rho, omega, and phi meson-nucleon scattering lengths from QCD sum rules.
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Biomedical subjects
Publications and source records attributed to Y Koike.
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To develop a new method for accurately predicting creatinine clearance (Ccr) in the debilitated elderly without urine collections, the total muscle volume of both thighs (MV thigh), as a new predictive parameter, was calculated using computed tomography in 68 debilitated patients aged 61-92 years. A regression line between 24-hour urinary creatinine excretion and MV thigh was divided by serum creatinine (Scr), and then the following formula was derived: Ccr (ml/min) = 9 x [MV thigh (cm3) - 100]/[1,000 x Scr (mg/dl)] Predicted Ccr by the new method more closely correlated with measured Ccr (r = 0.862) than did predicted Ccr by Cockcroft and Gault's method (the C-G method) (r = 0.727). Statistical analysis of prediction error (= predicted Ccr-measured Ccr) suggested that the new method could provide more accurate and less biased estimations of Ccr than did the C-G method, even in patients with renal insufficiency. By using computed tomography, we have proposed a more accurate method for predicting Ccr of the debilitated elderly than the C-G method, although the new method has inherent disadvantages of radiation exposure and high cost.
The sympathetic and parasympathetic systems both contain efferent and afferent neurons. The efferent pathway consists of preganglionic neurons with myelinated axons the cell bodies of which are within the central nervous system and postganglionic neurons with unmyelinated axons the cell bodies of which are peripheral. The preganglionic sympathetic fibers arise in the intermediolateral column of the thoracic and upper lumber cord segments, and reach the sympathetic chain whence postganglionic fibers are distributed to the whole body, where they have particular influence on the control of blood pressure, heart rate, swating and pupillary responses. The parasympathetic outflow is grouped into both brainstem nuclear complex and spinal sacral segments. The activities of the sympathetic and parasympathetic systems are partially reflex in nature, which, however, are controlled by numerous descending influences integrated in the hypothalamus and reticular formation. Orthostatic hypotension is the most dramatic circulatory expression of autonomic failure. As one stands, the pull of gravity pools blood in distensible veins below the heart. Diminished venous return reduces cardiac output and unless autonomic compensatory mechanism-baroreflex function performs, subsequent blood pressure fall occurs. This hemodynamic responses to upright posture can be evaluated by the head-up tilt test. More than a 30-mmHg fall of the systolic blood pressure is thought to be an abnormal response; orthostatic hypotension. The next test to study the orthostatic hypotension is to evaluate the site of the baroreflex arc lesions. Plasma noradrenaline (NA) and vasopressin (AVP) responses to the head-up tilt test are available to detect the site of the lesion.(ABSTRACT TRUNCATED AT 250 WORDS)
We retrospectively evaluated the ability of Scatchard binding equation method to predict the unbound serum valproic acid (VPA) concentration in 37 pediatric patients with epilepsy receiving VPA monotherapy. The correlation between predicted and observed unbound serum concentrations was high and significant (r = 0.873, p < 0.001). Mean prediction error (ME), mean absolute prediction error (MAE), and root mean squared error (RMSE) were calculated, and served as a measure of prediction bias and precision. The 95% confidence intervals of ME did not include 0, showing a bias to overpredict unbound concentration. The MAE and RMSE were not small in magnitude (MAE 17.4 mumol/l, RMSE 22.8 mumol/l). The current method using the in vivo population mean binding parameters from healthy young adults may be limited in the predictive performance of unbound serum VPA concentration.
This study examines the effect of the psychotropic drug minaprine on memory impairment in Mongolian gerbils subjected to a 5-min bilateral common carotid artery occlusion, as assessed by their performance in an 8-arm radial maze task. Gerbils were initially trained on the 8-arm radial maze until their mean error was 0-1 for 5 days. This task was repeated before the ischemia was performed and again 7 days after it. Then the animals were immediately sacrificed for histopathological examination. Severe memory impairment occurred in the control gerbils; whereas when minaprine 75 mg/kg was given orally 30 min before the 5-min occlusion, memory impairment was significantly reduced. Histopathological analysis of the control gerbils showed nearly complete loss of the pyramidal neurons in the CA1 region of the hippocampus, whereas the minaprine-treated gerbils showed complete preservation of the pyramidal neurons. These findings suggest that minaprine has memory-impairment-prevention and neuroprotective effects against short-term ischemia in gerbils.
alpha 2-Plasmin inhibitor (alpha 2PI) was purified from plasma or from the culture media of Hep G2 cells by one-step immunoaffinity chromatography procedure. Majority of alpha 2PI purified from plasma was the previously recognized plasma alpha 2PI with NH2-terminal Asn (Asn-alpha 2PI), whereas majority of alpha 2PI purified from the culture media was retaining the "pro" peptide of 12 amino acids with NH2-terminal Met (Met-alpha 2PI). When Hep G2 cells were cultured in serum-free media, the alpha 2PI secreted to the media was totally in a form of Met-alpha 2PI. Incubation of Met-alpha 2PI with human plasma induced the complete conversion of Met-alpha 2PI to Asn-alpha 2PI. The results indicate that alpha 2PI is synthesized and secreted from liver cells as Met-alpha 2PI and Met-alpha 2PI is converted to Asn-alpha 2PI by proteolytic cleavage in plasma during the circulation.
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We compared the degrees of impairment between intended voluntary movement and its simultaneous automatic associated movement in Parkinson's disease (PD). We studied wrist dorsiflexion as a movement associated with grip in 20 patients with PD and in 20 normal controls. The patients showed a significantly smaller dorsiflexion as compared with the controls. The decrease in associated movement was related to the severity of clinical stage of the disease, while gripping was performed well in each stage. The temporal relationship between grip and associated movement was the same for both groups of subjects. The patients showed no disturbance of amplitude or velocity for a single motor act of wrist dorsiflexion. Persons with PD have a greater reduction of automatic associated movement than intended voluntary movement. This may be one of the bases of clinical symptoms of PD patients in early stages of the disease.
The effects of three phosphatase inhibitors including okadaic acid, calyculin A and tautomycin were evaluated on platelet Ca2+ mobilization. Calyculin A and tautomycin at appropriate concentrations appeared to have a selective inhibitory effect on thrombin-induced Ca2+ influx, but not on [Ca2+]i release from intracellular Ca2+ storage sites. In contrast, pretreatment with okadaic acid at concentrations that effectively lowered Ca2+ influx also suppressed Ca2+ release from intracellular Ca2+ stores. In a system that specifically evaluates the effects of agents on Ca2+ influx induced by the Ca(2+)-depleted state of intracellular Ca2+ storage sites, the three phosphatase inhibitors attenuated Ca2+ influx in a dose dependent manner and showed complete inhibition at appropriate concentrations. These findings suggest that protein phosphorylation/dephosphorylation plays an important role in mediating signals to open Ca2+ channels when Ca2+ depletion in intracellular Ca2+ stores is caused by thrombin. In contrast, Ca2+ influx induced by thapsigargin, a Ca(2+)-ATPase inhibitor, was only partially suppressed by pretreatment with each of the three phosphatase inhibitors. Based on these findings, we suggest that the Ca(2+)-depleted state of intracellular Ca2+ stores by thapsigargin induces the opening of Ca2+ channels via phosphatase inhibitor-insensitive pathways. All the phosphatase inhibitors, at the highest concentrations tested in the present study, only partially inhibited Mn2+ entry induced by thrombin. These findings suggest that there are at least two types of divalent ion channels on platelet plasma membranes and that one of them, that preferentially allows Mn2+ entry, is resistant to the inhibitory effects of phosphatase inhibitors.
Cardiac scintigraphy with meta-[123I]iodobenzylguanidine (MIBG) is used to assess cardiac sympathetic function. We performed [123I]MIBG scintigraphy in 7 patients with neurological diseases presenting orthostatic hypotension and other autonomic failures (AF), 22 neurological patients without AF, and 9 healthy subjects. Thallium scintigraphy and echocardiography were also performed in all subjects. In this series, patients with any evidence of cardiac dysfunction were excluded. No [123I]MIBG accumulation was observed in all patients with AF, and cardiac defects were noted in 7 patients (5 with Parkinson's disease [PD], 2 with spinocerebellar degenerations [SCD]), and in some patients without AF. In contrast, the distribution of [123I]MIBG was normal in all the healthy subjects. No decrease in [123I]MIBG accumulation was resulted from drug therapy (droxidopa, amezinium and thyrotropin-releasing hormone). In conclusion, reduced accumulation on [123I]MIBG scintigraphy may be due to myocardial beta-adrenoceptor dysfunction or reduced central sympathetic activity of the heart, or both.
The design, synthesis and structure-activity relationships of transition-state inhibitors containing the dihydroxyethylene isostere at the scissile site are described. The compounds with (2S,3R,4S)-4-amino-5-cyclohexyl-1-morpholino-2,3-pentanediol at the P1-P1 site are potent renin inhibitors. (2S,3R,4S)-4-[N-[(2S)-3-Ethylsulfonyl-2-(1-naphthylmethyl)propiony l]-L- norleucyl]amino-5-cyclohexyl-1-morpholino-2,3-pentanediol (2) (BW-175), which is the most potent inhibitor (IC50: 3.3 nM against human renin) in this series, poorly inhibits cathepsin D (IC50: 26000 nM) and pepsin (IC50: > 100000 nM), and thus it is specific for renin. Compound 2 contains only one amino acid and showed an oral bioavailability of 2.8% at 10 mg/kg and 9.7% at 30 mg/kg in rats. The interaction between renin and inhibitor 2 is discussed on the basis of molecular modeling studies.
We investigated the effects of optokinetic stimulation (OKS) on the soleus H reflex in ten healthy male subjects who were held in a fixed standing position. Upward and downward OKSs (60 degrees/s) were presented randomly. The H reflex amplitude decreased during upward OKSs and increased during downward ones (Kruskal-Wallis test, p < 0.02). Change in the H reflex amplitude was more marked during downward stimulation (p < 0.01). The H reflex was enhanced more during the acceleration phase of downward OKS than during the constant phase (p < 0.01), but it fluctuated during the former phase. These results suggest that OKS affects alpha motoneurone activity and that information from the visual system modulates the condition of the motor program at the spinal level.
A 77-year-old male presented with gradual development of right hemiparesis. Postcontrast computed tomography (CT) revealed enhanced lesions in the left parietal and right paraventricular areas. Stereotactic brain biopsy led to a histological diagnosis of metastatic carcinoma. The lesions were treated by radiosurgery using the Leksell gamma unit. CT showed reduced size of the lesions after irradiation. The primary lesion could not be found and he died from pneumonia. Autopsy 3 weeks after the irradiation disclosed histological tumor necrosis, with greater tumor cell kill effects toward the center of the tumor.
The usefulness of 80-Hz amplitude-modulation following response (AMFR) detected by phase spectral analysis to predict the hearing threshold during sleep was evaluated in 20 normal adults, 8 normal children and 37 children with hearing impairment. The onset effect of tonal stimulus on 80-Hz steady state response was studied in normal adults during sleep and a threshold of 80-Hz AMFR detected by phase spectral analysis was compared with that of ABR elicited by tone pips in children during sleep. Although 80-Hz AMFR is not appropriate for the assessment of hearing in adults, it appears useful for evaluating hearing in young children during sleep. Hearing prediction by 80-Hz AMFR appears to be more accurate than that by ABR elicited with tone pips. The onset effect of stimulus on 80-Hz AMFR with modulation depth of 95% was less than 80-Hz SSR evoked by clicks.