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Biomedical subjects

S Ikeda

Publications and source records attributed to S Ikeda.

At least 19 recordsLinked to original sources

Lack of modulation of Ib inhibition during antagonist contraction in spasticity.

OBJECTIVE: To examine the modulation of non-reciprocal group I (Ib) inhibition during tonic contraction of antagonist muscles in patients with spasticity vs normal subjects. METHODS: The authors studied 10 patients with spastic paraplegia due to cervical compression myelopathy and 16 age-matched normal subjects. Ib inhibition to soleus motoneurons was recorded as the change in size of the H-reflex of the soleus, evoked by conditioning stimulus to the nerve innervating the medial gastrocnemius muscle. The extent of inhibition was studied at rest and during tonic contraction of the pretibial muscles of variable strength. RESULTS: In the resting state, the extent of inhibition in the patients did not differ from normal controls. During antagonist contraction, the extent of inhibition increased both in the normal subjects and patients. The increment was smaller in the patients, especially in those with severe spastic gait. The smaller increment in the inhibition was correlated with the time required to walk 10 m in the patients. CONCLUSION: The authors observed a lack of modulation of Ib inhibition during tonic antagonist contraction in patients with spasticity, especially those with gait disturbance. Disturbed central modulation of non-reciprocal (Ib) interneurons may be responsible for spasticity.

Aged↗

Retinoids during the in vitro transition from bovine morula to blastocyst.

BACKGROUND: The conversion of retinol (ROH) to retinoic acid (RA) is crucial during development but has been not studied during blastocyst formation. METHODS AND RESULTS: In vitro-produced bovine morulae were treated for 24 h with citral (which inhibits the synthesis of RA from ROH), citral + all trans retinoic acid (ATRA), ATRA or no additives. Citral interfered with blastocyst development, whereas exogenous RA had no effect. RA, however, reversed the effect of citral on development and stimulated cell proliferation. Neither citral nor RA changed the apoptotic index, but RA triggered an increase in the apoptotic frequency of the inner cell mass. Citral and RA reduced the necrotic index. Na/K-ATPase alpha1-subunit mRNA concentrations (analysed by real-time PCR) increased after hatching and showed dependence on retinoid activity, but no evidence was found of any retinoid effect on p53 expression. Nevertheless, the p53 mRNA concentration increased in response to proliferation in hatched blastocysts. CONCLUSION: The preimplantation bovine embryo metabolizes endogenous ROH to RA, which participates in important cell processes. The true extent of the influence of RA is unknown, although the modulation of retinoid metabolism seems to be a means of increasing cell proliferation. This knowledge might be used to improve embryo quality and the efficiency of stem cell derivation.

Acyclic Monoterpenes↗

A case of a Japanese neonate with congenital ichthyosiform erythroderma diagnosed as Netherton syndrome.

We report a 6-day-old Japanese girl showing generalized erythroderma accompanied by yellowish, exfoliative scaling that was accentuated on the face and scalp. Histological analysis showed psoriasiform dermatitis with acanthotic epidermis and premature shedding of the stratum corneum. Measurement of trypsin-like hydrolytic activity in SC showed six-fold greater activity compared with age-matched controls. DNA analysis revealed two mutations, 375delAT and 966insC, in exons 5 and 11, respectively, of the SPINK5 gene. Although at 4 weeks the child was still too young to display characteristic hair abnormalities or atopic diathesis, we diagnosed Netherton syndrome based on enzyme assay and DNA analysis.

Carrier Proteins↗

Investigation on the growth of coprophagy-prevented rats with supplemented vitamin B12.

The growth of coprophagy-prevented rats was compared under administration of normal levels of vitamin B12 and supplemented amounts. Two experiments in which supplemented amounts of vitamin B12 were administered were conducted under different conditions. Six rats per group were fed under coprophagy-allowed (conventional feeding) and coprophagy-prevented conditions respectively. In the first experiment, coprophagy-prevented rats were fed only feed containing recommended vitamin B12 level and forced fed hydrous faeces, vitamin B12 and folic acid respectively. In the second experiment, coprophagy-prevented rats were fed AIN-93G at the recommended vitamin B12 level (25 microg/kg diet), at 100 times the level and at 1000 times the level respectively. Body weight, feed consumption and amounts of each faeces type were determined in both experiments. In a comparison of body weight gain, we learned that coprophagy prevention reduced the values, but that there was no significant difference in the forced feeding group in the first experiment. Similar results were recognized in the second experiment. Vitamin B12 supplementation was not able to raise feed intake significantly and hence it obviously was not a severely limiting factor under the respective experimental condition which depressed feed intake.

Animal Feed↗

Apoptosis-independent poor morphology of bovine embryos produced by multiple ovulation.

In multiple ovulation and embryo transfer (MOET) programmes in cattle, a considerable number of morphologically poor-quality embryos continue to be produced; this is one of the limiting factors of the technique. Apoptosis has often been implicated in developmental arrest and fragmentation; these are regarded as poor traits of embryonic quality in mammalian pre-implantation embryos. In the present study, apoptosis was assessed in morphologically poor-quality embryos in comparison with good-quality embryos that were recovered from a MOET programme. Retarded embryos (two to 16 cell stage), morulae with severe fragmentation and morphologically good-quality morulae recovered from superstimulated cows at day 7 post-insemination were subjected to TdT-mediated dUTP nick-end labelling (TUNEL) and Hoechst staining. Cell nuclei that showed both TUNEL staining and apoptotic morphology were considered to be apoptotic. Apoptotic index (AI) was calculated as the percentage of apoptotic cells per embryo. Fifteen of 17 retarded embryos and 10 of 15 morphologically poor-quality morulae did not show signs of apoptosis. The mean AIs in the morphologically poor-quality embryos (two to 16 cell stage, 2.2%; poor morulae, 1.3%) were as low as that in the good-quality embryos (2.9%). These results suggest that another mode of developmental arrest and/or fragmentation that is independent of apoptosis occurs in morphologically poor-quality embryos recovered from MOET programmes.

Animals↗

Abilities of cumulus and granulosa cells to enhance the developmental competence of bovine oocytes during in vitro maturation period are promoted by midkine; a possible implication of its apoptosis suppressing effects.

We previously reported that when midkine (MK), a heparin-binding growth differentiation factor was used in in vitro maturation (IVM) culture of bovine cumulus-enclosed oocytes (CEOs), their developmental competence to the blastocyst stage after in vitro fertilization (IVF) was enhanced and the effect of MK might be mediated by its action upon mural granulosa cells and cumulus cells that closely surround the oocyte. In the present study, when denuded oocytes (DOs) were matured in IVM medium with or without MK (200 ng/ml) in the presence or absence of isolated cumulus cell masses and subjected to IVF, the enhancing effects of MK on the developmental competence of DOs to the blastocyst stage after IVF were exerted only in the presence of cumulus cells. In addition, we prepared the conditioned media of granulosa cells cultured with or without 200 ng MK/ml (CMMK+ or CMMK- respectively) and examined their effects on the IVM of DOs in terms of their developmental competence to the blastocyst stage after IVF. The supplementation of CMMK+ into IVM medium at 40% (v/v) significantly enhanced the blastocyst development compared with the no additive control and the CMMK- supplemented groups. Furthermore, the effects of MK during IVM of bovine CEOs on the cumulus cell apoptosis were investigated. CEOs were cultured up to 24 h in IVM medium without (control) or with 200 ng MK/ml. The genomic DNA was extracted from CEOs at 0, 6, 12, 18 and 24 h of IVM and subjected to ligation-mediated PCR (LM-PCR) to detect the apoptotic internucleosomal DNA fragmentation. DNA fragmentation was scarcely detected at the start of IVM, whereas it increased time-dependently as the IVM culture progressed. The degree of the fragmentation was significantly lower in the MK-treatment group compared with the control group at 18 and 24 h of IVM. The apoptosis-suppressing effect of MK on cumulus cells was further confirmed in situ by using TUNEL on CEOs. In conclusion, data from the present study further confirmed that MK enhances the developmental competence of bovine oocytes via cumulus and granulosa cells. It was also demonstrated that MK suppresses the apoptosis that occurs in cumulus cells during the period of IVM of bovine CEOs. The putative soluble factor(s) from cumulus cells was suggested from the experiment using CMMK+ . MK may promote the production of such factors in part by its anti-apoptotic effects on cumulus cells.

Animals↗

Cost-effectiveness of Liple (LipoPGE1) for arteriosclerosis obliterans patients in Japan: an economic evaluation using the EQ-5D instrument.

AIM: This study was conducted to evaluate the health-related quality of life (HRQOL) and cost-effectiveness of LipoPGE(1) when added to the conventional treatment of arteriosclerosis obliterans (ASO) patients. The research design consisted of a before and after-treatment study without comparison groups. We collected data from May 1999 through July 2001 at 473 institutions located throughout Japan. The subjects were ASO patients who experienced pain at rest or had ulcers of the extremities. METHODS: The observation period was a 2-month period that commenced with the start of administration of LipoPGE1. The HRQOL score (utility value) was obtained from the EQ-5D instrument, and the incremental cost-effectiveness ratio was calculated on the basis of quality-adjusted life years (QALYs). RESULTS: The mean utility value for the 2 months after the start of the administration of LipoPGE(1) was 0.672, and it was a significantly higher (P<0.0001) than the 0.616 before administration of LipoPGE(1). The incremental cost-effectiveness ratio was 18,807 US dollar/QALY assuming that drug efficacy persisted for 1 year after the end of LipoPGE1 therapy, and 75,227 dollar/QALY assuming a duration of just 3 months. CONCLUSIONS: We concluded that when LipoPGE1 is added to the conventional treatment of ASO patients, the HRQOL of the patient improves, and it is highly cost-effective.

Adolescent↗

[Surgical treatment for clinical stage II and III small cell lung cancer patients].

To evaluate a surgical resection in multidisciplinary treatment for clinical stage (c-stage) II and III small cell lung cancer (SCLC) patients, we examined the postoperative prognosis concerning in 18 patients who underwent complete surgical resection. Five-year survival rate of 8 c-stage II and 10 c-stage III patients showed 62.5% and 46.7%, respectively. Of these, 7 patients underwent preoperative induction chemotherapy resulting in down-staging to c-stage 0-I, and their survival rate at 5 years after sugery was as good as 68.6%. However, in 4 (57.1%) of 7 patients, tumor cells proved to be alive by pathological assessment of lymph nodes. As a consequence, it was suggested that surgery for c-stage II and III SCLC patients is a meaningful treatment considering their prognoses. In particular, even though the patients show a favorable response of preoperative chemotherapy, to completely eliminate remnant tumor cells, a surgical resection may be necessary.

Antineoplastic Combined Chemotherapy Protocols↗

A multilayer membrane amperometric glucose sensor fabricated using planar techniques for large-scale production.

This paper reports on a multilayer membrane amperometric glucose sensor fabricated using planar techniques. It is characterized by good reproducibility and suitable for large-scale production. The glucose sensor has 82 electrode sets formed on a single glass substrate, each with a platinum working electrode (WE), a platinum counter electrode (CE) and an Ag/AgCl reference electrode (RE). The electrode sets are coated with a membrane consisting of five layers: gamma-aminopropyltriethoxysilane (gamma-APTES), Nafion, glucose oxidase (GOX), gamma-APTES and perfluorocarbon polymer (PFCP), in that order. Tests have shown that the sensor has acceptably low dispersion (relative standard deviation, R.S.D.=42.9%, n=82), a wide measurement range (1.11-111 mM) and measurement stability over a 27-day period. Measurements of the glucose concentration in a control human urine sample demonstrated that the sensor has very low dispersion (R.S.D.=2.49%, n=10).

Biosensing Techniques↗

Chronic exercise accelerates the degeneration-regeneration cycle and downregulates insulin-like growth factor-1 in muscle of mdx mice.

The aim of this study was to examine the effects of chronic running exercise on degenerative-regenerative processes in the hindlimb muscles of dystrophin-deficient mdx mice. The number of large-sized degenerative-regenerative groups (DRGs) was markedly decreased, whereas that of small-sized DRGs was unchanged by exercise. Expression of insulin-like growth factor-1 (Igf1), as well as a myogenic factor MyoD (Myod1), was downregulated in mdx muscles by exercise. The downregulation of Igf1 may well correlate with the decrease in the population of early regenerating fibers, which existed predominantly in DRGs, because IGF-1 was mainly localized in these fibers. Our data indicate that chronic exercise may accelerate the active cycle of degeneration-regeneration in mdx skeletal muscles. This means that mdx skeletal muscles can temporarily cope with work-induced injury by enhancing muscle regeneration and repair, but we speculate that an early decline of IGF-1 will accelerate age-dependent muscle wasting and weakness in the later stage of life in mdx mice.

Adaptation, Physiological↗

Domino liver transplantation in living donors.

Domino liver transplantation (DLT) has been developed as a method to expand the donor pool. In living donors DLT, the prime concern is to avoid any disadvantage to the donor and the first recipient. Seven DLTs were performed among 211 patients who underwent living donor liver transplantation. The domino recipients included six with hepatocellular carcinoma and one with citrullinemia. The domino grafts were obtained from patients with familial amyloid polyneuropathy (FAP) including the left liver in three cases and the right liver in four. Among the seven domino recipients, a 64-year-old woman with advanced hepatocellular carcinoma died of lung metastasis. The other six domino recipients are alive without FAP symptoms. In living donor liver transplantation, because the vessels of the graft from the first donor are not long enough for anastomosis, the hepatic vessels must be left as long as possible when removing the liver from the FAP patients in order to ensure sufficient safety for vascular reconstruction. With careful decision making during the procedure, such as where to divide the vessels in the FAP patients, DLT may help address the shortage of liver grafts.

Amyloid Neuropathies, Familial↗

Effects of ultraviolet B irradiation, proinflammatory cytokines and raised extracellular calcium concentration on the expression of ATP2A2 and ATP2C1.

BACKGROUND: Darier disease (DD) and Hailey-Hailey disease (HHD) are autosomal dominantly inherited skin disorders that histologically share the characteristics of suprabasal separation and acantholysis of epidermal keratinocytes. Various mutations in the DD gene (ATP2A2) and the HHD gene (ATP2C1) (respectively encoding the calcium pumps of the sarco/endoplasmic reticulum and the Golgi apparatus) have recently been described in multiple families with DD and HHD. Mutations in ATP2A2 or ATP2C1 have been suggested as causing the conditions via the mechanism of haploinsufficiency. Ultraviolet (UV) B irradiation is thought to be an aggravating factor in both diseases. OBJECTIVES: To examine the effects of various stimuli on ATP2A2 and ATP2C1 mRNA expression, and to examine the role of calcium pumps during keratinocyte differentiation. METHODS: The effects of UVB irradiation, of UVB-inducible inflammatory cytokines produced by keratinocytes and of high-calcium medium (1.8 mmol L(-1) as opposed to 0.08 mmol L(-1) Ca2+) on ATP2A2 and ATP2C1 mRNA expression were quantified in cultured normal human keratinocytes using reverse transcription-polymerase chain reaction. RESULTS: Expression of ATP2A2 and ATP2C1 mRNA was suppressed immediately after exposure to UVB irradiation, and modulation of mRNA expression was achieved in keratinocytes cultured with proinflammatory cytokines. The mRNA expression of both genes was increased significantly after the shift to high extracellular Ca2+ concentration. CONCLUSIONS: The results suggest that modulation of ATP2A2 and ATP2C1 mRNA expression by UV or cytokines might contribute to the clinical presentations unique to DD and HHD, and that the controlled expression of these genes plays an important role in keratinocyte homeostasis, function and differentiation.

Calcium↗

Effects of drugs and anticytokine antibodies on expression of ATP2A2 and ATP2C1 in cultured normal human keratinocytes.

BACKGROUND: Darier's disease (DD) and Hailey-Hailey disease (HHD) are skin disorders arising, respectively, from autosomal dominant mutations in ATP2A2, encoding the sacro/endoplasmic reticulum calcium ATPase, and ATP2C1, encoding the Golgi apparatus calcium ATPase. Exposure to ultraviolet (UV) B irradiation exacerbates the skin lesions, which can be treated with corticosteroids and retinoids. OBJECTIVES: To investigate the molecular basis for DD and HHD. METHODS: We used quantitative reverse transcriptase-polymerase chain reactions to examine the effects of UVB irradiation on ATP2A2 and ATP2C1 mRNA levels in cultured normal keratinocytes. RESULTS: We observed that UVB irradiation reduced ATP2A2 and ATP2C mRNA levels. The addition of retinoids or corticosteroids to the cell culture inhibited the UVB-induced suppression of both ATP2A2 and ATP2C1 mRNA levels, and UVB-induced suppression of ATP2C1 mRNA was also inhibited by the addition of ciclosporin, tacrolimus and vitamin D(3). The addition of anti-interleukin (IL)-6 antibody to the cell culture prevented the UVB-induced suppression of ATP2A2 and ATP2C1 mRNA; in contrast, the addition of anti-IL-8 antibody slightly accelerated the suppression. CONCLUSIONS: These results suggest that drugs effective for DD and HHD act by modulating ATP2A2 and ATP2C1 mRNA expression, respectively, and that the proinflammatory cytokines IL-6 and IL-8 play important roles in the regulation of ATPA2 and ATP2C1 expression in homeostasis and/or inflammation of the skin.

Antibodies↗

Sensitivity of adult T-cell leukaemia lymphoma cells to tumour necrosis factor-related apoptosis-inducing ligand.

Tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces apoptosis in many transformed cells, but not in normal cells, and hence TRAIL has recently emerged as a novel anti-cancer agent. Adult T-cell leukaemia lymphoma (ATLL) is a neoplasm of T-lymphocyte origin aetiologically associated with human T-lymphotropic virus type 1 (HTLV-I), and is resistant to standard anti-cancer therapy. We thus characterized the sensitivity of ATLL cells to TRAIL in this study. Although most primary ATLL cells and cell lines expressed TRAIL death receptors on their surface, they showed only restricted sensitivity to TRAIL. Among the 10 ATLL cell lines examined, one was sensitive, but two had insufficient death-receptor expression, two had an unknown resistant mechanism with abrogation of the death signal upstream of caspase-8, and the remaining five showed attenuation of the signal in both extrinsic and intrinsic pathways by X-linked inhibitor of apoptosis and Bcl-2/Bcl-xL respectively. Furthermore, the level of HTLV-I tax expression was significantly correlated to TRAIL resistance. Interestingly, ATLL cells themselves expressed TRAIL on the cell surface. Constitutive production of TRAIL may offer resistance, thus allowing the development of TRAIL-resistant ATLL cells. Consequently, the resistant mechanism in ATLL cells against TRAIL was assigned to multiple factors and was not explained by a definitive single agent.

Antineoplastic Agents↗

A case of chromomycosis caused by Fonsecaea pedrosoi and a review of reported cases of dematiaceous fungal infection in Japan.

We report a case of chromomycosis caused by Fonsecaea pedrosoi that developed in the left buttock of a 63-year-old female farmer. About 4 years ago, the patient developed erythema in the left buttock, which gradually spread. At the first consultation, we noted a well-defined, red-brown, infiltrated erythematous plaque (8 x 6 cm). Histopathological examination revealed a granulomatous lesion, containing sclerotic cells, associated with giant cells in the upper dermis. The causative fungus was difficult to identify due to low conidiogenesis, but was eventually identified by slide culture as F. pedrosoi. Excision and skin graft were performed, and no recurrence has been observed after 2 years. In Japan, 212 cases of dematiaceous fungal infection were reported in the period from 1982 to 2001. The causative fungus was F. pedrosoi in the majority of cases (126/212; 66%), followed by Exophiala jeanselmei (36/212; 19%). Similar incidence of dematiaceous fungal infection was reported in male and female patients. The upper limbs were affected most frequently in both male and female patients. Ten cases were associated with visceral lesions.

Ascomycota↗

Age associated axonal features in HNPP with 17p11.2 deletion in Japan.

OBJECTIVE: To clarify age related changes in the clinicopathological features of hereditary neuropathy with liability to pressure palsy (HNPP) in Japanese patients with deletion of 17p11.2, particularly concerning axonal abnormalities. METHODS: Forty eight proband patients from 48 HNPP families were assessed as to clinical, electrophysiological, and histopathological features, including age associated changes beyond those in controls. RESULTS: Motor conduction studies showed age associated deterioration of compound muscle action potentials in nerves vulnerable to repetitive compression (median, ulnar, and peroneal nerves), but not in others such as the tibial nerve. Sensory conduction studies revealed more profound reduction of action potentials than motor studies with little age related change. Large myelinated fibre loss was seen in the sural nerve irrespective of age at examination. CONCLUSIONS: Irreversible axonal damage may occur at entrapment sites in motor nerves in HNPP patients, progressing with aging. Sensory nerves may show more profound axonal abnormality, but without age association. The electrophysiological features of HNPP are presumed to be a mixture of abnormalities occurring from early in life and acquired features caused by repetitive insults at entrapment sites. Unlike Charcot-Marie-Tooth disease type 1A, age associated axonal damage may not occur unless the nerves are subjected to compression.

Action Potentials↗