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Biomedical subjects

Y Yufu

Publications and source records attributed to Y Yufu.

At least 19 recordsLinked to original sources

Modulation of expression of multidrug resistance gene (mdr-1) by adriamycin.

The acquired resistance to various drugs in cancer is mediated by P-glycoprotein (P-gp) which is encoded by the mdr-1 gene. An increased level of mdr-1/P-gp was demonstrated after chemotherapy administered to treat cancer in humans. To clarify the direct effect of anticancer drugs on mdr-1/P-gp expression, we investigated the change in transport of adriamycin (ADR), and the expression of the mdr-1 gene and P-gp in an ADR-treated, multidrug-resistant leukemic cell line (K562/ADR500). The addition of ADR induced the over-expression of mdr-1/P-gp, which led to a transient decrease in the intracellular accumulation of ADR although the difference was not statistically significant. A maximal effect was observed after 4 h incubation, returning to the baseline level after further incubation for 12-24 h. The phosphorylation of P-gp was inversely correlated with the levels of P-gp. These observations suggest that ADR itself modulates both the expression and function of P-gp. Determination of the optimal schedule for administering adriamycin is essential to achieving the optimal effect in treating cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem

Anemia and neutropenia in a case of copper deficiency: role of copper in normal hematopoiesis.

We present a patient who developed severe anemia and neutropenia after receiving parenteral nutrition for 2.5 years. The serum levels of copper and ceruloplasmin were low, and the bone marrow showed the presence of ringed sideroblasts and vacuolated immature cells. The administration of copper chloride by bolus injection led to a rapid improvement in anemia and neutropenia. The number of progenitor cells (colony-forming unit-granulocyte-macrophage and erythrocyte) present before the copper supplementation was well preserved. It is therefore suggested that copper enzymes play an important role in the maturation of hematopoietic cells.

Aged

Cardiac tamponade in chronic myelomonocytic leukemia: a case report.

Serous effusion is a rare complication of chronic myelomonocytic leukemia. We present a patient with chronic myelomonocytic leukemia who developed a massive pericardial effusion with cardiac tamponade as early manifestations. Numerous clumps of monocytes were observed in the effusion. The patient obtained rapid relief following the intravenous administration of etoposide (100 mg daily for 5 days). Few reports have documented details of such a case.

Cardiac Tamponade

[CD7 (+) stem cell leukemia presenting different phenotypes in lymph node and bone marrow].

A 27-year-old male with systemic lymphadenopathy was diagnosed as lymphoblastic-type lymphoma by inguinal lymph node biopsy in September, 1990. Bone marrow at the initial diagnosis contained 55.4% lymphoblasts with a phenotype of peroxidase (-), CD7 (+), CD4 (-), CD8 (-). Lymphadenopathy and lymphoblasts in bone marrow disappeared after MACOP-B therapy. In December, 1990, however, the patient again noticed swelling of cervical lymph nodes. At this time, the bone marrow contained 36.4% myeloblasts with a peroxidase (+), CD7 (+), CD13 (+), CD33 (+) phenotype. Cytogenetic and genetic study revealed that the lymphoblasts at the initial diagnosis and the myeloblasts at relapse shared an common abnormal karyotype, 11p-, and the same rearranged band of T-cell receptor delta, gamma, beta genes, suggesting that these two blasts originated from the same clone. The blasts obtained from the cervical lymph node at relapse were still negative for peroxidase, in contrast to the blasts from bone marrow. These findings suggest that this leukemia originated from a stem cell and differentiated along multilineage pathways.

Adult

Alterations in thrombin-induced protein tyrosine phosphorylation of platelets from patients with chronic myelogenous leukemia.

Thrombin is known to stimulate platelet protein tyrosine kinase (PTK). We studied thrombin-induced tyrosine-specific protein phosphorylation in normal platelets and those from patients with chronic myelogenous leukemia (CML) and other myeloproliferative disorders (MPD) using immunoblotting with antiphosphotyrosine (anti-P-Tyr) antibody. In resting platelets, two major phosphotyrosyl (P-Tyr) proteins with molecular masses of 120 kDa (p120) and 60 kDa (p60) were consistently detected both in normal subjects and in CML and other MPD patients. In addition to these P-Tyr proteins, a 36 kDa protein (p36) was predominantly phosphorylated only in CML platelets, using antilipocortin II antibody, we identified this p36 protein as lipocortin. Thrombin enhanced the tyrosine phosphorylation of p120 and p60, not only in normal platelets, but also in CML platelets, although the response was more delayed and the duration was shorter in CML platelets than those in normal platelets. Interestingly, decreased thrombin-induced aggregation was associated with a transient stimulation of p36 phosphorylation in CML platelets. These results suggest that the tyrosine phosphorylation of p36, which was probably identical to lipocortin, inhibits thrombin-induced platelet aggregation through anti-phospholipase A2 (anti-PLA2) activity.

Annexins

P190-type bcr/abl expressed in myeloid colonies in a patient with Ph1-positive acute lymphoblastic leukemia.

In Philadelphia chromosome (Ph1)-positive acute lymphoblastic leukemia (ALL), some cytogenetic studies have suggested clonal derivation from a multipotential stem cell. The role of the product of the chimeric gene, P190, is not, however, well understood. We examined the expression of P190-type bcr/abl in single hematopoietic colonies obtained at various clinical stages of a patient with Ph1-positive ALL, using the polymerase chain reaction (PCR). Seven out of 58 colonies examined expressed P190-type bcr/abl. Five out of seven colonies were granulocyte/macrophage (GM) colonies and two were erythroid colonies. The cell lineages of these colonies were confirmed by testing for the expressions of the myeloperoxidase (MPO) gene in the GM colonies and the beta-globin gene in the erythroid colonies. These results suggest transformation of multipotential stem cell in this patient and confirm that expression of the P190-type bcr/abl fusion gene permits stem cell differentiation leading to Ph1-positive ALL.

Adult

Polyneuropathy in acute megakaryoblastic leukemia.

Peripheral neuropathy is a rare complication in leukemia. The authors report a patient with acute megakaryoblastic leukemia (AMKL) and progressive symmetric polyneuropathy. Intense infiltration of leukemic cells in a peripheral nerve was observed at autopsy. This is the first report of AMKL with peripheral nerve involvement to the knowledge of the authors.

Extremities

Recent studies on scrub typhus and Rickettsia tsutsugamushi in Shandong Province--China.

In an outbreak of scrub typhus occurred 138 cases in 1986 in Menying County of Shandong Province of China which were confirmed through clinical and epidemiological surveys and laboratory techniques. In the endemic areas, the predominant species of mite is Leptotrombidium (L.) scutelarae and the predominant rodent is Apodemus agrarius, which may be the main vector and reservoir. Several strains of Rickettsia tsutsugamushi (R.T.) were obtained from mites, wild mice and patients, of which 3 human strains (SDH871, SDH875, SDH878) cause illness and some deaths in mice, except SDH871. The LD50 of SDH878 is 3.4. Cross-protection was observed among the strains, SDH871, SDH878, and prototype strain karp. Also the antibodies in mucoid peritoneal fluid were detectable with high titer. Shandong R.T. belongs to the serotype of the Gilliam strain.

Adult

Two bcr/abl fusion gene products, P210bcr/abl and P190bcr/abl, are equally sensitive to the protein tyrosine phosphatase of mature granulocytes.

Two bcr/abl fusion gene products with tyrosine kinase activity have been found in two phenotypes of Philadelphia chromosome (Ph1)-positive leukemia. P210bcr/abl (P210) is associated with Ph1-positive chronic myelogenous leukemia (CML), while P190bcr/abl is associated with Ph1-positive acute leukemia. We compared the susceptibility of 32Pi-labeled P210 from K-562 cells and P190 from MR-87 cells to protein tyrosine phosphatase (PTPase). PTPase, present in the lysate of mature granulocytes from CML patients as well as in the lysate of these cells from normal subjects, effectively dephosphorylated the CML-associated P210 and the acute leukemia associated P190. This PTPase activity was specifically inhibited by ZnCl2; it was not present in lymphocyte lysates, and was not inhibited by neutralization with anti-CD45 antibody. Since P210 and P190 were equally sensitive to the PTPase, the difference in leukemic phenotypes associated with the expression of these two tyrosine kinases cannot be explained by the differential dephosphorylation of P210 and P190.

Cellular Senescence

Enhanced synthesis of heat shock proteins and augmented thermotolerance after induction of differentiation in HL-60 human leukemia cells.

The effects of the induction of differentiation were investigated on the expression of heat shock proteins (hsps) and thermotolerance. The synthesis of the major hsps in response to heat stress was markedly enhanced in HL-60 human leukemia cells after differentiation. An increased amount of mRNA transcripts for hsp 70 was also noted. In addition, induction of differentiation resulted in acquisition of greater resistance to heat, which may be advantageous since cells in the peripheral blood must survive many stresses.

Blotting, Northern

The transferrin receptor system is not involved in the pathogenesis of hematological disorders with 3q inversion.

To clarify the idea that an alteration of the transferrin receptor (TF-R) gene, localized to 3q26, may be of pathogenetic significance in hematological disorders with 3q anomaly, we studied the TF-R systems of erythroblasts from both functional and genetic aspects. The patient described here had refractory anemia with an excess of blasts (RAEB), with paracentric inversion, inv(3)(q21q26). The patient had the characteristic findings of micromegakaryocytosis and thrombocytosis, with giant platelets. There was no functional abnormality of TF-R as far as number of binding sites, affinity, molecular weight, or recycling kinetics were concerned. Furthermore, we could not recognize any rearrangement of the TF-R gene with Southern blot analysis. These data suggest that TF-R is not involved in the pathogenesis of leukemogenesis and thrombocytosis of the disease.

Chromosome Inversion

Abnormality of platelet membrane glycoprotein GPIIb in a myelodysplastic syndrome with 3q inversion presenting with marked dysmegakaryopoiesis.

Platelet membrane glycoproteins were analyzed in a case of myelodysplastic syndrome with inv(3) (q21q26) presenting with prominent dysmegakaryopoiesis by three different labelling techniques for surface proteins. Markedly decreased level of platelet membrane glycoprotein GPIIb was observed in the patient's platelets by terminal sialic acid labelling method, whereas no significant changes in the levels of glycoproteins including GPIIb could be detected either by penultimate galactose labelling or by tyrosine/histidine labelling. These results indicate a decreased sialylation of GPIIb in the patient's platelets, implying aberrant process in thrombopoiesis in the disease.

Bone Marrow Examination

[Two cases of familial occurrence of aplastic anemia].

It is quite rare that aplastic anemia except Fanconi's type occurs in members of a single family. Here we reported two patients with aplastic anemia, a 14-year-old female and a 49-year-old her mother. In both cases, hematological findings were compatible to that of a typical aplastic anemia. In the case of daughter, CFU-E formation of control bone marrow cells was significantly inhibited by the addition of the patient's bone marrow cells, suggesting the presence of cellular immune mechanism. In the case of mother, no inhibitory activity on CFU-C formation of control bone marrow cells was detected in the patient's serum, though the ratio of helper/suppressor T lymphocytes in the peripheral blood was increased. We could not sufficiently clarify the common immune mechanism causing aplastic anemia in both cases. It was noticeable, however, that both cases share HLA DR2, which is frequently found in patients with various autoimmune diseases and is believed to relate closely to the pathogenesis of autoimmune diseases. This evidence suggests the possibility that genetically inherited susceptibility may also be the important factor for causing aplastic anemia.

Adolescent

Down-regulation of a Mr 90,000 heat shock cognate protein during granulocytic differentiation in HL-60 human leukemia cells.

Modulation of the synthesis of heat shock proteins in HL-60 human promyelocytic leukemia cells during differentiation was studied by metabolic labeling with [35S]methionine and Northern blot analysis. HL-60 cells were found to synthesize constitutively a high level of a Mr 90,000 protein (heat shock cognate protein, hsc90), which was very closely related to Mr 90,000 heat shock protein, hsp90, as far as molecular weight, isoelectric point, peptide maps, immunoreactivity, and encoded mRNA were concerned. Differentiation induction by dimethyl sulfoxide markedly decreased the level of the hsc90 expression, but preserved the ability to preferentially express hsp90 in response to heat stress. These results suggest distinct regulatory mechanisms of the synthesis between hsc90 and hsp90 although they are indistinguishable by conventional protein or mRNA analysis, and indicate that hsc90 has some role in cell growth and differentiation.

Cell Differentiation

[Rapid bone marrow dissemination of gastrointestinal lymphomas after surgical resection].

We describe two cases of gastrointestinal lymphoma associated with rapid bone marrow dissemination after surgical resection. Case 1: A 73-year-old male was diagnosed as having malignant lymphoma originating from ileocaecal region (diffuse medium-sized, B cell type). Tumor (8 x 8 cm) was resected but infiltrated to the peritoneum and curative operation could not be done. Two weeks after operation, elevation of LDH, pancytopenia and bone marrow infiltration of lymphoma cells developed and he died of respiratory failure. Case 2: A 69-year-old female was diagnosed as having remnant gastric lymphoma (diffuse large, B cell type). Tumor size was 5 x 4 cm and swelling of the third lymph nodes was found, so curative operation could not be done. Two months after operation bone marrow infiltration of lymphoma cells was observed and she is now undergoing chemotherapy. Surgical resection is performed in the majority of patients with localized gastrointestinal lymphoma. But the operation of the advanced case must be carefully done, because the operative procedure may sometimes facilitate growth and metastasis of tumor.

Aged