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Biomedical subjects

M Shimoyama

Publications and source records attributed to M Shimoyama.

At least 163 records · Page 9Linked to original sources

[Two autopsied cases of radiation-induced gliosarcoma].

Two autopsied cases of radiation induced gliosarcoma are presented in detail with a review of the literatures. Case 1 was that of a 36-year-old female who was found to have a metastatic choriocarcinoma in the right occipital lobe and received radiation therapy of 45 Gy. Four years later CT scan showed a new enhanced tumor in the cerebellum within the previously irradiated field. Total removal was performed and histological diagnosis of the tumor was a gliosarcoma. She died 12 months after the operation. Case 2 was that of a 63-year-old male who had a protoplasmic astrocytoma in the left temporal lobe and received radiation therapy of 60 Gy after surgery. The tumor recurred in the left temporal base after 9 years. Histological finding of the surgical specimens showed gliosarcoma. The patient died 2 months after he was operated on. The tumors had obviously two defined neoplastic components. One was gliomatous features with anaplastic glial cells which stained for glial fibrillary acidic protein. The other was malignant mesenchymal features with spindle shaped fibrosarcoma cells which contained numerous reticulin fibers. Postmortem examination revealed these similar features. Criteria for identifying a tumor as a radiation induced neoplasm have been proposed by Fajado. The main criterion is that the induced tumor should occur in the previously irradiated field. Secondly, it should appear after a latent period. Thirdly, the pathology should be different from the initial neoplasm. Our cases fulfil these criteria.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Evaluation of cardiotoxicity in new anthracycline analog ME 2303. ME 2303 Study Group].

ME 2303 is a new anthracycline analog which differs from adriamycin in the sugar moiety. ME 2303 displays a higher antitumor activity against L 1210 and P 388 Leukemia than adriamycin. To evaluate the cardiotoxicity of ME 2303, ECG tracings (21 patients) and Holter ECGs (9 patients) were recorded before and after the administration of ME 2303 for various malignancies (mean dose 123.8 mg/m2), and some of the electrocardiographic parameters were analyzed. Control ECGs were normal in 17 patients, in 4 patients minor ECG findings like sinus tachycardia (2 patients), low voltage (1 patient) and flattening of the T wave (1 patient) were observed. After treatment, no relevant ECG changes were observed except one case who showed a flat T in pretreatment ECG. In this patient developed ST-T changes were seen after treatment. The basic rhythm was sinus rhythm in all of the cases, and the heart rate showed no significant changes. ME 2303 had no effects on the specialized conduction system. With regard to arrhythmia, no increase in number and severity was observed. In Holter ECG no development of ST-T changes was seen after treatment.

Adult↗

Synergistic effect of cyclosporin A and verapamil in overcoming vincristine resistance of multidrug-resistant cultured human leukemia cells.

Reversal of vincristine (VCR) resistance by cyclosporin A (CyA) or the combination of CyA and verapamil (VER) was investigated by using four P-glycoprotein (P-gp)-associated human multidrug-resistant (MDR) cell lines (K562/ADM, KYO-1, HEL and CMK). Drug sensitivity was expressed as 50% inhibitory concentration (IC50). The degree of reversal of resistance was expressed as x-fold decrease by dividing the IC50 value without modifier(s) by that with modifier(s). CyA overcame P-gp-associated MDR significantly in all four MDR cell lines. Reversal of VCR resistance by CyA appeared to be dose-dependent. In the case of low-grade MDR cell lines (KYO-1, HEL and CMK), CyA at the low concentration of 0.5 microgram/ml was still effective. The degree of reversal of VCR resistance in this condition was greater (6.3- to 16-fold decrease) in the low-grade MDR cell lines than in a high-grade MDR cell line (K562/ADM) (2.9-fold decrease). At a high concentration (5 micrograms/ml) of CyA, however, it was greater (240-fold decrease) in the high-grade MDR cell lines than in the low-grade MDR cell line (20- to 100-fold decrease). This indicates that concentration of CyA required for overcoming drug resistance in MDR cells was dependent on the degree of drug resistance. CyA overcame VCR resistance more efficiently than VER. The combination of CyA and VER enhanced reversal of VCR resistance in a supra-additive or at least an additive manner and overcame VCR resistance at low concentrations of both modifiers that are clinically achievable with safety.

Cyclosporins↗

[Premedication in children--a clinical trial of bromazepam and chloral hydrate suppositories].

We performed a study on 141 pediatric patients between 6 months and 7 years of age who underwent scheduled radical operation for inguinal hernia, to evaluate bromazepam suppository and chloral hydrate suppository as anesthetic premedication for short pediatric operations. The study was also focused on the difference of the effects of the two drugs between two age groups: younger than 5 years, and 5 years and older. The younger age group required a larger bromazepam dose compared with the older age group, and in the younger group even the larger bromazepam dose did not produce a high sedative effect as chloral hydrate. In the older group, bromazepam and chloral hydrate were equally effective. In respect to emergence from anesthesia, bromazepam delayed emergence compared with chloral hydrate after which children awoke from anesthesia very clearly. Thus, chloral hydrate suppository seemed more useful as premedicants in short pediatric operations for its high sedative effect without affecting emergence.

Anti-Anxiety Agents↗

[Human T-cell leukemia virus type I and adult T-cell leukemia-lymphoma].

Adult T-cell leukemia-lymphoma (ATL) is a unique T-cell leukemia-lymphoma that is closely associated with human T-cell leukemia virus type I (HTLV-I). HTLV-I is also associated with a benign disease, HTLV-I associated myelopathy. Main routes of the infection is through breast milk feeding from carrier mother to her baby, from carrier husband to wife, and by blood transfusion of carrier blood to recipient patients. The presence of anti-HTLV-I antibody is a definite sign of the carrier of HTLV-I, then screening of the antibody has been introduced with success to prevent the HTLV-I infection. Mechanism of leukemogenesis by the virus is not known. It is important to note that age-dependent occurrence of HTLV-I associated ATL can be simply described by a Weibull model. This suggests that ATL leukemogenesis might be the result of accumulation of numerous critical events, most likely somatic mutations, which are estimated to be five from the analysis. Although HTLV-I infection plays a primary role in the pathogenesis of ATL as an initiator, it may be only a prerequisite for accumulation of later events. The presence of HTLV-I negative ATL suggests that factor(s) other than HTLV-I infection may be involved in the leukemogenic process of ATL.

Adult↗

[Recent advances in clinical research on T-cell lymphoma].

Immunophenotypic analysis on 34 cases of T-cell malignancies using monoclonal antibodies against T-cell receptors (TCR) revealed 25 cases of alpha beta-type and two of gamma delta-type. The two patients with gamma delta-type showed cutaneous involvement of tumor cells. Immunoblastic lymphadenopathy (IBL)-like T-cell lymphoma is divided into three histologic categories; inconspicuous type, patchy type and diffuse type. DNA hybridization analysis revealed that 11 of 16 cases showed clonal rearrangement of TCR beta-chain gene without rearrangement of immunoglobulin heavy chain gene, providing strong evidence for clonal proliferation of T-cells. Among 185 patients with adult T-cell leukemia (ATL), 18 cases (9.7%) were found not to be associated with human T-cell leukemia virus type I (HTLV-I). They consisted of 10 of acute type, five of chronic type, two of lymphoma type and one of smoldering type, indicating a diversity in clinical features. Two Japanese patients with ATL developed secondary monoclonal B-cell lymphomas of diffuse, large cell, non-Burkitt type. They were seropositive for HTLV-I but negative for human immunodeficiency virus (HIV). They also suffered from pulmonary tuberculosis, and one from adenovirus type 11-induced hemorrhagic cystitis, indicating an immunodeficient state. Epstein-Barr virus genome was found in lymphoma cells from one patient. It is suggested that opportunistic B-cell lymphomas may occur in the immunodeficient stage of ATL.

Human T-lymphotropic virus 1↗

Arginine-specific ADP-ribosyltransferase from rabbit skeletal muscle sarcoplasmic reticulum is solubilized as the active form with trypsin: partial purification and characterization.

Arginine-specific ADP-ribosyltransferase from rabbit skeletal muscle sarcoplasmic reticulum was solubilized as the active form with trypsin. The enzyme was partially purified by subsequent chromatography, successively on DE-52, Con A-Sepharose and Sephadex G-75. An approximately 2,000-fold purification was achieved from the 105,000 x g supernatant of trypsin-treated membrane with a recovery of 2.8%. Dithiothreitol, which activates hen liver nuclear ADP-ribosyltransferase, inhibited the enzyme.

Animals↗

DNA-regulated arginine-specific mono(ADP-ribosyl)ation and de-ADP-ribosylation of endogenous acceptor proteins in human neutrophils.

Arginine-specific mono(ADP-ribosyl)ation and de-ADP-ribosylation reactions of endogenous acceptor proteins were examined using human neutrophils. The cells contained arginine-specific ADP-ribosyltransferase, acceptor proteins and hydrolase catalyzing the release of ADP-ribose from the ADP-ribose/acceptor conjugate. One major acceptor protein with an apparent molecular mass of 27 kDa was detected in the neutrophils. The ADP-ribosylation of this protein was greatly enhanced when double-stranded DNA was added. The release of ADP-ribose from the ADP-ribosyl core-histones was suppressed. These findings provide clues as to the physiological function of neutrophil ADP-ribosyltransferase.

ADP Ribose Transferases↗

Effect of cerulein on in vivo release of acetylcholine from the rat striatum.

An effect of cerulein on in vivo release of acetylcholine (ACh) from the rat striatum was examined by means of intracerebral dialysis. Intraperitoneal administration of cerulein (25-200 micrograms/kg) enhanced a spontaneous release of ACh in a dose-dependent manner. Intraperitoneal administration of cerulein (100 micrograms/kg) also enhanced the K+-evoked (30 mM) release of ACh. Bilateral subdiaphragmatic vagotomy reduced the increase of both K+-evoked and that of spontaneous release of ACh induced by cerulein administration. Pretreatment with haloperidol (0.5 mg/kg, i.p.) had no effect on increase in spontaneous release of ACh brought about by cerulein administration (100 micrograms/kg, i.p.). These results suggested that peripherally administered cerulein stimulated striatal cholinergic neurons, that its stimulatory effect on striatal ACh release was not mediated by striatal dopamine D2 receptors and that the action of cerulein was, in part, mediated via vagal afferent impulses.

Acetylcholine↗

DNA-dependent mono(ADP-ribosyl)ation of p33, an acceptor protein in hen liver nuclei.

A non-histone acceptor protein for hen liver nuclear ADP-ribosyltransferase was purified to an apparently homogeneous state through salt extraction and chromatography on hydroxyapatite, phenyl-Sepharose, carboxy-methyl-cellulose, Sephadex G-75, phenyl 5-PW, mono S and Radial PAK C18. This protein was termed p33. The ADP-ribosylation of p33 was enhanced more than 60-fold by double-stranded DNA. Single-stranded DNA, RNA and poly(L-glutamate), but not deoxyribonucleotide, were partially effective. DNA-dependent ADP-ribosylation was also observed when whole histones were used as acceptor. DNA required for the maximal ADP-ribosylation depended on the dose of the acceptor protein; the optimal mass ratio of DNA to the acceptor protein was 1:1 with both p33 and whole histones. DNA decreased the Km for NAD and concomitantly increased the Vmax value, but did not alter the Km for p33. These results are consistent with the idea that p33 may participate in chromatin processes such as replication or transcription, through modification by nuclear ADP-ribosyltransferase.

ADP Ribose Transferases↗

Detection of mRNA for the tax1/rex1 gene of human T-cell leukemia virus type I in fresh peripheral blood mononuclear cells of adult T-cell leukemia patients and viral carriers by using the polymerase chain reaction.

Expression of human T-cell leukemia virus type I (HTLV-I) is not detectable by immunofluorescence analysis or RNA blot analysis in most fresh peripheral blood mononuclear cells of patients with adult T-cell leukemia or of asymptomatic HTLV-I carriers. However, in this work, mRNA for the HTLV-I tax1/rex1 genes was detected in fresh peripheral blood mononuclear cells of adult T-cell leukemia patients and asymptomatic HTLV-I carriers by using reverse transcription followed by the polymerase chain reaction. By using fresh peripheral blood mononuclear cells, the expression of tax1/rex1 mRNA was detected in five of the six adult T-cell leukemia patients and four of the eight HTLV-I carriers examined. The amounts of tax1/rex1 mRNA detected corresponded to approximately 10(5) to 10(6) times less than that in the HTLV-I-infected MT-2 cell line. These results indicate that, in some individuals infected with HTLV-I, the provirus in circulating blood cells is transcribed in vivo. Thus the expression of viral antigens in circulating blood cells in vivo is suggested.

Adult↗

Effect of repeated irradiation of low-power He-Ne laser in pain relief from postherpetic neuralgia.

In order to investigate the efficacy of repeated irradiation of low-power helium-neon laser in pain relief, we irradiated 36 outpatients suffering from postherpetic neuralgia. Each patient underwent 20 trials of irradiation on several points around the painful area at a frequency of 2 or 3 times a week. The efficacy of the laser at the end of 20 trials was noticed on 88.9%, and the degree of pain relief was 55.3%, which correlated with the number of trials. These results suggest that the irradiation of He-Ne laser is an effective and safe treatment for postherpetic neuralgia.

Adult↗

Phenotypic heterogeneity of lymphoma of the skin.

We studied surface markers present in 56 cases of lymphoma of the skin by immunohistochemical staining, using the ABC (avidin-biotin-peroxidase complex) and PAP (peroxidase-antiperoxidase complex) methods. Of these cases, 49 were T-cell lymphoma and 7 were B-cell lymphoma. Ten of the 49 cases of T-cell lymphoma were adult T-cell leukemia/lymphoma (ATL). Twenty-five of 31 cases of T-cell lymphoma except ATL analyzed by the ABC method showed a helper/inducer phenotype (Leu2a-,Leu3a+), two cases showed a suppressor/cytotoxic phenotype (Leu2a+, Leu3a-), one case showed Leu2a+Leu3a+, one case showed an inducer phenotype (Leu2a-, Leu3a+, Leu9+), and one case showed OKT11+, Leu2a-, Leu3a-, Leu1-, Leu9+, CD25+, Leu10+, CD30+. One CD8+ lymphoma was Pagetoid reticulosis, and a CD4+, CD8+ lymphoma was lymphomatoid papulosis with erythematous plaque. Cutaneous T-cell lymphoma (CTCL), previously described by Edelson et al., is defined as a helper T-cell lymphoma with marked affinity for the skin. In our study, 5 cases of T-cell lymphoma of the skin were not CTCL as described by Edelson et al. These results show that T-cell lymphoma of the skin is heterogeneous in nature. In other words, CTCL is one type but represents a major proportion of T-cell lymphomas of the skin.

Humans↗

Multidrug resistance in cultured human leukemia and lymphoma cell lines detected by a monoclonal antibody, MRK16.

Forty cultured human leukemia and lymphoma cell lines never exposed to anticancer agents in culture, apart from doxorubicin (ADM)-resistant K562/ADM, were examined for reactivity with a monoclonal antibody, MRK16 in F(ab')2 form [MRK16-F(ab')2], which recognizes P-glycoprotein (P-gp). The relative resistance index to various drugs was calculated by dividing the 50% growth inhibitory concentration (IC50) of the test cell line by IC50 of K562, which was the negative control in the antibody experiment. MRK16-F(ab')2 reacted with four cell lines, K562/ADM, KYO-1, HEL and CMK, which had relative resistance index values of 2 or more to vincristine (VCR), vindesine, vinblastine, ADM, daunorubicin, mitoxantrone (MIT), etoposide (VP-16) and actinomycin-D (ACT-D). The level of resistance to VCR and ADM in these cell lines decreased significantly in the presence of 10 microM verapamil in vitro. Significant expression of mRNA of P-gp gene was also detected in K562/ADM, KYO-1 and HEL. MRK16-F(ab')2 did not react with 36 other cell lines. Among them, three cell lines, PL-21, P31/FUJ and KOPM-28, had relative resistance index values of 2 or more to anthracyclines, MIT and VP-16, but not to vinca alkaloids or ACT-D. The level of ADM-resistance in these cell lines did not decrease significantly in the presence of 10 microM verapamil. Five cell lines, ATL-1K, HL-60, KMOE-2, ML-1 and U266, had relative resistance index values of 2 or more to some of the drugs, but not to the others, and 19 other cell lines did not. These results indicate that the reactivity of MRK16-F(ab')2 correlates with a relative resistance index of 2 or more to all these drugs in cultured human leukemia and lymphoma cell lines.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

A novel multidrug resistance in cultured leukemia and lymphoma cells detected by a monoclonal antibody to 85-kDa protein, MRK20.

A monoclonal antibody, MRK20, in F(ab')2 form [MRK20-F(ab')2], which reacts with 85-kDa membrane protein in a doxorubicin (ADM)-resistant subline (K562/ADM) of human myelogenous leukemia cell line, K562, was examined for reactivity with 41 cultured human leukemia and lymphoma cell lines. None of these cell lines had ever been exposed to any anticancer agent in vitro except K562/ADM. The relative resistance index to various drugs was calculated by dividing the 50% growth-inhibitory concentration (IC50) of the test cell line by IC50 of K562 (the negative control in the antibody experiment). MRK20-F(ab')2 reacted with seven cell lines, KYO-1 derived from chronic myelogenous leukemia in blastic crisis (CMLbc), CMK from acute megakaryoblastic leukemia, HEL from erythroleukemia, P31/FUJ from acute monocytic leukemia, KOPM-28 from CMLbc, PL-21 from acute promyelocytic leukemia and K562/ADM. MRK20-F(ab')2 did not react with 34 other cell lines. All seven MRK20-F(ab')2-positive cell lines had relative resistance index values of 2 or more to anthracyclines (ADM, pyrarubicin, daunorubicin), mitoxantrone, etoposide, bleomycin, and pepleomycin. There was no distinct correlation between the reactivity to MRK20-F(ab')2 and a higher relative resistance index than 2 to vinca alkaloids, actinomycin-D, cisplatin, 4-hydroperoxycyclophosphamide, nimustine hydrochloride, methotrexate or cytarabine. These results indicate that MRK20-F(ab')2 detects a novel multidrug resistance to anthracyclines, mitoxantrone, etoposide, bleomycin and pepleomycin in cultured human leukemia and lymphoma cells.

Antibiotics, Antineoplastic↗

Multi-step carcinogenesis model for adult T-cell leukemia.

The age-specific occurrence of adult T-cell leukemia (ATL) was analyzed using 357 cases collected during nationwide surveys carried out between 1982 and 1985 in Japan. A simple Weibull distribution function fitted well as a model. The mode of ATL onset was log-linear in this model and the curves for males and females overlapped completely. The presence of age-dependent accumulation of leukemogenic events within human T-cell leukemia virus type 1-immortalized T cells was suggested prior to the development of ATL, and the approximate number of independent leukemogenic events in ATL is estimated to be five. This stochastic analysis supported a multi-step carcinogenesis as an appropriate model for ATL.

Adult↗

Potentiation of growth-inhibitory activity of 9-beta-D-arabinofuranosyladenine by 2'-deoxycoformycin in human cultured cell lines derived from leukemias and lymphomas.

Growth-inhibitory activity of 2'-deoxycoformycin (DCF) and 9-beta-D-arabinofuranosyladenine (Ara-A) used either singly or in combination was assessed in 30 human cultured cell lines (seven T-cell, nine B-cell, five non-T,non-B and nine myeloid cell lines) derived from leukemias and lymphomas. DCF had little activity even at 100 microM on any of the cell lines, while Ara-A had an obvious inhibitory effect on them, especially on non-T,non-B cell lines at 10 microM or less. Lymphoid cell lines were apparently more sensitive to the combined use of Ara-A and DCF than myeloid cell lines. DCF potentiated the antiproliferative activity of Ara-A not only in T-cell lines with high adenosine deaminase (ADA) activity, but also in some other cell lines with low ADA activity. DCF was stable in the culture medium, but Ara-A in the medium containing cultured cells was rapidly inactivated. DCF completely inhibited the inactivation of Ara-A in the medium containing P12/ICH or NALM-6, but not in the medium containing Daudi. This suggests that there is some unknown mechanism(s) of inactivation of Ara-A other than ADA in Daudi, which was insensitive to Ara-A in the presence of 1 microM DCF. The capacity of DCF to inhibit degradation of Ara-A in the medium containing these cultured cells correlated with the level of Ara-A sensitivity potentiated by DCF. In all seven T-cell lines, seven of the nine B-cell lines, all five non-T,non-B cell lines, and only three of nine myeloid cell lines, the IC50 value for Ara-A decreased to 5 microM or less in the presence of 1 microM DCF. These results suggest that the combination of DCF and Ara-A may be effective against various types of lymphoid malignancies and some myeloid leukemias.

Adenosine Deaminase↗