Biomedical subjects

K Hirano

Publications and source records attributed to K Hirano.

At least 73 records · Page 4Linked to original sources

PubMed2001

Compound melanocytic nevus arising in a mature cystic teratoma of the ovary.

A 28-year-old woman complained of irregular menstruation. Abdominal ultrasound and magnetic resonance imaging (MRI) examinations revealed a cystic tumor in the left ovary. A histological examination of the resected ovary revealed that the lesion was a mature cystic teratoma. In this tumor, components such as skin with appendages, a thyroid gland, mucosa of the digestive tract and a submandibular gland were observed. Interestingly, compound melanocytic nevus was also present in the skin component. To the best of our knowledge, this is the sixth reported case of nevus arising in a mature cystic teratoma of the ovary. Despite the extreme rarity of such a lesion, pathologists should recognize the possibility of such lesions occurring in ovarian teratoma.

Adult↗

PubMed2001

CC-chemokine receptor 6 and its ligand macrophage inflammatory protein 3alpha might be involved in the amplification of local necroinflammatory response in the liver.

It is not fully understood how antigen-specific or-nonspecific T cells migrate into the liver in various liver diseases. Macrophage inflammatory protein (MIP)-3alpha is a chemokine that is expressed mostly in the liver, and the receptor CCR6 is reported to be expressed on memory T cells. In the present study, we focused on the expression of CCR6 on T cells from peripheral blood (PB) and inflamed liver, and analyzed the involvement of MIP-3alpha and CCR6 in the immunopathogenesis of liver diseases. Intrahepatic T cells showed significantly (P <.0001) higher percentages of CCR6(+)CD4(+) T cells compared with PB, which is significantly (P =.037) correlated with the necroinflammatory response in the liver. Most of intrahepatic CCR6(+)CD4(+) cells were also positive for CCR5, which is known to express on T-helper 1 cells. MIP-3alpha was stained in the cells located near piecemeal necrosis, where dendritic cells (DCs) are often observed, and coculture of activated DCs with apoptotic cells induced MIP-3alpha production from the DCs. These data suggest that MIP-3alpha is produced by periportal DCs and/or macrophages after necroinflammatory response, leading to the recruitment of activated T cells into the liver. This process could be important to augment the local immune response in the livers of various liver diseases. The finding might be important not only for the understanding of immunopathogenesis of liver diseases but also for the therapeutic strategy to control the local immune response in the liver.

Antigens, CD↗

PubMed2001

Secretory meningioma: clinicopathologic features of eight cases.

The clinical and morphological features of eight patients with meningothelial meningiomas with numerous pseudopsammoma bodies (secretory meningiomas) are presented. The six female and two male patients ranged in age from 43 to 68 years. Tumours were located at the petroclival region in two, the lateral parasellar region in two, the petrous apex in one and the sphenoid ridge in three patients. On magnetic resonance imaging, they were iso or hypointense on T1-weighted images, and hyper or isointense on T 2-weighted images. Peritumoral brain edema was absent in five cases, and was mild to moderate in three cases. Serum carcinoembryonic antigen (CEA) levels were measured preoperatively in three patients, with one having an elevated serum CEA level which re turned to normal following tumour resection. Immunohistochemical analysis on the resected tumour tissues, pseudopsammoma bodies and surrounding tumour cells were shown to be CEA-positive. Ultrastructurally, pseudopsammoma bodies were composed of granular and filamentous materials located predominantly in the intracellular lumina, which were lined by microvilli. While these morphological features of focal epithelial and secretory differentiation of tumour cells call attention to the broad spectrum of differentiation properties of meningiomas, the biological behavior of the eight tumours reported herein corresponded to those of meningiomas in general.

Adult↗

PubMed2001

Decreases of metallothionein and aminopeptidase N in renal cancer tissues.

Good molecular markers for investigating the biochemical differences between renal cancer and surrounding tissues have not yet been developed. Sixteen kidney samples (clear cell RCC) were investigated to determine the differences in the protein components between renal cancer and surrounding tissues, using HPLC analysis. The metallothionein (MT) and zinc levels were consistently lower in renal cancer tissues compared with in surrounding tissues. The mean concentration of MT in normal tissues surrounding renal tumors was about 15 times higher than that in cancer tissues. An immunohistochemical study confirmed that the expression of MT in renal cancer tissues was lower than that in adjacent normal tissues. The activities of aminopeptidases (APs) were significantly decreased in renal cancer tissues compared with in adjacent normal tissues. An immunohistochemical study and Western blot analysis confirmed that the expression of AP-N in renal cancer tissues was also lower than in adjacent normal tissues. These results suggest that the immunohistochemical detection of MT and AP-N could provide useful information as a pathological diagnostic tool for classifying renal cancer and surrounding tissues.

Biomarkers, Tumor↗

PubMed2001

Modulation of reactive oxygen species in endothelial cells by peroxynitrite-treated lipoproteins.

Peroxynitrite has been implicated in the oxidative modification of low-density lipoprotein (LDL) particles, and nitrotyrosine residues in the LDL have been detected in atherosclerotic plaques. Studies have suggested that lipoproteins modified by peroxynitrite lead to the onset of atherosclerotic vascular disease. We therefore prepared in vitro lipoproteins oxidatively modified by peroxynitrite (NO(2)-lipoprotein) and investigated the effect of NO(2)-lipoprotein on the viability of cultured endothelial cells. After exposure of a high-density lipoprotein (HDL) to peroxynitrite, some intermolecular complexes of apolipoproteins in HDL were detected on immunoblotting with monoclonal antibodies against apolipoprotein AI and AII, suggesting that nitration of HDL by peroxynitrite causes intermolecular cross-linking of the apolipoproteins in the particles. Treatment with 1 mM peroxynitrite increased the 3-nitrotyrosine level to 28.5 mmol/mol of tyrosine residues in the prepared NO(2)-HDL, as quantitated by HPLC, and the amount in NO(2)-lipoprotein depended on the peroxynitrite concentration. HDL exhibited a shorter lag phase and the reaction plateaued more rapidly than that with LDL. To clarify whether or not NO(2)-lipoproteins affect the function of endothelial cells, we first examined the viability of cultured human aortic endothelial cells (HAECs) exposed to NO(2)-lipoproteins. Incubation with either NO(2)-HDL or NO(2)-LDL significantly reduced the HAEC viability at 72 h. The results of RT-PCR and Western blotting showed that NO(2)-HDL markedly suppressed at 48 h not only the expressed levels of mRNA and protein but also the activity of catalase in HAECs. In contrast, NO(2)-LDL significantly reduced the expression and activity of Cu(2+),Zn(2+)-superoxide dismutase (CuZn-SOD) in the cells. Neither NO(2)-HDL nor NO(2)-LDL interfered with nitric oxide production or expression of cyclooxygenases and NADPH oxidase in HAECs. Increased radical production in NO(2)-lipoprotein-treated HAECs implied that reactive oxygen species such as superoxide anions and hydroxyl radicals may contribute to the mechanism of the toxic effect induced in endothelial cells by NO(2)-lipoprotein. Overall, NO(2)-lipoprotein may lead to deterioration of the vascular function through these endothelial cell responses.

Arteriosclerosis↗

PubMed2001

Histopathologic findings of cornea verticillata in a woman heterozygous for Fabry's disease.

PURPOSE: To report the histopathologic findings of the cornea verticillata observed in a woman who was heterozygous for Fabry's disease. METHOD: A 67-year-old woman was found to have a whorl-like corneal opacity on her visit to the Department of Ophthalmology. Aichi Saiseikai Hospital. Her visit was because of a sudden loss of vision in her right eye owing to a central retinal artery occlusion in association with an ophthalmic artery occlusion. The patient died suddenly of an acute heart failure; with family consent, an autopsy was performed and the right eye was removed for histopathologic examination by light and electron microscopy. RESULTS: Low levels of alpha-galactosidase in the leukocytes together with the corneal finding led to the diagnosis of heterozygous Fabry's disease. Light microscopy revealed a 0.3- to 0.5-microm thick layer between the epithelial and Bowman's layers. Oil red O positive deposits were accumulated in the subepithelial layer, and the density varied in different regions. Electron microscopy showed that subepithelial layer differed in thickness, and the basal lamina reduplicated regionally. We were not able to determine the structure that correlated with the "ridge" in the central part of the cornea. CONCLUSION: The oil red O positive deposits and their variation in density in the subepithelial area of the cornea may have caused the characteristic whorl-like corneal opacity in this woman who was heterozygous for Fabry's disease.

Aged↗

PubMed2001

Optical coherence tomography for the noninvasive evaluation of the cornea.

PURPOSE: To determine the optical coherence tomographic (OCT) characteristics of normal corneas and to characterize the OCT images of abnormal corneal lesions. METHODS: Eleven eyes from 10 patients were examined at the Cornea Service of the Nagoya University Hospital: 4 had corneal pathologies, 4 underwent keratoplasty, and 2 were normal controls; 1 enucleated eye was also examined. OCT (OCT 2000 Zeiss-Humphrey) was used to study the normal cornea and various corneal abnormalities. We compared the OCT images to the observations made by slit-lamp biomicroscopy. RESULTS: Fluid spaces were detected as black images. A highly reflective reflex was observed at the interface of different tissues, and intensive backscattering (reflex) was seen when the incident ray hit the laminated layers vertically. Corneal opacities were not clearly imaged when they were diffuse and mild, or when they were arranged axially in a small area, as was the scar of the graft-host junction. It was possible to obtain images from the region of the cornea that was not clearly visible by slit-lamp examination because of a corneal opacity. CONCLUSION: OCT is a noncontact and noninvasive technique that can be performed safely on diseased corneas. OCT can provide objective documentation of corneal disorders that cannot be obtained by slit-lamp examination. The use of OCT in conjunction with other conventional instruments should provide a more complete image of the cornea.

Adult↗

PubMed2001

Late-onset form of lattice corneal dystrophy caused by leu527Arg mutation of the TGFBI gene.

PURPOSE: To report two Japanese patients who were clinically diagnosed with late-onset and sporadic lattice corneal dystrophy (LCD) in whom a Leu527Arg mutation in the TGFBI gene was found. METHODS: Molecular genetic analysis was performed on DNA extracted from peripheral leukocytes from the patients. Exons 4, 11, and 12 of the TGFBI gene were amplified by polymerase chain reaction and directly sequenced. Histopathologic study was performed on the corneal tissue obtained during deep lamellar keratoplasty (DLK) from one of the patients. RESULTS: Patient 1 was a 74-year-old man who noticed a visual disturbance at the age of 72 years. Deep stromal opacities with nodular deposits and thick lattice lines were observed only in the right cornea, and DLK was performed. Patient 2 was an 82-year-old man who had LCD (similar in appearance to that in patient 1) in both eyes without visual disturbance. Neither of the patients had a family history of corneal problems and had no episode of corneal erosion. A heterozygous single base-pair transition (CTG to CGG, leucine to arginin) was detected in codon 527 of the TGFBI gene in both patients. No mutation was found in codons 124, 501, 518, 546, or 555. Histopathologically, relatively large amyloid deposits in the deep corneal stroma and ribbons of amyloid deposits just beneath the Bowman's layer were observed in the corneal tissue of patient 1. CONCLUSIONS: Clinical features and pathologic findings of the late-onset form of LCD with an L527R mutation in the TGFBI gene were made clear.

Aged↗

PubMed2001

Triple anterior chamber after full-thickness lamellar keratoplasty for lattice corneal dystrophy.

PURPOSE: To report a patient with lattice corneal dystrophy type I (LCDI) who developed a triple anterior chamber after full-thickness lamellar keratoplasty (LKP). METHODS: A 46-year-old woman underwent a full-thickness LKP in her right eye for visual disturbances caused by LCDI. Her visual acuity was 20/200 OD before surgery. A complete ophthalmic examination, including slit lamp biomicroscopy and optical coherence tomography (OCT), was performed before and after surgery. Molecular genetic analysis was performed on DNA extracted from the peripheral leukocytes. RESULTS: The surgery was performed uneventfully; however, extra spaces posterior to the graft, along with the severe graft edema, were observed to form a triple anterior chamber a few days after surgery. The extra spaces resolved in 3 weeks with no surgical treatment, and her visual acuity improved to 20/20 OD without correction 3 months after surgery. The triple anterior chamber was clearly demonstrated by OCT, but not by slit lamp biomicroscopy. A heterozygous single base-pair transition (CGC to TGC, arginin to cysteine) was detected in codon 124 of the TGFBIgene in the patient. CONCLUSION: The separation of the graft and the host's deep corneal tissue and a Descemet's membrane detachment in the host's cornea caused the triple anterior chamber. The Descemet's membrane detachment demonstrated the weak adhesion of the stroma and the Descemet's membrane, probably resulting from a dysfunction of the TGFBI protein caused by the mutation of the TGFBIgene. OCT is useful for the objective documentation of the posterior corneal region even with severe corneal edema.

Anterior Chamber↗

PubMed2001

Surface ultrastructure of collagen fibrils and their association with proteoglycans in human cornea and sclera by atomic force microscopy and energy-filtering transmission electron microscopy.

PURPOSE: We aimed to investigate the possible association of proteoglycans with D-periodic collagen fibrils in the human cornea and sclera, using energy-filtering transmission electron microscopy (EF-TEM) and atomic force microscopy (AFM). METHODS: Human cornea and sclera were digested with keratanase to eliminate keratan sulfate proteoglycans (KSPGs). For EF-TEM observation, surface proteoglycans were detected by cupromeronic blue (CB) staining. For AFM observation, cornea and sclera were treated with sodium hydroxide before and after keratanase digestion, and the surface topology of collagen fibrils was analyzed. RESULTS: With CB staining, numerous CB-positive short filaments of surface proteoglycans (proteoglycan filaments) were observed in the interfibrillar spaces of cornea and sclera associated with collagen fibrils. AFM imaging showed that the depth and periodicity of D-periodic collagen fibrils in keratanase-treated corneal collagens were deeper and more regular than in untreated ones. Moreover, the depth and periodicity of keratanase-untreated corneal collagens were shallow and irregular in comparison with keratanase-untreated scleral collagens. On the other hand, there was no difference in depth or regularity between keratanase-treated and -untreated scleral collagen fibrils. Using AFM imaging, additional thin grooves sub-bands were detected on the surface of keratanase-treated corneal collagen fibrils. The grooves were not detected in keratanase-untreated collagen fibrils nor in scleral collagen fibrils with or without keratanase digestion. Comparing densitometry waves, the grooves of D-periodic corneal collagen sub-bands corresponded to a and c bands. CONCLUSION: Using AFM and EF-TEM to study corneal and scleral collagen fibrils and their association with proteoglycans, we conclude that KSPG is found in ample amounts in the human cornea in comparison with sclera. Moreover, we topologically detected KSPG attached to a and c bands of collagen fibrils.

Aged↗

PubMed2001

Hydroxyfasudil, an active metabolite of fasudil hydrochloride, relaxes the rabbit basilar artery by disinhibition of myosin light chain phosphatase.

Fasudil hydrochloride (AT877, hexahydro-1-(5-isoquinolinesulfonyl)-1H-1,4-diazepine hydrochloride, identical to HA1077) inhibits cerebral vasospasm after subarachnoid hemorrhage in experimental animals and humans. In the current study, the vasorelaxing mechanism of hydroxyfasudil, a hydroxylated metabolite of fasudil hydrochloride, was determined in the rabbit basilar artery. The effects of hydroxyfasudil on tension, intracellular Ca2+ concentration ([Ca2+]i), and phosphorylation of the myosin light chain were examined using the isolated and intact or permeabilized rabbit basilar artery without endothelium in vitro. In the intact rabbit basilar artery, hydroxyfasudil elicited a concentration-dependent relaxation of the artery precontracted with 1 nmol/L endothelin-1 (ET-1) plus 20 mmol/L KCl without any significant decrease in [Ca2+]i as determined by fura-2 microfluorometry (IC50: 5.1 +/- 4.6 micromol/L). The relaxation induced by hydroxyfasudil was accompanied with dephosphorylation of the myosin light chain. In the permeabilized preparation, hydroxyfasudil inhibited the contraction induced by ET-1, guanosine 5'-O-(3-thiotriphosphate), or the catalytic subunit of rho-associated kinase, but it did not inhibit Ca2+-induced contraction under the condition of inhibited myosin light chain phosphatase. Hydroxyfasudil showed a greater relaxant effect under decreased adenosine triphosphate (ATP) levels. The present study indicated that hydroxyfasudil relaxes the rabbit basilar artery mainly by disinhibiting myosin light chain phosphatase through the inhibition of rho-associated kinase and that this effect depends on the intracellular ATP concentration.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed2001

Blood transfusion increases radical promoting non-transferrin bound iron in preterm infants.

BACKGROUND: Blood transfusion has been recognised as a risk factor for the development of retinopathy of prematurity (ROP) or chronic lung disease (CLD) in preterm infants, but the precise mechanism involved is not understood. AIM: To investigate the level of non-transferrin bound "free" iron, which has the potential to promote the generation of reactive oxygen species, and its redox status in the plasma of preterm infants immediately before and after blood transfusion. METHODS: Twenty one preterm infants with a median gestational age and birth weight of 27 weeks and 1021 g respectively were prospectively enrolled in the study. Sixteen of the 21 infants developed ROP and/or CLD. The infants were transfused with concentrated red blood cells at a median age of 32 days. The plasma concentration of total bleomycin detectable iron (BDI) was measured and also the ferrous iron (Fe(2+)) activity by bleomycin-iron complex dependent degradation of DNA. RESULTS: Even before blood transfusion, BDI was detectable in one third of the blood samples, and all but one sample had ferrous iron activity. After transfusion, both BDI and ferrous iron activity were significantly increased, in contrast with the situation in full term infants. Plasma ascorbic acid (AA) concentration was significantly decreased after blood transfusion, whereas the level of its oxidation product, dehydroascorbic acid (DHAA), and the DHAA/AA ratio were significantly increased compared with before the transfusion. The activity of plasma ferroxidase, which converts iron from the ferrous to the ferric state, was appreciably decreased in preterm infants, as expected from their very low plasma caeruloplasmin concentration. CONCLUSIONS: Plasma non-transferrin bound iron was significantly increased in preterm infants after blood transfusion and existed partly in the ferrous form, because of the low ferroxidase activity and the reduction of ferric iron (Fe(3+)) by ascorbic acid. This finding was specific to preterm infants and was not observed in full term infants after blood transfusion. Non-transferrin bound "free" iron may catalyse the generation of reactive oxygen species, which may be responsible for the clinical association of blood transfusion with ROP and CLD.

Anti-Bacterial Agents↗

PubMed2001

Point mutation (-69 G-->A) in the promoter region of cholesteryl ester transfer protein gene in Japanese hyperalphalipoproteinemic subjects.

Cholesteryl ester transfer protein (CETP) transfers cholesteryl ester (CE) from HDL to apolipoprotein (apo) B-containing lipoproteins and plays a crucial role in reverse cholesterol transport, which is a major protective system against atherosclerosis. Genetic CETP deficiency is the most common cause of a marked hyperalphalipoproteinemia (HALP) in the Japanese, and various mutations have been identified in the coding region as well as in the exon/intron boundaries in the CETP gene. In the present study, we identified a novel mutation in the promoter region of the CETP gene. This mutation was a G-to-A substitution at the -69 nucleotide of the promoter region (-69 G-->A), corresponding to the second nucleotide of the PEA3/ETS binding site (CGGAA) located upstream of the putative TATA box. Four (2.0%) of 196 unrelated subjects with a marked HALP (HDL cholesterol >/=2.59 mmol/L=100 mg/dL) were revealed to be heterozygous for the -69 G-->A mutation, and the allelic frequency of the mutant was 0.0102 in the subjects with a marked HALP. The subjects with the -69 G-->A mutation had low plasma CETP levels. Reporter gene assay showed that this mutation markedly reduced the transcriptional activities in HepG2 cells (8% of wild type). These results suggested that this mutation would be dominant negative. In conclusion, a novel -69 G-->A mutation in the CETP gene causes the decreased transcriptional activity leading to HALP.

Carrier Proteins↗

PubMed2001

Downregulation of angiotensin II type 1 receptor by hydrophobic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in vascular smooth muscle cells.

3-Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors, so-called statins, reduce the relative risk of a major coronary event by lowering the serum cholesterol level. In addition, statins may confer beneficial effects by cholesterol-lowering independent mechanisms, which are incompletely characterized. Because angiotensin II (Ang II) plays crucial roles in the pathogenesis of cardiovascular diseases, we examined the effect of statins on the expression of the Ang II type 1 receptor (AT(1)-R) in cultured vascular smooth muscle cells (VSMCs). Cerivastatin and fluvastatin reduced the AT(1)-R mRNA and the AT(1)-R protein levels; however, pravastatin lacked this effect. Cerivastatin and fluvastatin suppressed the AT(1)-R promoter activity measured by luciferase assay but did not affect AT(1)-R mRNA stability, suggesting that the suppression occurs at the transcriptional level. Coincubation of VSMCs with mevalonate or geranylgeranyl pyrophosphate but not with farnesyl pyrophosphate reversed the cerivastatin-induced AT(1)-R downregulation. Overexpression of dominant-negative Rho A also suppressed AT(1)-R mRNA expression. Treatment with cerivastatin for 24 hours reduced the calcium response of VSMCs to Ang II. Taken together, statins downregulate AT(1)-R expression through a mevalonate-dependent, geranylgeranyl pyrophosphate-dependent, and Rho A-dependent manner and attenuate the biological function of Ang II. Downregulation of AT(1)-R may contribute to the cholesterol-independent beneficial effect of statins on the cardiovascular system.

Animals↗

PubMed2001

Triggering the induction of myofibroblast and fibrogenesis by airway epithelial shedding.

Myofibroblasts have been thought to participate in subepithelial fibrosis in asthma, but the mechanism of myofibroblast induction has not been fully understood. In this study we investigated injury-related myofibroblast induction in a coculture system of guinea-pig epithelial cells and fibroblasts cocultured in a human amnion chamber. After pseudostratified epithelial cells were mechanically scraped, migrated flat epithelial cells differentiated into cuboidal appearances on Day 4 and then returned to their original shapes on Day 8. During the course of the epithelial redifferentiation, it was found by Northern blot analysis, immunohistochemistry for alpha-smooth muscle actin, and electron microscopic observation that the myofibroblasts were transiently induced on Day 4. The myofibroblast induction was inhibited by the blocking of transforming growth factor (TGF)-beta1 and thrombospondin (TSP)-1, indicating that the activation of TGF-beta1 by TSP-1 would induce myofibroblasts. This finding was also supported by a transient upregulation of TSP immunoreactivity and TSP-1 messenger RNA (mRNA) in fibroblasts. Interestingly, epithelial injury reduced TGF-beta1 immunoreactivity in the amnion membrane but did not affect TGF-beta1 mRNA in epithelial cells and fibroblasts, indicating that TGF-beta1 supplied from the extracellular matrix can participate in myofibroblast induction. Concurrently with myofibroblast induction, procollagen type I and III mRNAs were upregulated in fibroblasts, and obvious collagen deposition was observed ultrastructurally around the myofibroblasts compared with the fibroblasts. These results indicate that induced myofibroblasts can be functionally more active in producing collagen than are resting fibroblasts. The present study suggests that epithelial injury stimulates TGF-beta1 release from the extracellular matrix and its activation via TSP-1 production, causing collagen synthesis through myofibroblast induction.

Actins↗

PubMed2001

Tissue inhibitor of metalloproteinases-2 gene polymorphisms in chronic obstructive pulmonary disease.

Proteinase/antiproteinase imbalance is the most widely accepted theory for development of chronic obstructive pulmonary disease (COPD). Mutations of tissue inhibitor of metalloproteinases-2 (TIMP-2) that downregulate its activity may increase the activities of matrix metalloproteinases and result in the degradation of the lung matrix. Polymorphisms of the TIMP-2 gene were investigated in 88 COPD patients and 40 control subjects. The variations were examined by single-strand conformational polymorphism analysis followed by sequencing. Two polymorphisms were identified, +853 GIA and -418 G/C nucleotide substitutions. There was a significant deviation in the genotypic frequencies at +853 and the allele frequencies for G were significantly higher in the COPD patient group than in the control group. For locus -418, the allele frequencies for C in the COPD patient group also tended to be higher than those in the control group. The +853 G/A nucleotide substitution was a silent variant. The -418 G/C substitution was located in the consensus sequence for the Sp1 binding site. These polymorphisms may be associated with the development of chronic obstructive pulmonary disease, decreasing the transcription and stability of the messenger ribonucleic acid, and available as genetic markers of susceptibility to the disease.

Aged↗

PubMed2001

A novel and simple type of liposome carrier for recombinant interleukin-2.

The strong interaction between recombinant interleukin-2 (IL-2) and liposome was characterized and its possible application to drug-delivery control considered. The liposomes were prepared with egg phosphatidylcholine, distearoyl-phosphatidylglycerol (DSPG), dipalmitoyl-phosphatidylcholine, dipalmitoyl-phosphatidylglycerol or distearoyl-phosphatidylcholine (DSPC). Small and hydrophobic liposomes were selected, which were composed of saturated and long-fatty-acid-chain phospholipids. When the composition and the mixture ratio of IL-2 and the liposomewere optimized, morethan 95% ofthe lyophilized IL-2 (Imunace, 350000 JRU) was adsorbed consistently onto the DSPC-DSPG liposome (molar ratio, 10:1; 25 micromol mL(-1); 30 nm in size). Merely mixing IL-2 lyophilized with liposome suspension is convenient pharmaceutically. After intravenous administration to mice, liposomal IL-2 was eliminated half as slowly from the systemic circulation as free IL-2, with more than 13 and 18 times more IL-2 being delivered to the liver and spleen, respectively. After subcutaneous administration of liposomal IL-2 to mice, the mean residence time of IL-2 in the systemic circulation was 8 times that of free IL-2. These results show that IL-2 consistently adsorbs onto the surface of liposomes after optimization of its composition and mixing ratio. Intravenous and subcutaneous administration to mice demonstrates the gradual release of IL-2. Further trials are warranted using these liposomes.

Algorithms↗

PubMed2001

Antidiabetic effect of an acidic polysaccharide (TAP) from Tremella aurantia and its degradation product (TAP-H).

Continuous oral administration of the acidic polysaccharide (TAP) solution (0.5 g/l) and the TAP-H (degradation products of TAP) solution (1.5 g/l) instead of water for 10 weeks were found to depress plasma glucose increases in diabetes using genetically non-insulin-dependent diabetic model (KK-Ay) mice. TAP and TAP-H significantly lowered levels of insulin, total-cholesterol and triglyceride in the blood of the mice. In excretion to feces, TAP and TAP-H significantly increased the total bile acid, while the cholesterol content of both groups was less than that of the control. Furthermore, TAP and TAP-H significantly decreased the plasma lipoperoxide level. The study shows that TAP and TAP-H have an antidiabetic effect on diabetes model mice.

Animals↗