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Biomedical subjects

S Yuasa

Publications and source records attributed to S Yuasa.

At least 109 records · Page 6Linked to original sources
PubMed1993

Effect of human serum on the in vitro anti-HIV-1 activity of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) derivatives as related to their lipophilicity and serum protein binding.

Several derivatives of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) were examined for their inhibitory effects on the replication of human immunodeficiency virus type 1 (HIV-1) in MT-4 cells in the presence of various concentrations (10-50%) of human serum (HS). Although all HEPT derivatives proved to be highly potent inhibitors of HIV-1 in the presence of 10% fetal bovine serum, some of them were less inhibitory to HIV-1 replication in the presence of HS. The HEPT derivatives were found to be highly bound to HS proteins. Both the anti-HIV-1 activity and HS protein binding of the compounds appeared to be related to their lipophilicity.

Acetylcysteine↗
PubMed1993

Obstructed migration of Purkinje cells in the developing cerebellum of the reeler mutant mouse.

It has been considered that cortical malformation in the brain of the reeler mutant mouse is due to a defect in the process of neuroblast migration during development. We examined the process of Purkinje cell migration in the cerebellar primordium of the reeler mutant immunohistochemically and electron-microscopically, employing a specific marker for Purkinje cells and markers for radial glia. To facilitate the recognition of the homozygote of the reeler mutation (r1) at the embryonic stage, we introduced the chromosome carrying the autosomal semi-dominant mutation, hammer-toe (Hm), by crossbreeding and backcross into the heterozygote of the reeler mutation, which is an autosomal recessive and located on the homologous chromosome. Using this double heterozygous strain (+/rl-Hm/+), the homozygote of rl can be selected from littermates by the normal appearance of the feet. Both the heterozygous rl embryos and non-carriers harbor the Hm locus and show the Hm phenotype as a deformity of the feet that can be recognized from the 15th day of gestation. In the cerebellar primordium of control mice, Purkinje cells migrated radially from the ventricular zone towards the cortex. In contrast, most of the migratory Purkinje cells remained in the intermediate zone, and their migration towards the cortex was obstructed in the cerebellum of the reeler mutant. A disorganized arrangement of both the processes and cell bodies of the radial glia was demonstrated in the cerebellar primordium of the reeler by labeling them with the antibody against tenascin, a neuron-glial adhesion molecule, and the monoclonal antibody 1D11, a marker for immature astroglia. Electron-microscopic observations revealed apposition of the migratory cells to the radially oriented glial processes in the intermediate zone of the control cerebellum. In contrast, the apposition of leading processes of the migratory neuroblasts to disorganized processes of the radial glia was observed in the intermediate zone of the reeler cerebellum. These findings suggest that the obstructed migration and disordered cortical alignment of Purkinje cells in the reeler cerebellum is due to dysgenesis and abnormal development of radial glia, resulting in disturbance of contact guidance in the process of Purkinje cell migration.

Animals↗
PubMed1993

Left superior temporal blood flow increases in schizophrenic and schizophreniform patients with auditory hallucination: a longitudinal case study using 123I-IMP SPECT.

Serial assessments of regional cerebral blood flow were performed using 123I-IMP SPECT in two schizophrenic and three schizophreniform patients with persistent auditory hallucination. The initial SPECT study in the period with prominent auditory hallucination revealed an increased accumulation of 123I-IMP in the left superior temporal area which corresponded to the auditory association cortex. In the follow-up SPECT study performed after clinical improvement, the distribution of 123I-IMP had normalized. One of the case with schizophrenia showed a similar increased uptake of 123I-IMP in the left superior temporal area in the third SPECT scan performed when a psychotic relapse with auditory hallucination occurred. MRI scans in two of the five patients demonstrated reduced volume of the temporal lobes. These findings suggest that the auditory hallucinations in schizophrenia may be involved in functional hyperactivity in the left superior temporal cortex which might be based partly on structural abnormalities in the temporal lobes.

Adult↗
PubMed1993

Expression of tenascin and BDNF during the migration and differentiation of grafted Purkinje and granule cells in the adult rat cerebellum.

It is believed that 'cell-adhesion molecules' and neurotrophic factors play important roles in the host-graft interactions during the reconstruction of injured brain by neural transplantation. In this study, we have examined the expression of such molecules and factors during the migration and differentiation of grafted Purkinje and granule cells in the adult rat cerebellum. Cerebellar primordium at the 14th gestational day (E14) was transplanted into adult rat cerebellum. Purkinje cells which had migrated from the grafted tissue into the host molecular layer were identified immunohistochemically with a specific marker, anti-spot 35 antibody, as well as by labeling them with bromodeoxyuridine (BrdU) during their final mitotic period. In the grafted site, transient expression of a neuron-glia cell adhesion molecule, tenascin, was detected immunohistochemically. This molecule was expressed transiently in the host tissue adjacent to the migratory Purkinje cells, as well as within the grafted tissue. Tenascin was not detected in intact host tissue apart from the grafted tissue. In the light of tenascin expression in the migratory process of Purkinje and granule cells during cerebellar development, the induction of this molecule in the host tissue might be involved in the migration of grafted Purkinje and granule cells. Furthermore, gene expression of brain-derived neurotrophic factor (BDNF) was found by in situ hybridization and the expression of NGF receptor was found immunohistochemically in the areas where grafted Purkinje and granule cells developed. These findings suggest the involvement of the neurotrophic factor in the growth and differentiation of the grafted cerebellar primordium.

Animals↗
PubMed1993

Fate and behavior of genetically labeled cerebellar cells after transplantation into mouse cerebellum.

A foreign gene coding the bacterial enzyme, chloramphenicol acetyltransferase (CAT), was introduced into a primary culture of the mouse cerebellar primordium by a retrovirus vector which harbors the neomycin-resistant gene. Following selection of the gene-transferred cells based on neomycin resistance, most of the selected cells expressed the CAT gene product as well as a marker for astrocytes, glial fibrillary acidic protein (GFAP), when examined immunocytochemically. These cells were transplanted into the adult mouse cerebellum, and the surviving cells were examined immunohistochemically by marking them with anti-CAT antibody. The distribution of CAT-immunopositive cells coincided with that of GFAP-immunopositive cells observed in serial sections of grafted sites at 10 days after transplantation. Some of the transplanted CAT-immunopositive cells extended processes and exhibited the morphological appearance of fibrous astrocytes. Migration of the genetically labeled cells into the host molecular layer was also observed and the morphological plasticity of the differentiated primary cells was shown according to the grafted sites. These results indicate that stable marking of cells for grafting can be accomplished by retrovirus-mediated introduction of a foreign gene into the primary culture, and that the fate and behavior of the labeled donor cells can be analyzed immunohistochemically following transplantation into neural tissue.

Animals↗
PubMed1993

Doppler sonographic measurement of phasic renal artery blood flow velocity in patients with chronic glomerulonephritis.

The phasic arterial blood flow velocity at the renal hilus was measured by Doppler sonography in 25 healthy subjects and 78 patients with chronic glomerulonephritis. Doppler velocity waveform was analyzed to give peak systolic velocity (S), end-diastolic velocity (D), resistive index (RI), and pulsatility index (PI). Creatinine clearance correlated with S (r = 0.76), D (r = 0.80), RI (r = -0.74), and PI (r = -0.85). Color Doppler sonography facilitated the detection of blood flow and permitted the measurement of absolute blood flow velocity, which previously had been difficult to determine. These results suggest that renal arterial blood flow as detected by Doppler ultrasonography may be useful for noninvasive, direct, rapid, and simple evaluation of renal function, although various modifying factors also need to be considered.

Adult↗
PubMed1993

[Migration of donor Purkinje cells in the host adult rat cerebellum].

It is considered that cell adhesion molecules play important roles in the host-graft interaction during the reconstruction of the injured nervous system by neural transplantation. In this article, we report the expression of such molecules during the migration and differentiation of donor Purkinje cells in the adult rat cerebellum. Cerebellar primordium at the 14th day of gestation was transplanted into the adult rat cerebellum. Purkinje cells which had migrated from the grafted tissue into the host molecular layer were identified immunohistochemically with anti-spot 35 antibody, a specific marker for Purkinje cells in the cerebellum, as well as by labeling them with bromodeoxyuridine at their final mitotic period. In the grafted site, transient expression of a neuron-glia cell adhesion molecule, tenascin, was detected immunohistochemically. This molecule was expressed in the host tissue adjacent to the migratory Purkinje cells as well as within the donor immature tissue. Tenascin was not detected in the host tissue far distant from the grafted tissue. In considering the expression of tenascin in the migratory process of Purkinje cells during cerebellar development, this molecule induced in the host tissue may be involved in the migration of donor Purkinje cells.

Animals↗
PubMed1993

Selective and synergistic inhibition of human immunodeficiency virus type 1 reverse transcriptase by a non-nucleoside inhibitor, MKC-442.

In the search for 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine derivatives, we have found 6-benzyl-1-(ethoxymethyl)-5-isopropyl-uracil (MKC-442) to be a highly potent and selective inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). The IC50 value of MKC-442 for HIV-1 RT was 8 nM. MKC-442 did not inhibit HIV-1 RNase H, other RTs, or DNA polymerase alpha. Because its inhibitory pattern showed noncompetitive inhibition with regard to nucleotide substrates, its mode of action was considered to be allosteric inhibition. From the results of combination studies, MKC-442 was found to produce synergistic inhibition of HIV-1 RT with 3'-azido-2',3'-dideoxythymidine (AZT) 5'-triphosphate (AZT.TP). The dose of AZT.TP required for 50% inhibition was reduced to one tenth of control in the presence of a half dose of MKC-442. Although other allosteric inhibitors (Nevirapine, L-696,229, and R82,913) had the same specificity for enzyme inhibition, they did not show synergism with AZT.TP in the combination index and synergy plot analyses. Synergistic inhibition of HIV-1 replication by MKC-442 and AZT has also been observed in HIV-1-infected MT-4 cells. These results suggest that MKC-442 is a unique inhibitor of HIV-1 RT, and combination therapy with MKC-442 and AZT could be advantageous in the treatment of acquired immune deficiency syndrome.

Antiviral Agents↗
PubMed1993

Effect of a high linoleate and a high alpha-linolenate diet on general behavior and drug sensitivity in mice.

Semi-purified diets supplemented with either a high linoleate (n-6) (safflower) oil or a high alpha-linolenate (n-3) (perilla) oil were fed to mouse mothers and their offspring through 6 weeks of age. The proportions of n-3 and n-6 highly unsaturated fatty acids in brain phospholipids reflected the n-3/n-6 balance of the diets while no difference was found in phospholipid compositions or cholesterol/phospholipid ratios. In the elevated plus maze task, the total number of entries into the open- and enclosed-arms was smaller and the time spent in the dark enclosed arms tended to be longer in the perilla group than the safflower group. The time required to reach a safe platform in Morris's water maze test was less in the perilla group, but no significant difference was observed in the entries into the arms darkened with a movable cover in Y-maze dark-preference task. The safflower group was more sensitive to pentobarbital; the anesthesia onset time was less and the anesthetic time was longer than in the perilla group. Increased locomotion induced by scopolamine injection was less in the safflower group as compared with the perilla group. These results indicate that in mice the dietary alpha-linolenate/linoleate balance affects the n-3/n-6 ratio of brain phospholipid acyl chains and that this is accompanied by general behavioral changes as well as changes in sensitivities to drugs known to affect behavior.

Analgesia↗
PubMed1993

[A case of an elderly SLE patient associated with acute renal failure].

It has been described that a rapid worsening in renal function is uncommon in the elderly patient with lupus nephritis. We report a case of a 76-year-old man with rapidly progressive lupus nephritis. On admission, laboratory studies revealed massive proteinuria, telescoped urine, thrombocytopenia and azotemia. Hypocomplementemia and the positive presence of anti-DNA antibody and lupus anticoagulant were also noted. Because of a rapid deterioration of renal function, he was started on a regimen of steroid pulse therapy and plasmapheresis. Serum levels of complements gradually increased after initiation of these treatments, and three weeks later, improvements of renal function and nephrotic syndrome were obtained. A renal biopsy specimen taken five months after admission showed diffuse membranous glomerulonephritis. In addition, we examined renal arterial blood flow with Doppler ultrasound, and significant improvements of the velocity and pulsatility were observed during recovery of the renal function.

Acute Kidney Injury↗
PubMed1993

[Emergency aorto-coronary bypass surgery for patients with right ventricular infarction].

Infarction of the right ventricle occurs with acute inferior myocardial infarction and results in a unique syndrome, characterized by distended neck vein, hypotension, heart block and spontaneous recovery in right ventricular function with time. We performed aorto-coronary surgery for four patients with right ventricular infarction. Three of them had emergency surgery. Surgical indications were refractory angina pectoris in two and cardiogenic shock in one. Postoperative courses in these patients were stormy and two died. Low output syndrome rarely improved with volume load alone and required inotropic and vasoactive drugs. Antiarrhythmic therapy including artificial pacing was especially important in keeping IABP support effectively. Remaining case, on the other hand, were conservatively supported by IABP and drug therapy through the first two weeks after infarction and then operation was done for unstable angina. Postoperative course in this patient was uneventful. In conclusion, delayed surgical intervention may be considered in patients with right ventricular infarction if their hemodynamic condition in the early stage of infarction can be conservatively managed.

Aged↗
PubMed1993

[Combined carotid endarterectomy and coronary artery bypass grafting: a report of two cases].

We reported two cases of successful combined carotid endarterectomy and coronary artery bypass grafting. The first case was a 60-year-old male who had unstable angina pectoris and a history of two times of cerebral infarction. He was revealed to have severe stenosis of left internal carotid artery as well as diffuse stenosis of right and left coronary arteries. The second case, 67-year-old male with a history of cerebral infarction, was admitted because of anterior myocardial infarction. Coronary angiography revealed left main trunk disease and carotid angiography also revealed critical stenosis of bilateral internal carotid arteries. We discussed the management of the patients having coexistent such coronary and carotid artery disease.

Aged↗
PubMed1993

[Acute aortic dissection without opacification of the false lumen on the initial aortogram: a case report].

A 50-year-old woman was admitted to the intensive care unit 40 min after the onset of severe chest and back pain with consciousness loss. Emergency computed tomography and aortography demonstrated an acute type A dissection without opacification of the false lumen. The patient was initially treated with antihypertensive drugs. Recurrent back pain and bilateral pleural effusion appeared 3 days after onset of the pain. Both the right radial and carotid pulses were reduced. Emergent operation was performed when computed tomography and aortography repeated 5 days after onset of the pain demonstrated the intimal flap in the ascending aorta with the opacified false lumen. The site of intimal tear in the proximal arch was resected and a 26 mm Dacron graft was inserted during deep hypothermia and circulatory arrest. The postoperative course was uneventful.

Aortic Dissection↗
PubMed1992

Scanning eye movements in schizophrenic patients. Relationship to clinical symptoms and regional cerebral blood flow using 123I-IMP SPECT.

Eye movements during the Benton Visual Retention Test were examined using an eye-mark recorder in 32 schizophrenic patients and 32 normal controls. The patients had significantly fewer eye fixations, longer mean duration of fixation and shorter length of mean scan path than the controls. In the patients, these eye movement parameters were significantly correlated with the negative symptom score but not with the positive symptom score on the Positive and Negative Syndrome Scale. These parameters had a significant correlation with the composite score on the Scale for the Assessment of Negative Symptoms (SANS). In particular, they were highly correlated with avolition-apathy and affective flattening or blunting scores on SANS subscales. Thus, examination of scanning eye movements seemed to be a good objective index of negative symptoms. Secondly, regional cerebral blood flow (rCBF) was examined using N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) and single photon emission computer tomography in 17 of 32 patients. With regard to the relationship between the eye movement parameters and rCBF, the mean duration of fixation was negatively correlated with 123I-IMP uptake in the left superior frontal area and left basal ganglia. The mean length of the scan path was correlated with uptake in the left superior frontal area. These findings suggest that the characteristic eye movements of schizophrenic patients are likely to be related with dysfunction of the frontal-basal ganglia neural circuit.

Adult↗
PubMed1992

Successful resection of pheochromocytoma in a hemodialysis patient.

A 45-year-old woman with a pheochromocytoma who had been on regular hemodialysis for 4 years and underwent successful surgery is described. Careful preoperative management, including the use of prazosin and weight control, was carried out to prevent severe intraoperative and postoperative cardiovascular complications. Prazosin was given at an initial dose of 0.5 mg/day, and the dosage was increased to 20 mg/day prior to surgery. The increase in intravascular volume led to a gain of 3 kg in body weight. No deterioration of the cardiovascular or respiratory function was caused by these maneuvers, and surgery was performed without significant complications except for a rapid rise of blood pressure during tumor resection. To our knowledge, only one similar case report could be found in the English literature.

Adrenal Gland Neoplasms↗
PubMed1992

[Synthesis of metabolites of mosapramine. I. Synthesis of alcoholic metabolites].

Four alcoholic metabolites of (+-)-3-chloro-5-[3-(2-oxo-1,2,3,5,6,7,8,8a-octahydroimidazo[1,2-a] pyridine-3-spiro-4'-peperidino)propyl]-10,11-dihydro-5'-dibenz[b,f ] azepine(mosapramine), a new antipsychotic drug, were synthesized in order to determine their chemical structures. A mixture of 10-ethoxy-3-chloro-10,11-dihydro-5H-dibenz[b,f]azepine and 11-ethoxy isomer was used as a starting material. Isomeric intermediates, i.e. 10-oxo-3-chloro-5-(3-chloropropyl)-10,11-dihydro-5H-dibenz[b,f]azepine and 11-oxo isomer, were separated by chromatography with silica gel. The metabolites were obtained by NaBH4 reduction of the corresponding 10-oxo or 11-oxo compounds followed by introduction of spiro-piperidine moieties into propyl side chain.

Antipsychotic Agents↗
PubMed1992

[Synthesis of metabolites of mosapramine. II. Synthesis of phenolic metabolites of mosapramine and their pharmacological activities].

Four phenolic metabolites of (+-)-3-chloro-5-[3-(2-oxo-1,2,3,5,6,7,8,8a-octahydroimidazo[1,2- a]pyridine-3-spiro-4'-piperidino)propyl]-10,11-dihydro-5H-dibenz [b,f]azepine (mosapramine), a new antipsychotic drug, were synthesized in order to determine their chemical structures. Pharmacological activities of the three main metabolites were compared with those of mosapramine. The activities of the metabolites were far less potent than those of mosapramine.

Animals↗