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Biomedical subjects

S Matsubara

Publications and source records attributed to S Matsubara.

At least 181 records · Page 10Linked to original sources

Pulsed intravenous methylprednisolone therapy for inflammatory myopathies: evaluation of the effect by comparing two consecutive biopsies from the same muscle.

To examine the effect of pulsed intravenous methylprednisolone (IVMP) on polymositis (PM) and dermatomyositis (DM), two biopsies were taken from the same muscle before and after IVMP in one case each of PM and DM. After IVMP, numerous muscle fibers were seen undergoing regeneration. Among all subsets of infiltrating cells that decreased in number, macrophages in the perivascular area decreased markedly. Also conspicuous was decrease of CD8+ cells in the endomysium in PM and that of B-cells in the perivascular area in DM. Among infiltrating cells, frequency of those which expressed the signal transducers and activators of transcription 1 (STAT-1) fell considerably, but remained still abnormally high. Regions on the endothelial cells of blood vessels that expressed MHC antigens and intercellular adhesion molecules 1 (ICAM-1) also decreased but remained more widespread than normal. These results agreed with the favorable clinical effect of IVMP, but showed that many of the immunological parameters remained abnormal.

Adult↗

Spread of HSV-1 to the suprachiasmatic nuclei and retina in T cell depleted BALB/c mice.

Following uniocular anterior chamber inoculation of the KOS strain of HSV-1 in euthymic BALB/c mice, virus spreads from the injected eye to the brain, and from the brain to the optic nerve and retina of the uninjected eye by day 7 post inoculation (p.i.), but the optic nerve and retina of the injected eye are not infected with virus. Infection of the optic nerve and retina of the injected eye is observed only in athymic mice or in mice depleted of both CD4+ and CD8+ T cells. To determine the role of T cells in virus spread, adult female BALB/c mice were thymectomized and T cell depleted. Mice were co-injected with the KOS strain of HSV-1 and RH116, a thymidine kinase-negative mutant of KOS containing the Escherichia coli lac Z gene. Animals were sacrificed on days 3-7 p.i., and the eyes and brains were examined for blue-stained, virus-infected cells. A difference in the timing of virus infection was observed in the area of the suprachiasmatic nuclei only in mice depleted of both CD4+ and CD8+ T cells, and in this group, the contralateral suprachiasmatic nucleus was infected two days earlier. Since one route by which virus could infect the retina of the injected eye is via connections of the contralateral suprachiasmatic nucleus to the ipsilateral optic nerve, these findings suggest that (a) retinitis observed in the injected eyes of mice depleted of both CD4+ and CD8+ T cells results from virus infection of the contralateral suprachiasmatic nucleus followed by spread of virus to the ipsilateral optic nerve and retina and (b) early HSV-1 infection of the contralateral suprachiasmatic nucleus is prevented by a T cell dependent mechanism.

Animals↗

Cellular and subcellular localization of nicotinamide adenine dinucleotide phosphate diaphorase activity.

OBJECTIVE: To determine the cellular and subcellular distribution of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) in the human placenta and thereby to shed light on the possible role of nitric oxide (NO) and NO synthase in this tissue. METHODS: NADPH-d activity in 10 term placenta and in 10 first-trimester placentas was examined by enzyme histochemistry and by both light microscopy and electron microscopy. RESULTS: Light microscopy revealed that NADPH-d activity was marked in the syncytiotrophoblasts, moderate in the endothelium of cord vessels, and weak in the amniotic epithelia and chorionic trophoblasts. At the electron-microscopic level, NADPH-d activity was apparent as small patches distributed throughout the cytoplasm of the syncytiotrophoblasts. CONCLUSION: NO might be generated in the syncytiotrophoblast of the human placenta and might play a role in the regulation of placental hemodynamics or in the signaling between the syncytium and the villous mesenchyme.

Amnion↗

Effect of T-440, a novel type IV phosphodiesterase inhibitor, on allergen-induced immediate and late asthmatic reaction and leukocyte infiltration into the airways of guinea pigs.

Type IV phosphodiesterase (PDE IV) is expressed in many tissues including airway smooth muscle and inflammatory cells, suggesting that this isozyme has a regulatory role in the pathogenesis of bronchial asthma. We investigated the effect of a novel selective PDE IV inhibitor, T-440, on immediate asthmatic reaction (IAR), late reaction (LAR) and leukocyte infiltration into the airways after allergen challenge in guinea pigs. Inhalation of ovalbumin by sensitized guinea pigs induced an immediate increase in specific airway resistance that peaked at 15 min. LAR was only produced in combination with chronic treatment with metyrapone, an inhibitor of the biosynthesis of adrenocortical steroids, and was suppressed by administration of dexamethasone, suggesting that the expression of LAR is dependent on an intrinsic steroid hormone. These reactions were accompanied by increases in the number of eosinophils and neutrophils recovered in bronchoalveolar lavage fluid. Oral administration of T-440 significantly inhibited IAR, LAR and the infiltration of eosinophils, whereas it suppressed neutrophil accumulation with relative low potency. These findings imply that the inhibition of PDE IV activity is a reasonable target for the management of obstructive airway diseases associated with airway inflammation such as asthma.

Administration, Inhalation↗

Quantitative analysis of growth hormone (GH) pre-mRNA expression in cultured rat anterior pituitary cells by an intron-specific and competitive PCR method.

We have developed a novel method of quantifying growth hormone(GH) pre-mRNA expression in anterior pituitary cells. DNA-free total RNA extracted from cultured rat anterior pituitary cells was reverse transcribed(RT) to cDNA, and RT products were subsequently quantitated by competitive PCR using intron-specific primers of rat GH gene. After 6-h of incubation in treated cells, dexamethasone(Dex) and triiodo-L-thyronine(T3) significantly increased GH pre-mRNA levels(3.2- and 2.2-fold compared to non-treated cells, respectively). However, Northern blot analysis did not detect significant changes in GH mRNA levels. After 24-h incubation with Dex and T3, significant increases in GH mRNA levels were detected on Northern blots, but GH pre-mRNA levels did not differ between treated and non-treated cells. These findings suggest that both Dex and T3 treatments rapidly increase GH pre-mRNA levels in normal somatotropes. This method has high sensitivity and widespread application to the analysis of pre-mRNAs of target genes.

Animals↗

The effect of iodine-based contrast agents on the levels of radiation-induced chromosomal aberrations.

The effects of iodine-based contrast agents on the repair of radiation-induced chromosomal damage were investigated employing peripheral blood from a healthy male donor. The blood samples were irradiated with 0.5-4.0 Gy 137Cs gamma rays. Contrast agents and NaCl solutions of various concentrations were added to the blood within the first 15 min or at 60 min after irradiation, and the samples were subsequently cultured for 45 h at 37 degrees C. Significantly elevated frequencies of chromosomal abnormalities caused by postirradiation treatment with hypertonic contrast agents appeared to increase with increasing hypertonicity. Elevated aberration frequencies were found to be greatest in the samples treated within 15 min of irradiation. The contrast agents had little effect if they were added at 60 min after irradiation, probably because the process of chromosome rejoining had been completed. Isotonic iodine-based contrast agents did not enhance the frequencies of chromosomal aberrations to a significant degree.

Adult↗

[Small hand muscle atrophy as an initial sign in HTLV-I associated myelopathy].

A 68-year-old female had been well until the age of 52 when she noticed weakness and atrophy of her right small hand muscles. She began to have gait disturbance at the age of 63. On admission, neurological examinations revealed atrophy and weakness of the small hand muscles on both sides as well as spastic paraparesis. As the antibody titer for human T-lymphotropic virus type I (HTLV-I) was elevated both in the serum and CSF, a diagnosis of HTLV-I associated myelopathy (HAM) was made. Electrophysiological studies showed neurogenic changes and suggested anterior horn cell involvement. After oral administration of prednisolone, her spasticity and gait disturbance improved slightly. Small hand muscle atrophy can be one of the initial signs of HAM, and may mimic amyotrophic lateral sclerosis and cervical spondylosis.

Aged↗

[Smoking behavior, knowledge and attitudes of freshmen students].

A questionnaire on smoking behavior, knowledge of smoking-related diseases and attitudes toward the passive exposure to smoking was administered and results analyzed for differences in (1) region, (2) major area of study in the university, (3) grade and (4) date of survey on smoking behavior, knowledge and attitude of the freshmen students. (1) 294 urban and 217 provincial university students, (2) 138 freshmen at the Department of Pharmacology and 156 freshmen at the Department of Technology, (3) 136 freshmen of Y. University and 158 freshmen in senior high school of Yamaguchi prefecture, and (4) 217 freshmen surveyed in 1990 and 136 freshmen surveyed in 1995 were the subjects. The results were as follows; 1) The percentage who had smoked once ranged from 0 to 3% among the senior high school girls and female students at minor universities. However, the percentage for male students ranged from 26% to 44% in each survey. There were clear gender differences in smoking behavior. 2) The proportion of students who admitted that they had smoked cigarettes was 30.9% for urban students and 38.6% for provincial university students, but was not a significant difference. There were no significant differences between urban and provincial students regarding knowledge of smoking-related diseases or attitudes toward passive smoke. 3) The proportion of students who admitted that they had smoked cigarettes was 44.0% for the Department of Pharmacology and 26.2% for the Department of Technology, a significant difference. There were no significant differences between pharmaceutical and engineering students in knowledge of smoking-related diseases or attitudes toward passive smoke. 4) The proportion of students who admitted that they had smoked cigarettes was 27.4% for university freshmen and 1.6% for senior high school freshmen. There was a significant difference between the two. The percentage who replied that the smoker must be considerate to non-smokers tended to be higher in the senior high school students than the university students. However, there was no significant differences between the two groups of students in knowledge of smoking-related diseases or attitudes toward passive smoke. 5) Although the proportion of students who admitted that they had smoked cigarettes was 38.6% in the 1990 survey and 27.4% in the 1995 survey, this was not a significant difference. The percentage of students in the 1990 survey who indicated an awareness of the relationship between smoking and coronary heart diseases was significantly greater than the percentage of students who indicated a similar awareness in the 1995 survey. These results suggest that the differences in the grade and the department of the university (or the nature of school) must be considered when surveying smoking behavior. It does not appear to be necessary, however, to consider regional differences or the date of survey, if students were surveyed relatively recently, concerning smoking behavior, knowledge of smoking-related diseases and attitudes toward the effect of passive exposure to smoking.

Adolescent↗

[Crescentic glomerulonephritis in a patient with rheumatoid arthritis].

A 56-year-old female with rheumatoid arthritis was admitted because of bilateral hip pain. In a few months of her hospitalization, a relatively abrupt renal dysfunction was emerged besides complement breakdown, and renal biopsy revealed crescentic glomerulonephritis. Immunofluorescence study showed peripheral granular deposits of IgG, IgM, and C3 in the glomeruli. Cresents were predominantly composed of macrophages and glomerular epithelial cells. Amyloid nephropathy, renal vasuculitis, and association of other collagen vascular diseases were negligible for the causative factor. It was suggested that immune complexes were formed in the glomeruli, in which both humoral and cellular immune responses were to be induced, that brought cescents formation in the lesions. Crescentic glomerulonephritis in patients with rheumatoid arthritis is rare and a possible pathogenetic mechanisms involved in the development of renal dysfunction are discussed with the special reference to immune complex-induced inflammation.

Antigen-Antibody Complex↗

Digitalization of the mother in treating hydrops fetalis in monochorionic twin with Ebstein's anomaly. Case report.

Hydrops fetalis thought to be due to Ebstein's anomaly was seen at 22 weeks' gestation in one of two fetuses with a monochorionic placenta. Hydrops was treated with maternal digitalization and resolved by the 28th week of gestation. Hydrops did not recur while maternal digitalization continued. A clinical diagnosis of twin-to-twin transfusion syndrome required termination of the pregnancy at 33 weeks of gestation. The twin with Ebstein's anomaly died 22 hours after birth. The other twin survived and was normal at 19 months of age. Thus, administration of digitalis to the mother controlled hydrops fetalis in one fetus, and ultimately led to the survival of the healthy infant.

Adult↗

[A case of primary mediastinal choriocarcinoma].

A 27-year-old man with primary mediastinal choriocarcinoma was reported. He was admitted with complaint of right chest pain and dyspnea. Chest X-ray film and computed tomography of the chest revealed a bulky mass at anterior mediastinum and right pleural effusion. Physical examination revealed bilateral gynecomastia, and the serum beta-HCG level was cap at 500 ng/ml. The specimens obtained by percutaneous needle biopsy of the mediastinal mass showed cytotrophoblasts and syncytiotrophoblasts. He received 4 cycles of anti-cancer chemotherapy, and underwent resection for a residual mass, in which viable cancer cells remained in histological examination. In spite of additional chemotherapy, multiple lung metastasis developed rapidly. High dose chemotherapy, with carboplatine (200 mg/m2 x 4 days), etoposide (250 mg/m2 x 4 days) and cyclophosphamide (50 mg/kg x 2 days) was performed in combination with peripheral blood stem cell autotransplantation. However, brain metastasis set in and he died of respiratory failure 9 months after the onset of symptoms.

Adult↗

[Hallucination in opsoclonus-polymyoclonus syndrome].

Here we report 2 cases of opsoclonus-polymyoclonus syndrome (OPS) associated with viral encephalitis. They had sleep disturbance, and visual hallucination. Case 1 had auditory hallucination in addition, and case 2 had dreamlike behavior. Those hallucination, which were colorful and vivid, usually appeared at the bed time. Their hallucinations were similar to peduncular hallucinations and you may also call hypnagogic hallucinations, which are often seen in patients with narcolepsy. Dreamlike behavior is observed during REM sleep in patients with brainstem damage or sometimes in the healthy elderly people. The presence of sleep disturbance, hypnagogic hallucination, and dreamlike behavior suggests that there may be some relationship between OPS and REM sleep. Considering that REM sleep is suppressed by serotonergic projection of the dorsal raphe nucleus in addition to several reports about brainstem lesion with serotonergic abnormalities in this disorder, we considered that dysfunction of serotonergic neurons of the dorsal raphe nucleus might be related in the development of OPS.

Adolescent↗

Midkine as a novel target gene for the Wilms' tumor suppressor gene (WT1).

Midkine (MK) is a heparin-binding growth factor which is strongly expressed during the midgestation period of mouse embryogenesis. Wilms' tumor is an embryonal kidney malignancy in infants, and WT1 has been identified as its tumor suppressor gene. The high expression level of MK in all Wilms' tumor specimens so far examined and the presence of two WT1 elements (5'-GCGGGGGCG-3') in the human MK promoter region led us to examine the possible role of the WT1 gene product in the regulation of MK gene expression. A gel shift assay verified the complex formation between the WT1 gene product and WT1 consensus sequence of MK gene. DNase1 footprint analysis also demonstrated that the downstream WT1 element was protected from DNase1 cleavage by the addition of the WT1 protein. The human MK promoter fused with the chloramphenicol acetyltransferase gene (phMK2.3kCAT) was co-transfected with an effector plasmid containing the WT1 gene into several cell lines. Transient transfection assays showed suppression of the MK promoter by WT1 co-transfection in recipient cells; deletion of the WT1 binding site abolished the suppression. The evidence reported in this study indicates that MK gene is a newly identified WT1 target gene.

3T3 Cells↗

Characterization of a small-cell-lung-carcinoma cell line from a patient with cancer-associated retinopathy.

We examined the biologic properties of a small-cell-lung-carcinoma (SCLC) cell line (designated MN-1112) established from a patient with SCLC who showed paraneoplastic retinopathy syndrome. Morphologic and immunocytochemical analyses showed that MN-1112 cells possess features of the classic type of SCLC. MN-1112 cells grew in suspension forming relatively large clumps of cells with a doubling time of 72 hr. By light-microscope examination, the cells were relatively small and had scanty cytoplasm. The cells produced NSE, ACTH and CK (BB isozyme); they also expressed recoverin, a novel photoreceptor protein, detected by Northern-blot and Western-immunoblot analysis using human-recoverin-specific DNA probe and anti-bovine-recoverin polyclonal antibody. This report shows that human recoverin is expressed in cultured SCLC cells. Our results support the hypothesis that, in cancer-associated retinopathy (CAR) patients, auto-immune antibody targeting for ectopic recoverin in SCLC is initially produced and cross-reacts with the retinal protein, resulting in the retinal degeneration that occurs in CAR patients.

Aged↗

Monocyte chemotactic factor in rheumatoid arthritis synovial tissue. Probably a cross-linked derivative of S19 ribosomal protein.

The extracts of rheumatoid arthritis-synovial lesions from seven patients possessed a strong chemotactic activity for monocytes and a negligible one for polymorphonuclear leukocytes. These results are consistent with a prominent histological feature of the synovial lesion, the mononuclear cell predominant infiltration. The major monocyte chemotactic factor in the synovial tissue extracts was purified to a single protein peak in reverse phase high performance liquid chromatography with a C4 column. NH2-terminal amino acid analysis of the initial 20 residues yielded a single sequence. Surprisingly, this sequence was completely identical to that of S19 ribosomal protein. The purified sample demonstrated two protein bands in SDS-polyacrylamide gel electrophoresis with apparent molecular masses of 34 and 68 kDa. These sizes were 2 and 4 times that of S19 ribosomal protein, suggesting that the chemotactic factor would be a dimer or tetramer of S19 ribosomal protein cross-linked by factor XIIIa. A recombinant human S19 ribosomal protein was prepared as a fusion protein with a maltose binding protein in Escherichia coli. After treatment with factor XIIIa, cross-linked recombinant S19 ribosomal protein exhibited the monocyte chemotactic activity, although the untreated recombinant protein did not.

Amino Acid Sequence↗

Changes in renal blood flow measured by radionuclide angiography following exhausting exercise in humans.

We measured renal blood flow (RBF) repeatedly in six male volunteers following exhausting cycling exercise using radionuclide angiography (RA) with technetium 99 m phytate (99 mTc-phytate), which is a nondiffusible radio-active tracer for kidney imaging and which is taken up quickly by the liver after injection into the circulation. The relationships between changes in RBF and creatinine clearance (Ccr), urine volume (UV) and plasma hormone involved in the regulation of renal function were also investigated. A bolus of 99 mTc-phytate (92.5 MBq.ml-1) was injected into the brachial vein via a catheter, while each subject was maintained in a supine position with his back to a scinticamera, which was connected to a computer for data processing. The pool transit time (PTT) was calculated from the time-concentration flow curve in the left kidney following injection of the bolus. The PTT normalized by the PTT of the heart (PTTn: kidney PTT/heart PTT), and the change in the reciprocal of PTTn (1/PTTn) were used as indices of the change in RBF. The resting RBF was also measured simultaneously by both RA and the para-aminohippuric acid (PAH) clearance method (CPAH). Post-exercise RBF was measured only by RA within 60 s of exercise, then again within 30 and 60 min of exercise on different days, since RBF can be measured successively only three times even with the use of 99 mTc-phytate. The resting value of 1/PTTn was converted to the value of CPAH corrected for haematocrit, and post-exercise change of 1/PTTn (RBF) was represented as a change in the value of CPAH in order to express a definite numerical change, rather than a percentage change, from resting RBF. The RBF decreased by 53.4% immediately after exercise, and remained decreased by 17.5% 30 min after and by 21.1% 60 min after exercise in comparison with the resting value. The RBF was found to be correlated with changes in Ccr (r = 0.773, P < 0.001), UV (r = 0.598, P < 0.001), and the concentrations of plasma angiotensin II (r = -0.686, P < 0.001) and noradrenaline (r = 0.652, P < 0.001) after exercise. However, there were no significant correlations between the changes in plasma aldosterone ([Ald]) and plasma noradrenaline, or in [Ald]p1 and plasma angiotensin II concentrations. The change in [Ald]p1 did not coincide with the variation in reabsorption of Na+ in the renal tubules. Results of the present study showed that change in Ccr after exhausting exercise depended mainly on change in RBF and that changes in UV and osmolality after exhausting exercise were induced not only by change in RBF, but also by changes in reabsorption of water and solutes in the renal tubules. It is suggested that changes in reabsorption of water and solutes might be influenced by metabolites induced by exercise and an increased release of hormones, other than aldosterone, involved in the regulation of renal function.

Adult↗

Cancer-associated retinopathy syndrome: a case of small cell lung cancer expressing recoverin immunoreactivity.

Cancer-associated retinopathy (CAR) syndrome is a rare paraneoplastic neuropathy syndrome often found in patients with small cell lung cancer (SCLC). Serological studies have indicated that the process could include autoimmune reactions directing retinal antigens. Recently, the CAR antigen was identified as a photoreceptor protein, recoverin, by screening retinal proteins using the CAR patient's serum. The present case of SCLC showed rapidly deteriorated bilateral visual acuity lacking the inflammatory findings at the retina which were compatible with CAR. The immunohistochemical study revealed that the cancer cells expressed recoverin or recoverin-like immunoreactivity. This is the first observation in CAR syndrome. The presence of recoverin or recoverin-like immunoreactivity in SCLC with CAR syndrome supports the hypothesis that the cancer-retina immunologic cross-reaction contributes to visual loss in this syndrome.

Aged↗

LET dependence of cell death, mutation induction and chromatin damage in human cells irradiated with accelerated carbon ions.

We investigated the LET dependence of cell death, mutation induction and chromatin break induction in human embryo (HE) cells irradiated by accelerated carbon-ion beams. The results showed that cell death, mutation induction and induction of non-rejoining chromatin breaks detected by the premature chromosome condensation (PCC) technique had the same LET dependence. Carbon ions of 110 to 124keV/micrometer were the most effective at all endpoints. However, the number of initially induced chromatin breaks was independent of LET. About 10 to 15 chromatin breaks per Gy per cell were induced in the LET range of 22 to 230 keV/micrometer. The deletion pattern of exons in the HPRT locus, analyzed by the polymerase chain reaction (PCR), was LET-specific. Almost all of the mutants induced by 124 keV/micrometer beams showed deletion of the entire gene, while all mutants induced by 230keV/micrometer carbon-ion beams showed no deletion. These results suggest that the difference in the density distribution of carbon-ion track and secondary electron with various LET is responsible for the LET dependency of biological effects.

Carbon↗