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Biomedical subjects

M Sasaki

Publications and source records attributed to M Sasaki.

At least 19 recordsLinked to original sources

Membrane-potential-dependent uptake of tryptamine by rat intestinal brush-border membrane vesicles.

The effect of membrane potential on the uptake of tryptamine, an organic cation, by rat intestinal brush-border membrane vesicles was studied. In the presence of an outwardly directed H(+)-gradient, the initial uptake of tryptamine was stimulated remarkably and the overshoot phenomenon was observed. In contrast, the uptake was depressed by an inwardly-directed H(+)-gradient. The effect of H(+)-gradient on the uptake of tryptamine was maintained in the presence of FCCP, whereas it vanished when voltage-clamped vesicles were used. Moreover, the uptake of tryptamine was linearly augmented with increase of the valinomycin-induced inside-negative K+ diffusion potential. These results suggest that tryptamine is taken up into intestinal brush-border membrane vesicles depends upon the ionic diffusion potential. The effect of several indole derivatives and amine compounds on the uptake of tryptamine was also examined. The uptake of tryptamine was inhibited by all amine compounds used, but anionic and zwitterionic compounds had no effect, suggesting that these amines interact on brush-border membrane and cause an inhibitory effect.

Amines

A single-base-pair substitution abolishes D-amino-acid oxidase activity in the mouse.

Mutant ddY/DAO- mice lacking D-amino-acid oxidase (DAO) activity were examined for the cause of their lack of enzyme activity. Total RNA was extracted from the kidney of the ddY/DAO- mice and cDNA was synthesized. After cDNA encoding DAO was amplified by the polymerase chain reaction it was cloned into a plasmid and sequenced. Comparison of the DAO cDNA sequence with that of normal BALB/c mice revealed the presence of a single-base substitution (G----A) which causes a Gly-181----Arg substitution in the middle of the enzyme molecule. The mutant DAO cDNA was inserted into an expression vector and was expressed in transfected COS-1 cells. The transfected cells synthesized the DAO mutant protein, but they did not show DAO activity. In contrast, when cells were transfected with an expression vector carrying wild-type DAO cDNA, where the substituted base-pair was replaced by a normal base-pair, they showed DAO activity. These results indicate that the single base-pair substitution is the cause of the loss of DAO activity in the ddY/DAO- mice.

Animals

[Fluid-fluid levels in bone and soft tissue tumors demonstrated by MR imaging].

Fluid-fluid levels in bone tumors have been described in aneurysmal bone cysts and other cystic tumors of bones and soft tissue tumors. We experienced three bone tumors (simple bone cyst, bone metastasis, and osteosarcoma) and three soft tissue tumors (fibrosarcoma, two cases of cavernous hemangioma) that showed fluid-fluid levels on MR, and investigated their cause. Causes included blood in the cystic spaces, hemorrhage in the tumor, the telangiectatic component of the osteosarcoma, and the cavernous component of the hemangioma. No specific diagnosis could be made based on the finding of fluid-fluid levels. We conclude that fluid-fluid levels on MR are rather nonspecific findings in bone and soft tissue tumors and that the diagnosis should be made on the basis of other radiological and clinical findings.

Adult

Detection of cytomegalovirus DNA in pulmonary specimens: confirmation by in situ hybridization in two cases.

Papanicolaou stained bronchial brush and imprint pulmonary smears containing intranuclear and cytoplasmic inclusion bearing alveolar pneumocytes suggestive of cytomegalovirus infection were destained and reprocessed for in situ hybridization using a biotinylated probe for cytomegalovirus DNA. Two cases were processed in this way. A hybridization signal for viral DNA was noted in each case. However, no reddish brown staining reaction products were noted in any of the control samples. This simple and rapid nonradioactive detection system is a valuable supplement to routine pulmonary cytology for the definitive diagnosis of this virus infection, and this technique is also appropriate for retrospective study.

Cytodiagnosis

Clinical and immunological evaluation of intraoperative radiation therapy for patients with unresectable pancreatic cancer.

The clinical efficacy of intraoperative radiation therapy (IORT) and the changes of immunological parameters were investigated. Nine patients with unresectable pancreatic cancer were treated with IORT (2,500-3,500 cGy) and the changes of various immunological parameters were compared with those in 11 patients with advanced cancer who received external beam irradiation therapy (XRT), 2,500-3,500 cGy. After IORT, 71% of patients obtained pain relief, two of the nine patients showed a partial response, and the serum CA 19-9 level decreased in six patients. However, the median survival was only 210 days. Natural killer activity, lymphokine-activated killer activity, and interferon gamma-activated killer activity were not inhibited by IORT, and phytohemagglutinin-induced blastogenesis was actually augmented after IORT, whereas all these parameters were inhibited by XRT. Thus, it is suggested that IORT may augment or at least stabilize systemic antitumor immunity.

Aged

Somatosensory evoked potential correlates of psychophysical magnitude estimations for air-puff stimulation of the foot in man.

Short air-puff stimuli were applied to the sole of the right foot to obtain both psychophysical and neurophysiological responses. The detection threshold (So) was first determined, and six levels of stimulus intensity above threshold were adopted for magnitude estimation. Somatosensory evoked potentials (SEPs) were also recorded over the foot projection area (2 cm posterior to Cz) for the six stimulus intensities. Six components (N40, P45, N55, P70, N80 and P90) were recorded within 100 ms following stimulation. A power function with an exponent of 0.94 provided an adequate description of the magnitude estimation values as a function of stimulus intensity, as was verified by the high correlation coefficient (r = 0.87; P < 0.001). Similarly, stimulus-amplitude functions of P45-N55, N55-P70 and P70-N80 SEP components were well represented by power functions with exponents of 0.62, 0.63 and 0.78, respectively. The SEP latencies as a function of stimulus intensity had negative power functions. The latency functions of the P45 and N55 components had the largest negative power exponents (-0.17 and -0.15) and showed the highest negative correlations (r = -0.70 and -0.71, respectively) with the stimulus intensity. These results suggest that both the amplitude and the latency information encoded in the SEPs may contribute to the magnitude estimation of the stimulus.

Adult

Somatosensory evoked potential correlates of psychophysical magnitude estimations for air-puff stimulation of the face in man.

Air-puff stimuli were applied to the skin of the face to obtain psychophysical and neurophysiological responses. Six levels of stimulus intensity above threshold were adopted for numerical magnitude estimation and for recording somatosensory evoked potentials (SEPs). A power function with an exponent of 0.71 provided an adequate description of the magnitude estimation values as a function of stimulus intensity, as was verified by the high correlation coefficient (r = 0.86, P less than 0.001). Six SEP components (N15, P20, N30, P40, N50 and P65) were recorded during the 100 ms following stimulation. Stimulus-amplitude functions of the various SEP components were well represented by power functions. The P20-N30 component had the highest power exponent (0.66) and also the highest correlation coefficient (r = 0.55, P less than 0.001). The SEP latencies as a function of stimulus intensity had negative power functions. The latency function of the P20 component had the largest negative power exponent (-0.10) and showed the highest negative correlation (r = -0.62) with the stimulus intensity. These results suggest that processing of intensity information occurs at a relatively early stage within the central nervous system, and that both the amplitude and latency information encoded in the SEPs may contribute to stimulus processing.

Adult

Input-output relation of the somatosensory system for mechanical air-puff stimulation of the index finger in man.

This study examined input-output relation of the somatosensory system in response to mechanical air-puff stimuli applied to the volar aspect of the tip of the index finger. Compound sensory nerve action potentials (SNAPs) from the median nerve at the wrist and cerebral somatosensory evoked potentials (SEPs) were simultaneously recorded at six levels of stimulus intensity above threshold. Using the time-integral of the SNAPs and SEPs as measures of peripheral and central neural activity, a strongly accelerating power function with an exponent of 1.35 was found to describe peripheral neural function, while central neural function was described by a negatively accelerating function with a power exponent of 0.50, suggesting suppression of SEPs by recruitment of units with increasing stimulus intensity. It was concluded that input-output relation of the somatosensory system can be described by a decelerating power function with the exponent of 0.37.

Action Potentials

Dimethylsulfoxide enhances the absorption of chemotherapeutic drug instilled into the bladder.

We examined the effect of dimethylsulfoxide (DMSO) on the absorption of a chemotherapeutic drug instilled into the bladder. Female Wistar rats with bladder tumors underwent intravesical instillation of normal saline (S group) or 50% DMSO (D group) prior to the administration of pirarubicin (tetrahydropyranyl-Adriamycin). The absorption of pirarubicin was estimated histologically by observing its fluorescence. In the S group, fluorescence of pirarubicin was observed only in the epithelial layer of normal or hyperplastic regions and in the cells of superficial layers of the tumor. In the D group fluorescence was observed in the entire bladder wall of normal or hyperplastic regions and extended to deeper regions of the tumors than in the S group. These findings indicate enhancement of the absorption of pirarubicin by pretreatment with DMSO.

Absorption

Central nervous system changes in mitochondrial encephalomyopathy: light and electron microscopic study.

An autopsy case of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) is reported. It presented with generalized muscle atrophy, stroke-like episodes, schizophrenia-like mental disorder and progressive dementia. Serum lactate and pyruvate levels were high. In the biopsied muscles, ragged-red fibers were observed by light microscopy and aggregation of abnormal mitochondria with paracrystaline formation by electron microscopy. The most characteristic neuropathological findings were infarct-like lesions widespread in the cerebral cortex. In addition, this case showed some unusual pathological features: (1) diffuse moderate fibrillary gliosis in the whole cerebral and cerebellar white matter, which might have been due to metabolic disturbances; (2) several focal lesions with demyelination and numerous spheroids in the pontocerebellar fibers; and (3) marked degeneration of the posterior columns and spinocerebellar tracts. Electron microscopic examination revealed that abnormal mitochondria were markedly aggregated in smooth muscle cells and endothelium of the cerebral and cerebellar blood vessels. These fine structural findings suggest a "mitochondrial angiopathy".

Acidosis, Lactic

Regional cerebral glucose metabolism in patients with Parkinson's disease with or without dementia.

By means of positron emission tomography, the cerebral glucose metabolism in 5 patients with Parkinson's disease with dementia was compared with that in 9 patients without dementia, and that in 5 normal volunteers. The metabolic rates for glucose were measured by placing one hundred regions of interest. In the demented patients, cerebral glucose metabolism was diffusely decreased compared with that of the non-demented patients and the normal controls. The most significant decrease in glucose metabolism was observed in the angular gyrus (49.7% of the normal controls). The glucose metabolism in the cingulate, pre- and postcentral, occipital and subcortical regions was relatively spared (62.1 to 85.5% of the normal controls). In the patients without dementia, the glucose metabolism in each region was not significantly different from that in the normal controls. These results suggest that diffuse glucose hypometabolism in the cerebral cortex may correlate with that of patients with Parkinson's disease with dementia.

Aged

Establishment of animal liver metastatic model for C-1300 murine neuroblastoma and immunotherapy for it using OK-432, streptococcus preparation.

Intrasplenic administration of 1 x 10(6) C-1300 murine neuroblastoma cells induced spleen tumor in 78.6% of mice and liver metastasis in 64.3%. When mice were pretreated with carrageenan, an antimacrophage agent, the incidence of spleen and liver tumors in this system was lower, possibly due to the rebound increase in macrophage activity following the disappearance of the carrageenan effect. Continuous daily intraabdominal injection of 1 KE of OK-432 streptococcus preparation markedly reduced the appearance of liver metastasis (P less than 0.01), whereas the spleen mass was not reduced to such an extent. However, the survival rate of the OK-432-treated group did not differ greatly from that of the nontreated group. These results demonstrate the usefulness of the model of liver metastasis induced by intrasplenic administration of tumor cells and the effectiveness of OK-432 against liver metastasis formation.

Animals

Increased striatal 18F-dopa uptake and normal glucose metabolism in idiopathic dystonia syndrome.

Striatal 18F-Dopa uptake and glucose metabolism were studied by positron emission tomography with 6-L-[18F]fluorodopa and [18F]fluorodeoxyglucose, respectively, in 8 patients with idiopathic dystonia. Patients with abnormal findings on the brain CT and MRI were excluded from this study. The clinical diagnosis consisted of torsion dystonia in 3 patients, focal dystonia limited in the arm in 3 and cervical dystonia (spasmodic torticollis) in 2. The 18F-Dopa uptake, corrected by nonspecific retention in the cerebellum, at 120 min post-administration was evaluated, and increased 18F-Dopa uptake in the putamen and in the caudate head was observed in the patients with idiopathic dystonia compared to the normal controls. The striatal glucose metabolism in the patients with idiopathic dystonia showed no difference with the normal controls. These findings suggest that pathogenetic mechanism of idiopathic dystonia involves increased presynaptic activity of the dopaminergic system in the striatum.

Adult

D-glucose transport activities in erythrocytes and hepatocytes of dogs, cats and cattle.

1. The activities of D-glucose transport and hexokinase were investigated in erythrocytes or hepatocytes of dogs, cats and cattle. 2. The mean D-glucose transport activity in erythrocytes of dogs was 6.0 nmol/min/mg protein, half the value of hepatocytes. 3. The activities of D-glucose transport in erythrocytes and hepatocytes or hepatic hexokinase of cats were about one-third of those of dogs. 4. Cattle with low blood glucose concentrations showed considerably low activities of D-glucose transport and hexokinase, about one-third of those of dogs.

Animals

Amniotic tissue transplantation: clinical and biochemical evaluations for some lysosomal storage diseases.

Amniotic epithelial cells has been used for transplantation in patients with lysosomal storage diseases as an enzyme replacement therapy. But its clinical effect is still the question under debate. We performed amniotic tissue transplantation on patients with different lysosomal storage diseases: one with Tay-Sachs disease, one with juvenile Gaucher disease and one with juvenile metachromatic leukodystrophy. The patient having juvenile Gaucher disease received this grafting twice. Objective clinical improvement was observed in the first trial where this patient showed an increase of soluble beta-glucosidase one week after implantation. No clinical or biochemical changes were seen in the other patients. Although there are some advantages to amniotic tissue transplantation, original methods should be modified to cell transplantation in order to avoid graft-versus-host reaction which could happen in repeated implantation.

Adolescent