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Biomedical subjects

I Kino

Publications and source records attributed to I Kino.

At least 55 records · Page 3Linked to original sources

Cytochrome P-450 lA1 genotype in lung cancer patients and controls in Rio de Janeiro, Brazil.

Mspl restriction fragment length polymorphism in cytochrome P-450 IA1 (CypIA1) gene, which has been associated with lung cancer susceptibility in Japanese, was studied in persons from Rio de Janeiro, in the framework of a hospital-based, age, race (black or nonblack), and gender-matched case-control study (n = 222; 110 cases and 112 controls). Contrary to the hypothesis, there was no difference in the frequency of the C genotype (Mspl site-present homozygous), even after racial breakdown. There were no significant differences between cases and controls when categorized according to tobacco consumption. The lifetime quantity of tobacco smoked was not different among lung cancer patients with three different genotypes (A, Mspl site-absent, homozygous; B, heterozygote; and C). The background frequency of the Mspl polymorphism C genotype is a little less than 10%, similar to that of the Japanese healthy population. The CyplA1 Mspl polymorphism itself does not seem to be related to susceptibility to bronchial carcinogenesis in this area.

Adult↗

[Pathogenesis and progression of scirrhous carcinoma].

The aim of the present paper is to elucidate the pathogenesis of gastric scirrhous carcinoma with special reference to fibrogenesis in cancer stroma and to the mode of cancer invasions. First, there are two hypotheses concerning the origin of the marked increase of collagen fibers in this type of carcinoma. One is thought to be production by fibroblasts stimulated by cancer cells; the other is synthesis by neoplastic cells. Our studies revealed that gastric cancer cells enhanced collagen production by fibroblasts in vitro, suggesting the contribution to the formation of stromal collagen in human gastric scirrhous cancer. However, one of four gastric scirrhous cancer cell lines, NKPS, was found to slightly from collagen fibers in the brain of the nude mouse. We also calculated the number of fibroblastic cells in gastric scirrhous and normal stroma by microscopical image analysis. The results showed that fibroblastic cells in scirrhous stroma were increased four-fold over those in normal stroma. This finding suggests that the mechanism by which fibrous stroma is produced in scirrhous carcinoma may be affected by the increased fibroblastic cells which were stimulated by many kinds of growth factors produced by cancer cells. It is also well known that the infiltrative growth and dispersion of scirrhous cancer cells within the gastric wall is very fast. To assess the mode of cancerous invasion of this carcinoma, we examined the urokinase-type plasminogen activator (uPA) activity of both types of cells (cancer cells and fibroblasts) with a coculture method. Scirrhous cancer cells enhanced production of uPA by fibroblasts. However, non-scirrhous gastric cancer cells produced much uPA by themselves. This finding suggests that scirrhous cancer cells can invade the gastric wall by use of uPA produced by enhanced fibroblasts, but that non-scirrhous cancer cells synthesize much uPA by themselves and can infiltrate the gastric wall.

Adenocarcinoma, Scirrhous↗

Minute adenomas of the depressed type in familial adenomatous polyposis of the colon. A pathway to ordinary polypoid adenomas.

BACKGROUND: It has been thought that colorectal adenomas are polypoid from their beginning. Although depressed adenomas have been described, they have been considered an unusual form and have not been studied systemically. METHOD: More than 5000 colorectal adenomas in 24 resected large intestines of patients with familial adenomatous polyposis were examined by dissecting microscopic study. These adenomas were classified by their surface appearance as depressed, flat, or polypoid type. The frequencies and sizes of the three types were determined. RESULTS: In addition to ordinary polypoid adenomas, many adenomas of the depressed type were found. Of the 5287 adenomas detected, 635 (12.0%) were depressed, 967 (18.3%) were flat, and 3685 (69.7%) were polypoid. Depressed adenomas constituted approximately 15% of all adenomas smaller than 1.5 mm diameter. However, they were rare in those of 1.5-2.0 mm diameter and were not found among those of more than 2.0 mm in diameter. CONCLUSION: These findings suggest that some ordinary polypoid adenomas originate from minute depressed adenomas.

Adenoma↗

Identification of protein-tyrosine kinase genes preferentially expressed in embryo stomach and gastric cancer.

For identification of the protein-tyrosine kinases that are expressed in embryo stomach and gastric cancer, a 16-day rat embryo stomach and two human gastric cancer cDNA expression libraries were screened with an anti-phosphotyrosine antibody. Eight cDNAs encoding protein-tyrosine kinase were isolated, and Northern blot analysis revealed that five out of eight clones were highly expressed in rat embryo stomach, but not in adult rat stomach. From nucleotide sequence analysis, these five cDNAs were identified as elk, erk, esk, TTK and fyn, respectively. We report here that the expression levels of two families of receptor type tyrosine kinase genes, elk/erk and esk/TTK are developmentally regulated in rat stomach and highly expressed in human gastric cancer tissues. These findings suggest that elk/erk and esk/TTK genes play important roles in embryonic development and carcinogenesis of the stomach.

Adenocarcinoma↗

Over-expression of HOX-8, the human homologue of the mouse Hox-8 homeobox gene, in human tumors.

A human ovarian yolk sac tumor cDNA library was screened for homeobox genes with an oligonucleotide probe under low stringent condition. Three homeobox genes were isolated, two of which were identified as HHO.c1 and HB24. The third was highly homologous with the mouse Hox-8 gene and was designated as HOX-8. Studies on RNAs from 25 human tumor tissues and cell lines showed that the profile of HOX-8 expression was different from those of HHO.c1 and HB24. The expression of HOX-8 was not detected in hematopoietic tumor cells, in which HHO.c1 and HB24 were highly expressed. HOX-8 was expressed at higher levels in a variety of tumors of epithelial origin than in their corresponding normal tissues more frequently than HHO.c1 and HB24. All three homeobox genes were highly expressed in a yolk sac tumor, an immature tumor of gonadal origin. These results suggest that HOX-8 plays a more important role in human tumors of epithelial origin than those of hematopoietic origin.

Animals↗

Effects of pyrroloquinoline quinone (PQQ) and PQQ-oxazole on DNA synthesis of cultured human fibroblasts.

The effects of pyrroloquinoline quinone (PQQ) and PQQ-oxazole (PQQ-glycine adduct) on DNA synthesis were examined using cultured human fibroblasts. Confluent fibroblasts were cultured in serum-free Dulbecco's modified Eagle's media, and various concentrations of PQQ and PQQ-oxazole were added to the media. After incubation for 24 h, [3H]thymidine was added to the media as an indicator for DNA synthesis of the cells. The thymidine incorporation into the cells was significantly enhanced even in the presence of very low concentrations of PQQ (0.003-0.03 microM); it remained significantly enhanced, up to 30 microM PQQ. However, the incorporation remarkably decreased at 750-1500 microM of PQQ. In contrast to the results for PQQ, DNA synthesis was not stimulated by addition of 0.003-3 microM PQQ-oxazole, but it was slightly enhanced at concentrations 15-750 microM. In morphological examination of the cultured human fibroblasts, cell density was increased by addition of 0.003-30 microM PQQ when compared with that of the control, supporting the above biochemical data. However, there were no distinct differences in morphological effect between PQQ and PQQ-oxazole.

Adult↗

Nuclear DNA content of isolated crypts of background colonic mucosa from patients with familial adenomatous polyposis and sporadic colorectal cancer.

The DNA content of the upper one third of the crypt epithelium was compared with that of the lower two thirds in the background colorectal mucosa of eight cases of familial adenomatous polyposis (FAP) and eight control cases of sporadic colorectal cancer (SCRC). Intact crypts were isolated by incubating fresh lesion free colorectal mucosa in calcium and magnesium free Hanks' balanced salt solution (CMFH) containing 30 mM EDTA for 30 minutes at 37 degrees C and then agitating in CMFH. The crypts were then separated from the lamina propria, fixed in 70% ethanol and under a dissecting microscope divided manually into upper and lower portions. Each portion was digested with pepsin to obtain a suspension of single nuclei, and smears of the nuclei were stained with 4',6,-diamidino-2-phenylindole dihydrochloride (DAPI). Nuclear DNA was determined using a cytophotometric microscope. Results showed that the DNA content of the epithelium of the upper one third of crypts was diploid in both FAP and SCRC cases, and that proliferative fractions with diploid peaks were present in the lower two thirds of the crypts in both groups. These results support our previous finding that the proliferative compartment of background crypts is confined to the lower two thirds and does not extend to the upper parts of the crypts.

Adenomatous Polyposis Coli↗

Mutational heterogeneity among individual tumors in a case of multiple primary malignancy of the colon.

c-Ki-ras mutations were analyzed from quintuple colon tumors in a 75-year-old patient with no family history of colon cancer. Polymerase chain reaction-amplified DNA was sequenced for mutations in c-Ki-ras exon 1. Detected mutations were confirmed with allele-specific PCR which amplified only mutant sequences. Five tumors were histopathologically diagnosed as: adenoma with moderate atypia, adenoma with moderate atypia bearing a focal cancer, adenoma with severe atypia bearing a focal cancer, intramucosal carcinoma, well differentiated adenocarcinoma (advanced). Transitions, G-A, were found at the second base of codon 12 for the adenoma with severe atypia bearing a focal cancer and for the well- differentiated adenocarcinoma. The same substitution was found at the second base of codon 13 in the adenoma with mild atypia bearing a focal cancer. No base substitution at codon 12 or 13 was found for the intramucosal carcinoma nor for the adenoma with moderate atypia. These findings demonstrated there to be heterogeneous genetic and histopathological alterations in the individual tumors of the present case of synchronous malignancy of the colon.

Adenine↗

Genes preferentially expressed in embryo stomach are predominantly expressed in gastric cancer.

Eight complementary DNA (cDNA) clones highly expressed in fetal rat stomach but not in normal adult rat stomach were isolated after screening 2 x 10(4) independent recombinants from a subtracted cDNA library. The cDNA library was first prepared from RNAs of total stomach at 16 days gestational period, and this cDNA library was subtracted by cDNAs prepared from adult rat total stomach RNA, using a novel PCR-based cDNA subtraction method. Northern blot analysis revealed that as many as six of eight clones thus isolated were overexpressed in at least some of the human or rat gastric cancers. From analysis of partial nucleotide sequence, four cDNA clones were identified as profilin, pro-alpha 1 (1) collagen, nucleolar protein B23.2, and elongation factor 1 alpha subunit. The remaining two clones were derived from novel genes. These novel genes, L-1 and L-2, are developmentally well regulated in the stomach. The present results clearly show that genes expressed preferentially in embryo stomach are most likely to be highly expressed in gastric cancer. The method described here provides us with a rapid method for identification of genes with significantly increased expression in cancer.

Animals↗

Inflammatory myoglandular polyps of the colon and rectum. A clinicopathological study of 32 pedunculated polyps, distinct from other types of polyps.

Hitherto unclassified colorectal polyps were identified in 32 patients (23 men and 9 women; mean age, 53 years). The only symptom, which was observed in less than half the patients, was passage of blood or occult blood. Endoscopic examination revealed solitary pedunculated, red polyps with a smooth surface. These polyps were found in the left colon, especially in the sigmoid. Their characteristic features were inflammatory granulation tissue in the lamina propria mucosae, proliferation of smooth muscle, and hyperplastic glands with occasional cystic dilatation. The etiology of this type of polyp is unknown, but it could involve chronic trauma from the fecal stream and from peristalsis of the bowel. These polyps can be differentiated from juvenile polyps and inflammatory polyps by the presence of abundant smooth-muscle cells in the inflamed lamina propria mucosae. They also can be differentiated from Peutz-Jeghers polyps, which appear as hamartomatous structures with tree-like proliferation of muscularis mucosae covered by colonic mucosa without inflammatory granulation tissue. Their locations and macroscopic appearance distinguish these polyps from mucosal prolapse syndrome and polyps developed after colostomy. In addition, these new polyps differ from inflammatory cap polyps in that they lack a fibrin cap. We propose the name inflammatory myoglandular polyps for these polyps, which are distinct clinicopathologically from other types of colorectal polyps.

Adolescent↗

Epidermal inclusions in abdominal lymph nodes. Report of two cases studied immunohistochemically.

Abdominal lymph nodes from men aged 48 and 62 years with gastric adenocarcinoma were examined histologically. A few of the lymph nodes contained epidermal epithelium, although there was no metastasis. Scattered squamous epithelial nests and epidermal cysts were found within the lymph nodes, and small amounts of pancreatic tissue were present adjacent to the epidermal inclusions. Some squamous cell nests showed cyst formation, and some others showed squamous cell nests together with mucin-containing cells forming luminal structures. Immunohistochemically, the squamous cell nests stained weakly for CA19-9 but were negative for CEA or CA125. These lesions were considered to be similar to lymphoepithelial cysts of the pancreas.

Abdomen↗

Peripheral motor neuropathy in spontaneously diabetic WBN/Kob rats: a morphometric and electron microscopic study.

The morphology and function of peripheral motor nerves of WBN/Kob rats of the newly identified strain with late onset and long-lasting diabetes were studied in comparison with those of nondiabetic age-matched rats. The most conspicuous and frequent change seen by electron microscopy in the diabetic rats was myelinopathy, initiated by vesicle formation in granular material accumulated in the myelin lamella. Initial changes developed into myelin blebbing or distention, demyelination and remyelination. A decreased population of nerve fibers in diabetic rats of advanced age suggested that the final stage of these changes was neuronal loss resulting from complete destruction of the neurons. The myelinopathy was consistently more frequent and conspicuous in diabetic rats than in age-matched nondiabetic rats, but the difference was not significant in rats of over 28 months old, because of the age-dependent increase of the change in older rats. The conduction velocity was significantly less in diabetic rats than in age-matched nondiabetic animals at 20 months but not at 28 months of age, because at the older age nondiabetic rats also showed a reduced conduction velocity. These findings showed that male WBN/Kob rats develop diabetic motor neuropathy, but that the essential changes in diabetic neuropathy are indistinguishable morphologically and functionally from those in age-dependent neuropathy.

Animals↗

Mixed medullary-follicular carcinoma of the thyroid. Immunohistochemical and electron microscopic studies.

A case of mixed medullary-follicular carcinoma of the thyroid is reported. Grossly, the tumor was a solid, grayish-white, well circumscribed mass without lymph node metastasis. Microscopically, the tumor showed both medullary and follicular areas. The follicular areas occupied discrete portions of the tumor, and were considered to be neoplastic. Tumor cells in the medullary area were polyhedral or spindle-shaped. There was no amyloid deposition within the tumor. Immunohistochemically, tumor cells in the medullary area were positive for calcitonin and negative for thyroglobulin. Some cells lining the follicles were positive for thyroglobulin. By electron microscopy, two types of tumor cell were observed. One type contained numerous cytoplasmic secretory granules, whereas the other type had few granules and showed a prominent rough endoplasmic reticulum. These findings suggested that this mixed medullary-follicular carcinoma of the thyroid presented neoplastic changes within a common cell lineage.

Adenocarcinoma↗

Morphometrical and cell kinetic studies of normal human colorectal mucosa. Comparison between the proximal and the distal large intestine.

Morphometric and cell kinetic studies were performed on normal mucosa in 30 specimens of surgically resected colorectum. The average crypt length was 372 +/- 57 microns in the proximal colon and 506 +/- 65 microns in the distal colon, and the average cell numbers per crypt column in these regions were 76.4 +/- 8.9 and 80.3 +/- 8.8, respectively. In the proximal and distal colon, goblet cells constituted 23.3 +/- 3.4% and 25.2 +/- 4.0%, respectively, of the total cells in each crypt, and in both regions entero-chromaffin cells constituted about 1%. The labeling indices of the proximal and distal colon were 9.4 +/- 3.9% and 8.2 +/- 2.2%, respectively. Combined microautoradiography and periodic acid-Schiff reaction on selected cases revealed that the labeling indices of columnar cells and goblet cells were 11.0 +/- 2.0% and 7.0 +/- 3.2%, respectively. It was suggested that the increased number of larger goblet cells in crypts of the sigmoid colon and rectum resulted in an increase of crypt length and a decrease in the labeling index. These results provide information on the morphological and cell kinetic characteristics of normal mucosa of the colon and rectum.

Adult↗

Cell kinetics analysis of background colonic mucosa of patients with intestinal neoplasms by ex vivo autoradiography.

Studies of the cell kinetics of the colonic crypts could explain the morphogenesis of colonic adenomas and results suggest that a derangement of the proliferative zone of the colonic crypts takes place before adenoma development. This study was conducted to determine whether this is the case or not. The labelling distribution and labelling index (LI) of the colonic crypts was examined with ex vivo autoradiography. Eight patients with intestinal neoplasms, three with familial polyposis coli, four with ordinary colon cancer, and one with two colonic adenomas. Similar labelling distributions and absent upward shift of the active proliferative zone in crypts were observed in patients with familial polyposis and in those with non-polyposis cancer, or adenomas. The non-proliferative zone of the crypts was well preserved in all eight patients. The mean of the labelling index of the three patients with familial polyposis coli was 8.35% (3.17), values expressed as means (SD) and that of the five patients with non-polyposis cancer, or adenomas was 8.55% (3.20). None of the eight patients showed derangement of the proliferative zone of colonic crypts. This result is compatible with the hypothesis that adenomas are detected first as 'buds of adenomas', which sprout into the lamina propria mucosae in the middle part of normal crypts.

Adenocarcinoma↗