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Biomedical subjects

K Hatake

Publications and source records attributed to K Hatake.

At least 91 records · Page 5Linked to original sources
PubMed1996

Simultaneous expression of keratan sulphate epitope (a sulphated poly-N-acetyllactosamine) and blood group ABH antigens in papillary carcinomas of the human thyroid gland.

The monoclonal antibody 5-D-4 recognizes heavily sulphated forms of keratan sulphate epitope. It reacted strongly with the cell surfaces of most thyroid papillary carcinomas from all the individuals examined, independently of the blood group of the patients. Cells of follicular variants of papillary carcinomas were also labelled by 5-D-4. In contrast, no labelling with this antibody was observed in other types of thyroid neoplasms, or in normal tissues. The reactivity of 5-D-4 with papillary carcinomas was markedly reduced or abolished by prior digestion with endo-beta-galactosidase, keratanase II, or N-glycosidase F. Although keratanase digestion had no effect on 5-D-4 labelling, it revealed the binding sites of Griffonia simplicifolia agglutinin II (GSA-II), which recognizes terminal N-acetylglucosamine in a limited number of carcinoma cells from some individuals. Blood group ABH antigens, which are simultaneously expressed together with keratan sulphate epitope in cancer cells, were eliminated by digestion with endo-beta-galactosidase and N-glycosidase F, but were resistant to keratanase and keratanase II treatment. These results indicate that keratan sulphate oligosaccharides are cancer-associated and are probably oncofoetal antigens, as are the blood group antigens in human thyroid glands. The results suggests that poly-N-acetyllactosamine, which is ubiquitously and consistently produced in papillary carcinomas, is modified in two different ways: sulphation on the 6-position of at least some units of either galactose or N-acetylglucosamine or both, and decoration of non-reducing termini with the blood group antigens. Along with the endo-beta-galactosidase-GSA-II labelling procedure, labelling with 5-D-4 may be a useful diagnostic means for distinguishing papillary carcinoma from other types of thyroid neoplasms.

ABO Blood-Group System↗
PubMed1996

Therapy-related leukemia with a novel 21q22 rearrangement.

We present a case of a 59-year-old Japanese man with therapy-related acute myeloblastic leukemia (AML) after the chemotherapy for non-Hodgkin's lymphoma (NHL). Accumulated doses of cyclophosphamide, procarbazine, doxorubicin, mitoxantrone, and etoposide were 18,300 mg, 3000 mg, 580 mg, 100 mg, and 4150 mg, respectively, which had been administered for the treatment of NHL. Myeloblasts in the peripheral blood increased 43 months after the onset of NHL. He was diagnosed as having AML (M2; FAB classification). The karyotype of the bone marrow cells in the present case contained the following abnormalities: t(2;21)(q21;q22), t(8;21)(q22;q22), and add(13)(q34). In the present case, 645 base pairs of chimeric mRNA were detected by reverse transcription-polymerase chain reaction, indicating the presence of AML1/MTG8 rearrangement. Translocation (2;21)(q21;q22) has not been described previously to our knowledge. It is interesting that the breakpoint of 21q22 existed both in t(2;21) and t(8;21). The disrupted AML1 gene resulting from two 21q22 rearrangements may be involved in the pathogenesis of AML in the present case. The clinical importance of therapy-related AML having the 21q22 rearrangement remains to be examined.

Aclarubicin↗
PubMed1996

Philadelphia chromosome-negative cells with trisomy 8 after busulfan and interferon treatment of Ph1-positive chronic myelogenous leukemia.

A 48-year-old Japanese man with Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia (CML) was treated with busulfan followed by interferon-alpha (IFN-alpha). Ten months after IFN-alpha treatment, Ph1(-) cells with trisomy 8 were detected by the conventional banding technique and fluorescence in situ hybridization (FISH) analysis. Add(Y)(q12) was also found in Ph1(-) cells with trisomy 8. Although Ph1(+) cells disappeared after the treatment with IFN-alpha, Ph1(-) cells with trisomy 8 did not. We summarize four previous case reports of Ph1(+) CML developing Ph1(-) cells with trisomy 8. All four patients had received busulfan and IFN-alpha. These drugs may be related to the ontogenesis of Ph1(-) cells with trisomy 8, but the significance of Ph1(-) cells with trisomy 8 is not known, and further observation is needed.

Antineoplastic Agents↗
PubMed1996

Fas ligand in human serum.

The Fas ligand (FasL), a member of the tumor necrosis factor family, induces apoptosis in Fas-bearing cells. The membrane-bound human FasL was found to be converted to a soluble form (sFasL) by the action of a matrix metalloproteinase-like enzyme. Two neutralizing monoclonal anti-human FasL antibodies were identified, and an enzyme-linked immunosorbent assay (ELISA) for sFasL in human sera was established. Sera from healthy persons did not contain a detectable level of sFasL, whereas those from patients with large granular lymphocytic (LGL) leukemia and natural killer (NK) cell lymphoma did. These malignant cells constitutively expressed FasL, whereas peripheral NK cells from healthy persons expressed FasL only on activation. These results suggested that the systemic tissue damage seen in most patients with LGL leukemia and NK-type lymphoma is due to sFasL produced by these malignant cells. Neutralizing anti-FasL antibodies or matrix metalloproteinase inhibitors may be of use in modulating such tissue damage.

Animals↗
PubMed1996

Tretinoin induces bone marrow collagenous fibrosis in acute promyelocytic leukaemia: new adverse, but reversible effect.

In 11/13 acute promyelocytic leukaemia (APL) cases treated with tretinoin (RA) we observed RA-induced inaspirable collagenous fibrosis of the bone marrow. To study the mechanism of RA on collagen production, we cultured a human bone marrow derived stromal cell line and an osteoblastic cell line with RA in vitro. 10(-7) and 10(-6)M of RA stimulated collagen production. Clinical and experimental observation may be important to understand this adverse effect of RA as it is useful in cancer chemoprevention as well as treatment for APL. This adverse effect is spontaneously reversible after stopping RA or following chemotherapy.

Adult↗
PubMed1996

Therapy-related chronic myelomonocytic leukaemia with bone marrow eosinophilia associated with der(11)t(1;11)(q21;q14).

A 19-year-old male with chronic myelomonocytic leukaemia (CMML) with bone marrow eosinophilia terminating in myeloblastic transformation is described. Before the appearance of CMML, he received a total dose of 2,894 mg of nimustine for the treatment of a pontine glioma over 12 years. Peripheral blood count showed leucocytosis with mature neutrophils and monocytes. Bone marrow smears showed myeloid hyperplasia with increased blasts and abnormal eosinophils and dysplastic features in the myeloid and megakaryocytic cells. A karyotype analysis of the bone marrow cells indicated 46, XY, der(11)t(1;11)(q21;q14). No bcr/abl rearrangement was observed in the cells. He was treated with hydroxyurea to control the leucocyte count, but myeloblastic transformation developed.

Antineoplastic Agents↗
PubMed1996

Two cases of mature B-cell acute lymphocytic leukemia with normal karyotype in adults.

Acute lymphocytic leukemia with mature B-cell phenotype (B-ALL) is a rare type of ALL. Although B-ALL cells commonly have a characteristic chromosomal translocation that includes 8q24 (the location of the c-myc protooncogene), the leukemic cells of the two patients reported in this paper showed normal karyotypes. This finding was confirmed by Southern blot analysis of bone marrow cells in case 1. A c-myc probe was used, and no rearrangement or amplification of c-myc expression was found; B-ALL with the translocation including 8q24 is reported to show high levels of expression of rearranged c-myc. Investigation of anti-Epstein-Barr virus (EBV) antibody revealed that both cases 1 and 2 had a past history of EBV infection. However, at least in case 1, integration of the EBV genomic DNA into the leukemic cells was not detected by the polymerase chain reaction in which specific primers for EBV were employed. The difference in pathophysiology between B-ALL with and without the 8q24 translocation is unclear, however, the prognosis of the two patients with B-ALL with the normal karyotype was as poor as that of B-ALL with the chromosomal translocation.

Aged↗
PubMed1996

Binding of macrophage colony-stimulating factor to serum proteins.

Although three molecular forms of macrophage colony-stimulating factor (M-CSF) have been reported, Western blot analysis of immunoaffinity-purified M-CSF from human blood has shown that the major species of M-CSF in the serum has a molecular weight (MW) of 85 kD. Superose-12 gel filtration chromatography of immunoaffinity-purified serum M-CSF showed the presence of M-CSF-positive fraction in a higher MW area compared with the elution profile of recombinant human (rh) 85-kD M-CSF. Western blot analysis of the higher MW fraction showed that the M-CSF was the same as rh 85-kD M-CSF (not proteoglycan form of M-CSF), indicating that, in the serum, M-CSF exists bound to some serum proteins. To detect the serum proteins, we performed M-CSF-bound column chromatography. The eluate contained at least three serum proteins including albumin and IgG. This result was supported by chromatography using biotinylated M-CSF and avidin-agarose. The binding between rhM-CSF and albumin or IgG was also demonstrated by high-performance liquid chromatography (HPLC) fractionation of the mixture and enzyme-linked immunosorbent assay (ELISA) of the fractions. In the serum, a fraction of M-CSF seems to be complexed with serum proteins such as albumin and IgG.

Animals↗
PubMed1996

[Retrospective analysis on 21 patients with follicular lymphoma].

We retrospectively analyzed the clinical data of the 21 patients with follicular lymphoma admitted to our institution from 1977 to 1994. The frequency of follicular lymphoma was 9.1% in the 231 patients with non-Hodgkin's lymphoma. Overall survival rates at 1 year, 3 years, and 5 years were 90.2%, 78.2%, and 52.1%, respectively. The median follow-up of surviving patients and time to treatment failure (TTF) was 43 months and 30 months, respectively. The median time from disease progression to death was 171 days. In univariate analysis, factors associated with poor survival were stage IV (Ann Arbor staging system), anemia (hemoglobin level less than 10g/dl), bone marrow involvement, two or more extranodal sites, and failure in induction of complete remission (CR) in the entire course. Factors associated with short TTF were anemia, bone marrow involvement, and failure in induction of CR. In multivariate analysis, induction of CR affected survival and TTF independently.

Adult↗
PubMed1996

Histochemical demonstration and analysis of poly-N-acetyllactosamine structures in normal and malignant human tissues.

Poly-N-acetyllactosaminyl structures carry a variety of physiologically and pathologically important carbohydrate antigens and are presumed to have essential roles in the process of cellular recognition, differentiation, malignant transformation and cancer metastasis. Monoclonal antibodies, lectins and endo-beta-galactosidase are useful histochemical tools for detecting and analyzing poly-N-acetyllactosamines in tissue sections. I (branched structure) and i (linear structure) antigens recognized by monoclonal antibodies have been shown to be differentiation antigens in mouse embryo and mouse and human teratocarcinoma cells as well as in human erythrocytes. They are also oncofoetal antigens and are expressed in carcinoma cells in several tissues and organs. Immobilized lectins specific to poly-N-acetyllactosamine structures have been successfully applied for fractioning glycoproteins with poly-N-acetyllactosamine, but histochemical use of these lectins has been restricted to some animal tissues. Among them, pokeweed mitogen agglutinin was used to detect branched poly-N-acetyllactosamine in normal and malignant human colon, demonstrating that it has a highly selective affinity for colorectal carcinomas. Griffonia simplicifolia agglutinin-II staining following endo-beta-galactosidase digestion procedure revealed the presence of poly-N-acetyllactosamine structures with or without blood group-specificities in several normal human tissues. By using this procedure, it was demonstrated that the blood group-related antigens oncofoetally expressed in thyroid carcinoma cells are carried by poly-N-acetyllactosamines containing a domain susceptible to the enzyme digestion. Staining with lectins specific to poly-N-acetyllactosamine in combination with endo-beta-galactosidase digestion demonstrated that poly-N-acetyllactosaminyl structures ubiquitously and consistently produced in thyroid papillary carcinomas are highly heterogeneous in their chain length and branching status and quite different from those produced in other thyroid neoplasms. Staining with monoclonal antibodies or lectins combined with endo-beta-galactosidase digestion procedures have been proven to be powerful tools for localizing and analyzing different types of poly-N-acetyllactosamine structures in normal and malignant tissues.

Animals↗
PubMed1996

[Thrombotic complication in the course of aplastic anemia-paroxysmal nocturnal hemoglobinuria syndrome; possible involvement of dysplasminogenemia (plasminogen Tochigi) in the pathogenesis of thrombosis].

A 44-year-old Japanese man having aplastic anemia (AA)-paroxyamal nocturnal hemoglobinuria (PNH) syndrome was referred to our hospital because of purpuras due to thrombocytopenia in July 1994. He suffered from pneumonia after admission, complicated with cerebral, splenic, and left renal infarction. Pulmonary infaction was also confirmed by perfusion lung scan. He had a plasma plasminogen (PLG) functional activity of 54.4% with a normal level of PLG antigen. The gel isoelectrofocusing pattern of the plasminogen derived from the patient showed 10 normal bands and 10 additional doublet bands with slightly higher isoelectric points than the normal components. Abnormal PLG is converted by urokinase to an inactive two-chain plasmin molecule. These findings were similar to those of a case with dysplasminogenemia (PLG Tochigi) reported by Aoki et al. He was given warfarin for the prevention of thrombosis in December 1994. As of October 1995, these was no recurrence of thrombosis. The cause of thrombosis in the present case have been the association with PNH, predisposition to PLG Tochigi, or the complication of pneumonia. This is the first report of AA/PNH syndrome associated with dysplasminogenemia.

Adult↗
PubMed1996

[Paternity probability in the cases of incest].

To calculate the paternity probability in the cases of incest where the alleged father was either the father or the brother of the plaintiff's mother, some algebraic expressions applicable to a simple codominant diallelic genetic marker system were derived by modifying the formulas of Essen-Möller and Komatsu (the both formulas gave the same result). The paternity probability in the incest case is generally lower than that in usual case, because in the former case an allele present in the mother is sometimes found in both the alleged father and the child (plaintiff), even if the alleged father is not true father. The paternity probability in the incest case, however, becomes higher than that in usual case when an allele is common to both the alleged father and the child but not to the mother. The mean value of paternity probability becomes lower, as the relationship becomes closer between the alleged father and the mother.

Alleles↗
PubMed1996

[A method to calculate the probability of paternity between relatives--a paternity case where the putative father was a deceased granduncle].

To test paternity in a case where the putative father was a deceased uncle of mother (plaintiff's granduncle), we designed a new method to calculate the probability of paternity likelihood. The putative father's genotypes of red cell antigens, HLA and short tandem repeat (STR) polymorphism were estimated from those of mother and sister of the plaintiff. When the probability was calculated from the frequencies in the unrelated individuals (the standard method), a significant bias might be introduced since the putative father and the plaintiff were likely to have the same alleles come from their common ancestry. Therefore, we designed a new method to calculate the likelihood ratio from the frequencies in the group of mother's uncles estimated from mother's genotypes. The probability (0.9299) calculated with our method was found to be lower than that (0.9992) done with the standard method indicating that the new method could remove the bias introduced from the incest.

Adult↗
PubMed1996

Tec protein tyrosine kinase is involved in the signaling mechanism of granulocyte colony-stimulating factor receptor.

Granulocyte colony-stimulating factor (G-CSF) is a critical cytokine to promote the growth, differentiation, and functional activation of myeloid cells. Despite its important roles, little is still understood how one cytokine can trigger such pleiotropic effects. By using mouse cell lines which can grow or differentiate in response to G-CSF, we investigated whether Tec protein tyrosine kinase is involved in either of the signaling pathways. Interestingly, Tec is shown to be tyrosine phosphorylated and activated by the G-CSF stimulation in both cell growth and differentiation mechanisms. Vav is also shown to be associated with Tec and tyrosine phosphorylated in response to G-CSF. Tec is a good candidate for protein-tyrosine kinases involved in both growth and differentiation mechanisms of myeloid cells.

Animals↗