Biomedical subjects

K Nagashima

Publications and source records attributed to K Nagashima.

At least 307 records · Page 17Linked to original sources

PubMed1994

[Clinicopathologic analysis of ossification in spinal meningioma].

Calcification such as psammoma body is sometimes found especially in spinal cord meningioma but ossification of the meningeal tumor was rarely observed. Two cases of ossificated spinal cord meningiomas, located extramedullary intradurally apart from spinal bone, were clinicopathologically analyzed. The patients were 75-year-old female with meningioma at T9-10 level and 60-year-old female with one at T6-8 level. With pathological examination, concentration of psammoma bodies is not related to the formation of bone tissue. Metaplasia of arachnoid cell is seemed to be the origin of the bone structure.

Aged↗

PubMed1993

Identification of androgen receptor in the rat spinal motoneurons. Immunohistochemical and immunoblotting analyses with monoclonal antibody.

Androgens play an important role in motoneuron growth, development and regeneration. We proved the existence of androgen receptor (AR) in the motoneurons of the rat spinal cord by the immunohistochemical stain and Western blotting. The possibility that AR protein in spinal cord is expressed in tissue-specific form is proposed, being different from other androgen-dependent tissues. AR abnormality in X-linked spinal and bulbar muscular atrophy (SBMA) among a variety of motor neuron diseases were reported recently. Our study may give some clue to the AR abnormality leading to the degeneration of motoneurons.

Animals↗

PubMed1993

Origin of JC polyomavirus variants associated with progressive multifocal leukoencephalopathy.

JC polyomavirus (JCV) DNAs from the urine of nonimmunocompromised individuals (designated archetypal isolates) regularly contain a regulatory sequence that may have generated various regulatory sequences of JCV isolates derived from the brain of patients with progressive multifocal leukoencephalopathy (PML). In this report, we constructed a phylogenetic tree for 14 isolates (7 archetypes and 7 PML types) from DNA sequence data on the VP1 (major capsid protein) gene. According to the phylogenetic tree, the 14 isolates diverged into types A and B, each of which contained archetypal and PML-type isolates. Each type further diverged into several groups containing archetypal and PML-type isolates. We conclude that PML-type isolates are polyphyletic in their origin and do not constitute a unique lineage. This conclusion suggests that PML-type JCV isolates are generated from archetypal strains during persistence in the hosts. Furthermore, the present phylogenetic analysis indicates that an ancestral JCV carried the archetypal regulatory sequence and that this structure has been conserved in the course of JCV evolution.

Base Sequence↗

PubMed1993

Structural requirement of CRK SH2 region for binding to phosphotyrosine-containing proteins. Evidence from reactivity to monoclonal antibodies.

The SH2 region of signal-transducing proteins mediates binding to phosphotyrosine-containing proteins. We analyzed the structure-function relationship of the SH2 region of the human CRK protein by using a series of monoclonal antibodies (mAbs). Seventeen mAbs against the CRK SH2 region were classified into 5 groups according to the reactivity with mutant CRK proteins expressed in COS7 cells and in Escherichia coli and by epitope scanning with synthetic nonapeptides. Two groups of mAbs (groups A and B) were reactive only with intact SH2. Mutation(s) in either the amino-terminal B box or the carboxyl-terminal C box, which are the two subdomains of SH2, abolished the reactivity of the CRK mutants to the mAbs of groups A and B. Group A mAbs competed the binding of the CRK SH2 region to the phosphotyrosine-containing proteins. Moreover, the spectrum of the CRK mutants which were recognized by group A mAbs coincided with that of the CRK mutants which could bind phosphotyrosine-containing proteins, suggesting that group A mAbs were directed against the site of binding to phosphotyrosine-containing proteins. Group C mAbs, directed against the region between the B and C boxes, were reactive with both wild-type and mutant CRK proteins and did not affect the capacity of SH2 to bind phosphotyrosine-containing proteins. Contrary to group A and B mAbs, mAbs belonging to groups D and E, which were mapped onto the C box, did not bind well to the native CRK proteins, but bound to CRK mutants with mutation(s) in either the B or the C box. These results suggest that the B and C boxes, which are separated by a hinge region, coordinately form the functional SH2 domain that binds to the phosphotyrosine-containing proteins and to the group A mAbs.

Animals↗

PubMed1993

BK virus infection of the human urinary tract.

By screening consecutive autopsy cases with an antibody that recognizes human polyomaviruses, we found a case of malignant lymphoma in which the virus infection was confined to epithelia of the renal calyces, renal pelvis, ureter, and urinary bladder. The virus was confirmed as BK virus by a specific monoclonal antibody against BK virus T antigen, and numerous virus particles were identified by electron microscopy. The results showed that BK virus is a human urotheliotrophic virus.

Antibodies, Monoclonal↗

PubMed1993

Overexpression of the HIV-1 gag-pol polyprotein results in intracellular activation of HIV-1 protease and inhibition of assembly and budding of virus-like particles.

Some retroviruses, including HIV-1, regulate the relative amounts of gag and pol gene products by a translational frameshift mechanism. The consequences of altering the ratios of the Gag and Pol proteins were tested using vaccinia virus expression vectors, in which the gag and pol genes were fused by placing them in the same open reading frame. Immunoblotting of cell lysates indicated that a protein of approximately 160 kDa, the expected translation product of the fused gag-pol gene, was the dominant species detected with HIV-specific antiserum during the first several hours of infection with this recombinant virus. Subsequently, the full-length polyprotein diminished in amount and a series of Gag-related intermediate size proteins appeared. Later in infection, p24 and myristoylated p17 Gag proteins predominated and larger amounts of intracellularly processed reverse transcriptase, integrase, and protease were detected compared to the amounts formed with the wild-type gag-pol gene. Large numbers of budding, immature, and mature retrovirus-like particles were visualized by electron microscopy when the wild-type gag-pol gene was expressed, whereas no particles were detected in cells that expressed the fused gag-pol gene. The block to virus assembly was partially overcome by (i) inhibition of the HIV-1 protease with a peptidomimetic inhibitor, (ii) mutagenesis of the active site of the protease, or (iii) shortening of the Gag-Pol polyprotein by deletion of most of the reverse transcriptase gene. Nevertheless, budding was inefficient and the structures appeared immature and frequently aberrant. These results indicated that overproduction of the full-length Gag-Pol polyprotein and increased intracellular protease activity were both detrimental to viral assembly. Further experiments indicated that intracellular processing of Gag and Gag-Pol polyproteins occurred in the absence of particle formation when myristoylation was prevented.

Animals↗

PubMed1993

DNA-sequence rearrangement required for the adaptation of JC polyomavirus to growth in a human neuroblastoma cell line (IMR-32).

Infection of a human neuroblastoma cell line (IMR-32) with the JC polyomavirus (JCV) strain Mad-1 with subsequent serial passage results in the generation of a virus adapted to growth in IMR-32 (K. Akatani, M. Imai, M. Kimura, K. Nagashima, and N. Ikegami, J. Med. Virol., in press). To understand the basis of this adaptation, we molecularly cloned JCV DNAs from the adapted virus. The cloned JCV DNAs consisted of essentially three species (M1-IMRa, -IMRb, and -IMRc) with rearranged regulatory regions. Two TATA sequences are present in the regulatory region of the parental virus Mad-1, but one distal from the origin of replication was commonly deleted in M1-IMRa, -IMRb, and -IMRc. We showed that these regulatory regions were required for the efficient growth of JCV in IMR-32. Various JCV strains should be propagated in IMR-32, if their regulatory regions are replaced with those defined in this study. Since it is difficult to propagate JCV in cells other than primary human fetal glial cells, this system may be useful for structural and immunological studies of JCV.

Adaptation, Biological↗

PubMed1993

Histochemical demonstration of copper in LEC rat liver.

Livers of LEC rats were histochemically stained for copper according to the modified Timm's method, which includes trichloroacetic acid (TCA) treatment. TCA pretreatment was effective in removing zinc and iron, leaving as the major metal in the liver. Hepatocytes in 3-month-old rats were stained intensely by the modified Timm's method, both in frozen sections and in paraffin-embedded specimens. The centrilobular hepatocytes were usually stained, but positive cells were also randomly distributed in the hepatic lobes, showing a mosaic pattern. The staining was intensified in 8- compared to 3-month-old LEC rats. In contrast hepatocytes from LEA rats, the normal counterpart of LEC rats, were faintly stained for copper. Proliferating cholangioles found in older LEC rats were shown to lack copper deposition, and hepatocellular carcinoma showed less copper deposits than the hepatocytes surrounding the tumor. The copper staining was augmented in livers of LEC rats subjected to copper-loading, but was less intense in the livers treated with D-penicillamine. The staining intensity under the various experimental conditions showed good correlation with the copper concentration. Lysosomal deposition of copper in hepatocytes was demonstrated by electron microscopic analysis for copper. Thus the modified Timm's method was shown to produce valuable results in demonstrating copper in LEC rat livers, providing important information for an understanding of the mechanism of copper deposition and hepatic disease of the animal.

Animals↗

PubMed1993

Specific tropism of Japanese encephalitis virus for developing neurons in primary rat brain culture.

Among all the neural cells in fetal rat brain culture developing neurons showed the highest rate of infection by Japanese encephalitis virus (JEV). JEV specifically bound to these cells as measured by immuno-staining. These results indicate that developing neurons are the major target of JEV, and that the initial specific binding of virus to these cells may be one of the reasons for the neurotropism of JEV.

Animals↗

PubMed1993

Identification and partial characterization of a glycoprotein species with high affinity for methylmercury in peripheral nervous tissues of man and experimental animals.

A small amount of a glycoprotein species (21-kDa glycoprotein) with high affinity for methylmercury (MeHg) was detected in the post-nuclear or post-mitochondrial supernatant fraction of the homogenate of rat sciatic nerve on electrophoresis and autoradiography after binding of Me203Hg to the fraction. The 21-kDa glycoprotein was also found in the subcellular fractions of mouse, hamster, guinea pig, rabbit and human peripheral nervous tissues. Experiments with the cellular fractions of the tissues revealed that the 21-kDa glycoprotein is localized mainly in the myelin fraction, whereas it was not found in the cellular fractions of brain, spinal cord and nonneural tissues, such as kidney and liver. The specific binding activity of the 21-kDa glycoprotein with MeHg was 12-15 fold that of the major myelin protein, Po. It was shown that the interaction of the 21-kDa glycoprotein with MeHg was mediated through sulfhydryl groups in experiments with iodoacetamide and dithiothreitol. The amino acid compositions of the rat and human 21-kDa glycoproteins were similar but very different from that of a typical metallothionein. The N-terminal amino acid sequences of the two components of the rat 21-kDa glycoprotein were identical to those of P0 and PMP-22, respectively. The in vitro binding of MeHg was also observed in the myelin fraction obtained from the sciatic nerves of MeHg-dosed rats.

Amino Acid Sequence↗

PubMed1993

Pleomorphic carcinoma of the pancreas with osteoclast-like giant cells.

We studied two cases of pleomorphic carcinoma of the pancreas with osteoclast-like giant cells. The cut surface of both tumors was firm and whitish-tan in color, with extensive hemorrhage and necrosis. Microscopically, these tumors were composed mainly of pleomorphic mononuclear cells and numerous bizarre giant cells, with a spindle-cell sarcomatoid appearance and adenocarcinomatous elements exhibiting varying degrees of differentiation. Multinucleated giant cells resembling osteoclasts were frequently located around sites of necrotic hemorrhage. Immunohistochemically, most tumor cells of sarcomatous areas and some anaplastic giant cells were positive for vimentin and cytokeratin. Both carcinoembryonic antigen and CA 19-9 were detected in tumor cells in one case, forming ducts or glands. These findings suggest that the tumors in these two cases originated from pancreatic-duct cells with mesenchymal differentiation. In contrast, osteoclast-like giant cells in both cases showed strong immunoreactivity with vimentin and with KP1 and PG-M1 (CD68), which are monoclonal antibodies that react with a histiocyte-macrophage-associated antigen; however, there was no reaction with any epithelial markers. Thus, osteoclast-like giant cells are not epithelial in nature, suggesting that their origin of histiocyte-macrophage lineage is possibly induced as a paraneoplastic product.

Aged↗

PubMed1993

Usefulness of resting thallium-201 delayed imaging for detecting myocardial viability in patients with previous myocardial infarction.

To test the feasibility of resting thallium-201 (201Tl) initial and delayed scintigraphy for detecting the area of viable myocardium, we performed single photon emission computed tomography (SPECT) in 57 patients with previous myocardial infarction (MI). All had received coronary arteriography (CAG) and left ventriculography (LVG). Initial and delayed myocardial imagings were carried out 10 min and 2 hours, respectively, after the injection of 201Tl at rest. Redistribution was judged by visual interpretation and/or the circumferential profile curve, and found in the infarcted or its adjacent area in 40 of the 57 cases (70.2%). A negative washout (net increase of 201Tl uptake in delayed image) was detected in 17 of these 40 cases. In 10 of the 57 patients, both exercise and rest-injected 201Tl myocardial images were obtained at exercise and rest, and compared visually. The areas of abnormal perfusion were smaller in the resting delayed images than those seen after exercise in 9 of the 10 cases, and were equal in one case. Thus, resting 201Tl delayed myocardial scintigraphy appears to reduce the underestimation of the size of the viable myocardium by the usual 201Tl images obtained after exercise or by single initial images obtained at rest in patients with previous MI.

Adult↗

PubMed1993

Thallium-201 myocardial SPECT findings at rest in sarcoidosis.

In 41 patients with sarcoidosis (diagnosed according to criteria recommended by the Committee on Diffuse Pulmonary Disease, Ministry of Health and Welfare, Japan 1988), thallium-201 (201Tl) myocardial SPECT was performed to investigate: (1) the ability of 201Tl SPECT to detect cardiac involvement of sarcoidosis with images recorded at rest and 2 hours later, and (2) the relationships between 201Tl myocardial SPECT findings and the activity of sarcoidosis or endomyocardial biopsy findings. As to the abnormal findings in 201Tl myocardial SPECT, (1) a low density area was seen in 13 of 41 cases (31.7%) and non-uniform uptake was found in 17 cases (41.5%), (2) the mean washout ratio (n = 39) was 16.5 +/- 7.4%, which is significantly (p < 0.05) lower than that found in normal subjects, 23.9 +/- 7.5% (n = 10). Of the 19 patients judged visually to be normal, 5 patients had a reduced mean washout ratio less than 12%. Thus, the incidence of abnormal findings including all types of abnormality, on 201Tl myocardial SPECT in sarcoidosis was 63.4% (26/41 cases). In studying the relationship between 201Tl myocardial SPECT findings and the activity of sarcoidosis (as measured by the serum ACE (angiotensin converting enzyme) or lysozyme level, or the presence of more than 30% symphocyte fraction in BALF (broncho-alveolar lavage fluid)), 20 (80%) of 25 cases with 201Tl abnormality were judged to be active sarcoidosis, while only 6 (37.5%) of 16 cases with normal findings on 201TI SPECT were judged to be active.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Graft vascular disease in the great vessels and vasa vasorum.

To determine whether the great vessels were subject to transplantation-associated arteriosclerosis (graft vascular disease) we studied sections of aorta and pulmonary arteries from 19 cardiac explant cases. Sections of the same vessels from five autopsied hearts from patients who had received liver and/or kidney transplants with immunotherapy as well as from eight recipient hearts served as controls. In addition, eight donor hearts (three aortae and eight pulmonary arteries) that were not used for heart transplantation were examined. Intimal proliferation was noted in the aorta but affected the pulmonary arteries only slightly, whereas the vasa vasorum of both vessels were involved and were occluded or stenosed by thickened intima containing recanalized capillaries. On morphometric study the ratio of intima to media in the aorta was significantly higher in the heart transplant group than in the control group (0.14 +/- 0.14 [n = 19] v 0.02 +/- 0.02 [n = 16]; P < .01). This intimal thickening was not correlated with the use of cyclosporine or with other clinicopathologic factors. The cytomegalovirus infection rate was higher in the heart transplant group (85%) than in the control group (40%).

Adolescent↗

PubMed1993

Posterior interosseous nerve paralysis related to focal radial nerve constriction secondary to vasculitis.

A case of posterior interosseous nerve paralysis is reported with discussion of some characteristics that appear to distinguish it from entrapment neuropathy and neuralgic amyotrophy. The surgical implications are also discussed. More than ten similar cases have been reported, but the pathogenesis of this condition is still controversial. The patient presented with posterior interosseous nerve paralysis related to focal radial nerve constriction secondary to vasculitis in the perineurium. The constriction site was resected and the radial nerve was sutured. The patient recovered completely after 8 months.

Adult↗

PubMed1993

Correlation between histopathologic features and magnetic resonance images of spinal cord lesions.

The authors report a correlation between histopathologic features and magnetic resonance images of spinal cord lesions in 19 human spinal cords with various types of lesions. Abnormally high T2-weighted image signal intensities appeared nonspecifically in mildly altered lesions or areas with edema. In the gray matter, a low T1-weighted image in addition to a high T2-weighted image signal intensity appeared in severely altered lesions with necrosis, myelomalacia, or spongiform change. In the white matter, abnormally high T1-weighted image intensities appeared in severely altered lesions. Based on these preliminary results, it appears that a correlation between the degree of histopathologic alteration of the spinal cord and magnetic resonance images in clinical cases can be made. This is the first study to clarify the correlation between histopathologic features and magnetic resonance images of the diseased human spinal cord.

Aged↗

PubMed1993

Structure of 85 kDa subunit of human phosphatidylinositol 3-kinase analyzed by using monoclonal antibodies.

An 85 kDa subunit (p85 alpha) of phosphatidylinositol 3-kinase (PI-3K) has one SH3 and two SH2 regions [SH2(N) and SH2(C)], which direct protein-protein interaction. We have established eighteen hybridomas producing monoclonal antibodies against p85 alpha to study the structure-function relationship of this protein. Epitope mapping using a series of deletion mutants expressed in E. coli showed that the monoclonal antibodies bound to at least 5 distinct epitope regions, which were well dispersed on p85 alpha except for its carboxyl-terminus. Monoclonal antibodies against amino-terminal regions and polyclonal antibodies against carboxyl-terminal regions immunoprecipitated p85 alpha expressed in human cells and in E. coli. On the other hand, monoclonal antibodies against the central part of p85 alpha failed to immunoprecipitate p85 alpha efficiently; however, they could immunoprecipitate p85 alpha mutants with deletion of either the amino- or the carboxyl-terminal region. Similar results were obtained by immunocytochemistry using confocal microscopy. These results suggested that steric hindrance prevents binding of monoclonal antibodies to the central part of p85 alpha where SH2(N) is located. The SH2(N) may have a distinct function from SH2(C), which is located at the carboxyl-terminal region and has been shown to mediate the binding of PI-3K to activated growth factor receptors.

Animals↗

PubMed1993

A case of Johanson-Blizzard syndrome complicated by diabetes mellitus.

We report a girl with Johanson-Blizzard syndrome complicated by diabetes mellitus. She presented several characteristic malformations, such as aplasia of the alae nasi, deafness, dwarfism, absence of permanent teeth and malabsorption caused by disturbance of pancreatic exocrine function. At 11 years of age, glycosuria was detected at a routine outpatient examination. Repeated oral glucose tests showed a slowly progressive decline of insulin secretion and elevated blood glucose levels. The responsive secretion of insulin to glucagon or arginine loading was also low. The blood level of HbAlc was elevated over 9%. Based on these findings, insulin therapy was started when the patient was 13 years old. Our case suggests that diabetes mellitus might be considered as one of complications of Johanson-Blizzard syndrome.

Abnormalities, Multiple↗