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Biomedical subjects

T Nobori

Publications and source records attributed to T Nobori.

At least 73 records · Page 4Linked to original sources
PubMed1992

Synthesis and pharmacological studies of N-substituted 6-[(2-aminoethyl)amino]-1,3-dimethyl-2,4(1H,3H)-pyrimidinediones, novel class III antiarrhythmic agents.

A series of 6-[(2-aminoethyl)amino]-1,3-dimethyl-2,4(1H,3H)- pyrimidinedione derivatives were synthesized and studied for their class III electrophysiological activity and class II (beta-blocking) effects in in vitro and in vivo models. Structure-activity relationships are discussed for a series of compounds. Several members of this series prolonged the action potential duration at 75% repolarization of isolated canine Purkinje fibers and were 10-30-fold more potent than d-sotalol. 1,3-Dimethyl-6-[[2-[N-[3-(4-nitrophenyl)propyl]-N- (hydroxyethyl)amino]ethyl]amino]-2,4-(1H,3H)-pyrimidinedione (40), is one of the most potent compounds in this series.

Animals↗
PubMed1992

A polymerase chain reaction-based method for isolation of gene-specific sequences from the interferon-alpha gene cluster.

The interferon-alpha gene is a gene family of over 20 distinct genes having 80-95% homology with one another at a nucleotide level. Because of the high homology in the gene cluster, the available interferon-alpha gene probes can hybridize to multiple bands of different size on Southern blot analysis of restricted human genomic DNA. We used the polymerase chain reaction with the primers synthesized from Alu repetitive sequence and the conserved sequences of the interferon-alpha gene cluster to generate specific probes for individual interferon-alpha genes. The amplification products were subcloned into a plasmid vector and analyzed by DNA sequencing and Southern blotting of the restricted human placental DNA. One clone, which derived from interferon-alpha 14 gene, produced a single 5.2-kb band in Southern blots of the HindIII-restricted human placental DNA. This stands in contrast to the 10 bands of different size that were detected with a cDNA for the interferon-alpha I' gene. Our results indicate that a polymerase chain reaction-based method can be used to isolate gene-specific sequences from the interferon-alpha gene cluster. Since a variety of human cancers has been found to have the complete or partial deletion of the interferon-alpha gene cluster, the gene-specific probe generated by this method may aid in determining the breakpoints in the vicinity of the gene cluster.

Animals↗
PubMed1992

Molecular analysis of deletions of the short arm of chromosome 9 in human gliomas.

Previous studies have suggested that structural abnormalities involving the short arm of chromosome 9 are frequently associated with gliomas. The alpha-, beta-, and omega-interferon (IFNA, IFNB1, and IFNW, respectively) and the methylthioadenosine phosphorylase (MTAP) genes have been mapped to the short arm of chromosome 9, band p22. Homozygous deletions of these genes have been reported in many leukemia- and glioma-derived cell lines. In this report, we present a detailed analysis of partial and complete homozygous or hemizygous deletions of DNA sequences on 9p in human cell lines and primary tumor samples of glioma patients. Ten of 15 (67%) glioma-derived cell lines had hemizygous or homozygous deletion of IFN genes or rearrangement of sequences around these genes, while 13 of 35 (37%) primary glioma tumor samples had hemizygous (8 tumors) or homozygous (5 tumors) deletion of the IFN genes. The shortest region of overlap of these deletions maps in the interval between the centromeric end of the IFN gene cluster and the MTAP gene. In the cell lines and primary tumors examined, these gross genomic alterations were seen only in association with high grade or recurrent gliomas. Our observations confirm that loss of DNA sequences on 9p, particularly the IFN genes, occurs at a significant frequency in gliomas, and may represent an important step in the progression of these tumors. These results are consistent with a model of tumorigenesis in which the development or progression of cancer involves the loss or inactivation of a gene or several genes that normally act to suppress tumorigenesis. One such gene may be located on 9p; this gene may be closely linked to the IFN genes. Nevertheless, loss of the IFN genes, when it occurs, may play an additional role in the progression of these tumors.

Brain Neoplasms↗
PubMed1992

A new instrument for use with Nd:YAG in tonsillectomy.

In tonsillectomy, unexpected bleeding can be one of the most troublesome surgical procedures to perform. To resolve some inherent problems, we have developed a new elevator with contact Nd:YAG laser probe for blunt dissection around the tonsillar capsule. Of 63 cases of laser tonsillectomies performed over 5 years, 51 cases were performed using conventional contact Nd:YAG laser probe and a chisel type dissector. Tonsillectomy in the remaining 12 cases was undertaken by the newly developed elevator with contact Nd:YAG laser probe. We compared clinical evaluation between laser and conventional procedures. Additionally, the advantage of laser tonsillectomy is discussed.

Adult↗
PubMed1991

Absence of methylthioadenosine phosphorylase in human gliomas.

All normal mammalian tissues contain methylthioadenosine phosphorylase, which plays a role in the recycling of purines and methionine consumed during polyamine synthesis. A complete deficiency of methylthioadenosine phosphorylase has been reported in some human leukemias and lymphomas and in a few solid tumors. The exact incidence of the enzyme deficiency among fresh human tumor specimens has been difficult to establish because the measurement of enzyme catalytic activity is laborious and requires carefully preserved specimens. We have generated two antibodies against methylthioadenosine phosphorylase and have used them to develop a simple immunoblot assay for the enzyme. Specifically, studies showed that all cells with catalytically active methylthioadenosine phosphorylase had a 32-kDa band that reacted with the anti-enzyme antibodies. In a reciprocal manner, all malignant cell lines that were naturally deficient in methylthioadenosine phosphorylase activity lacked detectable immunoreactive enzyme protein. The immunoassay was used to analyze human gliomas. Seventy-five % (9 of 12) of the gliomas were completely methylthioadenosine phosphorylase deficient. This common metabolic difference between most gliomas and all normal cells is a potential target for tumor-specific chemotherapy.

Animals↗
PubMed1991

A polymorphic region defined by pCN2 (the 3' nontranslated region of N-ras) maps to chromosome 9cen-p12.

Abnormalities of chromosome 9p have been reported in human leukemias and lymphomas, and in cell lines lacking the enzyme methylthioadenosine phosphorylase. It has been shown pCN2, the 3' nontranslated region of the N-ras oncogene, crosshybridizes with unknown DNA segments on chromosome 6, 9p, and 22, in addition to the N-ras oncogene itself on chromosome 1p. To use pCN2 to study chromosome 9p abnormalities in malignancies, we undertook to localize the pCN2 crosshybridizing region in chromosome 9p. By analyzing the copy numbers of the pCN2 crosshybridizing bands associated with chromosome 9p among various chromosomally aberrant human cell lines, we mapped the pCN2 hybridizing region to 9cen-p12. Since there is no other available probe in this region, pCN2 should prove very useful in studying abnormalities of chromosome 9p in human malignancies.

Blotting, Southern↗
PubMed1990

[Sensorineural hearing loss following the decompression of the facial nerve].

This study aims to ascertain whether sensorineural hearing loss occurs after the decompression of the facial nerve. Nine patients have undergone decompression of the facial nerve (limited to the vertical segment) by the transmastoid approach were selected as the subjects of this study because the influence of disinfectants and surgical trauma on the inner ear seems to be less severe in this operation than in tympanoplasty. Additionally, this approach seems to be more suitable for judgement of the effect of the drilling noise induced acoustic trauma on the inner ear than tympanoplasty. Though high tone abrupt sensorineural hearing loss was occurred in the operated ear in seven patients, no changes in hearing level were found in the contralateral side ear. Bekesy audiometry performed in only one case revealed Jerger II which suggested some disorder in the cochlea. Not only acoustic trauma induced by the drilling noise but also labyrinthitis occurred via the opened facial canal and the internal ear canal seemed to be the cause of sensorineural hearing loss following the decompression of the facial nerve.

Adult↗
PubMed1990

[A comparative study of UFT enteric-coated granules with UFT capsules on the occurrence of side effects in patients with head and neck cancers--a special attention to the upper gastrointestinal tract disorders].

A comparative study on the occurrence of gastrointestinal side effects between UFT enteric-coated granules (UE) and UFT capsules (UC) was made by crossover method in 50 patients with head and neck cancer who were treated by these drugs as a surgical and/or radiation adjuvant chemotherapy. UE was significantly low in the occurrence of upper gastrointestinal side effects; remarkably low in such side effects as nausea and vomiting, in particular. On the other hand, there was little difference between UE and UC in the occurrence of such side effects as diarrhea, stomatitis, dry mouth and hematotoxic signs. The present result suggests that UE is clinically useful for treating the patients with cancer, with less occurrence of gastrointestinal side effects.

Adult↗
PubMed1989

Poly(ADP-ribose) polymerase inhibits DNA synthesis initiation in the absence of NAD.

Poly(ADP-ribose) polymerase (ADPRP) is a nuclear enzyme that transfers ADP-ribose from NAD+ to diverse nuclear proteins. Previously, the function of ADPRP was considered to relate exclusively to its catalytic activity. However, recent experiments have shown that ADPRP is actually an abundant DNA-binding protein, and that the potential catalytic activity of the enzyme is more than 100-fold greater than the measured rates of NAD+ turnover in intact cells. To better understand the role of ADPRP, we have used highly purified ADPRP and a monospecific autoantibody to examine the effects of ADPRP on in vitro DNA synthesis in the presence or absence of NAD+ substrate. The data show that DNA synthesis initiation is blocked by ADPRP and that auto-poly (ADP-ribosyl)ation reverses the process by diminishing the DNA binding capacity of the protein. These results suggest that ADPRP actually is a structural DNA binding protein, whose catalytic activity serves to modulate its interaction with DNA.

Animals↗
PubMed1988

Laserthermia on head and neck malignancies--experimental and clinical studies.

In recent years, remarkable progress has been made in thermotherapy. However, there is little information on localized laser hyperthermia (laserthermia) or on conventional hyperthermia technique applied to head and neck cancers. We have developed a ceramic probe to insert into tumor tissue and irradiate the Nd:YAG laser omnidirectionally. This probe can heat a spherical range of 1.5 cm to 43 degrees C. This paper concerns experimental and clinical studies on the effectiveness of laserthermia using our technique in the tumor of head and neck regions. The results obtained were as follows: histological findings and biochemical studies of arachidonic acid metabolites on normal rabbit tongue after laserthermia showed very slight effect and relatively short duration of the concomitant inflammation. The combination of laserthermia and CDDP chemotherapy was found to give a much better cytocidal effect on the tumor tissue in nude mice implanted with human thyroid cancer cells. In a clinical study on 21 cases with head and neck cancers, four cases showed complete and 13 cases showed partial remission after combined treatments of laserthermia and radiochemotherapy. Both basic experimental and clinical results have indicated a role for laserthermia in the treatment of head and neck cancer. Possible uses include the treatment of early cancer as well as advanced or recurrent cancer, where its therapeutic effect may be increased by combination with radiotherapy or chemotherapy.

Animals↗
PubMed1988

Incorporation of N4-behenoyl-1-beta-D-arabinofuranosylcytosine into DNA as 1-beta-D-arabinofuranosylcytosine.

BHAC is a newly synthesized lipophilic derivative of ara-C. To clarify its pharmacological mode of action, P388 murine leukemic cells were incubated with two different types of 14C-labeled BHAC, [cytosine-2-14C]BHAC and [acyl-1-14C]BHAC, and DNA was extracted with phenol. The phenol-extracted DNA was then hydrolyzed by nuclease P1 and analyzed with high-performance liquid chromatography (HPLC). The radioactivity of DNA, from the cells incubated with [cytosine-2-14C]BHAC, was detected as ara-CMP. But the radioactivity of DNA, from the cells incubated with [acyl-1-14C]BHAC, was hardly detected. On the other hand, the main radioactivity of the acid soluble fraction was determined as ara-CTP. On the basis of our results, BHAC is not phosphorylated directly to produce N4-behenoyl-ara-CTP, but is mainly converted to ara-C which subsequently produces ara-CTP, the active metabolite of the drug, and which is then incorporated into DNA.

Animals↗
PubMed1988

[A phase II study of Futraful suppository in head and neck cancer].

A phase II study of FT-207 suppository (Futraful Suppository) for head and neck cancer was conducted at the Kagoshima University Hospital Dept. of Otorhinolaryngology and its 6 affiliated hospitals. Forty cases with head and neck cancer were entered in the trial, of which 37 were perfectly evaluable. Partial response (PR) (16.7%) was achieved in one of 6 patients with maxillary cancer, in 2 of 9 cases with oral cancer (22.2%), in one of 7 with laryngeal cancer (14.3%), in 3 of 13 with pharyngeal cancer, while 2 of the same 13 achieved a complete response (CR) (38.5%), for a total response rate of 24.3%. FT-207 suppository was continuously administered as standard, at a dose of 750 mg each twice daily, or 1,500 mg/day. The response rate was dose-dependent; 2 CR cases with a total dose of 105 g for administration over a total period of more than 150 days. Adverse effects appearing in 35.0% of the overall were mainly anorexia, nausea and vomiting; none of them, however, were serious.

Aged↗
PubMed1988

[Experimental and clinical studies on laserthermia in head and neck cancers].

A synthetic ceramic probe allows a wider angle of irradiation and diffusion of low power energy, below 3W, using an interstitial technique for producing local hyperthermia of Nd: YAG laser (Laserthermia). We studied the influences of this laserthermia procedure in experimental animals and patients with head and neck cancer. The histological findings after laserthermia in the rabbit tongues showed no marked tissue damage in the heated area. Biochemical analysis of arachidonic acid cascade metabolites in these tissues revealed an immediate increase of 12-, 15- HETEs and PGE2 and 3 at days after hyperthermia, but at 8 days these metabolites returned to control levels. The effectiveness of laserthermia on human thyroid cancer implanted in nude mice was compared with that in cisplatin treatment and in combined therapy with both. The most predominant effectiveness was found in the animals receiving therapy combining cisplatin and laserthermia. Laserthermia in combination with radio-chemotherapy was applied in 21 cases with head and neck cancer. Good efficacy was obtained in 17 patients, especially in those with oropharyngeal cancer, showing CR in 4 cases and PR in 13 cases.

Animals↗
PubMed1987

Cross-resistance to ouabain in a murine leukemia cell variant selected for cis-dichlorodiammineplatinum(II) resistance.

A murine leukemic cell line (R1.1) variant (R1.1/CDDPR-E8) resistant to cis-dichlorodiammineplatinum(II)(CDDP) was also found to be resistant to ouabain, a postulated specific inhibitor of sodium-potassium ATPase. The variant established by the culture of parental cells in step by step increasing concentrations of CDDP, exhibited 11-fold higher resistance to CDDP than the parental R1.1 cells. The present study suggests that a mutational change leading to an alteration in cell membrane characteristics associated with ouabain has also changed the sensitivity of cells against CDDP. Alternatively, the present data may indicate that the cytotoxicity of CDDP is closely linked to its effects on cell membrane.

Animals↗