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Biomedical subjects

M Fujii

Publications and source records attributed to M Fujii.

At least 343 records · Page 19Linked to original sources

[The disturbance of reversible operation in space in the early stage of Alzheimer's disease].

Constructional apraxia is one of the neuropsychological findings frequently observed in the early stage of the Alzheimer's disease, which may result from the visuo-spatial disturbances. The visual space consists of a variety of visual information processing, viewer-centered coordinate system, objects-centered coordinate system, integration of both coordinate systems, and verifying visual representation with the knowledge in the memory. The reversible operation in space, or mental rotation appears to play an important role in visuo-spatial functions, which refers to the operation of the visual representation at one orientation in viewer-centered coordinate system to construct the representation in object-centered coordinate system so that one can look like if it were presented at another orientation. To the present, little is known about reversible operation or mental rotation in patients with Alzheimer's disease. In this present paper, we attempted to investigate the ability of reversible operations in space so as to understand the mechanisms underlying constructional apraxia, or visuo-spatial disturbances in the early stage of Alzheimer's disease. The subjects were 12 patients with Alzheimer's disease in early stage (AD group), 12 patients with multi-infarcts dementia as disease control (MID group), 12 age matched persons as healthy control (HC group). In perspective taking tasks, that requires the subjects to imagine the spatial arrangement of the objects at the different view points from the subjects' one, AD group showed more severe deficits than MID group and HC group. Moreover, in a task that the subjects were asked to assume the photo-angle of the photograph taken of the model which was in front of them, AD group was imparied compared to the control groups. These disturbances were closely associated with deficits in Block Design test of WAIS. These results clearly demonstrate that the patients with Alzheimer's disease have disturbance in reversible operation in space and that the disturbance may be responsible for visuo-spatial dysfunctions, not only the constructional apraxia, but also a variety of performance deficits in the early stage of Alzheimer's disease.

Aged↗

v-Rel activates the proto-oncogene c-Jun promoter: a correlation with its transforming activity.

v-Rel is a transforming protein of the reticuloendotheliosis virus, and is a transcription factor regulating various cellular genes. We found that v-Rel activates the promoter of the proto-oncogene c-jun in a transient transfection assay system. Moreover, the expression of endogenous c-jun was augmented in cells expressing exogenous v-Rel, but not c-Rel. The transcriptional activities of v-Rel to the tested promoters containing the kB-site are lower than that of c-Rel, but that to the c-jun promoter was much higher than that of c-Rel. The N-terminal DNA binding domain of v-Rel, which is responsible for its high transforming activity of v-Rel was also responsible for the high transcriptional activity to the c-jun promoter. Thus, the activity of v-Rel upon the c-jun promoter correlates well with its transforming ability. Since c-Jun plays pivotal roles on cell proliferation in various types of cells, the activation of c-jun expression by v-Rel may be an essential step for the oncogenic transformation caused by v-Rel.

Binding Sites↗

Dual phasic suppression of viral replication following de novo human immunodeficiency virus type 1 (HIV-1) infection in lymphocytes of asymptomatic HIV-1 carriers.

Replication of human immunodeficiency virus type 1 (HIV-1) is suppressed in asymptomatic HIV-1 carriers (ACs). By using an in vitro experimental system, the mechanism of this suppression was investigated. Following in vitro infection of a laboratory HIV-1 strain, the peripheral blood mononuclear cells (PBMC) of ACs transiently supported a low level of viral replication, then the virus production rapidly decreased. PCR analysis revealed that HIV-1 proviral DNA integrated in the PBMC of ACs following infection gradually decreased. Such tapering consequences of in vitro HIV-1 infection in the PBMC of ACs were abrogated by depletion of CD8+ T cells from the culture. Furthermore, the viruses subsequently produced by the PBMC of an AC were less able to replicate than the virus produced by CD8+ cell-depleted PBMC of the same donor. These observations suggested that the CD8+ T cell-mediated suppression of HIV-1 replication in ACs may involve both cytocidal and cytostatic mechanisms: the former kills the cells producing viruses, and the latter inhibits viral spread by reducing viral infectivity.

CD8-Positive T-Lymphocytes↗

[Usefulness of directional coronary atherectomy as a bail-out device for acute closure after coronary angioplasty].

The usefulness of directional coronary atherectomy (DCA) as a bail-out device for acute closure (reclosure) after percutaneous transluminal coronary angioplasty (PTCA) was evaluated. PTCA was performed in 1,023 patients (182 with acute myocardial infarction) between January 1993 and January 1994 in our hospital. Thirty-one patients (11 with acute myocardial infarction) suffered acute closure (reclosure) after PTCA. In six patients (five with acute myocardial infarction), DCA was performed as a rescue treatment for acute closure (reclosure). In three of these patients, angioscopy was performed before DCA, which demonstrated intimal tear and some thrombi although coronary angiography showed no evidence of thrombus. Bail-out DCA was successful in all six patients without complications. DCA is useful as a bail-out device for acute closure (reclosure) after PTCA when the thrombus is not massive.

Angioplasty, Balloon, Coronary↗

Inhibition of the proliferation of Ehrlich ascites tumor cells by hydrostatic pressure.

The effect of high pressure on the viability of Ehrlich ascites tumor cells was examined. The tumor cells were subjected to various pressures (0.1-150 MPa) for 30 min at 37 degrees C. The viability of pressure-treated cells was examined by the dye exclusion method. The number of stained cells increased significantly at pressures above 130 MPa. In addition, the pressure-treated cells were intraperitoneally inoculated into the mice. The tumor cells which were subjected to pressures below 110 MPa proliferated in the peritoneal cavity of the mice, so that the mice died. In contrast, the mice, which were inoculated with the tumor cells treated at pressures above 130 MPa, remained alive. These results suggest that the destruction of the tumor cells begins to occur at about 130 MPa.

Animals↗

Regulation of selenoprotein P mRNA expression in comparison with metallothionein and osteonectin mRNAs following cadmium and dexamethasone administration.

Selenium is recognized as an essential trace element and an antidote for carcinogens, heavy metals etc., and also as an environmental pollutant causing dysfunction of both the brain and peripheral tissues. Selenoprotein P (SelP) contains 10 selenium per molecule in the form of selenocysteines. To clarify whether SelP involved in selenium requirement and toxicity, SelP mRNA expression was compared with the expression of metallothionein (MT) and osteonectin (OST) mRNAs, the protein products of which are known to have antidote effects. MT and OST are induced by diverse forms of stress and immediately affect genes with stress promoter sequences. Cd and dexamethasone were used to examine such secondary regulation. Basal expression of SelP mRNA was high both in NRK cells and in rat kidney and brain but dexamethasone induction was observed only in NRK cells. Dexamethasone, but not Cd, decreased expression of OST mRNA in NRK cells, while OST mRNA in the kidney and brain increased after Cd administration in rats. Induction of MT mRNA was observed in response to Cd and dexamethasone in all cells and tissues examined, while the net increase was little because its basal expression was faint. Moreover, in situ hybridization indicated that SelP mRNA expression was localized to the cerebellum, one of the targets of selenium toxicity. The cerebellum is also a target for methyl-Hg intoxication, symptoms of which are ameliorated by selenium. Thus, SelP seems to be involved in both selenium homeostasis and detoxication mechanisms even though SelP mRNA is not always inducible.

Animals↗

[Comparison of effects between single vs five-day injection of granisetron for combination chemotherapy with cisplatin and 5-fluorouracil for head and neck cancer].

Recently, granisetron (KYT), one of the 5-HT3 receptor antagonists, has been developed and proved to have a strong effect for cisplatin (CDDP)-induced emesis. The combination chemotherapy with CDDP and 5-fluorouracil (5-FU), which has great efficacy for head and neck cancer, induces nausea and vomiting as side effects. We compared the effects of KYT for CDDP plus 5-FU-induced emesis between two administration schedules. Forty patients were randomized to two groups. KYT was administered either on day 1 for twenty patients (Group A), or for consecutive 5 days in another twenty patients (Group B). Additional antiemetics were administered in thirteen patients in Group A and seven patients in Group B for severe nausea and vomiting even after KYT administration. The times of additional antiemetics administration were more frequent in Group B. The nausea score was statistically lower in Group B and the duration of nausea or vomiting was statistically longer in Group A. The frequency of vomiting was the same in the two groups on day 1, but it was controlled faster in Group B. Appetite loss was lower on day 7 in Group B. It was concluded that vomit and nausea were controlled better in Group B after day 4. Additional antiemetics were not effective, and 5 consecutive administrations of KYT for chemotherapy with CDDP plus 5-FU was effective for late emesis.

Adolescent↗

Cholecystokinin antagonistic activities of loxiglumide.

Cholecystokinin (CCK) antagonistic activities of loxiglumide ((+/-)-4-(3,4-dichlorobenzamido)-N-(3-methoxypropyl)-N-pentylgl utaramic acid, CR1505, CAS 107097-80-3) were investigated in the gastrointestine and gallbladder in vivo. Intravenous administration of loxiglumide antagonized the CCK-induced reduction of gastric emptying in rats, acceleration of intestinal transport in mice, increase in ileal motility in rabbits, gallbladder contraction in guinea pigs and acceleration of gallbladder emptying in mice. Orally administered loxiglumide also antagonized the CCK-induced gallbladder emptying in mice. Furthermore, egg yolk-stimulated gallbladder emptying in mice was also inhibited by loxiglumide, indicating that this agent antagonizes not only exogenous but also endogenous CCK. These results demonstrate that loxiglumide is an intravenously and orally effective, potent CCK antagonist.

Animals↗

General pharmacological profile of the novel cholecystokinin-A antagonist loxiglumide.

The general pharmacological properties of a novel cholecystokinin-A antagonist, loxiglumide ((+/-)-4-(3,4-dichlorobenzamido)-N-(3-methoxypropyl)-N-pentylgl utaramic acid, CR 1505, CAS 107097-80-3) on central nervous system, autonomic nervous system, cardio-respiratory system, gastrointestinal system, hematological and miscellaneous systems were investigated in experimental animals. 1. Central nervous system: At a dose of 30 mg/kg, i.v. loxiglumide showed ptosis in one of 6 mice, but at doses of 3 and 10 mg/kg, i.v. no change on gross behavior in mice. Loxiglumide had no effect on locomotor activity and thiopental-induced hypnosis, anti-convulsive activity, analgesic activity in mice and rectal temperature changes in rats. 2. Autonomic nervous system: In vitro, loxiglumide at concentrations of 10(-4) and 3 x 10(-4) mol/l slightly inhibited agonist-induced contractions in the isolated guinea pig ileum and spontaneous rhythmic contractions in the isolated non-pregnant rat uterus. But loxiglumide had no effect on oxytocin-induced contraction in isolated non-pregnant rat uterus. 3. Cardio-respiratory system: Loxiglumide had no effect on heart rate and electrocardiogram in anesthetized dogs. But it slightly increased blood pressure and decreased the frequency of respirations at a dose of 30 mg/kg, i.v. Furthermore, loxiglumide slightly decreased femoral arterial blood flow at doses of more than 3 mg/kg, i.v. On the other hand, it had no effect on contractile force or contraction rate in the isolated guinea pig atrium and resting tension in the isolated rabbit aorta. 4. Gastrointestinal system: Loxiglumide increased bile secretion at doses of 10 and 30 mg/kg, i.v. in anesthetized rats and at doses of 3, 10 and 30 mg/kg, i.v. in anesthetized dogs. However, total bile acid output was not affected by loxiglumide. On the other hand, loxiglumide had no effect on pancreatic secretion, gastric secretion and gastric emptying in rats and intestinal transport activity in mice. 5. Hematology: In vitro, in the case of samples without bovine serum albumin, at concentrations of more than 1.9 x 10(-3) mol/l loxiglumide showed hemolysis, while in the case of samples with bovine serum albumin, at concentrations of more than 6.9 x 10(-3) mol/l loxiglumide showed hemolysis, and its maximal potency was weak compared to albumin-free conditions. On the other hand, in vivo, loxiglumide had no effect on hemolysis. In addition, it had no effect on platelet aggregation, prothrombin time and activated partial thromboplastin time. 6. Miscellaneous pharmacological actions: Loxiglumide had no effect on local anesthetic activity in guinea pigs and renal function in mice. These results suggest that loxiglumide seems to produce no serious side effects on the central nervous system, autonomic nervous system, cardio-respiratory system, gastrointestinal system, hematological and miscellaneous systems at pharmacologically effective doses.

Animals↗

Preparation of DNA-peptide conjugate using oxime resin.

In order to prepare oligonucleotide-peptide conjugate molecules bearing additional functions, such as cellular membrane permeability, nuclease resistance, which are indispensable to antisense and triplex oligonucleotides for their practical use in vivo, it is found that application of oxime resin (Kaiser resin) to automated DNA synthesis and succeeding cleavage of DNA fragment bound to oxime resin by various nucleophiles, such as amines, alkoxides and protected peptides, give DNA conjugate molecules conventionally in moderate to good yields.

Amines↗

Computerized Image Analysis of Clustered Microcalcifications on Mammography: Morphome- tric Comparison between Mammography and Pathology.

The clusters of microcalcifications under 2 cm in greatest dimension were analyzed in terms of size and shape by an image processor with a computer after being magnified 33 times. The mean diameter of mammographic microcalcifications was 188 µ m in benign cases, 226µ m in cribriform or papillary type cancer cases, 213 µ m in intermediate type cancer cases, and 324µ m in comedo type cancer cases, showing significant differences among the groups. The size distribution of mammographic microcalcifications in the comedo type was characteristic, showing a second peak in distribution between 500 and 700µ m. The radiodensity of microcalcifications compared to the breast parenchyma, the caliber of breast ducts containing the malignant calcifications, and the unit volume of calcium deposits within the ductal lumens were greater in cancer cases. The size and shape of mammographic microcalcifications were considered to be related to a combination of the caliber of breast ducts, unit volume of calcium deposits within the ductal lumens, and the density of breast ducts containing calcium deposits. Duct calibers were generally larger in cases of cancer lesions than cases of benign lesions such as duct papillomatosis, thus calcium deposits and microcalcifications were greater in the cancer lesion. Uneven distrubution of size and form of microcalcifications over 250 µ m in size, and increased radiodensity of calcifications were useful parameters for differential diagnosis rather than the density of calcifications.

Journal Article↗

Formation of crossline as a fluorescent advanced glycation end product in vitro and in vivo.

Crossline is one of the major advanced glycation end products resulting the reaction mixture of free amino group(s) such as epsilon-one in lysine with D-glucose in vitro. To study crossline formation on proteins in vitro and in vivo, polyclonal antiserum to the crossline hapten was prepared. This antiserum reacted with bovine and human serum albumin that had been modified by prolonged incubation with glucose as well as with crossline itself. Antisera did not react with unmodified serum albumin or the other Maillard-related compounds. Crossline was formed in a time-dependent manner when a mixture of six different proteins was incubated with glucose at pH 7.2 or 9.0. Crossline levels could be measured in rat lens proteins and the levels increased with age. The crossline content of lens proteins in diabetic rats was more than two-fold higher than that of age-matched controls. Results of this study suggest that most proteins containing advanced glycation end products have crossline-like structures. Measurement of crossline-like structures in biological specimens may provide an index of aging and of the development of diabetic complications.

Animals↗

A panel of radiation hybrids defining the 7q31-q32 region of human chromosome 7.

Mouse A9 cells containing human chromosome 7 tagged with pSV2neo were irradiated with X-rays and fused to A9 cells to isolate G418-resistant clones. From these clones, we selected radiation hybrids that contained 10-40 Mb of human DNA apparently at a single site of their genome by FISH analysis using human repetitive sequences as a probe. Then we made a panel of hybrids that contained various fragments of the 7q31-q32 region and cover its entire region altogether by PCR with STS markers of human chromosome 7. This panel is useful in chromosome transfer experiments since the dominant selective marker neo gene is attached to human DNA.

Animals↗

A proteinase inhibitor from egg yolk of hen is an ovoinhibitor analog.

A proteinase inhibitor, tentatively termed vitelloinhibitor, was purified from yolk of hen's ovarian follicles. It resembled egg-white ovoinhibitor not only in inhibitory spectrum (active for bovine trypsin and bovine chymotrypsin) but also in thermal stability, pH stability, antiserum reactivity and amino-acid composition. However, vitelloinhibitor had different molecular weight from that of ovoinhibitor. An alpha 2-proteinase inhibitor preparation, isolated from laying hen's serum in the present study, was found to exhibit two bands, and the larger one of the latter corresponded to vitelloinhibitor in molecular weight. The partial N-terminal amino-acid sequence of vitelloinhibitor was the same as those of the two components of serum inhibitor and all three agreed with that of ovoinhibitor. Vitelloinhibitor is likely to be an ovoinhibitor analog derived from a serum precursor, which might be the larger component of alpha 2-proteinase inhibitor.

Amino Acid Sequence↗