's disease and VIP neurons are therefore believed to participate in the relaxation of smooth muscle.
The physiologic status of the anorectum after low anterior resections or pull-through operations of the rectum was evaluated clinically and by manometric studies. It was demonstrated that the presence of a normal anal resting pressure and an anorectal reflex were important to achieve postoperative continence after sphincter-saving operations. In patients with anastomotic leaks and poor function, a marked high-pressure zone in the anal canal and an anorectal reflex were not found, but as local inflammation resulting from the anastomotic leak disappeared, these parameters returned to normal. A normal anorectal reflex was found in one of three patients after Bacon-type pull-through operations, but the remaining two showed an increase of anal canal pressure during colonic distention. These results indicate that an elevation of anal-canal pressure in response to colonic distention plays a significant role in fecal continence at the time of "a sense of urgency" if internal sphincter function is impaired.
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Responses to intratumor immunochemotherapy by intralesional injections of BCG and 5-fluorouracil (5-FU) emulsion, prior to resection of a transplanted primary tumor, were investigated using a host-tumor system consisting of C3H/He mice and MH134. A significant prolongation of survival and suppression of lymph node metastasis were attained by the combined use of BCG and 5-FU emulsion, compared to treatment with either BCG or 5-FU emulsion alone. However, this did not alter the survival rate of the combined regimen group as compared with those of the latter treatment groups. When rechallenged with the same tumor cells after resection of the primary lesion, mice treated with BCG alone exhibited a marked tumor growth suppression while the control and BCG + 5-FU emulsion group showed a less effective suppression. No such effects were observed in the group given 5-FU emulsion alone. Assessment by the splenic plaque-forming cell assay with sheep erythrocytes revealed a marked inhibition in the development of humoral immunity in the animals treated with 5-FU emulsion alone. Concomitant administration of BCG was effective to some extent in preventing the depression of these immune functions. The data obtained indicate that the clinical response to immunochemotherapy is determined by a balance between the antitumor effect of the antitumor agent administered and its influence on the host's immune functions.
Based on the propensity of fat emulsion to be absorbed mainly into lymphatic capillaries and regional lymph nodes, preoperative oral administration of 5-FU emulsion was attempted as an adjuvant chemotherapy to surgery for gastric carcinoma. In our previous studies, it was demonstrated that the mean 5-FU level in the regional lymph nodes was higher in patients who received the 5-FU solution. Since 1974, we have administered 5-FU emulsion preoperatively to 167 patients with gastric cancer (500 mg X 10 days) and examined histologically the effect of this regimen on the metastatic foci in the lymph nodes. A positive change, such as marked necrosis or marked degeneration, was found in 58% of the metastatic lesions. Sixty-four patients with advanced cancer who received the preoperative 5-FU emulsion also received a curative resection between 1974 to 1977 in addition to postoperative chemotherapy (MMC 40 mg and 5-FU more than 5000 mg) (Group A). Their survival rate was compared with that of the curatively operated advanced cancer patients from 1959 to 1973 who received the same postoperative chemotherapy only (Group B, N = 59) and with that of patients, from 1959 to 1970, who received no chemotherapy (Group C, N = 222). The 5 year survival rate of Group A was 0.53 +/- 0.07, which was higher than that (0.49 +/- 0.07) of Group B and that (0.40 +/- 0.10) of Group C. Comparing the 5-year survival rates of the 3 groups from several points of view, such as a stage of cancer progress absence of serosal invasion, the 5-year survival rate of group A was higher than that of other groups. Although these differences between Group A and B were not statistically significant, but those between Group A and B were significant. From these results it is suggested that preoperative oral 5-FU emulsion might be effective as an adjunct to surgery for gastric cancer.
The purposes of this work were twofold: firstly to determine whether intratumor chemoimmunotherapy was more effective than either treatment alone or systemic therapy and; secondly to study how the intratumor therapy affected on the development of the tumor-specific immunity. Inbred male C3H/He mice and mouse ascited hepatoma 134 (MH 134) of C3H origin were used as host-tumor system. Mitomycin C was used as the chemotherapeutic agent and BCG as the immunopotentiating agent. Intratumor treatment of MMC + BCG led to complete cure in 85 percent of the mice. The lymph node metastases were markedly inhibited in the group treated with MMC + BCG compared to the groups treated with MMC alone or BCG alone. The growth of rechallenged tumor was investigated; 79% of mice treated with MMC + BCG were immune to rechallenge, whereas 57% of mice treated with BCG alone. The number of PFC and DTH against SRBC of the mice treated with MMC intraperitoneally significantly decreased compared to that treated with MMC intratumorally.
To examine FT-207 cardiotoxicity, medical records of 223 cancer patients from 23 institutions throughout Japan were subjected to analysis. ECG changes occurred in 11/108 patients and 4/115 patients after iv and po administration of FT-207 respectively. ST . T wave changes resembling to coronary T wave occurred in 4 patients without subjective or objective symptoms of cardiac disturbance after surgery followed by iv injection for a given period. These 4 patients did not show symptoms such as chest pain and tachycardia accompanying with ECG changes described in foreign literatures concerning 5-FU, and it was not clear whether these ECG changes reflected cardiac disturbance or not. On the other hand, other ECG changes consisted of non-specific changes in ST . T wave, and they were considered to be of no significance in clinical evaluation because of influence of background factors such as surgery and adjunct chemotherapy. Although this surveillance did not provide a given relationship between FT-207 and cardiac disturbance, it is recommended that especially iv injection should be taken with ECG monitoring.
Recently, immunosuppressive acidic protein (IAP) and immunosuppressive substance (IS) were reported by two institutions, and they have been currently under extensive clinical investigations. As these two acidic proteins seemed to be very similar glycoproteins, we tried to elucidate clinically the dissimilarities between these two substances. The mean value of IAP of 106 healthy donors was 378 +/- 100 micrograms/ml, and as 95% of them was under 550 micrograms/ml, therefore, the upper limit of normal value of IAP was determined to be 550 micrograms/ml. On the other hand, the mean value of IS was 553 +/- 125 micrograms/ml and the upper limit of normal value was 750 micrograms/ml. In 110 gastric cancer patients, the incidence of the abnormal value of IS (43%) was higher than that of IAP (33%), and abnormal values were observed at earlier stage in IS than that observed in IAP. The reaction of skin tests was more highly correlated with the value of IS than the value of IAP. From these facts, it was suggested that the value of IS was more predictable than that of IAP as the parameter of the immunosuppression of the gastric cancer patients.
The effect of PSK on the induction of intestinal tumors by DMH in Wistar rats was examined. One hundred and fifty-one rats were divided into two groups. Seventy-two rats were treated with DMH alone and 79 rats were treated with DMH and PSK. All animals were subjected to a sequential autopsy and all lesions within the GI tract were examined macroscopically and histologically. Tumor incidence in the DMH and PSK treated group was significantly lower than that in the DMH treated alone, and peritoneal disseminations and distant metastases were also significantly decreased in the PSK treated rats. The number of circulating lymphocytes dropped in the 25th and 35th week in the group treated with DMH alone, but the drop in the PSK treated group was not remarkable. DTH reaction to PPD and antibody forming capacity to SRBC were well maintained in the PSK treated rats than in those treated with DMH alone. The most interesting findings in these experiments were the differences concerning the serum blocking activities and serum immunosuppressive factor in these two groups; these were markedly reduced in PSK-treated rats. From these experiments, the mechanisms may be explained by the competitive action of PSK against the immunosuppressive factor produced by a tumor-bearing host.
Since somatostatin is a local hormone controlling gastric acid secretion and gastrin release, quantitative histopological distribution of the G-cells and D-cells in the canine whole stomach was investigated by the specific immunoperoxidase staining technique. The G-cells were identified only in the pyloric antrum and the estimated total number of G-cells was 15.5 X 10(6) cells. Most of the D-cells were also found in the pyloric antrum but a few were found scattered diffusely throughout body and fundus of the stomach. The estimated total number of D-cells was 11 X 10(6) cells in the pyloric antrum and 4 X 10(6) cells in the corpus and fundus. The G-/D-cell ratio in the antrum was 1.4:1. The number of G-cells as well as D-cells per unit mucosal surface area was significantly higher on the greater curvature and the proximal part of the antrum than on other areas of the antrum. Thus, the pattern of distribution in G-cells was similar to that of D-cells and there was a highly significant correlation between G- and D-cells per unit mucosal surface area. It would appear that under normal conditions, the number of G- and D-cells in the antrum are in good balance and may play an important role in the control mechanisms related to gastric secretion.
Leucocytes from patients with gastric cancer and other malignant and non-malignant diseases of the gastrointestinal tract as well as from healthy controls were tested for leucocyte migration inhibition test (LMI) using five different, allogeneic 3M KCl soluble extracts from gastric cancer tissues. The normal range of migration index (MI) was considered to be between 0.77 and 1.18 by calculating the mean MI +/- 2SD of ten healthy controls with cancer extracts. MIs out of this range were considered to be pathologic. In LMI test with a single tumor extract, pathologic MI was found in 48% of 79 gastric cancer patients, such being significantly higher than in those (4-21%) of three other groups of patients. In the panel mode of LMI, i.e., testing each blood sample with five different tumor extracts, 79% (62/79) of patients with gastric cancer were reactive, while 25% (5/20) of colorectal cancer patients showed "positive" reaction and no "positive" reactivity was observed in two other groups of patients. Thus, the "positive" reactivity in patients with gastric cancer was observed significantly higher than those in the other 3 groups of patients. Gastric cancer extracts had a wide range of cross-reactivity when compared with colorectal tumor extracts which showed a relatively restricted cross-reactivity. Thus, the LMI tests, particularly when tested by a panel mode, seems to express cell-mediated immunity against tumor associated antigens of gastric cancer.
The monocyte count in the peripheral blood, chemotactic responsiveness (MCR) and chemotactic factor inactivator (CFI) were measured in 66 patients with gastric cancer. Monocyte counts in advanced gastric cancer patients were significantly increased. MCR was significantly depressed in gastric cancer patients in the advanced stage of the disease, as compared with findings in the control groups. Sixty-seven percent of the patients with stage IV carcinoma had abnormally depressed responses. The CFIs were significantly higher in gastric cancer patients than in the control groups, and there was a positive correlation between the degree of inhibition and extent of cancer progress. These data support the hypothesis that qualitative and quantitative abnormalities of circulating monocytes, as macrophage precursors, may hinder immunological host defense mechanisms.
Leucocytes from patients with colorectal and other malignant and non-malignant gastrointestinal diseases as well as those from normal subjects were tested by the leucocyte migration inhibition test (LMT), employing the method of Clausen, using five different allogenic 3M KCl soluble extracts of colorectal cancer tissue. The normal range of migration index (Ml) was found to be greater than 0.82 and less than 1.20 by calculating the mean Ml +/- 2SD of ten normal subjects with cancer extracts. Mls out of this range were considered to be pathological. In LMIT with a single tumour extract, a pathological Ml was found in 46% of 50 colorectal cancer patients, a significantly higher figure than found in the three other groups of patients (4% to 16%). In the panel mode of LMIT, that is, testing each blood sample with five different tumour extracts, 40/50 (80%) of patients with colorectal cancer were reactive, while 2/15 (13%) of gastric cancer patients showed a "positive" reaction; no positive reactivity was observed in the other two groups of patients. Thus "positive" reactivity was significantly commoner in patients with colorectal cancer than in patients belonging to the other groups. The frequency of "positive" reactivity was higher in patients with Dukes C carcinoma than in those with Dukes A or B carcinomas, though differences were not significant. In the follow-up study, marked depression of reactivity was seen 10 to 14 days after curative resection. In patients without recurrence, leucocyte migration was found to be in the normal range during the two four weeks after surgery. "Positive" reactivity reappeared in patients with local recurrence. Thus the LMIT, particularly when tested by a panel mode, by demonstrating cell-mediated immunity against tumour-associated antigens of colorectal cancer, provides a method of monitoring colorectal cancer activity.
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Intrarectal administration of 5-fluorouracil (5-FU) emulsion was compared experimentally with that of 5-FU solution as to the degree of absorption and tissue distribution. For the 5-FU levels in the rectal wall, the levels in the emulsion group remained at high levels during the 6 hour period after administration while the levels in the solution group decreased rapidly. For the 5-FU levels in the lymph nodes, those in the emulsion group were significantly higher (more than four times) and remained at relatively high levels for a longer period than those in the solution group. In the thoracic lymph, 5-FU levels in the emulsion group remained more than two times higher throughout the experimental period. The results suggest tha preoperative intrarectal administration of 5-FU emulsion may be effective as an adjunct to surgery for rectal cancer with lymph node metastasis, because of the long duration of high concentration resulting in the rectal lymphatics and rectal wall.