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The goal of this study was to clarify morphogenetic development in colorectal neoplasms with depressions by examining isolated crypts and their pit patterns.Twelve colorectal neoplasms with depressions were examined endoscopically, stereomicroscopically, and histopathologically. The pit pattern was defined according to Kudo's classification. The HCl digestion method was used to isolate the crypts. For scanning electron microscopy observations of the surface structure, specimens were mounted on brass stubs, coated with gold, and then observed.In isolated crypts with bifurcation extending to the middle or all the way to the lesion surface, the crypt orifice was round with a type IIIS pit pattern. In those with bifurcations extending up to the upper portion, the crypt orifice was oval with a type IIIS pit pattern. Some crypts were almost completely separated into two. The orifice diameter of a nonbifurcated crypt was 95.1 +/- 28.1 microm, whereas the diameters of crypts with bifurcations extending to the middle or the upper part were 114.7 +/- 40.8 and 208.1 +/- 71.4 microm, respectively. Thus, the orifice diameter of a crypt with the bifurcation reaching the upper part was about twice that of orifices of nonbifurcated crypts or those with bifurcations extending to the middle.Our results indicate that colorectal neoplasms with depressions may enlarge by a process of crypt bifurcation in which a single crypt divides into two crypts.

Mantle cell lymphoma (MCL) comprises 2.5%-7% of all non-Hodgkin's lymphomas, and the gastrointestinal tract is involved in about 20% of cases. Multiple lymphomatous polyposis (MLP) is an uncommon disease that is regarded as the intestinal form of MCL. We present a rare case of gastrointestinal MCL without MLP, and demonstrate that rituximab was effective for the treatment of this patient. A 61-year-old man presented with continuous diarrhea and hematochezia for a period of 5 months. Superficial lymph nodes were not palpable, but both tonsilla were enlarged. The level of soluble interleukin (IL)2-receptor was 3480 U/ml (normal

Serum antibody against carbonic anhydrase (CA) II has been described as a serological marker for distinguishing autoimmune cholangitis (AIC) from primary biliary cirrhosis (PBC). To validate this finding in a Japanese population, we evaluated sera from patients with PBC and AIC for antibody to human CA II. An enzyme-linked immunosorbent assay was employed to quantify serum antibody against CA II in patients with PBC (n = 40), AIC (n = 23), autoimmune hepatitis (n = 10), and extrahepatic obstructive jaundice (n = 10). Compared with the finding of a 4% prevalence of anti-CAII antibody in healthy subjects (n = 24), a significantly higher prevalence of anti-CA II antibody was detected in patients with PBC (35%) and AIC (30%) (P < 0.05), but not in patients with autoimmune hepatitis and patients with obstructive jaundice. No significant difference was observed between PBC and AIC patients. These results showed that AIC and PBC would be indistinguishable by anti-CA II antibody testing in Japanese patients. However, the finding of serum anti-CA II antibody in patients with PBC and AIC supports the disease concept of autoimmune exocrinopathy.

Carbonic anhydrase (CA) catalyzes the reversible hydration of CO(2) to bicarbonate and a proton, and alpha-class CA has been reported to facilitate the acid acclimation of Helicobacter pylori (hpalphaCA). The purpose of this study was to characterize the beta-class CA of H. pylori (hpbetaCA) and elucidate the role of this enzyme as a possible drug target for eradication therapy.We isolated DNA clones of independent H. pylori strains obtained from patients with gastritis (n = 15), gastric ulcer (n = 6), or gastric cancer (n = 16), and then studied genetic polymorphisms. In addition, the susceptibility of H. pylori to sulpiride, an antiulcer drug and efficient inhibitor of both hpalphaCA and hpbetaCA, was studied with an in vitro killing assay.DNA sequences of all 37 hpbetaCA clones encoded a 221 amino acid polypeptide with a variety of polymorphisms (57 types of amino acid substitution at 48 residue positions). There was no polymorphism functionally relevant to the gastric lesion type. One strain included unique residues that were not seen in the other 36 clones from Japanese patients but which were found in a strain obtained from the United Kingdom. Sulpiride had killing effects at concentrations greater than 200 microg/ml for H. pylori, including strains resistant to clarithromycin, metronidazole, or ampicillin.Helicobacter pylori might have evolved independently in the Caucasian and Japanese populations. Dual inhibition of alpha-and beta-class CAs could be applied as alternative therapy for eradication of H. pylori.

We developed and evaluated the clinical usefulness of a scoring system that subclassified type VI: pit patterns.We studied 119 colon cancer lesions (pTis, n = 26; pT1, n = 93) and 22 tubular adenoma lesions with severe atypia in which a type VI: pit pattern was visible under a stereomicroscope. Four type VI: pit pattern formation appearances (existing pits, marginal irregularities of the gland duct, narrowing of the gland duct lumen, and unclear outline of the gland duct) were defined, and the relationship between each appearance and the invasive depth of the cancer was evaluated.When the four type VI: pit pattern appearances were considered in a logistic regression analysis, the odds of a more invasive submucosal cancer were significantly increased by the appearance of marginal irregularities, a narrowed lumen, and an unclear outline. In the logistic regression analysis results, when 0.63 was used as the cutoff score for prediction of a more invasive submucosal cancer, 80 cases in the less invasive group were classified correctly (specificity, 1.0), whereas 53 (86.9%) of the 61 cases in the more invasive group were classified correctly (sensitivity, 0.869).It is important first to understand the usability and limitations of objective scoring of type V pit pattern findings and then to apply this score to the determination of cancer depth in order to accurately identify lesions suitable for endoscopic treatment.

The relationship between the three-dimensional configurations of superficial and protruded-type colon tumors with a type IIIL pit pattern was examined to evaluate their morphological development.Forty-five isolated crypts of superficial-type adenomas and 65 isolated crypts of protruded-type adenomas were evaluated, all derived from segments of 12 colorectal lesions removed by surgery or endoscopic resection. For isolation of the crypts, an HCl-digestion method was used. Morphological features of the isolated crypts were observed by scanning electron microscopy (SEM). We investigated the configuration, length, and width of the isolated crypts in a comparison of the superficial and protruded-type tumors. The configuration and surface structure of the crypts were classified into three types (scores 1 to 3) by the shape and degree of branching and protuberances on their surface.The average lengths of the isolated crypts of the superficial and protruded types were 310.9 +/- 122.9 micro m ( n = 45) and 434.4 +/- 163.3 micro m ( n = 65), respectively ( P0.001), and the average widths of the superficial and protruded types were 140.4 +/- 68.2 micro m and 171.5 +/- 73.3 micro m, respectively ( P = 0.02). The average scores for the degree of branching and protruberances in the superficial and protruded types were 1.178 +/- 0.442 and 1.569 +/- 0.529, respectively ( P0.0001). In terms of configuration, in the isolated crypts, the superficial-type tumors exhibited a two-layer structure and the protruded type had the shape of a spindle with protuberances.In colorectal tumors with a type IIIL pit pattern, the isolated crypts of protruded-type tumors displayed more roughness on their surface structure and were longer than those of superficial-type tumors. This suggested that the three-dimensional configuration of the isolated crypt constitutes an important factor in the formation of the gross configuration of colorectal tumors. Colorectal superficial and protruded-type tumors may develop with different growth patterns.

The incidence and prevalence of primary biliary cirrhosis show wide geographic differences. The frequency of this disease in Japan is lower than in Northern Europe. To elucidate the immunoreactivity of serum with enzymes of the 2-oxo-acid dehydrogenase complex (2-OADC) and the M2 mitochondrial antigenic complex in Japanese patients, we examined sera from 107 patients with primary biliary cirrhosis from three geographically different regions of Japan. The sera were assayed by immunofluorescence on frozen tissue sections, immunoblotting on bovine heart mitochondria and recombinant E2 subunit of branched chain oxo-acid dehydrogenase complex (BCOADC-E2), ELISA using recombinant E2 subunit of human pyruvate dehydrogenase complex (PDC-E2) and purified porcine 2-oxoglutarate dehydrogenase complex (OGDC), and enzyme inhibition assay using procine PDC and OGDC. Of the 107 sera, 95 (88%) reacted by immunofluorescence, 102 (95%) by immunoblotting with at least one of the M2 autoantigens, although only 78 (73%) reacted with PDC-E2; 72 (67%) by ELISA with PDC-E2; and 81 (76%) with PDC by the enzyme inhibition assay. Thus, the frequency of reactivity with PDC-E2 by all assays was lower for Japanese than the reported frequency for Caucasian patients with primary biliary cirrhosis, whereas the frequency of reactivity by immunoblotting and ELISA against 2-OADC enzymes other than PDC was relatively higher. The relative frequency of reactivity of autoantibodies to the M2 autoantigens was similar for the three different regions of Japan. The different autoantibody profiles for Japanese and Caucasian patients with primary biliary cirrhosis point to immunogenetic and environmental determinants of this disease, which should provide new insights into its autoimmune origins.