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Biomedical subjects

A Shimizu

Publications and source records attributed to A Shimizu.

At least 181 records · Page 10Linked to original sources
PubMed1998

CyclinG contributes to G2/M arrest of cells in response to DNA damage.

To investigate regulation mechanisms of G2/M phase transition, we studied the association of cell cycle progression with p53-dependent p21/waf-1 and cyclinG expression. We used doxorubicin (DOX) and sodium butyrate (NaB) to accumulate p53 protein. DOX treatment resulted in an apparent increase of cells in the G2/M fraction, whereas NaB arrested cells at G1. P53 protein induction in response to DOX accompanied up-regulation of p21/waf-1 and cyclinG expression. However, cyclinG was undetectable in NaB-treated cells. These results implied a putative association between increases in the proportion of cells accumulating in the G2/M fraction and enhanced cyclinG expression. Antisense oligo DNAs (AS) complementary to cyclinG mRNA inhibited the cyclinG protein expression induced by DOX treatment. This inhibition resulted in a marked reduction in the number of cells arrested at G2/M and accumulating at G1. A role for cyclinG in G2/M phase transition control is implied.

Animals↗
PubMed1998

Clinicopathologic and immunohistochemical studies of papillary thyroid microcarcinoma presenting with cervical lymphadenopathy.

Although most papillary thyroid microcarcinomas (PMCs) are of little clinical significance, patients with PMCs occasionally have an unfavorable outcome, especially when they present with bulky nodal metastasis or distant metastasis. We have attempted to identify "high-risk" PMCs by evaluating clinical, pathologic, and immunohistochemical prognostic factors. Among 190 patients with a PMC, 156 without clinically apparent nodal metastasis had a benign course. The remaining 34 patients, who presented with cervical lymphadenopathy of at least 1 cm, were studied. Three of the four patients who developed distant metastasis died of the disease, and the other died of local recurrence. All patients who developed distant metastasis or died of the disease had both nodal metastasis of at least 3 cm and a nonencapsulated type of primary lesion. All patients who developed distant metastasis showed both extracapsular extension of the metastatic lesions in lymph nodes and positive staining for transforming growth factor-beta3 (TGFbeta3) (a potent growth inhibitor) in the primary lesion. The Ki-67 (an indicator of cell proliferation) labeling indices in the primary and metastatic nodal lesions of patients who died of cancer were significantly higher than those of the others with nonfatal disease. None of the patients showed P53 (nuclear tumor-suppressor phosphoprotein) overexpression. In conclusion, patients with PMC who have both 3 cm or larger lymphadenopathy and a nonencapsulated type of primary lesion may be regarded as high-risk patients. Immunohistologic positivity for Ki-67 and TGFbeta3 in cancer cells is a potential indicator of aggressively malignant PMC.

Adult↗
PubMed1998

Fracture of the axis after dome-like cervical laminoplasty.

We describe a case of fracture of the axial neural arch that occurred after a dome-like cervical laminoplasty and caused dural compression. Cervical laminoplasty with dome-like laminoplasty of the axis was performed on a patient with cervical myelopathy due to ossification of the posterior longitudinal ligament extending from C2 to C6. After temporary neurological remission, the patient experienced unanticipated neurological deterioration with posterior cervical pain. Radiographs, magnetic resonance imaging and computed tomography of the cervical vertebrae showed a fractured axial lamina that was compressing the cervical cord. After total axial laminectomy, permanent neurological improvement was obtained. Our experience suggests that care should be taken to avoid an excessive dome-like laminoplasty and that the possibility of axial fracture should be borne in mind.

Aged↗
PubMed1998

Novel dithiocarbamate carbapenems with anti-MRSA activity.

A new series of 1beta-methyl carbapenems, in which a disubstituted-aminothiocarbonylthio moiety was attached to the C-2 position of the carbapenem nucleus, were prepared and evaluated for anti-MRSA activity. These derivatives showed good in vitro antibacterial activity against high-level MRSA, and the finding of good affinity for PBP-2' supported these results. Some of the compounds having favorable protein-binding affinity showed excellent in vivo anti-MRSA activity.

Animals↗
PubMed1998

Identification of receptors and Smad proteins involved in activin signalling in a human epidermal keratinocyte cell line.

BACKGROUND: Activin A is a multifunctional protein, which is a member of the transforming growth factor-beta (TGF-beta) superfamily. Smad proteins have recently been shown to transduce signals for the TGF-beta superfamily of proteins, and Smad2 was implicated in activin signalling in Xenopus embryos. RESULTS: We identified the receptors and Smad proteins activated by activin A in a human epidermal keratinocyte cell line, HaCaT. The major activin receptors expressed on HaCaT cells were activin type II receptor (ActR-II) and activin type IB receptor (ActR-IB). We have also shown that in HaCaT cells, activin A induced the phosphorylation of Smad3 and, to a lesser extent, of Smad2. On the other hand, TGF-beta induced an efficient phosphorylation of both Smad2 and Smad3. Activin A preferentially induced the nuclear translocation of Smad3 in HaCaT cells, whereas TGF-beta strongly induced the nuclear translocation of Smad2, as well as other Smads. Moreover, a constitutively active form of ActR-IB efficiently stimulated the formation of a heteromeric complex between Smad3 and Smad4 in COS cells transfected with Smad cDNAs. CONCLUSIONS: These results suggest that activin A binds to a receptor complex of ActR-II and ActR-IB, and preferentially activates Smad3 in HaCaT human keratinocytes.

Activin Receptors↗
PubMed1998

Human gnathostomiasis caused by Gnathostoma doloresi, with particular reference to the parasitological investigation of the causative agent.

Gnathostomiasis caused by Gnathostoma doloresi Tubangui was observed in a 46-year-old Japanese man, a clerk, who resided in the Fukuoka prefecture of Kyushu district, in southern Japan. The first symptom noted by the patient was epigastric pain, which occurred 3 days after he had consumed the raw flesh of a brook trout, Oncorhynchus masou masou (Brevoort), from a trout farm in neighbouring Kumamoto prefecture. Three days later, he developed creeping eruptions on his trunk. The eruptions spread and the patient was admitted to hospital 18 days after eating the trout. No nematode larvae were found in any of four skin biopsies collected on admission. However, vesicles appeared on the lower abdomen of the patient 20 days after he had eaten the trout, and a small nematode was removed from one of them. One day after the nematode had been excised, a cutaneous swelling suddenly occurred on the patient's lower left jowl and this persisted for a week. All the skin abnormalities gradually decreased from day 25 post-ingestion and had disappeared by day 30. The isolated nematode was identified as an advanced third-stage larva of G. doloresi, based on its morphology and the number of hooklets on its head-bulb.

Animals↗
PubMed1998

Differential localization of Th1 and Th2 cells in autoimmune gastritis.

The vast majority of CD4+ T cells infiltrating into gastric mucosa (GM) and in the draining (gastric) lymph node (GLN) shows an activated/memory phenotype, CD45RB(low) L-selectin(low) CD44(high), in neonataly thymectomized BALB/c mice bearing autoimmune gastritis (AIG), indicating that these cells are actively involved in this disease. CD4+ T cells sort-purified from GLN expressed mRNAs encoding for both IFN-gamma and IL-4. However, those infiltrating into GM expressed very low levels of IL-4 mRNA, even though they strongly expressed IFN-gamma mRNA. Among CD4+ T cells separated from AIG mice expressing detectable levels of either IFN-gamma or IL-4 by intracellular staining, less than one-seventh expressed IL-4 and thus most of them expressed IFN-gamma in GM, whereas roughly half and one-third expressed IL-4 in GLN and spleen respectively. These findings indicate that the Th1 cells predominantly infiltrate into autoimmune lesions and Th2 cells are mainly resident in the regional LN. We further set up an in vitro model system of transendothelial migration using a murine endothelial cell line, F-2, and found that Th1 cells in CD4+ T cells separated from lymphoid tissues of AIG mice preferentially passed through the monolayer of endothelial cells while only a small portion of Th2 cells did so. This differing ability of transendothelial migration and localization might explain the dominance of Th1 cells destroying the tissue in focal lesions without inhibition by the Th2 cells, in spite of both subsets being simultaneously activated in AIG mice, and the functions of each T cell subset seems to be mutually exclusive.

Animals↗
PubMed1998

Cellular distribution of a GPI-anchored complement regulatory protein CD59: homodimerization on the surface of HeLa and CD59-transfected CHO cells.

Human glycosyl phosphatidylinositol-anchored protein CD59 was solubilized in detergent-insoluble complexes (DICs) and in post-nuclear pellets by a two-step solubilization procedure using Triton X-100 and octylglucoside. CD59 molecules are recovered in both fractions, the amount being greater in the latter fraction in all cell types tested. Specific labeling of surface CD59 molecules revealed that the CD59 detected in DICs originated from intracellular compartments, whereas that in post-nuclear pellets was in part derived from the cell surface. Cross-linking of surface proteins with chemical cross-linker followed by Western blotting with anti-CD59 antibody revealed cross-linked products with molecular masses of 28-36 kDa on HeLa and human CD59 cDNA-transfected CHO cells; the CD59-associating molecules were estimated to be 13-18 kDa in size. The cross-linked products were extracted in the post nuclear pellets, and CD59 existed mainly as a cross-linked form on the cell surface. Two-dimensional electrophoresis of the cross-linked products revealed no trace of molecules other than CD59. The cross-linked products showed the same N-terminal sequences as CD59 and a strikingly similar amino acid composition to that of CD59. Thus, most likely, the cross-linked products are CD59 dimers. The finding that CD59 localized on outer membranes is all in the form of dimers suggests the importance of dimerization for CD59 functioning.

Animals↗
PubMed1998

The region of alpha-lactalbumin recognized by GroEL.

The binding constants between disulfide-intact or various disulfide-reduced bovine alpha-lactalbumins and an Escherichia coli chaperonin, GroEL, were determined by using the equilibrium dialysis method. The disulfide-intact and one-disulfide (Cys6-Cys120)-reduced alpha-lactalbumins were shown not to bind with GroEL both in the presence and absence of Ca2+. The two-disulfide (Cys6-Cys120 and Cys28-Cys111)-reduced alpha-lactalbumin, which has the native-like tertiary structure in its beta-domain region and an unfolded alpha-domain in the presence of Ca2+, showed considerable binding with GroEL. The binding free energy of the two-disulfide-reduced alpha-lactalbumin in the presence of Ca2+ is close to that of the molten globule state of disulfide-intact alpha-lactalbumin. This result suggests that GroEL binds to the unfolded alpha-domain of alpha-lactalbumin regardless of the conformation of the beta-domain. The fully disulfide-reduced and two-disulfide-reduced alpha-lactalbumins were found to bind more strongly with GroEL in the absence of Ca2+ than the two-disulfide-reduced alpha-lactalbumin in the presence of Ca2+, thus indicating that the unfolding of the beta-domain of alpha-lactalbumin leads to stronger interaction with GroEL.

Binding, Competitive↗
PubMed1998

Remarkable destabilization of recombinant alpha-lactalbumin by an extraneous N-terminal methionyl residue.

A recombinant bovine alpha-lactalbumin, possessing an additional N-terminal methionyl residue, was expressed in Escherichia coli. In order to address the effects of the N-terminal methionyl residue on conformational stability, the thermal stability of the recombinant alpha-lactalbumin was investigated by measuring temperature-dependence of circular dichroism spectra, and it was compared with that of authentic alpha-lactalbumin from bovine milk. The thermal stability of the recombinant alpha-lactalbumin was significantly lower than that of authentic alpha-lactalbumin. The enthalpy change of unfolding of the recombinant protein was found to be the same as that of the authentic one when compared at the same temperature. Therefore, the N-terminal methionyl residue seems to destabilize the conformation of recombinant alpha-lactalbumin through some entropic effects.

Animals↗
PubMed1998

Comparative histopathology of hepatic allografts and xenografts in the nonhuman primate.

Liver transplantation was performed in the following groups: Group 1, baboon-to-baboon allografting (n=8) (control group); Group 2, ABO-compatible vervet monkey-to-baboon xenografting (n=8); Group 3, ABO-incompatible vervet monkey-to-baboon xenografting (n=6); Group 4, pig-to-baboon xenografting (n=2); and Group 5, pig-to-rhesus monkey xenografting (n=6). Immunosuppressive therapy (cyclosporine, cyclophosphamide, and methylprednisolone) was begun 2-7 days before liver transplantation (LTx) and continued indefinitely after LTx. The liver grafts were biopsied pre-LTx and subsequently post-LTx at approximately 1 hr, 2-3 hr, 7-10 days, 20-30 days, 60 days, 120 days, and at euthanasia or spontaneous death. There were 19 successful LTxs with grafts functioning from one hour to 123 days. No pig liver (Groups 4 and 5) survived more than 5.5 hr, as there was an immediate severe vascular response after reperfusion, typical of hyperacute rejection (congestion and hemorrhage). Vascular rejection was not seen in allografts (Group 1), but early mild-to-moderate congestion and neutrophil infiltration were present in concordant xenografts (Groups 2 and 3), which were associated with moderate deposition of immunoglobulin, C3, and fibrinogen. Lymphoid cell infiltration, bile duct damage, and portal vein endothelialitis in the portal zones occurred later in both allografts (Group 1) and concordant xenografts (Groups 2 and 3), developing earlier in the presence of ABO-incompatibility (Group 3). In concordant xenografts it was usually followed by fibrosis.

Animals↗
PubMed1998

Phylogenetic evidence for the existence of novel thermophilic bacteria in hot spring sulfur-turf microbial mats in Japan.

So-called sulfur-turf microbial mats, which are macroscopic white filaments or bundles consisting of large sausage-shaped bacteria and elemental sulfur particles, occur in sulfide-containing hot springs in Japan. However, no thermophiles from sulfur-turf mats have yet been isolated as cultivable strains. This study was undertaken to determine the phylogenetic positions of the sausage-shaped bacteria in sulfur-turf mats by direct cloning and sequencing of 16S rRNA genes amplified from the bulk DNAs of the mats. Common clones with 16S rDNA sequences with similarity levels of 94.8 to 99% were isolated from sulfur-turf mat samples from two geographically remote hot springs. Phylogenetic analysis showed that the phylotypes of the common clones formed a major cluster with members of the Aquifex-Hydrogenobacter complex, which represents the most deeply branching lineage of the domain bacteria. Furthermore, the bacteria of the sulfur-turf mat phylotypes formed a clade distinguishable from that of other members of the Aquifex-Hydrogenobacter complex at the order or subclass level. In situ hybridization with clone-specific probes for 16S rRNA revealed that the common phylotype of sulfur-turf mat bacteria is that of the predominant sausage-shaped bacteria.

Bacteria↗
PubMed1998

Herpes simplex virus myelitis: clinical manifestations and diagnosis by the polymerase chain reaction method.

Herpes simplex virus (HSV) myelitis has previously been reported to be a form of acute ascending necrotizing myelitis caused by HSV type 2 (HSV-2). We studied neurological symptoms, clinical course, magnetic resonance imaging (MRI) findings, and diagnosis by polymerase chain reaction (PCR) methods in 9 patients with HSV myelitis. In 6 cases, disease onset was marked by sensorimotor disturbances of lower extremities and urinary disturbances, with the transverse myelopathy gradually ascending to the cervicothoracic spinal cord level. The other 3 cases showed transverse myelopathy without an ascending pattern. Six cases showed acute progression, while 3 cases showed a subacute course. There were 2 cases with recurrent episodes. Three patients recovered, however, in the remaining 6 patients severe sequelae such as paraplegia persisted despite antiviral therapy. MRI showed a hyperintense lesion on T2-weighted images. Gadolinium enhancement was observed in 2 cases, and 1 case showed a hyperintense lesion both on T1- and on T2-weighted images, suggesting hemorrhagic necrosis. HSV-2 was detected by PCR techniques in all 6 cases with an ascending pattern. HSV-1 DNA was detected in 2 and HSV-2 DNA in 1 of the 3 cases with a nonascending pattern. Our findings demonstrate diverse clinical manifestations of HSV myelitis.

Adult↗
PubMed1998

Human parvovirus B19 capsid antigen in granulocytes in parvovirus-B19-induced pancytopenia after bone marrow transplantation.

A patient with refractory anemia with an excess of blasts in transformation developed pancytopenia and a concurrent interstitial pneumonia 110 days after allogeneic bone marrow transplantation. Bone marrow examination showed 0.4% giant proerythroblasts and 86.2% granulocytes, some of them large with a bizarre configuration and the others of normal size. Serum folate level was found low, 0.6 ng/ml. Immunocytochemistry with a B19-specific monoclonal antibody MAB8292 revealed B19 capsid antigen only in erythroblasts and large, bizarre granulocytes, but not in granulocytes of normal size. In situ hybridization of bone marrow cells using digoxigenin-labeled DNA probes detecting parvovirus B19 also demonstrated positive signals in 8.5% of marrow cells. Parvovirus B19 DNA was isolated from the serum and the bronchoalveolar lavage fluid of this patient by the polymerase chain reaction. These findings suggest that neutropenia may be caused by an involvement with parvovirus B19 though a deficiency of folic acid may have in part contributed to the genesis of neutropenia in the patient. The relevance of parvovirus B19 to the interstitial pneumonia remains unclear.

Adult↗
PubMed1998

Recovery of damaged glomerular capillary network with endothelial cell apoptosis in experimental proliferative glomerulonephritis.

Capillary repair can occur in damaged glomeruli in recovery models of glomerulonephritis (GN). In order to clarify whether capillary repair is an essential component in glomerular recovery from GN, we have examined the development of the capillary repair after inflammatory injury in both the repairing glomeruli and the segmental sclerotic scar lesions in Thy-1 GN. Mesangiolytic glomerular damage was induced in rats with anti-Thy-1.1 antibody administration. Diffuse mesangiolysis and segmental microaneurysmal ballooning developed in damaged glomeruli by day 3, with reduction of endothelial cellularity. Thereafter, histological proliferative GN developed between day 5 and week 3. Endothelial cell proliferation began on day 1 and peaked on day 5, and the number of glomerular endothelial cells increased and exceeded the level of control values on day 7. Angiogenic glomerular capillary repair occurred through the process of not only capillary regeneration from remaining endothelial cells in capillary aneurysmal lesions but also new capillary growth derived from the glomerular vascular poles by day 7. The number of glomerular capillary lumina also increased to the level of controls by week 3. Subsequently, mesangial proliferative GN resolved, and most of the glomeruli recovered to their normal structure with the reconstruction of the capillary network by weeks 4-6. In the glomerular capillary repair, significant apoptosis of glomerular endothelial cells was present during the period of mild endothelial cell hypercellularity between day 7 and day 10 (0.06 +/- 0.02 apoptotic endothelial cells/glomerular cross section vs. 0.00 +/- 0.00 in controls, mean +/- SEM; p < 0.05. In Thy-1 GN, most of the damaged glomeruli recovered with angiogenic capillary repair. However, segmental sclerotic scar lesions remained in 10-30% of the glomeruli with an incomplete repair of glomerular capillaries. Therefore, it is concluded that following the destruction of the glomerular capillary network in GN, angiogenic capillary repair plays an essential role in the recovery of damaged glomeruli, and incomplete capillary repair leads to sclerotic scar lesions in damaged glomeruli. Glomerular capillary repair occurs through the process of capillary regeneration from remaining endothelial cells as well as new glomerular capillary growth from the glomerular vascular poles. In glomerular capillary repair, apoptosis is necessary in regulating the number of intrinsic endothelial cells.

Animals↗
PubMed1998

Relative usefulness of measures of heart rate variability and neuroendocrine activity as indicators of autonomic nervous abnormality in patients with left ventricular dysfunction.

The aim of the study was to assess the relationship between changes in heart rate variability (HRV) and parameters of neuroendocrine activation in patients with various levels of left ventricular dysfunction. Measurements of HRV, plasma norepinephrine (PNE), and plasma atrial natriuretic peptide (ANP) were performed in 17 age- and gender-matched control subjects (group C) and in 39 patients with ischemic heart disease or cardiomyopathy who were subdivided into 3 equal groups according to their left ventricular ejection fraction: group N (normal); group M (mildly impaired); and group S (severely impaired). Spectral analysis of HRV (from 10-min electrocardiograms) was analyzed by the method of coarse-graining spectral analysis. PNE and ANP were significantly elevated in group S only (p<0.05). Log low-frequency power and log total power for group M were significantly lower than for group N (p<0.05). Log high-frequency power was significantly lower for group M than for group C (p<0.05). Thus, assessment of changes in HRV, which were observed earlier in the progress of left ventricular dysfunction than changes in neuroendocrine factors, may be a useful non-invasive method for the early detection of autonomic abnormality in patients with left ventricular dysfunction.

Aged↗
PubMed1998

Hb Peterborough [beta 111(G13)Val-->Phe] in Japan; rapid identification by ESI/MS using proteolytic digests of oxidized globin.

A variant hemoglobin was found in a Japanese female whose hemoglobin was studied to clarify the cause of a low Hb A1c value, found during a routine medical examination. The detection and identification of the variant was performed by electrospray ionization mass spectrometry. Its structure was revealed to be the same as Hb Peterborough [beta 111(G13)Val-->Phe]. For sequence determination, oxidized globin as well as non-derivatized globin were cleaved by trypsin and lysyl endopeptidase. An abnormal peptide was found in digests of oxidized globin, as shown by electrospray ionization mass spectrometry. Cysteic acid in oxidized peptides enhanced the abundance of fragment ions in tandem mass spectrometry, which helped to quickly and accurately determine the substitution in beta T-12, a peptide in the core region. Electrospray ionization mass spectrometry analysis of the hemolysate also showed a low level of glycated hemoglobin. The patient's hemolysate showed decreased stability in the isopropanol test. An abnormal band was detected on isoelectrofocusing on the cathodic side of normal Hb A. This is the second report of Hb Peterborough and the first of its occurrence in Japan.

Adult↗