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Biomedical subjects

S Iwamoto

Publications and source records attributed to S Iwamoto.

At least 91 records · Page 5Linked to original sources
PubMed1997

Prolonged bed rest impairs response of the small arteries to cold pressor test.

Cold pressor test (CPT) has been known to increase vascular resistance through adrenergic stimulation. To assess the effect of prolonged bed rest (BR) on sympathetic neural control, blood flow velocity of the proper palmar digital artery (resistance vessel) was measured in 10 healthy volunteers during a 90 seconds CPT by pulsed Doppler ultrasound using a 7.5 MHz linear transducer before and after 20 days BR. Blood flow velocity in the proper palmar digital artery decreased during the first half of the CPT both before and after BR, but decreases in peak flow velocity became less prominent (p<0.05) after BR (-48+/-20%) than before bed rest (-61+/-25%). The only subject whose lower body negative pressure tolerance time was prolonged after BR showed prominent decreases in peak flow velocity during the first half of the CPT after BR. Peak flow velocity returned to the pre-test value during the latter half of the CPT in 7 subjects before BR, but in only 2 subjects after BR (p<0.05). Thus, 20 days BR impairs the response of the small digital arteries to CPT, suggesting that a decrease in a adrenergic stimulation occurs after prolonged BR.

Adolescent↗
PubMed1997

[A case of papillary adenocarcinoma of the stomach with liver metastases and carcinomatous peritonitis treated effectively by methotrexate/5-fluorouracil sequential chemotherapy].

A 54-year-old male was admitted to receive treatment by anticancer drug for advanced gastric cancer with liver metastases and carcinomatous peritonitis. Upper gastrointestinal series showed a Borrmann type 4 gastric cancer occupying the body and antrum, and a pathological diagnosis of papillary adenocarcinoma was made by endoscopic biopsy. Two cycles of neoadjuvant chemotherapy consisting of 5-FU and low-dose CDDP (FP therapy) were given. No effect was observed, so that the next chemotherapy schedule of sequential MTX/5-FU therapy was performed. We adopted the intermediate (MTX: 100 mg/m2 and 5-FU 600 mg/m2 weekly) dose regimen. When six courses of this regimen were completed, the primary lesion of the stomach was decreased to 60% and the metastatic liver tumor to 72%, basel on criteria for the evaluation of clinical effects of solid cancer chemotherapy. However, pylorous stenosis remained, and we performed gastrojejunostomy and biopsy of the regional lymph node to determine the response to the chemotherapy. A pathological examination of lymph node revealed metastatic papillary adenocarcinoma with xanthogranulomatous change, and was judged as an effect showing grade 2. He was discharged and had the outpatient hospital treatment. He died of exacerbation of carcinomatous peritonitis 10 months after his initial admission. The response duration for sequential MTX/5-FU therapy was 4 months. This therapy was usually effective in patients with poorly differentiated adenocarcinoma of the stomach. Our result indicates that this therapy can be effective for not only poorly differentiated adenocarcinoma but also papillary adenocarcinoma of the stomach in an advanced stage.

Adenocarcinoma, Papillary↗
PubMed1996

Small-Angle X-ray Diffraction of Muscle Using Undulator Radiation from the Tristan Main Ring at KEK.

Time-resolved X-ray diffraction of muscle has demanded ever-increasing flux into small sample volumes with low beam divergence. Results are reported of static and time-resolved small-angle X-ray diffraction studies on muscle fibers using a hard X-ray undulator installed in the Tristan main ring at KEK, Tsukuba, Japan, as an innovative source of synchrotron radiation more intense and better collimated than that available with the Photon Factory bending-magnet beamline. Static studies used the low divergence of the source to obtain detailed high-quality diffraction patterns of stable muscle states. The diffraction patterns from live skeletal muscles showed the numerous (over 100) meridional reflections. The well collimated beam from the undulator made it possible to clearly resolve, with an angular resolution of ca 700 nm, the closely spaced diffraction peaks arising from the two halves of the thick filaments centred on the M lines in a sarcomere, in addition, the diffraction peaks from the thin filaments on opposite sides of the Z bands could be resolved with an angular resolution of ca 1000 nm. The detailed structure of the meridional pattern defines the nature of the molecular packing in the thick and thin filaments. Time-resolved experiments using a focusing mirror aimed to prove cross-bridge states in striated muscle fibers by collecting X-ray diffraction data at a 0.185 ms time resolution from sinusoidally oscillating chemically skinned rabbit muscle fibers during active contraction and in rigor. When sinusoidal length changes at 500 Hz with a peak-to-peak amplitude of 0.6% of the muscle length were applied to a small fiber bundle, the tension showed a simple elastic response during the length oscillation. In the active muscle the intensity of the 14.5 nm myosin-based meridional reflection changed out of phase with the tension change during the oscillating length change. In contrast, in the rigor muscle it occurred in phase with the tension change. The high time-resolved experiments provide an insight into the coupling between conformational changes and force generation of the actomyosin cross-bridges. These studies provide a preview of the expected gains for muscle studies from the more widespread use of undulator radiation at third-generation synchrotron sources.

Journal Article↗
PubMed1996

Molecular genetic basis of red cell markers and its forensic application.

(1) The polymerase chain reaction (PCR) was used to amplify Rh-related cDNAs from erythroid cells cultured by the selective two-phase liquid culture system for human erythroid progenitors in peripheral blood. Two Rh polypeptide cDNAs have been isolated from the PCR products and tentatively designated RhPI cDNA and RhPII cDNA. Both cDNA clones have an open reading frame composed of 1251 nucleotides. The RhPI cDNA clone shows a single nucleotide substitution with no amino acid substitution compared with the published sequence. The RhPII cDNA clone differs from the above by 41 nucleotide substitutions in the open reading frame, resulting in 31 amino acid substitutions. Besides these cDNA clones, eleven and five truncated isoforms of the RhPI and RhPII cDNAs, have been isolated, respectively. (2) The promoter region of the Duffy gene was cloned by IPCR of 1.1 kb SacI fragment and the 3' flanking sequence was cloned by IPCR of 1.9 kb EcoRI fragment. The IPCR products contained the known Duffy cDNA sequence without introns. By comparing the coding area of the Duffy gene in 28 Duffy positive individuals, we elucidated that one base change that results in an amino acid substitution (GAT(Asp44)-->GGT(Gly)) is in accordance with the Fya/Fyb polymorphism. This fact proves that the Duffy cDNA and its gene encode the Duffy blood group system. (3) Two common alleles in Esterase D (EsD) polymorphism, EsD1 and EsD2 were characterized by the substitution of one amino acid (Gly-Glu) caused by the point mutation of one nucleotide (G-A). The point mutation between cDNAs of EsD1 and EsD2 alleles was detectable as restriction fragment length polymorphism (RFLP) using Ssp1. The RFLP makes it possible to determine the EsD phenotypes using DNA samples from forensic materials without EsD enzymatic activity. (4) The authors report studies on 19 pairs of donors and recipients in bone marrow transplantation. A broad range of genetic markers at 42 gene loci, including one DNA marker 11 red blood cell markers, five human lymphocyte antigen types, 12 serum protein markers, five red cell enzyme markers, and eight salivary markers was evaluated before and after BMT over about 2 months. As a result, 11 out of 42 gene loci of genetic markers in recipients were transformed into the donor type.

Base Sequence↗
PubMed1996

Characterization of the Duffy gene promoter: evidence for tissue-specific abolishment of expression in Fy(a-b-) of black individuals.

We have previously identified a novel first exon of Duffy gene and two inverse GATA motifs in the 600 bp 5' flanking region. The proximal GATA is positioned downstream from the start position of endothelium and upstream from that of erythroid. One base substitution (-365T --> C) was found in the proximal GATA motif from three black Fy(a-b-) individuals, and was regarded as a common polymorphic mutation in black Fy(a-b-) individuals. The upstream sequence of the novel first exon was inserted in the upstream of chloramphenicol acetyltransferase (CAT) gene and transfected in human erythroleukemia cell line (HEL) and human microvascular endothelial cells (HMvEC). The black type mutation abolished the CAT transcription in HEL cells but not in HMvEC. Deletion mutagenesis study revealed that the proximal GATA motif represent the erythroid regulatory core region for Duffy gene. Gel shift assay showed that the proximal GATA motif is the target sequence of GATA-1. These studies indicate that the black type mutation abolishes Duffy gene expression in erythroid but not in postcapillary venule endothelium, which is compatible with the Northern blot and immunohistochemical observation in black Fy(a-b-) individuals.

Base Sequence↗
PubMed1996

Hydroxylforms of p-boronophenylalanine as potential boron carriers on boron neutron capture therapy for malignant brain tumors.

Hydroxylforms of boronophenylalanine (BPA) were synthesized by conjugation with a cascade of polyols to decrease the BPA uptake of normal parenchyma without affecting uptake into the tumor. We determined their tumor cell killing effect on boron neutron capture therapy (BNCT) against BPA using the human glioma cell line T98G. The thermal neutron doses yielding the D37 (dose used to inhibit 63% colony formation) values of dl-p-BPA(OH)n were 1.45 x 10(12)nvt (n = 1), 1.33 x 10(12)nvt (n = 2), 3.37 x 10(12)nvt (n = 4), and 1.72 x 10(12)nvt (n = 0). The relative tumor cell killing effect on BNCT of dl-p-BPA(OH)n against dl-p-BPA, which was defined as the ratio of D37-BPA to D37-BPA(OH)n, was 1.18 (n = 1) 1.29 (n = 2), and 0.51 (n = 4). The tumor:normal brain ratio of dl-p-BPA(OH)n in 9L rat brain tumor models was improved 1.2- (n = 1) and 1.4-fold (n = 2) against that of dl-p-BPA without a decrease of its uptake into the tumor. The water solubility of BPA(OH)n increased against BPA, and the toxicity represented as the IC50 value of dl-p-BPA(OH)2 was nearly one half that of dl-p-BPA, being established in our previous works. Hydroxylforms of BPA, especially dl-p-BPA(OH)2, might be more suitable boron carriers of BNCT to malignant brain tumors since the radiation injury to the normal parenchyma surrounding the tumor is reduced.

Animals↗
PubMed1996

Hemostasis activation during sclerotherapy of lower extremity varices.

The influence of compression sclerotherapy upon hemostasis activation was investigated in 41 consecutive patients with lower extremity varices by serial measurement of thrombin-antithrombin III complexes (TAT), D-dimer, fibrinogen and C-reactive protein (CRP). Blood sampling was carried out before operation and on the 7th and 28th post-operative day in patients randomly assigned to either the control group (n = 18), in which high ligation of sapheno-femoral junction and local excision of varices were performed, or the sclerotherapy group (n = 23) in which the comparable surgical intervention and compression sclerotherapy using hypertonic saline were performed simultaneously. In both groups, the TAT, D-dimer and fibrinogen concentrations at day 7 were significantly elevated compared to the value before operation while CRP showed no significant change during the observation period. In the sclerotherapy group, higher incidence of superficial thrombosis was observed and the TAT concentration at day 7 was significantly higher than that in the control group (p < 0.01), and the TAT at day 28 was still significantly elevated compared to the pre-operative level (p < 0.05). However, no relationship between TAT and D-dimer concentrations and the extent of superficial thrombosis was observed. We conclude that compression sclerotherapy for lower extremity varices causes latent activation of coagulation system and can be a risk factor for venous thromboembolism.

Antithrombin III↗
PubMed1996

Platelet microparticles: a carrier of platelet-activating factor?

Platelet-activating factor (PAF) has been considered to be released in a soluble form from activated platelets. Also a considerable number of microparticles were released from stimulated platelets. To evaluate the possibility that microparticles contain PAF, the amount of PAF in whole activated platelets, microparticles and the suspending medium was determined by means of bioassay. The total amount of PAF released from 3 x 10(8) platelets activated with thrombin (0.5 U/ml) plus collagen (10 micrograms/ml) for 10 minutes was 4.6 +/- 1.5 x 10(-12) mol (n = 8, mean +/- S.D.). Eighty-seven percent of the PAF released from platelets was associated with microparticles. PAF released in microparticles is susceptible to plasma acetylhydrolase and may be localized on the outer surface of microparticles. This is the first report implicating the role of microparticles as a novel carrier of mediators formed in the cells.

Acetylesterase↗
PubMed1996

Tumor necrosis factor alpha and lymphotoxin stimulate human myeloblastic leukemia cell (ML-1) invasion through a reconstituted basement membrane (Matrigel) with concomitant induction of 92 kDa gelatinase secretion.

We have examined the effects of tumor necrosis factor alpha (TNF) and lymphotoxin (LT) on gelatinase (72 kDa and 92 kDa) and tissue inhibitor of metalloprotease 1 (TIMP1) secretion by human myeloblastic leukemia cells (ML-1) in vitro. TNF (0.1-30 ng/ml) significantly stimulated 92 kDa gelatinase secretion in a dose-dependent manner, but did not significantly stimulate 72 kDa gelatinase secretion. LT also significantly stimulated 92 kDa gelatinase secretion, but the stimulation was less effective compared to TNF. TNF, but not LT, concentrations at 30 ng/ml slightly stimulated TIMP1 secretion. Because 92 kDa gelatinase is thought to play a pivotal role in tumor invasion, we examined the effect of TNF or LT on ML-1 cell invasion through a reconstituted basement membrane (Matrigel). Exposure of ML-1 cells to TNF (3, 10, and 30 ng/ml) or LT (3, 10, and 30 ng/ml) stimulated ML-1 cell invasion through Matrigel in a dose-dependent manner in vitro. The data suggest that TNF- and LT-stimulated 92 kDa gelatinase secretion could play an important role in TNF- or LT-stimulated ML-1 cell invasion.

Antibodies, Monoclonal↗
PubMed1996

Identification of a novel exon and spliced form of Duffy mRNA that is the predominant transcript in both erythroid and postcapillary venule endothelium.

The Duffy gene has been shown not to be split by introns, even in its 5' untranslated region, and to be expressed not only in erythroid but in postcapillary venule endothelium of almost every organ in the body. To further investigate the transcriptional start position in erythroid and postcapillary venule endothelium, we performed 5'-rapid amplification of cDNA ends (5'-RACE). While every positive clone of 5'-RACE encoded the identical sequence of previously identified cDNA downstream from nucleotide 203, the upstream sequences were different. The upstream sequences corresponded to the sequence from nucleotide -279 to -308/-357 in erythroblasts and from -279 to -355/-383 in lung and were regarded as comprising a novel exon. This novel exon encoded seven residues initiated with a methionine, linked to nucleotide 203 in-frame and in agreement with the GT-AG splicing rule. The major erythroid transcriptional start position was identified in human erythroleukemia cells by primer extension and in bone marrow by ribonuclease protection analysis at 34 bases upstream from the first ATG codon. Distinctively, in lung and kidney, the transcription was started at 82 bases upstream from the ATG. Both Northern blotting and reverse transcription-polymerase chain reaction followed by Southern analysis indicated a predominance of the novel spliced form of mRNA of about 50- to 200-fold comparing with the unspliced form, in every studied organ and erythroid lineage cells. The spliced form of cDNA has been transfected into a human erythroleukemic cell line, K562, and the expressed protein reacted with Duffy-specific murine monoclonal antibody Fy6. These studies indicate that the product from the spliced form of mRNA is the major product of the Duffy gene in the erythroid lineage and postcapillary venule endothelium.

Amino Acid Sequence↗
PubMed1996

The coagulofibrinolytic state of patients with primary varicose veins of the lower legs.

The relationship between a local hypercoagulable state and primary varicose veins of the lower legs was investigated by measuring the plasma levels of D-dimer (DD) and the thrombin-antithrombin-III complex (TAT) in 122 consecutive patients before treatment, and in 46 patients after surgical intervention and compression sclerotherapy. Elevated levels of DD and TAT were found in 25% and 20%, respectively, of the 122 patients, being significantly elevated in the patients with thrombophlebitis compared to the patients with no dermal symptoms, pigmentation, or stasis dermatitis. There was no significant difference in either parameter among eight groups of patients classified according to their valvular incompetence. The levels of DD and TAT were elevated before treatment in 25% and 20%, respectively, of 45 treated patients, but became significantly reduced after treatment. These results indicate that even though the local hypercoagulable state in varicose veins without thrombophlebitis is too subtle to be detected by systemic parameters such as DD and TAT, a local hypercoagulable state can be detected in a certain proportion of patients with venous stasis by these parameters.

Adult↗
PubMed1996

Surgical treatment for the recurrence of colorectal cancer.

We report the results of a retrospective study conducted on patients who developed recurrence following surgery for colorectal cancer, and present a practical plan to improve the survival rates. Of 974 patients who underwent surgery for colorectal cancer in our hospital during the 20 years between 1974 and 1993, 152 developed recurrence, as local recurrence in 70 (7.2%), as liver metastasis in 47 (4.8%), and as pulmonary metastasis in 35 (3.6%). The number of patients who underwent reoperation or curative resection was 54 (77.1%) and 13 (24.1%), respectively, of those with local recurrence, 16 (34.0%) and 6 (37.5%) of those with liver metastasis, and 6 (17.1%) and 6 (100.0%) of those with pulmonary metastasis. The 3- and 5-year survival rates were 13.4% and 8.9%, respectively, after reoperation for local recurrence, 14.4% and 0%, after reoperation for liver metastasis, and 53.3% and 53.3% after reoperation for pulmonary metastasis. Although evaluation was difficult owing to the small number of patients with lung metastasis, resection of a pulmonary lesion resulted in a good outcome. Furthermore, a significant difference in 3- and 5-year survival rates was observed between patients who underwent reoperation and those who underwent conservative treatment, for whom the survival rates were 0% and 0% following local recurrence, 4.6% and 0% following liver metastasis, and 0% and 0% following lung metastasis, at 3 and 5 years, respectively. These findings indicate that aggressive surgery for recurrence may result in a better outcome.

Colorectal Neoplasms↗
PubMed1996

Evidence that the p75 neurotrophin receptor mediates perineural spread of desmoplastic melanoma.

BACKGROUND: The desmoplastic variant of melanoma has a striking propensity for neurotropism. This neurotropism may reflect Schwannian differentiation. The migration of Schwann cells along embryonic nerves is reportedly regulated by the 75 kd neurotrophin receptor (p75NTR) and one of its cognate ligands, nerve growth factor (NGF). OBJECTIVE: The purpose of this study was to test the hypothesis that the mechanism of perineural spread in desmoplastic melanomas is analogous to that of neurotropism in Schwann cells, which apparently depends on expression of p75 neurotrophin receptor and its ligands. METHODS: Immunolabeling of p75NTR in histologic sections of spindle cell and desmoplastic melanomas was compared and contrasted with that of epithelioid melanomas. RESULTS: The histologic material consisted of spindle cell melanoma specimens from 11 patients, of which seven exhibited features of desmoplastic melanoma. All spindle cell melanoma specimens expressed the p75NTR in at least 10% of the cells, and most expressed p75NTR in more than 50% of cells. In contrast, 10 of 11 control melanomas of conventional epithelioid phenotype expressed lower levels of p75NTR (0% to 10% of cells). CONCLUSION: There is a strong correlation between expression of p75NTR and the desmoplastic phenotype, supporting the hypothesis that the propensity of these melanomas for neurotropism involves p75NTR and its ligands. Immunolabeling for p75NTR may be a useful marker for the neurotropic phenotype, as well as for detecting perineural spread in histologic sections of melanomas.

Adult↗
PubMed1995

Synthesis and biological properties of water-soluble p-boronophenylalanine derivatives. Relationship between water solubility, cytotoxicity, and cellular uptake.

Water-soluble p-boronophenylalanine (BPA) derivatives having cascade polyols, the monohydroxy derivative BPA(OH) (4), the dihydroxy analogue BPA(OH)2 (5), and the tetrahydroxy analogue BPA(OH)4 (6), were synthesized in order to elucidate a relationship between the molecular structures and the cellular uptake. Biological properties of these compounds in addition to BPA (1) itself were investigated. Water solubility increased in the order of BPA < BPA(OH) < or = BPA(OH)2 > BPA(OH)4. Cytotoxicity to B-16 melanoma and TIG hybrobrast cells decreased in the order of BPA >> BPA(OH) > or = BPA(OH)2 > BPA(OH)4. The cellular uptake by both B-16 and TIG cells decreased in the order of BPA > BPA(OH) > or = BPA(OH)2 > BPA(OH)4, whereas the uptake ratio of B-16/TIG increased in the order of BPA < BPA(OH) < or = BPA(OH)2 < BPA(OH)4. The latter ratio indicates the selectivity on the uptake by a cancer to normal cell.

Antineoplastic Agents↗
PubMed1995

Cloning and expression of the gene of hemocytin, an insect humoral lectin which is homologous with the mammalian von Willebrand factor.

Invertebrate lectins play an important role in a non-specific self-defense mechanism, as invertebrates do not synthesize specific antibodies. We report the cloning of several overlapping cDNAs encoding the entire silkworm (Bombyx mori) lectin, which we propose to call hemocytin. The sequence (10477 bp) encoded 3133 amino acids. The characteristics features of the carbohydrate-recognition domain of C-type animal lectin were revealed at C-terminal sequence of hemocytin. When cDNA encoding this region was introduced into baculovirus vector, hemagglutinating activities were detected in the culture fluid of a recombinant virus-infected cells. These activities were inhibited by D-mannose, N-acetyl-D-galactosamine, and D-maltose which are haptenic saccharides of authentic hemocytin. Analysis of dot and Northern blot hybridization revealed that hemocytin gene was transcribed in hemocytes of the silkworm at larval-pupal metamorphosis and/or after the injection of Escherichia coli and lipopolysaccharide. After silkworm larvae were injected with C-terminal portion of hemocytin, aggregation of hemocytes was observed in the hemolymph. Hemocytin has significant homology with mammalian von Willebrand factor which involves in platelet adhesion to subendothelium. Also, hemocytin has a homologous region with coagulation factor V and VIII. These results suggest that hemocytin molecule is an adhesive protein and relates to hemostasis or encapsulation of foreign substances for self-defense.

Amino Acid Sequence↗
PubMed1995

Genomic organization of the glycoprotein D gene: Duffy blood group Fya/Fyb alloantigen system is associated with a polymorphism at the 44-amino acid residue.

The Duffy blood group antigen has been characterized by its roles on red blood cells: as a receptor for the malarial parasites and as a promiscuous receptor for chemokine superfamily. Recently, the Duffy blood group associated glycoprotein D (gpFy) cDNA has been cloned (Chaudhuri et al: Proc Natl Acad Sci USA 90:10793, 1993). In this report we describe the organization of genomic DNA coding for the gpFy and elucidate the molecular nature of Fya/b polymorphisms. By a Southern blotting analysis probed with gpFy cDNA, gpFy gene was shown to be composed of three DNA fragments; 1.1-kb Sac I, 1.9-kb EcoRI, and their intervening 47-bp fragments. We cloned the 1.1-kb Sac I and 1.9-kb EcoRI fragments by inverted polymerase chain reaction (IPCR) procedure. The promoter region of the gpFy gene was cloned by IPCR of 1.1-kb Sac I fragment and the 3' flanking sequence was cloned by IPCR of 1.9 kb EcoRI fragment. The both IPCR products contained on both side the known gpFy cDNA sequence without introns, as expected. Although no TATA or CCAAT boxes are present in the promoter sequence, several transcription factor binding site motifs are contained, including AP-1, HNF-5, TCF-1, ApoE B2, W-element, H-APF-1, and Sp-1. The 3' flanking region has two additional polyadenylation signals, other than that used in the cDNA, and also has an indirect and a direct repeat sequence clustered with the 5' flanking region. These facts indicate a possibility that the gpFy gene has been evolved by multiple retrotransposition events. By comparing the coding area of the gpFy gene in 28 Duffy-positive individuals, we elucidated that one base change that results in an amino acid substitution [GA-T(Asp44)-->GGT(Gly)] is in accordance with the Fya/Fyb polymorphism. This fact proves that the gpFy cDNA and its gene described in this report encode the Duffy blood group system.

Amino Acid Sequence↗