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Biomedical subjects

T Morita

Publications and source records attributed to T Morita.

At least 91 records · Page 5Linked to original sources
PubMed2001

Applicability of various amphiphilic polymers to the modification of protein release kinetics from biodegradable reservoir-type microspheres.

The effects of various amphiphilic polymers on the kinetics of protein release from reservoir-type microspheres, prepared by a solid-in-oil-in-water emulsion-solvent evaporation method, were investigated. Bovine serum albumin (BSA), as a model protein, was firstly micronized through co-lyophilization with amphiphilic polymers, such as poly (ethylene glycol) (PEG), polyvinylpyrrolidone (PVP), and pluronic F68. This process was based on the aqueous phase separation of protein and amphiphilic polymer induced by freezing-condensation. Mixing of poly(lactic-co-glycolic acid) (PLGA) and poly(lactic acid) (PLA) (at a ratio of 4:6) in a methylene chloride solution provided a'polymer-alloy' structure, where the preformed solid BSA microparticles were selectively distributed in the inner PLGA-rich phase. The reservoir-type microspheres obtained through this process showed high entrapment efficiencies (more than 85%) and reduced initial burst releases (less than 10%). Although PVP did not modify the BSA release profile, PEG and pluronic F68 enhanced the BSA release, with no increase of the initial burst effect, responding to their loading percentage: 3% loading of PEG or pluronic F68 resulted in typical zero-order release kinetics. The abilities of these amphiphilic polymers to modify the protein release profile could be predicted from their partitioning characteristics in the polymer-alloys and in the methylene chloride/water system.

Biodegradation, Environmental↗
PubMed2001

On-chip capillary electrophoresis for alkaline phosphatase testing.

We fabricated an on-chip capillary electrophoresis device for blood analysis. An on-chip capillary electrophoresis device was photolithographically fabricated on a glass chip. Alkaline phosphatase (ALP) was employed as a sample enzyme. Small amounts of enzyme in the mixture of other proteins were detected with the electrophoretically mediated microanalysis (EMMA) method. Fluorescein diphosphate was used as fluorogenic substrate. The detection of ALP activity was achieved with laser-induced fluorescence monitoring fluorescein that was produced in enzyme reaction in capillary. Several methods to reduce the adhesion of protein are also discussed.

Alkaline Phosphatase↗
PubMed2001

Multiple accumulation of Vdelta2+ gammadelta T-cell clonotypes in intestinal mucosa from patients with Crohn's disease.

The gammadeltaT cells have been known to play an important role in the regulation of the mucosal immune system, but the relationship between these cells and the pathogenesis of Crohn's disease (CD) has remained obscure. We now demonstrate the T-cell receptor (TCR) Vdelta2 gene transcripts characterize antigenic immune response in the intestinal mucosa from patients with CD. TCR Vdelta2 gene transcripts of six patients with CD and six controls were subcloned and 20 randomly selected clones from each sample were subjected to nucleotide sequencing. Sequence analysis demonstrated that the different clones in the intestinal mucosa of CD were significantly increased (11.833 +/- 0.946) compared to controls (7.167 +/- 1.470) (P = 0.0374). The presence of intraindividual dominance and oligoclonality of TCR Vdelta2 gene transcripts in normal controls appears reflect positive selection and expansion of specific gammadelta T cells in normal controls. By contrast TCR Vdelta2 gene transcripts in the intestinal mucosa of CD can express different clonotypes. We conclude that accumulation of multiple Vdelta2+ gammadelta T-cell clonotypes are involved in the pathogenesis of CD.

Adolescent↗
PubMed2001

Adenovirus-mediated transfer of type IV collagen alpha5 chain cDNA into swine kidney in vivo: deposition of the protein into the glomerular basement membrane.

Gene therapy of Alport syndrome (hereditary nephritis) aims at the transfer of a corrected type IV collagen alpha chain gene into renal glomerular cells responsible for production of the glomerular basement membrane (GBM). A GBM network composed of type IV collagen molecules is abnormal in Alport syndrome which leads progressively to kidney failure. The most common X-linked form of the disease is caused by mutations in the gene for the alpha5(IV) chain, the alpha5 chain of type IV collagen. Full-length human alpha5(IV) cDNA was expressed in HT1080 cells with an adenovirus vector, and the recombinant alpha5(IV) chain was shown to assemble into heterotrimers consisting of alpha3(IV) and alpha4(IV) chains, utilizing a FLAG epitope in the recombinant alpha5(IV) chain. The results indicate that correction of the molecular defect in Alport syndrome is possible. Previously, we had developed an organ perfusion method for effective in vivo gene transfer into glomerular cells. In vivo perfusion of pig kidneys with the recombinant adenovirus resulted in expression of the alpha5(IV) chain in kidney glomeruli as shown by in situ hybridization and its deposition into the GBM was shown by immunohistochemistry. The results strongly suggest future possibilities for gene therapy of Alport syndrome.

Adenoviridae↗
PubMed2001

Purification, cDNA cloning and characterization of the vascular apoptosis-inducing protein, HV1, from Trimeresurus flavoviridis.

Hemorrhagic snake venom induces apoptosis in vascular endothelial cells (VEC). In previous reports, we described the purification and cDNA cloning from Crotalus atrox of a vascular apoptosis-inducing protein (VAP1) that specifically induces apoptosis in vascular endothelial cells. We report here the purification and cDNA cloning of another vascular apoptosis-inducing protein, HV1, from crude venom of Trimeresurus flavoviridis. The protein, namely HV1, was purified as an inducer of apoptosis in cultured vascular endothelial cells. HV1 was a homodimeric protein with a molecular mass of 110 kDa. HV1 cDNA encoded a protein with 612 amino-acid residues. The amino-acid sequence predicted from the cDNA was highly homologous to VAP1. The amino-acid sequence of HV1 indicated that HV1 belongs to the metalloprotease/disintegrin family, and that it is a multidomain polypeptide with a proprotein domain, a metalloprotease domain, a disintegrin-like domain and a cysteine-rich domain. In the disintegrin-like domain, the sequence DECD, replaces the RGD sequence that has frequently been found in such domains. This replacement also occurs in VAP1. Our results indicate HV1 as the first identified homolog of VAP1.

Amino Acid Sequence↗
PubMed2001

Primary testicular plasmacytoma with hydrocele of the testis.

A case of primary testicular plasmacytoma complicated with hydrocele of the testis is reported. An 86-year-old man presented with hydrocele of the right testis. High inguinal orchiectomy was performed as the preoperative aspiration cytology of the hydrocele fluid showed atypical cells. Immunohistochemical study of the right testis revealed testicular plasmacytoma positive for IgG. He remained well 9 months after the orchiectomy. This is the second reported case where the preoperative diagnosis of testicular plasmacytoma was made based on the hydrocele fluid cytology.

Aged↗
PubMed2001

Primary signet ring cell carcinoma of female urethra.

A 69-year-old woman presented with difficulty in urination and bloody fluid discharge from the urethra. Based upon a diagnosis of primary urethral carcinoma, she underwent total cysto-urethrectomy and hysterectomy with pelvic lymph node dissection and urinary diversion of ileal conduit. Microscopically, the tumor was composed of mucinous adenocarcinoma and signet ring cell carcinoma. There was no recurrence 17 months after the surgery.

Adenocarcinoma, Mucinous↗
PubMed2001

Malignant fibrous histiocytoma of the right spermatic cord: a case report.

The patient was a 47-year-old male, who visited Hidaka Hospital with a chief complaint of swelling in the right inguinal region and the scrotum. With a diagnosis of a right spermatic cord tumor, right high orchiectomy was performed. Since an inflammatory type of malignant fibrous histiocytoma (MFH) was diagnosed from histopathological findings, chemotherapy and radiation therapy were performed as postoperative treatment. Malignant fibrous histiocytoma with the primary focus of the spermatic cords is a rare disease. To our knowledge, this is the 20th case of MFH of the spermatic cord in Japan (the 42nd in the world) and it is the second case of inflammatory type of MFH in Japan.

Combined Modality Therapy↗
PubMed2001

Dialysis-related amyloidosis of the heart in long-term hemodialysis patients.

BACKGROUND: Dialysis-related amyloidosis (DRA) predominantly occurs in the osteoarticular structures, but it also systemically appears in the extra-articular tissues as well. However, the pathological characteristics of DRA in the hearts of hemodialysis (HD) patients have rarely been reported. METHODS: We studied the pathological characteristics of DRA in the hearts of 18 HD patients, including its relationship to calcification. Furthermore, we studied the immunohistochemical localization of advanced glycation end products (AGEs) using monoclonal anti-imidazolone and anti-Nepsilon-(carboxymethyl)lysine (CML) antibodies. RESULTS: beta2-microglobulin (beta2m) amyloid deposits were detected in the hearts of seven patients who had undergone HD for more than 10 years. beta2m amyloid deposits in the left atrium were localized in the endocardium, the myocardium, and the walls of small blood vessels, whereas in the left ventricle, they were localized only in the walls of small blood vessels. The extent and prevalence of DRA in the heart were severe in the patients on HD for more than 15 years. Most calcification areas near mitral valve were dotted with beta2m amyloid deposits, while diffuse fine calcification was localized within the beta2m amyloid tissues in some cases. Imidazolone and CML were localized not only in massive beta2m amyloid deposits, but also in cardiac myocytes. CONCLUSION: DRAs were localized extensively in the hearts of long-term HD patients. A strong affinity was observed between beta2m amyloid deposits and calcification.

Adult↗
PubMed2001

Localization of imidazolone in the peritoneum of capd patients: a factor for a loss of ultrafiltration.

The presence of dicarbonyl compounds, potent precursors of advanced glycation end products (AGEs), has been recognized in unused peritoneal dialysis (PD) fluids. Accumulation of AGEs has been implicated in the alteration of peritoneal membrane properties during continuous ambulatory peritoneal dialysis (CAPD) therapy. To determine whether imidazolone, an AGE specifically derived from 3-deoxyglucosone (3-DG), contributes to a decrease in ultrafiltration (UF) capacity of the peritoneal membrane in CAPD patients, we immunohistochemically evaluated the localization of imidazolone in peritoneal tissues from CAPD patients. Mesothelial thickening in the peritoneum was found in six of seven CAPD patients. Imidazolone distinctly accumulated in peritoneal tissues of CAPD patients, whereas it was hardly detected in those of patients with nonrenal disease. CAPD patients with a low UF capacity showed more extensive peritoneal deposition of imidazolone and more pronounced mesothelial thickening than those with a normal UF capacity. A CAPD patient with sclerosing peritonitis showed the most abundant localization of imidazolone among all CAPD patients. Gas chromatography/mass spectrometry showed that unused PD fluids contained high 3-DG concentrations (mean, 34.6 +/- 14.1 [SD] microgram/mL). In conclusion, the accumulation of imidazolone was noted in peritoneal tissues of CAPD patients, which preceded a decrease in UF capacity. Imidazolone modification may alter the quality of peritoneal membranes, presumably leading to a loss of UF and finally the development of sclerosing peritonitis.

Epithelium↗
PubMed2001

A successfully treated case of disseminated tuberculosis-associated hemophagocytic syndrome and multiple organ dysfunction syndrome.

We report the case of a patient who presented with disseminated tuberculosis-associated hemophagocytic syndrome (HPS). A 40-year-old man was admitted because of fatigue, fever, and renal dysfunction. Chest radiograph and computed tomography scan showed diffuse reticulonodular shadow, and Mycobacterium tuberculosis was identified. Peripheral blood counts decreased rapidly, and bone marrow aspiration revealed hemophagocytosis by macrophages. Despite antituberculous and steroid pulse therapy, multiple organ dysfunction syndrome developed. After plasma exchange and continuous hemodiafiltration were started, hypercytokinemia and vital signs improved dramatically. Although disseminated tuberculosis-associated HPS carries a poor prognosis, acute blood purification may be an effective means of treating HPS involving multiple organ dysfunction syndrome.

Adult↗
PubMed2001

Evaluation of endoscopic and histopathological features of serrated adenoma of the colon.

BACKGROUND AND STUDY AIMS: The aim of this study was to reveal the clinical features of serrated colonic adenoma by investigating its endoscopic features using a magnifying videoscope. MATERIALS AND METHODS: 68 colorectal serrated adenomas presented for colonoscopic examination were included in this study. A magnifying videoscope with a zoom ranging from x 1 to x 100 magnification was employed to observe the pit patterns of colonic lesions, and 39 of the serrated adenoma specimens were evaluated using this. Some pit patterns appeared as elongated oval and stellar-like orifices of the crypts; we termed these type which was detected III(SA) patterns. Other pit patterns showed a flower petal-like or pineal form, and this was termed a type IV(SA) pit pattern. RESULTS: In the entire sample of serrated adenomas, 53 were of the protruded type, and 15 were superficial, for a protruded/superficial ratio of 3.5 : 1. The protruded type of serrated adenoma predominated in the distal portion. The superficial type was preferentially located in the proximal portion of the colon (P < 0.0001). Among the 13 superficial types in which the magnifying videoscope was used, all 13 showed the type III(SA) basic pit pattern. In these serrated adenomas of the superficial type, an additional IV(SA) pit pattern was found in 23.1% (3/13), which was detected in 53.8% (14/26) in the protruded type. Small serrated adenomas measuring less than 10 mm in diameter were preferentially mild to moderate atypia (odd's ratio = 15.9, P = 0.0216). CONCLUSION: The pit pattern may prove useful for the endoscopic diagnosis of serrated adenoma. Furthermore, endoscopic treatment is indicated for serrated adenoma; in particular those of 10 mm or more in diameter should be treated because of the possibility of high-grade glandular intraepithelial neoplasia.

Adenoma↗
PubMed2001

How to distinguish garlic from the other Allium vegetables.

The establishment of international monographs for herbs is in progress. Here, we propose both a marker compound and a method for its analysis for the identification of garlic bulbs and their products. The constituents in 26 kinds of fresh edible parts of Allium vegetables and three types of garlic preparations were analyzed. Sulfur compounds are the most characteristic constituents in garlic, but manufacturing processes of garlic products dramatically affect these constituents. Thus, no sulfur compound could be specified as a universal marker of identification applicable for any type of garlic. On the other hand, garlic contains other characteristic compounds, namely, saponins. After analyzing Allium vegetables and garlic preparations, we concluded that sapogenins, especially beta-chlorogenin, may be a viable candidate for identifying and distinguishing garlic from other Allium vegetables.

Allium↗
PubMed2001

Comparative biochemistry of disintegrins isolated from snake venom: consideration of the taxonomy and geographical distribution of snakes in the genus Echis.

Species in the genus Echis have been classified mainly based on their morphological appearance and the analytical patterns of their serum. However, re-classification of the genus Echis has recently been suggested by taxonomists, toxicologists, and clinicians, since there have been problems with the current classification, such as the efficacy of antivenoms used for treating bites and the broad geographical distribution of Echis snakes. In this study, we purified five novel disintegrins, the platelet aggregation inhibitors pyramidin A and B from the venom of Echis pyramidum, ocellatin from the venom of Echis ocellatus, and leucogastin A and B from the venom of Echis leucogaster, to compare their sequences and allow us to re-evaluate the classification of various species in the genus Echis. Comparison of the amino acid sequences of five new and four known isolated disintegrins from snake venoms of six Echis species and their distribution strongly support the recent re-classification of the genus Echis.

Africa↗
PubMed2001

Purification and characterization of a new RGD/KGD-containing dimeric disintegrin, piscivostatin, from the venom of Agkistrodon piscivorus piscivorus: the unique effect of piscivostatin on platelet aggregation.

Piscivostatin, a novel dimeric disintegrin containing Arg-Gly-Asp (RGD) and Lys-Gly-Asp (KGD) sequences, was isolated from the venom of Agkistrodon piscivorus piscivorus. The molecule consisted of two chains designated as the alpha and beta chains, comprising 65 and 68 amino acid residues, respectively. Piscivostatin had two binding motifs recognized by platelet glycoprotein IIb/IIIa (GPIIb/IIIa), and the biological activity of dimeric disintegrin piscivostatin toward platelet aggregation differed from those of other monomeric disintegrins such as trimestatin and echistatin. We measured platelet aggregation by the laser light scattering method during the process of ADP-induced platelet aggregation. Both dimeric and monomeric disintegrins inhibited the formation of small (9 to 25 microm in diameter), medium-sized and large aggregates (25 to 70 microm in diameter) in a dose-dependent manner. The platelet aggregates disaggregated after reaching a maximal number on either treatment with ADP alone or monomeric disintegrin/ADP. However, the small aggregates did not disaggregate on treatment with piscivostatin/ADP even when applied over time. When washed platelets were incubated with an anti-GPIIb/IIIa monoclonal antibody, PT25-2, which induces conformational changes of GPIIb/IIIa to a form accessible to fibrinogen and other adhesion proteins without platelet activation, piscivostatin induced a platelet shape change alone with no aggregate formation. The present study indicated that piscivostatin has two unique contradictory activities; acting as a double inhibitor of platelet aggregation and platelet aggregate dissociation.

Agkistrodon↗
PubMed2001

P-hydroxylation of phenobarbital: relationship to (S)-mephenytoin hydroxylation (CYP2C19) polymorphism.

The aim of the current study was to compare the pharmacokinetics of phenobarbital (PB) in extensive metabolizers (EMs) and poor metabolizers (PMs) of S-mephenytoin. Ten healthy volunteers (5 EMs and 5 PMs) were given 30 mg PB daily for 14 days. PB and p-hydroxyphenobarbital (p-OHPB) in serum and urine were measured by high-performance liquid chromatography (HPLC). Urinary excretion (12.5% versus 7.7%) and formation clearance (29.8 versus 21.1 mL/h) of p-OHPB, one of the main metabolites of PB, were significantly lower (p < .05) in PMs than in EMs. However, area under the serum concentration-time curve (153.3 in the EMs versus 122.9 microg x h/mL in the PMs), total (210.8 versus 254.9 mL/h) and renal clearance (53.1 versus 66.1 mL/h) of PB were identical between the two groups. To compare the inducibility of CYP2C19, mephenytoin was also given prior to and on the last day of PB treatment. The urinary level of 4'-hydroxymephenytoin was analyzed by a validated gas chromatograpy/mass spectrometry (GC/MS) method. The mephenytoin hydroxylation index did not change in either EMs (1.42 versus 1.42) or PMs (341.4 versus 403.5), showing that CYP2C19 was not induced by treatment with PB. These results indicated that the p-hydroxylation pathway of PB co-segregates with the CYP2C19 metabolic polymorphism. However, the overall disposition kinetics of PB were not different between EMs and PMs, and therefore polymorphic CYP2C19 seems have no major clinical implications.

Adult↗