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H Kuwabara

Publications and source records attributed to H Kuwabara.

At least 109 records · Page 6Linked to original sources
PubMed1991

Measurements of glucose phosphorylation with FDG and PET are not reduced by dephosphorylation of FDG-6-phosphate.

To improve the measurements of glucose metabolism in the human brain, we imposed biologic constraints on the deoxyglucose model with and without dephosphorylation of FDG-6-phosphate (the k4*- and k3*-models). The constraints included constant transport and phosphorylation ratios (tau and phi) and a common partition volume (K1/k2) for tracer [18F]FDG and glucose. In the presence of significant dephosphorylation, the k3*-model yielded time-dependent estimates of the phosphorylation coefficient (k3*), while the K4*-model yielded time-independent estimates. However, the two models yielded practically identical measurements of regional cerebral glucose metabolism in PET studies of six normal volunteers when the phosphorylation affinity ratio (the k3*/k3 ratio of FDG and glucose) and tracer circulation time were 0.30 and 20 min for the k3*-model and 0.33 and 45 min for the k4*-model.

Brain↗
PubMed1990

Blood-brain transfer and metabolism of 6-[18F]fluoro-L-dopa in rat.

In a study designed to reveal the rates of blood-brain transfer and decarboxylation of fluoro-L-3,4-dihydroxyphenylalanine (FDOPA), we discovered a major discrepancy between the DOPA decarboxylase activity reported in the literature and the rate of FDOPA decarboxylation measured in the study. "Donor" rats received intravenous injections of 6 mCi fluorine-18-labeled FDOPA. The donor rats synthesized methyl-FDOPA. Arterial plasma, containing both FDOPA and methyl-FDOPA, was sampled from the donor rats at different times and reinjected into "recipient" rats in which it circulated for 20 s. The blood-brain clearance of the mixture of labeled tracers in the plasma was determined by an integral method. The individual permeabilities were determined by linear regression analysis, according to which the average methyl-FDOPA permeability in the blood-brain barrier was twice that of FDOPA, which averaged 0.037 ml g-1 min-1. The permeability ratio was used to determine the fractional clearance from the brain of FDOPA (and hence of methyl-FDOPA), which averaged 0.081 min-1. In the striatum, the measured average FDOPA decarboxylation rate constant (kD3) was 0.010 min-1, or no more than 1% of the rate of striatal decarboxylation of DOPA measured in vitro and in vivo. We interpreted this finding as further evidence in favor of the hypothesis that striatum has two dopamine (DA) pools, of which only DA in the large pool is protected from metabolism. Hence, no more than 1% of the quantity of fluoro-DA theoretically synthesized was actually retained in striatum.

Animals↗
PubMed1990

Michaelis-Menten constraints improved cerebral glucose metabolism and regional lumped constant measurements with [18F]fluorodeoxyglucose.

In the three-compartment model of transfer of native glucose and [18F]fluorodeoxyglucose (FDG) into brain, both transport across the blood-brain barrier and phosphorylation by hexokinase can be described by the Michaelis-Menten equation. This permits the use of fixed transport (tau = K*1/K1) and phosphorylation (psi = k*3/k3) ratios and a common partition volume (Ve = K1/k2) for tracer and glucose. By substituting transfer constants of FDG for those of glucose, using tau and psi, the lumped constant was determined directly by positron tomography. The same constraints also eliminated k*2 and k*3 from the model, thus limiting the parameters to K* [equivalent to K*1k*3/(k*2 + k*3)], K*1, and the cerebral vascular volume (Vo). In six healthy elderly men (aged 61 +/- 5 years), time-activity records of cerebral cortical regions were analyzed with tau = 1.1 and psi = 0.3. The results were compared with those of the conventional FDG method. At 20 min, the goodness of fit by the new equation was as good as that of the conventional method at 45 min. The estimates obtained by the constrained method had stable coefficients of variation. After 20 min, regional differences between the estimates were independent of time, although we observed steady decreases of K* and (k*3). The decrease strongly suggested dephosphorylation of FDG-6-phosphate, particularly after 20 min. All estimates of variables with the constrained method were more accurate than those of the conventional method, including the cerebral glucose metabolic rate itself, as well as physiologically more meaningful, particularly with respect to k*2 and k*3.

Aged↗
PubMed1990

Reduction of functional capillary density in human brain after stroke.

The blood flow of brain tissue often returns to normal after an ischemic episode. As "luxury" rather than "reactive" reperfusion, this hyperemia is associated with low metabolism. It is not known to what extent the high blood flow accompanies a high, normal, or low density of capillaries. The resolution of this question may indicate whether the functional capillary density is variable and, if so, whether it is coupled to blood flow or metabolism. To answer these questions, we defined functional capillaries as capillaries that transport glucose. We then calculated the density of functional capillaries (Dcap) and the mean time of transit of blood through the capillaries (tcap) from hemodynamic variables obtained in vivo by positron tomography of five patients afflicted by cerebral ischemic stroke. Each patient was studied twice, within 36 h of the insult and 1 week later. We identified nominally "ischemic" regions in the first study as cortical gray matter regions, contiguous with the ischemic focus, in which the magnitude of blood flow did not exceed 20 ml 100 g-1 min-1. In these regions, values of metabolism and functional capillary density were proportionately low compared with normal values obtained in the contralateral hemisphere. The studies revealed a reduction of the functional density of exchange vessels in postischemic brain tissue as soon as 36 h after the insult. In "ischemic" regions, within 36 h of the insult, the net extraction of oxygen was inversely related to the capillary transit time and appeared to be limited mainly by the low functional density of the capillaries. Contrary to expectations, the reduced density persisted, even when more than adequate perfusion of the tissue returned. For these reasons, we concluded that changes of the capillary density were associated with changes of the metabolism of the tissue rather than with blood flow.

Adult↗
PubMed1990

Metabolic brain imaging. Direct regional measurement of transfer coefficients and lumped constant.

In the deoxyglucose method of measuring brain glucose utilization, the Michaelis-Menten formalism implies 1) symmetrical transport across the blood brain barrier, 2) identical ratios between forward and backward transport across the blood brain barrier for substrates of the same carrier, and 3) constant transport (tau) and phosphorylation (phi) ratios between native substrate and tracer. Incorporation of these assumptions into the fluoro-deoxyglucose method in humans allowed us to replace the brain blood transfer (k2*) and phosphorylation (k3*) coefficients by the coefficients of net (K*) and undirectional (K1*) transfer in the operational equation of the method, and to calculate the lumped constant directly. The reduction of the number of essential parameters amounts to a constraint of the freedom of the transfer coefficients to assume any value. On this basis, we were able to improve the estimates of the transfer coefficients. Seven healthy, older subjects were studied by this method. The values of K1*, k2* and k3* changed in parallel to K*. The values of the regionally calculated lumped constant ranged from 0.48 to 0.73 with a mean of 0.58.

Aged↗
PubMed1990

[Eaton-Lambert syndrome manifested by respiratory failure associated with small cell carcinoma of the lung].

A 63-year-old man with Eaton-Lambert syndrome manifested by marked respiratory failure was reported. He began to notice blepharoptosis and diplopia in September, 1987, followed by weakness and easy fatigability in bulbar, neck and limb muscles in association with impotence by February, 1988. On admission in August, 1988, Gowers' sign, decreased tendon reflexes and muscle weakness improved by the injection of edrophonium were found. Anti-acetylcholine receptor antibody was negative. Single muscle action potential evoked in the thenar muscle was abnormally low in amplitude with the stimulation of the median nerve: repetitive nerve stimulation study revealed the waning at the low rates, but the waxing at the high rate (30 Hz), suggesting the diagnosis of Eaton-Lambert syndrome. Early gastric cancer (adenocarcinoma) was diagnosed from needle biopsy specimens in August, 1988, but no other neoplasm including thymoma or lung cancer was found. After subtotal gastric resection in September, 1988, he failed into respiratory failure, requiring artificial ventilation for seven months. Plasmapheresis and drugs such as anticholinesterase, guanidine hydrochloride, and corticosteroid were ineffective for the recovery from weakness in respiratory muscle. Lung cancer was suspected, based on a chest X-ray in March, 1989, and one month later he died of pneumonia. At autopsy, small cell carcinoma of the lung was observed, but there was neither recurrence nor metastasis of the gastric cancer. Emphasis was placed on the respiratory failure in Eaton-Lambert syndrome which has rarely been reported.

Adenocarcinoma↗
PubMed1989

Quantitative correlation between cardiovascular and plasma epinephrine response to mental stress.

To investigate the quantitative correlations between cardiovascular and endogenous catecholamine response to mental stress, we gave a mental arithmetic test to 20 young healthy men. A direct and non-invasive haemodynamic measurement was performed by serial M-mode echocardiography. Heart rate, blood pressure, cardiac output, stroke volume, ejection fraction, left ventricular end-systolic pressure-volume ratio and plasma epinephrine increased over the baseline period during the test. The peripheral resistance and left ventricular end-systolic volume decreased, whereas left ventricular end-diastolic volume and plasma norepinephrine were unaltered. Furthermore, the degree of change in each haemodynamic parameter showing significant reaction, was well correlated with that of the increase in plasma epinephrine. The data suggest that acute mental stress induces endogenous epinephrine secretion resulting in a beta-adrenergic activated state in the cardiovascular system, namely, positive chronotropism, positive inotropism and vasodilatation.

Adult↗
PubMed1989

The effect of nimodipine on the evolution of human cerebral infarction studied by PET.

Fourteen patients were studied by positron emission tomography (PET) within 48 h of onset of a hemispheric ischemic stroke and again 7 days later. After the first set of PET scans, the patients were randomized to receive either nimodipine (n = 7) or a carrier solution (n = 7) by intravenous infusion. The infusions were maintained until the end of the second PET studies. CBF, cerebral blood volume (CBV), oxygen extraction ratio (OER), CMRO2, and CMRglc were measured each time. These metabolic and perfusion measurements were performed by standard methods. A surface map of each metabolic and perfusion measurement in the cortical mantle was generated by interpolating between the available slices. The various surface maps representing the physiological characteristics determined in the same or subsequent studies were aligned so that all data sets could be analyzed identically using an array of square regions of interest (ROIs). The functional status of each ROI was recorded at the two intervals following the cerebrovascular accident to characterize the evolution of the infarct, penumbra, and normal brain regions. We presumed the ischemic penumbra to be cortical regions in the proximity of the infarct and perfused at CBF values between 12 and 18 ml/100 g/min on the first PET scan, while densely ischemic regions had CBF of less than 12 nl/100 g/min and normally perfused brain greater than 18 ml/100 g/min. In the densely ischemic zone, CBF increased more in the nimodipine-treated group than in the carrier group. As well, in this region nimodipine reversed the decline in CMRO2 noted in the carrier group, the difference in the changes being significant. In the penumbra zone, comparable trends were noted in OER and CMRO2 but the difference in the changes between the two groups did not reach statistical significance. Changes in CMRglc and CBV were comparable between the two groups in both cortical regions.

Adult↗
PubMed1987

The role of ventricular and cisternal drainage in the early operation for ruptured intracranial aneurysms.

In a series of 177 patients with ruptured supratentorial aneurysms we studied retrospectively the results of early and delayed operation without aggressive removal of subarachnoid blood clots but ventricular and cisternal drainage. The early and delayed groups were comparable demographically and neurologically. The overall results for the early group were a good outcome in 65%, poor outcome in 10% and death in 24%, compared to 53, 20 and 27% respectively in the delayed group. Thus, patients with an early operation and CSF drainage had better results. Permanent ischaemic neurological deficits due to cerebral vasospasm accounted for the poor outcome in 10 and 21% of the patients in the early and delayed groups, respectively and rebleeding accounted for the poor outcome in 5 and 10% in the early and delayed groups respectively. The mean amount of haemoglobin in the cerebrospinal fluid from cisternal drainage was 6.4 g, corresponding to about 40 ml of whole blood, during the 12-day period after SAH. The level was higher in patients with larger subarachnoid clots or with symptomatic vasospasm than in those with smaller clots or without such vasospasm. Early operation combined with ventricular and cisternal drainage is considered to be a useful surgical method for patient with a ruptured aneurysm.

Adult↗
PubMed1986

Liquid ionization mass spectrometry of phospholipids.

Several phosphatidylcholines (PC) and a phosphatidylethanolamine (PE) were subjected to liquid ionization (LI) mass spectrometry, in which a sample is ionized through energy transfer from metastable argon atoms under atmospheric pressure. Commercially available and synthesized, saturated or unsaturated fatty acid containing phospholipids and their mixtures were studied. A sample either as a concentrated chloroform-methanol solution or with glycerol (matrix) gave characteristic peaks such as MH+ and four fragment ions. One of the fragment ions (e.g., m/z 551 of PC 16:0, 16:0) containing both fatty acid residues has been commonly observed with other ionization methods such as CI, FD, and FAB, but the other fragment ions have not been observed in other mass spectra with one exception on desorption CI. Ions b and d (e.g., m/z 464 and 328, respectively, for PC 16:0, 16:0) contain one fatty acyl residue and the other ion containing the phosphorylcholine moiety appears at m/z 196 for PC. Thus the masses of the MH+ ion and these fragment ions provide useful structural information even in the case of a mixture. The ion b (e.g., m/z 488 of PC 18:0, 18:2) observed during an early period of heating was formed mainly by the loss of one acyl group at sn-1 of the glycerol backbone and thus may be used to differentiate the positional specificities of the constituent fatty acids. The temperature of the sample, however, should be controlled precisely, because it has a significant effect on the mass spectrum. The present method (LI) also provided useful information for a mixture of PC and PE.

Mass Spectrometry↗
PubMed1986

Facioscapulohumeral dystrophy associated with mental retardation, hearing loss, and tortuosity of retinal arterioles.

A rare case of facioscapulohumeral muscular dystrophy with an early onset and progression is described. The patient had mental retardation, sensorineural hearing loss, and marked tortuosity of the retinal arterioles. On reviewing previous reports of related cases, our case and those of Small shared similar clinical manifestations, although the retinal findings in our patient were different from the typical Coats' disease of Small's patients. However, we postulate that these cases represent a specific nosological entity, although genetic transmission has yet to be proven.

Child↗