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Biomedical subjects

A Yoshida

Publications and source records attributed to A Yoshida.

At least 181 records · Page 10Linked to original sources
PubMed2000

DNA vaccines.

DNA vaccination or genetic immunization is a rapidly developing technology that offers new approaches for the prevention and therapy of disease. Regarding the inoculation method of DNA vaccine, we recommend the gene gun delivery system, which is a highly reliable method compared to intramuscular inoculation. DNA vaccines could have potential advantages over other types of vaccines in that these vaccines can induce strong cellular immune responses, cytotoxic T lymphocytes and type 1 helper T cells, without resorting to live organisms or complicated protein formulation. The cellular immune responses are especially required for the protection against infections with intracellular pathogens such as viruses and Mycobacterium tuberculosis and protection against cancers, suggesting that they seem to be suitable targets of DNA vaccines. We describe here that their application to bacterial infections requires optimization of codon usage in the DNA vaccines to the host animal to improve translational efficiencies of the bacteria genes. DNA vaccines for a variety of pathogens and cancers have now entered phase I/II human clinical trials.

Animals↗
PubMed2000

Paragonimiasis miyazakii associated with bilateral pseudochylothorax.

A 37-year-old man who suffered from bilateral pleural effusions, subcutaneous abdominal induration and blood eosinophilia, was admitted to our hospital. He had ingested raw crabs at a pub-restaurant before the onset of his symptoms. His pleural effusions were chyliform containing cholesterol crystals, and a high level of immunoglobulin E (36,580 IU/ml) and anti-Paragonimus miyazakii antibody were detected. He was effectively treated with praziquantel. This case suggests that paragonimiasis should be strongly suspected if blood eosinophilia, pseudochylothorax, and a high level of immunoglobulin E in pleural effusion are detected.

Adult↗
PubMed2000

The H9/M8166 tropism of various HIV-1 mutants is determined by distinct cellular factors (review).

We have previously shown that a number of human immunodeficiency virus type 1 (HIV-1) mutants generated in vitro display a replication-defect in a cell-dependent manner. Of the mutants of this category, those of gag, vif, and env mutants do not grow at all in lymphocytic H9 (non-permissive) cells, but quite well in M8166 (permissive) cells. To determine whether the cell-dependent growth of the mutants is functionally related to each other, a number of double mutants were constructed, and monitored for their replication and biochemical property in various cells. The results obtained have indicated that there are multiple cellular factors responsible for the growth phenotype. Together with our previous findings on the host cell-dependent mutants of HIV-1, it is concluded that number of distinct cellular factors are involved in the various steps in HIV-1 replication cycle.

Animals↗
PubMed2000

Mutational analysis of HIV-1 gag proteins (review).

The mature Gag proteins of human immunodeficiency virus type 1 (HIV-1) are major components of infectious virions, and thought to carry out numerous functions throughout the HIV-1 replication cycle. We have recently generated numerous gag gene mutants of HIV-1 to genetically study the functions of the Gag proteins. Through the biological and biochemical analyses, our HIV-1 gag mutants have been grouped into early (defective for uncoating/reverse transcription), late (defective for virion release/maturation), and early/late (defective for both steps) mutants. Many mutants are found to efficiently inhibit the replication of wild-type virus. Worthy of note, there are some early mutants which show host cell-dependent replication potential.

DNA Mutational Analysis↗
PubMed2000

Opioid analgesic-induced apoptosis and caspase-independent cell death in human lung carcinoma A549 cells.

We characterized anticancer effects of opioid analgesics that are clinically used for cancer patients for pain relief. Treatment with 100 microM buprenorphine, a representative analgesic, induced cell death of human carcinomas, such as A549 (squamous epithelial cell of lung cancer), MCF-7 (breast cancer) and N417 (small cell of lung cancer), but not in KATO III (gastric cancer) cells as evaluated by alamar blue assay. Among 18 clinically utilized and related analgesics, buprenorphine and loperamide showed potent inhibition of cell viability. However, these anti-cancer effects were not affected by opioid receptor antagonists nor by pertussis toxin. Buprenorphine-induced cell death occurred as early as 1 h after the addition, and its T1/2 of cell viability inhibition was 3 h. The cell death manifested the characteristics of apoptosis, such as DNA-laddering and nuclear fragmentation, which were sensitive to a caspase inhibitor, Z-Asp-CH2-DCB. The nuclear fragmentation was independent of cell cycle phase specificity. The activity of caspase-3-like protease which is known to be closely related to apoptotic DNA laddering was markedly enhanced by buprenorphine. However, the inhibition of cell viability by buprenorphine was not affected by the caspase inhibitor. These findings suggest that some opioid analgesics induce typical apoptotic features sensitive to the caspase inhibitor, while also inhibition of cell viability insensitive to the inhibitor.

Analgesics, Opioid↗
PubMed2000

Japanese sisters associated with pseudohomozygous familial hypercholesterolemia and sitosterolemia.

Pseudohomozygous familial hypercholesterolemia is a rare condition of unknown etiology. Sitosterolemia is a rare autosomal recessively inherited disorder that is characterized by premature coronary artery disease, cutaneous xanthomas, and increased plasma plant sterols and 5alpha-stanols. Only a few cases of both sitosterolemia and pseudohomozygous familial hypercholesterolemia have been reported. In this study, we report two sisters with both conditions. With a low-cholesterol diet (< 250 mg/day), serum cholesterol concentration decreased rapidly to an almost normal level and cutaneous xanthomas gradually regressed and finally disappeared; however, plant sterol levels did not change during the period. Plant sterols should be measured in patients considered to have pseudohomozygous familial hypercholesterolemia. The two conditions in this family may have been the results of a single gene mutation. The findings also indicate that low cholesterol diet therapy is effective for the treatment of hypercholesterolemia but not of sitosterolemia in this family.

Child↗
PubMed2000

Torsade de pointes associated with hypokalemia after anthracycline treatment in a patient with acute lymphocytic leukemia.

Severe dose-dependent anthracycline cardiotoxicity is reported to cause myocardial damage resulting in congestive heart failure. However, torsade de pointes, a life-threatening arrhythmia caused by chronic anthracycline cardiotoxicity, has not been reported previously. A 16-year-old girl who developed torsade de pointes after 6 months of chemotherapy for acute lymphocytic leukemia (French-American-British classification L2) is described. When the patient was readmitted to the hospital because of syncope, peripheral blood and bone marrow analysis indicated a relapse. In addition, the patient was hypokalemic. Twenty-four-hour ambulatory electrocardiographic monitoring demonstrated QT prolongation and an episode of torsade de pointes. The electrocardiographic changes and arrhythmia improved after correction of the hypokalemia. An inverse correlation between leukocyte count and hypokalemia was observed. The patient died from pulmonary hemorrhage. Autopsy examination demonstrated myocardial degeneration consistent with damage induced by antineoplastic antibiotics. The cumulative dose of anthracycline and anthraquinone was less than the conventional dose limit associated with chronic cardiotoxicity, even for children who are more sensitive to anthracyclines. Torsade de pointes can occur in the setting of chronic anthracycline cardiotoxicity. Therefore, children or young adults who are more sensitive to anthracycline need careful observation that includes electrolyte monitoring, especially for potassium.

Adolescent↗
PubMed2000

[Therapeutic effect and clinical findings in patients with MPO-ANCA associated vasculitis syndrome].

We investigated to clarify the clinical findings, course and therapeutic effect in the patients with MPO (myeloperoxidase)-ANCA (anti-neutrophil cytoplasmic antibody) associated vasculitis syndrome. We analyzed clinical findings and data of 19 cases of MPO-ANCA associated vasculitis. These patients were diagnosed with clinical symptoms (fever, arthralgia, body weight loss, etc.), laboratory data (high titer of CRP, leukocytosis, thrombocytosis, and high titer of MPO-ANCA) and pathologic findings of necrotizing vasculitis. They were 14 male and 5 female aged 18 to 84 years (mean 65 years) and were treated with prednisolone and immunosuppressive agents, and additional therapy included pulse therapy and plasma exchange. Seven cases were dead within 3 months. Post-mortum examination showed that these cases died of pneumonitis, cerebral events and gastric bleeding. There was no mortal case induced by over-immunosuppression. In survival cases, the MPO-ANCA levels decreased rapidly after these therapies and these antibodies were maintained low levels (360 to 25 EU/l). Comparison of fatal cases and survival cases, there were difference in the initial dose of prednisolone (27 mg/day vs. 56 mg/day), the ratio of double filtration plasmapheresis (14% vs. 42%), and the ratio of immunosuppressive therapy (14% vs. 83%). The measurement of MPO-ANCA is useful makers of the diagnosis and effectiveness of the therapy in patients with MPO-ANCA associated vasculitis. We recommend the aggressive therapy, including prednisolone, immunosuppressive agents and plasma exchange for MPO-ANCA associated vasculitis. We believe that the aggressive therapy improve the survival rate of the patients with MPO-ANCA associated vasculitis.

Adolescent↗
PubMed2000

Intravitreal injection of hyaluronidase cannot induce posterior vitreous detachment in the rabbit.

PURPOSE: To investigate whether intravitreal injection of hyaluronidase can induce posterior vitreous detachment (PVD) in the rabbit. METHODS: One eye each of 12 New Zealand white rabbits received intravitreal injection via the pars plana of 20 IU of hyaluronidase (0.1 mL reconstituted in sterile balanced salt solution [BSS]) into the midvitreous cavity. The fellow eye of each rabbit received a vitreous injection of 0.1 mL of BSS. At 3 and 6 months after intravitreal injection, four and eight rabbits were killed, respectively, and the eyes were enucleated. After fixation, scanning electron microscopy was performed to study the vitreoretinal interface. RESULTS: At 3 and 6 months after injection, scanning electron microscopy showed that the retinal surfaces in eyes that received either hyaluronidase or BSS were covered with vitreous collagen fibers. No eyes, even those that received hyaluronidase over a period of 6 months, had the smooth retinal surface consistent with a bare internal limiting lamina that suggests the development of PVD. CONCLUSION: Hyaluronidase cannot induce PVD in the rabbit over a 6-month period after vitreous injection.

Animals↗
PubMed2000

MHC-I expression in HTLV-1-positive and -negative cells.

The expression level of major histocompatibility class I (MHC-I) and the extent of down-regulation of MHC-I after an anti-MHC-I antibody treatment in numerous human T-cell leukemia virus type 1 (HTLV-1)-positive and -negative lymphocytic cell lines were examined. While there was no clear correlation between the expression level of MHC-I and the presence of HTLV-1 genome, a relatively low level of MHC-I down-regulation was generally induced in HTLV-1-positive cells by the antibody. The results may suggest the potential involvement of MHC-I in HTLV-1 leukemogenesis.

Antibodies, Monoclonal↗
PubMed2000

[Clinical effects of trandolapril in chronic glomerulonephritis patients with renal insufficiency].

Trandolapril is a newly developed angiotensin converting enzyme inhibitor (ACEI) whose characteristic is that it undergoes hepatic excretion. ACEI appears to have a specific reno-protective and antiproteinuric role in patients with chronic glomerulonephritis(CGN). Although renally excreted ACEI tend to accumulate and cause side-effects in patients with renal dysfunction, the pharmacokinetics of trandolapril were not affected by renal dysfunction. We compared the effect of other renally excreted ACEI with those of trandolapril on serum creatinine (s-Cr), creatinine clearance(Ccr), proteinuria and total protein(TP) in CGN patients who switched from another ACEI to trandolapril. Twelve hypertensive patients with chronic renal failure(nine males and three females, ranging from 30 to 72 years of age) who were treated by other renally excreted ACEIs for long periods(2 to 8 years) with some effects on proteinuria and renal function, were enrolled in the present study. After ACEI therapy, s-Cr had decreased(2.09 to 1.80 mg/dl, p < 0.01) as well as proteinuria(1.65 to 0.71 g/day, p < 0.01). A single daily oral dose of 1 mg of trandolapril was administered to these patients regardless of their blood pressure status and renal functions. After change to trandolapril therapy, s-Cr(2.25 to 2.06 mg/dl, p < 0.01) and urinary protein(1.82 to 1.34 g/day, p < 0.05) significantly decreased. On the contrary, both Ccr and TP significantly increased at the level of 39.4 to 44.4 ml/min(p < 0.05) and 6.80 to 7.02 g/dl (p < 0.01), respectively. No apparent side effects, such as hyperkalemia, hyponatremia, anemia or worsening of the existing renal dysfunction except for coughing, were observed in these patients. Furthermore, none of the 12 patients treated with trandolapril required discontinuation of the compound. In conclusion, it was shown from this study that trandolapril is effective for the treatment of hypertensive patients with renal insufficiency irrespective of the original diseases. Thus, it can be envisaged that trandolapril is one of the most appropriate agents compared to other renally excreted ACEI for these patients with renal insufficiency. We recommend the change from other ACEIs to trandolapril, when renal dysfunction might be due to ACEI accumulation.

Adult↗
PubMed2000

Injury-specific expression of activating transcription factor-3 in retinal ganglion cells and its colocalized expression with phosphorylated c-Jun.

PURPOSE: To ascribe activating transcription factor (ATF)-3 as a specifically induced transcription factor after ON injury and to describe its putative role as a modulator of c-Jun transactivation. METHODS: The adult rat optic nerve was crushed intraorbitally, and expression profiles of ATF-3, ATF-2, and phosphorylated c-Jun (p-c-Jun) were examined by immunohistochemistry and ISH. Western blot analysis for ATF-3 and -2 were also performed. Furthermore, colocalized detection of c-Jun mRNA with ATF-2 or -3 was attempted with a combined method of simultaneous immunohistochemistry and in situ hybridization. RESULTS: In response to optic nerve injury, substantial expression of ATF-3 as well as that of p-c-Jun was observed in the retinal ganglion cells, whereas no expression of ATF-3 was seen in other noninjured retinal cells. In contrast, ATF-2 was normally expressed abundantly in both retinal ganglion cells and displaced amacrine cells, but expression dropped in retinal ganglion cells after nerve injury. The expression profiles of ATF-2 and -3 after optic nerve injury were confirmed by Western blot analysis. A higher degree of colocalization was observed for ATF-3 and c-Jun than the modest codetection for ATF-2 and c-Jun. CONCLUSIONS: The transcription factor ATF-3 is specifically induced upon optic nerve injury and colocalizes with p-c-Jun in surviving ganglion cells. These findings suggest that both ATF-3 and c-Jun are crucial to trigger various transcriptional responses and may act synergistically during the survival phase of the optic nerve in the injury model.

Activating Transcription Factor 2↗
PubMed2000

Markers of undiagnosed incidental cancer in comparison with clinical prostatic cancer.

We propose that carcinoembryonic antigen (CEA) may be a tumor marker for prostatic cancer in addition to prostate specific antigen (PSA), gamma-seminoprotein and prostate acid phosphatase (PAP). The tests were done on 15 sera and autopsy specimens of prostatic cancer. Eight of them were clinical cancers and the remaining seven were incidental ones. We measured serum PAP, PSA, CEA and CA 19-9 and immunohistochemically evaluated these specimens. In clinical cancers, serum PAP, PSA, CEA and CA 19-9 were 1272.9 +/- 3094.4, 146.7 +/- 233.6, 36.3 +/- 36.0 and 80.4 +/- 92.0. Immunohistochemically, all were positive for PAP, PSA, CEA and CA 19-9. In incidental cancers, serum PAP, PSA, CEA and CA 19-9 were 2.4 +/- 1.5, 7.9 +/- 16.9, 128.1 +/- 182.7 and 201.8 +/- 416.1. We conclude that the patients with higher levels of plasma PAP or PSA should go through CEA and CA 19-9 measurement in order to diagnose clinical prostatic cancer.

Acid Phosphatase↗
PubMed2000

[Siblings with age-related macular degeneration in a pedigree].

BACKGROUND: The pathogenesis of age-related macular degeneration remains unknown. Environmental and genetic factors have been shown to be associated with in this disease. We report siblings with age-related macular degeneration. CASES: The proband (the third of 6 siblings) was found to have retinal pigment epithelial abnormalities and drusen of the right macula, and serous retinal detachment, drusen, and choroidal neovascularization of the left macula. Examination of the eldest siblings showed choroidal neovascularization, subretinal hemorrhage, and serous retinal detachment of the right macula. The left eye of the proband and the right eye of the eldest siblings were treated with laser photocoagulation. The fourth sibling was examined, and findings included retinal pigment epithelial abnormalities of both maculas and drusen of the right eye. The sixth sibling had drusen of the left macula. CONCLUSION: We report a family in which two siblings had age-related macular degeneration and two other siblings had abnormalities of the maculas.

Aged↗
PubMed2000

Preventive effect of local plasmid DNA vaccine encoding gD or gD-IL-2 on herpetic keratitis.

PURPOSE: The goal of this study was to evaluate the effectiveness of a local plasmid DNA vaccine encoding herpes simplex virus (HSV) type 1 glycoprotein D (gD) or gD-interleukin (IL)-2 (chimeric gene of gD and human IL-2) in preventing murine herpetic keratitis. METHODS: Plasmids containing gD (pHSDneo1), gD-IL-2 (pHDLneo1), or vaccine vector (pHSGneo) were injected subconjunctivally with BALB/c mice on days 0 and 7 (90 microgram x 2). Immunization was indicated by positive virus-neutralizing antibody titer, swollen pinna (due to delayed-type hypersensitivity [DTH] reaction), and release of (51)Cr from splenic and/or local cytotoxic effector cells on day 28. In another group of the immunized mice, corneas were challenged with HSV-1 (CHR3 strain, 10 microliter of 3 x 10(6) plaque-forming units [PFU]/ml). Mice were evaluated for clinical signs of epithelial or stromal keratitis on days 1 through 8 and days 10 and 14 or measured on days 2, 4, or 6 for viral titers in the eyes, trigeminal ganglia, and brain. RESULTS: All gD-DNA-injected mice obtained specific immunity. Furthermore, gD-IL-2-DNA elicited a higher DTH reaction and more vigorous cytotoxic effector cell activity. Stromal keratitis scores were lower for all immunized mice compared with control mice, although the difference in epithelial keratitis scores was not statistically significant. Viral titers in eyes, trigeminal ganglia, and brains were suppressed in all immunized mice. CONCLUSIONS: Local immunization with plasmid DNA encoding gD or gD-IL-2 induces humoral and cellular immunity against HSV-1 and inhibits development of stromal keratitis. gD-IL-2 DNA induces greater cell-mediated immunity than gD DNA alone. A plasmid encoding gD-IL-2 is therefore a promising candidate for a vaccine against HSV-1.

Animals↗