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J Watanabe

Publications and source records attributed to J Watanabe.

At least 145 records · Page 8Linked to original sources
PubMed1998

Development of emulsion type new vehicle for soft gelatin capsule. I. Selection of surfactants for development of new vehicle and its physicochemical properties.

Screening of surfactants was carried out to develop an oil in water (o/w) emulsion type new vehicle for a soft gelatin capsule (SGC), using polyethyleneglycol 400 (PEG 400) as hydrophilic phase and medium chain triglyceride (Miglyol 810), propyleneglycol dicaprylate (Sefsol 228) or soybean oil as hydrophobic phase (PEG 400: hydrophobic phase: surfactant = 87:10:3) and by means of simple homogenization. Polyoxyethylene (20) cetylether (BC-20TX), which can form homogeneous and viscous white gels using the above hydrophilic and hydrophobic phase combination, was selected as a model surfactant for developing the new vehicle. Using Miglyol 810 as hydrophobic phase, a model new vehicle formulation (PEG 400:water:Miglyol 810: BC-20TX = 77:10:10:3) was prepared, and its physicochemical properties were evaluated. The particle size distribution of the new vehicle, after diluting about 3000 times with water, ranged from about 0.5 to 50 microns. Furthermore, the new vehicle had thixotropic property at room temperature (about 25 degrees C) and temperature-dependent gel-sol transforming property with the transformation temperature of about 37 degrees C. These properties meet the requirement for encapsulation of the new vehicle in SGC and suggest that it can be expected to form the o/w emulsion state in the aqueous environment in the stomach. The rheological properties would also make it advantageous for use in other dosage forms such as suppository, cataplasm or liniment.

Capsules↗
PubMed1998

[Pharmacokinetic analysis of scavenger receptor-mediated uptake of mucopolysaccharides in various cells].

Although the scavenger receptor-mediated uptake has been qualitatively investigated in the research fields of biochemistry and pathology, pharmacokinetic characteristics of the scavenger receptors are poorly understood. In this review, we summarized basic findings on scavenger receptors reported in available literature, and introduced our recent studies on the quantitative characteristics of the scavenger receptor-mediated uptake. High molecular weight fractionated [3H]heparin (HMWFH, 16,000-24,000 Da), one of the model mucopolysaccharides, was investigated to elucidate its uptake mechanism into isolated rat Kupffer cells, isolated peritoneal macrophages and liver parenchymal cells in primary culture. The equilibrium bindings of HMWFH to isolated Kupffer cells and peritoneal macrophages were concentration-dependent with the respective dissociation constants (Kd) of 5.7 and 6.0 nM and with the respective maximum binding capacities (Bmax) of 1.5 and 1.9 pmol/10(6) cells. Several ligands of scavenger receptors inhibited the binding of HMWFH to macrophages, suggesting the involvement of scavenger receptors in the uptake of HMWFH by these macrophages. It was also suggested that the scavenger receptor-mediated uptake is different from the receptor-mediated endocytosis of polypeptides and phagocytosis, based on the evidence of the now inhibitory effects of an inhibitor of receptor-mediated endocytosis of polypeptides(phenylarsine oxide) and phagocytosis inhibitors (cytochalasine B and colchicine) on the internalization. The involvement of scavenger-like receptors was also suggested in the uptake of HMWFH by liver parenchymal cells in primary culture by demonstrating inhibitory effects of ligands for scavenger receptors. The internalization into liver parenchymal cells by scavenger-like receptors was not affected by an inhibitor of receptor-mediated endocytosis of polypeptides and phagocytosis inhibitors, similarly to the results in the macrophage scavenger receptors. The Kd of 53.5 nM and Bmax of 32.8 pmol/10(6) cells in parenchymal cells were both in the order of magnitude larger than those in isolated Kupffer cells, suggesting the binding of HMWFH to scavenger-like receptors in parenchymal cells with lower affinity and higher capacity. On the other hand, an apparent internalization rate constant (kint, app) of 0.0056 min-1 was comparable with that in Kupffer cells (0.0118 min-1). Thus, we demonstrated the involvement of scavenger receptors in the uptake of HMWFH by rat Kupffer cells, peritoneal macrophages and liver parenchymal cells, and succeeded in characterizing the uptake kinetically. These findings should provide useful information for not only establishing the rational clinical use of mucopolysaccharides but also developing new drugs such as antiatherosclerotic agents and peptides delivered to cells with scavenger receptors.

Animals↗
PubMed1998

Isolation and identification of acetyl-CoA carboxylase inhibitors from green tea (Camellia sinensis).

An aqueous methanol extract from green tea showed potent acetyl-CoA carboxylase inhibitory activity. An active compound was isolated from the extract and identified as (-)-epigallocatechin gallate by instrumental analyses. The IC50 value of (-)-epigallocatechin gallate was 3.1 x 10(-4) M. Among tea catechins and related compounds, nearly equal activity was found in (-)-epigallocatechin gallate and (-)-epicatechin gallate, whereas (+)-catechin, (-)-epicatechin, (-)-epigallocatechin, gallic acid and methyl gallate each had no inhibitory activity. These results indicate that the 3-O-gallate group of the catechin structure was necessary for this activity. (-)-Epigallocatechin gallate inhibited triglyceride accumulation in 3T3-L1 cells at a concentration of 1.0 x 10(-7) M or higher.

Acetyl-CoA Carboxylase↗
PubMed1998

Carbamazepine-induced sinus node dysfunction and atrioventricular block in elderly women.

We report on four elderly women in whom carbamazepine was suspected of inducing sinus node dysfunction (3 patients) and atrioventricular block (1 patient). Patients were treated with carbamazepine, 200 to 600 mg a day, for trigeminal neuralgia (n = 3) or epilepsy (n = 1). After 1 to 16 months of carbamazepine therapy, these patients were admitted to our emergency room because of bradyarrhythmia. Their conduction disturbances on electrocardiographic monitoring disappeared immediately after the cessation of carbamazepine intake. Provocation tests were performed on three patients. Because of renal insufficiency, one patient could not undergo the provocation test. Her carbamazepine clearance was markedly decreased. Carbamazepine induced sinus arrest in two patients within 48 hours after intake, but did not induce atrioventricular block in the remaining patient. In two patients, computer simulation of carbamazepine pharmacokinetics was performed and disclosed a clear-cut relationship between the plasma concentration of carbamazepine and the frequency of sinus arrest. During the test, the maximum plasma carbamazepine concentration in these two patients did not exceed the therapeutic range. However, it did exceed the range in the one with a negative test. Our results suggest that careful monitoring of ECG and plasma drug concentration is required with carbamazepine therapy, especially in elderly women.

Aged↗
PubMed1998

Involvement of macrophage scavenger receptors in protection against murine malaria.

Macrophage scavenger receptor A (MSR-A) deficient mice MSR-A(-/-) were infected by the intraperitoneal injection of the Plasmodium berghei NK65 strain in the erythrocytic stage. The MSR-A(-/-) mice died significantly earlier than the control mice (P=0.060). In the surviving mice, two peaks of parasitemia were observed: the first 5-7 days and the second at 2-3 weeks after infection. Death of all MSR-A(-/-) mice occurred at either peak of parasitemia, suggesting that MSR-A protects mice from severe infection. This model may be useful for the study of molecular mechanisms of macrophage functions in malaria infection.

Animals↗
PubMed1998

Determination of accuracy of quantitative immunohistochemical results with an antigen-immobilized filter model system.

To determine accuracy of quantitative immunohistochemical results, serially diluted liver cell lysates from methylcholanthrene (MC)-treated rats containing cytochrome P-450 (P-450) 1A were immobilized on nitrocellulose (NC) filters and stained by the indirect immunoperoxidase method under saturation conditions. The stained filters were processed for image analysis and the relationship between the resulting immunostaining intensity due to P-450 1A and the antigen amount immobilized on the filters was examined. The relationship examined in the filters fitted with an exponential curve. Thus, the intensity due to P-450 1A is not simply proportional to the antigen amount. Subsequently, immunostaining intensity due to P-450 1A was measured in sections from control and methylcholanthrene (MC)-treated rats by image analysis with an image processor, and the antigen content in cell lysates from control and MC-treated animals was measured immunochemically by quantitative single radial immunodiffusion. Although immunochemically measured P-450 1A content in the lysates increased markedly (26 times), average staining intensity in sections increased slightly (2-3 times) after MC injection. However, when the exponential curve obtained from the filter binding assay was used as a standard curve to convert staining intensity in sections to molar content of P-450 1A, the resulting content was compatible with the immunochemical content. The divergence between the increase in immunochemically measured P-450 1A content and that in immunostaining intensity in sections after MC injection is therefore attributed primarily to the curvilinear relationship between the intensity and the content.

Animals↗
PubMed1998

[Influences of trabeculectomy combined with the use of mitomycin C on corneal endothelial cells].

We used a specular microscope to evaluate the corneal endothelial cells in 119 eyes before and 2 to 3 weeks after trabeculectomy with topical mitomycin C. The endothelial cell density per square millimeter averaged 2,569 +/- 487 (mean +/- standard deviation) before surgery and 2,444 +/- 536 after surgery, showing a decrease of 4.98%. The hexagonality decreased by 1.7%, the coefficient of variation increased by 1.9, and the average cell area increased by 6.82%. There were no statistical differences as a whole in these values. Decrease in hexagonality was more frequent in eyes with prior intraocular or glaucoma surgery. Eyes treated by laser trabeculoplasty showed a decrease in endothelial cell density, an increase in coefficient of variation and an increase in hexagonality. Eyes with postoperative flat anterior chamber showed significant changes in each parameter. The findings show that trabeculectomy with topical mitomycin C does not significantly affect the corneal endothelial cells at 2 to 3 weeks after surgery.

Administration, Topical↗
PubMed1998

Primary hemangiopericytoma of the superior mediastinum: a case report.

We present a case of hemangiopericytoma arising in the superior mediastinum. A 48-year-old man demonstrated a superior mediastinal mass lesion on chest x-ray and was admitted to our hospital. A CT scan of the chest showed a well-circumscribed, heterogenously-enhanced mass, 7.0 x 6.5 x 6.5 cm in size, located in the right superior posterior mediastinum, compressing the trachea. The tumor was extirpated by surgical resection. Based on the histological findings, electron microscopic findings, and immunohistochemical studies, the tumor was diagnosed as hemangiopericytoma.

Diagnosis, Differential↗
PubMed1998

[Glaucoma with microcornea; morphometry and differential diagnosis].

To evaluate the characteristics of 10 glaucomatous cases with microcornea, we measured corneal diameter, curvature, axial length, and depth of anterior chamber, and examined the eyes with a specular microscope and an ultrasound biomicroscope. The ten cases examined in this study included 1 case of cornea plana, 2 cases of sclerocornea, 2 cases of nanophthalmos, and 5 cases of anterior microphthalmos. Three of the 10 cases were combined with open angle glaucoma, and the others with closed angle glaucoma. Open-angle glaucoma seemed like developmental glaucoma with angle maldevelopment. The closed angle type may appear at a younger age than in patients who have simple pupilary block. There are probably complex mechanisms related with closed angle glaucoma with microcornea. While differential diagnosis among these cases is relatively easy, we should evaluate how or why the intraocular pressure rises as far as possible before forming a treatment plan for each patient.

Adolescent↗
PubMed1997

FMLP actions and its binding sites in isolated human coronary arteries.

The chemoattractant f-Met-Leu-Phe (FMLP) can modulate human coronary arterial tone without the involvement of peripheral leukocytes. We investigated the actions of FMLP and its cellular mechanism in human coronary arteries isolated 2-3 h after death. A single dose of FMLP (0.01-10 microM) produced transient contraction (or, followed by relaxation) responses in most human coronary rings examined. These responses to FMLP were in large part mediated by the generation of cyclooxygenase products, mainly thromboxane A2 (TXA2) and prostaglandin I2 (PGI2). Radiolabeled N-formyl hexapeptide. 125I-f-Nle-Leu-Phe-Nle-Tyr-Lys bound densely to intimal and adventitial sites that accumulated macrophages (CD68-positive) with a Kd of 14-29 nM and, further, weakly to the media with a Kd of 2.4-3.6 microM. Several cell types including macrophages, endothelial cells and smooth muscle cells were positively immunostained for both TXA2 synthase and PGI2 synthase. However, there was no significant relation between the magnitude of the responses to FMLP and dense macrophage accumulation in the intimal plaques or the adventitia. A reverse transcription-polymerase chain reaction showed predominant expression of FMLP receptor homologues, FPRH1 and FPRH2 mRNA, in human coronary medial tissues relative to that in leukocytes. In conclusion. FMLP produced transient tension changes in human coronary arteries, mainly via the generation of TXA2 and PGI2. This effect of FMLP did not appear to be mediated by the activation of densely accumulated intimal and/or adventitial macrophages, but by the activation of unidentified medial tissue cells which might have functional FMLP receptor homologues.

Adolescent↗
PubMed1997

Effects of mitomycin C on the expression of proliferating cell nuclear antigen after filtering surgery in rabbits.

BACKGROUND: The aim of the study was to evaluate the effects of mitomycin C on the cell replication activity in wound healing following experimental filtration surgery. METHODS: Trabeculectomy with or without application of mitomycin C was performed on albino rabbit eyes. At 1, 4, 7, 14, and 28 days after surgery, the expression of proliferating cell nuclear antigen, a marker of cell proliferation, in the filtering site was examined immunohistochemically using a streptavidin-biotin complex method. RESULTS: In control eyes that underwent trabeculectomy but did not receive mitomycin C, the number of immunoreactive cells increased 4-7 days after operation and decreased markedly at around 14 days. The filtering site was obstructed histologically at 4-7 days after operation. In the mitomycin C-treated eyes, immunoreactive cells appeared 4 days after surgery but disappeared by 7 days at the surgical site. The number of immunoreactive cells in the treated eyes was much lower than that in control eyes. CONCLUSION: The cell replication activity was markedly inhibited by administration of mitomycin C. The filtering site remained open for 28 days after surgery, whereas it was completely obstructed within 7 days in control eyes. Immunocytochemistry for proliferating cell nuclear antigen, as used in this study, is a simple and reliable method for detection of cell replication activity.

Animals↗
PubMed1997

Mediastinal parathyroid adenoma detected by 99mTc-methoxyisobutylisonitrile: report of a case.

We report herein the case of a 30-year-old man in whom ectopic mediastinal parathyroid adenoma was detected by 99mTc-methoxyisobutylisonitrile scintigraphy (99mTc-MIBI). The patient presented with a history of recurrent renal stones and was diagnosed as having primary hyperparathyroidism due to elevated serum levels of calcium and intact parathyroid hormone (i-PTH) levels. On admission, his serum calcium value was 12.1 mg/dl and the i-PTH level was 137 pg/ml. Ultrasonography, computed tomography (CT), and 201TlCl-99mTcO4- subtraction scintigraphy (Tl-Tc) were performed but none of these imaging techniques was able to detect an enlarged parathyroid gland. Selective venous sampling revealed that the serum i-PTH level was highest at 422 pg/ml in the left brachiocephalic vein. Exploration of the neck also proved unsuccessful. Finally, we performed 99mTc-MIBI which revealed and delineated an enlarged parathyroid gland in the upper mediastinum. Tumor extirpation was subsequently performed through a left thoracotomy. Pathologically, the tumor was confirmed to be a parathyroid adenoma and the serum calcium and i-PTH levels returned to within the normal ranges postoperatively.

Adenoma↗
PubMed1997

The effects of vinblastine on the expression of human immunodeficiency virus type 1 long terminal repeat.

Previous work by our group has demonstrated induction of the HIV-LTR following exposure of cells to various DNA-damaging agents such as ultraviolet (UV) light, cisplatin, and doxorubicin. The current experiments were designed to determine the relative effects of the anti-mitotic drug vinblastine on expression of the HIV-LTR. Using human cervical carcinoma (HeLa) cells stably transfected with the chloramphenicol acetyl transferase (CAT) reporter transcriptionally driven by the HIV-LTR promoter, we demonstrated a 9-10-fold induction at 48-72 h following vinblastine treatment. Previous experiments had demonstrated repression of cisplatin or doxorubicin-mediated HIV induction by treatment with salicylic acid. The vinblastine induction also was repressed by salicylic acid treatment, but not by treatment with indomethacin, suggesting a role for the NF kappa B pathway in the inductive response. When UV exposure was coupled to the vinblastine treatment, there was no additive or synergistic effect evident, suggesting similar paths of induction between the two agents. Northern blots demonstrated that these agents were operating at the level of transcription and that salicylic acid inhibited vinblastine-mediated induction of HIV-LTR-CAT mRNA only if administered at the same time as vinblastine; addition of salicylic acid 2 h later had no effect on transcript accumulation. All combinations of treatments with vinblastine and/or salicylic acid markedly reduced cell survival.

Cell Survival↗
PubMed1997

Immunohistochemical localization of type II and type I collagens in articular cartilage of the femoral head of dexamethasone-treated rats.

The immunohistochemical localization of type II and type I collagens was examined in the articular cartilage of the femoral head of growing rats injected systemically with 5 mg kg-1 dexamethasone for 2 weeks every other day. The intensities of immunostaining for type II collagen, measured by microphotometry, was highest in the flattened cell layer and high in the hypertrophic cell layer, moderate in the proliferative cell and transitional cell layers and low in the superficial layer. After dexamethasone administration, the intensities decreased markedly in the flattened cell layer and slightly in the hypertrophic cell layer, although the decreases in other layers were negligible. The staining intensities for type I collagen were highest in the flattened cell layer, low in the superficial and transitional cell layers and very low in the proliferative and hypertrophic cell layers. After dexamethasone administration, the intensities increased markedly in the flattened cell layer and slightly in the superficial and proliferative cell layers, but did not change in the transitional and hypertrophic cell layers. Thus, dexamethasone administration caused a decrease in type II collagen and an increase in type I collagen in the matrix of the surface portion of articular cartilage. The composition of isoforms of collagen in the matrix changed after the steroid administration. The results strongly that the shift in collagen composition from type II to type I predominance is a cause of the degeneration of the articular cartilage after glucocorticoid administration.

Animals↗
PubMed1997

Pathologic and clinical findings in patients with cyclosporiasis and a description of intracellular parasite life-cycle stages.

Cyclospora cayetanensis has been observed in the feces of persons with prolonged diarrhea. A description of the symptoms and histopathologic findings for patients with cyclosporiasis is presented. The intracellular life-cycle stages of these parasites in the enterocytes of patients will also be described. Seventeen Peruvian patients positive for Cyclospora organisms were surveyed and underwent endoscopy, and their symptoms were recorded. Patients presented with gastrointestinal symptoms, including diarrhea, flatulence, weight loss, abdominal discomfort, and nausea. Jejunal biopsies showed an altered mucosal architecture with shortening and widening of the intestinal villi due to diffuse edema and infiltration by a mixed inflammatory cell infiltrate. There was reactive hyperemia with vascular dilatation and congestion of villous capillaries. Parasitophorous vacuoles contained sexual and asexual forms. Type I and II meronts, with 8-12 and 4 fully differentiated merozoites, respectively, were found at the luminal end of epithelial cells. These findings demonstrate the complete developmental cycle associated with host changes due to Cyclospora organisms.

Animals↗
PubMed1997

Helicobacter pylori populations in Peruvian patients.

Helicobacter pylori is an extremely diverse species. The characterization of strains isolated from individual patients should give insights into colonization and disease mechanisms and bacterial evolution. We studied H. pylori isolates from patients in the Japanese-Peruvian Polyclinic in Lima, Peru, by determining metronidazole susceptibility or resistance and by random amplified polymorphic DNA (RAPD) fingerprinting (a measure of overall genotype). Strains isolated from several biopsy specimens from each of 24 patients were studied. Both metronidazole-susceptible and -resistant strains were isolated from 13 patients, whereas strains of more than one RAPD type were isolated from only seven patients. We propose that the homogeneity in RAPD fingerprints for strains isolated from most persons reflects selection for particular H. pylori genotypes during chronic infection in individual hosts and the human diversity in traits that are important to this pathogen. Carriage of related metronidazole-resistant and -susceptible strains could reflect frequent metronidazole use in Peru and alternating selection for resistant and susceptible phenotypes during and after metronidazole therapy.

Adult↗
PubMed1997

Rapid recurrence of Helicobacter pylori infection in Peruvian patients after successful eradication. Gastrointestinal Physiology Working Group of the Universidad Peruana Cayetano Heredia and The Johns Hopkins University.

Helicobacter pylori is associated with gastritis, peptic ulcer disease, and gastric cancer. Since gastric cancer is common in Peru, eradication of H. pylori may help to reduce the occurrence of gastric cancer. This study involved three randomized trials to determine the efficacy of four different triple-drug therapy regimens. The most successful regimen was furazolidone combined with bismuth subsalicylate and amoxicillin, which eradicated infection in 82% of patients. Patients successfully treated were followed every 2-3 months to determine the recurrence rate of H. pylori infection. Of 105 patients with H. pylori eradication documented by pathology and culture, 52% (55) returned for follow-up endoscopy, and in 73% (40) of these 55 the infection recurred during the 8-month follow-up period. Thirty-five patients from whom H. pylori was eradicated and who were tested for antibodies to H. pylori remained consistently seropositive. Rapid recurrence of H. pylori infection after successful eradication suggests that measures other than antimicrobial therapy are needed to fight H. pylori in developing countries.

Adult↗