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Biomedical subjects

I Maekawa

Publications and source records attributed to I Maekawa.

At least 19 recordsLinked to original sources

[Assay of flow cytometry for the effect of cepharanthine on resistance to doxorubicin].

The biochemical activity of cepharanthine and the possible mechanism by which it reverses the resistance to doxorubicin in P388 leukemia cells were examined in vitro. The microfluorometric analysis of the cellular level of doxorubicin in drug-resistant cells showed that cepharanthine markedly enhanced the sensitivity of doxorubicin against resistant cells in the cellular level. Cepharanthine also enhanced the inhibitory effect of doxorubicin on the incorporation of thymidine into DNA in resistant cells. The analysis of DNA histogram obtained by flow cytometry showed that doxorubicin exerted its growth-inhibitory effect by blocking the cell cycle at the G2 phase in P388 cells. At higher concentrations, doxorubicin prolonged the S phase and inhibited cell cycle progression to the G2/M phase in cells. The treatment with cepharanthine potentiated these blocking effects induced by doxorubicin in cells. It seems that the modifications of the biological effect of doxorubicin by cepharanthine are due to the change of their ability to induce DNA damage in cells.

Alkaloids

[A case of primary intracerebral malignant lymphoma in systemic lupus erythematosus].

The patient, a 44-year-old female, was admitted to our department because of right hemiparesis and left oculomotor nerve palsy on February 7, 1986. Neither lymphadenopathy nor hepatosplenomegaly was present. She had been treated with prednisolone for systemic lupus erythematosus (SLE) for one and a half year before admission. The CT scan revealed a homogeneously enhanced mass lesion from the midbrain through the thalamus on the right side. The whole body gallium scintigram showed no abnormal uptake except in the brain. Stereotaxic biopsy was performed. Histopathological diagnosis was malignant lymphoma, diffuse, large cell type (International Working Formulation). The enhanced mass lesion disappeared after radiation therapy. Subsequently, she received chemotherapy. She remained well until May 1988 when she died because of the systemic lymphadenopathy. The association of malignant lymphoma and SLE has appeared occasionally in the literature. Primary intracerebral malignant lymphoma associated with SLE is much rarer but it should be considered in the differential diagnosis of symptoms of the central nervous system in a patient with SLE. Therefore, biopsy of a cerebral mass lesion is mandatory if appropriate therapy such as radiation and chemotherapy is to be administered.

Adult

HTLV-I associated myelopathy (HAM) after blood transfusion in a patient with CD2+ hairy cell leukemia.

Hairy cell leukemia complicating hemolytic anemia developed in a 46-year-old woman. Morphologically and cytochemically typical hairy cells were found to express both CD20 and CD2 antigens. Expression of surface IgG of kappa-chain type and the rearrangement of Ig but not T-cell receptor beta genes confirmed a B-cell origin of the leukemia. Blood transfusion was followed by disappearance of the hemolysis and a marked improvement of the leukemia. However, the patient developed progressive spastic spinal paraplegia about seven months after transfusion and was diagnosed as having HTLV-I associated myelopathy (HAM) by the demonstration of HTLV-I antibodies in serum and cerebrospinal fluid. HTLV-I infection via the transfusion may have been involved in the hematologic improvement seen in this patient. Autopsy showed demyelination, vacuolar degeneration, gliosis, and perivascular cuffing in the white matter of spinal cord without evidence of leukemic infiltration.

Anemia, Hemolytic

[The roles of anesthetics and daily used drugs in cardiovascular changes during normovolemic hemodilution (NVHD)].

The changes of cardiovascular parameters and serum cathecholamine levels associated with normovolemic hemodilution (NVHD) were studied under three different conditions: Group 1; the patients for cardiac surgery who were taking cardiac drugs, and were anesthetized with fentanyl 30 micrograms.kg-1, Group 2; the patients with no-cardiac disease and taking no drugs, who were anesthetized with fentanyl 30 micrograms.kg-1 and Group 3; the patients with no-cardiac disease and taking no drugs, who were anesthetized with 0.75% halothane. Cardiac function was compared among three groups. After NVHD, blood pressure and heart rate of group 3 were significantly higher than those of group 1 and 2. Moreover, serum epinephrine and norepinephrine were elevated significantly after NVHD in only group 3. From this study, we conclude that, (1) daily used drugs do not predict hypotension during NVHD, and (2) high dose fentanyl anesthesia is associated with hypotension during NVHD.

Cardiovascular Agents

[An investigation of drug-induced hematologic disorders in Japan--result of Hokkaido].

Patients with drug-induced hematologic disorders were clinically analysed. Fifty-nine cases were registered from 6 hospitals in Hokkaido. These were 21 cases of male and 38 of female. Age-distribution was 18 to 84 years old. Types of hematologic disorders were as follows, 9 cases of pancytopenia, 16 of bicytopenia and 31 of monocytopenia. Leukocytopenia only and leukocytopenia with another disorders were high incidence (85%). Decision of causal drug are done by DLST (drug lymphocyte stimulation test); 5 cases, drug-rechallenge; 3 cases and clinical course only; 31 cases. In 11 fatal cases by this lesion, there included 7 cases of pancytopenia.

Adolescent

Effect of chlorpromazine on the toxicity of doxorubicin in mice.

The effect of chlorpromazine (CPZ) on the toxicity of doxorubicin (DOX) were investigated in mice. CPZ significantly enhanced the acute toxicity and bone marrow toxicity induced by DOX. These results suggest the potentiation of DOX toxicity by CPZ is due to increase of sensitivity of mice to DOX.

Animals

Influence of chlorpromazine on the toxicity of pirarubicin in mice.

The influence of chlorpromazine (CPZ) on the toxicity of pirarubicin (THP) was examined in mice. CPZ significantly enhanced the acute toxicity and bone marrow toxicity induced by THP. These results demonstrate that that in vivo combination of THP and CPZ at high doses will result in an increase of toxicity in mice.

Animals

An autopsy case of triple cancers including signet-ring cell carcinoma of the breast--report of a rare case with reference to a review of the literature.

A 67 year old Japanese woman who had been suffering from general fatigue was diagnosed as having metastasis of signet-ring cell carcinoma of the bone marrow from a biopsied specimen. A clinical effortive search to the systemic organs revealed a tumor of 4 x 3 cm in size in the lower part of her left breast, which was subsequently diagnosed as the primary site histopathologically. The patient was immediately treated surgically, however, her general condition generally deteriorated and she expired 5 months after the operation. Autopsy revealed dissemination of tumor cells in the bone marrow, bilateral pleura, and soft tissue around the operated site. The autopsy additionally revealed squamous cell carcinoma of keratinizing type in the uterine cervix and well differentiated tubular adenocarcinoma in the gallbladder. A review of the literature revealed this case to be the first reported case of triple cancers including signet ring-cell carcinoma of the breast, proven by autopsy in Japan.

Adenocarcinoma

An autopsy case of malignant fibrous histiocytoma of the mediastinum, presenting multiple metastases to the small intestine and to the brain--a rare case report with a review of the literature.

An autopsy case of malignant fibrous histiocytoma (MFH) of the mediastinum in a 25-year-old Japanese man is described. He initially complained of general fatigue and intermittent tarry stool, and was radiographically revealed to have a huge mass within the mediastinum as well as multiple nodules within the abdominal cavity, respectively. The mediastinal tumor could not be resected because of direct tumor invasion into surrounding tissues. Within the abdominal cavity, three distinct tumor nodules were discovered in the jejunum, which could be resected surgically. Histopathologically, the components of both lesions were very similar, and the present case was interpreted as multiple metastases of mediastinal MFH to the intestinal wall. In spite of various kinds of treatment, the mediastinal tumor rapidly enlarged, causing SVC syndrome. Brain CT findings suggested multiple metastases which were considered to be the cause of death. Autopsy confirmed that the main tumor nodule was located within the mediastinum, with brain metastases. The present case of mediastinal MFH is considered to be the youngest case as well as the first case presenting intestinal metastases.

Adult

Reversal of resistance to doxorubicin with cepharanthine in murine P388 leukemia cells.

Cytotoxic effect in vitro and antitumor effect in vivo of doxorubicin (DOX) combined with cepharanthine were investigated on DOX-resistant murine P388 leukemia (P388/R) cells. Cepharanthine was minimally cytotoxic in the cell line, but reversed DOX-resistance in a dose-related manner in P388/R cells. The administration of cepharanthine to mice bearing the P388 leukemia enhanced the antitumor activity of DOX. These results indicate that cepharanthine is an effective agent to reverse DOX-resistant cells.

Alkaloids

[Tumor lysis syndrome at the induction therapy of the first remission in two cases of T-ALL].

The anti-tumor therapy followed by tumor lysis syndrome may cause the metabolic disorders including hyperkalemia, hyperphosphatemia and hyperuricemia. It should be known that it occurs frequently in lymphoproliferative diseases, especially in Burkitt's lymphoma. Two cases of T-ALL accompanied by this syndrome, from which the patients were recovered, at the induction therapy of the first complete remission are reported here. Case 1. A 28-year-old man received VP therapy under the diagnosis of T-ALL with massive hepatosplenomegaly and bilateral enlarged kidneys. During the therapy, metabolic disorders with both renal failure and ventricular tachycardia happened. They were resolved by certain series of treatments. The patient was brought to a complete remission with normal size of liver, spleen and kidneys. Case 2. A boy aged 15 having received the intrasubarachnoidal infusion of MTX and 1-Ad-VP therapy under the diagnosis of T-ALL accompanied by this syndrome which was improved by an appropriate treatment, and the patient was lead to the remission. The risk factors of this syndrome, such as 1-high drug sensitivity of the tumor; 2-renal dysfunction; 3-rapid cytokinetics of the tumor cell; 4-bigger size of the tumor, as well as the preventive treatment of this syndrome are reviewed.

Adolescent

[Measurement of antibodies to human T-lymphotropic virus type-1 (HTLV-1) in cerebro-spinal fluid in patients infected HTLV-1 by blood transfusion].

Although determination of the presence of antibodies to HTLV-1 in cerebro-spinal fluid (CSF) is very important for the diagnosis of HTLV-1-associated myelopathy (HAM), these antibodies in CSF have not yet been completely investigated so far in patients without overt HAM. We examined antibodies to HTLV-1 in CSF of leukemia patients who were infected with this virus via blood transfusion. All of 5 patients showed positive antibody titer, one of 5 patients was a patient with overt HAM. According to Western-blotting analysis in CSF, IgG p-19, 24 and 28 antibodies were positive in 4 patients without overt HAM, but IgM antibody was negative. In contrast, IgG antibodies as well as IgM p-24 antibody were positive in patients with overt HAM. These results suggest that further studies on antibodies to HTLV-1, especially on IgM antibody, in CSF of HTLV-1 infected patients with or without overt HAM may be helpful to better understanding of the mechanism on onset of HAM following blood transfusion.

Adult

[Hairy cell leukemia of European-American type with dual T and B-cell phenotype].

A 46-year-old woman was admitted because of palpitation and conjunctival jaundice. Physical examination revealed hepatosplenomegaly and purpura without lymphadenopathy. Blood count showed 4.7 g/dl hemoglobin with increased reticulocytosis. The platelet count was 1.5 X 10(4)/microliters and the leukocyte count was 6,000/microliters with 17% abnormal mononuclear cells (hairy cells). Hairy cells had nuclei of frequently folded shape and abundant cytoplasma with irregular edges on blood films. The hair-like cytoplasmic projections of the cells were clearly seen under the phase-contrast microscopy. Hairy cells were strongly positive for tartrate resistant acid phosphatase. Bone marrow aspiration was unsuccessful. The biopsy specimens showed small patchy and scattering infiltrations by hairy cells. Surface marker studies of hairy cells revealed that they were strongly positive for SmIg (IgG kappa). They also reacted with alpha B 1, alpha Tac, alpha Leu-M 5 monoclonal antibodies and a rabbit anti-hairy cell serum (alpha HC-M). 53% of hairy cells were shown to react with alpha B 1 and alpha OKT 11 simultaneously by double labelling. The southern blot analysis of peripheral blood mononuclear cells showed IgH chain genes rearrangement and germ line patterns of T-cell receptor genes. Hemolysis was promptly disappeared after blood transfusion. Moreover, the red blood cells, platelets and leukocytes have spontaneously returned to normal levels with disappearance of circulating hairy cells and palpable spleen one year after admission.

B-Lymphocytes

Non-T, non-B acute lymphocytic leukemias: cellular origin based on molecular analyses of immunoglobulin and T-cell alpha- and beta-chain receptor gene rearrangements.

Fifteen non-T, non-B acute lymphocytic leukemia (ALL) cases were investigated for determining cellular origin based on molecular (immunoglobulin and T-cell alpha-receptor (TcR alpha) and T-cell beta-receptor (TcR beta) genes) and immunophenotypical analyses. As defined by monoclonal antibodies, they were classified into 2 groups; 12 cases as common ALL antigen (CALLA)-positive ALL and 3 cases as CALLA-negative ALL. Southern blot analysis revealed that 11 CALLA-positive ALL cases contained rearranged JH gene and 2 of them contained rearranged Jx genes, similar to recent views that most CALLA-positive leukemic cells are neoplastic B-cell precursors. One CALLA-positive ALL case, whose leukemic cells were also Leu-1 positive, showed no rearrangement of JH and TcR beta genes. On the other hand, non-T, non-B CALLA-negative ALL, so called null ALL, consisted of heterogenous groups with regard to lymphocyte differentiation and lineage; one out of 3 null ALL cases may be truely undifferentiated as shown neither JH nor TcR beta gene rearrangement, but other 2 cases showed either JH or TcR beta gene rearrangement. Dual rearrangements of Ig and TcR beta genes occur frequently in 3 out of 15 non-T, non-B ALL cases, but all cases of bigenotype showed no doubly marked profile and retained a completely fidelous immunophenotypic pattern. We further investigated the possibility that analysis of TcR alpha gene may be useful for determining cellular origin of non-T, non-B ALL leukemic cells.

Genotype

[Smoldering adult T-cell leukemia complicating severe respiratory failure--an autopsy case report].

An autopsy case of smoldering adult T-cell leukemia (ATL) is presented. 67 year-old woman was admitted to our hospital with complaints of fever, cough and increasing dyspnea on October 2, 1985. Laboratory findings revealed high LDH, azothermia and slightly leukocytosis with low percentage of flower cells. CRP was strongly positive. Gas disturbance was markedly. Anti-ATLA antibody using indirect immunofluorescence method was X40 positive. Subsets of peripheral lymphocytes showed OKT 4 dominant. (OKT 3; 67.5%, OKT4; 60.6%, OKT8; 8.8%). A chest X-ray film revealed cardiomegaly and fine granular shadows in bilateral lower pulmonary fields. Diagnosis of interstitial pneumonitis was defined in transbronchial lung biopsy (TBLB) specimen. O2 therapy, steroid therapy added antibiotics were ineffective, respiratory failure and renal failure were progressive, she died by septic shock in 39th hospital days. In autopsy, no characteristic histological changes of ATL were found in lymph node, bone marrow, spleen, liver, kidney and lung. Sepsis was the cause was of death. Finally this case diagnosed smoldering ATL and pulmonary fibrosis due to bronchial ectasia with repeated pulmonary bacterial infections. The pulmonary complications of patients with ATL were discussed.

Aged