Search PubMed⌕ Search

Biomedical subjects

N Tada

Publications and source records attributed to N Tada.

At least 37 records · Page 2Linked to original sources

Acinar-islet cell tumor of the pancreas: report of a malignant pancreatic composite tumor.

An unusual case of malignant pancreatic composite tumor with both components of acinar cell tumor (ACT) and islet cell tumor (ICT) was investigated histologically, immunohistochemically, and ultrastructurally. The pancreatic tumor with central cyst formation was found on computerized tomographic examination of a 72-year-old man reporting appetite and weight loss. The ACT component was present in the original pancreatic region and the ICT region was adjacent to the ACT. ACT was immunohistochemically positive for pancreatic amylase, whereas ICT had argyrophil tumor cells immunohistochemically positive for chromogranin A. There were several tumor cell nests positive for both pancreatic amylase (acinar differentiation) and chromogranin A (islet differentiation). We speculated that ICT may have arisen from the de-differentiated tumor cells in the ACT after the occurrence of ACT.

Aged↗

Separate cis-acting DNA elements control cell type- and tissue-specific expression of collagen binding molecular chaperone HSP47.

HSP47 is a collagen-binding heat shock protein and is assumed to act as a molecular chaperone in the biosynthesis and secretion of procollagen. As the synthesis of HSP47 is closely correlated with that of collagen in various cell lines and tissues, we performed a promoter/reporter assay using HSP47-producing and nonproducing cells. 280 base pairs (bp(s)) of upstream promoter were shown to be necessary for the basal expression but not to be enough for the cell type-specific expression. When the first and the second introns were introduced downstream of this 280-bp region, marked up-regulation of the reporter activity was observed in HSP47-producing cells but not in nonproducing cells. This was confirmed in transgenic mice by staining the lacZ gene product under the control of the 280-bp upstream promoter and the introns. Staining was observed in skin, chondrocytes, precursor of bone, and other HSP47/collagen-producing tissues. A putative Sp1-binding site at -210 bp in the promoter, to which Sp3 and an unidentified protein bind, was shown to be responsible for this up-regulation when combined with the introns. However no difference in the binding to this probe was observed between HSP47-producing and nonproducing cells. The responsible region for cell type-specific up-regulation was found to be located in a 500-bp segment in the first intron. On electrophoresis mobility shift assay using this 500-bp probe, specific DNA-protein complexes were only observed in HSP47-producing cell extracts. These results suggest that two separate elements are necessary for the cell type-specific expression of the hsp47 gene; one is a putative Sp1-binding site at -210 bp necessary for basal expression, and the other is a 500-bp region within the first intron, required for cell type-specific expression.

3T3 Cells↗

Comparison of gene arrangements of chloroplasts between two centric diatoms, Skeletonema costatum and Odontella sinensis.

We have cloned and sequenced 3.4 kbp, 2.5 kbp, 1.9 kbp, 1.6 kbp and 0.5 kbp segments of a marine centric diatom, Skeletonema costatum, chloroplast DNA. These segments contain 28 genes. The genes which are not encoded on chloroplast genomes of chlorophyll a+b plants are found such as the psaD, ycf33, ycf35 and ycf47 genes. The gene sequences were compared with that of Odontella sinensis. At nucleic acid level, the ycf genes have lower homologies (69-87%) with O. sinensis than the other genes (78-100%), and some differences in the gene arrangement are found between two centric diatoms, O. sinensis and S. costatum.

Chloroplasts↗

[Examination of subjective symptoms of fatigue in young men. From the viewpoint of age, subjective fatigue feeling and daily activity condition].

OBJECTIVE: The purpose of this study was to examine the characteristics of subjective symptoms of fatigue (SSF) in high school and college students from the viewpoints of age, subjective feelings of fatigue and an association with daily activity conditions. METHODS: A questionnaire consisting of 54 items on SSF, including feelings of subjective feelings of fatigue, type of fatigue and daily activity conditions was administered to male students aged 15-20 yrs. Data from 1972 subjects, responding to the questionnaire were used for statistical analysis. RESULTS: A Cronbach alpha coefficient of 0.97 indicated the reliability of the SSF items. In analyzing the results for frequency and means of SSF items, it was determined that complaints regarding drowsiness were very high compared to other SSF factors and the degree of mental fatigue symptoms is lower in the higher age-groups. Most students had subjective feelings of fatigue, which related closely to SSF regarding languor and drowsiness. It was considered that daily activity conditions regarding sleep are important to improving chronic fatigue because students with stronger subjective feelings of fatigue tend to have complaints about living conditions such as sleeplessness at night, waking in the morning, and physical condition during the day. CONCLUSION: It is characteristic of SSF in young men that complaints of drowsiness are relatively high and most of the students have subjective feelings of fatigue. It is considered that improving the activities of daily living factors that produce drowsiness is important.

Activities of Daily Living↗

[Primary hyperchylomicronemia and gene defects].

Primary Hyperchylomicronemia is known as a syndrome in which the accumulation of chylomicron occurs in the circulation. The main clinical symptoms of this disorder are the huge increase in plasma trigriceride and cholesterol, and the presence of xanthomatous eruption, lipemia retinalis, hepatosplenomegaly, and the complication of acute pancreatitis. With gene analysis, a deficiency of lipopreteinlipase (LPL) or apolipoprotein C-II is revealed as a main cause of primary chylomicronemia. Furthermore, in some cases, abnormalities of remnant receptors, the presence of antibody against LDL, apolipoprotein C-II, and LDL receptor are reported as causes of chylomicronemia syndrome. In the present paper, we summarized the major gene polymorphism and characteristics of clinical symptom of these disease.

Apolipoprotein C-II↗

[Remnant hyperlipidemia and gene polymorphism].

Remnant lipoproteins are intermediate metabolites of triglyceride-rich lipoproteins, such as chylomicron (CM) and very-low density lipoprotein (VLDL) in the circulation. Several lines of evidence have suggested that remnant lipoproteins are atherogenic. It is well known that some of the inherited dyslipidemias cause remnant hyperlipidemia and are accompanied with marked skin and tendon xanthomas, corneal arcus and premature or accelerated atherosclerosis. Among them, lipid abnormalities, clinical features and gene polymorphism of familial dyslipoproteinemia and hepatic lipase deficiency were reviewed. Even if one has affected alleles associated with these disorders, sometimes abnormal lipid profiles are difficult to reveal in the overnight fasting plasma. So, a tolerance test like a fat overloading may be required to elucidate such abnormalities.

Apolipoproteins↗

The B-cell transmembrane protein CD72 binds to and is an in vivo substrate of the protein tyrosine phosphatase SHP-1.

BACKGROUND: Signals from the B-cell antigen receptor (BCR) help to determine B-cell fate, directing either proliferation, differentiation, or growth arrest/apoptosis. The protein tyrosine phosphatase SHP-1 is known to regulate the strength of BCR signaling. Although the B-cell co-receptor CD22 binds SHP-1, B cells in CD22-deficient mice are much less severely affected than those in SHP-1-deficient mice, suggesting that SHP-1 may also regulate B-cell signaling by affecting other signaling molecules. Moreover, direct substrates of SHP-1 have not been identified in any B-cell signaling pathway. RESULTS: We identified the B-cell transmembrane protein CD72 as a new SHP-1 binding protein and as an in vivo substrate of SHP-1 in B cells. We also defined the binding sites for SHP-1 and the adaptor protein Grb2 on CD72. Tyrosine phosphorylation of CD72 correlated strongly with BCR-induced growth arrest/apoptosis in B-cell lines and in primary B cells. Preligation of CD72 attenuated BCR-induced growth arrest/death signals in immature and mature B cells or B-cell lines, whereas preligation of CD22 enhanced BCR-induced growth arrest/apoptosis. CONCLUSIONS: We have identified CD72 as the first clear in vivo substrate of SHP-1 in B cells. Our results suggest that tyrosine-phosphorylated CD72 may transmit signals for BCR-induced apoptosis. By dephosphorylation CD72. SHP-1 may have a positive role in B-cell signaling. These results have potentially important implications for the involvement of CD72 and SHP-1 in B-cell development and autoimmunity.

Animals↗

Effects of transjugular intrahepatic portosystemic shunt (TIPS) on esophageal motor function and gastroesophageal reflux.

The effects of transjugular intrahepatic portosystemic shunt (TIPS) placement on esophageal motor function and gastroesophageal reflux were investigated in patients with esophageal varices. In six men with esophageal varices, esophageal manometry and upper gastrointestinal endoscopy were performed before and 15-20 days after TIPS placement. Intraesophageal pH monitoring was performed in the four patients with severe esophageal varices (defined as the largest sized varices) following TIPS placement. Findings were compared with those in six healthy men (controls) who underwent esophageal manometry and intraesophageal pH monitoring. The esophageal varices resolved or were reduced after TIPS placement. Resting lower esophageal sphincter (LES) pressures were similar in the study group before and after TIPS placement and in the control subjects. The incidence and progression of esophageal contractions were similar in the study group before and after TIPS placement and in the control subjects. At 3 cm above the LES, the amplitude of esophageal contraction after TIPS placement was significantly higher than that before TIPS placement. At 3 and 8 cm above the LES, the amplitude of esophageal contraction in the control subjects was significantly higher than that in the study group before and after TIPS placement. Esophageal acid exposure time after TIPS placement was similar to that in the controls. TIPS placement is a useful treatment that improves esophageal motor function without the occurrence of pathologic gastroesophageal reflux.

Esophageal and Gastric Varices↗

[Transjugular intrahepatic portosystemic shunt for the treatment of refractory ascites].

Five cirrhotic patients with refractory ascites were treated with transjugular intrahepatic portosystemic shunt (TIPS). Before TIPS, although patients were received salt restriction (5 g/day), diuretic therapy (furosemide 112 mg/day, spironolactone 140 mg/day), albumin infusion and paracentesis, ascites did not show improvement. After TIPS, urine volume and urinary sodium excretion increased significantly. Mean body weight decreased significantly from 73 kg before TIPS to 63 kg a month after TIPS. Improvement of ascites after TIPS were associated with a significant reduction in the dose of diuretics. On discharge, complete resolution of ascites was found in 2 patients and mild ascites remained in 3 other patients. Four patients presented 6 episodes of shunt stenosis in the follow-up period, and were treated with balloon dilatation. Ascites increased on shunt dysfunction and showed improvement after balloon dilatation. Post-TIPS encephalopathy was seen in 2 patients and one of 2 was disabled. In conclusion, although post-TIPS shunt dysfunction and encephalopathy are common. TIPS is an effective therapy for refractory ascites in patients with cirrhosis.

Ascites↗

Introduction of an osteopontin gene confers the increase in B1 cell population and the production of anti-DNA autoantibodies.

Osteopontin (OPN) is an Arg-Gly-Asp-containing phosphoprotein that is secreted by activated T cells. The concentration of serum OPN protein is elevated in autoimmune-prone MRL-lpr mice as well as in patients with systemic lupus erythematosus. Previously, it was shown that OPN induces the polyclonal activation of B cells, resulting in the augmented production of immunoglobulin, indicating that OPN plays some role in the development of autoimmune disease. However, the link between OPN and development of autoimmune disease remains unclear. To analyze the role of OPN in immune system and autoimmune diseases, we have generated two kinds of transgenic mice: one carries the immunoglobulin (Ig) enhancer/SV40 promoter and the other carries the cytomegalovirus enhancer/chicken beta-actin (CAG) promoter. In both groups of transgenic mice, the B1 cell population in peritoneal cavity was markedly increased and titer of IgM and IgG3 antibodies in the serum was considerably higher than that in wild-type mice. Most important, the titer of the IgM class of anti-double-stranded DNA antibody was significantly elevated in transgenic mice. These results strongly suggest that OPN may have an important role in the propagation and differentiation of B1 cells and production of autoantibodies.

Animals↗

[Lipid and lipoprotein profile of Japanese centenarians--high prevalence of hypo beta lipoproteinemia].

To study the relationship between lipids and longevity, we examined the level of serum lipids and apolipoproteins, and the susceptibility of low density lipoprotein (LDL) to oxidation of 45 centenarians (15 men, 30 women, mean age 101.1 +/- 1.4) living in the Tokyo metropolitan area. The average levels of total cholesterol (TC), of LDL-C of high-density lipoprotein cholesterol (HDL-C), and of apolipoproteins A1 and B were significantly lower in centenarians than in healthy middle-aged controls. The frequency of hypobeta-lipoproteinemia (apoB < 60 mg/dl) in centenarians was almost ten times as high as in controls. The time course of copper-mediated LDL, oxidation (assessed by monitoring 234 nm diene absorption (lag time)) did not significantly differ between the two groups. Analysis of LDL subfractions by non-denaturated gradient-gel electrophoresis showed a predominance of large, buoyant LDL particles (pattern A) in 75%, and a predominance of small dense LDL particles (pattern B) in 25% of centenarians. We also assessed activities of daily living (ADL) and cognitive function in the centenarians. Centenarians were divided into two groups according to the median ADL score, and were classified into five groups with a scale clinical dementia. In subjects with good ADL scores, the mean concentration of HDL-3-C was significantly higher than in those with poor ADL scores. Average levels of HDL-C were also significantly lower in subjects with moderate or severe dementia than in those with normal cognitive function. These findings suggest that centenarians have protective phenotypes of lipids and lipoproteins that protect them from atheroscierosis.

Activities of Daily Living↗

[Rapid onset of hemolytic anemia after allogeneic bone marrow transplantation from an unrelated ABO major mismatched donor].

A 46-year-old woman with chronic myelogenous leukemia received allogeneic bone marrow transplantation from an unrelated human leukocyte antigen (HLA) matched (but mixed lymphocyte culture (MLC) positive to graft-versus host disease (GvHD) donor. The blood type of the recipient was A type Rh (+) while the donor blood type was B type Rh (+). The patient received busulfan 8 mg/kg, cyclophosphamide 120 mg/kg, and total-body irradiation 10 Gy before bone marrow transplantation. Short-term administration of methotrexate and cyclosporin was given for prophylaxis of GvHD. The mononuclear cells harvested from the donor were concentrated by COBE Spectra before bone marrow transplantation. Although engraftment of transplanted bone marrow in the recipient was confirmed on day 11, the patient suffered from severe anemia on day 10. Since the direct Coombs' test to A type red blood cells was positive, and anti-A antibody titer increased 16-fold, we diagnosed her anemia as hemolytic anemia caused by ABO mismatched transplantation. In addition to hemolytic anemia, she had skin symptoms of acute GvHD grade II, microangiopathic hemolytic anemia, and died of multiple organ failure on day 44. This experience indicated that some allogeneic transplant recipients are at risk of severe hemolytic anemia in the early stage after unrelated ABO mismatched donor and that it is necessary to establish proper treatment and prophylaxis.

ABO Blood-Group System↗

Intracellular generation of amyloid beta-protein from amyloid beta-protein precursor fragment by direct cleavage with beta- and gamma-secretase.

Two amyloid beta protein precursor (beta APP) fragments involving Met and 103 amino acids of C-terminus of beta APP (delta NOR-beta) and its KM-NL substitution (delta NL-beta) were expressed in COS-7 cells to clarify the proteolytic cleavages to generate amyloid beta protein (A beta). The 4.5-kD protein, A beta with additional N-terminal amino acids, and 4-kD A beta were directly produced and released from 12.5-kD expression proteins without any production of 11.4-kD C-terminal fragment starting at N-terminus of A beta and 3-kD "p3" A beta derivative. Intracellular 4-kD A beta was also detected. The substitution of KM-NL of beta APP found in Swedish familial Alzheimer's disease (AD) promoted the production of intracellular A beta and its release with no increase in level of 11.4-kD C-terminal fragment. These results suggested the presence of a distinct pathway in which A beta is directly cleaved at both N- and C-termini from beta APP fragment intracellularly to release A beta. Since KM-NL substitution enhanced intracellular A beta generation, this pathway may be associated with amyloidogenesis in AD.

Alzheimer Disease↗

Multiple myeloma-associated systemic vasculopathy due to crystalglobulin or polyarteritis nodosa.

Systemic vasculopathy is a rare complication of multiple myeloma (MM). We describe a patient diagnosed with MM who developed clinical features of systemic vasculopathy including gangrene, livedo reticularis, hypertension, renal failure, and perforation of the small intestine. Histopathologic examination of the small intestine revealed necrotizing vasculitis in the small arteries, along with crystalline deposits in the small vessels. To our knowledge, previously reported cases of systemic vasculopathy associated with MM include at least 9 cases due to crystalglobulin deposition in vessels and 2 due to polyarteritis nodosa. Deposits of crystalglobulin may have induced systemic necrotizing vasculitis in our patient.

Adult↗

Numerical simulation of a turning alpine ski during recreational skiing.

While downhill snow skiing, recreational alpine skiers enjoy making turning motions with their skis. These motions are mainly induced by skidding, while turning by alpine ski racers is made by carving a trace in the snow. In the present study we treat the turning motions by recreational alpine skiers. This "skidding" turning motion is made possible by centripetal forces acting on the ski and skier dynamic motion systems, with these forces arising due to the skier placing the ski's longitudinal axis at an angle that is inclined away from the velocity vector and edging the ski into the snow. When snow is soft, the edged ski creates a snow impacting force, whereas a snow cutting force occurs when it is hard. Here, we calculate the former force using a three-dimensional water jet analogy, while the latter one using conventional metal cutting theory, after which the corresponding equations of motion for each system are derived and numerically solved. This methodology enables simulating the curvilinear and rotational motion of the ski and skier systems. Resultant simulations quantitatively show for the first time that the resultant radius of curvature of a ski track while downhill skiing is strongly dependent on the location of the ski boot on the ski's longitudinal axis and also on its side-cut (midlength taper).

Biophysical Phenomena↗