Biomedical subjects

K Inada

Publications and source records attributed to K Inada.

At least 73 records · Page 4Linked to original sources

PubMed1998

[An adult case of intrathoracic chest wall type lipoma by VATS resection].

A 48-year-old woman without symptoms was pointed out an abnormal shadow on chest X-ray film taken at the mass survey. Image diagnosis led to intrathoracic chest wall type lipoma. The tumor was surgically removed by video assisted thoracoscopic surgery (VATS), and the diagnosis of lipoma pathohistologically. VATS resection was an useful procedure for intrathoracic lipoma because VATS itself must be less invasive and lipoma was not invasive. CT and MRI were useful for evaluation of extent of tumor, but not effective for differential diagnosis of liposarcoma from lipoma. So surgical resection by VATS should be considered, if possible.

Endoscopy↗

PubMed1998

Nuclear matrix protein, tumor necrosis factor-alpha, and nitrite/nitrate levels in patients with multiple organ dysfunction syndrome.

Nuclear matrix protein (NMP), an indicator of apoptosis, was analyzed in patients with multiple organ dysfunction syndrome (MODS). Blood levels of tumor necrosis factor-alpha (TNF-alpha) and nitrite/nitrate (NOx) were also measured in these patients to determine the involvement of these factors in the production of NMP. Forty-six patients with MODS were studied, 21 (45.7%) of whom died. NMP and TNF-alpha were measured by enzyme-linked immunosorbent assay (ELISA). NOx was measured by the Griess's method. Marshall's multiple organ dysfunction score (MOD score) was used as an indicator of organ failure. The severity of organ failure was assessed by use of the acute physiology and chronic health evaluation II score (APACHE II score). The number of organs that failed was found to be significantly correlated with the NMP level. The NMP level was also correlated significantly with MOD score and APACHE II score, as well as with TNF-alpha and NOx levels. NMP and NOx levels in the group that died significantly exceeded those in the surviving group. Results suggest that apoptosis can occur in the presence of MODS, and that its extent increases as the number of failing organs increases. The results also suggest that TNF-alpha and NO are involved in the induction of apoptosis.

Adolescent↗

PubMed1997

Effects of carbon tetrachloride administration on initiation of liver cell foci by the non-hepatocarcinogens N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and benzo(a)pyrene (B(a)P).

In a development trial for an initiation bioassay system, cell proliferation kinetics after partial hepatectomy (PH) or CCl4 administration (1 ml/kg b.w., i.g.) and the effect of administration time after PH or CCl4 treatment on liver cell foci induction by the direct and indirect non-hepatocarcinogens, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and benzo(a)pyrene (B(a)P) were investigated. Male F344 rats were killed 12, 18, 24, 36, 48, 72 or 96 h after PH or CCl4 treatment and liver cell proliferation was examined with the bromodeoxiuridine (BrdU) labeling method. Appreciable increase in the BrdU labeling index was observed 18-36 h after PH with a peak at 24 h, and 18-72 h following treatment with CCl4 with a peak at 48 h. MNNG (80 mg/kg i.g.) or B(a)P (100 mg/kg i.g.) were administered to 7-week-old male F344 rats at various times after PH or CCl4 treatment and lesion induction was assessed using the resistant hepatocyte model. MNNG caused significant numbers of glutathione S-transferase placental form (GST-P)-positive liver cell foci in rats when given 12-36 h after PH, with a peak at 24 h. In contrast, the numbers of foci induced by B(a)P were maximal with exposure at 12 h after PH. In the CCl4 study, both MNNG and B(a)P induced significant increase in GST-P-positive liver cell foci when given 12-72 h after CCl4 treatment, with a peak at 48 h, the results being directly in line with the changes in BrdU labeling. From these findings, it is concluded that initiation assay protocols with a CCl4 proliferative stimulus to hepatocytes may prolong the appropriate administration period for effective detection of the initiation potential of both direct and indirect carcinogens targeting sites other than the liver.

Animals↗

PubMed1997

Overexpression of c-fos inhibits down-regulation of a cyclin-dependent kinase-2 inhibitor p27Kip1 in splenic B cells activated by surface Ig cross-linking.

Splenic B cells activated by surface Ig (sIg) cross-linking transiently express the c-fos gene within 0.5 h and then enter into S phase of the cell cycle within 48 h. To investigate a role of c-fos in cell cycle progression, we used splenic B cells from IFN-alphabeta-inducible c-fos transgenic mice (Mx-c-fos). In the absence of IFN, the cell cycle progression of Mx-c-fos B cells stimulated with anti-IgM Ab was similar to that in control B cells. The cell cycle was arrested in G1 phase when we added IFN to the culture within 12 h after anti-IgM Ab stimulation, suggesting that overexpression of c-fos until mid-G1 phase perturbs activation of the cell cycle regulatory machinery. In control B cells, cyclin E and cdk2 were induced within 24 to 48 h after stimulation, and this induction was accompanied by down-regulation of a cdk2 inhibitor p27Kip1. As a consequence of these activation processes, cdk2 kinase activity was induced in B cells in the late G1 phase. However, kinase activity was not detected in Mx-c-fos B cells, presumably because the down-regulation of p27 was perturbed. These data suggest that c-Fos can negatively control cell cycle regulatory machinery in sIg-stimulated B cells.

Animals↗

PubMed1997

Highly metastatic hepatocellular carcinomas induced in male F344 rats treated with N-nitrosomorpholine in combination with other hepatocarcinogens show a high incidence of p53 gene mutations along with altered mRNA expression of tumor-related genes.

The carcinogenic and metastatic processes are thought to consist of a sequence of steps, and animal models featuring highly metastatic lesions are clearly necessary to allow analysis of the whole process of transformation from preneoplastic changes to high grade metastatic tumors, and to access effectiveness of therapeutic treatments of advanced cancers in vivo. The purpose of the present study was to establish a model and to screen for reported genetic alterations in induced lesions. In the present study, it was confirmed that lung metastasis of hepatocellular carcinomas (HCCs) induced in male F344 rats by N-nitrosomorpholine (NNM), given in the drinking water at a dose of 120 ppm for 24 weeks, was significantly enhanced by additional carcinogenic pretreatments and that a single i.p. injection of 100 mg/kg body weight N-diethylnitrosamine (DEN) alone was sufficient for that purpose. Molecular biological analyses of the induced lesions revealed point mutations in the p53 gene in 60.9% of HCCs, and elevated expression of mRNAs for p53, c-myc, c-fos, TGF-alpha, TGF-beta1, alpha-fetoprotein, GST-P, and GGT, and decreased mRNA expression of EGF and EGFR in HCCs when compared to controls. No obvious association of gene alterations with metastatic potential of primary tumors was found except for an increase in the incidence of p53 mutations. Since the process of metastasis is thought to be sequential and selective, further comparative analysis of metastatic and primary lesions should clarify the mechanisms involved in the multi-step process of metastasis.

Animals↗

PubMed1997

Induction of invasive squamous cell carcinomas in the forestomach of (C3H x MSM)F1, MSM, and C3H mice by N-methyl-N-nitrosourea and mutational analysis of the H-ras and p53 genes.

Genetic analysis of tumors developing in F1 hybrids between genetically separate strains of mice makes it possible to search for loss of heterozygosity (LOH), information on which provides clues to finding tumor-suppressor genes. For this purpose, however, reproducible carcinogenic conditions for the organ of interest need to be first determined. In the present study, a forestomach model of squamous cell carcinomas (SCCs), induced in (C3H x MSM)F1 mice by N-methyl-N-nitrosourea (MNU), was established and mutational changes in the H-ras and p53 genes were examined in tumors. Male (C3H x MSM)F1, MSM and C3H mice were given MNU by i.g. intubation once a week at a dose of 0.03 mg/g body weight for 10 weeks, then kept without further treatment. At experimental weeks 38-46, markedly invasive SCCs were observed in the forestomach at incidences of 9/14 (64.3%), 9/16 (56.3%), and 2/10 (20.0%), respectively. In the three strains of mice, DNA analysis of SCCs by PCR-SSCP analysis followed by direct DNA sequencing revealed low incidences of point mutations in the H-ras (4/20, 20%) and p53 (3/20, 15%) genes. The results demonstrate the usefulness of the present animal experimental protocol for induction of high grade SCC in the forestomach of (C3H x MSM)F1 mice, and suggest the possibility that point mutations in the H-ras or p53 genes may play some role in pathways leading to the development of such lesions.

Animals↗

PubMed1997

Haemodynamic comparison of sevoflurane and isoflurane anaesthesia in surgical patients.

PURPOSE: To compare the haemodynamic responses to surgical incision during sevoflurane and isoflurane anaesthesia and to compare the haemodynamic effects of each anaesthetic alone with those obtained using an equipotent mixture of each anaesthetic plus N2O during steady-state surgical stimulation. METHODS: Twenty-four patients undergoing gastrectomy were randomized to receive sevoflurane (n = 12) or isoflurane (n = 12). At 1.5 MAC, haemodynamic measurements were performed before and after surgical incision. During intestinal anastomosis, patients in each group were given (in random order) either 1.5 MAC of the designated anaesthetic or 0.85 MAC of the volatile plus 0.65 MAC N2O. Haemodynamic measurements were repeated under each condition. RESULTS: One patient in the sevoflurane group and two in the isoflurane group were excluded from the incision study because of hypotension. In both groups, incision increased the heart rate (HR), mean arterial pressure, mean pulmonary arterial pressure (MPAP), pulmonary capillary wedge pressure (PCWP), cardiac index, and systemic vascular resistance index (SVRI). There were no intergroup differences in the effects of incision. Inclusion of N2O resulted in an increase of MPAP (P < 0.05) in both groups, an increase of central venous pressure and PCWP in the sevoflurane group (P < 0.005), and a decrease of HR (P < 0.005) and an increase of SVRI (P < 0.05) in the isoflurane group. There were no intergroup differences in the effects of N2O. CONCLUSIONS: At 1.5 MAC, sevoflurane and isoflurane do not prevent the haemodynamic response to incision. The haemodynamic effects of each volatile anaesthetic with N2O are minimal compared with those of equi-MAC volatile alone.

Adult↗

PubMed1997

Interleukin-10 and interleukin-1 receptor antagonists increase during cardiac surgery.

BACKGROUND: It has been reported that inflammatory cytokines such as interleukin-8 and 6 (IL-8, IL-6) increase during cardiac surgery and caused postoperative cardiac dysfunction. Therefore, it is important to investigate changes of suppressive cytokines such as IL-10, interleukin-4 (IL-4) and interleukin-1 receptor antagonist (IL-1ra) during cardiac surgery. METHOD: Serum levels of cytokines and IL-1ra were measured in 10 patients during cardiac surgery with cardiopulmonary bypass. Six blood samples were drawn after inducing anaesthesia. In each sample, serum IL-10, IL-4, IL-8, IL-6 and IL-1ra were measured by enzyme linked immunosorbent assay. RESULTS: Serum IL-6 and IL-8 concentration (19.1 +/- 8.8 pg.ml-1, and 13.4 +/- 5.2 pg.ml-1, preoperatively) increased to 227.5 +/- 191 pg.ml-1 and 81.0 +/- 56 pg.ml-1 at 60 min after declamping aorta (P < 0.01, respectively). Serum IL-10 concentration increased at 60 min after declamping the aorta compared with the preoperative value (from 1.0 +/- 0 pg.ml-1 to 552.0 +/- 158 pg.ml-1 P < 0.001]). Similarly, serum IL-1ra concentration increased from the preoperative value of 1331 +/- 896 pg.ml-1 to 43353 +/- 12812 pg.ml-1 at 60 min after declamping the aorta (P < 0.001). Positive correlations were obtained between IL-10 and IL-8, and between IL-10 and IL-6 (gamma = 0.7, gamma = 0.8, P < 0.001, respectively). CONCLUSION: These findings demonstrate that pro- and anti-inflammatory cytokines increase to maintain their balance during cardiac surgery.

Adolescent↗

PubMed1997

Lidocaine tape relieves pain due to needle insertion during stellate ganglion block.

PURPOSE: To investigate the efficacy of lidocaine tape, a new preparation of lidocaine for cutaneous topical anaesthesia in the form of a self-adhesive tape, in alleviating the pain of needle insertion during stellate ganglion block. METHODS: In a double-blind, placebo controlled study, 30 adult outpatients undergoing stellate ganglion block were allocated to receive all of the following five treatments in random order: placebo tape applied to the intended site of the block (control), or lidocaine tape applied for 7, 15, 30, and 60 min. After the block was performed using a 24-gauge needle, the pain associated with needle insertion was assessed using a visual analogue scale (10 cm VAS) and the four-point verbal rating score (VRS 0-3). RESULTS: With placebo tape, the VAS and VRS scores were 2.4 +/- 1.27 (0.5-4.8) (mean +/- SD (range)) and 1.5 (1-2) (mean (range)), respectively. The pain scores were reduced (P < 0.01) by lidocaine tape after application for 7 min (1.6 +/- 1.06 and 1.0 (0-2) for VAS (mean +/- SD) and VRS (mean (range)), respectively), 15 min (1.5 +/- 1.00 and 1.0 (1-2)), 30 min (1.5 +/- 1.08 and 1.0 (1)), and 60 min (0.6 +/- 0.70 and 0.6 (0-1)). Skin erythema was more frequent with lidocaine tape than with placebo tape (seven minutes of lidocaine tape vs placebo tape, P < 0.05; 15, 30, and 60 min of lidocaine tape vs placebo, P < 0.0005). CONCLUSION: Stellate ganglion block without analgesia is fairly painful in some patients, even when using a 24-gauge needle, and needle pain is reduced by lidocaine tape after an application time of seven minutes or more.

Adult↗

PubMed1997

Reciprocal control of colon-specific sulfomucin and sialosyl-Tn antigen expression in human colorectal neoplasia.

Histochemical reports claim that sulfomucins decrease and sialylated mucins increase during colon carcinogenesis. We examined the expression of colon-specific sulfomucins and sialosyl Tn antigen (STN) in normal small intestine, normal colorectal mucosa and colorectal tumours at different stages of progression immunohistochemically, using MAb 91.9H specific for colonic sulfomucins and MAb TKH-2 for STN. No expression of sulfomucins recognized by MAb 91.9H was found in normal small intestine, whereas STN staining was pronounced. The converse was the case in normal colorectal mucosa. Sulfomucins were still found in adenomas, but the amounts decreased with depth of invasion in cancers (P < 0.001). In contrast, no STN could be detected in benign lesions, but staining became increasingly evident with invasion (P < 0.001). This reciprocal control of expression of colon-specific sulfomucins and STN evident in tumour progression indicates that the mucous phenotype shifts from the colonic to the small intestinal type.

Adenoma↗

PubMed1997

Intestinalization of gastric signet ring cell carcinomas with progression.

Recent developments in mucin histochemistry and immunohistochemistry have made reliable determination of the gastric and intestinal phenotypes of gastric carcinoma cells possible. Phenotypic expression changes from gastric epithelial cell type to intestinal epithelial cell type with the growth of gastric tumours in experimental animals. We studied cell differentiation in gastric signet ring cell carcinomas with progression in 203 surgically obtained specimens. The results showed that the proportion of gastric phenotype carcinomas, in which over 90% of the tissue consists of gastric epithelial cell type cells, decreases with the depth of invasion. The proportion of mixed phenotype carcinomas (between 10% and 90% of the tissue made up of gastric and/or intestinal epithelial cell type cells) increases. The intestinal phenotype (over 90% intestinal epithelial cell type carcinoma cells) was found in four carcinomas (about 2%) involving the serosa. No clear relationship was evident between phenotypic expression of carcinoma cells and the degree of intestinal metaplasia of the surrounding mucosa. Progression of gastric signet ring cell carcinomas is associated with a phenotypic shift from gastric to intestinal type expression.

Carcinoma, Signet Ring Cell↗

PubMed1997

Effect of active fragments of arginine-vasopressin on the disturbance of spatial cognition in rats.

The effect of arginine8-vasopressin (AVP1-9) and its metabolite C-terminal fragments on the scopolamine-induced disruption of spatial cognition were investigated using an 8-arm radial maze task in rats. AVP1-9 (10 micrograms/kg s.c.) markedly improved the disruption of spatial cognition by treatment with scopolamine (0.5 mg/kg i.p.), and 60% of the rats recovered to a normal level. The main metabolite of AVP1-9, AVP4-9 (0.5 and 1 ng/kg s.c.) also significantly improved the scopolamine-induced deficit of spatial memory. The activity of AVP4-9 was determined to be about 10000 fold greater than that of AVP1-9. An intracerebroventricular (i.c.v.) injection of 10 fg of AVP5-8, however, showed a lower activity. Both AVP6-8 and AVP5-7, which are both metabolites of AVP5-8, demonstrated no activity. The scopolamine-induced disruption of spatial memory was found to improve after a microinjection of AVP4-9 (1 fg) into the ventral hippocampus (VH) region, but not into the dorsal hippocampus (DH). In an in vivo microdialysis study, the scopolamine-induced acetylcholine (ACh) release from the VH was slightly potentiated by treatment with AVP4-9 (10 fg i.c.v.). In addition, an AVP4-9 analogue, No. 302, which is a synthetic hexapeptide and has a longer half-life, also demonstrated a markedly improved effect, which had a 10-fold higher activity than that with AVP4-9. AVP4-9 is the most potent activity of all the endogenous metabolites of the AVP1-9 and the new synthetic AVP4-9 analogue, No. 302 (obtained from Nippon Chemiphar Co.), substituting Ser for Cys-Cys in hexapeptide, has higher activity than that of AVP4-9. These results indicated [Ser6] hexapeptide has an important role in behavioral activity. Based on these results, it is possible that AVP1-9 and its metabolite AVP4-9 could, thus, be useful in treating cholinergic dysfunction diseases, such as Alzheimer's disease. Hexapeptide may play an important role in improving the spatial memory by promoting the release of ACh in the VH region.

Acetylcholine↗

PubMed1997

The effects of chronic administration of nimodipine on age-related changes in nitric oxide and its synthase in senescence-accelerated mouse brain.

The levels of nitric oxide (NO) and NO synthase (NOS) activities in the brain of young-adult (3 months old), aged (11 months old) and nimodipine-administered (11 months old) senescence-accelerated mouse (SAM), of which SAMP8 sub-strain is inferior in acquisition of learning and has a lower content in testosterone, were compared. Nimodipine, which is L-type calcium ion channel blocker and has memory-enhancing effects, was administered orally for 5 months. In the cerebral cortex of aged SAMP8, NOS activity was increased compared with that of young-adult SAMP8. Though nimodipine did not alter the contents of NO in any brain regions compared with those in aged SAMP8, nimodipine increased NOS activity in the aged cerebellum. Our data suggest that nimodipine may increase NOS activity through elevation of testosterone level, as testosterone increases NOS only in the cerebellum, although further work is clearly needed to ascertain effects of nimodipine on testosterone metabolism and maintenance in the acquisition of learning.

Age Factors↗

PubMed1997

Elevated plasma levels of interleukin-1 receptor antagonist and interleukin-10 in patients with acute myocardial infarction.

The study was undertaken to measure plasma interleukin-1 (IL-1) receptor antagonist and IL-10 concentrations in patients with acute myocardial infarction and to analyze their relationship to the hemodynamics, severity, and prognosis of myocardial infarction in its acute stages. We attempted to define the kinetics of IL-1 receptor antagonist and IL-10 in patients with acute myocardial infarction (n = 34, age 42-91 years, mean 68 years). Plasma IL-1 receptor antagonist and IL-10 levels were measured by enzyme-linked immunosorbent assay. Patients in group A (n = 17) had uncomplicated acute myocardial infarction (Killip class I). Patients in group B (n = 17) had severe acute myocardial infarction (Killip class II, III, or IV). Peak Il-1 receptor antagonist and IL-10 levels in group B were significantly higher (p < 0.05) than those of group A. In group B, the peak IL-1 receptor antagonist levels were significantly correlated with white blood cell counts (r = 0.63, p = 0.006), pulmonary capillary wedge pressure (r = 0.78, p = 0.0002), and cardiac index (r = -0.51, p = 0.04). Peak IL-10 levels were significantly correlated with white blood cell counts (r = 0.60, p = 0.01), the pulmonary wedge pressure (r = 0.73, p = 0.0008), and cardiac index (r = -0.50, p = 0.04). Moreover, a significant correlation was found between the peak IL-1 receptor antagonist and IL-10 levels (r = 0.91, p < 0.0001). The peak IL-1 receptor antagonist levels in nonsurvivors (n = 13) were significantly higher (p < 0.01) than those in survivors (n = 21). The plasma IL-1 receptor antagonist and IL-10 levels were closely correlated with the severity of hemodynamics in acute myocardial infarction and with the clinical status of patients with severe acute myocardial infarction. Results suggest that plasma IL-1 receptor antagonist and IL-10 can serve as prognostic indicators in cases of sever acute myocardial infarction.

Adult↗

PubMed1997

Denervation promotes the development of cancer-related lesions in the gastric remnant.

Innervation of the gastric mucosa plays an important role in its defense mechanism. In a previous study, gastrectomy with denervation promoted tumorigenesis in the gastric body in rats after administration of a carcinogenic agent. In this study we investigated the induced gastric mucosal changes from the viewpoint of mucin histochemistry. Gastrectomy with denervation promoted the development of intestinal metaplasia, dysplasia, and carcinoma in the gastric body. Proliferating cell nuclear antigen labeling indexes as a marker for cell kinetics were significantly elevated in the denervated group. Analysis of mucin histochemistry by staining with paradoxical concanavalin A (PCA) and galactose oxidase-Schiff (GOS), which are markers for expression of the gastric phenotype, revealed that these mucins were positive in submucosal adenocystic proliferation and carcinoma at the anastomotic site. Conversely, in the gastric body these mucins disappeared with progression of dysplasia, and carcinoma cells contained neither PCA- nor GOS-positive mucins. These results suggest that there are two different processes of carcinogenesis in the gastric remnant, depending on the location, and that denervation of the remnant gastric mucosa promotes the development of cancer-related lesions in the gastric body.

Animals↗

PubMed1997

Bone remodeling with resorbable bioactive glass and hydroxyapatite.

Particulate resorbable bioactive glass and resorbable hydroxyapatite did not inhibit the growth of periodontal ligament cells and osteoblasts in cultures. Both cell types promoted the activation of alkaline phosphatase around the surface of bioactive glass particles. When bioactive glass and hydroxyapatite were cultured with peripheral blood lymphocytes/monocytes, the number of nonadherent and adherent cells was the same as observed with a control. Resorbable bioactive glass activated the cells necessary for bone formation better than hydroxyapatite and suppressed the formation of osteoclasts for bone resorption. Resorbable bioactive glass and resorbable hydroxyapatite were found to be harmless to periodontium cells and lymphocytes/monocytes.

Absorption↗

PubMed1997

Dose-dependent promoting effects of catechol on glandular stomach carcinogenesis in BALB/c mice initiated with N-methyl-N-nitrosourea.

The effects of catechol administration in the diet on stomach carcinogenesis in mice after initiation with N-methyl-N-nitrosourea (MNU) in the drinking water were investigated in a development trial for a new experimental protocol. Male 6-week-old BALB/c mice were given MNU in the drinking water intermittently for a total of three one-week periods, with one-week intervals, at the concentration of 120 ppm (groups 1 and 2). Groups 3 and 4 served as non initiated controls. From week 7, groups 1 and 3 were divided into three subgroups and the mice were fed on diet containing 0.05% (groups 1a and 3a), 0.2% (groups 1b and 3b), 08% (groups 1c and 3c) or 0% (groups 2 and 4) catechol for 29 weeks. At week 20, appreciably enhanced development of pepsinogen 1-altered pyloric glands was noted in all catechol-treated groups, in a partially dose-dependent manner (12.8 +/- 12.5, 13.8 +/- 11.7, and 24.0 +/- 12.7/100 pyloric glands respectively, for groups 1, 2 and 3). The incidences of adenomas (groups 1, 2 and 3) were also increased. At week 35, dose-dependent induction of adenocarcinomas in groups 1 (3/19), 2 (3/19) and 3 (14/20) was evident. In addition, the depth of invasion of the adenocarcinomas was enhanced by catechol in a dose-dependent manner, though the histological type was not influenced. Thus, the administration of catechol in the diet strongly enhanced the preneoplastic and neoplastic lesions in mouse glandular stomach induced by MNU in the drinking water, in a dose-dependent manner.

Adenocarcinoma↗

PubMed1997

Dose-dependent induction of both pepsinogen-altered pyloric glands and adenocarcinomas in the glandular stomach of C3H mice treated with N-methyl-N-nitrosourea.

The dose-response relation for the appearance of pepsinogen isozyme 1 (Pg 1)-altered pyloric glands (PAPG) and the related induction of adenocarcinomas were examined in male C3H mice given N-methyl-N-nitrosourea (MNU) in their drinking water at the concentration of 120 ppm (group 1), 60 ppm (group 2), 30 ppm (group 3) or 0 ppm (group 4) for 30 weeks and then normal tap water. Animals were killed at weeks 10, 30 and 42. Adenomatous hyperplasias and adenocarcinomas were noted from week 30 and their induction was dose-dependent at week 42. Almost all cells of pyloric gland cell type in those lesions had little or no immunohistochemically demonstratable Pg 1 content, as was also the case for the cells in PAPG, whose numbers per 100 normal-appearing pyloric glands were found to be MNU dose-dependent at all experimental time points. The numbers of PAPG at week 10 significantly correlated with the incidences of adenomatous hyperplasias and adenocarcinomas at week 42. Investigation of proliferation by immunohistochemical detection of bromodeoxyuridine (BrdU) labeling in the PAPG at week 10 demonstrated elevation (P < 0.05) as compared to normal pyloric glands. Intestinal metaplasia was not a feature in the present experiment and the results suggest that in mice, PAPG might be a preneoplastic lesion involved in gastric chemical carcinogenesis.

Adenocarcinoma↗