Biomedical subjects

T Kakihara

Publications and source records attributed to T Kakihara.

At least 37 records · Page 2Linked to original sources

PubMed1996

Both acute phase and constitutive serum amyloid A are present in atherosclerotic lesions.

The polymorphic protein, serum amyloid A (SAA), consists of acute phase isotypes and a constitutive isotype. Both are associated mostly with high density lipoproteins (HDL) in the circulation. In the present study, both SAA isotypes were detected by immunohistochemistry and immunoblotting using monoclonal antibodies in atherosclerotic lesions. As the distribution of SAA was identical with that of apolipoprotein B and SAA is known to be associated also with low density lipoproteins (LDL), SAA may also be delivered to the artery wall by LDL.

Aged↗

PubMed1996

Analysis of Met235 to Thr variant of the angiotensinogen gene in relation to the blood pressure and family history of essential hypertension in Japanese children.

A recent study reported a significant relationship between a T704-->C (Met235-->Thr) variant in exon 2 of the angiotensinogen gene in adults and essential hypertension. In the present study, this variant was detected in 131 Japanese children using a polymerase chain reaction. The allele frequency of the variant was 0.76. The genotype frequency of the homozygote for the allele was 0.59, and children who were homozygous had higher systolic blood pressure than those with the other two genotypes. No relationship was found between children's polymorphism and a family history of essential hypertension. These findings suggest that this molecular variant of the angiotensinogen gene may play some role in the regulation of blood pressure in Japanese children.

Angiotensinogen↗

PubMed1996

Positive reaction of monoclonal antibody (TO73) with resistant leukemic cells.

We previously reported the characteristics of a murine monoclonal antibody (TO73) against the multidrug-resistant (MDR) human leukemic cell line. In the present study, we have studied the clinical significance of TO73 by examining its reactivity with primary and relapsed leukemic cells. Of 20 patients with primary leukemia and 15 patients with relapsed leukemia, none and four cases, respectively, reacted with TO73 (p < 0.05). Furthermore, three of the four positive cases were also positive for P-glycoprotein. These results indicate that TO73 preferentially reacts with leukemic cells resistant to chemotherapy and may be a new marker for refractory leukemia.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1995

Expression of the c-kit gene product in normal and neoplastic mast cells but not in neoplastic basophil/mast cell precursors from chronic myelogenous leukaemia.

The expression of the c-kit gene product has been examined in normal mast cells, mast cell neoplasms, and basophil/mast cell precursors obtained from patients with chronic myelogenous leukaemia (CML). Formalin-fixed, paraffin-embedded sections or smears fixed with formalin vapour were studied by immunohistochemical methods, using a polyclonal antibody against the c-kit gene product. Normal and neoplastic mast cells showed a positive immunoreaction for c-kit gene product, but neoplastic basophil/mast cell precursors from CML patients lacked c-kit gene product by immunohistochemical and flow cytometric methods, even in cells having mast cell granules, together with or without basophil granules. Mast cell tryptase was, however, expressed in normal and neoplastic mast cells and basophil/mast cell precursors containing mast cell granules. In addition, cells of monocyte/macrophage lineage lacked c-kit gene product. These findings indicate that the c-kit gene product may play an important role in the development and function of mast cell but not of cell of basophil and monocyte/macrophage lineage.

Animals↗

PubMed1995

Non-X histiocytoma, similar to fibrous histiocytoma, in an infant.

A case is presented of a female infant with an atypical histiocytoma. A gradually enlarging brown lesion was noted on the left side of the chest at the age of 2 weeks. Microscopic study of a biopsy revealed an ill-defined infiltration of spindle cells with indented nuclei. The tumor cells were positive for CD14, HLA-DR, lysozyme, alpha-1-antitrypsin and alpha-1-antichymotrypsin, and negative for CD1, CD3, CD8, CD10, CD19, CD68 and S-100 by immunohistochemistry. Electron microscopy demonstrated no distinct Birbeck's granules, but aberrant granules were seen in a small number of cells. At 7 months of age, a nodule with similar histologic features was noted in the nuchal region, but was incompletely resected. The patient remains recurrence-free at 36 months of age. This case is thought to be a benign form of non-X histiocytoma.

Diagnosis, Differential↗

PubMed1995

Screening for neuroblastoma: a 9-year birth cohort-based study in Niigata, Japan.

Between April 1985 and March 1994 (9 years), 229,346 babies were born in Niigata prefecture, and 201,888 (88.0%) underwent mass screening (MS) for neuroblastoma at 6 months of age. To date, 29 infants have been screen-detected as having neuroblastoma (1:7908). All screen-detected patients survived after removal of the primary tumor. In the same birth cohort, 17 additional children were clinically diagnosed as having neuroblastoma. The cumulative incidence rate of neuroblastoma at 5 years of age was 10.5 per 100,000 live births in the 5-year birth cohort before MS was introduced, and 18.6 per 100,000 in the first 5-year birth cohort after MS was introduced. These values were not statistically different. The birth cohort incidence rate increased significantly to 22.2 per 100,000 (p < 5% compared with before MS) after the method of MS was changed to high-power liquid chromatography (HPLC), even though this latest birth cohort has not been followed for 5 years. The population-based mortality rate from neuroblastoma was 5.9 per 100,000 in the 5-year birth cohort before MS, and 4.5 per 100,000 after MS in the first 5-year birth cohort, using the vanillymandelic acid (VMA) spot test. These values were not statistically significant. In contrast, no death was observed in the next 4-year birth cohort after MS using HPLC; however, this birth cohort has not yet been followed for 5 years.

Chi-Square Distribution↗

PubMed1994

Leukemic cell membrane from acute myelogenous leukemias with massive mast cell infiltration has a mast cell differentiation activity under culture condition containing interleukin 3.

Five cases of acute myelogenous leukemia with massive mast cell infiltration in bone marrow and leukemic tumors of the soft tissue were examined to elucidate the relationship between leukemic cells and mast cells. Leukemic cells in each case showed no basophil/mast cell features and differentiated to neutrophil-like cells in liquid culture. Isolated mast cells failed to proliferate with or without growth factors used irrespective of culture conditions. Mononuclear cell fraction obtained from all patients gave rise to relatively numerous mast cells in interphase culture using IL-3 but not in other culture systems. The simultaneous addition of leukemic cell membrane and IL-3 or delayed addition of leukemic cell membrane produced more numerous and mature mast cells in the upper layer of interphase culture using IL-3. However, addition of leukemic cell membrane alone failed to increase the number of mast cells. Similar results were obtain using mononuclear cells obtained from volunteers and cord blood cells. These results indicate that a cell to cell contact or interstitial substance together with IL-3 are essential requirements for growth and maturation of mast cell precursors and that the cell membrane itself in some cases of leukemia has the ability to induce maturation of mast cell precursors.

Adolescent↗

PubMed1994

Characterization of newly established adriamycin resistant human leukemic cell lines (KY-ADR1 and KY-ADR2).

New adriamycin (ADR) resistant human leukemic cell lines (KY-ADR1 and KY-ADR2) have been established. KY-ADR1 was selected from a cytosine arabinoside (Ara C) resistant cell line by gradually increasing the concentration of ADR and KY-ADR2 from the parental cell line, KY-821, by the same method. The IC50s of both cell lines were 4.3 x 10(-5) and 3.6 x 10(-5) M ADR, respectively. Both lines revealed a similar cross resistance to various anticancer drugs, but KY-ADR1 was resistant to Ara C, whereas KY-ADR2 was sensitive. MDR1 gene was over-expressed and P-glycoprotein was expressed on the cytoplasmic membrane in both lines. Neither verapamil nor cyclosporin A could completely reverse ADR resistance. In addition, no significant changes in topoisomerase II and glutathione-s-transferase levels were detected. These findings indicate that ADR resistance in both cell lines is mainly mediated by P-glycoprotein and some other mechanism may be present. Interestingly, growth of both cell lines was stimulated by natural IL-1 and not affected by TNF alpha and IFN gamma, whereas growth of parental KY-821 was inhibited by these factors. These cell lines will provide new biological aspects on drug resistant leukemic cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1994

Low expression of the deoxycytidine kinase (dCK) gene in a 1-beta-D-arabinofuranosylcytosine-resistant human leukemic cell line KY-Ra.

Molecular change of the deoxycytidine kinase (dCK) gene in a 1-beta-D-arabinofuranosylcytosine-resistant human leukemic cell line (KY-Ra) was investigated. KY-Ra showed the same restriction pattern of genomic DNA and the same nucleotide sequences of the dCK gene as the parental cell line. However, the amount of deoxycytidine kinase mRNA was markedly decreased in KY-Ra compared to the parental cell line. This is the first report showing that the down regulation of dCK gene expression may be affected by a different mechanism than mutation.

Base Sequence↗

PubMed1993

Different effects of various hematopoietic growth factors on myelomonocytic cell line (KY-821) and its drug-resistant sublines.

Human myelomonocytic leukemic cell line, designated as KY-821, and its sublines KY-Ra, KY-VCR, and KY-MTX, which were resistant to cytosine arabinoside, vincristine, and methotrexate, respectively, were compared for response to various hematopoietic growth factors. Cells of KY-Ra and KY-VCR proliferated in response to natural interleukin-1 (nIL-1), whereas the proliferation of KY-821 and KY-MTX was inhibited. Unexpectedly, recombinant IL-1 alpha and IL-1 beta had no effect on the proliferation of each cell line. The effect of nIL-1 was partially deleted by an addition of optimal anti-IL-1. Supernatants of each cell line had no IL-1 activity. Interferon gamma (IFN gamma) and tumor necrosis factor alpha (TNF alpha) also had an inhibitory effect for KY-821 and KY-MTX, but lacked such effect in KY-RA and KY-VCR. nIL-1, IFN gamma and TNF alpha could not differentiate between any of the cell lines but IFN gamma and TNF alpha induced monocytic surface antigens. In addition, there was no difference in the number of IL-1 and TNF alpha receptors in each cell line. These results indicate that there is a difference in biological effects between nIL-1 and recombinant IL-1 species and acquirement of resistance for some types of drugs may associate closely with different responses to hematopoietic growth factors, probably through altered postmembranous transduction.

Animals↗

PubMed1993

Induction of surface antigen recognized by new monoclonal antibody, YU311, on 1-beta-D-arabinofuranosylcytosine-resistant human leukemic cell line.

A new monoclonal antibody, YU311, against an antigen expressed on 1-beta-D-arabinofuranosylcytosine(ara-C)-resistant human leukemic cell line with decreased deoxycytidine kinase activity was generated. YU311 reacted with ara-C-resistant human leukemic cell line (KY-Ra), but not with its parental cell line (KY-821) which was sensitive to ara-C. YU311 recognized the 92-kDa membrane protein. Furthermore, YU311 inhibited the growth of KY-Ra in suspension medium with and without ara-C. In immunocytochemistry, there was no difference in expression of usual differentiation antigens between KY-Ra and KY-821. These findings indicate that antigenic change could occur in ara-C-resistant human leukemic cells with stable expression of differentiation antigens and that the 92-kDa membrane protein may be one of the membrane proteins which regulate cell growth of KY-Ra.

Animals↗

PubMed1993

Small round and spindle cell sarcoma with neuronal differentiation and oncocyte-like features of the thoracic wall: a case report with histological, immunohistochemical and ultrastructural examinations.

A case of small round and spindle cell sarcoma with neuronal differentiation and oncocyte-like features is presented. The tumor was encountered in a 32 year old Japanese woman with an initial presentation of palpable tumor in the left lateral region of the thorax. The resected tumor was a partially well encapsulated whitish medullary one and consisted of small round and spindle tumor cells, together with so-called rhabdoid cells in the small round cell area. Although pseudorosettes were often observed, true rosette formation could not be detected anywhere. Ultrastructurally, despite a histologic variety of tumor cells, most tumor cells possessed numerous mitochondria, some of which occasionally contained abnormal filamentous or crystalloid structures. Various amounts of microfilaments were present in most tumor cells and microtubules were present in a few. A minority of small round cells possessed a small number of neurosecretory granules, especially in short cytoplasmic processes. A positive immunoreaction for neuron specific enolase was found by immunohistochemical examination in several small round tumor cells and for neurofilaments in lesser numbers. Despite the lack of S-100 protein, MB2 was detected in both small round and spindle cells. On the basis of these findings, the tumor of the present case corresponds to malignant peripheral nerve sheath tumor with neuronal differentiation and oncocytic features.

Adult↗

PubMed1992

Neoplastic basophil/mast cell precursors from chronic myelogenous leukemia display heterogeneous responses for a hematopoietic factor.

The response of neoplastic basophil/mast cell precursors to various hematopoietic factors was examined. Blastic or promyelocytic immature cells were obtained from six patients in basophilic crisis of chronic myelogenous leukemia. In all cases, after 14 days suspension culture more then 90% of the cells had basophilic features. 3H-thymidine uptake was markedly increased by the addition of GM-CSF in two cases, G-CSF in one, and IL-3 in two. In clonogenic cell assays, numerous colony formations were obtained when using the same growth factors as in the 3H-thymidine uptake assay. In addition, IL-3 induced colony formation in one case, despite a lack of thymidine uptake IL-4 had a synergistic effect on colony formation with IL-3 in one other case. None of the factors used showed any effect on differentiation. These findings indicate that the proliferation of neoplastic basophil/mast cell precursors may be regulated by various growth factors but response patterns are divergent.

Basophils↗

PubMed1992

Distribution of antigens detected with MB1, MB2 and MB3 on non-hematopoietic human organs and various tumors.

We have examined the distribution of antigens detected by MB1, MB2 and MB3 on non-hematopoietic normal human tissues and various types of benign and malignant tumors. MB1 and MB2 reacted with various organs, such as the epithelium of various glands, smooth muscle cells, vascular endothelial cells, and peripheral nerve tissue. The distributions of these two antibodies were essentially identical. Reactivity with MB3 was confined to the ductal epithelium of salivary glands, the pancreas, and sweat glands, and the cortex of the adrenal gland. Immunoblotting analysis demonstrated that MB1 and MB2 reacted with a few bands of an extract of myometrial cytoskeletal fraction and salivary gland cytosol fraction, whereas MB3 failed to show any bands on these materials. The reactivities of MB1 and MB2 with various neoplasms were similar to those in normal organs, with slight variations of staining pattern and preponderance in well differentiated tumors. Exceptionally, carcinoid tumor and small round cell tumors, such as small cell carcinoma or neuroblastoma, were not reactive with MB1 and MB2. MB3 reacted with several cases of well differentiated benign and malignant epithelial tumors in various organs, and exceptional cases of malignant schwannoma and glioma. These results indicate that the antigens detected by MB1 and MB2 are distributed broadly on non-hematopoietic normal organs, whereas those detected by MB3 are confined to exceptional cases of epithelial and non-epithelial tumors. Thus, although the use of MB1, MB2 and MB3 is of little value for differential diagnosis of various tumors, these three antibodies may be useful for determining of the origin of some tumor types.

Antibodies, Monoclonal↗

PubMed1992

Vincristine-resistant human leukemia cell line: new monoclonal antibodies to a 65kDa membrane protein.

A vincristine-resistant human myelomonocytic leukemic cell line (KY-VCR) was established. KY-VCR exhibited approximately a 2.5 x 10(6)-fold increase in resistance to vincristine compared to the parental cell line. KY-VCR showed a decreased uptake and, an increased efflux of vincristine, and cross-resistance to Adriamycin and Actinomycin D. The M(r) 200,000 membrane glycoprotein was overexpressed in KY-VCR. Furthermore, two antibodies, designated TO73 and TO77, preferentially reacting with KY-VCR were obtained. Enzyme linked immunosorbent study indicated that both antibodies recognized the same epitope and TO77 the wide portion. Immunoprecipitation analysis demonstrated that the antibodies recognized M(r) 65,000 membrane protein, which was distinct from overexpressed glycoprotein in KY-VCR. The induction of membrane protein identified by the antibodies may play a role in drug resistance. KY-VCR cells and two antibodies to them may be very useful for the study of drug resistance and prediction of drug efficacy.

Antibodies, Monoclonal↗

PubMed1991

Abnormal granulopoiesis of leukemic cells with basophil/mast cell features. Cytochemical and ultrastructural observations.

We have carried out cytochemical and ultrastructural examination of human leukemic cells showing basophil/mast cell features derived from patients with acute myelogenous leukemia or basophilic crisis in chronic myelogenous leukemia. Leukemic cells in each case initially showed metachromasia with toluidine blue and various degrees of positivity for astra blue. Other cytochemical results showed considerable variety among cases. The number of granules increased in short-term culture in every case. Ultrastructurally, small membrane-bound granules with or without myelinoid bodies or glycogen particles were present in immature blasts, followed by production of other granule types. In some cases, leukemic cells before and after liquid culture contained the typical basophil granules with or without myelinoid bodies, but the matrix was more loose than normal. Granules showing whorl or scroll matrix profiles, which were typical for mast cells, were present in two cases. In one case, immature leukemic cells contained theta granules, and some mature forms after short-term culture contained typical basophil/mast cell granules as well as theta granules. Leukemic cells occasionally contained multivesicular granules predominantly. These results indicate that leukemic cells with basophil/mast cell features show a heterogeneous configuration and contain abnormal granules differing from normal ones. This abnormal granulopoiesis may be attributable to the results of leukemic events and may be a hallmark for recognition of leukemic basophils/mast cells.

Adolescent↗

PubMed1991

Unusual pancreatic tumor resembling solid and cystic tumor, with somatostatin production and aberrant crystalloid structures.

An unusual pancreatic tumor in a middle-aged man is reported. The tumor was a large encapsulated mass with necrosis and hemorrhage, and microscopically, it showed a predominant microcystic pattern with solid pattern areas. The clinical and histological features of this tumor were similar to those of solid and cystic tumor. Immunohistochemical studies showed that the tumor was positive for alpha 1-AT, NSE, CA 19-9 and somatostatin. Electron microscopy studies showed neurosecretory granules, intercellular junctions, annulate lamellae and aberrant crystalloid structures. These findings indicated that the tumor had differentiated into acinar, ductal and endocrine cells, suggesting that solid and cystic tumor originates from multipotential immature cells.

Adult↗

PubMed1991

Hypereosinophilic syndrome associated with obliterative left ventricular chamber and systemic obliterative arteriosclerosis.

An extremely rare case of hypereosinophilic syndrome is reported. The patient had congestive heart failure due to left ventricular obliteration by a giant thrombus in the apex. Arteriosclerosis obliterans resulted in serious lower extremity gangrene. Combination therapy with a corticosteroid and hydroxyurea caused a marked reduction in eosinophil count, and heart failure recovered in stages. Although the patient was discharged, he returned to our hospital 3 months later with acute myeloblastic leukemia and subsequently died of respiratory failure with pneumonia.

Arteriosclerosis Obliterans↗