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Biomedical subjects

S Nakazawa

Publications and source records attributed to S Nakazawa.

At least 73 records · Page 4Linked to original sources
PubMed1999

Acute myeloid leukemia with hypergranular cytoplasm accompanied by t(X;11)(q24;q23) and rearrangement of the MLL gene.

This report describes a unique case of acute myeloid leukemia with hypergranular cytoplasm and t(X;11)(q24;q23). The breakpoint on 11q23 was identified within the MLL gene. The hypergranular cytoplasm of leukemic cells and the associated coagulopathy resembled a characteristic of acute promyelocytic leukemia, despite the absence of RARalpha gene rearrangement in this case. The Xq24 site possibly played a role in this atypical blast phenotype.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Endoluminal ultrasonography for pancreatic diseases.

Endoluminal ultrasonography was performed on 146 patients with pancreatobiliary diseases by using high-frequency, thin ultrasonic probes, and the usefulness of the new technique in diagnosis of pancreatic diseases was reported. The ultrasound probe could be inserted into the main pancreatic duct in 43 of 46 patients (93.5%), and images of the lesions could be obtained in 42 patients (91.3%). Endoluminal ultrasonography revealed a hypoechoic mass with clear margins and central echogenicity in patients with pancreatic carcinoma. Endoluminal ultrasonography showed normal pancreatic parenchyma as a fine reticular pattern and did not reveal the tumors surrounding the stenosis in patients with focal pancreatitis. Endoluminal ultrasonography in patients with intraductal papillary adenocarcinoma of the pancreas revealed cystic lesions with mural nodules more than 4 mm, mucus echoes, and solid tumors with mixed echo patterns. There were no severe complications, and acute pancreatitis occurred in none of 46 patients, but high-level serum amylase after examination occurred in 5 patients (10.9%). Endoluminal ultrasonography is useful for differential diagnosis in patients with small pancreatic tumors or cystic lesions, especially intraductal papillary tumors of the pancreas. Endoluminal ultrasonography is recommended as a precise examination for the diagnosis of cystic lesions of the pancreas or stenosis of the main pancreatic duct after ERCP and EUS.

Adenocarcinoma, Mucinous↗
PubMed1999

DNA damage-associated cell cycle and cell death control is differentially modulated by caffeine in clones with p53 mutations.

Caffeine is known to potentiate the cytotoxic effects of DNA damaging agents and increases the sensitivity of p53-deficient cells to X-irradiation (X-IR). We have analyzed the cell cycle and cell death control after X-IR in the absence or presence of caffeine in hematological cell lines with various configurations of the p53 gene; EBV-immortalized lymphoblastoid cells with heterozygous p53 mutation (wt/mt), human leukemia cell lines HL60 and KOPM28 with no and mutant p53 expression, respectively. These cell lines display an impaired G0/G1 checkpoint and G2 delay following X-IR, and resistance to apoptosis, which are in accordance with findings previously reported. When irradiated in combination with caffeine, all these cell lines overrode the G2 delay and accumulated at G0/G1. The cell cycle modifications in these cell lines correlated with the increase in radiation-induced p34Cdc2 kinase activity by caffeine. These cell cycle control modifications by caffeine, however, were not associated with enhancement of radiation-induced apoptosis or reduction of clonogenic growth activity in these cell lines. These results suggest that the cytocidal effect of caffeine may need to be verified independently of its cell cycle regulatory activities at least in some cases with p53 mutation.

Amino Acid Substitution↗
PubMed1999

The KOR-SA3544 antigen predominantly expressed on the surface of Philadelphia chromosome-positive acute lymphoblastic leukemia cells is nonspecific cross-reacting antigen-50/90 (CD66c) and invariably expressed in cytoplasm of human leukemia cells.

We previously reported a novel monoclonal antibody KOR-SA3544 which predominantly reacted with a surface antigen (sSA3544) expressed on Philadelphia chromosome (Ph1)-positive acute lymphoblastic leukemia (ALL). In the present study, we demonstrate that the antibody specifically recognized nonspecific cross-reacting antigen (NCA)-50/90 (CD66c), one of the carcinoembryonic antigen (CEA)-related glycoproteins encoded by a member of the CEA gene family. In addition, we show that the SA3544 antigen (NCA-50/90) was invariably expressed in cytoplasm of all of the human leukemic cell lines examined (sSA3544-positive B-lymphoid two, sSA3544-negative T or B-lymphoid and non-lymphoid 24) regardless of the presence or absence of surface expression of this antigen. Immunoelectromicroscopic examination revealed that the cytoplasmic antigen was mainly present in granules in sSA3544-positive leukemia cells, whereas it was diffusely present in cytosol in sSA3544-negative leukemia cells. Thus, among members of the CEA family, NCA-50/90 was first demonstrated to be expressed not only on the surface of some leukemia cells, but also in cytoplasm of various types of leukemia cells.

Antibodies, Monoclonal↗
PubMed1999

p16/MTS1/INK4A gene is frequently inactivated by hypermethylation in childhood acute lymphoblastic leukemia with 11q23 translocation.

The p16 gene encoding a specific inhibitor of cyclin-dependent kinases 4 and 6 has been reported to be inactivated at a variety of rates in malignant tumors. We studied frequency and mechanism of inactivation of the p16 gene in various types of childhood acute lymphoblastic leukemia (ALL) using 36 leukemic cell lines established from children (B precursor-ALL, 28; B-ALL/Burkitt's lymphoma, 3; and T-ALL, 5). On Southern blot, homozygous deletions or hemizygous deletions with rearrangement were detected in 14 cell lines. The expression of p16 protein was not observed on Western blot in 18 of 22 cell lines with intact p16 gene, but induced in 16 cell lines after treatment with the demethylating agent, indicating the silencing of the p16 gene by hypermethylation. Of note, the p16 gene was inactivated by hypermethylation of the 5' CpG island in nine of nine cell lines with 11q23 translocation, but was restored with the treatment of the demethylating agent. Partial methylation of the p16 gene was also demonstrated in three of eight primary leukemia samples with this translocation, suggesting that the p16 gene inactivation by hypermethylation might play a role in the leukemogenesis and disease progression of ALL with 11q23 translocation.

Blotting, Southern↗
PubMed1999

Endosonography and endoscopic magnetic resonance imaging.

Endosonography is an important modality for the diagnosis and staging of oesophageal, gastric, colorectal and pancreatobiliary malignancy. It is also recognized as a reliable method for the evaluation of submucosal tumours of the gastrointestinal tract, for differentiating benign lesions from giant gastric folds, and for the localization of pancreatic endocrine tumours. The latest development, that of endosonographic fine-needle aspiration, provides for the cytological diagnosis of gastrointestinal tumours. This new technique may also be used for endoscopic therapy. High-frequency probes can be used to make a more accurate diagnosis of superficial carcinoma of the gastrointestinal tract, for three-dimensional imaging of gastrointestinal tumours and for intraductal ultrasonography of the bile duct and pancreatic duct. Endoscopic magnetic resonance imaging provides information not obtainable with endosonography or other modalities. It has high potential in the diagnosis and staging of gastrointestinal and pancreatobiliary tumours.

Biliary Tract Neoplasms↗
PubMed1999

Surface-rendering imaging of gastrointestinal lesions by three-dimensional endoscopic ultrasonography.

BACKGROUND AND STUDY AIMS: In three-dimensional endoscopic ultrasonography (3D-EUS), a surface-rendering method can provide both a surface image and a cross-sectional ultrasonographic image. We evaluated the usefulness of this imaging method for digestive tract lesions. PATIENTS AND METHODS: A total of 30 patients underwent 3D-EUS with surface-rendering using a 3D probe system which arranged individual radial scanning images into 128 points on a computer monitor to outline the surface of a lesion. A complete surface image of the lesion was displayed on the computer monitor using lines obtained from 40 radial scanning images. RESULTS: Surface-rendering images of lesions were similar to endoscopic images. The surface-rendering method permitted precise correlation of two-dimensional images depicting a slice of a lesion with the corresponding surface of the lesion. Unlike conventional endoscopy, this approach permitted observations of lesions at any desired angle. Complete images of lesions were achieved in 14 patients and were half-completed in another five, but could not be obtained in 11 patients: in six the distance between the lesion and the 3D probe was too short to avoid artifacts, while in five the lesion was larger than the longitudinal scanning length of 4 cm or greater than 90 in extent in radial scanning images. Artifacts caused by heartbeat led to irregular images in four patients, including three with esophageal cancer and one with gastric cancer. CONCLUSIONS: Despite some problems, surface-rendering imaging should prove useful for diagnosis, and the method will improve as software is perfected.

Colonic Neoplasms↗
PubMed1999

Decreased activity of plasma cholesteryl ester transfer protein in children and adolescents with insulin-dependent diabetes mellitus.

The aims of the present study were to determine whether the activity of cholesteryl ester transfer protein (CETP) is altered in the plasma of children and adolescents with insulin-dependent diabetes mellitus (IDDM), and whether high-density lipoprotein-cholesterol (HDL-C) levels reflect CETP activity. Plasma CETP activity was measured by a micromethod for radioisotopic assay, using exogenous lipoproteins as donor and acceptors. The study subjects were 22 Japanese children and adolescents with IDDM (8M, 14F) with a mean age of 13.0 y. They were non-obese and did not suffer from any significant nephropathy. The age-matched control group consisted of 20 children (10M, 10F) with a mean age of 12.7y. Serum triglycerides were significantly decreased, while the levels of HDL-C and apolipoprotein (apo) A1 were markedly increased, in the IDDM patients. Plasma CETP activity was significantly lower in the IDDM patients than in the control children. None of the anthropometric indices nor the biochemical data correlated significantly with CETP activity in the IDDM patients. Suppression of CETP along with the putative activation of lipoprotein lipase due to peripheral hyperinsulinism appears to induce synergistically the increase in HDL-C in IDDM children.

Adolescent↗
PubMed1999

Effect of peroxisome proliferator on extracellular glutathione peroxidase in rat.

Glutathione peroxidase (GPX) activity measured using tert-butyl hydroperoxide as a substrate detects solely cellular/classical GPX (cGPX) in rat liver and kidney, and extracellular/plasma glutathione peroxidase (EC-GPX) in rat serum. To investigate the effect of peroxisome proliferator on EC-GPX, we measured activities of GPX and catalase in rat liver, kidney and serum, and then we performed immunoblot and Northern blot analyses in the kidney. Rats were fed on a diet containing either 2% (w/w) di-2-ethylhexyl phthalate (DEHP) or 0.25% (w/w) clofibrate for two or three weeks, respectively. Catalase activity was increased 1.4-fold (p < 0.001) in the treated liver, but not in the kidney. GPX activity was decreased to 59.2% (DEHP) and 70.4% (clofibrate) of the control (p < 0.001) in the serum but was unaltered in the liver and kidney. The immunoreactivity for EC-GPX was also significantly decreased in the DEHP-treated kidney compared with the control. The mRNA levels of EC-GPX and cGPX were unaltered. The immunostaining for 4-hydroxy-2-nonenal, a maker of lipid peroxide, was more intense in the treated kidney compared with the control. These results suggest that EC-GPX is post-transcriptionally decreased by peroxisome proliferator through the oxidative stress in the renal tubules. This may be a new deleterious effect of an endocrine disruptor DEHP.

Aldehydes↗
PubMed1999

Association of angiotensin-converting enzyme gene polymorphism with lipid profiles in children and adolescents with insulin-dependent diabetes mellitus.

We attempted to clarify the association between angiotensin-converting enzyme (ACE) gene polymorphism and the other predictive factors for macroangiopathy in children and adolescents with uncomplicated insulin-dependent diabetes mellitus (IDDM). Sixty-three patients were divided into 3 groups according to the ACE genotypes. The lipid profiles were evaluated according to ACE genotypes. The level of lipoprotein(a) (Lp(a)) in the II genotype was significantly lower than that in groups with the D allele. Lp(a) significantly correlated with apo B/apo A-I (p < 0.001, r = 0.63) and atherogenic index (AI = (total cholesterol - high-density lipoprotein cholesterol)/high-density lipoprotein cholesterol; p = 0. 004, r = 0.36). We suggest that the D allele may affect the level of Lp(a) and the other lipid profiles in IDDM.

Adolescent↗
PubMed1999

Responsiveness of peripheral blood B cells to recombinant CD40 ligand in patients with systemic lupus erythematosus.

OBJECTIVE: To investigate the immunopathological significance of CD40/CD40 ligand system for B cell hyperactivation in SLE patients, the expression and the function of CD40 on B cells were compared with those of normal controls. METHODS: Expression of CD40 was evaluated by flow cytometry. DNA synthesis of B cells were measured by 3H - TdR incorporation. Antibody production was assessed by ELISA. RESULTS: There was no significant difference between SLE and normal controls in CD40 expression on peripheral blood B cells. Recombinant CD40 ligand-leucine zipper fusion protein (CD40L-LZ) significantly enhanced 3H - TdR incorporation by both SLE and normal B cells (P<0.01). 3H - TdR incorporation of SLE B cells without stimuli (P<0.001) and with CD40L-LZ stimulation (P<0.05) were significantly lower in SLE patients compared with normal controls. Active SLE B cells spontaneously produced significantly larger amounts of total IgG than normal B cells (P<0.05). CD40L-LZ significantly increased the production of total IgG by SLE B cells (P<0.05), but not by normal B cells. Active SLE B cells spontaneously produced IgG anti-dsDNA and IgG anti-ssDNA antibodies. CD40L-LZ significantly increased the production of these autoantibodies by SLE B cells (P<0.05). B cells from normal controls do not produce these autoantibodies spontaneously nor in response to CD40L-LZ. CONCLUSION: These findings indicate that signalling via CD40 plays an important role in B cell proliferation and autoantibody production in human SLE.

Autoantibodies↗
PubMed1999

Neonatal catecholaminergic ventricular tachycardia--a case report.

A case of neonatal catecholaminergic ventricular tachycardia is reported. Episodes of fetal tachycardia were detected in a female baby and just after birth, sustained monomorphic ventricular tachycardia of complete left bundle branch block pattern and inferior axis were recorded, suggesting a right ventricular outflow origin. Routine examination did not reveal overt heart disease. Ventricular tachycardia was induced by crying or sucking, elicited by isoproterenol infusion, and was suppressed by intravenous injection of ATP or propranolol. The baby's arrhythmia was controlled with oral propranolol. The ventricular tachycardia seemed to be caused by triggered activity.

Adenosine Triphosphate↗
PubMed1999

Growth hormone advances spermatogenesis in premature rats treated with gonadotropin-releasing hormone agonist.

To clarify the effect of GH on the development of seminiferous tubules in premature male rats, we investigated whether GH accelerates spermatogenesis under the condition of gonadotropin deprivation. Male Wistar rats aged three weeks were divided into three groups and subjected to administration of either long-acting GnRH agonist (GnRHa) or a combination of GnRHa and rat GH, with normal saline solution as control. After the 4-week treatment, sperm density and motility in the right epididymis were measured and seminiferous tubules of right testes were histologically examined. Sperm density and motility were significantly higher in GnRHa+GH-treated rats than in GnRHa-treated rats. In histological examination, the numbers of germ cells in various stages were increased in GnRHa+GH-treated rats compared with GnRHa-treated rats, with the number of mature spermatid being noticeably higher in GnRHa+GH-treated rats. These results suggest that administration of GH decreases loss of germ cells at various stages of spermatogenesis under the condition of gonadotropin withdrawal.

Analysis of Variance↗
PubMed1999

The involvement of growth hormone-binding protein in altered GH-IGF axis in IDDM.

UNLABELLED: High GH and low IGF-I are well known in IDDM patients. To delineate this altered GH-IGF-I axis in IDDM, we investigate the role of GH-binding protein (GHBP) in relation to the metabolic and nutritional states. MATERIALS AND METHODS: Forty seven patients with IDDM, mean 13.7 years, were evaluated. Blood samples were obtained before insulin injection and breakfast to test for plasma glucose (PG), IGF-I, IGFBP-1, IGFBP-3, total and complex GHBP (tGHBP and cGHBP), and HbA1c. Urine samples were collected in the morning for urinary GH (uGH). The difference between tGHBP and cGHBP is defined as fGHBP. The levels of PG and HbA1C were not correlated with each level of tGHBP, cGHBP, fGHBP or uGH. The levels of tGHBP, cGHBP and fGHBP were not all correlated with uGH. Both the levels of IGF-I and body mass index (BMI) were positively correlated with fGHBP. The duration of IDDM was negatively correlated with tGHBP, cGHBP and fGHBP. DISCUSSION: As the previous report of the relationship between GH binding reserve to GHBP and IGF-I or BMI in non-diabetic subjects, fGHBP again showed statistical links with these parameters in IDDM. We therefore suggest that GHBP, especially its free form, may reflect a malmetabolic state of IDDM liver, resulting in an altered GH-IGF-I axis.

Adolescent↗
PubMed1999

Ligation of CD40 induced tumor necrosis factor-alpha in rheumatoid arthritis: a novel mechanism of activation of synoviocytes.

OBJECTIVE: To determine the immunopathological significance of CD40/CD40 ligand (CD40L) interaction in rheumatoid arthritis (RA). METHODS: The expression of CD40 ligand (CD40L) in synovial tissues (ST) from patients with RA was examined by immunohistochemistry. Tumor necrosis factor-alpha (TNF-alpha) was measured by ELISA. Expression of CD40 on ST cells was quantified by anti-CD40 monoclonal antibodies and 125I labelled anti-mouse IgG. RESULTS: Immunohistochemistry showed CD40L+ T cells in RA ST. Ligation of CD40 on RA ST cells significantly increased the production of TNF-alpha in a dose dependent fashion. Adherent, but not non-adherent, fraction of ST cells responded to ligation of CD40 to produce TNF-alpha. Interferon-gamma (IFN-gamma), interleukin 4 (IL-4), or IL-13 acted synergistically with CD40 ligation to enhance TNF-alpha production by ST cells. IL-10 exerted inhibitory effects on both CD40 ligation induced and CD40 ligation plus IFN-gamma induced TNF-alpha production by ST cells. CONCLUSION: These data indicate activated T cells participate in synovial inflammation of RA via CD40L to stimulate the production of TNF-alpha by ST cells. The effect of CD40 ligation is modulated by the presence of several cytokines, e.g., IFN-gamma, IL-4, IL-10, and IL-13.

Arthritis, Rheumatoid↗