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Biomedical subjects

F Sakai

Publications and source records attributed to F Sakai.

At least 181 records · Page 10Linked to original sources

Sleep apnea, narcolepsy, and dreaming: regional cerebral hemodynamics.

Regional cerebral flow after inhalation of xenon 133 as well as polysomnography were recorded during daytime sleep and the awake state in patients with narcolepsy and sleep apnea. Brainstem-cerebellar (BSC) gray matter blood flow (Fg) values in the awake state were reduced below normal (p less than 0.05) in both narcolepsy and sleep apnea; in sleep apnea, bihemispheric Fg values were also reduced in the awake state. After sleep onset, Fg paradoxically increased in narcolepsy but decreased further in sleep apnea. Maximal regional Fg changes occurred in BSC regions in both groups of patients. Oral administration of methylphenidate hydrochloride (Ritalin) increased resting Fg values in awake narcoleptics, particularly in BSC regions, but attentuated Fg increases during sleep onset. Regional Fg values during visual dreaming or hypnagogic hallucinations in narcoleptics were maximally increased in right parietooccipital regions. In narcoleptics, impaired control of sleep-wake and REM mechanisms is attentuated by methylphenidate. In patients with sleep apnea, brainstem functional activity is low in the awake state but becomes critically reduced during sleep, culminating in apnea-stimulated arousal followed by repetitive cycles as sleep recurs.

Adult↗

Effect of differential spinal cord transection on human cerebral blood flow.

Regional cerebral blood flow (rCBF) was measured by 133Xe inhalation in 17 patients with chronic spinal cord transection. This was done to investigate any effects such spinal cord deafferentation might have on resting rCBF and to test whether resulting chronic preganglionic sympathectomy influenced cerebral vasomotor CO2 responsiveness and autoregulation. Thirteen patients had complete cervical cord transection (CCT) at levels C4--C6 (age 37 +/- 15 years, time interval, 2 months--20 years). Four patients had complete thoracic cord transection at levels T3--4, T8 and T12 (TCT; age 49 +/- 22 years; time interval 2--5 months). CO2 responsiveness was tested by induced hypercapnia in 11 patients with CCT and 2 patients with TCT. Autoregulation was tested in 10 patients with CCT and 4 patients with TCT by decreasing cerebral perfusion pressure during postural tilting. Mean resting hemispheric Fg values (MHFg) were significantly reduced only in patients with CCT (MHFg = 69 +/- 12 ml/100 g brain/min), while brain stem-cerebellar Fg values (BSC Fg) were reduced significantly both in patients with CCT (BSC Fg = 85 +/- 10) and with TCT (BSC Fg = 88 +/- 12) compared to values measured in healthy normals (N = 21, MHFg = 81 +/- 10, BSC Fg = 98 +/- 10). Hemispheric CO2 responsiveness showed a trend toward reduction in patients with CCT but this was not statistically significant. Hemispheric autoregulation was significantly impaired in CCT compared to healthy normals but improved with time and rehabilitation.

Adult↗

Association of gross virus-associated cell-surface antigen with liposomes.

Gross Cell-Surface Antigen (GCSAa) was obtained from W/Fu (C58NT)D lymphoma cells by Nonidet P40(NP40) or 3M KCl extraction and further purified by Sephadex G200 filtration. GCSAa was associated with lipids (dipalmitoylphosphatidycholine, cholesterol and dicetylphosphate, in molar ratios of 7:2:1) to form multilamellar liposomes. The amount of protein associated with liposomes was found to be proportional to the protein concentration of the sensitizing cellular extract and to the amount of phospholipids used and, under defined conditions, 22-55% of the protein of the cellular extract could be associated with liposomes. Analysis of disrupted sensitized liposomes showed that the GCSAa-specific activity of the liposome-associated proteins was quite similar to that of the proteins of the sensitizing cellular extract. Ultracentrifugation of disrupted liposomes showed that about 75% of the liposome-associated GCSAa activity was firmly associated with lipids and that little GCSAa was trapped within aqueous compartments between lipidic lamellae. 1.8--8.0% of the liposome-associated GCSAa was expressed at the liposome surface. No striking differences in degree of GCSAa association were found between liposomes sensitized by NP40 or by 3M KCl extracts. Storage experiments at +4 degrees C showed that GCSAa-sensitized liposomes were fairly stable.

AKR murine leukemia virus↗

Induction of antibody response to liposome-associated Gross-virus cell-surface antigen (GCSAa).

The immunogenicity of a soluble fraction containing Gross-virus-associated cell-surface antigen (GCSAa) obtained from (C58NT)D lymphoma cells either by detergent (NP40) solubilization or by 3M KCl extraction, was studied in syngeneic W/Fu rats. Rats immunized by 2 s.c. injections of soluble antigen or soluble antigen mixed with empty liposomes and emulsified in complete Freund's adjuvant (CFA) failed to produce significant levels of cytotoxic antibodies to GCSAa. On the other hand, rats similarly immunized by negatively charged liposomes containing NP40-solubilized GCSAa, and emulsified in CFA, developed high and persistent levels of cytotoxic antibodies, and their response could even mimic that induced by viable (C58NT)D cells. A similar response could also be obtained in rats immunized with liposome-associated NP40-solubilized GCSAa, but without CFA. Rats immunized by comparable amounts of liposome-assocated 3M KCl-extracted GCSAa developed only low levels of cytotoxic antibodies, and their response was of shorter duration. These results strongly suggest that inclusion into liposomes of a solubilized proteic tumour-associated cell-surface antigen can provide an immunogen as potent as viable tumour cells in inducing an antibody response, and that the solubilization method may be critical.

AKR murine leukemia virus↗

Cerebral embolism: local CBF and edema measured by CT scanning and Xes inhalation.

Serial CT scans were made in baboons after cerebral embolization during stable Xe inhalation for measuring local values for CBF and lambda (brain-blood partition or solubility coefficients), followed by iodine infusion for detecting blood-brain barrier (BBB) damage. Supplementary 133Xe CBF measurements were made at corresponding intervals. Persistent zones of zero flow surrounded by reduced flow were measured predominantly in subcortical regions, which showed gross and microscopic evidence of infarction at necropsy. Overlying cortex was relatively spared. Reduced lambda values attributed to edema appeared within 3--5 minutes and progressed up to 60 minutes. Damage to BBB with visible transvascular seepage of iodine began to appear 1--1 1/2 hours after embolism. In chronic animals, lambda values were persistently reduced in areas showing histologic infarction. Contralateral hemispheric CBF increased for the first 15 minutes after embolism, followed by progressive reduction after 30 minutes (diaschisis).

Afferent Pathways↗

Local cerebral blood flow measured by CT after stable xenon inhalation.

A safe, practical, clinically applicable, noninvasive method for measuring local cerebral blood flow (LCBF) using inert xenon (Xes) and a 60 sec CT scanner has been developed in the baboon. Direct measurement of expired Xes concentration after short inhalation (4--7 min) of 40% Xes and the use of computer-programmed autoradiographic formulas allow accurate, reproducible measurements of LCBF using serial 60 sec scans of regions as small as 0.04 cm3. LCBF measurements are possible with a single 1 min scan. The method reduces radiation exposure, obviates a costly fourth-generation scanner, avoids anesthetic effects of Xes, and reduces the 30 min/scan saturation period. It is less expensive than emission tomography and minimizes problems of overlap and Compton scatter inherent in 133Xe and positron-emission blood flow measurements. Regions of zero perfusion are demonstrable in three dimensions. Tissue solubility and partition coefficients, as well as LCBF, are measured in vivo with high resolution and reproductibility so that minor regional changes in physical properties of tissue that alter solubility are measured. These enhance the potential clinical usefulness of CT scanning.

Administration, Intranasal↗

BBM-928, a new antitumor antibiotic complex. I. Production, isolation, characterization and antitumor activity.

A complex of the antitumor antibiotic BBM-928 was produced by an actinomycete strain No. G455-101. Four components, BBM-928 A, B, C and D, were isolated in crystalline form and characterized. They were shown to be cyclic depsipeptide antibiotics containing a quinoline nucleus as the chromophore. BBM-928 A is a monoacetyl derivative of BBM-928 B and a diacetyl derivative of BBM-928 C. BBM-928 components exhibit antimicrobial activity against Gram-positive and acid-fast bacteria. BBM-928 A is highly active in mice against various experimental tumors including leukemia P388, leukemia L1210, melanoma B16, LEWIS lung carcinoma and sarcoma 180. BBM-928 B is less active than BBM-928 A, and BBM-928 C has no antitumor activity.

Animals↗

[Evaluation of nephrotoxic site in rat proximal tubule: intrarenal distributions of three enzymes and effects of mercuric chloride and gentamicin on their excretion into urine (author's transl)].

Intrarenal distributions of three enzymes, gamma-glutamyl transpeptidase (gamma-GTP), alkaline phosphatase (Al-p) and leucine aminopeptidase (LAP) were determined using six segments of nephrons. These enzymes were localized only in the proximal tubule. Intra-proximal distributions of the enzymes, however, were not uniform. The order of each enzyme activity in three segments of the proximal tubule, S1, S2 and S3 was as follows: Formula: (See Text) With subcutaneous administration of HgCl2 (1.0 mg/kg/day), urinary excretions of all three enzymes were increased from the 1st to the 2nd day and then decreased to the control level. However, after intraperitoneal administration of gentamicin sulfate (40 mg/kg/day), only Al-p activity in urine was significantly increased on the 1st day. Because of the lack of increasing blood levels of these enzymes after treatment, increased urinary excretions of the enzymes probably originate from the kidney, particularly the proximal tubule. The prominently increased excretion of gamma-GTP and LAP after HgCl2 treatment means that HgCl2 might damage S2 and S3, because the excretory patterns of the three enzymes were similar to their distribution profiles in S2 and S3. On the other hand, the toxic action of GM may be localized in S1 portion, in which Al-p activity proved to be highest among the three enzymes.

Alkaline Phosphatase↗

Pathogenesis of transient ischemic attacks within the vertebrobasilar arterial system.

Regional cerebral blood flow (rCBF) was measured by xenon 133 inhalation in 36 patients with vertebrobasilar arterial insufficiency (VBI), three patients with brain stem infarction, and 15 age-matched normal controls before and after inducing postural hypotension. Probes mounted over the suboccipital area by means of a helmet were used to measure rCBF over the brain stem and cerebellar regions. When lying flat, rCBF values measured over both cerebral hemispheres and the brain stem-cerebellar regions in patients with VBI were not significantly different from normal controls. Unlike carotid transient ischemic attacks, regional flow reduction rarely persisted for three weeks after transient ischemic symptoms in patients with VBI. When postural hypotension was induced, rCBF became significantly reduced in patients with VBI whether or not they were treated with papaverine. Dysautoregulation was restricted to vertebral, basilar, and posterior cerebral arterial distribution in patients with VBI of 1 to 12 months' duration, but was more widespread and involved both cerebral hemispheres in long-standing VBI. Hemodynamic factors and dysautoregulation appear to play a part in the pathogenesis of symptoms of VBI.

Adult↗

Effects of advancing age on regional cerebral blood flow. Studies in normal subjects and subjects with risk factors for atherothrombotic stroke.

Regional cerebral blood flow (rCBF) was measured by 133Xe inhalation in 46 normal volunteers, aged 21 to 63 years, and 14 neurologically asymptomatic subjects above age 40 with risk factors for atherothrombotic stroke, including hypertension, diabetes mellitus, and hyperlipidemia. In normal volunteers, there was diffuse and progresive reduction of gray matter flow and weight as well as increases of cerebrovascular resistance (CVR) with advancing age. Reduction of gray matter flow with advancing age appears to be attributed in part to neuronal atrophy and in part to cerebral arteriosclerosis. Regional increases of CVR and reduction of gray matter flow with advancing age were most evident in the middle cerebral arterial (MCA) distribution and were enhanced by the association of risk factors. Development of cerebral arteriosclerosis with age and/or risk factors appears to be most evident in MCA distribution.

Adult↗

Regional cerebral blood flow measured by 133Xe inhalation in tracheostomized and laryngectomized men and women.

The question of contamination of cerebral clearance curves utilized for measuring regional cerebral blood flow by radioactivity derived from the nasopharyngeal air passages following inhalation of 133Xe was tested in patients with chronic tracheostomy. The peak counts for head curves were 5--9% higher when 133Xe was inhaled via a face mask than when inhaled via the tracheal stoma. Calculated flow values using standard recommended start-fit-times were not significantly different between these two different methods. Present results indicate that neither overestimation of fast flow values due to contamination from rapid 133Xe washout recorded from the air passages nor the underestimation of slow flow due to contamination from 133Xe trapped in the air sinuses produced significant measurement errors. However, if earlier start-fit-times were used, flow values were artificially high, particularly for brain stem/cerebellar probes because of an initial rapid decline in the head desaturation curves due to an arterial peak believed to be derived from the basilar artery.

Adult↗

Noninvasive measurement of cerebral vasopasm in patients with subarachnoid hemorrhage.

Regional cerebral blood flow (rCBF) was measured as fast flow clearance (F1) and the initial slope index (ISI2) after inhalation of 133Xe in 30 patients with subarachnoid hemorrhage (SAH). Vasomotor responsiveness to reduction in end-tibal PECO2 was examined in those patients who could carry out this procedure satisfactorily as a test for the presence or absence of vasospasm. F1 and ISI2 were significantly reduced in patients with recent SAH compared to 35 age-matched normal volunteers. The degree of reduction of F1 and ISI2 correlated directly with severity of the neurological deficit graded according to the Hunt and Hess rating scale. Topographic reductions of rCBF correlated with angiographically demonstrated vasospasm or intracerebral hematoma. The degree of impairment of cerebral vasomotor responsiveness to reduction of PECO2 by hyperventilation also correlated with the severity of vasospasm demonstrated angiographically in 16 patients. The reductions of rCBF values were maximal during the first week after SAH but returned gradually toward normal by the 5th week. Individual patients with SAH whose lowest F1 values were above 50 ml/100 g brain/min tolerated surgical intervention best. Non-invasive measurements of rCBF after SAH appear to be helpful in estimating the presence and time course of vasospasm, in recognizing the development of normal pressure hydrocephalus, and in planning medical and surgical management.

Adolescent↗

Normal human aging and cerebral vasoconstrictive responses to hypocapnia.

Cerebral vasoconstrictive capacitance was measured during voluntary hyperventilation hypocapnia in 22 healthly normal volunteers aged 21--65 years by serial 133Xe inhalation estimates of rCBF by the initial slope index method of Risberg (ISI2) in the steady state followed by the hypocapnic state. End-tidal PCO2 was monitored by a capnograph. There was significant linear correlation between reduction of PECO2 and the ISI2 values. Significant reduction of cerebral vasoconstrictive response to hypocapnia was found with normal advancing age which is attributed to (1) minor atherosclerosis or loss of elasticity of cerebral vessels with advancing age, (2) the presence of an ischemic threshold during hyperventilation at which CBF tends to stabilize.

Adult↗

Regional cerebral blood flow, diaschisis, and steal after stroke.

Regional CBF was measured by 133Xe inhalation in unilateral cerebral infarction, carotid TIAs, and normal volunteers. Regional CBF values were bilaterally and symmetrically reduced in patients measured within 3 weeks after stroke. Later, rCBF values returned toward normal in the contralateral hemisphere of patients with infarction and in both hemispheres with carotid TIAs. In cases with carotid occlusive disease, flow reduction was seen in the contralateral posterior cerebral artery distribution, with hyperemia in ipsilateral occipital lobe caused by interhemispheric steal. Brainstem-cerebellar flow values were increased following acute cerebral infarction if patients were alert but reduced if consciousness was impaired.

Adult↗