Effects of EMD in combination with bone swaging and calcium phosphate bone cement on periodontal regeneration in one-wall intrabony defects in dogs.

BACKGROUND AND OBJECTIVE: Although the application of EMD is a widely accepted periodontal-regenerative therapy, its effects on noncontained intrabony defects are unpredictable because of the lack of a space-making property. The combined use of EMD and autogenous bone grafts reportedly stimulates significant periodontal regeneration in intrabony defects. The aim of the present study was to evaluate the effects of EMD in combination with bone swaging (BS) and injectable calcium phosphate bone cement (CPC), which was placed into the spaces between the grafted swaged bone and the proximal host bone, on periodontal healing in one-wall intrabony defects in dogs. MATERIAL AND METHODS: One-wall intrabony defects (3 mm wide and 5 mm deep) were surgically created on the mesial and distal sides of the bilateral mandibular premolars in four dogs. The 16 defects were assigned to one of the following treatments: EMD only, BS only, EMD with BS (EMD + BS), or EMD with BS and CPC (EMD + BS + CPC). The animals were killed 8 wk after surgery for histologic evaluation. RESULTS: The height of newly formed bone was significantly greater in the EMD + BS + CPC group (3.73 ± 0.30 mm) than in the BS-only (2.74 ± 0.33 mm; p < 0.05) and EMD + BS (2.88 ± 0.98 mm; p < 0.05) groups. The area of newly formed bone was significantly larger in the EMD + BS + CPC group (5.68 ± 1.66 mm(2)) than in the EMD-only (3.68 ± 0.33 mm(2); p < 0.05), BS-only (3.48 ± 1.26 mm(2); p < 0.05) and EMD + BS (3.38 ± 1.37 mm(2); p < 0.05) groups. The EMD-only (4.63 ± 0.42 mm), EMD + BS (4.67 ± 0.30 mm) and EMD + BS + CPC (4.78 ± 0.54 mm) groups showed significantly greater cementum formation than did the BS-only group (3.93 ± 0.56 mm; p < 0.05). CONCLUSION: These results indicate that treatment with EMD + BS + CPC promotes favorable periodontal healing in one-wall intrabony defects in dogs.

[Release of gamma-aminobutyric acid from cat colon].

The release of gamma-aminobutyric acid was confirmed in isolated cat colon loaded with tritiated gamma-aminobutyric acid. Thirty to 180 minutes after loading the spontaneous efflux of tritium appeared to fit a single exponential curve with an efflux rate coefficient of 0.002 per minute. Electrical stimulation produced frequency-dependent increases in the tritium efflux and in the contractions. Even 120 minutes later over 91 percent of the total radioactivity in the superfusates was attributable to tritiated gamma-aminobutyric acid. The acid release and the contractions induced by electrical transmural stimulation were inhibited by tetrodotoxin and by a calcium-free medium. Release of the acid was not significant during contractions elicited by nicotine and acetylcholine. These findings indicate that gamma-aminobutyric acid is released from the terminals of neurons in the myenteric plexus of the colon.

Renal histology before and after effective enzyme replacement therapy in a patient with classical Fabry's disease.

A 38-year-old man underwent renal biopsy because of proteinuria. It revealed swelling and vacuolation of glomerular epithelial cells, as well as myelin-like structures characteristic of Fabry's disease. Detection of decreased plasma activity of alpha-galactosidase A confirmed the diagnosis. Enzyme replacement therapy was provided with recombinant agalsidase-beta, resulting in improvement of his symptoms. When renal biopsy was repeated, specific staining for globotriaosylceramide showed that renal deposits were decreased by enzyme therapy.

Enhanced effect of gastrin on rat stomach carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine.

This study deals with the effects of gastrin on the incidence of gastric tumors in rats induced by N-methyl-N'-nitro-N-nitrosoguanidine. Inbred Basel-Wistar rats received N-methyl-N'-nitro-N-nitrosoguanidine in drinking water (50 micrograms/ml for 32 weeks) in order to produce gastric carcinoids. A treatment with s.c. injection of pentagastrin (300 micrograms/kg, once daily for 4 weeks) was started at the beginning of N-methyl-N'-nitro-N-nitrosoguanidine treatment simultaneously, on the 4th, 8th, 16th, and 32nd week after start of N-methyl-N'-nitro-N-nitrosoguanidine treatment, respectively. At autopsy, from the 55th to 60th week after start of the experiment, only in the eighth-week group of gastrin-treated rats was the incidence of gastric carcinoid significantly higher than in the gastrin-untreated group of rats receiving N-methyl-N'-nitro-N-nitrosoguanidine alone. The incidence of adenocarcinoma in the glandular stomach also was high only in the fourth-week group of gastrin-treated rats. However, these effects could not be seen in other gastrin-treated or untreated groups of rats. The data suggest that gastrin treatment in the early stage of rat stomach carcinogenesis by N-methyl-N'-nitro-N-nitrosoguanidine is effective in increasing the development of gastric tumors.

A phorbol ester and A23187 act synergistically to release acetylcholine from the guinea pig ileum.

Electrical stimulation of guinea pig ileum preloaded with [3H]choline provokes the release of [3H]acetylcholine (ACh) in a Ca2+-dependent manner. This release was markedly increased by the tumor-promoting phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA). The combination of the ionophore A23187 and TPA produced the release of [3H]ACh up to a level equal to or exceeding a maximal response induced by electrical stimulation. A23187 alone gave only a minor response and TPA alone had no apparent effect on the [3H]ACh release. Thus, protein kinase C probably plays a role in cell surface signal transduction related to the release of transmitters from nerve endings.

Expression of the GABAB receptor in Xenopus oocytes and inhibition of the response by activation of protein kinase C.

The functional GABAB receptor was expressed in Xenopus oocytes by injecting mRNA obtained from the cerebellum of the rat. Application of GABA in the presence of bicuculline induced a hyperpolarization under current-clamp conditions and an outward current under voltage-clamp conditions. Baclofen mimicked the effect of GABA in the presence of bicuculline, and the effect of baclofen was antagonized by phaclofen. The GABA-induced outward current was slightly inhibited by treatment with GDP-beta-S and was completely inhibited by treatment with GTP-gamma-S. The activation of protein kinase C by 12-O-tetradecanoylphorbol-13-acetate (TPA), but not 4 alpha-phorbol-12,13-didecanoate, suppressed the GABAB receptor-mediated hyperpolarization, and the effect of TPA was antagonized by sphingosine. Thus, activation of protein kinase C inhibits the expressed GABAB receptor-mediated response.

Effect of Helicobacter pylori eradication on subsequent development of cancer after endoscopic resection of early gastric cancer.

Although epidemiological studies strongly suggest an association between gastric cancer and Helicobacter pylori infection, there has been no clinical report indicating that cure of the infection prevents cancer. We conducted a nonrandomized H. pylori eradication trial in patients whose gastric cancer was removed by endoscopic resection (ER). We investigated the effect of treatment on the histopathology of the gastric mucosa, as well as on the incidence of metachronous gastric cancer during the long-term clinical and endoscopic follow-up. One hundred and thirty-two patients with early gastric cancer underwent ER and had H. pylori infection. Sixty-five (group A) were treated with omeprazole and antibiotics to eradicate the infection, and 67 (group B) were not. All patients were followed for 2 years post ER. After eradication treatment in group A, the disappearance of neutrophil infiltration in the antrum and body of the stomach was observed as was a decrease of the severity of intestinal metaplasia. Endoscopy after ER detected no new gastric cancers in these patients. After 3 years of follow-up, 6 (9%) of the 67 patients in group B had a new early-stage, intestinal-type gastric cancer endoscopically diagnosed. The above results suggest that H. pylori eradication may improve neutrophil infiltration and intestinal metaplasia in the gastric mucosa and inhibit the development of new carcinomas. This finding should be confirmed in a randomized, controlled trial.

Endothelin receptors in kainic acid-induced neural lesions of rat brain.

Seven days after an intracerebroventricular injection of 0.8 microgram kainic acid, a time of neural tissue-repair after damage, we applied our receptor autoradiographic method to examine changes in the endothelin receptors in kainic acid-induced neural lesions of the rat brain. There were belt-shaped areas with the de novo expressed [125I]endothelin-1 binding sites in the damaged hippocampus CA1, CA3, and CA4 subfields. We also noted a homogeneous zone with a low binding-density, the area sandwiched by the belt-shaped areas. In a "remote" area corresponding anatomically to the deep soma layer of the piriform cortex plus lateral parts of amygdaloid complex we noted a well-defined area with "punched hole-figure" of low density [125I]endothelin-1 binding sites. The lesion was surrounded by areas rich in binding sites. The de novo expressed [125I]endothelin-1 binding sites were characterized endothelin B receptor. Microglia were present in the area with "punched hole-figure" and in the hippocampus pyramidal cell layer with neuronal death. In contrast to microglia, astrocytes were rich with hypertrophia in kainic acid-induced neural lesions anatomically corresponding to areas with the de novo endothelin B receptor. Taken together with the present observations of microscopic evidence of cellular distribution, we suggest that the de novo expressed endothelin B receptor was carried by astrocytes aggregating in neural lesions. In light of our findings, the possibility that astrocytes can be activated by the endothelin B receptor in response to neural tissue repair after damage to neurons would have to be considered.

The Leu13-motilin (KW-5139)-evoked release of acetylcholine from enteric neurones in the rabbit duodenum.

1. Involvement of cholinergic mechanisms in the contractile response to Leu13-motilin (LMT, KW-5139) was investigated in rabbit duodenal segments, and longitudinal muscle-myenteric plexus (LM-MP) preparations preincubated wtih [3H]-choline. 2. Contractile response to LMT (0.1 nM-1 microM) consisted of an initial rapid (phasic) contraction and a tonic contraction slowly fading to a sustained plateau. LMT caused a concentration-dependent phasic contraction of rabbit isolated duodenal segments. The EC50 value was 2.5 nM and the maximum amplitude of the contraction was 103% of the response induced by acetylcholine (ACh, 100 microM). Neither tetrodotoxin nor atropine changed the EC50 value or the maximum amplitude of the response to LMT. 3. Both atropine and tetrodotoxin decreased the amplitude and accelerated fading of the tonic contraction produced by LMT. 4. LMT (30 nM-3 microM) induced an increase of 3H-outflow, in a concentration-dependent manner. The LMT-induced increase of 3H-outflow was prevented by removal of external Ca2+ or by the presence of tetrodotoxin. 5. Porcine motilin (10 nM-1 microM) also stimulated the release of 3H at a similar concentration-range to that seen with LMT. 6. Pretreatment with LMT (3 microM for 20 min) decreased LMT- and the porcine motilin-evoked release of 3H but did not alter the high K(+)-evoked release. 7. Our results suggest that LMT and porcine motilin stimulate the release of ACh from enteric neurones through the same receptor, and that the release of ACh plays a role in tonic components of contraction in the rabbit duodenum.

Release of gamma-aminobutyric acid and acetylcholine by neurotensin in guinea-pig ileum.

The release of gamma-aminobutyric acid (GABA) and acetylcholine (ACh) from the strips of guinea-pig ileum was investigated in the presence of neurotensin. Neurotensin evoked the release of [3H]-GABA from the strips preloaded with [3H]-GABA, and the evoked release was Ca2+-dependent and tetrodotoxin-sensitive. Hexamethonium, scopolamine, [D-Pro2,D-Trp7,9] substance P and pretreatment with substance P did not alter the neurotensin-evoked release of [3H]-GABA. Pretreatment with neurotensin inhibited the release of [3H]-GABA evoked by neurotensin but not by high K+, thereby indicating that neurotensin induced a specific desensitization of its own receptor. These observations indicate that neurotensin may stimulate the GABAergic neurone through its own receptor. Neurotensin evoked the release of [3H]-ACh from strips preloaded with [3H]-choline and this release was Ca2+-dependent and tetrodotoxin-sensitive. The evoked release of [3H]-ACh was not affected by hexamethonium, scopolamine and [D-Pro2,D-Trp7,9] substance P. Bicuculline partly inhibited the neurotensin-evoked release of [3H]-ACh; thus neurotensin seems to induce a release of ACh partly through the release of endogenous GABA. All this evidence indicates that neurotensin induces release of GABA as well as ACh from the myenteric neurones of the guinea-pig ileum.

Presynaptic muscarinic and alpha-adrenoceptor-mediated regulation of GABA release from myenteric neurones of the guinea-pig small intestine.

The effects of cholinomimetic and sympathomimetic drugs on the release of [3H]-gamma-aminobutyric acid ([3H]-GABA) evoked by high K+ from the isolated small intestine of the guinea-pig were investigated, in the presence of tetrodotoxin. Acetylcholine and oxotremorine, at concentrations ranging from 10(-9) to 10(-6) M inhibited the evoked release of [3H]-GABA in a concentration-dependent manner, while nicotine was without effect. Scopolamine and pirenzepine inhibited the effect of oxotremorine, while hexamethonium had no effect. The IC50 values for scopolamine and pirenzepine of the oxotremorine (3 X 10(-8) M)-induced inhibition were 1.02 X 10(-9) M and 9.78 X 10(-10) M, respectively. Noradrenaline, but not isoprenaline inhibited the evoked release of [3H]-GABA. Clonidine (10(-10)-10(-6) M) reduced the evoked release of [3H]-GABA in a concentration-dependent manner, but phenylephrine had no effect. The inhibitory effect of clonidine was antagonized by yohimbine but not by prazosin. These findings provide evidence for the localization of M1-muscarinic and alpha 2-adrenoceptors on GABAergic nerve terminals and their involvement in the presynaptic control of the release of GABA from the guinea-pig small intestine.

Dual effects of 5-hydroxytryptamine on the release of gamma-aminobutyric acid from myenteric neurones of the guinea-pig ileum.

The effects of 5-hydroxytryptamine (5-HT) on the release of gamma-aminobutyric acid (GABA) were examined in the longitudinal muscle-myenteric plexus (LM-MP) preparation of guinea-pig ileum. 5-HT increased the spontaneous release and inhibited the electrically-evoked release of [3H]-GABA. The 5-HT-evoked release was Ca2+-dependent and tetrodotoxin-sensitive, and was antagonized by (3 alpha-tropanyl)-1H-indole-3-carboxylic acid ester (ICS 205-930), but not by methysergide and ketanserin. The inhibitory effect of 5-HT was antagonized by methysergide, but not by ketanserin and ICS 205-930. 8-Hydroxy-2-(di-n-propylamino)tetralin mimicked the inhibitory effect of 5-HT. Thus, 5-HT may exert an excitatory effect on the enteric GABAergic neurone via the 5-HT3 receptor and an inhibitory effect via the 5-HT1A receptor.

Regulation of the substance P-induced contraction via the release of acetylcholine and gamma-aminobutyric acid in the guinea-pig urinary bladder.

1. The action of substance P (SP) on the release of gamma-aminobutyric acid (GABA) and acetylcholine (ACh) and on contraction were studied in strips of the guinea-pig urinary bladder. Substance P induced a dose-dependent contraction of strips of guinea-pig urinary bladder (EC50 = 1.2 x 10(-9) M). This contraction was not altered by tetrodotoxin, but with a dose of 10(-9) M and less, there was a complete inhibition by 10(-6) M) atropine. Contractions initiated by 3 x 10(-9) M) SP or more were partly inhibited by atropine. The EC50 value of substance P in the presence of atropine was 7.0 x 10(-9) M. 2. Substance P induced a Ca2+-dependent and tetrodotoxin-resistant release of [3H]-acetylcholine (ACh) from strips of urinary bladder preloaded with [3H]-choline (EC50 = 4.9 x 10(-10) M), and this release was antagonized by [D-Pro2,D-Trp7,9] substance P. 3. Bicuculline increased the substance P-induced contraction and the release of [3H]-ACh from the strips. 4. Substance P induced a Ca2+-dependent and tetrodotoxin-sensitive release of [3H]-gamma-aminobutyric acid (GABA) from strips preloaded with [3H]-GABA (EC50 = 2.6 x 10(-9) M), and this release was antagonized by [D-Pro2,D-Trp7,9] substance P. 5. Therefore, substance P appears to exert excitatory effects on the contractility of urinary bladder predominantly by stimulating its own receptor located on the cholinergic nerve terminals. GABA released by substance P inhibits stimulation of the cholinergic neurone. However, the direct action of substance P on the cholinergic neurone is more potent that the indirect action via GABA release.

Localization of endothelin ETB receptors on the myenteric plexus of guinea-pig ileum and the receptor-mediated release of acetylcholine.

1. The type of endothelin (ET) receptor located on the myenteric neurones of guinea-pig ileum was determined by receptor autoradiography and function of the receptor was examined by release experiments of acetylcholine (ACh) from the longitudinal muscle myenteric plexus (LM-MP) preparations. 2. Specific [125I]-ET-1 binding sites were distributed in muscle layers, myenteric and submucous plexuses, and mucosa layers. High-grain densities were detected in both myenteric and submucous plexuses. 3. Binding in the myenteric plexus was abolished by incubation with either IRL 1620 (endothelin ETB receptor agonist) or BQ 788 (endothelin ETB receptor antagonist), but not with BQ 123 (endothelin ETA receptor antagonist). The [125I]-IRL 1620 binding sites were evident in the myenteric plexus. Thus, the endothelin receptor located on the myenteric neurones is of the ETB type. 4. ET-1 (10(-10)-3 x 10(-8) M) and ET-3 (10(-10)-3 x 10(-8) M) evoked 3H outflow from LM-MP preparations of ileum preloaded with [3H]-choline, in a concentration-dependent manner. There was no significant difference between maximum amounts of ET-1-evoked and ET-3-evoked 3H outflow. 5. ET-1 and ET-3 evoked outflow of 3H was BQ 788-sensitive, but BQ 123-insensitive. Both evoked outflows of 3H were Ca(2+)-dependent and tetrodotoxin-sensitive. 6. These results indicate that the endothelin ETB receptor is located on the enteric cholinergic neurones and that stimulation evokes the release of ACh.

Expression of CD44 abnormal transcripts in human gastric carcinomas.

Twenty gastric carcinoma cases were studied for the detection of CD44 aberrant transcripts using a cDNA/PCR/blot-hybridization technique which can detect splice variants containing an aberrant exon 11 of the CD44 gene. All the tumor tissues as well as their metastatic foci demonstrated overexpression of CD44 splice variants of more than 1.0 kbp than corresponding normal gastric mucosas. Six out of nine (66.7%) well-differentiated or intestinal type gastric cancers overexpressed more than three aberrant transcripts, whereas ten out of eleven (90.9%) poorly differentiated or diffuse type cancers overexpressed single or two lower molecular weight variants. These results indicate that the detection of CD44 transcription variants can serve as a powerful tool for the diagnosis of gastric cancer. It is also suggested from the difference in variant expression pattern that well-differentiated type and poorly differentiated type gastric carcinomas have different genetic pathways.

Changes in Helicobacter pylori-induced gastritis in the antrum and corpus during long-term acid-suppressive treatment in Japan.

BACKGROUND: Several studies have shown that acid-suppressive therapy aggravates corpus gastritis in patients with Helicobacter pylori infection, promoting the development of atrophic gastritis. AIM: To study the effects of long-term use of antisecretory agents on the H. pylori-positive gastric mucosa in Japan, a country with a high incidence of gastric cancer. METHODS: A total of 141 H. pylori-positive patients who had peptic ulcers or reflux oesophagitis were treated for 3 years with either omeprazole (20 mg/day) alone (n=7) or with omeprazole for primary therapy (8 weeks), followed by famotidine (40 mg/day) for maintenance therapy (n=134). Endoscopy was performed before, during, and after treatment. Biopsy specimens were taken from the greater curvature of the antrum and corpus and were examined histologically. RESULTS: The long-term use of famotidine after 8 weeks of treatment with omeprazole distinctly decreased H. pylori density and neutrophil infiltration in the antrum, but did not change H. pylori density in the corpus. The gastritis score increased in patients who had no, or only mild corpus gastritis before treatment (n=74), and significantly decreased in those who had moderate or severe gastritis before treatment (n=60). In four of the seven patients who received long-term treatment with omeprazole alone, neutrophil infiltration and H. pylori density decreased not only in the antrum but also in the corpus. There was no increase in intestinal metaplasia or mucosal atrophy as assessed endoscopically during follow-up. CONCLUSION: Changes in corpus gastritis in response to acid-suppressive therapy depend on the severity of gastritis before treatment. Long-term use of acid-suppressive therapy apparently does not accelerate the development of atrophy or intestinal metaplasia in Japanese patients.

Gastric corpus IL-8 concentration and neutrophil infiltration in duodenal ulcer patients.

BACKGROUND: The purpose of the present study was to examine the association between interleukin-8 (IL-8) in the gastric body due to Helicobacter pylori infection and histological gastritis, as well as elucidating the effect of acid secretion inhibitors on H. pylori associated body gastritis in duodenal ulcer patients. METHODS: Twenty H. pylori-negative patients, 20 H. pylori-positive patients with chronic gastritis without peptic ulceration, and 20 H. pylori-positive duodenal ulcer patients (DU) were studied. Four biopsy samples were taken, each from the greater curvature of the antrum and body of the stomach. Biopsies were histologically investigated by ELISA to determine the density of H. pylori, the degree of neutrophil infiltration and the IL-8 concentration in the mucosa. RESULTS: In the gastric mucosa of H. pylori-negative subjects, no IL-8 and hardly any neutrophil infiltration were observed. In contrast, enhanced IL-8 production and increased neutrophil infiltration were present in those infected with H. pylori. In H. pylori-positive patients, a significant correlation was observed between the IL-8 concentration and the degree of neutrophil infiltration, but no correlation was found in the body mucosa of those with DU. Twelve of 20 DU patients demonstrated hardly any neutrophil infiltration, despite the increased mucosal IL-8 content in the body. The administration of omeprazole in DU patients markedly increased mucosal neutrophil infiltration even though it did not cause any significant change in the H. pylori density and IL-8 concentration in the body. Although the effect of omeprazole was transient, a significant increase in neutrophil infiltration continued in comparison with the status before omeprazole administration in those subsequently undergoing maintenance treatment with H2-blockers. CONCLUSION: In H. pylori-positive chronic gastritis, IL-8 concentration is enhanced in the mucosa of the body, and is associated with increased neutrophil infiltration. However, in DU patients, despite increases in body IL-8 concentration, neutrophil infiltration is reduced and the gastritis may be localized in the antrum.

Alpha 1-antitrypsin, alpha 1-antichymotrypsin, and alpha 2-macroglobulin in human gastric carcinomas: a retrospective immunohistochemical study.

One hundred twenty-six gastric carcinomas (68 advanced cancers and 58 early cancers) were examined immunohistochemically for alpha 1-antitrypsin (AAT), alpha 1-antichymotrypsin (ACT), and alpha 2-macroglobulin (AMG) within tumor cells. The incidence of these three protease inhibitors was markedly higher in advanced than in early cancers, regardless of the histologic type of gastric carcinoma. In advanced cancers the incidence of both AAT and AMG was significantly higher in well-differentiated adenocarcinomas than in poorly differentiated adenocarcinomas, but no difference was observed in the expression of ACT between these two types of advanced carcinomas. Eighty per cent of the AAT-positive advanced carcinomas had ACT, and 40 per cent of these tumors also contained AMG. The two-year survival rates clearly indicated that well-differentiated adenocarcinomas with AAT have worse prognoses than well-differentiated adenocarcinomas without AAT, but there was no relation between the expression of ACT or AMG and prognosis. These results strongly suggest that the presence of protease inhibitors in gastric carcinomas is related to the invasive growth of the tumors and that AAT is a tissue tumor marker of well-differentiated adenocarcinomas of the stomach. It may also serve as a biologic marker of high malignancy in patients with these gastric cancers.

Argyrophil cells in early gastric carcinoma: an immunohistochemical and ultrastructural study.

Eighteen argyrophil cell carcinomas in 101 early gastric carcinomas were explained histologically, ultrastructurally, and immunohistochemically for polypeptides, carcinoembryonic antigen (CEA), lysozyme, and human chorionic gonadotrophin (hCG). Seven of these 18 tumors had gastrin, and two of seven tumors also contained somatostatin. In all of these 18 tumors CEA were demonstrated. Seven had lysozyme and five of seven tumors also contained gastrin; hCG were present in four of the 18 tumors and two of four tumors had gastrin, CA, mucin, and lysozyme simultaneously. Argentaffin cells were found in seven of 18 tumors. Of the above seven tumors containing gastrin, three had argentaffin cells. Ultrastructurally, several types of secretory granules were noted and tumor cells resembling D1- or P cells were present in nine of the 18 tumors. Macroscopically, many of the tumors showed IIc or IIc + III type. Histologically, the 18 tumors consisted of six well differentiated adenocarcinomas and 12 poorly differentiated adenocarcinomas including signet-ring cell carcinoma. These 12 tumors frequently developed in the stomach of young females. In view of our previous investigations, it was suggested that the IIc-type argyrophil cell carcinoma histologically showing poorly differentiated adenocarcinoma may be related to scirrhous carcinoma of the stomach.