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Biomedical subjects

S Fujimori

Publications and source records attributed to S Fujimori.

At least 19 recordsLinked to original sources

Effect of pre-induction of heat shock proteins on indomethacin-induced small-intestinal lesion in rats.

Systemic hyperthermia induces the synthesis of heat shock proteins (HSPs) in several organs. However, the mechanism of induction and the functions of HSPs in the small-intestinal mucosa have not been established. We examined the expression of HSPs in the small-intestinal mucosa after systemic hyperthermia, and evaluated the cytoprotective function of pre-induced HSPs on experimentally induced mucosal damage. HSP expression was investigated by Western blot and densitometric analysis before and after hyperthermia (42.5 degrees C; 20 min). Expression of a 72-kDa heat shock protein (HSP72) and a 73-kDa heat shock protein (HSP73), both of which are endogenous cytoprotectants in vitro significantly increased, peaking 6-9 h after hyperthermia, without any pathologic alterations, whereas the expression of a 60-kDa heat shock protein (HSP60) did not increase. To investigate the influence of pre-induction of HSPs on small-intestinal damage, rats received indomethacin (10 mg/kg; orally) with or without pre-treatment with hyperthermia. Small-intestinal damage caused by indomethacin was not influenced by pre-induction of HSP72 and HSP73. We demonstrated that systemic hyperthermia induced HSP72 and HSP73, although pre-induction of these proteins did not have a cytoprotective function in the small-intestinal damage caused by indomethacin.

Animals

Analysis of bile acids in colon residual liquid or fecal material in patients with colorectal neoplasia and control subjects.

Bile acids are believed to play a role in the etiology of colorectal cancer. To examine the relationship between bile acids and colorectal neoplasia, bile acids in colon residual liquid or fecal material were analyzed in 18 patients with colorectal adenoma, 12 patients with colorectal cancer, and 18 healthy control subjects. High-performance liquid chromatography combined with immobilized 3 alpha-hydroxysteroid dehydrogenase in column form showed a significant elevation in the proportion of deoxycholic acid (P < 0.05), lithocholic acid (P < 0.05), secondary bile acids (deoxycholic acid plus lithocholic acid) (P < 0.02), and the chenodeoxycholic acid-lithocholic acid family (chenodeoxycholic acid plus lithocholic acid) (P < 0.05) in the colon residual liquid or fecal material of the patients with colorectal adenoma compared with proportions in the control subjects. A similar trend was noted in the patients with colorectal cancer compared to the control subjects. These findings suggested that an increase in the proportion of secondary bile acids, in particular, of lithocholic acid, was closely related to the pathogenesis of colorectal neoplasia.

Adenoma

An asymptomatic germline missense base substitution in the hypoxanthine phosphoribosyltransferase (HPRT) gene that reduces the amount of enzyme in humans.

A 40-year-old normouricemic (5.5 mg/dl) male showed 46% hemolysate and 37% lymphoblast hypoxanthine phosphoribosyltransferase (HPRT) activities but was otherwise completely free of symptoms. His genomic DNA and cDNA had a missense base substitution (CAT-to-CGT in codon 60) leading to the amino-acid substitution His-to-Arg. Western blot analysis revealed that the amount of HPRT protein in lymphoblasts from this individual was 25%-50% of normal cells, suggesting that the decrease in the amount of enzyme protein was responsible for the partial deficiency. This provides the first clear evidence that a genomic missense mutation at the HPRT locus leads to a decrease in the amount of the enzyme protein but that otherwise it has no evident adverse effects in the hemizygote (asymptomatic mutation).

Adult

Induction of a 72-kDa heat shock protein and cytoprotection against thioacetamide-induced liver injury in rats.

Heat shock proteins are ubiquitous intracellular proteins induced by various physiological stress-related events. A 72-kDa heat shock protein (HSP72) has been reported to be an endogenous cytoprotectant in variety of cells in vitro. In order to study the cytoprotective function of HSP72 in the liver, the effect of preinduction of HSP72 in rat liver by systemic hyperthermia on thioacetamide-induced hepatic injury was investigated in this study. Expression of HSP72 in the liver was investigated by immunoblot and densitometric analysis. Rats were injected with thioacetamide (100 mg/kg, subcutaneously) with or without preinduction of HSP72 by hyperthermia. Serum AST and ALT concentrations were measured before and after thioacetamide injection in both group. Histologic alteration of the liver was evaluated also. Systemic hyperthermia (42.5 degrees C, 20 min) significantly induced HSP72 in the liver. Thioacetamide-induced hepatic injury was clearly prevented by preinduction of HSP72 by hyperthermia. Prevention of hepatocyte damage was more clear in the area around central veins where HSP72 induction was apparent. Our findings might suggest that HSP72 has an important function in the liver with respect to cytoprotection. These results might be important for understanding the mechanism of "adaptive cytoprotection" in the liver mediated by the function of heat shock proteins as "molecular chaperons" as reported in vitro.

Alanine Transaminase

Synthesis of a new potent anti-angiogenic agent, 17 alpha-acetoxy-9 alpha-fluoro-6 alpha-methylprogesterone (9 alpha-fluoromedroxyprogesterone acetate [FMPA]).

A new anti-angiogenic agent, 17 alpha-acetoxy-9 alpha-fluoro-6 alpha-methylprogesterone (9 alpha-fluoromedoroxyprogesterone acetate [FMPA, 9] was synthetized in a 10-step sequence. FMPA (9) had about two orders of magnitude stronger anti-angiogenic activity than medroxyprogesterone acetate (MPA), as estimated in a bioassay involving chorioallantoic membranes of growing chick embryos.

Animals

Virus neutralizing antibody titer to feline immunodeficiency virus isolates of subtypes A, B and D in experimentally or naturally infected cats.

Six strains of feline immunodeficiency virus (FIV) classified into subtypes A, B and D were examined by cross-neutralization test using Kumi-1 cells (CD4+, CD8+, and CD9+), an interleukin-2 dependent feline T-lymphocyte cell line. Neutralizing activities against these six FIV strains were also investigated in 50 FIV-antibody-positive serum samples collected from different geographical regions in Japan. The cross-neutralization test revealed that antisera against the six strains tended to possess high neutralizing activity against the homologous strain. These antisera were also capable of neutralizing viral strains of the same subtype. However, some of the antisera were broadly crossreactive with all six FIV strains. Serum samples collected from naturally infected cats in the field showed various neutralization patterns for the six FIV strains. These observations reflect the antigenic diversity in FIV strains prevailing in the field. There were also broadly crossreactive serum samples, and 36% (18/50 samples) showed neutralization for all six FIV strains.

Animals

Significance of serum iron and ferritin in patients with colorectal adenomas.

BACKGROUND: Colorectal adenomas are often detected on mass screening, although detection rates with fecal occult blood tests are low. The relationship between colorectal adenomas and the resulting blood loss was examined indirectly, using serum iron and ferritin levels. METHODS: Serum iron and ferritin concentrations were measured in 184 men with colorectal adenomas (> or = 1 cm in 92; < 1 cm in 92) and in 92 healthy male controls. Values in the three groups were compared. In the patients with adenomas > or = 1 cm, serum iron and ferritin levels were compared on the basis of the site, number, histology, and degree of dysplasia of the adenoma. RESULTS: The mean serum iron level was significantly lower in patients with adenomas > or = 1 cm than in controls (P < 0.05), although this level did not differ significantly between those with adenomas < 1 cm and controls. The mean serum ferritin level also was significantly lower in patients with adenomas > or = 1 cm than in those with adenomas < 1 cm and controls (P < 0.05, P < 0.01, respectively), although this level did not differ between those with adenomas < 1 cm and controls. There was no difference in mean serum iron or ferritin levels on the basis of the site, number, histology, or degree of dysplasia of the adenoma. CONCLUSIONS: We conclude that decreased serum iron and ferritin levels are related only to adenoma size and that adenomas > or = 1 cm may bleed steadily, resulting in iron deficiency. However, low dietary intake of iron and fiber may be one of the causes of low serum iron and ferritin.

Adenoma

[PRPP synthetase superactivity].

Phosphoribosylpyrophosphate(PRPP) synthetase(PRS) catalyzes the formation of PRPP from ATP and ribose-5-phosphate. PRPP is an important substrate for the synthesis of purine, pyrimidine, and pyridine dinucleotides. Human PRS exists as complex aggregates composed of the 34 kDa catalytic subunits(PRS1 and PRS2) and other 39 kDa component designated PRPP synthetase-associated protein (PAP39). PRS superactivity is an X-chromosome linked disorder, characterized by gout and uric acid overproduction resulting from accelerated synthesis of PRPP and purine nucleotides. Among the nearly 30 affected families identified to date, there are several families in which PRS superactivity with purine nucleotide feedback resistance are associated with neurodevelopmental abnormalities in addition to hyperuricemia and gout. Different nucleotide substitutions in the PRPS1 gene encoding PRS1 have identified in six unrelated affected families with purine nucleotide feedback-resistant PRS superactivity.

Gout

Induction and intracellular localization of a 72-kDa heat shock protein in rat gastric mucosa after water-immersion stress.

We investigated the expression and changes in the intracellular localization of a 72-kDa heat shock protein (HSP72) in rat gastric pyloric and fundic mucosa before and after water-immersion stress. Severe mucosal damage was found in the fundic mucosal area of the stomach after this stress. However, no mucosal lesion developed in the pyloric mucosal area. HSP72 in both the soluble and insoluble fractions of the pyloric and the fundic mucosal areas was significantly increased after water-immersion stress, peaking 6h after the initiation of the stress. The increase in HSP72 was more significant in the pyloric mucosal area than in the fundic mucosal area under both normal and stress conditions. The increase of HSP72 in the pyloric mucosal cells occurred prior to the formation of the mucosal lesions, whereas the increase of HSP72 in the fundic mucosal cells was observed after ulcer formation. An immunohistochemical study showed that HSP72 was constitutively expressed in the cytoplasm of the gastric mucosal cells, and that the intranuclear induction of HSP72 was remarkably intense in the pyloric mucosal cells, especially in the proliferative zone, compared with the fundic mucosal cells. Our results may suggest that HSP72 has an important cytoprotective function in gastric mucosal cells and that there is a "biophysical" difference between pyloric and the fundic mucosal cells.

Animals

Novel colorectal adenocarcinoma-associated 40- and 47-kDa protein antigens recognized by anti-60-kDa heat shock protein antibody.

Expression of 40- and 47-kDa proteins recognized by anti-60-kDa heat shock protein antibody was investigated in colorectal adenocarcinoma tissue. In all cases of colorectal adenocarcinoma tissue (n = 9), 40- and 47-kDa proteins were detected by immunoblot analysis. However, expression of these two proteins was extremely low or was not expressed in control tissue. There was no correlation between the quantity of these two bands and histologic type or the location of the tumors. Our results first demonstrate the accumulation of structurally altered 60-kDa heat shock protein-associated antigens in carcinoma tissue and suggest that these two proteins could be a possible candidate for tumor-specific 60-kDa heat shock protein-related protein antigens.

Adenocarcinoma

Cranioplasty with split-thickness calvarial bone.

Cranioplasty with autogenous split-thickness calvarial bone was performed in 10 patients. Follow-up for a mean of 19 months (range 2-43 mos) showed satisfactory protection of the brain and cosmetic reconstruction. No serious complication was seen except in one patient with postoperative epidural abscess. Split-thickness calvarial bone graft is recommended in patients with previous infection or high risk of infection, in poorly vascularized recipient sites resulting from multiple operations or irradiation, and in younger patients aged more than 7 years.

Adolescent

[A study of psychologically optimal level of item difficulty].

For the purpose of selecting items in a test, this study presented a viewpoint of psychologically optimal difficulty level, as well as measurement efficiency, of items. A paper-and-pencil test (P & P) composed of hard, moderate and easy subtests was administered to 298 students at a university. A computerized adaptive test (CAT) was also administered to 79 students. The items of both tests were selected from Shiba's Word Meaning Comprehension Test, for which the estimates of parameters of two-parameter item response model were available. The results of P & P research showed that the psychologically optimal success level would be such that the proportion of right answers is somewhere between .75 and .85. A similar result was obtained from CAT research, where the proportion of about .8 might be desirable. Traditionally a success rate of .5 has been recommended in adaptive testing. In this study, however, it was suggested that the items of such level would be too hard psychologically for many examinees.

Adaptation, Psychological

Clinical significance of serum iron and ferritin in patients with colorectal cancer.

To clarify the significance of serum iron and ferritin as indicators of iron loss caused by continuous bleeding, and, thus, to determine their value as markers of colorectal cancer, values for the two were compared in male patients with early and advanced colorectal cancer and age-matched male controls. The mean value of serum iron levels in patients with advanced colorectal cancer was significantly decreased compared with values in patients with early colorectal cancer and controls, 50.5 +/- 38.6 micrograms/dl vs 93.0 +/- 32.1 micrograms/dl and 107.1 +/- 32.9 micrograms/dl, respectively (p < 0.001). The mean value of serum ferritin levels in patients with early and advanced colorectal cancer was also significantly decreased compared with controls, 80.5 +/- 35.0 ng/ml (p < 0.01) and 48.8 +/- 72.8 ng/ml (p < 0.001), respectively, vs 117.1 +/- 46.8 ng/ml. However, there was no significant difference between mean serum iron levels in patients with early colorectal cancer and controls. Eighteen (78.3%) of the 23 patients with advanced colorectal cancer and 3 (16.7%) of the 18 patients with early colorectal cancer had serum iron levels below 85 micrograms/dl and serum ferritin levels below 60 ng/ml. Levels of both serum iron and ferritin, without clinically evident anemia, are useful indicators of advanced colorectal cancer.

Aged

Regulation of 60-kDa heat shock protein expression by systemic stress and 5-hydroxytryptamine in rat colonic mucosa.

Bowel dysfunction such as irritable bowel syndrome caused by stress is well described. Previous reports suggest that 5-hydroxytryptamine (5-HT) mediates alteration of bowel motility. In this study, the effects of water-immersion stress and the administration of 5-HT on the expression of a 60-kDa heat shock protein (HSP60) in rat colonic mucosa were investigated. The effect of YM-060, a 5-hydroxytryptamine 3 (5-HT3) receptor antagonist, on the expression of this protein was also studied. Water-immersion stress and the administration of 5-HT induced synthesis of HSP60 in rat colonic mucosa. The induction of HSP60 and the number of defecations were clearly inhibited by the oral administration of YM-060. Our results suggest that the induction of HSP60 in rat colonic mucosa by water-immersion stress may be associated with gastrointestinal motility mediated by 5-HT, especially via 5-HT3 receptors.

Animals