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Biomedical subjects

F Itoh

Publications and source records attributed to F Itoh.

At least 127 records · Page 7Linked to original sources
PubMed1996

Double determinant immuno-polymerase chain reaction for detecting soluble intercellular adhesion molecule-1.

A sensitive method for the detection of antigens in sera, termed double determinant immuno-polymerase chain reaction (DDI-PCR), was developed using two monoclonal antibodies (MoAbs) in which the antigens are sandwiched and a specific DNA molecule as a marker. Instead of the antigen itself, the first MoAb to bind the circulating antigens was immobilized. After the biotinylated second MoAb was bound to the antigen, free streptavidin was used to attach a biotinylated DNA to the biotinylated second MoAb. The biotinylated DNA complexed with antigen-antibody-streptavidin was amplified by PCR. The PCR products were analyzed by Southern blot hybridization after agarose gel electrophoresis. Compared with the conventional ELISA using soluble intercellular adhesion molecule-1 (sICAM-1) in the supernatant of cultured Panc-1 cells as an antigen, our DDI-PCR was 10(3) times more sensitive in detection limit. In both the culture medium and sera from gastric cancer patients of high sICAM-1 titer, an approximately 10(3)-fold enhancement in detection sensitivity was obtained compared with ELISA. In addition, the DDI-PCR system can detect the antigen in sera at a level below the detection limit of traditional ELISA methods with high sensitivity. Thus, DDI-PCR has the significant advantage that it can be readily applied to any antigen-antibody system with two MoAbs without making any original molecules.

Animals↗
PubMed1996

Dopamine receptor affinities in vitro and stereotypic activities in vivo of cabergoline in rats.

An ergot alkaloid derivative, cabergoline, and its metabolites were investigated for their affinities for dopamine D1 and D2 receptors in rat striatum in vitro in comparison with those of bromocriptine and pergolide. The affinity for D1 receptors was in the following order: pergolide > des-dimethylaminopropyl cabergoline (FCE21904) > cabergoline > or = bromocriptine > or = des-methyl cabergoline (FCE27395) > or = des-ethylcarbamoyl cabergoline (FCE21590). From the effects of GTP on these affinities for the D1 receptor, cabergoline, some of its metabolites, and pergolide were characterized as agonists in contrast to bromocriptine which was classified as an antagonist. The affinity for D2 receptors was ranked as follows: pergolide > or = cabergoline > or = FCE27395 > or = FCE21904 > bromocriptine > FCE21590 > carboxylic acid-type derivative of cabergoline (FCE21589). The affinity of each compound for the D2 receptor was much higher than that for the D1 receptor. The selectivity of cabergoline for D2 receptor was higher than those of bromocriptine and pergolide. Furthermore, these ergot alkaloids were investigated for eliciting stereotypy after subcutaneous administration to normal rats. Pergolide potently induced stereotypy at doses of 0.5 and 1.0 mg/kg, cabergoline slightly induced it only at a high dose of 2.0 mg/kg, whereas bromocriptine did not induce it at any of the doses tested, 10-40 mg/kg. These results suggest that pharmacological properties of cabergoline for the D1 and D2 receptors differ from those of bromocriptine and pergolide.

Animals↗
PubMed1996

Effect of cabergoline, a long-acting dopamine D2 agonist, on reserpine-treated rodents.

We studied the characterization of cabergoline, a new ergot alkaloid derivative and a selective dopamine D2 receptor agonist, in comparison to bromocriptine and pergolide in reserpine-treated rodents. Cabergoline (0.25-1.0 mg/kg, s.c.) improved dose-dependently the reserpine-induced akinesia that was assessed on the locomotor activity, and the efficacy lasted longer than those of bromocriptine (1.25-5.0 mg/kg, s.c.) or pergolide (0.0625-0.5 mg/kg s.c.). Cabergoline (ED50 = 1.10 mg/kg, at 4 h after the administration of drugs) also reversed catalepsy, the failure to correct an externally imposed posture, and its efficacy was stronger and longer than bromocriptine (ED50 = 4.65 mg/kg, at 4 h). Further, reserpine-induced rigidity was improved equally by cabergoline (0.125-1.0 mg/kg, i.v) and bromocriptine (1.0 mg/kg, i.v.). When cabergoline was administered together with 3(3,4-dihydroxyphenyl)-L-alanine (L-DOPA), the effects were additive. Our results indicate that the long-lasting effects of cabergoline could be beneficial for treating Parkinson's disease.

Animals↗
PubMed1996

Non-glutamate type pyrrolo[2,3-d]pyrimidine antifolates. II. Synthesis and antitumor activity of N5-substituted glutamine analogs.

The glutamic acid moiety of N-[4-[3-(2,4-diamino-7H-pyrrolo[2, 3-d]pyrimidin-5-yl)propyl]benzoyl]-L-glutamic acid (1b, TNP-351) and related compounds was replaced with some N5-substituted glutamines. Antifolates (4A-S) were effectively prepared by coupling pyrrolo[2,3-d]pyrimidine carboxylic acids (11a, b) with some properly protected N5-substituted glutamine derivatives (10A-S), which were prepared by coupling Boc-Glu-OMe (7) with various amines (8A-S) using a suitable condensing reagent, followed by hydrolysis. The inhibitory effects of the resulting products on dihydrofolate reductase (DHFR), thymidylate synthetase (TS) and the growth of murine fibrosarcoma Meth A cells in culture were examined. All N5-substituted glutamine analogs (4A-S) inhibited DHFR much more strongly than TNP-351 and some analogs exhibited the same potent growth inhibition of Meth A cells as TNP-351. Some typical analogs (4Bb, 4Db, 4F, 4Oa) were also examined for inhibitory effects on the growth of methotrexate (MTX)-resistant human CCRF-CEM cells in culture and for in vivo antitumor activities against murine leukemia and solid tumors. MTX-resistant cells, with a defect in transport and decreased polyglutamylation activity, showed little cross resistance to the analog (4Oa) having a tetrazole moiety as a substituent of glutamine, which exhibited potent antitumor activities. These results demonstrate that the antifolate analogs (4) with N5-substituted glutamine in place of glutamic acid are novel potent DHFR inhibitors with activity against MTX-resistant tumors. The potent antitumor activity of these analogs (4) may result from their effective uptake via reduced folate carrier in combination with their potent inhibition of DHFR.

Animals↗
PubMed1996

Venous hemangioma of the temporalis muscle.

A 14-year-old girl presented with a diffuse venous hemangioma of the right temporalis muscle. The muscle had become swollen, thinning the underlying zygomatic and temporal bones. Magnetic resonance (MR) imaging demonstrated a diffuse isointense area containing high intensity foci on the T1-weighted images, and a serpiginous high intensity pattern on the T2-weighted images. A biopsy specimen revealed irregularly dilated veins in the fibrous stroma of the muscle. Diffuse abnormal signals on MR images may be a pathognomonic feature of intramuscular venous hemangiomas.

Adolescent↗
PubMed1996

Effect of growth hormone-releasing factor on the response to insulin of cows during early and late lactation.

The euglycemic clamp technique was used to determine the effect of bovine growth hormone-releasing factor on glucose kinetics and on the response to insulin of 4 dairy cows during early lactation (mean, 35 d postpartum) and of 6 dairy cows during late lactation (mean, 194 d postpartum). Beginning 3 d prior to experiments, cows were injected twice daily with either saline or 2.5 micrograms/kg of growth hormone-releasing factor. On the day of the experiment, saline or the releasing factor (0.0119 microgram/kg per min) was infused into each cow for 5 h. After a basal period, insulin was infused at 1 and then at 6 mU/kg per min; plasma glucose concentrations were maintained at basal concentrations by the infusion of normal glucose. Growth hormone-releasing factor reduced the glucose infusion rate that was required to maintain euglycemia during the insulin infusions during late lactation but had no effect during early lactation. During the insulin infusions of the late lactation experiment only, the rates of glucose appearance, disappearance, and metabolic clearance were lower when plasma growth hormone was elevated. The results demonstrated that elevated concentrations of growth hormone decreased the responsiveness of peripheral tissues to high concentrations of insulin during late lactation but apparently had little effect during early lactation.

Animals↗
PubMed1996

Ruptured aneurysm of the middle meningeal artery associated with occlusion of the posterior cerebral artery. Case report.

The authors describe the case of a 69-year-old man with an intracerebral hemorrhage due to rupture of a nontraumatic aneurysm of the middle meningeal artery (MMA). The ipsilateral posterior cerebral artery (PCA) was occluded, and dural anastomoses developed as the main collateral pathway between the MMA and the cortical branch of the PCA, on which the aneurysm was located. It is considered that increased hemodynamic stress to the collateral pathway contributed to the formation of the aneurysm.

Aged↗
PubMed1996

[Detection of tumor markers by genetic diagnostic methods and its clinical application].

Since the development of the polymerase chain reaction (PCR) method of DNA amplification in 1985, numerous improvements, modifications, and novel applications of PCR have been devised. These developments eventually made it possible to examine minute clinical samples. It has become clear that cancer arise and progress through the accumulation of various genetic alterations. Certain genetic changes are now considered to be molecular markers useful not only for early diagnosis but also for predicting the behavior of cancer and the clinical outcome of patients. Some molecular markers are also useful for diagnosis of inherited cancer and susceptibility to cancer. We describe the latest improvements of detecting these molecular markers and clinical application of them in digestive cancer.

Biomarkers, Tumor↗
PubMed1996

[Genetic diagnosis of colorectal cancer].

Accumulating evidences that carcinogenesis requires multiple gene alterations of oncogenes and tumor suppressor genes have recently emerged. In addition, genes related to invasion and metastasis are also important in understanding development of colorectal cancer. In this study, clinical significance and application of tumor suppressor genes and invasion related genes such as APC (adenomatous polyposis coli), DCC (deleted in colorectal carcinoma) tumor suppressor genes and invasion related gene, matrilysin were studied. In the mouse tumor induced by mutagen contained in cooked food, PhIP (2-amino-1-methyl-6- phenylimidazo [4,5-b] pyridine), nonsense mutations of APC gene that is similar to human colorectal cancer have been observed. These results suggested the quite interesting issue of mutagen contained in daily food having etiological role of colorectal cancer. DCC gene alteration, decreased expression of DCC mRNA was detected in 60% of advanced colorectal cancer. In all cases with liver metastasis, DCC expression was absent or markedly decreased, a finding that detection of DCC expression have an clinical importance that predicts metastatic potential of colorectal cancer. Matrilysin, the member of MMPs (matrix metalloproteinases) which degrade matrix components such as type IV collagen, laminin or fibronectin. In most of colorectal cancer, matrilysin was overexpressed in tumor cells. Matrilysin-transfected colorectal cancer cells showed more invasive ability in vitro and gained metastatic potential in SCID mice. Suppression of matrilysin expression by treated with all-trans retinoic acid (ATRA) or introduction of anti-sense matrilysin decreased the invasive ability in vitro. This result suggests that matrilysin plays an important role in invasion and metastasis and have a possibility of new anti-invasion therapy.

Animals↗
PubMed1996

[Two cases of severe cytomegalovirus pneumonitis treated with permissive hypercapnia].

Two patients with severe cytomegalovirus (CMV) pneumonitis were treated with permissive hypercapnia. Case 1 was a 66-year-old male who suffered ventricular septal perforation caused by acute myocardial infarction. Case 2 was a 54-year-old male who sustained a blunt chest injury. In both cases, hypoxia with reduction of lung compliance developed after their operations. They were mechanically ventilated and we limited their peak inspiratory pressure, disregarding hypercapnia (i.e. permissive hypercapnia). During permissive hypercapnia, the maximum arterial partial pressure of carbon dioxide (PaCO2) was 96 mmHg in case 1 and 141 mmHg in case 2. Duration of hypercapnia (PaCO2 > 50mmHg) was 22 days in case 1 and 29 days in case 2. The patients were weaned from the respirator after two months of mechanical ventilation. In conclusion, the permissive hypercapnia was a useful method in the treatment of severe CMV pneumonitis.

Aged↗
PubMed1995

Suppression of matrilysin inhibits colon cancer cell invasion in vitro.

Matrilysin is a member of the matrix metalloproteinase gene family, which is believed to play an important role in tumor invasion and metastasis. We examined the effects of over- and under-expression of matrilysin on the ability of colon cancer cells to migrate across an artificial membrane in vitro. Introduction of matrilysin caused colon cancer cells to become more invasive as assessed by an in vitro invasion assay. In contrast, expression of matrilysin was down-regulated by all trans-retinoic acid or by introduction of anti-sense matrilysin in BM314 colon cancer cells. This down-regulation caused these cells to become less invasive. We demonstrated a correlation between matrilysin level and the invasive potential of human colon cancer cells, implying an important role for matrilysin in the control of tumor invasion in vitro.

Colonic Neoplasms↗
PubMed1995

Expression of matrix metalloproteinase matrilysin (MMP-7) was induced by activated Ki-ras via AP-1 activation in SW1417 colon cancer cells.

The matrix metalloproteinase matrilysin (MMP-7) is a member of the matrix metalloproteinase gene family, which is believed to play an important role in tumor invasion and metastasis. We have previously found that matrilysin mRNA is specifically expressed in colorectal cancers and adenomas and that its message is localized in the tumor cells themselves. We examined the effects of activated Ki-ras oncogene on the expression of matrilysin in colon cancer cells. We showed that both mRNA and the enzymatic activity of matrilysin were induced by the introduction of activated Ki-ras into SW1417 colon cancer cells. To understand the mechanisms regulating this induction, we analyzed alterations of AP-1 activity induced by activated Ki-ras, using the chloramphenicol acetyltransferase assay. AP-1 activity in SW1417 cells expressing activated Ki-ras was higher than that in control cells. The gel-shift assay also showed higher levels of AP-1 binding protein in SW1417 cells expressing activated Ki-ras than those in control cells. Our results suggest that activated Ki-ras may play a role in inducing expression of matrilysin through an AP-1-dependent pathway in colon cancer cells.

Choline O-Acetyltransferase↗
PubMed1995

Double determinant immuno-polymerase chain reaction: a sensitive method for detecting circulating antigens in human sera.

A sensitive method for the detection of antigens in sera, termed double determinant immunopolymerase chain reaction (double determinant immuno-PCR) was developed, using two monoclonal antibodies (MoAbs), in which the antigens are sandwiched, and a specific DNA molecule is used as a marker. Instead of the antigen itself, the first MoAb to bind the circulating antigens was immobilized. After the biotinylated second MoAb was bound to the antigen, free streptavidin was used to attach a biotinylated DNA to the biotinylated second MoAb. The biotinylated DNA complexed with antigen-antibody-streptavidin was amplified by PCR, and the PCR products were analyzed by Southern blot hybridization after agarose gel electrophoresis. Compared with the conventional enzyme linked immunosorbent assay (ELISA) using soluble intercellular adhesion molecule-1 (sICAM-1) in the supernatant of cultured Panc-1 cells as an antigen, our double determinant immuno-PCR was 10(3) times more sensitive in terms of the detection limit. Not only in culture medium, but also in sera from gastric cancer patients of high sICAM-1 titer, an approximately 10(3)-fold enhancement in detection sensitivity was obtained compared with ELISA. In addition, this system can detect the antigen in sera at a level below the detection limit of traditional ELISA methods with high sensitivity. Thus, double determinant immuno-PCR has the significant advantage that it can be readily applied to any antigen-antibody system for which two MoAbs are available.

Antibodies, Monoclonal↗
PubMed1995

Non-glutamate type pyrrolo[2,3-d]pyrimidine antifolates. I: Synthesis and biological properties of pyrrolo[2,3-d]pyrimidine antifolates containing tetrazole congener of glutamic acid.

Either the alpha- or gamma-carboxyl group of the glutamic acid moiety of N-[4-[3-(2,4-diamino-7H-pyrrolo[2,3-d]pyrimidin-5- yl)propyl]benzoyl]-L-glutamic acid (1b, TNP-351) and its related compound (1a) was replaced with a 1H-tetrazole ring, and the inhibitory effects of the resulting compounds on dihydrofolate reductase (DHFR) and the growth of murine fibrosarcoma Meth A cells were examined. The gamma-tetrazole analogs (2) were found to be much more potent DHFR inhibitors than TNP-351, and strongly inhibited the growth of Meth A cells. On the other hand, the alpha-tetrazole analogs (3) were much less active against Meth A cells, even though their DHFR-inhibitory activity was comparable to that of TNP-351. These findings suggest that the alpha-carboxyl group plays an important role in effective uptake via the reduced folate carrier, and a novel DHFR inhibitor could be obtained by chemically modifying the gamma-carboxyl moiety while leaving the alpha-carboxyl group intact.

Animals↗
PubMed1995

[A PCR method for examining diarrhea--Escherichia coli].

To identify diarrhea--Escherichia coli(E. coli), especially Enteroinvasive E. coli(EIEC), Verocytotoxin-producing E. coli(VTEC), and Enterotoxigenic E. coli(ETEC), confirmation of pathogenic factors is necessary. We developed a system using the polymerase chain reaction(PCR) that simultaneously confirms the pathogenic genes of these E. coli, and have used it in routine examination. This method is simple and does not require examination for each pathogenic factor. Multiple pathogenic genes could be rapidly detected.

Bacterial Toxins↗
PubMed1995

[Modification of vancomycin nephrotoxicity by other antibiotics in rats].

Vancomycin (VCM) was intravenously administered to rats for 14 days at doses of 150 mg/kg/day and 250 mg/kg/day alone or in combination with 1,000 mg/kg/day of latamoxef (LMOX), flomoxef (FMOX) or cefpirome (CPR) or 250 mg/kg/day of fosfomycin (FOM), and the influences of combined antibiotics on the VCM-induced renal damage were studied. The renal impairment caused by VCM alone was, morphologically, demonstrated mainly as regeneration of tubular epithelium: slight regeneration was observed in a half of rats administered 150 mg/kg/day and slight to extensive regeneration in all the rats administered 250 mg/kg/day. Clinical examinations found apparent increases in urinary LDH and MDH activities in rats administered 250 mg/kg/day, thus showing a good correlation with renal pathological changes. In addition, increase in kidney weight and increase in urinary NAG activity were noted, while changes in plasma urea-N and creatinine were mild, and gamma-GTP activity and protein in urine could not be used as a parameter of the renal impairment. The slight renal impairment as noted in rats administered VCM 150 mg/kg/day alone was not observed at all when LMOX or FMOX was administered concomitantly, and less pronounced even when FOM was administered concomitantly. When CPR was administered concomitantly, the changes were the same as those observed with VCM alone. The renal impairment in rats administered VCM 250 mg/kg/day was apparently less severe when combined with LMOX, FMOX and FOM than that in rats administered VCM alone, and this was supported by apparent reduction of clinical examination values as the parameter of VCM-induced nephrotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Expression of matrilysin mRNA in colorectal adenomas and its induction by truncated fibronectin.

Matrilysin is believed to have a role in tumor progression. Its expression correlates with the occurrence of colorectal cancer. We have examined the expression of matrilysin mRNA in various colorectal disorders and its localization using RT-PCR and in situ hybridization. We have also examined whether Matrilysin is induced by cell to matrix interaction. Matrilysin mRNA was detected in all adenoma tissues examined, whereas none was detectable in hyperplastic polyps, mildly inflamed regions of ulcerative colitis or normal colon tissues, and its message was localized in adenoma cells themselves. In addition, levels of enzyme activities of matrilysin were lower in adenomas compared with cancers in casein zymography. Matrilysin mRNA was induced by immobilized truncated fibronectin or RGD peptide. Thus, matrilysin may play an important role in colorectal carcinogenesis.

Adenoma↗