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Biomedical subjects

E Okada

Publications and source records attributed to E Okada.

At least 19 recordsLinked to original sources
PubMed1999

IL-15 expression plasmid enhances cell-mediated immunity induced by an HIV-1 DNA vaccine.

Cytokines are powerful regulators of the immune response. In this study, an HIV-1 envelope DNA vaccine and interleukin 15 (IL-15) expression plasmid were intranasally administered to mice. A significant increase in the HIV-1-specific DTH response and CTL activity, and decrease in the serum IgG/IgG2a ratio was observed in the group which received DNA vaccine and IL-15 expression plasmid compared to DNA vaccination alone. Restimulated immune lymphoid cells from mice which received both agents showed enhanced production of interferon-gamma (IFN-gamma) and reduced secretion of IL-4. However, administration of DNA vaccine with IL-15 and IL-2 or IL-12 expression plasmids did not alter the effect of IL-15 expression plasmid on the DNA vaccine. These results indicate that intranasal administration of DNA vaccine and IL-15 expression plasmid is capable of enhancing the T helper type 1 (Th1) dependent HIV-1-specific cell-mediated immunity, and that the IL-15 and IL-2 or IL-12 expression plasmids may not have a synergistic effect on the immune response induced by DNA vaccine in vivo.

Adjuvants, Immunologic↗
PubMed1999

Macrophage inflammatory protein-1alpha (MIP-1alpha) expression plasmid enhances DNA vaccine-induced immune response against HIV-1.

CD8+ cell-secreted CC-chemokines, MIP-1alpha, and MIP-beta have recently been identified as factors which suppress HIV. In this study we co-inoculated MIP-1alpha expression plasmid with a DNA vaccine constructed from HIV-1 pCMV160IIIB and pcREV, and evaluated the effect of the adjuvant on HIV-specific immune responses following intramuscular and intranasal immunization. The levels of both cytotoxic T lymphocyte (CTL) activity and DTH showed that HIV-specific cell-mediated immunity (CMI) was significantly enhanced by co-inoculation of the MIP-1alpha expression plasmid with the DNA vaccine compared with inoculation of the DNA vaccine alone. The HIV-specific serum IgG1/IgG2a ratio was significantly lowered when the plasmid was co-inoculated in both intramuscular and intranasal routes, suggesting a strong elicitation of the T helper (Th) 1-type response. When the MIP-1alpha expression plasmid was inoculated intramuscularly with the DNA vaccine, an infiltration of mononuclear cells was observed at the injection site. After intranasal administration, the level of mucosal secretory IgA antibody was markedly enhanced. These findings demonstrate that MIP-1alpha expression plasmid inoculated together with DNA vaccine acts as a strong adjuvant for eliciting Th1-derived immunity.

AIDS Vaccines↗
PubMed1999

Hyperhomocysteinemia is a risk factor for coronary arteriosclerosis in Japanese patients with type 2 diabetes.

OBJECTIVE: An increased plasma homocysteine level is an important risk factor for vascular disease, including coronary atherosclerosis, in the general population. However, the role of hyperhomocysteinemia in the development of coronary artery disease (CAD) in patients with type 2 diabetes is unknown. Therefore, we have endeavored to determine the relationship between plasma homocysteine levels and the presence of coronary arteriosclerosis in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: The study group consisted of 145 Japanese patients (95 men and 50 women) who underwent routine coronary angiography to assess chest pain or suspected CAD. Plasma total homocysteine level, lipid level, and parameters of fibrinolytic activity were measured. All patients were identified as diabetic or nondiabetic by the new American Diabetes Association (ADA) criteria. The diagnoses of all patients studied were confirmed by coronary angiography. The severity of coronary artery stenosis was quantified using CAD scoring on the basis of prior reports, and subjects were graded as nonstenotic, stenotic single-vessel, stenotic two-vessel, or stenotic three-vessel based on the number of stenotic coronary arteries. Patients were classified into two groups: those with stenotic vessels and those without stenotic vessels. RESULTS: The plasma homocysteine level was significantly higher in patients with than in patients without stenotic vessels (13.8 +/- 3.9 vs. 11.7 +/- 3.9 mumol/l, respectively; P = 0.0009). The number of stenotic coronary arteries, which was used to grade each case as nonstenotic, stenotic single-vessel, stenotic two-vessel, or stenotic three-vessel, was related only to the total homocysteine level in the diabetic (diabetes mellitus [DM]) group, but it was associated with lipoprotein(a) in the nondiabetic (non-diabetes mellitus [non-DM]) group. Spearman's rank correlation test demonstrated that the plasma homocysteine level was strongly correlated with CAD score, both in the entire study group and in the DM group (P = 0.003 for the entire group and P = 0.011 for the DM group). Hyperhomocysteinemia, which was defined as total homocysteine level > 14.0 mumol/l, was seen in 57 (39.3%) of the patients. The CAD score was highest in diabetic patients with hyperhomocysteinemia (P < 0.05). CONCLUSIONS: There seems to be a clear relationship between hyperhomocysteinemia and an increased risk of coronary arteriosclerosis in Japanese patients with type 2 diabetes.

Aged↗
PubMed1998

A theoretical study of the signal contribution of regions of the adult head to near-infrared spectroscopy studies of visual evoked responses.

Near-infrared (NIR) spectroscopy has been used in studies of the cerebral hemodynamic response to visual processing. In this paper, we present theoretical results from finite element and Monte Carlo modeling in order to help understand the contribution to the NIR signal from different parts of the head. The results from the models show that at the typical optode spacings used in these studies, an infrared spectroscopy measurement of intensity is sensitive to the outer 1-2 mm of the cortical gray matter and the partial optical path length in the gray matter is approximately 10 mm, compared with a total optical path length of 400 mm. When the NIR measurement is of change in mean photon arrival time (or phase shift), the signal comes from the upper 2-4 mm of the cortical surface and there is an increased lateral spread of the contributing tissue. We predict that for a 4-cm separation of input and detection optodes at 800 nm, a 1 microM change in hemoglobin concentration in the cortex corresponds to an attenuation change of approximately 0.001 OD (optical density) or 1 ps mean time change. Movement of the brain caused by this increase in volume will cause an absorption change of approximately half this magnitude, but does not affect the photon arrival time at 4-cm spacing. A discrepancy between the predicted and the experimentally measured intensities may support the supposition that the NIR signal is actually very sensitive to changes occurring in the pial cerebral vessels lying on the brain surface.

Adult↗
PubMed1998

The lateral thigh V-Y flap for the repair of ischial defects.

The lateral thigh fasciocutaneous flap described by Maruyama et al in 1984 is a useful method for the repair of ischial and trochanteric defects. We clinically re-evaluated the potential vascular territory of the nutrient artery for this flap, i.e., the first profunda perforator, and have newly designed the postero-lateral thigh V-Y flap in the area including the proximal two-thirds of the posterior thigh. This flap was applied to five difficult or recurrent ischial defects, and satisfactory results were obtained in all cases. For the reconstruction of ischial defects, the postero-lateral thigh V-Y flap has the following advantages; the proximal and well-vascularised portion of the flap is inserted into the area of the previously excised pressure sore, and this flap can potentially be readvanced if a recurrent pressure sore should develop. A Z-plasty can be performed to prevent excessive tension on the skin closure at the junction of the V-Y advancement flap. The postero-lateral thigh V-Y flap can be considered one of the first-line options for both primary and recurrent ischial pressure sores.

Adult↗
PubMed1998

Fiberscope-assisted evaluation of prereconstructed and postreconstructed external auditory canal.

The malignant tumors of the external auditory canal often invade the middle ear area through the narrow canal, so it is difficult to determine the surgical excisional margin. A patient undergoing external auditory canal reconstruction following excision of a squamous cell carcinoma using a chondrocutaneous flap and fiberscope-assisted preoperative and postoperative diagnoses are described. We obtained good patency of the canal postoperatively. This technique is quite simple and easy to use. We believe fiberscope-assisted surgery is useful for extracting lesions in small areas. In the future, its application will extend to the area of plastic surgery.

Aged↗
PubMed1998

A simple method for earlobe reconstruction.

We describe a technique for earlobe construction using the V-shaped flap with rotation and transposition techniques. This technique produces a natural appearing lobule without unpleasant secondary deformity. This method has been used on two patients, with very good results.

Adult↗
PubMed1998

Expression of thrombomodulin in atherosclerotic lesions and mitogenic activity of recombinant thrombomodulin in vascular smooth muscle cells.

Thrombomodulin (TM), a thrombin receptor protein found on the endothelial cell surface, contains 6 tandem epidermal growth factor (EGF)-like structures. Recombinant human TM peptide containing these 6 EGF-like domains (rTME1-6) exhibits mitogenic activity in Swiss 3T3 cells. We examined the localization of TM in atherosclerotic lesions and the effects of rTME1-6 on the growth of cultured rat vascular smooth muscle cells (SMCs). Immunohistochemical analysis demonstrated that TM antigen was localized on monocytes, macrophages, and vascular SMCs. In cultured vascular SMCs, rTME1-6 accelerated [3H]thymidine uptake into DNA in a dose-dependent manner up to 3.4 times the control level. This mitogenic activity was abolished by addition of polyclonal anti-human TM antibody. The rTME1-6-induced mitogenesis was enhanced by EGF. However, a neutralizing monoclonal antibody against the EGF receptor (monoclonal antibody 225) did not inhibit the mitogenic activity of rTME1-6. Calphostin C, a specific protein kinase C inhibitor, and lavendustin-A, an inhibitor of EGF receptor-specific protein tyrosine kinase, inhibited the mitogenic activities of both rTME1-6 and EGF. Finally, rTME1-6 treatment increased the level of phosphorylated mitogen-activated protein kinase in SMCs. Together, these results suggest that TM expression in atherosclerotic lesions may be associated with promotion of atherosclerosis through its mitogenic activity in vascular SMCs.

Aged↗
PubMed1998

Effects of substitution of Val for Leu11 of ovine angiotensinogen on renin activity.

A mutant angiotensinogen, L11V, in which Val11 was substituted for Leu11 of ovine angiotensinogen was prepared to have the same scissile peptide bond as the human one. The mutation didn't vary Km and kcat of human renin for the ovine substrate, but decreased those of rat renin to one half and one fortieth, respectively. Distances between the P1' subsite of angiotensinogens and the 224th (human renin numbering) residue in the S1' subsite of renins were estimated by molecular modelings. The marked decrease in kcat of rat renin for L11V could be attributed to the elongated distance between Val11 of L11V and Val221 of rat renin. It was also suggested that the distance is the reason why the human substrate cannot be cleaved by heterologous renins.

Amino Acid Sequence↗
PubMed1997

Cationic liposomes are a strong adjuvant for a DNA vaccine of human immunodeficiency virus type 1.

Liposomes have been widely used to enhance the immune response. In the present investigation, we studied their in vivo immunomodulation of an HIV-1-specific DNA vaccine candidate (pCMV160/REV) constructed with the cytomegalovirus (CMV) promoter-conjugated HIV-1 env and rev DNA plasmids. By immunizing with pCMV160/REV and cationic liposomes through various routes (intramuscular, intraperitoneal, subcutaneous, intradermal, and intranasal), we induced higher levels of both antibody production and delayed-type hypersensitivity (DTH) than by using DNA vaccine alone. The HIV-1-specific cytotoxic T lymphocyte (CTL) activity was observed to be stronger on immunization with the DNA vaccine and cationic liposome combination. The intramuscular, intraperitoneal, and intranasal inoculation routes were more effective in inducing strong DTH and antibody responses than the subcutaneous and intradermal routes. Taken together, these results suggest that cationic liposomes can be highly effective when used with DNA vaccines and administered by various routes.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Intranasal immunization of a DNA vaccine with IL-12- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-expressing plasmids in liposomes induces strong mucosal and cell-mediated immune responses against HIV-1 antigens.

A DNA vaccine constructed with the CMV promoter conjugated to env gp160 and rev genes has been shown to induce an effective Th1-type immune response when inoculated via an intramuscular route. In the present study, we obtained high levels of both humoral and cell-mediated immune activity by intranasal administration of this DNA vaccine. The production of mucosal IgA Ab in feces and vaginal fluid was stimulated significantly by intranasal DNA administration. This route of administration resulted in a significant level of HIV-1-neutralizing Abs in feces and serum. Cytokine assays revealed that intranasal administration of this DNA vaccine induces a Th2-type immune response. Interestingly, cationic liposomes greatly enhanced these activities. Abs against HIV-1 were present for at least 10 mo. Coadministration of the DNA vaccine with IL-12- and granulocyte/macrophage-CSF-expressing plasmids induced high levels of HIV-specific CTLs and an increase in delayed type hypersensitivity when administered by the intranasal route. These results clearly demonstrate that intranasal administration of this DNA vaccine with liposomes, together with IL-12- and/or granulocyte/macrophage-CSF-expressing plasmids, induces a strong level of anti-HIV-1 immune response.

Administration, Intranasal↗
PubMed1997

Primary osteosarcoma of the urinary bladder.

Primary osteosarcoma of the bladder, together with transitional cell carcinoma, occurred in a 74-year-old female presenting with haematuria and lumbago. She was treated with chemotherapy and radical cystectomy. Though it was conceived to be curative, she died of a recurrence 5 months after the operation. Primary osteosarcoma of the bladder is an unusual and highly malignant disease. In spite of radical therapy, the outcome has been dismal with some exceptions.

Aged↗
PubMed1997

HIV-1-specific cell-mediated immune responses induced by DNA vaccination were enhanced by mannan-coated liposomes and inhibited by anti-interferon-gamma antibody.

The adjuvant effect of mannan-coated liposomes on human immunodeficiency virus type-1 (HIV-1) DNA vaccine and the mechanism of this enhancement were studied. Coating of cationic liposomes with mannan significantly enhanced the ability of this vaccine to induce an HIV-specific delayed-type hypersensitivity (DTH) response. HIV-specific cytotoxic T-cell (CTL) activity elicited by DNA vaccination was also significantly enhanced with the mannan-liposome cocktail. This mannan-liposome-mediated activity was greatly inhibited by in vivo injection of anti-interferon (IFN)-gamma antibody, which suggests that IFN-gamma plays an important role in this HIV-specific immune response. The results of both isotype-specific antibody and cytokine analysis revealed that mannan-liposome-mediated DNA vaccination enhances Th1-mediated immunity.

AIDS Vaccines↗
PubMed1997

Investigation of the effect of discrete absorbers upon the measurement of blood volume with near-infrared spectroscopy.

This paper derives an analytical model for investigating the effect of the distribution of absorbers upon light attenuation in a scattering medium. Results from this are found to agree with those of Monte Carlo simulations. The implications of this model are then examined for their likely effect upon the measurement of cerebral blood volume (CBV) using near-infrared (NIR) spectroscopy. We conclude that, given the small diameter of the majority of cerebral blood vessels, the distribution of the blood will have little effect upon the measurement of CBV. Where changes to the blood volume occur in the larger (> 0.2 mm diameter) vessels on the surface of the brain, NIR spectroscopy is likely to underestimate the change.

Animals↗
PubMed1997

Bilobed fasciocutaneous flap for primary repair of a large upper arm defect with secondary closure of the donor site without a skin graft.

Primary repair of 2 patients with large upper arm defects with the bilobed fasciocutaneous flap is reported. In this procedure the repair of a large soft-tissue defect with a flap prepared adjacent to the defect and closure of the flap donor site are performed at the same time without a skin graft. This procedure enabled regional reconstruction and provided excellent aesthetic results. It is simple and reliable. In addition, primary repair of large upper arm defects can be expected.

Aged↗
PubMed1997

The V-Y advancement myotarsocutaneous flap for upper eyelid reconstruction.

The V-Y advancement myotarsocutaneous flap was used to avoid excessive scarring during reconstruction of a full-thickness upper eyelid defect following surgical excision of a malignant tumor. This method has a number of advantages: It has a short operative time, it is a one-stage procedure, it does not require lining by auricular or septal cartilage, the technique is relatively simple, and the scar is inconspicuous, since both flap margins are placed in skin creases. The V-Y myotarsocutaneous flap is best suited for the repair of full-thickness upper eyelid defects ranging from 25 to 50 percent of the lid width when the remaining lateral canthal structures are adequate to support the flap.

Basal Cell Carcinoma↗
PubMed1997

Immunohistochemical studies of proliferating cell nuclear antigen and cathepsin D in transitional cell carcinoma of the urinary bladder.

Immunohistochemical staining for proliferating cell nuclear antigen (PCNA) and cathepsin D was performed on 60 transitional cell carcinoma (TCC) specimens from 60 patients with bladder cancer. The percentage of PCNA-positive cells (PCNA-labelling index) was determined by counting 500 or 1,000 cells, and cathepsin D expression was graded according to the extent of immunoreactivity to anti-cathepsin D antibody. The PCNA-labelling index was significantly higher in high-grade and high-stage tumors compared to that in low-grade and low-stage tumors. Cathepsin D was highly positive in grade-1 tumors. In contrast, 82% of grade-3 tumors and 76% of advanced tumors showed negative or low reactivity to anti-cathepsin D. Groups of high PCNA-labelling index and negative cathepsin D had significantly poorer prognoses compared to those of the low PCNA group and cathepsin D highly positive group, respectively, in univariate analyses. However, neither of these two factors were independent prognostic factors in multivariate analyses. These results suggest that the PCNA-labelling index and cathepsin D expression may indicate the malignant potential of TCC and may be able to provide additional information for predicting survival when stratifying for grade of bladder cancer.

Adult↗