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Biomedical subjects

J M O'Brien

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

At least 55 records · Page 3Linked to original sources
PubMed1994

Cervicovaginal prolactin: a marker for spontaneous preterm delivery.

OBJECTIVE: Our purpose was to determine whether the presence of prolactin in cervicovaginal washings is associated with preterm birth. STUDY DESIGN: A cohort of 80 patients underwent a washing of the ectocervix and vaginal fornices with a normal saline solution. The cohort consisted of two groups: 40 inpatients requiring tocolysis and 40 asymptomatic outpatients. The saline solution aspirates were centrifuged, the supernatant was stored at -70 degrees C, and a radioimmunoassay for prolactin was run in batch fashion. A prolactin concentration greater than the detection limit of the assay was considered a positive test result. RESULTS: Prolactin was identified in significantly more symptomatic patients than asymptomatic controls (50% vs 5%, p < 0.0001). In symptomatic patients cervicovaginal prolactin had an 80% positive predictive value and a 65% negative predictive value for delivery at < or = 34 weeks' gestation. Patients testing positive for prolactin had significantly shorter latency from testing to delivery (16 +/- 17 vs 34 +/- 24 days, p = 0.02) and had significantly lower birth weights (1985 +/- 729 vs 2583 +/- 696 gm, p = 0.01) compared with patients testing negative. Prolactin was also identified in two asymptomatic patients, both of whom were delivered before term. CONCLUSIONS: Cervicovaginal prolactin is a biochemical marker for preterm delivery, a shorter latency period to delivery, and lower birth weight in symptomatic patients. This test may also prove to be a valuable marker for preterm birth in asymptomatic women.

Adult↗
PubMed1994

Thyroid ophthalmopathy.

Thyroid ophthalmopathy, idiopathic orbital inflammation, and orbital infection can occasionally demonstrate overlapping clinical features. It is essential to distinguish between these processes because appropriate treatments are distinct in each case. In the past year, the pathophysiology of thyroid ophthalmopathy has been the topic of many reports. Orbital inflammation, particularly the fibrotic form, has been recognized to represent a distinct disease entity that may require more specifically directed treatment. In some cases cytotoxic therapies may be indicated. Orbital infection, particularly in the setting of orbital abscess, may be treated conservatively with antibiotic therapy and observation or more aggressively with surgical drainage procedures. In several recent studies, appropriate management of such infectious processes appears to be related to patient age, as well as to the specific clinical pattern of presentation.

Eye Diseases↗
PubMed1993

Tempting fate: control of communicable disease in England.

Recent changes in the NHS have left many defects in the systems for the control of communicable diseases and infection and their surveillance and the management of outbreaks. Clear, explicit legislation is needed, placing the responsibilities on health authorities. New teams led by consultants need to be set up to investigate and manage outbreaks of communicable diseases of all types.

Communicable Disease Control↗
PubMed1993

Subcellular localization of Cdc42p, a Saccharomyces cerevisiae GTP-binding protein involved in the control of cell polarity.

The Saccharomyces cerevisiae Cdc42 protein, a member of the Ras superfamily of low-molecular-weight GTP-binding proteins, is involved in the control of cell polarity during the yeast cell cycle. This protein has a consensus sequence (CAAX) for geranylgeranyl modification and is likely to be associated, at least in part, with cell membranes. Using cell fractionation and immunolocalization techniques, we have investigated the subcellular localization of Cdc42p. Cdc42p was found in both soluble and particulate pools, and neither its abundance nor its distribution varied through the cell cycle. The particulate form of Cdc42p could be solubilized with detergents but not with NaCl or urea, suggesting that it is tightly associated with membranes. An increase in soluble Cdc42p was observed in a geranylgeranyltransferase mutant strain (cdc43-2ts) grown at the restrictive temperature. In addition, Cdc42p from a cdc42C188S mutant strain (that has an alteration at the prenylation consensus site) was almost exclusively in the soluble fraction, suggesting that membrane localization is dependent on geranylgeranyl modification at Cys-188. Immunofluorescence and immunoelectron microscopy experiments demonstrated that Cdc42p localizes to the plasma membrane in the vicinity of secretory vesicles that were found at the site of bud emergence, at the tips and sides of enlarging buds, and within mating projections (shmoo tips) in alpha-factor-arrested cells. These results indicate that Cdc42p is localized to the bud site early in the cell cycle and suggest that this localization is critical for the selection of the proper site for bud emergence and for polarized cell growth.

Amino Acid Sequence↗
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↗