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Biomedical subjects

M Shibata

Publications and source records attributed to M Shibata.

At least 37 records · Page 2Linked to original sources

Cardio-ankle vascular index (CAVI) for the monitoring of the atherosclerosis after heart transplantation.

Atherosclerosis has been reported to progress rapidly after heart transplantation. A quantitative diagnosis is required for the diagnosis of atherosclerosis after heart transplantation. In this study, we compared brachial-ankle pulse wave velocity (baPWV) and cardio-ankle vascular index (CAVI) for the diagnosis. The average values of both baPWV and CAVI in the seven cases after heart transplantation were found to be signif-icantly large in comparison to the average values of the normal healthy people of the same age group. When comparisons were made before and after the heart transplantation in a particular case, CAVI was stable and baPWV changed sharply. A lot of parameters such as blood pressure, blood volume, etc. have been reported to influence baPWV. The results of this study suggested that CAVI was a stable parameter in comparison to baPWV even after heart transplantation. Thus, CAVI may be useful in the diagnosis of arteriosclerosis after heart transplantation.

Adolescent↗

Chaos analysis of electro encephalography and control of seizure attack of epilepsy patients.

In order to evaluate the EEG of patients with epilepsy, chaos analysis was performed for the subdural EEG time series data. The chaos attractor was reconstructed in the phase space and the correlation dimension. KS entropy calculated from the Lyapunov exponents was evaluated. Before the seizure attack, the KS entropy showed a lower value when compared with the time series data recorded during healthy condition. The results of our study suggest that it is possible to predict the seizure attack by the chaos analysis of the EEG signal. Further, we aim at developing an automatic control system for predicting a seizure attack by the use of local cooling of the focus with Peltier elements.

Algorithms↗

The influence of age on apoptotic and other mechanisms of cell death after cerebral hypoxia-ischemia.

Unilateral hypoxia-ischemia (HI) was induced in C57/BL6 male mice on postnatal day (P) 5, 9, 21 and 60, corresponding developmentally to premature, term, juvenile and adult human brains, respectively. HI duration was adjusted to obtain a similar extent of brain injury at all ages. Apoptotic mechanisms (nuclear translocation of apoptosis-inducing factor, cytochrome c release and caspase-3 activation) were several-fold more pronounced in immature than in juvenile and adult brains. Necrosis-related calpain activation was similar at all ages. The CA1 subfield shifted from apoptosis-related neuronal death at P5 and P9 to necrosis-related calpain activation at P21 and P60. Oxidative stress (nitrotyrosine formation) was also similar at all ages. Autophagy, as judged by the autophagosome-related marker LC-3 II, was more pronounced in adult brains. To our knowledge, this is the first report demonstrating developmental regulation of AIF-mediated cell death as well as involvement of autophagy in a model of brain injury.

Aging↗

Evaluating dressing materials for the prevention of shear force in the treatment of pressure ulcers.

OBJECTIVE: Shear force is believed to affect pressure ulceration. Therefore, dressing materials that reduce shear force may prevent ulceration and facilitate healing. METHOD: We measured the following three properties: the coefficient of friction between the outer layer of the dressings and the patient's clothes; the degree of adhesiveness between the inner layer of the dressing and the patient's skin; the transmissibility of shear force of the dressing. RESULTS: The coefficients of static friction were 1.01 for hydropolymer, 0.72 for hydrofoam and 0.48 for hydrocolloid. Adhesiveness was tested by rolling different sized ball bearings down a slope and over the adhesive lining under both wet and dry conditions. Under dry conditions, the heaviest ball bearing that stopped rolling for five seconds was 111.9g for both hydrofoam and hydrocolloid. Under wet condition, it was 11.9g for hydrofoam and under 1g for hydrocolloid. Tests showed the very low transmissibility (I N buffer) of shear force for hydrofoam, with significant differences between the dressings. Clinical observation has identified good results for hydrofoam when used under highly exuding conditions and for hydrocolloid when used with relatively slight or decreased exudate. CONCLUSION: Existing dressing materials are being developed and evaluated for wound healing. However, if innovations in the raw materials from which dressings are manufactured could lead to a reduction in shear force and the prevention of pressure ulcers, then dressing materials could be discussed from a viewpoint that is quite different from wound healing.

Bandages↗

Observation by an air-shower array in Tibet of the multi-TeV cosmic-ray anisotropy due to terrestrial orbital motion around the Sun.

We report on the solar diurnal variation of the galactic cosmic-ray intensity observed by the Tibet III air shower array during the period from 1999 to 2003. In the higher-energy event samples (12 and 6.2 TeV), the variations are fairly consistent with the Compton-Getting anisotropy due to the terrestrial orbital motion around the Sun, while the variation in the lower-energy event sample (4.0 TeV) is inconsistent with this anisotropy. This suggests an additional anisotropy superposed at the multi-TeV energies, e.g., the solar modulation effect. This is the highest-precision measurement of the Compton-Getting anisotropy ever made.

Journal Article↗

Physiological studies on vasoactive intestinal peptide in rat small bowel isografts.

BACKGROUND: Vasoactive intestinal peptide (VIP) is released by stimulation of nonadrenergic noncholinergic (NANC) inhibitory nerves. In order to evaluate the function of VIP in jejunal isografts, we examined the enteric nerve responses in isografted rat jejunum compared with normal jejunum. METHODS: Orthotopic entire small bowel transplantation (SBT) with portocaval drainage was performed from Lewis rats to Lewis rats. Grafted tissue specimens were obtained 130 days after SBT (n = 8). As controls, normal segments of the jejunum were obtained from nontransplanted Lewis rats (n = 20). A mechanograph was used to evaluate in vitro jejunal responses to electrical field stimulation (EFS) of the adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers and VIP. RESULTS: The isografted jejunum was more strongly innervated by excitatory nerves, especially NANC excitatory nerves, than the normal jejunum (P <.05). VIP mediated relaxation reactions of NANC inhibitory nerves in the normal but to a lesser extent in the isografted jejunum (P <.05). CONCLUSIONS: The increased NANC excitatory nerves and the decreased effects of VIP in mediating NANC inhibitory nerves may largely relate to the peristaltic abnormalities seen in the isografted LEW rat jejunum.

Animals↗

Prognostic index of liver cirrhosis with ascites with and without hepatocellular carcinoma.

BACKGROUND: In Japan, the incidence of liver cirrhosis caused by hepatitis viruses is higher, and cirrhosis is more likely to be complicated by hepatocellular carcinoma, than in Western countries. The aim of this study was to predict the outcome in liver cirrhosis with ascites with and without hepatocellular carcinoma. METHODS: The subjects were 146 patients with liver cirrhosis complicated by ascites. Forty-six factors were evaluated concerning clinical laboratory parameters and extracted prognostic factors using the Cox proportional hazards model. RESULTS: The mean duration of the follow-up period was 634.9 days, during which 89 (61%) of the patients died, 27 (18.5%) survived, and 30 (20.6%) were lost to follow-up. The cumulative survival rate after the onset of ascites was 59.7% after 1 year, 44.5% after 2 years, and 29.5% after 5 years. Multivariate analysis indicated 9 factors, i.e. age, total bilirubin (T-Bil), alkaline phosphatase (ALP), blood urea nitrogen (BUN), alpha-fetoprotein (AFP), mean arterial pressure (MAP), gastrointestinal bleeding, infection, and portal vein tumor thrombosis (PVTT), as independent prognostic factors. The prognostic index (PI) was calculated by the following formula using these 9 factors. PI = 0.045 x age + 0.180 x T-Bil + 0.088 x ALP + 0.020 x BUN + 0.467 x AFP + (-0.022 x MAP) + 0.662 x gastrointestinal bleeding + 0.521 x infections + 0.882 x PVTT. CONCLUSION: Prediction of the outcome using PI based on the 9 factors provides additional information for the determination of the therapeutic approach in cirrhotic patients with ascites with and without hepatocellular carcinoma.

Age Factors↗

Autoantibodies from primary biliary cirrhosis patients with anti-p95c antibodies bind to recombinant p97/VCP and inhibit in vitro nuclear envelope assembly.

We have reported previously that p95c, a novel 95-kDa cytosolic protein, was the target of autoantibodies in sera of patients with autoimmune hepatic diseases. We studied 30 sera that were shown previously to immunoprecipitate a 95 kDa protein from [(35)S]-methionine-labelled HeLa lysates and had a specific precipitin band in immunodiffusion. Thirteen sera were available to test the ability of p95c antibodies to inhibit nuclear envelope assembly in an in vitro assay in which confocal fluorescence microscopy was also used to identify the stages at which nuclear assembly was inhibited. The percentage inhibition of nuclear envelope assembly of the 13 sera ranged from 7% to 99% and nuclear envelope assembly and the swelling of nucleus was inhibited at several stages. The percentage inhibition of nuclear assembly was correlated with the titre of anti-p95c as determined by immunodiffusion. To confirm the identity of this autoantigen, we used a full-length cDNA of the p97/valosin-containing protein (VCP) to produce a radiolabelled recombinant protein that was then used in an immunoprecipitation (IP) assay. Our study demonstrated that 12 of the 13 (93%) human sera with antibodies to p95c immunoprecipitated recombinant p97/VCP. Because p95c and p97 have similar molecular masses and cell localization, and because the majority of sera bind recombinant p97/VCP and anti-p95c antibodies inhibit nuclear assembly, this is compelling evidence that p95c and p97/VCP are identical.

Adenosine Triphosphatases↗

Regulation of FLRG expression in rat primary astroglial cells and injured brain tissue by transforming growth factor-beta 1 (TGF-beta 1).

Follistatin-related gene (FLRG) is a member of the follistatin family of proteins and interacts with transforming growth factor (TGF) superfamily proteins like follistatin. To understand the expression level of FLRG in brain tissue, we examined whether primary neurons and glial cells from rat embryos express FLRG mRNA and produce its protein product. FLRG and follistain mRNAs were mainly expressed in astroglial cells, while activin A mRNA was abundant in primary neurons. TGF-beta1 highly enhanced expression levels of FLRG mRNA in astroglial cells, compared with those of follistatin and activin A mRNAs. Particularly, TGF-beta1 facilitated the secretion of FLRG protein from primary astroglial cells in a dose-dependent manner. Moreover, changes in expression levels of FLRG mRNA and protein in brain tissue were also analyzed after a penetrating injury, using quantitative polymerase chain reactin (PCR) and immunohistochemical methods. Expression levels of FLRG mRNA were significantly increased in damaged regions after penetrating injury together with those of activin A and TGF-beta1 mRNAs. Immunohistochemical observations showed that positive signals of FLRG protein were colocalized in glial fibrillary acidic protein-positive reactive astroglial cells located in damaged regions after a penetrating injury. The expression of follistatin mRNA rather decreased in damage regions after the brain injury. These results suggest that FLRG is synthesized in and secreted from astroglial cells. In particular, FLRG, but not follistatin, may play a role in the regulation of activin A in brain wound healing in response to TGF-beta1.

Animals↗

Primary motor cortex stimulation within the central sulcus for treating deafferentation pain.

Nine patients with post-stroke pain, six with brachial plexus injuries, two with phantom limb pain, one with spinal cord injury, and one with brain stem injury were treated with a modified motor cortex stimulation (MCS) protocol. Preoperative pharmacological tests were performed with phentolamine, lidocaine, ketamine, thiopental, morphine, and placebo. We placed a grid electrode in the subdural space to decide upon the best stimulation point for pain relief over a few weeks with the purpose of determining the placement of a Resume electrode. In five patients, Resumes were implanted in the interhemispheric fissure to reduce lower extremity pain. In five other patients, Resumes were placed within the central sulcus to stimulate area 4 and area 3b. In addition, electrodes were also placed on the surface of the precentral gyrus. Fourteen of the 19 patients showed pain reduction (6 excellent, 3 good, and 5 fair) using the MCS with our results indicating area 4 within the central sulcus to be the optimal stimulation point for pain relief. We speculate that conventional method may sometimes fail to stimulate area 4 and that focal stimulation of the primary motor cortex within the central sulcus may improve the efficacy of this treatment. Our pharmacological tests show that patients with ketamine sensitivity seem to be good candidates for MCS. Test stimulation with a subdural multi-grid electrode and Resumes in the cetral sulcus were helpful in locating the best stimulation point for pain relief.

Adult↗

Delayed grafting of BDNF and NT-3 producing fibroblasts into the injured spinal cord stimulates sprouting, partially rescues axotomized red nucleus neurons from loss and atrophy, and provides limited regeneration.

Ex vivo gene therapy, utilizing modified fibroblasts that deliver BDNF or NT-3 to the acutely injured spinal cord, has been shown to elicit regeneration and recovery of function in the adult rat. Delayed grafting into the injured spinal cord is of great clinical interest as a model for treatment of chronic injury but may pose additional obstacles that are not present after acute injury, such as the need to remove an established scar, increased retrograde cell loss and/or atrophy, and diminished capacity for regeneration by neurons which may be doubly injured. The purpose of the present study was to determine if delayed grafting of neurotrophin secreting fibroblasts would have anatomical effects similar to those seen in acute grafting models. We grafted a mixture of BDNF and NT-3 producing fibroblasts or control fibroblasts into a complete unilateral cervical hemisection after a 6-week delay. Fourteen weeks after delayed grafting we found that both the neurotrophin secreting fibroblasts and control fibroblasts survived, but that only the neurotrophin secreting grafts provided a permissive environment for host axon growth, as indicated by immunostaining for RT-97, a marker for axonal neurofilaments, GAP-43, a marker for elongating axons, CGRP, a marker for dorsal root axons, and 5-HT, a marker for raphe spinal axons, within the graft. Anterograde tracing of the uninjured vestibulospinal tract showed growth into neurotrophin producing transplants but not into control grafts, while anterograde tracing of the axotomized rubrospinal tract showed a small number of regenerating axons within the genetically modified grafts, but none in control grafts. The neurotrophin expressing grafts, but not the control grafts, significantly reduced retrograde degeneration and atrophy in the injured red nucleus. Grafts of BDNF + NT-3 expressing fibroblasts delayed 6 weeks after injury therefore elicit growth from intact segmental and descending spinal tracts, stimulate modest regenerative growth by rubrospinal axons, and partially rescue axotomized supraspinal neurons and protect them from atrophy. The regeneration of rubrospinal axons into delayed transplants was much less than has been observed when similar transplants were placed acutely into a lateral funiculus or, after a 4-week delay, into a hemisection lesion. This suggests that the regenerative capacity of chronically injured red nucleus neurons was markedly diminished. The increased GAP43 reactivity in the corticospinal tracts ipsilaterally and contralaterally to the combination grafts suggests that these axons remain responsive to the neurotrophins, that the neurotrophins may stimulate both regenerative and sprouting responses, and that the grafted cells continue to secrete the neurotrophins.

Animals↗

Activation of caspase-12 by endoplasmic reticulum stress induced by transient middle cerebral artery occlusion in mice.

We sought to clarify the involvement of caspase-12, a representative molecule related to endoplasmic reticulum (ER) stress-induced cell-death signaling pathways, in neuronal death resulting from ischemia/reperfusion in mice. Transient focal cerebral ischemia (1 h) was produced by intraluminal occlusion of the middle cerebral artery (MCA). We assessed the expression patterns of caspase-12, Bip/GRP78, an ER-resident molecular chaperone whose expression serves as a good marker of ER stress, and caspase-7 by Western blotting and/or immunohistochemistry. Double-fluorescent staining of caspase-12 immunohistochemistry and the terminal deoxynucleotidyl transferase-mediated DNA nick-end labeling (TUNEL) method was performed to clarify the involvement of caspase-12 in cell death. We confirmed that ER stress was induced during reperfusion in our model, as witnessed by up-regulated Bip/GRP78 expression in the MCA territory. Western blot analysis revealed that caspase-12 activation occurred at 5-23 h of reperfusion, and immunoreactivity for caspase-12 was enhanced mainly in striatal neurons on the ischemic side at the same time points. We found the co-localization of caspase-12 immunoreactivity and DNA fragmentation detectable by the TUNEL method. We did not detect the presence of caspase-7 in the ER fraction at the period of caspase-12 cleavage. Our results imply that cerebral ischemia/reperfusion induces ER stress and that caspase-12 activation concurred with ER stress. Caspase-12 seems to be involved in neuronal death induced by ischemia/reperfusion. Caspase-7 is not likely to contribute to the cleavage of caspase-12 in our experimental model.

Animals↗

Management of haemophilia B inhibitor patients with anaphylactic reactions to FIX concentrates.

Allergic reactions to concentrates containing factor IX (FIX) are serious complications in the treatment of haemophilia B patients with inhibitor. We have established a therapeutic protocol for such cases using an initial skin test followed by step-wise infusions of FIX concentrates under hydrocortisone cover. We have successfully treated three patients whose treatment with FIX had been suspended.

Anaphylaxis↗

Ferguson Smith type multiple keratoacanthomas and a keratoacanthoma centrifugum marginatum in a woman from Japan.

We report a case of multiple keratoacanthomas on the sun-exposed skin of a 37-year-old woman from Japan. She had experienced 4 similar episodes of evolution and involution of multiple keratoacanthomas during a period of 10 years since she was 27 years old. She was given the diagnosis of Ferguson Smith type keratoacanthoma. This is the seventh Japanese case of Ferguson Smith type keratoacanthoma described in detail in the literature. In addition, the patient was found to have an annular, coral reef-like eruption on the front of her neck, which was diagnosed as a keratoacanthoma centrifugum marginatum. A combination of different variants of keratoacanthoma in 1 patient is uncommon, and only 2 patients with the same combination of lesions, as that seen in our patient, have been reported. Our patient was treated by a relatively low dose (0.5 mg/kg body weight) of etretinate. Both variants of keratoacanthoma showed good response to the treatment. Effectiveness of etretinate for treating keratoacanthoma centrifugum marginatum has only been reported in a few cases. Our patient had no relapse during a period of 15 months after cessation of etretinate treatment.

Adult↗

Decay scheme of 126La isomers.

The beta+/EC decay of 126La produced by the 94Mo(36Ar, 3pn) reaction has been studied using the on-line isotope separator connected to an AVF cyclotron. Gamma-ray singles, gamma-gamma angular correlation and internal conversion electron measurements were carried out. From analysis of these data, 33 new levels in 126Ba were found and the decay scheme containing 137 gamma-rays and 50 excited states was constructed. The probable spin and parity of the two beta-decaying states in 126La were found to be 4+/-, 5+/- for the high-spin isomer with a half-life of 54(2) s and 0-, 1+/-, 2- for the low-spin isomer with a half-life shorter than 50 s.

Journal Article↗

Exercise prescription based upon cardiac vagal activity for middle-aged obese women.

OBJECTIVE: The purposes of this study were to examine a new method to determine exercise intensity for obese people based on the cardiac vagal activity and to determine the effect of this approach on myocardial stress. SUBJECTS: Forty-three middle aged obese female volunteers (age 43.7+/-6.5 y; height 1.56+/-0.05 m; body mass 66.5+/-9.3 kg; body mass index 27.3+/-2.8 kg m(2); percentage body fat 40.7+/-5.9%). MEASUREMENT: In the first experiment, 43 subjects performed a ramp exercise test on a bicycle ergometer with measurement of ECG and gas exchange parameters. In the second experiment, 11 subjects performed 45 min of constant walking exercise on a treadmill at a level corresponding to exercise intensity determined by vagal activity obtained from a ramp bicycle test. Blood pressure, endothelin 1 (ET-1), catecholamine, atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP) were measured before and after exercise. RESULTS: The heart rate variability power decreased with increasing work rate, and changed little after reaching individual-specific work rate. We presumed that vagal activity disappeared at this point and that the heart rate at this exercise intensity was determined as the vagal activity threshold (T(VA)). The results showed a significant positive correlation (r=0.742, P<0.0001) between T(VA) and ventilatory threshold (VT) heart rates, although the mean heart rate of T(VA) (114.3+/-8.5 beats/min) was significantly lower (P<0.001) than that at VT (119.0+/-11.7), suggesting the cardiac vagal withdrawal occurred prior to the onset of lactate acidosis (lactic acid accumulation). Furthermore, exercise intervention experiment at T(VA) indicated that ET-1, catecholamine and BNP levels were not significantly different before and after exercise. However, ANP levels increased significantly after exercise (pre-exercise 18.6+/-5.38 vs post-exercise 44.0+/-24.87 pg/ml, P<0.001), which in turn brought about a significant post-exercise reduction in the blood pressure (SBP 117.6+/-13.7 vs 110.5+/-7.4 mmHg, P<0.05; DBP 78.6+/-6.7 vs 73.5+/-6.6 mmHg, P<0.01). CONCLUSION: Our data suggest that it is possible to determine the exercise intensity (T(VA)) on the basis of cardiac vagal response. These results also suggest that exercise at T(VA) level is a safe exercise intensity in the light of cardiac stress, and that T(VA) may be recommended for obese people who might possess lower cardiac sympatho-vagal activity.

Adult↗

Toxicological study of a new maintenance fluid, Veen 3G, in rats.

A study of the different volume and infusion rates of a new maintenance fluid, Veen 3G, on the general conditions of rats was investigated during the 14 days after infusion. In Experiment I, 100 ml/kg and 200 ml/kg of Veen 3G were infused at a rate of 300 ml/kg/h in male and female rats. Results were compared with those for Gurunon Ringer solution (GRS) in male and female rats. We observed only transient polyuria in animals administered by each dose of Veen 3G and GRS for 0-15 min after infusion. Necropsy was not observed in any of the animals tested 14 days after infusion. In Experiment II, 200 ml/kg of Veen 3G was infused at rates of 200, 400, 800 and 1600 ml/kg/h in male rats. At 800 and 1600 ml/kg/h, irregular respiration and decrease in movement were observed concomitantly with polyuria. Three out of 4 rats died immediately after the infusion of Veen 3G at a rate of 1600 ml/kg/h, and one rat was still alive 14 days after the infusion. In this experiment, 200 ml/kg Veen 3G was safe when we infused at a rate of less than 400 ml/kg/h in male rats. Since this rate is about 27-80 times higher than that used clinically in maintenance treatment, Veen 3G is suggested to be safe, with the exception of polyuria, in clinical situations at the standard infusion rate (5-15 ml/kg/h).

Animals↗