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Biomedical subjects

M Go

Publications and source records attributed to M Go.

At least 37 records · Page 2Linked to original sources
PubMed1993

Evolutionary clustering and functional similarity of RNA-binding proteins.

RNA-binding proteins (RNPs) involved in splicing, processing and translation regulation contain one to four RNA-binding domains. We constructed a phylogenetic tree for the RNA-binding domains, including those of poly(A)-binding protein (PABP), splicing factors, chloroplast RNPs, hnRNPs, snRNP U1-70K, nucleolin and Drosophila sex determinants. Proteins with similar functions were found to have closely related RNA-binding domains and common domain organizations. In light of these observation, one can assume the function of an RNA-binding protein, based on the evolutionary relationship between its RNA-binding domain(s) and domain organization, as compared with other RNPs.

Animals↗
PubMed1993

Inositol 1,4,5-trisphosphate 3-kinase highest levels in the dendritic spines of cerebellar Purkinje cells and hippocampal CA1 pyramidal cells. A pre- and post-embedding immunoelectron microscopic study.

Inositol 1,4,5-trisphosphate 3-kinase (InsP3 3-kinase) plays a crucial role in calcium homeostasis by regulating InsP3 levels. We have reported the highest concentrations of InsP3 3-kinase in the dendrites of cerebellar Purkinje cells and hippocampal pyramidal cells of the CA1 sector of the Ammon's horn. We here investigate its subcellular localization by pre- and post-embedding immunoelectron microscopic study. In both populations of neurons, the major structure expressing a high level of InsP3 3-kinase is the dendritic spines.

Animals↗
PubMed1993

Protein anatomy: functional roles of barnase module.

Globular proteins are composed of several modules that are contiguous polypeptide segments of compact conformation. Module boundaries are closely correlated with the intron positions of genes that encode proteins. The modules may thus have a one-to-one correspondence with exons in primordial genes. They may also be vestiges of polypeptide segments that initially appeared as primordial proteins in prebiological evolution. Clarification as to whether modules disconnected from one another have functional potentiality may validate these possibilities. Thus, in this study, each module of a protein was synthesized and assessed for functional potentiality. For this purpose, barnase, a bacterial ribonuclease, was decomposed into six modules (M1-M6), which were examined to determine whether they have an affinity for RNA and RNase activity. M2, M3, and M6, all of which form a shallow but wide cavity for RNA binding in native barnase, were found to bind to RNA and to possess RNase activity. However, M1 and M5, which support the other modules from the back side, and M4 did not bind to RNA and had no RNase activity. Protein modules with catalytic functions are described in this paper for the first time. That some modules of barnase possess catalytic activity indicates that protein modules may possibly have functioned as primitive catalysts in prebiological evolution.

Amino Acid Sequence↗
PubMed1993

Protein anatomy: spontaneous formation of filamentous helical structures from the N-terminal module of barnase.

This paper reports the conformation of the N-terminal module (24 amino acid residues) of barnase in aqueous solution. This module contains the first of three helices in the intact protein. Circular dichroism spectra showed the peptide fragment to have a predominantly random coil structure immediately following dissolution in aqueous solution and to be gradually converted to a helical structure at 5 degrees C. This was mediated by aggregation, and an electron micrograph indicated the aggregate to be comprised of filamentous helical structures. Scanning tunneling microscopy showed the filamentous structures to be made up of protofilamentous structures containing many disks apparently stacked on top of each other. A monomer of the peptide predominantly took on a random coil conformation in aqueous solution and the multimer, a stable helical structure. A local amino acid sequence would thus appear to determine the secondary structure corresponding to that in a native protein but stability to be governed by other factors such as tertiary interactions. Helical wheel representation indicated the peptide fragment to have the features of an amphiphilic helix. Hydrophobic burial may provide the driving force for producing a stable helical structure in aqueous solution.

Amino Acid Sequence↗
PubMed1993

Secondary structural features of modules M2 and M3 of barnase in solution by NMR experiment and distance geometry calculation.

Proteins consist of structural units such as globular domains, secondary structures, and modules. Modules were originally defined by partitioning a globular domain into compact regions, each of which is a contiguous polypeptide segment having a compact conformation. Since modules show close correlations with the intron positions of genes, they are regarded as primordial polypeptide pieces encoded by exons and shuffled, leading to yield new combination of them in early biological evolution. Do modules maintain their native conformations in solution when they are excised at their boundaries? In order to find answers to this question, we have synthesized modules of barnase, one of the bacterial RNases, and studied the solution structures of modules M2 (amino acid residues 24-52) and M3 (52-73) by 2D NMR studies. Some local secondary structures, alpha-helix, and beta-turns in M2 and beta-turns in M3, were observed in the modules at the similar positions to those in the intact barnase but the overall state seems to be in a mixture of random and native conformations. The present result shows that the excised modules have propensity to form similar secondary structures to those of the intact barnase.

Amino Acid Sequence↗
PubMed1993

Localization of hydrogen-bonds within modules in barnase.

Proteins in eukaryotes are composed of structural units, each encoded by discrete exons. The protein module is one such structural unit; it has been defined as the least extended or the most compact contiguous segment in a globular domain. To elucidate roles of modules in protein evolution and folding, we examined roles of hydrogen bonds and hydrophobic cores, as related to the stability of these modules. For this purpose we studied barnase, a bacterial RNase from Bacillus amylolique-faciens. Barnase is decomposed into at least six modules, M1-M6; the module boundaries are identified at amino acid residues 24, 52, 73, 88, and 98. Hydrogen bonds are localized mainly within each of the modules, with only a few between them, thereby indicating that their locations are designed to primarily stabilize each individual module. To obtain support for this notion, an analysis was made of hypothetical modules defined as segments starting at a center of one module and ending at the center of the following one. We found that the hydrogen bonds did not localize in each hypothetical module and that many formed between the hypothetical modules. The native conformations of modules of barnase may be specified predominantly by interactions within the modules.

Algorithms↗
PubMed1993

Long-term impact of conservative management on localized prostate cancer. A twenty-year experience in Japan.

The clinical outcome of 107 patients with localized prostate cancers over the past twenty years was analyzed retrospectively. Immediate endocrine therapy was administered in 55 patients after diagnosis. The other group of 52 patients did not receive any anti-tumor treatment until progression. Overall, 22 patients (21%) died of prostate cancer, while 45 (42%) died of other known causes. During a mean observation period of thirty-seven months, 27 (25%) experienced progression of the disease (local in 9, distant metastasis in 25, and both in 7 patients). The cancer-specific survival rates for these 107 patients were 78 percent at five years and 71 percent at ten years. The timing of endocrine therapy and age at diagnosis did not influence patient's prognosis. Tumor stage failed to demonstrate any prognostic significance after being controlled for other factors including tumor grade. Poorly differentiated histology appeared to be the sole and the strongest predictor for both tumor progression and cancer death. Prostate cancer may not differ significantly among races once it becomes clinically manifest. Expectant management for localized prostate cancer in well and moderately differentiated cancer may be justified because of the higher probability of dying of other intercurrent causes especially in the elderly group of patients. However, definitive forms of therapy should be considered for the group of patients with poorly differentiated tumor who have reasonably long life expectancy.

Age Factors↗
PubMed1993

Repeat of a helix-turn-helix module in DNA-binding proteins.

Helix-turn-helix motif is one of the common motifs observed in DNA-binding proteins. The motif interacts with DNA double helix and recognizes specific base sequences. It is assumed that the helix-turn-helix motif appears only once in seven prokaryotic transcriptional repressors of which 3-D structures have been determined by X-ray crystallographic studies. These prokaryotic repressors consist of several alpha-helices connected with turns. We report here that these repressors are decomposable into helix-turn-helix modules and their connectors. A module is defined as a compact structural unit with consecutive amino acid residues in a globular protein. Each of the helix-turn-helix motifs in the seven proteins corresponds approximately to a single helix-turn-helix module consisting of approximately 13 amino acids. Identification of modules of seven prokaryotic repressors and comparisons of their tertiary structures led to the conclusion that three of these DNA-binding proteins contain more than one helix-turn-helix module with a structure similar to the helix-turn-helix motif. The difference in module organization of these DNA-binding proteins paves the way for further classification of the DNA-binding proteins with the helix-turn-helix motif. The structural repertoire of these transcriptional regulators was increased through different utilizations in the number of helix-turn-helix and other modules. The difference in DNA base recognition ability in these helix-turn-helix modules is ascribed to a difference in size of a side chain at the fifth residue from Gly, on the turn.

Amino Acid Sequence↗
PubMed1993

15-Deoxyspergualin "rescue therapy" for methylprednisolone-resistant rejection of renal transplants as compared with anti-T cell monoclonal antibody (OKT3).

A randomized trial with OKT3, an anti-T cell monoclonal antibody or with 15-deoxyspergualin against methylprednisolone-resistant rejection crisis was performed in 25 posttransplant patients immunosuppressed with prednisolone and cyclosporine. At least temporary reversal of rejection was observed in 58.3% of patients treated with 15-deoxyspergualin. This reversal rate may be quite comparable to 61.5% seen in patients treated with OKT3. Adverse effects with 15-deoxyspergualin were related to bone marrow suppression, while those with OKT3 were pyrexia, gastrointestinal symptoms, and herpes infection. In contrast to OKT3, which may act by modulating T cell surface antigen, 15-deoxyspergualin may be effective somewhere in the later stages of the rejection cascade.

Adult↗
PubMed1993

[Immunohistochemical study of proteoglycans and collagens in the mouse cochlear duct].

Immunohistochemical studies of proteoglycans and collagens (type I and type IV) in the cochlear duct, and of the effects of cisplatin (CDDP), were performed. In cells of the organ of Corti and in the middle layer of the stria vascularis, heparan sulfate proteoglycan (HSPG) and collagens (type I and IV) or collagen-like substances were found. HSPG in these locations appeared to play important roles in the production of auditory sense. The tectorial membrane contained HSPG and collagens (type I and IV). However, no data supporting the concept that elements of the tectorial membrane are derived from interdental cells was obtained. In the basilar membrane, no HSPG, chondroitin sulfate (Chs), or collagens (type I and IV) were detected. The unique structures containing these substances reacted strongly with anti-HS (heparan sulfate), anti-HSPG-CP (core protein) and anti-collagen (type I and IV) antibodies that developed in the middle layer of the stria vascularis after the administration of CDDP. However, no change was observed in the tectorial membrane, the spiral prominence, the basilar membrane, or the spiral limbus. The decrease in HSPG in cells of the organ of Corti, and the changes in the stria vascularis, may help solve the well known contradiction between the severity of morphological damage and of the hardness of hearing.

Animals↗
PubMed1993

[Prognosis of incidental (stage A) prostatic cancer].

Incidentally discovered prostatic cancer can pursue a benign clinical course or it can rapidly progress. For the purpose of this study, we summarized pathological and clinical results of 107 (5.3%) stage A prostatic cancer patients in 2008 transurethral resection of the prostate for clinically diagnosed benign prostatic hyperplasia. For each patient, 3.9 slides, 13.6 tissue chips per slide and 52.5 tissue chips per patient (from 16 to 140 chips) were examined microscopically. The survival rates of patient with well, moderately and poorly differentiated groups were 62, 37 and 12% at 10 years, and those with Gleason score 2 to 4, 5 to 7 and 8 to 10 group were 63, 42 and 0% respectively. The survival rates in stage A1 (well differentiated or Gleason score 4 or less in less than 5% of the tissue removed during transurethral resection of the prostate) and stage A2 (anything other than stage A1) were 63 and 41% at 10 years, respectively. And cancer specific survival rates in stage A1 and stage A2 were 96% and 64% at 10 years, respectively. The number of cancer specific death were 1 in 30 (3.3%) in stage A1 group and 14 in 77 (18.2%) in stage A2 group. Our results indicated that tumors with low potential for aggressive behavior had a volume extent of less than 5% and a well differentiated group. Aggressive treatments should be recommended to all patients who were diagnosed stage A2 prostatic cancer.

Aged↗
PubMed1992

Identification of an amino acid residue involved in the substrate-binding site of rat liver uricase by site-directed mutagenesis.

Computer analysis has shown that a conserved amino acid sequence (Leu 160 to Lys 164) of rat liver uricase is also present in other enzymes with purine substrates. The significances of the amino acids in this sequence were studied by site-directed mutagenesis. Replacement of Lys 164 by Glu or Ile resulted in loss of uricase activity and decrease in binding of the competitive inhibitor xanthine. The far ultraviolet circular dichroic spectra of the mutant uricases were identical to that of the wild type protein, indicating that the replacement of Lys 164 by other amino acids did not result in serious modification of the conformation of uricase. These findings suggest that this amino acid is involved in the substrate-binding site of the enzyme.

Amino Acid Sequence↗
PubMed1992

Quantitative and qualitative changes of serum albumin in CAPD patients.

This study was conducted to assess quantitative and qualitative changes in serum albumin in CAPD patients. For twenty-six CAPD patients as well as age-, sex- and dialysis history-matched HD patients, biochemical and physiological parameters including urea kinetics were determined. Albumin was qualitatively evaluated by HPLC. The CAPD patients showed significant decreases in serum albumin and the reduced form of albumin accompanied by a lower protein catabolic rate(PCR) compared to the HD patients. Thirty five % of CAPD patients showed mild to moderate hypoalbuminemia, associated with a higher incidence of peritonitis and longer hospital stay. Patients with hypoalbuminemia had less of the reduced form of albumin. A weak positive correlation was found between serum albumin concentration and KT/V, and PCR. Thus, in CAPD patients, there occur quantitative and qualitative changes in serum albumin. Hypoalbuminemia may be a risk factor for peritonitis and is due in part to insufficient dialysis and protein intake. Intermolecular change in albumin may possibly be due to uremia per se.

Adult↗
PubMed1992

[Effect of angiotensin II(AII) on peritoneal transport during peritoneal dialysis in rat].

Ultrafiltration volume (UFV) in peritoneal dialysis is expressed as the difference between net transcapillary ultrafiltration (TCUF) and lymphatic absorption (LA) in peritoneal cavity. An increase in LA results in a decrease in UFV. Endogenous hormones may modulate peritoneal membrane permeability and LA. This study was conducted to assess the effect of angiotensin II(AII) on peritoneal permeability and LA in rat. Rats (BW, approximately 300g) with normal renal function were dialyzed for 4 hours using 30ml of hypertonic dialysate (dextrose concentration: 3.86%). AII was added in dialysate at the concentration of 10(-9)-10(-2) mol/30ml. Peritoneal membrane permeability and UFV were studied by clearance of urea N and inorganic phosphate, albumin excretion, glucose absorption and LA. LA was calculated by the concentration change of dextran 70 in dialysate. AII decreased UFV from 15.7 +/- 2.8ml/4hr(control) to 5.7 +/- 1.5(AII 10(-4) mol/dwell). LA was increased in a dose dependent fashion (ED50:0.25 x 10(-6)mol) with no change in TCUF and clearances of urea N and inorganic phosphate. Ten types of AII analogue were used to investigate the site of action for LA in 8 amino acids of AII. [beta-Asp1], [Val5], [Ile3, Val5] and [Sar1] AII showed agonistic action against LA. [Sar1, Thr8], [Sar1, Ile8], [Sar1, Leu8], [Sar1, Ala8], [Sar1, Val5, Ala8] and [Sar1, Gly8] AII had no effect on LA, which found the importance of the 8th amino acid of AII for LA. These actions of AII analogue against LA were similar to those for vascular smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1992

[A case of middle lobar bulla associated with severe bronchial asthma].

We experienced a case of middle lobar bulla associated with severe bronchial asthma. Bulla occurs favoritely at apical area and S6, and middle lobar bulla which is very rare has been reported to cause higher ventilatory disorder compared with superior lobar bulla, when it becomes giant. The pathogenesis of the present middle lobar bulla remains unknown, but steroid administration to bronchial asthma may possibly have influenced pleura and/or lung parenchyma. We would like to make its further observation, paying attention to its possible recurrence and its occurrence at other sites.

Adult↗
PubMed1991

Diversity of a ribonucleoprotein family in tobacco chloroplasts: two new chloroplast ribonucleoproteins and a phylogenetic tree of ten chloroplast RNA-binding domains.

Two new ribonucleoproteins (RNPs) have been identified from a tobacco chloroplast lysate. These two proteins (cp29A and cp29B) are nuclear-encoded and have a less affinity to single-stranded DNA as compared with three other chloroplast RNPs (cp28, cp31 and cp33) previously isolated. DNA sequencing revealed that both contain two consensus sequence-type homologous RNA-binding domains (CS-RBDs) and a very acidic amino-terminal domain but shorter than that of cp28, cp31 and cp33. Comparison of cp29A and cp29B showed a 19 amino acid insertion in the region separating the two CS-RBDs in cp29B. This insertion results in three tandem repeats of a glycine-rich sequence of 10 amino acids, which is a novel feature in RNPs. The two proteins are encoded by different single nuclear genes and no alternatively spliced transcripts could be identified. We constructed a phylogenetic tree for the ten chloroplast CS-RBDs. These results suggest that there is a sizable RNP family in chloroplasts and the diversity was mainly generated through a series of gene duplications rather than through alternative pre-mRNA splicing. The gene for cp29B contains three introns. The first and second introns interrupt the first CS-RBD and the third intron does the second CS-RBD. The position of the first intron site is the same as that in the human hnRNP A1 protein gene.

Amino Acid Sequence↗
PubMed1991

RNase-like domain in DNA-directed RNA polymerase II.

DNA-directed RNA polymerase is responsible for gene expression. Despite its importance, many details of its function and higher-order structure still remain unknown. We report here a local sequence similarity between the second largest subunit of RNA polymerase II and bacterial RNases Ba (barnase), Bi, and St. The most remarkable similarity is that the catalytic sites of the RNases are shared with the eukaryotic RNA polymerase II subunits of Drosophila melanogaster and Saccharomyces cerevisiae. Several amino acids conserved among the RNases and the RNase-like domains of the RNA polymerase subunits are located in the neighborhood of the catalytic sites of barnase, whose three-dimensional structure has been resolved. This observation suggests the functional importance of the RNase-like domain of the RNA polymerase subunits and indicates that the RNase-like domain may have RNase activity. The location of the RNase-like domain relative to the region necessary for RNA polymerization is similar to the relative proximity of 5'----3' or 3'----5' exonuclease and the region of polymerase activity of DNA polymerase I. The RNase-like domain might work in proofreading, as in RNA-directed RNA polymerase of influenza virus, or it may contribute to RNA binding through an unknown function.

Amino Acid Sequence↗