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Biomedical subjects

C Kimura

Publications and source records attributed to C Kimura.

At least 37 records · Page 2Linked to original sources
PubMed1998

Mechanism of UV-induced apoptosis in human leukemia cells: roles of Ca2+/Mg(2+)-dependent endonuclease, caspase-3, and stress-activated protein kinases.

Ultraviolet light (UV) induced rapid apoptosis of U937 leukemia cells, concurrent with DNA fragmentation and cleavage of poly(ADP-ribose)polymerase (PARP) by activated caspase-3. The in vitro reconstitution of intact HeLa S3 nuclei and apoptotic U937 cytosolic extract (CE) revealed that (i) Ca2+/Mg(2+)-dependent, Zn(2+)-sensitive endonuclease activated in the apoptotic CE induced DNA ladder in HeLa nuclei at pH 6.8-7.4, (ii) activated caspase-3 cleaved PARP in HeLa nuclei, and (iii) when the apoptotic CE was treated with the caspase-3 inhibitor (1 microM Ac-DEVD-CHO) or the caspase-1 inhibitor (10 microM Ac-YVAD-CHO), the former, but not the latter, caused a 50% inhibition of DNA fragmentation and the complete inhibition of PARP cleavage in HeLa nuclei. Similarly, Ac-DEVD-CHO (100 microM) inhibited apoptosis and DNA ladder by 50% and PARP cleavage completely in UV-irradiated U937 cells, but Ac-YVAD-CHO (100 microM) did not. Thus, UV-induced apoptosis of U937 cells involves the Ca2+/Mg(2+)-dependent endonuclease pathway and the caspase-3-PARP cleavage-Ca2+/Mg(2+)-dependent endonuclease pathway. The former pathway produced directly 50% of apoptotic DNA ladder, and the latter involved activated caspase-3 and PARP cleavage, followed by formation of the remaining 50% DNA ladder by the activated endonuclease. In UV-irradiated B-cell lines, further, p53-dependent increase of Bax resulted in a greater caspase-3 activation compared to its absence. However, UV-induced activation of JNK1 and p38 was not affected by the caspase-1 and -3 inhibitors in U937 cells, so that caspases-1 and -3 do not function upstream of JNK1 and p38.

Apoptosis↗
PubMed1998

Clinical, pathological, and genetic features of limb-girdle muscular dystrophy type 2A with new calpain 3 gene mutations in seven patients from three Japanese families.

We report on the clinical, pathological, and genetic features of 7 patients with limb-girdle muscular dystrophy type 2A (LGMD2A) from three Japanese families. The mean age of onset was 9.7+/-3.1 years (mean+/-SD), and loss of ambulance occurred at 38.5+/-2.1 years. Muscle atrophy was predominant in the pelvic and shoulder girdles, and proximal limb muscles. Muscle pathology revealed dystrophic changes. In two families, an identical G to C mutation at position 1080 the in calpain 3 gene was identified, and a frameshift mutation (1796insA) was found in the third family. The former mutation results in a W360R substitution in the proteolytic site of calpain 3, and the latter in a deletion of the Ca2+-binding domain.

Age of Onset↗
PubMed1998

Clinical application of expanded free flaps based on primary or secondary vascularization.

Prefabricated free flaps using an expansion technique were used for four reconstructive cases, including two leg reconstructions and two facial reconstructions. In this series, the prefabricated free flaps created by using the expander were classified into two types: the expanded flap based on the conventional vascular pedicle, which is called the expanded flap with primary vascularization; and the expanded flap based on the vascular pedicle in the carrier, which is called the expanded flap with secondary vascularization. The expanded flap with primary vascularization that is created in the trunk has a good indication for leg reconstruction, because it provides an wide and thin flap with minimal donor site morbidity. The expanded flap with secondary vascularization created in the pectoral region has a good indication for facial reconstruction, because it provides good color and texture matches. Although there are some disadvantages in the tissue expansion technique, the prefabricated free flaps using the expander are very effective in facial and leg reconstruction.

Adolescent↗
PubMed1998

A case of congenital infantile fibrosarcoma of the right hand.

Congenital infantile fibrosarcoma is a rare soft-tissue malignant tumor that usually presents as a mass involving the arm or leg. We report a case of congenital fibrosarcoma on the right hand of a newborn infant. The patient was a 12-day-old male. From the time of delivery, he had a red tumor on his dorsal right hand. The tumor was initially associated with bleeding within a hemangioma and compressed. The course was observed. It appeared that the tumor might be malignant because it increased in size to 10 x 8 x 3 cm, and ulceration and bleeding appeared on the surface after 10 days. A biopsy suggested a fibrosarcoma. The tumor was resected 32 days after birth at the narrow margin in consideration of preservation of function. However, a recurrence was observed under the graft after 2 weeks and another resection was performed. Because the tumor had passed through the interosseous muscle and invaded the palm of the hand, the middle finger, ring finger, and little finger had to be amputated. One year and 7 months postoperatively, no recurrence or metastasis has been observed.

Fibrosarcoma↗
PubMed1998

Bremazocine recognizes the difference in four amino acid residues to discriminate between a nociceptin/orphanin FQ receptor and opioid receptors.

We investigated the molecular basis of the discrimination between nociceptin/orphanin FQ receptor (NociR) and opioid receptors (OPRs) by bremazocine, a non-type-selective opioid ligand. Construction of several chimeric receptors between NociR and kappa-opioid receptor (KOPR) and mutant NociRs followed by binding experiments with [3H]bremazocine showed that the mutation of only four amino acid residues of NociR, Ala216, Val279, Gln280 and Val281, to the amino acid residues located at the corresponding position of KOPR, Lys227, Ile290, His291 and Ile292, made it possible for the resultant mutant NociR to bind bremazocine with high affinity. Considering that these four amino acid residues are conserved among mu-, delta- and kappa-OPRs, the present result suggests that bremazocine recognizes the difference in these four amino acid residues to discriminate between NociR and OPRs.

Amino Acid Sequence↗
PubMed1998

Effects of acute glucose overload on histamine H2 receptor-mediated Ca2+ mobilization in bovine cerebral endothelial cells.

[Ca2+]i and whole-cell membrane current were measured in microvascular endothelial cells from bovine brain. The effects of histamine on [Ca2+]i were examined, and the acute effect of changing extracellular glucose concentration on Ca2+ homeostasis was investigated. Application of 10 micromol/l histamine evoked an initially transient and then sustained increase in [Ca2+]i in normal Krebs solution, but only the transient component in Ca2+-free solution, thereby indicating that histamine mobilizes Ca2+ both from intracellular store sites and extracellular space. The effects of histamine on [Ca2+]i were inhibited by the H2 antagonists, ranitidine and cimetidine, but not by the H1 antagonist, pyrilamine. Incubation of the cells for 2 h in solutions containing low (1.1 and 2.3 mmol/l) or high (23 mmol/l) concentrations of glucose did not influence the resting level of [Ca2+]i. Treatment with low concentrations of glucose did not impair histamine-induced Ca2+ mobilization. On the other hand, when histamine was applied to the cells pretreated with 23 mmol/l glucose, it failed to mobilize Ca2+ from both intracellular store sites and extracellular space. The effect of histamine was mimicked by dibutyryl cyclic AMP, but glucose overload failed to inhibit this, suggesting that glucose overload inhibits H2 receptor-mediated cyclic AMP production. Glucose overload-induced impairment of histamine action was reversed by pretreatment with staurosporine and calphostin C and mimicked by phorbol-12,13-dibutyrate, thereby suggesting the involvement of protein kinase C in the high glucose-induced inhibition of Ca2+ mobilization. Whole-cell membrane current measurement showed that there was no difference in the membrane currents between control and high glucose-treated cells. These results indicate that in bovine brain microvascular endothelial cells, histamine induces Ca2+ release from intracellular store sites and subsequent entry from the extracellular space through the activation of H2 receptors. Glucose overload acutely inhibits histamine-induced Ca2+ mobilization by the activation of protein kinase C.

Animals↗
PubMed1997

Hyperpolarization-activated Cl- current elicited by pituitary adenylate cyclase activating polypeptide in Xenopus oocytes.

We examined the electrophysiological effect of pituitary adenylate cyclase activating polypeptide (PACAP) in isolated Xenopus laevis oocytes in vitro. In conventional two-electrode voltage clamp experiments, PACAP (1-10 microM) activated an inward rectifier current at membrane potentials more negative than -60 mV without causing any significant change in currents at potentials more positive than -60 mV both in the follicle-enclosed oocyte and in the defolliculated oocyte. This current reversed at -22.5 mV, close to the theoretical value of Cl- equilibrium potential and the reversal potential of this current was shifted positively by reducing [Cl-]o. This current was blocked by Cl- channel blocker SITS and Ba2+. Furthermore, VIP and adenylate cyclase activator forskolin did not elicit the currents. In conclusion, PACAP elicited the hyperpolarization-activated Cl- current in Xenopus laevis oocytes. This current may modulate the membrane potential of the oocyte, thereby affecting the oocyte physiology.

Animals↗
PubMed1997

Congenital ectopic nails reconstructed with local skin flaps.

Congenital ectopic nails are quite unusual and characterized by development of nail-like tissue on the tips of one or more fingers. We present the case of a boy with congenital ectopic nails on both little fingers. To prevent tapering of the fingertips following surgery, we used subcutaneous pedicle flaps and obtained a satisfactory cosmetic result.

Choristoma↗
PubMed1997

Cis-acting elements conserved between mouse and pufferfish Otx2 genes govern the expression in mesencephalic neural crest cells.

Previous studies suggested that the Otx2 gene plays an essential role in the development of cranial skeletons and nerves of mesencephalic neural crest origin. To clarify this role, we have identified the cis-acting elements in mouse and pufferfish Otx2 genes responsible for the expression in the crest cells using a transgenic approach with the lacZ reporter gene. In mouse, 49 bp sequences in the proximal 5' region upstream were essential and sufficient to direct the transgene expression in the cephalic mesenchyme. In pufferfish, the 1.1 kb distal region, located far downstream (from +14.4 to +15.5 kb), had almost identical activity. Between them, several DNA sequences were conserved, and mutational analyses indicated that motif A was critical for the transgene expression in the premandibular region while motif B was critical in both premandibular and mandibular regions. Motif B, CTAATTA, contains the core motif for binding of homeodomain proteins while motif A, TAAATCTG, does not match any known consensus binding sequences for transcriptional factors. The cephalic mesenchyme that expressed beta-galactosidase under these cis-elements is most likely to correspond to mesencephalic crest cells. Thus the molecular machinery regulating Otx2 expression in these cells appears to be conserved between mouse and fish, implying a crucial role of the Otx2 gene in development of the neural-crest-derived structures of the gnathostome rostral head.

Animals↗
PubMed1997

Plasma levels of brain natriuretic peptide as an index for evaluation of cardiac function in female gene carriers of Duchenne muscular dystrophy.

The level of plasma brain natriuretic peptide (BNP) was elevated in 8 of 15 female gene carriers of Duchenne muscular dystrophy (DMD), and the level correlated with indices of cardiac function. In one of these carriers, whose clinical course was followed for one year, the plasma BNP level was elevated before the development of cardiac symptoms, further increased with the evolution of cardiac symptoms, and then decreased after treatment for cardiac failure. These results suggest that the plasma BNP level may be useful for the early detection of cardiac dysfunction and for evaluating the efficacy of cardiac treatment in female DMD carriers.

Adult↗
PubMed1997

[Clinical efficacy of silver sulfadiazine (AgSD: Geben cream) for ulcerative skin lesions infected with MRSA].

The clinical efficacy was evaluated on 1% silver sulfadiazine (AgSD) cream (Geben cream) for the treatment of ulcerative skin lesions infected with MRSA (methicillin-resistant Staphylococcus aureus). 1% AgSD cream was applied once a day to cutaneous ulcers such as burns or decubitus or various other ulcers, infected with MRSA, in 13 patients. MRSA was eradicated in 45.5% of 11 evaluable patients. The clinical efficacy rate of 1% AgSD cream was 72.7% in this series of treatment. No side effects were noted in any of the patients, either locally or systemically. The results of the present study have indicated that 1% AgSD cream is useful for cutaneous ulcers such as burns or decubitus, infected with MRSA.

Administration, Topical↗
PubMed1996

Phenotypes correlating to metastatic properties of pancreas adenocarcinoma in vivo: the importance of surface sialyl Lewis(a) antigen.

Metastasis to the liver often occurs in patients during the natural course of pancreatic cancer. Using carcinoma cell lines established from 9 such patients, we examined phenotypes of cell lines to search for correlations with their potential to metastasize to the liver. Anti-asialo GMI-treated nude mice were used. PCI-43, -55, -24 and -6, in this order, had frequent metastases, while PCI-10, -19, -35, -64, and -66 did not. In vitro doubling time, surface expression of sialyl Lewis(a) (SLe(a)), VLA-4/6, LFA-I/3, CEA, E-selectin, VCAM-I, NCAM, Mac-I, HLA-ABC/ DR/DQ, ICAM-I/2, production of interleukin-I alpha, tumor necrosis factor-alpha, and matrix metalloproteinase, as well as susceptibility to cytotoxicity by natural killer cells, were all examined. Expression of surface SLea was significantly associated with metastasis; numbers of metastatic colonies of SLe(a)-positive and -negative cell lines were 21.6 +/- 33.9 and 6.5 +/- 14.3 (p < 0.01), respectively. Moreover, the intensity of surface SLe(a) expression of each PCI line correlated with the number of metastatic colonies in the liver. When anti-SLe(a) monoclonal antibody (MAb) was administered, the development of liver metastasis by PCI-43 cells was significantly repressed, as compared with a control MAb. Although a reverse correlation between surface ICAM-I expression and liver metastasis was noted, the species-restricted function of ICAM-I makes interpretation difficult. Collective evidence indicates that expression of SLe(a) is an important positive mediator in the hematogenous metastasis of pancreas carcinoma.

Adenocarcinoma↗
PubMed1996

Inhibition of hepatocellular carcinoma development and erythrocyte polyamine levels in ODS rats fed on 3'-methyl-4-dimethylaminoazobenzene by hemicalcium ascorbate, 2-O-octadecylascorbic acid, and ascorbyl palmitate.

We examined the modifying effect of hemicalcium ascorbate (Ca-Asc), and its lipophilic derivatives, 2-O-octadecylascorbic acid (CV-3611) and ascorbyl palmitate (AscP), on hepatocarcinogenesis by 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) in ODS rats (a mutant unable to synthesize ascorbic acid). Male 14-week-old ODS rats were given a modified AIN-A diet or the diet containing 0.06% 3'-Me-DAB, and drinking water containing 0.1% ascorbic acid. Rats were divided into the following eight groups: Group 1, no treatment (basal diet alone); Group 2, Ca-Asc; Group 3, CV-3611; Group 4, AscP;Group 5, 3'-Me-DAB; Group 6, 3'-Me-DAB + Ca-Asc; Group 7, 3'-Me-DAB + CV-3611; and Group 8, 3'-Me-DAB + AscP. Ca-Asc (2 g/kg), CV-3611 (0.2 g/kg), and AscP (0.6 g/kg) was administered once every day by gavage. 3'-Me-DAB was given in the basal diet. After 17 weeks, animals were killed by exsanguination, and the liver was weighed and processed for histological examination. Treatment by CV-3611 exerted a marked inhibitory effect on the development of 3'-Me-DAB-induced hepatocellular carcinomas (HCC) as measured by multiplicity. Although less effective than CV-3611, Ca-Asc and AscP also showed inhibitory effect. We have also studied the correlation of erythrocyte (RBC) polyamine levels and HCC development. RBC polyamine levels were inhibited by Ca-Asc and its derivatives, indicating it may be a marker of hepatocarcinogenesis.

Animals↗
PubMed1995

Mouse Otx2 functions in the formation and patterning of rostral head.

The anterior part of the vertebrate head expresses a group of homeo box genes in segmentally restricted patterns during embryogenesis. Among these, Otx2 expression covers the entire fore- and midbrains and takes place earliest. To examine its role in development of the rostral head, a mutation was introduced into this locus. The homozygous mutants did not develop structures anterior to rhombomere 3, indicating an essential role of Otx2 in the formation of the rostral head. In contrast, heterozygous mutants displayed craniofacial malformations designated as otocephaly; affected structures appeared to correspond to the most posterior and most anterior domains of Otx expression where Otx1 is not expressed. The homo- and heterozygous mutant phenotypes suggest Otx2 functions as a gap-like gene in the rostral head where Hox code is not present. The evolutionary significance of Otx2 mutant phenotypes was discussed for the innovation of the neurocranium and the jaw.

Abnormalities, Multiple↗
PubMed1995

E-selectin expression induced by pancreas-carcinoma-derived interleukin-1 alpha results in enhanced adhesion of pancreas-carcinoma cells to endothelial cells.

Cellular adhesion of sialyl-Lewis-a(SLea)-positive pancreas carcinoma to endothelial cells (EC) is augmented by activation of EC via up-regulated E-selectin expression on EC. Co-cultivation of pancreas-carcinoma cells, PCI-24, with human umbilical-vein endothelial cells (HUVEC) for 5 hr at the PCI-to-HUVEC ratio of 1:10 induced E-selectin expression on the endothelial-cell surface, augmenting SLea-positive pancreas-carcinoma cell attachment with HUVEC. Culture supernatants of 6 tested pancreas-carcinoma cell lines contained soluble, E-selectin-inducing factor(s). The E-selectin-inducing effect by the supernatants was blocked by the protein-kinase-C inhibitor, H7. Antibodies against SLea and E-selectin but not SLex or ICAM-1 blocked the increased pancreas-carcinoma-to-endothelial attachment. Paraformaldehyde(PFA)-fixed PCI-24 cells also induced E-selectin on vascular endothelial cells upon direct contact with endothelial cells, indicating the presence of a membrane-bound form. The 6 pancreas-carcinoma lines all produced IL-1 alpha mRNA and protein but not IL-1 beta or TNF-alpha protein and/or mRNA. Absorption of IL-1 alpha from the supernatants by IL-1 alpha-specific antibody almost completely abolished E-selectin-inducing activity. Anti-IL-1 alpha antibody also abolished the E-selectin-inducing activity of PFA-fixed PCI. IL-1 alpha production by PCI cells was up-regulated by TNF-alpha. These observations suggest that substance(s) produced by pancreas-carcinoma cells, in this case, IL-1 alpha, may contribute to pancreas-carcinoma-cell colonization in non-inflamed, distant locations in vivo, by activating vascular endothelial cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1995

Effect of intraocular lens design on posterior capsule opacification after continuous curvilinear capsulorhexis.

We compared the effect of biconvex and convex-plano (posterior plano) intraocular lenses on posterior capsule opacification (PCO) following continuous curvilinear capsulorhexis (CCC) in 212 eyes. During the three years following surgery, the cumulative frequency of neodymium:YAG laser posterior capsulotomy, calculated with the Kaplan-Meier method, was significantly higher in patients in the biconvex group (32.5% by the third year) than in those in the convex-plano group (5.9% by the third year) (P < .05, Wilcoxon's test; P < .01, Cox-Mantel's test). Measured with the tracing method, the area within a 5 mm diameter central circle that developed Elschnig pearls was 2.93 +/- 4.91 mm2 in the biconvex group and 1.66 +/- 2.37 mm2 in the convex-plano group. In the study, PCO was less severe in the convex-plano group than in the biconvex group following CCC. These results are contrary to those reported previously in patients with can-opener capsulotomy.

Adult↗