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Biomedical subjects

H Maeda

Publications and source records attributed to H Maeda.

At least 577 records · Page 32Linked to original sources

Molecular analysis of a patient with Beckwith-Wiedemann syndrome, rhabdomyosarcoma and renal cell carcinoma.

We described a patient with Beckwith-Wiedemann syndrome associated with rhabdomyosarcoma (RMS), and renal cell carcinoma (RCC). Karyotypes of peripheral lymphocytes and RMS cells were normal. DNA analyses showed maternal loss of heterozygosity (LOH) at 11p15 region in RMS but not in RCC. The insulin-like growth factor II gene (IGF2) was found to be expressed at a moderate level in RMS but not in RCC by in situ hybridization. Each of parental allele-derived IGF2 transcript was detected in RCC, while maternal allele-derived transcript was weak in RMS because of maternal LOH. These results suggest that (1) loss of imprinting (LOI) of IGF2 might be responsible for BWS, (2) on the other hand, LOI itself might not induce tumor occurrence in tissues where the control of tissue-specific expression of IGF2 is maintained, (3) increased expression of IGF2 due to maternal loss of a putative controller gene for IGF2 at 11p15 might predispose to sustaining tumorigenic mutations and tumor progression, (4) loss of a putative onco-suppressor gene at 11p15 might induce RMS occurrence. The cause of RCC was thought to be different from that of RMS.

Abdominal Neoplasms↗

Antitumor effects of human recombinant macrophage colony-stimulating factor against rat brain tumors.

The tumoricidal effects of M-CSF were examined using two subcutaneously-transplanted rat brain tumor cell lines, 9L and T9 gliomas. In rats treated with high-dose M-CSF (16 million U/kg administered for 4 days a week for 3 weeks), 9L glioma growth was inhibited by 81.9% following subcutaneous (s.c.) injection and by 70.5% after intraperitoneal (i.p.) injection and T9 glioma growth was inhibited by 69.2% after i.p. injection. After short-term treatment with high-dose M-CSF (32 million U/kg administered s.c. for 6 consecutive days, 9L glioma growth was inhibited by 82.1%. All these inhibitory effects differed significantly compared with the respective untreated control groups. However, treatment with low-dose M-CSF (1.6 million U/kg administered s.c. for 4 days a week for 3 weeks) showed no significant effects against 9L and T9 glioma growth compared with the untreated controls. No significant effects of M-CSF against cell proliferation, measured as PCNA expression, were observed in any group. Significant hematopoietic effects on the leukocyte counts were observed only in the groups treated with high dose M-CSF. These results suggest that M-CSF at a high dose which produces hematopoietic effects on peripheral leukocytes inhibits the growth of gliomas. This inhibitory effect may have been due to a tumoricidal mechanism of M-CSF that depended on the production or release of some hematopoietic soluble factors, but was independent of PCNA expression by the tumors.

Animals↗

Adenovirus-mediated transfer of human lipase complementary DNA to the gallbladder.

BACKGROUND/AIMS: Despite many improvements in current therapy, exocrine pancreatic insufficiency remains a significant problem in cystic fibrosis. To establish a new therapy for exocrine pancreatic insufficiency, the feasibility of transferring the human pancreatic lipase complementary DNA to the gallbladder as a possible target using a recombinant adenovirus vector was evaluated. METHODS: The adenovirus vector AdCMV. Lip was constructed using the cytomegalovirus immediate early promoter to drive the human pancreatic lipase complementary DNA. In vitro infection of the human gallbladder epithelial cell line HS-181 and ex vivo infection of the sheep gallbladder with AdRSV. beta-gal (an adenovirus vector containing the Escherichia coli lacZ [(beta-galactosidase] gene) or AdCMV. Lip were evaluated. RESULTS: The supernatant from AdCMV. Lip-infected HS-181 showed the secretion of active lipase for at least 2 weeks in vitro. The epithelium of gallbladder infected with AdRSV.beta-gal ex vivo showed the expression of the beta-galactosidase. The fluid from the gallbladder lumen infected with AdCMV. Lip showed the increased lipase activity. CONCLUSIONS: These observations show that an adenovirus vector can transfer a human pancreatic enzyme in vitro and ex vivo, suggesting the feasibility of in vivo gene therapy for exocrine pancreatic insufficiency in cystic fibrosis.

Adenoviridae↗

Fetal heart rate variation described using a probability distribution matrix.

We devised a new method using a probability distribution matrix to simultaneously describe variation in the characteristics of fetal heart rate (FHR) and beat-to-beat difference (DFHR) between the present and the immediately following FHR. The FHRs were plotted in columns, DFHRs in rows and probabilities in the corresponding elements of the matrix. The age-related changes of FHR data obtained from 743 fetuses at 23-40 weeks gestation were analysed using a pulsed Doppler cardiotocograph with an autocorrelation system. While keeping an almost symmetrical spread around 0 beats/min of DFHR, three particular probability distribution patterns of FHR versus DFHR emerged with advance in gestation: (i) oval with a monomodal peak from 23/24 to 29/30 weeks, (ii) ellipsoid with a monomodal peak and plateau from 31/32 to 33/34 weeks and (iii) elongated ellipsoid with bimodal peaks from 35/36 weeks of gestation onwards. The probability distribution matrix presented enables one to condense any amount of FHR data into one uniform description. This allows analysis of data, en bloc, achieving a quantitative inter-group comparison, on an equivalent scale.

Age Factors↗

Involvement of oxygen radicals in the differentiation of rat myelomonocytic leukemia cells in vitro and in vivo.

We have found that LPS induces the differentiation of an LPS-resistant subline (LR) of rat myelomonocytic leukemia cell line, c-WRT-7, in vivo, which are resistant to the differentiation inducing effects of LPS in vitro. Furthermore, we have found that the differentiation of LR cells induced by LPS is inhibited by superoxide dismutase, which is one of radical scavengers. Accordingly, we have examined the differentiation inducing effects of xanthine oxidase, a potential source of oxygen radicals, on LR cells in vitro and in vivo. Xanthine oxidase induced the differentiation of LR cells into macrophage-like cells in vitro; and superoxide dismutase inhibited the differentiation of LR cells induced by xanthine oxidase both in vitro and in vivo. These results suggest that oxygen radicals are involved in the differentiation inducing effects of LPS.

Animals↗

Construction of recombinant Marek's disease virus type 1 (MDV1) expressing the Escherichia coli lacZ gene as a possible live vaccine vector: the US10 gene of MDV1 as a stable insertion site.

This paper describes the construction of a recombinant Marek's disease virus serotype 1 (MDV1) in which the Escherichia coli lacZ gene was inserted into the open reading frame homologous to the US10 gene of herpes simplex virus 1 (HSV1). The recombinant virus replicated as well in cell culture as the parental MDV1 K-554 strain. Chickens immunized with the virus were protected against challenge with virulent MDV1, and produced a high level of antibodies against beta-galactosidase as well as against MDV1 antigens. The antibody titres persisted for at least 16 weeks. These results demonstrate that the US10 gene of MDV1 is an effective site for the insertion of foreign genes from which to construct a polyvalent live vaccine for poultry.

Animals↗

Histological and topographical characteristics of canine granulomatous leptomeningitis.

Histological and topographical characteristics of granulomatous leptomeningitis were studied in 14 laboratory beagle dogs (12 males, two females), 8 to 19 months old. The dogs, which were either saline-treated controls or drug-treated animals in four different toxicity studies, remained clinically normal during the experimental period, and granulomatous leptomeningitis was identified as an incidental finding by routine histopathological examination. There were no macroscopical lesions in the brain or other organs. Microscopical lesions of the central nervous system were of three types, namely (1) a diffuse inflammatory type, characterized by diffuse infiltration of macrophages, (2) a granulomatous type, characterized by non-caseating granulomas, or (3) a fibrotic type, featuring dense connective tissue. Each of the 14 cases fell into one of three disease phases, early, fulminating and healing. In the early phase, only diffuse inflammatory-type lesions were seen. In the fulminating phase, all three types of lesion were present. In the healing phase, discrete granulomas were relatively few and fibrosis was prominent.

Animals↗

Chediak-Higashi syndrome in rats: light and electron microscopical characterization of abnormal granules in beige rats.

Chediak-Higashi syndrome (CHS) is a rare disease occurring in several animal species. Recently, mutant beige rats with CHS were found among DA strain rats in Japan. In the present study, histological examination of beige rats revealed giant granules in the hepatocytes, renal proximal tubules, submandibular ducts, thyroid follicular cells, granulocytes, mast cells, melanocytes, retinal pigment epithelial cells and globular leucocytes. Ultrastructurally, these granules varied from enlarged lysosomes, which were amorphous, granular or filamentous, to giant mast cell granules, crystalloid granules of eosinophils and slightly enlarged neutrophil granules. These findings bore many similarities to those in the beige mouse, which is a well known animal model for CHS, but some differences were apparent. Thus the giant granules of beige rats were larger and more easy to observe than those in beige mice. The study indicated that the beige rat may prove useful as an animal model for CHS.

Acid Phosphatase↗

Plasma cell granuloma of the bladder: a case report.

Plasma cell granuloma of the lung has been reported often but extrapulmonary cases are rare. A case of plasma cell granuloma of the bladder involving the omentum is reported. Transurethral biopsy of the bladder did not aid in diagnosis because the lesion was deeply seated, and differential diagnosis with hematoxylin and eosin staining was difficult due to atypical plasma cells. Immunohistochemistry established the final diagnosis.

Female↗

Cancellous bone behavior in hindlimb immobilized rats during and after naproxen treatment.

Temporary immobilization creates bone loss. The purpose of this investigation was to use an agent to protect the skeleton from bone loss bone during temporary immobilization. Eighty-nine 6-month-old retired breeder Sprague-Dawley female rats were used. Animals were randomly divided into six groups of equal numbers. Four groups were given drinking water from day 0, containing naproxen (100 or 200 mg/l). At day 7, half the animals in all groups had their right hindlimb immobilized. At day 49, half the immobilized rats and non-immobilized controls were sacrificed. The remaining rats were remobilized and the drug was stopped. At day 91, all remaining rats were sacrificed. Gastrocnemius and soleus muscle weights were determined. Right tibiae were analyzed for cancellous bone mass, bone structural and bone dynamic variables. At the close of immobilization, bone mass was lower in the right (immobilized) hindlimb of the immobilized group than in the non-immobilized group. Immobilized rats drinking 100 mg/l naproxen water had significantly higher bone mass in their immobilized limbs than did untreated immobilized rats, but all rats drinking 200 mg/l naproxen water had lower bone mass than controls. After 6 weeks of recovery, bone mass in the immobilized limb of untreated formerly immobilized rats improved, but remained below untreated never-immobilized rats. Formerly immobilized rats that had been treated with 100 mg/l naproxen water had normal bone mass after 6 weeks of recovery. Naproxen, an agent that mildly depresses activation frequency, prevents some of the transient bone mass and structural deterioration during temporary immobilization. Such treatment facilitates a more rapid return to normal bone mass, though not to normal structure. The more rapid recovery occurs because the difference from normal is less, not because of more rapid formation in recovering animals.

Analysis of Variance↗

Potentiation of infectivity and pathogenesis of influenza A virus by a house dust mite protease.

Common house dust mites (e.g., Dermatophagoides farinae) excrete a serine-type (Df) protease. Df protease obtained from cultured mites enhanced viral replication in vitro via proteolytic cleavage of viral hemagglutinin (HA) into HA1 and HA2, which confers potent viral infectivity. Its potency is 2- to 5-fold higher than bovine trypsin or human plasmin. Df protease also markedly accelerated virus propagation in vivo: A minute quantity of protease (estimated delivered amount, 0.8-3.2 micrograms) produced approximately 4- to 100-fold increases in infectious virus in the mouse lung. Similar augmentation of viral replication by Df protease was observed in ferret models of nasopharyngeal infections of influenza virus. All extracts from ordinary house dust contained a serine-type protease that cleaved HA into HA1 and HA2. Thus, mite protease in house dust may enhance the pathogenesis of influenza virus.

Amino Acid Sequence↗

Adoptive transfer of a Th2-like cell line prolongs MHC class II antigen disparate skin allograft survival in the mouse.

The MHC class II alloantigen-reactive CD4+ Th2-like cell line, HR2, was established. It was derived from the spleen cells of C57BL/6 (B6) mice immune to an MHC class II-disparate mutant mouse, B6.CH-2bm12 (bm12) which carries the I-Abm12 antigen. This cell line, HR2, secretes IL-4 and IL-10 in an antigen-specific manner, and can also proliferate in an autocrine manner through IL-4. To investigate the in vivo role of this Th2-like CD4+ T cell line in transplantation immunity, an adoptive cell transfer study using the skin allograft system was performed. Skins grafted from bm12 to B6 were rejected at 12.1 +/- 0.6 days in control B6 mice which received no treatment. Whereas skin graft survival was prolonged in B6 experimental mice which had received 2 x 10(7) HR2 cells, 75% of the grafts survived for > 40 days. Moreover, since skin grafts from fully allogeneic third party donor BALB/c mice were rejected at 12.0 +/- 0.4 days by B6 mice which had received the same number of HR2 cells, it was demonstrated that HR2 is involved in the regulation of bm12 skin graft rejection. Furthermore, cytotoxic T lymphocyte (CTL) activity by spleen cells from HR2 transferred B6 mice was not induced even by in vitro secondary stimulation, although CTL activity was induced well in spleen cells of control B6 mice which had rejected the graft. The underlying mechanism has not been fully clarified; however, these results demonstrate that Th2-like CD4+ T cells suppress allograft rejection.

Animals↗

Isolation and localization of the 120 kDa protein in the liver of genetically obese Zucker rats.

The genetically obese Zucker rat is a well-characterized model of early-onset human obesity. The 120 kDa protein was recently found in the liver cytosol of obese Zucker rats at levels higher than that in lean Zucker rats. We isolated this protein using precipitation with ammonium sulfate, DEAE-Sephacel chromatography, and preparative polyacrylamide gel electrophoresis; the product showed a single band on SDS-polyacrylamide gel electrophoresis. Immunoblotting analysis revealed that the 120 kDa protein was predominantly localized in the liver cytosol of obese Zucker rats. The amount of this protein in lean Zucker rats was less than one-fifth of that found in obese Zucker rats. Further, there were only trace amounts of this protein in the lung tissues, and no detectable amount in other tissues, such as kidney, epididymal adipose tissue, brain, spleen, skeletal muscle, or serum, in either strain of rat. These data suggest that the 120 kDa protein contributes to the abnormal lipid metabolism in obese Zucker rats.

Ammonium Sulfate↗

Functional oligomerization of purified human papillomavirus types 16 and 6b E7 proteins expressed in Escherichia coli.

Purified non-fused soluble human papillomavirus type 16 and 6b E7 proteins expressed in Escherichia coli were found to form oligomers. For both proteins, several degrees of oligomerization were demonstrated by gel filtration, dynamic laser light scattering and scanning electron microscopy. Oligomerization was dependent on the concentration of E7 protein. Oligomerized E7 proteins were able to bind the retinoblastoma gene product pRB and stimulated DNA synthesis when introduced into cells.

Base Sequence↗

Augmentation of host resistance against bacterial infection by treatment with leustroducsin B, a new CSF inducer.

We tested the in vivo activity of leustroducsin B (LSN B), a new colony-stimulating factor (CSF) inducer isolated from the culture broth of Streptomyces platensis, with mice infected with Escherichia coli. Treatment with LSN B augmented the host resistance to lethal infection of E. coli at doses between 0.1 mg/kg and 1 mg/kg. Serum interleukin-6 (IL-6) levels were found to increase after this treatment, and superoxide anion generation of neutrophils was enhanced in vivo, suggesting that LSN B augmented the host resistance at least in part by inducing IL-6, which subsequently enhanced the bactericidal activity of the neutrophils.

Animals↗

Enhanced vascular permeability in solid tumor is mediated by nitric oxide and inhibited by both new nitric oxide scavenger and nitric oxide synthase inhibitor.

A newly discovered nitric oxide radical scavenger, an imidazolineoxyl N-oxide derivative, was used to investigate the role of nitric oxide radical (.NO) in the vascular permeability enhancement of solid tumor. Sarcoma-180 solid tumor in ddY mice was used for this experiment. Electron spin resonance spectroscopy was used to quantitate the reacted and unreacted scavenger. The results showed that extensive extravasation, assessed by intravenous injection of Evans blue, could be greatly suppressed by both .NO scavenger administered orally and .NO synthase inhibitor administrated intraperitoneally. This indicates that .NO is responsible for the vascular permeability in solid tumors.

Amino Acid Oxidoreductases↗

Improvement of macrophage dysfunction by administration of anti-transforming growth factor-beta antibody in EL4-bearing hosts.

An experimental therapy for improvement of macrophage dysfunction caused by transforming growth factor-beta (TGF-beta) was tried in EL4 tumor-bearing mice. TGF-beta was detected in cell-free ascitic fluid from EL4-bearers, but not in that from normal mice, by western blot analysis. The ascites also showed growth-suppressive activity against Mv1Lu cells, and the suppressive activity was potentiated by transient acidification. To investigate whether the functions of peritoneal macrophages were suppressed in EL4-bearers, the abilities to produce nitric oxide and tumor necrosis factor-alpha (TNF-alpha) upon lipopolysaccharide (LPS) stimulation were measured. Both abilities of macrophages in EL4-bearing mice were suppressed remarkably on day 9, and decreased further by day 14, compared with non-tumor-bearing controls. TGF-beta activity was abrogated by administration of anti-TGF-beta antibody to EL4-bearing mice. While a large amount of TGF-beta was detected in ascitic fluid from control EL4-bearers, little TGF-beta was detectable in ascites from EL4-bearers given anti-TGF-beta antibody. Furthermore, while control macrophages exhibited little or no production of nitric oxide and TNF-alpha on LPS stimulation in vitro, macrophages from EL4-bearers administered with anti-TGF-beta antibody showed the same ability as normal macrophages. These results clearly indicate that TGF-beta contributes to macrophage dysfunction and that the administration of specific antibody for TGF-beta reverses macrophage dysfunction in EL4-bearing hosts.

Animals↗