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Biomedical subjects

K Nagashima

Publications and source records attributed to K Nagashima.

At least 217 records · Page 12Linked to original sources
PubMed1997

[Progressive multifocal leukoencephalopathy].

Progressive multifocal leukoencephalopathy (PML) is the only polyomavirus infection in human caused by JC virus. Clinically PML is diagnosed by neurological signs, supported by MRI and PET, but its pathologic diagnosis at brain biopsy remains to be a confirmative method, although the PCR method, using csf, gives a predictive value. Virological study of the regulatory region of viral genome has suggested that PML-inducing viral type may be derived from the urine-excreted virus (archetype) by mechanisms involving nucleotide deletion and duplication. Viral neurotropism has been shown to be closely related to transcriptional function of the viral promoter-enhancer which cellular proteins bind to and is activate by. Of these, NF-1 binding proteins, glial factor-1, Tst-1 (SCIP, Oct-6) and others should be tested for their specificity to human glial cell.

Humans↗
PubMed1997

Michelin tire syndrome: a congenital disorder of elastic fibre formation?

We describe a 15-month-old girl with Michelin tyre syndrome. She had hirsuties and marked skin folds. Histological examination showed fragmented elastic fibres in addition to smooth muscle hamartoma. On electron microscopy, decreased deposition of elastin was observed. We speculate that elastic fibre abnormalities may account for the characteristic skin changes in the Michelin tyre syndrome.

Connective Tissue Diseases↗
PubMed1997

Distribution of herpes simplex virus types 1 and 2 genomes in human spinal ganglia studied by PCR and in situ hybridization.

Clinical data indicate that the recurring herpes simplex virus (HSV) from oro-labial lesions is HSV subtype 1 and that the virus from genital lesions is HSV-2. This suggests that HSV-1 and HSV-2 reside in latent forms in the trigeminal ganglia and sacral ganglia, respectively. However, the distribution of latent HSV-1 and HSV-2 infections in human spinal ganglia has not been fully examined. This report concerns the application of polymerase chain reaction (PCR) and in situ hybridization (ISH) to such a study. By using PCR and employing the respective primers, HSV-1 and HSV-2 DNAs were detected in 207 of 524 samples from 262 spinal ganglia (from the cervical to the sacral ganglia) examined on both sides. The percentages of HSV-1 and HSV-2 detected in a given set of ganglia were similar, indicating an absence of site preference. By ISH, few but positive hybridization signals were detected evenly in sacral ganglia sections. The data suggest that regional specificity of recurrent HSV infections is not due to regional distribution of latent virus, but that local host factors may be important for recurrences.

Adult↗
PubMed1997

The role of topoisomerase I in HIV-1 replication.

The mechanisms involved in the restriction of the cellular tropism of HIV-1 to cells of primate origin remain to be clearly defined. However, a number of studies have shown that this is determined not only at the level of the cellular receptor(s) or virus entry, but at a number of additional and later stages in virus replication. We have recently reported that the reverse transcription of HIV-1 RNA is markedly enhanced by the association of the gag encoded nucleocapsid p15 protein and cellular topoisomerase 1. In the present study we have now investigated if the recruitment of cellular topoisomerase I during virus replication is important in determining the cellular tropism of HIV-1. Employing a stable murine cell line, L929, expressing both human CD4 and topoisomerase I, it could be demonstrated that effective proviral DNA synthesis occurred following infection. In contrast in cells expressing only human CD4 proviral DNA synthesis was not detected. In addition we have co-expressed fusin, a protein known to act as an accessory factor as the virus entry stage in infection of T cell tropic HIV-1, to support viral entry completely. However no progeny virus could be detected after HIV-1 infection. These results suggest that reverse transcription in vivo is critically dependent on the presence of cellular topoisomerase I, and support the view that involvement of this enzyme is in HIV-1 replication. Moreover the findings suggest that other factors which remained to be identified, are involved in restricting HIV-1 replication in non-primate cells.

Animals↗
PubMed1997

The role of topoisomerase I in HIV-1 replication.

The mechanisms involved in the restriction of the cellular tropism of HIV-1 to cells of primate origin remain to be clearly defined. However, a number of studies have shown that this is determined not only at the level of the cellular receptor(s) or virus entry, but at a number of additional and later stages in virus replication. We have recently reported that the reverse transcription of HIV-1 RNA is markedly enhanced by the association of the gag encoded nucleocapsid p15 protein and cellular topoisomerase I. In the present study we have investigated if the recruitment of cellular topoisomerase I during virus replication is important in determining the cellular tropism of HIV-1. Employing a stable murine cell line, L929, expressing both human CD4 and topoisomerase I, it could be demonstrated that effective proviral DNA synthesis occurred following infection. In contrast in cells expressing only human CD4, proviral DNA synthesis was not detected. In addition we have co-expressed fusin, a protein known to act as an accessory factor as the virus entry stage in infection of T cell tropic HIV-1, to support viral entry completely. However no progeny virus could be detected after HIV-1 infection. These results suggest that reverse transcription in vivo is critically dependent on the presence of cellular topoisomerase I, and support the view that involvement of this enzyme is important in HIV-1 replication. Moreover the findings suggest that other factors which remained to be identified, are involved in restricting HIV-1 replication in non-primate cells.

Animals↗
PubMed1997

Detection of varicella-zoster virus DNA in patients with acute peripheral facial palsy by the polymerase chain reaction, and its use for early diagnosis of zoster sine herpete.

Varicella-zoster virus (VZV) reactivation without cutaneous vesicles (zoster sine herpete) has been demonstrated in 8 to 25% of patients with acute peripheral facial palsy (APFP) by serological methods. To make an early diagnosis of zoster sine herpete, VZV DNA in oropharyngeal swabs from patients with APFP was examined by the polymerase chain reaction (PCR). VZV DNA was detected in oropharyngeal swabs from 6 of 36 (17%) patients with APFP by PCR. VZV DNA was detected in the oropharyngeal swabs from the six patients at their initial visit (2 to 4 days after the onset of APFP), while the anti-VZV IgM and IgG antibody titers were not increased significantly. In contrast, VZV DNA was undetectable in the oropharyngeal swabs at the time when the VZV specific antibody response appeared. These results indicate that detection of VZV DNA in oropharyngeal swabs by PCR is more useful than currently available serological assays for the early diagnosis of zoster sine herpete in patients with APFP.

Acute Disease↗
PubMed1997

[A clinical study of arthroscopic cystectomy on popliteal cysts associated with rheumatoid arthritis].

PURPOSE: We performed a prospective study of arthroscopic cystectomy on popliteal cysts associated with rheumatoid arthritis. MATERIALS: We performed arthroscopic cystectomy on three patients, four knees, and an open excision of a cyst on one patient, one knee, who had pain and swelling in the popliteal region. Of these five rheumatoid knees, three were grade I on the Larsen radiographic scale, one was II, and one was III. OPERATIVE METHOD: First, we performed synovectomy on the posterior compartment using a multi-portal approach. Second, we confirmed a small communication hole between the posterior compartment and the Popliteal cyst after the synovectomy with an angled arthroscope through the anterior compartment. Third, we enlarged the communication hole and performed a cystectomy (the excision of the membranous septum and the contents of the cyst) from the inside by using a motorized shaver. Finally, we performed a synovectomy on the anterior compartment. The follow-up period ranged from 1 year 6 months to 3 years, 4 months (the mean was 2 years, 4 months). EVALUATION: We assessed the results using objective oriteria based on the evaluation of swelling, pain and subjective criteria based on the evaluation of the range of motion of the knee and confirmation of the disappearance of the cyst using MRI. RESULT: We had good results in this study. All the four knees on which the arthroscopic cystectomy was performed had a reduction of pain and swelling right after the operation. The absence of the cyst was verified using MRI. We had no patient whose ROM was aggravated. However, synovitis and popliteal cysts reoccurred in one knee after the open excision (this case had the vasculitis, larsen grade III radiographically, and severe rheumatism). DISCUSSION: The recurrence rate of the popliteal cyst was very high (over 50%) when a cyst was performed open exision using a posterior approach. Open synovectomy of an anterior compartment needed the manipulation in several cases because of limited knee movement. We had a reduction in pain and a disappearance of the cyst right after operation. Further more, there was no restriction in ROM resulting from this operative method. CONCLUSION: Arthroscopic cystectomy is a superior procedure for treating the popliteal cysts associated with rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed1997

Antiproliferative activity in vitro and in vivo of the spicamycin analogue KRN5500 with altered glycoprotein expression in vitro.

The spicamycin analogue KRN5500 (NSC 650426; SPA) is derived from Streptomyces alanosinicus. The unique structure contains a purine, an aminoheptose sugar, glycine, and a tetradecadiene fatty acid. SPA potently inhibits the growth of certain human tumor cell lines in vitro (IC50 for growth <100 nM) and displays marked activity in vivo in Colo 205 colon carcinoma xenografts. Selective inhibition of labeled precursor incorporation was not evident at 1 or 4 h of exposure to the drug, but at 8 h, [3H] leucine incorporation was inhibited by approximately 40% at or below the IC50 for cell growth. Because of the structural similarity of SPA to inhibitors of glycoprotein processing, we examined the effect of SPA on indicators of glycoprotein synthesis and processing in HL60TB promyelocytic leukemia and Colo 205 colon carcinoma cells. Brief periods of exposure ( approximately 30 min) to SPA at the IC50 for growth increased incorporation of [3H]mannose. When examined by Western blotting after prolonged (40-48 h) incubation with lectins that target mannose-containing carbohydrates, Galanthus nivalis agglutinin and concanavalin A, a qualitative change in the pattern of mannose-containing glycoproteins was observed in HL60TB cells. Significant changes in the pattern of surface glycoprotein expression in intact cells were demonstrated by flow cytometry using fluorescence-labeled lectins. An increase in the number of cells binding G. nivalis agglutinin (indicating terminal mannose) was noted, but a decrease in the amount of lectin bound per cell was noted for wheat germ agglutinin (detecting sialic acid and terminal beta-N-acetyl glucosamine residues). Electron microscopy revealed loss of microvilli, and the Golgi apparatus appeared inflated. Our findings, therefore, raise the possibility that cells exposed to SPA have altered glycoprotein processing after exposure to low concentrations of drug, prior to the occurrence of overt cytotoxicity. These effects are consistent with a prominent early effect of SPA on the enzymatic machinery or organelles important for proper glycoprotein processing and emphasize the novelty of this agent's likely mechanism of action.

Animals↗
PubMed1996

Senescence-accelerated mouse. Neurochemical studies on aging.

Senescence-accelerated mouse (SAMP8) is known as a murine model of accelerated aging and memory dysfunction. The binding activity of [3H] 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxam ide (PK-11195) as a neurochemical marker of gliosis markedly increased with aging in the cerebral cortex and hippocampus of SAMP8. Immunoreactivity for glial fibrillary acidic protein (GFAP) was also enhanced. A beta-amyloid precursor protein (APP)-like immunoreactivity and 27-kDa-carboxyl terminal fragments of APP increased in SAMP8 brain. In addition, anti-APP antibody stained reactive astrocytes surrounding spongy degeneration in brain stern of SAMP8. These results suggest that astrocytosis and production of APP-derived fragments occur markedly in SAMP8 brains.

Aging↗
PubMed1996

Interaction between the amino-terminal SH3 domain of CRK and its natural target proteins.

CRK is a human homolog of chichen v-Crk, which is an adaptor protein. The SH2 domain of CRK binds to several tyrosine-phosphorylated proteins, including the epidermal growth factor receptor, p130(Cas), Shc, and paxillin. The SH3 domain, in turn, binds to cytosolic proteins of 135-145, 160, 180, and 220 kDa. We screened expression libraries by Far Western blotting, using CRK SH3 as a probe, and identified partial cDNA sequences of four distinct proteins, including C3G, DOCK180, EPS15, and clone ST12. The consensus sequence of the CRK SH3 binding sites as deduced from their amino acid sequences was Pro+3-Pro+2-X+1-Leu0-Pro-1-X-2-Lys-3. The interaction of the CRK SH3 domain with the DOCK180 peptide was examined with an optical biosensor, based on the principles of surface plasmon resonance. A low dissociation constant of the order of 10(-7) resulted from a high association rate constant (kassoc = 3 x 10(4)) and low dissociation rate constant (kdiss = 3 x 10(-3)). All CRK-binding proteins except clone ST12 also bound to another adaptor protein, Grb2. Mutational analysis revealed that glycine at position +1 of ST12 inhibited the binding to Grb2 while retaining the high affinity binding to CRK SH3. The result suggests that the amino acid at position +1 also contributes to the high affinity binding of the peptides to the SH3 domain of Grb2, but not to that of CRK.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Studies of cardiotonic agents. 8. Synthesis and biological activities of optically active 6-(4-(benzylamino)-7-quinazolinyl)-4,5-dihydro-5-methyl-3(2H)- pyridazinone (KF15232).

We previously reported that (+/-)-6-(4-(benzylamino)-7-quinazolinyl)-4,5- dihydro-5-methyl-3(2H)-pyridazinone (+/-)-1, KF15232) showed potent cardiotonic activity with a strong myofibrillar Ca(2+)-sensitizing effect. As an extension of our work, we attempted to synthesize optically active 1. (+/-)-4-(4-(Benzylamino)-7-quinazolinyl)-3-methyl-4-oxobutyric acid (-)-menthyl ester (6) was separated into both diastereoisomers, and each was converted to optically pure 1 (> 99% ee) in an enantioselective manner. In order to determine the absolute configuration of the isomers, an alternative synthesis of optically active 1 was employed. The precursor of (-)-1 ((+)-9) was obtained by enantioselective synthesis from (R)-D-alanine. Consequently, we concluded that the absolute configuration of (-)-1 at the 5-position of the pyridazinone ring was R. The cardiotonic effects and inhibitory activities to PDE III and V of racemic 1 and (-)-1 were more potent than those of (+)-1. These compounds also demonstrated greater vasorelaxant effects in guinea pig aorta. In contrast, (+)-1 showed only weak cardiotonic and vasodilating effects, although the compound displayed potent Ca(2+)-sensitizing activity. Racemic and (-)-1 attracted our interest for the treatment of congestive heart failure.

Animals↗
PubMed1996

Immunologic and Ultrastructural Characterization of HIV Pseudovirions Containing Gag and Env Precursor Proteins Engineered in Insect Cells

Expression of human immunodeficiency virus (HIV) Gag precursor protein (Pr55) by recombinant baculoviruses in insect cells results in the assembly and budding of Pr55 as virus-like particles, or Gag pseudovirions. The ultrastructural morphology, size, and sucrose sedimentation rate of Gag pseudovirions are indistinguishable from immature lentivirus particles produced by HIV-infected human cells. Recombinant baculoviruses were engineered to express individually Pr55 and HIV Env glycoprotein precursor (gp160). These recombinant baculoviruses were used to co-infect insect cells to produce chimeric HIV Gag pseudovirions containing gp160 in experiments to develop methodologies for producing complex noninfectious particulate vaccines for HIV. Coexpression of HIV Pr55 and gp160 resulted in the apparent incorporation of gp160 into Gag pseudovirions as determined by immunoblotting with envelope-specific monoclonal antibodies. Furthermore, results from indirect immunogold electron microscopy using monoclonal antibodies to HIV gp120, a component of the Env glycoprotein precursor, suggested that HIV gp160 was specifically incorporated during the budding process into the outer surface of chimeric Gag pseudovirions. Parallel labeling experiments to localize gp120 and Pr55 epitopes on HIV-infected H9 lymphocytes provided results similar to those obtained with chimeric Gag pseudovirions producing recombinant baculovirus-infected insect cells. Parameters influencing immunoelectron microscopy results in cell-surface and postembedding labeling experiments are discussed.

Journal Article↗
PubMed1996

Cranial fasciitis.

We report a case of cranial fasciitis in a 14-month-old boy. The lesion grew at the site of a previous head trauma, rapidly destroying the skull. Surgery disclosed that the lesion was highly vascular and adhered to the dura. Because histopathological study of a frozen section did not show malignancy, the authors decided not to perform dural excision after total removal of the lesion. No recurrence of the lesion was seen. The authors stress that this rate fibroblastic lesion must be included in the differential diagnosis of pediatric skull tumors and that careful histopathological observation is needed to avoid extensively invasive surgery.

Craniocerebral Trauma↗
PubMed1996

Age-related changes in biomechanical properties of the Achilles tendon in rabbits.

We investigated age-related changes in the mechanical properties of rabbit Achilles tendon. The animals used were immature (age 3 weeks, body mass 380 g), young adult (age 8-10 months, body mass 4.1 kg) and old (age 4-5 years, body mass 5.1 kg) rabbits. The cross-sectional area of the tendon increased with growth and the tensile strength of the young adult [67.3 (SEM 4.2) MPa] and old [66.7 (SEM 3.8) MPa] tendon was significantly higher than that of the immature tendon [23.9 (SEM 3.8) MPa]. However, there was no statistically significant difference in tensile strength between mature and old tendons. These differences may be attributable to the change in body mass. The gradient of the stress-strain curves, that is, the tangent modulus of the mature tendon [618.0 (SEM 87.0) MPa], was higher than that of the immature [281.0 (SEM 104.6) MPa] and old [530.5 (SEM 91.0) MPa] tendon, although the difference was not significant. The elongation at failure was approximately 16 percent for all age groups. These results would suggest that rabbit Achilles tendon is highly compliant during growth.

Achilles Tendon↗
PubMed1996

Effect of gamma knife irradiation on relaxation and contraction responses of the common carotid artery in the rat.

This report concerns a pilot study of the short- and long-term effects of gamma knife radiosurgery on vascular responses. The investigation was carried out on male Sprague-Dawley rats, and the relaxation and contraction responses of the right common carotid artery (CCA) were assessed following irradiation (100 Gy). The non-treated CCA of the same animals served as internal controls. Non-irradiated rats were used to control the effect of normal aging on vascular function. Isometric tension was determined on in vitro preparations of arterial rings. Acetylcholine-mediated, endothelium-dependent relaxation was impaired one month after radiosurgery, as was endothelium-independent relaxation induced by sodium nitroprusside, but the effect on the latter was minimal. The irradiated CCA was also impaired with respect to contraction responses induced by norepinephrine, endothelin-1 or phorbol dibutyrate. This impairment appeared to be biphasic, as it was evident one day after radiosurgery, followed by a partial recovery one week later, and again manifest after one month. At the light microscope level, the carotid arteries appeared to be well preserved throughout the experiment. However, obvious ultrastructural changes were noted in endothelial and smooth muscle cells of specimens obtained three months after radiosurgery. The present data indicate that high dose gamma knife radiosurgery affects the functions of both, the vascular endothelium and the vascular smooth muscles in an apparent time-dependent fashion. Because of its increasing application to patients, there is the need for studying the effects of gamma knife radiosurgery on cerebral arteries, since functional vascular changes may occur in the absence of obvious histological alterations. Our results on CCAs point to the feasibility of such experimental investigations.

Animals↗