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Biomedical subjects

K Ichimura

Publications and source records attributed to K Ichimura.

At least 91 records · Page 5Linked to original sources

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↗

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↗

[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↗

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↗

Capillary permeability in experimental rat glioma and effects of intracarotid CDDP administration on tumor drug delivery.

We have examined the capillary permeability within and adjacent to experimental rat gliomas, and the effect of intracarotid administration of cisplatin in this model. Permeability to 14C-sucrose was 25-fold and six-fold higher within the brain tumor and in the tumor periphery and adjacent tissue respectively than in the normal cortex. Intracarotid administration of cisplatin resulted in ten-fold increase in experimental gliomas and also a significant increase in the tumor periphery and adjacent tissue, when compared to the intravenous route. Intracarotid administration of cisplatin to rat did not cause acute vascular damage in either the brain or brain tumor at the dosage used.

Animals↗

Can Rouvière's lymph nodes in non-malignant subjects be identified with MRI?

The lateral retropharyngeal lymph nodes lie between the carotid artery and prevertebral muscles. These are most obvious anterior to the arch of C1, but can be seen to the level of the soft palate. The uppermost-positioning nodes anterior to the atlas are called as the nodes of Rouvière. Introduction of CT and MR has provided us the chance to detect them. In order to find out the frequency of identifying them in normal subjects, I examined axial MR images which had been taken for the last 3 years. A total of 90 patients (86 adults and 4 children) with a variety of diseases except for malignancies were selected. All 4 children showed Rouvière's nodes bilaterally, while only 5 of 86 adults (5.8%) depicted them. The lymph nodes were identified as isointense masses as nasopharyngeal lymphoid tissues (adenoids), when presented, with the size ranged from 4 to 13 mm. The nodes with a diameter of 5 mm or more were easily identified particularly with T2-weighted images. The benign reactive adenopathy appeared indistinguishable from that demonstrated in patients with malignant tumors in the head and neck.

Adolescent↗

Trismus in patients with malignant tumours in the head and neck.

In order to elucidate the causal mechanism of trismus in head and neck cancer, 21 patients manifesting trismus out of 212 patients with malignant tumours in the head and neck (treated in Tokyo University Branch Hospital from 1983 to 1991) were reviewed. Nine patients developed trismus either by infiltration of the muscles of mastication or by reflex spasm. Trismus was considered to have developed as a result of irradiation in five cases and of surgical intervention in seven cases. In some cases of oropharyngeal cancer, CT revealed no evidence of tumour invasion into the infratemporal fossa when trismus occurred, suggesting that trismus was caused either by the reflex spasm of muscles or by microinvasion too small to be seen in CT films. Maxillary sinus tumours were often without trismus even when they extended posteriorly to the infratemporal fossa.

Adult↗

Inhibition of the multidrug efflux pump in isolated hepatocyte couplets by immunosuppressants FK506 and cyclosporine.

Fluorescence image analysis of isolated rat hepatocyte couplets, which retain a bile canaliculus between them, has shown the presence of transport systems for the bile acid and non-bile acid organic anion in the canalicular membrane. The cells also transported Fura-2 and BCECF, which are fluorescent indicators of intracellular Ca2+ and H+ concentrations, respectively, into the canaliculus. Both Fura-2 and BCECF transports were inhibited by progesterone, verapamil, vinblastine, and daunomycin, indicating that the transports are due to a multidrug efflux pump (P-glycoprotein) in the canalicular membrane. Interestingly, the transport by the multidrug efflux pump was inhibited by immunosuppressants FK506 (tacrolimus) and cyclosporine, their half-maximal inhibitory concentrations in the cell suspension being 10 microM and 0.6 microM, respectively. In contrast, the reported immunosuppressive potency of FK506 is 10- to 100-fold that of cyclosporine. Inhibition by immunosuppressants of the multidrug efflux pump, which is a transporter of cytotoxic and other drugs and present in normal human tissues--such as kidney, liver, the blood-brain barrier, and colon--may, at least partly, explain side effects caused by cyclosporine in these tissues of transplant recipients. FK506 at its clinical concentrations may not inhibit the multidrug efflux pump.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Low incidence of seizures in patients with chronic subdural haematoma.

A total of 129 patients treated for chronic subdural haematoma were studied retrospectively to evaluate the incidence of seizures. None of 73 patients who were given prophylactic antiepileptic drug treatment developed seizures. Only two of 56 patients not given prophylaxis, developed early postoperative seizures. In these two, surgical technique was thought to be responsible. One patient developed complex partial seizures preoperatively. The incidence of seizures was therefore low, and similar to that previously reported for minor head injury. This study suggests that routine use of antiepileptic prophylaxis is not justified in patients with chronic subdural haematoma caused by minor head injuries, or other causes when there are no additional lesions present on CT scans.

Adolescent↗

[Surgical approach to the nasal valve stenosis].

Nasal valve, originally defined by Mink (1903), has changed its concept and is now regarded as slit-like opening between the caudal end of the upper lateral cartilage and the septum. Contrary to Caucasians whose smallest area of the nose lies at the nasal valve, the narrowest part of Japanese nose situates at the area between the anterior portion of the inferior turbinate and the septum. Thus, we have fewer chance to experience patients with stenotic nasal valve. Six patients complaining nasal obstruction resulted from nasal valve stenosis, mainly due to dislocated or collapsed upper lateral cartilage, underwent surgery during the last 2 years and a half. Cases of septal deformity, even it it produced valve stenosis, were excluded in this study. Surgical intervention was directed toward reconstruction of normal anatomic relationships, usually by widening the nasal valve angle and preventing collapsibility. Three underwent open rhinoplasty with gull-wing columellar skin incision, whereas 3 others were operated on via transnostril approach. History of midfacial trauma caused us to choose open rhinoplasty for restoring the function and structure. Immediate postoperative result was excellent in the aspect of appearance and subjective data regardless of surgical approach. Open rhinoplasty provided a splendid long-term result without remarkable complications. On the other hand, 2 cases operated via transnostril approach complained recurrence of stuffy nose.

Adult↗

[Evidence for the presence of endothelium-derived relaxing factor in nasal blood vessels].

It has widely been recognized that the vascular endothelium plays an important role in the regulation of vascular tension. Endothelium-derived relaxing factor (EDRF) is a potent vasodilator produced by vascular endothelial cells in response to acetylcholine (ACh) and a variety of other substances. Recent studies have indicated its pharmacological and biochemical effect on vascular smooth muscle tension. The role of the vascular endothelium in the vasodilatory response to ACh stimulation was studied in isolated mucosa from the canine nasal fossa. (1) In the presence of intact endothelium, dose-dependent relaxation was induced by administration of ACh (10(-8)-10(-5)M) under sustained constriction by methoxamine. (2) After endothelial cell injury had been induced by administration of 15-hydroperoxyeicosa tetraenoic acid (15-HPETE), the relaxing response to ACh was abolished with the induction of contraction. (3) Pretreatment with a cyclo-oxygenase inhibitor (indomethacin) did not change the vasodilatory response to ACh stimulation. These results indicate that endothelium is necessary for relaxation in response to ACh, and suggest the presence of EDRF in vessels of the canine nasal mucosa.

Acetylcholine↗

[Molecular biological analysis of neurofibromatosis type 2 gene].

Neurofibromatosis type 2 is a hereditary disorder characterized by bilateral vestibular and other schwannomas as well as various other central nervous system neoplasms such as gliomas, meningiomas, and neurofibromas. The region containing the NF2 gene has been localized to 22q12 both by linkage analysis and deletion mapping of NF2-related tumors. Recently a candidate gene, named Merlin, was cloned by means of defining a constitutional interstitial deletion in an NF2 patient. The Merlin gene product belongs to a family of proteins which include moesin, ezrin and radixin, involved in linking the cytoskeleton to the cell membrane. Merlin thus forms a novel class of tumor suppressor genes, and an analysis of its function in vivo and the clinical implications of its loss in schwannoma cells remains to be explored.

Cell Line↗

Plasma endothelin-1 concentration in the inferior turbinate.

Endothelin (ET)-1 has the most potent vasocontrictive action of any substance known to date. Three milliliters of blood was removed from both the inferior turbinate and from the antecubital vein of six patients who underwent nasal surgery under general anesthesia. After centrifugation of the blood samples, the plasma was sent for radioimmunoassay of the plasma levels of ET-1. The plasma ET-1 level in the nasal blood vasculature was 6.4 +/- 1.0 pg/mL (mean +/- SEM), which was almost equivalent to that found in the antecubital vein (5.3 - 2.7 pg/mL) (N = 6). These values were greater than the normal range (1.5 +/- 0.5 pg/mL) probably because of the effect of general anesthesia. These results indicate that ET-1 is present in similar levels in the blood vessels of the inferior turbinate and the antecubital vein. A hypothesis that adrenaline induces ET production was not confirmed because topically applied adrenaline did not raise the plasma ET-1 level either in the nasal vasculature or in the peripheral vein.

Adult↗

Constitutional translocation t(4;22) (q12;q12.2) associated with neurofibromatosis type 2.

We report on a female patient with bilateral acoustic neurinomas and other tumors in the central nervous system (neurofibromatosis type 2: NF2) and the constitutional translocation, t(4;22) (q12;q12.2). The precise identification of the translocation breakpoint (q12.2) on chromosome 22 implies the refined localization of a gene responsible for NF2, and would provide a clue to its molecular characterization and to the isolation of the gene. Chromosomes of a paraspinal neurinoma from the patient were also analyzed, and the same karyotype as seen in cultured peripheral lymphocytes was found. The patient's father was also a carrier of the translocation, but he had no clinical symptoms of NF2, nor did other relatives. Several explanations are offered for the different expression of the translocation between the patient and her father.

Adult↗

Effects of inorganic iodide, epidermal growth factor and phorbol ester on hormone synthesis by porcine thyroid follicles cultured in suspension.

Porcine thyroid follicles cultured in suspension for 96 h synthesized and secreted thyroid hormones in the presence of thyrotropin (TSH). The secretion of newly synthesized hormones was assessed by determining the contents of thyroxine (T4) and triiodothyronine (T3) in the media and by paperchromatographic analysis of 125I-labelled hormones in the media where the follicles were cultured in the presence and absence of inhibitors of hormone synthesis. The hormone synthesis and secretion was modified by exogenously added NaI (0.1-100 microM). The maximal response was obtained at 1 microM. Thyroid peroxidase (TPO) activity in the cultured follicles with TSH for 96 h was dose-dependently inhibited by NaI. One hundred microM of NaI completely inhibited TSH-induced TPO activity. Moreover, both epidermal growth factor (EGF: 10(-9) and 10(-8) M) and phorbol 12-myristate 13-acetate (PMA: 10(-8) and 10(-7) M) inhibited de novo hormone synthesis. An induction of TPO activity by TSH was also inhibited by either agent. These data provide direct evidences that thyroid hormone synthesis is regulated by NaI as well as TSH at least in part via regulation of TPO activity and also that both EGF and PMA are inhibitory on thyroid hormone formation.

Animals↗