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Biomedical subjects

T Tsuji

Publications and source records attributed to T Tsuji.

At least 271 records · Page 15Linked to original sources

Benign gastric ulcer associated with Canidida infection in a healthy adult.

A case of benign gastric ulcer associated with Candida infection in a healthy adult is reported. The patient was a 46-year-old man complaining of epigastralgia. Endoscopic examination of the upper digestive tract revealed an elevated lesion with ulceration having an unclear border and thick exudates. The clinical diagnosis based on endoscopic findings was a benign gastric ulcer; however, biopsy was performed to distinguish it from malignant lymphoma. Histological examination of biopsy samples obtained from the base and the edge of the ulcer revealed numerous Candida. Therefore, the patient was diagnosed with Candida-infected gastric ulcer. The ulcer resolved after the administration of antiulcer drugs for 2 months. Predisposing factors for fungal infection were excluded. These observations suggest that Candida-infected gastric ulcer should be suspected in patients with a gastric submucosal tumor-like lesion with a thick, yellowish-white coated ulcer of unclear border on its summit, and this lesion should be distinguished from malignant diseases.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Expression of multidrug resistance protein in metastatic colorectal carcinomas.

To clarify the relationship between multidrug resistance protein (MRP) and clinicopathologic features, the influence of adjuvant chemotherapy, and prognosis of patients who underwent resection of metastatic liver carcinomas originating from colorectal carcinomas, we examined the expression of MRP in tumor tissues by immunostaining. Specimens of 38 primary colorectal tumors and 44 metastatic liver tumors of colorectal origin were examined (metastatic group). We also examined 28 nonmetastatic colorectal carcinomas. The percentages of nonmetastatic tumors and of primary and metastatic tumors of the metastasis group that expressed MRP were similar. MRP expression in primary and metastatic tumors did not correlate with any clinicopathologic features. The use of adjuvant chemotherapy after operation for primary colorectal carcinomas was associated with increased MRP expression among metastatic liver tumors. Expression of MRP in the tumor did not influence the prognosis or survival rate after resection of primary or metastatic tumors. Our data suggest that MRP expression in metachronous liver metastases from colorectal carcinomas may be induced by administration of anticancer drugs but is not associated with clinicopathologic features of the tumor, liver metastasis, or prognosis.

ATP-Binding Cassette Transporters↗

Osteoporosis in hemiplegic stroke patients as studied with dual-energy X-ray absorptiometry.

OBJECTIVES: To compare bone mineral densities (BMDs) of the affected and unaffected limbs in stroke patients at multiple sites; to study longitudinal changes during a 3-month rehabilitation program; and to relate BMDs to demographic, impairment, and disability variables. DESIGN: Descriptive study. SETTING: Tertiary rehabilitation center. PATIENTS: One hundred four consecutive hemiplegic inpatients, 69 men, age 56.5 +/- 13.2 yrs, 47 with left-sided brain lesion. Median days from onset to admission and median length of stay days were 83 and 105.5, respectively. MAIN OUTCOME MEASURES: BMDs of proximal humerus, distal radius, femoral neck, and calcaneus bilaterally, and third lumbar vertebra, measured with dual-energy x-ray absorptiometry (DXA), were compared between affected and unaffected sides at admission and discharge. RESULTS: Stroke Impairment Assessment Set (SIAS) motor scores, Functional Independence Measure (FIM) scores, grip strength, and awake/sleep heart rate counts (activity index) improved significantly at discharge. Affected/unaffected BMD ratios were 88.3% to 98.4% at admission and 79.6% to 98.8% at discharge, lowest for the humerus. Discharge/admission ratios were 89.1% to 97.8% for the affected and 97.4% to 100% for the unaffected side. All BMDs were intercorrelated (R = .438 to .873). They correlated significantly with age, body weight, grip strength, FIM scores, and activity index. Factors selected to explain BMD with multiple regression analysis differed according to the site and timing of the measurement. CONCLUSIONS: BMDs of the affected side were lower and most marked in the humerus. Longitudinally, not only the affected but the unaffected BMDs decreased. Age, sex, duration of stroke, anthropometric measurements, motor paralysis, muscle strength, and activity level contributed differently to bone loss according to the site and timing of the measurement.

Absorptiometry, Photon↗

Bridging activity as a mode of stress testing for persons with hemiplegia.

OBJECTIVE: To establish a stress testing protocol for hemiplegic persons using graded bridging activity at the rates of 3 to 24 repetitions per minute. DESIGN: Paired comparisons of exercise parameters and admission and discharge data between hemiplegic and control groups. SETTING: Inpatient rehabilitation program of a tertiary rehabilitation center in Japan. PATIENTS: (1) Preliminary study: five hemiplegic patients. (2) Comparison with normal subjects: 39 hemiplegic patients and 10 age-matched controls. (3) Study of reproducibility: five hemiplegic patients and five controls. (4) Longitudinal changes: 30 hemiplegic patients. MAIN OUTCOME MEASURES: Oxygen consumption (VO2), heart rate (HR), and HR oxygen coefficient (regression coefficient between HR and VO2). RESULTS: The testing protocol was applicable to 88.6% of hemiplegic patients. The relationship between HR and VO2 was linear, and HR oxygen coefficient was significantly lower in hemiplegic patients than the controls. The intraclass correlation coefficients were greater than 0.7 for VO2, HR, and HR oxygen coefficient, indicating satisfactory reproducibility. HR decreased longitudinally for the same stress levels and the HR oxygen coefficient increased, indicating improved fitness level. CONCLUSIONS: The bridging activity protocol is a useful mode for stress-testing hemiplegic persons. The linearity between HR and VO2 with this protocol allows us to use the indices of fitness obtainable from this relationship.

Activities of Daily Living↗

An autocrine or a paracrine role of adrenomedullin in modulating cardiac fibroblast growth.

OBJECTIVE: The aim of the present study was to determine the role of adrenomedullin (AM) in cardiac fibroblasts. METHODS: The production and secretion of AM were examined in cultured neonatal rat cardiac fibroblasts, and the effects of AM on proliferation and protein synthesis of these cells were assessed by [3H]thymidine and [3H]phenylalanine incorporation, respectively. RESULTS: Cultured cardiac fibroblasts secreted AM into the medium time-dependently at a rate of 20.3 +/- 3.0 fmol/5 x 10(4) cells/48 h, mean +/- S.D. Northern blot analysis showed expression of preproAM mRNA of 1.6 kb in these cells. In addition, 10(-6) mol/l of angiotensin II (Ang II) and endothelin-1 (ET-1) significantly increased the AM secretion by 55 and 48%, respectively. Synthetic AM significantly reduced 10(-6) mol/l Ang II- or 10(-7) mol/l ET-1-stimulated [3H]thymidine and [3H]phenylalanine incorporation in a dose-dependent manner, and these effects were attenuated by a calcitonin gene-related peptide (CGRP) type 1 receptor antagonist, CGRP(8-37). Synthetic AM also had a dose-dependent stimulatory effect on cAMP accumulation in these cells, which was significantly attenuated by CGRP(8-37). A cAMP analogue, 8-bromo-cAMP, mimicked the AM effects, inhibiting the Ang II-stimulated [3H]thymidine and [3H]phenylalanine incorporation. Blockage of the effect of endogenous AM by anti-AM monoclonal antibody not only significantly reduced the basal level of intracellular cAMP, but also enhanced the [3H]thymidine and [3H]phenylalanine incorporation into the cells. CONCLUSIONS: Cultured neonatal rat cardiac fibroblasts produce and secrete AM, and the secreted AM may inhibit proliferation and protein synthesis of these cells. AM may exert these inhibitory effects partly by elevating intracellular cAMP. It is suggested that AM has an important role in modulating the growth of cardiac fibroblasts in an autocrine or a paracrine manner.

8-Bromo Cyclic Adenosine Monophosphate↗

A simple immunoradiometric assay for measuring the entire molecules of adrenomedullin in human plasma.

We developed a one-step two-site immunoradiometric assay (IRMA) using two kinds of monoclonal antibodies, which enables us to directly measure the entire molecules of adrenomedullin (AM) (the sum of mature-type AM (abbreviated, m-AM) amidated at the C-terminus and Gly-extended non-amidated AM) in human plasma using a small amount of sample (100 microl) without prior extraction. The detection limit of this assay was 0.5 pmol/l for a 100-microl sample. Intra- and inter-assay precisions were 3.4-7.3% and 5.8-7.6%, respectively. The dilution curves of plasma samples showed good linearity and analytical recovery was 89-118%. The mean total AM in plasma of healthy subjects was 9.00+/-2.13 pmol/l, whereas m-AM was 1.05+/-0.24 pmol/l. This method, together with our previously reported simplified method to specifically measure m-AM (Ohta et al., Clin Chem 1999;45:244-251), allows facile estimation of the plasma concentration of AM-Gly by subtracting m-AM from the total AM measured by the procedure described in this paper. We were able to show that the concentration of total AM in patients with sepsis was markedly higher than that in the healthy controls and that the ratios of m-AM/total AM were significantly different between the controls and patients.

Adrenomedullin↗

Gastric ulcers in SCID mice induced by Helicobacter pylori infection after transplanting lymphocytes from patients with gastric lymphoma.

BACKGROUND & AIMS: Several studies have indicated that host factors are important in Helicobacter pylori-induced gastroduodenal diseases. We examined the pathological role of host immune responses in H. pylori infection by reconstituting components of the human immune system into severe combined immunodeficient (SCID) mice by transplantation of peripheral blood mononuclear cells (PBMCs) from H. pylori-infected patients. METHODS: PBMCs obtained from patients with mucosa-associated lymphoid tissue (MALT) lymphoma were injected intraperitoneally into SCID mice, designated MALToma-hu-SCID mice. One month after transplantation, H. pylori was administered orally to the mice. The mice were killed and examined for pathological changes and immunologic features. RESULTS: Human lymphocytes were detected in hu-SCID mice, and T- and B-cell functions were preserved for 1 month. Administration of H. pylori led to gastric ulcers with bleeding in the MALToma-hu-SCID mice. The gastric mucosa of control mice injected with Escherichia coli or transplanted with PBMCs from patients with peptic ulcers or gastritis or from healthy volunteers showed no pathological changes. CONCLUSIONS: Host immune responses against H. pylori appear to be involved in the development of gastric ulcers in patients who have MALT lymphoma.

Animals↗

Evaluation of anti-herpesvirus activity of (1'S,2'R)-9-[[1',2'-bis(hydroxymethyl)cycloprop-1'-yl]methyl]- guanine (A-5021) in mice.

The anti-herpesvirus activity of (1'S,2'R)-9-[[1',2'-bis(hydroxymethyl)cycloprop-1'-yl]methyl]guani ne (A-5021) was evaluated in murine cells and in several murine models of herpes simplex virus (HSV) infection. Against HSV type 1 (HSV-1), A-5021 was 15-30- and 30-60-fold more active, and against HSV type 2 (HSV-2), it was 2- and 8-fold more active than acyclovir and penciclovir in Balb/3T3 cells, respectively. When antiviral compounds were administered orally (once daily) to mice infected intraperitoneally with HSV-1 (Tomioka), A-5021 was more active than acyclovir or famciclovir in spite of its relatively low oral bioavailability. A-5021 was as active as penciclovir when the antiviral compounds were given intravenously (three times daily) to mice infected intraperitoneally with HSV-2 (186). In mice with a cutaneous HSV-1 (KOS) infection, three times daily oral therapy with A-5021 at 25 mg/kg per day produced more significant reduction in severity of skin lesions than equivalent treatment with acyclovir or famciclovir. In mice infected intracerebrally with HSV-1 (Tomioka), complete survival was observed in the group treated intravenously with A-5021 at 25 mg/kg per day (three times daily), while more than 50% of mice died in the groups treated intravenously with acyclovir of up to 100 mg/kg per day (three times daily). Moreover, A-5021 was more effective than acyclovir in clearing infectious virus from the brain. These findings demonstrate that A-5021 has potent anti-HSV activity in several murine models.

3T3 Cells↗

Ultraviolet A1 (340-400 nm) phototherapy for cutaneous T-cell lymphoma.

BACKGROUND: The results of a recent study suggested that ultraviolet A1 radiation (UVA1R; 340-400 nm) phototherapy for atopic dermatitis works through induction of apoptosis in skin-infiltrating helper T cells, indicating the possibility that other helper T cell-mediated skin diseases may respond to UVA1R as well. OBJECTIVE: The purpose of this open pilot study was to assess the therapeutic effectiveness of UVA1 phototherapy for cutaneous T-cell lymphoma (CTCL). METHODS: UVA1 phototherapy was used as monotherapy in patients (n = 3) with histologically proven CTCL (stages IA and IB). For daily whole body UVA1 irradiations, either a high-dose (n = 2; 130 J/cm2 UVA1 per exposure) or medium-dose (n = 1; 60 J/cm2 UVA1) regimen was used. Therapeutic effectiveness was assessed clinically and histologically. RESULTS: In each of the 3 patients, skin lesions began to resolve after only a few UVA1 radiation exposures. Complete clearance was observed between 16 and 20 exposures, regardless of whether the high- or medium-dose regimen had been employed. CONCLUSION: These studies suggest that patients with CTCL stages IA and IB can be treated effectively with UVA1 phototherapy.

Aged↗

Rapid ex vivo expansion of human umbilical cord hematopoietic progenitors using a novel culture system.

Cell numbers limit the widespread clinical use of cord blood (CB) for gene therapy and marrow replacement in adults; a simple and effective method for ex vivo expansion of CB primitive progenitor cells (PPC) is required. Recently, the combination of thrombopoietin (TPO) and Flk-2/Flt-3 ligand (FL-2) was reported to support slow proliferation of CB-PPC in stroma-free liquid culture. We established a novel culture system in which the murine stromal cell line HESS-5 dramatically supports the rapid expansion of cryopreserved CB-PPC in synergy with TPO/FL-2. Furthermore, while HESS-5 cells directly adhered to human progenitors during culture, the cultured human cells could easily be harvested without contamination by HESS-5 cells. Within 7 days of culture, a 100-fold increase in CD34bright/CD38dim cells was obtained in serum-containing culture. When HESS-5 cells were physically separated from human progenitor cells in the presence of TPO/FL-2, synergy was blocked, suggesting that HESS-5 cells support proliferation of PPC by direct cell-to-cell interaction. The hematopoietic-supportive effects of this xenogeneic coculture system were then assessed in a very short-term (5 days) serum-free culture. Expansion was further enhanced by addition of stem cell factor (SCF) or interleukin-3 (IL-3). As a result, a 50- to 100-fold increase in CD34bright/CD38dim cells was noted. Colony-forming units in culture (CFU-C) and mixed colonies (CFU-GEMM) were enhanced by 10- to 30-fold and 10- to 20-fold, respectively. Moreover, generation of long-term-culture-initiating cells (LTC-IC) from CD34bright/CD38dim cells was amplified by 25-fold. The severe-combined immunodeficient (SCID) mouse-repopulating cell (SRC) assay confirmed extensive ability of the expanded cells to reconstitute long-term hematopoiesis. These results indicate that this xenogeneic coculture system, in combination with human cytokines, can rapidly generate PPC from cryopreserved CB.

Animals↗

Vascular smooth muscle differentiation of murine stroma: a sequential model.

Previous studies by our group showed that stromal cells from human long-term marrow cultures were mesenchymal cells following a vascular smooth muscle pathway. The present study using 58 immortalized stromal lines from different hematopoietic sites was conducted to verify whether this hypothesis also held true for murine stroma. Principal components analysis performed using cytoskeletal and extracellular matrix proteins allowed the segregation of five factors explaining more than 70% of the variance. Factor I, including osteopontin and vimentin, and factor II, laminins and fibronectins, were representative of the mesenchyme. The remaining three factors were representative of vascular smooth muscle: factor III, including alphaSM actin, SM alpha actinin, SM22alpha, EDa+ fibronectin, and thrombospondin-1; factor IV, metavinculin and h-caldesmon; and factor V, smooth muscle myosin SM1 and desmin. All lines expressed factors I and II; 53 lines expressed factor III, 35 lines expressed factor IV; and 11 lines expressed factor V. A second principal components analysis including membrane antigens indicated the cosegregration of vascular cell adhesion molecule-1 with osteopontin and that of Ly6A/E with vimentin, whereas CD34 and Thy-1 appeared to be independent factors. The heterogeneity of vascular smooth muscle markers expression suggests that harmonious maintenance of hematopoiesis depends on the cooperation between different stromal cell clones.

Animals↗

Morphological onset and early diagnosis in apical hypertrophic cardiomyopathy: a long term analysis with nuclear magnetic resonance imaging.

OBJECTIVES: A long-term follow-up study with nuclear magnetic resonance (NMR) imaging was undertaken to detect the morphological onset and to establish the early diagnosis in apical hypertrophic cardiomyopathy (HCM). BACKGROUND: A spadelike configuration on left ventriculogram (LVG) is regarded as a diagnostic criterion for the classical apical HCM. There also exists a segmented hypertrophy at the apical level without indicating the spadelike features (a nonspade configuration). To detect the hypertrophied myocardium of the nonspade configuration, circumferential scrutiny of the apex is required. Although both configurations can be underlying causes of giant negative T waves, etiological relationship between the two is not clarified. METHODS: The criteria for the spadelike configuration defined on left ventricular short-axis NMR images were as follows: (apical maximal thickness > or = 15 mm), (apical anterior thickness over basal anterior thickness > or = 1.3) and (apical posterior thickness over basal posterior thickness > or =1.3). Thirteen patients who had predominant hypertrophy (> or = 15 mm) at the apical level without the spadelike configuration underwent NMR imaging twice before and after 54+/-10 months' follow-up. RESULTS: Apical hypertrophy that had been confined to the lateral wall in four, the anterior-lateral wall in two, and the septal-anterior wall in one developed to become circumferential hypertrophy that fulfilled the criteria for the spadelike configuration after the follow-up period. CONCLUSIONS: The spadelike configuration can begin with the nonspade configuration and therefore, both can constitute a single disease entity of apical HCM. The early diagnosis of apical HCM can be achieved by identifying the hypertrophy frequently confined to the lateral wall at the apical level.

Adult↗

Relationship between HLA-DR antigen and HLA-DRB1 alleles and prostate cancer in Japanese men.

PURPOSE: Human leukocyte antigens (HLA) are cell surface glycoproteins playing a key role in the immune system. In some cancers, changes in major histocompatibility complex (MHC) class I and II expression, usually a reduction or loss of these molecules, appear to provide a mechanism whereby tumour cells may escape host immunity. We investigated the relationship between HLA, especially class II, molecules and prostate cancer in Japanese men using molecular techniques. MATERIALS AND METHODS: HLA class II typing was performed by the polymerase chain reaction-sequence specific primer (PCR-SSP) method of analysis and/or a commercial rapid assay based on the PCR followed by reverse dot-blot hybridization of the PCR products (Inno-LiPA assay). Allele frequencies were calculated. HLA allele frequencies reported in 1216 healthy Japanese individuals were used as the control data. Differences in allele frequency between subjects and the control group were analyzed by the chi-square test. The relationship between HLA antigens/alleles and prostate cancer is expressed in terms of relative risk (RR). RESULTS: The frequencies of HLA-DR4 were significantly higher in Japanese men with prostate cancer than in the healthy control group (gene frequency 36.2% vs. 26.3% in control, p<0.05), although the relative risk of prostate cancer was less than 2. Furthermore, the frequencies of HLA-DRB1-0406, 0410 and 1405 allele were significantly higher in the prostate cancer group than in the control group (allele frequency was 7.3%, 4.5% and 5.4% vs. 3.03%, 1.79% and 2.22%, p<0.05, respectively). RR of those HLA-DRB1 allele for prostate cancer was 2.6 in each allele. CONCLUSIONS: HLA molecules may be useful for the early detection of prostate cancer as a risk factor, and also for recognizing cancer activity by using them as a marker helpful in the choice of appropriate treatment by predicting prognosis.

Alleles↗

Cytokine profile in the liver of primary biliary cirrhosis.

We characterized the cytokine profile in the liver of patients with primary biliary cirrhosis (PBC). Total RNA was extracted from the biopsy specimens of 9 patients with early-stage PBC, 10 with chronic hepatitis C (CHC), and 4 normal controls. cDNA was prepared and amplified with a polymerase chain reaction using primers for interferon (IFN)-gamma and interleukin (IL)-2, -4, -5, -6, -10, -12 (p40), and -15. Cytokines such as IFN-gamma and IL-5, -6, -10, -12, and -15 were expressed in most cases of PBC. Expression rates of IL-5 and IL-6 were higher than in CHC and controls. The higher expression rate of IL-5 in PBC was associated with eosinophil infiltration. IL-2 and IL-4 were rarely detected. Semiquantitative analysis revealed that the expression of IFN-gamma and IL-10 was reversed in PBC and CHC: high IFN-gamma and low IL-10 in PBC and high IL-10 and low IFN-gamma in CHC. These results suggest that cytokine expression is skewed in PBC and both Th1 and Th2 cytokines may play a role in the pathogenesis.

Adult↗

Bone mineral density in steroid-dependent asthma assessed by peripheral quantitative computed tomography.

Chronic use of systemic glucocorticoids results in progressive bone loss and pathologic fractures. This study identified the predictive variables for bone loss and used peripheral quantitative computed tomography (pQCT) to measure changes in cortical and trabecular bone in patients receiving systemic glucocorticoid therapy of prednisone 15.4 g. Eighty-four asthmatic patients were included in the study. Vertebral fractures were diagnosed via plain spinal radiograms. pQCT was used to measure cortical and trabecular bone mineral density. Multiple regression analysis identified variables with predictive value. The cumulative dose of glucocorticoid correlated with the bone mineral density (p<0.05) and the trabecular bone density (p<0.01). Among patients > or = 65 yrs of age, the cumulative dose of glucocorticoid correlated with the occurrence of vertebral fractures (p<0.05), total bone mineral density (p<0.01) and cortical bone mineral density (p<0.01). Bone mineral density in the distal radius measured by pQCT and the vertebral bodies by axis QCT were correlated, regardless of whether systemic glucocorticoids were administered. Glucocorticoid administration not only decreases trabecular but also cortical bone mineral density. Since cortical bone provides strength and stiffness, it appears that the loss of cortical bone is responsible for the increased incidence of fracture seen in patients receiving systemic glucocorticoid therapy.

Aged↗

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

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

Antigens, CD↗

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

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

Adult↗

CD34high+ CD38(low/-) cells generated in a xenogenic coculture system are capable of both long-term hematopoiesis and multiple differentiation.

CD34+ cells isolated from human umbilical cord blood (HUCB) are thought to have potential in clinical applications such as transplantation and gene therapy. Recently, we developed a xenogenic coculture system involving HUCB-CD34+ cells and murine bone marrow stromal cells, HESS-5 cells, in combination with human interleukin-3 and stem cell factor. Under these xenogenic coculture conditions, the numbers of CD34high+ cells and primitive progenitor cells, such as CD34high+ CD38(low/-) cells and high proliferative potential colony-forming cells (HPP-CFCs), increased dramatically by a factor of 102.1, 66.5 and 104.9, respectively. In the present study, we used a secondary culture of B progenitor cells and long-term culture (LTC)-initiating cells to characterize and compare the progenitor capability of re-isolated CD34high+ CD38(low/-) cells, which have been identified as one of the most primitive progenitor cells, with that of freshly isolated CD34high+ CD38(low/-) cells. Compared with freshly isolated CD34high+ CD38(low/-) cells, the re-isolated CD34high+ CD38(low/-) cells were equally as capable of proliferating and differentiating into myeloid and B progenitor cells. No significant differences were observed in the frequency of LTC-initiating cells in the re-isolated CD34high+ CD38(low/-) cells compared with that in freshly isolated CD34high+ CD38(low/-) cells. Furthermore, the re-isolated CD34high+ CD38(low/-) cells were capable of long-term reconstitution and multiple differentiation in non-obese diabetic mice with severe combined immunodeficiency disease (NOD/SCID mice). The results demonstrate that this xenogenic coculture system can be used for successful in vitro expansion of HUCB-progenitor cells that possess the capability for both long-term hematopoiesis as well as multipotent differentiation into myeloid and lymphoid cells both in vivo and in vitro.

ADP-ribosyl Cyclase↗