Biomedical subjects

T Higashi

Publications and source records attributed to T Higashi.

At least 91 records · Page 5Linked to original sources

PubMed1999

Effects of imidapril on NOS expression and myocardial remodelling in failing heart of Dahl salt-sensitive hypertensive rats.

OBJECTIVES: To elucidate the relationship between renin-angiotensin system and nitric oxide in hypertensive heart failure, we evaluated the effects of long-term treatment with imidapril, angiotensin-converting enzyme inhibitor, on endothelial-cell nitric oxide synthase (eNOS) and inducible NOS (iNOS) expression in the left ventricle (LV) and its relation to myocardial remodelling in failing heart of Dahl salt-sensitive hypertensive rats (DS) fed a high-salt diet. METHODS: In DS rats fed an 8% NaCl diet after the age of 6 weeks, a stage of concentric left ventricular hypertrophy at 11 weeks (DSLVH) was followed by a distinct stage of fatal left ventricular failure with chamber dilatation at 18 weeks (DSCHF). Imidapril (DSCHF-I, n = 7, 1 mg/kg/day, subdepressor dose) or vehicle (DSCHF-V, n = 7) were given from DSLVH to DSCHF stage for 7 weeks, and age-matched (18 weeks) Dahl salt-resistant rats fed the same diet were served as control group (DR-C, n = 7). RESULTS: Markedly increased left ventricular end-diastolic diameter and reduced fractional shortening in DSCHF-V was significantly ameliorated in DSCHF-I using transthoracic echocardiography. The level of eNOS mRNA and protein in the LV was significantly suppressed in DSCHF-V compared with DR-C, and significantly increased in DSCHF-I compared with DR-C and DSCHF-V. The iNOS mRNA and protein and the fibrosis factor expression of type I collagen mRNA were significantly increased in DSCHF-V compared with DR-C, and significantly decreased in DSCHF-I compared with DSCHF-V. DSCHF-V demonstrated a significant increase in wall-to-lumen ratio, perivascular fibrosis, and myocardial fibrosis. These changes in the microvasculature were improved significantly by imidapril. CONCLUSIONS: Subdepressor dose of imidapril may ameliorate the endothelial damage not only by inhibiting production of angiotensin II but also by promoting eNOS and inhibiting iNOS mRNA and protein expression in the LV, and this increased eNOS mRNA and protein level may have a role in the improvement of congestive heart failure and myocardial remodelling.

Analysis of Variance↗

PubMed1999

Contribution of PET in the detection of liver metastases from pancreatic tumours.

AIM: Although uptake of 2-deoxy-2-[fluorine-18]fluoro-D-glucose (FDG) in the liver is basically high, metastatic liver tumours are known to be positive on positron emission tomography (PET). The purpose of this study is to evaluate the diagnostic accuracy of FDG-PET in detecting hepatic metastases from pancreatic cancer. METHODS: Thirty-four patients with histologically proven malignant tumours of the pancreas underwent FDG-PET, computed tomography (CT) and transabdominal ultrasound (US). The findings of PET, CT and US were compared with the histopathologic findings at surgery or with clinical follow-up and the diagnostic accuracy of PET was evaluated. RESULTS: PET showed 28 regions of high FDG uptake (SUV = 3.3-9.1) in 13 patients. Twenty-six foci were metastatic lesions confirmed by surgery (n = 11), clinical follow-up (n = 10) or autopsy (n = 5). FDG-PET accurately differentiated seven metastatic lesions from cysts when the diagnosis by US or CT was unreliable because of the small size of the lesion. In two patients who had areas of high uptake in the liver, no metastases were detected by surgery. FDG-PET showed no areas of increased uptake in 21 patients. Surgery revealed no metastatic lesions in the liver in 20 of 21 patients, but a liver metastasis was found at surgery in one patient. The diagnostic accuracy of FDG-PET was 90%, which was comparable with that of US or CT. CONCLUSION: Our data suggest that PET is reliable in detecting liver, metastases from pancreatic cancer.

Adenocarcinoma↗

PubMed1999

In vitro and in vivo glucuronidation of 24,25-dihydroxyvitamin D3.

Glucuronidation of 24,25-dihydroxyvitamin D3 has been investigated in in vitro and in vivo experiments. Three positional isomers of 24,25-dihydroxyvitamin D3 monoglucuronide were synthesized from 24,25-dihydroxyprovitamin D3 derivatives with Koenigs-Knorr reaction and used as standard samples. In the presence of the rat liver microsomal fraction and uridine-5'-diphosphoglucuronic acid, 24,25-dihydroxyvitamin D3 gave 3- and 24-glucuronides as the main products in almost equal amounts, but only a small amount of the corresponding 25-glucuronide was obtained. 24,25-Dihydroxyvitamin D3 monoglucuronide was deconjugated with rat intestine homogenate, which indicated the entero-hepatic circulation of 24,25-dihydroxyvitamin D3. After the administration of 24,25-dihydroxyvitamin D3 to rats, its 3- and 24-glucuronides were identified from the bile as inferred from the in vitro experiment. However, the in vivo glucuronidation occurred at the 24-position in preference to the 3-position, and the corresponding 25-glucuronide was not detected. These glucuronides were identified in comparison with standard samples based on their chromatographic behavior during high-performance liquid chromatography and data obtained from liquid chromatography-electrospray ionization-mass spectrometry, which was helpful in identifying these compounds.

24,25-Dihydroxyvitamin D 3↗

PubMed1999

Benidipine stimulates nitric oxide synthase and improves coronary circulation in hypertensive rats.

We evaluated the effects of long-term treatment with benidipine, a long-acting calcium antagonist, on endothelial cell-type nitric oxide synthase (eNOS) activity and eNOS mRNA expression in the left ventricle (LV) and its relation to coronary flow reserve, and microvascular remodeling in renovascular hypertensive rats (RHR: 2K-1C Goldblatt). Benidipine (5 mg/kg/day) was given to RHR (B-RHR, n = 11) for 6 weeks. Vehicle-treated RHR (U-RHR, n = 11) and age-matched sham-operated rats (ShC, n = 11) served as control group. Coronary flow reserve was measured in conscious rats using colored microspheres. Fifty-micrometer slices of the LV were incubated with L-arginine to measure nitrite production using the Griess method and eNOS mRNA expression was determined by reverse transcription-polymerase chain reaction. An increased blood pressure in RHR was significantly decreased by benidipine. Nitrite production and eNOS mRNA expression in the LV of U-RHR was significantly lower than that of ShC. This suppression of nitrite production and eNOS mRNA expression was significantly reversed in B-RHR. U-RHR demonstrated a significant decrease in coronary flow reserve and capillary density, and a significant increase in wall-to-lumen ratio, perivascular fibrosis, myocardial fibrosis, and myocyte cross-sectional area. These impaired factors were improved significantly by benidipine. These findings suggest that benidipine therapy may increase nitrite production and eNOS mRNA expression not only by lessening the endothelial damage by the reduction of blood pressure levels, but also by the stimulation of NOS activity and eNOS mRNA, and this increased NOS activity and eNOS mRNA expression may play a role in the amelioration of coronary flow reserve and microvascular remodeling.

Animals↗

PubMed1999

Expression of membrane cofactor protein (MCP, CD46) in human liver diseases.

Membrane cofactor protein (MCP, CD46) is one of the complement regulatory proteins, and is widely distributed in human organs and protects cells from complement-mediated cytotoxicity. We analysed the distribution and the intensities of MCP in liver diseases and evaluated the role of MCP during hepatocarcinogenesis. Western blot analysis revealed that relative densities (density of the sample/density of the standard sample) of MCP in 27 HCC, 18 liver cirrhosis, nine chronic hepatitis and 12 normal liver were 0.63+/-0.23, 0.21+/-0.07, 0.25+/-0.10 and 0.11+/-0.03 (mean+/-s.d.) respectively. MCP expression in hepatocellular carcinoma (HCC) was significantly higher than that in both liver cirrhosis and chronic hepatitis (P < 0.01). The difference in the tumour sizes, the grades of differentiation and viral marker status did not affect the expression. Immunohistological analysis revealed that MCP was distributed mainly in the basolateral membrane of the hepatic cord in non-cancerous liver, along with endothelial cells and bile duct cells. In HCC, the protein was observed on the membrane in a non-polarized fashion. These data suggest that HCC cells acquire the increased MCP expression in a development of HCC and may escape from tumour-specific complement-mediated cytotoxicity.

Antigens, CD↗

PubMed1999

Expression of MAGE-1 and -3 genes and gene products in human hepatocellular carcinoma.

MAGE gene family encodes peptides recognized by autologous cytotoxic T lymphocytes in a major histocompatibility complex (MHC) class-I restricted fashion. In the present study, we have performed reverse-transcription polymerase chain reaction (RT-PCR) for the genes, as well as immunohistochemical analysis and Western blotting of MAGE-1 and -3 proteins in 33 surgically resected hepatocellular carcinomas (HCCs). MAGE-1 and -3 mRNAs were constitutively expressed exclusively in 78 and 42% of HCCs respectively. On immunohistochemistry with monoclonal antibodies, 77B for MAGE-1 and 57B for MAGE-3, MAGE-1 and -3 proteins were recognized in cytoplasm of only six among 33 (18%) and two of 29 HCCs (7%) respectively. The distribution pattern was mostly focal in HCC nodules. By contrast, the Western blot analysis revealed that the MAGE-1 (46 kDa) and -3 proteins (48 kDa) were expressed in 80 and 60% of 15 HCCs examined respectively. The proteins of MAGE-1 and -3 were also expressed exclusively in HCCs regardless of the histological grading and clinical staging. Our results indicate that the detection of the genes by RT-PCR or the proteins by Western blotting is useful for differentiating early HCCs from non-cancerous lesions, and that the peptides derived from MAGE-1 and -3 proteins might be suitable targets for immunotherapy of human HCC.

Adult↗

PubMed1999

A method for detecting breakthrough of organic solvent vapors in a charcoal tube using semiconductor gas sensors.

This study developed a method for detecting organic vapors that break through charcoal tubes, using semiconductor gas sensors as a breakthrough detector of vapors. A glass column equipped with two sensors was inserted in Teflon tubing, and air containing organic vapor was introduced at a constant flow rate. After the output signal of the sensors became stable, a charcoal tube was inserted into the tubing at the upstream of the sensors. The resistance of the sensors was collected temporally in an integrated circuit (IC) card. The vapor concentration of the air near the sensors was measured with a gas chromatograph (GC) equipped with a flame ionization detector (FID) at intervals of 5 minutes to obtain the breakthrough curve. When the relative humidity was zero, the output signals of the sensors began to change before the breakthrough point (1% breakthrough time). This tendency was almost the same for methyl acetate, ethyl acetate, isopropyl alcohol (IPA), toluene, and chloroform. For dichloromethane and 1,1,1-trichloroethane, the time when the sensor output signals began to rise was almost the same as the breakthrough point. When the relative humidity was 80 percent, the sensors could also detect many vapors before the breakthrough point, but they could not perceive dichloromethane and chloroform vapors. A personal sampling system with a breakthrough detector was developed and its availability is discussed.

Air Pollution, Indoor↗

PubMed1999

Autoimmune pancreatitis with F-18 fluoro-2-deoxy-D-glucose PET findings

Two cases of pancreatitis induced by autoimmunity with PET images using F-18 fluoro-2-deoxy-D-glucose (FDG) are reported. The patients had abdominal pain and were thought to have possible pancreatic neoplasms. In one patient, PET showed intense uptake of the entire pancreas, but a Ga-67 scan yielded a negative result. Because the serum immunoglobulin G level was high, autoimmune pancreatitis was diagnosed in this patient. He underwent steroid therapy and fully recovered. In another patient with positive antinuclear antibodies and hyperglobulinemia, focal intense uptake was found in the head of the pancreas on the FDG PET. She also recovered with steroid therapy. Autoimmune pancreatitis is a relatively new form of chronic pancreatitis and should be kept in mind when making a differential diagnosis of pancreatic cancer with the assistance of FDG PET.

Journal Article↗

PubMed1999

Complete response to twice-a-day interferon-beta with standard interferon-alpha therapy in acute hepatitis C after a needle-stick.

A 25-year-old male physician with acute hepatitis C after needle-stick injury was treated with combination therapy including twice-a-day interferon-beta (IFN-beta) and standard interferon-alpha (IFN-alpha). The infecting strain was of genotype 1b. Pretreatment hepatitis C virus (HCV) RNA levels were high. Because severe paresthesias occurred with initial daily administration of 5 million units (MU) of lymphoblastoid IFN-alpha, the dose was reduced to 3 to 6 MU of IFN-alpha2b three times a week. However, HCV RNA was not cleared from serum after 20 weeks of standard IFN-alpha2b treatment. A 4-week course with IFN-beta, at the dosage of 3 MU twice daily i.v. drip, was then started and followed by an 18-week course with IFN-alpha2b, 6 MU thrice weekly. After IFN-beta treatment, HCV RNA was cleared from serum without severe adverse effects, including paresthesias. Total amounts of IFN administered were 20 MU of lymphoblastoid IFN-alpha, 648 MU of IFN-alpha2b, and 252 MU of IFN-beta. Complete response and avoidance of chronic HCV infection were achieved. Thus, combination therapy with twice-a-day IFN-beta and standard IFN-alpha was effective in treating an acute hepatitis C patient with a high viral load and sensitivity to adverse effects of high-dose IFN-alpha.

Acute Disease↗

PubMed1999

Relationship between serum leptin and fatty liver in Japanese male adolescent university students.

OBJECTIVE: The aim of this study was to elucidate the relationship between serum leptin levels and fatty liver in male adolescents. METHODS: We investigated the relationship between the concentration of circulating leptin and fatty liver by measuring the serum concentration of leptin in 284 male students who received the matriculation health examination in Okayama University in 1996 (n = 197; age, 18-20 yr) or 1997 (n = 87; age, 18-20 yr). RESULTS: Serum leptin levels correlated positively with body mass index (BMI), percent body fat (%FAT), thickness of skin fold (TSF), and serum concentration of ALT in 197 subjects. Examination of serum leptin in 67 subjects with BMI > or = 24.2 but < 28.6 kg/m2 showed a progressively higher levels in subjects with high serum ALT. Serum leptin levels in subjects with abnormally high serum ALT (> or = 37 IU/L) were significantly higher (p < 0.05) than in subjects with normal serum ALT, independent of BMI, %FAT, and TSF. Serum leptin levels were also significantly higher in subjects with fatty liver (detected by abdominal ultrasonography), independent of BMI and %FAT, compared with subjects without fatty liver. Stepwise multiple regression analysis showed that serum leptin level was an independent risk factor for fatty liver. In addition, serum leptin levels correlated with serum ALT (r = 0.518; p < 0.0005) and cholinesterase (r = 0.511; p < 0.0005) levels in 48 subjects with fatty liver. CONCLUSIONS: Our results demonstrated that serum leptin concentrations are high in male adolescents with simple obesity and are associated with high serum ALT or fatty liver, independent of BMI and %FAT, suggesting that the concentration of circulating leptin correlates with fatty liver caused by accumulation of visceral fat.

Adipose Tissue↗

PubMed1999

Focal (segmental) dyshidrosis in syringomyelia.

The features or mechanisms of dyshidrosis have not been sufficiently clarified. Neither has the difference between hyperhidrosis and hypohidrosis. To clarify the features and mechanisms of dyshidrosis (hyperhidrosis and hypohidrosis) in syringomyelia, the clinical features focusing on hidrosis of 30 patients with syringomyelia and Chiari malformation located from a syringomyelia database were prospectively analysed. The patients were classified into three groups: eight patients (26.7%) had segmental hypohidrosis, 10 (33. 3%) had segmental hyperhidrosis, and 12 (40.0%) had normohidrosis. We found that the Karnofsky functional status for the hyperhydrosis and normohidrosis groups were significantly higher than for the hypohidrosis group (p=0.0012), with no significant differences between the hyperhidrosis and normohidrosis groups. The duration from the onset of syringomyelia to the current dyshidrosis was significantly longer in the hypohidrosis group than in the hyperhidrosis group (p=0.0027). A significant correlation was identified between the duration from the onset of syringomyelia to the time at study and the performance score (r=-0.599, p=0.0003). The results substantiate previous hypotheses that in its early stage syringomyelia causes segmental hyperactivity of the sympathetic preganglionic neurons, and hyperactivity of these gradually subsides as tissue damage progresses. Focal hyperhidrosis may be regarded as a hallmark of a relatively intact spinal cord, as well as normohidrosis.

Adolescent↗

PubMed1999

Levels of 24,25-dihydroxyvitamin D3, 25-hydroxyvitamin D3 and 25-hydroxyvitamin D3 3-sulphate in human plasma.

The concentrations of (24R)-24,25-dihydroxyvitamin D3[24,25(OH)2D3], 25-hydroxyvitamin D3[25(OH)D3] and its 3-sulphate [25(OH)D3(3)S] in the plasma of healthy subjects, patients with chronic renal failure, patients with climacteric syndrome, pregnant women and foetuses were determined using the enzyme-linked immunosorbent assay and high-performance liquid chromatography. 25(OH)D3(3)S was not detected in about one-third of the plasma samples from patients with chronic renal failure (n = 26). The three metabolites in maternal plasma reached the highest levels in the second trimester of pregnancy followed by a decrease to the values obtained in the first trimester. Older healthy women (age range 44-71 years) showed higher levels of 24,25(OH)2D3 and 25(OH)D3 in the plasma than did young healthy women (age range 21-29 years), whereas no clear difference was observed between the older healthy women and patients with climacteric syndrome. The level of 25(OH)D3(3)S in the plasma was higher in the latter patients than in healthy women.

24,25-Dihydroxyvitamin D 3↗

PubMed1999

New metabolic pathway of (24R)-24,25-dihydroxyvitamin D3: epimerization of the 3-hydroxy group.

A new metabolic pathway of (24R)-24,25-dihydroxyvitamin D3 [24,25(OH)2D3] was clarified in the in vivo experiments. After the administration of 24,25(OH)2D3 to rats, a new monoglucuronide of a vitamin D metabolite was obtained from the bile together with 24,25(OH)2D3 3- and 24-glucuronides. The genin of the metabolite was identified as 3-epi-24,25(OH)2D3 in comparison with the synthetic sample based on the data from 1H-NMR, GC/MS, and LC/atmospheric pressure chemical ionization-MS. The conjugation position was determined to be the 24-hydroxy group by the LC/electrospray ionization-MS and -MS/MS/MS combined with derivatization. To our knowledge, this is the first reported instance of the epimerization of the 3-hydroxy group of vitamin D compound with no hydroxy group at the 1alpha-position.

24,25-Dihydroxyvitamin D 3↗

PubMed1999

[Development of analysis of vitamin D metabolites].

Vitamin D (D) plays important roles for homeostasis of serum calcium and so on, in human after metabolic activation. The measurements of concentrations of D metabolites in biological fluids are important for clinical and nutritional diagnoses. In these respects, developments of analysis of D metabolites, especially the phase I reaction products (free metabolites), have been carried out. In the first part of this report, the advance in developments of analysis of the free metabolites is reviewed according to the methodology over the last five years. The phase II reaction products (conjugated metabolites) of D, which are poorly understood compared to the free metabolites, are recently found in many kinds of animals, and much interest is focused on their physiological roles. In the second part, an overview of the identification and quantification of the conjugated D metabolites in biological fluids is presented mainly from our studies.

Animals↗

PubMed1999

Combined effect of cigarette smoke and mineral fibers on the gene expression of cytokine mRNA.

To investigate which parameters are stimulated by mineral fibers and whether cigarette smoke enhanced a fiber-induced response, we examined the level of cytokine mRNA from alveolar macrophages (AMs) and lungs of rats exposed to mineral fibers and cigarette smoke in vivo. Male Wistar rats were given a single intratracheal instillation of 2 mg of Union Internationale Contre le Cancer chrysotile or refractory ceramic fiber (RF1). The animals then inhaled a side stream of smoke 5 days per week for 4 weeks. The expression of manganese superoxide dismutase, inducible nitric oxide synthase (iNOS), basic fibroblast growth factor (bFGF), interleukin-1[alpha] (IL-1[alpha]), interleukin-6 (IL-6), and tumor necrosis factor-[alpha] (TNF[alpha]) mRNA from lipopolysaccharide-stimulated AMs and lungs of rats exposed to mineral fibers and/or cigarette smoke were assessed using semiquantitative reverse-transcriptase polymerase chain reaction. Exposure only to cigarette smoke increased in IL-1[alpha] mRNA levels in AMs. Chrysotile stimulated the expression of IL-1[alpha], TNF[alpha], and IL-6 in AMs, and the expression of bFGF in lungs. RF1 resulted in increased expression of IL-1[alpha] and TNF[alpha] in AMs. Cigarette smoke stimulated the gene expression of iNOS in AMs and IL-6 and bFGF in lungs treated with chrysotile; IL-1[alpha] in AMs and bFGF in lungs did the same in lungs with RF1. Among these cytokines, message levels of IL-1[alpha], iNOS, and bFGF were increased in rats stimulated with mineral fibers, and the stimulating effects of mineral fibers were enhanced by cigarette smoke. Therefore, IL-1[alpha], iNOS, and bFGF would be the possible parameters of the lung remodeling induced by mineral fibers.

Animals↗

PubMed1999

A clearance model of inhaled man-made fibers in rat lungs.

A clearance model of inhaled man-made fibers (MMFs) was developed, and the calculated fiber numbers and dimensions were compared with the experimental ones using a glass fiber (GF), ceramic fiber (RF1) and two potassium octatitanate whiskers (PT1, TW). If the translocation rate by macrophages is constant and the effect of dissolution and disintegration can be ignored, the fiber number is expected to decrease exponentially with time. In the experimental study, however, the fiber number did not always decrease exponentially. In the case of RF1, the fiber number decreased almost exponentially and the diameter decreased linearly with the time. The clearance rate constant of GF during 3 to 6 months after the end of one-month exposure was greater than that during 1 to 3 months. On the contrary, the clearance rate constants of PT1 and TW during 1 to 6 months were greater than next six months. The diameter and the length of GF did not change significantly. The fiber length of PT1 tends to become longer with time although the diameter did not change significantly. Our theoretical model gives a satisfactory fit to these experimental results.

Administration, Inhalation↗

PubMed1999

Effects of mineral fibers on the gene expression of proinflammatory cytokines and inducible nitric-oxide synthase in alveolar macrophages.

To determine which parameters are useful for the risk assessment of man-made mineral fibers (MMMFs), we examined the gene expression of interleukin-1 alpha (IL-1 alpha), tumor necrosis factor alpha (TNF alpha), interleukin-6 (IL-6) and inducible nitric-oxide synthase (iNOS) in mineral fiber-exposed alveolar macrophages (AMs). Male Wistar rats were intratracheally exposed to saline or mineral fibers suspended in saline (2 mg of crocidolite, chrysotile, alumina silicate refractory fiber (RF1) or potassium octatitanate whisker (TW)). Bronchoalveolar lavage was performed 4 weeks after the fiber-instillation, and the recovered AMs were stimulated by lipopolysaccharide for 2 or 6 hours. Expression of IL-1 alpha, TNF alpha, IL-6 and iNOS from AMs was observed using reverse transcription-polymerase chain reaction (RT-PCR). The levels of IL-1 alpha and IL-6 mRNA induced by mineral fiber exposure were greatest in AMs exposed to TW, crocidolite, chrysotile and RF1 in that order. However, both gene expression of iNOS and TNF alpha were not elevated in both crocidolite and TW exposure, despite their high pathological potential. These data suggested that IL-1 alpha and IL-6 may be useful indicators for the risk assessment of MMMFs.

Administration, Inhalation↗

PubMed1999

The relationship of glycosylation and isoelectric point with tumor accumulation of avidin.

UNLABELLED: Radiolabeled avidin markedly accumulated in intraperitoneal tumors and was cleared rapidly from circulation when given intraperitoneally. This study investigated the mechanisms of the tumor localization of avidin. METHODS: Avidin was deglycosylated through endoglycosydase-H digestion and/or neutralized by acetylation of its lysine amino acids with acetic acid N-hydroxysuccinimide ester. Avidin and modified avidins were analyzed using sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS/PAGE) and isoelectric focusing. A tumor model was established by intraperitoneal injection of human colon cancer cells, LS180, in nude mice. Avidin and modified avidins were labeled with 111In using diethyleneamine pentaacetic acid-biotin and were administered intraperitoneally into the tumor-bearing mice. The biodistribution of radioactivity was examined 2 and 24 h postinjection. RESULTS: Deglycosylated avidins revealed a major band of smaller molecules on SDS/PAGE. The isoelectric point of neutralized avidins was reduced to less than 5, whereas that of unneutralized avidins was more than 9.5. Biodistribution study demonstrated that liver uptake was decreased by deglycosylation and kidney accumulation was decreased by neutralization, respectively. The blood clearance was remarkably slowed by combined modification of deglycosylation and neutralization. The tumor uptake of radioactivity was reduced by either deglycosylation or neutralization and was further decreased with combined modification. CONCLUSION: Both high glycosylation and positive charge of avidin contributed to its accumulation in tumor. This study may facilitate development of a new vehicle for the delivery of therapeutic agents to intraperitoneal tumors.

Animals↗