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Biomedical subjects

S Shoji

Publications and source records attributed to S Shoji.

At least 73 records · Page 4Linked to original sources
PubMed1999

Exacerbation of myasthenia gravis in a patient after interferon-beta treatment for chronic active hepatitis C.

We report the case of a 53-year-old female patient, who developed bilateral blepharoptosis, limb weakness, dysphagia, and dyspnea several days after human natural interferon-beta (IFN-beta) treatment for chronic active hepatitis C. A positive edrophonium test, an elevated anti-acetylcholine receptor antibody titer, and decrements in the amplitude of muscle action potentials evoked by repetitive stimulation confirmed the diagnosis of myasthenia gravis (MG). Since she had been suffering from drooping of her right eyelid, fluctuating diplopia and easy fatiguability of limbs before receiving IFN-beta, her symptoms of MG were considered to be exacerbated by IFN-beta. It is recommended that IFN-beta should be used with particular care in patients with known MG or its compatible symptoms.

Antiviral Agents↗
PubMed1999

Proapoptotic activity of Caenorhabditis elegans CED-4 protein in Drosophila: implicated mechanisms for caspase activation.

CED-4 protein plays an important role in the induction of programmed cell death in Caenorhabditis elegans through the activation of caspases. However, the precise mechanisms by which it activates caspases remain unknown. To investigate the conservation of CED-4 function in evolution, transgenic Drosophila lines that express CED-4 in the compound eye were generated. Ectopic expression of CED-4 in the eyes induced massive apoptotic cell death through caspase activation. An ATP-binding site (P-loop) mutation in CED-4 (K165R) causes a loss of function in its ability to activate Drosophila caspase, and an ATPase inhibitor blocks the CED-4-dependent caspase activity in Drosophila S2 cells. Immunoprecipitation analysis showed that both CED-4 and CED-4 (K165R) bind directly to Drosophila caspase drICE, and the overexpression of CED-4 (K165R) inhibits CED-4-, ecdysone-, or cycloheximide-dependent caspase activation in S2 cells. Furthermore, CED-4 (K165R) partially prevented cell death induced by CED-4 in Drosophila compound eyes. Thus, CED-4 function is evolutionarily conserved in Drosophila, and the molecular mechanisms by which CED-4 activates caspases might require ATP binding and direct interaction with the caspases.

Adenosine Triphosphate↗
PubMed1999

Effective adenovirus-mediated gene expression in adult murine skeletal muscle.

We established an efficient method for obtaining expression of a foreign marker gene transferred in vitro into myoblasts and in vivo into adult mouse skeletal muscles using adenovirus vector. After infection of the C2 myoblasts with the adenovirus vector containing the beta-actin promoter with cytomegalovirus (CMV) enhancer (CAG promoter) AxCALacZ, significantly greater number of cells express beta-galactosidase when compared with the adenovirus vector expressing the lacZ gene under the control of the SR alpha viral terminal repeat promoter (AxSRLacZL) or the myosin heavy chain (MHC) IIB promoter (AxMHCLacZ). We also injected AxCALacZ into the skeletal muscles of 5- to 6-week-old C57BL/10 mice and determined that more than 60% of their muscle fibers expressed the lacZ gene 7 days after injection. The CAG promoter may have application in the development of gene therapy for Duchenne muscular dystrophy (DMD) using adenovirus vector.

Adenoviridae↗
PubMed1999

L-threo-3,4-dihydroxyphenylserine enhances the orthostatic responses of plasma renin activity and angiotensin II in multiple system atrophy.

We evaluated the effect of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) on the response of blood pressure and vasoactive factors during head-up tilt in patients with multiple system atrophy (MSA). After the daily oral administration of 300 mg L-threo-DOPS for 2 weeks we observed a significant reduction in the decline of systolic blood pressure during 60 degrees head-up-tilt. In concordance with this result, we detected significant increases in postural changes in plasma renin activity and angiotensin II following L-threo-DOPS treatment. The enhanced responses of these vasoactive mediators by L-threo-DOPS during head-up tilt may contribute to the improvement in orthostatic hypotension in patients with MSA.

Adult↗
PubMed1999

Serum levels of 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D, and 25-hydroxyvitamin D in nondialyzed patients with chronic renal failure.

BACKGROUND: In patients with chronic renal failure (CRF), abnormalities in vitamin D metabolism are known to be present, and several factors could contribute to the abnormalities. METHODS: We measured serum levels of three vitamin D metabolites, 1,25(OH)2D, 24, 25(OH)2D and 25(OH)D, and analyzed factors affecting their levels in 76 nondialyzed patients with CRF (serum creatinine> 1.6 and < 9.0 mg/dl), 37 of whom had diabetes mellitus (DM-CRF) and 39 of whom were nondiabetic (nonDM-CRF). RESULTS: Serum levels of 1,25(OH)2D were positively correlated with estimated creatinine clearance (CCr; r = 0.429; P < 0.0001), and levels of 24,25(OH)2D were weakly correlated with CCr (r = 0.252, P < 0.05); no correlation was noted for 25(OH)D. Serum levels of all three vitamin D metabolites were significantly and positively correlated with serum albumin. Although there were no significant differences in age, sex, estimated CCr, calcium and phosphate between DM-CRF and nonDM-CRF, all three vitamin D metabolites were significantly lower in DM-CRF than in nonDM-CRF. To analyze factors influencing vitamin D metabolite levels, we performed multiple regression analyses. Serum 25(OH)D levels were significantly and independently associated with serum albumin, presence of DM and serum phosphate (R2 = 0.599; P < 0.0001). 24,25(OH)2D levels were significantly and strongly associated with 25(OH)D (beta = 0.772; R2 = 0.446; P < 0.0001). Serum 1,25(OH)2D levels were significantly associated only with estimated CCr (R2 = 0. 409; P < 0.0001). CONCLUSIONS: These results suggest that hypoalbuminemia and the presence of DM independently affect serum 25(OH)D levels, probably via diabetic nephropathy and poor nutritional status associated with diabetes, and that 25(OH)D is actively catalyzed to 24,25(OH)2D in CRF, probably largely via extrarenal 24-hydroxylase. Serum levels of 1,25(OH)2D were significantly affected by the degree of renal failure. Thus, this study indicates that patients with CRF, particularly those with DM, should receive supplements containing the active form of vitamin D prior to dialysis.

24,25-Dihydroxyvitamin D 3↗
PubMed1999

Blockage of HIV-1 production through inhibition of proviral DNA synthesis by N,O-didecanoyl serinal dimethylacetal.

Six serinal derivatives were synthesized and tested for their anti-human immunodeficiency virus type-1 (HIV-1) activity against HIV-1-infected cells. Of the 6 serinal derivatives tested, only N,O-didecanoyl serinal dimethylacetal (DDSD) was found to strongly suppress progeny virus production from acute HIV-1-infected CEM cells, while not suppressing the HIV-1 p24 production from latent HIV-1-infected ACH-2 cells after stimulation with phorbol 12-myristate 13-acetate. DDSD also inhibited the synthesis of HIV-1 proviral DNA at 20-50 microM, not only 1 h but also 24 h after HIV-1 infection. Taken together, DDSD is a potent inhibitor of HIV-1 production, and may become a unique leading compound for chemotherapy of acquired immunodeficiency syndrome.

Acetals↗
PubMed1999

Abundant expression and cytoplasmic aggregations of [alpha]1A voltage-dependent calcium channel protein associated with neurodegeneration in spinocerebellar ataxia type 6.

Spinocerebellar ataxia type 6 (SCA6) is one of the eight neurodegenerative diseases caused by a tri-nucleotide (CAG) repeat expansion coding polyglutamine (CAG repeat/polyglutamine diseases) and is characterized by late onset autosomal dominant cerebellar ataxia and predominant loss of cerebellar Purkinje cells. Although the causative, small and stable CAG repeat expansion for this disease has been identified in the [alpha]1A voltage-dependent calcium channel gene (CACNA1A), the mechanism which leads to predominant Purkinje cell degeneration is totally unknown. In this study, we show that the calcium channel mRNA/protein containing the CAG repeat/polyglutamine tract is most intensely expressed in Purkinje cells of human brains. In SCA6 brains, numerous oval or rod-shaped aggregates were seen exclusively in the cytoplasm of Purkinje cells. These cytoplasmic inclusions were not ubiquitinated, which contrasts with the neuronal intra-nuclear inclusions of other CAG repeat/polyglutamine diseases. In cultured cells, formation of perinuclear aggregates of the channel protein and apoptotic cell death were seen when transfected with full-length CACNA1A coding an expanded polyglutamine tract. The present study indicates that the mechanism of neurodegeneration in SCA6 is associated with cytoplasmic aggregations of the [alpha]1A calcium channel protein caused by a small CAG repeat/polyglutamine expansion in CACNA1A.

Animals↗
PubMed1999

Gastric tumor induction by 1,2-dimethylhydrazine in Wistar rats with intestinal metaplasia caused by X-irradiation.

Five-week-old male Wistar rats were X-irradiated with a total of 20 Gy in 2 equal fractions at a 3-day interval. 1,2-Dimethylhydrazine (DMH) solution was injected i.m. into the back musculature at a dose of 20 mg/kg body weight weekly for 10 weeks, beginning 20 weeks after the final irradiation. Twelve months after the initial carcinogen treatment, tumors in the fundus of the glandular stomach were observed in 5 of 23 animals receiving both X-irradiation and DMH treatment. No tumors of the glandular stomach were observed in the DMH and X-ray alone or nontreatment groups. It is concluded that the presence of intestinal metaplasia may increase sensitivity to the induction of gastric tumors by carcinogens like DMH.

1,2-Dimethylhydrazine↗
PubMed1999

Increase of CD26/dipeptidyl peptidase IV expression on human gingival fibroblasts upon stimulation with cytokines and bacterial components.

CD26/dipeptidyl peptidase IV (DPPIV) is a cell surface ectoenzyme which participates in immune and inflammatory reactions. We found that CD26 was only partially expressed on human fibroblasts from periodontal tissues, whereas fibroblasts from lung and skin expressed CD26 constitutively as revealed by flow cytometry. We examined the possible upregulation of CD26 expression on human gingival fibroblasts in response to various stimulants. Interleukin-1alpha (IL-1alpha); tumor necrosis factor alpha; gamma interferon; lipopolysaccharide from Porphyromonas gingivalis, Prevotella intermedia, and Escherichia coli; and Prevotella glycoprotein augmented CD26 expression on gingival fibroblasts. Among the stimulants, IL-1alpha exhibited the most potent activity. Enzymatic activity of CD26 induced by IL-1alpha on fibroblasts was determined colorimetrically in terms of Gly-Pro hydrolysis of a synthetic chromogenic substrate, Gly-Pro p-nitroanilide. Among various inhibitors tested, diprotin A and phenylmethylsulfonyl fluoride inhibited the enzymatic activity, suggesting that the enzyme induced by IL-1alpha was DPPIV. The upregulation of CD26 mRNA expression upon stimulation with IL-1alpha was also revealed by a quantitative reverse transcription-PCR assay. In the kinetic experiment, 48 h and several days were required for maximum CD26 mRNA accumulation and CD26 molecule expression on the cell surface, respectively. The addition of cycloheximide at 2 h before IL-1alpha stimulation almost completely inhibited the accumulation of CD26 mRNA. These results suggested that induction of CD26 on human gingival fibroblasts is regulated at the transcriptional level and is also dependent on a de novo-synthesized protein factor(s).

Cytokines↗
PubMed1999

Clinical, neuropathological, and molecular study in two families with spinocerebellar ataxia type 6 (SCA6).

To clarify the clinical, neuropathological, and molecular characteristics of spinocerebellar ataxia type 6 (SCA6), two unrelated Japanese families with SCA6 were studied. A clinical feature of the two families was late onset "pure" cerebellar ataxia. Pathologically, three SCA6 brains consistently showed Purkinje cell dominant cortical cerebellar degeneration. Morphometric analysis showed that loss of the cerebellar granule cells and inferior olivary neurons were very mild compared with the severity of Purkinje cell loss. There was no obvious ubiquitin immunoreactive nuclear inclusions. All affected patients had identical expanded alleles, and the expansion was also homogeneously distributed throughout the brain without mosaicism. The present study showed that SCA6 is characterised by Purkinje cell dominant cortical cerebellar degeneration, highly stable transmission of the CAG repeat expansion, and lack of ubiquitin immunoreactive nuclear inclusions.

Adult↗
PubMed1999

[A case of delayed cerebral infarction occurring in puerperium preceded by herpes zoster ophthalmicus in late pregnancy].

Delayed central neurological symptoms following herpes zoster ophthalmicus (HZO) such as "herpes zoster ophthalmicus and delayed contralateral hemiparesis" are considered to be due to ipsilateral intracranial vasculopathy. We experienced a rare case with cerebral infarction occurred in puerperium following HZO in late pregnancy. A healthy 30-year-old woman had left HZO at weeks 35 of gestation. She was given acyclovir (ACV) for external use and improved with small pigmentation on the left eye-lid. Seven weeks after the onset of HZO, she suddenly developed aphasia and right hemiparesis. Cerebral angiogram showed narrowing on M 1 segment of the ipsilateral middle cerebral artery. The occlusion was seen on peripheral portion of the angular artery on the same side. In cerebrospinal fluid (CSF), cell count was slightly elevated, but concentration of protein and sugar were normal. Varicella-zoster titer was increased in both serum and CSF. She was treated with intravenous ACV (1500 mg/day) for 10 days. On the next day after the treatment, the cell count was normalized and on 18th day, varicella-zoster titer was decreased in CSF. Higher brain function improved and no relapses occurred. This is a first case of delayed cerebral infarction occurring in puerperium preceded by herpes zoster ophthalmicus in late pregnancy, as far as we searched. We should treat carefully pregnant or lactating patients with HZO, considering delayed cerebral infarction.

Acyclovir↗
PubMed1999

Pressure pain threshold with and without iontophoretic anesthesia of the masseter muscle in asymptomatic males.

AIMS: The pressure pain threshold (PPT) in the superficial masseter muscle was measured with and without cutaneous anesthesia to determine whether there would be a difference in PPT scores. METHODS: In 14 healthy male subjects, cutaneous tissues in the target areas were anesthetized with lidocaine with the help of an iontophoretic device. As a control, physiologic saline solution was applied iontophoretically to the contralateral masseter site. The subject and the PPT examiner did not know which side contained anesthesia, and the selection of which side to anesthetize was done in a random fashion. Multiple PPT measurements were made in the target sites before and immediately after the iontophoretic anesthesia. RESULTS: The PPT level on the lidocaine side was not statistically different from the PPT level recorded on the control side (339.0 +/- 87.6 kPa and 337.5 +/- 77.7 kPa, respectively). CONCLUSION: Pressure pain sensation in the human masseter is not derived predominantly from the cutaneous tissues, but from the muscle itself.

Adult↗
PubMed1999

[Effect of intravenous immunoglobulin therapy in a case of idiopathic recurrent brachial and lumbosacral plexopathy].

We report a case of a 23-year-old woman with idiopathic brachial and lumbosacral plexopathy who presented a relapsing course of weakness and numbness following acute onset of pain in the right shoulder or pelvic girdle area. On her first admission, the patient recovered gradually with oral prednisolone. But after about 1 year, her symptoms worsened. In the second admission, oral prednisolone had no effect on her symptoms, so intravenous immunoglobulin (IVIG; 0.1 g/kg/day, 5 days) therapy was tried. The patient improved about 2 weeks after IVIG therapy. About 1 year later, her symptoms worsened and was administered again. In the third admission, IVIG therapy of which dose was the same as that in the previous admission had an effect on her symptoms. The dose of IVIG in our case was relatively low, compared with those in cases reported before (0.2-2 g/kg/day). This findings suggest that a relatively low-dose IVIG therapy is effective for idiopathic plexopathy.

Adult↗