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Biomedical subjects

M Shindo

Publications and source records attributed to M Shindo.

At least 19 recordsLinked to original sources
PubMed2006

Suppression of tumor growth by intra-muscular transfer of naked DNA encoding adrenomedullin antagonist.

We have recently reported that the intra-tumoral injection of adrenomedullin (AM) antagonist (AMA; AM (22-52)) peptides significantly reduced the in vivo growth of a pancreatic cancer cell line in severely combined immunodeficient (SCID) mice. In the present study, we examined the effects of intra-tumoral and intra-muscular transfers of naked DNA encoding AMA on the in vivo growth of cancer cell lines. We demonstrate that these treatments induce the regression of a pancreatic cancer cell line and a breast cancer cell line inoculated in SCID mice. Furthermore, CD31-positive cells disappear completely from tumor tissues, following treatment, indicating that neo-vascularization is entirely inhibited. These results suggest that the intra-tumoral or intra-muscular transfer of naked DNA encoding AMA might be a promising alternative modality for treating human cancers.

Adrenomedullin↗
PubMed2006

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↗
PubMed2006

JTP-426467 acts as a selective antagonist for peroxisome proliferator-activated receptor gamma in vitro and in vivo.

AIM: JTP-426467 was identified as a result of screening in search of selective antagonist for peroxisome proliferator-activated receptor gamma (PPARgamma). We examined whether JTP-426467 functioned as a PPARgamma antagonist in vitro and in vivo and investigated physiological effects of JTP-426467. METHODS: The effect of JTP-426467 as a PPARgamma antagonist was studied in a cell-based reporter assay and an adipocyte differentiation assay. Target mRNA expression levels were determined by branched DNA (bDNA) assay. To examine the effects as a PPARgamma antagonist in vivo, a competitive study between JTP-426467 and BRL49653 (rosiglitazone), a PPARgamma agonist, was performed using KK-Ay mice. The effects of JTP-426467 alone after administration to KK-Ay mice were also explored. JTP-426467 antagonized PPARgamma activity in a reporter assay system, but not PPARalpha. RESULTS: JTP-426467 inhibited the expression of hormone-sensitive lipase (HSL) mRNA, an adipocyte-abundant gene, but not PPARgamma itself or cyclophilin mRNA (as constitutive mRNA), and also suppressed triglyceride accumulation in differentiated stromal vascular fraction cells (SVFs). JTP-426467 antagonized PPARgamma agonistic action by BRL49653 in KK-Ay mice on high-fat diet, in terms of plasma glucose, body weight gain and interscapular brown adipose tissue (IBAT) weight. JTP-426467 alone inhibited body weight gain and decreased plasma leptin level in KK-Ay mice. CONCLUSIONS: JTP-426467 acted as a pure and potent PPARgamma antagonist in vitro. Interestingly, JTP-426467 completely antagonized the effects of PPARgamma agonist BRL49653 in an obese diabetic model. JTP-426467 may be a useful tool for the study of PPARgamma in biological and physiological function.

Adipocytes↗
PubMed2005

Long-period accelerometer monitoring shows the role of physical activity in overweight and obesity.

CONTEXT: Physical activity (PA) plays an important role in obesity. A new accelerometer has been developed to assess total energy expenditure as well as PA. OBJECTIVE: To investigate the association of PA with overweight and obesity in Japanese men and women, a large cross-sectional study was performed using a single-axis accelerometer. DESIGN, SETTING AND PARTICIPANTS: Population-based cross-sectional study of Japanese 18-84 y of age. Height, body weight and PA were measured in 400 male and 388 female Japanese volunteers from 1999 to 2000. The outcome measurements were overweight and obesity, which are defined as a body mass index >/=25 kg/m(2). PA was measured for 1 to 4 weeks and was then categorized into three activity levels, which were defined as light, moderate and vigorous PA. RESULTS: Prevalence of overweight and obesity was 22.3%. Number of steps and time spent in moderate and vigorous PA per day were lower in overweight and obese individuals. No difference was found in time spent in light PA. Individuals who are in the 4th and 5th quintile of moderate and vigorous PA showed a significantly lower body mass index. When odd ratios (ORs) of overweight and obesity estimated by logistic regression were used as effect measures, overweight and obesity were negatively associated with vigorous PA (ORs=0.91). CONCLUSION: These results indicate that overweight and obese individuals have a lower step rate and are spending less time for moderate to vigorous PA. Participation in vigorous PA is an important predictor of overweight and obesity.

Adolescent↗
PubMed2004

Precision spectroscopy of pionic 1s states of Sn nuclei and evidence for partial restoration of chiral symmetry in the nuclear medium.

Deeply bound 1s states of pi(-) in (115,119,123)Sn were preferentially observed using the Sn(d,3He) pion-transfer reaction under the recoil-free condition. The 1s binding energies and widths were precisely determined and were used to deduce the isovector parameter of the s-wave pion-nucleus potential to be b1=-(0.115+/-0.007)m(-1)(pi). The observed enhancement of |b(1)| over the free piN value (b(free)1/b1=0.78+/-0.05) indicates a reduction of the chiral order parameter, f*pi(rho)2/f2pi approximately 0.64, at the normal nuclear density, rho=rho(0).

Journal Article↗
PubMed2003

The I allele of the angiotensin-converting enzyme gene is associated with an increased percentage of slow-twitch type I fibers in human skeletal muscle.

The insertion (I) allele of the human angiotensin-converting enzyme (ACE) gene is associated with lower serum and tissue ACE activity, and with greater endurance performance and enhanced mechanical efficiency of trained muscle. We tested the hypothesis that the ACE-I allele may be associated with increased slow-twitch fiber, which is more efficient than fast-twitch fiber in low-velocity contraction, by examining the association between the ACE genotype and skeletal muscle fiber (SMF) types in 41 untrained healthy young volunteer subjects (31 males, 10 females, age 24 +/- 3 years). Skeletal muscle samples were taken from the left vastus lateralis using the needle-biopsy method. Slow-twitch type I fibers and fast-twitch type IIa and IIb fibers were classified histochemically based on staining for myosin adenosine triphosphatase (ATPase) activity at different pH values. Amylase-periodic acid-Schiff staining was used to visualize capillaries around fibers. ACE-II subjects had significantly (p < 0.01) higher percentages of type I fibers (50.1 +/- 13.9%vs 30.5 +/- 13.3%) and lower percentages of type IIb fibers (16.2 +/- 6.6%vs 32.9 +/- 7.4%) than ACE-DD subjects. The linear trends for decreases in type I fibers and increases in type IIb fibers from ACE-II --> ID --> DD genotypes were significant as assessed by an analysis of variance. The ratio of type I:II fibers also differed according to the ACE genotype. A multivariate logistic regression analysis showed that the ACE-I allele had significant additive and recessive (codominant) effects on the increased type I fibers and the ratio of type I:II fibers. No specific pattern of capillarization was observed among the three ACE genotypes. In conclusion, the ACE-I allele was associated with increased type I SMF, which may be a mechanism for the association between the ACE genotype and endurance performance.

Adult↗
PubMed2002

Abnormal conditioning effect of transcranial magnetic stimulation on soleus H-reflex during voluntary movement in Parkinson's disease.

OBJECTIVES: The objective of this study is to clarify the participation of cortical motor control abnormality in the motor dysfunction of Parkinson's disease (PD), especially at the onset of movement. METHODS: Conditioning effects of transcranial magnetic simulation (TMS) on the soleus (SOL) H-reflex evoked with tibial nerve stimulation were examined in 19 patients with PD and 10 normal volunteers. Experiments were done at rest, during tonic plantarflexion (PF), and at PF onset. Stimulus intensity of TMS was maintained at less than 5% of the motor threshold in each situation. Seven patients underwent pallidotomy and were examined twice, once before and once after the operation. RESULTS: Short latency subthreshold TMS stimulation did not facilitate the SOL H-reflex neither during tonic PF nor at PF onset in the patients with PD, though it was evident in normal subjects. In some patients, paradoxical inhibition appeared at PF onset. The facilitation increase at PF onset, as compared to that at rest, was negatively correlated with the motor part of the unified Parkinson's disease rating scale and with the rigidity grade. Pallidotomy improved both modulation and the clinical scores. CONCLUSIONS: Cortical activity for the proper execution of reciprocal control between the agonist and antagonist seems to be disturbed in PD.

Aged↗
PubMed2002

Association of angiotensin-converting-enzyme gene polymorphism with the depressor response to mild exercise therapy in patients with mild to moderate essential hypertension.

We studied the association of angiotensin I-converting enzyme (ACE) gene polymorphism with the depressor response to exercise therapy in 64 Japanese subjects with mild to moderate essential hypertension. Each subject performed 10 weeks of mild (lactate threshold intensity: approximately 50% maximum oxygen consumption) exercise therapy on a bicycle ergometer. Systolic blood pressure (SPB), diastolic blood pressure (DPB), and mean arterial pressure (MAP) were significantly decreased by exercise therapy in subjects with the ACE-II and ID genotypes but not in DD subjects. The time-by-genotype interaction effects were significant for DBP and MAP. According to a multiple logistic regression analysis, the age- and baseline plasma renin activity-adjusted relative risk (odds ratio) for the lack of a depressor response conferred by the D allele (assuming an additive effect) was 2.72 [95% confidence interval (CI), 1.07-6.91; p = 0.034]; for DD genotypes, as compared with the DI and II genotypes (assuming that the D allele is recessive), it was 11.7 (95% CI, 2.25-60.6; p = 0.003). ACE gene I/D polymorphism is associated with the depressor response of essential hypertensives to mild exercise therapy, which suggests that genetic features may underlie, at least in part, the heterogeneity of the depressor response in essential hypertensives to mild exercise therapy.

Blood Pressure↗
PubMed2002

Peripheral mechanisms in tremor after traumatic neck injury.

Tremor is a rare manifestation after neck injury, and its physiological mechanism has not been elucidated. We studied the effects of torque loading and ischaemic nerve block on coarse postural tremor in the right upper extremity, which had developed in association with a C7-C8 radiculopathy after traumatic neck injury in a 55 year old man. Loading reduced the tremor frequency from 6.1 Hz to 4.2 Hz with corresponding electromyography (EMG) bursts at the same frequencies as the tremor. Ischaemic nerve block also reduced the tremor frequency from 6.2 Hz to 2.8 Hz, and the time course of the frequency was not in parallel with that of the size of the maximal M wave. A significant reduction of the tremor frequency by loading and ischaemic nerve block indicates a mechanical reflex mechanism underlying the tremor, and association of synchronous EMG bursts suggests an increase in gain in the stretch reflex loop. The stretch reflex loop plays an important role in generation of oscillation in tremor after neck injury.

Cervical Vertebrae↗
PubMed2001

Diacylglycerol kinase gamma is one of the specific receptors of tumor-promoting phorbol esters.

Diacylglycerol kinase (DGK) and protein kinase C (PKC) are two different enzyme families that interact with diacylglycerol. Both enzymes contain cysteine-rich C1 domains with a zinc finger-like structure. Most of the C1 domains of PKCs show strong phorbol-12,13-dibutyrate (PDBu) binding with nanomolar dissociation constants (K(d)'s). However, there has been no experimental evidence that phorbol esters bind to the C1 domains of DGKs. We focused on DGK gamma because its C1A domain has a high degree of sequence homology to those of PKCs, and because DGK gamma translocates from the cytoplasm to the plasma membrane following 12-O-tetradecanoylphorbol-13-acetate treatment similar to PKCs. Two C1 domains of DGK gamma (DGK gamma-C1A and DGK gamma-C1B) were synthesized and tested for their PDBu binding along with whole DGK gamma (Flag-DGK gamma) expressed in COS-7 cells. DGK gamma-C1A and Flag-DGK gamma showed strong PDBu binding affinity, while DGK gamma-C1B was completely inactive. Scatchard analysis of DGK gamma-C1A and Flag-DGK gamma gave K(d)'s of 3.1 and 4.4 nM, respectively, indicating that the major PDBu binding site of DGK gamma is C1A. This is the first evidence that DGK gamma is a specific receptor of tumor-promoting phorbol esters.

Amino Acid Sequence↗
PubMed2001

A novel tandem [2 + 2] cycloaddition-Dieckmann condensation with ynolate anions. Efficient synthesis of substituted cycloalkenones and naphthalenes via formal [n + 1] cycloaddition.

A novel tandem [2 + 2] cycloaddition-Dieckmann condensation via ynolate anions is described. Ynolate anions are useful for the formation of reactive beta-lactone enolates via a pathway not involving the enolization of the corresponding beta-lactones. The [2 + 2] cycloaddition of ynolate anions with delta- or gamma-keto esters, followed by Dieckmann condensation, gives bicyclic beta-lactones, which are easily decarboxylated to produce synthetically useful 2,3-disubstituted cyclopentenones and cyclohexenones in one pot. This tandem reaction was applied to a novel, one-pot synthesis of highly substituted naphthalenes.

Journal Article↗
PubMed2001

Immunotherapy using heat-shock protein preparations of leukemia cells after syngeneic bone marrow transplantation in mice.

Heat-shock proteins (HSPs) act as molecular chaperones binding endogenous antigenic peptides and transporting them to major histocompatibility complexes. HSPs chaperone a broad repertoire of endogenous peptides including tumor antigens. For the immunotherapy of tumors, a strategy using HSPs may be more advantageous than other procedures because the identification of each tumor-specific antigen is not necessary. In this study, the efficacy of immunotherapy against minimal residual leukemia cells using HSP preparations was evaluated. HSP70 and GP96 were purified from syngeneic leukemia cell line A20 and immunized into BALB/c mice during the reconstitution period of the immune system after syngeneic bone marrow transplantation. In this procedure, all mice not immunized were dead within 60 days of A20 inoculation, whereas the survival times of HSP-immunized mice were significantly prolonged. In addition, the depletion of either CD4(+) or CD8(+) T lymphocyte significantly abrogated this efficacy, indicating that both CD4(+) and CD8(+) T lymphocytes were required for tumor cell rejection. Moreover, the vaccination of HSPs elicited a specific response of potent CD8(+) T lymphocytes cytotoxic against A20 in vitro. These observations suggest that immunization of the complex of HSPs and peptides derived from leukemia cells leads to immune responses. These immune responses are sufficient to reject minimal amounts of leukemia cells for relatively immunocompromised mice after syngeneic bone marrow transplantation.

Animals↗
PubMed2001

Effect of moderate exercise on immune senescence in men.

The purpose of this study was to examine the relationship between active compared to inactive lifestyles and immunocompetence in men. Subjects, all male volunteers, regularly exercising moderately were separated into three age groups: young (20-39 years), middle-aged (40-59 years) and elderly (more than 60 years). Age-matched sedentary male subjects served as controls in each group. Immunological assessments were, total leucocyte count, lymphocyte subpopulation counts, natural killer cell activity and neutrophilic phagocytosis. Total leucocyte and T-cell (CD3+) counts were not significantly different among the groups. Among T-cell subsets, there was a slight increase in helper T-cell (CD3+CD4+) and a decrease in cytotoxic/suppressor T-cell (CD3+CD8+) concentrations in the older sedentary subjects, resulting in an age-associated significant increase in the CD4:CD8 ratio among those control groups. However, among the exerciser groups, no such increase and decrease in the T-cell subpopulations or an age-related increase of the CD4:CD8 ratio were observed. Considering the components of innate immunity, the concentration of NK-cells (CD16+CD56+) significantly increased in the elderly exercisers, compared to that of the age-matched control subjects, or of the young group. The phagocytotic activity of neutrophils showed an age-associated decline, but of lesser degree in the elderly exercisers than in the elderly controls. Taken together, these results suggest that habitual and moderate training in later life is associated with a lesser age-related decline in certain aspects of circulating T-cell function and innate immunity.

Adult↗
PubMed2001

Gluteal muscle necrosis following transcatheter angiographic embolisation for retroperitoneal haemorrhage associated with pelvic fracture.

Transcatheter angiographic emobilisation has been used as an effective control of haemorrhage associated with pelvic fracture. Although few complications of this procedure have been reported, gluteal muscle necrosis occurs occasionally. We assessed the type of pelvic fracture, concomitant injury, embolic site, embolic materials, and outcome in cases of gluteal muscle necrosis associated with angiographic embolisation for pelvic fracture-related haemorrhage, and investigated the factors associated with the development of gluteal muscle necrosis, one of the fatal complications of transcatheter angiographic embolisation. Five out of the 151 patients (incidence, 3.3%) who underwent transcatheter angiographic embolisation for haemorrhagic shock due to pelvic fracture developed gluteal muscle necrosis after embolisation. The five cases had injury severity scores ranging from 26 to 59 (mean 46.4). Three patients died (mortality, 60%) of subsequent sepsis and disseminated intravascular coagulation. These cases showed that transcatheter angiographic embolisation with gelatin sponge and/or steel coil, while effectively controlling bleeding, may also result in gluteal muscle necrosis. Aggressive management including intraarterial antibiotic treatment may have a role, but our numbers are too small to confirm this.

Adolescent↗
PubMed2001

Toward the identification of selective modulators of protein kinase C (PKC) isozymes: establishment of a binding assay for PKC isozymes using synthetic C1 peptide receptors and identification of the critical residues involved in the phorbol ester binding.

Conventional and novel protein kinase C (PKC) isozymes contain two cysteine-rich C1 domains (C1A and C1B), both of which are candidate phorbol-12,13-dibutyrate (PDBu) binding sites. We previously synthesized C1 peptides (of approximately 50 residues) corresponding to all PKC isozymes and measured their PDBu binding affinity. While many of these peptide receptors exhibited PDBu affinities comparable to the respective complete isozyme, some of the C1A peptides could not be used because they undergo temperature dependent inactivation. This problem was however eliminated by 4 degrees C incubation or elongation of the 50-mer C1 peptides at both N- and C-termini to increase their folding efficiency and stability. These findings enabled us to determine the K(d)'s of PDBu for all PKC C1 peptides (except for theta-C1A) and establish the value of these peptides as readily available, stable, and easily handled surrogates of the individual isozymes. The resultant C1 peptide receptor library can be used to screen for new ligands with PKC isozyme and importantly C1 domain selectivity. Most of the C1 peptide receptors showed strong PDBu binding affinities with K(d)'s in the nanomolar range (0.45-7.4 nM). Two peptides (delta-C1A and theta-C1A) bound PDBu over 100-fold less tightly. To identify the residues that contribute to this affinity difference, several mutants of delta-C1A and theta-C1A were synthesized. Both the G9K mutant of delta-C1A and the P9K mutant of theta-C1A showed K(d)'s of 2-3 nM. This approach provides a useful procedure to determine the role of each C1 domain of the PKC isozymes by point mutation.

Amino Acid Sequence↗
PubMed2001

Pretreatment apoptotic scores do not predict response to radiation therapy in oropharyngeal squamous cell carcinoma.

The prognostic value of tumor apoptosis was studied in patients with oropharyngeal squamous cell carcinoma treated with radical radiotherapy. Forty-eight patients with oropharyngeal squamous cell carcinoma who received radical radiotherapy between 1990 and 1995 were enrolled in the study. The radiation treatment for all patients involved the administration of 65 Gy in 26 fractions over a 6.5-week period. The apoptotic index (AI; the apoptotic cell count per 1000 tumor cells ) was distributed from 0 to 10 with a median at 2 and a mode of 1. There was a significant linear correlation between the AI and mitotic index (MI) (r=0.393, 95% confidence interval: 0.129-0.605). The cause-specific 5-year survival for patients with AI greater than the median was 46% and for the counterpart was 41%. There was no difference in cause-specific survival between AI/MI greater than the median (50%) and AI/MI smaller than the median (36%). The number of patients was too small to draw definite conclusions, but the AI and the AI/MI before treatment were not shown to have a prognostic value for oropharyngeal squamous cell carcinoma in our study. The primary sites and treatment methods may influence the prognostic value of AI even for the same histological types.

Adult↗