Isolation and sequence analysis of CDC43, a gene involved in the control of cell polarity in Saccharomyces cerevisiae.
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Alkyl and Aryl Transferases↗
Biomedical subjects
J M O'Brien
Publications and source records attributed to J M O'Brien.
Granulomatous prostatitis: a clinicopathological study.
In a clinicopathological study of granulomatous prostatitis, we have found two distinct histological patterns. Approximately one third of cases consisted of localized, often elongated or stellate lesions, resembling rheumatoid nodules. Where clinical details were available, most of these cases had a history of previous transurethral resection. The remaining cases showed more diffuse involvement of the prostate, with lesions centred on ducts and glands, and were not associated with previous prostatic surgery or systemic illness. Immunohistochemical studies of the associated inflammatory infiltrate showed an apparently random distribution of T- and B-lymphocytes in the former group, while in the latter group there was a concentration of T-cells in and around damaged ducts and glands, suggesting a possible immune-mediated destruction of these structures.
Adult↗
Action spectra of the antileukemic and antiviral activities of merocyanine 540.
Action spectra of the antileukemic and antiviral activities of merocyanine 540 (MC540) were determined using L1210 leukemia cells and human Herpes simplex virus type 1. The major peak of both action spectra aligned closely with the absorption spectrum of membrane-bound dye monomer, and by implication, the action spectrum of 1O2 generation. These results are compatible with the notion that the antileukemic and antiviral activities of MC540 are primarily attributable to membrane-bound monomer and at least in part mediated by 1O2.
Animals↗
Modulation by thiols of the merocyanine 540-sensitized photolysis of leukemia cells, red cells, and herpes simplex virus type 1.
This paper reports on the role of endogenous and exogenous thiols in the merocyanine 540 (MC 540)-sensitized photoirradiation of L1210 leukemia cells, human erythrocytes, and human Herpes simplex virus type 1. Several measures taken to decrease the intracellular content of glutathione enhanced the cells' sensitivity to MC 540-sensitized photoirradiation while stimulation of glutathione biosynthesis or supplementation of the extracellular or extraviral thiol content decreased the photosensitivity of cells and viruses. Taken together, these data suggest that endogenous and exogenous thiols can modulate the sensitivity of cells and enveloped viruses to MC 540-sensitized photoirradiation. They also pose new questions as to the mechanism of MC 540-sensitized photolysis.
Animals↗
Mutational analysis of CDC42Sc, a Saccharomyces cerevisiae gene that encodes a putative GTP-binding protein involved in the control of cell polarity.
The Saccharomyces cerevisiae CDC42 gene product, a member of the ras superfamily of low-molecular-weight GTP-binding proteins, is involved in the control of cell polarity. We have analyzed the effects of three CDC42 mutations (Gly to Val-12, Gln to Leu-61, and Asp to Ala-118) in the putative GTP-binding and hydrolysis domains and one mutation (Cys to Ser-188) in the putative isoprenylation site. The first three mutations resulted in either a dominant-lethal or dose-dependent dominant-lethal phenotype when present on plasmids in haploid cdc42-1ts or wild-type strains. Both wild-type and cdc42-1ts cells carrying plasmids (pGAL) with either the CDC42Val-12 or CDC42Leu-61 alleles under the control of a GAL promoter were arrested with a novel phenotype of large cells with elongated or multiple buds. Cells carrying pGAL-CDC42Ala-118 were arrested as large, round, unbudded cells reminiscent of cdc42-1ts arrested cells. The different phenotype of the CDC42Ala-118 mutant versus the CDC42Val-12 and CDC42Leu-61 mutants was unexpected since the phenotypes of all three analogous ras mutants were similar to each other. This suggests that aspects of the biochemical properties of the Cdc42 protein differ from those of the Ras protein. The cdc42Ser-188 mutant gene was incapable of complementing the cdc42-1ts mutation and was recessive to both wild-type and cdc42-1ts. In double-mutant alleles, the cdc42Ser-188 mutation was capable of suppressing the dominant lethality associated with the three putative GTP-binding and hydrolysis mutations, suggesting that isoprenylation is necessary for the activity of the wild-type and mutant proteins.
Amino Acid Sequence↗
Neuronal and glial properties of a murine transgenic retinoblastoma model.
Antigenic properties of a murine transgenic model for hereditary retinoblastoma, induced by a chimeric gene coding for Simian virus 40 large T antigen, an oncogene that inactivates the retinoblastoma susceptibility gene product, were studied by immunohistochemistry. All transgenic mice develop bilateral intraocular retinal tumors in the inner nuclear layer with Homer Wright-like rosettes, and one quarter develop midbrain tumors resembling trilateral retinoblastoma. Cell lines TE-1 and TM-1 were established from intraocular and metastatic tumors, respectively. Intraocular tumors reacted with antibodies to neuron-specific enolase and synaptophysin, while vimentin, glial fibrillary acidic, and S-100 proteins were detected only in reactive glia derived from adjacent retina. The midbrain tumors showed weak reactivity to synaptophysin, and they blended with reactive astrocytes positive for glial markers. The tumors were negative for cytokeratins. Finally both derived cell lines expressed synaptophysin and individual neurofilament triplet proteins in immunofluorescence and Western blotting, supporting their essentially neuronal nature. The antigenic profile resembles human retinoblastoma, but differences in morphology and antigen distribution suggest a more close relationship to neurons of the inner nuclear layer than to photoreceptor cells.
Animals↗
Adolescents' reactions to the death of a peer.
In recent years, more attention has been given to the fact that grieving is a process, especially in the work of Elizabeth Kubler-Ross. The literature has focused on many aspects of bereavement, including how the process may be different at different ages. Much of the research on adolescents has focused on reactions to the suicide of a peer. The purpose of this study was to explore adolescent reactions to the death of a peer by means other than suicide. Semistructured interviews were conducted with ten college students about their experience of losing a friend in high school. Results indicated that even after a few years, the adolescents were still struggling through the grieving process. Implications for future research and suggestions for practitioners faced with similar crises are offered.
Adolescent↗
Primitive neuroectodermal tumor of the midbrain in a murine model of retinoblastoma.
The first heritable model of retinoblastoma was established by retina-specific expression of simian virus 40 T-antigen (SV40 T-ag) in transgenic mice. Bilateral, multifocal ocular tumors were observed in 100% of transgene-bearing mice. Central nervous system neoplasms occurred at a lower rate (27%) and represented the murine counterpart of human trilateral retinoblastoma. The authors characterized the transgenic brain tumors and found them to be primitive neuroectodermal tumors (PNET) of the midbrain. Murine brain tumors do not involve the pineal gland and most closely resemble undifferentiated suprasellar or parasellar tumors occasionally observed in human trilateral retinoblastoma. The murine malignancies arose from the subependymal cells of the cerebral aqueduct. Immunohistochemical and ultrastructural examination revealed that the transgenic brain tumors were undifferentiated and lacked all antigens associated with normal murine neuronal, glial, and ependymal cells.
Animals↗
Isolation and sequence analysis of CDC43, a gene involved in the control of cell polarity in Saccharomyces cerevisiae.
The Saccharomyces cerevisiae CDC43 gene product is involved in establishing cell polarity during the cell-division cycle. When grown at restrictive temperatures, temperature-sensitive cdc43 mutants are unable to form buds and display delocalized cell-surface deposition [Adams et al., J. Cell Biol. (1990) in press]. We have isolated a cdc43-complementing plasmid from a yeast genomic-DNA library and localized the CDC43 gene, by subcloning and transposon-mutagenesis experiments, to a 1.2-kb region of DNA that contained only one significant ATG-initiated open reading frame of 213 codons. The putative CDC43 gene product contains a possible nuclear-localization signal sequence, a cysteine-rich domain and a histidine-rich domain, and a region that is similar in structure to alpha-helix-turn-alpha-helix structural domains present in some prokaryotic and eukaryotic DNA-binding proteins.
Alkyl and Aryl Transferases↗
Retinoblastoma in transgenic mice.
Retinoblastoma, a malignancy of the eye occurring in young children, has been widely studied as a model for genetic predisposition to cancer. This disease is caused by mutations in both alleles of an anti-oncogene (the retinoblastoma gene, Rb) that inactivate or eliminate the Rb encoded protein, p105Rb (refs 1 and 2). Here we report that expression of a viral oncogene, the simian virus 40 T antigen, in the retina of transgenic mice produces heritable ocular tumours with histological, ultrastructural and immunohistochemical features identical to those of human retinoblastoma. Furthermore, we demonstrate a specific association between p105Rb and T antigen in mouse retinoblastoma tumour cells. Thus, the occurrence of these tumours is in vivo evidence for oncogenesis due to the ocular-specific expression of an Rb-binding oncoprotein that can functionally inactivate the Rb protein. As an animal model for heritable retinoblastoma, these mice should allow the study of the ontogeny, pathogenesis and treatment of this malignant disease.
Animals↗
A transgenic mouse model for trilateral retinoblastoma.
We present a murine model of trilateral retinoblastoma. Ocular retinoblastoma and central nervous system tumors are observed in a line of mice formed by the transgenic expression of SV40 T-antigen. An oncogenic protein known to bind to the retinoblastoma gene product (p105-Rb) is specifically expressed within retinal cells in this model. All animals that carry this genetic alteration develop multifocal retinal tumors. Midbrain tumors are observed in 15% of ocular tumor-bearing animals, and these arise ventral to the cerebral aqueduct at the level of the pineal gland. Both ocular and central nervous system neoplasms are heritable in heterozygous offspring through 10 sequential generations of breeding. Retinal tumors display the gross appearance, invasive properties, light and electron microscopic features, and immunohistochemical staining characteristics of human retinoblastoma. The light and electron microscopic characteristics as well as immunocytochemical features of undifferentiated midline central nervous system neoplasms further correlate with human trilateral retinoblastoma. We postulate an alternative mechanism of retinoblastoma tumorigenesis that involves functional inactivation of retinoblastoma protein locally in the face of an intact retinoblastoma gene locus.
Animals↗
Squamous cell carcinoma arising in a chronic hydrocoele.
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Aged↗
Evaluation of merocyanine 540-sensitized photoirradiation as a means to inactivate enveloped viruses in blood products.
Dry or wet heat, solvents, and detergents combined with ultraviolet irradiation provide effective means of sterilizing soluble blood products such as albumin or factor VIII. For obvious reasons, these procedures are not applicable to cellular blood components. We have recently shown that simultaneous exposure to the photosensitizer, merocyanine 540 (MC 540) and white light rapidly inactivates the Friend erythroleukemia virus complex and Friend virus-transformed cells, but causes relatively little damage to pluripotent hematopoietic stem cells. In this communication, we show that several lipid-enveloped human pathogenic viruses are also highly susceptible to MC 540-sensitized photoirradiation, and we report on an initial evaluation of the ability of MC 540-sensitized photoirradiation to sterilize blood products.
2,3-Diphosphoglycerate↗
Trilateral retinoblastoma in transgenic mice.
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Animals↗
Therapeutic approaches for ophthalmic problems in juvenile rheumatoid arthritis.
Juvenile rheumatoid arthritis is a disease of children which is chronic and painful, with the potential to produce permanent disability and blindness in a significant portion of cases. The treatment we provide these children may also disable them. Managing this disease process and caring for these patients is a challenging task in which therapeutic efficacy must be continually balanced against treatment morbidity. With respect to ocular disease, we must particularly recognize the difficulties parents have in treating a characteristically asymptomatic process with interventions that can produce unpleasant symptomatology. The importance of discussion of therapeutic decisions with parent and child cannot be overemphasized. Children with JRA should be carefully classified and those at greatest risk for development of ocular disease should receive frequent ophthalmologic screening exams. Early intervention and aggressive medical management of intraocular inflammation will minimize morbidity and permanent visual compromise. Patients should also be closely monitored for ocular side effects of therapies directed against articular disease. Procedures employed for treatment of cataract, glaucoma, corneal, and vitreal opacities must take into account the risk and complications of surgical intervention in the JRA patient prone to perioperative inflammation.
Anti-Inflammatory Agents, Non-Steroidal↗
Male factor infertility.
Male factors are responsible for or contributory to half of infertility cases. Through history, physical exam, and basic tests, the clinician can successfully perform the majority of evaluations. The use of semen analysis, postcoital test, and serum hormonal levels are described. Causal factors are discussed. The use of more specialized testing and information concerning referral are also detailed.
Humans↗
Inactivation of Friend erythroleukemia virus and Friend virus-transformed cells by merocyanine 540-mediated photosensitization.
The Friend virus complex was used as a model to study the effects of merocyanine 540 (MC 540)-mediated photosensitization on enveloped viruses. Simultaneous exposure to the lipophilic dye MC 540 and white light inactivated cell-free virus, cell-associated virus, and virus-transformed cells. When used under experimental conditions that are known to preserve most mature blood cells, at least some coagulation factors, and a significant portion of the pluripotent hematopoietic stem cell compartment, MC 540-mediated photosensitization reduced virus titers by greater than or equal to 4 log and the concentration of in vitro clonogenic erythroleukemia cells by greater than or equal to 5 log. Animals that received a single intravenous injection of photosensitized virus were resistant to a subsequent challenge with live virus. High sensitivity to MC 540-mediated photosensitization appears to be a property that is shared by other enveloped viruses. Thus, photosensitization mediated by MC 540 may be of benefit in the sterilization of blood products (in particular, cellular products), the production of vaccines, and selected areas of antiviral therapy.
Animals↗