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Biomedical subjects

M Kumagai

Publications and source records attributed to M Kumagai.

At least 55 records · Page 3Linked to original sources
PubMed2000

[Evidence based chemotherapy for pediatric cancers].

The curability of pediatric cancer has been improved to nearly seventy percent. This change has been achieved by refinements in treatment strategy and supportive care. More than seventy percent of patients with ALL can be cured by modern chemo-radiotherapy with reduced late effects. The stratification of the patients by risk factor, introduction of CNS prophylaxis, shortening of the duration of chemotherapy and intensification of the chemotherapy with agents such as HD-MTX have contributed to this remarkable success. Burkitt's lymphoma is a tumor for which the curability has improved from almost zero to ninety percent. With Wilms' tumor, clinical trials have been used to optimally refine the treatment strategy. The NWTS first compared the efficacy of combined VCR and Act-D with the single use of each drug. The difference was significant. The results of the systematic trials were then used to improve the survival rate of patients with Wilms' tumor from twenty to ninety percent and shorten the duration of chemotherapy to six months. On the other hand, tumors remain with which less than half of patients can survive for long. Advanced neuroblastoma and AML are typical such tumors. With these diseases, refinements in the treatment based on evidence derived from clinical trials have been insufficient. Further intensification of the treatment or novel approaches to control tumor growth are warranted for these diseases. In this article, I would like to describe the "standard" therapy for each tumor and the evidence on which improvements in those strategies have been based.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

[Intraocular lens calculation for cataract treated with photorefractive keratectomy using ray tracing method].

PURPOSE: Conventional methods (such as the SRK-II formula) do not accurately calculate the power of the intraocular lens (IOL) after refractive surgery. Therefore, we compared a new formula including a ray tracing method to the conventional method for foldable IOL lens implantation. METHOD: Foldable IOLs (MA 60 BM) were implanted in 26 patients (32 eyes) using the phakoemulsification technique. The power of the IOL was measured preoperatively using the SRK-II formula in all cases. From the results of postoperative refractive errors of these cases, the power of IOL calculated by the ray tracing method was compared to the SRK-II formula. Cataract patients first treated with photorefractive keratectomy (PRK) received IOL implants using our ray tracing method and their postoperative refraction was measured. RESULTS: The average postoperative refractive error was 1.32 D in SRK-II formula, 0.95 D in the ray tracing method with Ray 1 used and 0.89 D with Ray 2 used. Postoperative refraction of both eyes first treated with PRK was--1.00 D. CONCLUSION: The average postoperative refractive error was reduced in the ray tracing method using Olsen's predicted ACD (Ray 2) compared to SRK-II formula. This new tracing method appears to be useful for determination of IOL power and it may be applied for IOL calculation for cataract surgery after refractive surgery.

Cataract↗
PubMed2000

[Reconstruction of chest wall using myocutaneous flap].

Reconstruction of chest wall using myocutaneous flap has been performed in 2 cases. A 72-year-old female referred to our hospital for locally recurrent left breast cancer without any distant metastases. The other patient was a 77-year-old female, having locally recurrent liposarcoma of the left lateral chest wall. Chest wall was resected with wide margin of normal tissue, and myocutaneous flaps of latissimus dorsi were used for reconstruction of skin defect (13 x 8 cm and 14 x 10 cm) in both cases. Although additional split-thickness skin graft was required for one of them, myocutaneous flaps were useful for the reconstruction of widely defected chest wall. By using this technique, wider margin can be obtained, which could decrease the risk for local recurrence of malignant tumor.

Aged↗
PubMed1999

Functional interaction between Oct-1 and retinoid X receptor.

The retinoid X receptor (RXR) is a member of the nuclear hormone receptor superfamily and heterodimerizes with a variety of other family members such as the thyroid hormone receptor (TR),1 retinoic acid receptor, vitamin D receptor, and peroxisome proliferator-activated receptor. Therefore, RXR is supposed to play a key role in a ligand-dependent regulation of gene transcription by nuclear receptors. In this study, we have identified the octamer-binding transcription factor-1 (Oct-1) as a novel interaction factor of RXR. In vitro pull-down assays using RXR deletion mutants showed that the interaction surfaces were located in the region encompassing the DNA binding domain (C domain) and the hinge domain (D domain) of RXR. We also showed that RXR interacted with the POU homeodomain but not with the POU-specific domain of Oct-1. Gel shift analysis revealed that Oct-1 reduced the binding of TR/RXR heterodimers to the thyroid hormone response element (TRE). In transient transfection assays using COS1 cells, Oct-1 repressed the T3-dependent transcriptional activity of TR/RXR heterodimers, consistent with in vitro DNA binding data; however, transcriptional activation by Gal4-TR(LBD) (LBD, ligand binding domain), which lacks its own DNA binding domain but retains responsiveness to T3, was not influenced by Oct-1. These results suggest that Oct-1 functionally interacts with RXR and negatively regulates the nuclear receptor signaling pathway by altering the DNA binding ability of the receptors.

Animals↗
PubMed1999

1,25-Dihydroxyvitamin D3 suppresses the expression of the VCAM-1 receptor, VLA-4 in human leukemic HL-60 cells.

Very late antigen-4 (VLA-4) is the complex with alpha4 and beta1 integrins, which is the receptors to fibronectin and VCAM-1. We evaluate the effect of 1,25(OH)2D3 on the expression of VLA-4 in human leukemic HL-60, U937 cells and human melanoma A375 cells. Flow cytometric analysis demonstrate that the expression of alpha4 integrin is negatively regulated in the cell lines we studied. The expression of beta1 integrin is also decreased in HL-60 and U937 cells. The mRNA expression of alpha4 integrin is significantly decreased by the treatment with 1,25(OH)2D3, whereas 1,25(OH)2D3 does not alter the expression of beta1 mRNA. The adhesion assay demonstrate that the number of adherent cells treated with 1, 25(OH)2D3 is significantly lower than that untreated on VCAM-1-coated wells. Because VCAM-1 is highly expressed in the endothelial cells, it is possible that 1,25(OH)2D3 prevents the attachment of the cells from the endothelial cells in vivo.

Antigens, CD↗
PubMed1999

Hyperdiploid acute lymphoblastic leukemia with 51 to 65 chromosomes: a distinct biological entity with a marked propensity to undergo apoptosis.

To determine the cellular basis for the excellent clinical outcome of hyperdiploid acute lymphoblastic leukemia (ALL), defined by a modal chromosome number of 51 to 65, we assessed the growth potential of leukemic cells from 129 children with newly diagnosed ALL. Flow cytometric analysis was used to compare leukemic cell recoveries at the beginning and at the end of 7-day cultures on allogeneic bone marrow-derived stromal layers. The median percentage of cell recovery after culture was 91% (range, <1% to 550%). Among the 25 hyperdiploid cases, only two had cell recoveries above the median value, compared with 63 of 104 cases with different ploidies (P <.001); 21 had recoveries within the first quartile, in contrast to only 12 of the 104 other cases. Cell recoveries in the 16 cases with duplications of chromosomes 4 and 10, a feature previously associated with a superior outcome, were all within the first quartile. Flow cytometric studies indicated that rapid induction of apoptosis was the underlying cause of low cell recoveries in cases with hyperdiploidy. The demise of hyperdiploid cells on stroma was not due to failure to adhere with stromal elements (as shown by electron microscopy) or to deficiencies of interleukin-1 (IL-1), IL-2, IL-3, IL-4, IL-6, IL-7, IL-11, stem-cell factor, interferon- (IFN-), tumor necrosis factor- (TNF-), or to combinations of these cytokines. Inactivation of IL-4, IFN- and TNF-, which if secreted by stromal layers could be toxic to ALL cells, failed to improve the survival of hyperdiploid blasts. We conclude that leukemic cells bearing 51 to 65 chromosomes have a marked propensity to undergo apoptosis. The stringent survival requirements of these cells, together with their potentially higher sensitivity to antileukemic drugs, may well account for the high cure rates achieved in patients with this form of ALL.

Adolescent↗
PubMed1999

Sevoflurane exposure time and the neuromuscular blocking effect of vecuronium.

PURPOSE: To determine the effect of sevoflurane exposure time on the duration of vecuronium neuromuscular blockade. METHODS: In 40 adult patients anesthesia was induced with 1.5-2 mg x kg(-1) propofol and 3-5 microg x kg(-1) fentanyl and the trachea was intubated without the aid of muscle relaxant. Patients were randomized into four groups of 10. In group 1, 0.05 mg x kg(-1) vecuronium was administered with N2O and anesthesia was maintained by propofol infusion and fentanyl. Vecuronium was administered with sevoflurane 2% in 30 patients, commencing at the same time (group 2) and at 30, and 60 min after sevoflurane (groups 3, 4). Adductor pollicis force of contraction to train-of-four ulnar nerve stimulation was recorded. Times from vecuronium injection to 95%, maximal block, and recovery times to 25% recovery were recorded. RESULTS: There were no differences in times to 95% and maximal block in the four groups. Recovery times were longer in groups 3 and 4 than in groups 2 and 1 (P < 0.01). Times to 5% recovery were 15.0 +/- 3.7, 17.8 +/- 4.8, 28.2 +/- 9.9, and 29.5 +/- 9.5, and to 25% recovery were 22.3 +/- 5.2, 27.2 +/- 6.4, 42.3 +/- 16.3, and 50.5 +/- 16.4 in groups 1, 2, 3, and 4 respectively. No differences were found between group 1 and group 2 nor between group 3 and group 4. CONCLUSION: Sevoflurane produced time-dependent potentiation of vecuronium. After 30 min exposure, 25% recovery was prolonged by 89% and after 60 min by more than 100% compared with the control group.

Adult↗
PubMed1999

DNA polymerase activity in encysting Entamoeba invadens.

Using an axenic encystation system of Entamoeba invadens as a model for E. histolytica encystation, we examined the level of DNA polymerase activity in E. invadens during encystation induced in vitro. We first characterized the DNA polymerase activity of trophozoites of E. invadens, comparing it with that of E. histolytica, and found that the activity of E. invadens was lower than that of E. histolytica at pH 2, 4, and 6 and was higher at pH 8 and 10. The activity of E. invadens was completely inhibited by high concentrations of K(-). Among inhibitors of mammalian DNA polymerases, aphidicolin and N-ethylmaleimide inhibited the activity, but 2',3'-dideoxythymidine-5'-triphosphate did not. Thus, the sensitivity of the E. invadens activity to salt and inhibitors of mammalian DNA polymerases was basically the same as that recorded for E. histolytica in our previous results. The level of DNA polymerase activity in cysts decreased as encystation proceeded as compared with that of trophozoites. The results indicate that encystation is accompanied by a reduced level of DNA polymerase activity, which correlates with the previous finding that nuclear division occurs during cyst maturation in the absence of DNA synthesis.

Animals↗
PubMed1999

Laparoscopic cholecystectomy in gallstone patients with acute cholecystitis.

It remains controversial whether patients with gallstones with acute cholecystitis should be operated on early, or whether surgery should be delayed until the acute phase subsides. To help resolve this question, we retrospectively studied 109 patients with acute cholecystitis, 56 of whom underwent laparoscopic cholecystectomy after acute cholecystitis had subsided (delayed group) and 53 of whom underwent early laparoscopic cholecystectomy--within 7 days after admission (early group). On admission, the inflammatory findings in the two groups were very similar; however, at operation, the inflammatory findings were alleviated in the delayed group, while they remained unchanged in the early group. The mean operative time for the two groups was very similar. As for intraoperative complications, there was no conversion to laparotomy in either group, and there were no major complications in either group. The total hospital stay was 37.7 +/- 14.4 days for the delayed group and 12.7 +/- 2.0 days for the early group, showing a highly significant difference (P < 0.001). Early laparoscopic cholecystectomy seems to be better than delayed treatment for patients with gallstones with acute cholecystitis.

Acute Disease↗
PubMed1999

Preliminary evaluation of human immunodeficiency virus type 1 (HIV-1) immunogen in children with HIV-1 infection.

The safety and preliminary activity of human immunodeficiency virus type 1 (HIV-1) immunogen were evaluated in 10 HIV-1-infected children with disease stage N1,2 or A1,2. Multiple inoculations of 2. 5 or 10 units (U) of HIV-1 immunogen were safe and well tolerated without an acceleration of disease progression. When antiretroviral agents were coadministered, the 10 U dose appeared to be associated with more sustained reduction in plasma HIV-1 RNA than the 2.5 U dose (median log10 HIV-1 RNA at month 18, 3.07 vs. 4.01 copies/mL in 10 U [n=4] vs. 2.5 U [n=3], respectively; P=.034). Levels of regulated-on-activation, normal T cell-expressed and -secreted chemokine produced from HIV-1 immunogen-stimulated lymphocytes in vitro were increased in the children who had HIV-1 immunogen-specific antibody responses (P<.02) and appeared to be inversely correlated with levels of plasma HIV-1 RNA (P<.01). These preliminary data warrant larger studies to determine the effectiveness of adjunctive therapy with HIV-1 immunogen in children with HIV-1 infection.

AIDS Vaccines↗
PubMed1999

Characterization of two novel retinoic acid-resistant cell lines derived from HL-60 cells following long-term culture with all-trans-retinoic acid.

Either all-trans-retinoic acid (RA) or vitamin D3 (VD) induces differentiation of the myeloid leukemia cell line HL-60. RA is available for the treatment of acute promyeloleukemia, although the development of resistance to the agent is a serious problem for differentiation-inducing therapy. To approach the mechanisms of resistance to RA, we developed two novel cell lines, HL-60-R2 and R9, which were subcloned after exposure to increasing concentrations of RA. The growth rate of HL-60-R2 cells was significantly increased by RA treatment, whereas the growth rate of HL-60-R9 was not affected. RA induces apoptosis in the parental HL-60 cells. The number of apoptotic cells, however, was not increased and nitroblue tetrazolium (NBT) reduction was not altered by 1 microM RA in either of the cloned cell lines. Treatment with VD induced monocytic differentiation and increased the expression of CD11b in HL-60 and HL-60-R9 cells, but not in HL-60-R2 cells. Flow cytometric and G-banding analysis demonstrated that R2 cells were near-triploid. The sequencing analysis revealed a deletion of three nucleotides in the sequence of the RAR alpha gene in HL-60-R9 cells, resulting in deletion of codon 286. No mutation was found in HL-60-R2 cells. Taken together, these data indicate that the resistance to RA is caused by the mutation in RAR alpha of HL-60-R9, but by other factor(s), which also affect the VD-response pathways, in HL-60-R2. The abnormal response to VD may be associated with the abnormal ploidy of the R2 cells.

Antineoplastic Agents↗
PubMed1999

A pharmacologic study on CO2 responsiveness of intracranial pressure in rats with chronic hypercapnia.

STUDY OBJECTIVES: To investigate intracranial pressure (ICP) changes and their mechanisms in chronic hypercapnia. DESIGN: After 12 male Wistar rats were maintained in CO2-mixed air (mean PaCO2, 71.0 mm Hg) for 21 weeks, their ICP levels were measured during the breathing of 0, 5, 10, 12, and 14% CO2-mixed air before and after the i.v. administration of nitro-L-arginine methyl ester (L-NAME). The ICP responses to i.v. norepinephrine and i.v. adenosine were also tested. Ten rats that were maintained in room air served as the control group. RESULTS: The mean ICP in the study group (5.9 mm Hg) was not significantly different from the mean ICP in the control group. In the study group, the ICP response to changes in PaCO2 was significantly blunted when compared to the response seen in the control group. In both groups, i.v. norepinephrine significantly increased the ICP. In the control group but not in the study group, i.v. L-NAME suppressed the ICP response to changes in PaCO2. In both groups, i.v. adenosine significantly increased the ICP. CONCLUSIONS: The ICP response to PaCO2 was blunted in rats with chronic hypercapnia, and the mechanism of this reduced response may involve nitric oxide.

Adenosine↗
PubMed1999

Distributions of adipocyte, blood vessel, and muscle fiber in human lateral petrygoid muscle during ageing.

The composition of adipocyte, blood vessel, and muscle fiber during ageing from 30 to 90 years of age was examined by a computer analyzing system in human lateral petrygoid muscle. The human lateral petrygoid muscle, the intramuscular connective tissue with adipocyte and blood vessel, displayed a specific change in morphology during ageing. Numerous adipocyte appeared around the blood vessel in the perimysium of the human petrygoid muscle from 60 years of age. The percentage and size of adipocyte and vein per 10,000 micron 2 of the cross sectional area in the muscle increased as well. However, the cross sectional area of muscle fiber was almost constant. The increase of adipocyte was related with changes of blood vessel and connective tissue in the perimysium.

Adipocytes↗
PubMed1999

Polymorphism of the endoglin gene in patients with intracranial saccular aneurysms.

OBJECT: Endoglin, a transforming growth factor beta-binding protein, is a glycoprotein expressed on the surface of human vascular endothelial cells. Mutations of this gene are responsible for hereditary hemorrhagic telangiectasis and are associated with sporadic intracerebral hemorrhage as a risk factor. The purpose of this study was to examine the polymorphism of this gene in patients with intracranial aneurysms. METHODS: The authors identified the mutations and insertion polymorphism around exon 7 of the endoglin gene in 82 patients with intracranial saccular aneurysms (aneurysm group) and 114 control volunteers (control group). A 6-base insertion (GGGGGA) was found in intron 7 at 26 bases beyond the 3' end of exon 7. The homozygous insertion of intron 7 of the gene was present in 20.7% of the aneurysm group compared with 6.1% of the control group (chi2 = 9.837, p = 0.0073). The insertion allele frequency was significantly higher in the aneurysm group (67 [40.8%] of 164) than that in the control group (63 [27.6%] of 228) (chi2 = 7.48, p = 0.0062). The most notable clinical characteristic of the 17 patients with homozygous insertion in the aneurysm group was the relatively high percentage of patients with hypertension and of those with multiple aneurysms. CONCLUSIONS: The data provide evidence of an association between aneurysm development and a polymorphism at a genetic variant of endoglin in patients with these lesions.

Adult↗
PubMed1999

[Anesthetic management of a patient with Eaton-Lambert syndrome with chronic respiratory failure].

A 66-year-old male with colon cancer was scheduled for left hemicolectomy. He had a past history of respiratory failure due to chronic obstructive pulmonary disease (COPD). Anesthesia method chosen was general anesthesia with sevo-flurane combined with epidural anesthesia. Respiration was managed with assisted ventilation using laryngeal mask airway and muscle relaxation was obtained with suxamethonium chloride given intermittently. After the operation, he did not seem to have COPD because of the relation between arterial PCO2 and bicarbonate in the perioperative period. Therefore, after obtaining informed consent from this patient, we determined the relation between arterial and spinal fluid acid-base balance under acetazolamide administration. He was more sensitive to central respiratory response because his respiration increased following the decrease of spinal fluid bicarbonate. We further examined and diagnosed him as Eaton-Lambert syndrome by evoked electromyography and by Ca2+ channel antibody.

Aged↗
PubMed1998

Fosfomycin (FOM: 1 R-2S-epoxypropylphosphonic acid) suppress the production of IL-8 from monocytes via the suppression of neutrophil function.

We investigated the influence of fosfomycin (FOM) on the production and the mRNA expression of interleukin-8 (IL-8) by monocytes. In the incubation of whole blood stimulated by N-Formyl-Met-Leu-Phe (FMLP), FOM significantly suppressed the production and the mRNA expression of IL-8 by monocytes and its inhibitory action was concentration-dependent (FOM: 50-200 microg/ml). However, FOM did not influence the production and the mRNA expression of IL-8 in the incubation of fractionated mononuclear cell stimulated by FMLP. The supernatant of FMLP-stimulated polymorphonuclear leukocyte (PMNL) could induce the mRNA expression of IL-8 by monocyte. The supernatant of FMLP-stimulated PMNL which was pre-treated with FOM significantly (P < 0.05) inhibited the expression of IL-8 mRNA by monocyte. Moreover, FOM suppressed the production of leukotriene B4 (LTB4) from neutrophil in a concentration-dependent manner. When LTB4 was added to the fractionated mononuclear cells directory, the expression of IL-8 mRNA was enhanced (P < 0.05). The present study indicated that FOM suppress the production of LTB4 from neutrophils and suppress the expression of IL-8 mRNA by LTB4 from monocytes. It was also demonstrated that LTB4 produced by neutrophil is one of the factor which promotes the expression of IL-8 mRNA in monocytes.

Anti-Bacterial Agents↗