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Biomedical subjects

M Kawamura

Publications and source records attributed to M Kawamura.

At least 433 records · Page 24Linked to original sources

Bone morphogenetic protein-induced muscle- and synovium-derived cartilage differentiation in vitro.

Muscle- and synovium-derived mesenchymal-type cells differentiated into cartilage in response to a coating of partially purified rabbit bone morphogenetic protein (BMP) on a substratum of plastic. Observed by means of phase contrast microscopy, light microscope histochemistry, and electron microscopy, the sequence of events on a BMP-coated plastic substratum is the same as that observed on a substratum of bone matrix. The plastic eliminates the possibility of any endogenous allogeneic matrix-derived BMP contaminating the system. The differentiation of cartilage from synoviocytes and subsynovial cells resembles the pathologic process occurring in human chondromatosis.

Animals↗

[A "retinoic acid syndrome" observed in two cases of acute promyelocytic leukemia].

Two cases of acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA) developed fever, dyspnea and chest pain. A chest roentgenogram showed bilateral pleural effusion (case 1) and bilateral interstitial infiltration (case 2). The first case was a 50-year-old female in her first relapse, who was initially diagnosed as having pleuritis tuberculosa and was treated with anti-tuberculotic agents. Her symptoms continued for 44 days and complete remission was achieved 53 days after commencing ATRA therapy. The second case was a previously untreated 46-year-old male. His case had been diagnosed as adult respiratory distress syndrome and he had been treated with prednisolone. His symptoms rapidly improved and complete remission was achieved 38 days after the ATRA therapy. This was the first report of patients in Japan considered to have developed "retinoic acid syndrome (RAS)". In our five APL cases treated with ATRA, the syndrome was not always accompanied by peripheral blood leukocytosis even though the two cases with RAS showed higher leukocyte counts than the other two cases without RAS and also had DIC. We should pay attention to the severe respiratory symptoms that develop in APL patients after ATRA treatment and immediate steroid therapy is required for such patients.

Adult↗

Mutational analysis of human lipoprotein lipase by carboxy-terminal truncation.

We have previously reported a Trp382 (TGG)-->stop (TGA) mutation that causes familial lipoprotein lipase (LPL) deficiency. Expression study of the Trp382-->stop mutant showed that the truncated LPL was catalytically inactive with a marked reduction in the expressed mass. To investigate the minimal amino-terminal sequence of human LPL required for an active enzyme, a series of carboxy-terminal (C-terminal) truncated LPLs were expressed in vitro, and the enzyme activity, mass, and LPL mRNA levels were analyzed. The lipolytic activity showed a stepwise reduction between LPL-437 (Cys438-->stop; 68% of normal LPL activity in medium) and LPL-434 (Phe435-->stop; 3%). Without affecting LPL mRNA levels, LPL mass was reduced with the mutants not larger than LPL-437. In terms of specific activity, a significant difference was observed between LPL-436 (Lys437-->stop; 88% of that of normal LPL in medium) and LPL-435 (Val436-->stop; 22%), implying the importance of the role of Val436 in LPL action. Furthermore, our results unexpectedly showed that LPL-446 (Ser447-->stop), which is considered to be a common polymorphic form of LPL, exhibited higher activity than normal LPL (185% in medium). These results demonstrate that the C-terminal region of human LPL is closely associated with the expression of enzyme mass and catalytic activity.

Amino Acid Sequence↗

Bronchoplastic procedures for tuberculous bronchial stenosis.

Thirty-six patients underwent tracheobronchoplastic procedures for treatment of tuberculous tracheobronchial stenosis. The modes of operations were left upper sleeve lobectomy in 13 patients, sleeve resection of the left main bronchus in 12 patients (two underwent concomitant left upper lobectomy), right upper sleeve lobectomy in five patients, sleeve resection of the right intermediate bronchus in two patients, right sleeve superior segmentectomy of the lower lobe in one patient, sleeve resection of the trachea with concomitant left pneumonectomy in one patient, carinal resection with right upper sleeve lobectomy and middle lobectomy in one patient, and dilatation of the left main bronchus with a free skin graft reinforced with a steel wire in one patient. One patient died of pulmonary edema of unknown cause on the first postoperative day. Anastomotic stenosis occurred in seven patients. One of these patients underwent reoperation and six underwent endoscopic dilatation. One patient died in the hospital of massive bleeding during endoscopic dilatation 4 months after operation. Slight to moderate stenosis resulted in the remaining patients. Although there are some complications, we believe bronchoplastic operation is worthwhile for restoring pulmonary function in patients with tuberculous tracheobronchial stenosis.

Adult↗

[Multidisciplinary treatment for a patient with recurrent thymoma associated with myasthenia gravis (MG), pure red cell aplasia (PRCA), and hypogammaglobulinemia].

The patient is 62-year-old female. When she was 43 years old, MG occurred. At age of 49 years thymoma was found and complete thymectomy (stage III) and postsurgical irradiation were performed. At age of 57 years pleural dissemination of the thymoma was found. Chemotherapy was effective but did not obtain total tumor cell kill. Though chemotherapy has been repeated for each tumor regrowth, the regimen used at first recurrence became ineffective and the interval between tumor regrowth became shorter. This year, when she is 62 years old, PRCA and hypogammaglobulinemia were accompanied with the forth tumor regrowth.

Agammaglobulinemia↗

Changes in cystathionine gamma-lyase levels in rat liver during lactation.

Rat liver cystathionine gamma-lyase activity increased rapidly with the onset of lactation, reaching a maximum value at week 2 and slowly decreasing thereafter. In non-lactating rats, from which the litters had been removed on the day of birth, the activity of this enzyme increased only minimally. The enzyme activity in the presence and absence of pyridoxal 5'-phosphate (PLP) did not differ significantly, indicating that the cystathionine gamma-lyase in lactating rat liver was also saturated with PLP as control rat. We then investigated whether the increased activity was caused by increases in the enzyme concentration. An antibody, prepared form purified rat liver cystathionine gamma-lyase was utilized for the detection of enzyme content by immunoblot analysis and enzyme immunoassay. On immunoblot analysis, this antibody stained purified cystathionine gamma-lyase, as well as staining a single polypeptide from liver cytosolic proteins that co-migrated with the purified enzyme at about 40 kDa. Changes in the staining intensity of the antibody paralleled the activity of the enzyme. The enzyme immunoassay showed that the content of liver cystathionine gamma-lyase at weeks 0, 1, 2 and 5 of lactation was 1.67, 2.33, 5.19, and 2.17 mg per g of liver, respectively, whereas in the non-lactating rats, the enzyme concentration at week 2 was found to be 2.20 mg per g of liver. The changes in enzyme concentration detected by enzyme immunoassay were also consistent with enzyme activity. We concluded that the increased cystathionine gamma-lyase activity in the lactating rat liver was a result of an increase in enzyme concentration.

Animals↗

Transmigration routes and a delayed systemic hypotension in rats after intraperitoneal injection of endotoxin from Escherichia coli.

An intraperitoneal injection of endotoxin (ETX; 3 mg/kg) to rats caused gradual decrease in the systemic arterial blood pressure for up to 3 hr, together with decrease in heart rate, increase in hematocrit, and changes in the core temperature (an initial increase and a subsequent decrease). Pretreatment of rats with indomethacin (10 mg/kg, p.o.) prevented the decrease in the systemic blood pressure and the changes in other three parameters. The intraperitoneal injection of ETX also induced a gradual increase in exudation of plasma for up to 3 hr, with increased levels of prostaglandin (PG) E2 and 6-keto-PGF1 alpha in the peritoneal exudate. Indomethacin inhibited the exudation of plasma. The levels of ETX in the arterial and portal venous plasmas began to increase 5 min after the intraperitoneal injection of ETX, and reached levels on the order of micrograms per milliliter plasma 10-20 min after the injection. The levels of ETX in the right and left thoracic lymph nodes, but not in the mesenteric lymph nodes, increased in parallel with those in the systemic arterial plasma. In conclusion, the delayed hypotension may be attributable to the mesenteric vasodilatation induced by PGs generated in the peritoneal cavity, and the ETX injected entered the systemic circulation mainly through lymphatic vessels, but in the initial stage, a part of ETX may be transmigrated into portal vein through damaged intestine.

Animals↗

Oxidation of low density lipoprotein by thiols: superoxide-dependent and -independent mechanisms.

Oxidatively damaged low density lipoprotein (LDL) may cause macrophages to accumulate cholesterol in an unregulated manner, initiating the development of atherosclerotic lesions. Cultured smooth muscle cells oxidize LDL by a superoxide (O2.-)-dependent mechanism that requires L-cystine and redox-active transition metal ions in the incubation medium. To test the hypothesis that cellular reduction of L-cystine to a thiol might be involved, we exposed LDL to L-cysteine, glutathione, and D,L-homocysteine. In a cell-free system each thiol modified LDL by a pathway that required either Cu2+ or Fe3+. Thiol- and Cu(2+)-modified LDL underwent lipid peroxidation and exhibited a number of properties of cell-modified LDL, including increased mobility on agarose gel electrophoresis and fragmentation of apolipoprotein B-100. Superoxide dismutase inhibited modification of LDL by L-cysteine/Cu2+, whereas catalase and mannitol were without effect. In striking contrast, superoxide dismutase had little effect on oxidation of LDL by Cu2+ and either homocysteine or glutathione. Moreover, only L-cysteine/Cu(2+)-modified 125I-labeled LDL was degraded more rapidly than 125I-labeled LDL by human monocyte-derived macrophages: superoxide dismutase in the reaction mixture blocked the facilitated uptake of L-cysteine/Cu(2+)-modified 125I-labeled LDL, suggesting involvement of O2.-. These results indicate that LDL oxidation by L-cysteine and Cu2+ requires O2.- but not H2O2 or hydroxyl radical. The reaction may involve the metal ion-dependent formation of L-cystine radical anion which is oxidized by oxygen, yielding O2.- and the disulfide. LDL modified by L-cysteine and smooth muscle cells exhibit similar physical and biological properties, indicating that thiol-dependent generation of O2.- may be the oxidative mechanism in both systems. Thiols also promote lipid peroxidation by O2(.-)-independent reactions but human macrophages fail to rapidly degrade these oxidized LDLs.

Cell-Free System↗

[Echocardiographic observation of intraoperative circulatory collapse in a patient with hypertrophic obstructive cardiomyopathy].

Two-dimensional Doppler echocardiography was used as an intraoperative cardiac function monitor in anesthetic management of a 79-year-old male with hypertrophic obstructive cardiomyopathy (HOCM) who underwent pulmonary lobectomy for lung cancer. Circulatory collapse occurred after thoracic epidural anesthesia (TEA), and was aggravated with following induction of general anesthesia. The collapse did not improve with phenylephrine nor atropine and necessitated ethylephrine and dopamine. During the above course, left ventricular outflow tract pressure gradient measured with continuous wave Doppler method was almost in proportion to cardiac output measured with thermo-dilution method. This means that TEA and the administration of inotropics did not worsen the left ventricular outflow tract obstruction. Left ventricular filling property estimated by trans-mitral flow velocity spectra improved when hemodynamics was stabilized with continuous infusion of dopamine, while it had been impaired during preoperative period and at the beginning of anesthesia. Our observation suggests that TEA for HOCM patient is a relative indication because it may exert negative inotropic effect, and that careful titration with inotropics is not contraindicated when undesired cardiac depression is proved by echocardiography.

Aged↗

[Alloesthesia without impairment of consciousness after right putaminal small hemorrhage].

Alloesthesia is a condition in which a sensory stimulus, given on one side of the body, is perceived to be at the corresponding area on the opposite side. In our previous study (Kawamura, Hirayama et al., 1987), we suggested that it may be useful for localization because this phenomenon was observed most frequently in patients with a right putaminal hemorrhage of medium or large size, an average of 42 ml on CT scans, presenting a slight disturbance of consciousness and, in about half of the patients, anosognosia. We also suggested that since alloesthesia is produced not only in cerebral but also in spinal cord lesions, it seems to represent an elementary sensory disturbance of sensory pathways, not a higher cortical dysfunction. We recently observed alloesthesia in two other patients with smaller right putaminal hemorrhages, 7 ml and 6 ml, respectively, who exhibited no disturbance of consciousness, but had impairment not only of superficial but also of proprioceptive sensations. In Patient 1, superficial sensations were intact on admission, except those on the left side of the face. Cortical somatosensory evoked potentials (SEPs) after stimulating the median nerve were measured on Patient 1 on the 11th hospital day when a left hemihypalgesia had developed due to enlargement of the hematoma from 7 to 14 ml. Stimulation of the clinically affected side (left) evoked no N20 from the contralateral scalp. Right-sided stimulation was normal. The fact that both patients showed alloesthesia with no accompanying disturbance of consciousness supported our view of its mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Anatomical measurements of the internal anal sphincter--the relative site of the dentate line in the internal anal sphincter].

Not only the length and the width of the internal anal sphincter but also the relative site of the dentate line in the internal anal sphincter were investigated in 62 resected specimens obtained by abdominoperineal resection of the rectum for malignancy. Mean length and width of the internal sphincter were 25.8 +/- 4.1mm (mean +/- standard deviation) and 4.0 +/- 1.1mm, respectively. The length of the internal sphincter from its distal end to the level of the dentate line was 11.3 +/- 3.1mm, which corresponded to 44% of the total length of the internal sphincter. The individual difference in the site of the dentate line in the internal sphincter was objectively demonstrated. It seems to be therefore important to modulate the extent of sphincterotomy in order to minimize postoperative anal dysfunction on the surgery for fissure or fistula-in-ano, in which sphincterotomy is widely practiced up to the level of the dentate line.

Adult↗

TCV-116, a novel angiotensin II receptor antagonist, prevents intimal thickening and impairment of vascular function after carotid injury in rats.

Inhibitory effects of TCV-116 [(+-)-1-(cyclohexyloxycarbonyloxy)ethyl2-ethoxy-1-[[2'-(1H- tetrazol-5- yl)biphenyl-4-yl]methyl]-1H-benzimidazole-7-carboxylate], a novel angiotensin II AT1 subtype receptor antagonist, on the proliferation of vascular smooth muscle cells and the impairment of endothelium-dependent vascular relaxation were examined in the rat carotid balloon injury model. DNA content in the carotid artery was increased 3 days after carotid balloon injury and reached a plateau 14 days after the injury. Beneficial effects of TCV-116 in this model were examined 14 days after the injury. Oral administration of TCV-116 at 1 and 10 mg/kg/day significantly inhibited the increase in DNA content by 69 and 85%, respectively. Histological examination demonstrated that TCV-116 at 1 and 10 mg/kg significantly inhibited intimal thickening by 43 and 58%, respectively. Cilazapril (10 mg/kg/day p.o.) also inhibited intimal thickening by 48%. Contracting or relaxing vascular responses to phenylephrine or sodium nitroprusside did not differ between uninjured and injured arteries. However, acetylcholine-induced endothelium-dependent relaxation was greatly reduced in injured arteries; maximal relaxation was 6 +/- 2% (n = 17). TCV-116 at 1 and 10 mg/kg significantly ameliorated the impairment of vascular relaxation; maximal relaxation was 25 +/- 8 (n = 7) and 51 +/- 12% (n = 5), respectively. In uninjured arteries, L-NG-monomethyl arginine (300 microM), an inhibitor of endothelium-derived relaxing factor synthesis, inhibited acetylcholine (10 microM)-induced relaxation by 58 +/- 4% (n = 5). Scanning electron micrographs demonstrated that TCV-116 (10 mg/kg/day) enhanced restoration of endothelial cells in the carotid artery 14 days after injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Establishment of a new human pre-B acute lymphoblastic leukemia cell line (KMO-90) with 1;19 translocation carrying p53 gene alterations.

A new human pre-B acute lymphoblastic leukemia cell line (KMO-90) was established from the bone marrow sample of a 12-year-old girl with acute lymphoblastic leukemia (ALL) carrying 1;19 chromosome translocation. KMO-90 cells expressed HLA-DR, CD10, CD19, and CD22 antigens. These cells had also cytoplasmic immunoglobulin lacking surface immunoglobulin, indicating that these had a pre-B phenotype. Chromosome analysis of this cell line showed 48, XX, +8, +19, t(1;19)(q23;p13). Southern blot analysis showed the same sized rearrangements of the E2A gene in KMO-90 cells as those in the original leukemic cells. By means of reverse transcriptase-polymerase chain reaction analysis, we detected E2A/PBX1 fusion transcripts in KMO-90 cells. KMO-90 is useful when studying the role of the 1;19 translocation in the etiology of pre-B ALL. Furthermore, we studied alterations of the p53 gene in this cell line by polymerase chain reaction, single-strand conformation polymorphism analysis. KMO-90 cells were identified to have a point mutation at codon 177 (CCC-->TCC) of the p53 gene, suggesting that alterations of the p53 gene may have an important role in the establishment of this cell line.

Antigens, Surface↗

Osteogenesis in sintered bone combined with bovine bone morphogenetic protein.

Bone morphogenetic protein (BMP) was combined with true bone ceramic (TBC) in an attempt to produce a bone grafting material possessing the cancellous structure, osteoconductivity, and osteoinductivity of biologic bone. To determine the osteogenetic ability of this material (BMP-TBC) within bone marrow, BMP-TBC and TBC alone were implanted in the femoral condyles of Japanese White rabbits, and histographs of these implants, taken serially, were compared. Woven bone formation was observed both at the periphery and within surface pores of the BMP-TBC implants one week after implantation; these implants thus became secured to the host bone bed at an earlier stage than did TBC alone. The amount of new bone formation increased at a significantly higher rate with BMP-TBC than with TBC alone during the first four weeks. Therefore the BMP in BMP-TBC implants acts at an early stage on BMP-responding cells entering the pores of the TBC. These data also suggest that TBC, as a carrier for BMP, provides a favorable environment for the promotion of new bone formation.

Animals↗

Reduction and inactivation of the sarcoplasmic Ca(2+)-ATPase by 2-mercaptoethanol--contrast to the (Na+,K+) ATPase.

The sarcoplasmic Ca(2+)-ATPase was reduced with 300 mM 2-mercaptoethanol at elevated temperatures (40-45 degrees C) with a concomitant loss of ATPase activity. The reduction and inactivation of the Ca(2+)-ATPase proceeded rapidly in the absence of Ca2+. The Ca(2+)-ATPase was also inactivated with 2-mercaptoethanol in the presence of diluted SDS (0.4 mg/ml) even at 20 degrees C. In contrast to the (Na+, K+) ATPase, the inactivated Ca(2+)-ATPase in the presence of diluted SDS was sedimented by the centrifugation at 100,000 x g for 30 min.

Animals↗

Boy with a chromosome del (3)(q12q23) and blepharophimosis syndrome.

We report on a 6-year-old boy with de novo 46,XY,del(3)(q12q23) and bilateral blepharophimosis, ptosis, epicanthus inversus, in addition to multiple other anomalies. Since 4 previously reported cases of interstitial deletion of 3q involving 3q23 band are clinically similar, we propose this blepharophimosis sequence due to 3q23 deletion as a further "contiguous gene syndrome."

Adult↗

A strategy for delivering peptides into the central nervous system by sequential metabolism.

Most peptides do not enter the central nervous system because of their hydrophilic character and the presence of peptidolytic enzymes in the lipoidal blood-brain barrier. To achieve brain delivery of a peptide conjugate, an opioid peptide (enkephalin) was placed in a molecular environment that disguises its peptide nature and provides biolabile, lipophilic functions to penetrate the blood-brain barrier by passive transport. The strategy also incorporates a 1,4-dihydrotrigonellinate targetor that undergoes an enzymatically mediated oxidation to a hydrophilic, membrane-impermeable trigonellinate salt. The polar targetorpeptide conjugate that is trapped behind the lipoidal blood-brain barrier is deposited in the central nervous system. Analgesia was observed with "packaged" enkephalin but not with the unmodified peptide or lipophilic peptide precursors.

Amino Acid Sequence↗