Inhibition by kappa-casein glycomacropeptide and lactoferrin of influenza virus hemagglutination.
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Animals↗
Biomedical subjects
M Tanimoto
Publications and source records attributed to M Tanimoto.
Detection of minimal residual disease in Philadelphia chromosome positive acute lymphoblastic leukemia: rationale for bone marrow transplantation from the polymerase chain reaction point of view.
Bone marrow transplantation (BMT) is performed as curative therapy for acute lymphoblastic leukemia (ALL). In most patients, BMT is performed at the time of remission which implies that the number of leukemic cells is less than 5% of all hematopoietic cells, namely, 0 to 10(10) leukemia cells in the body. Thus, some patients may well undergo BMT despite the fact that no leukemic cells are left in the body. In this respect, more accurate diagnosis of complete remission status would be to the patients' benefit. To detect minimal residual disease (MRD) not found by light-microscopy, further strategies are required after achieving hematological remission. Cytogenetic methods, Southern blot analysis and conventional immunological techniques can all provide accurate diagnosis, however, the sensitivity of these techniques for the detection of MRD is just as low as that of the light microscopy. Recently, polymerase chain reaction (PCR) has become available for the detection of low levels of chimeric bcr-abl transcripts in Philadelphia chromosome positive (Ph1) ALL patients. With this assay, investigators have reported MRD in patients after chemotherapy or BMT. Most patients who achieve hematological remission after conventional chemotherapy still have bcr-abl transcript detectable by PCR, confirming the general concept that this particular leukemia needs BMT in order to cure the disease. Some patients who had MRD prior to BMT continued disease free survival > 1 year after BMT with a negative PCR result and in these patients, MRD seems to have been eradicated by the BMT procedure.(ABSTRACT TRUNCATED AT 250 WORDS)
Bone Marrow Transplantation↗
Transduction of a drug-sensitive toxic gene into human leukemia cell lines with a novel retroviral vector.
To investigate the possibility of killing tumor cells by the expression of an exogenously introduced toxic gene, we have constructed a novel retroviral vector (LTRNL) which has the polyA signal deleted herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene. The vector becomes toxic by treating cells expressing HSV1-tk with the antiherpetic drugs acyclovir or ganciclovir (GCV). Cells of the human leukemia lines (K562, MEG-01) were infected with this vector and two transduced cell lines (K562/LTRNL, MEG-01/LTRNL) were established. Southern blot analysis confirmed the integration of the HSV1-tk transgene in these cells and Northern blot analysis exhibited the expression of 4.8-kb viral mRNA containing the HSV1-tk gene. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay for the in vitro cytotoxic effects of GCV to these cells demonstrated that concentrations of about 2.5 microM for K562/LTRNL and 1.25 microM for MEG-01/LTRNL cells resulted in 50% inhibition of cell growth after 72 hr. Subcutaneous tumors of MEG-01/LTRNL in KSN nude mice, but not those of uninfected MEG-01 cells, showed durable regressions after exposure of the mice to 40 mg/kg of GCV given subcutaneously once a day for 15 days. This study indicates that the LTRNL-infected human leukemia cells exhibit inducible susceptibility to GCV.
Acyclovir↗
Autologous BMT in high risk patients with CALLA-positive ALL: possible efficacy of ex vivo marrow leukemia cell purging with monoclonal antibodies and complement.
Autologous BMT (auto-BMT) has been conducted for 17 high-risk common ALL antigen (CALLA)-positive non-T cell type ALL patients. Ex vivo purging of leukemia cells from infused BM cells was performed using complement and three kinds of mouse monoclonal antibodies reactive to CALLA-positive leukemia cells: NL-1 (IgG2a), NL-22 (IgM), and HL-47 (IgM). Minimal residual leukemia cells in BM were examined by PCR method in Philadelphia chromosome (Ph1)-positive ALL cases. BCR/ABL chimeric transcript, which was positive in BM samples before purging, was shown to be absent after ex vivo purging in all three cases tested. Among four Ph1-positive cases transplanted in first CR, three cases survived in CR remission 77, 29 and 26 months after BMT, and one case died without relapse 4 months after BMT. The other four Ph1-negative cases transplanted in the first CR also remained in CR except one who relapsed. The results of minimal residual leukemia cell studies and clinical data indicate the effectiveness of our ex vivo leukemia cell purging method and auto-BMT in the early stage of CR for patients with high risk ALL.
Adolescent↗
[Evaluation of pulmonary venous flow patterns in left heart failure: a study using transesophageal Doppler echocardiography].
Pulmonary venous flow (PVF) patterns in left heart failure were evaluated using transesophageal pulsed Doppler echocardiography in 30 patients with dilated hearts (DH) and 30 normal subjects. Eighteen patients had myocardial infarction and 12 patients had dilated cardiomyopathy. The diagnostic criteria by using M-mode echocardiography were left ventricular end-diastolic dimensions (LVDd) of 5.5 cm or more and % LV fractional shortening (%FS) of less than 30%. Peak velocities of the first systolic (PVS1) and second systolic (PVS2) forward waves of PVF, %FS and total amplitude of mitral annular motion in the patient group were significantly decreased compared with the normal group. However, there were no differences in these parameters between the 22 patients (DH-1 group) with a mean pulmonary capillary wedge pressure (PCWP) of less than 18 mmHg and 8 patients (DH-2 group) with a PCWP of 18 mmHg or greater. Peak velocities of the diastolic forward wave of PVF and the early diastolic wave (D) of the LV inflow velocity in the DH-1 group were significantly decreased, and the peak velocity of the atrial contraction wave (A) of the LV inflow velocity was increased compared with those of the normal group. D of the LV inflow velocity, peak velocity of the diastolic forward wave, and peak velocity of the atrial systolic backward wave of the PVF in the DH-2 group were significantly increased compared with those of the DH-1 group. Significant positive correlations were observed between peak velocity of the diastolic forward wave and D or PCWP in the patient group, but the latter relationship was not linear. The A/D ratio of the LV inflow velocity was significantly decreased, and the ratio of the amplitudes of atrial contraction wave to total vertical deflection on the apexcardiogram of the DH-2 group were significantly increased compared with those of the DH-1 group. A patient with extensive myocardial infarction associated with development of severe LV dysfunction (PCWP = 23 mmHg) and a "pseudonormalization" pattern of LV inflow velocity demonstrated markedly increased peak velocities of the diastolic and atrial systolic forward wave, and decreased PVS2. However, the peak velocities of the diastolic and atrial systolic forward wave were decreased, and that of PVS2 was increased with fair improvement of LV dysfunction (PCWP = 10 mmHg) and with compensatory augmentation of the atrial contraction wave A of LV inflow velocity.(ABSTRACT TRUNCATED AT 400 WORDS)
Cardiomyopathy, Dilated↗
Unexpected heterogeneity of PML/RAR alpha fused mRNA detected by nested polymerase chain reaction in acute promyelocytic leukemia.
We have analyzed ten APL patients using reverse transcription polymerase chain reaction (RT-PCR) technique to detect PML/RAR alpha fused mRNA. All patients in this study had PML/RAR alpha fused mRNA (three cases of the short type and seven cases of the long type), although the chromosomal translocation t(15;17) was not detected in one patient. After ethidium bromide staining, two-thirds of the short type and all cases of the long type were found to have multiple PCR products (192 and 93 base pair (bp) bands in the short type and 666, 522, 263, and 164 bp in the long type). A total of six distinct fused mRNAs were sequenced (P1R1, P1R2, P3R1, P2R1, and P2R2). Southern hybridization analysis showed only one rearranged band in each of the patients. These results suggest that the longest mRNAs in each type are the authentic fused mRNAs and the other smaller mRNAs are generated through splicing events. In RAR alpha, a novel fusion point (R2) was identified within the fourth exon. This uncommon splicing may be caused by the instability of the splicing mechanism of the rearranged PML/RAR alpha gene. Among the ten APL patients, no correlation was observed between the type of fused mRNA and the clinical characteristics examined.
Adult↗
Macrophage colony-stimulating factor stimulates growth progression of the G1-phase fraction and induces monocytic differentiation of the G2/M-phase fraction in human myeloid leukemia cells.
The human myeloid leukemia cell line (NKM-1) proliferates in response to exogenous macrophage colony-stimulating factor (M-CSF) in serum-free medium. This CSF alone, however, does not induce any feature of cell differentiation in NKM-1 cells. We showed that terminal monocytic differentiation is partially observed only when NKM-1 cells are sequentially treated with 1,25-dihydroxyvitamin D3 and M-CSF, as evaluated by cell morphology, analysis of surface antigens, and phagocytic function. To determine whether there might be an association between the actions of M-CSF and special phases of the cell cycle, we separated D3-treated cells into cycle-specific fractions by centrifugal elutriation. G1-enriched cells were mostly stimulated for growth progression with M-CSF. On the other hand, G2/M-enriched cells were significantly induced into monocytic differentiation. The cell percentage in the G2/M phase has clearly correlated with that of terminally differentiated cells by M-CSF. These results suggest that two distinct actions of M-CSF to stimulate cell proliferation and differentiation could work on different phases of the cell cycle: cell growth in the G1 phase and cell differentiation in the G2/M phase.
Calcitriol↗
[One family having 5 members with hypertrophic cardiomyopathy with similar pattern of left ventricular inflow and distribution of hypertrophy].
We examined, in one family, 5 cases of hypertrophic cardiomyopathy (HCM) with a similar pattern of left ventricular inflow (LVIF) and distribution of hypertrophy. Its clinical background and significance were discussed. Because a variety of morphologic expressions of HCM may be observed in the same family, distribution of left ventricular hypertrophy (LVH) varies in even first-degree relatives of the family. In all five cases in this study, however, LVH was localized between the anterior wall and the interventricular septum. On the other hand, typical pattern of LVIF in HCM is "decreased peak velocity and prolonged deceleration time of the early diastolic wave (E), and compensatory augmentation of the atrial contraction wave (A)". All of the five cases in this study had a pattern of three characteristic peaks of LVIF, which showed the mid-diastolic wave between the E and A waves. The above findings suggested that the myocardial characteristics of the five cases in this family were very similar, and could be important clues clarifying the mode of inheritance of HCM.
Adult↗
Three distinct candidate point mutations of the von Willebrand factor gene in four patients with type IIA von Willebrand disease.
Type IIA von Willebrand disease (vWD) is the most common type II vWD and is characterized by the selective loss of large and intermediate sized multimers. One explanation for this disorder has been postulated to be a qualitative defect in von Willebrand factor (vWF) which results in increased susceptibility to proteolysis at the bond between residues Tyr842 and Met843. Four missense mutations that may cause type IIA vWD have recently been identified near the cleavage site. We analyzed the molecular basis for type IIA vWD in six patients. A 512 bp DNA sequence spanning the proteolytic cleavage site was targeted for PCR amplification and sequencing. We exploited a difference in restriction sites between the vWF gene and the pseudogene and have designed allele-specific oligomer used with PCR to distinguish these two genes. Three candidate missense mutations; Ser743 (TCG)----Leu (TTG), Leu799 (CTG)----Pro (CCG), and Arg834 (CGG)----Trp (TGG) were identified in 4 out of 6 patients. The amino acid substitution at Arg834 has been reported previously, but the other substitutions at Ser743 and Leu799 are novel candidate mutations locating 99 and 43 amino acids to the N-terminal side of the cleavage site, respectively. Our results indicate that amino acid substitutions located relatively distant from the cleavage site may also be involved in type IIA vWD.
Base Sequence↗
Detection of Philadelphia chromosome-positive acute lymphoblastic leukemia by polymerase chain reaction: possible eradication of minimal residual disease by marrow transplantation.
Minimal residual disease (MRD) in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph1 ALL) who received allogeneic (n = 9) or autologous (n = 6) bone marrow transplantation (BMT) was evaluated by the polymerase chain reaction (PCR) for the bcr-abl transcript. Twelve patients received BMT at the time of hematologic and cytogenetic remission. However, MRD was detected in 8 of 10 patients evaluated. Seven patients, including three who had MRD before BMT, continue to have a disease-free survival 5 to 64 months after BMT. Twenty-one specimens obtained from these patients at various times after BMT did not show MRD. In three patients, MRD detected just before BMT seems to be eradicated by BMT protocol. The other eight patients developed cytogenetic or hematologic relapses 2 to 8 months after BMT. Seven of 14 samples from these patients demonstrated MRD, which preceded clinical relapse by 3 to 9 weeks. Thus, this technique for the detection of MRD appears to be useful for the more precise assessment of various antileukemia therapies and for early detection of leukemia recurrence.
Adolescent↗
Immunolocalization of Ku-proteins (p80/p70): localization of p70 to nucleoli and periphery of both interphase nuclei and metaphase chromosomes.
Distribution on both nuclei and metaphase chromosomes of Ku-proteins, recognized by autoantibodies from a patient with systemic lupus erythematosus, has been studied using a specific monoclonal antibody (mAbH6) that recognizes p70, one Ku-protein. Observation with either a conventional fluorescent microscope or a confocal laser scanning microscope revealed mAbH6-stained p70 antigen localized on both nuclear periphery and nucleoli of human interphase cells. The specific staining of nucleoli with mAbH6 has been confirmed using isolated nucleoli from rat liver in which the staining was seen as fine granules surrounding nucleolar DNA. During mitosis p70 antigen moved away from association with the nuclear envelope region to localization on the periphery of condensed chromosomes with no apparent staining of chromosome interior. The p70 antigen was copurified with DNA fragments by immunoaffinity column chromatography using mAbH6. The mAbH6 staining of both nuclear periphery and nucleoli was lost upon digestion with DNase I at low concentrations. These results suggest that p70 antigen is connected with these nuclear structures through DNA.
Amino Acid Sequence↗
Impaired secretion of the elongated mutant of protein C (protein C-Nagoya). Molecular and cellular basis for hereditary protein C deficiency.
Genetic analysis of a heterozygous protein C-deficient patient revealed a novel deletion of a single guanine residue (8857G) among four consecutive guanine nucleotides [380Trp(TGG)-381Gly(GGT)] in exon IX, which encodes the carboxyl-terminal region of protein C. This deletion results in a frameshift mutation and substitution of the last 39 amino acids (381Gly-419Pro) with 81 abnormal amino acid residues, and we have designated this elongated variant as Protein C-Nagoya. A mutagenic primer was designed which replaced the third guanine residue upstream from the deletion with cytosine, thereby creating a new AvaI site in an otherwise normal allele. Analysis of the polymerase chain reaction products derived from this mutagenic primer showed that the abnormal allele has been inherited in this family. To elucidate how this molecular abnormality leads to protein C deficiency, an expression plasmid containing this mutation was transfected into COS 7, BHK, and psi-2 cells, and the secretory process of the expressed Protein C-Nagoya was analyzed. ELISA and immunoprecipitation analysis with [35S]methionine labeling indicated that the mutant protein C, which was larger in size than normal, was mostly retained within the cells, and only a small portion of it was secreted into the medium. These results suggest that most of Protein C-Nagoya undergoes degradation within the producing cells, and this frameshift mutation apparently leads to protein C deficiency by impairment of secretion of the elongated protein C into plasma.
Amino Acid Sequence↗
Inhibition by lactoferrin and kappa-casein glycomacropeptide of binding of Cholera toxin to its receptor.
Inhibition from binding of Cholera toxin (CT) to Chinese hamster ovary (CHO)-K1 cells and ganglioside GM1 by lactoferrin (Lf) and kappa-casein glycomacropeptide (GMP) from cow's milk was examined. Both Lf and GMP effectively reduced the CT-derived morphological changes in CHO-K1 cells. The competitive binding assay demonstrated that both Lf and GMP inhibited the binding of CT to GM1, although their affinity for CT was lower than that of GM1. The inhibitory effect of Lf and GMP seemed to be attributed to their terminal sialic acid, although the sugar chain sequence only partially fitted to the CT-receptor.
Animals↗
Properties of agents that effectively entrap liquid lipids.
A droplet of an oil-in-water emulsion of methyl linoleate in a saccharide or protein solution that contained with a surfactant, a stabilizer, or both was dehydrated by drying equipment for a single droplet that resembled a spray drier. The lipid exposed on the surface of dehydated samples was extracted and measured by gas chromatography. Gum arabic or gelatin without additives resulted in little lipid being exposed; they were good entrapping agents. Little lipid was exposed with a pullulan solution containing lecithin, sugar ester, carboxymethylcellulose, or sodium caseinate but much was exposed with a maltodextrin solution containing any of the surfactants tested. When both the surfactant lecithin and the stabilizer xanthan gum were added to the emulsion prepared in a maltodextrin solution, lipid was not detected. The results suggested that effective entrapping agents of liquid lipids cause much emulsification, stabilize the emulsion (that is, they cause the continuous phase to be very viscous), and create a dehydrated matrix of fine, dense network layers.
Chemical Phenomena↗
[Recent advances in the chemotherapy of leukemias].
Most recent progress in the treatment of leukemia and choice of therapies for obtaining "cure" from leukemia are discussed. Chemotherapy can now provide about 40% long term survival in acute myeloblastic leukemia (AML) and about 20% disease-free survival in acute lymphoblastic leukemia (ALL) of adults. Bone marrow transplantation (BMT) should be applied for the patients at risk in those leukemias (Cytogenetic abnormalities for AML and prognostic factors in ALL). In CML patients, BMT offers the only cure. Update result of interferon (IFN) therapy for CML is still a matter of controversy. Ex vivo treatment of autologous cells with IFN or drugs may be beneficial for CML patients without HLA identical donor.
Antineoplastic Combined Chemotherapy Protocols↗
[Mitral valve prolapse associated with partial absence of commissural chordal insertion: report of two cases].
We reported 2 cases of mitral valve prolapse (MVP) associated with partial absence of the chordae tendineae. Case 1 was a 25-year-old man who was admitted to our hospital for further examinations of an apical pansystolic murmur (Levine 4/6) and the abnormal shadow on his chest radiograph. He was diagnosed as having grade 3 + mitral regurgitation (MR) by the Sellers classification and pulmonary varix by cardiac catheterization. Transesophageal echocardiography revealed MVP of the rough zone of the anterior mitral leaflet and MR blowing into the pulmonary varix. Case 2 was a 60-year-old man who was admitted to our hospital because of congestive heart failure and apical pansystolic murmur (Levine 4/6). Parasternal echocardiography revealed prolapse of both the anterior and posterior mitral leaflets and moderate MR. In both cases, absence of insertion of anterolateral commissural chordae was confirmed after surgery, and the abnormalities of chordal arrangement and insertion were considered as causes of MVP in these cases.
Adult↗
Clinical characteristics of chronic cutaneous graft-versus-host disease in Japanese leukemia patients after bone marrow transplantation: low incidence and mild manifestations of skin lesions.
We investigated the incidence of chronic graft-versus-host disease (GVHD) and skin and oral lesions in chronic GVHD in 90 Japanese leukemia patients surviving over 100 days after bone marrow transplantation (BMT) from HLA-compatible siblings. The clinical characteristics of chronic cutaneous GVHD occurring in eight of these patients are summarized. There were some differences from previous reports in the USA and Europe. The incidence (8/29: 28%) of skin lesions in chronic GVHD was low in contrast to the previously reported high incidence (79-90%). Cutaneous manifestations in six out of eight patients with chronic GVHD tended to be mild, and lichen-planus-like eruptions in the skin and scleroderma-like lesions, which are well known as representative cutaneous manifestations of chronic GVHD, were rare. Furthermore, our statistical analysis indicated that there was no relationship between pretransplant total body irradiation and GVHD prophylaxis or acute GVHD and the onset of chronic cutaneous GVHD. The present study suggests that the differences from previous reports in the USA and Europe concerning chronic cutaneous GVHD may be attributable to differing genetic backgrounds in Japanese and western populations.
Acute Disease↗
New flavor symmetry and nonleptonic decays of D and B mesons.
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Journal Article↗