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Biomedical subjects

J M O'Brien

Publications and source records attributed to J M O'Brien.

At least 73 records · Page 4Linked to original sources
PubMed1993

Amniotic fluid index in hospitalized hypertensive patients managed expectantly.

OBJECTIVE: To determine the relationship between low amniotic fluid (AF) index and fetal growth retardation (FGR), fetal distress, and cesarean delivery in patients hospitalized for hypertensive disease, and to describe changes in AF status in relation to the severity of maternal disease. METHODS: The AF index in 142 hospitalized hypertensive patients was followed per an inpatient protocol with semi-weekly testing; medical records were reviewed to obtain delivery data. RESULTS: Fetal growth retardation was significantly associated with an AF index of 5.0 cm or less or 7.0 cm or less (P < .001) at initial assessment, with positive predictive values of 86 and 52%, respectively. However, the sensitivity of an AF index of 5.0 cm or less or 7.0 cm or less to detect FGR was limited (21 and 46%, respectively). Fetal distress and cesarean delivery were not associated with an AF index of 5.0 cm or less or 7.0 cm or less throughout observation in this cohort. Based upon a definition of oligohydramnios as an AF index of 7.0 cm or less, the AF status worsened from an initial normal value in 39% of patients whose final diagnosis was severe preeclampsia, versus only 14% of patients who were diagnosed as having mild disease. The AF index also normalized in ten patients who were originally diagnosed with oligohydramnios and admitted for expectant management. Only one of these women was diagnosed with severe preeclampsia. CONCLUSIONS: 1) Depending on the definition, the incidence of oligohydramnios ranges from 10-30% in hypertensive patients requiring hospitalization; 2) an AF index of 5.0 cm or less at initial evaluation predicts FGR but lacks sensitivity; 3) the AF status frequently changes with serial assessment, and these changes appear to be related to the severity of hypertensive disease; and 4) the frequency of the obstetric complications studied depends more upon the severity of hypertensive disease than on its potential effect of inducing oligohydramnios.

Cesarean Section↗
PubMed1993

Investigation of the role of the ras protooncogene point mutation in human uveal melanomas.

PURPOSE: Genetic alterations have been observed in a wide variety of neoplastic processes, including Burkitt's lymphoma, chronic myelogenous leukemia, promyelocytic leukemia, and solid tumors of the colon, skin, and breast. The polymerase chain reaction (PCR), dot blotting, and direct double-stranded DNA sequencing were used to assess ras gene activation in human uveal melanomas for three candidate genes: c-Ha-ras1, c-Ki-ras2, and N-ras at codons 12, 13, and 61. METHODS: Samples of 49 human uveal melanomas were obtained. Amplifiable high molecular weight DNA was obtained from 39 of these. PCR amplification of regions centering on three candidate ras genes was performed. PCR-amplified DNA was evaluated by dot blot and double-stranded DNA sequencing utilizing standard methods. RESULTS: No point mutations were identified in screening the c-Ha-ras gene nor were any genetic alterations found in the c-Ki-ras2 gene at codons 12 and 13. Only wild-type sequences were found at codon 61. No ras mutations were detected in any uveal melanomas studied. CONCLUSIONS: This study provides no evidence to support an association between ras protooncogene mutations and human uveal melanomas at codons 12, 13, or 61.

Adult↗
PubMed1992

Merocyanine 540-sensitized photoinactivation of enveloped viruses in blood products: site and mechanism of phototoxicity.

The amphipathic dye, merocyanine 540 (MC540), which preferentially photosensitizes enveloped viruses and virus-infected cells, is currently being evaluated in preclinical models as a blood sterilizing agent. In this communication, we report on an initial analysis of the site and nature of MC540-mediated photodynamic damages to human herpes simplex virus type 1 and human cytomegalovirus. The comigration of dye molecules and virions on a gel filtration column, the red-shift of the fluorescence emission spectrum of virus-containing fractions, and the distribution of MC540-treated virions in an aqueous two-phase partition system were indicative of MC540 binding to the enveloped viruses and localizing in a lipophilic environment (most likely the viral envelope). Fluorescence quenching and fluorescence resonance energy transfer experiments suggested that both dye monomers and dimers were capable of partitioning into the lipid bilayer of the viral envelope. Adsorption and penetration assays and immunohistochemical analyses of viral antigen expression showed that MC540-sensitized irradiation interfered with early phases of the infectious process, the adhesion to the host cell, the penetration of the host cell, and the translocation of the virus into the nucleus of the host cell. The inactivation of viruses was inhibited if oxygen in the medium was displaced by argon, enhanced if air was displaced by pure oxygen or if water was replaced by deuterium oxide. This suggested that the MC540-sensitized photoinactivation of enveloped viruses is an oxygen-dependent process and that singlet oxygen is one but not necessarily the only mediator of the antiviral effects of MC540.

Animals↗
PubMed1992

Merocyanine-sensitized photoinactivation of enveloped viruses.

A wide range of enveloped viruses, including human herpes simplex virus type 1, human cytomegalovirus, human T cell leukemia/lymphoma virus type I, human immunodeficiency virus type 1, Sindbis virus, and Friend erythroleukemia virus, are highly susceptible to merocyanine 540 (MC 540)-sensitized photoinactivation. By contrast, human pluripotent hematopoietic stem cells, red cells, factor VIII, and von Willebrand factor are much less sensitive. This suggests that MC 540 may be useful for the inactivation of enveloped viruses in blood and blood products. The dye has a low acute systemic toxicity, is rapidly eliminated from the blood stream, and has little or no mutagenic potential. The currently available data support the view that MC 540-sensitized photo-inactivation interferes with early events in the infectious process, notably the ability of the virus to adhere to and penetrate its host cell. The viral envelope is a major target of photodynamic damages which appear to be mediated at least in part by singlet molecular oxygen.

Animals↗
PubMed1992

The antineoplastic effect of vitamin D in transgenic mice with retinoblastoma.

Vitamin D has been shown to inhibit growth of human retinoblastoma in tissue culture and nude mouse heterografts. We have described a heritable transgenic mouse model of retinoblastoma. The in vivo efficacy of 1,25-dihydroxycholecalciferol (vitamin D3) was examined by administering this agent to transgenic mice with retinoblastoma. Forty-six 8-10-week-old transgene-bearing mice were injected intraperitoneally for 5 wk. Experimental animals received 0.05 microgram (15 animals) or 0.025 microgram (15 animals) of vitamin D. Sixteen control animals received only a mineral oil vehicle. Eyes were enucleated at 5 mo and were examined histologically by two investigators in a masked fashion. All control animals demonstrated bilateral involvement of retinoblastoma. Four eyes in the low-dose group and six eyes in the high-dose group had no evidence of retinoblastoma. Eyes treated with vitamin D3 showed less extensive involvement of the retina by retinoblastoma. Vitamin D-treated animals demonstrated tumors confined to the retina, whereas control animals demonstrated larger tumors, more often invading the vitreous, anterior chamber, and choroid. Thus, Vitamin D inhibited the growth and local extension in a dose-dependent fashion.

Animals↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗