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Biomedical subjects

N Chino

Publications and source records attributed to N Chino.

At least 55 records · Page 3Linked to original sources

Reproducibility of dual-energy X-ray absorptiometry in the upper extremities in stroke patients.

Bone mineral loss after stroke in affected extremities can increase the prevalence of fractures that interrupt the rehabilitation programme and lower the level of activity. In stroke rehabilitation, precise bone mineral measurement is needed in order to assess the risk of fractures. We defined five regions-of-interest of the upper extremity (proximal humerus, distal forearm, distal radius, distal ulna and hand) consistently, so that the position was comfortable for hemiplegic patients to maintain during the measurement. The aim of this study was to determine whether our method using dual-energy X-ray absorptiometry is useful in hemiplegic patients. Ten normal subjects and 15 hemiplegic patients were studied. In normal subjects the reproducibility of our method was evaluated by repeated measurements of both the right and left sides. In hemiplegic patients the reproducibility was evaluated by repeated measurements of the affected side. The coefficient of variation (CV) values were obtained for BMD (0.7-1.7%) and BMC (0.7-2.3%) in normal subjects, and BMD (1.3-2.1%) and BMC (1.7-5.4%) in hemiplegic patients. The CV for the side-to-side BMD and BMC ratios in the normal subjects ranged from 1.1% to 2.2% and from 1.8% to 3.1%, respectively. Our study shows that the reproducibility of our method is sufficient for application to hemiplegic patients.

Absorptiometry, Photon↗

Identification of biologically active and inactive human uroguanylins in plasma and urine and their increases in renal insufficiency.

Uroguanylin, a 16-amino acid peptide, is an endogenous activator of intestinal and possibly renal guanylate cyclase C (GC-C). Using two synthetic topological isoforms of human uroguanylin, one bioactive, the other inactive, we prepared two antisera specific for the individual isoforms and developed sensitive radioimmunoassay (RIAs). The respective plasma concentrations of the bioactive and inactive uroguanylins in the normal individuals tested were 5.0 +/- 0.3 fmol/ml (mean +/- SE) and 1.6 +/- 0.1 fmol/ml. These concentrations increased in chronic renal failure (CRF). The major endogenous uroguanylin molecule in normal human urine was 16 amino acids long, whereas in the plasma and urine of CRF patients the major molecule was 10-kDa prouroguanylin. The RlAs established are promising tools for clarifying the physiological functions and pathophysiological implications of uroguanylin in water and electrolyte homeostasis.

Biomarkers↗

Oxidative folding of omega-conotoxin MVIIC: effects of temperature and salt.

Oxidative folding of omega-conotoxin MVIIC, a highly basic 26-amino acid peptide with three disulfide bonds, predominantly gave two products with mismatched disulfide bonds in 0.1M NH4OAc buffer (pH 7.7) at 21 degrees C both in the presence and absence of redox reagents such as reduced and oxidized glutathione. A low reaction temperature (5 degrees C) and a high salt concentration in buffer such as 2M (NH4)2SO4 were necessary to obtain the correctly folded biologically active product. The folding reaction was found to proceed via a two-stage pathway of (I) the formation and (II) the rearrangement of the mismatched disulfide bonds. Both the reaction temperature and the salt strongly affected the equilibrium between mismatched and correctly formed disulfide bonds in the second stage. Such an effect of salts on the rearrangement reaction could be explained by anion binding at a low concentration and the salting out effect at a high concentration by analyzing the rank order of their effectiveness. The anion-binding effect was also confirmed by examining the folding of the tetra-acetylated peptide at the Lys side chains. CD study suggested that the yield of the biologically active product was correlated with its conformational change as functions of temperature and salt concentration.

Acetates↗

Voluntary contraction shortens peripheral conduction time in response to transcranial magnetic stimulation of the brain.

We investigated the effects of voluntary contraction on peripheral conduction time in response to transcranial magnetic stimulation (TMS) of the brain in 10 normal subjects. We obtained surface recordings of compound muscle action potentials (CMAP) from the abductor digiti minimi muscle (ADM) and nerve action potentials (NAP) from the ulnar nerve, at rest and during contraction (10% of maximal voluntary contraction) in response to TMS delivered at 100% output using a coil shaped like a figure 8. The distance between the two recording electrodes was 10 cm. The distal latency in response to TMS was calculated by subtracting the NAP latency from the CMAP latency. Distal latency was also measured by recording ADM responses to supramaximal electrical stimulation (ES) 10 cm proximal to the recording electrode. TMS-induced distal latency was significantly shorter during voluntary contraction than at rest (P < 0.0001). There was no significant difference between TMS-induced distal latency during contraction and ES-induced distal latency. TMS-induced distal latencies at rest and during contraction were correlated with the ES-induced distal latencies (r2 = 0.468, P = 0.028 and r2 = 0.769, P = 0.0009, respectively). Our results showed that the peripheral conduction time in response to TMS was related to the activity of the target muscle and to the fastest conduction velocity of the target nerve. Voluntary contraction reduced the peripheral conduction time in response to TMS.

Adult↗

Functional assessment of patients with spinal cord injury: measured by the motor score and the Functional Independence Measure.

There is some information about the Functional Independence Measure (FIM) score of patients with spinal cord injury (SCI), but there are a few publications dealing with the relationship between the FIM score and the motor score of the American Spinal Injury Association (ASIA). We have studied the relationship of all FIM items with the motor score, and reviewed the disability of patients with spinal cord injury in greater detail. The purpose of this study was to describe the characteristics of impairment and disability in patients with SCI, using the FIM and motor score of the ASIA. The subjects were 100 inpatients with SCI (Frankel A, B). Neurological level, days from the onset, and the FIM were examined. In addition to these items, the ASIA motor scores were calculated for 22 tetraplegic patients. We investigated the relationships among these various respects. We also examined the changes of the physical items of the FIM score (physical FIM) over time for 18 patients. The mean FIM scores of those with tetraplegia with C4, C5, C6, C7, C8 lesions, and those with paraplegia with above T5 levels, and those below T6 were 35, 61, 82, 90, 116, 114 and 114 respectively. The FIM score reached the plateau in approximately 10 months, 6 months and 3 months post-injury, in tetraplegia, paraplegia above T5 and that below T6 respectively. The FIM scores in C6 patients were widely distributed from 56 to 104. On the other hand, the ASIA motor score could subdivide C6 patients and related well to the FIM score. The mean FIM scores for each neurological level were similar to those previously reported, thus they appeared to be plateau scores. With regard to the motor score, we feel that it could reflect the disability of the patients better than considering the neurological levels alone. Also considering the changes in the physical FIM score over time within a year from the onset of the injury, there were differences in the ADL improvement patterns among patients with different neurological levels. It appears that timing of the highest physical FIM improvement for each neurological level can exist. Thus it is important not to delay the start of the rehabilitation of patients with spinal cord injury in proper time.

Activities of Daily Living↗

Characterization of a class of peptide boronates with neutral P1 side chains as highly selective inhibitors of thrombin.

Z-D-Phe-Pro-boroMpg-OPin (9a)1,2 has been shown previously to be a highly specific inhibitor of thrombin in spite of lacking an arginine-like guanidino group at the P1 site. A range of compounds have been synthesized based upon this lead compound, varying the neutral side chain at the P1 site. Of the 20 examples based upon the structures at P2 and P3 of Z-D-X-Pro (X being Phe or beta,beta-diphenylalanine), all were found to be effective inhibitors of thrombin (Ki's between 10 and 100 nM). Furthermore all exhibited a high specificity toward thrombin having values for a Ki(trypsin)/Ki(thrombin) ratio of between 10- and 100-fold. High ratio values were found for a number of the compounds tested against a range of serine proteinases (plasmin, factor Xa, kallikrein, urokinase, protein Ca, chymotrypsin, elastase, and cathepsin G). As far as potency toward thrombin, compounds containing the methoxypropyl group at P1 were favored over those with a methoxy grouping on a shorter alkyl chain (8) or without the methoxy group (1-5). The compounds display potent anticoagulant activity with values for 18 in thrombin time of 0.63 microM and in activated partial thromboplastin time of 2.0 microM. 11B NMR has been used to confirm interaction of the boron atom with the active site. From the high specificity shown with all the compounds we propose that the compounds, constitute a new class of thrombin inhibitors.

Boronic Acids↗

[Lys(-2)-Arg(-1)]endothelin-1 solution structure by two-dimensional 1H-NMR: possible involvement of electrostatic interactions in native disulfide bridge formation and in biological activity decrease.

Addition of the Lys(-2)-Arg(-1) dipeptide, present in the precursor protein, to the N-terminus of endothelin-1 (ET-1), to form a 23-residue peptide (KR-ET-1) has been shown to greatly improve formation of native disulfide bridges and to dramatically decrease biological activity. Conformational analysis was carried out on this peptide. During protonation of the carboxyl groups, CD spectra showed a decrease in the helical contribution, and NMR spectra displayed strong chemical shift modifications, suggesting the importance of electrostatic interactions in the KR-ET-1 conformation. CD spectra and two-dimensional NMR experiments were performed to investigate the KR-ET-1 three-dimensional structure in water in the carboxylic acid and carboxylate states. Distance and angle constraints were used as input for distance geometry calculations. The KR-ET-1 carboxylic acid conformation was found to be very similar to ET-1, with a helix spanning residues 9-15 and an unconstrained C-terminal part. In contrast, in the carboxylate state, large changes in Arg(-1) and Phe14 chemical shifts and long-range NOEs were consistent with a conformation characterized by a helix extension to Leu17 and a stabilized C-terminal section folded back toward the N-terminus. In addition, thanks to NOEs with Cys11 and Phe14, the Arg(-1) side chain appeared well-defined. Simulated annealing and molecular dynamics calculations, supported an Arg(-1)-Glu10 salt bridge and an electrostatic network involving the charged groups of Trp21, Asp18, and Lys(-2). Moreover, stabilization of the KR-ET-1 C-terminal part is probably reinforced by hydrophobic interactions involving the Val12, Tyr13, Phe14, Leu17, Ile19, Ile20, and Trp21 side chains. In vitro, native disulfide bond formation improvement observed for KR-ET-1 could be ascribed to electrostatic interactions and more specifically to the Arg(-1)-Glu10 salt bridge. In vivo, similar interactions could play an important role in the native folding of the ET-1 precursor protein. On the other hand, modification in the environment and a reduced mobility of the KR-ET-1 Trp21 key residue, when compared to ET-1, could explain, at least in part, the strong decrease in biological activity.

Acetates↗

Solution structure of omega-conotoxin MVIIC determined by NMR.

The solution structure of the P- and Q-type Ca2+ channel blocker, omega-conotoxin MVIIC (a peptidic neurotoxin composed of 26 amino acid residues), has been determined by 1H-NMR and simulated annealing calculations. The resulting calculated structures converged very well to a conformation with an average value of pairwised RMSD for N, C alpha and C' of 0.62 A. Lys-25 is buried in the molecule and less flexible so that among the four Lys residues, its side chain provides the lowest reactivity on biotinylation and the mono-biotinylation in this residue less influences the biological activity.

Amino Acid Sequence↗

A new method of estimating the distribution of muscle fiber conduction velocities.

A computer-assisted method of estimating the distribution of muscle fiber conduction velocities is described. An electrode array composed of 2 stimulating and 4 recording electrodes is used to record surface muscle action potentials (MAPs) in response to direct muscle stimulation. The velocity distribution and the single muscle fiber action potential (SFAP) are calculated from the recorded MAPs by an iterative method of estimation. The estimation is based on the assumption that the spatial orientation of each muscle fiber viewed from the recording electrodes is the same along the muscle fibers and a MAP is recorded as a linear summation of all SFAPs. The accuracy of this estimation is demonstrated using simulated MAPs. The method is also tested on MAPs containing simulated amplifier noise, stimulus artifact, and errors in distance between electrodes. Finally we applied this method to MAP recordings of the biceps brachii in 23 healthy subjects. The velocity distribution was successfully estimated in 20 cases. The average of the estimated distributions was smaller than that described by previous workers. The reasons for the difference are discussed.

Adult↗

Motor unit firing behavior in slow and fast contractions of the first dorsal interosseous muscle of healthy men.

The motor unit recruitment threshold and firing rate were evaluated during slow and fast contraction of the first dorsal interosseous (FDI) muscle by healthy young men. Using a special quadrifilar electrode myoelectric activity was recorded during voluntary isometric contraction. Motor unit action potentials (MUAPs) were decomposed into individual MUAP trains by the electromyography (EMG) signal decomposition technique. Recruitment thresholds of the motor units decreased with the increase in the speed of contraction, and there was no recruitment reversal despite the increase. In terms of rate coding, the firing rates of the motor units increased as the speed of contraction increased; however, a high threshold motor unit always had a lower firing rate than a low threshold motor unit regardless of the contraction speed. At all contraction speeds, recruitment and rate coding may act through the same mechanism. If excitation of the motoneuron pool occurs rather than excitation of an individual motoneuron, a low threshold motor unit is easier to recruit and fire repetitively than a high threshold one. The motor unit firing behavior during fast contraction basically may be the same as during slow contraction.

Action Potentials↗

Macro-EMG and motor unit recruitment threshold: differences between the young and the aged.

The relationship between macro-EMG (electromyography) and motor unit recruitment threshold was studied in the first dorsal interosseous (FDI) muscle of normal young and aged subjects. During voluntary isometric contraction, motor unit action potentials (MUAP) were collected by a special quadrifilar electrode and decomposed to each MUAP train (MUAPT) using an EMG signal decomposition technique. Macro-EMG was obtained from the electrode shaft, then triggered and averaged for each MUAPT. A positive linear correlation was observed in both the young and aged subjects. However, the correlation coefficients were significantly lower in the aged individuals than in the young individuals.

Action Potentials↗

An evaluation of stroke patients in rehabilitation medicine.

Strokes are one of the most important subjects of clinical and research studies of rehabilitation medicine. A system for evaluating stroke patients, however, is not yet completely established. In 1980, WHO instituted International Classification of Impairments, Disabilities, and Handicaps (ICIDH). Since the introduction of the concepts of ICIDH, many studies and research on rehabilitation medicine utilizing this classification have been published. The concepts of ICIDH have been applied to some diseases of the neuro-musculo-skeletal systems such as those of stroke patients. This paper reviews the methods of functional assessment and evaluation of stroke patients categorized by using ICIDH, and also it aims at presenting a new system for evaluating the level of impairment that we originally developed.

Cerebrovascular Disorders↗

[A case of polyarthritis developed on the non-paralytic side in a hemiplegic patient].

A 37-year old house wife who developed polyarthritis localized to contralateral to hemiplegic side was reported. The patient had been on the physical therapy program for right hemiplegia which occurred at the age of 33. The polyarthritis are chronic and showed significant responses to salazosulfapyridine. Her serum contained rheumatoid factor (RF) of high titer and hand X-ray showed characteristic erosive changes in PIP and MCP joints. Presence of morning stiffness, positive RF, bone erosion, isotope accumulation, HLA-DR4 and responses to DMARD are all consistent with a diagnosis of rheumatoid arthritis. Review of the literature revealed that fifteen patients had been reported in whom occurrence of neurological disorders and rheumatic conditions were described. In most of these patients including the present case, the rheumatic symptoms did not occur or subsided in the hemiplegic side of neurological disorders. Possible mechanisms of inactivation on rheumatic inflammation were discussed.

Adult↗

Waveform analysis of compound nerve action potentials: a computer simulation.

A compound nerve action potential (CNAP) recorded from surface of the skin is composed of single nerve fiber action potentials propagating at various conduction velocities (CVs). Based on this assumption, we constructed two CNAPs simulating those at the digit elicited by stimulation of the median nerve at the wrist (CNAP-Wr) and the elbow (CNAP-El). Distribution of the nerve fiber CVs used for the simulation was estimated from actual recordings of 12 healthy subjects. Mean ratio of the CNAP amplitude (CNAP-Wr/CNAP-El) was 2.2, and that of the duration was 0.76. First, to analyze how CV distributions affect CNAP waveforms artificially in our computer program, we altered mean CV or standard deviation (SD) of the estimated distribution, and reconstructed CNAPs. Results indicated that as the mean CV was made slower, the ratio of the CNAP amplitude increased and that of the duration decreased. Similar changes of the ratios were also shown when the SD of the CV distribution was increased without changing the mean CV. Secondly, to make constructed CNAPs more similar to actual recordings, we added artificial noise to the constructed waves and had 11 electromyographers read onset and peak latencies. The average of maximum CVs calculated from the onset latencies of CNAPs-Wr was 62m/sec, and that from the latency difference between CNAPs-Wr and -El was 70m/sec. Both CVs were slower than the genuine maximum (77m/sec) given to the simulation program. The mean CV calculated from latency difference of the major positive peaks of the CNAPs was 62m/sec being close to the mode (62m/sec) or mean (60m/sec) value of the given distribution.

Action Potentials↗

Muscle damage progression in Duchenne muscular dystrophy evaluated by a new quantitative computed tomography method.

The progression of muscle damage was studied in the lower extremity and trunk muscles of patients with Duchenne muscular dystrophy (DMD) with a new quantitative computed tomography (CT) method. The degree of muscle fiber loss and fat tissue replacement was quantified using the indices of percent cross-sectional area (%CSA) of muscle and fat, or the percentages of the area having the CT numbers of normal muscle and fat. A cross-sectional study in 71 patients showed that as the disability stage progressed, both CT number and %CSA of muscle decreased while %CSA of fat increased. The rate of progression was different for each muscle, and the order of involvement was clarified. The CT findings were also significantly correlated with muscle strength, indicating validity of our method. Our findings of the natural course of muscle involvement would be useful in providing appropriate rehabilitative care as well as assessing the efficacy of therapeutic interventions.

Adolescent↗