Biomedical subjects

K Niwa

Publications and source records attributed to K Niwa.

At least 109 records · Page 6Linked to original sources

PubMed1997

Fibroblasts spread on immobilized fibrin monomer by mobilizing a beta1-class integrin, together with a vitronectin receptor alphavbeta3 on their surface.

Human and murine fibroblasts were found to spread far more avidly on fibrin monomer monolayers than on immobilized fibrinogen, indicating that removal of fibrinopeptides by thrombin is a prerequisite for the fibrin-mediated augmentation of cell spreading. In fact, cell spreading was not efficiently augmented on monolayers of a thrombin-treated dysfibrinogen lacking the release of fibrinopeptide A due to an Aalpha Arg-16 --> Cys substitution. Since a synthetic Arg-Gly-Asp (RGD)-containing peptide inhibited the fibrin-mediated cell spreading, subsequent dissociation of the carboxyl-terminal globular domain of the Aalpha-chains appears to render the RGD segments accessible to the cell-surface integrins. In support of this, fibrin-augmented cell spreading was inhibited by an antibody recognizing a 12-kDa peptide segment with gamma Met-89 at its amino terminus, which is located in close association with the RGD segment at Aalpha 95-97 in the helical coiled-coil interdomainal connector. The fibrin-mediated augmentation of cell spreading was inhibited not only by an antibody against human vitronectin receptor (LM 609) but also by an antibody against the beta1 subunit of integrin (mAb13), suggesting that the beta1-class integrin together with a vitronectin receptor, alphavbeta3, is mobilized onto the surface of fibroblasts upon contact with the fibrin monomer monolayer.

Animals↗

PubMed1997

A possible role of endogenous inhibitor for nitric oxide synthesis in the bovine ciliary muscle.

The present experiments were designed to investigate the possible role of endogenous methylarginine derivatives such as NG-monomethyl-L-arginine, asymmetrical NG,NG-dimethyl-L-arginine and symmetrical NG,N'G-dimethyl-L-arginine for the nitric oxide synthesis in the bovine ciliary muscle. The contents of asymmetrical NG,NG-dimethyl-L-arginine and symmetrical NG,N'G-dimethyl-L-arginine in the bovine ciliary muscle were determined to be 370.2 +/- 27.6 (n = 5) and 182.4 +/- 22.9 (n = 5) pmoles g-1 wet weight, respectively by means of the automated high-performance liquid chromatography. NG-Monomethyl-L-arginine was below the assay limits. On the basis of the total tissue water content (0.792 +/- 0.006 ml g-1 wet weight, n = 14), the concentrations of asymmetrical NG,NG-dimethyl-L-arginine and symmetrical NG,N'G-dimethyl-L-arginine were tentatively estimated to be (4.7 +/- 0.3) x 10(-7) M (n = 5) and (2.3 +/- 0.3) x 10(-7) M (n = 5), respectively. A23187 (10(-7)-3 x 10(-4) M) produced a concentration-dependent relaxation of the ciliary muscle strips which had been contracted with 10(-5) M carbachol. Authentic asymmetrical NG,NG-dimethyl-L-arginine (3 x 10(-6)-3 x 10(-4) M), but not symmetrical NG,N'G-dimethyl-L-arginine (3 x 10(-4) M), inhibited the 10(-6) M A23187-induced relaxation in a concentration-dependent manner. The inhibition with asymmetrical NG,NG-dimethyl-L-arginine (10(-4) M) was reversed by an addition of 3 x 10(-3) M L-arginine, but not by 3 x 10(-3) M D-arginine. The A23187 (10(-6) M)-induced relaxation was enhanced by 3 x 10(-3) M L-arginine or superoxide dismutase (50 U ml-1), whereas it was inhibited by carboxy-PTIO (3 x 10(-4) M), a scavenger of nitric oxide, or methylene blue (10(-5) M), an inhibitor of guanylate cyclase. The carbachol-induced contraction was enhanced by asymmetrical, NG,NG-dimethyl-L-arginine (10(-5) M) and inhibited by 3 x 10(-3) M L-arginine. Any effect of prostanoid formation during the A23187-induced relaxation was ruled out by using indomethacin (10(-5) M). Sodium nitroprusside (10(-5) M), a donor of nitric oxide, also produced a relaxation, which was inhibited by methylene blue (10(-5) M) or carboxy-PTIO (3 x 10(-4) M) and was augmented by superoxide dismutase (50 U ml-1), but unaffected by asymmetrical NG,NG-dimethyl-L-arginine (3 x 10(-4) M) or L-arginine (3 x 10(-3) M). These results lead us to speculate that the nitric oxide synthesized endogenously from L-arginine may play a role for mediating relaxation of the bovine ciliary muscle and that the endogenous asymmetrical NG,NG-dimethyl-L-arginine may be involved in inhibiting the biosynthesis of nitric oxide when there are increased intracellular concentrations of the methylarginine under certain circumstances.

Animals↗

PubMed1997

Prediction of incontinence following low anterior resection for rectal carcinoma.

PURPOSE: This study was performed to predict incontinence following low anterior resection for rectal cancer. METHODS: Preoperatively, 21 patients were evaluated via patient history and a physical examination that included anal manometric studies. Six months postoperatively, repeat manometric studies and clinical evaluations were performed to assess the level of continence. Degree of continence was graded based on severity of the dysfunction and grade of the continence score. RESULTS: The formula used for predicted postoperative resting pressure is as follows: predicted postoperative resting pressure = 0.42 x preoperative resting pressure +1.56 x length of remaining rectum +12.37 (R2 = 0.58; P < 0.001). It was demonstrated that patients with low predicted postoperative resting pressures (< 30 mmHg) had incontinence, and those with high predicted postoperative resting pressures (> 35 mmHg) were continent. There were significant correlations between length of the remaining rectum and ratio of the decrease in maximum resting pressure (postoperative/preoperative maximum resting pressure; r = 0.63; P < 0.01). CONCLUSIONS: Continence following low anterior resection may be influenced by maximum resting pressure function of the internal anal sphincter; if it is injured during surgery, incontinence will occur. We may be able to foretell incontinence by using the predicted postoperative resting pressure formula, which is calculated by using preoperative resting pressure measurements and then determining the length of the remaining rectum.

Aged↗

PubMed1997

Exposure of bovine oocytes to EGF during maturation allows them to develop to blastocysts in a chemically-defined medium.

When cumulus-enclosed bovine oocytes were cultured for 24 h in serum-free medium containing 0 to 50 ng/ml EGF, the proportions of oocytes reaching metaphase II were higher (P < 0.05) in the presence of 30 ng/ml EGF (88.1 +/- 1.3%) than under control conditions (65.5 +/- 3.5%) or in the presence of 10 ng/ml (73.9 +/- 4.5%) and 50 ng/ml (73.6 +/- 4.0%) EGF. When oocytes matured under these conditions were inseminated in vitro, the proportions of oocytes penetrated were higher (P < 0.05) in 10 to 50 ng/ml EGF (96.7 +/- 3.3 to 100%) than in its absence (77.9 +/- 8.9%). However, the proportions of penetrated oocytes with male and female pronuclei did not differ among the different groups (96.7 +/- 3.3 to 100%). When oocytes were matured under the same conditions, fertilized in vitro, and cultured until 192 h post insemination in a chemically-defined medium, the proportion of embryos at the >/=2-cell stage was higher (P < 0.05) in the groups treated with 30 ng/ml (96.1 +/- 2.5%) and 50 ng/ml (90.6 +/- 3.5%) EGF than in the controls (71.8 +/- 3.1%) at 48 h post insemination. Although there were no differences in the proportions (37.3 +/- 5.3 to 47.2 +/- 5.8%) of >/=morulae at 144 h post insemination among treatments, the proportion of embryos developing to the blastocyst stage was higher (P < 0.05) in the presence of 10 to 50 ng/ml EGF (16.5 +/- 2.0 to 20.8 +/- 4.9%) than in control medium (3.4 +/- 2.1%). The mean blastocyst cell number at 192 h post insemination did not differ between culture media in the presence (91 to 107 cells) and the absence (116 cells) of EGF (10 to 50 ng/ml) during maturation. Thus, higher proportions of oocytes matured in serum-free medium with EGF than without EGF could develop to the blastocyst stage in a chemically-defined medium after in vitro fertilization. These results indicate that EGF can induce not only nuclear maturation but also cytoplasmic maturation of cumulus-enclosed bovine oocytes in vitro.

Journal Article↗

PubMed1997

Stage-specific requirement of phosphate for development of rat 1-cell embryos in a chemically defined medium.

Rat 1-cell embryos, recovered from naturally mated females, were cultured in a chemically defined medium (mR1ECM). When examined after 24, 56, 64 and 80 h of culture, embryos developed to the 2-cell (100%), 4-cell (93%), 4-cell to 8-cell (97%) and > or = 8-cell (95%) stages, respectively. When 0.4 M phosphate (NaH2PO4) was added to the medium after 0, 24, 56 and 64 h of culture, percentages (0-67%) of embryos that developed to the blastocyst stage after 115 h of culture were lower than that (86%) in the medium without phosphate. However, addition of phosphate after 80 h of culture accelerated blastocyst formation; a significantly higher percentage (94%) of blastocysts was obtained after 110 h of culture in this medium compared with when phosphate was not added (67%). When phosphate was added to the medium after 64 h, almost all (97%) 8-cell embryos developed to the blastocyst stage by 100 h of culture but development of 4-cell to 7-cell embryos was inhibited (22-63%). Acceleration of blastocyst formation was caused by addition of phosphate rather than by the exchange of the medium. The stimulatory effect of phosphate on embryo development was observed at concentrations of 0.1-1.2 mM. The mean numbers of cells (54.5-60.9 cells) in blastocysts examined after 115 h of culture were increased by the addition of 0.4-1.6 mM phosphate at 80 h as compared with blastocysts from cultures without phosphate (46.6 cells).

Animals↗

PubMed1997

Transformation of sperm nuclei into metaphase chromosomes in maturing pig oocytes penetrated in vitro.

Cumulus-free pig oocytes at the germinal vesicle (GV) stage were incubated in modified Brackett & Oliphant's medium with 5% fetal calf serum and 5mM caffeine with or without cryopreserved, ejaculated spermatozoa. When oocytes were transferred into modified tissue culture medium (TCM-199B at pH 7.4) supplemented with 10 IU/ml eCG, 10 IU/ml hCG and 1 microg/ml oestradiol-17beta after 8 h of incubation with spermatozoa and cultured for 0-48 h, 86-99% of oocytes were penetrated. Most (95-100%) oocytes penetrated 0-16 h after transfer had decondensed sperm chromatin. However, 24 h after transfer 47% and 33% of penetrated oocytes contained recondensed sperm chromatin and sperm metaphase chromosomes, respectively. The proportion of penetrated oocytes containing sperm metaphase chromosomes increased after 36-48 h of transfer (51-65%). The transformation of sperm nuclei to metaphase chromosomes was obtained in 75% and 79% of anaphase I (AI) to telophase I (TI) and metaphase II (MII) oocytes, respectively, but only in 38% of metaphase I (MI) oocytes. Moreover, such transformation was observed only in 1 of 30 oocytes at the stages of GV breakdown to prometaphase I and none of 69 oocytes at the GV stage. The transformation of sperm nuclei into metaphase chromosomes was completely inhibited in oocytes penetrated by eight or more spermatozoa. Well-developed male and female pronuclei were observed in only 3 (4%) of 77 oocytes penetrated 48 h after transfer. The proportion of oocytes reaching MII was greatly inhibited by sperm penetration; only 18% of penetrated oocytes, but 87% of non-inseminated oocytes, reached MII by 48 h after transfer. None of the oocytes penetrated by seven or more spermatozoa reached MII. Most (75%) oocytes were inhibited from the transition from MI to MII even though they were cultured for 48 h. The present results indicate that: (1) the cytoplasm of maturing oocytes possesses an activity for transforming sperm nuclei into metaphase chromosomes, (2) immature pig oocytes penetrated by spermatozoa can undergo meiotic maturation to MI, and (3) the transition of such oocytes from MI to MII is inhibited, suggesting that an activity of mitogen-activated protein kinase may be retarded.

Animals↗

PubMed1997

Stage-dependent development of rat 1-cell embryos in a chemically defined medium after fertilization in vivo and in vitro.

The present study was conducted to examine the development of rat 1-cell embryos cultured in a chemically defined medium (mR1ECM) soon after penetration of eggs in vivo or in vitro. When eggs were recovered from naturally mated females at 0600-0900 h on the following day, no penetrated eggs with male pronuclei were observed. However, the percentage of pronuclear eggs had increased significantly at 1000-1100 h (17%) and 1200-1300 h (65%). When penetrated eggs recovered at 0600-0900 h were cultured in mR1ECM, blastocyst formation (22-46%) was significantly less frequent than in those (79-93%) recovered at 1000-1300 h. After collection at 0600-0800 h, preculture of penetrated eggs in modified Krebs-Ringer bicarbonate solution (mKRB) for up to 1200-1300 h improved their development to the blastocyst stage from 42% to 78%. Pronuclei were formed in almost all (98-100%) of the penetrated eggs examined after 6-20 h of insemination in mKRB. When penetrated eggs were transferred from mKRB into mR1ECM after 4-30 h of insemination, the percentages (47-64%) of blastocyst formation were significantly higher than those (1-20%) for eggs transferred after 1-3 h or after 40 h of insemination. When a total of 70 morulae or early blastocysts that had been produced by in vitro fertilization and developed in vitro were transferred to 7 pseudopregnant rats, 5 recipients into which 48 embryos had been transferred maintained their pregnancies and 25% of the embryos developed into late fetuses or pups. The results of the present study indicate that rat 1-cell embryos recovered from oviducts before pronuclear formation, or produced by in vitro fertilization, can develop to the blastocyst stage in vitro and that one or more factors in mKRB are necessary to maintain their development in mR1ECM.

Animals↗

PubMed1997

Stage-specific requirement of cysteine during in vitro maturation of porcine oocytes for glutathione synthesis associated with male pronuclear formation.

The present study was designed to clarify the duration of maturation of porcine oocytes when cysteine promotes male pronuclear (MPN) formation through oocyte glutathione (GSH) synthesis. When cumulus-oocyte complexes (COCs) were cultured in a serum-free maturation medium supplemented or not supplemented with 0.57 mM cysteine, about 90% of oocytes reached metaphase I (M-I) to metaphase II (M-II) and M-II at 36 and 48 h of culture, respectively. When cysteine was added to medium at 0, 12, 24, and 36 h of culture and COCs were cultured for a total of 48 h, oocyte GSH concentrations at the end of culture and the incidence of MPN formation after sperm penetration in vitro were both higher than the values in oocytes cultured for 48 h without cysteine. In contrast, the GSH concentration at 48 h and the incidence of MPN formation were not increased when cysteine was present only during the first 24 h of maturation culture. When cysteine was added to medium every 3 h from 36 h of culture on, a higher incidence of MPN formation was obtained in oocytes cultured in the presence of cysteine from 36 to 42 h than from 36 to 45 h of culture, although GSH concentrations were higher in oocytes cultured with cysteine from 36 to 42 h than from 39 to 42 h of culture. These results suggest that the presence of cysteine in maturation medium is critical only between 42 and 48 h of culture when porcine oocytes are in the late M-I to M-II stage of development. At that time cysteine is utilized for GSH synthesis, which is subsequently instrumental in the formation of MPN after sperm penetration in vitro.

Animals↗

PubMed1997

Amino acids in maturation medium and presence of cumulus cells at fertilization promote male pronuclear formation in porcine oocytes matured and penetrated in vitro.

The present study was conducted to examine the ability of porcine oocytes to achieve male pronuclear (MPN) formation when they are matured and penetrated in vitro under various culture conditions. When cumulus-enclosed oocytes were cultured for 24-48 h in modified Whitten's medium (pH 7.4) supplemented with 10% porcine follicular fluid, 10 IU eCG/ml, and 10 IU hCG/ml (designated mWM-FG), nuclear maturation of oocytes reaching metaphase II was completed by 36 h after the start of culture. However, there were no differences in the proportions (94-95%) of oocytes penetrated in vitro by cryopreserved ejaculated spermatozoa or in the rates (35-45%) of MPN formation between oocytes cultured for 36 and 48 h. When cumulus-enclosed oocytes were cultured for 36 h in mWM-FG supplemented with 2% (v:v) minimal essential medium (MEM) essential amino acids (EAA) with the addition of 0.1 mM glutamine and/or 1% (v:v) MEM nonessential amino acids (NEAA) and inseminated in vitro, 93-97% of oocytes were penetrated regardless of the presence of amino acids during maturation, but the rates of MPN formation were higher in the presence (79-84%) than in the absence (51%) of any amino acids. The addition of EAA+NEAA and/or 0.57 mM cysteine to mWM-FG also did not affect sperm penetration in vitro, while it promoted MPN formation (76-83%) in penetrated oocytes as compared with those matured in the absence of amino acids and cysteine (53%). When oocytes were freed from cumulus cells after culture in mWM-FG, sperm penetration rates were not different between cumulus-enclosed (100%) and cumulus-free (92%) oocytes, but the rate of MPN formation was higher in cumulus-enclosed (53%) than in cumulus-free (28%) oocytes. When EAA+NEAA+cysteine was added to mWM-FG, MPN formation was not improved in cumulus-free oocytes but was much improved (78%) in cumulus-enclosed oocytes. These results indicate that MPN formation in porcine oocytes is promoted by the addition of amino acids and/or cysteine in simple maturation medium and by the presence of cumulus cells at fertilization in vitro.

Amino Acids↗

PubMed1997

[A case of myeloradiculoneuropathy associated with persistent high titers of anti-GM1 and anti-GD1b antibodies].

A 60-year-old woman was admitted to our hospital with bilateral weakness of the lower limbs. She had been suffering from spastic paraparesis of unknown origin for 12 years since she was 48. Myelopathy with the Th6 level appeared when she was 52 and underwent gradual deterioration. On admission, she showed spastic paraparesis and myelopathy with the Th6 level. A thoracic spinal MRI examination revealed a wholly thin spinal cord. EMG demonstrated that the conduction velocity of the peroneal nerve was 37.8m/sec, and F waves were not evoked on stimulation of the peroneal nerve. Although the anti-GM1 and anti-GD1b antibody titers in the serum were increased on admission, their values decreased transiently after whole plasmapheresis. There was accompanying impairment of the radiculoneuropathy and myelopathy. It is important to measure the titers of anti-ganglioside antibodies in patients with myeloradiculoneuropathy of unknown origin, and whole plasmapheresis is considered to represent a useful treatment for this type of illness.

Autoantibodies↗

PubMed1997

[A patient with spontaneous intracranial hypotension--comparison between MRI findings and meningeal pathology].

We report a 44-year-old woman with spontaneous intracranial hypotension (SIH) who developed an acute, severe, nonthrobbing headache. The headache remained more severe in the occipital region and was markedly worse with upright posture. Cerebrospinal fluid (CSF) examination revealed an opening pressure of 55 mmH2O, and the CSF contained 38 cells/mm3 and 57 mg/dl of protein. The results of other laboratory examinations were unremarkable. T1-weighted MR images (MRI) of the head revealed an extensive diffuse pachymeningeal gadolinium enhancement and bilateral subdural fluid accumulation. On the 21st hospital day, a meningeal biopsy was performed through a right parietal craniotomy. On histologic examination, the dural border cell layer demonstrated nonspecific granulation tissue with mild inflammatory changes. The remaining layers of the dura mater and the arachnoid membrane showed no obvious pathological changes. We speculated that the inflammatory changes of the dural border cell layer correspond to the zone of pachymeningeal gadolinium enhancement of the MRI. The granulation tissue of the dural border cell layer and subdural fluid accumulation may represent secondary reactive phenomena, and were suspected to have been caused by downward displacement of the brain due to decreased intracranial pressure.

Adult↗

PubMed1996

Silver-stained nucleolar organizer regions in the uterine myomatous tumors.

The numbers of silver-stained nucleolar organizer regions (AgNORs) were counted in uterine myomatous tumors, and compared with those in corresponding normal myometria. The mean number of AgNORs in myomatous tumors tended to increase according to the neoplastic changes. The mean number of AgNORs in leiomyosarcoma (6.4 +/- 0.9) was significantly higher than that in cellular leiomyoma (4.5 +/- 0.7, P < 0.01). or leiomyoma (3.0 +/- 0.5, P < 0.001). In the normal myometria, the mean number of AgNORs (3.3 +/- 0.4) in the premenopausal women showed a higher tendency than that in the post-menopausal women (2.4 +/- 0.5). These results therefore suggest that AgNOR counts may be useful for diagnosis of cellular activity in uterine myomatous tumors.

Female↗

PubMed1996

Characterization of the ATP-dependent LTC4 transporter in cisplatin-resistant human KB cells.

An active efflux pump for cis-diamminedichloroplatinum(II) (cisplatin) has been identified in cisplatin-resistant KCP-4 cells isolated from human epidermoid carcinoma KB-3-1 cells. The adenosine triphosphate(ATP)-dependent transport of leukotriene C4 (LTC4), an endogenous substrate for the glutathione S-conjugate export pump(GS-X pump), has been found in membrane vesicles prepared from KCP-4 cells. Multidrug resistance-associated protein (MRP) has also been identified as an ATP-dependent LTC4 transporter. To examine whether the GS-X pump expressed in KCP-4 cells in MRP, we investigated the expression of MRP in KCP-4 cells and compared the LTC4 transporting activity of GS-X pump expressed in KCP-4 cells with that of MRP. The level of MRP gene expression in KCP-4 cells was low and similar to that in KB-3-1 cells. MRP was not detected in membrane vesicles prepared from KB-3-1 and KCP-4 cells by immunoblot analysis. The ATP-dependent transport of LTC4 in KCP-4 and C-A120 vesicles showed saturable kinetics with an apparent Km of 0.18 microM and 0.25 microM, respectively. [3H]LTC4 transport in KCP-4 vesicles was more inhibited by 2,4-dinitrophenyl-S-glutathione(DNP-SG), bis-(glutathionato)-platinum(II) (GS-platinum) complex and glutathione disulfide(GS-SG) and less by LTD4 compared with that in C-A120 vesicles. The character of the LTC4 transporter expressed in KCP-4 vesicles is similar but not identical to that of MRP. Our results suggest that a glutathione S-conjugate export pump which is different from MRP exists in cisplatin-resistant KCP-4 cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1996

Chronological observation of mouse endometrial carcinogenesis induced by N-methyl-N-nitrosourea and 17 beta-estradiol.

Chronological observation of the neoplastic endometrial lesions induced by N-methyl-N-nitrosourea (MNU) and 17 beta-estradiol (E2) were studied. E2 induced cystic glandular hyperplasia, but adenomatous hyperplasia was induced predominantly by MNU. Atypical hyperplasia and adenocarcinoma were induced cooperatively by E2 and MNU, and first found at week 12; the incidence of adenocarcinoma increased in accordance with the week-course. Some atypical hyperplasia might be changed to adenocarcinoma. Mean AgNORs numbers in (pre)neoplastic lesions increased in accordance with neoplastic changes. This model was useful for clarifying histogenesis of human endometrial carcinogenesis.

Adenocarcinoma↗

PubMed1996

A gamma Gly-268 to Glu substitution is responsible for impaired fibrin assembly in a homozygous dysfibrinogen Kurashiki I.

A new type of gamma Gly-268 (GGA) to Glu (GAA) substitution has been identified in a homozygous dysfibrinogen by analyses of the affected polypeptide and its encoding gene derived from a 58 year-old man manifesting no major bleeding or thrombosis. The functional abnormality was characterized by impaired fibrin assembly most likely due to failure to construct properly aligned double-stranded fibrin protofibrils. This presumption was deduced from the following findings: (1) Factor XIIIa-catalyzed cross-linking of the fibrin gamma-chains progressed in a normal fashion, indicating that the contact between the central E domain of one fibrin monomer and the D domain of another took place normally; (2) Nevertheless, factor XIIIa-catalyzed cross-linking of the fibrinogen gamma-chains was obviously delayed, suggesting that longitudinal association of D domains of different fibrin monomers, ie, D:D association was perturbed; (3) Plasminogen activation catalyzed by tissue-type plasminogen activator was not as efficiently facilitated by polymerizing fibrin monomer derived from the patient as by the normal counterpart. Therefore, gamma Gly-268 would not be involved in the 'a' site residing in the D domain, which functions as a complementary binding site with the thrombin-activated 'A' site in the central E domain, but would be rather involved in the D:D self association sites recently proposed for human fibrinogen. Thus, the gamma Glu-268 substitution newly identified in this homozygous dysfibrinogen seems to impair proper alignment of adjacent D domains of neighboring fibrin molecules in the double-stranded fibrin protofibril, resulting in delayed fibrin gel formation.

Afibrinogenemia↗

PubMed1996

Expression of the multidrug-resistance-associated protein (MRP) gene in human colorectal, gastric and non-small-cell lung carcinomas.

MRP has been identified as another multidrug-resistance (MDR) gene and may be involved in an alternative MDR mechanism in some solid tumors. We investigated the expression of MRP mRNA in multidrug-resistance KB sublines (KB-8-5, KB-C2, C-A40 and C-A120), human non-small-cell lung carcinomas (NSCLC), gastric and colorectal carcinomas, and compared it with that in drug-sensitive human KB cells. MRP gene expression was elevated in 8 of 9 (89%) squamous-cell carcinomas of the lung. Furthermore, MRP expression in 4 squamous-cell carcinomas (L13, 18, 19 and 20) was more than 3.6 times higher than in KB-3-1 cells, and the average MRP mRNA expression level of all squamous-cell carcinomas was significantly higher than that of adenocarcinoma of the lung and of colorectal and gastric carcinomas. These results suggested that the MRP is responsible, at least in part, for drug resistance in some squamous-cell carcinomas of the lung.

ATP-Binding Cassette Transporters↗

PubMed1996

Measurement of ventricular volumes by cine magnetic resonance imaging in complex congenital heart disease with morphologically abnormal ventricles.

This study assessed the validity of cine magnetic resonance imaging (MRI) for measuring right and left ventricular volumes by using Simpson's rule in children with complex congenital heart disease. Forty-five patients with complex congenital heart disease (average age 2.6 years) and 10 controls (average age 2.3 years) were evaluated. The whole heart was encompassed by contiguous transverse sections. Ventricular volumes were calculated by adding luminal areas determined in each section at end diastole and end systole. End-diastolic and end-systolic volumes by MRI in both groups correlated well with those by ventriculography (r>0.89). Comparison of the ejection fraction in both ventricles in both groups yielded a good correlation between MRI and ventriculography (r>0.67). MRI technique in both groups had low intraobserver and interobserver variation (<6%). Cine MRI provides a suitable noninvasive means of quantifying ventricular volume in children with complex congenital heart disease.

Child↗

PubMed1996

[Effect of preoperative oral 5-fluorouracil on cell cycle of advanced cervical squamous cell carcinoma].

Using flow cytometry, we examined the correlations between the tumor stage and the cell cycle in subjects with advanced cervical squamous cell carcinoma as well as between the changes of cell cycle caused by 5-FU and their prognoses. Before 5-FU treatment, 75.9 +/- 9.6% of the patients were at G1 phase, 16.8 +/- 3.9% at S and 7.3 +/- 4.5% at G2/M. The change of cell cycle was not accompanied by the progression of tumor stage. Sixteen patients received oral 5-FU (300 mg/day) for at least 2 weeks before operation. In the patients at stage I, the cell cycle was not changed even after 5-FU treatment. They have been cancer-free for 3 postoperative years. While early recurrence was found in 4 of 5 cases at stage II or III showing progression at G1, all 6 cases who had regressed or remained unchanged at G1 were free from recurrence (p = 0.0152). These results suggested that the cell cycle is not necessarily correlated with the progression of tumor stage in patients with this kind of carcinoma, and that the change of cell cycle due to preoperative oral 5-FU could be a predictive indicator for their prognoses. Especially for those with poor prognoses who had shown progression at G1, more potent adjuvant chemotherapy should be planned.

Administration, Oral↗