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Biomedical subjects

J Tamura

Publications and source records attributed to J Tamura.

At least 91 records · Page 5Linked to original sources

Synthetic approach towards sulfated chondroitin di-, tri- and tetrasaccharides corresponding to the repeating unit.

Chondroitin di-, tri- and tetrasaccharides, as well as their 4-, 6-mono- and 4,6-disulfates as their 4-methoxyphenyl glycosides, were systematically synthesized. Target disaccharides having beta GalNAc-(1-->4)-beta GlcA sequences were obtained starting from the corresponding pivotal chondroitin disaccharide precursor. A trisaccharide intermediate, which was synthesized by coupling of glucuronate imidate with a known disaccharide acceptor, was transformed into the sulfated and non-sulfated chondroitin trisaccharides. Chondroitin tetrasaccharide and the corresponding 4-disulfate, 6-disulfate as well as 4,6-tetrasulfate were also obtained based on the strategy developed above starting from the reported tetrasaccharide having [beta GalN3-(1-->4)-beta GlcA2] sequence.

Carbohydrate Sequence↗

Possible involvement of protein kinase C in the aberrant regulation of erythropoiesis in polycythemia vera.

To examine the possible involvement of protein kinase C (PKC) in the regulation of aberrant erythropoiesis of polycythemia vera (PV), we investigated the effects of PKC inhibitors on in vitro burst-forming unit of erythroid (BFU-E)-derived colony formation by bone marrow (BM) and peripheral blood (PB) cells obtained from five PV patients. 1-(Isoquinoline-sulfonyl)-2-methylpiperazine dihydrochloride (H-7), an inhibitor of PKC, suppressed the colony formation by BM and PB cells of PV patients in a dose-dependent manner, similar to those in the normal individuals. However, the 50% inhibitory concentrations (IC50) of H-7 in PV BM and PB cells were significantly higher than those in normal BM and PB cells, respectively. The BFU-E-derived colony formation by PV BM and PB cells was also less affected by Staurosporine, another PKC inhibitor, than those in a normal subject. Furthermore, in the study of PV, the IC50 of endogenous colonies formed in the absence of erythropoietin was much higher than that of colonies formed by the stimulation of erythropoietin. By contrast, N-(2-guanidinoethyl)-5-isoquinolinesulfonamide dihydrochloride (HA1004), a cyclic AMP-dependent kinase inhibitor, did not have such inhibitory effects. These findings suggest that PKC, as a second messenger, is involved in the regulation of aberrant erythropoiesis of PV.

Adult↗

Internal tandem duplication of FLT3 associated with leukocytosis in acute promyelocytic leukemia. Leukemia Study Group of the Ministry of Health and Welfare (Kohseisho).

FLT3 is a member of receptor tyrosine kinases expressed in leukemia cells, as well as in hematopoietic stem cells. Recently, a somatic alteration of the FLT3 gene was found in acute myeloid leukemia, as an internal tandem duplication (FLT3/ITD) which caused elongation of the juxtamembrane (JM) domain of FLT3. Here we characterized the FLT3/ITD and investigated its clinical significance in acute promyelocytic leukemia (APL). Seventy-four newly diagnosed patients with APL, who were treated with the same protocol in a multi-institutional study, were studied for the FLT3/ITD. Genomic and message sequences of the FLT3 gene were amplified by means of polymerase chain reaction (PCR), and elongated PCR products were sequenced. Fifteen patients (20.3%) had FLT3/ITD, all of which were transcribed in frame. Location of the duplicated fragments (six to 30 amino acids) varied from patient to patient. However, they always contained either Y591 or Y599, but the tyrosine kinase domain was not significantly affected. This finding implied that signal transduction of FLT3 is amplified by the duplication. Clinically, the presence of FLT3/ITD was related to high peripheral white blood cell counts as well as peripheral leukemia cell counts (P < 0.0001), high LDH level (P = 0.04), and low fibrinogen concentration (P = 0.04). These data suggest that FLT3/ITD plays a significant role in progression of APL.

Adult↗

Regulation of chondroitin sulfate biosynthesis by specific sulfation: acceptor specificity of serum beta-GalNAc transferase revealed by structurally defined oligosaccharides.

The relationship between sulfation and polymerization in chondroitin sulfate (CS) biosynthesis has been poorly understood. In this study, we investigated the specificity of bovine serum UDP-GalNAc: CS beta-GalNAc transferase responsible for chain elongation using structurally defined acceptor substrates. They consisted of tetra- and hexasaccharide-serines that were chemically synthesized and various regular oligosaccharides with a GlcA residue at the nonreducing terminus, prepared from chondroitin and CS using testicular hyaluronidase. The enzyme preparation was obtained from fetal bovine serum by means of heparin-Sepharose affinity chromatography. The preparation did not contain the alpha-GalNAc transferase recently demonstrated in fetal bovine serum (Kitagawa et al., J. Biol. Chem., 270, 22190-22195, 1995), that utilizes common acceptor substrates. The beta-GalNAc transferase used as acceptors, two hexasaccharide-serines GlcA beta 1-3GalNAc beta 1-4GlcA beta 1-3Gal beta 1-3Gal beta 1-4Xyl beta 1-O-Ser and GlcA beta 1-3GalNAc(4-sulfate) beta 1-4GlcA beta 1-3Gal (4-sulfate) beta 1-3Gal beta 1-4Xyl beta 1-O-Ser, but neither the monosulfated hexasaccharide-serine GlcA beta 1-3GalNAc(4-sulfate) beta 1-4GlcA beta 1-3Gal beta 1-3Gal beta 1-4Xyl beta 1-O-Ser nor tetrasaccharide-serines with or without a sulfate group at C-4 of the third sugar residue Gal-3 from the reducing end. The results indicated that the sulfate group at the Gal-3 C-4 markedly affected the transfer of GalNAc to the terminal GlcA. In addition, a sulfate group at C-4 of the reducing terminal GalNAc of regular tetrasaccharides remarkably enhanced the GalNAc transfer, suggesting that the enzyme recognizes up to the fourth saccharide residue from the nonreducing end. The level of incorporation into a tetra- or hexasaccharide containing a terminal 2-O-sulfated GlcA residue was significant, whereas there was no apparent incorporation into tetra- or hexasaccharides containing a terminal 3-O-sulfated GlcA or penultimate 4,6-O-disulfated GalNAc residue. These results indicated that sulfation reactions play important roles in chain elongation and termination.

Animals↗

Characterization of serum beta-glucuronyltransferase involved in chondroitin sulfate biosynthesis.

We studied a glucuronyltransferase involved in chondroitin sulfate (CS) biosynthesis in a preparation obtained from fetal bovine serum by heparin-Sepharose affinity chromatography. This enzyme transferred GlcA from UDP-GlcA to the nonreducing GalNAc residues of polymeric chondroitin. It required Mn2+ for maximal activity and showed a sharp pH optimum between pH 5.5 and 6.0. The apparent Km value of the glucuronyltransferase for UDP-GlcA was 51 microM. The specificity was investigated using structurally defined acceptor substrates, which consisted of chemically synthesized tri-, penta-, and heptasaccharide-serines and various odd-numbered oligosaccharides with a GalNAc residue at the nonreducing terminus, prepared from chondroitin and CS by chondroitinase ABC digestion followed by mercuric acetate treatment. The enzyme utilized a heptasaccharide-serine GalNAc beta 1-4GlcA beta 1-3GalNAc beta 1-4GlcA beta 1-3Gal beta 1-3Gal beta 1-4Xyl beta 1-O-Ser and a pentasaccharide-serine GalNAc beta 1-4GlcA beta 1-3Gal beta 1-3Gal beta 1-4Xyl beta 1-O-Ser as acceptors. In contrast, neither a trisaccharide-serine Gal beta 1-3Gal beta 1-4Xyl beta 1-O-Ser nor an alpha-GalNAc-capped pentasaccharide-serine GalNAc alpha 1-4GlcA beta 1-3Gal beta 1-3Gal beta 1-4Xyl beta 1-O-Ser that is a model compound of the reaction product formed by the action of the alpha-GalNAc transferase recently demonstrated in fetal bovine serum (Kitagawa et al., J. Biol. Chem., 270, 22190-22195, 1995) was utilized as an acceptor. Besides, all nonsulfated odd-numbered oligosaccharides except for the trisaccharide GalNAc beta 1-4GlcA beta 1-3GalNAc served as acceptors and the transfer rates roughly increased with increasing chain length. Moreover, 6-O-sulfation of nonreducing terminal GalNAc markedly enhanced GlcA transfer, whereas 4-O-sulfation had little effect on it. These results indicated that at least two glucuronyltransferases are involved in the biosynthesis of CS and that sulfation reactions may play important roles in chain elongation.

Animals↗

Acute myeloid leukemia accompanied by multiple thrombophlebitis.

A 66-year-old woman suffering from fever and thrombophlebitis was referred to our hospital. A peripheral blood examination revealed hyperleukocytosis with 96% blast cells and thrombocytopenia. The patient was diagnosed as having acute myeloid leukemia (AML) accompanied by disseminated intravascular coagulation (DIC). A marked decrease in protein C (PC) antigen and activity were observed. In this case, PC levels were lower than those observed in AML with DIC. Induction therapy for leukemia and treatment of DIC were started on the first day of hospitalization. The patient achieved complete remission, with PC antigen and activity levels normalized.

Aged↗

Treatment of refractory cases of atopic dermatitis with acidic hot-spring bathing.

The incidence of refractory atopic dermatitis has increased in teenagers and young adults. The purpose of this study was to control the skin symptoms of such patients in daily life. Seventy patients repeatedly took a 10-min 42 degrees C acidic hot-spring bath twice daily. The skin symptoms were improved in 76% of cases. In 30 of 42 responders examined Staphylococcus aureus, detected on the skin surface, disappeared or decreased through balneotherapy. In contrast, S. aureus remained unchanged in 8 of 10 non-responders examined. Thus, the balneotherapy using acidic hot-spring water may be useful for controlling the skin symptoms of acute flares of refractory cases of atopic dermatitis.

Adolescent↗

[Physical therapy in a pool as rehabilitation for chronic obstructive pulmonary disease in the elderly].

The pulmonary function test and arterial blood gas analysis were performed before and after a 2-month rehabilitation program in a pool filled with 38 degrees C hot-spring water in 15 elderly patients (75.7 +/- 3.7 years of age; 12 males and 3 females; 6 cases of pulmonary emphysema and 9 cases of bronchial asthma) and 10 young patients (56.4 +/- 14.2 years of age, 7 males and 3 females; 4 cases of pulmonary emphysema and 6 cases of bronchial asthma) with stable chronic obstructive pulmonary disease treated at Gunma University Hospital between 1995 and 1996. After the exercise program, the ratio of forced expired volume in one second to forced vital capacity (FEV1.0%) was significantly increased (p < 0.05), while the ratio of forced vital capacity to predicted normal value (%VC) did not change in either group. Furthermore, a tendency toward an increase in peak flow (PF) and maximal expiratory flow at 25 and 50 percent (V25 and V50) was observed in both groups. An increase in PaO2 was observed in both groups, while an decrease in PaCO2 was observed in the young group (p < 0.05). These effects were observed more clearly in patients with asthma than in those with emphysema. The changes in pulmonary function and arterial blood gas were considered to be resulted from respiratory muscle training and expiration into water in addition to an increase in cardiac output by hydraulic pressure. Therefore, physical therapy in a pool filled with hot-spring water may be useful in treating chronic obstructive pulmonary disease in elderly as well as in young patients.

Aged↗

Transient sick sinus syndrome associated with immunoblastic lymphadenopathy.

We describe a very rare case of immunoblastic lymphadenopathy (IBL) accompanied with a sick sinus syndrome (SSS) in a 64-year-old male. SSS presented with progression of the IBL and subsided with improvement of the IBL following high dose prednisolone (PSL) therapy. The clinical course of this patient strongly suggested cardiac involvement in IBL and being the cause of the transient SSS. To our knowledge, this is the first case of IBL demonstrating SSS as a possible complication of the disease. This case may provide further information for the treatment of similar patients with IBL.

Electrocardiography↗

Bone bonding ability of bioactive bone cements.

The bone bonding ability of three types of bioactive bone cement A, B, and C consisting of glass or glass ceramic powder and bisphenol-alpha-glycidyl methacrylate resin was evaluated. Type A contained MgO-CaO-SiO2-P2O5-CaF2 glass powder; Type B, MgO-CaO-SiO2-P2O5-CaF2 glass ceramic powder; and Type C, MgO free CaO-SiO2-P2O5-CaF2 glass powder. Rectangular plates (2 x 10 x 15 mm) of Types A, B, C, and polymethylmethacrylate cements were implanted into the tibial metaphyses of male rabbits and the failure load measured by mechanical failure testing (detaching test) 10 and 25 weeks after implantation. The failure loads of Types A, B, C, and polymethylmethacrylate cements were respectively, 29.52, 41.48, 28.22, and 0.29 N at 10 weeks and 33.42, 41.27, 33.64, and 0.20 N at 25 weeks. Examination of the bone cement interface revealed that all the bioactive bone cements achieved direct bone contact with the bone. These results showed that all three types of bioactive bone cement have the ability to bond to bone, and the cement containing glass ceramic powder revealed higher bonding strength than did those containing glass powder.

Animals↗

Eosinophilic gastroenteritis presenting with acute pancreatitis.

We present the findings on a 27-year-old male with eosinophilic gastro-enterocolitis accompanied with acute pancreatitis. Acute pancreatitis may be induced by pancreatic duct obstruction caused by marked swelling of the papillary region of the duodenum due to eosinophil infiltration. After prednisolone treatment, clinical manifestations rapidly improved; the serum amylase decreased and the peripheral eosinophilia was recovered. The serum interleukin-5 (IL-5) level was high at diagnosis and decreased by prednisolone therapy; however, IL-5 was detected by enzyme immunoassay even during clinical remission. These results indicate that eosinophilia is mediated by IL-5, and detectable levels of IL-5 indicate the possibility of relapse.

Acute Disease↗

Serum beta-2-microglobulin in patients with multiple myeloma treated with alpha interferon.

In ten patients with multiple myeloma (MM), serum beta-2-microglobulin (B2M) levels were monitored in order to clarify the influence of alpha interferon (IFN) administration. Despite decreases in M-protein and the absence of renal dysfunction, the levels of serum B2M were sustained above those prior to melphalan-prednisolone and IFN therapy in seven patients with MM for six months. Serum B2M did not increase in ten patients with MM treated only by melphalan-prednisolone. Furthermore, serum B2M levels in a patient who achieved a complete response were sustained above her prior level and returned to normal after cession of IFN therapy. Our study suggests that the serum B2M level is increased by treatment with IFN, and does not prove the condition of the disease.

Adolescent↗

Splenectomy for en bloc node dissection in gastric cancer: a possible cause of portal vein thrombosis.

A 48-year-old woman underwent total gastrectomy, splenectomy, and distal pancreatectomy with en bloc regional lymph node dissection for gastric carcinoma. Dull pain in the right upper quadrant and the back developed postoperatively. Contrast-enhanced computed tomography and ultrasonography disclosed portal vein thrombosis (PVT). Heparin and urokinase were given in conjunction with antibiotics. This treatment resulted in clinical improvement, but failed to achieve complete thrombolysis. Cavernous transformation of the portal system was confirmed. Although PVT after splenectomy has been reported mainly in patients with hematological disorders, our case suggests that splenectomy for en bloc node dissection in gastric carcinoma is a possible cause of PVT.

Female↗

Intussusception caused by primary malignant melanoma of the small intestine.

Whether melanoma develops as a primary tumor in the small bowel remains controversial. A 57-year-old male Japanese presented signs of intestinal obstruction. Ultrasonography and computed tomography disclosed an abdominal mass with multiple concentric rings, characteristic of intussusception. At surgery, a spherical tumor, 3.8 cm in diameter, with scattered pigmentation was found to lead the intussusception. Segmental intestinal resection with regional lymph node dissection was performed. Pathological examination revealed diffuse infiltration of malignant melanoma cells. Nodal metastasis was seen only in the mesenteric node draining from the tumor-bearing intestinal segment. Twelve months after surgery, melanoma recurred in the liver and para-aortic lymph nodes, where a malignancy of the digestive organs frequently metastasizes; however, no extraperitoneal melanoma was found after repeated examinations. Thus, this case suggests that primary malignant melanoma can originate in the small intestine and be a cause of intussusception in the adults.

Humans↗

Mechanical and biological properties of two types of bioactive bone cements containing MgO-CaO-SiO2-P2O5-CaF2 glass and glass-ceramic powder.

In this study two types of bioactive bone cement containing either MgO-CaO-SiO2-P2O5-CaF2 glass (type A) or glass-ceramic powder (type B) were made to evaluate the effect of the crystalline phases on their mechanical and biological properties. Type A bone cement was produced from glass powder and bisphenol-a-glycidyl methacrylate (BIS-GMA) resin, and type B from glass-ceramic powder containing apatite and wollastonite crystals and BIS-GMA resin. Glass or glass-ceramic powder (30, 50, 70, and 80 by wt %) was added to the cement. The compressive strength of type A (153-180 MPa) and B (167-194 MPa) cement were more than twice that of conventional polymethylmethacrylate (PMMA) cement (68 MPa). Histological examination of rat tibiae showed that all the bioactive cements formed direct contact with the bone. A reactive layer was seen at the bone-cement interface. In specimens with type A cement the reactive layer consisted of two layers, a radiopaque outer layer (Ca-P-rich layer) and a relatively radiolucent inner layer (low-calcium-level layer). With type B cement, although the Ca-P-rich layer was seen, the radiolucent inner layer was absent. Up to 26 weeks there was progressive bone formation around each cement (70 wt %) and no evidence of biodegradation. The mechanical and biological properties of the cements were compared with those of a previously reported bone cement containing MgO-free CaO-SiO2-P2O5-CaF2 glass powder (designated type C).

Animals↗

Cyclophosphamide-induced apoptosis induces phocomelia in the mouse.

Phocomelia (absence of upper fore and/or hind limbs) was induced in mouse fetuses using cyclophosphamide. On day 11 of gestation, pregnant mice were injected intraperitoneally with 10 ml/kg of saline containing cyclophosphamide (CP) at a dosage of 20 mg/kg body weight. On day 18, the fetuses were removed by Caesarean section from dams given CP on day 11 and were examined for external anomalies. Of 22 fetuses from CP-treated dams, 13 were dead or absorbed, but the surviving 9 fetuses were found to have phocomelia with various other external anomalies. In order to examine the direct cytotoxic effect of CP on fetal limb buds, fetuses were removed at 8, 16, 24, and 48 h after CP administration on day 11, revealing the presence of frequent pyknotic nuclei and apoptotic bodies in hematoxylin and eosin (H & E) preparations. Cell-nuclei and apoptotic bodies were frequently observed by nick end-labeling in limb buds. Transmission electron microscopy demonstrated the typical changes of apoptosis. DNA extracted from the fetal limb buds submitted to CP was analysed by agarose gel electrophoresis, showing the ladder pattern characteristic of internucleosomal cleavage. These findings suggest that cyclophosphamide causes apoptosis in mouse fetal limb buds and that this process induces the external anomalies of phocomelia.

Animals↗