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Biomedical subjects

K Koizumi

Publications and source records attributed to K Koizumi.

At least 73 records · Page 4Linked to original sources
PubMed2000

Molecular design of polyvinylpyrrolidone-conjugated interleukin-6 for enhancement of in vivo thrombopoietic activity in mice.

Functional polyvinylpyrrolidone (PVP) was synthesized as a novel polymeric modifier for polymer-conjugated cytokines, and its efficiency and applicability as a drug delivery system (DDS) were evaluated. PVP with a carboxyl group at one end of the main chain was prepared by radical polymerization (M(n): 6000, M(w)/M(n): 1.14) with the aid of 4,4'-azobis(4-cyanovaleric acid) as a radical initiator and 3-mercaptopropionic acid as a transfer agent. Interleukin-6 (IL-6) was covalently conjugated via the formation of amino bonds between the lysine amino groups of IL-6 and PVP. PVP-conjugated IL-6, in which 60% of the fourteen lysine amino groups of IL-6 were estimated to be coupled with PVP (M-PVP-IL-6), showed more than 50-fold greater thrombopoietic potency in vivo than native IL-6. No side effects, such as body weight loss, were observed in the M-PVP-IL-6 treated mice. These results indicate that PVP as a polymeric modifier is a promising DDS for clinical application of cytokines and other therapeutic agents.

Animals↗
PubMed2000

A member of Forkhead family transcription factor, FKHRL1, is one of the downstream molecules of phosphatidylinositol 3-kinase-Akt activation pathway in erythropoietin signal transduction.

The phosphatidylinositol 3-kinase (PI3K) signaling pathway is important for the regulation of a number of cellular responses. Serine/threonine kinase Akt (protein kinase B; PKB) is downstream of PI3K and activated by growth factors. This study found that erythropoietin (EPO) induced tyrosine phosphorylation of Akt in a time- and dose-dependent manner in EPO-dependent human leukemia cell line UT-7/EPO. In vitro kinase assay using histone H2B and glucose synthase kinase as substrates demonstrated that Akt was actually activated by EPO. EPO-induced phosphorylation of Akt was completely blocked by a PI3K-specific inhibitor, LY294002, at 10 micromol/L, indicating that activation of Akt by EPO is dependent on PI3K activity. In addition, overexpression of the constitutively active form of Akt on UT-7/EPO cells partially blocked apoptosis induced by withdrawal of EPO from the culture medium. This finding suggested that the PI3K-Akt activation pathway plays some role in the antiapoptotic effect of EPO. EPO induced phosphorylation of a member of the trancription factor Forkhead family, FKHRL1, at threonine 32 and serine 253 in a dose- and time-dependent manner in UT-7/EPO cells. Moreover, results showed that Akt kinase activated by EPO directly phosphorylated FKHRL1 protein and that FKHRL1 phosphorylation was completely dependent on PI3K activity as is the case for Akt. In conjunction with the evidence that FKHRL1 is expressed in normal human erythroid progenitor cells and erythroblasts, the results suggest that FKHRL1 plays an important role in erythropoiesis as one of the downstream target molecules of PI3K-Akt.

DNA-Binding Proteins↗
PubMed2000

Desulfurization of alkylated forms of both dibenzothiophene and benzothiophene by a single bacterial strain.

Thirty-five bacterial strains capable of converting dibenzothiophene into 2-hydroxybiphenyl were isolated. Among them Rhodococcus erythropolis KA2-5-1 was chosen for further characterization because of its ability to retain high desulfurization activity stably. PCR cloning and DNA sequencing of a KA2-5-1 genomic DNA fragment showed that it was practically identical with dszABC genes from Rhodococcus sp. IGTS8, a representative carbon-sulfur-bond-targeted dibenzothiophene-degrading bacterium. KA2-5-1 desulfurized a variety of alkyl dibenzothiophenes through the specific cleavage of their C-S bonds. In addition, unexpectedly, KA2-5-1 also attacked alkyl benzothiophenes in a C-S-bond-targeted fashion. The purified monooxygenase, encoded by dszC of KA2-5-1, converted benzothiophene and dibenzothiophene into benzothiophene sulfone and dibenzothiophene sulfone, respectively, with the aid of an NADH-dependent oxidoreductase. This result raises the possibility that the same enzymatic step may be involved in desulfurization of alkylated forms of both dibenzothiophene and benzothiophene in KA2-5-1 cells.

Alkylation↗
PubMed2000

Novel antiarthritic agents with 1,2-isothiazolidine-1,1-dioxide (gamma-sultam) skeleton: cytokine suppressive dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase.

Various 1,2-isothiazolidine-1,1-dioxide (gamma-sultam) derivatives containing an antioxidant moiety, 2,6-di-tert-butylphenol substituent, were prepared. Some compounds, which have a lower alkyl group at the 2-position of the gamma-sultam skeleton, showed potent inhibitory effects on both cyclooxygenase (COX)-2 and 5-lipoxygenase (5-LO), as well as production of interleukin (IL)-1 in in vitro assays. They also proved to be effective in several animal arthritic models without any ulcerogenic activities. Among these compounds, (E)-(5)-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2-ethyl-1, 2-isothiazolidine-1,1-dioxide (S-2474) was selected as an antiarthritic drug candidate and is now under clinical trials. The structure-activity relationships (SAR) examined and some pharmacological evaluations are described.

Animals↗
PubMed2000

Gallium-67 scintigraphic findings in a patient with breast lymphoma complicated with Sjögren syndrome.

We report here a patient with mucosa associated lymphoid tissue (MALT)-lymphoma of the breast complicated with Sjögren syndrome. It is speculated that Ga-67 could accumulate not only in lymphoma lesions but also in benign lymphoproliferative locations of Sjögren syndrome. Gallium-67 scintigraphy might be useful for the diagnosis and therapeutic monitoring of MALT-lymphoma complicated with Sjögren syndrome.

Adult↗
PubMed2000

Efficacy of autologous platelet-rich plasma in thoracic aortic aneurysm surgery.

OBJECTIVE: Allogenic blood transfusion can transmit viral infection or cause immunological side effects. Recently, improved operative techniques have required less frequent transfusions in thoracic aortic aneurysm surgery. This study examined the efficacy of using autologous platelet-rich plasma in thoracic aortic aneurysm surgery. METHOD: Eight patients underwent nine operations using an autologous platelet-rich plasma program. The control group consisted of 15 historic patients matched for operative procedure and age. All operations were performed by the same surgeon. The platelet-rich plasma program required the collection of platelet-rich plasma prior to the infusion of heparin; platelet-rich plasma transfusions were administered following neutralization by heparin. RESULTS: The volume of platelet-rich plasma averaged 252 +/- 14.3 ml; total platelets in the platelet-rich plasma were 2.27 +/- 0.20 x 10(11) cells. The median number of homologous red blood cells transfused during the operative day was 0 units (range 0 to 12) in the platelet-rich plasma group and 3 units (range 0 to 25) in the controls. The median number of homologous fresh frozen plasma was 0 units (range 0 to 20) in the platelet-rich plasma group, and 5 units (range 0 to 30) in the controls. The platelet-rich plasma group received significantly fewer transfusions. CONCLUSION: Autologous platelet-rich plasma transfusion was an effective way to reduce homologous blood transfusions in thoracic aortic aneurysm surgery.

Adult↗
PubMed2000

Radiographic diagnosis of early colorectal cancer, with special reference to the superficial type of invasive carcinoma.

The possibility of radiographically diagnosing carcinoma with submucosal involvement (invasive carcinoma) is discussed based on 119 invasive carcinomas of the large bowel that had been treated surgically and colonoscopically over a period of 9 years (1989-1997) at the Cancer Institute Hospital in Tokyo. Of these lesions, 38 were superficial-type invasive carcinoma, accounting for 31.9% (38/119) of all invasive colorectal carcinomas, including 36 lesions (94.7%, 36/38) of types IIa and IIa + IIc and 2 lesions (5.3%, 2/38) of type IIc + IIa. No pure type IIc was seen. The radiographic images obtained were correlated with macroscopic findings and analyzed in terms of visualization of the lesion's contour, central depression, converging folds, and basal indentation. A definitive diagnosis of superficial invasive carcinoma can be made radiographically if a lesion measures 10 mm and reveals moderate to severe basal indentation in a complete or nearly complete profile radiographic image. Attention should be paid to the presence of superficial-type advanced carcinomas measuring 10 mm or less, which is not infrequently experienced in Japan. Polypoid invasive carcinoma can be definitively diagnosed in the same way with much more certainty than can the superficial type because few polypoid advanced carcinomas are less than 20 mm. The size and the radiographic sign of the basal indentation are the most important indicators for the diagnosis of invasive carcinoma.

Adenoma↗
PubMed2000

Low resistance against novel 2-benzylamino-1,3,5-triazine herbicides in atrazine-resistant Chenopodium album plants.

The effects of nine novel 2-benzylamino-1,3,5-triazines on photosynthetic reactions were measured in thylakoids isolated from wild-type and atrazine-resistant plants of Chenopodium album. The resistant plants have a mutation of serine for glycine at position 264 of the D1 protein. The measurement of oxygen evolution and chlorophyll a fluorescence induction indicated a 2-4-fold stronger inhibition by the 6-trifluoromethyl analogues of Photosystem II-dependent electron flow than atrazine. Analogues having a 6-methyl-, 6-monofluoromethyl or 6-difluoromethyl substitution were weak inhibitors, indicating that the 6-trifluoro group is very important for strong inhibition. All the nine novel 2-benzylamino-1,3,5-triazines were almost as active in wild-type as in atrazine-resistant thylakoids, indicating that the benzylamino substitution may be important for the lack of resistance in the atrazine-resistant plants.

Journal Article↗
PubMed2000

Pars plana vitrectomy for regression of choroidal neovascularization with age-related macular degeneration.

OBJECTIVE: In age-related macular degeneration, the posterior vitreous surface often remains attached to a higher degree than expected for the patient's age, suggesting the involvement of the posterior vitreous membrane in the pathophysiology of choroidal neovascularization. Thus, we performed simple pars plana vitrectomy and artificial posterior vitreous detachment in order to induce regression of choroidal neovascularization. METHODS: Vitrectomy was performed in 12 eyes of 11 patients with age-related macular degeneration in whom the posterior vitreous surface remained attached, and in whom there was evidence of highly active choroidal neovascularization. The posterior vitreous membrane was artificially detached during surgery, but photocoagulation and/or a subretinal procedure for choroidal neovascularization was not performed. Patients underwent fluorescein and indocyanine green angiography both pre- and postoperatively to assess the status of choroidal neovascularization. RESULTS: Six months after surgery, 6 of the 12 eyes showed regression of choroidal neovascularization, and in 2 eyes it had disappeared completely. Subretinal exudative changes in 8 eyes had improved. Visual acuity testing showed improved vision in 4 eyes, unchanged vision in 4 eyes, and worsening of vision in 4 eyes. The final best corrected visual acuity was 10/20 or better in one eye, 10/ 20 to 20/200 in 7 eyes, and 20/200 or worse in 4 eyes. CONCLUSION: The results of the present study suggest the involvement of the posterior vitreous membrane in the pathophysiology of age-related macular degeneration. Furthermore, the minimally invasive pars plana vitrectomy may represent a new treatment for age-related macular degeneration.

Aged↗
PubMed2000

Mesp2 initiates somite segmentation through the Notch signalling pathway.

The Notch-signalling pathway is important in establishing metameric pattern during somitogenesis. In mice, the lack of either of two molecules involved in the Notch-signalling pathway, Mesp2 or presenilin-1 (Ps1), results in contrasting phenotypes: caudalized versus rostralized vertebra. Here we adopt a genetic approach to analyse the molecular mechanism underlying the establishment of rostro-caudal polarity in somites. By focusing on the fact that expression of a Notch ligand, Dll1, is important for prefiguring somite identity, we found that Mesp2 initiates establishment of rostro-caudal polarity by controlling two Notch-signalling pathways. Initially, Mesp2 activates a Ps1-independent Notch-signalling cascade to suppress Dll1 expression and specify the rostral half of the somite. Ps1-mediated Notch-signalling is required to induce Dll1 expression in the caudal half of the somite. Therefore, Mesp2- and Ps1-dependent activation of Notch-signalling pathways might differentially regulate Dll1 expression, resulting in the establishment of the rostro-caudal polarity of somites.

Animals↗
PubMed2000

Effective high-dose chemotherapy combined with CD34+-selected autologous peripheral blood stem cell transplantation in a patient with cutaneous CD30-negative large T cell lymphoma.

Generalized multiple cutaneous tumors developed in a 60-year-old Japanese man. Skin biopsy revealed atypical large T lymphocytes infiltrating the dermis. CD30 staining was negative in the tumor cells. The diagnosis of CD30-negative cutaneous large T cell lymphoma was made. Axial and inguinal lymphadenopathy was present, but there was no evidence of bone marrow involvement. Seven cycles of chemotherapy and local electron beam irradiation were administered and complete remission (CR) was attained. As CD30-negative cutaneous large T cell lymphoma has a poor prognosis despite intensive chemotherapy, high-dose chemotherapy followed by CD34+-selected autologous peripheral blood stem cell transplantation (CD34+-APBSCT) was prescribed. The clinical course after CD34+-selected APBSCT was complicated with CMV infection occurring twice but administration of ganciclovir resolved the symptoms. He has remained in CR for 16 months after CD34+-APBSCT. This appears to be the first case report of CD34+-APBSCT in a patient with CD30-negative cutaneous large T cell lymphoma. Bone Marrow Transplantation (2000) 25, 1315-1317.

Antigens, CD34↗
PubMed2000

Epstein-Barr virus-negative high grade B cell lymphoma of donor origin developing 19 months after unrelated allogeneic bone marrow transplantation.

A 22-year-old man, in first complete remission of acute myelogenous leukemia, developed a high grade B cell lymphoma 19 months after an allogeneic bone marrow transplant (allo-BMT) from an HLA-identical unrelated donor. Biopsy of a cervical lymph node revealed a lymphoma that was negative for Epstein-Barr virus-encoded small nuclear RNAs (EBERs) in situ hybridization. Genotypic analyses identified the lymphoma to be of donor origin, and there was no evidence of the Epstein-Barr virus (EBV) DNA in the lymphoma by Southern blot analysis. The lymphoma went into complete remission, following four courses of combination chemotherapy, but relapsed after a month and the patient died of congestive heart failure. The patient was thought to be persistently immunosuppressed 11 months after cessation of immunosuppressants, and the lymphoma was thought to be induced by one or more factors other than EBV.

Adult↗
PubMed2000

Large scale purification of human blood CD34+ cells from cryopreserved peripheral blood stem cells, using a nylon-fiber syringe system and immunomagnetic microspheres.

Isolation of large numbers of human peripheral blood CD34+ cells could lead to therapeutic applications, including purging of malignant cells from blood cell transplantations, purging of T cells from allogeneic bone marrow, and even blood cell transplantation. This procedure has limitations if there are not sufficient numbers of progenitor cells in the leukapheresis concentrates available for selection after detection of tumor cells in apheresis products. Use of frozen/thawed peripheral blood mononuclear cell (PBMC) samples would make feasible pooling of two or even more stem cell harvests collected at different time points and the total number of CD34+ progenitor cells available would increase. We established an efficient method for purification of CD34+ cells from cryopreserved apheresis products, using a nylon-fiber syringe system and immunomagnetic microspheres. We compared purity, recovery rate and clonogenicity of CD34+ cells purified from fresh (n = 22) and cryopreserved apheresis products (n = 14), using a nylon-fiber syringe system and immunomagnetic microspheres. The purity of CD34+ cells from cryopreserved products was less than that from fresh products (85.9 +/- 14.4% vs 94.6 +/- 10.0%), but the recovery rate of CD34+ cells and colony-forming cells was comparable between fresh and cryopreserved products. One patient underwent grafting with peripheral blood CD34+ cells selected after freezing, with good success. Therefore, these cells are capable of rapidly reconstituting hematopoiesis after high-dose chemotherapy. Bone Marrow Transplantation (2000) 26, 787-793.

Antigens, CD34↗
PubMed2000

Milk-borne insulin with trypsin inhibitor in milk induces pancreatic amylase development at the onset of weaning in rats.

BACKGROUND: The physiologic significance of milk-borne hormones and growth factors for internal organs of suckling animals is poorly understood. In this study the significance of milk-borne insulin was evaluated, as well as its combination with trypsin inhibitor, and its role in the development of pancreatic digestive capacity at the time of weaning was investigated. METHODS: Experiments were performed using insulin-deficient milk formula (standard formula), insulin (20 ng/ml) formula, or insulin with trypsin inhibitor (1 U/ml) formula by a rat artificial-rearing technique. RESULTS: In 17-day-old rats administered standard formula, the plasma insulin level was as low as that in 14-day-old rats. When insulin-trypsin inhibitor formula was administered to rat pups, the plasma insulin level was significantly higher than those in rats given standard or insulin formula. In rats artificially reared on standard formula, the usual developmental increases in pancreatic amylase activity and plasma insulin concentration at the beginning of weaning did not occur. Insulin formula elevated the pups' plasma insulin concentration and amylase activity at the onset of weaning but not to the levels observed in mother-reared rats. In rats reared on insulin-trypsin inhibitor formula, the developmental increases in the plasma insulin concentration and amylase activity observed in mother-reared rats were induced. CONCLUSIONS: The present study demonstrates the necessity of milk-borne insulin for the development of pancreatic amylase during the weaning period.

Aging↗
PubMed2000

Various imaging modalities for the detection of salivary gland lesions: the advantages of 201Tl SPET.

The aim of this study was to compare dual-isotope (99Tc(m) and 201Tl) SPET imaging with computed tomography (CT) and magnetic resonance imaging (MRI) in the differentiation of various lesions of the major salivary glands. Twenty-two patients underwent dual-isotope SPET imaging, of whom 12 also had CT and 15 also had an MRI study. The uptake ratio and retention index for 99Tc(m) and 201Tl were calculated by drawing regions of interest on the involved and normal glands. Both CT and MRI were interpreted by two radiologists. All malignant tumours were detected by all three modalities. Warthin's tumours were detected by dual-isotope SPET imaging; however, MRI failed to differentiate Warthin's tumour from pleomorphic adenoma. Of 13 other benign tumours, dual-isotope SPET correctly diagnosed 12. Of 16 tumours showing a cold defect on the 99Tc(m) images, parametric analysis with 201Tl gave an accuracy of 94%, whereas CT gave an accuracy of 70-90%. MRI was 73-91% accurate in differentiating between benign (Warthin's) and malignant tumours. We believe that dual-isotope SPET imaging (99Tc(m) and 201Tl), together with semi-quantitative analysis, is the method of choice for differentiating between various lesions of the major salivary glands.

Adenolymphoma↗
PubMed2000

Effective cancer targeting using an anti-tumor tissue vascular endothelium-specific monoclonal antibody (TES-23).

Immunoconjugate targeting of solid tumors has not been routinely successful because the endo-thelial cells of blood vessels act as a physical barrier against the transport of macromolecules, such as antibodies. In the present study, we attempted to achieve tumor vascular targeting with an anti-tumor tissue endothelium-specific monoclonal antibody (TES-23). TES-23, an IgG1 monoclonal antibody raised against rat KMT-17 fibrosarcoma-derived endothelial cells, was covalently conjugated with neocarzinostatin (NCS) in a previous study. The TES-23-NCS conjugate induced tumor hemorrhagic necrosis, and showed marked anti-tumor effects against rat KMT-17 fibrosarcoma. This result prompted us to investigate whether this approach would be applicable to various other types of solid tumors. One hour after injection of (125)I-labeled TES-23 into BALB / c mice bearing Meth-A fibrosarcoma and Colon 26 adenocarcinoma, the tumor accumulation of TES-23 was greater than that of the control IgG. In the present study, we report the anti-tumor effects of this monoclonal antibody in mice bearing Meth-A fibrosarcoma. Mice treated with the immunoconjugate showed improved survival with no side effects. This result indicates that common antigens may be found in different kinds of tumor endothelial cells, and that TES-23 might recognize these antigens.

Animals↗