Biomedical subjects

Y Abe

Publications and source records attributed to Y Abe.

At least 307 records · Page 17Linked to original sources

PubMed1998

Polymorphism in the Ialpha1 germ-line transcript regulatory region and IgA productivity in patients with IgA nephropathy.

Enhanced in vivo and in vitro production of IgA has been reported in patients with IgA nephropathy (IgAN) and their family members. It is generally considered that IgA1 is a prominent subclass of IgA in IgAN. Although genetic mechanisms of IgA class switch recombination in IgAN have been studied enthusiastically, the critical factors that induce IgA1-specific class switching in IgAN have yet to be elucidated. A large body of data indicates that the germ-line transcript of Ig constant region (C(H)) genes that precedes actual class switching has regulatory effects on class switch recombination. To analyze structural abnormalities in the Ialpha1 germ-line transcript regulatory gene, a region about 1000 bp long located upstream of Ialpha1 exons was surveyed by the PCR-single strand conformation polymorphism method, and the polymorphism detected was confirmed by subsequent DNA sequencing. Three hot spots for point mutation were detected upstream of the promoter region of the Ialpha1 germ-line transcript, and the mutations were observed more frequently in patients than in controls. Patients with the mutations showed higher levels of serum IgA and higher in vitro IgA synthesis. In the luciferase assay, the regulatory gene with the mutations showed a potent effect for induction of the Ialpha1 germ-line transcript. The polymorphism in the Ialpha1 regulatory region possibly causes enhanced IgA production in some patients with IgAN.

Base Sequence↗

PubMed1998

Disulfide bond structure of human epidermal growth factor receptor.

The extracellular domain of the human epidermal growth factor receptor (sEGFR) consists of 621 amino acid residues, including 50 cysteines. The connections of the 25 disulfide bonds in the recombinant sEGFR protein, obtained from Chinese hamster ovary cells, have been determined using N-terminal sequencing and matrix-assisted laser desorption/ionization mass spectroscopy. We identified a basic repeat of eight cysteines with a 1-3, 2-4, 5-6, and 7-8 disulfide pairing pattern in the two cysteine-rich regions of sEGFR. By comparison to other cysteine-rich motifs, it was concluded that the cysteine-rich repeat of sEGFR belongs to the laminin-type EGR-like (LE) structural motif. Three-dimensional structure models of the two cysteine-rich regions have been built, based on the three-dimensional structures of the LE domains from the laminin gamma1 chain and secondary structure predictions for the EGF receptor.

Amino Acid Sequence↗

PubMed1998

Inhibition of tumor growth by ribozyme-mediated suppression of aberrant epidermal growth factor receptor gene expression.

BACKGROUND: Amplification and rearrangement of the epidermal growth factor receptor (EGFR) gene is frequently associated with malignant gliomas. One type of EGFR mutation in primary gliomas results in overexpression of an aberrant EGFR messenger RNA (mRNA) that lacks sequences of exons II through VI of the human EGFR gene. We observed that the aberrantly spliced EGFR mRNA contains a ribozyme cleavable sequence (5'-AAG GUA AUU-3') created by the joining of EGFR exon I to exon VII. We hypothesized that an appropriately designed ribozyme RNA could mediate site-specific cleavage of the aberrant EGFR mRNA and reduce the growth of aberrant EGFR-producing tumor cells. METHODS: We synthesized aberrant EGFR mRNA substrates and a sequence-specific hammerhead ribozyme (abEGFR-rib) to examine the ribozyme's activity in vitro. We also constructed an abEGFR-rib plasmid and introduced it into ERM5-1 cells, which are murine NIH3T3 cells transfected to express an aberrant EGFR complementary DNA. We measured the growth potential of the cotransfected cells in culture and in nude mice. RESULTS: The synthesized abEGFR-rib efficiently and specifically cleaved aberrant EGFR mRNA substrates in vitro. Expression of the transfected abEGFR-rib suppressed expression of aberrant EGFR mRNA in ERM5-1 cells and reduced the growth of tumors formed by the cotransfected cells in nude mice. Finally, the incorporation of bromodeoxyuridine, a measure of mitotic activity, was also decreased in abEGFR-rib-producing ERM5-1 cells in vivo. CONCLUSION: Ribozymes targeted to aberrant EGFR mRNA can inhibit the growth of tumors formed by cells that express this mRNA.

Animals↗

PubMed1998

Molecular cloning and functional expression of chicken luteinizing hormone receptor.

A complementary DNA for chicken luteinizing hormone (LH) receptor containing the entire coding region was isolated from chicken F1 granulosa cell cDNA library. Nucleotide sequence analysis revealed that there are characteristic GC-rich regions around the N-terminal part. Chicken LH receptor consists of a 19-residue signal peptide, a 366-residue extracellular domain, a 267-residue region containing seven transmembrane segments, and a 76-residue cytoplasmic C-terminal tail. The deduced amino acid sequence of the chicken LH receptor shares 67%, 69%, and 69% identity with the human, rat and porcine LH receptor sequences, respectively, and 51% with chicken FSH receptor. However, an insertion of about 30 amino acid residues is found in chicken LH receptor in the extracellular domain about 44 amino acid residues upstream of the first transmembrane segment. In addition, alternative splicing seems likely to occur at the point where the insertion starts (nucleotide position 933), resulting in the truncated forms of chicken LH receptor with only the extracellular domain. Northern blot analysis revealed the presence of multiple transcripts of LH receptor, a major 3.0-kb and minor 7-kb and 1.5-kb bands, in chicken F1 to F3 granulosa cells. The full length chicken LH receptor cDNA was transiently expressed in COS-7 cells and the transfected cells displayed a concentration-dependent increase in cAMP production when exposed to varying concentrations of chicken LH. This clearly indicates that the cloned cDNA encodes a functional chicken LH receptor protein.

Amino Acid Sequence↗

PubMed1998

Cloning and characterization of a novel endothelin receptor subtype in the avian class.

Endothelin 3 (EDN 3) and the endothelin receptor B (EDNRB) are involved in the development of neural crest and particularly of the melanocytes and the enteric nervous system. We reported previously that the avian EDNRB gene is expressed in the neural fold before crest cell migration and later on in all the neural crest derivatives except, at any developmental stage, in the melanocytic lineage. However, quail melanoblasts proliferate in response to EDN 3 stimulation in vitro. These observations prompted us to search for another type of endothelin receptor (EDNR). We report here the cloning by reverse transcriptase-PCR of an avian cDNA encoding a subtype of EDNR, which we have called EDNRB2, because its deduced amino acid sequence is more closely related to that of EDNRB than to either the mammalian EDNRA or to the Xenopus EDNRC. Its expression pattern differs from that of the "classical" avian EDNRB because it is strongly expressed in melanoblasts and melanocytes. EDNRB2 transcripts are also abundant in the liver and kidney. Our pharmacological studies showed that EDNRB2 binds with similar affinity to EDN 1, EDN 2, and EDN 3, further confirming that this receptor belongs to the B type, although it displays a low affinity for sarafotoxin-c, a known EDNRB-selective agonist.

Amino Acid Sequence↗

PubMed1998

Full-matrix least-squares refinement of lysozymes and analysis of anisotropic thermal motion.

Crystal structures of turkey egg lysozyme (TEL) and human lysozyme (HL) were refined by full-matrix least-squares method using anisotropic temperature factors. The refinement converged at the conventional R-values of 0.104 (TEL) and 0.115 (HL) for reflections with Fo > 0 to the resolution of 1.12 A and 1.15 A, respectively. The estimated r.m.s. coordinate errors for protein atoms were 0.031 A (TEL) and 0.034 A (HL). The introduction of anisotropic temperature factors markedly reduced the R-value but did not significantly affect the main chain coordinates. The degree of anisotropy of atomic thermal motion has strong positive correlation with the square of distance from the molecular centroid. The ratio of the radial component of thermal ellipsoid to the r.m.s. magnitude of three principal components has negative correlation with the distance from the molecular centroid, suggesting the domination of libration rather than breathing motion. The TLS model was applied to elucidate the characteristics of the rigid-body motion. The TLS tensors were determined by the least-squares fit to observed temperature factors. The profile of the magnitude of reproduced temperature factors by the TLS method well fitted to that of observed B(eqv). However, considerable disagreement was observed in the shape and orientation of thermal ellipsoid for atoms with large temperature factors, indicating the large contribution of local motion. The upper estimate of the external motion, 67% (TEL) and 61% (HL) of B(eqv), was deduced from the plot of the magnitude of TLS tensors determined for main chain atoms which were grouped into shells according to the distance from the center of libration. In the external motion, the translational portion is predominant and the contribution of libration and screw motion is relatively small. The internal motion, estimated by subtracting the upper estimate of the external motion from the observed temperature factor, is very similar between TEL and HL in spite of the difference in 54 of 130 amino acid residues and in crystal packing, being suggested to reflect the intrinsic internal motion of chicken-type lysozymes.

Animals↗

PubMed1998

A novel class of orally active non-peptide bradykinin B2 receptor antagonists. 1. Construction of the basic framework.

A novel class of potent, selective, and orally active non-peptide bradykinin (BK) B2 receptor antagonists were designed and synthesized starting from 8-benzyloxyimidazo[1,2-a]pyridine derivative 2. The unique screening lead (2) was discovered by a two-step intentional random screening process, involving recognition of the relationship between BK and angiotensin II (Ang II) and the common structural features. Systematic chemical modification of 2 elucidated the structural requirements essential for B2 binding affinity leading to the identification of 8-[[3-(N-acylglycyl-N-methylamino)-2,6-dichlorobenzyl]oxy]-3-halo- 2- methylimidazo[1,2-a]pyridine skeleton as the basic framework of this new series of B2 antagonists. A molecular modeling study suggested the key role of the N-methylanilide moiety at the 3-position of the 2,6-dichlorobenzene ring to allow these compounds to adopt the characteristic active conformation. The representative lead compounds inhibited the specific binding of [3H]BK to guinea pig ileum membrane preparations expressing B2 receptors, with nanomolar IC50S and also displayed in vivo functional antagonistic activities against BK-induced bronchoconstriction in guinea pigs at an oral dose of 1 mg/kg. Pharmacokinetic studies of compounds 47c and 50b in rats highlighted their excellent oral bioavailabilities, indicating that they represent the first orally active non-peptide B2 antagonists reported to date.

Administration, Oral↗

PubMed1998

Nonspecific and immune-specific up-regulation of cytokines in rabbit dermal tuberculous (BCG) lesions.

To our knowledge, this is the first sequential study of cytokines in tissue sections of developing and healing tuberculous (BCG) lesions. In situ hybridization, immunohistochemical, and RT-PCR techniques were used. Cytokine mRNAs showed a biphasic pattern. The percentage of mononuclear cells (MN) containing IL-1beta, TNF-alpha, MCP-1, and IL-8 mRNAs was highest in 1- to 3-day lesions, apparently because of the nonspecific inflammatory response caused by the tubercle bacilli in the BCG vaccine. At 5 days, this percentage was significantly reduced. With IFN-gamma, the peak and trough were delayed by 2 days. By 9 days, the percentage of MN containing the mRNAs of all five cytokines had again increased and the rabbits had become tuberculin-positive. In general, MCP-1 and TNF-alpha proteins and the vascular adhesion molecules, ICAM, VCAM, and perhaps ELAM, peaked at about 3 days. Many mononuclear cells surrounding the central areas of solid and liquefied caseous necrosis contained chemokine IL-8 mRNA. IL-8 is known to attract PMN, and PMN were present nearby. In contrast, MN containing chemokine MCP-1 mRNA were present more peripherally in areas rich in macrophages and lymphocytes. The early nonspecific cytokine response seems to be an adjuvant effect of the mycobacteria in BCG vaccine in that it causes a rapid entry of macrophages, lymphocytes, granulocytes, and probably dendritic cells into local sites of antigen deposition. This effect should be considered in developing improved vaccines for the prevention of tuberculosis, because BCG vaccines producing a strong early cytokine response should be more immunogenic than BCG vaccines with similar antigens producing a weak response.

Animals↗

PubMed1998

Somatosensory homunculus as drawn by MEG.

We studied a detailed somatosensory representation map of the human primary somatosensory cortex using magnetoencephalography. Somatosensory-evoked magnetic fields following tactile stimulation of multiple points in the right hemibody (including the tongue, lips, fingers, arm, trunk, leg, and foot) were analyzed in five normal subjects. We were able to estimate equivalent current dipoles (ECDs) following stimulation of the tongue, lips, fingers, palm, forearm, elbow, upper arm, and toes in most subjects and those following the stimulation of the chest, ankle, and thigh in one subject. The ECDs were located in the postcentral gyrus and generally arranged in order along the central sulcus, which is compatible with the somatosensory "homunculus." Linear distances, averaged in five subjects, from the receptive area of the thumb to that of the tongue, little finger, forearm, upper arm, and toes were estimated to be 2.42 +/- 0.28, 1.25 +/- 0.28, 2.21 +/- 0.72, 2.75 +/- 0.63, and 5.29 +/- 0.48 cm, respectively. The moment of each ECD, which suggested the size of the cortical areas responsive to the stimulation, was also compatible with the bizarre proportion of the homunculus with a large tongue, lips, and fingers. According to these results, we were able to reproduce a large part of the somatosensory homunculus quantitatively on an individual brain MRI.

Brain Mapping↗

PubMed1998

Pathological Analysis of the Radial and Internal Thoracic Artery.

To evaluate the usefulness of the radial artery (RA) as a graft material for coronary artery bypass grafting (CABG), histologic studies of the RA were performed and compared with the internal thoracic artery (ITA). Specimens were obtained from both ends of 12 RAs and the distal side of the ITA during the operation. The degree of arteriosclerosis was evaluated using an NIH Image 1.57 system. The pathological index of arterioslerotic change was expressed as the ratio of cross-section (Rx: internal luminal area/tunica media area). The mean arteriosclerotic ratio (Rx) of the 12 proximal sides of the RA specimens was 0.18 +/- 0.03, the 12 distal sides 0.27 +/- 0.17, and the 12 ITAs was 0.14 +/- 0.05, respectively. There was significant difference between the distal side of the RA and the ITA. The distal side of the RA was a little greater than the proximal, but there was no significant difference between the proximal side of the RA and the ITA. From the microscopic findings, the tunica media of the RA is poor in elastic fibers and rich in smooth muscle cells compared with the ITA. The internal elastic lumina of the RA is developed as well as the ITA, but more calcification was found in the distal RA than in the others. According to these results, although care must be taken for arteriosclerosis of the distal RA, it can be expected to be a suitable bypass material for CABG.

Journal Article↗

PubMed1998

Multifocal clear cell meningioma in the spine: a case report.

Clear cell meningioma is a rare morphologic form of meningioma. This case report describes a very rare case of multifocal clear cell meningioma in the thoracic and lumbar spine. A 9 year old patient presented with back pain and popliteal pain, which were aggravated by trunk motion and knocking. Magnetic resonance imaging (MRI) suggested a meningioma at the L2 level. An intradural extramedural tumor attached to the cauda equina was surgically removed and pathological diagnosis was clear cell meningioma. The patient began to complain of back pain at the Th12 level 4 months postoperatively. Retrospective analysis of MRI before the first operation revealed the small tumors at Th12 and L5 levels; comparison with a new MRI showed the rapid growth in 4 months. Adjunctive surgical resection was carried out and the back pain disappeared. These tumors had the same pathological findings. In conclusion, in young patients with suggested meningioma in the lumar spine, clear cell meningioma should also be considered, and the possibility of multifocal occurrence and postoperative recurrence must be taken into account.

Age of Onset↗

PubMed1998

Composite glandular-neuroendocrine carcinoma of the hilar bile duct: report of a case.

We report herein an unusual case of a composite glandular-neuroendocrine carcinoma of the hilar bile duct. A 71-year-old Japanese woman was admitted to our hospital suffering from general fatigue, progressive jaundice, and a high fever. Computed tomography and angiography findings revealed a solid hypervascular mass in the hepatic hilus. Thus, a subsegmentectomy of the liver (S4, S5) and bile duct resection with lymph node dissection were performed. A tumor measuring 6.0 x 3.0 cm was found to be located in the bile duct of the hepatic hilus. Histologically, the tumor was composed of well-differentiated adenocarcinoma and small cell neuroendocrine carcinoma cells, with a histological transition between the two components. Grimelius' method revealed the presence of diffuse positive tumor cells in neuroendocrine carcinoma. The neuroendocrine tumor cells were also diffusely immunoreactive to chromogranin A. To the best of our knowledge, only 22 previous cases of composite glandular-neuroendocrine carcinoma in the biliary tract have been reported; however, this is the first case report of a clearly composite tumor of the hilar bile duct.

Adenocarcinoma↗

PubMed1998

Schwannoma of the penis: report of a case and review of the literature.

A case of schwannoma located in the penile shaft in a 65-year-old male is described. Special stain using S-100 immunoperoxidase was useful in establishing the diagnosis in this case. We reviewed the literature on penile schwannoma and focussed on the diagnosis of this rare ailment.

Aged↗

PubMed1998

Effect of subtotal thyroidectomy on natural history of ophthalmopathy in Graves' disease.

Graves' ophthalmopathy is a complex disease whose pathogenesis is thought to be autoimmune. The treatment of Graves' disease is considered to be related to the progression of Graves' ophthalmopathy. There have been no long-term prospective studies on the natural course of Graves' ophthalmopathy. In this study we assessed the influence of subtotal thyroidectomy on the outcome of Graves' ophthalmopathy, comparing it with that of radioactive iodine treatment. Altogether 287 untreated patients with Graves' disease referred to Ito hospital in 1989 were followed prospectively for 5 years. A group of 67 patients were treated with radioactive iodine, and 18 patients underwent surgery. Proptosis of the eyes was measured in all patients using Hertel's exophthalmometer. The mean value of proptosis in patients with untreated Graves' disease was 14. 8 +/- 0.2 mm (mean +/- SEM), and after 5 years it increased slightly to 15.0 +/- 0.2 mm. The mean changes of proptosis in patients treated surgically and patients given radioactive iodine were -0.01 +/- 0.22 and 0.93 +/- 0.28 mm, respectively (p < 0.05). In patients treated by subtotal thyroidectomy, ophthalmopathy did not change in 77.8%; it progressed in 5.6% and was alleviated in 16.7%. In patients treated with radioactive iodine, the ophthalmopathy did not change in 86.6%, progressed in 10.4%, and was alleviated in 3.0%. These findings indicate that surgery can be a better treatment than radioactive iodine for Graves' patients with ophthalmopathy.

Adult↗

PubMed1998

Surgical options for distal radial fractures: indications and limitations.

Distal radial fractures are common problems for the orthopedic surgeon, and various surgical treatments have been reported. However, each method has its indications, pitfalls, and limitations. It is important to select the appropriate procedure for the fracture pattern. We studied 115 consecutive patients including 45 patients with distal radial fractures treated with percutaneous pinning, 67 patients treated with external fixation, and 32 patients treated with assisted wrist arthroscopy. Percutaneous pinning was useful in extra-articular fractures and minimally comminuted intra-articular fractures, but was inadequate for patients with severe osteopenia and markedly comminuted intra-articular fractures. External fixation was indicated when intra-articular comminution was present. However, the dorsomedial fragment was often not reduced and maintained by this technique; additional pinning was needed to reduce this fragment. A dynamic-type fixator was feasible for younger patients who required early functional recovery. Arthroscopy provided accurate visualization of the wrist joint and the intra-articular fracture.

Adult↗

PubMed1998

Alterations in tumour suppressor gene p53 correlate with inhibition of thrombospondin-1 gene expression in colon cancer cells.

If activation of the p53 gene is involved in the progression or metastasis of colon cancer, it may affect the angiogenic phenotype in vivo. To verify this hypothesis, we studied the correlation between p53 accumulation and expression of thrombospondin-1 (TSP1) in colon cancer specimens. Levels of TSP1 gene expression were estimated by Northern blotting in 65 colon cancers. Accumulation of p53 and the distribution of TSP1 protein were evaluated immunohistochemically. Various levels of TSP1 gene expression were seen in colon cancers, while p53 accumulation was confirmed in 42 of the 65 colon cancers. The level of TSP1 gene expression demonstrated a significant inverse correlation with p53 accumulation in colon cancer. Colon cancer cells expressed TSP1 protein and p53 accumulation reciprocally in the same nests. These results suggest that alterations in the tumour suppressor gene p53 may inhibit TSP1 expression in colon cancer.

Adenocarcinoma↗

PubMed1998

Streptococcal and staphylococcal superantigen-induced lymphocytic arteritis in a local type experimental model: comparison with acute vasculitis in the Arthus reaction.

Many pathogenic bacteria produce superantigenic exotoxins. To study their pathogenetic role, in particular to test whether these toxins are able to induce vasculitis, we developed a local-type experimental model in rabbits. Toxins were injected along the intermediate auricular artery of the ear. The histology of ear skin, including the artery, was examined after single or repeated injections. Repeated injections of streptococcal erythrogenic toxins produced chronic-type arteritis characteristic of lymphocytic infiltration, whereas single injection induced no acute-type vasculitis. Staphylococcal enterotoxin B and toxic shock syndrome toxin-1 also induced the same type of arteritis, although weaker in degree. In human patients these lesions are similar to those of Kawasaki disease, a systemic vasculitis with unknown etiology. The Arthus reaction to human serum albumin in immunized rabbits included acute-type vasculitis similar to polyarteritis nodosa when examined in this model. Microvasculitis lesions similar to leukoclastic vasculitis were combined in the Arthus reaction but not in the superantigen-induced lesions. Our experimental model described here is widely applicable to the study of the etiology and pathogenesis of human diseases involving vasculitis lesions.

Animals↗

PubMed1998

Enteric absorption of FK 506: estimation by a block liver perfusion technique in rats.

This perfusion model enables a pharmacokinetic study of enteral absorption and hepatic metabolic rate simultaneously. FK 506 is absorbed mainly via the proximal small intestine and metabolized rapidly by the liver during single passage. These results may lead to further analyses of absorption and metabolism of FK 506 under various conditions.

Animals↗