[A case of IGF-II producing rectal cancer with recurrent hypoglycemia].
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Biomedical subjects
Publications and source records attributed to H Eguchi.
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We studied four patients with inv(11)(p15q22) associated with malignant myeloid diseases by using fluorescence in situ hybridization (FISH) with phage and cosmid probes mapped and ordered on 11q22-24. Two of the four patients had non-Hodgkin's lymphoma or acute lymphoblastic leukemia as the primary malignancy and had received cytotoxic chemotherapy, including topoisomerase II inhibitors. The other two had de novo acute myeloid leukemia or myelodysplastic syndrome. FISH analysis showed that all 11q breakpoints were located centromeric to the MLL gene and between cosmids CN2900 and CN1323. We identified a yeast artificial chromosome (YAC) clone that spanned the inv(11) breakpoints on 11q. From this YAC, we identified a P1 clone, which included the breakpoints in at least three of the four patients. It is highly likely that the same gene on the P1 clone is rearranged in leukemic cells of each patient. This gene may be one of the targets for topoisomerase II inhibitors.
Surgical resection, transcatheter arterial embolization (TAE) and percutaneous ethanol injection therapy (PEIT) are effective for hepatocellular carcinoma (HCC), but the recurrence rate is high. We have devised a new therapy of transarterial immuno-embolization (TIE) with OK-432, fibrinogen and thrombin, and 2 cases are reported. Case 1: A 78-year-old Japanese male with HCC (diameter, 4 cm in subsegment 5) received TIE. The tumor size was markedly decreased, and the patient survived for more than 3 years without recurrence. Case 2: A 61-year-old Japanese male with HCC (diameter, 4.5 cm in segment 5) received hepatic subsegmentectomy following TIE. Histological examination of resected specimens following TIE showed massive infiltration of mononuclear cells in the main tumor. Tumor recurrence had developed three times thereafter, but was effectively treated by TIE. TIE may be an effective therapy for HCC.
An intermittent and cyclic regimen with All-Trans Retinoic Acid (ATRA) and intensive chemotherapy was conducted due to pharmacokinetic studies on ATRA for acute promyelocytic leukemia (APL) in children. We have treated 17 children with APL using ATRA for remission induction followed by an intermittent schedule of ATRA plus intensive chemotherapy (APL-ATRA protocol). There were 10 males and 7 females. The median age was 9.0 years old. The median baseline white blood cell count was 12.1 x 10(3)/microliter, hemoglobin 7.8 g/dl, platelet 4.5 x 10(4) microliters at diagnosis. Sixteen patients showed t(15; 17) translocation. RT-PCR analysis was available in 15 patients and showed PML/RAR alpha rearrangement in all patients. Overall, 13 or 17 newly diagnosed patients (88%) achieved complete remission and EFS was 67%. Compared to the control (same chemotherapy without ATRA regimen), remission induction and EFS were significantly increased. The toxicity of ATRA consisted of retinoic acid syndrome in 1 and pseudotumor cerebli in another. Other toxicities included headache, chelitis, gastrointestinal trouble and bone pain. These results suggest that intermittent and cyclic regimen with ATRA and intensive chemotherapy (APL-ATRA protocol) is highly effective for APL patients.
We reported an association of smoking-induced lung cancer susceptibility with the human cytochrome P450 1A1 (CYP1A1) polymorphisms in our previous studies. To investigate a relationship between genetically determined individual predispositions and mutations of target genes in the early stage of lung carcinogenesis, we examined p53 mutations in relation to germ line polymorphisms of the CYP1A1 and GSTM1 genes, using surgical specimens of 148 non-small cell lung cancer patients who were smokers. The frequency of p53 mutations among heavy smokers was higher than in patients who had never smoked [P < 0.01; odds ratio (OR), 3.74; 95% confidence interval (CI), 1.46-9.56]. By single-strand conformational polymorphism, aberrant migration bands of p53 gene fragments were detected in 56 cases (38%). Smokers with susceptible rare homozygous alleles of either the MspI or Ile-Val polymorphism of the CYP1A1 gene have a 4.5-fold (P < 0.005; OR, 4.48; 95% CI, 1.64-12.26) or 5.5-fold (P < 0.01; OR, 5.52; 95% CI, 1.55-19.64) higher risk of having a mutation of the p53 gene than those with nonsusceptible predominant homozygous alleles of the gene. Non-small cell lung cancer patients with a susceptible CYP1A1 genotype were at remarkably high risk of having a mutation of the p53 gene when the genotype was combined with a deficient genotype, GSTM1(-). However, there was no difference between the types of p53 mutation and genotypes of the drug-metabolizing enzymes. These results showed that CYP1A1 germ line polymorphisms, which were associated with the genetic predisposition for lung cancer, were related to cigarette smoking-associated p53 mutations.
A total of 125 children, who were diagnosed as having high-risk acute lymphoblastic leukemia (ALL), were treated with two consecutive protocols designated as AL851 (1985-1988) and ALHR88 (1988-1990). All patients received induction therapy consisting of vincristine (VCR), prednisolone (PSL), daunorubicin (DNR), and I-asparaginase (I-Asp). In the ALHR88 protocol, the patients whose blasts in the bone marrow (BM) were > or = 25% on day 14 of induction therapy and who were classified into T-cell type received additional cytosine arabinoside (AraC). After consolidation with intermediate-dose methotrexate (MTX), reinduction therapy including VCR, dexamethasone, and adriamycin followed by high-dose AraC was done for all patients. Intrathecal MTX and 24Gy of cranial irradiation were used to prevent central nervous system leukemia. A maintenance therapy consisting of 6-mercaptopurine, cyclophosphamide, MTX, DNR, VCR, and AraC was administered for 3 years after achieving a complete remission (CR). CR was achieved in 51/55 (92.7%) for AL851 and 68/70 (97.1%) for ALHR88. The 5-year event-free survival rates were 49.1 +/- 6.7% in AL851 and 62.5 +/- 6.1% in ALHR88. The factors related to a poor prognosis were a high initial leukocyte count of greater than 50 x 10(9)/L (P < 0.001), an L2 morphology of leukemic cells by FAB classification (P = 0.009), the chromosomal abnormality (P = 0.004) and high residual leukemic cells in BM (> or = 25%) on day 14 of induction therapy (P < 0.001). Taking these factors into consideration, more intensive protocols were started in 1990 for the patients with high-risk ALL.
We developed a sandwich enzyme immunoassay system for intact rat osteocalcin to improve the region specificity for the detection of this molecule. We synthesized two peptides of N-terminal 20 residues and C-terminal 10 residues of rat osteocalcin. After conjugating these peptides with carrier protein, we obtained anti-N- and anti-C-terminal rat osteocalcin antibodies in rabbits raised against these two peptides, respectively. By using these antibodies, we measured intact rat osteocalcin levels in a two-site immunoassay manner. These antibodies did not show the cross-reactivity to human osteocalcin. The immunoreactive peak corresponding to the intact molecules was detected by our intact osteocalcin method after high-performance liquid chromatographic fractionation of osteocalcin fragments in plasma from uremic rats. Furthermore, the intact rat osteocalcin was stable over 8 hours at 25 degrees C. Intact rat osteocalcin levels extracellularly secreted from ROS 17/2.8 cells were measured by this method, showing time- and dose-dependent significant increases when administered 1,25(OH)2D3. The inhibition for the secretion of intact osteocalcin by actinomycin D was also detected quantitatively with this method. In ovariectomized rats, intact osteocalcin levels in plasma were acutely elevated after ovariectomy, and its elevation was significantly depressed by 17beta-estradiol administration. These data suggest that this sandwich method is able to measure the intact form of osteocalcin secreted by osteoblasts. As the antibodies identify the specific regions of osteocalcin molecule, this method would be useful for sensitive estimation of bone turnover for various experimental conditions in rats.
PURPOSE: To elucidate the pathogenesis of Sweet syndrome, one patient with aplastic anemia was evaluated. PATIENT AND METHODS: A 15-year-old girl presented with intermittent fever and progressive pallor for 3 months after non-A, non-B, non-C hepatitis. Aplastic anemia was diagnosed and therapy was begun with recombinant granulocyte colony-stimulating factor (G-CSF), methylprednisolone pulse therapy, antilymphocyte globulin and cyclosporin A. There was only an increase in the neutrophil counts. We continued G-CSF therapy of 300 micrograms/m2 on alternate days for 7 months. At this time the white blood cell count was 10,000/microliters and the patient developed high-grade fever and a painful, erythematous, tender plaque (3 X 3 cm) on the left thigh. We diagnosed the lesion as a skin infection and stopped G-CSF therapy and started antibiotics. Cultures were negative. The lesion slowly resolved, G-CSF was restarted after 2 months, and 1 month later disseminated lesions occurred. Antibiotic therapy was not effective. RESULTS: Biopsy of the lesion demonstrated infiltration of the dermis by sheets of neutrophils. We stopped G-CSF and began corticosteroid therapy. The skin lesions resolved rapidly. CONCLUSION: We postulated that Sweet syndrome was induced by G-CSF treatment.
A 30-year-old primigravida, delivering by cesarean section, went into shock with cardiac arrest due to pulmonary thromboembolism. Thrombolytic therapy with recombinant-tissue-type plasminogen activator (rt-PA) induced a rapid improvement in both the hemodynamic and respiratory conditions. This case shows the marked efficacy of rt-PA in treating massive pulmonary thromboembolism. Close attention must be given to the patient in such a case, however, because the risk of hemorrhagic complication exists.
Dissolved O2 concentration ([O2]) in nutrient solution was controlled at 0.01, 0.10 and 0.20 mM with accuracy of +/- 0.005 mM in a newly developed hydroponic system, and the effects of [O2] on water uptake and growth of cucumber plants (Cucumis sativus L.) were analyzed. For evaluating water uptake rate under the control of [O2], water flux at the stem base was measured on-line with +/-5% in accuracy, 1 mg s-1 in resolution and 1 min in time constant by heat flux control (HFC) method. Water uptake rate was drastically increased by lighting to the plant at each [O2], and water uptake per day was depressed in proportion to decrease in [O2]. In the plants grown for 10 days, leaf area, fresh weight and dry weight of leaves decreased at lower [O2], while stem length and number of leaves were scarcely affected. These facts suggest that membrane permeability of root cells reduces at lower [O2] through respiration-dependent processes, and growth is inhibited through leaf turgor loss caused by the depressed water uptake of roots in O2-deficient nutrient solution in hydroponics.
The adhesion of melanoma cells to the extracellular matrix (ECM) protein is likely to be essential in their invasive metastatic processes. Treatment with 12-O-tetradecanoyl phorbol-13-acetate (TPA), a potent protein kinase C (PKC) activator, preferentially induced the expression of alpha 2 beta 1 integrin, the receptor for collagen/laminin. The number of cells attached to type I collagen, but not laminin, was increased by treatment with TPA. Prior exposure to PKC inhibitors such as H-7 (20 mumol/l) and calphostin C (50 mumol/l) had no effect on TPA-induced alpha 2 beta 1 integrin expression and cell attachment to type I collagen, whereas prior exposure to the calmodulin antagonist W-7(50 mumol/l) inhibited these TPA-induced events. The augmented adhesion was also inhibited by anti-alpha 2 antibody. These data suggest that the increased attachment of melanoma cells to type I collagen appears to be mediated by the preferential augmentation of integrin alpha 2 beta 1, and the activation of calmodulin kinase, but not via the activation of PKC. Analysis of the expression of integrins and of cell attachment to ECMs is important in elucidating the mechanisms involved in the progression and metastasis of malignant melanoma.
We report the successful treatment of a patient with plaque-stage mycosis fungoides with long-term and intravenous administration of recombinant human interferon-gamma (IFN-gamma) and discuss the possible mechanisms of this therapy. A 55-year-old female patient had been resistant to existing treatments and had suffered repeated exacerbations over a 5-year period. Four weeks after initiation of 2 x 10(6) U/day of IFN-gamma, a > 10% decrease in the affected surface area was noted. Twenty-two weeks after the administration of 228 x 10(6) U of IFN-gamma, complete remission (CR) was obtained. The CR continued for 13 weeks, but this was followed by an exacerbation. The second CR was obtained after the IFN-gamma dosage was increased to 16 x 10(6) U/week. The dosage was then gradually reduced by 2-4 x 10(6) U every 2 or 3 months. She was treated with a total dose of 2814 x 10(6) of IFN-gamma. She has been followed up for more than 6 years, and there has been no recurrence of mycotic skin lesions nor any visceral involvement. During therapy, no serious side-effects were noted. Long-term administration of IFN-gamma is useful for the treatment of patients with intractable mycosis fungoides. A gradual decrease in the dose of IFN-gamma is important for maintaining remission.
Fiberoptic bronchoscopy was performed on 11 children aged from 6 months to 3 years and weighing between 2.1 and 12.5 kg using the laryngeal mask airway (LMA). The LMA allows observation of subglottic stenosis which can not be seen under tracheal intubation. The smaller prototype of the fiberoptic bronchoscope whose diameter is 1.8mm has no provision for angulation at the tip. However, using the LMA as a guide it was easy to reach the subglottic stenosis even using this smaller bronchoscope.
A monoclonal antibody (10B) against the N-terminal sequence of human osteocalcin was selected to characterize its epitope and species specificity. The cross-reactivity of 10B with human and rat osteocalcin demonstrated that the reactivities of 10B with both human and rat osteocalcins were very similar. The pin technology method was used to determine the epitope and clearly demonstrated that the epitope recognized by 10B was localized to residues 12-16, the sequence of which is identical in rat and human osteocalcin molecules. This monoclonal antibody was found to be useful for designing region-specific sandwich immunoassay systems for human and rat N-terminal osteocalcin (N-OC) molecules using rabbit anti-hN20 and anti-rN20 polyclonal antibodies, respectively. The osteocalcin levels in serum determined by this N-OC method were stable during prolonged storage at 25 degrees C and the method could be usefully applied in the development of immunoassay systems for many osteocalcin molecules from many other species.
The HepG2-specific P450 2C factor motif (HPF1-motif) is conserved in many hepatic cytochrome P450 genes (CYP). Its functional importance for rabbit CYP2C genes has led to the proposal that the HPF1 motif acts as a common regulator for the liver-specific expression of CYP2 genes with hepatic nuclear factor (HNF)-4 being the corresponding trans-activator. The HPF1-like elements in the rat CYP2C genes 2C7, 2C11, 2C12, and 2C13 have been studied with regard to functional importance and binding of the orphan receptors HNF-4, apoAI regulatory protein-1 (ARP-1), and v-erbA-related receptors (EAR) 3 and 2. Binding activity in rat liver nuclear extracts includes these orphan receptors as judged from electromobility supershift experiments and from results obtained with expressed receptors, although the element in CYP2C11 did not bind HNF-4. Mutations of the HPF1-like elements in the CYP2C7, CYP2C11, and CYP2C12 promoters had marginal effects on the expression of luciferase reporter gene constructs transiently transfected into HepG2 cells, whereas for CYP2C13 the activity was reduced to 60% of the wild type construct. Coexpression of HNF-4 in COS-7 cells had limited effect on the luciferase activity generated from the 2C promoters, maximally 3-fold. Our data indicate that the HPF1 elements in the rat CYP2C genes have limited functional importance and that HNF-4 is not a major trans-activator for any of these genes.
Unstimulated human fibroblasts show low or undetectable ICAM-1 expression. Interferon-beta (IFN-beta) at concentrations of 10, 100, and 1000 IU/ml in the presence of tumor necrosis factor-alpha (TNF-alpha) significantly increased the ICAM-1 expression of fibroblasts in a dose-dependent manner. Treatment with IFN-beta alone, however, did not up-regulate the ICAM-1 expression. Furthermore the attachment of peripheral blood mononuclear cells (PBMCs) to cytokine-treated fibroblasts was increased. This augmented attachment was partly inhibited by anti-ICAM-1 antibody. These results suggest that IFN-beta and TNF-alpha may cooperatively modulate the attachment of PBMCs in the dermis.
Although there is no concept of insulin resistance in traditional Kampo (Chinese) medicine and Indian medicine, we had the hypothesis that some drug in a mixture of crude drugs which was believed to ameliorate diabetes mellitus may have had the effect of improving insulin resistance. To test this hypothesis, the effects of Seishin-renshi-in (Chinese medicine) and Gymnema sylvestre (Indian medicine) on the insulin resistance of streptozotocin-induced diabetic rats was studied by the glucose clamp technique. Oral administration of Seishin-renshi-in (800 mg/kg/day) with injections of a minimum dose of Ultralente insulin decreased urine volume and urinary glucose excretion during a 7-day treatment period and improved the insulin stimulated glucose uptake in peripheral tissues, as well as improving the insulin suppressed hepatic glucose output during glucose clamp. However, G. sylvestre (120 mg/kg/day) treatment did not improve insulin resistance. We conclude that Seishin-renshi-in, with a small dose of insulin, improved insulin resistance in streptozotocin-induced diabetic rats, but Gymnema sylvestre did not.
The Ah receptor (Ahr) is a ligand-dependent transcription factor that positively regulates inducible expression of the CYP1A1 gene. Based on the sequence information of the human Ahr and the intron-exon junctions of the mouse counterpart, an analysis of single-strand conformational polymorphism (SSCP) was carried out to detect subtle base differences in the coding region of the gene among individuals. We found that the Ahr protein has at least two forms of variants in a Japanese gene pool, and that these variants can be ascribed to one amino acid replacement of Arg by Lys at codon 554. The frequencies of Arg-coded and Lys-coded alleles were 0.57 and 0.43, respectively. We found, however, that this germ line polymorphism of the Ahr gene did not show a significant association with aryl hydrocarbon hydroxylase (AHH) inducibility nor with lung cancer incidence.