Biomedical subjects

J Yanai

Publications and source records attributed to J Yanai.

At least 37 records · Page 2Linked to original sources

PubMed1996

Thoracoabdominal aortic aneurysm in an infant treated by thromboexclusion with thoracoabdominal aortic bypass. A case report.

A case of a huge thoracoabdominal aortic aneurysm in an eighteen-month-old boy is reported. Surgical treatment was successfully performed by thromboexclusion of the aneurysm with thoracoabdominal aortic bypass using a low-porosity woven Dacron graft 10 mm in diameter and of sufficient surplus length. During the early postoperative period, he developed moderate hydronephrosis, owing to compression of the left ureter by the graft, but no further deterioration was seen. Follow-up angiographies performed four and six years after surgery revealed straightening of the graft and slight stretching of the aorta at the distal anastomosis, but no stenosis was found. Now, seven and a half years after surgery, he has no pressure gradient between upper and lower extremities.

Angiography, Digital Subtraction↗

PubMed1995

GTPase activity in mouse hippocampus membranes following prenatal exposure to heroin and phenobarbital.

Low Km high affinity GTPase activity, with and without muscarinic receptor stimulation with 1 mM carbachol, was measured in membrane preparations of mouse hippocampus prenatally exposed to phenobarbital or heroin. Basal and carbachol-stimulated low Km GTPase activities after prenatal exposure to phenobarbital exhibited a statistically significant (P < 0.05) decrease both in Km and Vmax values. Basal Vmax values were reduced from 152 +/- 10 in controls to 112 +/- 13 (pmol/mg protein/min, mean +/- SEM) in exposed mice. The Km values in the offspring of mice treated with phenobarbital were reduced from 1.55 +/- 0.21 to 0.96 +/- 0.11 (microM, mean +/- SEM); Vmax and Km values after carbachol stimulation were similarly affected. Prenatal exposure to heroin did not change the GTPase activities, basal or carbachol-stimulated, with only a non-significant increase in both Vmax and Km values. It is postulated that these changes in G alpha protein activity may be related to the teratogenic effect of these drugs.

Animals↗

PubMed1995

An avian model for the reversal of 6-hydroxydopamine induced rotating behaviour by neural grafting.

A new animal model of parkinsonism was established in 'Black Silkie' chickens by means of unilateral injections of 6-hydroxy-dopamine into the substantia nigra. Apomorphine produced a strong contralateral turning pattern in the lesioned chickens, amphetamine had no effect. 6-OHDA treated animals received embryonic transplants of substantia nigra cell suspensions which caused them to cease rotating (P < 0.01). This finding allows us to add an avian model, which offers unique methodological advantages, for reversal of 6-OHDA-induced rotating behavior by transplantation.

Animals↗

PubMed1995

Alterations in hippocampal hemicholinium-3 binding and related behavioural and biochemical changes after prenatal phenobarbitone exposure.

Previous studies demonstrated postsynaptic septohippocampal cholinergic alterations after early exposure to phenobarbital. The present study was designed to ascertain possible corresponding presynaptic alterations while confirming the known behavioral deficits and extending previous findings on postsynaptic cholinergic alterations. Pregnant heterogeneous mice received milled mouse food containing 3 g/kg phenobarbital on gestation days 9-18. At age 50 days, [3H]hemicholinium-3 binding, which labels the presynaptic transporter for high affinity choline uptake, was increased in treated mice by 100% (P < 0.001). This change was not accompanied by a change in the affinity of the transporter to the ligand. Another group of offspring was tested for hippocampus-related behaviors. Consistent with our previous studies in the Morris maze, treated animals took longer to reach the platform in the place test as compared to control, and swam fewer times over the missing platform location in the spatial probe test. In the eight-arm maze, the treated offspring needed more entries than control to visit all the arms. In the spontaneous alternation test, the treated mice showed fewer alternations than controls. Biochemically, as in our previous results, prenatal phenobarbital exposure resulted in an increase in the degree of stimulation of inositol phosphate formation by carbachol (P < 0.05), an action presumed to occur at postsynaptic muscarinic receptors. While the present results show that the effect of a combination of raised K+ in the presence of physostigmine and carbachol was significantly greater in barbiturate-treated mice (P < 0.05), the action of K+ in the presence of physostigmine, but without carbachol, was not affected by the phenobarbital treatment. The results point to the uniqueness of outcome of early insults where alterations along nerve conduction cascades do not necessarily follow the common rules in that upregulation could simultaneously occur both pre- and post synaptically.

Animals↗

PubMed1995

Neuron transplantation into mice hippocampus alters sensitivity to barbital narcosis.

The role of several hippocampal innervations in the sensitivity to barbital-induced narcosis was studied in selected mice strains. The outbred and inbred mouse strains HS/lgb, SABRA/HUC, C57BL, CBA/LAC, and BALB/c were tested for barbital-induced sleep (315 mg/kg). The relatively short sleeping HS/lbg (HS) and the longest sleeping BALB/c (BALB) were chosen for further investigation. Cholinergic (ACh), serotonergic (5-HT), and noradrenergic (NE) innervations were studied in HS strain; whereas BALB, which possesses both an unusually high sensitivity to barbital and unique NE innervations in the cortex and hippocampus, was employed in a detailed study of the NE innervations. Transplantation of embryonic NE cells from the mouse embryo into the hippocampus of adult HS mice increased barbital narcosis by 65% (p < 0.05), whereas transplantation of 5-HT cells decreased barbital narcosis by 54% (p < 0.001). Transplantation of ACh cells had no significant effect on barbital-induced narcosis. BALB mice were subjected to NE cell transplantation into the hippocampus and cortex. Similarly to HS, BALB receiving NE transplants into their hippocampus slept 34% longer than control after barbital challenge (p < 0.025). Noradrenergic cell transplantation into frontal cortex had no effect on barbital sleep. The results suggest that (a) enhancement by neural grafting of the NE innervation to the hippocampus accentuates and enhancement of the 5-HT innervations attenuates the sensitivity to barbital narcosis, whereas ACh innervations have no effect on the sensitivity to barbital narcosis, and (b) the unusually high sensitivity of BALB mice to barbital may not be related to its unique NE innervations.

Acetylcholine↗

PubMed1995

Embryonic cultures but not embryos transplanted to the mouse's brain grow rapidly without immunosuppression.

Embryos and embryocultures can be successfully transplanted into various bodily organs. However immunosuppression or homogenicity are required for the success of such experimental manipulation. Since the brain is considered immunologically privileged, we transplanted 2-4 cell embryos of C57BL x BALB/c, embryonic stem cells (ES) or embryoid bodies (EB) cultures into the hippocampus of the heterogeneous mouse stock HS/IBg. Both ES and EB cultures developed into an extensive growth, eventually larger than the brain itself, causing the death of the host in less than 29 days. The growth was identified as teratoma, mostly made of immature cells and tissues of diverse origin. Thus, the overall histological picture was that of a malignant teratoma. On the other hand, no embryos were found at any time after the transplantation; apparently, they could not survive in the host brain. The growth rate and the relative lack of rejection suggest that the brain offers a unique medium for ES and EB cultures but, not to embryos.

Animals↗

PubMed1994

Effects of chronic prenatal, neonatal and adult exposure to barbiturates on mitochondrial benzodiazepine receptors in mouse testis.

In the present study we investigated the effect of chronic exposure to phenobarbital, administered to mice during the prenatal or neonatal period, as well as to adult mice, on mitochondrial benzodiazepine receptors in the testis. Three modes of treatment were investigated: (1) offspring of pregnant mice receiving food containing 3 g/kg phenobarbital until gestational day 18 were killed at 22 or 50 days of age and assayed for receptor binding (prenatal group); (2) offspring of untreated mice were injected subcutaneously once daily with 50 mg/kg phenobarbital on days 2-21 of age and killed at 22 or 50 days of age (neonatal group); (3) adult mice were injected subcutaneously once daily for 3 weeks with 50 or 100 mg/kg phenobarbital (adult group). Prenatal or neonatal exposure to phenobarbital did not alter the testicular weight in all groups (except for the neonatally exposed group killed at 22 days of age), or the mitochondrial benzodiazepine receptor binding characteristics. However, the maximal number of these receptors in the testes of mice in the adult group receiving 100 mg/kg phenobarbital was significantly increased (42%, P < 0.05), compared to controls. The administration of 50 mg/kg phenobarbital to the adult group also induced an increase (27%, non-significant) in testicular mitochondrial benzodiazepine receptors. Phenobarbital administration did not affect the receptor affinity values or the weight of the testis. It is unclear whether these receptor alterations due to chronic phenobarbital exposure of adult mice reflect functional changes in the testis.

Animals↗

PubMed1994

Transesophageal echo-guided balloon dilatation for postoperative pulmonary venous obstruction.

Pulmonary venous obstruction (PVO), or stenosis, is still a major complication of postoperative total anomalous pulmonary venous return, being very complex in its pathogenesis. For some types of PVO, surgery is effective, but a reoperation under cardiopulmonary bypass is generally difficult and carries a high risk. The operative balloon dilatation method performed under the guidance of transesophageal echography and fluoroscopic monitering is simple as well as safe. We describe herein the technique involved in performing this procedure through the case of a 10-month-old boy.

Catheterization↗

PubMed1994

Reversal of early phenobarbital-induced cholinergic and related behavioral deficits by neuronal grafting.

The present experiment was performed to assess the possible restoration of normal maze behavior, as well as parallel muscarinic receptor binding capabilities, in mice pre- or neonatally exposed to phenobarbital. Mice were exposed to phenobarbital prenatally by feeding the mother phenobarbital (3 gkg milled food) on gestation days 9-18 (PreB mice), or neonatally, by daily injections of 50 mg/kg Na phenobarbital to the pups on days 2-21 (NeoB). At adulthood, PreB and NeoB mice were 61.3% and 65% deficient, respectively, in the hippocampus-related Morris maze behavior, as compared to control. Both groups had a 58% increase in their hippocampal muscarinic receptors maximal binding (Bmax) (p < 0.001); the dissociation constant (Kd) was not affected by the phenobarbital exposure. Treated animals and their respective controls received septal cholinergic embryonic graft into the hippocampus. The viability of the transplants was confirmed by AChE histochemistry. Nine weeks later the grafted mice showed significant improvement in the Morris maze (52% for both PreB and NeoB (p < 0.001)). Their Bmax was also reduced from early phenobarbital exposed animals' levels by 15% for PreB and by 25% for NeoB (p < 0.001). The results suggest that early phenobarbital-induced behavioral deficit and their related biochemical alterations can be partially corrected by the appropriate neural grafting, and thus provide further support to the apparent relationship between the early phenobarbital-induced septohippocampal cholinergic alterations and the hippocampus-related behavioral deficits.

Acetylcholinesterase↗

PubMed1993

Hippocampal gamma-aminobutyric acid and benzodiazepine receptors after early phenobarbital exposure.

Mice were exposed to phenobarbital (PhB) prenatally (PreB offspring) by feeding their mothers 3 g/kg PhB in milled food on gestation days 9-18, or neonatally by directly injecting pups of intact mothers with daily dose of 50 mg PhB on postnatal days 2-21 (NeoB offspring). At age 22 or 50 days, the offspring were tested for gamma-aminobutyric acid (GABA) up take in the hippocampus and in the rest of the brain. In addition, [3H]muscimol and [3H]flunitrazepam binding in the hippocampus and cortex were measured in the offspring at age 22 and 50 days. Long-term decrease in GABA uptake was found in the NeoB group. A 23% decrease was found in 22-day-old mice (P < 0.001) and a 22% decrease in 50-day-old mice (P < 0.05). In addition, there was a 22% decrease in GABA uptake in the brain of 22-day-old PreB mice (P < 0.05). An increase of 52% in [3H]muscimol binding (P < 0.001) and 45% (P < 0.001) in [3H]flunitrazepam binding were measured in the hippocampus in the 22-day-old NeoB mice; no differences were found in affinity. The differences were short-term and could no longer be detected at age 50 days. No differences were found in the cortex; unlike NeoB, PreB mice did not differ from controls. The results suggest upregulation of the GABAergic system in early PhB exposed mice.

Animals↗

PubMed1993

Differential development of cholinergic nerve terminal markers in rat brain regions: implications for nerve terminal density, impulse activity and specific gene expression.

During critical developmental periods, cholinergic activity plays a key role in programming the development of target cells. In the current study, ontogeny of cholinergic terminals and their activity were contrasted in 4 brain regions of the fetal and neonatal rat using choline acetyltransferase activity, which is unresponsive to changes in impulse flow, and [3H]hemicholinium-3 binding, which labels the high-affinity choline transporter that upregulates in response to increased neuronal stimulation. In all 4 regions (cerebral cortex, midbrain + brainstem, striatum, hippocampus) choline acetyltransferase activity increased markedly from late gestation through young adulthood, but generally did so in parallel with the expansion of total membrane protein, reflective of axonal outgrowth and synaptic proliferation. In contrast, [3H]hemicholinium-3 binding was extremely high in late gestation and immediately after birth, declined in the first postnatal week and then rose again into young adulthood. The ontogenetic changes reflected alterations primarily in the number of binding sites (Bmax) and not in binding affinity. Only the latter phase of development of [3H]hemicholinium-3 binding corresponded to the ontogenetic changes in choline acetyltransferase activity; in the hippocampus, there were disparities even in young adulthood, where [3H]hemicholinium-3 binding showed a spike of activity centered around the 5th to 6th postnatal week, whereas choline acetyltransferase did not. Correction of binding for membrane protein development did not eliminate any of the major differences in developmental patterns between the two markers. These results suggest that development of the choline transporter binding site is regulated independently of the outgrowth of the bulk of cholinergic nerve terminals.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1993

Septohippocampal cholinergic changes after destruction of the A10-septal dopaminergic pathways.

Mice were injected bilaterally into the septum with 6-hydroxydopamine and 6 weeks later the hippocampi were assayed for activity of choline acetyltransferase, muscarinic receptor binding capabilities and for formation of inositol phosphate in response to direct (carbachol) or presynaptically elicited (K+) stimulation of the postsynaptic receptors. Levels of dopamine in the septum were reduced by 70% in the lesioned animals and hippocampal choline acetyltransferase was elevated by the same amount. The Bmax of muscarinic binding was significantly reduced without changes in Kd; nevertheless, carbachol-induced stimulation of formation of inositol phosphate was unaffected. The response to K+ was markedly elevated in the 6-hydroxydopamine-treated animals. Thus, the regulatory effect of A10-septal dopaminergic pathways on the septohippocampal cholinergic innervations is both on the presynaptic and postsynaptic levels.

Animals↗

PubMed1993

Hippocampal cholinergic alterations and related behavioral deficits after early exposure to ethanol.

The present study was designed to ascertain septohippocampal cholinergic alterations and their related behavioral deficits after early exposure to ethanol. Mouse pups were exposed to ethanol, 3 g/kg by daily subcutaneous injection on postnatal days 2-14. At age 50 days, the ethanol-exposed mice had significant reductions from control levels in eight-arm maze performance. For example, on the fourth testing day, the number of correct entries in the ethanol group was 21% below control levels (P < 0.05) and the number of trials needed to enter all arms was 48% above control (P < 0.001). It took the ethanol-exposed mice twice the time to reach criterion than it did control (P < 0.01). A 33% increase from control level in muscarinic receptor number (Bmax) was found in the treated mice of age 22 days and a 64% increase at age 50 days (P < 0.001). However, no differences between control and treated groups could be detected in the presynaptic component of the cholinergic innervation, choline acetyltransferase activity. The results suggest that early ethanol exposure acts on hippocampal function similarly to phenobarbital, probably via alterations in postsynaptic processes in the septohippocampal cholinergic pathways.

Acetylcholine↗

PubMed1992

Alterations in septohippocampal cholinergic innervations and related behaviors after early exposure to heroin and phencyclidine.

Mice were exposed to diacetylmorphine (heroin) or phencyclidine (PCP) prenatally or neonatally. At a later age, they were tested for hippocampus-related behavioral deficits and concomitant alterations in the septohippocampal cholinergic innervations. Actually, this is an application of the previously established phenobarbital neuroteratogenicity model to heroin and PCP. Prenatal exposure was accomplished transplacentally by injecting the mother 10 mg/kg heroin or PCP on gestation days 9-18. Neonatal administrations were applied directly by injections of 10 mg/kg of either drug to the pups between neonatal days 2-21. At the age of 50 days, mice exposed to heroin and PCP prenatally exhibited a 107% and 159% increase in their muscarinic cholinergic receptors Bmax, respectively. Neonatal exposure to heroin or PCP caused an 83% and 76% increase in the receptors respectively. On the behavioral level, both prenatal and neonatal exposure to heroin or PCP reduced performance in the hippocampus related eight-arm maze and Morris mazes. Depending on the drug, the test and the period of drug administration, the reduction ranged between 10% and 75%. The results suggest that heroin and PCP induce alterations in the septohippocampal cholinergic innervations and in related behavioral performance. Further studies are necessary in order to connect the biochemical and behavioral events in causal relationships.

Aging↗

PubMed1992

Hippocampal cholinergic alterations and related behavioral deficits after early exposure to phenobarbital.

Mice were exposed to phenobarbital (PhB) prenatally and neonatally. Prenatal exposure was accomplished by feeding the mother PhB (3 g/kg milled food) on gestation days 9-18. Neonatal exposure was accomplished by daily injections of 50 mg/kg sodium PhB directly to the pups on days 2-21. Long-term biochemical alterations in the pre- and postsynaptic septohippocampal system, as well as related behavioral deficits, were assessed in the treated animals. Significant increase in B(max) values for binding of [3H]QNB to muscarinic cholinergic receptors was obtained on both ages 22 and 50 in prenatally (40-90%, respectively, p less than 0.001) and neonatally exposed (58-89%, p less than 0.001) mice whereas Kd remained normal. Similarly, a significant increase of inositol phosphate (IP) formation in response to carbachol was found after both prenatal and neonatal exposure to PhB (p less than 0.05). No alterations in choline acetyltransferase (ChAT) activity were observed in the prenatally or neonatally treated animals. The early exposed mice showed deficits in the performance in Morris water maze, a behavior related to the septohippocampal pathway. The results suggest that early exposure to PhB induces alterations in postsynaptic components of the hippocampal cholinergic system and concomitantly to impairment in hippocampus-related behavior.

Animals↗

PubMed1992

Eight-arm maze performance, neophobia, and hippocampal cholinergic alterations after prenatal oxazepam in mice.

Outbred CD-1 mice were exposed to oxazepam (15 mg/kg PO twice/day) on days 12-16 of fetal life, i.e., at a critical ontogenetic stage of Type II benzodiazepine (BDZ) receptor increase, and fostered at birth to untreated dams. At adulthood, radial arm maze performance, activity-habituation test in an open-field arena (either single 15-min test or three 5-min sessions at 24-h intervals), approach to a novel stimulus object, and amphetamine or scopolamine effects thereon were assessed in male progeny. Overall, the oxazepam exposed (OX) mice were much less efficient in the radial arm maze task than the vehicle exposed (VEH) animals. Pre-test scopolamine injection, but not amphetamine, significantly impaired the arm maze performance of OX mice when compared with the corresponding VEH-scopolamine animals. In separate nonlearned behavioral tasks, prenatal oxazepam did not affect either baseline activity levels in the open field or the response to the amphetamine and the scopolamine challenge, while it considerably increased the latency of first approach to a novel object and produced a deficit of habituation in the course of the subsequent exploratory period. Concomitant investigation at the neurochemical level showed that the adult OX animals had a significant increase in both Bmax and in the affinity (Kd) of cholinergic muscarinic receptors in the hippocampal formation when compared to the vehicle-exposed controls.

Amphetamine↗

PubMed1990

Effect of prenatal and neonatal chronic exposure to phenobarbital on central and peripheral benzodiazepine receptors.

Phenobarbital (PhB) was administered to pregnant mice during days 9-18 of gestation. [3H]Muscimol binding to cerebellum, [3H]flunitrazepam binding to cerebellum and olfactory bulb, and [3H]PK 11195 binding to olfactory bulb, heart and kidney were assay in the of offspring at 22 and 50 days of age. The chronic prenatal administration of PhB did not affect either gamma-aminobutyric acid (GABA) receptors, central benzodiazepine receptors (CBR), or peripheral benzodiazepine binding sites (PBS) in these tissues. In the next stage of the study, we investigated a possible modulatory effect of chronic postnatal PhB treatment during days 2-21 of age on the same receptors measured at 22 and 50 days of age. PhB exposure of neonates resulted in a significant down-regulation of GABA receptors and CBR in the cerebellum and of PBS in the heart. The effects were demonstrated on day 22 of age and were undetectable by day 50 of age. CBR at the olfactory bulb and PBS at the olfactory bulb and kidney were not altered by the drug treatment. It is concluded that in utero exposure to PhB does not affect benzodiazepine receptor ontogenesis, and the effects of postnatal treatment are transitory only.

Aging↗

PubMed1990

Vascular abnormalities in congenital cutis laxa--report of two cases.

Two cases of Japanese girls with congenital cutis laxa associated with cardiovascular abnormalities are described. Case 1: A 12-year-old girl has been under our observation from the age of 6 months. Cardioangiogram revealed dilatation of the ascending aorta, meandering of the descending aorta and the coronary arteries, coiling of the carotid and innominate (brachiocephalic) arteries, and hypoplasia of the pulmonary arteries. Case 2: A 2.8/12-year-old girl died after our follow-up from the age of 3 months. The cause of death was congestive heart failure secondary to peripheral stenosis of the pulmonary arteries. In both cases, skin biopsy revealed a decreased number of elastic fibers and an increased amount of acidic mucopolysaccharides. The same histological features were observed in the pulmonary arteries and other arteries as well. Electron microscopic findings were diffuse thinning of elastic fibers and reduced elastic content. The high blood level of elastase (167.8 micrograms/l) in case 1 may cast a light on the unknown etiology of the disease.

Abnormalities, Multiple↗