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Biomedical subjects

N Ito

Publications and source records attributed to N Ito.

At least 487 records · Page 27Linked to original sources
PubMed1990

Carcinogenicity of captafol in F344/DuCrj rats.

Captafol was administered at dietary levels of 0 (control), 750 and 1,500 parts per million (ppm) to groups of 50 male and 50 female F344/DuCrj rats for 104 weeks, and then all animals were maintained without captafol for a further 8 weeks, and killed in week 113. Renal cell carcinoma was found in eight of 50 male rats treated with 1,500 ppm and in one of 50 male rats treated with 750 ppm of captafol. The incidences of renal adenomas, including micro-adenomas, and basophilic altered cell tubules were significantly higher in both sexes treated with captafol than in controls, and the increases were apparently dose-dependent except that of adenomas in females. The incidences of neoplastic and preneoplastic lesions of the kidney in captafol-treated animals were higher in males than in females. Captafol also induced hepatocellular carcinomas in four of 50 female rats in the 1,500 ppm group. The incidences of hyperplastic (neoplastic) nodules and foci of cellular alterations in the liver were also significantly increased in both sexes treated with captafol, the increases being dose-dependent. In conclusion, captafol induced renal cell carcinomas in male rats and hepatocellular carcinomas in female rats.

Adenoma↗
PubMed1990

Preparation and opioid activities of N-methylated analogs of [D-Ala2,Leu5]enkephalin.

Analogs of opioid pentapeptide [D-Ala2,Leu5]enkephalin were prepared using two kinds of N-methylation reactions, namely quaternization and amide-methylation. Quaternization reaction with CH3I-KHCO3 in methanol was applied to the deprotected N-terminal group of the pentapeptide derivatives affording trimethylammonium group-containing analogs. [Me3+Tyr1,D-Ala2,Leu5]enkephalin and its amide were found to show opioid activity on guinea pig ileium assay only slightly lower than the parent unmethylated peptides. Application of amide-methylation reaction using CH3I-Ag2O in DMF to the protected pentapeptide yielded a pentamethyl derivative in which all of the five N atoms were methylated. Deprotection of the derivative gave pentamethyl analogs of [D-Ala2,Leu5]enkephalin, which showed no significant activity on the guinea pig ileum assay and opiate-receptor binding assay.

Amino Acid Sequence↗
PubMed1990

Gastric and intestinal phenotypic expression of human stomach cancers as revealed by pepsinogen immunohistochemistry and mucin histochemistry.

Gastric and intestinal phenotypic expression in 223 surgically obtained primary gastric cancers and their histogenetic relationship to intestinal metaplasia in the surrounding gastric mucosa were studied by mucin histochemistry and pepsinogen (Pg) immunohistochemistry. Histochemical differentiation of mucins (paradoxical concanavalin A, the galactose oxidase-Schiff sequence and sialidase-galactose oxidase-Schiff) and immunohistochemical staining of Pgs I and II, allowed differentiation of gastric cancer cells from different histological categories into gastric elements including mucous neck cells, pyloric gland cells and surface mucous cells or intestinal elements including goblet cell and intestinal absorptive cell types. Of 122 papillary and tubular adenocarcinomas, 33 (27.1%) consisted mainly of gastric-type cells and 42 (34.4%) predominantly of intestinal-type cells. The remainder (38.5%) consisted of mixtures of gastric- and intestinal-type cells. Of 101 poorly differentiated adenocarcinomas, signet ring cell carcinomas and mucinous adenocarcinomas, 59 (58.4%) consisted mainly of gastric-type cells and 20 (19.8%) mainly of intestinal-type cells. Seven out of 35 papillary and tubular adenocarcinomas consisting mainly of gastric-type cancer cells were surrounded by mucosa with intestinal metaplasia. Conversely, 10 out of 40 papillary and tubular adenocarcinomas consisting mainly of intestinal-type cancer cells were observed in nonmetaplastic gastric mucosa. Thus no relationship as regards intestinal phenotypic expression was found between gastric cancers and surrounding gastric mucosa.

Histocytochemistry↗
PubMed1990

Comparative sequential changes in serum and biliary levels of bile acid components after a single dose of D-galactosamine or partial hepatectomy in the rat.

In order to characterize changes in bile acid profile during liver cell damage and regeneration, levels of bile acids in serum and bile were determined by high performance liquid chromatography (HPLC) in F344 rats treated with a single dose of D-galactosamine (galactosamine, 300 mg/kg, i.p.) or subjected to two-thirds partial hepatectomy (PH). In the serum, galactosamine caused elevation of conjugated bile acids such as taurocholic acid (TCA) and tauro-beta-muricholic acid (T beta MCA) at the 24 and 48-h time points, whereas unconjugated bile acids including cholic acid (CA) at 24 h and hyodeoxycholic acid (HDCA) at 48 h were increased after PH. In the bile, elevation of TCA showed most remarkable elevation at the 24-h time point in the galactosamine-treated group. All components of biliary bile acids showed rapid decreases from 24 to 48 h. The results demonstrated that while liver tissue damaged by galactosamine is able to conjugate bile acids it allows leakage into the blood stream. In contrast, the results for rats subjected to PH indicated that liver cells during DNA synthesis are not capable of conjugating all free bile acids with taurine although a similar leakage occurs. It is concluded that obvious elevation of serum TCA or CA and biliary T beta MCA could be a useful indicator of hepatocellular proliferation.

Animals↗
PubMed1990

Duration of pressure overload alters regression of coronary circulation abnormalities.

Using a rat model of ascending aortic banding and debanding, we examined how the duration of pressure overload affects reversibility in coronary circulation abnormalities after relief of pressure overload. Four-week banding increased left ventricular dry weight-to-body weight ratio to 158 +/- 8% of that of sham-operated controls. In isolated nonworking hearts perfused with crystalloid solution, peak mean coronary flow rate (CFR) was measured after brief ischemia. CFR and CFR/dry tissue weight significantly decreased (75 +/- 5 and 54 +/- 3% of that of controls at 100 mmHg of coronary perfusion pressure; 75 +/- 5 and 54 +/- 4% at 150 mmHg, respectively). Four weeks after debanding was performed, CFR and CFR/dry tissue weight increased to similar levels in controls. On the other hand, 10-wk banding produced the same degree of myocardial hypertrophy and decreases in CFR and CFR/dry tissue weight as in 4-wk banded rats. Four weeks after debanding was performed, CFR had not changed. CFR/dry tissue weight increased because of regression of myocardial hypertrophy but was significantly lower than that in rats debanded after 4 wk of banding. Thus the duration of pressure overload does not affect the degree of coronary circulation abnormalities in the progression process but does affect it in the regression process.

Animals↗
PubMed1990

Histochemical localization and analysis of blood group-related antigens in human pancreas using immunostaining with monoclonal antibodies and exoglycosidase digestion.

We examined the distribution of blood group-related antigens using an indirect immunoperoxidase method with monoclonal antibodies (MAb) directed to A, B, H, Lewis a (Lea), Lewis b (Leb), Lewis x (Lex), and Lewis y (Ley) antigens and Type 1 precursor chain in human pancreas. Effects of prior digestion with exoglycosidases on MAb stainings were simultaneously investigated. A, B, H, Leb, and Ley antigens were detected in acinar cells and interlobular duct cells but not in centroacinar cells, intercalated duct cells, and islet of Langerhans cells. The expression of these antigens in acinar cells was not dependent on Lewis type and secretor status of the tissue donors, whereas that in interlobular duct cells was strictly dependent on secretor status. The distribution pattern of these antigens in acinar cells was not homogeneous, i.e., cells producing H antigens expressed both Leb and Ley antigens but not A or B antigens, whereas those producing A or B antigens did not secrete Leb and Ley as well as H antigens. Digestion with alpha-N-acetylgalactosaminidase or alpha-galactosidase resulted in the appearance of Leb and Ley antigens as well as H antigen in acinar cells producing A and/or B antigens. Type 1 precursor chain was not detected in pancreatic tissues from secretors but appeared in acinar cells producing H antigen after alpha-L-fucosidase digestion, which also disclosed Lex but not Lea antigen in acinar cells expressing both Leb and Ley. In some non-secretors, MAb against Type 1 precursor chain reacted with acinar cells without enzyme digestion. Although Lea antigen was not detected in acinar cells, it was found in centroacinar cells, intercalated duct cells, and interlobular duct cells from all individuals examined except two Le(a-b-) secretors. After sialidase digestion, Lex antigen appeared in centroacinar and intercalated duct cells from some individuals. Sialidase digestion also elicited reactivity with MAb against Type 1 precursor chain in islet of Langerhans cells from some individuals. These results demonstrate the complexity in the pattern of expression and regulation of blood group-related antigens in different cell types of human pancreas. Such complexity may largely be ascribed to differences in individual genotypes and in gene expression patterns of different cell types.

ABO Blood-Group System↗
PubMed1989

Amino acid residues stabilizing a Bacillus alpha-amylase against irreversible thermoinactivation.

The alpha-amylase of Bacillus licheniformis (BLA) is stable and active at high temperature. More than 80% of its activity is retained after heat treatment at 90 degrees C for 30 min, and the optimum temperature for its activity is 80-85 degrees C. In contrast, the alpha-amylase of Bacillus amyloliquefaciens (BAA), the amino acid sequence of which shows 80% homology with that of BLA, is rapidly inactivated at 90 degrees C. Various chimeric genes were constructed from the structural genes for the two enzymes, and their products were analyzed for stability as to irreversible thermoinactivation. Two regions in the amino acid sequence of BLA comprising Gln178 (region I) and the 255th-270th residues (region II), respectively, were shown to determine the thermostability of BLA. Region I plays a major role in determining the thermostability. By means of site-directed mutagenesis of the BAA gene, deletion of Arg176 and Gly177 in region I and substitutions of alanine for Lys269 and aspartic acid for Asn266 in region II were shown to be responsible for the enhancement of the thermostability. Mutant BAAs containing the above deletion and substitutions showed almost the same thermostability as BLA as to irreversible thermoinactivation. Nevertheless, the mutant BAAs showed a temperature optimum as low as that of BAA (65 degrees C), indicating that they are still susceptible to reversible inactivation at temperatures higher than 65 degrees C.

Amino Acid Sequence↗
PubMed1989

The relative value of glycated albumin, hemoglobin A1c and fructosamine when screening for diabetes mellitus.

We compared the usefulness of three glycated serum proteins, glycated albumin (GA), glycated hemoglobin (HBA1c) and fructosamine (FA), for diabetic screening purposes. We measured these indices in 302 adults, most of whom underwent yearly physical examinations. We measured GA and HbA1c with high precision using high-performance liquid chromatography (interassay coefficients of variation 4.9 and 4.0%, respectively) and FA using commercial reagents (interassay coefficient of variation 1.65%). All the individuals underwent a 75-g oral glucose tolerance test, which revealed significant correlations between the values of the three glycated proteins and the four plasma glucose concentrations measured as well as the sum of these glucose concentrations, sigma BS (GA, r = 0.80; HbA1c, r = 0.80; FA, r = 0.65). On the basis of the test, 130 of the subjects were classified as normal (N), 123 as borderline and 49 as having diabetes mellitus (D) according to the criteria of the Japan Diabetes Society. Of the 123 borderline cases, 26 showed impaired glucose tolerance (IGT) according to the WHO criteria. The normal group values of GA, HbA1c and FA were 17.8 +/- 0.17% (mean +/- SEM), 5.02 +/- 0.03%, and 2.55 +/- 0.02 mM/l, respectively. Borderline and IGT subjects had significantly more GA and HbA1c than normal but not more FA (P less than 0.01). We divided the subjects into 10 groups on the basis of their sigma BS values; those with values higher than 671 +/- 4.7 mg/dl had significantly more GA and HbA1c than normal, while those with values higher than 1068 +/- 40.9 mg/dl (the most extreme cases) had significantly more FA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Modification by catechol and resorcinol of upper digestive tract carcinogenesis in rats treated with methyl-N-amylnitrosamine.

Modifying effects of the environmental contaminant catechol, and its isomers resorcinol and hydroquinone, on methyl-N-amylnitrosamine (MNAN)-induced carcinogenesis were studied in male F344 rats. Groups of 15 rats were given three i.p. injections of 25 mg/kg of body weight of MNAN within the initial 2-wk period, and commencing 1 wk thereafter they were administered 0.8% catechol, 0.8% resorcinol, or 0.8% hydroquinone in powdered basal diet or were given basal diet alone for 49 wk. Additional groups of 10 to 15 rats were similarly treated without prior carcinogen exposure. Histological examination after sacrifice at wk 52 revealed that the incidences of tongue papillomas and esophageal squamous cell carcinomas in the groups given MNAN followed by catechol (57.1% and 64.3%) or resorcinol (50% and 58.8%) were significantly higher than those in the carcinogen only controls (9.1, and 0%, respectively). Hydroquinone also enhanced the development of esophageal squamous cell carcinomas but was less active than catechol or resorcinol. The incidence of alveolar hyperplasia in the lungs of the group given MNAN followed by catechol (0%) was, in contrast, significantly reduced as compared to the control value (54.5%). Hydroquinone and resorcinol showed a similar but non-significant tendency. These results indicated that the environmental contaminant, catechol and its isomers, may play a role in the development of human upper gastrointestinal cancer, in addition to exerting modifying effects in other organs.

Animals↗
PubMed1989

Lack of modifying effects of linolic acid hydroperoxides and their secondary oxidative products on combined 7,12-dimethylbenz[a]anthracene and 1,2-dimethylhydrazine-initiated mammary gland, ear duct and colon carcinogenesis in female Sprague-Dawley rats.

Effects of hydroperoxides, autoxidation products of linolic acid (HPO) and secondary oxidative products of HPO (SOP) (5% each in diet) were examined in female Sprague-Dawley rats. HPO and SOP administration was carried out during or subsequent to two injections of dimethylhydrazine (DMH) (40 mg/kg body wt s.c.), and a single i.g. dose of 7,12-dimethylbenz[a]anthracene (DMBA) (50 mg/kg body wt). No significant differences in the incidences of tumors in the mammary gland, colon, ear duct and hematopoietic system associated with HPO or SOP treatment were evident, during or after carcinogen exposure. The present results therefore indicate that the environmental contaminants, HPO and SOP, lack any potential for modification of mammary gland or colon carcinogenesis under the conditions of the investigation.

1,2-Dimethylhydrazine↗
PubMed1989

Promotion by dihydroxybenzene derivatives of N-methyl-N'-nitro-N-nitrosoguanidine-induced F344 rat forestomach and glandular stomach carcinogenesis.

Modifying effects of resorcinol, hydroquinone, p-tert-butylcatechol (PTBC), p-methylcatechol (PMC), and o-methylcatechol on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced forestomach and glandular stomach carcinogenesis were investigated in F344 rats. Groups of 15 to 16 male 6-wk-old animals were given a single intragastric administration of 150 mg/kg of body weight of MNNG and starting 1 wk later were administered powdered diet containing 0.8% resorcinol, 0.8% hydroquinone, 1.5% PTBC, 1.5% o-methylcatechol, 1.5% PMC, or basal diet alone for 51 wk. Additional groups of 10 to 15 rats each were treated with the phenolic compounds or received basal diet without prior carcinogen exposure. Histological examination after sacrifice at Wk 52 revealed that squamous cell carcinoma development in the forestomachs of rats treated with MNNG followed by PTBC (75%, P less than 0.001) or MNNG followed by PMC (100%, P less than 0.001) was significantly greater than in animals receiving MNNG alone (20%). Treatment with PMC alone also resulted in a 40% yield of papilloma. In the glandular stomach, incidences of adenomatous hyperplasias in rats treated with MNNG followed by PTBC (31.3%, P less than 0.05) or PMC (100%, P less than 0.001) and the incidence of adenocarcinomas in rats treated with MNNG followed by PMC (100%, P less than 0.001) were significantly higher than in controls. In addition, PMC alone induced a 100% yield of adenomatous hyperplasias and 6.7% of adenocarcinomas. Thus, the results demonstrated that PTBC and PMC treatment significantly enhances forestomach and glandular stomach carcinogenesis and that PMC itself may possess weak carcinogenic potential in these organs. The ortho-position appears to be important for this dihydroxybenzene activity.

Adenocarcinoma↗
PubMed1989

Cell proliferation induced by uracil-calculi and subsequent development of reversible papillomatosis in the rat urinary bladder.

The sequence of cellular alterations in urinary bladder epithelium associated with uracil-induced reversible urolithiasis was investigated in male F344 rats. Initial changes were submucosal edema with occasional mucosal erosion or ulceration which appeared on Day 2 of uracil administration. Simple hyperplasia of bladder epithelium was already evident at this time and calculus formation was noted as early as Day 4. Labeling indices in the bladder epithelium assessed by bromodeoxyuridine incorporation were about 32% on Day 4 and then gradually decreased to 6% at Week 8 and 4% at Week 25 of chronic treatment. Histologically, a direct progression from simple hyperplasias, through papillary hyperplasias to papillomatosis, accomplished by Week 5, was evident. Dysplastic lesions were also apparent by Week 25. Topographically, papillomatosis was composed of marked interconnecting mucosal ridges of relatively uniform width. No polyp-like protrusions were present and the vascular pattern revealed by resin perfusion casting demonstrated that these mucosal lesions were supported by a uniform plexus of capillary vessels. After withdrawal of uracil from the diet the labeling index dropped dramatically to 0.002% after 1 week and urolithiasis and papillomatosis had disappeared by Weeks 2 and 3, respectively. The findings suggest that papillomatosis associated with uracil-calculi is a hyperplastic rather than a neoplastic response and that induction of putative neoplastic lesions is directly related to prolonged vigorous cell proliferation.

Animals↗
PubMed1989

Changes in gap junction protein (connexin 32) gene expression during rat liver carcinogenesis.

A rat liver gap junction (GJ) cDNA probe that detects mRNA encoding the 32 Kd GJ-protein (connexin 32) was employed to study GJ-protein gene expression in rat liver tumors induced by a single exposure to diethylnitrosamine (DEN) followed by exposure to 2-acetylaminofluorene (AAF)/CCl4/AAF or induced by systemic administration of N-ethyl-N-hydroxyethylnitrosamine (EHEN). All carcinomas generated by these carcinogens showed markedly reduced levels of GJ-protein mRNA. This may indicate that GJ-protein levels and gap-junctional intercellular communication (GJIC) capacity are also severely compromised. Moreover, all hyperplastic nodules also showed a reduced level of GJ-protein mRNA. Taken together with our earlier finding that the liver tumor promoter phenobarbital inhibits GJ-protein gene expression, these results suggest that deranged GJIC is a relatively early event in liver multistage carcinogenesis. A range of other cDNA probes was also used to characterize gene expression in the DEN-induced tumors. Induction of expression was seen for glutathione S-transferase (placental form) (GST-P), gamma-glutamyltranspeptidase (GGT), and c-raf but not for c-Ha-ras or c-myc.

Animals↗
PubMed1989

Relationship between human seminal kallikrein-kinin system and spermatogenesis.

The concentration of kallikrein and the activity of angiotensin converting enzyme (ACE) in the semen specimens mainly from patients with male sterility and from those who were subjected to vasoligation, and in the prostatic fluid specimens from normal controls were determined by radioimmunoassay (RIA) and the modified Cushman's method, respectively. The kallikrein level in the semen from normal control was 40.4 +/- 21.3 ng/ml which was more than 10 times that in the blood. The value tended to increase with the decrease of the number of sperm. But there was no significant correlation between the kallikrein level and the sperm motility. The seminal kallikrein level from the patients subjected to vasoligation and that in the prostatic fluid from the normal male were 20-28 ng/ml. Therefore, that amount was considered to be secreted from the prostate gland. The results of column chromatography suggested that kallikrein combined with the other substances to form a high molecular compound in the semen. The ACE activity was 94.9 +/- 10.9 nmol/ml/min in the semen from the normal control, which was about three times that in the blood. Similar to kallikrein, it tended to decrease with the increase of the number of vasoligation and that in the prostatic fluid from the normal males was higher than that in the semen from the normal control and patients with male sterility, it was estimated that the considerable amount of ACE was secreted from the prostate gland.

Humans↗
PubMed1989

Localization of kallikrein in human male genital organ.

Male genital organs (testis, epididymis, seminal vesicle and vas deferens) were stained by the peroxidase-antiperoxidase (PAP) method to clarify the localization of kallikrein. Sertoli cells of the testis, epithelial cells of the epididymis, and adenocytes of the prostate gland were specifically stained showing that endogenous kallikrein was localized in these cells.

Epididymis↗
PubMed1989

Histochemical demonstration of O-glycosidically linked, type 3 based ABH antigens in human pancreas using lectin staining and glycosidase digestion procedures.

Histochemical analyses of the chemical structures of sugar sequences with or without blood group specificity were carried out by combined stepwise digestion of tissue sections with exo- and endoglycosidases and subsequent lectin stainings in formalin-fixed, paraffin-embedded human pancreas. In acinar cells from blood group A or AB secretor individuals, sequential digestion with alpha-N-acetylgalactosaminidase and alpha-L-fucosidase imparted reactivity with peanut agglutinin (PNA) in cells reactive with Dolichos biflorus agglutinin as well as those with Ulex europaeus agglutinin I(UEA-I). Simple fucosidase digestion imparted the PNA reactivity only in UEA-I reactive cells. Sequential digestion with alpha-galactosidase and fucosidase likewise liberated the PNA binding sites in Griffonia simplicifolia agglutinin I-B4 reactive cells from blood group B and AB secretors. Sialidase digestion liberated the PNA binding sites not only in acinar cells but also intercalated duct cells, islet cells of Langerhans and endothelial cells. The PNA reactivity obtained by these enzyme digestions was eliminted by endo-alpha-N-acetylgalactosaminidase (endo-GalNAcdase) digestion. Preexisting PNA affinity in acinar cells from non-secretors was also susceptible to endo-GalNAcdase treatment. Following the endo-GalNAcdase digestion, fucosidase or sialidase digestion recovered the PNA reactivity in acinar cells from nonsecretors. These results show that ABH determinants carried on O-glycosidically linked type 3 chain (D-galactose-(beta 1-3)-N-acetyl-D-galactosamine alpha 1-serine or threonine) are secreted in pancreatic acinar cells and suggest that product coded by the secretor gene is required for the complete conversion of type 3 precursor chains into H determinants.

ABO Blood-Group System↗
PubMed1989

Comparison of enzyme phenotypes in human bladder tumours and experimentally induced hyperplastic and neoplastic lesions of the rat urinary bladder. A combined histochemical and immunohistochemical approach.

The expression of a number of enzymes involved in drug metabolism, membrane function etc. was compared in hyperplastic and neoplastic lesions of the rat bladder and in human bladder tumours. Transitional cell carcinomas (TCC) in both rat and Man were characterized by decreased alkaline phosphatase (ALP) and increased gamma-glutamyl transpeptidase (GGT), beta-glucuronidase (beta-G1), succinate dehydrogenase (SD) and glucose-6-phosphate dehydrogenase (G6PD) activities. In addition, binding for antibodies specific for different cytochrome P-450 species (UT50, PB3a, MC1, MC2) and microsomal epoxide hydrolase (mEHb) was elevated in both murine and human tumours. Comparison of the enzyme phenotype in hyperplastic lesions induced by freeze ulceration or uracil administration with that in preneoplastic papillary or nodular hyperplasia (PNH) and TCC suggested, however, that most of the alteration in enzyme content or activity was non-specific and related to requirements for epithelial cell proliferation. On the other hand, the decreased ALP, and increased GGT and beta-G1 activity appeared more directly related to neoplastic transformation. The results suggested that qualitative differences exist between reactive hyperplasia and preneoplastic or neoplastic lesions in the urinary bladder. The finding of increased cytochrome P-450, in clear contrast to the reduction characteristic of preneoplastic hepatic lesions, may be important with regard to the observed difference in neoplastic transformation between the bladder and liver in response to drug metabolising enzyme inducers.

Alkaline Phosphatase↗