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Biomedical subjects

T Tashiro

Publications and source records attributed to T Tashiro.

At least 271 records · Page 15Linked to original sources
PubMed1989

Responsiveness of human lung cancer/nude mouse to antitumor agents in a model using clinically equivalent doses.

The responses of 14 lines of human lung cancer xenografts in BALB/c-nu/nu mice to eight known antitumor agents were investigated. These xenografts consisted of four small-cell carcinomas (SCLC) and ten non-small-cell carcinomas (four large cell, three squamous cell, and three adenocarcinomas; NSCLC). The doses used in the experiments were the maximum tolerated dose (MTD) in nude mice and the "rational dose" (RD), the latter considered to be pharmacokinetically equivalent to the clinical dose. When given at MTDs, all drugs except 5-fluorouracil (5-FU) and methotrexate (MTX) were extremely effective against NSCLC as well as SCLC. The response rates of drug-sensitive SCLC to mitomycin C (MMC), ACNU, and vinblastine (VLB) were 100%, and those to Adriamycin (ADR) and vincristine (VCR) were 75%. In addition, the response rates of even drug-resistant NSCLC to MMC and VLB were 70% and 90%, respectively. In contrast, the response rates of NSCLC to RDs of the drugs were reduced to less than 40% and corresponded well to the respective clinical rates. In SCLC, a good correlation of experimental and clinical response rates was observed with four drugs [cyclophosphamide (CPM), ACNU, VLB, and 5-FU]. As a result, we emphasize that a more reasonable prediction of the clinical effectiveness of antitumor agents can be made by a protocol using clinically equivalent doses.

Adenocarcinoma↗
PubMed1989

Axonal transport studied in a single vertebrate neuron: the giant electromotor neuron of the electric catfish, Malapterurus electricus.

Axonal transport was studied using a single vertebrate neuron, the giant electromotor neuron of the electric catfish, Malapterurus electricus. The electric organs of this strongly electric fish are innervated by two neurons whose axons form one electric nerve each. After injection of [35S]methionine into the spinal cord at the level of the two perikarya radioactively labelled material is exported by fast flow as a small wave with a velocity of 5.8 mm/h and a somal release time of 91 min (29 degrees C). Slow flow investigated between 15 and 39 days had a velocity of 1.36 mm/d at 29 degrees C. Analysis of radiolabelled proteins by polyacrylamide gel electrophoresis revealed different patterns of labelling between slow and fast flow. The relative molecular mass of the two major proteins labelled on slow flow correspond to actin and tubulin. Labelled proteins of higher relative molecular mass may correspond to neurofilament proteins. Our results suggest that this vertebrate single-neuron and single-axon system can be used successfully for axonal transport studies.

Animals↗
PubMed1989

Antitumor activity of a new platinum complex, oxalato (trans-l-1,2-diaminocyclohexane)platinum (II): new experimental data.

Antitumor activity of a new platinum complex, oxalato (trans-l-1,2-diaminocyclohexane) platinum (II) (l-OHP), was studied. This water-soluble platinum complex showed a more prominent life-prolonging effect on a mouse leukemia L1210 than cisplatin (DDP). By an intermittent treatment schedule cured mice were observed at the optimal dose. In addition, a subline of L1210 having a 40-fold resistance to DDP (L1210/DDP) showed lack of cross-resistance to l-OHP both in vivo and in vitro. Especially in vivo l-OHP was more active against L1210/DDP than against the original L1210, and all mice were cured at doses of 6.25 and 3.12 mg/kg. l-OHP was also effective against several mouse tumors such as P388 leukemia, B16 melanoma, Lewis lung carcinoma, colon 26 and colon 38 adenocarcinomas, and M5076 fibrosarcoma, though its antitumor spectrum was somewhat different from that of DDP. The synthesis of both DNA and RNA in L1210 cells was inhibited by about 50% with exposure to 10 microM of l-OHP for 1 h, followed by postincubation in drug-free medium for 6-24 h, while only the inhibition of DNA synthesis was observed by DDP in the same experiment. If severe toxicity is not observed in preclinical study, l-OHP expected to be a new clinically active Pt complex.

Animals↗
PubMed1989

Antitumor activity of steroid-containing platinum (II) complexes of 1R,2R-cyclohexanediamine and 2-(aminomethyl)-cyclohexylamine isomers against leukemia L1210.

Various steroid-containing platinum (Pt) complexes of 1R,2R-cyclohexanediamine (= 1R,2R-dach) and cis-dl- and trans-dl-2-(aminomethyl)cyclohexylamine (= amcha) were synthesized and their antitumor activity was screened against leukemia L1210 according to the Pt Analog Study Protocol. Among the Pt complexes prepared, Pt 1R,2R-dach complexes of cortisone, hydrocortisone, methylprednisolone, testosterone, estriol and progesterone showed very high antitumor activity. Pt complexes of cis-dl- and trans-dl-amcha prednisolone, Pt(17-OH-progesterone) (trans-dl-amcha), Pt complexes of cis-dl- and trans-dl-amcha progesterone were found to be very effective.

Animals↗
PubMed1989

Synthesis and antitumor activity of fused tetracyclic quinoline derivatives. 1.

Several fused tri- and tetracyclic quinolines (I and II) with [2-methoxy-4-[(methylsulfonyl)amino]phenyl]amino or [3-(N,N-dimethylamino)propyl]amino side chains were prepared, and their DNA intercalative properties, KB cytotoxicity, antitumor activity (P388 leukemia), and ability to induce topoisomerase II dependent DNA cleavage were investigated. Some compounds having both intercalative ability and KB cytotoxicity were found to be inactive in vivo. However, a positive correlation was seen between the ability to induce topoisomerase II dependent DNA cleavage and antitumor activity in vivo. The indeno- (13a), benzofuro- (21a), and benzothieno- (22a) quinoline derivatives exhibited potent antitumor activities in vitro and in vivo, comparable to those of m-AMSA. They also intercalate DNA and induce topoisomerase II dependent DNA cleavage. Extended screening of 13a showed it to be active against solid tumors such as M5076 sarcoma, B16 melanoma, and colon 38 carcinoma.

Animals↗
PubMed1989

The significance of low serum pepsinogen levels to detect stomach cancer associated with extensive chronic gastritis in Japanese subjects.

Serum pepsinogen levels were measured in 137 stomach cancer patients and compared with those of 288 normal cancer-free subjects. The serum pepsinogen levels of stomach cancer patients, especially pepsinogen I and the pepsinogen I/pepsinogen II ratio were significantly lower than those of normal controls and correlated well with the extent of chronic gastritis associated with the cancerous stomach. These results were in good accordance with the results of previous studies indicating that the cancer derived from the stomach where chronic gastritis/intestinal metaplasia is extensive. The high sensitivity and specificity of this non-invasive serum test to detect chronic gastritis suggested the possibility of its application to the mass screening of stomach cancer.

Adenocarcinoma↗
PubMed1989

A simplified concept for a bileaflet atrioventricular valve that maintains annular-papillary muscle continuity.

We have developed a simplified concept for a bileaflet atrioventricular prosthesis that can be constructed from a simple sheet of glutaraldehyde preserved pericardium. The valve has no rigid ring or stent and no cloth sewing ring. Insertion of the valve reestablishes normal continuity between the annulus and the papillary muscles. We have replaced the mitral valve in nine dogs using this prosthesis. All valves have been competent with excellent valve opening areas as confirmed by echo-Doppler assessment. Studies up to 4 1/2 months have confirmed excellent hemodynamics and there has been no evidence of early tissue failure. Possible advantages of this simple valve design are improved hemodynamics, ease of construction and insertion, and low cost.

Animals↗
PubMed1989

[A histopathological study on pseudomonas pneumonia diagnosed by immunostaining with monoclonal antibody].

Pseudomonas pneumonia is one of the fatal opportunistic infections. We examined Pseudomonas aeruginosa in the autopsied lung tissues by the immunostaining (Biotin-Streptoavidin peroxidase complex method). Out of 185 autopsied cases, fifty-three cases had bacterial pneumonia. We performed the immunostaining to these 53 cases, of which 14 cases (26.4%) were diagnosed as pseudomonas pneumonia. All of the 14 cases had severe underlying diseases which were hematologic malignancies in six, solid malignancies in five and so on. Of ten of them pseudomonas pneumonia was considered to be the direct cause of death. P. aeruginosa was observed in alveolar space in all cases, and in bronchial and bronchiolar lumen in many cases. P. aeruginosa was also detected in alveolar and vascular walls. Histopathologically necrotizing vasculitis and alveolar destruction were characteristic, and intra-alveolar hemorrhage, fibrinous exudate, abscess formation, coagulation necrosis and thrombosis were observed in most cases. Necrotizing vasculitis and intra-alveolar hemorrhage were more severe in the cases of leukopenic patients.

Adult↗
PubMed1989

[A clinicopathological study on cytomegalovirus infection].

A clinicopathological study was carried out in 200 autopsied cases experienced in our department from 1981 to 1988. Cytomegalovirus infection was detected in 18 cases (9.0%). Eleven patients were male and 7 were female, and their ages ranged from 21 to 72 with a mean of 58.1 years. Primary diseases were mainly Non-Hodgkin's lymphoma (7 cases) and Adult T-cell leukemia (4 cases), and corticosteroid had been administered to all of them. The most commonly involved organ was lung (77.8%), followed by adrenal (55.6%), esophagus, pancreas, ovary (22.2%), stomach, small intestine, thyroid (16.7%), liver, kidney, tongue (11.1%), and so on. Concomitant infections were frequently complicated, which were bacterial pneumonia (5 cases), fungal pneumonia (3 cases), disseminated varicella-zoster infection (2 cases) and herpes simplex virus esophagitis or stomatitis (5 cases), while, ten patients died of cytomegalovirus pneumonia. Cytomegalovirus infection was one of the fatal opportunistic infections in immunocompromised, especially cell-mediated immunity impaired, hosts such as the patients with lymphocytic malignancies.

Adult↗
PubMed1989

Lymphocyte subpopulations of peripheral blood in tsutsugamushi disease.

We examined lymphocyte subpopulations in the peripheral blood and serum concentrations of immunoglobulin (Ig) in 8 patients with tsutsugamushi disease. In 7 of the 8 cases, there was a 4-fold or greater increase in IgG and IgM antibody titers between the initial and convalescent serum specimens. In one case, there was no increase, but IgM antibodies were detected with diagnostically significant antibody titers. The percentages of CD8- and CD2-positive lymphocytes measured before treatment were found to be significantly higher than during the recovery stage of patients with tsutsugamushi disease. The CD4/CD8 ratio in the peripheral blood calculated before treatment was significantly lower than that during the recovery stage. Serum concentrations of IgG and IgM in patients during the recovery stage were significantly higher than pretreatment levels, respectively.

Adult↗
PubMed1989

[A pathological study on herpes simplex virus infections in adults].

A pathological study was carried out in 200 autopsied cases experienced in our department from 1981 to 1988. Eight patients (4.0%) had herpes simplex virus (HSV) infections in their visceral organs. Another one patient was diagnosed as HSV hepatitis through necropsy of liver. The nine patients (five of them were male) ranged in age from 34 to 70 years (mean, 58). Four patients had non-Hodgkin's lymphoma, and the other included one with adult T-cell leukemia, one with multiple myeloma, one with idiopathic interstitial pneumonia and one with bronchial asthma, however, one did not have any underlying disease. Two patients died of HSV fulminant hepatitis and one died of HSV diffuse interstitial pneumonia. The most commonly involved organ was esophagus (7/8), followed by tongue (5/8), liver (3/9), spleen, pancreas, lymph node (2/8), and lung, adrenal, tonsil (1/8). Typical herpetic changes such as ballooning degeneration of cells, multinucleated giant cells, ground-glass nuclei and Cowdry type A intranuclear inclusions were observed at the margin of the ulcer or coagulation necrosis. Indirect immunoperoxidase stain revealed HSV-1 antigen in all of the 9 cases, HSV particles were demonstrated in 2. Seven patients had concomitant infections with one or more pathogens in addition to HSV, which included cytomegalovirus in 5, aspergillus in 4, candida in 3 and bacteria in 3.

Adult↗
PubMed1989

[Transoral transclival approach to vertebral-posterior inferior cerebellar artery aneurysm. Case report].

A 61-year-old male was hospitalized for subarachnoid hemorrhage. Cerebral angiography revealed a small left vertebral-posterior inferior cerebellar artery aneurysm, 5 mm to the right of the midline and in the lower third level of the clivus--the so-called "no man's land." It was felt that surgery through the lateral suboccipital approach would likely result in neurological deficits, since the aneurysm would be obscured by the tortuous parent artery or the basilar artery. Therefore, the transoral transclival approach was undertaken and the aneurysm was successfully obliterated. Postoperatively, the patient developed transient right hemiparesis and mild meningitis without evidence of liquorrhea, but fully recovered with conservative management. Certain specific sites of aneurysms, as well as excessive tortuosity of the parent artery, are considered to be indications for the transoral transclival approach. Meningitis is the most worrisome complication of this approach, and mortality is high. Effective preventative measures, which were taken in this case, include tight closure of the dura mater and the pharyngeal mucous membrane, use of the smallest possible clip, and continuous cerebrospinal fluid drainage.

Arteries↗
PubMed1989

Magnitude estimates for electrical pulses: evidence for two neural mechanisms.

The hypothesis that there are two neural mechanisms for electrocutaneous stimulation--one that is sensitive to low current and is adaptive to repeated stimulation and another that is responsive to high current and is less adaptive--was tested in a control and four main experiments. In the main experiments, magnitude estimates obtained for single electrical pulses (of 2-msec duration) were described by a simple power function for each combination of high- and low-current levels and 10 trial blocks. The results were: (1) The slope of the power function for low current was steeper than was that for high current; (2) for low current, the intercept of the power function decreased with increasing block, whereas for high current, it remained constant over blocks; (3) this decrease of the intercept for low current disappeared when judgmental blocks were separated by a rest period of 8 min; (4) the modulus did not affect the slope; (5) for a large modulus combined with low current, the intercept decreased rapidly over trial blocks, whereas for a small modulus combined with high current, the intercept increased over trial blocks. The first four findings support the two-mechanism hypothesis, but the last one may also be interpretable in terms of the regression to absolute scale values.

Adolescent↗
PubMed1989

DNA strand scission by antitumor antibiotics. Detection of C-4'-hydroxylated abasic sites in DNA.

Detection of C-4'-hydroxylated abasic site in calf thymus DNA was investigated. Upon heating with neutral hydrazine (90 degrees C, 5 min) C-4'-hydroxylated abasic site formed by photo-excited Co(III)bleomycin was converted to the fragments having 3'-phosphoro-3''-pyridazinylmethylate as illustrated on Scheme 1. Subsequent enzymatic digestion of the reaction mixture provided four kinds of pyridazine mononucleotides (1, 2, 3, and 4). The fact that the amount of free bases released from calf thymus DNA corresponded well to the amount of pyridazines indicates this reaction can be used for detection of C-4'-hydroxylated abasic site in DNA. By this assay, we first identified the formation of C-4'-hydroxy abasic sites in calf thymus DNA by neocarzinostatin.

Antibiotics, Antineoplastic↗
PubMed1989

[Case of multiple macroaneurysms of the retinal arteries].

A 74-year-old female with acquired macroaneurysms of the retinal arteries of the left eye is presented. During a follow-up period of three years of this rare case, six macroaneurysms developed one after another. Three of them were treated by argon laser photocoagulation because of severe complications such as retinal haemorrhage and exudation onto the macula. However, recovery of visual function of the final stage following treatment was unsatisfactory. Concerning the unusual clinical course of this case, we speculate that severe arteriolosclerosis of the retinal vessels played a fundamental role in this pathological condition.

Aged↗
PubMed1989

[A study of adequate energy, amino acid, and carbohydrate requirements in postoperative total parenteral nutrition--the effect of branched chain amino acid (BCAA) and carbohydrate mixture of glucose, fructose, and xylitol (GFX)].

This study was performed to elucidate adequate energy and amino acid (AA) requirements for TPN patients after abdominal surgery. The effects of AA formula, rich in BCAA (30% BCAA), as a nitrogen source and the carbohydrate mixture of glucose, fructose, and xylitol (GFX = 4:2:1), on nitrogen sparing were also studied. Forty-nine patients having undergone major abdominal surgeries, were divided into 5 groups. The regimens were as follows: G1: 40kcal/kg, standard amino acid (21% BCAA) 1.5g/kg. day, G2: 40kcal/kg, 30% BCAA 1.5g/kg.day, G3: 30kcal/kg, 21% BCAA 1.5g/kg.day, G4: 30kcal/kg, 30% BCAA 1.5g/kg.day, G5: 40kcal/kg, 21% BCAA 1.5g/kg.day. Glucose was the sole carbohydrate energy source in G1 through G4. In G5, GFX was used. (1) Accumulated nitrogen balances during the week immediately after operation were significantly higher in G1 and G2 where higher energy intakes were administered than G3 and G4. (2) The nitrogen balances during the 2nd or 3rd postoperative days in G2 or G4, using 30% BCAA as a nitrogen source, were higher than in G1 or G3 respectively. (3) The changes in serum rapid turnover proteins were not significantly different among these groups. (4) The accumulated nitrogen balance in G5 tended to be higher than that of G1. These results indicate that BCAA rich amino acid formula will induce a more favorable nitrogen sparing effect than a conventional AA formula on TPN patients under surgical stress.

Adult↗
PubMed1989

[The prospect for cisplatin analogs from the experimental standpoint].

In the last decade a number of cisplatin analogs have been extensively synthesized to develop new Pt complexes with better antitumor activity and less nephrotoxicity than cisplatin. Antitumor Pt complexes consist of two carrier ligands and two or four leaving groups according to Pt valence. Our screening results of over 500 Pt complexes suggested that the carrier ligands influenced antitumor activity, especially the antitumor spectrum, while the leaving groups affected water solubility, stability, toxicity, and so forth. Recently, more than 10 cisplatin analogs have been clinically tested. In Japan four complexes have been evaluated in phase II. Most of them showed less nephrotoxicity than cisplatin. Instead, myelotoxicity was often observed. These complexes were significantly effective against various murine Their antitumor spectra, however, were somewhat different from each other. The Pt complexes such as cisplatin, carboplatin and 254-S, having the same carrier ligands, diammine, showed a quite similar spectrum. Sensitivity of cell lines derived from human tumors to these analogs were also examined in vivo and/or in vitro. So far as reported, their antitumor spectra were not so different from that of cisplatin. The cross-resistance patterns of cisplatin-resistant sublines to the complexes also depend on types of carrier ligands. Besides, L-1210/DDP showed cross-resistance only to a few carrier ligands, whereas P388/DDP did so to all of them tested. Thus, it might be a reasonable trial to search for a carrier ligand, the complexes of which would show a unique and broad antitumor spectrum including cisplatin-resistant lines and, in addition, not only against murine tumors but against human tumor cells.

Animals↗