Biomedical subjects

S Kawakami

Publications and source records attributed to S Kawakami.

At least 55 records · Page 3Linked to original sources

PubMed2001

Sustained ocular delivery of tilisolol to rabbits after topical administration or intravitreal injection of lipophilic prodrug incorporated in liposomes.

To improve the retention time of tilisolol in the precorneal area or vitreous body, we prepared liposomes incorporating the O-palmitoyl prodrug of tilisolol. O-Palmitoyl tilisolol was completely incorporated in the liposomes. After topical administration of O-palmitoyl tilisolol liposomes to the rabbit eye, O-palmitoyl tilisolol rapidly disappeared from the tear fluid. The inclusion of 2% carmellose sodium slightly prolonged the retention of O-palmitoyl tilisolol in the tear fluid. After intravitreal injection of O-palmitoyl tilisolol liposomes, there was a relatively prolonged retention of O-palmitoyl tilisolol in the vitreous body. At 24 and 48 h after intravitreal injection of O-palmitoyl tilisolol liposomes, the tilisolol concentration in the vitreous body was significantly higher compared with the concentration after intravitreal injection of tilisolol liposomes.

Administration, Topical↗

PubMed2001

Effect of instillation method on the absorption of phenolsulphonphthalein as a model drug from the liver and small intestinal serosal surface in rats.

We have examined the effect of the instillation method on the absorption of a drug from the liver and the small intestinal serosal surface in rats. We performed continuous microinstillation via an infusion pump and bolus instillation via a syringe, using phenolsulphonphthalein (phenol red) as the model drug. After continuous microinstillation of phenolsulphonphthalein 2.35 mg in 235 microL for 5 min on the liver and small intestinal serosal surface in rats, the AUC (area under the curve) of the plasma concentration profile up to 60 min was significantly higher compared with bolus instillation. A similar trend was observed after continuous microinstillation of phenolsulphonphthalein 2.35 mg in 117.5 microL for 2.5 min. The calculated absorption rate constants (Ka) after continuous microinstillation of phenolsulphonphthalein based on a two-compartment model with first-order absorption were higher than those after bolus instillation on the liver and small intestinal serosal surface at either instillation concentration. Moreover, Ka was increased after continuous microinstillation of 2.35 mg in 117.5 microL at either instillation site. Instillation of phenolsulphonphthalein on the liver surface resulted in a 1.2- to 2.3-fold higher Ka compared with the small intestinal serosal surface. This tendency was marked after continuous microinstillation of 2.35 mg in 117.5 microL. In conclusion, absorption could be enhanced by instilling a small amount of drug solution on the liver surface gradually and continuously, suggesting a promising approach for instillation site-selective drug delivery in the peritoneal cavity.

Algorithms↗

PubMed2001

Serum progesterone and estradiol-17beta concentrations, and lapaloscopic observations of the ovary in the cheetah (Acinonyxjubatus) with pregnant mare serum gonadotropin and human chorionic gonadotropin treatments.

In 3 adult female cheetahs, induced-superovulation treatment was conducted, by means of 200 IU of pregnant mare serum gonadotropin (PMSG) and 100 IU of human chorionic gonadotropin (hCG) 80 hr after PMSG. The administration of PMSG created a sharp increase in the estradiol-17beta concentration, resulting in 232 pg/ml 8 hr later in one specimen out of three. The hCG administration showed an increase in the progesterone concentration of 2.29 ng/ml 46 hr later. In addition, after direct observation of the ovary surface by laparoscopy, 5 follicles in the right ovary over 2 mm in diameter, and 7 corpora lutea (5 in the right ovary and 2 in the left) were found. It is assumed that ovulation can be induced with hCG after 80 hr on PMSG during a cheetah's diestrus or proestrus.

Acinonyx↗

PubMed2001

Hepatic necrosis with cholestasis induced by long-term voglibose administration.

A 76-year-old woman admitted to our hospital for jaundice had been treated for diabetes mellitus with insulin for 9 years and voglibose had been added for the 39 months preceding admission. Elevated serum bilirubin and transaminase concentration began to normalize with initiation of corticosteroid treatment 1 week after discontinuation of voglibose. In the in vitro testing of the patient's peripheral blood, lymphocytes showed stimulation by voglibose. In dramatic contrast to an initial liver biopsy specimen that demonstrated cholestasis with submassive and zonal necrosis, the follow-up specimen was normal 1 year later. We believe that patients treated with voglibose should be monitored long-term with monthly determinations of transaminases and bilirubin in serum.

Aged↗

PubMed2001

High-resolution CT analysis of small peripheral lung adenocarcinomas revealed on screening helical CT.

OBJECTIVE: The purpose of this study was to determine the correlation between high-resolution CT morphologic features of small peripheral lung adenocarcinomas and tumor growth patterns. MATERIALS AND METHODS: We examined high-resolution CT morphologic features of 59 small, surgically resected peripheral lung adenocarcinomas (diameter, 6-20 mm) that were detected on screening for lung cancer using low-dose helical CT. Among these adenocarcinomas, 14 (24%) were visible and 45 (76%) were invisible on conventional chest radiography. The correlation between high-resolution CT morphologic features and tumor growth patterns was analyzed. RESULTS: Sixteen (94%) of 17 type A (Noguchi's classification) adenocarcinomas appeared as nodules of pure ground-glass attenuation (high-resolution CT type I). Ten (71%) of 14 type B tumors appeared as heterogeneous, low-attenuation nodules (type II). Seven (29%) of 24 type C tumors appeared as nodules with ground-glass attenuation in the periphery and a high-density central zone (type III), and 12 (50%) of 24 type C tumors appeared as homogeneous nodules with soft-tissue density (type IV). Among tumors with a replacement growth pattern, the size and CT values of type C tumors were larger than those of type A or type B tumors (p < 0.05), whereas the percentage of ground-glass attenuation and retained air space in type C tumors was smaller than those in type A or type B tumors (p < 0.01). All (100%) four type D tumors appeared to be homogeneous nodules with soft-tissue density (type IV). CONCLUSION: Small peripheral lung adenocarcinomas shown on CT exhibit four high-resolution CT patterns that corresponded to the histopathologic findings of different tumor growth patterns.

Adenocarcinoma↗

PubMed2001

Parotid masses: prediction of malignancy using magnetization transfer and MR imaging findings.

OBJECTIVE: We determined the most accurate criteria for predicting malignancy of masses in the parotid gland using magnetization transfer ratios. SUBJECTS AND METHODS: Lesion-to-muscle magnetization transfer ratios obtained with a spoiled gradient-recalled acquisition in a steady state sequence with a 1-kHz off-resonance pulse were measured in 72 parotid masses (52 benign lesions, 20 malignant tumors). Various MR imaging findings and lesion-to-muscle magnetization transfer ratios were simultaneously assessed using a logistic model to determine the useful factors for predicting malignancy. We also studied the clinical usage of magnetization transfer ratios. RESULTS: Of the MR imaging findings, poorly defined margins showed the highest accuracy, 81%, with 60% sensitivity and 88% specificity. Of the lesion-to-muscle magnetization transfer ratios, a ratio of greater than 0.71 was most accurate (85%), with 90% sensitivity and 83% specificity. All four recurrent tumors and 10 (91%) of 11 secondary tumors were correctly diagnosed using the magnetization transfer ratio analysis. The logistic model revealed that the margin characteristics (p = 0.084) and lesion-to-muscle magnetization transfer ratios (p < 0.001) were statistically significant predictors for malignancy. A combined criteria of poorly defined margins and a lesion-to-muscle magnetization transfer ratio of greater than 0.71 raised the accuracy to 86% and specificity to 96%, but the sensitivity decreased to 60%. CONCLUSION: A combination of MR imaging findings and lesion-to-muscle magnetization transfer ratios was the most accurate predictor of malignancy.

Female↗

PubMed2001

Tracheal invasion by thyroid carcinoma: prediction using MR imaging.

OBJECTIVE: The purpose of this study was to evaluate the accuracy of MR imaging in predicting tracheal invasion by thyroid carcinomas and to determine MR imaging criteria for diagnosing tracheal invasion. MATERIALS AND METHODS: MR imaging was performed on the normal trachea of one cadaver and 30 healthy subjects as a standard of reference. Then, MR imaging findings in 67 patients with thyroid carcinoma were reviewed and correlated with surgical and pathologic findings. A logistic regression model was used to determine which MR imaging features were significant for predicting tracheal invasion. RESULTS: Twenty-three (34%) of the 67 patients had tracheal invasion. Logistic regression model analysis revealed that significant MR characteristics for determining tracheal invasion included soft-tissue signal in the tracheal cartilage (p < 0.001), intraluminal mass (p < 0.001), and degree of tumor circumference around the trachea (p = 0.001). The highest accuracy (90%) for determining tracheal invasion was achieved using a combination of findings. A case was considered positive for tracheal invasion if there was soft-tissue signal in the cartilage, an intraluminal mass, or a tumor that abutted a circumference of the trachea of 180 degrees or greater. Using these factors resulted in seven false-positive diagnoses because soft-tissue signal in the cartilage was sometimes seen in healthy trachea. Although intraluminal mass invariably reflected deep tracheal invasion, soft-tissue signal in the cartilage rarely indicated actual cartilage invasion but rather indicated tumor extension between the cartilaginous rings. CONCLUSION: Tracheal invasion by thyroid carcinomas can be accurately diagnosed with MR imaging, and using a combination of criteria is the most accurate method of predicting this phenomenon.

Adult↗

PubMed2001

Enhanced gene transfection in macrophages using mannosylated cationic liposome-polyethylenimine-plasmid DNA complexes.

We have previously reported that plasmid DNA and cholesten-5-yloxy-N-(4-[(1-imino-2-beta-D-thiomannosylethyl)amino]butyl) formamide(Man-C4-Chol)/dioleoylphosphatidylethano-lamine(DOPE)(6:4) liposome complexes (DNA/Man-complexes) exhibit efficient gene transfection in macrophages via mannose receptor-mediated endocytosis. To further enhance gene transfetion, polyethylenimine (PEI) was incorporated into this liposome complex (DNA/Man-PEI-complexes), noticing a pH-buffering capacity in endosomes and DNA-condensing activity of PEI. In mouse peritoneal macrophages, the uptake and transfection activity of DNA/Man-PEI-complexes were 2-times and 6-times higher than those of DNA/Man-complexes, respectively. Furthermore, the presence of 1 mg/ml mannan significantly inhibited both the uptake and transfection efficiency of DNA/Man-PEI-complexes. These results suggested that the newly developed multifunctional DNA/Man-PEI-complexes exhibit highly improved gene transfection in macrophages via mannose receptor-mediated endocytosis.

Animals↗

PubMed2001

Lingual calcinosis circumscripta in a captive sitatunga.

Calcinosis circumscripta (CC) was found in a 10-yr-old female sitatunga (Bovidae; Tragelaphus spekei). At necropsy, there were two white coalescing nodules (3 x 5 x 2 cm, 2 x 2 x 1.5 cm) on the ventral side of the tongue. The cut surface of the nodules had multiple, well-circumscribed loculi with chalky appearance and gritty consistency, separated by thin strands of connective tissue. Histologically, the nodules contained multiple loculi of various sizes and shapes, which consisted of amorphous material that was pale basophilic with H&E stain, surrounded by fibrous connective tissue. Around the loculi were numerous foreign body giant cells and epithelioid macrophages; occasional lymphocyte aggregations also were seen. The amorphous material was positive for PAS and von Kossa's stain. Calcinosis circumscripta is rare in the Bovidae.

Animals↗

PubMed2001

Malignant melanoma of the palpebral conjunctiva in a captive fallow deer.

A case of malignant melanoma in the conjunctiva of the eyelid of a captive 13-yr-old female fallow deer (Dama dama) was studied. The black tumor that protruded to the palpebral conjunctiva of the right lower eyelid consisted of an infiltrative growth of melanin-containing neoplastic cells with marked cytological atypia. The tumor involved the conjunctiva of the right lower eyelid and infiltrated to the conjunctival epithelial layer, but did not reach the palpebral skin. Numerous mitotic figures and lymphatic invasions were observed. This is a very rare case of a malignant melanoma arising from the palpebral conjunctiva in a wild ruminant.

Animals↗

PubMed2001

[Gynecologic and obstetric disorders presenting with abdominal pain].

This article briefly reviews the clinical settings and imaging findings of gynecologic/obstetric disorders presenting with abdominal pain. MR imaging is considered to be an excellent modality for the diagnosis of these disorders because of its high sensitivity to blood. Although CT allows images to be obtained within a shorter time than does MR imaging, the possibility of pregnancy should be excluded prior to the examination. Hemorrhagic ovarian cyst exhibits hyperintensity on T1-weighted images or hematocrit effect on CT or MR images. Hemoperitoneum associated with hemorrhagic cyst strongly indicates rupture of the cyst. Rupture of endometrial cysts and dermoid cysts can cause acute chemical peritonitis. In ectopic pregnancy, findings of hematosalpinx associated with strong enhancement of the tubal wall frequently contribute to the diagnosis. Torsion of the adnexa can be diagnosed by the pedicle between the ovary and uterus, and the lack of contrast enhancement. Tuboovarian abscess is recognized as a cystic mass having a thick wall that is strongly enhanced. Among complications of uterine leiomyoma, red degeneration shows characteristic MR findings, hyperintense rim on T1-WI, hypointense rim on T2-WI, and lack of contrast enhancement. Because of the high incidence of OHSS associated with normal pregnancy, CT is contraindicated.

Abdomen, Acute↗

PubMed2001

[Study of neoadjuvant chemotherapy for invasive bladder cancer with MEC (methotrexate, epirubicin, cisplatin) therapy].

Eighteen patients with locally invasive bladder cancer were treated with 1 or 2 cycles of neoadjuvant chemotherapy consisting of methotrexate, epirubicin and cisplatin (MEC). All patients underwent radical cystectomy and pelvic lymph node dissection. Down-staging was observed in twelve (complete pathological response in 3 and partial pathological response in 9) patients (response rate were 67%). Four of the 18 patients died of disease and all of them had not achieved down-staging. Multivariate analysis revealed nodal status to be the only independent predictor. With regard to side effects, gastrointestinal symptoms and myelo-suppression were observed in almost all patients. Thrombocytopenia was observed in 13 patients (72%) including 7 patients who showed symptoms over grade 3. Gastro-intestinal symptoms and leukocytopenia disappeared with granisetron and granulocyte colony stimulating factor. There were no treatment-related deaths in this study. These results indicate that MEC therapy was safely performed and showed a high response rate in patients with locally invasive bladder cancer.

Aged↗

PubMed2001

[Efficacy of a single-day administration of levofloxacin for the prevention of urinary tract infections after urogenital examinations and treatments for outpatients].

The clinical efficacy of a single-day oral administration of levofloxacin (LVFX) for the prevention of urinary tract infections (UTI) after urogenital examinations and treatments for outpatients was assessed. A single-day oral administration of LVFX, 100 mg three times a day, was compared to a single dose intra-muscular injection of 100 mg netilmicin sulfate or 100 mg dibekacin sulfate. Three of 219 cases (1.4%) and 7 of 304 cases (2.3%) contracted UTI in the single-day oral administration group and the single dose intra-muscular injection group, respectively. Adverse reactions were observed in 3 of 219 cases (1.4%) and 27 of 304 cases (8.8%) in the single-day oral administration group and the single dose intra-muscular injection group, respectively. In the single dose intra-muscular injection group, UTI and adverse reactions were more severe than in the single-day oral administration group. Therefore, a single-day oral administration of LVFX was superior to a single dose intra-muscular injection of netilmicin sulfate or dibekacin sulfate in the prevention of UTI with less probability of the adverse effects. A single-day oral administration of LVFX was concluded to be sufficient for the prevention of UTI caused by examinations and treatments for outpatients.

Administration, Oral↗

PubMed2000

Biodistribution characteristics of mannosylated, fucosylated, and galactosylated liposomes in mice.

The in vivo disposition behavior and pharmacokinetic characteristics of galactosylated (Gal), mannosylated (Man) and fucosylated (Fuc) liposomes were compared in this study. For the preparation of the glycosylated liposomes, cholesten-5-yloxy-N-(4-((1-imino-2-beta-D-thiogalactosyle thyl)amino)a lkyl)formamide (Gal-C4-Chol) (Kawakami et al., Biochem. Biophys. Res. Commun. 252 (1998) 78-83) and its mannosylated and fucosylated derivatives (Man-C4-Chol and Fuc-C4-Chol, respectively) were synthesized. The glycosylated liposomes are composed of distearoylphosphatidylcholine (DSPC), cholesterol (Chol), and Gal-C4-Chol (or Man-C4-Chol or Fuc-C4-Chol) with the molar ratio of 60:35:5. After intravenous injection in mice, these three types of [(3)H]cholesteryl hexadecyl ether-labeled glycosylated liposomes were rapidly eliminated from the circulating blood and preferentially recovered in the liver. In contrast, DSPC/Chol (60:40) liposomes without glycosylation were retained for a long time in the circulating blood. The uptake ratios by parenchymal cells (PC) and nonparenchymal cells (NPC) (PC/NPC ratios) for 0.5% Gal, Man and Fuc liposomes were found to be 15.1, 0.6 and 0.2, respectively. The effect of predosing glycosylated proteins and liposomes on the hepatic uptake of 0.5% (3)H-labeled Gal, Man, and Fuc liposomes was investigated and the results support the conclusion that Gal, Man, and Fuc liposomes are taken up by the liver via asialoglycoprotein receptors in PC, mannose receptors in NPC, and fucose receptors in NPC, respectively. Interestingly, Gal liposomes were taken up by NPC rather than by PC at a high dose (5%). Together with the finding that 5% Gal liposomes inhibit the hepatic uptake of (3)H-labeled Fuc liposomes, this suggests that Gal-liposomes administered at a high dose will also be taken up by fucose receptors in NPC, that are considered to act as galactose particle receptors.

Animals↗

PubMed2000

Double-labeled donor probe can enhance the signal of fluorescence resonance energy transfer (FRET) in detection of nucleic acid hybridization.

A set of fluorescently-labeled DNA probes that hybridize with the target RNA and produce fluorescence resonance energy transfer (FRET) signals can be utilized for the detection of specific RNA. We have developed probe sets to detect and discriminate single-strand RNA molecules of plant viral genome, and sought a method to improve the FRET signals to handle in vivo applications. Consequently, we found that a double-labeled donor probe labeled with Bodipy dye yielded a remarkable increase in fluorescence intensity compared to a single-labeled donor probe used in an ordinary FRET. This double-labeled donor system can be easily applied to improve various FRET probes since the dependence upon sequence and label position in enhancement is not as strict. Furthermore this method could be applied to other nucleic acid substances, such as oligo RNA and phosphorothioate oligonucleotides (S-oligos) to enhance FRET signal. Although the double-labeled donor probes labeled with a variety of fluorophores had unexpected properties (strange UV-visible absorption spectra, decrease of intensity and decay of donor fluorescence) compared with single-labeled ones, they had no relation to FRET enhancement. This signal amplification mechanism cannot be explained simply based on our current results and knowledge of FRET. Yet it is possible to utilize this double-labeled donor system in various applications of FRET as a simple signal-enhancement method.

DNA Probes↗

PubMed2000

Disposition characteristics of emulsions and incorporated drugs after systemic or local injection.

Lipid emulsions are useful tools for controlling the in vivo disposition of drugs and plasmid DNA. The dispositions of lipid emulsions are determined by their tissue interaction depending on the anatomical and physiological characteristics of each tissue and the physicochemical and biological properties of lipid emulsions. In addition, the retention of drugs is another issue, as too rapid a release of the drug would lead to failure of exerting its therapeutic potency. This review presents an overview about the disposition profiles and various physicochemical properties of lipid emulsions and incorporated drugs after systemic or local injection. Controlled biodistribution of lipid emulsions and incorporated drugs are also discussed.

Animals↗

PubMed2000

Controlled biodistribution of galactosylated liposomes and incorporated probucol in hepatocyte-selective drug targeting.

Two types of galactosylated liposomes containing cholesten-5-yloxy-N-(4-((1-imino-2-beta-D-thiogalactosyle thyl)amino)b utyl)formamide (Gal-C4-Chol) as a homing device were prepared to study the biodistribution of liposomal carriers and the incorporated drug. Distearoylphosphatidylcholine (DSPC)/cholesterol (Chol)/Gal-C4-Chol (60:35:5) (Gal DSPC), DSPC/Chol (60:40) (DSPC), egg yolk phosphatidylcholine (eggPC)/Chol/Gal-C4-Chol (60:35:5) (Gal eggPC), and eggPC/Chol (60:40) (eggPC) liposomes labeled with [(3)H]cholesteryl hexadecyl ether (CHE) were tested and [(14)C]probucol, with a partition coefficient between octanol and water (PC(oct)) of 10(10.8), was selected as a model drug with lipophilicity suitable for liposomal incorporation. After intravenous injection of the combination of [(14)C]probucol and [(3)H]liposomes, the liver uptake of [(3)H]CHE was the highest in Gal DSPC liposomes, followed by Gal egg PC liposomes, egg PC liposomes, and DSPC liposomes in that order. [(14)C]Probucol incorporated in Gal DSPC liposomes exhibited lower liver uptake than [(3)H]CHE, suggesting that substantial release from liposomes had taken place. In contrast, [(14)C]probucol incorporated in Gal eggPC liposomes was more stably incorporated under in vivo conditions. Co-administration with galactosylated bovine serum albumin significantly inhibited the liver uptake of [(14)C]probucol in both types of galactosylated liposomes, suggesting that the hepatic uptake of liposomes should be mediated by asialoglycoprotein receptors being [(14)C]probucol incorporated in them.

Animals↗

PubMed2000

Ultramicroanalysis of reducing carbohydrates by capillary electrophoresis with laser-induced fluorescence detection as 7-nitro-2,1,3-benzoxadiazole-tagged N-methylglycamine derivatives.

A method for ultramicroanalysis of carbohydrates using capillary electrophoresis with laser-induced fluorescence detection was developed, based on precapillary conversion to 7-nitro-2,1, 3-benzoxadiazole (NBD)-tagged N-methylglycamines. Although the derivatization involves two-step reactions, i.e., reductive N-methylamination followed by condensation with NBD-F, they can be carried out in a one-pot fashion and proceed quantitatively within ca. 50 min in total. Since the reaction conditions are mild, it does not cause desialylation. The derivatives can be well separated by capillary electrophoresis and sensitively detected by argon laser-induced fluorescence. It allowed detection of monosaccharides of down to nanomolar concentrations for analytical sample solution, which correspond to the attomole injected amounts, and good linearity was observed over a wide range. It was also successfully applied to analysis of N-glycans in a microgram quantity of a glycoprotein. Studies on the cleanup of derivatized product are also described in relation to N-glycan analysis.

4-Chloro-7-nitrobenzofurazan↗