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Biomedical subjects

K Ichimura

Publications and source records attributed to K Ichimura.

At least 109 records · Page 6Linked to original sources
PubMed1994

CDKN2 (p16/MTS1) gene deletion or CDK4 amplification occurs in the majority of glioblastomas.

Forty-six glioblastomas, 16 anaplastic astrocytomas, and 8 astrocytomas were studied for the loss of the CDKN2 (p16/MTS1) gene on 9p. The CDKN2 locus was homozygously deleted in 19 of 46 glioblastomas (41%) and 1 allele was lost in an additional 13 cases (28%). The deleted regions were limited centromerically in some cases by the MTS2 locus and telomerically by the 1063.7 locus. CDKN2 was homozygously deleted in 3 of 16 anaplastic astrocytomas (19%) and 2 further cases showed loss of 1 allele. Amplification of the CDK4 gene was present in 7 of 14 (50%) glioblastomas and 3 of 11 (27%) anaplastic astrocytomas with no losses at the CDKN2 locus as well as in 2 of 32 (6%) glioblastomas with CDKN2 losses. Thus one or more of these two genes were shown to be aberrant in 85% of glioblastomas and 50% of anaplastic astrocytomas. None of the 8 astrocytomas showed abnormalities of these genes.

Alleles↗
PubMed1994

Amplification of multiple genes from chromosomal region 12q13-14 in human malignant gliomas: preliminary mapping of the amplicons shows preferential involvement of CDK4, SAS, and MDM2.

We have investigated 234 tumors of the central nervous system for amplification of 9 different loci from 12q13-14 and report that about 15% of the anaplastic astrocytomas and glioblastomas show amplification at this chromosomal region. The genes most frequently amplified were CDK4 and SAS (18 of 19 cases). MDM2 was coamplified with CDK4 and SAS in 11 tumors while one glioblastoma showed only MDM2 amplification. Some amplicons additionally included GADD153 (9 cases), GLI (6 cases), A2MR (3 cases), and the anonymous locus D12S8 (2 cases). Either MDM2 or CDK4 and SAS showed the highest amplification level in each individual amplicon and amplification of these genes was consistently accompanied by strong overexpression. Our results thus suggest CDK4, SAS, and MDM2 as main targets for the amplification; however, the possibility exists that all amplicons share a common amplified region between MDM2 and CDK4/SAS which might contain one or more as yet unidentified genes.

Astrocytoma↗
PubMed1994

A common region of homozygous deletion in malignant human gliomas lies between the IFN alpha/omega gene cluster and the D9S171 locus.

Deletions of the 9p-localized type-I interferon (IFN) genes and adjacent loci often occur during the development of malignant glioma. We have applied restriction fragment length polymorphism and microsatellite analysis to 12 loci covering this region of 9p and 3 loci on 9q in 74 human glial tumor tissues to define and further localize the smallest region of hemizygous or homozygous deletion common to the tumors. Three regions of homozygous deletion were evident among the panel of tumors; only one of these, however, residing between D9S171 and the IFN alpha/omega gene cluster, was involved in multiple cases (13 glioblastomas). Hemizygous deletion of this same region was observed in an additional 27 tumors. In total these data indicate the frequent inactivation of a novel tumor suppressor gene residing adjacent to and centromeric of the type-I IFN genes in malignant gliomas.

Alleles↗
PubMed1994

DNA amplifications and elevated expression of proto-oncogene in addition to altered DNA ploidy in metastatic brain tumors.

The histopathological characteristics, proto-oncogene amplification, immunohistopathology of the c-erbB-2 product distribution, and the DNA content of nuclei were examined in metastatic brain tumors, which consisted of seven adenocarcinomas, a large cell carcinoma, a squamous cell carcinoma, a renal cell carcinoma and a mucoepidermoid carcinoma. A very high incidence of DNA changes was seen in these tumors. Proto-oncogene amplification and abnormal DNA content in the nuclear portion were found in 64% (7/11) and 67% (6/9) of cases, respectively. We also found double oncogene alteration in three cases metastasizing from lung, esophagus and kidney, and triple oncogene alteration in one case metastasizing from breast. We could not identify the common alterations in the group of metastatic brain tumor cells. These data suggest that the proto-oncogene amplifications and the alteration of DNA ploidy pattern may contribute to the metastatic process.

Brain Neoplasms↗
PubMed1994

Surgically induced angiogenesis to compensate for hemodynamic cerebral ischemia.

BACKGROUND AND PURPOSE: The ischemic brain may stimulate angiogenesis to compensate for impaired circulation. We examined the conditions promoting such angiogenesis to provide the basis for surgical treatment. METHODS: The degree of cerebral hemodynamic stress was studied in patients with moyamoya disease using the stable xenon-enhanced computed tomographic acetazolamide tolerance test and positron emission tomography. Patients were subjected to surgery in which scalp arteries were placed on the cerebral cortex without vessel-to-vessel anastomosis. Formation of the newly vascularized collateral network connecting the implanted artery to cortical arteries was assessed angiographically 12 to 17 months after surgery. RESULTS: Preoperative average resting cerebral blood flow for cortex that developed revascularization of cortical arteries was not significantly different from that for cortex that did not. However, cortex that developed revascularization had an average preoperative increase of blood flow by acetazolamide treatment of -3.29 +/- 4.6 mL/min per 100 cm3 (n = 20), which was significantly less (P = .0034) than that of cortex that did not show revascularization (20.7 +/- 4.3 mL/min per 100 cm3; n = 9). Good revascularization developed when the cortex showed increase of blood flow by acetazolamide treatment of less than 0 (steal phenomenon). Preoperative positron emission tomography data indicated that revascularization developed when the cortex was under "misery perfusion." Postoperative hemodynamics were ameliorated by revascularization. CONCLUSIONS: Angiogenesis to connect the implanted scalp arteries to the cerebral cortical arteries was selectively initiated when ischemia of hemodynamic origin existed.

Acetazolamide↗
PubMed1994

[Influence of the angle between the nasal cavity axis and nosepiece in acoustic rhinometry].

We evaluated the influence of the angle between the nasal cavity axis and the nosepiece (made with acrylics) in acoustic rhinometry (AR). This study was composed of three experiments. In the first experiment, the influence of angulation on nasal volume was evaluated using a silicone nasal model based on a cast of the nasal cavity of a cadaver. The angle between the nosepiece and the horizontal plane was changed by 10 degrees, 40 degrees or 70 degrees, vertically; the angle between the nosepiece and the sagittal plane was similarly changed horizontally. The nasal volume, obtained as the AR area-distance curve from 6.9-14.1cm, was measured under each condition. While the horizontal change in angle did not significantly influence the result obtained by AR, in the vertical change, the measured value rose as the angle was decreased from 70 degrees to 10 degrees. In the second experiment, an evaluation in healthy subjects (5 males, 4 females, mean age 28.6 years) revealed the same tendency in changing the horizontal angle, whereas vertically a change of 10 degrees produced a significant decrease over that seen with angles of 40 degrees and 70 degrees. This result contradicted that obtained in the model study mentioned above. In studying the effect of changing the vertical angle, the volume of the posterior 5 cm and that of the anterior 2 cm of the nasal cavity was evaluated in the same subjects. The volume of the posterior 5 cm did not differ significantly among angles, while that of the anterior 2 cm showed the same trend as observed with the whole nasal cavity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[Vasoactivity of human nasal mucosa in response to sensory neurotransmitters (a study of nasal geometrical change with acoustic rhinometry)].

Intranasal blood flow is regulated not only by autonomic but also by sensory nervous systems. Sensory neurotransmitters are reported to control resistance vessels. Our investigation of intranasal vasoactivity before and after applying sensory neurotransmitters was conducted using acoustic rhinometry. Acoustic rhinometry is a modern method of evaluating the cross-sectional area and volume of the nasal cavity. Its characteristics are that it is a non-traumatic procedure, minimal time is required for measurements and reliability is high. In the present experiment, calcitonin gene-related peptide (CGRP) and substance P (SP) were used as the sensory neurotransmitters. Six males (26-39 years old), without nasal abnormalities, were examined for one hour with acoustic rhinometry before and after administration of these transmitters. Nose drops of these preparations were introduced into one nasal cavity of each candidates, while in the head tilt position. After application of nose drops, both sides were evaluated with acoustic rhinometry in regard to minimal cross sectional area (MCSA) and nasal volume. Both CGRP and SP decreased the MCSA and volume on the applied side within ten minutes, which was followed by a plateau level for 1 hour. The opposite sides showed no significant change in either MCSA or volume. Changes in the MCSA ratio increased dose-dependently as the concentration of CGRP or SP increased. Changes in the volume ratio decreased when the concentration of SP was increased from 10(-8) to 10(-7) M, while it converted and then rose at 10(-6) M. CGRP has a potent vasodilator effect on vascular smooth muscles. SP also induces relaxation of vascular tone via endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[Combined CDDP-THP-PEP chemotherapy (PTP therapy) for head and neck squamous cell carcinoma--a group study].

A group study of chemotherapy for head and neck squamous cell carcinoma, using CDDP, THP and PEP, was carried out on 32 cases at the department of Otolaryngology, University of Tokyo, and 7 affiliated hospitals. The combined chemotherapy, which we call "PTP therapy", consisted of 30 mg/m2 of THP on day 1, 70 mg/m2 of CDDP on day 2, and 5 mg/body/day of PEP on 4 successive days. The overall response rate was 78.1% (CR: 15.6%; PR: 62.5%). No major side effect was observed in any case. PTP therapy is useful in neoadjuvant chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Effects of laminectomy and retained extradural foreign body on cauda equina adhesion.

The histologic effects of posterior lumbar surgery and retained extradural foreign bodies on the cauda equina were investigated in rats over time. The following four groups of rats were provided: Group 1, sham operation (laminar exposure alone); Group 2, laminectomy alone; Group 3, laminectomy with retained extradural silk thread; Group 4, laminectomy with extradural kaolin; and the control. Histological study was performed on the transverse sections of laminectomized (L5) and nonlaminectomized (L4) areas. In Group 1, adhesive changes involving the cauda equina, consisting of dilatation of nutrient vessels, and eosinophilic exudative changes between the adhering cauda rootlets were seen the day after surgery, but the fibrinous adhesion was resolved spontaneously in all rats after 1 week without permanent sequelae. In Groups 2 and 3, postoperative adhesion of the cauda equina roots was conspicuous, but it resolved by 6 weeks. In Group 4, obvious adhesion persisted through the 12th week after surgery. Destruction of the myelin sheath and axonal loss of the cauda equina occurred in the first week after surgery in all the experimental groups except in the sham group. The severity and extent of the neural degeneration were mostly parallel to the severity of inflammatory changes in the epidural areas. At the nonlaminectomized area (L4) in each group, the arachnoid and cauda equina tended to congregate the day after surgery, but these changes were all transitory. The severity and persistency of the arachnoiditis and neural degeneration directly corresponded to the magnitude of the inflammation and wound healing processes. This seems to imply that careful surgical intervention with no use of foreign bodies is necessary to reduce postoperative adhesive arachnoiditis.

Animals↗
PubMed1993

Amplification and overexpression of the MDM2 gene in a subset of human malignant gliomas without p53 mutations.

The MDM2 (murine double minute 2) gene has recently been shown to code for a cellular protein that can complex the p53 tumor suppressor gene product and inhibit its function. We studied a series of 157 primary brain tumors and report here that the MDM2 gene is amplified and overexpressed in 8-10% of glioblastomas and anaplastic astrocytomas. Thus, MDM2 represents the second most frequently amplified gene after the epidermal growth factor receptor gene in these tumor types. Sequencing of the p53 transcripts in the cases with MDM2 amplification revealed no mutations and restriction fragment length polymorphism analysis showed, with one exception, no losses of alleles on chromosome 17. Our results indicate that amplification and overexpression of MDM2 may be an alternative molecular mechanism by which a subset of human malignant gliomas escapes from p53-regulated growth control.

Astrocytoma↗
PubMed1993

[A simple assay of peroxidase activity in cultured thyroid follicles using tetramethylbenzidine as substrate].

Thyroid peroxidase (TPO) is well known to be an essential enzyme for the biosynthesis of thyroid hormone. The changes of TPO activities in thyroid tissue have already been reported in pathophysiological and experimental conditions by several assay methods. Most of these assay methods, however, need relatively large amounts of tissue (over 10mg wet tissue) to obtain enzyme fraction for assay by homogenization and fractionation of the tissue. Therefore, it is difficult to apply these methods to relatively small numbers (less than 10(6) cells) of thyroid cells. In the present study, we attempted to develop a new and simple method for the assay of TPO activity using tetramethylbenzidine (TMB) as substrate. The reaction mixture were composed of 250 microliters of commercially available tetramethylbenzidine solution containing H2O2 (TM-Blue; TSI-CDP) and 250 microliters of cell lysate obtained by freeze-thawing in 0.1M citrate buffer (pH 4.8). Various doses of known amounts of horseradish peroxidase (HRP; 0-1000 microU) were assayed as a standard at the same time. TPO activity in cell lysate was expressed as the activity corresponding to HRP activity. In this assay method, TPO activity of sonicated-cell lysate was higher than that of nonsonicated-cell lysate, and the activity in sonicated cell lysate was linearly correlated with cell numbers. Next, the effects on the TPO activity of the direct addition of various agents into the reaction mixture were also examined. Both methylmercaptoimidazole (MMI) and NaN3 strongly inhibited TPO activity in sonicated-cell lysate as well as in mitochondria-microsomal fraction of thyroid tissue with the respective IC50 value of less than 5 microM and less than 0.1 mM. In the present method, the authors could demonstrate the following: 1) After 4 days of suspension culture with TSH (0.5 mU/ml), TPO activity of the follicles increased 3.2-5.6 fold when compared with that cultured in the absence of TSH. 2) (Bu)2cAMP (DBC; 1 mM) and forskolin (20 microM) also increased TPO activity of the follicles by 2.9-5.2 and by 2.9-6.2 fold. 3) The addition of NaI (0-100 microM) into medium dose-dependently inhibited the induction of TPO activity by TSH. 4) EGF (10(-8) M) and PMA (10(-6) M) as well as NaI (100 microM) also inhibited the induction of TPO activity in the follicles by TSH, DBC and forskolin during culture for 4 days. Accordingly, it is indicated that these agents may inhibit an induction of TPO activity at least in part at the step of post-cAMP.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Calcification inhibitors in human ligamentum flavum.

To examine the presence of substances which inhibit calcification in human ligamentum flavum, the inhibitory effect of an Na2HPO4 extract of the flavum was determined in terms of the in vitro calcium uptake of the ligamentum flavum matrix. Additionally, grafts of extracted and non-extracted dry ligamentum flavum matrices were transplanted into the dorsal muscles of rats, and calcification in the grafts was examined radiologically and histochemically. In order to determine if component cells of human ligamentum flavum produce calcification inhibitors, ligamentum flavum cells were cultured, and the crystal inhibitor activity of the culture medium was measured by a seed test which used hydroxyapatite as the nucleus of precipitation. The calcification reaction system demonstrated that the ligamentum flavum extract contains an inhibitory factor for calcium uptake by the ligamentum flavum matrix. The seed test revealed that human ligamentum flavum cells produce calcification inhibitor activity.

Adolescent↗