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Biomedical subjects

S Ohno

Publications and source records attributed to S Ohno.

At least 469 records · Page 26Linked to original sources

Diverse incidences of individual oligopeptides (dipeptidic to hexapeptidic) in proteins of human, bakers' yeast, and Escherichia coli origin registered in the Swiss-Prot data base.

Oligopeptidic permutations of the 20 amino acid residues give rise to proteins of diverse functions. Our long-term goal is to produce a lexicon of oligopeptides, classifying them into at least five categories: (i) ubiquitous, (ii) function specific, (iii) group specific, (iv) species specific, and (v) nonexistent. To begin with, we report on the varying frequencies of individual oligopeptides (dipeptidic to hexapeptidic in length) found among 2862 human proteins, 1942 Saccharomyces cerevisiae proteins, and 2672 Escherichia coli proteins registered in the Swiss-Prot data base (version 29.0, released in June 1994). At all lengths (dipeptides to hexapeptides), homooligopeptides were very prominent among the most frequently occurring varieties in proteins of human and bakers' yeast origins. However, this was not the case with E. coli. While all of the expected 20(3) varieties of tripeptides were found among human proteins, three tripeptides (Cys-Cys-Trp, Trp-Trp-Cys, and Trp-Trp-His) were missing from the bakers' yeast proteins. Three tripeptides (Cys-Ile-Trp, Cys-Met-Tyr, and Cys-Trp-Trp) were also absent from E. coli proteins. Inasmuch as the Swiss-Prot data base already contained 67% of the expected total of 4000 E. coli proteins, it is virtually certain that 96,000 varieties of hexapeptides containing at least one or another of the three missing tripeptides noted above shall be nonexistent in E. coli. Furthermore, the observation of missing tripeptides in the bakers' yeast proteins suggests that nonexistent hexapeptides shall be highly phylum specific. Because of the sample size, only a small fraction of the 20(6) varieties of hexapeptides were expected to be encountered in the present survey. Indeed, only 1.2-1.5% of the possible hexapeptides were found, and the average copy number of observed hexapeptides varied between 1.06 and 1.25. Nevertheless, 33 varieties of hexapeptides occurred in 102-169 copies among human proteins. Furthermore, 15 of the 33 varieties contained such rarely used residues as Tyr, His, Cys, and Trp.

Amino Acid Sequence↗

Growth pattern and p53 overexpression in patients with early gastric cancer.

BACKGROUND: The growth pattern of early gastric carcinoma, based on a volumetric analysis, reflects well biologic characteristics of the tumor. The penetrating growth (Pen) type tumor has an unfavorable prognosis, compared with a superficially spreading (Super) type. Abnormality of the p53 suppressor gene plays an important role in alteration of cells leading to development of cancer. p53 point mutations are present even in an early stage of carcinoma. METHOD: In 159 patients with early gastric carcinoma, overexpression of p53 was studied immunohistochemically, using a monoclonal antibody (PAb 1801), and the relationship between growth pattern and p53 overexpression was analyzed. RESULTS: Early gastric carcinoma was grouped into 43 of the Super type, 37 of the expansively penetrating growth (Pen-A) type, 16 of the infiltratively penetrating growth (Pen-B) type, and 63 of the Small mucosal type limited to the mucosal layer. The Pen-A type tumors were characterized by the highest incidence of p53 positive expression and poorest postoperative course. Between the Pen-A type and the Super type, there were significant differences in the incidence of the p53 positive expression (43% vs. 16%), the frequency of recurrence (16% vs. 7%), and disease free interval (574 days vs. 2926 days). CONCLUSION: The authors' observations show that the p53 gene plays an important role in expansion of gastric carcinoma, even in the early stages.

Gene Expression↗

A protein kinase C isozyme, nPKC epsilon, is involved in the activation of NF-kappa B by 12-O-tetradecanoylphorbol-13-acetate (TPA) in rat 3Y1 fibroblasts.

In order to examine whether PKC is involved in the activation of NF-kappa B by TPA, we overexpressed a variety of PKC isozymes in rat 3Y1 fibroblasts and monitored the expression of the co-transfected reporter NF-kappa B gene. In contrast to TPA response element (TRE), where overexpression of a variety of PKC isozymes results in enhanced activation by TPA, activation of NF-kappa B by TPA is not enhanced by overexpression of PKC isozymes such as cPKC alpha, nPKC delta, or nPKC theta. However, the overexpression of nPKC epsilon does result in enhancement. A kinase-negative point mutant of nPKC epsilon, where Lys at the ATP binding site is altered to Arg, does not cause this enhancement of NF-kappa B activation. Further, the kinase-negative nPKC epsilon partially suppresses endogenous NF-kappa B activity. These results suggest that nPKC epsilon is specifically involved in the activation of NF-kappa B when cells are treated with TPA.

Animals↗

Why ontogeny recapitulates phylogeny.

In development, mammalian embryos successively develop notochord, somites, gill pouches and three sets of kidneys: pronephros, mesonephros and metanephros. Hence, Ernst Haeckel's dictum "ontogeny recapitulates phylogeny." The reason for this dictum appears to be the immortality of genes. Genes, once well entrenched, appear to linger for a long time even after the forfeiture of their raison d'être. The genes for dental enamel and dentin of the chicken are good examples. Furthermore, genes once doomed may resurrect themselves. For example, genes for red and green opsins of higher primates arose as alleles of the once doomed but resurrected red opsin locus.

Amino Acid Sequence↗

Macroscopic intraoperative diagnosis of serosal invasion and clinical outcome of gastric cancer: risk of underestimation.

Data on 715 Japanese patients with gastric cancer were studied retrospectively with regard to the relationship between macroscopic and microscopic diagnoses of serosal invasion and clinicopathological factors affecting the accuracy of the macroscopic diagnosis. Although there was no macroscopic evidence of serosal invasion intraoperatively (S0 or S1), there was histological evidence of cancer cells on the serosal surface in 69 patients (9.7%). In these serosal invasion-positive cases, the tumors were larger; were located more commonly in the upper third, lesser and greater curvatures of the stomach; were Borrmann type 3 or type 4 tumors, and of an undifferentiated histologic type with an infiltrative growth pattern more commonly, and had more extensive lymphatic and vascular vessel invasion and lymph node metastasis (P < 0.01). Total gastrectomy was done more often for the serosal invasion-positive group, but the extent of lymph node dissection was comparable. Cases of a noncurative resection because of a positive surgical margin were more frequent in the serosal invasion-positive group (8/69 vs. 14/646, P < 0.01), and most had undifferentiated and infiltrative cancers. The 10-year survival rates were 49.2% and 85.5% for patients with and without serosa invasion, respectively. These findings clearly show that the serosal surface, especially in cases of the undifferentiated or infiltrative type of gastric cancer, must be closely inspected intraoperatively.

Aged↗

Active sites of ligands and their receptors are made of common peptides that are also found elsewhere.

The simultaneous emergence in evolution of a ligand and its receptor might have entailed their active sites being drawn from the pool of common oligopeptides. This was tested on the principal components of cell-matrix interaction: the RGD (Arg-Gly-Asp) site of matrix proteins and the EKKD (Gly-Lys-Lys-Asp) site of integrin cell-surface receptor. In the 32 diverse proteins scrutinized, which totalled 14,806 residues, there were 104 Arg-Gly dipeptides. Most common of the tripeptides beginning with Arg-Gly were Arg-Gly-Leu, Arg-Gly-Gly, and Arg-Gly-Asp; each was found in ten copies. RGD tripeptide was one of the commonest; the fortuitous presence of an RGD site was noted in two enzymes, fibrinogen, a pituitary hormone precursor, and a viral structural protein. The 32 proteins also contained 121 Lys-Lys dipeptides. Of the tetrapeptides centered by Lys-Lys, the commonest was Lys-Lys-Lys-Lys, in four copies. Second most common were Gly-Lys-Lys-Lys, Val-Lys-Lys-Leu, and Glu-Lys-Lys-Asp; each occurred in three copies. The fortuitous presence of an EKKD site was noted in three proteins--an intracellular transport protein, a pituitary hormone precursor and a protein of the cerebrospinal fluid. In most instances, protein-protein interaction between the fortuitously present active sites appears to bring about deleterious consequences. Occasionally, however, the fortuitous active site appears to confer a new function to a protein bearing it.

Amino Acid Sequence↗

Prevalence of HTLV-I-associated uveitis in the Kanto Plain, Japan.

BACKGROUND: Seroprevalence of antibody to human T-lymphotropic virus type I (HTLV-I) is high in the island of Kyushu, Japan. Reports on the etiological analysis of HTLV-I in patients with uveitis primarily document cases in this island. We studied the seroprevalence of HTLV-I at the Department of Ophthalmology in Yokohama City University Hospital and in Odawara Municipal Hospital, which are in the Kanto Plain on the island of Honshu, Japan. METHODS: The subjects were 741 patients who visited the two hospitals. The presence of serum antibodies against HTLV-I was assessed using the method of particle agglutination. RESULTS: Of 454 patients with nonuveitic ocular diseases, 9 (1.98%) were seropositive. Of 143 patients with definite diagnosis of uveitis, 1 (0.70%) was seropositive. Of 144 patients with non-specific uveitis (etiology undefined), 8 (5.56%) were seropositive. Thus, the prevalence of serum antibodies to HTLV-I was higher in patients with non-specific uveitis than in patients with specific uveitis or nonuveitic ocular diseases. Common ocular symptoms of 8 HTLV-I-infected patients with non-specific uveitis were compatible with the clinical features of uveitis described as HTLV-I-associated uveitis (HAU). CONCLUSION: It is important to suspect HAU in patients with uveitis of unknown etiology, even outside known areas of prevalence.

Adult↗

Different organization of intermediate filaments in columnar cells of rat large intestinal mucosa as revealed by confocal laser scanning microscopy and quick-freezing and deep-etching method.

The relationship between cell differentiation and ultrastructural changes of intermediate filaments (IF) was studied in columnar cells of large intestinal mucosa of rats by confocal laser scanning microscopy and quick-freezing and deep-etching method. A feature of the IF in immature columnar cells was minibundle formation with prominent branching, which organized the meshwork structures. The minibundles, which appeared to be formed by the attachment of two or more IF in side-to-side fashion, were loosely distributed throughout the cytoplasm. In contrast, in mature columnar cells, the IF were densely distributed under the terminal web in the cytoplasm and beneath the upper part of the lateral membrane regions, whereas the other areas of the cytoplasm contained only a small number of IF. Minibundle formation was not observed, and the branching was rarely identified. The changes in the distribution and density of IF, which are expressed in specific areas of mature columnar cells, apparently represent a characteristic of intracellular differentiation. It is suggested that the dissociation of minibundled IF, which was often observed in the immature columnar cells, is an important step in the acquisition of functional polarity in cells of this type.

Animals↗

Freeze-fracture immunocytochemistry for intracellular localization of serotonin in mast cells stimulated with compound 48/80.

Changes of intracellular localization of serotonin in rat mast cells were examined by freeze-fracture immunocytochemistry, to prevent the translocation of the serotonin antigen. Rat peritoneal cells including mast cells were stimulated in vitro with compound 48/80, at 17 degrees C for 0, 30 or 60 s for exocytosis to occur. The mast cells were fixed, quickly frozen and freeze-fractured to expose the antigen on the fractured surface. They were immunostained with serotonin antibody, and the immunoreactions on the fractured surface were examined on ultrathin sections by electron microscopy. Unstimulated mast cells exhibited serotonin localization mostly in each intragranular matrix. In contrast, mast cells stimulated for 30 s exhibited increased serotonin in their intergranular cytoplasm. Mast cells showed more distinct immunoreactions in the cytoplasm where degranulation would be promoted after 60 s. It is suggested that intracellular release of serotonin occurred in the stimulated mast cells.

Animals↗

Two types of aminoacyl-tRNA synthetases could be originally encoded by complementary strands of the same nucleic acid.

The lack of even a marginal similarity between the two aminoacyl-tRNA synthetase (aaRS) classes suggests their independent origins (Eriani et al., 1990; Nagel and Doolittle, 1991). Yet, this independence is a puzzle inconsistent with the common origin of transfer RNAs, the coevolutionary theory of the genetic code (Wong, 1975, 1981) and other associated data and ideas. We present here the results of antiparallel 'class I versus class II' comparisons of aaRSs within their signature sequences. The two main HIGH- and KMSKS-containing motifs of class I appeared to be complementary to the class II motifs 2 and 1, respectively. The above sequence complementarity along with the mirror-image between crystal structures of complexes formed by the opposite aaRSs and their cognate tRNAs (Ruff et al., 1991), and the generally mirror ('head-to-tail') mapping of the basic functional sites in the sequences of aaRSs from the opposite two classes led us to conclude that these two synthetases emerged synchronously as complementary strands of the same primordial nucleic acid. This conclusion, combined with the hypothesis of tRNA concerted origin (Rodin et al., 1993a,b), may explain many intriguing features of aaRSs and favor the elucidation of the origin of the genetic code.

Amino Acid Sequence↗

Microsatellite polymorphism between the tumor necrosis factor and HLA-B genes in Behçet's disease.

Behçet's disease is associated with the HLA-B51 antigen. However, it has not yet been clarified if the HLA-B51 gene itself is the susceptibility gene related to this disease or if it is some other non-HLA gene in linkage disequilibrium with HLA-B51. Therefore, we screened one of the HSP70 genes, HUM70t (HSP70-Hom), around the class III region and the microsatellite sequence located between the HLA-B and TNF genes for genetic polymorphism in BD. A comparison between patients with BD and healthy controls revealed no significant difference in the frequency of the HUM70t polymorphism. In the microsatellite sequence, Tau-a, in the region between the HLA-B and TNF genes, the frequency of 14 repetitions of GT was increased significantly and that of 11 repetitions was decreased significantly in the patient group. Further, the allelic distributions of the B51 antigen-associated microsatellite polymorphism differed significantly between patients and healthy controls, and in the B51 antigen-negative subjects, analysis of the microsatellite polymorphism also revealed a significant difference in the haplotype frequency between the patient and control groups. These results suggest that the HLA-B51 gene may not be the primary locus responsible for BD, and implicate some other gene(s) located between the TNF and HLA-B genes.

Base Sequence↗

Direct expression of pig testicular 3 alpha/beta (20 beta)-hydroxysteroid dehydrogenase in Escherichia coli.

The cDNA coding for pig testicular 3 alpha/beta (20 beta)-hydroxysteroid dehydrogenase was expressed in Escherichia coli by placing it under the control of an isopropylthiogalactoside (IPTG) inducible tac promoter. Production of 3 alpha/beta (20 beta)-HSD was demonstrated by Western blotting and by catalytic activity with 5 alpha-dihydrotestosterone as a substrate for 3 alpha/beta-HSD, and progesterone and 17 alpha-hydroxyprogesterone as substrates for 20 beta-HSD in the presence of NADPH. The 3 alpha/beta (20 beta)-HSD enzyme was detected in a soluble fraction of the lysate of E. coli added to IPTG to induce the synthesis of the protein. Its molecular weight was estimated to be 30.5 kDa by SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Recombinant 3 alpha/beta (20 beta)-HSD was purified to apparent homogeneity as determined by SDS-PAGE by column chromatography using DEAE-cellulose. The purified enzyme reduced not only steroids but also prostaglandins and other carbonyl compounds including aldehydes, ketones and quinones as demonstrated in native enzymes purified from pig testes. The amino terminus of the purified enzyme was serine which was coded next to the ATG start codon, and the sequence of the amino terminal 24 residues was identical with the coding amino acid in the cDNA; whereas, the amino terminus of the native 3 alpha/beta (20 beta)-HSD was not detected suggesting that the N-terminal amino acid was blocked.

3-Hydroxysteroid Dehydrogenases↗

Lymphatic invasion and potential for tumor growth and metastasis in patients with gastric cancer.

BACKGROUND: Lymph node metastasis is a risk factor for the occurrence of peritoneal dissemination and liver metastasis in patients with gastric cancer. METHODS: We analyzed data on 324 patients with serosally invasive gastric cancer with respect to the relation between lymphatic invasion and potential for tumor growth and metastasis. All these patients were curatively treated in the Department of Surgery II, Kyushu University. RESULTS: Lymphatic invasion was evident in 214 patients, in whom vascular invasion was more frequent and the rate of lymph node metastasis was higher compared with patients with no lymphatic invasion. There was no difference in tumor size. The type of recurrence varied, and the prognosis was poor in patients with lymphatic invasion. The DNA ploidy pattern was higher, and the levels of proliferating cell nuclear antigen labeling and argyrophilic nucleolar organizer regions count were significantly higher in tumor tissues with lymphatic invasion than in those without invasion. CONCLUSIONS: Gastric cancers with characteristics of lymphatic invasion have higher proliferating activities, and metastases to distant organs are likely.

Cell Division↗

Histological suggestions of 'paratransformation' in oesophageal squamous cell carcinoma.

We have postulated that oesophageal squamous cell carcinoma arises from multifocal areas and not from one cell, and we present the circumstantial evidence for field carcinogenesis in oesophageal cancer. Among 290 cases examined with oesophageal squamous cell carcinoma, lymphatic permeation or intramural metastasis was evident in 110 cases. Of these carcinomatous transformation of the epithelium adjacent to either lymphatic vessel permeation or intramural metastasis of the squamous cell carcinoma was recognized in six cases. It is considered that the cancer tissue either in the lymphatic vessel or intramural metastasis promotes a malignant transformation of the squamous epithelium over these foci. 'Paratransformation' is therefore thought to be one of the potential models of origin for oesophageal squamous cell carcinoma.

Aged↗

Spherical aberration and glare disability with intraocular lenses of different optical design.

We implanted several kinds of intraocular lenses (IOLs), calculated the spherical aberration using a computed ray-tracing system, and investigated the correlation between glare disability and spherical aberration and the difference in glare disability among the different IOL types. Type A IOLs (convex-plano), except for those with high power, had the smallest spherical aberration. Type B IOLs (biconvex, anterior more curved) had the smallest spherical aberration at high power. Type D IOLs (biconvex, posterior more curved) had the largest spherical aberration. The correlation between glare disability and spherical aberration was statistically significant for types A, B and C (equiconvex) IOLs. There was no correlation between glare disability and spherical aberration for Type D IOLs, although they showed the smallest glare disability of the four types. These results indicate that the spherical aberration of an IOL, which is calculated by an optical design program, may be a good criterion for selecting an IOL design.

Aged↗

Correlation between sialyl Tn antigen and lymphatic metastasis in patients with Borrmann type IV gastric carcinoma.

The expression of sialyl Tn (STn) antigen in 180 patients with Borrmann type IV gastric carcinomas was examined immunohistochemically. The rate of positive STn staining was 32% (57/180) for the primary tumours, and this positive staining correlated well with tumour extension, lymph node metastasis (P < 0.05) and peritoneal dissemination (P < 0.01). One-third (5/15) of patients with positive STn-staining cancer cells had a high level of serum STn. Lesions with positive STn staining were related to a lower survival rate for the patients (P < 0.05). Proliferative activity of the tumour, as measured by proliferating nuclear antigen (PCNA) labelling percentage and argyrophilic nucleolar organiser region (AgNOR) count, was significantly higher (41.5 +/- 13.0%, 3.78 +/- 0.98) in the STn-positive group than in the STn-negative group (34.2 +/- 13.2%, 3.48 +/- 0.85) (P < 0.01, P < 0.05 respectively). Estimating STn antigen may be useful for predicting the likelihood of lymph node metastasis or peritoneal dissemination and the clinical prognosis for patients with Borrmann type IV gastric carcinoma.

Adult↗

Development of esophageal cancer after endoscopic injection sclerotherapy for esophageal varices: three case reports.

We report here three cases of squamous-cell carcinoma of the esophagus following endoscopic injection sclerotherapy for esophageal varices. All three patients were men and cigarette smokers, with a mean age of 58.3 +/- 5.0 years. Hepatitis B and C virus infection tests were negative, and alcoholic cirrhosis was present in each patient. The interval between sclerotherapy and the development of carcinoma was 9, 10, and 33 months, in the respective cases. The sclerosant used was 5% ethanolamine oleate with a mean total volume of 51.0 +/- 18.9 ml. While we have no evidence of a direct relationship between sclerotherapy and esophageal cancer, in patients with alcoholic cirrhosis who have risk factors for esophageal cancer there may be an acceleration of the potential malignancy, as a result of the chronic inflammation related to sclerotherapy. Such patients should be closely followed, using endoscopy.

Carcinoma, Squamous Cell↗