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Biomedical subjects

S Shoji

Publications and source records attributed to S Shoji.

At least 109 records · Page 6Linked to original sources
PubMed1998

Developmental malformations and intrauterine deaths in gamma-ray-irradiated scid mouse embryos.

PURPOSE: To examine the induction by radiation of developmental malformations and intrauterine deaths in severe combined immunodeficiency (scid) mice. MATERIALS AND METHODS: The scid embryos, as well as those of C.B-17 control mice, were irradiated with graded doses of 60Co gamma-rays on gestation day 8. RESULTS: Intrauterine deaths in scid mice increased with radiation dose, and their frequency was substantially higher than in C.B-17 mice. The LD50 for intrauterine death in scid mice was 0.58 Gy and 1.25 Gy in C.B-17 mice. In addition, after irradiation scid mice showed several types of developmental malformations, including meningoencephalocele, spina bifida, eye defects, tail defects and oedema. Malformation incidences were higher in scid than in C.B-17 mice: 33.3% in scid mice irradiated with 0.75 Gy and 13.0% in C.B-17 mice irradiated with 1.0 Gy. However, when malformation incidences were plotted against intrauterine deaths, all the data, irrespective of the type of mouse, essentially fell along a single straight line. CONCLUSIONS: These results suggest that some mechanism common to both scid and normal mice induces developmental malformations. This mechanism involves cell killing. Residual DNA damage, such as double-strand breaks, could be associated with radiation-induced teratogenesis.

Abnormalities, Radiation-Induced↗
PubMed1998

Characterization of gyrA, gyrB, grlA and grlB mutations in fluoroquinolone-resistant clinical isolates of Staphylococcus aureus.

The distribution of fluoroquinolone resistance-associated point mutations in genes encoding the subunits of DNA gyrase and DNA topoisomerase i.v. was examined in 110 clinical isolates of Staphylococcus aureus. Point mutations were detected by polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis and mutations were further characterized by sequencing of PCR products. Mutations at Ser84 of GyrA were widely distributed among isolates exhibiting various degrees of fluoroquinolone resistance, and border zones between mutant and non-mutant strains based on drug susceptibility were generally distinct. Mutations at Ser80 of GrlA were also widely distributed, but border zones between mutant and non-mutant isolates were in this case less distinct and several GrlA mutants were highly susceptible to sparfloxacin and tosufloxacin. Only two gyrB mutants and one grlB mutant were observed among the isolates: all contained a previously unreported mutation. GyrA and grlA mutations thus appear to impart high levels of fluoroquinolone resistance in many S. aureus clinical isolates.

Anti-Infective Agents↗
PubMed1998

Eosinophil degranulation in the presence of lung fibroblasts.

BACKGROUND: Although eosinophils (Eos) and fibroblasts (Fb) are closely approximated in the bronchial submucosae of asthmatics, and are believed to play important roles in the pathogenesis of bronchial asthma, the interaction between Eos and Fb has not been thoroughly elucidated. In this study, we have examined eosinophil cationic protein (ECP) release from human Eos cultured in the presence of human lung Fb. METHODS: Eos from healthy donors were cultured with or without C5a for 16 h in the presence of human fetal lung Fb which had previously been incubated with or without some cytokines for 4 h. ECP in supernatants was measured by RIA. RESULTS: ECP release was potentiated only when both Eos and Fb were activated by C5a and TNF, respectively, while it was not significantly potentiated when either Eos or Fb were activated. ECP release from Eos activated by C5a was also potentiated when Fb were stimulated by IL-1beta. The enhancement of ECP release in cocultured Eos and Fb with stimulation was partly inhibited by monoclonal antibodies against GM-CSF and was accompanied by the enhancement of adhesion of Eos to Fb. CONCLUSIONS: This study shows that the stimulation of both Eos and Fb increases ECP release. It is suggested that Fb may influence Eos degranulation and play a role in the pathogenesis of bronchial asthma.

Asthma↗
PubMed1998

Severity of exercise-induced bronchoconstriction is related to airway eosinophilic inflammation in patients with asthma.

Exercise-induced bronchoconstriction (EIB) is widely prevalent in asthmatic patients. Eosinophilic airway inflammation is considered to be a major factor in the pathogenesis of asthma. However, the effects of eosinophilic airway inflammation on EIB have been elucidated insufficiently. To examine the relationship between the severity of EIB and eosinophilic inflammation, sputum induction and exercise challenge were performed in 21 asthmatic patients. Significantly higher percentages of eosinophils and levels of eosinophil cationic protein (ECP) were found in induced sputum in EIB-positive asthmatics (median (range), eosinophils: 23.5 (11.0-61.0)%; ECP: 1,475 (74.8-17,701) ng x mL(-1)) than in EIB-negative asthmatics (eosinophils: 6.0 (1.0-41.5)% (p=0.006); ECP: 270.6 (10.8-7,700) ng x mL(-1) (p=0.049)). There was a significant correlation between the severity of EIB and the sputum eosinophil percentage (r=0.59, p=0.009) and the level of ECP (r=0.47, p=0.037). The area under the curve of the forced expiratory volume in one second for 30 min after exercise correlated with the percentage of eosinophils (r=0.60, p=0.008) and the level of ECP (r=0.45, p=0.04). There was no correlation between airway responsiveness to methacholine on the one hand and EIB, sputum eosinophils or ECP on the other. In conclusion, these results provide evidence that the severity of bronchoconstriction evoked by exercise is more closely related to eosinophilic airway inflammation than airway hyperresponsiveness to methacholine in asthmatic patients.

Adolescent↗
PubMed1998

Caenorhabditis elegans anti-apoptotic gene ced-9 prevents ced-3-induced cell death in Drosophila cells.

ced-9, a member of the bcl-2 gene family in Caenorhabditis elegans plays a central roles in preventing cell death in worms. Overexpression of human bcl-2 can partially prevent cell death in C. elegans. However, it remains to be elucidated whether ced-9 can regulate cell death when expressed in other organisms. We demonstrated that the CED-9 protein is co-localized with BCL-2 in COS cells and Drosophila Schneider's L2 (SL2) cells, suggesting that the site of CED-9 action is located to specific cytoplasmic compartments. Overexpression of ced-9 only poorly protected cells from the death induced by ced-3 in HeLa cells, but ced-9 significantly reduced the cell death induced by ced-3 in Drosophila SL2 cells. Furthermore, apoptosis of SL2 cells that was induced by a Drosophila cell-death gene, reaper, was shown to be partially prevented by ced-9, bcl-2 and bcl-xL. These results suggest that the signaling pathway that is required for the anti-apoptotic function of bcl-2 family members, including ced-9, is conserved in Drosophila cells. In addition, SL2 cells provide a unique systems for dissecting the main machinery of cell death.

Animals↗
PubMed1998

Comparison of tumorigenesis between accelerated heavy ion and X-ray in B6C3F1 mice.

The effects of heavy ion and X-ray irradiation on tumorigenesis in B6C3F1 mice were compared. Six-week-old animals were divided into 6 groups and exposed to 0.426 Gy heavy ion irradiation of 290 MeV/u carbon-ion beam (LET 60-210 KeV/micron) at the dose rate of 0.4 +/- 0.2 Gy/min; 0.5 Gy of X-ray irradiation at 0.1 Gy/min or 5 Gy of X-ray irradiation at 1 Gy/min. The mice were killed and an autopsy performed 13.5 months after the whole body irradiation. Body weights were heaviest for both sexes in the 0.5 Gy group and lightest in the 5 Gy one. Total tumor incidences in the males were 30, 56 and 13% respectively in the heavy ion, 5 Gy and 0.5 Gy X-irradiated groups, stomach tumors, lymphomas and adrenal tumors being the most common outcome of the high dose X-rays. Liver tumor induction did not differ significantly among the groups. In the females tumorigenicity was significantly lower for heavy ion than for 0.5 Gy and 5 Gy X-ray irradiation (P < 0.05), the respective incidences, mainly ovary one, being 73%, 17% and 41%. Non-cancerous lesions, such as graying of the hair, glomerular sclerosis and amyloidosis appeared in the 5 Gy group. These findings indicate that 0.426 Gy of heavy ion irradiation induced lower carcinogenicity than 5 Gy of X-irradiation and higher carcinogenicity than that of 0.5 Gy X-irradiation in male mice.

Animals↗
PubMed1998

Codon 972 polymorphism of the insulin receptor substrate-1 gene in impaired glucose tolerance and late-onset NIDDM.

OBJECTIVE: To assess the relevance of a Gly-->Arg substitution in codon 972 of the insulin receptor substrate-1 gene in impaired glucose tolerance (IGT) and NIDDM. RESEARCH DESIGN AND METHODS: The genotype of 1,106 Japanese subjects consisting of 310 subjects with NIDDM, 305 subjects with IGT, and 491 normal control subjects was analyzed by an allele-specific assay using polymerase chain reaction and restriction fragment length polymorphism. RESULTS: The frequency of the variant allele was not different between subjects with NIDDM (0.021) and normal control subjects (0.020). However, subjects with IGT showed a significantly higher prevalence of the variant allele (0.041, P = 0.027). We found two homozygous individuals for the variant; both had IGT with mild insulin resistance. The allelic frequency tended to be lower in normal control subjects aged > 50 years than in younger control subjects. Conversely, in the subjects with IGT or NIDDM, the Gly972Arg substitution was more frequently found in subjects aged > 50 years. Furthermore, NIDDM patients with the variant allele had older ages of diagnosis than patients without the variant. CONCLUSIONS: The codon 972 variant may be associated with IGT and a subset of late-onset NIDDM in the elderly Japanese population.

Adult↗
PubMed1998

Clinical implication of protein levels of IL-5 in induced sputum in asthmatic patients.

To determine whether protein levels of interleukin-5 (IL-5) in induced sputum reflect the degree of eosinophilic inflammation, we evaluated the role of IL-5 on clinical characteristics in stable asthmatic patients. IL-5 level, differential eosinophil count, and level of eosinophil cationic protein (ECP) in induced sputum were all significantly higher for asthmatics than for normal controls. Both eosinophil counts and ECP levels in induced sputum were inversely correlated with the degree of airflow limitation (FEV1/FVC). In addition, patients with measurable IL-5 in sputum had significantly more eosinophils, higher levels of ECP in sputum, and lower FEV1 (percent predicted) than did patients with levels of IL-5 beneath the limit of detection. However, we found no significant difference in IL-5 levels between atopic and nonatopic asthmatics. IL-5 level in induced sputum is a good indicator of eosinophilic inflammation in atopic and nonatopic asthmatic patients.

Adult↗
PubMed1998

[A case of livedo vasculitis associated with mononeuritis multiplex].

Livedo vasculitis is characterized by recurrent livedo reticularis of lower extremities and the histopathological findings of segmental hyalinizing vasculitis in the skin. We report a case of a 26-year-old female who manifested mononeuritis multiplex 7 years after the onset of livedo vasculitis. She showed sensori-motor disturbances in the right median and ulnar nerves and sensory deficits of the bilateral peroneal nerves. Sural nerve biopsy revealed a remarkable loss of large and small myelinated fibers and a few vasculitic changes. Steroids therapy was effective for these neurological symptoms. But paroxysmal numbness appeared later recurrently in the regions of affected nerves with painful ulcerations in the right leg. Laboratory tests indicated increased levels of serum thrombin-antithrombin complex (TAT), and antithrombotic drugs (argatroban) remarkably ameliorated the recurrent symptoms and skin lesions. These findings suggest that the pathogenesis of livedo vasculitis might be related to alterations of the blood coagulation system.

Adult↗
PubMed1998

Cocaine administered in vitro to brain slices from rats treated with cocaine chronically in vivo results in a gamma-aminobutyric acid receptor-mediated hyperpolarization recorded from the dorsolateral septum.

Previous reports of membrane hyperpolarizations, associated with acute application of cocaine, have been recorded from brain slice preparations containing aminergic nuclei and have always been attributed to cocaine's ability to elevate levels of local biogenic amines followed by activation of their receptors. The majority of these studies were conducted with brain slices obtained from rats that had not received prior chronic in vivo treatment with cocaine. We observed that cocaine alone, at 3 microM, could induce a membrane hyperpolarization (COC-HYP) in 100% of rat dorsolateral septal nucleus (DLSN) neurons from brain slices of rats treated chronically with cocaine for either 14 or 28 days in vivo. The DLSN is a nucleus absent of biogenic amine cell bodies, but does contain biogenic amine terminals with GABAergic cell bodies and terminals. Cocaine applied to brain slices from rats not previously administered cocaine or administered cocaine for up to seven days in vivo yielded a maximum incidence of COC-HYPs at only 50%. COC-HYPs recorded from DLSN neurons were not blocked by previous treatment with amine receptor antagonists or by a TTX and zero calcium medium. Based on these results, the ability of DLSN neurons to respond to a cocaine challenge with a COC-HYP did not involve inhibition of amine reuptake/uptake or action potential release of neuroactive substances. Rather, the COC-HYP, with an apparent reversal potential of -80 mV, was reduced by the GABA receptor antagonists-bicuculline and CGP-55845A. Lowering extracellular Na+ or Cl-, lowering of temperature, or previous superfusion with the GABA uptake blocker NO-711 could block the COC-HYP. In summary, our data suggest that COC-HYPs, after application of a cocaine challenge to brain slices from rats treated chronically (14-28 days, but not acutely, 7 days) with cocaine are due to cocaine-induced changes in GABA release and/or transporter function. The latter changes in transporter function may involve the reversal of the GABA transporter with release of GABA and subsequent activation of postsynaptic GABAA and GABAB receptors.

Animals↗
PubMed1998

[A case of hypertrophic cranial pachymeningitis associated with intramedullary lesion developed seizure marching from right lower extremity].

A case of hypertrophic cranial pachymeningitis associated with intramedullary lesion was reported. A 57-year-old male presented with the symptoms of Jacksonian seizure and weakness of right lower extremity. Neurological examination showed weakness and muscular atrophy of right lower extremity (MMT 1-2) and hyperreflexia. Superficial sensation and position sense were normal, however cortical sensory disturbance was recognized in his right lower extremity. MRI revealed diffuse dural thickening with gadolinium enhancement in the left convexity and hyperintense lesion in the bilateral (left dominant) frontal to parietal lobe on T2 weighted image. Magnetic resonance angiography (MRA) and digital subtraction angiography (DSA) showed occlusion of the superior sagittal sinus. Histological examination revealed extensive fibrous tissue with lymphocytes infiltration around the vessels. The cause of the intramedullary lesion in this patient may have been related to the occlusion of superior sagittal sinus, due to thickening dura mater and influence of inflammation.

Angiography, Digital Subtraction↗
PubMed1998

Dysfunction of the hypothalamic-pituitary system in mitochondrial encephalomyopathies.

We investigated endocrine function in patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), myoclonus epilepsy associated with ragged-red fibers (MERRF), and chronic progressive external ophthalmoplegia (CPEO). Hypothalamic-pituitary function was impaired in all three patients with MELAS or MERRF, but none of four with CPEO. A MELAS patient with dwarfism and impaired adolescent development had decreased growth hormone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). A MERRF patient had emaciation and low adrenocorticotropin. A patient with mitochondrial encephalomyopathy transitional between MELAS and MERRF showed delayed, blunted LH and FSH response to LH-releasing hormone stimulation. We concluded that patients with mitochondrial encephalomyopathies, especially MELAS or MERRF, are likely to have hypothalamic-pituitary dysfunction.

Adult↗
PubMed1998

[A case report of steroid-responsive progressive encephalomyelitis with rigidity showing muscle stiffness limited to the upper body].

A 37-year-old female presented with progressive encephalomyelitis with rigidity for a period of about three months. Spasms began with several minutes of paroxysmal painful muscle stiffness in the left upper limb, followed by pain and muscle spasms in the upper limbs, shoulders, neck and back. The paroxysmal painful spasms were easily evoked by light touches and startling. The patient had contracture in the upper limbs and difficulty in relaxing the muscles. She also developed brain stem signs such as left sixth nerve palsy. The serum antinuclear antibody was positive (1 : 160). The cerebrospinal fluid examination revealed mild pleocytosis and protein elevation. Brainstem MRI, cervical MRI, and electroencephalography were normal. Surface electromyography in the arm and neck muscles showed continuous motor unit discharge elicited by passive movement of the right arm. Diazepam and baclofen were minimally beneficial. After treatment with intravenous injection of high-dose methylprednisolone and sequential oral prednisolone administration, the patient showed substantial improvement. This disorder may be part of a clinical spectrum that has an underlying autoimmune basis.

Administration, Oral↗
PubMed1997

The p2gag peptide, AEAMSQVTNTATIM, processed from HIV-1 Pr55gag was found to be a suicide inhibitor of HIV-1 protease.

The p2gag peptide (AEAMSQVTNTATIM) processed from HIV-1 Pr55gag by HIV-1 protease was identified as a suicide inhibitor of the enzyme (Ki = 30 microM and IC50 = 10 microM for the synthetic peptide substrate, succinyl-SQNYPIVQ), and potently inhibited the proteolytic cleavage of the viral precursor protein (Pr55gag) into functional structural units (p17gag and p24gag) in vitro. The nonapeptide (AEAMSQVTN) derived from N-terminus of the p2gag peptide exhibits a potent inhibitory action on HIV-1 protease, but the other peptides (AEAMSQ, AEAMSQV, AEAMSQVT, VTN and VTNTATIM) do not. It was determined by exclusion gel chromatography that HIV-1 protease after treatment of the synthetic p2gag peptide dissociated from the active dimeric form to an inactive monomeric form. The p2gag peptide and HIV-1 protease were also detected in HIV-1 viral particles using both matrix-assisted laser desorption/ionization time-of-flight mass spectrometric (MALDI TOF-MS) and western immunoblot analyses. Taken together, these results suggest that the p2gag peptide is the inhibitor of preventing dimerization of HIV-1 protease and that the enzyme activity is completely suicide inhibited with the accumulated p2gag peptide producing by the processing of Pr55gag during viral maturation.

Dimerization↗
PubMed1997

Alpha1-antichymotrypsin polymorphism in Japanese cases of Alzheimer's disease.

We examined the possible involvement of alpha1-antichymotrypsin (ACT) polymorphism in the risk for Alzheimer's disease (AD) in a Japanese population. No differences between AD and control subjects have been shown in the genotype distributions and allele frequencies of ACT. No modification of the risk for AD was observed, either alone or in combination with the apolipoprotein epsilon4 (ApoE-4) allele. Our results from a Japanese population failed to confirm the previous data in which the ACT polymorphism was shown to affect the ApoE-4-associated risk for AD.

Aged↗