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Biomedical subjects

Y Saga

Publications and source records attributed to Y Saga.

At least 73 records · Page 4Linked to original sources

[A new technique for the treatment of ectopically erupting permanent first molars].

The problem and treatment of the ectopically erupting permanent first molars have been addressed by many authors since they were first mentioned in the literature by Chapman in 1923. Many treatments involve techniques using the primary second molar. It is better for correcting the eruption of the permanent first molar into normal occlusion to maintain the primary second molar in its normal position. However severe mobility and root resorption are often present when an ectopic eruption is found. An 8-year-old male with ectopic eruption of the maxillary right permanent first molar was examined and treated. The right primary second molar demonstrated severe mobility and root resorption, and therefore a new appliance using the primary first molar was designed. After 4 months from the beginning of the treatment the mobility of the primary second molar decreased, and after 6 months the permanent first molar almost erupted in its normal position.

Child↗

Case report: secondary penile carcinoma.

We report a case of secondary penile carcinoma with primary tumor in the pancreas. Immunoperoxidase tissue staining of carbohydrate antigen 19-9, carcinoembryonic antigen and prostate-specific antigen was useful for diagnosis of original tumor.

Adenocarcinoma↗

[Image diagnosis of hyperparathyroidism].

Between January, 1983 and January 1988, the diagnosis of hyperparathyroidism was made on 14 patients (8 primary and 6 secondary), and was identified operatively in all. The procedures for image diagnosis were computed tomography (CT), ultrasonography and scintigraphy. Scintigraphy was performed using Tc-99m and Tl-201 by a subtraction technique. For primary hyperparathyroidism, the accuracy of localization was 100% by CT, 87.5% by ultrasonography, 100% by scintigraphy, and 100% by the combination of these three methods. For secondary hyperparathyroidism, it was 68% by CT, 68% by ultrasonography, 36% by scintigraphy and 84% by the combination of these three methods. Ultrasonography and CT were quite useful for imaging of small abnormal parathyroid glands. The accuracy of scintigraphy in secondary hyperparathyroidism was low. Because the swellings of glands do not occur equally in most secondary hyperparathyroidism cases, we consider that large glands absorb the majority of injected radionuclides. Some discussion on merits and demerits of each image procedure was done.

Adult↗

[Diffusion of sulbactam and cefoperazone into the prostatic tissue].

Diffusion of sulperazone (SBT) and cefoperazone (CPZ) into the prostatic tissue was studied in 20 cases. Two g of SBT/CPZ was injected intravenously and 1 hour later, prostatic tissue was obtained surgically and venous blood was drawn simultaneously. The serum concentration of CPZ (58.0 micrograms/ml +9.2) was higher than that of SBT (25.9 micrograms/ml +/- 9.3) and the prostatic tissue concentration of CPZ (14.9 micrograms/ml +/- 6.1) was higher than that of SBT (10.9 micrograms +/- 6.1). However, the SBT concentration ratio of prostatic tissue to serum level (P/S ratio) was significantly higher (42.5%) than that of CPZ (25.9%). The SBT concentration in the prostatic tissue was high enough to enhance the antibacterial activity of CPZ. SBT/CPZ was appraised to be an effective chemotherapeutic agent for infections of prostate caused by susceptible organisms, especially by beta-lactamase producing bacteria.

Aged↗

Structural features of Ly-5 glycoproteins of the mouse and counterparts in other mammals.

The Ly-5 system of the mouse defines a set of transmembrane glycoprotein isoforms (T200, B220, etc) that hallmark various lineages and stages of hematopoietic differentiation. These isoforms are the products of a single Ly-5 gene comprising 34 exons, 32 of them (Exs-3-34) protein-coding and three (Exs-5-7) selectively represented in different isoforms (e.g., all three in isoform B220 but none in isoform T200). Probable structural features of Ly-5 glycoproteins, largely inferred from Ly-5 gene composition, are presented and compared with the rat L-CA and human LCA/T200 systems, which are phylogenetic counterparts of Ly-5 as an index of the extent and nature of structural conservation. The outer (N-terminal) region of the Ly-5 T200 isoform comprises three broadly similar domains (Exs-4, 8, 9) with salient features that jointly favor free interaction with the aqueous environment and are shared by the L-CA and human LCA/T200 systems despite an overall interspecies protein sequence similarity in this region of only about 50%. In the larger B220 isoform this region includes epitopes dictated by the selective exons Exs-5, 6, 7, these being more conserved than the shared exons Exs-4, 8, 9 and no doubt sustaining the differential functions of the respective isoforms. Comparison of the genomic sequences of Ex-5 in the Ly-5 and human systems suggests that a shift in splice donor site accounts for an extra 23 amino acids in the human Ex-5-coding domain, which is the only salient structural difference between the mouse Ly-5 and human systems. The inner extracellular region (Exs-10-16) includes subregions of high variability, but again there are shared salient interspecies similarities such as sites and numbers of Cys residues that imply a conserved, tightly-folded conformation, in contrast to the more open conformation predicted for the outer extracellular region. The transmembrane region (Ex-17) is highly conserved, as is the very large cytoplasmic region (Exs-17-34) which may interact with the plasma membrane but probably does not traverse it.

Amino Acid Sequence↗

Organization of the Ly-5 gene.

A single Ly-5 gene is known to generate a variety of transmembrane glycoprotein isoforms that distinguish various cell lineages and stages of differentiation within the hematopoietic developmental compartment of the mouse. Systems homologous to Ly-5 are known in rats and in humans. The complete exon-intron organization of the Ly-5 gene is described in this report. The Ly-5 gene occupies about 120 kilobases of chromosome 1 and comprises 34 exons, of which 32 (Ex-3 to Ex-34) are protein coding. Ex-1, Ex-2, and parts of Ex-3 and Ex-34 are untranslated. In all cDNA clones examined, either Ex-1 or Ex-2 was represented, but not both, implying that Ex-1 and Ex-2 in Ly-5 mRNA may be mutually exclusive. Primer extension and S1 nuclease protection mapping were used to identify initiation (cap) sites for transcription. The finding of putative cap sites for Ex-1 and Ex-2, and of corresponding TATA-like sequences, suggests the presence of two promoters. In both Ex-1+ and Ex-2+ cDNA clones the next exon is Ex-3, which has a translation-initiating codon. The intron between Ex-3 and Ex-4 is unusually long, about 50 kilobases. Evidence is given that Ex-5, like Ex-6 and Ex-7 (studied previously), is another alternative exon that is selectively programmed, alone or together with Ex-6 or Ex-7 or both, to generate actual or potential Ly-5 isoforms by alternative splicing.

Animals↗

Differential usage of three exons generates at least five different mRNAs encoding human leukocyte common antigens.

Leukocyte common antigens (LCAs, also known as T200 and CD 45) are integral membrane proteins expressed exclusively on hematopoietic cells. These molecules exhibit varying molecular masses and epitopes when expressed in different cell types. To determine the genetic bases for the generation of this diversity, three classes of human LCA cDNA clones that are different near their 5' ends have been isolated. These differences arose as a result of differential usage of three exons as determined from an analysis of a genomic DNA clone. Furthermore, Northern blot analysis with LCA exon-specific probes demonstrates the existence of at least two more LCA mRNA forms that are generated by differential splicing. A comparison of the human and mouse LCA protein sequences revealed a marked difference only in the extracellular domain.

Amino Acid Sequence↗

Allelic variants of Ly-5 in inbred and natural populations of mice.

Allelic variants of Ly-5 in inbred commensal and other natural populations of mice were analyzed by patterns of restriction fragment length polymorphisms (RFLP) and Southern hybridization using an Ly-5 cDNA probe and by cell-surface staining with a panel of antibodies directed against polymorphic and nonpolymorphic Ly-5 determinants. New Ly-5 alleles were defined by RFLPs generated by both Eco RI and Bam HI restriction enzyme digests. The Mus musculus subspecies and other species within the genus Mus showed a strong correlation between allelic variants defined by restriction enzymes and serologic specificities. The data also suggest the conservation of the Ly-5 gene throughout the genus Mus.

Alleles↗

Alternative use of 5' exons in the specification of Ly-5 isoforms distinguishing hematopoietic cell lineages.

Previous inferences that Ly-5 glycoprotein isoforms of murine hematopoietic cells are generated by alternative splicing of primary transcripts of a single Ly-5 gene are supported by the present study. A cDNA library was prepared from B cells by extension from primer representing a known T-cell cDNA sequence. Three different Ly-5 clones from this library included sequences missing in T-cell cDNA clones. From the constitution of cDNA clones and of the Ly-5 gene, and from S1 nuclease mapping, it is concluded that at least two exons, provisionally numbered Ex-6(B) and Ex-7(B), in the 5'-proximal region are mainly represented in mRNA of the B-cell lines examined but not of the T-cell lines examined. Also, exons 1 and 2 appear to be used alternatively in different species of B-cell mRNA and probably also in different species of T-cell mRNA.

Animals↗

Sequences of Ly-5 cDNA: isoform-related diversity of Ly-5 mRNA.

The Ly-5 system of the mouse is expressed exclusively by hematopoietic cells and comprises a series of glycoprotein isoforms that typify different hematopoietic cell lineages. The 200-kDa isoform of T cells and the 220-kDa isoform of B cells are known to differ in peptide composition. The complete 1152 amino acid sequence of the 200-kDa isoform protein deduced from cDNA sequence appears to comprise a leader sequence of some 30 residues, an external N-terminal domain of 370 residues, a probably single transmembrane domain of 22 residues, and an unusually large cytoplasmic domain of 730 residues. Both the external and cytoplasmic domains include regions of internal homology suggestive of evolution from a smaller ancestral gene. RNA transfer blotting has previously shown that B-cell mRNA for Ly-5 is larger than T-cell mRNA. S1 nuclease protection mapping with Ly-5 cDNA probes suggests that this difference can be ascribed to interpolation of an extra B-cell sequence located at the 5' end of B-cell mRNA, probably immediately following the leader sequence. From restriction mapping of overlapping Ly-5 genomic clones spanning 60 kilobases it is concluded that Ly-5 isoforms are generated by differential processing of transcripts of a single gene, rather than from a family of linked Ly-5 genes.

Amino Acid Sequence↗

Cloning of Ly-5 cDNA.

A notable feature of Ly-5, among immunogenetic systems that identify glycoproteins of the cell surface and define the surface phenotype of cells according to their lineage, is that the Ly-5 locus specifies a range of molecular isoforms that distinguish cells of different stages and branches of hematopoietic development. The composition of the Ly-5 locus is of much interest in regard to how these isoforms are constructed and differentially regulated according to cell lineage. We describe here a cDNA clone, pLy-5-68, that identifies Ly-5. The Ly-5 specificity of the pLy-5-68 clone was first indicated by a restriction fragment length polymorphism (RFLP), which in Southern blotting distinguishes genomic DNA of C57BL/6 (B6) mice (Ly-5a) from that of B6-Ly-5b congeneic mice whose genome is the same as B6 except for the segment of chromosome 1 that bears Ly-5b. For the following reasons it is unlikely that pLy-5-68 represents a gene linked to Ly-5 that was carried over with Ly-5b during serial backcrossing to make the B6-Ly-5b congeneic strain. In all mouse strains tested, the serological Ly-5 allotype (Ly-5.1 vs. Ly-5.2) accorded with the RFLP pattern. Cells of the ST/bJ mouse strain have unique Ly-5 serological reactions and ST/bJ DNA gives a unique (third) RFLP pattern (Ly-5c) with pLy-5-68. All Ly-5+ cell types reacted positively with pLy-5-68 in RNA transfer blotting, and all Ly-5- cell types tested did not. The difference in size of mRNA reactive with pLy-5-68 in cells expressing the 200-kDa Ly-5 isoform as compared with cells expressing the 220-kDa Ly-5 isoform corresponded with the difference in size of the protein components of those isoforms.

Amino Acid Sequence↗

A novel cyclic AMP metabolism exhibited by giant cells and its possible role in the sexual development of Dictyostelium discoideum.

In Dictyostelium discoideum cyclic AMP (cAMP) metabolism during macrocyst development, i.e., the sexual cycle of this organism, and in giant cells, i.e., fusion products from opposite mating-type cells, was investigated. The pattern of change in cAMP levels during macrocyst development differed considerably from that observed during fruiting-body formation, i.e., the asexual cycle. Giant cells produced and excreted considerable amounts of cAMP. Adenylate cyclase activity catalyzing cAMP production in giant cells was comparable to that of unfused cells. However, the activity of membrane-bound phosphodiesterase in giant cells was extremely low, and no extracellular phosphodiesterase was excreted. A phosphodiesterase inhibitory protein was secreted in excess by giant cells.

3',5'-Cyclic-AMP Phosphodiesterases↗

Macrocyst development in Dictyostelium discoideum. II. Mating-type-specific cell fusion and acquisition of fusion-competence.

The early events of macrocyst development in Dictyostelium discoideum have been investigated using a new culturing system. When cells of opposite mating-types, HM1 and NC4, are cultured together at the appropriate temperature in the dark, giant cells appear, ingest the surrounding amoebae, and develop into macrocysts. Although these giant cells have been assumed to be the products of the fusion of opposite mating-type cells, no experimental evidence to prove this assumption has been obtained using such mixed-culture systems. In order to avoid the complexities involved in mixed-culturing, we have developed a new system involving the separate culture, and later mixing, of opposite mating-type cells. This has enabled us to obtain direct evidence that giant cells are produced by fusion between opposite mating-type cells. Cell fusion occurs immediately after mixing and is completed within 30 min. As a number of cells fuse simultaneously, giant cells produced by this method are very large multinucleated cells, and not binucleated zygotes. Using this system we also discovered the following facts related to giant cell formation: (1) cells can acquire their fusion competence without the presence of cells of the opposite mating-type; (2) only HM1 cells require darkness to acquire their fusion competence; (3) the restrictive temperature, 25 degrees C, inhibits the induction of fusion competence in HM1 cells, but not in NC4 cells.

Darkness↗

Macrocyst development in Dictyostelium discoideum. III. Cell-fusion inducing factor secreted by giant cells.

A factor was discovered that markedly enhances the degree of fusion activity between cells of the opposite mating-type strains, MI1 and NC4, in the sexual cycle of Dictyostelium discoideum. This factor, designated cell-fusion inducing factor (CFIF), was detected initially in supernatants taken from 24 h dark-grown mixed cultures of HM1 and NC4 cells, and subsequently shown to be secreted by giant cells - the fusion products of HM1 and NC4 cells. HM1 cells, cultured in the dark at appropriate temperature, normally acquire fusion-competence specific to NC4 cells. The addition of CFIF to such dark-grown HM1 cultures results in a marked increase in their fusion-competence. In addition, when CFIF is added to light-grown HM1 cultures, in which cells normally do not acquire the ability to fuse with NC4 cells, fusion-competence is induced. The fusion-competence of NC4 cells is unaffected by CFIF, being quite high under the culture conditions used here. Experiments, using actinomycin D, daunomycin and cycloheximide showed that the secretion of CFIF from giant cells requires synthesis of RNA and protein. Possibly, cell fusion triggers production of CFIF, which is rapidly released into the external medium.

Biological Products↗

Macrocyst development in Dictyostelium discoideum. I. Induction of synchronous development by giant cells and biochemical analysis.

In Dictyostelium discoideum, cytological and physiological studies on macrocyst formation revealed that this process consists of at least two steps: the production of giant cells, which are believed to be formed from the fusion of cells of two opposite mating types, and the subsequent induction of macrocyst development by the giant cells. The conditions that had been considered formerly to be required for macrocyst formation, such as darkness at the presence of two cells of complementary mating types in heterothallic strains, were actually required only for the production of the giant cells. Once giant cells are produced, the surrounding cells can aggregate and form macrocysts even in the light. Furthermore, it was demonstrated that giant cells can switch the developmental mode of the surrounding cells to macrocyst formation. That is, if a critical number of the isolated giant cells are introduced into a cell population of a single strain of NC4, which normally would produce only fruiting-bodies, macrocysts are formed instead. When in the presence of giant cells, the development of macrocysts may be initiated by starvation. Therefore, if all cells are made to starve simultaneously development begins and proceeds synchronously. Using this technique of synchronous development, the developmental kinetics of enzyme activities were assayed during macrocyst and fruiting-body formation. Considerable differences in the patterns of those enzyme activities were demonstrated between the two developmental modes of D. discoideum.

Acetylglucosaminidase↗

Differentiation of Dictyostelium discoideum mutant cells in a shaken suspension culture and the effect of cyclic AMP.

In Dictyostelium discoideum, 16 mutants in which cells differentiate into spores and stalk cells without normal morphogenesis were isolated. All these mutants are rapidly developing and capable of differentiating in a shaken suspension of phosphate buffer. The developmental kinetics of specific activities of enzymes in one of the mutants, HTY 1851, cultured in the suspension was compared with that in the parental strain, X2, developed on a solid surface. Most of the enzyme activities appeared much earlier and the peaks of the activities were lower in HTY1851 than X2, but the order or appearance of the activities was the same in both the strains cultured under the conditions described above. These results suggest that the biochemical steps in the development of the mutant in a shaken suspension are essentially the same as those of the parental strain X2 on a solid surface. It was also found that addition of cyclic AMP (2.5 X 10-5 M to 1 X 10-4 M) to the mutant cell suspension 6-8 h after the initiation of development induced an increase in the number of spores and the specific activities of some enzymes to values twice as high as those of an untreated control.

Cell Differentiation↗

High-grade endometrial stromal sarcoma after treatment with tamoxifen in a patient treated for breast cancer.

Tamoxifen has been widely used in breast cancer treatment. In recent years, the occurrence of uterine malignancies in patients receiving long-term tamoxifen therapy has attracted attention. Most of these malignancies are endometrial adenocarcinomas, but low-grade endometrial stromal sarcomas have occasionally been reported. Here we report a woman who developed a high-grade endometrial stromal sarcoma after receiving postmastectomy tamoxifen therapy. The patient underwent a left mastectomy at age 45 and subsequently received oral tamoxifen for 3 years. At age 51, she was diagnosed with endometrial stromal sarcoma, for which a radical hysterectomy was performed. High-grade endometrial stromal sarcoma was diagnosed by postoperative histologic examination. Immunostaining for the estrogen receptor was negative in sarcoma cells, but positive in the residual endometrial epithelium and the nucleus of adjacent stromal cells within the tumor. The patient has now survived disease-free for 37 months after surgery.

Administration, Oral↗