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Biomedical subjects

A Kume

Publications and source records attributed to A Kume.

At least 73 records · Page 4Linked to original sources
PubMed1994

Quantitative autoradiography of 4'-ethynyl-4-n-[2,3-3H2]propylbicycloorthobenzoate binding to the GABAA receptor complex.

4'-Ethynyl-4-n-[2,3-3H2]propylbicycloorthobenzoate ([3H]EBOB) binding to the GABAA receptor complex was characterized autoradiographically in rat brain and then its binding in human brain was investigated. [3H]EBOB binding was saturable, specific and identified a single population of binding sites. The Kd obtained from saturation studies was 4.59 nM. Picrotoxin produced dose-dependent inhibition of [3H]EBOB binding and saturation analysis indicated a competitive interaction. Isoguvacine inhibited [3H]EBOB binding with regionally different effects. Bicuculline increased [3H]EBOB binding only in the cerebellar granule cell layer. In human cerebellum, a high level of [3H]EBOB binding sites was seen in the granule cell layer. These results suggest that [3H]EBOB binds to the picrotoxin binding site associated with the GABAA receptor complex, that regional differences in GABAA agonist and antagonist modulation of [3H]EBOB binding reflect underlying regional differences in GABAA receptor subunit composition, and that there is a species difference in GABAA receptor distribution between human and rat cerebellum.

Adult↗
PubMed1994

Evaluation of tracheal mucosal blood flow during an extended radical operation for esophageal carcinoma: clinical and experimental studies.

Using the hydrogen gas clearance method, a plate-type probe was attached to the surface of the cuff of an endotracheal tube in order to measure the ischemic changes in the tracheal mucosa produced by peritracheal lymph node dissection. In eight human subjects with intrathoracic esophageal carcinoma, the tracheal mucosal blood flow was 40.1 ml/100 g per minute after they had undergone a right thoracotomy and then decreased to 13.0 ml/100 g per minute after they had further received an extended radical operation preserving the right bronchial artery. No tracheal ulcers were seen. The same ischemic changes in the tracheal mucosa were also measured in dogs. The right bronchial artery contributes about one-third of the total blood flow to the trachea and this was thus calculated to be about 10-14 ml/100 g per minute.

Animals↗
PubMed1994

Zinc inhibition of t-[3H]butylbicycloorthobenzoate binding to the GABAA receptor complex.

The effect of Zn2+ on t-[3H]butylbicycloorthobenzoate ([3H]TBOB) binding to the GABAA receptor complex was studied autoradiographically in rat brain. Zn2+ inhibited [3H]TBOB binding in a dose-dependent manner at physiological concentrations. Saturation analysis revealed noncompetitive inhibition in various brain regions. The inhibitory effect of Zn2+ had regional heterogeneity; regions showing the greatest inhibition of [3H]TBOB binding were cortical laminae I-III, most areas of hippocampus, striatum, septum, and cerebellar cortex. Regions with relatively less inhibition of [3H]TBOB binding included cortical laminae V-VI, thalamus, superior colliculus, inferior colliculus, and central gray matter. The effect of Zn2+ and those of other GABAA ligands, such as benzodiazepines, bicuculline, isoguvacine, and picrotoxin, on [3H]TBOB binding seemed to be additive. Ni2+, Cd2+, and Cu2+ also inhibited [3H]TBOB binding with a regional heterogeneity similar to that produced by Zn2+. These results are consistent with Zn2+ acting at the previously detected recognition site on the GABAA receptor complex, distinct from the picrotoxin, GABA, and benzodiazepine sites. The regional heterogeneity of the Zn2+ effect may reflect differential regional distribution of GABAA receptor subtypes among brain regions. Other divalent cations probably act at the Zn2+ binding site.

Animals↗
PubMed1994

A study of parkinsonism in multiple system atrophy: clinical and MRI correlation.

We investigated clinical and MRI correlation in 18 patients with clinically-diagnosed multiple system atrophy (MSA) and 16 age-matched controls, using 1.5 T magnetic resonance imaging (MRI). We evaluated the severity of parkinsonism in each MSA patient. In assessing the MRI findings, we examined three parameters quantitatively: width of the pars compacta of the substantia nigra (SNc); putaminal hypointensity on T2-weighted images; and putaminal atrophy. As in previous studies, SNc width was narrowed and the putaminal signal intensity was decreased in patients with MSA compared with controls. The clinical severity of parkinsonism did not correlate significantly with the SNc width or the score of putaminal hypointensity in MSA. However, not only did putaminal atrophy occur, but correlated well with the severity of parkinsonism in MSA. A significant correlation could not be established between narrowing of SNc and shrinkage of the putamen. These findings suggest that putaminal atrophy is associated with the clinical manifestations of parkinsonism and do not support the hypothesis that transsynaptic degeneration occurs in MSA.

Adult↗
PubMed1994

Ultrasound imaging of the retrohepatic vena caval wall by percutaneous endocaval sonography (PECS).

Small-aperture endoluminal ultrasound imaging devices, comprising a 7.5- or 20-MHz transducer placed percutaneously inside the inferior vena caval lumen, were evaluated for the imaging of the retrohepatic vena caval wall, both in normal dogs and hospital patients with hepato-biliary carcinoma. Using 20-MHz systems, a three-layered appearance of the retrohepatic vena caval wall was delineated, both in dogs and humans, although the imaging field was limited. For dogs, the depth of the two complex inner layers measured sonographically coincided with the distance from the luminal surface to the outer surface of the muscular layer as determined in histological sections, while the total depth of the three layers measured sonographically proved to be larger than the distance from the luminal surface to the surface of the hepatic parenchyma determined histologically. Endocaval sonography could also establish a negative diagnosis of carcinomatous infiltration to the retrohepatic vena caval wall in patients. Our results suggest that percutaneous endocaval sonography (PECS) might be useful for diagnosing carcinomatous infiltration to the retrohepatic vena caval wall.

Aged↗
PubMed1994

Quantitative autoradiography of [3H]t-butylbicycloorthobenzoate binding to the gamma-aminobutyric acid receptorA complex.

The picrotoxinin ligand [3H]t-butylbicycloorthobenzoate ([3H] TBOB) was evaluated as an autoradiographic ligand to study gamma-aminobutyric acidA (GABAA) receptors. Specific [3H]TBOB binding was approximately 80% of total binding, was saturable and identified a single population of binding sites with regional Kd approximating 30 nM. [3H]TBOB binding was inhibited by picrotoxin, isoguvacine and pregnenolone sulfate. The benzodiazepines clonazepam and zolpidem produced complex effects with concentration-dependent inhibition and enhancement of [3H] TBOB binding. [3H]TBOB binding was regionally heterogeneous with high levels of binding in globus pallidus and layer IV of neocortex, intermediate levels of binding in other neocortical laminae and the cerebellar molecular layer and low levels of binding in the striatum and septum. The regional distribution of [3H]TBOB binding correlated poorly with the regional distribution of [3H]muscimol binding, somewhat better with the regional distribution of [3H]flunitrazepam binding and [35S]t-butylbicyclophosphorothionate binding and quite well with the regional distribution of [3H]zolpidem binding. [3H]TBOB binding site autoradiography is a convenient technique for studying GABAA receptor pharmacology in a regionally specific manner.

Animals↗
PubMed1993

Neuronal cell loss of the striatonigral system in multiple system atrophy.

We investigated the longitudinal as well as lateral loss of striatal and nigral cells and its distribution in 7 cases of multiple system atrophy. Loss of striatal small cells and nigral pigmented cells was more prominent in the caudal part than in the rostral and mid-parts. Cell loss was especially high in the dorsolateral zone of the caudal putamen and in the lateral zone of the caudal nigra. These findings indicate that MSA predominantly disturbs the striatal and nigral efferent systems, which interlink the caudal and dorsolateral putamen with the caudolateral nigra. In less severe cases, the rostral to mid-parts of the putamen or substantia nigra were almost intact while its caudal portion was clearly affected. The degenerative process of MSA seems to occur initially in the caudal parts of the putamen and substantia nigra, extending later to the rostral parts. Thus striatal small cells and nigral pigmented cells degenerate according to anatomical relationship. In MSA, degeneration of the striatonigral system could well be explained as being transsynaptic.

Aged↗
PubMed1993

Cerebrospinal fluid 28-kDa calbindin-D as a possible marker for Purkinje cell damage.

To examine the clinical value of 28-kDa calbindin-D (CaBP) in cerebrospinal fluid (CSF) as a marker for the damage to Purkinje cells, we measured CSF CaBP levels using an enzyme immunoassay method in 107 patients with cerebellar and other neurological diseases, and 26 controls. The mean CaBP level was markedly elevated in patients with cerebellar diseases, and the elevation of CaBP level was more frequent in the diseases involving Purkinje cells, such as multiple system atrophy (MSA) and subacute cerebellar degeneration in association with lung cancer. Further, in MSA patients, the CaBP levels decreased with duration of illness. The mean levels of CaBP were also elevated in some of the other diseases. We conclude that the elevations of CaBP levels are not specific for cerebellar diseases, but CSF CaBP may be a useful marker for examining the Purkinje cell involvement in cerebellar diseases.

Adolescent↗
PubMed1992

Hemi-parkinsonism in multiple system atrophy: a PET and MRI study.

We selected 6 patients presenting with hemi-parkinsonism from a total of 20 patients with probable multiple system atrophy (MSA) and studied their nigrostriatal lesions using magnetic resonance (MR) imaging and positron emission tomography (PET) with 18F-labeled 2-deoxy-2-fluoro-D-glucose (FDG). T2 weighted MR images demonstrated a decreased signal intensity in the putamen of all patients. This decreased signal was more intense in the nucleus contralateral to the affected body side in 5 patients. A decreased signal in the substantia nigra was found, expanding more on the contralateral side in 3 patients. T1-weighted images showed that the contralateral putamen was smaller in size than the ipsilateral. These findings indicated that the iron deposit and the neuronal cell loss in the degenerative process were more remarkable in the contralateral nuclei. FDG uptake in 5 patients had likewise declined more in the contralateral than in the ipsilateral putamen. The study shows that these patients have the nigrostriatal lesions as described in previous reports on MSA and that an asymmetric lesion relating to clinical signs is present in the nigrostriatal system. When a patient presents with hemi-parkinsonism alone, MR imaging and PET/FDG are useful for the clinical diagnosis of MSA.

Adult↗
PubMed1992

MRI of anterior spinal artery syndrome.

In this serial MRI study a 24 year old man presenting anterior spinal artery syndrome was examined. In the acute stage, spin echo sequences showed an enlarged cervical cord on a T1 weighted image and high signal intensity in the enlarged portion of the cord on a T2 weighted image. The findings were interpreted as oedema in the grey and white matter subsequent to ischaemia. In the chronic stage, inversion recovery techniques revealed a distinct focus in the anterior two thirds of the cord at the low cervical level.

Adult↗
PubMed1991

The glycine cleavage system. Molecular cloning of the chicken and human glycine decarboxylase cDNAs and some characteristics involved in the deduced protein structures.

A cDNA encoding chicken glycine decarboxylase (pCP15b) was isolated using an antibody specific to this protein. Additional cDNAs were cloned with the aid of the genomic fragments obtained by using the pCP15b cDNA probe. No initiator methionine codon is found in the currently elucidated cDNA sequence, and an ATG codon in an exon is assigned to this role. The precursor glycine decarboxylase deduced from the 3514-base pair nucleotide sequence is comprised of 1,004 amino acids (Mr = 111,848). The 1,020 amino acid residues are encoded for the precursor form of human glycine decarboxylase (Mr = 112,869) in the 3,783-base long cDNA sequence of two 1.9-kilobase pair cDNAs with a pentanucleotide overlap. The pyridoxal phosphate binding site lysine and a glycine-rich region, which is suggested to be responsible for the attachment of the phosphate moiety of pyridoxal phosphate, are found in close proximity in both the chicken and human enzymes. This region essential for the enzyme action is suggested to be embedded in a segment rich in beta-turns and random coils and is surrounded by conserved and repetitive amino acid sequences. It is suggested that these structures are involved in the organization of the active site of glycine decarboxylase.

Amino Acid Oxidoreductases↗
PubMed1991

The glycine cleavage system. The coupled expression of the glycine decarboxylase gene and the H-protein gene in the chicken.

Regulation of the transcription of the glycine decarboxylase gene and the H-protein gene was examined in chicken. Northern analysis suggested and run-off transcription confirmed that the glycine decarboxylase gene transcription is exclusively tissue-specific and takes place at different efficiencies in liver, kidney, and brain which are the chicken tissues exhibiting the glycine cleavage activity. No evidence for the glycine decarboxylase gene transcription was obtained in heart, spleen, and skeletal muscle. Basal and tissue-specific transcription of the H-protein gene can be distinguished. The tissue-specific transcription coordinates with transcription of the glycine decarboxylase gene in active tissues, while low abundance H-protein and its mRNA, products of the basal transcription, exist in inactive tissues together with small amounts of T-protein. Apparently, T-protein is synthesized by a process similar to that for H-protein. Glycine decarboxylase mRNA levels show a linear relationship with H-protein mRNA levels and with specific activities of the glycine cleavage reaction in active tissues. Tissue-specific distribution of the glycine cleavage activity is primarily determined by the expression of the glycine decarboxylase gene. The coordinate and tissue-specific transcription of the genes for the constituent proteins plays a key role in determining the magnitude of the glycine cleavage activity in chicken tissues and, thereby, the tissue-specificity of glycine metabolism.

Amino Acid Oxidoreductases↗
PubMed1991

A histometrical and comparative study on Purkinje cell loss and olivary nucleus cell loss in multiple system atrophy.

We examined pathologically 21 cases of multiple system atrophy (MSA). Density of Purkinje cell in 16 cases and of olivary nucleus cell in 20 cases was quantitatively measured, and their distribution as well as degree were studied. Contrary to the findings of previous reports, Purkinje cell loss was more pronounced in the vermis than in the hemispheres. Olivary nucleus cell loss was more outstanding in the accessory nucleus than in the inferior nucleus. A topographical characteristic of cell degeneration exists between the Purkinje layer and the olivary nucleus. Significant sparing of the nodulus apparently related to that of the vestibular system was found. While the common distribution of cell loss was seen, its degree varied considerably case by case. The degree was related to both duration of illness and, to some extent, clinical subtypes of MSA.

Atrophy↗
PubMed1990

One of the two genomic copies of the glycine decarboxylase cDNA has been deleted at a 5' region in a patient with nonketotic hyperglycinemia.

One of eight patients with nonketotic hyperglycinemia resulted by the lesion in glycine decarboxylase showed the deletion of 0.6-kb SacI and 1.5-kb PstI fragments identified by the cDNA for this protein. A genomic clone, lambda HGDG10, encodes a 5' region of this cDNA in an organized structure and can produce these two fragments. The other clone, lambda HGDG8, carries a processed gene. Southern analysis using a limited segment of this cDNA demonstrated that the 1.7-kb and 1.5-kb PstI fragments predicted from its recognition sites in both genomic clones occur actually in the human genome, indicating that at least two copies of glycine decarboxylase cDNA exist in the haploid genome, and the patient has the glycine decarboxylase gene deleted at a 5' region.

Amino Acid Oxidoreductases↗
PubMed1989

Isolation and characterization of s-myc, a member of the rat myc gene family.

A 9-kilobase-pair clone containing a myc-related gene that we have designated s-myc was isolated from a rat genomic library. The entire nucleotide sequence of the cloned DNA was determined, showing that the s-myc gene contains an open reading frame consisting of 1287 base pairs without introns. In vitro transcription-translation analysis of s-myc indicated that this gene produces a protein of approximately 50 kDa. The amino acid sequence predicted from the DNA sequence showed that the s-Myc protein is closely related to the murine N-Myc protein but lacks an acidic amino acid-rich sequence commonly present in the Myc-family proteins. Studies on transfection of s-myc into rat RT4-AC tumor cells revealed that the gene produces a polyadenylylated transcript of approximately 4.7 kilobases and that its high-level expression suppresses the tumor-igenicity of RT4-AC tumor cells in nude mice.

Amino Acid Sequence↗
PubMed1989

Spinal pencil-shaped softening. Report of an autopsy case studied using a three-dimensional model.

The pathologic features of a case of spinal pencil-shaped softening (PS) were studied by detailed step-sectioning and reconstruction using a three-dimensional (3D) model. The spinal cord was obtained at autopsy from a patient who had developed paraplegia due to extradural involvement of lung cancer. Above and below the area of transverse necrosis were PSs containing necrotic debris. They compressed the surrounding tissue and extended longitudinally over several segments. The PS was continuous with the area of transverse necrosis. These findings support the hypothesis that PS is formed by penetration of necrotic debris. The 3D model revealed that the PS was cylindrical to spindle-shaped. It showed a remarkable change in width along its course, with an unusual expanding shape. The PS was mainly located in the ventral part of the posterior column but was also observed in other locations in the segment near the transverse necrosis. Detailed step-sectioning showed that the PS changed in width mainly in response to intrapial pressure, and that it occurred where the parenchymal tissue was fragile. The expansion produced by penetration of necrotic debris may thus play an important role in the morphogenesis of this unusual lesion. Furthermore, the condition of the surrounding tissue may also be an important factor influencing the width and location of PS.

Aged↗