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Biomedical subjects

T Andoh

Publications and source records attributed to T Andoh.

At least 145 records · Page 8Linked to original sources

[Advanced breast cancer with remarkable response to the combination therapy of mitoxantrone (MIT) and medroxyprogesteron acetate (MPA) after failure of anthracycline therapy: a case report].

A 67-year-old advanced breast cancer patient with multiple bone metastases showed a remarkable response to the combination therapy of mitoxantrone (MIT) and medroxyprogesteron acetate (MPA) after failure of anthracycline therapy. Eight course of CTF (cyclophosphamide, THP-adriamycin, 5-fluorouracil) and subsequent 4'-epi-adriamycin were performed for locally advanced breast cancer and multiple bone metastases, but the ulcerated breast cancer enlarged. Then the combination therapy of MIT (10 mg/day) and MPA (1,200 mg/day) was carried out. Seven months after treatment, the ulcerated breast cancer disappeared completely and the serum levels of CA 15-3, TPA and CEA decreased within the normal range. These results suggest that combination therapy with mitoxantrone may well be effective against the anthracycline-resistant breast cancer.

Aged↗

Cloning of the mouse cDNA encoding DNA topoisomerase I and chromosomal location of the gene.

The mouse cDNA encoding DNA topoisomerase I (TopoI) was cloned and the nucleotide sequence of 3512 bp was determined. The cDNA clone contained an open reading frame encoding a protein of 767 amino acids (aa), which is 2 aa longer than its human counterpart. Overall aa sequence homology between the mouse and human, and between the mouse and yeast (Saccharomyces cerevisiae) sequences was 96% and 42%, respectively. The mouse TopI gene was mapped at position 54.5 on chromosome 2 from linkage analyses of a three-point cross test with Geg, Ada, and a as marker genes.

3T3 Cells↗

Injection of anti-topoisomerase I IgG into nuclei of mouse L929 cells leads to inhibition of transcription of exogenously introduced SV40 large T antigen gene.

Affinity-purified anti-topoisomerase I IgG was microinjected into nuclei of mouse L929 cells and the effect on transcription of cellular RNA and exogenous SV40 T antigen mRNA was investigated. Synthesis of stable cellular RNA synthesis as measured by [3H]-uridine incorporation followed by autoradiography was inhibited by about 50%. A plasmid containing the entire early region of SV40 genome was microinjected with the antibody, and messenger RNA for T antigen was measured by in situ hybridization. At 24 h after injection of the antibody the accumulation of the mRNA was reduced by about 60%, and at 48 h by about 50%. These results are consistent with the interpretation that topoisomerase I is essentially involved in the transcriptional process in active chromatin.

Animals↗

Long-term survival in malignant intracranial germ-cell tumors: a report of two cases and a review of the literature.

The authors report the successful treatment of two cases of malignant germ-cell tumor. A 12-year-old patient with a pineal immature teratoma and increase of alpha-fetoprotein serum levels was treated with total excision and cisplatin, vinblastine, and bleomycin (PVB) in combination given twice. One year later, he had a recurrence of tumor in the right occipital lobe, which was totally removed, and yolk sac tumor was verified. As subsequent adjuvant chemotherapy, PVB was given in four courses over 1.5 years, together with one course of cisplatin-etoposide (PE) therapy. The patient is well 5 years and 9 months after the first operation. In the second case, a 19-year-old patient with a pineal mixed germ-cell tumor, composed of germinoma, yolk sac tumor, and embryonal carcinoma, was treated with total excision, followed by four courses of PVB therapy and one of PE. She has done well in the 4.5 years since the initial treatment. Thus, aggressive extirpation of the lesion and subsequent combination chemotherapy using cisplatin and other multiple drugs, given in at least four courses over 1.5 years, even if tumor markers return to within normal limits, might provide successful treatment for malignant germ-cell tumors.

Adult↗

Effects of continuous negative extrathoracic pressure ventilation on left ventricular dimensions and hemodynamics in dogs.

It has been reported that continuous negative extrathoracic pressure ventilation (CNETPV) depresses cardiac output less than continuous positive pressure ventilation (CPPV) does, and this difference may be related to the different effects of two ventilatory modes on preload. We performed simultaneous measurements of hemodynamics and left ventricular short axis dimensions by transesophageal echocardiography (TEE) to evaluate left ventricular preload and function during CNETPV and CPPV in normal dogs. Hemodynamic measurements and simultaneous TEE recording were performed at 5 successive periods; 1) the first control period of intermittent positive pressure ventilation (IPPV1), 2) CNETPV with negative end-expiratory pressure (NEEP) of -10 cmH2O (CNET10), 3) CNETPV with NEEP of -15 cmH2O (CNET15), 4) the second control period of IPPV (IPPV2), and 5) CPPV with PEEP of 15 cmH2O (CPPV15). Left ventricular end-systolic and end-diastolic dimension (LVESD and LVEDD), ejection fraction (EF) and fractional shortening (FS) were measured from TEE recordings. Both CNET10 and CNET15 induced no significant changes in hemodynamics and left ventricular dimensions, compared with those during IPPV1. However, CPPV15 reduced cardiac output and stroke volume (SV) and increased heart rate significantly, compared with IPPV2. CPPV15 significantly decreased LVEDD compared with IPPV2. Neither EF nor FS showed any significant change throughout the experiment. These results indicate that CNETPV preserved cardiac output because it maintained the preload and the left ventricular function.

Journal Article↗

Regulation of proteasome expression in developing and transformed cells.

The proteasome is a unique protease complex found in all eukaryotic cells and has multiple functions for essential activities. In this work we showed that it is expressed at high level in immature, rapidly growing cells, such as those in early embryonic tissues and cancer cells (Fig. 7). The increase of its expression is down-regulated on differentiation of the cells. However, lymphatic blastocytes grow rapidly and express high levels of proteasomes, but are differentiated. Therefore, the proteasome is not expressed at high levels only in immature cells, but is also involved specifically in nuclear activities of cells during rapid growth, possibly regulating proteinous factors in the cell cycle.

Animals↗

Phospholipase C activity in cerebrospinal fluid following subarachnoid hemorrhage related to brain damage.

Phosphoinositide-specific phospholipase C (PLC) activities were measured in CSF from patients after subarachnoid hemorrhage (SAH). Their PLC activities were significantly higher than those in control CSF. Moreover, there was an obvious correlation between the PLC activity in CSF collected on day 3 and the preoperative clinical grade. The PLC activity was also closely correlated with the level of neuron-specific enolase as a marker of brain damage. Furthermore, the PLC activities were partially purified from CSF of patients after SAH and were immunologically identified to be PLC beta, PLC gamma, and PLC delta. These results suggest that PLCs are released into the CSF from brain tissue in conjunction with the initial hemorrhage and that their activity may reflect the extent of brain damage.

Aneurysm, Ruptured↗

Production of less chronic nephrotoxicity by cyclosporine G than cyclosporine A in a low-salt rat model.

Chronic tubulointerstitial nephropathy during long-term cyclosporine A (CsA) use has led to a search for equally effective but safer analogues. In this study we evaluated one of these analogues, cyclosporine G (CsG), in a rat model of chronic cyclosporine nephrotoxicity. CsG has immunosuppressive effects equivalent to CsA when dosed on a weight basis. Pair-fed Sprague-Dawley rats kept on a low-salt rice diet were given CsA 15 mg/kg, CsG 15 mg/kg, CsG 25 mg/kg, or vehicle subcutaneously. After 21 days, CsA animals had a lower glomerular filtration rate, measured by inulin clearance (0.16 +/- 0.04 ml/min/100 g) and higher serum creatinine (0.94 +/- 0.06 mg/dl) than CsG 15 mg/kg (GFR: 0.41 +/- 0.10 ml/min/100 g and serum creatinine: 0.68 +/- 0.09 mg/dl), CsG 25 mg/kg (GFR: 0.39 +/- 0.16 ml/min/100 g) or control rats (GFR: 0.62 +/- 0.06 ml/min/100 g; serum creatinine: 0.56 +/- 0.03 mg/dl), respectively (P < 0.05). The CsA group had considerable cortical and medullary injury (interstitial fibrosis and tubular atrophy), whereas both groups of CsG animals had more limited changes. Despite the same or larger doses of CsG on a weight basis, cyclosporine blood levels were significantly lower in CsG than CsA rats. We conclude that CsG, an analogue of cyclosporine with immunosuppressive activity equivalent to that of CsA, produced less nephrotoxicity in a model of chronic renal injury in rats, using both functional and structural parameters.

Animals↗

Effects of adenosine triphosphate (ATP) on somatosensory evoked potentials in humans anesthetized with isoflurane and nitrous oxide.

In order to examine the usefulness of adenosine triphosphate (ATP) as an adjuvant to anesthesia for surgery requiring intraoperative somatosensory evoked potential (SSEP) monitoring, we have studied the effects of ATP on SSEPs in patients anesthetized with isoflurane and nitrous oxide (N2O). A control recording of SSEP was performed while anesthesia was maintained with 0.5% end-tidal concentration of isoflurane in 60% N2O. The recordings were repeated after an ATP infusion had been added to this basal anesthesia at the rates of 100 micrograms.kg bw-1.min-1 and 200 micrograms.kg bw-1.min-1. SSEP was also studied when end-tidal isoflurane concentration was increased to 1.5% after cessation of ATP infusion. An infusion of ATP combined with 0.5% isoflurane and 60% N2O effectively inhibited an increase in blood pressure during surgery. The amplitude of the cortical component of SSEP was lowered by 1.5% isoflurane, which also increased both cortical and spinal latencies as well as central conduction time (CCT). In contrast ATP infusions at both rates induced no significant changes in latencies, amplitude and CCT. The results indicate that ATP infusion combined with 0.5% isoflurane in 60% N2O can be a useful anesthetic technique for intraoperative SSEP monitoring because adequate anesthetic depth can be maintained by a low concentration of anesthetics without further suppression of SSEPs.

Adenosine Triphosphate↗

Radiosensitization and inhibition of deoxyribonucleic acid repair in rat glioma cells by long-term treatment with 12-O-tetradecanoylphorbol 13-acetate.

Patients with brain tumors often undergo radiotherapy, and the cellular resistance is a major obstacle. It has been suggested that protein kinase C (PKC) may be one of a number of important regulatory enzymes in cell response to ionizing radiation. We therefore investigated the effect of PKC depletion on deoxyribonucleic acid (DNA) damage and repair after radiation in C6 cells using a microgel electrophoresis method to explore the role of PKC in glioma radioresistance. When cells are embedded in agarose on slides, lysed, and subjected to an electric field, broken DNA is able to migrate toward the anode. A significant increase in the length of DNA migration was observed in the cells exposed to irradiation. Inhibition of PKC activity by prolonged treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) or staurosporine, a potent PKC inhibitor, before irradiation enhanced radiation-induced DNA damage and attenuated the repair of damaged DNA. The half-times of DNA repair in parent C6 cells and PKC-depleted C6 cells were about 30 and 60 min, respectively, and the extent of DNA migration was still seen in the PKC-depleted cells even at 120 min after irradiation. In addition, the C6 cell clonogenicity after irradiation was also attenuated by long-term exposure of the cells to 12-O-tetradecanoylphorbol 13-acetate. These data suggest that PKC may play an important role in regulating the cell response to irradiation. The inhibitors of PKC might represent a new class of pharmacological agents to manipulate the radiosensitivity of gliomas.

Animals↗

Effect of interferon-gamma on ACNU-induced DNA damage and cytotoxicity in human glioblastoma cells.

Interferons (IFNs) are a natural body defense with powerful effects on tumor growth, including gliomas. The direct effects of IFN-gamma on (1-4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU)-induced deoxyribonucleic acid (DNA) damage and cytotoxicity were investigated in two human glioblastoma cell lines, A-172 and T98G, using a single cell microgel electrophoresis technique and a microculture tetrazolium assay. The results demonstrated a synergistic effect of IFN-gamma with ACNU on intracellular damage in both cell lines. 10 micrograms/ml ACNU induced a cell inhibition rate of 23.9% in A-172 cells, and almost no effect on T98G cells. 1000 U/ml IFN-gamma and 10 micrograms/ml ACNU caused a significant increase in cell inhibition, 51.2% for A-172 and 72.3% for T98G cells. DNA damage in individual A-172 and T98G cells exposed to ACNU was enhanced significantly by IFN-gamma (p < 0.001). The findings suggest a direct effect of IFN-gamma on ACNU-induced cell damage in human glioma, in addition to its effect on immunomodulation.

Brain Neoplasms↗

BU-4794F, a new beta-1,3-glucan synthase inhibitor.

New beta-1,3-glucan synthase inhibitor (BU-4794F) was isolated from the culture broth of Gilmaniella sp. FA4459. Structural studies indicated that it was a novel member of the papulacandin group of antibiotics.

Antifungal Agents↗

[Anesthesia in a patient with carnitine deficiency syndrome].

A patient with carnitine deficiency syndrome for tracheostomy and resection of tracheal granuloma was anesthetized with nitrous oxide and sevoflurane and vecuronium bromide. Potentiation of effect of vecuronium was minimal, and anesthetic course was uneventful. Carnitine is essential for transportation of long chain fatty acids into mitchondrial matrix. Its deficiency causes metabolic failure in skeletal muscle and accumulation of acyl-CoA in central nervous system. Carnitine deficiency syndrome is associated with a number of metabolic disorders of fatty acid. Signs and symptoms of the syndrome include skeletal muscle weakness, cardiomyopathy, liver disfunction, central nervous system disorders, hypoketotic hypoglycemia and so forth. Since fasting, infection, or shivering have been shown to deteriorate carnitine deficiency syndrome, there is a risk of triggering the acute episode perioperatively. Moreover, there is a possibility of prolonged effect of muscle relaxants and delay in emergence from anesthesia due to preexisting brain damage. These problems should be considered in perioperative period.

Adolescent↗

Role of DNA topoisomerase II in chromosome dynamics in mammalian cells.

ICRF-193, a bis-(2,6-dioxopiperazine) derivative and a non-cleavable-complex-forming-type topoisomerase II inhibitor, inhibited cell division but allowed cells to traverse the cell cycle, leading to the accumulation of polyploid cells with 8C complements or more of DNA. Analysis of the mechanism of how cell division is inhibited by ICRF-193 revealed that: (1) replication of DNA was inhibited only at terminal stages; (2) CDC2 kinase was activated and cells enter absence-of-chromosome-segregation ('ACS') M-phase, where chromosomes are not fully condensed and are not separated, but other mitotic events, such as nuclear-envelope breakdown and cytoskeletal reorganization forming the spindle apparatus, take place, i.e. chromosome dynamics could be uncoupled from the other mitotic events which are normally co-ordinated with the former in mitosis; (3) cells successfully exit from mitosis to the next G1-phase to continue the cell cycle; (4) progression through 'ACS' M-phase appears to be lethal to the cells. All of these observations could be accounted for by inactivation of topoisomerase II activity of the cells caused by the drug. ICRF-193 was thus shown to be a valuable agent in elucidation of the role of topoisomerase II in genetic processes in vivo.

Animals↗

[The evaluation of tumor blood flow measured by single photon emission CT].

The blood flow was measured in brain tumors (tumor blood flow: TBF). A total of 83 patients were studied. These included cases of 29 gliomas, 25 meningiomas, 10 metastatic brain tumors and others. Measurements of TBF were performed using the 133Xe gas inhalation technique, the N-isopropyl-p-[123I] iodoamphetamine intravenous injection method, and SPECT. The results showed that TBF was variable, and was higher in meningioma. There was a significant correlation between TBF and the number of vessels in the operative specimen. Higher TBF tumors had a tendency to bleed profusely during operation. IMP E1 images were closely similar to Xe-SPECT images in TBF value. In cases with glioma, moderate correlation was noted between Xe-SPECT and IMP E2 image. A discrepancy in TBF values between IMP E2 image and Xe-SPECT image was observed. There was low activity on IMP E2 image and high TBF value in Xe-SPECT image. This was true especially in cases with angioblastic meningioma. In conclusion, TBF was considered to be helpful not only for preoperative diagnosis, but also for estimation of bleeding from tumors during operation and treatment.

Adolescent↗

Proton nuclear magnetic resonance studies on water structure in peritumoral edematous brain tissue.

Spin-lattice relaxation times (T1) of water protons and cross-relaxation times (TIS) between irradiated protein and water protons were measured to study the water structure in peritumoral edematous brain tissue of rats. Despite small changes in T1, water, and electrolyte contents, TIS values of water protons were significantly reduced in peritumoral edematous brain tissue when compared to those of the controls. Results indicate that the water structure in brain tissues may become altered at an early stage of edemic formation without causing any significant changes in cellular hydration. TIS might serve as a sensitive parameter for studying the water structure in a variety of tissues, such as in edematous brain tissue.

Animals↗

Proton NMR studies on ischemic rat brain tissue.

The spin-lattice relaxation time (T1) of water protons and the cross-relaxation time (TIS) between irradiated protein protons and observed water protons were measured in order to study water-macromolecular interactions in ischemic rat brain tissues. Tissues were obtained by bilateral common carotid artery occlusion from stroke-prone spontaneously hypertensive rats. Water, Na, and K contents were measured in ischemic brain tissue at the same time. Water and Na content increased while the TIS value and K content decreased following ischemic insults. The T1 value did not change until 180 min after ischemia had been induced. Changes in the TIS value occurred earlier than changes observed for the T1 value, water, and electrolyte contents. Results indicate that the value of TIS may be useful for detecting cerebral ischemia and that the physical structure of water-macromolecular interaction may be altered soon after ischemic onset in brain tissue.

Animals↗

Intracranial cavernous angioma in the 1st year of life and a review of the literature.

Three cases of symptomatic cavernous angioma occurring in the 1st year of life are presented. All three patients were treated with radical extirpation. Postoperatively, two of them improved, but the third died due to cerebral herniation secondary to recurrence of bleeding of the lesion. The clinical characteristics of cavernous angioma in the 1st year of life are briefly discussed and a review of the literature presented, including 16 previous cases operated on directly.

Brain Neoplasms↗