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Biomedical subjects

N Yamada

Publications and source records attributed to N Yamada.

At least 667 records · Page 37Linked to original sources
PubMed1990

Synthesis and cytostatic activity of the antitumor antibiotic chartreusin derivatives.

In order to overcome the rapid biliary excretion of chartreusin, which diminished its activity when administered iv, a series of 3',4'-O-substituted derivatives of chartreusin were synthesized. Exo-type of 3',4'-O-benzylidene-chartreusin was found active both by ip and iv administration. Therefore, this compound was selected for further modification on its 6-phenol to obtain broader spectra and better pharmacokinetic parameters than the original compound. Several 6-O-acyl-3',4'-O-exo-benzylidene-chartreusins had high antitumor activity against some murine tumors both by iv and po administration.

Aminoglycosides↗
PubMed1990

[A hepatocellular carcinoma showing sarcomatous features and an extensive metastasis].

A 47-year-old female was admitted for a right hypochondrial pain and was diagnosed as having a hepatic tumor with a cystic lesion. After a right and a caudal lobectomy, she died of hepatic failure due to a tumoral recurrence. At autopsy, a cystic tumoral nodule, 15 x 7 cm in size, and numerous other nodules were revealed in the liver. Metastases were seen in both lungs, the left kidney, the colon, the mesenterium, the peritoneum, the diaphragm, and the para-pancreatic lymph nodes. The hepatic tumors consisted of four types of tumor cells: spindle, round, mixed (spindle and round cells), and cells with pseudoalveolar features. All tumor cells showed a positive immunohistochemical reaction to polyclonal keratin, low molecular monoclonal keratin, alpha 1 anti-trypsin, vimentin and to actin in their cytoplasms. This is considered a very rare case.

Actins↗
PubMed1990

[Studies on immunoreactive somatostatin and gastrin contents of the gastric mucosa in patients with duodenal ulcer--comparison to patients with fundic gland polyposis and normal subjects].

The immunoreactive gastrin (IRG) and somatostatin (IRS) contents in gastric mucosa were measured from the same biopsy specimen of the same patients with duodenal ulcer (DU) at the active stage and healing stage, and compared to those of patients with fundic gland polyposis (FP) and endoscopically normal subjects whose gastric mucosa had only slight atrophic change (Control). The IRS in both the antrum and the gastric body of DU were significantly lower than those of the other two groups, and those showed no difference between the two stages. In all groups, there was a significant positive relation between the IRG and IRS in the antrum. In DU, particularly at the active stage, the relative decrease of the IRS against the IRG was prominent compared to the other two groups. In FP, which has similar background gastric mucosa and ability of acid output to those of DU, it was found that somatostatin was secreted sufficient to control gastrin secretion and acid output. Whereas in DU, secretion of somatostatin was reduced and, particularly at the active stage, it was considered that somatostatin, which could control increased gastrin secretion and increased acid output, was not secreted.

Adult↗
PubMed1990

[Effects of combination chemotherapy with topical application of 5-FU ointment to mice's tongue and UFT].

After oral administration of UFT and lingual topical application of 5-FU ointment to normal mice, the change of the concentration of 5-FU and Uracil in the tongue, liver and blood serum were studied. We compared with UFT only group, 5-FU ointment only group and the both combination chemotherapy group. 1. As for the tongue concentrations, 5-FU levels in both combination chemotherapy group and 5-FU ointment only group were higher compared to UFT only group. There was no difference between combination chemotherapy and 5-FU ointment only group. Uracil at 21-days in combination chemotherapy group were higher than others. 2. The liver concentrations of 5-FU at 21-days was significantly higher. 3. The blood serum concentrations of 5-FU in both combination chemotherapy and 5-FU ointment only groups revealed similar results. Thereafter, combination chemotherapy in oral region with topical application of 5-FU ointment and UFT may be effective.

Administration, Oral↗
PubMed1990

[Mechanism of antitumor effect of a benzoylphenylurea derivative, HO-221].

HO-221, N-[4-(5-Bromo-2-pyrimidinyloxy)-3-chlorophenyl]-N'-(2-nitrobenzoyl ) urea is a novel benzoylphenylurea derivative. We previously reported HO-221 showed significant antitumor activities against various experimental tumor models, and was especially effective against the solid tumor. In this report we studied the mechanism of action of the compound. The inhibitory activity of HO-221 and 6 kinds of antitumor agents on DNA polymerase alpha was examined in vitro. HO-221 inhibited DNA polymerase alpha activity strongly. From the comparison with IC50 values of individual agents, the inhibitory activity of HO-221 was almost equivalent to aphidicolin and ara-CTP. By double reciprocal plot analysis, the inhibition of HO-221 was found to be non-competitive with the dCTP unlike that of aphidicolin and ara-CTP. Furthermore, HO-221 showed almost no effect on RNA polymerase activity and the protein synthesis. The effect of HO-221 on cell cycle progression of HL-60 cells was examined by flow cytometry analysis. The compound accumulated cells at S phase at a low concentration. The compound showed accumulation of cells in G1, G1-S and G2 + M phases. At higher concentrations, HO-221 increased the G1 phase of tumor cells, stopping the cell cycle progression. Therefore, G1 and S phase accumulation by HO-221 was considered to be correlated with the inhibition of DNA polymerase alpha dependent DNA synthesis. These results suggest that HO-221 is a novel antitumor agent with different mechanism of action from the known antitumor agents.

Animals↗
PubMed1990

[Antitumor effect of a benzoylphenylurea derivative HO-221].

HO-221, N-[4-(5-Bromo-2-pyrimidinyloxy)-3-chlorophenyl]-N'-(2-nitrobenzoyl ) urea is a novel benzoylphenylurea derivative. We had interested in various pharmacological actions of benzoylphenylurea compounds. Therefore, many compounds were synthetized and tested in various screening systems. In the process with these tests, we found HO-221 which showed an excellent antitumor activity. The antitumor activity of HO-221 was judged from the survival time and the tumor weight of experimented tumor-bearing animals. HO-221 preparation was orally administered. The compound exhibited significant effects against various animal tumors (P388, L1210, M5076, LLC, C38, S180, W256), and especially effective against the solid tumors. HO-221 was also markedly effective to MX-1 and LX-1 implanted into nude mice. However, the effect against mouse B16 melanoma was moderate. In addition, HO-221 showed a schedule dependency and once every 4 or 7 days treatments were most effective. The antitumor activities of the compound against advanced L1210 and Lewis lung tumors were examined. Tegafur and ara-C were used as reference drug for the study. Three agents showed the antitumor activities against L1210. Against Lewis lung carcinoma, HO-221 showed both the increase of life span and the tumor growth inhibition. On the other hand, tegafur and ara-C were ineffective for the increase of life span.

Animals↗
PubMed1990

[Ultrafast CT scanner; preliminary experience in Japan].

We evaluated the usefulness of Ultrafast CT scanner C-100 (UFCT) in 30 patients' clinical practice. UFCT was very useful not only for cardiac studies but for other body organs' studies. Simultaneous multilevel ultrafast scans of UFCT enabled us to analyse cardiac ventricular motion not only by the ejection fraction but by the change of wall thickness. We could get ultra-early contrast phase images (within one minute images from contrast medium injection start) of contiguous 15, 1 cm interval levels by high quality single slice mode of UFCT. These ultra-early phase images and late phase images would be helpful for tissue characterization.

Adolescent↗
PubMed1990

[Evaluation of aortic dissection by ultrafast computed tomography].

We report usefulness of ultrafast CT (UFCT) in evaluation of aortic dissection, according to the results of examination of 51 patients. By volume mode study of UFCT, aortic dissection was diagnosed in all patients. Fine structures such as intimal tear and ulcer-like projection were depicted in detail. Pulsatile movement of true and false channels was detected by cine study. Precise flow analysis of both channels was available by flow mode study of UFCT. In morphological and functional assessment of aortic dissection, UFCT is superior to conventional scanners, and may be preferable to DSA or MRI.

Aortic Dissection↗
PubMed1990

[Melatonin secretion in intracranial tumor].

UNLABELLED: The secretion of melatonin (MLT) was examined in 6 ICT patients, 2 men and 4 women, who showed marked midline shift of CT scan findings with intracranial hypertension signs (headache, nausea, vomiting). Their ages ranged from 22 to 40 years. The controls, 6 healthy men and 4 healthy women (follicular stage) were aged from 18 to 35. With the subject recumbent, blood was drawn at 14, 20, 02 and 08 hour (Lights out, 9 pm; sunrise, 6 am). After separation of plasma by centrifugation, MLT was extracted by SEP-PAK C18 cartridge and determined by radioimmunoassay (RIA). ( METHOD: The extracted MLT, the antiserum and the 3H-MLT were incubated overnight at 4 degrees C, the antibody-combined and free 3H-MLT were separated using ammonium sulfate, and the radioactivity of the precipitate containing combined 3H-MLT was measured by liquid scintillation.) Plasma MLT concentrations of controls were 42.5 +/- 7.0 (Mean +/- SEM) pg/ml at 14 hr, 50.9 +/- 8.2 pg/ml at 20 hr, 165.1 +/- 22.7 pg/ml at 02 hr, and 49.1 +/- 5.4 pg/ml at 08 hr. The value of 14 hr. significantly differed from 02 hr, (P less than 0.01) showing a diurnal rhythm. The patients' MLT levels (pg/ml) were 19.8 +/- 6.2 at 14 hr, 15.9 +/- 5.2 at 20 hr, 52.0 +/- 17.2 at 02 hr, and 20.3 +/- 3.5 at 08 hr. These values were significantly lower than in controls (P less than 0.01) except at 14 hr. (P less than 0.05), showing no diurnal rhythm except 2 cases. In conclusion, in ICT with midline shift of CT scan melatonin secretion was inhibited and diurnal rhythm disappeared in four cases (67%).

Adolescent↗
PubMed1990

Metabolism of apoB-100 in lipoproteins separated by density gradient ultracentrifugation in normal and Watanabe heritable hyperlipidemic rabbits.

We have examined the capability of a previously developed compartmental model to explain the kinetics of radioiodinated apolipoprotein (apo) B-100 in very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), and low density lipoproteins (LDL) separated by density gradient ultracentrifugation after intravenous injection of radioiodinated VLDL into New Zealand white (NZW) and Watanabe heritable hyperlipidemic (WHHL) rabbits. Our model was developed primarily from kinetics in whole blood plasma of apoB-100 in particles with and without apoE after intravenous injection of large VLDL, total VLDL, IDL, and LDL. When the initial conditions for this model were assumed to be an intravenous injection of radiolabeled VLDL, the plasma VLDL and LDL simulations for NZW rabbits and the VLDL, IDL, and LDL simulations for WHHL rabbits were found to be inconsistent with the observed density gradient data. By adding a new pathway in the VLDL portion of the model for NZW rabbits and a new compartment in VLDL for WHHL rabbits, and by assuming some cross-contamination in the density gradient ultracentrifugal separations, it was possible to bring our model, which was based upon measurements of 125I-labeled apoB-100 in whole plasma, into conformity with the data obtained by density gradient ultracentrifugation. The relatively modest changes required in the model to fit the gradient ultracentrifugation data support the suitability of our approach to the kinetic analysis of the metabolism of apoB-100 in VLDL and its conversion to IDL and LDL based upon measurements of 125I-labeled apoB-100 in whole plasma after injection of radiolabeled VLDL, IDL, and LDL. Furthermore, the differences in kinetics observed by us between data from whole plasma and data from plasma submitted to ultracentrifugal separation from the same or similar animals highlight the fact that small variations that can occur in the separation of lipoprotein classes by buoyant density can lead to confusing results.

Animals↗
PubMed1989

Gene polymorphism identified by PvuII in familial lipoprotein lipase deficiency.

We previously demonstrated that the PvuII polymorphism is a useful marker to analyze the genetic defects in familial lipoprotein lipase (LPL) deficiency. In this study, we have mapped this polymorphic site and cloned the gene fragments containing this site from a patient and a normal subject. Comparative sequence analysis revealed that a C-T transition occurred in the gene of the patient at the PvuII site in the intron 6. Interestingly, the sequence near the PvuII site showed a significant homology to the consensus sequence of the 3' splice site. In addition, the insertional event into the human LPL gene, which was recently reported for a population of Caucasian patients, was not observed for eight unrelated Japanese patients, suggesting that genetic defects underlying familial LPL deficiency should be heterogeneous among races.

Base Sequence↗
PubMed1989

[Evaluation of bone mineral density with dual energy quantitative computed tomography (DEQCT)].

Quantitative computed tomography (QCT) has been found useful in the evaluation of vertebral bone mineral density (BMD). It separates cortical from trabecular bone in the vertebral bodies. The accuracy of QCT, however, is limited because of the existence of unknown amounts of marrow fat in the trabecular bone. The purpose of this study is to investigate the precision and accuracy of QCT, with a particular emphasis on the advantage of dual energy technique over single energy technique, as well as to investigate age-related change of BMD in patients with no metabolic disorders. For evaluation of BMD, SOMATOM DR-H CT scanner was used, which provided dual energy scan with rapid kilovolt peak switching system. The lumbar vertebrae (L1-L3) were exposed at the middle portion together with the calibration phantom (Ca10(PO4)6(OH)2 200 mg/ml, 0 mg/ml). KV-separated images (KV-HI, KV-LO) and material-separated images (MAT-HI, MAT-LO) were calculated from dual-energy scan data. KV-separated data were considered as SEQCT data. In experiment, dipotassium hydrogen phosphate (K2HPO4) solution was used to simulate bone mineral, water to simulate lean soft tissue and ethanol (C2H5OH) to simulate fat. To investigate the variations originating from marrow fat, a series of phantoms (K2HPO4-C2H5OH-H2O mixtures) with a constant 10 gm% K2HPO4 concentration but with the various mixtures of C2H5OH ranging from 0-40% by volume was scanned with dual energy technique. The value of BMD obtained from KV-separated data was reduced about 12% per 10% fat by volume increase, while the value obtained by DEQCT technique was reduced 5.5% per 10% fat by volume increase. With the dual energy technique the error was greatly reduced. On the other hand, the higher precision of KV-separated images compared to MAT-HI images was obtained, as well as the relatively higher precision for determining high rather than low fraction of mineral. In conclusion, with the single energy technique, precision is high, and with the dual energy technique, accuracy is high. It was also noted that selection of the CT section was the most critical factor in clinical BMD analysis. Age-related change of BMD in vertebral trabecular and cortical bone was studied in 161 patients without bone metabolic disorders. There were two peaks of BMD in females in their 20s and 30s, and a single peak in males in their 20s.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1989

Hippocampal kindling enhances excitatory amino acid receptor-mediated polyphosphoinositide hydrolysis in the hippocampus and amygdala/pyriform cortex.

We recently demonstrated that a long-lasting increase in ibotenate-stimulated polyphosphoinositide (PPI) hydrolysis in the amygdala/pyriform cortex (AM/PC) is associated with seizure susceptibility of amygdala (AM)-kindled rats. The present study examined (1) whether ibotenate-stimulated PPI hydrolysis would be lastingly enhanced in the hippocampus (HIPP) and AM/PC of the HIPP-kindled rats and (2) whether similar changes would be found in the early stage of HIPP kindling. Although ibotenate-stimulated accumulation of [3H]inositol 1-phosphate ([ 3H]IP1) increased significantly in the HIPP 24 h, 5 days, and 15 days after the last seizure of fully developed HIPP-kindled rats, no statistically significant increase was found in the HIPP 30 days after the last seizure. In the AM/PC, 10(-3) M ibotenate-stimulated [3H]IP1 accumulation significantly increased by 91%, 91%, 86% and 90%, 24 h, 5 days, 15 days and 30 days after the last seizure, respectively. There was no significant increase in ibotenate-stimulated [3H]IP1 accumulation 7 days after the last stimulation in the HIPP and AM/PC of rats which had undergone electrical stimulation only 5 times in the HIPP. These results indicate that (1) PPI hydrolysis coupled to excitatory amino acid receptors increases long-lastingly in the AM/PC regardless of the primary kindled site, and (2) these changes do not occur in the early stage of HIPP-kindling.

Amygdala↗
PubMed1989

Lasting increase in excitatory amino acid receptor-mediated polyphosphoinositide hydrolysis in the amygdala/pyriform cortex of amygdala-kindled rats.

We previously demonstrated that ibotenate-stimulated polyphosphoinositide hydrolysis, determined as the accumulation of [3H]inositol 1-phosphate, significantly increased in the amygdala/pyriform cortex (AM/PC) 24 h and 7 days after the last seizure in AM-kindled rats. The present study examined whether the increase in ibotenate-stimulated polyphosphoinositide hydrolysis in the AM/PC is longer lasting. AM-kindled rats with a tripolar electrode implanted into the left AM and sham-operated controls were decapitated either 1, 2 or 4 weeks after the last seizure. Ibotenate (10(-3) M)-stimulated accumulation of [3H]inositol 1-phosphate significantly increased by 90% (P less than 0.01), 110% (P less than 0.001) and 73% (P less than 0.05) in the AM/PC 1, 2 and 4 weeks, respectively, after the last seizure. Four weeks after the last seizure, there were significant increases of a similar magnitude in the contralateral (right) AM/PC (by 83%, P less than 0.001) and the ipsilateral (left) AM/PC (by 63%, P less than 0.01). There was no change in the hippocampus or limbic forebrain at any of these times. Also 4 weeks after the last seizure, accumulation of [3H]inositol 1-phosphate significantly (P less than 0.05) increased at ibotenate concentrations of 2 x 10(-4) M, 5 x 10(-4) M and 10(-3) M in the kindled AM/PC. In light of the view that the AM/PC are the crucial brain structures for sustaining seizure susceptibility, the marked and lasting increase in the ibotenate-stimulated polyphosphoinositide hydrolysis coupled to excitatory amino acid receptors in the kindled AM/PC may be associated with the development of kindling and long-term maintenance of kindled events.

Amygdala↗