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Biomedical subjects

H Inoue

Publications and source records attributed to H Inoue.

At least 829 records · Page 46Linked to original sources

The FHIT gene, spanning the chromosome 3p14.2 fragile site and renal carcinoma-associated t(3;8) breakpoint, is abnormal in digestive tract cancers.

A 200-300 kb region of chromosome 3p14.2, including the fragile site locus FRA3B, is homozygously deleted in multiple tumor-derived cell lines. Exon amplification from cosmids covering this deleted region allowed identification of the human FHIT gene, a member of ther histidine triad gene family, which encodes a protein with 69% similarity to an S. pombe enzyme, diadenosine 5', 5''' P1, P4-tetraphosphate asymmetrical hydrolase. The FHIT locus is composed of ten exons distributed over at least 500 kb, with three 5' untranslated exons centromeric to the renal carcinoma-associated 3p14.2 breakpoint, the remaining exons telomeric to this translocation breakpoint, and exon 5 within the homozygously deleted fragile region. Aberrant transcripts of the FHIT locus were found in approximately 50% of esophageal, stomach, and colon carcinomas.

Acid Anhydride Hydrolases↗

Constitutive activation of NF-kappa B is essential for transformation of rat fibroblasts by the human T-cell leukemia virus type I Tax protein.

Human T-cell leukemia virus type I (HTLV-I) encodes a 40 kDa trans-acting protein, Tax, that regulates transcription of both the proviral and cellular genes, and can transform rat fibroblasts. To determine the functional importance of its trans-acting capacities in cell transformation, we have examined two representative pathways of transcriptional activation--HTLV-I long terminal repeat (LTR) mediated and NF-kappa B dependent--by mutational analysis of Tax. In contrast to a previous report, mutants lacking the ability to activate an NF-kappaB-dependent promoter failed to transform rat fibroblasts, whereas a mutation which abolishes the HTLV-I LTR-mediated trans-activation demonstrated a wild-type capacity for cell transformation. Stable expression of Tax competent for transformation caused enhanced DNA binding of NF-kappa B in rat fibroblasts. We also demonstrate that stable co-expression of the NFKB2 precursor, known as a member of the I kappa B proteins, with wild-type Tax blocked transformation as well as eliminated aberrant NF-kappaB activation by Tax without interference with the HTLV-I LTR-mediated trans-activation. Our results indicate that constitutive activation of NF-kappa B is essential for Tax-mediated transformation of rat fibroblasts.

Amino Acid Sequence↗

A novel function for nucleoside diphosphate kinase in Drosophila.

Nucleoside diphosphate (NDP) kinase is an enzyme that transfers the gamma-phosphate of nucleoside triphosphates to nucleoside diphosphates. Besides this well-defined role, recent evidence suggests that NDP kinase may be implicated in a wide variety of essential cellular processes. In this paper, we showed that the NDP kinase of Drosophila exhibited protein kinase activity as well as autophosphorylation. Ovalbumin was phosphorylated with guanosine 5'-(3-O-thio)triphosphate (GTP gamma S) or ATP. Protein kinase activity was not detected in NDP kinase mutant, abnormal wing discs (awd). These results suggest that this activity could be one of the functions of NDP kinase essential for normal fly development, since awd gene is lethal.

Animals↗

Expression of alpha-1,3-fucosyltransferase type IV and VII genes is related to poor prognosis in lung cancer.

To date, five alpha-1,3-fucosyltransferase genes (Fuc-TIII, IV, V, VI, and VII) have been cloned. To examine the role of alpha-1,3-fucosyltransferase in the synthesis of sialyl Lewis x and the prognosis of lung cancer, PCR amplification of five fucosyltransferase genes and immunohistochemical staining of sialyl Lewis x were performed in 333 patients with lung cancer who underwent surgical resection from 1980 to 1993. The frequencies of Fuc-TIII/V, Fuc-TVI, Fuc-TIV, and Fuc-TVII expression were 9%, 26%, 75%, and 66%, respectively. The frequency of sialyl Lewis x expression (75%) was comparable to Fuc-TIV and Fuc-TVII expression. However, the grading of sialyl Lewis x staining correlated only with the grading of Fuc-TVII gene amplification. Survival of the patients whose tumors showed strong expression of Fuc-TIV and/or FucT-VII was significantly shorter than that of the patients whose tumors did not express either Fuc-TIV or Fuc-TVII. These results suggest that Fuc-TIV and Fuc-TVII expression may be of prognostic value among patients with lung cancer by participating in the biosynthesis of sialyl Lewis x.

Adult↗

Energetically optimal left ventricular pressure for the failing human heart.

BACKGROUND: An energy-starved failing heart would benefit from more effective transfer of the mechanical energy of ventricular contraction to blood propulsion. However, the energetically optimal loading conditions for the failing heart are difficult to establish. In the present study, we analyzed the optimal left ventricular pressure to achieve maximal mechanical efficiency of the failing heart in humans. METHODS AND RESULTS: We determined the relation between left ventricular pressure-volume area and myocardial oxygen consumption per beat (VO2), stoke work, and mechanical efficiency (stroke work/VO2) in 13 patients with different contractile states. We also calculated the optimal end-systolic pressure that would theoretically maximize mechanical efficiency for a given end-diastolic volume and contractility. Left ventricular pressure-volume loops were constructed by plotting the instantaneous left ventricular pressure against the left ventricular volume at baseline and during pressure loading. The contractile properties of the ventricle were defined by the slope of the end-systolic pressure-volume relation. In patients with less compromised ventricular function, the operating end-systolic pressure was close to the optimal pressure, achieving nearly maximal mechanical efficiency. As the heart deteriorated, however, the optimal end-systolic pressure became significantly lower than normal, whereas the actual pressure remained within the normal range. This discrepancy resulted in worsening of ventriculoarterial coupling and decreased mechanical efficiency compared with theoretically maximal efficiency. CONCLUSIONS: Homeostatic mechanisms to maintain arterial blood pressure within the normal range cause the failing heart to deviate from energetically optimal conditions.

Adult↗

Another interpretation of burst imaging as a variation of line projection imaging.

Burst imaging and DUFIS realize fast imaging without rapid switching of magnetic field gradients. In this paper, some new aspects of burst imaging are explored. Interestingly, when one-dimensional Fourier transform is applied, Burst imaging becomes similar to line projection scanning, a concept proposed earlier by Mansfield and Maudsley (P. Mansfield, A. A. Maudsley, Planar spin imaging by NMR. J. Magn. Reson. 27, 101-119 (1977)). The line scanning interpretation is applied to two-dimensional Burst imaging, and the relationship between its two-dimensional k-space trajectory and line scanning interpretation is discussed.

Fourier Analysis↗

Expression of Fas antigen and Fas ligand in the rheumatoid synovial tissue.

To understand the role of apoptosis through Fas/Fas ligand (Fas-L) interaction in the pathogenesis of rheumatoid arthritis (RA), we examined the expression of Fas antigen, Fas-L, and apoptosis in synovial tissue obtained from eight patients with RA and five patients with osteoarthritis (OA). Immunohistochemical staining demonstrated the significant expression of Fas antigen and Fas-L in RA synovial tissue compared with that in OA synovial tissue. Immunohistochemical staining and the DNA nick end labeling (TUNEL) method were combined and revealed that approximately 10 to 30% of Fas antigen-expressing cells in the RA synovium showed DNA fragmentation characteristic for apoptosis. In double-staining analysis, Fas-L was expressed on up to 10% of CD45RO-, CD4-, CD8-, or CD56-positive mononuclear cells in RA synovial tissue. Our results suggest that activated T cells and natural killer cells infiltrating into the RA synovium may contribute to the induction of apoptosis of RA synovial and mononuclear cells through Fas/Fas-L interaction.

Aged↗

Fishing-rod-type abdominal wall lifter for gasless laparoscopic surgery.

We have designed a new abdominal wall lifter for gasless laparoscopic surgery which consists of stainless steel rods and iron lifters. They elevate the abdominal wall up like a dome-type camping tent, which does not disturb any manipulation of scope or X-ray camera. We received a good view of the peritoneal cavity without CO2 gas insufflation in ten patients with cholecystitis. This will be helpful for general laparoscopic surgery or laparoscopic assisted surgery with the use of conventional forceps or extracorporeal suturing through a valveless trocar.

Abdominal Muscles↗

Combined endoluminal-intracavitary thoracoscopic enucleation of leiomyoma of the esophagus. A new method.

Thoracoscopic enucleation of leiomyoma of the esophagus was successfully performed in three cases with a new technique called the "balloon push-out method." Instead of pulling the tumor, which is hard to grasp because of its delicate nature, we pushed it out of the esophageal wall with a balloon-mounted intraluminal endoscope in order to perform the operation faster and more safely. We found this technique to be very useful in this kind of operation.

Endoscopy↗

Immunohistochemically demonstrated variation in expression of cathepsin E between uracil-induced papillomatosis and N-butyl-N-(4-hydroxybutyl)nitrosamine-induced preneoplastic and neoplastic changes in rat urinary bladder.

Expression of rat urinary bladder cathepsin E in benign papillomatosis induced by uracil and various stages of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced carcinogenesis was investigated immunohistochemically. Seven-week-old, male F344/DuCrj rats were used. In the normal urothelium of control rats, cathepsin E stained in all layers of cells, although in umbrella cells and some basal cells the reaction was relatively weak. In rats given a diet containing 3% uracil for 5 weeks immunoreactivity of cathepsin E in uracil-induced papillomatosis was consistently homogeneous in all layers, but weaker than in normal urothelium. In rats given 0.05% BBN in drinking water for 12 weeks and subsequently maintained without treatment for 48 weeks cells with little cathepsin E, never observed in normal urothelium, appeared at 5 weeks above the basement membrane in the earliest stage of BBN-induced urinary bladder cancer (simple hyperplasia). Throughout the neoplastic process, groups of cells with a little cathepsin E were randomly distributed, with expression in the urothelium being markedly unstable. Almost all areas of squamous cell proliferation in TCC were negative for cathepsin E. Instability of cathepsin E expression in rat urothelium therefore appears characteristic for carcinogenesis and offers the possibility of using this feature as an early biomarker for urinary bladder carcinogenesis.

Animals↗

Telomere elongation observed in immortalized human fibroblasts by treatment with 60Co gamma rays or 4-nitroquinoline 1-oxide.

Telomeres are the tandemly repeated (TTAGGG)n sequences that make up the structural and functional ends of all chromosomes in mammals. Many lines of evidence indicate that telomeres stabilize chromosomes, prevent aberrant recombination, and direct chromosome attachment to the nuclear membrane. Since DNA polymerase requires a labile primer to initiate unidirectional 5'-3' DNA synthesis, some bases at the 3' end of each template strand are not copied unless special mechanisms bypass this end-replication problem. To overcome this problem, most eukaryotic cells use telomerase, an enzyme that elongates telomeres. However, this enzyme has not been detected in normal human cells, and these cells lose telomeres with cell division. Cellular senescence might be the result of this loss. Thus, activation of telomerase seems to be critical for the immortalization of human cell lines. In addition, substantial evidence indicates that immortalization in itself is a rate-limiting step for the malignant transformation of human cells. We have treated normal human fibroblasts (AD387, KMS-6, and OUMS-24 lines) intermittently with either 60Co gamma rays or 4-nitroquinoline 1-oxide (4NQO) during serial subcultivations, and have obtained three immortalized cell lines, SUSM-1, KMST-6, and OUMS-24F. In KMS-6 and OUMS-24, the mean terminal restriction fragment length significantly decreased as the population-doubling level increased. The rate of telomere loss was 40 and 50 bp/population doubling in the KMS-6 and OUMS-24 cell lines, respectively. Once these normal cell lines were immortalized, their telomeres became elongated. Similar data were obtained for AD387 cells and their immortalized SUSM-1 cells. These results suggest that telomeres play a critical role in cellular senescence and in the immortalization processes of human cells.

4-Nitroquinoline-1-oxide↗

An improved technique for low anterior resection using a PDS endoloop.

We describe herein the results of performing a new technique of low anterior resection of the rectum using a PDS endoloop, on ten patients with rectal cancer. This technique involves first preparing the rectosigmoid colon with an anvil as in the conventional low anterior resection; then, after the stapler is inserted transanally, two endoloops are solid over the colon and rectum. The rectum is ligated by pushing the knot of the endoloop and a second knot is applied 2 cm proximal to the first. Finally, the rectum is cut and the stapler is closed and fired to make a circular end-to-end anastomosis. The level of the anastomosis ranged from 2.5 to 6 cm with a mean of 4.7 cm in the ten patients, only one of whom developed a minor anastomotic leakage postoperatively. Moreover, no patient has developed local recurrence or distant metastasis to date. In summary, this technique offers certain advantages that allow the operation to be done with more skill and safety in a narrow pelvis.

Adenocarcinoma↗

Multiple osteocartilaginous exostosis. A follow-up study.

Deformity of the lower extremities in 26 patients with multiple cartilaginous exostosis was examined radiologically. Follow-up periods ranged between 3 and 33 years (mean 10.3 years). Twenty-four patients had deformity of the joints. A femoral neck-shaft angle (FNA) of more than 150 degrees was noted in 14 patients (26 of 51 hip joints) at diagnosis. After approximately 10 years of age, the FNA tended to decrease. Eleven patients (22 of 52 knee joints) had genu valgum (the femorotibial angle < mean -2 SD of normal control) which was caused by valgus deformity of the distal femur in one-third of the patients and that of the proximal tibia in two-thirds. Fifteen of 21 patients (29 of 42 joints) had valgus deformity of the ankle (antero-posterior mortise angle of the ankle > 94 degrees), and in half of them, the valgus deformity progressed with growth. Two patients (aged 10 and 11 years) underwent varus osteotomy of the tibia with partial excision of the fibula. However, their deformity relapsed. Surgical treatment for hip deformity is unnecessary during the growth stage. Progressive deformity of the knee and ankle should be detected in an early stage, and the surgical indication has to be examined.

Adolescent↗

The importance of doxorubicin and methotrexate dose intensity in the chemotherapy of osteosarcoma.

The relationship between dose intensity of cytotoxic agents and therapeutic results was examined in a retrospective analysis of 32 patients with non-metastatic high-grade osteosarcoma of the extremities. The average dose intensities of individual agents were 9.8 mg/m2/week for doxorubicin, 1.2 g/m2/week for methotrexate, and 10.5 mg/m2/week for cisplatinum. The dose intensities of doxorubicin and methotrexate were significantly correlated with the clinical results, while that of cisplatinum was not. These results indicate that maximal dose intensification of doxorubicin and methotrexate is an important determinant of treatment outcome for patients with osteosarcoma.

Adolescent↗

Morphological analysis of the cervical spinal canal, dural tube and spinal cord in normal individuals using CT myelography.

To verify the conventional concept of "developmental stenosis of the cervical spinal canal", we performed a morphological analysis of the relations of the cervical spinal canal, dural tube and spinal cord in normal individuals. The sagittal diameter, area and circularity of the three structures, and the dispersion of each parameter, were examined on axial sections of CT myelograms of 36 normal subjects. The spinal canal was narrowest at C4, followed by C5, while the spinal cord was largest at C4/5. The area and circularity of the cervical spinal cord were not significantly correlated with any parameter of the spinal canal nor with the sagittal diameter and area of the dural tube at any level examined, and the spinal cord showed less individual variation than the bony canal. Compression of the spinal cord might be expected whenever the sagittal diameter of the spinal canal is below the lower limit of normal, that is about 12 mm on plain radiographs. Thus, we concluded that the concept of "developmental stenosis of the cervical spinal canal" was reasonable and acceptable.

Adolescent↗

Electrophysiologic mechanisms of adverse effects of class I antiarrhythmic drugs (cibenzoline, pilsicainide, disopyramide, procainamide) in induction of atrioventricular re-entrant tachycardia.

We evaluated the electrophysiological mechanisms of adverse effects of class I antiarrhythmic drugs (cibenzoline in seven patients, pilsicainide in two, and disopyramide in two, and procainamide in three) in the induction of orthodromic atrioventricular re-entrant tachycardia (AVRT). In 14 patients (10 males, 4 females; mean age 37 +/- 18 years) who had inducible AVRT despite the administration of class I drugs, electrophysiological effects of class I antiarrhythmic drugs were evaluated using programmed electrical stimulation techniques. In 4 out of 6 patients with a manifest accessory pathway, class I drugs induced unidirectional conduction block of the accessory pathway (antegrade conduction block associated with preserved retrograde conduction) and enhanced the induction of AVRT with atrial extrastimulation. In eight patients with a concealed accessory pathway, the outward or inward expansion of the tachycardia induction zone was observed in patients who had greater prolongation of the conduction time than the refractory period of the retrograde accessory pathway after class I drugs. During ventricular extrastimulation, the induction of bundle branch re-entry after class I drugs initiated the AVRT in patients with either manifest or concealed accessory pathways. We conclude that the adverse effects of class I drugs are mainly due to induction of unidirectional retrograde conduction of the manifest accessory pathway and the greater prolongation of the retrograde conduction time of the concealed accessory pathway than the refractory period, regardless of the sub-classification of class I drugs.

Adolescent↗

Induction of apoptotic cell death in rat thymus and spleen after a bolus injection of methamphetamine.

We examined whether methamphetamine (MAP) induced apoptotic cell death in vivo. Male Wistar rats were injected intraperitoneally with 25 mg MAP/Kg body weight and were sacrifice at 4, 8 and 24 h. As early as 4 h after a single dose of MAP, DNA ladder bands representing DNA fragmentation into multiples of the internucleosomal DNA length of about 180 by were observed by gel electrophoresis in thymic and splenic DNA. DNA from control rats injected with 1 ml physiological saline/Kg body weight showed no ladder band patterns. The proportion of fragmented DNA from the thymus increased in a time-dependent manner up to 8 h and faint ladder band patterns were observed at 24 h, indicating that cell death via apoptosis occurred at an early stage and then apoptotic bodies were scavenged. DNA fragmentation in the thymus and spleen induced with MAP was also confirmed by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method in situ. In control thymus samples, stained cells were numerous in the cortex but sparse in the medulla. At the boundary area between the cortex and medulla, stained cells were seen as a layer. In the MAP-treated rats, stained cells were increased and dispersed equally in the cortex and medulla. In control spleen samples, stained cells were numerous in all areas excluding the germinal centers. Cells at the germinal centers were stained intensively in MAP-treated rat spleen. Light microscopical analyses allowed us to identify lymphocytes during the course of apoptotic cell death. Electron microscopic studies showed morphological landmarks for the process of cellular apoptosis in both organs e.g. lymphocytes with chromatin condensed into crescents at the periphery of the nuclei and apoptotic bodies. These result indicate that MAP induced cell death of the thymic and splenic lymphocytes via apoptosis.

Animals↗