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Biomedical subjects

T Kita

Publications and source records attributed to T Kita.

At least 109 records · Page 6Linked to original sources
PubMed2000

Transforming growth factor-beta(1) increases the expression of lectin-like oxidized low-density lipoprotein receptor-1.

Lectin-like oxidized low-density lipoprotein (Ox-LDL) receptor-1 (LOX-1) is a novel cell-surface receptor for Ox-LDL, which can be expressed by vascular endothelial cells, smooth muscle cells, and macrophages. On the other hand, transforming growth factor (TGF)-beta(1), which plays crucial roles in vascular remodeling and the pathogenesis of atherosclerosis, has been shown to inhibit expression of class A scavenger receptors and CD36 in macrophages. Here we provide the evidence that TGF-beta(1) (0.1-10 ng/mL) induces LOX-1 protein and mRNA expression in both bovine aortic endothelial cells and smooth muscle cells in a dose- and time-dependent fashion, probably at the transcriptional level. TGF-beta(1) also upregulates LOX-1 mRNA expression in murine peritoneal macrophages. Thus TGF-beta(1) can highly induce LOX-1 expression in vascular endothelial cells, smooth muscle cells, and macrophages, suggesting that TGF-beta(1) appears one of the key regulators that modulates expression of scavenger receptors.

Animals↗
PubMed2000

Clinical characteristics of clear cell carcinoma of the ovary: a distinct histologic type with poor prognosis and resistance to platinum-based chemotherapy.

BACKGROUND: A retrospective review of treatment results comparing women with clear cell carcinoma of the ovary (CCC) with a group with serous adenocarcinoma of the ovary (SAC) was conducted. METHODS: Between 1988-1998, 662 patients with epithelial ovarian carcinoma were identified through the medical records department and the tumor registry at 4 institutions. After the central pathologic review, 101 patients with pure or dominant (>/= 90%) CCC (15.3%) were entered into the current study. Two hundred thirty five patients with pure SAC were selected as a group for comparison. All patients underwent staging laparotomy followed by platinum-based chemotherapy. Distribution of the International Federation of Gynecology and Obstetrics (FIGO) disease stage, response to chemotherapy, and prognosis for patients with CCC were compared with the same values in patients with SAC. RESULTS: Patients with CCC were significantly more likely to have FIGO Stage I disease than were patients with SAC (48.5% vs. 16.6%). A high recurrence rate was noted in those patients with Stage IC CCC (37%). In those patients with Stage IC disease, the survival rates for patients with CCC were lower than those for patients with SAC. The 3-year and 5-year survival rates for Stage III CCC patients were significantly lower compared with Stage III SAC patients. The response rate to platinum-based chemotherapy in patients with CCC was significantly lower than that in patients with SAC. CONCLUSIONS: CCC is an intriguing histologic type of epithelial ovarian cancer that demonstrates a clinical behavior distinctly different from that of SAC.

Adenocarcinoma, Clear Cell↗
PubMed2000

Biosynthesis and post-translational processing of lectin-like oxidized low density lipoprotein receptor-1 (LOX-1). N-linked glycosylation affects cell-surface expression and ligand binding.

LOX-1 (lectin-like oxidized low density lipoprotein receptor-1) is a type II membrane protein belonging to the C-type lectin family that can act as a cell-surface receptor for atherogenic oxidized low density lipoprotein (Ox-LDL) and may play crucial roles in atherogenesis. In this study, we show, by pulse-chase labeling and glycosidase digestion, that LOX-1 is synthesized as a 40-kDa precursor protein with N-linked high mannose carbohydrate chains (pre-LOX-1), which is subsequently further glycosylated and processed into the 48-kDa mature form within 40 min. Furthermore, when treated with an N-glycosylation inhibitor, tunicamycin, both tumor necrosis factor-alpha-activated bovine aortic endothelial cells and CHO-K1 cells stably expressing bovine LOX-1 (BLOX-1-CHO) exclusively produced a 32-kDa deglycosylated form of LOX-1. Cell enzyme-linked immunosorbent assay, flow cytometry, and immunofluorescence confocal microscopy demonstrated that the deglycosylated form of LOX-1 is not efficiently transported to the cell surface, but is retained in the endoplasmic reticulum or Golgi apparatus in tumor necrosis factor-alpha-activated bovine aortic endothelial cells, but not in BLOX-1-CHO cells. Radiolabeled Ox-LDL binding studies revealed that the deglycosylated form of LOX-1 expressed on the cell surface of BLOX-1-CHO cells has a reduced affinity for Ox-LDL binding. Taken together, N-linked glycosylation appears to play key roles in the cell-surface expression and ligand binding of LOX-1.

Amidohydrolases↗
PubMed2000

The effect of endothelin-1 on lipopolysaccharide-induced cyclooxygenase 2 expression in association with prostaglandin E(2).

We demonstrated previously that endothelin-1 (10(-14) to 10(-8) M) promotes lipopolysaccharide-induced cyclooxygenase 2 expression and prostaglandin E(2) production through endothelin ET(B) receptors effects which are up-regulated by lipopolysaccharide. In the present study, we confirmed these findings and showed that prostaglandin E(2) (10(-6) to 10(-5) M) inhibited the lipopolysaccharide plus endothelin-1-induced cyclooxygenase 2 expression more profoundly as compared to its inhibition of the lipopolysaccharide-induced cyclooxygenase 2 expression. The endothelin ET(B) receptor selective antagonist, N-cis-2, 6-dimethylpiperidino-carbonyl-L-gamma-methyl-leucyl-D-L-methoxy carbon yl-tryptophanyl-D-norleucine (BQ788), partly inhibited this suppression. Interestingly, the expression of endothelin ET(B) receptors in macrophages was increased by lipopolysaccharide plus prostaglandin E(2) (10(-8) to 10(-5) M) about 1.6-fold compared with that evoked by lipopolysaccharide stimulation alone. We also showed that treatment with endothelin-1 at 10(-14) M (15 min) elevated an intracellular cyclic AMP concentration in macrophages stimulated by lipopolysaccharide or lipopolysaccharide plus prostaglandin E(2) (10(-6) M) for 6 h, and the elevation in the latter cells was more pronounced. These results suggested that endothelin-1 shows an opposite modulation of lipopolysaccharide-induced cyclooxygenase 2 expression in macrophages through endothelin ET(B) receptors, depending on the level of extracellular prostaglandin E(2), and the changes of intracellular cyclic AMP by endothelin-1 may be involved in this mechanism.

Animals↗
PubMed2000

Methamphetamine-induced striatal dopamine neurotoxicity and cyclooxygenase-2 protein expression in BALB/c mice.

The expression of cyclooxygenase-2 (COX-2) and striatal dopamine (DA) depletion in BALB/cAnNcrj (BALB/c) mice following a neurotoxic dose of methamphetamine (METH) was investigated. METH-treatment (4 mg/kg x 4, 2 h intervals, s.c.) induced a significant hyperthermia and a persistent depletion of striatal DA levels 72 h after the treatment. COX-2, a marker of the cytotoxic effect of inflammation and oxidative stress and thiobarbituric acid (TBA) were significantly induced in the striatum 72 h after the METH-treatment, but not in the hippocampus. These results suggest that COX-2 may participate in METH-induced neurotoxicity in striatum.

Animals↗
PubMed2000

A Cu(II)-mediated C-H oxygenation of sterically hindered tripyridine ligands to form triangular Cu(II)3 complexes.

Two sterically hindered tris-pyridyl methane ligands, tris(6-methyl-2-pyridyl)methane (L1) and bis(6-methyl-2-pyridyl)pyridylmethane (L2), are newly synthesized. Under aerobic conditions, Ln (n = 1 or 2) reacts with CuX2 (X = Cl or Br), oxygenated at the methine position to LnOH or LnOMe. The former alcoholate ligand creates trinuclear Cu(II) complexes [Cu3(X)(LnO)3](PF6)2 [(X, n) = (Br, 1) 1, (C1, 1) 2, (Br, 2) 3, or (C1, 2) 4] in which the alkoxide oxygen atoms bridge copper centers. The crystal structures of 1-4 are presented along with their magnetic susceptibility data. The weak antiferromagnetic coupling between the Cu(II) centers in this trinuclear arrangement is due to weak interaction of the magnetic orbitals (dz2) which are oriented along three alternate sides in a hexagon of the Cu3O3 core in 1-4. Under anaerobic conditions, L1 reacts with CuBr2 to form a square pyramidal complex [CuL1Br2] (9) with the ligand facially capping. [Cu(Br)2(L1OMe)] (10) was obtained after the suspension of 9 in MeOH was stirred under air for 48 h. In the presence of cyclohexene, 9 is converted to [Cu(Br)(L1)]m (m = 1 or 2) 5 quantitatively to give trans- 1,2-dibromocyclohexane, indicating that Br2 is generated during the reaction. The FAB MS spectrum of [18O]-1 prepared by the reaction of L1 with CuBr2 under 18O2 shows that the ligand of [18O]-1 is L1(18O-.) L1(18OH), L1OCD3, and bis(6-methyl-2-pyridyl) ketone were obtained from reaction of L1 with CuBr2 in CD3OD under 18O2. These results indicate that the origins of the O atom in L1OH and L1OMe are O2 and MeOH, respectively. On the basis of these results, a mechanism of the oxygenation of L1 in the present system will be proposed.

Journal Article↗
PubMed2000

A novel snail-related transcription factor Smuc regulates basic helix-loop-helix transcription factor activities via specific E-box motifs.

Snail family proteins are zinc finger transcriptional regulators first identified in Drosophila which play critical roles in cell fate determination. We identified a novel Snail -related gene from murine skeletalmusclecells designated Smuc. Northern blot analysis showed that Smuc was highly expressed in skeletal muscle and thymus. Smuc contains five putative DNA-binding zinc finger domains in its C-terminal half. In electrophoretic mobility shift assays, recombinant zinc finger domains of Smuc specifically bound to CAGGTG and CACCTG E-box motifs (CANNTG). Because basic helix-loop-helix transcription factors (bHLH) bind to the same E-box sequences, we examined whether Smuc competes with the myogenic bHLH factor MyoD for DNA binding. Smuc inhibited the binding of a MyoD-E12 complex to the CACCTG E-box sequence in a dose-dependent manner and suppressed the transcriptional activity of MyoD-E12. When heterologously targeted to the thymidine kinase promoter as fusion proteins with the GAL4 DNA-binding domain, the non-zinc finger domain of Smuc acted as a transcriptional repressor. Furthermore, overexpression of Smuc in myoblasts repressed transactivation of muscle differentiation marker Troponin T. Thus, Smuc might regulate bHLH transcription factors by zinc finger domains competing for E-box binding, and non-zinc finger repressor domains might also confer transcriptional repression to control differentiation processes.

Amino Acid Sequence↗
PubMed2000

Midazolam premedication reduces propofol requirements for sedation during regional anesthesia.

PURPOSE: Propofol is often used for sedation during spinal anesthesia. We investigated the effects of midazolam premedication on the propofol requirements and incidence of complications during sedation. METHODS: In a prospective randomized, controlled, and single-blinded study, 50 patients undergoing elective gynecological surgery were randomly divided into control and midazolam groups. Patients in the midazolam group received 2 mg midazolam im 30 min before arrival at the operation room. After spinal anesthesia was instituted with intrathecal injection of hyperbaric tetracaine, we provided sedation using continuous infusion of propofol. The level of sedation was controlled at a level between "eyes closed but rousable to command" and "eyes closed but rousable to mild physical stimulation" by adjusting the infusion rate. During sedation, the propofol requirements and complications were recorded and patients were asked, two hours after the end of operation, whether they remembered intraoperative events. RESULTS: In the midazolam group, the loading dose, steady state infusion rate, and overall infusion rate of propofol were 0.74 mg x kg(-1), 2.86 mg x kg(-1) x hr(-1), and 3.32 mg x kg(-1) x hr(-1), respectively, which were about 17% lower than those in the control group (P<0.05). Moreover, midazolam premedication reduced the incidence of intraoperative memory (P < 0.05), but had no effects on other complications. CONCLUSION: Midazolam premedication reduced propofol requirements and the incidence of intraoperative memory during sedation. These effects on sedation using propofol during spinal anesthesia are considered beneficial for patients.

Adult↗
PubMed2000

The role of tumor necrosis factor-alpha in diffuse axonal injury following fluid-percussive brain injury in rats.

The immunolocalization of tumor necrosis factor-alpha (TNF alpha) after diffuse axonal injury (DAI) is demonstrated using a midline fluid percussion rat model (moderate brain injury of 1000 mm Hg was generated) and the effects of TNF alpha on the axolemmal permeability using horseradish peroxidase as a tracer. In addition, the accumulation of beta-amyloid precursor protein (beta-APP) was investigated, which has recently been shown to be a reliable marker for the diagnosis of DAI in cases with fatal head injury. TNF alpha levels in brain tissues from the impact site and the cortex including the corpus callosum, gradually increased during the first 1 h, rose to a maximal elevation at 3 h, gradually decreased at 6 h and decreased further at 24 h. Horseradish peroxidase (HRP) tracer experiments revealed that primary axonal damage appeared as early as 15 min after impact but rapidly recovered and that 1 h after impact, secondary axonal damage occurred in the corpus callosum and the brain stem. By immunoelectron microscopy it was seen that beta-APP accumulated in the axon from 1 h after impact demonstrating that there was functional axonal damage. TNF alpha reactions were detected in the lysosomes of microglia 30 min after impact and 1 h after impact these reactions were mainly detected in the glial cells (such as microglia, astrocytes and oligodendrocytes) in the corpus callosum and the brain stem. It is generally accepted that TNF alpha directly induces primary demyelination and oligodendrocyte apoptosis. Therefore, TNF alpha conveyed from the microglial cells is one cofactor contributing to the formation of the delayed axonal damage observed at these sites. The present study suggests that TNF alpha conveyed from the glial cells may contribute to the pathogenic mechanism of DAI formation following fluid percussive brain injury.

Amyloid beta-Protein Precursor↗
PubMed2000

Induction and maintenance of immune effector cells in the gastric tissue of mice orally immunized to Helicobacter pylori requires salivary glands.

BACKGROUND & AIMS: Helicobactor pylori mostly colonizes the gastric mucus that contains salivary antibodies. We studied the role of saliva in the induction and maintenance of gastric immunity conferred by oral vaccination against H. pylori. METHODS: C57BL/6 mice underwent a sialoadenectomy before and after intragastric immunization using whole-cell sonicates of H. pylori and cholera toxin as an adjuvant. At 1 and 6 months after oral inoculation, we assessed the density of the H. pylori colonizing the stomach, specific antibodies in gastric secretion and sera, and the constituents of cellular infiltrates in the tissue. RESULTS: A sialoadenectomy before, but not after, immunization abrogated protection by the vaccination at 1 month after inoculation. Protected mice had more neutrophils, plasma cells, and lymphocytes, but fewer eosinophils, in the gastric tissue than nonprotected mice. Protected mice had a greater increase of immunoglobulin (Ig) G1 specific to H. pylori than IgG2a in sera. At 6 months after inoculation, oral immunization was less effective in mice who had a sialoadenectomy than in control immunized mice. The antibody titers in both gastric secretion and in sera did not correlate with the density of bacteria colonizing the stomach. CONCLUSIONS: It is suggested that, in intragastric immunization against H. pylori, saliva is necessary for both the induction and maintenance of optimal immunity in the stomach. Effective immunity was associated with an increased number of neutrophils and lymphocytes in gastric tissue.

Administration, Oral↗
PubMed2000

Overexpression of low density lipoprotein receptor eliminates apolipoprotein B100-containing lipoproteins from circulation and markedly prevents early atherogenesis in apolipoprotein E-deficient mice.

Apolipoprotein E (ApoE) plays a pivotal role in the metabolism of apolipoprotein B (apoB)-containing lipoproteins. The defective apoE gene in humans can cause elevated plasma levels of apoB-containing lipoproteins such as chylomicron remnant and intermediate density lipoprotein (IDL). In this study, we examined whether liver-selective high-level expression of low-density lipoprotein receptor (LDLR) could affect the lipoprotein profile and atherogenesis in apoE-deficient (apoE-/-) mice. ApoE knockout mice expressing LDLR transgene in liver [apoE-/-;Tg(LDLR+/-)] were prepared after mating apoE-/- mice with the human LDLR transgenic mice. The apoE-/-;Tg(LDLR+/-) and littermate apoE-/- mice were fed a normal diet and sacrificed at 18 weeks of age. (1) The plasma levels of cholesterol and triglyceride in apoE-/-;Tg(LDLR+/-) mice were 51 and 33% lower than those of apoE-/- mice, respectively. (2) In the plasma of apoE-/-;Tg(LDLR+/-) mice, the levels of apoB-containing lipoprotein were reduced and apoB100-containg particles were totally eliminated. (3) By histochemical analysis, apoE-/-;Tg(LDLR+/-) mice showed drastic suppression of early atherogenesis; the lesion area of these mice was 1/70 of that in the littermate apoE-/- mice. These results indicate that, even in apoE-defective subjects, induction of hepatic LDLR expression could protect from early atherogenesis.

Animals↗
PubMed2000

Regulatory factors of medical care expenditures for older people in Japan--analysis based on secondary medical care areas in Hokkaido.

For the purpose of clarifying determinants of medical care expenditure for older people in Japan, we analyzed the data on medical care expenditure for older people in 21 secondary medical care areas in Hokkaido, the second largest island of Japan. The annual amount of medical expenditure per insured older person can be reduced into three components: annual number of medical care bills per insured older person days of hospitalization or visits per medical care bill and amount of medical expenditure per day and per insured older person. The 21 secondary medical care areas in Hokkaido showed large differences in per capita amount of both inpatient and outpatient medical expenditures for older people. Per capita inpatient medical expenditure for men and women correlated positively with the days of hospitalization per bill and the per capita number of inpatient medical care bills per year, but inversely with the per capita amount of expenditure per day of hospitalization. The same held true for outpatient medical expenditure for men, but for women outpatient medical expenditure correlated positively with all three components. Multiple regression analysis indicated the more powerful effects of medical care demand or supply on inpatient medical expenditure, on the other hand, not much powerful effects of every index were indicated on outpatient medical expenditure.

Aged↗
PubMed2000

Methamphetamine-induced striatal dopamine release, behavior changes and neurotoxicity in BALB/c mice.

The behaviors associated with the neurotoxic effects of methamphetamine were evaluated in BALB/c mice. Hyperthermia and behavioral observations were measured 60 min after each subcutaneous injection of methamphetamine (4x4 or 8 mg/kg) or saline, each given 2 h apart. The behavioral observations included stereotyped behaviors, incidence of hemorrhage in breast, salivation and self-injurious behavior (SIB). Repeated administration of methamphetamine produced these behavioral changes and hyperthermia, but resulted in hypothermia by the final injection (8 mg/kg). In addition, the methamphetamine treatment induced a long-lasting dopamine depletion of similar magnitude in the 4 and 8 mg/kg-treated animals. In a time course study striatal monoamine levels were measured 60 min after each injection of these doses. The first and second injections of methamphetamine (8 mg/kg) produced a drastic increase in striatal 3-methoxytyramine; this failed to occur after the third or fourth injection of the same dose. In contrast, 4 mg/kg of methamphetamine also produced an increase in 3-methoxytyramine after the second and third injections of the drug and, in this case, these were maintained for the duration of the treatment. Striatal 3, 4-dihydroxyphenylacetic acid levels also drastically decreased following both doses of methamphetamine, suggesting inhibition of monoamine oxidase in striatum. Moreover, a single injection of methamphetamine increased striatal 2,3-dihydroxybenzoic acid formation. These results suggest that the incidence of hyperthermia, SIB and striatal dopamine neurotoxicity are closely linked to striatal dopamine release and inhibition of monoamine oxidase produced by methamphetamine in BALB/c mice.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2000

Altered Th1/Th2 commitment in human CD4+ T cells with ageing.

The human immune system undergoes continuous remodelling with the advancement of age. Since age-associated functional alterations in the immune system could be caused by a possible change in helper T cell regulation in elderly subjects, we comparatively studied the function of CD4+ T cells in peripheral blood obtained from both young and old healthy volunteers. Upon cell activation by phorbol myristate acetate and ionomycin, the proportion of CD4+ T cells containing interferon-gamma (IFN-gamma) was found to be greater in the old subjects. Utilizing a co-culture system, which activated CD4+ T cells via the TCR/CD3 complex and CD28, we found that CD4+ T cells from the old subjects secreted more IFN-gamma and IL-2, but less IL-4, than those from the young subjects. Upon cell activation by co-culture, CD4+ T cells from the old subjects expressed more CD26, CD40L, and LFA-1, but less CD30, than those from the young. These results together suggest that the microenvironment in which CD4+ T cells develop in older people may cause production of more cells committed to Th1 than that in younger subjects.

Adolescent↗
PubMed2000

Flow cytometry for the detection of enterohaemorrhagic Escherichia coli O157:H7 with latex beads sensitized with specific antibody.

To detect low concentrations of enterohaemorrhagic Escherichia coli O157:H7 rapidly, flow cytometry (FCM) was carried out with specific IgG-sensitized latex beads (IgG-Lx). It was found that test samples for FCM can be prepared for much shorter periods by culturing E. coli O157:H7 in trypto-soya broth at 42 degrees C and by treatment with 0.5% formalin at 37 degrees C. FCM with IgG-Lx performed with E. coli O157:H7 prepared by such a procedure revealed that the lowest number of E. coli O157:H7 prepared in pure culture detected by FCM was 10(3)/ml. Because similar findings have already been reported by FCM with immunomagnetic beads, FCM with IgG-Lx is also suggested to be a valuable technique to detect low numbers of E. coli O157:H7 rapidly in food stuffs.

Animals↗
PubMed2000

Chondrosarcomatous differentiation in metastatic deposit of serous papillary cystadenocarcinoma.

A rare case of serous papillary cystadenocarcinoma of the ovary showing chondrosarcomatous differentiation in a metastatic deposit late in the clinical course is reported. A 49-year-old female underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy for bilateral ovarian tumors. Histological diagnosis was serous papillary cystadenocarcinoma of both ovaries with lymph node metastasis. After six courses of chemotherapy, she was confirmed to be in complete remission following a second laparotomy. Following additional chemotherapy, a third laparotomy disclosed swollen left inguinal lymph nodes. In one of these nodes, approximately 5.0 cm in greatest diameter, the predominant histological features were: chondrosarcoma of the bone and soft tissue, with small foci of serous papillary adenocarcinoma and squamous epithelium. A histological transition between mesenchymal and epithelial areas was identified. Immunohistochemical positivity for broad-spectrum cytokeratin (AE1/AE3), vimentin, epithelial membrane antigen, and S-100 protein was observed in both chondrosarcomatous and epithelial areas. The current evidence may suggest that the chondrosarcomatous differentiation was derived from the metastatic epithelial component.

Cell Differentiation↗
PubMed2000

Magnetically suspended rotary blood pump with radial type combined motor-bearing.

A magnetically suspended centrifugal blood pump is being developed with a combined motor-bearing for long-term ventricular assist systems. The combined motor-bearing actively suspends a rotor in a radial direction to deal with radial force unbalance in the pump and rotates the rotor by using the electric magnetic field. Therefore, the pump has no mechanical parts such as bearings of the motor and has a long lifetime. The developed pump consists of a thin rotor with a semi open-type 6 vane impeller and a stator to suspend and rotate the rotor. The rotor has 4-pole permanent magnets on the circumferential surface. The outer diameter and the thickness of the rotor are 60 mm and 8 mm, respectively. Axial movement and tilt of the rotor are restricted by passive stability based on the thin rotor structure. Radial movements of the rotor, such as levitation in radial direction and rotation, are controlled actively by using electric magnets of the stator. The electric magnet coils to produce levitation and rotation forces are constructed on the periphery stator. The p +/- 2-pole algorithm and the synchronous motor mechanism are adopted to levitate and rotate the rotor. The radial gap between the rotor and the stator is 1 mm. A closed-loop circuit filled with water was connected to the developed pump to examine the basic performance of the pump and the magnetic suspension system. Maximum rotational speed, flow rate, and head were 2,800 rpm, 11 L/min, and 270 mm Hg, respectively. The rotor with the impeller could be suspended completely during the entire pumping process. We conclude the pump with the combined motor-bearing has sufficient performance for the blood pump.

Centrifugation↗