Biomedical subjects

M Makino

Publications and source records attributed to M Makino.

At least 37 records · Page 2Linked to original sources

PubMed2001

A comparative study of characteristics of current-type and conventional-type cationic bactericides.

We have synthesized new polycationic bactericides, polyloxyethylene(dimethyliminio)trimethylene(dimethyliminio)ethylene dichloridel (OXD) and poly(hexamethyleneguanidine phosphate) (HEP), in order to develop more active but less skin-irritative bactericides. The effects of these bactericides on Pseudomonas aeruginosa, Escherichia coli, Serratia marcescens, Klebsiella pneumoniae, methicillin resistant Staphylococcus aureus (MRSA) and the degree of their irritations on skin were compared with those of a widely used low molecular-weight cationic bactericide, benzalkonium chloride (BAC), and a polycationic bactericide, poly[2-hydroxyethylene(dimethyliminio)methylene chloride] (2HYC). The minimum bactericidal concentration (MBC) of OXD for 10 min contact incubation was 16 microg/ml against P. aeruginosa, E. coli, S. marcescens and K. pneumoniae, and >1000 microg/ml against MRSA. The MBC of HEP for 10 min contact incubation was 16 microg/ml against P. aeruginosa, 32 microg/ml against E. coli and K. pneumoniae, and 64 microg/ml against S. marcescens and MRSA. Itch, edema, erythema, heat, injury, desquamation and keratinization caused by skin irritation were examined in 21 subjects by patch tests. Only one subject treated with OXD experienced edema, and one subject with HEP experienced keratinization. However, BAC caused itch in 3 subjects, edema in 1, erythema in 10 and desquamation in 2, indicating that the incidence of skin irritation of BAC was higher than that of OXD or HEP. OXD and HEP had sterilization ability similar to BAC, however, they were less skin-irritative than BAC. This indicates that OXD and HEP can be used as safe bactericides.

Adult↗

PubMed2001

Studies on the constituents of the leaves of Morus alba L.

Two novel prenylflavanes (1, 2) and a glycoside (3) of 1 were isolated along with six known compounds, isoquercitrin (4), astragalin (5), scopolin (6), skimmin (7), roseoside II (8) and benzyl D-glucopyranoside (9), from the leaves of Morus alba. The inhibitory activities of compounds 1, 2 and 3 on the oxidation of human low density lipoprotein (LDL) were investigated.

Antioxidants↗

PubMed2001

Effect of eicosapentaenoic acid ethyl ester on hypothyroid function.

Thyroid hormones affect reactions in almost all pathways of lipid metabolism. It has been reported that plasma free fatty acid (FFA) concentration in hypothyroidism is generally within the normal range. In this study, however, we show that plasma FFA concentration in some hypothyroid patients is higher than the normal range. Symptoms of thyroid dysfunction in these individuals were less severe than those of patients with lower plasma FFA concentrations. From these findings we hypothesized that the change in FFA concentration must correlate with thyroid function. Using an animal model, we then examined the effect of highly purified eicosapentaenoic acid ethyl ester (EPA-E), a n-3 polyunsaturated fatty acid derived from fish oil, on thyroid function in 1-methyl-2-imidazolethiol (MMI)-induced hypothyroid rats. Oral administration of EPA-E inhibited reduction of thyroid hormone levels and the change of thyroid follicles in MMI-induced hypothyroid rats. These findings suggest that FFA may affect thyroid functions and EPA-E may prevent MMI-induced hypothyroidism.

Animals↗

PubMed2001

IL-12 and IL-18 synergistically induce the bactericidal activity of murine peritoneal cells against M. leprae.

We examined the effect of IL-12 and IL-18 on bactericidal activities of mouse peritoneal cell (PC) against Mycobacterium leprae (M. leprae). We demonstrated that IL-12 and IL-18 synergistically induced the NO-dependent bactericidal activity of PC by stimulating Natural Killer (NK) cells and T-cells through IFN-gamma production. IL-12 and IL-18 induced host cell death through NK-cells and T-cells. Therefore. IL-12 and IL-18 play an important role on direct killing of intracellular M. leprae and on indirect killing of them through inducing host cell death.

Animals↗

PubMed2001

Impaired IL-15 production associated with susceptibility of murine AIDS to mycobacterial infection.

LP-BM5 murine leukemia virus (MuLV) injection causes murine AIDS (MAIDS), a disease characterized by many functional abnormalities of immunocompetent cells. We show that MAIDS mice are susceptible to Mycobacterium bovis Bacille Calmette-Guérin (BCG) infection as assessed by survival rate and bacterial counts. The peritoneal exudate macrophages from MAIDS mice produced a significant level of interleukin (IL)-12 soon after inoculation with BCG, whereas IL-15 and tumor necrosis factor (TNF) production were severely impaired in BCG-infected MAIDS mice. The appearance of natural killer (NK) and CD4+ T helper type 1 (Th1) cells specific for mycobacterial antigen were depressed in MAIDS mice after BCG infection. Thus, it appeared that impaired production of IL-15, besides other inflammatory cytokines, in MAIDS mice may be involved in the poor responses of the NK and Th1 cells, resulting in an increased susceptibility to BCG.

Animals↗

PubMed2001

[Evaluation of efficiency of a multi-crystal scintillation camera Digirad 2020tc Imager using a solid-state detectors].

Digirad 2020tc Imager is the movable scintillation camera, consisting of combining multi-crystal scintillators (CsI(Tl)) and photo-diodes. Total numbers of element are 4096, which are further divided into 16 x 16 modules. Each module contains 4 x 4 elements. We have examined Digirad 2020tc according to NEMA (National Electrical Manufactures Association), and the following results are obtained; the maximum count rate; 221 kcps, total system uniformity; 1.3% (integral uniformity), 0.9% (differential uniformity), system spatial resolution; 6.97 +/- 0.72 mm (the LEHR collimator to 99mTc source at 10 cm), intrinsic energy resolution; 12.8%, total system sensitivity; 3270.8 cpm/MBq (with LEHR collimator using 99mTc source at 10 cm). Further more, we determined the contrast of an imaging using the pin-hole (100 microns phi) 99mTc source in order to know the signal per noise (S/N) ratio among the pixels (S/N; 93.4 +/- 46.2 (first pixels)). Although the physical dimension of the camera has a smaller field of view, comparing with the standard camera, Digirad 2020tc has the equivalent characteristics as well as that of the standard camera and its field view is enough to measure the adult lung perfusion using a diverging collimator. We will further examine Digirad 2020tc with its movable portability and expect applications in nuclear medicine.

Gamma Cameras↗

PubMed2000

Prognostic significance of reverse transcriptase-polymerase chain reaction measurement of carcinoembryonic antigen mRNA levels in tumor drainage blood and peripheral blood of patients with colorectal carcinoma.

BACKGROUND: The objective of this study was to assess the prognostic value of detecting circulating tumor cells in the tumor drainage blood and peripheral blood of patients with colorectal carcinoma. METHODS: A total of 53 patients with advanced colorectal carcinoma were studied. Tumor drainage blood and peripheral blood samples that were obtained during surgery were examined for carcinoembryonic antigen (CEA) mRNA using reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: In spiking experiments, the assay indicated a sensitivity limit of 1 carcinoma cell per 10(6) cells. CEA mRNA was detected in the tumor drainage blood of 36 of 53 patients (68%) and in the peripheral blood of 18 of 53 patients (34%). The rate of detection in both tumor drainage blood and peripheral blood was significantly higher in patients with lymph node metastasis, lymphatic invasion, or vascular invasion (P < 0.05). Among those patients who underwent potentially curative resection, the 2-year disease free survival rate of patients whose tumor drainage or peripheral blood was negative for CEA mRNA was significantly better than that of patients who showed CEA mRNA positivity of either sample (tumor drainage blood: 100% vs. 57%; P < 0.05; peripheral blood: 74% vs. 50%; P < 0.01), although the follow-up thus far has been only 9-30 months. CONCLUSIONS: The presence of CEA mRNA in the blood is a useful indicator of circulating tumor cells, and it is one of the determinant prognostic factors for patients with colorectal carcinoma. Moreover, the absence of CEA mRNA in tumor drainage blood was found to be a superior marker for disease free survival compared with that in peripheral blood.

Adult↗

PubMed2000

Production of functionally deficient dendritic cells from HTLV-I-infected monocytes: implications for the dendritic cell defect in adult T cell leukemia.

Adult T cell leukemia (ATL) is induced by an infection with human T lymphotropic virus type I (HTLV-I) and is accompanied by immunodeficiency. Monocyte-derived immature dendritic cells (DCs) donated by 11 ATL patients were suppressed in the ability to take up fluorescein isothiocyanate (FITC)-dextran and were down-regulated in the expression of CD1a and CD86 antigens (Ags). Monocytes from the patients showed impaired expression of CD14 and HLA-DR Ags. These results suggest intrinsic abnormalities of monocytes and a defect of DC maturation in ATL patients. Therefore, we examined the influence of HTLV-I infection of monocytes on their differentiation to DCs. Monocytes obtained from healthy donors were susceptible to HTLV-I infection in vitro. HTLV-I-infected monocytes were down-regulated in the expression of CD14 Ags, and immature DCs obtained from them expressed CD1a poorly and were impaired in the ability to take up FITC-dextran. Mature DCs differentiated from these cells could not stimulate autologous CD4(+) T cell or CD8(+) T cell proliferation, even after being secondarily pulsed with HTLV-I at an immature DC stage. These results suggest that HTLV-I-infected monocytes cannot properly differentiate to DCs and that this might be one of the important mechanisms producing dysfunctional DCs in ATL patients.

Adult↗

PubMed2000

Identification of a major heparin and cell binding site in the LG4 module of the laminin alpha 5 chain.

The G domain of the laminin alpha chains consists of five homologous G modules (LG1-5) and has been implicated in various biological functions. In this study, we identified an active site for cell and heparin binding within the laminin alpha5 G domain using recombinant proteins and synthetic peptides. Recombinant LG4, LG5, and LG4-5 modules were generated using a mammalian expression system. The LG4 and LG4-5 modules were highly active for cell binding, whereas the LG5 module alone showed only weak binding. Heparin inhibited cell binding to the LG4-5 module, whereas no inhibition was observed with EDTA or antibodies against the integrin beta(1) subunit. These results suggest that the LG4-5 module interacts with a cell surface receptor containing heparan sulfate but not with integrins. Solid-phase assays and surface plasmon resonance measurements demonstrated strong binding of the LG4 and LG4-5 modules to heparin with K(D) values in the nanomolar range, whereas a 16-fold lower value was determined for the LG5 module. Treatment with glycosidases demonstrated that N-linked carbohydrates on the LG5 module are complex-type oligosaccharides. The LG4-5 module, devoid of N-linked carbohydrates, exhibited similar binding kinetics toward heparin. Furthermore, cell binding was unaffected by removal of N-linked glycosylation. To localize active sites on the LG4 module, various synthetic peptides were used to compete with binding of the tandem module to heparin and cells. Peptide F4 (AGQWHRVSVRWG) inhibited binding, whereas a scrambled peptide of F4 failed to compete binding. Alanine replacements demonstrated that one arginine residue within F4 was important for cell and heparin binding. Our results suggest a critical role of the LG4 module for heparan sulfate-containing receptor binding within the laminin alpha5 chain.

Amino Acid Sequence↗

PubMed2000

Human interferon-alpha induces immobility in the mouse forced swimming test: involvement of the opioid system.

In a previous study, we indicated that human interferon (IFN)-alpha (IFN-alpha, 6 x 10(4) IU/kg, i.v.), but not human IFN-beta or -gamma, prolonged the immobility time of the forced swimming test in mice. In this study, we investigated the mechanism of the effect of human IFN-alpha. None of the mouse IFNs tested (IFN-alpha/beta, IFN-beta, and IFN-gamma, 3 x 10(5) U/kg, i.v.) changed the immobility time or the spontaneous locomotor activity in mice. Indomethacin (10 mg/kg, s.c.), a cyclooxygenase inhibitor, did not affect the increase in the immobility time induced by human IFN-alpha (6 x 10(4) IU/kg, i.v.). However, naloxone (1 mg/kg, s.c.), an opioid receptor antagonist, blocked the increasing caused by human IFN-alpha in the forced swimming test. These results suggest that the increase in the immobility time caused by human IFN-alpha in the forced swimming test might be mediated through opioid receptors, but not mouse IFN receptors.

Animals↗

PubMed2000

Production of IL-10 and IL-12 in CD40 and interleukin 4-activated mononuclear cells from patients with Graves' disease.

We investigated the effect of T cell-dependent B cell activation on the production of IL-10 and IL-12 by peripheral blood mononuclear cells (PBMCs) obtained from patients with Graves' disease vs Hashimoto's thyroiditis, type 1 diabetes or normal controls. Incubation of PBMCs, from each of the subject groups, with a combination of anti-CD40 monoclonal antibodies and interleukin 4 (IL-4)-activated B cells, as shown by an increased level of soluble CD23. There was also a notable increase in the number of CD23(+)cells in PBMCs from patients with Graves' disease as compared to the other subject groups. This combination of B cell stimulants increased production of IL-10 in PBMCs obtained from patients with Graves' disease relative to those patients with Hashimoto's thyroiditis, type 1 diabetes, or the control subjects. The production of IL-12 showed wide variation that depended on the basal IL-12 level. In subjects with a low basal IL-12 level there was a positive correlation between the production of IL-12 and that of IL-10 from PBMCs stimulated with anti-CD40 antibodies plus IL-4. On the contrary, in the patients with a high basal IL-12 level, no change or a decrease of IL-12 production was observed after the stimulation. Thus, T cell-dependent B cell activation via a CD40 pathway triggers the overproduction of IL-10 and overcome the effect of IL-12 to shift the Th(1)/Th(2)balance to Th(2)dominance in patients with Graves' disease but not in Hashimoto's thyroiditis or type 1 diabetes.

Adult↗

PubMed2000

Human interferon-alpha increases immobility in the forced swimming test in rats.

OBJECTIVES: We examined the immobility of the forced swimming test induced in an animal model by human interferon (IFN), which has often been reported to induce depression in clinical use. METHODS: In the present study, we examined the effects of human IFNs on results of the forced swimming test in rats. RESULTS: Single intravenous (IV) administration of human IFN-alpha (6x10(4) IU/kg), but not of human IFN-beta or -gamma, significantly increased immobility time in the forced swimming test in rats. Repeated administration of human IFN-alpha (6x10(3) IU/kg) also significantly increased the immobility time. On the other hand, none of the rat IFNs (rat IFN-alpha, -beta and -gamma, 6x10(4) IU/kg, IV) changed the immobility time. Neither human IFNs nor rat IFNs changed the locomotor activity of rats. CONCLUSIONS: These findings suggest that human IFN-alpha has a greater potential for inducing increase of the immobility in the rat forced swimming test than human IFN-beta and -gamma, and that the effect of human IFN-alpha might not be mediated through IFN-alpha/beta receptors.

Animals↗

PubMed2000

Mitochondrial DNA mutations in Leigh syndrome and their phylogenetic implications.

Of 100 patients with the clinical diagnosis of Leigh syndrome, 21 were found to have specific enzyme defects: 15 involving cytochrome c oxidase (COX); 4, pyruvate dehydrogenase complex (PDHC); one, complex I (reduced nicotinamide adenine dinucleotide [NADH]-coenzyme Q reductase) and one, complex II (succinate-ubiquinone reductase) deficiencies. In addition to the most common form of COX deficiency, mtDNA mutations in the adenosine triphosphatase (ATPase) 6 coding region were also commonly seen. Eighteen patients (18%) had mtDNA mutations at nucleotide position (np) 8993 or 9176. The mutated DNAs were present in a heteroplasmic state, comprising more than 90% of the DNA in muscle and/or blood samples from all patients. Patients with the T-to-G mutation at np 8993 usually had early onset of the disease with rapid progression, showing the typical clinical features of Leigh syndrome. On the other hand, those with the T-to-C 8993 mutation showed a milder and more chronic course. Patients with the mutation at np 9176 showed variable courses. Phylogenetic analysis of mtDNA D-loop sequences for the patients with the ATPase 6 mutations and normal Japanese subjects revealed that a T-to-G/C mutation at np 8993 and a T-to-C mutation at np 9176 occurred many times independently in the Japanese population.

Adenosine Triphosphatases↗

PubMed2000

Effects of 15-month aldose reductase inhibition with fidarestat on the experimental diabetic neuropathy in rats.

We examined the effects of long-term treatment with an aldose reductase inhibitor (ARI) fidarestat on functional, morphological and metabolic changes in the peripheral nerve of 15-month diabetic rats induced by streptozotocin (STZ). Slowed F-wave, motor nerve and sensory nerve conduction velocities were corrected dose-dependently in fidarestat-treated diabetic rats. Morphometric analysis of myelinated fibers demonstrated that frequencies of abnormal fibers such as paranodal demyelination and axonal degeneration were reduced to the extent of normal levels by fidarestat-treatment. Axonal atrophy, distorted axon circularity and reduction of myelin sheath thickness were also inhibited. These effects were associated with normalization of increased levels of sorbitol and fructose and decreased level of myo-inositol in the peripheral nerve by fidarestat. Thus, the results demonstrated that long-term treatment with fidarestat substantially inhibited the functional and structural progression of diabetic neuropathy with inhibition of increased polyol pathway flux in diabetic rats.

Aldehyde Reductase↗

PubMed2000

Involvement of central opioid systems in human interferon-alpha induced immobility in the mouse forced swimming test.

1. We investigated the mechanism by which human interferon-alpha (IFN-alpha) increases the immobility time in a forced swimming test, an animal model of depression. 2. Central administration of IFN-alpha (0.05 - 50 IU per mouse, i.cist.) increased the immobility time in the forced swimming test in mice in a dose-dependent manner. 3. Neither IFN-beta nor -gamma possessed any effect under the same experimental conditions. 4. Pre-treatment with an opioid receptor antagonist, naloxone (1 mg kg(-1), s.c.) inhibited the prolonged immobility time induced by IFN-alpha (60 KIU kg(-1), i.v. or 50 IU per mouse. i.cist. ). 5. Peripheral administration of naloxone methiodide (1 mg kg(-1), s. c.), which does not pass the blood - brain barrier, failed to block the effect of IFN-alpha, while intracisternal administration of naloxone methiodide (1 nmol per mouse) completely blocked. 6. The effect of IFN-alpha was inhibited by a mu(1)-specific opioid receptor antagonist, naloxonazine (35 mg kg(-1), s.c.) and a mu(1)/mu(2) receptor antagonist, beta-FNA (40 mg kg(-1), s.c.). A selective delta-opioid receptor antagonist, naltrindole (3 mg kg(-1), s.c.) and a kappa-opioid receptor antagonist, nor-binaltorphimine (20 mg kg(-1), s.c.), both failed to inhibit the increasing effect of IFN-alpha. 7. These results suggest that the activator of the central opioid receptors of the mu(1)-subtype might be related to the prolonged immobility time of IFN-alpha, but delta and kappa-opioid receptors most likely are not involved.

Animals↗

PubMed2000

Vascularized metacarpal bone graft for scaphoid non-union and Kienböck's disease.

A new vascularized bone graft from the base of the second metacarpal was used to treat scaphoid non-union and Kienböck's disease. In two patients with scaphoid non-union, the procedure promoted healing, even when the proximal segment was poorly vascularized. In one patient with Kienböck's disease, the graft held stable and wrist pain was markedly reduced. Further clinical experience may establish this procedure as an option for carpal bone fractures or disease.

Adult↗

PubMed2000

Reduced E-cadherin expression and enlargement of cancer nuclei strongly correlate with hematogenic metastasis in colorectal adenocarcinoma.

BACKGROUND: Synchronous and metachronous hematogenic metastases are frequently detected in patients with colorectal carcinoma. Once these metastases have developed, the prognoses of patients are poor. Previously, we reported that enlargement of cancer nuclei significantly correlated with metastatic potential of gastric cancer and hepatocellular carcinoma. Moreover, recently it has been reported that reduced expression of E-cadherin is associated with tumor metastasis. To evaluate the correlation between nuclear area (NA) of cancer cells and expression of E-cadherin, and to elucidate whether these factors correlate with clinical outcome in patients with colorectal carcinoma, 105 consecutive patients were investigated. METHODS: In each case, the NAs of 600 cancer nuclei were analyzed by means of a computer-assisted image analysis system and E-cadherin expression was detected immunohistochemically by an anti-E-cadherin monoclonal antibody. The expression levels of E-cadherin were divided into three groups according to the percentages of E-cadherin-positive cells (level 0: positive cells < or = 50%, level 1: 50% < positive cells < or = 80%, level 2: positive cells > 80%). RESULTS: The mean NA of cancer cells in 105 tumors was 57 microm2. The NAs of cancer cells enlarged in proportion to the decrease of E-cadherin expression levels (level 0, n = 48, 62 microm2; level 1, n = 35, 57 microm2, level 2, n = 22, 46 microm2, P = 0.002). The 10-year survival rates decreased in proportion to the reduced E-cadherin expression levels (80% in level 2, 64% in level 1, and 42% in level 0, P = 0.004). Moreover, the 10-year survival rate of 54 patients with large NA tumors (< or = 54 microm2, 36%) was significantly poorer than that of 51 patients with small NA tumors (< 54 microm2, 80%, P < 0.001). The NA of cancer cells was recognized as an important predictor for prognosis and hematogenic metastasis. Although reduced E-cadherin expression was not recognized as the risk factor for hematogenic metastasis, 80% of patients who developed hematogenic metastasis had tumors with both enlarged cancer nuclei and reduced E-cadherin expression. CONCLUSIONS: Detection of NA of cancer cells and E-cadherin expression in patients with colorectal carcinoma may reveal important information for hematogenic metastasis.

Adenocarcinoma↗

PubMed2000

A novel bisnorditerpenelactone from Mikania hirsutissima.

A novel bisnorkaurenic acid-type diterpenelactone, named mikanialactone (1), was isolated along with five known kaurenic acid-type diterpenes (2-6) from the aerial parts of Mikania hirsutissima DC (Compositae). The structure of the new bisnorditerpene was determined by spectroscopic means.

Brazil↗