Search PubMed⌕ Search

Biomedical subjects

T Fujimoto

Publications and source records attributed to T Fujimoto.

At least 307 records · Page 17Linked to original sources
PubMed1995

Prospective monitoring of minimal residual disease during the course of chemotherapy in patients with acute lymphoblastic leukemia, and detection of contaminating tumor cells in peripheral blood stem cells for autotransplantation.

A prospective study for detecting minimal residual disease (MRD) was conducted on children with acute lymphoblastic leukemia (ALL). Thirty-nine patients (38 B-lineage ALL, one T-ALL) with TCR delta rearrangements could be followed for 21 to 44 months (mean 30.9 months) excluding four patients who died. One hundred and ninety four bone marrow (BM) samples and 13 peripheral blood stem cell (PBSC) grafts were available for detection of MRD. Initially 34 cases were treated prospectively according to the CCLSG risk-stratified protocols for ALL (ALL874 or ALL911), and five cases according to the other protocols. Conventional chemotherapy was replaced by autologous PBSC transplantation (PBSCT) in five patients, by allogenic BM transplantation (BMT) in one patient, or suspended in another patient. Twenty-nine of 32 children in whom conventional chemotherapy could be continued without interruption remain in complete remission (CR). In 24 of the 29 patients MRD became undetectable within 12 months of their diagnosis. In five cases, BM samples obtained during maintenance therapy exhibited residual leukemia cells, and yet none of them relapsed (mean follow-up period 28.6 months). Our results thus indicate that intensive maintenance therapy for patients with PCR-positive results during consolidation therapy may prevent subsequent relapse. Nine events of relapse were diagnosed in eight patients (five BM, two isolated central nervous system (CNS), one combined BM and CNS, one isolated skin relapse). An increase or a re-emergence of MRD was detected in BM samples obtained from patients prior to BM relapse, but one patient remained in CR despite reappearance of leukemic cells following a PCR-negative status. Monitoring of MRD failed to predict isolated CNS or skin relapse. PBSCT allows high-dose cytoreduction therapy for patients with refractory neoplasia. In our study, leukemic cells were identified in eight of 13 PBSC grafts harvested from five patients. Three of four children who received PBSC grafts containing leukemic cells relapsed within 6 months after PBSCT. Monitoring of MRD as part of quality control of PBSC grafts may ultimately contribute to improvements in PBSCT procedures.

Child↗
PubMed1995

[A case of pulmonary metastasis from colon cancer successfully treated with high-dose 5'-DFUR].

We report a case, showing a complete response to high-dose 5'-DFUR, with pulmonary metastasis from colon cancer. A 52-year-old male patient underwent right hemicolectomy for ascending colon cancer in August, 1991. A recurrence of colon cancer developed in the left lower lung 16 months after surgery, and 5'-DFUR was administered at a dose of 1,600 mg/body/day. The pulmonary metastatic lesion was undetectable on chest X-ray film 9 weeks after the start of this therapy. The dose of 5'-DFUR was then reduced to 600 mg/body/day. Although this condition was maintained for 22 weeks, chest X-ray film again showed the metastatic lesion at the same site in the lung as before. The pulmonary metastasis was resected completely in April, 1994. This is suggested to be an effective therapy for pulmonary metastasis from colon cancer.

Adenocarcinoma↗
PubMed1995

[Renal involvement in Sjögren's syndrome--interstitial nephritis and glomerulonephritis].

Renal involvement is well recognized extraglandular manifestation of primary Sjögren's syndrome (SS). The most common histopathological lesion is an interstitial lymphocytic infiltrate with tubular atrophy and fibrosis. The clinical presentation may be hyposthenuria, overt or latent distal renal tubular acidosis and less commonly Fanconi's syndrome. These tubular dysfunctions correlate with the presence of interstitial lymphocytes. Immunoregulatory alterations consisting of impaired T-cell function and B-cell hyperactivity probably play a pathogenetic role in the development of interstitial nephritis in SS. Glomerulonephritis in SS has been described in a limited number of case reports. Variant modes of pathogenesis have been proposed in these cases where glomerulonephritis has been associated with immune complex deposition and cryoglobulinemia.

Glomerulonephritis↗
PubMed1995

Heterogeneous expression of glycoprotein Ib, IX and V in platelets from two patients with Bernard-Soulier syndrome caused by different genetic abnormalities.

Bernard-Soulier syndrome (BSS) is a rare inherited bleeding disorder, which is caused by deficiency or decrease of the platelet GPIb/IX/V complex. Analysis of two patients with BSS by flow cytometry of the blood revealed different expression patterns of the components of the GPIb/IX/V complex. In case 1, GPIX was completely absent but residual amounts of GPIb alpha and GPV were detectable; in case 2, GPIb alpha was completely absent. We amplified the coding regions of GPIb alpha, GPIb beta, GPV, and GPIX from the patients' genomic DNA with the polymerase chain reaction (PCR) and sequenced the PCR products. in case 1, we identified a point mutation in the GPIX coding region that changes the codon for tryptophan-126 (TGG) to a nonsense codon (TGA). In case 2, we found a deletion of nucleotide within seven adenine repeats at the position of 1932 to 1938 in the coding region of GPIb alpha, which causes a frame shift that results in 58 altered amino acids and a premature stop codon. These genetic changes alter the transmembrane domain of GPIX or GPIb alpha and, therefore, would prevent proper insertion of the proteins in the plasma membrane. Thus, abnormality of a single component protein (GPIX or GPIb alpha) alters the assembly of the GPIb/IX/V complex and causes heterogeneous surface expression of GPIb alpha, GPV and GPIX.

Adult↗
PubMed1995

Differential susceptibility of epidermal keratinocytes and neuroblastoma cells to cytotoxicity of ultraviolet-B light irradiation prevented by the oxygen radical-scavenger ascorbate-2-phosphate but not by ascorbate.

Human or mouse epidermal keratinocytes NHEK or Pam212 was less susceptible to ultraviolet (UV)-B irradiation than mouse neuroblastoma NAs1 cells in culture, undergoing apoptosis-like cell death as shown by cell fragmentation and cell membrane integrity disruption. UV susceptibility was appreciably reduced by the reactive oxygen species (ROS)-scavenger L-ascorbic acid-2-phosphate (Asc2P) endowed with long-lasting functions but not by L-ascorbic acid (Asc) for each cell type. DehydroAsc reduced UV susceptibility of Pam212 or NAs1 established cell lines but not of normal diploid NHEK cells destined to be thereafter submitted to cellular senescence. The susceptibility reduction may not be ascribed to extracellular Asc2P or DehAsc, which was removed by aspirating and/or rinsing upon irradiation after the intracellular channelyzer analysis and dead cell-specific DNA-intercalator ethidium homodimer/fluorometry, respectively. Thus, the three cell types differed in UV susceptibility partly because of their different ROS-scavenging abilities, which may be potently promoted by Asc2P or dehydroAsc but not Asc.

Animals↗
PubMed1994

Autologous bone marrow transplantation in children with advanced neuroblastoma.

BACKGROUND: Encouraging results have been reported with high dose chemotherapy and total body radiation followed by bone marrow autotransplantation in children with advanced neuroblastoma; however, relapse remains a significant problem. METHODS: The authors treated 22 children with advanced neuroblastoma with high dose chemotherapy, surgery, intraoperative radiation, and a bone marrow autotransplant (treated in vitro to remove tumor cells) followed by 13-cis-retinoic acid. RESULTS: The 3-year relapse rate was 25% (95% confidence interval [CI], 6-44%). The 3-year disease free survival rate was 72% (95% CI, 52-92%). Toxicities included hemolytic uremic syndrome, herpes infection, and hepatic venoocclusive disease. CONCLUSION: These data suggest that this treatment strategy offers an increased rate of 3-year disease free survival. The nonrandomized nature of this study and its use of multiple modalities precludes the analysis of the specific contribution of each treatment component and comparison with conventional therapy.

Bone Marrow Purging↗
PubMed1994

Design, synthesis, and conformation of a model peptide of endothelin with cystine-stabilized alpha-helix motif.

A model 16-peptide of endothelin-1 (MET-1), which has the minimized sequence homology to the corresponding part of endothelin-1 (ET-1), was designed to confirm the cystine-stabilized alpha-helix motif. The model structure consists of an extended structure, a beta-turn part, and an alpha-helix structure that is stabilized by two disulfide bonds. The alpha-helix segment was designed to emphasize the amphiphilic nature. In order to combine the extended structure and the alpha-helix segment, a D-Ala-Pro sequence was selected to fix the beta-turn. The model endothelin 16-peptide amide was synthesized by solid-phase synthesis on a 4-methylbenzhydrylamine resin. Its conformation was examined by CD and two-dimensional (2D) 1H-nmr measurements. MET-1 showed similar CD patterns to ET-1 in both buffer and 50% aqueous trifluoroethanol solution. The 2D nmr experiments in 50% aqueous ethylene glycol revealed that MET-1 closely resembles the conformation of ET-1 with an extended structure, an alpha-helix, and a beta-turn unit in the same position of the sequence. Furthermore, model peptides without disulfide bond(s) could not assume a stable structure in aqueous solution, while they did have similar alpha-helical content in 50% trifluoroethanol with MET-1. When the two disulfide bridges were simultaneously formed, the peptide with the correct disulfide bonds (MET-1) was obtained in threefold excess to the isomer (apamin type, MET-2). These findings obtained by the modeling of ET-1 showed an important role for the stabilization of peptide conformation with disulfide bonds.

Amino Acid Sequence↗
PubMed1994

31P-magnetic resonance spectroscopic study on the effect of glycerol on cold-induced brain edema.

The aim of the present study was to determine the effects of a hyperosmotic agent, 10% glycerol, on both brain energy metabolism and intracellular pH (pHi) in experimental vasogenic brain edema. Vasogenic brain edema was induced by cold injury applied to bilateral parietal portions in 13 mongrel dogs (7 glycerol, 6 control) while, 3 dogs were used as control. Before and at 24 hours after the injury, sequential phosphorous-31 magnetic resonance spectroscopy (31P-MRS) was performed for 2 hours in order to determine phosphocreatine (PCr), beta-adenosine triphosphate (beta-ATP), inorganic phosphate (Pi) levels and pHi. At 24 hours following cold injury, both PCr/Pi and ATP/Pi ratios significantly decreased from 7.75 to 3.97 and from 2.26 to 1.25, respectively. Furthermore, a moderate decrease in pHi of 7.16 to 7.01 was significantly demonstrated during the same experimental period. Administration of glycerol for 30 minutes significantly increased PCr/Pi from 3.97 to 5.06 and ATP/Pi from 1.25 to 1.72, respectively. Also, glycerol administration caused a significant increase in pHi from 7.01 to 7.11. This study indicates that cryogenic injury, in which formation and expansion of vasogenic brain edema a known to occur, results in disturbed brain energy metabolism and in intracellular acidosis; moreover, the administration of glycerol can ameliorate either or both of these derangements.

Acid-Base Equilibrium↗
PubMed1994

Specific tension of elbow flexor and extensor muscles based on magnetic resonance imaging.

Series cross-section images of the upper extremity were obtained for four men by magnetic resonance imaging (MRI) and anatomical cross-sectional areas (ACSA) of elbow flexor muscles [biceps brachii (BIC), brachialis (BRA), brachioradialis (BRD)] and extensor muscles [triceps brachii (TRI)] were measured. Physiological cross-sectional area (PCSA) was calculated from the muscle volume and muscle fibre length, the former from the series ACSA and the latter from the muscle length multiplied by previously reported fibre/muscle length ratios. Elbow flexion/extension torque was measured using an isokinetic dynamometer and the force at the tendons was calculated from the torque and moment arms of muscles measured by MRI. Maximal ACSA of TRI was comparable to that of total flexors, while PCSA of TRI was greater by 1.9 times. Within flexors, BRA had the greatest contribution to torque (47%), followed by BIC (34%) and BRD (19%). Specific tension related to the estimated velocity of muscle fibres were similar for elbow flexors and extensors, suggesting that the capacity of tension development is analogous between two muscle groups.

Adult↗
PubMed1994

31P magnetic resonance spectroscopy of the medial temporal lobe of schizophrenic patients with neuroleptic-resistant marked positive symptoms.

31P magnetic resonance spectroscopy was performed in 16 mediated schizophrenic patients with neuroleptic-resistant marked positive symptoms and in 16 healthy volunteers matched for age and sex in order to determine what changes in phosphorus metabolites are detected in such patients as compared to the controls. The schizophrenic patients showed an increased level of phosphodiesters in the bilateral medial temporal lobes. They also showed a decrease in the level of beta-ATP in the left medial temporal lobe. These findings suggest that schizophrenic patients with prominent positive symptoms refractory to neuroleptics may have a disturbance of bilateral membrane phospholipid and left-sided high-energy phosphate metabolism in the medial temporal lobe.

Adolescent↗
PubMed1994

A new clinical prognostic predictor for patients with biliary atresia.

The excretion of D-glucaric acid (DGA), a metabolite of the cytochrome P-450 pathway, is considered a marker of the viability of hepatocytes. Twelve cases of biliary atresia (BA) have been investigated, correlating the level of DGA, degree of histological alteration of liver parenchyma, and clinical outcome. Urine was collected in the preoperative period. Five patients had good bile flow after the Kasai operation and demonstrated mild liver fibrosis. The urine excretion level of DGA in this group was 17.2 +/- 3.1 mumol/d (control, 15.2 + 2.2 [67od] mmol/d). Seven patients had partial bile drainage or prolonged jaundice. They also had altered liver parenchyma and a very low level of DGA in the urine preoperatively (4.2 + 2.2 mumol/d). Urine excretion of DGA reflected the degree of alteration of liver parenchyma and closely correlated with clinical outcome. Measurement of DGA before the Kasai operation provides information concerning the present hepatic function and the postoperative prognosis. Once the activity of hepatocytes deteriorates, this test is quicker than the other liver function tests. It is noninvasive and is a useful clinical prognostic predictor in BA.

Biliary Atresia↗
PubMed1994

Abnormal distribution of nerve terminals in infantile hypertrophic pyloric stenosis.

Smooth muscle biopsy specimens obtained from nine infants with infantile hypertrophic pyloric stenosis (IHPS) and from three controls were studied immunohistochemically with respect to the distribution of nerve terminals and neurofilaments. To label nerve terminals and neurofilaments, monoclonal antibodies (MAb) 171B5 and 2F11 were used, respectively. In all specimens of the control group, nerve terminals were numerous in both the myenteric plexus and the muscle layer. There were abundant neurofilaments in the myenteric plexus and a moderate number in the muscle layer. In all specimens of the IHPS group, the density of nerve terminals and neurofilaments was reduced in the muscle layer. In the myenteric plexus, there was no such reduction. The results indicate poor neuronal innervation of the muscle layer in the pylorus of infants with IHPS. This poor innervation may be related to the pathogenesis of pyloric stenosis and hypertrophy.

Antibodies, Monoclonal↗
PubMed1994

Pregnancies following transfer of equine embryos cryopreserved by vitrification.

The objective of this study was to investigate the in vitro and in vivo developmental abilities of equine embryos cryopreserved by vitrification. Twenty-eight embryos were recovered from Native pony and Thoroughbred mares at Days 5 to 7 by nonsurgical uterine flushing (detection of ovulation=Day 0). The vitrification solution contained 40% ethylene glycol, 18% Ficoll, and 0.3 M sucrose in PBS. The embryos were placed for 1 to 2 min in vitrification solution (Group 1) or following exposure to 20% ethylene glycol in PBS for 10 to 20 min (Groups 2 and 3). Single embryos were loaded in 0.25-ml straws, cooled for 1 min in liquid nitrogen vapor and immersed in liquid nitrogen. Straws were warmed in water (20 degrees C, 20 sec), and the contents were expelled with 0.5 M sucrose in PBS. Then the sucrose was diluted in 1-step (Groups 1 and 2) or 4-steps (Group 3). Embryos (n=21) were cultured for 120 h in TCM199 supplemented with 10% fetal bovine serum at 37 degrees C in 5% CO2 in air and evaluated morphologically. Development to the hatching or hatched blastocyst stage was obtained in 0 7 , 4 7 and 4 7 embryos in Groups 1, 2 and 3, respectively. An additional 7 embryos were vitrified-warmed according to the treatment of Group 2 (4 embryos) and Group 3 (3 embryos). Five embryos were selected after in vitro culture for 4 h and were transferred nonsurgically into the uterine horn of Day-4 recipient mares. Transfer of 2 embryos (both Day-6 blastocysts: Group-2 treatment) resulted in pregnancies with a viable fetus at Day-60 of the gestation period.

Journal Article↗
PubMed1994

Cryopreservation of equine oocytes by 2-step freezing.

Immature equine oocytes were frozen-thawed with ethylene glycol (EG), 1,2-propanediol (PD) or glycerol (GL) in PBS and cultured to assess the rate of in vitro maturation (Experiment 1). Compact-cumulus oocyte complexes were collected from slaughterhouse ovaries and equilibrated for 10 min in the freezing medium containing 10% (V/V) cryoprotectant and 0.1 M sucrose. The 0.25-ml straws, loaded with 10 to 30 oocytes, were seeded at -6 degrees C and cooled to -35 degrees C at 0.3 degrees C/min before being plunged into liquid nitrogen. The straws were thawed rapidly in a 37 degrees C waterbath for 20 sec. The proportions of frozen-thawed oocytes reaching Metaphase II (MII) stage after in vitro maturation of 32 h were 15.8% (EG), 5.8% (PD) and 0% (GL), while 63.3% of the nonfrozen control oocytes matured in vitro. The fertilizing ability of immature and mature oocytes after freezing in EG was tested by the insemination of zona-free oocytes with stallion spermatozoa (Experiment 2). Spermatozoa were preincubated for 3 h with 5 mM caffeine, treated with 0.1 mu M ionophore A23187, and inseminated for 20 h at the concentration of 1 to 2 x 10(7)/ml with 6 to 10 oocytes in 50 mu l of Brackett and Oliphant (BO) medium. Immature oocytes (Group 1) were matured in vitro after thawing and then their zona pellucida removed using 0.5% protease. The zona of mature oocytes were removed immediately after thawing (Group 2) or maturation (nonfrozen controls). The oocytes, which had mechanically damaged plasma membrane or lost by artifact, were not examined for insemination. Significantly more control oocytes exhibited a polar body at the time of insemination (53.5%) than either frozen-thawed immature or mature oocytes (25.8 and 27.3%, respectively). Similar proportion of frozen-thawed and control oocytes were penetrated by spermatozoa (71.8 to 79.1%) and exhibited 2 or more pronuclei (73.6 to 80.8%). The mean numbers of spermatozoa per penetrated oocyte were 1.9, 3.0 and 2.5, respectively, for Groups 1 and 2 and for the control oocytes. These results indicate that immature equine oocytes mature to the MII stage in vitro following freezing and thawing in EG or PD but not in GL. Stallion spermatozoa can penetrate zona-free immature and mature oocytes following freezing/thawing in EG and form morphologically normal pronuclei.

Journal Article↗
PubMed1994

Correlation of third ventricular enlargement and EEG slow wave activity in schizophrenic patients.

Twenty-eight schizophrenic patients and 22 normal control subjects underwent magnetic resonance imaging (MRI) and topographic electroencephalography (EEG) in a study attempting to correlate morphological and electrophysiological findings. Schizophrenic patients had larger anterior horns of the lateral ventricles and third ventricles than normal control subjects. Schizophrenic patients showed more delta wave activity in the right parietooccipital region than normal control subjects. Alpha 2 wave activity was reduced in the entire region in schizophrenic patients. In schizophrenic patients, a significant positive correlation was seen between the area of the third ventricle and delta wave activity in the right occipital region. These results suggest that schizophrenic patients may have a dysfunction of diencephalic structures associated with morphological abnormality.

Adult↗
PubMed1994

Novel isoforms of human cyclic AMP-responsive element modulator (hCREM) mRNA.

The cyclic AMP-response element (CRE), a transcriptional enhancer, is regulated by CREB (CRE-binding protein) which is the leucine zipper protein phosphorylated by protein kinase A in response to cAMP signal. The highly homologous protein CREM (CRE-modulator) is thought to modulate CREB-stimulated transcription, and is also involved in transcriptional control during spermatogenesis. In this paper, we report two types of cDNAs of human CREM (hCREM), type 1 and type 2; type 1 is a group of human counterparts of the mouse CREM alpha and type 2 is a novel form having a distinct 5' exon which is unrelated to any species of the CREB and CREM isoforms so far described. This unique 5' region of type 2 hCREM may suggest its independent expression from type 1 CREM. The specific 5' region of type 2 hCREM consisted of 88 bp, containing an initiation codon for translation, but no possible phosphorylation site, suggesting different roles from type 1 CREM. Both type 1 and 2 hCREMs are expressed in lymphoid and non-lymphoid cell lines. Their excess expression by transfection induced suppression of cAMP-mediated activation of transcription, suggesting their negative regulation of CRE-mediated transcription.

Activating Transcription Factor 2↗