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Biomedical subjects

K Maeda

Publications and source records attributed to K Maeda.

At least 451 records · Page 25Linked to original sources

Spontaneous occlusion of a giant basilar tip aneurysm and a basilar artery due to the dissection of both structures: case report.

BACKGROUND: Spontaneous occlusion of a giant aneurysm with its parent artery is relatively rare. Complete occlusion of a giant aneurysm at the basilar bifurcation and a basilar artery due to the dissection of the basilar artery has never been reported. CASE DESCRIPTION: This 62-year-old man presented with left hemiparesis and right oculomotor palsy. Radiographic study showed a giant aneurysm at the basilar artery bifurcation with hemorrhage in its wall and an ischemic area in the right midbrain. Subsequent study revealed that thrombosis of the aneurysm rapidly progressed and that the parent basilar artery caused the dissection. Finally the giant aneurysm and the basilar artery were completely thrombosed. CONCLUSION: The dissection was considered to occur in the aneurysm wall first by the hemorrhage in it and progress proximally along the basilar artery. Intramural hemorrhage in the wall of a giant aneurysm can be a cause of dissection of its parent artery. This seems to be one of the mechanisms by which a giant aneurysm and its parent artery are spontaneously thrombosed.

Aortic Dissection↗

Immunohistology of skin and oral biopsies in graft-versus-host disease after bone marrow transplantation and cytokine therapy.

BACKGROUND: Early diagnosis of graft-versus-host-disease (GVHD) after bone marrow transplantation is often difficult, particularly when the patients are immunosuppressed by chemotherapy or irradiation. OBJECTIVE: To investigate the influence of cytokines on skin lesions after bone marrow transplantation. METHODS: Biopsy specimens of skin and oral mucosa were obtained from bone marrow transplant patients with GVHD and were subjected to histologic and immunohistochemical examination. RESULTS: Administration of granulocyte-macrophage colony-stimulating factor caused atopic dermatitis-like lesions in two patients, who had infiltration of neutrophils, eosinophils, and lymphocytes around the hair follicles of the skin and no signs of GVHD in other organs. Only patients who were treated with cytokines developed acute GVHD. Immunohistochemical examination of skin biopsies from 18 patients with acute GVHD and 11 patients with chronic GVHD after cyclophosphamide administration or irradiation showed that the maculopapular skin lesions characteristic of acute GVHD contained infiltrates of CD4+ and CD8+ lymphocytes. There was also an increase in numbers of epidermal keratinocytes expressing intercellular adhesion molecule-I and HLA-DR antigens. CONCLUSION: These findings support the involvement of cytokines in GVHD and suggest that immunostaining of skin biopsies may be useful for the early diagnosis of this condition.

Acute Disease↗

Neurochemical and metabolic consequences of elevated cerebrospinal fluid quinolinic acid concentrations in rat brain.

Quinolinic acid (QUIN) is an endogenous excitatory amino acid, which is elevated in brain tissues or cerebrospinal fluid (CSF) in several acute and chronic inflammatory central nervous system (CNS) diseases. The functional significance of this elevation is unknown but speculations of excitotoxicity have been raised. We have begun to address the pathologic consequences of elevated CSF QUIN by studying the effects of intracerebroventricular (i.cv) administration of QUIN on regional choline acetyltransferase (ChAT) activity, somatostatin content and glucose metabolism in the rat brain. QUIN (12 and 60 nmol) i.cv administration once a day for 7 days (total dose; 84 and 420 nmol, respectively) had minimal effect on somatostatin content and no effect on ChAT activity. In contrast, following continuous i.cv infusion of QUIN for 14 days using an osmotic minipump (480 nmol), ChAT activity dropped in the hippocampus and the striatum and somatostatin content was reduced in the frontal cortex, hippocampus, striatum and amygdala. Moreover, following the QUIN infusion, glucose utilization decreased in the basal nucleus of Meynert, frontal cortex, and portions of the basal ganglia and the limbic system. These results indicate that subchronic i.cv infusion of QUIN to rats results in selective regional neurochemical and metabolic changes distributed throughout the CNS. These results suggest target brain areas and transmitter systems which may be associated with neurologic syndromes characterized by elevated CSF QUIN levels.

Animals↗

Heparin-binding activity of feline herpesvirus type 1 glycoproteins.

Feline herpesvirus type 1 (FHV-1) possesses a very narrow host range, but the mechanism of its infection has not yet been analyzed. Heparan sulfate on the cell surface serves as a receptor for several herpesviruses. In this study, we determined that infection of FHV-1 is inhibited by addition of soluble heparin in cells cultures. Using heparin-affinity column, it was shown that FHV-1 gC is a major heparin-binding protein, and FHV-1 gB weakly binds to heparin, but FHV-1 gD does not. Furthermore, the FHV-1 gC expressed in insect cells can also bind to heparin despite of being immature glycosylation. Our results suggested that FHV-1 gC can bind to heparin as observed in other herpesviruses and that glycosylation of the gC does not affect its heparin-binding activity. In addition, mice immunized with the gC expressed in insect cells produced complement-dependent virus-neutralizing antibody.

Alphaherpesvirinae↗

The sensitivity of biological tissue to ultrasound.

Mammalian tissues have differing sensitivities to damage by physical agents such as ultrasound. This article evaluates the scientific data in terms of known physical mechanisms of interaction and the impact on pre- and postnatal tissues. Actively dividing cells of the embryonic and fetal central nervous system are most readily disturbed. As a diagnostic ultrasound beam envelopes a small volume of tissue, it is possible that the effects of mild disturbance may not be detected unless major neural pathways are involved. There is evidence that ultrasound can be detected by the central nervous system; however, this does not necessarily imply that the bioeffect is hazardous to the fetus. Biologically significant temperature increases can occur at or near to bone in the fetus from the second trimester, if the beam is held stationary for more than 30 s in some pulsed Doppler applications. In this way, sensory organs that are encased in bone may be susceptible to heating by conduction. Reports in animals and humans of retarded growth and development following frequent exposures to diagnostic ultrasound, in the absence of significant heating, are difficult to explain from the current knowledge of ultrasound mechanisms. There is no evidence of cavitation effects occurring in the soft tissues of the fetus when exposed to diagnostic ultrasound; however, the possibility exists that such effects may be enhanced by the introduction of echo-contrast agents.

Animals↗

Comparison of the melanogenesis in human black and light brown melanocytes.

We examined how and to what extent the constitution of melanin and the expression, as well as the activity, of melanosomal proteins influence the production of melanin pigment by human black and light brown melanocytes, Mel (b) cells and Mel (l) cells, respectively. Melanin pigment in Mel (b) and Mel (l) cells consisted of a mixture of eumelanin and pheomelanin, and Mel (b) cells contained a larger amount. The signal intensity ratio of eumelanin to pheomelanin was similar in both cell types, though the two cell types differed in appearance. Tyrosinase activity and the amount of tyrosinase-related protein (TRP-1) of Mel (b) cells were higher than those of Mel (l) cells. Dopachrome tautomerase (DCT) activity and the amount of 6H5MICA were reduced in Mel (b) cells in comparison with Mel (l) cells. No significant difference in DHICA-converting activity or catechol-O-methyltransferase activity was found between Mel (b) and Mel (l) cells. There was no correlation between DHICA-converting activity and amount of TRP-1. These results suggest that the difference in the pigmentation of the two human melanocyte cell lines, Mel (b) and Mel (l), is derived from differences in the activity and expression of tyrosinase, TRP-1 and DCT, which affect the content and constitution of melanin polymers.

Asian People↗

Galactosamine-induced apoptosis in the primary mouse hepatocyte cultures.

Galactosamine (GalN)-induced apoptosis was investigated in cultured hepatocytes from mice. The percentage of fragmented DNA measured by the ELISA method increased in a concentration-dependent manner from the very early stage, i.e. 0.5 hrs, after GalN-exposure. In addition, a ladder-like fragmentation pattern by agarose gel electrophoresis appeared first at 3 hr-exposure to 20 mM GalN, at 6 hr-exposure to 10 mM GalN and at 12 hr-exposure to 5 mM GalN, respectively. On the other hand, cytotoxicity indicated by leakage of lactate dehydrogenase from cultured hepatocytes to culture medium was first detected at 24 hrs after GalN-treatment. Morphologically, formation of blebs and apoptotic bodies was observed from 12 hr-exposure to 20 mM GalN and from 24 hr-exposure to 10 mM GalN, respectively. Thus GalN could induce apoptosis in primary hepatocyte cultures from mice.

Animals↗

Identification and DNA sequence analysis of the Marek's disease virus serotype 2 genes homologous to the thymidine kinase and UL24 genes of herpes simplex virus type 1.

The thymidine kinase (TK) gene has been used as a safe and convenient locus for expression of heterologous proteins in some alphaherpesviruses including herpesvirus of turkeys (HVT) antigenically related to Marek's disease virus (MDV) serotypes 1 (MDV1) and 2 (MDV2). In MDV2 strain HPRS 24 genome, genes equivalent to the TK and UL24 homologues of herpes simplex virus type 1 were identified and sequenced. The MDV2 UL24 gene overlaps the 5' end of the TK gene in a head-to-head orientation. The predicted region encoding for the MDV2 TK gene is 1,056 nucleotides, corresponding to a polypeptide of 352 amino acids in length. Putative nucleotide- and thymidine-binding sites were identified within the predicted amino acid sequence. The predicted region encoding for the UL24 gene is 948 nucleotides, corresponding to a polypeptide of 316 amino acids in length. By northern blot analyses using MDV2 TK- and UL24-specific DNA probes, four transcripts of approximately 7.8, 5.0, 3.5, and 1.1 kb for the TK gene, and a transcript of 3.8 kb for the UL24 gene were detected in MDV2-infected cells. Alignment of the amino acid sequence of MDV2 TK homologue with those published for TK homologues of other MDV serotypes showed 73.9% (MDV1 vs. MDV2), 58.2% (MDV1 vs. HVT), and 56.8% (MDV2 vs. HVT) identities. Comparison to other alphaherpesvirus TK homologues revealed amino acid sequence homologies varying from 34.5% to 27.8%. The putative MDV2 UL24 homologous protein had identity with the well conserved five motifs among alphaherpesviruses.

Amino Acid Sequence↗

Identification and characterization of the feline herpesvirus type 1 glycoprotein C gene.

The feline herpesvirus type 1 (FHV-1) gene encoding glycoprotein C (gC) has been sequenced and identified based on its genomic location and comparative analysis to other alphaherpesvirus gCs, and the expressed gC protein was also identified by using specific monoclonal antibodies. The FHV-1 gC gene was located within a 7.0 kbp EcoRI fragment, and was 1602 bp in length. The amino acid sequence deduced from the nucleotide sequence was predicted to encode a membrane glycoprotein containing a characteristic N-terminal hydrophobic signal sequence, nine potential N-linked glycosylation sites, and C-terminal transmembrane and cytoplasmic domains. The FHV-1 gC was expressed in COS-7 cells. When flowcytometric analysis was carried out, the gC expressed in COS-7 cells reacted with a panel of monoclonal antibodies against gp113: By immunoprecipitation analysis, the gC expressed in COS-7 cells possessed molecular masses of 125-150 kilodalton, and was similar in size to that in FHV-1-infected CRFK cells.

Alphaherpesvirinae↗

lpr T cells have lower ability to maintain bcl-2 expression ex vivo.

Autoimmune-prone lpr mice develop lymphoproliferative disorders, whereas their lymphocytes show accelerated apoptosis in culture. To elucidate whether the bcl-2 protein, a repressor of apoptosis, is critical to the discrepancy between in vivo and in vitro survival, we examined bcl-2 expression in T cells from +/+ and lpr mice during culture. The expression levels of bcl-2 in cultured T cells from lpr mice were significantly down-modulated compared to those from +/+ mice and freshly obtained T cells. Besides, the reduction of bcl-2 protein levels was inhibited in T cells cultured in the presence of T cell receptor (TCR) signalling. These results suggest that lpr T cells might be susceptible to apoptosis in vitro due to down-modulation of bcl-2 by withdrawal of TCR signalling.

Journal Article↗

Loss of p21WAF1/CIP1 expression correlates with disease progression in gastric carcinoma.

Previous studies have shown that tumour-suppressor genes play an important role in the progression of solid tumours. Recently, the p21WAF1/CIP1 tumour-suppressor protein has been reported to work as a critical downstream effector of p53 and a potent inhibitor of cyclin-dependent kinases. Thus, the p21WAF1/CIP1 gene is thought to play a central role in tumour suppression. In this study we investigated p21 protein expression in gastric carcinomas. A total of 172 primary gastric carcinoma specimens were immunohistochemically stained for p21 protein expression. Correlations between p21 expression and clinicopathological features were examined. Loss of p21 expression was observed in 104 of 172 tumour tissues (60.4%), and the frequency of p21 loss increased as the stage progressed. Expression of p21 in the primary tumour was frequently lost in patients with either lymph node, liver or peritoneal metastases as compared with patients without metastases. In patients with p21-negative tumours, the risk of recurrence following curative surgery was significantly higher, and the prognosis was significantly poorer than in patients with p21-positive tumours. Loss of p21 expression in primary gastric carcinoma correlates with disease progression. The status of p21 gene expression may have prognostic value in this disease.

Adult↗

Clearance of pentosidine, an advanced glycation end product, by different modalities of renal replacement therapy.

We recently demonstrated that pentosidine, an advanced glycation end product, accumulates markedly as albumin-linked form (Palb) and in free-form (Pfree) in the plasma of patients with end-stage renal failure. The present study was undertaken to examine the clearance of Palb and Pfree by different modalities of renal replacement therapy, that is, hemodialysis (HD), continuous ambulatory peritoneal dialysis (CAPD), and renal transplantation. HD cleared Pfree (9.4 +/- 4.3 nmol/kg/HD) but not Palb, by diffusion but not by membrane adsorption, whereas CAPD cleared both Palb (4.03 +/- 2.01 nmol/kg/day) and Pfree (2.43 +/- 1.24 nmol/kg/day). Plasma total pentosidine levels were significantly (P < 0.05) lower in CAPD (0.97 +/- 0.41 nmol/ml) than in HD (1.19 +/- 0.41 nmol/ml), as the result of a lower serum albumin level in the former patients. Indeed, Palb expressed per mg albumin was virtually identical in HD and CAPD. By contrast, Pfree was significantly lower in CAPD than in HD. Palb levels were significantly correlated with plasma Pfree levels in both HD and CAPD patients, but not in the CAPD dialysate. Pentosidine transport across the peritoneum occurs mainly by diffusion, both as Palb and Pfree. Interestingly, peritoneal Palb clearance (0.17 +/- 0.07 ml/min) significantly (P < 0.00001) exceeded albumin clearance (0.11 +/- 0.05 ml/min). Palb levels being significantly higher (P < 0.0005) in the peritoneal fluid (36.28 +/- 18.55 pmol/mg) than in the serum (27.12 +/- 11.71 pmol/mg), thus raises the possibility of a facilitated diffusion of Palb or an active transport mechanism for protein-linked pentosidine into the peritoneal cavity. After renal transplantation, plasma Pfree fell rapidly, remained barely detectable after one month, and returned to normal at six months. By contrast, Palb fell more slowly and remained significantly above normal at six months, but returned eventually to normal levels. These findings demonstrate that: (1) both HD and CAPD remove Pfree; (2) the peritoneal clearance of Palb, might contribute to the lower level of plasma pentosidine in CAPD than in HD patients; and (3) renal transplantation is the best therapeutic modality to normalize both Palb and Pfree levels.

Adult↗

Implication of an increased oxidative stress in the formation of advanced glycation end products in patients with end-stage renal failure.

Recent studies have demonstrated a marked increase in the level of advanced glycation end products (AGEs) in the plasma, skin and amyloid fibrils of hemodialysis (HD) patients. The presence of AGEs in (beta2m) forming amyloid fibrils has been established in a previous immunochemical study relying on a monoclonal anti-AGE antibody. In the present study, Western blot analysis and immunohistochemistry reveal that the epitope recognized by this antibody is N epsilon-(carboxymethyl)lysine (CML) and that CML is one of the AGE structures present in amyloid fibrils. Thus, two AGE structures, CML and pentosidine, are now recognized in dialysis-related amyloidosis. AGE accumulation in uremia is not accounted for by elevated glucose levels. Since CML and pentosidine formation are closely linked to oxidative processes, we tested the hypothesis that a high oxidative stress enhanced AGE formation in HD patients. We focused on ascorbic acid (AA) because AA is easily oxidized under oxidative stress and its oxidized form (oxiAA) is a source of CML and pentosidine. In vitro incubation of beta2m with AA under atmospheric oxygen resulted in: (1) the rapid appearance of characteristic physicochemical properties of AGEs (brown color, fluorescence, polymerization tendency); (2) the transformation of beta2m into AGE-modified beta2m recognized by a specific monoclonal antibody; and (3) the accelerated formation of CML in beta2m and beta2m-peptide, recognized by mass spectrometry. A similar in vitro incubation of human serum albumin disclosed a parallel production of pentosidine measured by high-performance liquid chromatographic assay. In HD patients, the degree of AA oxidation, assessed as the ratio of oxiAA to total ascorbate, was more than twice as high as that of normal subjects (0.87 +/- 0.16 vs. 0.35 +/- 0.11, P < 0.0001), suggesting the presence of an increased oxidative stress. Interestingly, plasma level of oxiAA was correlated with the plasma levels of protein linked (P < 0.01, r2 = 0.25) and free (P < 0.05, r2 = 0.22) pentosidine. Altogether these results demonstrate that AGE, that is, CML and pentosidine, production is accelerated under oxidative stress, even in the absence of glucose. They suggest that, in uremia, CML and pentosidine production is determined both by an increased oxidative stress and the availability of precursors such as oxiAA. Finally, both CML and pentosidine contribute to the AGEs present in dialysis-related amyloid fibrils.

Amino Acid Sequence↗

In vivo transfection of cis element "decoy" against nuclear factor-kappaB binding site prevents myocardial infarction.

The transcriptional factor nuclear factor-kappaB (NFkappaB) plays a pivotal role in the coordinated transactivation of cytokine and adhesion molecule genes that might be involved in myocardial damage after ischemia and reperfusion. Therefore, we hypothesized that synthetic double-stranded DNA with high affinity for NFkappaB could be introduced in vivo as "decoy" cis elements to bind the transcriptional factor and to block the activation of genes mediating myocardial infarction, thus providing effective therapy for myocardial infarction. Treatment before and after infarction by transfection of NFkappaB decoy, but not scrambled decoy, oligodeoxynucleotides before coronary artery occlusion or immediately after reperfusion had a significant inhibitory effect on the area of infarction. Here, we report the first successful in vivo transfer of NFkappaB decoy oligodeoxynucleotides to reduce the extent of myocardial infarction following reperfusion, providing a new therapeutic strategy for myocardial infarction.

Animals↗

Inhibitory effects of interleukin-10 on synovial cells of rheumatoid arthritis.

This paper describes the immunoregulatory effects of interleukin-10 (IL-10) on synovial cells in vitro. Synovial cells were cultured with IL-10 in the presence or absence of various cytokines. Following incubation, the costimulatory molecule expression on synovial cells and cytokine production in culture supernatants were analysed by an indirect immunofluorescence method and enzyme-linked immunosorbent assay, respectively. We also examined the effect of IL-10 on the function of synovial cells as antigen-presenting cells (APC). Synovial cells spontaneously express several kinds of costimulatory molecule and produce various kinds of cytokines. Stimulation of synovial cells with interferon-gamma (IFN-gamma), IL-1 beta, or 12-O-tetradecanoyl phorbol 13-acetate (TPA) markedly enhanced the expression of costimulatory molecules and cytokine production of these cells. Both spontaneous and up-regulated costimulatory molecule expression and cytokine production were significantly suppressed by the addition of IL-10. Autologous T-cell proliferation was stimulated by purified protein derivative (PPD) in IFN-gamma-treated synovial cells and treatment of these synovial cells with IL-10 also suppressed T-cell proliferation. Our results suggest that IL-10 has an inhibitory effect on synovial cells and is an important immunoregulatory component of the cytokine network in rheumatoid arthritis.

Arthritis, Rheumatoid↗

Growth hormone-releasing hormone (GHRH)-GH-somatic growth and luteinizing hormone (LH)RH-LH-ovarian axes in adult female transgenic mice expressing human GH gene.

We have examined alterations in the hypothalamo-pituitary GH-somatic growth axis and the hypothalamo-pituitary LH-ovarian axis in a line of transgenic ICR mice expressing human GH (hGH) under the influence of the whey acid protein promoter. Transgenic female mice weighed twice as much as control females and were infertile. The size of the anterior pituitary (AP) was 1/3 that of the controls. In transgenic mice, acinar cells in the mammary and mandibular glands displayed hGH-immunoreactivity, and plasma hGH was detected by radioimmunoassay. In the medial basal hypothalamus (MBH) of transgenic females, the immunoreactive-GHRH level was decreased (P<0.01). There was a corresponding reduction in the number of GHRH-immunoreactive neurons in the arcuate nucleus (ARC) and in the immunostaining of GHRH nerve terminals in the median eminence. The level of somatostatin (SRIH) in the MBH was increased (P<0.05), and SRIH-immunoreactive neurons in the periventricular nucleus (PeV) were increased in size and number in transgenic mice. The MBH level of LHRH in transgenic animals was greater (P<0.01) than in controls, although there was no apparent difference in the number of LHRH-immunoreactive neurons or in LHRH level in the preoptic area. There are fewer SRIH- and LHRH-immunoreactive neurons in the ARC in transgenic mice. Cells in the AP for GH, PRL, and LH were fewer in transgenic mice. The ovary suffered disturbance of follicular development and of corpora lutea formation. These results demonstrate that chronic overproduction of hGH may profoundly affect the organization of the GHRH/SRIH-GH-somatic growth axis and the LHRH-LH-ovarian axis due to reduction of GHRH-, SRIH- and LHRH-neurons in the ARC and increase of SRIH-neurons in the PeV.

Animals↗

Early diagnosis of mucosal squamous cell carcinoma of the esophagus: including two interesting cases of superficial spreading-type and multicentric-type squamous cell carcinomas.

We reviewed 10 patients with esophageal mucosal carcinoma in order to improve the early diagnosis of the disease. Histologically seven of the 14 lesions were carcinomas in situ (epithelial cancer), and the other seven lesions were carcinomas confined to the mucosa other than epithelial cancer (muscularis mucosae cancer), all 14 lesions were squamous cell carcinomas (SCC). One of these seven mucosal SCC, which demonstrated an extensive spreading-type SCC in which the size of the SCC was 7 cm long while extending entirely around the esophageal lumen in circumferential spread, is described in detail, and multiple epithelial cancers existed separately in one case. Eleven lesions diagnosed before operation showed abnormal findings on conventional endoscopy regardless of the size and depth of transmural invasion. An additional lesion was visible with dye endoscopy as an unstained area, but it was not visible with radiography or conventional endoscopy. Dye endoscopy using Lugol solution is very important because it allows detection and evaluation of the extent of esophageal mucosal cancer.

Aged↗