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Biomedical subjects

K Toyoshima

Publications and source records attributed to K Toyoshima.

At least 235 records · Page 13Linked to original sources

The ultrastructure of encapsulated sensory corpuscles in the fungiform papillae of monkeys.

Both simple and coiled simple encapsulated sensory corpuscles in the fungiform papillae of primate tongues were examined by light and electron microscopy. These were found to be composed of discoid axon terminals, with cytoplasmic lamellae of lamellar cells surrounding them. The axon terminals were characterized by the presence of distinct finger-like projections extending beyond the corpuscular basal lamina to make contact with collagen fibers, as well as numerous mitochondria, clear vesicles and a few dense-core vesicles in the axoplasm. The cytoplasmic lamellae of lamellar cells showed a number of caveolae on the plasma membrane. Further, desmosome-like contacts were found between adjacent lamellae and between the axon and the innermost lamella.

Animals↗

Factors influencing the prognosis of wheezy infants.

Forty-eight wheezy infants were followed up for 25 to 44 months. These infants were classified into three groups: those with asthma (developed asthma later), the wheezy group (had successive wheezing episodes), and the non-wheezy group (grew out of the wheezy episodes). Serum IgE levels at the first visit were not significantly different in the three groups, but the frequency of exposure to cigarette smoke was higher in the asthma and wheezy groups than in the nonwheezy group.

Asthma↗

Human c-erbB-2 remains on chromosome 17 in band q21 in the 15;17 translocation associated with acute promyelocytic leukemia.

Using the human c-erbB-2 cDNA as a probe, we applied in situ hybridization techniques to acute promyelocytic leukemia cells with a 15;17 chromosome translocation, t(15;17)(q;22;q21), and were able to localize the c-erbB-2 gene on chromosome 17 to band q12 or q21 and on the proximal side of the breakpoint in the translocation. From this finding and previous observations by others, we presume that the gene and the breakpoint are both in band q21.1 of chromosome 17. We suggest possible involvement of the c-erbB-2 gene in the development of the t(15;17)-associated acute promyelocytic leukemia.

Chromosome Mapping↗

Isolation and sequencing of cDNA clones homologous to the v-fgr oncogene from a human B lymphocyte cell line, IM-9.

Two c-fgr cDNA clones were isolated from a cDNA library derived from a human B lymphocyte cell line, IM-9. Sequence analysis of the clones showed that they contained inserts corresponding to nearly full-length human c-fgr mRNA, which could encode a polypeptide of 529 amino acids with a calculated molecular weight of 59,478. Although the amino acid sequence between Gly-78 and the carboxy-terminus of the c-fgr is highly homologous to the corresponding sequence of the c-yes protein, the homology between the two proteins is low in the amino-terminal proximal region. Northern blot hybridization analysis using the c-fgr specific sequence showed that the c-fgr mRNA was expressed at higher level in the liver than in the brain, lung, or kidney of a human fetus.

Amino Acid Sequence↗

[The erbB-related protooncogenes encoding growth factor receptors].

The c-erbB-2 gene was first identified by virtue of its cross-hybridization with v-erbB. Nucleotide sequence analysis of complementary DNA clones suggested that the c-erbB-2 gene encodes a growth factor receptor similar to that for EGF. Antibodies against the carboxyl terminal sequence of the c-erbB-2 protein immunoprecipitated a 185-kDa glycoprotein which showed protein-tyrosine kinase activity in vitro. Despite the extensive similarity between the c-erbB-2 protein and EGF receptor, neither EGF nor TGF-alpha bound to the c-erbB-2 protein. Phosphorylation of the c-erbB-2 protein was stimulated by TPA via protein kinase C in vivo. EGF also induced phosphorylation of the c-erbB-2 protein. This phosphorylation occurred not only on serine and threonine residues but also on tyrosine residues. Preliminary data suggested that the latter was mediated by the kinase activity of the EGF receptor. Southern blot analysis of DNAs from primary tumors revealed that the c-erbB-2 gene tends to be amplified in adenocarcinomas, mostly of the stomach and the breast. By screening both human genomic and cDNA libraries using v-yes DNA as a probe, we obtained DNA clones of the c-yes gene, the pseudogene of c-yes, c-fgr gene and c-src gene and two novel yes-related genes, fyn and lyn. Complete nucleotide sequence analysis of the cDNA clones of c-yes, fyn and lyn revealed that these genes encode proteins similar to p60src both in size and sequence.

Adenocarcinoma↗

Modified smooth endoplasmic reticulum in type II cells of rabbit taste buds.

Type II cells of taste buds from rabbit foliate papillae are characterized by a widespread system of smooth endoplasmic reticulum (SER), usually in the form of a loose network. In some cells, the SER is tightly compacted into a juxtanuclear aggregate that is continuous with the perinuclear space and that appears to merge with the Golgi complex. In other type II cells, the SER is in a honeycomb arrangement. Where type II cells confront nerves, they may have extensive smooth-membraned subsurface cisternae. The presence of manifold forms of SER in type II cells suggests that these cells may have a variety of secretory functions.

Animals↗

[Recent progress in oncogene studies].

Oncogene studies have become an area of general interest in the field of cancer research following the identification of the cellular counterparts of viral oncogenes. It may be possible to attribute some steps in the initiation or progression of cancer to point-mutations or altered expression of proto-oncogenes. Elucidation of the normal functions of proto-oncogene products as growth factors, growth factor receptors or other growth regulatory elements will facilitate biochemical analysis of the mechanisms of normal and malignant cell growth.

Genes, Viral↗

The product of the human c-erbB-2 gene: a 185-kilodalton glycoprotein with tyrosine kinase activity.

Antibodies were raised against a synthetic peptide corresponding to 14 amino acid residues at the COOH-terminus of a protein deduced from the human c-erbB-2 nucleotide sequence. These antibodies immunoprecipitated a 185-kilodalton glycoprotein from MKN-7 adenocarcinoma cells. Incubation of the immunoprecipitates with (gamma-32P)ATP resulted in the phosphorylation of this protein on tyrosine residues. These results indicate that the human c-erbB-2 gene product is the 185-kilodalton glycoprotein that is associated with tyrosine kinase activity. Although the c-erbB-2 protein was predicted to encode a protein very similar to epidermal growth factor (EGF) receptor, EGF did not stimulate this kinase activity either in vivo or in vitro.

Amino Acid Sequence↗

Nucleotide sequence of the protease-coding region in an infectious DNA of simian retrovirus (STLV) of the HTLV-I family.

A provirus clone of simian T-cell leukemia virus isolated from a pigtailed monkey (PT-STLV), which is 90% homologous to HTLV-I, was shown to be biologically active in transfection assay. In transfected cells, gp61env, Pr55gag, and the mature gag proteins p24, p21, and p15 were detected, and type C particles were produced. The virus could be transmitted from the transfectants to recipient cells by cocultivation. In this biologically active provirus clone, a coding frame, possibly for protease, was identified between the gag and pol genes. The corrected sequence of the protease region of HTLV-I was also found to have a single open reading frame overlapping the gag and pol genes, although it has an amber codon in the middle of the frame. Thus, a single coding frame, which is different from those of gag and pol, is common to proteases of the HTLV family including HTLV-I.

Animals↗

Amplification of c-erbB-2 oncogene in human adenocarcinomas in vivo.

There are two genes related to the viral erbB gene in the human genome. c-erbB-1 is the same as the gene for the epithelial-growth-factor (EGF) receptor, and c-erbB-2 encodes a receptor-like protein very similar to, but distinct from, the EGF receptor. Hybridisation analysis of DNA from 101 fresh human malignant tumours showed that the c-erbB-2 gene was amplified in 5 of 63 adenocarcinomas and none of 38 other types of tumours, whereas the c-erbB-1/EGF-receptor gene was amplified only in 1 of 8 squamous-cell carcinomas. Thus, the protein products of the amplified c-erbB-2 gene may have a role in the evolution of adenocarcinomas, as does the EGF receptor in some squamous-cell carcinomas.

Adenocarcinoma↗

Ultrastructure of the submandibular gland in the rabbit.

The secretory endpieces of the rabbit submandibular gland are unusual in that they consist of seromucous acini (not demilunes) that empty into serous tubules that in turn drain into intercalated ducts. Seromucous granules consist of a moderately dense spherule in a fibrillogranular matrix. Serous granules contain a feltwork of filaments, which are liberated as a tangled skein during exocytosis. Peculiar granulated cells that have secretory granules of complex morphology are present at each end of the serous tubules. Intercalated ducts are, cytologically speaking, relatively simple, but the duct cells may contain a few oblong secretory granules. Striated ducts are typical in structure, although postfixation with ferrocyanide-reduced osmium reveals significant amounts of glycogen in the basal processes. Modified mitochondria are present in striated duct cells, but their frequency varies from rabbit to rabbit. Such mitochondria contain either an array of parallel, rigid cristae linked by intermembranous bridges, or a bundle of helical filaments within an expanded crista. Interspersed with the striated duct cells, especially near the duct origin, are some highly vacuolated cells with sparse mitochondria. Excretory ducts consisting of stratified columnar (sometimes pseudostratified) epithelium often show bleb formation of the luminal surface of the tall cells.

Animals↗

Dividing type II cell in rabbit taste bud.

Examination of rabbit foliate papillae by electron microscopy revealed for the first time the existence of a dividing cell within a taste bud. The ultrastructure of this cell was in keeping with that of type II cells of the sort located in the center of taste buds. Whether this cell is capable of differentiating into other cell types is still unclear.

Animals↗

yes-related protooncogene, syn, belongs to the protein-tyrosine kinase family.

An src/yes-related novel gene named syn (SYN in human gene nomenclature) has been identified in the human genome on chromosome 6 and characterized by molecular cloning. Nucleotide sequence analysis of cDNA clones showed that the c-syn gene could encode a protein-tyrosine kinase that is very similar in primary structure to the v-yes and human c-src proteins. A 2.8-kilobase transcript of the c-syn gene, which differs in size from those of the c-yes, c-src, and c-fgr genes, was observed in various cell types. These results show that syn is a new member of the tyrosine kinase oncogene family.

Amino Acid Sequence↗

Structure, expression, and chromosomal location of the human c-fgr gene.

The nucleotide sequence of seven exons of the human c-fgr gene, a cellular homolog of the oncogene of Gardner-Rasheed feline sarcoma virus, was determined. Twenty-six independent genomic clones were obtained from a human gene library with a DNA clone of Y73 avian sarcoma virus oncogene, v-yes, as a probe under relaxed hybridization conditions. Restriction mapping and partial sequence analyses revealed that two of these clones were derived from the c-fgr gene, distinct from the c-yes gene. Interestingly, the splicing points of the c-fgr gene were identical with those of the c-src gene throughout the seven exons, suggesting that the two proto-oncogenes were generated by gene duplication of an ancestral gene containing intervening sequences. On RNA blot hybridization the major transcript was found to be 2.6 kilobase long. Two additional transcripts of 3.5 and 4.7 kilobases were also detected. Furthermore, karyotype analysis of several human-mouse hybrid cells and Southern blot analyses of DNAs of the hybrids with a human c-fgr locus-specific probe showed that this gene is located on chromosome 1.

Animals↗

Localization of a novel v-erbB-related gene, c-erbB-2, on human chromosome 17 and its amplification in a gastric cancer cell line.

The c-erbB-2 gene is a v-erbB-related proto-oncogene which is distinct from the gene encoding the epidermal growth factor receptor. By using two independent methods, hybridization of both sorted chromosomes and metaphase spreads with cloned c-erbB-2 DNA, we mapped the c-erbB-2 locus on human chromosome 17 at q21, a specific breakpoint observed in a translocation associated with acute promyelocytic leukemia. Furthermore, we observed amplification and elevated expression of the c-erbB-2 gene in the MKN-7 gastric cancer cell line. These data suggest possible involvement of the c-erbB-2 gene in human cancer.

Cell Line↗