Biomedical subjects

S Matsubara

Publications and source records attributed to S Matsubara.

At least 199 records · Page 11Linked to original sources

PubMed1996

Experimental autoimmune myositis in SJL/J mice produced by immunization with syngeneic myosin B fraction. Transfer by both immunoglobulin G and T cells.

An experimental autoimmune myositis (EAM) was produced by immunizing SJL/J mice with the myosin B (MB) fraction of the syngeneic muscle. Immunoblot analysis of the IgG of the EAM mice demonstrated antibodies against a variety of muscle proteins. The condition was then transferred to normal mice by both injecting immunoglobulin G or T cells from the EAM mice. This is the first model of transferrable EAM caused by syngeneic muscle fraction, and it has an unique resemblance to human inflammatory myopathies involving both humoral and cellular immune mechanisms.

Animals↗

PubMed1996

Expression of a photoreceptor protein, recoverin, as a cancer-associated retinopathy autoantigen in human lung cancer cell lines.

Recently, a photoreceptor protein, recoverin, has been recognised as an autoantigen of cancer-associated retinopathy (CAR), a rare paraneoplastic neurological syndrome often associated with patients with small-cell lung cancer (SCLC). Although until quite recently the specific expression of recoverin in cancer cells had not been indicated, Polans et al. (Polans AS, Witkowska D, Haley TL, Amundson D, Baizer L, Adamus G 1995, Proc. Natl. Acad. Sci. USA, 92, 9176-9180) demonstrated the specific expression of recoverin in lung tumour and primary cultured tumour cells from a CAR patient. We examined the expression of recoverin in human lung cancer cell lines by reverse transcription polymerase chain reaction (PCR), Northern blotting and Western immunoblotting. Recoverin was expressed in only one SCLC cell line from a patient with CAR. The sequence of recoverin cDNA from the cells was identical to the human recoverin sequence. These findings strongly support the hypothesis that the ectopic expression of wild-type recoverin in SCLC induces the cancer-retina immunological cross-reaction, leading to visual loss in CAR.

Biomarkers, Tumor↗

PubMed1996

Association between the direction of orthopedic headgear force and sutural responses in the nasomaxillary complex.

This study was designed to investigate biomechanical responses of the sutures in the nasomaxillary complex to orthopedic headgear forces applied in various directions. A three-dimensional analytic model of the craniofacial complex was used for finite element analysis. A posteriorly-directed force of 1.0 Kgf was applied to the maxillary first molars in 30 degrees inferior, parallel, and 30 degrees, 52.4 degrees and 60 degrees superior directions to the functional occlusal plane. Mean principal and shear stresses were evaluated at the sphenozygomatic, temporozygomatic, sphenomaxillary, frontomaxillary and frontozygomatic sutures and lamina cribrosa. As the force direction passed closer to the center of resistance (CRe) of the complex (52.4 degrees superior direction). normal stresses approached a certain level of uniform compressive stress (-2.5 gf/mm2) with gradual decrease in shear stresses, whereas variation in these stresses produced by the forces applied in other horizontal and inferior directions was greater. It is shown that stresses in the nasomaxillary sutures are varied by the direction of headgear force. Directing the line of force closer the CRe may produce the most optimal sutural modification effective for controlling forward and downward maxillary growth.

Biomechanical Phenomena↗

PubMed1996

Dexamethasone increases growth hormone (GH)-releasing hormone (GRH) receptor mRNA levels in cultured rat anterior pituitary cells.

To examine the effects of glucocorticoid (GC) on growth hormone (GH)-releasing hormone (GRH) receptor gene expression, a highly-sensitive and quantitative reverse-transcribed polymerase chain reaction (RT-PCR) method was used in this study. Rat anterior pituitary cells were isolated and cultured for 4 days. The cultured cells were treated with dexamethasone for 2, 6, and 24 h. GRH receptor mRNA levels were determined by competitive RT-PCR using a recombinant RNA as the competitor. Dexamethasone significantly increased GRH receptor mRNA levels at 5 nM after 6- and 24 h-incubations, and the maximal effect was found at 25 nM. The GC receptor-specific antagonist, RU 38486 completely eliminated the dexamethasone-induced enhancement of GRH receptor mRNA levels. Dexamethasone did not alter the mRNA levels of beta-actin and prolactin at 5 nM for 24 h, whereas GH mRNA levels were significantly increased by the same treatment. The GH response to GRH was significantly enhanced by the 24-h incubation with 5 nM dexamethasone. These findings suggest that GC stimulates GRH receptor gene expression through the ligand-activated GC receptors in the rat somatotrophs. The direct effects of GC on the GRH receptor gene could explain the enhancement of GRH-induced GH secretion.

Actins↗

PubMed1996

Induction of sister chromatid exchange in the presence of gadolinium-DTPA and its reduction by dimethyl sulfoxide.

RATIONALE AND OBJECTIVES: The authors investigate the frequency of sister chromatid exchange (SCE) after the addition of gadolinium (Gd)-DTPA to venous blood samples. METHODS: Venous blood was obtained from nonsmokers. Samples were incubated with Gd-DTPA alone or in combination with mitomycin C, cytarabine, and dimethyl sulfoxide (DMSO), and then evaluated for SCEs. RESULTS: The frequency of SCE increased with the concentration of Gd-DTPA and as each chemotherapeutic agent was added. Sister chromatid exchange frequencies were lower when the blood was treated with a combination of Gd-DTPA and DMSO compared with Gd-DTPA alone. DISCUSSION: The increase in frequency of SCE seen after the addition of Gd-DTPA was decreased by the addition of DMSO, indicating the production of hydroxyl radicals. The effect likely is dissociation-related.

Cells, Cultured↗

PubMed1996

Dose distribution and shrinkage of acoustic neurinomas 2 years after Gamma Knife treatment.

To examine the relationship between dose distribution and tumor shrinkage of acoustic neurinomas, correlation coefficients between distribution probabilities of some dose areas and residual tumor ratios of 21 cases were studied at 2 years. Approximating a dose-volume histogram to beta-distribution, two essential dose areas for tumor control were extracted: a dose area from 14.2 to 24.7 Gy contributed to tumor shrinkage, whereas a dose area from 27.3 to 29.4 Gy was contraindicated. Given that there are at least two different dose areas with reverse characters, a formula with two opposing logistic components is proposed to predict tumor control. With this formula, Gamma Knife treatment of acoustic neurinomas may be optimized.

Adult↗

PubMed1996

Immunosuppressant agent FK506 stimulates growth hormone (GH) secretion and gene expression of hypothalamic GH-releasing hormone in the rat.

Immunosuppressant agent FK506 has been reported to stimulate ACTH release from pituitary cells. We examined the effects of FK506 on GH release from the rat anterior pituitary cells and the effects of FK506 on hypothalamic GH- releasing hormone (GRH) and somatostatin (SS) gene expression in conscious male rats. In vitro experiments, the monolayer pituitary culture and reverse hemolytic plaque assay were employed to examine the GH release from the rat anterior pituitary cells. In in vivo experiments, the FK506 was administered for 7 days and then sequential blood sampling was performed every 20 min during 6 h in conscious rats. The hypothalamus was removed, and total RNA was extracted for Northern blot analysis. The FK506 significantly stimulated GH release from the rat anterior pituitary cells in a dose-dependent manner in vitro. In in vivo experiments, the area under the curve of GH surges was significantly increased in FK506-treated rats, although the peak height and the trough level of GH surges were not altered. Pituitary GH messenger RNA (mRNA) levels were significantly increased by the FK506 treatment. Hypothalamic GRH mRNA levels were significantly increased in FK506- treated rats, whereas hypothalamic SS mRNA levels were not altered. These findings indicate that FK506 stimulates GH secretion and gene expression of hypothalamic GRH in the rat.

Animals↗

PubMed1996

[Clinical and myopathological studies on rigid spine syndrome].

Rigid spine syndrome (RSS) is thought to be a group of heterogeneous muscle disorders. We reviewed the clinical and myopathologic findings of 55 patients with RSS including 49 previously reported and our own 6 patients. The results were as follows: the first, 80% showed restrictive ventilatory failure and 40% atrophy of the sternocleidomastoid muscle (SCM), which became manifest in the early stage of the illness, namely in less than 5 years from the onset. The second, paraspinal muscles usually began to be involved from the cervical semispinal muscle extending to other paraspinal muscles such as the more laterally located splenium muscle. The third, muscle biopsy demonstrated rimmed vacuoles (RV) in 41% of the 55 patients. RV were more frequently seen in the paraspinal muscles than the limb muscles, where marked myopathic changes of endomysial fibrosis and increased variation of the muscle fiber size were recognized. Based on the anatomical analysis of the paraspinal muscles, alligator sign, a radiological finding of the posterior opening between the cervical spine C1 and C2, seemed to result from the shortening of the cervical semispinal muscle due to its degeneration. This sign may, however, disappear as the whole paraspinal muscles including the semispinal muscles are affected. The RV seen in RSS seems to be a secondary, nonspecific structure related to the muscle degeneration. On the other hand, the above findings, namely the atrophy of SCM, restrictive ventilatory failure, and RV, have not been reported in Emery-Dreifuss muscular dystrophy (EDMD) so far. Accordingly, those findings and the absence of cardiac conduction abnormality are valuable for differential diagnosis of RSS from EDMD.

Adult↗

PubMed1995

A comparison of biological effects of modulated carbon-ions and fast neutrons in human osteosarcoma cells.

PURPOSE: To compare the biological effects of a 135 MeV/u carbon-ion beam and 13 MeV fast neutron beam using human osteosarcoma cells. METHODS AND MATERIALS: We have studied the clonogenic cell survival, recovery of potentially lethal damage (PLD) in plateau phase cells, and spheroid cure in multicellular spheroid after irradiation at various positions in the plateau and spread out Bragg peak (SOBP) of a 135 MeV/u carbon-ion beam and with 13 MeV neutrons. The carbon beam had a 4-cm range in water and a range filter was used to produce a 3-cm extended-peak region. The reference radiation was 137Cs gamma-rays. RESULTS: The relative biological effectiveness (RBE) values for 10% survival level of plateau phase cells for carbon-ions at the position of plateau, proximal peak, midpeak, and distal peak within the SOBP, and neutrons were 1.71, 2.48, 2.63, 3.47, and 2.29, respectively. Corresponding RBE values at 1% level were 1.64, 1.93, 2.06, 2.49, and 2.05. The extent of recovery from PLD was reduced after carbon-ions at proximal peak, midpeak, and distal peak, and neutrons, although not substantially reduced after carbon-ions at plateau. The RBE values for 50% spheroid cure level of spheroids for carbon-ions at the position of plateau, proximal peak, midproximal peak, middistal peak, and distal peak within the SOBP, and neutrons were 1.69, 1.88, 1.87, 1.94, 2.03, and 1.90, respectively. CONCLUSIONS: The biological parameters measured all indicate an approximately comparable biological effectiveness between 75-80 KeV/microns carbon-ions of the SOBP and 13 MeV neutrons in the human tumor model studied in vitro.

Carbon↗

PubMed1995

Late rectal complication following high dose rate intracavitary brachytherapy in cancer of the cervix.

PURPOSE: To examine the incidence of radiation-induced late rectal complications using a rectal reference point in patients with cancer of the uterine cervix. METHODS AND MATERIALS: The subjects were 253 patients with cancer of the cervix who underwent high dose rate intracavitary brachytherapy (HDR-ICR). The rectal point (RP) was defined according to the criteria recommended in the ICRU Report 38. The time-dose factor (TDF) and the biologically effective dose (BED) were calculated as components of the cumulative reference rectal dose using the rectal reference point dose in intracavitary brachytherapy combined with the external whole pelvis dose. RESULTS: Statistical comparison of factors affecting the incidence of late rectal complication was conducted using data for 161 patients. The incidence of late rectal complications in the 161 patients was 9 patients (5.6%) for grade 1, 51 patients (31.7%) for grade 2, 11 patients (6.8%) for grade 3, and 13 patients (8.1%) for grade 4. The TDF and BED values were significantly correlated with the incidence of late rectal complication, and also showed strong correlation (r = 0.976) with each other. Grade 4 rectal complication was not observed in any patients with TDF below 130 or BED below 147. The calculated incidence of complications ranged from 5 to 10% at TDF values from 104 to 124 and at BED values from 119 to 146. CONCLUSION: These data regarding the incidence of rectal complication may be useful in reducing the incidence of late rectal complications arising after HDR-ICR treatment of cervical uterine cancer by adjusting the dose per fraction and number of fractions of HDR-ICR in individual patients and by improving the technique of inserting the intracavitary radiation apparatus.

Female↗

PubMed1995

Characterization of [3H]clozapine binding sites in rat brain.

We examined the characteristics of [3H]clozapine binding sites in four rat brain regions (frontal cortex, limbic area, hippocampus and striatum) in order to elucidate the pharmacological profile of this unique atypical antipsychotic drug. The specific [3H]clozapine binding was found to be saturable and reversible in all these brain regions. Scatchard analysis of the saturation data indicated that the specific binding consisted of high- and low-affinity components. Displacement experiments showed that the muscarinic cholinergic receptor represented about 50% of [3H]clozapine binding in each brain area. Serotonin 5-HT2 and dopamine D4 receptor binding sites could also be detected by displacement experiments using ketanserin and nemonapride, respectively, in frontal cortex and limbic area, but not in hippocampus or striatum. Alpha-1, alpha-2, histamine H1, dopamine D1, D2, or D3 receptor components could not be determined within the high-affinity [3H]clozapine binding sites in any brain region. It is possible that the atypical property of clozapine may depend on the modulatory effect on dopaminergic function via 5-HT2 receptor blockade and/or may be mediated via D4 receptor blockade in the mesocortical and mesolimbic area.

Animals↗

PubMed1995

Long-term treatment with haloperidol or clozapine does not affect dopamine D4 receptors in rat frontal cortex.

We examined the effects of long-term treatment with haloperidol and clozapine on dopamine D4 receptors in rat frontal cortex. Dopamine D4 receptor binding sites were indirectly determined from the displacement experiments of [3H]clozapine binding using nemonapride. Three-weeks administration of haloperidol (0.5 mg/kg) or clozapine (10 mg/kg) did not significantly affect the D4 receptors in the frontal cortex. The density of D2 receptors, determined by [3H]spiperone binding to striatum, was increased by long-term treatment with haloperidol, but it was not significantly changed by that with clozapine.

Animals↗

PubMed1995

A retinoic acid-responsive element in human midkine gene.

Midkine is a growth/differentiation factor which is found as a product of a retinoic acid-responsive gene. The 2.3-kb upstream sequence of the human MK gene has cis acting elements which confer retinoic acid-induced expression of fused chloramphenicol acetyl-transferase (CAT) gene in F9 embryonal carcinoma cells. In the 5'-region of the human gene, a sequence resembling the DR5-type retinoic acid-responsive element (AGGTCA-related direct repeats separated by 5 nucleotides) was present in a small block of highly homologous 5'-sequences shared by the human and mouse genes. Deletion of this direct repeat reduced retinoic acid-induced CAT gene expression. The core element in the human gene differs from the consensus sequence of retinoic acid-responsive element in two nucleotides and from the retinoic acid responsive element of the mouse MK gene in one nucleotide.

Animals↗

PubMed1995

Central glucopenia induced by 2-deoxy-D-glucose stimulates somatostatin secretion in the rat.

The mechanisms involved in 2-deoxy-D-glucose (2-DG)-induced growth hormone (GH) suppression in the rat were examined. Conscious male rats were given 2-DG by intracerebroventricular (icv) injection and the pulsatile GH secretion was monitored for 6 h. The single icv injection of 2-DG (8 mg/rat) eliminated pulsatile GH secretion in conscious rats. Pretreatment with somatostatin (SS) antiserum completely restored the suppressed GH secretion in the 2-DG treated rats. Hypothalamic GH-releasing hormone (GRH) and SS mRNA levels were not altered by single and multiple icv injections of 2-DG. These findings suggest that 2-DG-induced GH suppression is primarily due to hypersecretion of SS without a significant change at the transcription level in the rat.

Animals↗

PubMed1995

Location of the centre of resistance for the nasomaxillary complex studied in a three-dimensional finite element model.

The purpose of this study was to investigate the location of the centre of resistance (CRe) for the nasomaxillary complex by the use of finite element analysis. A three-dimensional finite element model of the craniofacial complex, consisting of 2918 nodes and 1776 elements, was used for displacement analyses. Anteriorly and inferiorly directed forces of 9.8 N were applied at five different levels, parallel and perpendicular to the functional occlusal plane, respectively. For each loading condition, horizontal and vertical displacements of eight anatomic points in the complex and on the maxillary dentition were analysed. The complex exhibited an almost translatory displacement of approximately 1.0 microns in the forward direction when the horizontal force was applied at a point on the horizontal plane, passing through the superior ridge of the pterygomaxillary fissure, whereas the complex experienced clockwise or counter clockwise rotation when the forces were applied at the remaining levels. Furthermore, the downward forces produced anteriorly upward, or posteriorly upward rotation. However, the force applied at a point on the vertical plane passing through the posterior wall of the pterygomaxillary fissure, produced almost equal displacements of approximately 6.0 microns in an inferior direction for all the anatomic points. It is suggested that CRe of the nasomaxillary complex is located on the posterosuperior ridge of the pterygomaxillary fissure, registered on the median sagittal plane.

Biomechanical Phenomena↗

PubMed1995

Differential gene expression of growth hormone (GH)-releasing hormone (GRH) and GRH receptor in various rat tissues.

Growth hormone (GH)-releasing hormone (GRH) acts on specific receptors in the anterior pituitary to stimulate the synthesis and release of GH. Recent reports suggest that GRH is also synthesized in extrahypothalamic tissues. To evaluate the potential roles of extrahypothalamic GRH, we studied the gene expression of GRH and GRH receptors in various rat tissues by reverse transcribed (RT)-polymerase chain reaction (PCR). Total RNA was extracted from twenty-three rat organs and RT-PCR was performed with GRH and GRH receptor primers. Highly-sensitive RT-PCR-Southern blotting showed that GRH and GRH receptor mRNA coexist in the widespread tissues (14 of 25 tissues). GRH mRNA was relatively abundant in the cerebral cortex, brain stem, testis, and placenta, while GRH receptor mRNA was abundant in renal medulla and renal pelvis. Northern blot hybridization using poly A+ RNA indicated that the transcript of GRH receptor gene found in the renal medulla was similar to the longer transcript (about 4 Kb) of pituitary GRH receptor in the size. These results suggest that GRH plays a potential role not only in the neuroendocrine axis, but also in the autocrine and paracrine systems in extrahypothalamic tissues.

Animals↗

PubMed1995

Importance of impairment of the airway epithelium for ozone-induced airway hyperresponsiveness in guinea pigs.

We examined the relationship between ozone (O3)-induced airway hyperresponsiveness (AHR) and inflammation in guinea pigs. Inhalation of methacholine (MCh) was adopted in the time course study of AHR that was assessed by measuring pulmonary inflation pressure after O3 exposure (3 ppm, for 2 hr) because the degree of AHR detected by inhalation of MCh was greater than that detected by i.v. administration. AHR was detected up to 5 hr after O3 exposure and was not observed at 24 and 48 hr. In the bronchoalveolar lavage (BAL) study, the numbers of neutrophils, eosinophils, lymphocytes and macrophages in BAL fluid (BALF) reached maximum at 24 hr or later. On the other hand, the number of airway epithelial cells in the BALF significantly increased at 2 and 5 hr. In the histological study, disorder and impairment of the airway epithelium in the trachea and lung were observed at 2 and 5 hr. Changes in the airway epithelium were recovered at 48 hr, although an increase in leukocytes was observed in the lung. These results indicate that O3-induced AHR in guinea pigs is most probably associated with impairment of the epithelium rather than with infiltration of inflammatory cells in the airway.

Administration, Inhalation↗

PubMed1995

An outbreak (159 cases) of transient thyrotoxicosis without hyperthyroidism in Japan.

We report an outbreak of transient thyrotoxicosis that occurred between June and September 1993, in Matsuyama City, Ehime Prefecture. One hundred fifty-nine cases of thyrotoxicosis were identified, all in individuals without goiter. Thyroid autoantibodies were absent, and the serum thyroglobulin level was depressed. Ultrasonography of the thyroid disclosed no abnormal findings, while scintigraphy of the thyroid with 99mTc revealed poor uptake. About ten days after the onset, the serum thyroid hormone levels were normalized. No significant elevation of serum viral antibodies was found. These observations suggest that a thyrotoxicosis factitia may have been the cause of the present outbreak.

Adolescent↗