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Biomedical subjects

F Yamamoto

Publications and source records attributed to F Yamamoto.

At least 127 records · Page 7Linked to original sources

Effects of systemic hypoxia on pH outside rod photoreceptors in the cat retina.

We studied the effect of systemic hypoxia on intraretinal pH in the intact cat eye using double-barreled H(+)-sensitive microelectrodes. Hypoxia in the dark further acidified the extracellular space surrounding rods in the distal retina and this effect was maximal in the outer nuclear layer (ONL). An acidification occurred in response to essentially any decrease in PaO2 below the normoxic level. Light-evoked alkalinizations in the ONL were larger in amplitude during hypoxia than in normoxia and this difference increased with the severity of hypoxia. Background illumination suppressed the hypoxic acidification of the ONL, completely inhibiting it at rod saturating intensities, at levels of hypoxia down to PaO2s of 40 mmHg. Systemic hyperoxia produced a small alkalinization in the ONL, and a reduction in the amplitude of the light-evoked alkalinizations. This suggests that systemic hyperoxia can partially suppress the ongoing glycolysis of dark-adapted rods. Changes in blood flow during hypoxia also altered intraretinal pH. Hypoxia led to an alkalinization in the choroid in both dark and light adaptation that spread into the distal retina. This alkalinization is most likely caused by the increase in CO2 removal that occurs as systemic blood pressure, and as a consequence, choriocapillaris blood flow increase during hypoxia. The alkalinization attenuated the acidification that was observed outside rods during hypoxia. There was also an alkalinization of the proximal portion of the retina, which spread into the vitreous. This alkalinization was attributed to the autoregulatory increase in blood flow that occurs in the retinal vessels during hypoxia. These findings provide further evidence for the hypothesis that the energy metabolism of dark-adapted rods is exquisitely sensitive to systemic hypoxia so that any small decrease in PaO2 increases rod glycolysis. Rod-saturating illumination can completely suppress this increase in glycolysis for all but severe hypoxia. An increase in blood flow in the choriocapillaris during hypoxia appears to mitigate the effects of hypoxia on the distal retina.

Animals↗

Effects of intravenous acetazolamide on retinal pH in the cat.

Double-barreled H(+)-selective microelectrodes were used to study the effect on intravenous acetazolamide on intraretinal pH in the cat. Acetazolamide (11.4-27.8 mg kg-1 intravenously) caused a rapid acidification of the subretinal space. This change in pH originated in the most distal portion of the subretinal space and could not be attributed to a change in pH or PCO2 of the arterial blood. Slow light-evoked alkalinizations in distal retina, attributable to a decrease in rod photoreceptor energy metabolism, were relatively unaltered by acetazolamide. This result indicated that acetazolamide had not crossed the blood-retinal barrier in sufficient amounts to change this response. In time, following intravenous perfusion of acetazolamide, continuous depth profiles of intraretinal pH showed an acidification of the entire retina and the vitreous also became more acidic. These results indicate that the rapid or primary effect of acetazolamide is an acidification of the distal portion of the subretinal space, which is thought to originate in a change in the transport of H+ or HCO3- by the retinal pigment epithelium. This is followed by an acidification of the entire retina and vitreous, presumably due to diffusion of acid from the distal retina, although there could be additional causes.

Acetazolamide↗

Effects of intraocular pressure on pH outside rod photoreceptors in the cat retina.

Double-barreled H(+)-selective microelectrodes were used to study the effect of raising intraocular pressure (ocular hypertension) on intraretinal pH in the cat. A surprising alkalinizing response was observed in the subretinal space on the first experimental day in seven of 11 experiments. Of the three retinal regions studied, the alkalinizing response was present in the area centralis and in the adjoining near-discal region, but was absent in the superior temporal periphery. The alkalinizing response was relatively fragile, diminishing and then extinguishing with repetition of episodes of ocular hypertension. It was also never observed on the second experimental day. The alkalinizing response had a relatively low threshold, appearing with 10 mmHg elevations of intraocular pressure, i.e. when the perfusion pressure was still relatively high, but was also present across a wide range of perfusion pressures. It was maximal in amplitude in the most distal portion of the subretinal space and consisted of two components, an 'on' alkalinization during the episode of ocular hypertension, and an 'off' alkalinization following it. When the alkalinizing response was present in the subretinal space, it also could be recorded with placement of the microelectrode in the choroid. Elevations of systemic arterial blood pressure with epinephrine (intravenous), by raising perfusion pressure, also alkalinized the subretinal space, indicating that an increase in choroidal blood flow can produce this type of pH response. While pH recordings do not directly monitor blood flow, we tentatively interpreted the alkalinizing response with ocular hypertension as originating from a regional increase in choroidal blood flow, but we cannot rule out other explanations. Acidification of the subretinal space in response to ocular hypertension replaced the alkalinizing response when the latter extinguished, or acidification was the sole response in the absence of an alkalinization. The acidification also had a low threshold, was maximal in the most distal portion of the subretinal space, and increased in size with decreases in perfusion pressure. The acidification was reduced in amplitude by breathing 100% oxygen (hyperoxia). This was interpreted as suppression of the component of acidification that originated from an increase in glycolysis by the rod photoreceptors during ocular hypertension.

Animals↗

Effects of sodium iodate on the electroretinogram c-wave in the cat.

The c-wave of the vitreal electroretinogram decreased in amplitude and was replaced by a slow, polarity reversed potential following an i.v. infusion of sodium iodate, as first described by Noell. Intraretinal recordings showed that the negative-going c-wave, induced by iodate (30 mg/kg), was composed of reduced slow pIII and trans-epithelial c-wave. The effects of iodate on these components may originate from direct effects on the retinal pigment epithelial cells, namely, a large decrease in the trans-epithelial resistance. Other factors could have contributed to the change in the c-wave amplitude.

Animals↗

Positron labeled antioxidants: synthesis and tissue biodistribution of 6-deoxy-6-[18F]fluoro-L-ascorbic acid.

A one-pot synthesis of 6-deoxy-6-[18F]fluoro-L-ascorbic acid (18F-DFA) has been developed via nucleophilic displacement of a cyclic sulfate with no-carrier-added [18F]fluoride ion. Isolated radiochemical yields of around 15% were obtained with radiochemical purity of over 99% after overall synthesis time of 90 min. Tissue distribution studies with 18F-DFA in rats showed high uptake of radioactivity in the adrenals, kidneys, liver and small intestine--organs known to have high concentrations of L-ascorbic acid. The slow and low uptake of radioactivity in the brain was observed between 10 and 120 min after i.v. injection. In vivo behavior of 18F-DFA in mice bearing 3-methylcholanthrene-induced fibrosarcoma demonstrated its ability to accumulate in the tumor.

Animals↗

Ubiquitous presence in mammalian cells of enzymatic activity specifically cleaving 8-hydroxyguanine-containing DNA.

Here we report the finding of enzymatic activity that specifically cleaves DNA containing 8-hydroxyguanine (oh8Gua) residues in various mammalian cells. To detect this activity, we used a synthetic double-stranded DNA containing a single oh8Gua at a defined position as the substrate, and analyzed the products of enzymatic digestion by polyacrylamide gel electrophoresis. Two cleavage sites near the oh8Gua residue were detected with partially purified fractions from cow brain and rat liver, and also with preparations from all mammalian tissues examined. These results suggest that enzymatic activity for the removal of oh8Gua from DNA is widely distributed in mammalian cells.

Animals↗

Gallbladder mucosal function: studies in absorption and secretion in humans and in dog gallbladder epithelium.

The gallbladder is conventionally regarded as an absorptive organ such that dilute hepatic bile is both stored and concentrated. We studied 35 patients who had recovered from a percutaneous transhepatic gallbladder drainage performed for acute cholecystitis. After an overnight fast, gallbladder bile was dark brown in color and had a wide scatter in the lipid composition. Two hours after a meal, the gallbladder bile was opalescent white in color and had the composition of an extracellular fluid. This phenomenon was uniformly observed in all 35 patients and was also consistently reproducible when five patients were repeatedly studied. We used normal dog gallbladder epithelial cell monolayers grown in culture and examined sodium flux. Control gallbladder cells absorbed sodium. When secretin (0.5-2.5 x 10(-7) M) was added, there was a prompt reversal of sodium flux, resulting in net secretion. We conclude that secretion is a physiological function of the gallbladder mucosa. After feeding, the neural and humoral factors divert stored and newly secreted bile into the duodenum and induce active de novo secretion thus producing a gallbladder bile that is opalescent white with no lipids. Our results also have important implications on the origin of the pathological "white bile," the pathogenesis and treatment of gallbladder sludge, as well as the kinetic analysis of compounds undergoing enterohepatic recirculation.

Absorption↗

Light-evoked changes in [K+]o in proximal portion of light-adapted cat retina.

1. The M-wave is a light-adapted response of proximal retina consisting of phasic negative field potentials at light onset and offset that are spatially tuned for small stimuli. We measured light-dependent changes in extracellular K+ concentration ([K+]o) in proximal retina to investigate the hypothesis that the M-wave originates from Müller cell responses to changes in [K+]o. 2. Extracellular field potentials, and changes in [K+]o evoked in response to circular spots of light flashed on steady backgrounds, were recorded with double-barreled K(+)-sensitive electrodes placed in the retina at different depths. 3. Increases in [K+]o during illumination and at light offset were maximal in proximal retina, with the On [K+]o increase located more proximally than the Off increase. The [K+]o increase during illumination consisted of a phasic and sustained response, whereas the Off [K+]o increase was predominantly phasic. The spatial tuning of the [K+]o increases was similar to the tuning of the field potentials. 4. The Off-field potential was larger than the On potential; it tended to be maximal more distally and was more sharply localized in retinal depth. Stimulus-response characteristics of the field potentials were not altered by intravitreal tetrodotoxin (TTX; 3.8 microM) sufficient to block retinal ganglion cell action potentials. 5. There were no rod contributions to the proximal [K+]o increases and field potentials recorded at the background illuminations used in this study (9.5-11.5 log q.deg-2.s-1). 6. An intravitreal injection of L- or DL-2-amino-4-phosphonobutyric acid (APB; 1 mM) was used to block On-system neuronal responses in proximal retina and isolate Off-system responses. After APB the [K+]o response consisted of a sustained decrease in [K+]o during illumination followed by an overshoot at light offset, while the field potential was a sustained positive response at light onset followed by an initially phasic negative response at light onset followed by an initially phasic negative response at light offset. These responses retained spatial tuning. To isolate the On-system components, the APB-isolated responses were subtracted from the controls. The [K+]o response now consisted of a sustained increase during illumination followed by an undershoot at light offset. The field potential was a sustained negative potential with an initial phasic peak that decayed at Off. Results with kynurenate (KYN; 5 mM) and (+/-)cis-2,3-piperidine (PDA; 5 mM) confirmed the sustained nature of the On component.(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptation, Physiological↗

Photosensitized formation of 8-hydroxyguanine (7,8-dihydro-8-oxoguanine) in DNA by riboflavin.

Potosensitized formation of 8-hydroxyguanine in DNA by riboflavin was observed. A reaction mechanism involving guanine radical cation and hydration reaction was proposed. This hypothesis was confirmed by the incorporation of [18O]-atom within guanine moiety in isotopic experiments using [18O]-H2O. Photosensitized formation of oh8Gua by riboflavin was also observed in cellular DNA.

Animals↗

[Total repair for truncus arteriosus].

Total repair for truncus arteriosus using an external conduit was performed in 12 patients from 1978 through 1989. Six cases were infants (mean age: 3.4 months) and 6 were children (mean age; 1 years 9 months). Two cases had Collet-Edwards type II truncus and the other 10 cases had type I truncus. One of the infants was associated with an interruption of the aorta and another had a severe regurgitation of the truncal valve (TrV). For external conduits, we used a non-valved conduit in one infant, a composite valved conduit of Dacron containing a heterograft valve in 4 children and a valved pericardial roll made of an autologous or porcine pericardium in 5 infants and 2 children. One infant with a severe regurgitation of the TrV needed valve replacement along with enlargement of the annulus of the TrV. One infant who had replacement of the TrV died early postoperatively. Another infant died 10 months after total repair due to an infection of an external conduit. Cardiac catheterization was performed in all 10 survivors. The mean value for the systolic pulmonary/systemic pressure ratio decreased from 0.98 +/- 0.09 preoperatively to 0.36 +/- 0.09 postoperatively. Replacement of an external conduit was performed due to a conduit stenosis in 2 children and 1 infant, 10 years and 2 months, 7 years and 9 months, and 1 year and 8 months after the total repair, respectively. In one of these 2 children, replacement of the aortic valve was performed due to a severe aortic regurgitation. We conclude that our results of total repair for truncus arteriosus were satisfactory. However, it remains to be solved how to manage an infant with truncus arteriosus associated with a severe regurgitation of the TrV.

Bioprosthesis↗

[The effects of protease inhibitor upon the ischemia-reperfusion injury].

The purpose of the study is to investigate the effects of protease inhibitor (Nafamostat mesilate: NM) upon myocardial protection. Hearts were subjected to 20 min working control perfusion followed by 3 min cardioplegic infusion with the St. Thomas Cardioplegic Solution (ST) contained various concentrations of NM, and global ischemia for 33 min at 37 degrees C (Exp. 1) or 150 min at 20 degrees C (Exp. 2). Hearts were then converted to Langendorff reperfusion (the leakage of Creatine Kinase (CK) and Cathepsin B (Cat-B) ware measured) and 20 min working reperfusion. Various concentrations of NM added during Langendorff reperfusion (Exp. 3). During working perfusion cardiac functions (aortic flow (AoF), coronary flow (CoF), heart rate (HR), aortic pressure (AoP)) were measured, and expressed as the percent recovery of pre-ischemic control value. Post-ischemic recovery of AoF (%AoF) showed the bell-shaped dose-response curve, and the optimal dose was 3 microM (Exp. 1) and 10 microM (Exp. 2) respectively. There was a significant (p < 0.05) increase of %AoF in optimal dose compared with that in controls (64.2 +/- 1.2% vs 52.3 +/- 2.5% in Exp. 1, 68.9 +/- 3.1% vs 54.1 +/- 1.4% in Exp. 2). These increase of functional recovery reflected in the values for CK and Cat-B leakage. The addition of NM in ST reduced CK and Cat-B leakage significantly in the concentration of 5 microM (in Exp. 1) and 10 microM (in Exp. 2) respectively. But the addition of NM in reperfusate did not reduced CK leakage significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[The effects of potassium concentration in reperfusion solution upon myocardial protection].

The effects of potassium in reperfusion solution (RS) and the influence of sodium on this effect were studied. Experimental time course was as followed: 20 min working perfusion, 3 min cardioplegic infusion with St. Thomas Cardioplegic Solution followed by global ischemia for 33 or 35 min at 37.5 degrees C, 15 min early Langendorff reperfusion with several different potassium concentration modified with Krebs Henseleit Bicarbonate Buffer (KHBB) containing 145 mM and 110 mM sodium and 5 min late reperfusion with KHBB, followed by 20 min working perfusion. Potassium in RS possessed bell shaped dose response nature with optimal concentration of 10 mM in the condition of 145 mM sodium but 6 m in the condition of 110 mM in terms of percent recovery of aortic flow. Although higher potassium reperfusion produced less Creatine Kinase leakage.

Animals↗

[A case of microsurgically removed cavernous angioma in the midbrain].

The authors presented a case of microsurgically removed large cavernous angioma in the midbrain. A 46-year old woman was admitted to our service with bilateral nuclear oculomotor pareses and mild tetraparesis. MRI revealed a large round well-circumscribed high signal-intensity lesion on both T1 and T2 weighted image with low signal rim in the midbrain. This lesion was diagnosed preoperatively as a cavernous angioma. The operation was performed in three steps with intermittent hemorrhages by interhemispheric transcallosal-hippocampal commissure--velum interpositum-third ventricular approach and subsequent two infratentorial supracerebellar approaches and finally complete removal was performed. Histological examination of the surgical specimen revealed as a cavernous angioma having abnormal vessels with honeycomb appearance. The patient survived, although remains moderately disabled 6 months after the last operation.

Brain Neoplasms↗

[Significance of the cerebral venous system in the development of DIND in subarachnoid hemorrhage].

The significance of superficial venous system in the development of delayed ischemic neurological deficit (DIND) was studied retrospectively in 18 patients with ruptured aneurysm of the middle cerebral artery (MCA). Neck clipping of the aneurysms was performed via the pterional approach within 72 hours after onset of subarachnoid hemorrhage. All patients were in grade I or II of the Hunt and Hess Grading, and in group 2 or 3 on Fisher's CT classification. The age ranged from 32 to 71 with 48.1% being the mean age. The aneurysm was located on the left side in 5 patients, and on the right side in 13 patients. Arterial and venous phase were evaluated on the pre-and post operative angiograms in these patients. Arterial narrowing was divided into localized and diffuse types according to the degree, and its distribution in the arterial tree. In the venogram, opacification of the superficial sylvian veins (SSV) was the main thing evaluated. Arterial narrowing was observed in 16 cases (9; localized, 7; diffuse). In some cases, visualization of the SSV was poor or fair, and in others it was normal. DIND, including motor deficit or disturbance of consciousness, developed in 10 cases (transient; 6, permanent; 4). The patients with normal visualization of SSV on the postoperative angiogram had good outcome, even if they had diffuse arterial narrowing. On the other hand, the outcome was only fair or poor in those patients who had poor visualization of the SSV, irrespective of arterial narrowing.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[The effects of sodium concentration in reperfusion solution upon myocardial protection].

The effects of several sodium concentrations in reperfusion solution (RS) were studied. Experimental time course was as follows: 20 min working perfusion, 3 min cardioplegic infusion with St. Thomas Cardioplegic Solution followed by global ischemia for 33 min at 37.5 degrees C, 15 min early Langendorff reperfusion with various sodium concentrations modified with Krebs Henseleit Bicarbonate Buffer (KHBB) and 5 min late reperfusion with KHBB, followed by 20 min working perfusion. Percent recoveries of aortic flow and Creatine Kinase leakage showed that 110 mM sodium of RS possessed optimal protective properties with bell shaped dose response characteristics.

Animals↗

[Effects of endothelin on retinal blood vessels].

Endothelins (ETs), which are one of the most potent vasoconstrictors, were discovered in 1988. ETs are involved in the regulation of vascular smooth muscle and are thought to function like a local hormone. In this study, we measured changes in the caliber of retinal blood vessels caused by the intravitreal injection of ET 1 in rabbits, using fundus photography. The retinal artery showed an immediate vasoconstriction after the injection (0.1 ml) of ET 1 at 10(-6)M. However, ET 1 in lower concentrations (10(-7)M and 10(-8)M) caused vasodilations initially and subsequently vasoconstrictions. A dose-response relation was found. The blood vessel caliber reduced maximumly to 53% the value before injection. The vasoconstriction due to ET 1 may induce retinal ischemia and hypoxia. We speculate that ET 1 may be involved in the regulation of retinal blood vessels.

Animals↗